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November/December 2013
Volume 4 Number 6
http://magazine.embs.org
A MAGAZINE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY
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IEEEPULSE
NOVEMBER/DECEMBER 2013
Volume 4 Number 6
http://magazine.embs.org
A MAGAZINE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY
FEATURES
12
New World of 3-D Printing Offers

Completely New Ways of Thinking
by Leslie Mertz
pg.
15
Dream It, Design It, Print It in 3-D
22
Adding Value in Additive

Manufacturing
27
by Leslie Mertz
by Jim Banks
27
The Body Printed
32
Moving the Science of Behavioral

Change into the 21st Century: Part 2
by Shannon Fischer
by Niilo Saranummi, Donna Spruijt-Metz,

Stephen S. Intille, Ilkka Korhonen,
Wendy J. Nilsen, and Misha Pavel
34
Healthy Apps
41
Systems Modeling
of Behavior Change
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by Bonnie Spring, Marientina Gotsis,

Ana Paiva, and Donna Spruijt-Metz
by Daniel E. Rivera and Holly B. Jimison
COLUMNS & DEPARTMENTS
pg. 60
4 FROM THE EDITOR

8 PRESIDENTS MESSAGE
10 PERSPECTIVES ON
GRADUATE LIFE
50
66
68
70
RETROSPECTROSCOPE
CONTINUING EDUCATION
CHAPTER NEWS
CALENDAR
48 STATE OF THE ART
_____
Digital Object Identifier 10.1109/MPUL.2013.2279631
IEEEPULSE
NOVEMBER/DECEMBER 2013
IEEE PULSE 1
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IEEE PULSE
EDITOR-IN-CHIEF
Michael R. Neuman
Michigan Technological University
Houghton, Michigan, USA
DEPUTY EDITOR-IN-CHIEF
Silvestro Micera
Scuola Superiore SantAnna
Pisa, Italy
ASSOCIATE EDITOR
Cynthia Weber
Michigan Technological
University
Yongmin Kim
Pohang University of Science
and Technology
Pohang, South Korea
Patricia J. Soterin
Communications
Michigan Technological
University
Ann Brady
Director Program in Scientific
and Technical Communication
Michigan Technological University
CONTRIBUTING EDITORS
EDITORIAL BOARD
Shanbao Tong
Shanghai Jiao Tong University
Shanghai, China
Stuart Meldrum
Retired from Norfolk and
Norwich Health Care
NHS Trust
Norwich, UK
Semahat Demir
Istanbul Kltr University
Istanbul, Turkey
Samuel K. Moore
IEEE Spectrum
New York, New York, USA
A Look At
Jean-Louis Coatrieux
University of Rennes
France
Book Reviews
Retrospectroscope
Max Valentinuzzi
Universidad Nacional
de Tucumn and Universidad
de Buenos Aires
Argentina
IEEE PERIODICALS
MAGAZINES
DEPARTMENT
MANAGING EDITOR
Senior Design
Jessica Barragu
Jay R. Goldberg
Marquette University
Milwaukee, Wisconsin, USA
Janet Dudar
SENIOR ART DIRECTOR
State of the Art
Arthur T. Johnson
University of Maryland, USA
Continuing Education
Cristian A. Linte
Mayo Clinic
Rochester, Minnesota, USA
ASSISTANT
ART DIRECTOR
Gail A. Schnitzer
PRODUCTION
COORDINATOR
Theresa L. Smith
Students Corner
Subhamoy Mandal
Helmholtz Zentrum Munchen
Institut fur Biologische
und Medizinisch,
Germany
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MANAGER
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Fairfield, Connecticut, USA
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City University
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Keck Graduate Institute
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IBM Research
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Vanderbilt University
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PUBLISHING
OPERATIONS
Editorial Correspondence: Address to Michael R. Neuman, Department of Biomedical Engineering, Michigan
Technical University, 1400 Townsend Dr. Houghton, MI 49931-1295, USA. Voice: +1 906 487 1949. E-mail:
mneuman@mtu.edu.
__________
Indexed in: Current Contents (Clinical Practice), Engineering Index (Bioengineering Abstracts), Inspec, Excerpta Medica,
Index Medicus, MEDLINE, RECAL Information Services, and listed in Citation Index.
All materials in this publication represent the views of the authors only and not those of the EMBS or IEEE.
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FROM THE EDITOR
Binary BME
Michael R. Neuman
ngineering is involved with many

binary quantities. The most familiar
are the ones and zeros of digital electronics; yet, there are many more binary
situations, ranging from whether a signal
crosses a threshold to management decisions on whether to fund a project. Even
a decision on shall we break for lunch?
can be considered binary, with strong bias
toward the positive when we are hungry.
Binary quantities are concerned with
yes or no types of decisions: is it or
isnt it, has something occurred or not,
should we turn right or left when we
come to a fork in the road, and so on.
Essentially, binary quantities represent
two distinct alternatives: if you choose
one, you cannot choose the other; they
cannot coexist.
So what does this have to do with biomedical engineering? As I have said so
many times in this column, biomedical
engineering covers a wide range of activities as well as a wide variety of engineering and science disciplines. How, then,
could it possibly be binary? I certainly
consider biomedical engineering to be
more of a continuum than a dichotomy;
yet, I am seeing signs that a more binary
structure is emerging. There are biomedical engineers who are more concerned
with hardware: engineering devices
applied to mostly medical and some biological problems. These engineers focus
more on hardware and software and
often produce some sort of device that can
ultimately become a commercial product.
They can either be trained as a biomedical
engineer or in one of the more traditional

Date of publication: 6 November 2013
labs are concerned with applied biology

and look more like a life science laboratory in a medical school than a facility
for engineering activities.
These two types of biomedical engineering laboratories show the extreme
differences in the various areas that make
up biomedical engineering. One might
consider them to be at opposite ends of
the continuum of diverse disciplines in
engineering disciplines, such as mechanour interdisciplinary field. Nevertheless,
ical or electrical engineering. In the past,
these should not be considered binary
employers would often hire mechanical
poles of our discipline. Once you step into
engineers to work on the mechanical
one of these labs, however, you may get a
aspects of biomedical device production
different impression. Just ask one of the
or electrical engineers to deal with the
white-coat-wearing workers how she or
chips and passive components involved
he could optimize the biologic process she
in biomedical electronic design. Aspiring
or he is studying or how the reaction folbiomedical engineering students conlows the laws of thermosidered augmenting their
dynamics, and she or he
undergraduate degree
might not know what you
with a minor in one of
Biomedical
are talking about. On the
the traditional engineerengineering covers
other hand, the engineer
ing disciplines or perhaps
a wide range of
in the devices laboratory
even a joint degree, but
activities as well
wearing a T-shirt and blue
there was hardly ever
as a wide variety
jeans might give a simimore than minimal life
lar response when asked
sc ienc e i n t hei r bac kof engineering and
about the Krebs cycle.
ground. Often, these were
science disciplines.
Indeed, this dichotomy
the students who got the
of biomedical engineering
best jobs, at least accordmust be avoided, although some of us are,
ing to them. This was what people of my
in essence, becoming life scientists even
generation thought biomedical engineeras we still call ourselves biomedical engiing was all about, and those of us in acaneers. We work in areas such as tissue
demia designed curricula to support this
engineering or regenerative medicine,
kind of biomedical engineering activity.
proteomics, or molecular and cell biolThings can be quite different now.
ogy; therefore, it is sometimes difficult to
When I enter a biomedical engineerdifferentiate us from scientists who study
ing laboratory today, it is easy to think
only these fields. What then makes us
that maybe I am in the wrong place.
biomedical engineers? Work in these
The laboratory looks more like one that
areas can be biomedical engineering just
carries out basic life science research
as much as designing a prosthetic hand is
than an engineering laboratory. Oscilbiomedical engineering, even if the two
loscopes, signal generators, materials
areas seem quite different. I look at the
testers, and machine shops have been
more biological aspects of biomedical engireplaced by microscopes, cell cultures,
neering as being equally important in our
centrifuges, and biosafety cabinets. Lab
profession as are the physical aspects.
workers all wear white coats, and some
Just as a designer of a prosthetic hand
may even wear facemasks over their
needs to be familiar with robotics, elecmouths and noses. Petri dishes and
tronics, and biomechanics, a tissue engiincubators instead of circuit boards and
neer needs to be familiar with stem cell
hardness testers fill bench tops. These
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IEEE Medal for Innovations in Healthcare

Technology
RECOGNIZING THE EXTRAORDINARY
Nomination Deadline:
1 July (Annually)
For outstanding contributions and/or

innovations in engineering within the
fields of medicine, biology, and
healthcare technology.
Selection criteria include:

(a) impact on the
profession and/or
society
(b) succession of
significant technical or
other contributions
(c) leadership in
accomplishing
worthwhile goal(s)
(d) previous honors
(e) other achievements
as evidenced by
publications or patents or
other evidence
(f) quality of nomination
IEEE Medal for Innovations in Healthcare Technology,

established in 2009.
The areas of healthcare technology recognized by this
medal include, but are not limited to: bio-signal processing;
biomedical imaging and image processing; bioinstrumentation; bio-sensors; bio micro/nano technologies;
bio-informatics; computational biology and systems biology;
cardiovascular and respiratory systems engineering; cellular
and tissue engineering; bio-materials; bio robotics; biomechanics; therapeutic and diagnostic systems; medical
device design and development; healthcare information
systems; telemedicine; and emerging technologies in
biomedicine (e.g.biophotonics).
PRESENTED TO - An individual or team, up to five in
number
PRIZE Recipient(s) will receive a gold medal, a bronze
replica, certificate, and US$20,000 honorarium (shared
equally among all recipients).
SPONSOR - IEEE Engineering in Medicine and Biology
Society
Nomination guidelines and forms can be downloaded from
the IEEE Awards Web site at:
http://www.ieee.org/about/awards/medals/healthcare.html
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The End of an Incredible Journey

With this issue of IEEE Pulse, I end my term as editor-in-chief. It has been
a wonderful six-year journey and an opportunity to, hopefully, improve
this publication. As with any endeavor of this type, the leader may bask
in the successes achieved, but the credit goes to many individuals too
numerous to mention at this point, and there is too much of a risk of
forgetting someone who should not be forgotten. However, there are
some special people who I really want to mention. I want to give my
special thanks to Associate Editor Cynthia Weber, whose influence on
these pages will continue with our new editor-in-chief, Colin Brenan.
Cynthias experience in magazine production; academic experience in
writing and in teaching that important skill to scientists and engineers;
and her collegial, collaborative, and gentle approach to dealing with an
aging editor have been greatly appreciated. I also want to give special
thanks to Debby Nowicki, former managing editor of the magazine,
and Jessica Barragu, our current managing editor. Also, thanks go to
Deputy Editor Silvestro Micera. Their contributions to publishing an

attractive, colorful, and readable magazine have been very special. It
has been an incredible journey for me, and as with other wonderful
journeys, the end must come; but also as with any fantastic journey, the
memory of the experience will live on.
But wait a minutethe journey is not over! We are getting a new
driver and a very exceptional one. Colin Brenans ideas for taking this
magazine to the next level will make the journey even more exciting.
He will accelerate the pulse of IEEE Pulse and bring us to new media. His
experience as a successful entrepreneur will expand the focus of this
publication as well as increase its relevance to our subscribers in the
biomedical industry and beyond. I will be like you, dear readers,
anxiously awaiting the next issues of this IEEE Engineering in Medicine
and Biology Society flagship publication.
Mike Neuman
What now contributes to making biobiology, tissue culture techniques, and

medical engineering binary is that the
molecular biology. Indeed, on closer
biomedical engineers focused on applied
examination, these two areas are similar
biology and those focused on applied physin that each researcher applies an area of
ical science appear to be taking different
basic science or engineering to address an
pathways to their ultimate objectives. We
important problem in the life sciences or
must avoid the physical-science-oriented
clinical medicine. A biomedical engineer
biomedical engineer havworking in tissue engiing little understanding
neering must understand
and appreciation of the
basic biology to learn
A biomedical engineer
life science side of biohow to regenerate organs
working in tissue
medical engineering and
to replace failed ones. In
engineering must
the biology-oriented biodoing so, this professional
understand basic
medical engineer havapplies fundamental biolbiology to learn how
ing little understanding
ogy to an engineering
and appreciation for the
problem: how can we gento regenerate organs
chemistry, physics, and
erate replacement parts
to replace failed ones.
engineering background
for an individual patient?
so important for his or her
What makes it different
area of emphasis. I frequently hear gradufrom pure biology is that the biomedical
ate students working in tissue engineering
engineer can apply the quantitative engiasking why they need to know biomeneering approach to the biologic probchanics or medical instrumentation,
lem. (Biologists are catching on to this
while the device-oriented biomedical
approach, too.)
engineering students ask why basic biolIn practice, this is no different from
ogy is so important for them. Ultimately,
what the biomedical engineer designing
this is where the dichotomy develops. We
a prosthetic hand does. She or he needs to
all recognize the importance of breadth
understand hand anatomy, function, and
as well as depth in aspects of biomedical
biomechanics as well as basic and applied
engineering (see my column in the July/
physics to be able to apply these to the
August 2013 issue of IEEE Pulse) but often
design problem. Thus, the two approaches
fail to see the importance of crossing the
to biomedical engineeringbiological
increasingly diffuse interface between
and physicalare essentially doing the
physical science and biology when consame thing but starting from entirely difsidering breadth. By understanding
ferent origins. Does this make biomedical
the many advances of modern biology,
engineering binary? I hope not, but we
the device-oriented biomedical engimust be vigilant to avoid the development
neer is better equipped to design devices
of this binary thinking in the future.
while keeping the science related to the

application in mind, and similarly, the
biology-oriented biomedical engineer can
use the tools and techniques of the physical and engineering sciences to address
their life science problem.
To function optimally, these two areas
of biomedical engineering should not
be binary. Applied biologists have made
many contributions based on engineering principles. For example, a tissue engineered kidney need not look exactly like a
natural one. Tissue engineers have grown
replacement organ constructs on microfabricated silicon matrices that may not
look like a kidney but still can function like
one. Biomedical device engineers have
developed analytical sensors based on the
sensing molecules and structures in living
cells. Neither could do this without a good
understanding of much of the continuum
of biomedical engineering disciplines.
Binary biomedical engineering? If we
are moving in that direction, we need to
reverse our course. Device- and biologically based biomedical engineering are
both important and encompass exciting
new developments. Although our field
can, no doubt, sustain its rapid growth as
a binary discipline, we can do much better if we emphasize what interests us anywhere along the continuum of disciplines
but not forget the importance of being
familiar with other aspects of our important field as well. Let us leave binary
quantities for coin tossing and computer
science/engineering.
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CALL FOR NOMINATIONS

Submission Deadline: 17 January 2014
IEEE EMBS Achievement & Service Awards

Nominations are being sought for the following IEEE Engineering in Medicine and Biology Society
Awards for 2014. Each award recipient will receive a plaque/certificate, an honorarium, and
reimbursement in travel expenses associated with attending the EMBS Awards Presentation at the
36th Annual International Conference of the Society. The 2014 conference will be held in Chicago,
Illinois, USA, 27-31 August 2014 (http://embc.embs.org/2014/).
THE EMBS ACADEMIC CAREER ACHIEVEMENT AWARD

Honorarium $2,500 USD/Travel Reimbursement up to $1,500 USD
For outstanding contribution and achievement in the field of Biomedical Engineering as an educator,
researcher, developer, or administrator who has had a distinguished career of twenty years or more in the
field of biomedical engineering. Accomplishments may be technological or theoretical and need not have
proceeded the award date by any specific period of time. Individual must be a current member of EMBS.
THE EMBS PROFESSIONAL CAREER ACHIEVEMENT AWARD
For outstanding contribution advancing Biomedical Engineering and its professional practices as a
practicing biomedical engineer working in industry, government or other applied areas related to biomedical
engineering. Accomplishments include, but are not limited to, technological advances, improvements in
processes, or development of new products or procedures, and need not have preceded the award date by
any specified period of time. Individual must be a current member of EMBS.
THE EMBS EARLY CAREER ACHIEVEMENT AWARD
For significant contributions to the field of biomedical engineering as evidenced by innovative research
design, product development, patents, and/or publications made by an individual who is within 10 years of
completing their highest degree at the time of the nomination and are a current member of EMBS.
THE EMBS DISTINGUISHED SERVICE AWARD
For outstanding service and contributions to the Engineering in Medicine and Biology Society.
Accomplishments should be related to direct Society service and need not have preceded the award date
by any specific period of time and individual must be a current member of EMBS.
Nomination Procedure
The required nomination packet consists of a two-page nomination form (see http://www.embs.org/awardnomination-announcement), a current CV and letters from three references along with their address,
telephone, facsimile number and e-mail address. It is the responsibility of the nominator to contact the
references and solicit letters of endorsement.
The complete nomination packet must be submitted online at http://www.embs.org/award-nominationannouncement and received no later than 17 January 2014 for the nominee to be considered for 2014. It is
very desirable for nominations to be submitted well before the deadline.
For questions, please contact the EMB Executive Office (embs-awards@ieee.org).
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PRESIDENTS MESSAGE
Neural Engineering in the Limelight

Bruce Wheeler
he 6th International IEEE Engineering in Medicine and Biology Society

(EMBS) Neural Engineering Conference was held 26 November, 2013,
in San Diego, California (http://neuro.
embs.org/2013/). It was a resounding
success. Congratulations to the organizers of the conference, Dr. Metin Akay
(University of Houston) and Dr. Bin
He (University of Minnesota) for their
superb organization and promotion of
the conference. Their concept of recruiting the worlds top neural engineers and
neuroscientists as keynote speakers and
scheduling the conference immediately
before the annual meeting of the Society
for Neuroscience proved to yield great
results. The presence of more than 600
attendees made this conference a record
for both the Neural Engineering Conference and for the IEEE EMBS series of
special topic conferences (http://embs.
org/conferences-meetings).
The success of the conference is also
the culmination of a long and dedicated
development since the first Neural Engineering Conference held in Capri, Italy, in
2003. Dr. Akay showed great leadership
and foresight in starting the conference,
and he continued his efforts to steadily
grow the conference as it moved to different locations: Arlington, Virginia (2005),
Kohala Coast, Hawaii (2007), Antalya,
Turkey (2009), and Cancun, Mexico
(2011). The conference is notable for
being truly international but also for its

The second high-profile project is the

European Human Brain Project. It was
started in 2012, with more than a billion
euros in funding to be expended over a
decade across more than 80 institutions,
led by the Ecol Polytechnique Federale
de Lausanne. The high-level goals of the
projects are similar in that the work of
both should lead to a much greater understanding of how the brain functions and
strong emphasis on student awards and
provide the framework for investigating
involvement and a strong representation
both pathologies of the brain and how
of world leaders in neural engineering.
the normal brain functions. The Human
Neural engineering also takes center
Brain Project includes supercomputer
stage because of recent announcements
simulations of brain functioning based
regarding high-profile research programs
on exceptionally realistic
in Europe and the United
models with detail down
States. This past April, Presto the level of individual
ident Obama announced a
Neural engineering
neurons and conduction
US$100 million public/prialso takes center stage
channels. Neural engivate initiative to map the
because of recent
neers, especially those
brain with the aim of proannouncements
heavily involved in comviding more basic knowlregarding high-profile
putational modeling and
edge that ultimately will
research programs in
informatics, are central to
help address major neuthe effort.
rological disorders such as
Europe and the
The IEEE EMBS, led
autism and schizophrenia,
United States.
by Dr. He, which sponAlzheimers disease, and
sored the successful IEEE
epilepsy. Its nickname
EMBS Forum on Grand Challenges:
BRAIN, short for Brain Research through
Neural Engineering in 2010, will organize
Advancing Innovative Neurotechnoloanother forum on the BRAIN and Human
giesemphasizes the neural engineering
Brain projects. The EMBS has a publicatechnologies that will play a major role in
tion dedicated to neural engineering [1],
the initiative. Hence, we can look forward
and has published multiple special issues
to the greater development of functional
on neural engineering and braincommagnetic resonance imaging techniques,
puter interface technology.
high-density electrode arrays, optical and
Neural engineering is truly taking cenelectrical imaging of brain activity for
ter stage, and the IEEE EMBS is dedicated
human computer interfaces, and optogeto promoting the field and serving our neunetic technologies for brain stimulation
ral engineering members.
down to the single neuron level. Significant efforts will go toward what is becoming known as functional connectomics, or
Reference
the study of the connections within the
[1] IEEE Trans. Neural Syst. Rehab. Eng. [Online].
brain and how they encode information.
Available: http://embs.org/publications/ieee_________________
The IEEE International Neural Engineertransactions/ieee-transactions-onneural______________________
ing Conference brought together many
systems-and-rehabilitation-engineering
____________________
investigators who are at the cutting edge of
all of these technologies.
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CALL FOR NOMINATIONS 2014

IEEE EMBS Chapter Awards

Nominations are being sought for the following IEEE Engineering in Medicine and Biology
Society Awards for 2014. Each award recipient will receive a certificate, an honorarium, and
reimbursement in travel expenses associated with attending the EMBS Awards
Presentation at the EMBS Awards Presentation at the 36th Annual International Conference
of the Society. The 2014 conference will be held in Chicago, Illinois, USA, 27-31 August
2014 (http://embc.embs.org/2014/).
EMBS OUTSTANDING CHAPTER AWARD
Honorarium $1000 USD/Travel Reimbursement of up to $1,000 USD
For achievement in member development and delivering services to members of an EMBS Chapter during
the previous calendar year. A single EMBS Chapter will be selected based on activities, community
outreach and promotion of EMBS.
EMBS BEST NEW CHAPTER AWARD

Honorarium $500 USD/Travel Reimbursement of up to $1,000
For outstanding activities performed by a new EMBS Chapter within the first 12 months of Chapter
formation. A single EMBS Chapter will be selected based on activities, community outreach and promotion
of EMBS.
EMBS OUTSTANDING PERFORMANCE AWARD for an EMBS Student Branch Chapter/Club

Honorarium $500 USD/Travel Reimbursement up to $1,000 USD
For achievement in demonstrating outstanding performance in promoting student interest and involvement
in Biomedical Engineering during the previous calendar year. A single EMBS Student Branch Chapter or
Club will be selected based on activities demonstrating initiative, innovation, and creativity; areas of
progress and improvement; significant impact in biomedical engineering education; and contributions to the
profession.
EMBS BEST NEW STUDENT BRANCH CHAPTER or CLUB AWARD

Honorarium $300 USD/Travel Reimbursement of up to $1,000
For outstanding activities performed by a new EMBS Student Club or Chapter within the first 12 months of
formation. A single EMBS Student Branch Chapter or Club will be selected based on activities
demonstrating initiative, innovation, and creativity; areas of progress and improvement; significant impact in
biomedical engineering education; and contributions to the profession.
The required nomination packet consists of a one-page nomination form and supporting
documentation as outlined in the nomination form (see embs.org/chapter-award-nomination).
The complete nomination packet must be submitted via email to ____________________
embs-awards@ieee.org no later
than 17 January 2014. It is very desirable for nominations to be submitted well before the
deadline.
For questions, please contact the EMB Executive Office (embs-awards@ieee.org)
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PERSPECTIVES ON GRADUATE LIFE
The Home Stretch

Zen Liu
he days are getting shorter, temperatures have cooled, and multiple

moving vans have been spotted on
my block. The new class of graduate students has arrived.
Usually, I love meeting new people,
making new friends, and being useful.
There is no better time for this than new
student orientation, one of the rare periods
when graduate students are outgoing and
have the luxury of spending their time at
multiple social activities in one week. As
the vice president of the Engineering Graduate Student Council at Columbia University, I tend to get pretty excited about
welcoming the new kids and spend a great
deal of orientation week outside of the lab,
organizing and leading events. This year,
however, my emotions are mixed, and I
feel more reserved than in years past.
It has nothing to do with the new students themselves and everything to do
with the fact that I am starting my fourth
year in my Ph.D. program. The controlled
chaos of planning orientation week over
the last two months and now its arrival
have only reinforced, in the most agonizing way possible, that I have been here for
a really long time without a lot to show for
it. I feel frustrated, a little disappointed in
myself, anxious about my lack of progress,
and stir crazy. In each of the countless
introductions I have made this week (and
will still make in the weeks to come), the
same question inevitably gets lobbed at
me after the initial pleasantriesWhat
year of your Ph.D. are you in?
Toward the end of the last spring
semester, a visiting professor in my lab
kindly asked how my Ph.D. thesis was
progressing. I admitted to her that I felt
that I had achieved less than I should
have by that point, and I worried that I

was falling behind the rest of my classmates. I was already bracing myself for the
moment I would be forced to acknowledge
that I would be at Columbia much longer
than the department average of 5.5 years.
She chuckled knowingly and assured me
that my feelings were quite on point with
what all Ph.D. students should be experiencing as they look toward their fourth
year and predicted that my research
would be picking up soon enough. Before
I knew it, she foretold, I would be well on
my way to graduating.
I remember being a junior in college,
polling the graduate students I worked
with to see if they thought I should apply
to Ph.D. programs. At the time, I was
surprised by their thoughtful pauses
and how subdued and measured they
sounded when they finally responded.
From the outside looking in, their lives
seemed so interesting and exciting, even
liberating. They made their own schedules and performed groundbreaking
research every day. However, it was clear
from the way they spoke that they were
attempting to walk the fine line between
dissuading me from doing something I
might love and be great at and being honest about how stressful and disheartening graduate school can be at times. It is
a bold gamble, betting your future on the
outcome of some grand ideas and overly
optimistic plans you came up with while
soaping up in the shower. They told me
to go for it, but to remember it was an
endurance game, a measure of stamina,
and the somewhat pathetic desire to just
finish what you have started. I took their
words at face value and thought I understood, but the years have given them
greater weight and depth.
I am glad that I took the leap. I think
I really would have regretted not giving
graduate school a chance. I am not competitive by nature, but I have high expectations for myself. I would have always
wondered if I could have done it, should
have done itif I had what it takes. I went
into graduate school for all the usual and
right reasons: I loved science; I loved all
of my bench research experiences in college; I loved the idea of making a contribution to society by advancing the medical
field. It seemed like the perfect melding
of all my passions into one career. There
was no doubt in my mind that I would get
my Ph.D. degree, continue on into a postdoctoral program, and apply for a tenuretrack professorship position one day. I set
my sights on this career path at age 18,
and with every passing year, my desire to
achieve that position of status and success
and apparent wisdom grew stronger.
Then, I went to graduate school and
grew up. I discovered things about myself
that I thought would have been revealed
in college. I did not know that I had more
growing up to do. I learned that I was capable of feeling a level of anxiety and depression that was so debilitating I actively
avoided my lab and shunned my colleagues. I had panic attacks when I received
e-mails from my supervisor asking for
updates and data. It would take 15 min for
my heart rate to drop back down to normal
and for my jaw to unclench. I sought out
a therapist for the first time. I felt like an
imposter and a failure, and I did not know
how to cope. I had never expected to have
to cope. I learned that I need regular milestones and checkpoints with my supervisor
to feel like I have accomplished anything.
I need constant feedback to feel validated
in my work. I need guidance, maybe more
than the average graduate student should
expect. I need to feel supported.
With all of these revelations, I have
begun to wonder if going to graduate
school was really the right decision for
me. The emotional toll it has taken seems
to indicate that my personality is ill suited
for this type of environment. As I have
discovered, loving science is not enough
to make you a great Ph.D. student. There
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is some other fundamental quality that a

person needs to have to be good at this,
and I am not sure that I have it. I have no
idea what it is or what to call it, but I can
recognize it when I see it in other people.
I have had countless philosophical
discussions lately with myself and with
friends about the idea of having a true calling in life, which, for now, sounds a bit too
much like a fairy tale. There is no question
that my dream of becoming an academic
hotshot has faded completely, and I would
not be surprised if I ended up in a job that
does not even require a Ph.D. degree, to

say nothing of a biomedical engineering
background. Yet, I have to believe that I
wanted to be here and fought to be here
for a reason. I have to believe that I would
always be a better scientist than I would
be a musician or an artist or any other
thing I had considered becoming as a
child. Some days, I think I will never see
the light at the end of the tunnel (of my
thesis), and thatmore than anything
feels like failure. And then I tell myself to
calm down, to stay the course, and to wait
Looking Forward
Matthew C. Canver
do not recall a time prior to medical or

graduate school when worklife balance
was explicitly talked about. If you said
that you wanted to be a doctor, a scientist, lawyer, consultant, or banker, people
were always excited by your ambition and
encouraged you to follow your dreams. It
seems as if it is only years after you have
committed to any of these careers that
anyone mentions you will likely have long
working hours, which can be devastating
to your personal life and make a healthy
worklife balance a tough goal to achieve.
So you may think: maybe you just did not
do adequate research or shadow enough
people in these careers; maybe it is a sign
of immaturity or naivety to acknowledge
this complication so late in the game;
maybe if you had thoroughly looked into
your career, you would have known about
the long hours and the difficulty of maintaining a personal life with your given
profession. On the flip side, maybe these
concerns do not really manifest until a
certain age or stage of life, so they are easily overlooked by young students in the
early stages of their education and careers.
Regardless, worklife balance never
seems to be discussed with students. To

make matters worse, younger students

always look at the people at the end of the
long road: the attending physician, the
partner at the law or consulting firm, or
the principal investigator of a lab. Their
hours and overall lifestyle are generally
better than those in earlier stages of their
careers/training, they are generally making good money, and they are very knowledgeable in their field. Therefore, they do
not seem to give the best representation
for what their careers will actually be like.
In my own personal experience, I shadowed several attending surgeons. No one
ever suggested that I shadow residents,
medical students, or graduate students to
learn about their experiences during their
training, which all have a reputation for
being intense. Even if you had such an
experience, it is hard to find people willing to be completely honest about their
training or people without hindsight bias
(who, in hindsight, claim that everything
was not so bad).
All of that is to say that worklife balance is a tough problem to solve. On the
one hand, you want to be really good at
what you do and choose a respectable
career (best possible scientist or physician
in this case). On the other hand, you do
not want the path to becoming a good scientist and/or physician to consume such
for that magical moment that is supposed

to hit me this year, when all of my experiments will start working and my data will
become significant. I am waiting to feel
like I might someday graduate, at which
point I can finally check that task off my
lifes to-do list.
Zen Liu is currently a Ph.D. student in the
Department of Biomedical Engineering at
Columbia University.
a large portion of your life that you end

up a one-dimensional person with only
work in your life. The problem that I have
been witnessing is the following: there
will always be someone willing to give
up more of his personal life than you and
spend more time working. This is impossible to compete with unless you have luck
on your side or you match your competitors intensity. Therefore, are you forced to
make great sacrifices or accept mediocre
success? You could just hope to be some
combination of lucky and naturally talented to be able to achieve success without
destroying your personal life, but that is a
lot to hope for.
Working in a lab adds an additional
layer of complication due to the loose correlation between number of hours worked
and the resulting reportable data/progress.
It has always seemed that the general key
to success is to work really hard. If you
work really hard, it will likely be noticed
and rewarded. I am pretty sure that this
is the case in medicine from my limited
experience; however, this is far from the
case in research. The paradoxical problem is that you have to work more when
your experiments are not working (and
you have little to show for your efforts),
and you have to work a lot less when your
experiments are working (and you have a
lot to show for your efforts). It seems like
you are lazy and/or slacking when you do
not have a lot of data to present, regardless of how much you have been working.
(continued on page 65)
NOVEMBER/DECEMBER 2013 IEEE PULSE 11
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ith stories about everything from a threedimensional (3-D)-printed tracheal implant used
in an infant to a 3-D-printed replacement for
75% of a mans skull, a media firestorm is swirling
around this seemingly new technology, but what
exactly is 3-D printing? How is it being used today,
and what is its true potential in the biomedical arena? Renowned
robotics engineer Hod Lipson, coauthor of Fabricated: The New World
of 3D Printing [1], and director of the Creative Machines Lab at Cornell Universitys Sibley School of Mechanical and Aerospace Engineering in Ithaca, New York, spent some time with IEEE Pulse in
a wide-ranging conversation about the past, present, and future of
3-D printing and its implications for biomedical engineering.
IEEE Pulse: What is 3-D printing?
Lipson: Basically, its a process of manufacturing arbitrarily
shaped objects by depositing material layer by layer. Just as you
can imagine an ink-jet printer that spits out droplets of ink on a
piece of paper and creates a picture, a 3-D printer spits out droplets
of material and gradually builds up a 3-D object. There are maybe
two dozen different processes available and hundreds of materials.
Plastics, metals, and ceramicsthere is a whole range of materials,
different speeds, and resolutions. What is common to all of them
is that they all build up a 3-D object layer by layer from a stream of
raw materials in almost an unconstrained shape: Any shape that
you can imagine and that you can define in a computer design file,
you can fabricate.
IEEE Pulse: Although 3-D printing is catching fire
now, it isnt new. Whats its history?
Lipson: The technology has been around since the late
1980s, and its been used extensively for prototyping products.
If you look around, almost anything in your office or in your car
has probably been prototyped using a 3-D printer at some point
in its early design.
IEEE Pulse: Why is 3-D printing getting so much attention now?

Lipson: The awareness of this technology has shot up
because of two basic factors. One is the ability to print in engineering materials, which has made it possible to make the enduse products, not just prototypes. The second reason is that the
technology has crossed from the mainframe to the desktop, so
to speak. In other words, it has gone from being technology that
only existed in the back rooms of large industries to something
that is available at the consumer scale. While these consumerscale machines are still not a big part of industry, they have
played an important role in the awareness of this technology and
also in creating and exploring new business models.
IEEE Pulse: What pushed 3-D printing from the mainframe to the desktop?
Lipson: The technologys path is very similar to that of the
first desktop computers, which were initially kits that people
built at home. Those kits ushered the mainframe computer
onto the desktop, enabling hobbyists to create new applications that eventually developed into entirely new industries,
like gaming. Back in 2006, the same thing happened with
3-D printing technology. Two open-source 3-D printers came
out: one of them from our lab called the Fab@Home and the
other called RepRap out of the United Kingdom. Both of these
academic systems were open source and basically allowed
anyonefor a budget of about US$1,000to make his or her
own printer and start experimenting with new materials and
new processes. The availability of these open-source printers
really reduced the barrier of entry of people to start exploring
this technology and develop new ideas like food printing and
bioprinting.
IEEE Pulse: Describe the medical applications of 3-D
printing.
Lipson: One of the biggest industries to be affected by 3-D
printing is the medical instrumentation industry, particularly
those segments that fabricate small runs of parts that are relatively
By Leslie Mertz
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PHOTO COURTESY OF CORNELL UNIVERSITY
Q&A with Author,

Engineer, and
3-D Printing
Expert Hod Lipson
complex. If you want to make toothbrushes, for example, mass

production is the better solution because toothbrushes are fairly
simple and are made in the millions. On the other hand, when
youre making medical instruments, such as computed tomography and magnetic resonance imaging scanners, their parts are
more complex and are produced in far smaller quantitiesand
thats where 3-D printing technology has an advantage.
When you go from medical instrumentation to custom prosthetics and implants, you basically have a batch size of one: You
are making a unique implant just for one person, and that implant
can be very complex; it cannot be mass produced. Weve seen a

great deal of growth in the area of using 3-D printing implants
both out of engineering materials like metals and polymers and
more recently also implants that are printed with live cells. This is
what is known as bioprinting.
IEEE Pulse: How far along is bioprinting?
Lipson: Theres a lot of potential in the ability to put different
types of live cells all simultaneously into a single live implant.
But right now, were just at the beginning. At Cornell University, my colleagues Jonathan Butcher and Larry Bonassar and
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students have been able to print things such as knee meniscus,

things that would require a pastry chef, and also from a nutria heart valve, spinal disks, and other types of cartilage or bone.
tional point of view. That encompasses the ability to create foods
None of these have vascularity and are on the low end of anawith very controlled nutritional content that takes into account
tomical complexity.
an individuals biometrics and medical needs. When we openAs technology progresses, however, well see more and more
sourced our 3-D printer, thats what a lot of people wanted to do.
complex heterogeneous tissues being fabricated, such as liver
For example, we printed cookies with different sugar contents
tissue, kidney tissue, and so forth. This ability opens the door
based on biometrics [2].
to making increasingly viable live implants, as well as printing
Were also working hard at trying to embed the electronic
models for drug testing that bridge the gap between the petri
circuits into a 3-D print. In other words, we hope to move 3-D
dish and animal testing. It also opens the door to creating trainprinting from making passive plastic or metal parts to actually
ing and surgical training and planning
working with multiple active materials,
models for surgeons, which will likewise
such as printing wires, actuators, and batbridge the gap between training on stanteries. That would have great implications
dard models and cadavers.
for medical instrumentation and devices.
IEEE Pulse: What are some of the
IEEE Pulse: How far along is that
biggest biomedical applications for
work?
3-D printing today?
Lipson: Weve printed batteries, and
Lipson: One of the most successweve printed motors, but it turns out that
ful commercial cases for 3-D printing
its very difficult to print the whole thing
are Invisalign braces, which are familiar
together, all working at once. We are
almost there, but that last step of printto many people. (Invisalign braces are a
ing everything100%all at once, is
made-to-fit series of clear, removable,
trickier than we anticipated.
orthodontic aligners used to straighten
IEEE Pulse: What is your goal?
a patients teeth.) These braces are 3-D
Lipson: Our goal is to print a robot
printed, and they are unique to each
that will walk out of the printer, batteries
person who uses them. There are about
included!
50,000 braces printed each day. Chances
IEEE Pulse: Do you think that 3-D
are, somebody youll meet today is wearprinting is going to revolutionize
ing one of these 3-D printed prosthetics
FIGURE 1 Hod Lipson is holding one of his
medicine?
and possibly not even aware of it. These robots, parts of which were 3-D printed.
Lipson: Absolutely, I do think so.
braces are also a good example of a new (Photo courtesy of Cornell University.)
Personalized medicine is clearly on the
business model that takes advantage of the
horizonwith the personal genomics, etc. Three-dimensional
fact that 3-D printers can make unique, complex parts in a batch
printing could play an important role in the physical aspect of
size of one. It wouldnt be viable to do this in any other way, and,
personalization, ranging all the way from individualized nutriin this case, it is a big commercial success. Similar businesses are
tion to personalized prosthetic devices and medical implants and
evolving around hearing aid casings, crowns, and foot prosthetics.
bioprinting, to surgical training, and even to printing custom
IEEE Pulse: When you first began working with 3-D
medications that contain all of the medications a patient needs at
printing, were you getting into the field because you just
exactly the right level. There are just so many avenues that this
thought it was interesting technology or because of its
technology can affect and intersect medical treatment.
potential applications?
Three-dimensional printing is no longer just about printing a
Lipson: I definitely got into it as a user. I was designing robots.
plastic shell for an MRI scanner. Its really about completely new
We kept designing crazy robotic blueprints that were very difficult
ways of thinking about medicine and biomedical engineering.
to fabricate using conventional manufacturing. We got one of the
Im very optimistic.
early 3-D printers back in 1999 to try to fabricate our unconventional designs. One of our first robots was born, so to speak, using
__________ is a freelance science, medical, and
Leslie Mertz (lmertz@nasw.org)
a 3-D printer in late 1999 and appeared on the front page of The
technical writer, author, and educator living in northern Michigan.
New York Times under the headline Robots Making Robots. But
we very quickly realized that 3-D printers were not good enough.
For example, they could print the body of the robot, but not the
References
wires, the batteries, or the microprocessorswhat makes a robot
[1] H. Lipson and M. Kurman, Fabricated: The New World of 3D Printa robot. We started developing next-generation 3-D printers that
ing. Hoboken, NJ: Wiley, 2013.
could also print those other active components (Figure 1).
[2] J. Lipton and H. Lipson. (2013, May 31). Adventures in food printing:
IEEE Pulse: What is your lab today doing that would
3-D kitchen printers produce hits (a deep-fried scallop space shutintrigue IEEE Pulse readers?
tle) and misses (square milk), IEEE Spectrum [Online]. Available:
Lipson: One offshoot of bioprinting is food printing, which
htt p://spec tr um.ieee.org/consumer-elec tron ics/gadgets/
opens (doors to) a lot of very interesting possibilities both for
adventures-in-printing-food
________________
entertainment purposes, such as creating pastries and other
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Dream It, Design It,

Print It in 3-D
By Leslie Mertz
o maybe we are not

all driving to work
in a flying car or
are being beamed
up by a transporter
yet, but we should
be clearing out a space
in the lab and perhaps in
the office for a replicator.
Sure, they may not work
the same as the replicators
on Star Trek that instantaneously pop out hot, fullcourse meals to suit any
crew members whim, but
they can generate threedimensional (3-D) objects
to match your computer design.
Welcome to the world of additive technology known as 3-D printing. It is available now, it
is expanding to include a wide array of materials
and complex printed objects, and the cost is dropping. This combination of factors is allowing more
people, including those in the biomedical field, to
turn on their imaginations and think about the enormous number
of possibilities that could be afforded with a 3-D printer.
on his or her computer,

sends it to the printer, and
the printer deposits ink in
patterns to match the document. Three-dimensional
printers do the same thing,
but the users document is
exchanged for a design
file, the ink is replaced
with plastic or some other
material, and instead of
stopping at one layer, the
printer adds as many additional layers as needed to
build a 3-D object.
Although all 3-D printPHOTO COURTESY OF COLLIN LADD
ers follow this general
methodology, specific technologies vary from
one company to another, and sometimes within
companies (see Performance and Price). An
example is Stratasys Ltd., a leading manufacturer
of 3-D printers, which has headquarters both
in Minneapolis, Minnesota, and Rehovot, Israel
(Figure 1). Stratasys uses two primary technologies. The first is fused deposition modeling, in which thermoplastic material is heated and extruded as a 3-D bead, according
to Fred Fischer, materials and applications product director of
Stratasys. Were precisely controlling the deposition and the
location of that deposition to create the shape of the layer. Then,
we repeat that process over and over and over again. Since the
material is heated as its extruded, it fuses or bonds to the layers below, he noted. Since the 3-D printed part is built with
the same thermoplastics that are used in injection molding or
What Can
3-D Printing
Do for You?
Base Technology
Three-dimensional printers are somewhat analogous to the standard paper printer. For the latter, the user creates a document
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machining, it has very similar durability, mechanical properties,

and stability of the part over time.
The second technology used by Stratasys is called PolyJet.
PolyJet jets out droplets of a photopolymer, meaning that its
a liquid material that solidifies under ultraviolet light. PolyJet
basically prints the shape of each layer and hits that layer with
ultraviolet light to solidify it. Then, it repeats the process over and
over again, Fischer said.
PolyJet builds in minute layers and therefore allows ultrafine
detail and finishes, while also providing what Fischer described
as fast throughput. Fast in 3-D printing means several hours.
If youre an engineer, there are generally two times you start
a model: either in the morning to have it by the end of the day,
or at night before you go home so its done the next morning
when you come into the office, he said.
Many 3-D printed items are the brainchild of the user who
creates the design file. Sometimes, the application calls for a
reproduction of something that already exists. In these cases, 3-D
scanners are available to handle that aspect of the job. One such
scanner is a portable laser-line scanning measurement device
produced by FARO, which has its global headquarters in Lake
Mary, Florida. The FARO Edge ScanArm can be used in biomedical applications in a variety of forms, said Dan Alred, FARO
product marketing manager (Figure 2). One frequent application
involves using the scanner to capture an existing bone or joint
and employ the design file generated by that scan to optimize
the form and fit of prosthetics, he explained. Examples of this
could include full or partial hip replacements, or even matching
a prosthetic arm or hand to a patients remaining arm or hand.
Beyond prosthetics, Alred said researchers are also using
the ScanArm for purposes such as measuring the seating
posture of individuals who spend long periods of time in a
wheelchair, with a goal of improving the fit and eliminating
pain and discomfort, and to estimate the in vivo forces in
the knee joint as a way of understanding ways to treat and
prevent joint diseases.
Biomedical Applications
Since the inception of 3-D printing about 25 years ago, its
primary use has been prototypes. In these cases, a designer
or engineer creates a component with computer-aided design
FIGURE 1 An engineer removes a newly fabricated part from one

of the Stratasys 3-D printers, in this case, a Mojo desktop 3-D
printer. (Photo courtesy of Stratasys.)
Performance and Price

People ask me, Where is the industry going in the future? Should I
get in now; should I wait? said Fred Fischer, the materials and
applications product director of 3-D printer manufacturer Stratasys.
The market is moving in two different directions. At the most
simplistically defined, one is about price and the other is about
performance. It all depends on what the 3-D printer is expected to do.
Three-dimensional printers come in three general categories:
Big production models are mainly for companies and labs
that produce a high number of concept models, precision
prototypes, patterns or molds for tooling, or unique end
products sold on the commercial market. With our 3-D
Production Series system, the user can control virtually all of
the parameters in how the part is built, so as a result they
have the capability to further optimize the output for their
application, said Fischer. Using the two-dimensional
printing industry as an analogy, these are like the
production presses you might see in a newspaper
production facility, where its all about throughput and the
manufacturing of the end product itself. Production Series
3-D printers are about the size of a refrigerator or two
refrigerators stacked side to side and can cost anywhere
from US$70,000 to more than US$400,000, he said.
Medium-sized models are suited for work groups, a
dozen or two dozen engineers and designers that share
the 3-D printer and generally use it to refine and produce
working and durable prototypes for testing. The workgroup systems, which Stratasys calls its design series, are
approximately the size of a large dormitory refrigerator
and range in price from about US$25,000 to US$90,000.
Depending on the model, professional desktop 3-D
printers range from about US$10,000 to US$30,000.
Professional desktop models make it really affordable for
an engineer to create iterations of their designs
conveniently, confidentially, and quickly, Fischer said.
Those are the easiest to use. Theyre intended so that
you just bring your digital file in, hit print, print it on the
system, and then engage with the part. One of the
Stratasys models, called the Mojo, is about the size of a
wheeled beach cooler.
At the desktop end of the market, price is important. These
(printers) will continue to maintain performance capabilities, but the
price point will drop, similar to what has been seen in countless
other technology industries before this one, Fischer said. The
technology has gone from approximately US$100,000 to US$10,000
over the first 25 years, and I suspect in the next two and a half years,
youll see it go from US$10,000 to certainly less than US$5,000 and
probably well below that in terms of professional desktop printing.
At the other end of the spectrum, performance reigns.
Fischer continued, With production 3-D printers, the questions
are: How do additive technologies close the gap between them
and traditional technologies? And more specifically for the
plastics world, how do we advance additive technologies so the
cost of the part, the aesthetics of the output, and the mechanical
properties of the output are closer to injection molding or to
some of those other traditional technologies?
He added, Performance and price: those are the two
directions the market is moving in, and theyre intentionally
opposite directions.
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time needed for the surgery, the recovery

(CAD) software and prints it in 3-D to test
time of the patient, and the success of the
form, fit, and function before he proceeds to
surgery and the implant.
production tooling. The whole idea is that
3-D printers allow designers and engineers
to make changes much, much earlier in the
Combining Art and Science
design cycle and as a result dramatically
A major product application for 3-D printreduce the time and the cost to make those
ing today is in prosthetics. Our original goal
fixes, Fischer said.
was not to use 3-D printing necessarily. It
However, the applications for 3-D printing
was to solve a problem, said Scott Summit,
are rapidly widening. The fastest-growing
director of technology for San Franciscoareas today for additive or 3-D technology
based Bespoke Innovations, a start-up comare in the manufacturing space, Fischer said.
pany founded in 2009, and as of May 2012,
As the performance of these systems has
a division of the major 3-D printer manufacimproved, manufacturers have discovered
turer 3-D Systems of Rock Hill, North Carothat theres some merit to making their comlina. Bespoke does not build the prosthetics
ponents with additive technology instead of
themselves but designs and produces panels,
subtractive (e.g., carving from a larger piece
or fairings, that cover leg prosthetics.
of material) or some of the other more tradiThe fairings, which lie at the intersecFIGURE 2 FAROs Edge ScanArm
tional technologies on the marketplace.
tion of art and science, started with a simple
is a portable laser-line scanning
This is especially true for companies that measurement device used to scan
idea. Six years ago, I was teaching indushave low production volumes and parts or an existing structure, including a
trial design at Carnegie Mellon University
products that are either highly complex or that bone or joint, and help generate a
in Pittsburgh, and I was doing research on
design file for use by a 3-D printer.
require frequent modifications.
the side into prosthetic limbs, Summit said.
(Photo courtesy of FARO.)
One of the factors that makes additive
Prosthetic limbs have traditionally been
technology a good alternative is where the
the domain of orthopedic surgeons, prosproduct value is high, meaning that its not a commodity, but
thetists, and other very specialized professions, but not indusits an oddity. The medical device and certainly the medical
trial designers at all, so I was curious about what an industrial
implant industries are perfect examples of that, Fischer said. He
designer could bring to the table, he said.
described made-to-order jigs and fixtures built for specific operIt turned out that an industrial designer did have something
ating rooms as well as custom knee or hip implants and specially
to offer. The main thing I found was that a prosthetic limb
designed tools to help orthopedic surgeons during exacting
is designed entirely with biomechanical constraints in mind,
operations. In those cases, the volume of each of those parts
Summit said. So my thinking was that modern prosthetics are
may be just one, and those custom-made fixtures, tools, and
pretty incredible and weve all heard these miracle stories
implants then have many positive implications in terms of the
about what a modern prosthetic doesbut they only meet one
FIGURE 3 The Bespoke Fairing uses the mirrored

geometry from a scan of the persons surviving
leg to create a nearly exact replica of the original
shape. The fairing, however, is not intended
to fool the eye into overlooking the prosthetic
limb. Instead, it intends to turn the prosthetic
limb into something worthy of attention and
admiration, more like a watch than a
biomechanical device. (Photo courtesy
of Bespoke Innovations.)
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FIGURE 4 The Bespoke Fairing captures the wearers personality

in the product. In this case, the client chose a look which would
complement his lifestyle. The result suggests a hybrid of the clients body, as well as his motorcycle. (Photo courtesy of Bespoke
Innovations.)
he wishes to be perceived by the outside world. Some fairings are

sleek and metal-plated, some are rich leather fabrications, some are
intricately carved polymers, and others are decorated with striking
graphics or tattoos (Figures 3 and 4). Each is economically feasible
because of 3-D printingthey cost about US$4,000US$6,000.
The whole idea is not to create a fairing that looks like a
human limb but rather to create one to complement the customers style and creativity. It is more a piece of jewelry or artwork that
is designed to be looked at, Summit said. Customers tell him that
the fairings break down barriers. Where people would previously
glance and then quickly look away from an amputee, they are now
engaging in conversation about the cool-looking fairing. Its very
emotionally and psychologically uplifting on both sides, he said.
Bespoke is now expanding into all kinds of exoskeleton opportunities where we are pursuing needs of many types and where
the product created is worn outside of the body to address any
one of a number of challenges that can happen inside the body,
Summit said. One of the companys targeted areas is carpal tunnel syndrome, a nerve problem that can cause pain and weakness
in the hand, wrist, and elbow. Currently, the reason that people
often have continued trouble with carpal tunnel is that they dont
wear the brace, because they hate the brace: it looks horrible, its
uncomfortable, you cant sleep in it, it accumulates grimeits just
unappealing on many levels, he said. And because they dont
wear it, their carpal tunnel persists, and ultimately, very often they
need surgery. All of those issues can be addressed through good
design and a 3-D printer, Summit asserted (Figure 5).
Bespoke will be releasing new medical and body applications
by the end of 2013, including a 3-D printed device for people who
have hand arthritis or carpal tunnel syndrome, Summit said, but
details would not be available until closer to the release date. For
now, the company is receiving ample attention for its fairings. He
remarked, They really demonstrate the versatility of 3-D printing and all it can do to improve the quality of somebodys life
who has a very special, unique predicament.
facet of a human. They dont address the psychological or emotional needs, the entirety of a person.
From that realization, Summit worked with orthopedic surgeon Kenneth Trauner to found Bespoke Innovations and get into
the prosthetics business. The process for making a prosthetic fairing begins with image-based 3-D scanning technology to capture
images of both the prosthetic leg and the sound leg. Next, a 3-D
computer model mirrors the sound leg and superimposes it over
the prosthetic. This provides contralateral symmetry. (If the patient
is missing both legs, a stand-in is used to approximate the shape
and size of the patients natural legs.)
Once the mechanical fairing model is completed, the user and
Bespoke designers begin the creative part. They work with the client
to sift through dozens of patterns and the broad range of materials
that are now available for 3-D printing, including metal and polymers. Bespoke designers are also ready, willing, and able to make
modifications and create one-of-a-kind, flexible, durable, and lightweight fairings that match the users personality and how she or
Liquid Metal to Form Structures
FIGURE 5 The Bespoke Wrist Brace addresses the need for patient
compliance by offering a brace that fits the body, allows the
skin to breathe, and looks like anything but a medical product.
Three-dimensional scanning allows the users unique shape
to drive the contours of their brace, while the flexibility of 3-D
printing invites their taste preferences to inform the products
look and feel. (Photo courtesy of Bespoke Innovations.)
Current research projects showcase just how far 3-D printing has come and how far it has yet to go as printing materials
have moved from wax to plastics and more. One is the newly
announced development of liquid metals that can hold their
shape and show promise for use as conductive wires and other
structures that can be printed into 3-D printed devices [1]. These
devices could come out of the printer complete and ready to
function, marking a major advancement for 3-D printing.
A North Carolina State University research group has already
shown that liquid metal can form stackable beads and flexible
wires [2]. It is still in an early stage, but the work has drawn
considerable interest from the media, from other engineers, and
from at least one 3-D printing company.
Weve been working on this for about four years now, and
there were a couple of things that motivated us when we started,
said Michael Dickey, Ph.D., assistant professor of chemical and
biomolecular engineering at North Carolina State University in
Raleigh. One of them was patterning liquids. If you take two
raindrops and touch them together, they just form a bigger raindrop. The metal that we work with is almost exactly like water in
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Undergrad Turns Junk Parts into New 3-D Printing Technology

really excited about that, Ladd said. Eventually, the process switched
It is the age-old story:
over to a tapered glass micropipette that does not clog as easily, and
An undergrad meets a professor.
finally a pneumatic system that eliminates manual control of a
The professor gives the undergrad lab space to look into the
syringe. Short bursts of pneumatic pressure make droplets, and
possibility of a new and interesting technology.
steady pressure yields wire.
The undergrad has a lab accident that
Ladd also built a force meter to measure the
proves the technology is possible.
physical properties of the oxide skin that forms on
The undergrad builds equipment for the
the liquid metal. He described it: I just used this
technology out of spare parts from his
cantilever, kind of calibrated it with droplets that I
apartment.
weighed later, and then I went ahead and
The undergrad is the first author on a
extruded the wire and watched the displacement
research paper that receives worldwide
of the needle. Then, I took the displacement of the
attention.
needle and correlated it with the smallest radius
Okay, it may not be the typical research tale,
of the wire, which would be the first to give under
but it is what happened in the case of North
tension, and actually verified the critical surface
Carolina State Universitys Prof. Michael Dickey,
stress of the skin that we found with a rheometer.
Ph.D., and undergraduate student Collin Ladd
FIGURE S1 North Carolina State
Ladd ultimately earned his bachelor of science
(Figures S1 and S2).
University Prof. Michael Dickey
degree in chemistry in 2012, and the research on
It all began when Ladd approached Dickey likes to challenge his underliquid metal made news far and wide earlier this
with some ideas about making ink-jet printable graduate students. (Photo
year when the scientific paper was published.
circuit boards (to print a circuit on paper for courtesy of Michael Dickey.)
Although his work in Dickeys lab led to a good
disposable electronics). Ladd recalled the
research job, Ladd has decided to head to medical school. I have this
conversation: He said, Well, you know what? I dont know if thats
horrible problem of having a lot of interests, including electronics,
possible. Would you like to try it? Thats how it started.
engineering, and chemistry, so Im thinking that once I get my M.D., I
Soon, Dickey suggested Ladd work on patterning liquid metals,
might just come full circle and work on something like prosthetics
especially extruding liquid metals into fine, tiny, conductive wires.
and tie it all together.
We knew it could work, because one day I was trying to get liquid
Dickey is proud of and still rather amazed at
metal into a really small, 10-L syringe, Ladd
Ladds contributions to the liquid-metal project.
said. I had no idea the syringe was clogged, so
Sure, if you know what youre doing, the
Im pushing on the syringe as hard as I can, and it
machine that does the printing is fairly simple in
explodes and wire shoots out.
hindsight, but starting from scratch, its not
From there, Ladd began developing a slightly
obvious how to do it. And Collin did that. He
more sophisticated process: a syringe pump
figured out how to make wires and suspend
equipped with a nozzle to extrude liquid metal
droplets and get it all to function. Its remarkable,
wire. For that, he scavenged some parts from his
Dickey said.
room. Im a spare-electronics hoarder. I take
Dickey has a credo to never give undergraduate
everybodys broken printers or whatever, break
students mundane tasks, and it worked like a charm
them down into the useful parts, and then just box
this time around. Every once in a while, youll run
them, he said. So when I started working on the
into students like Collin who are really great, who
liquid-metal setup, I ended up building the first FIGURE S2 Using spare parts,
are creative, and who arent afraid to try things...
prototype for the syringe pump out of printer including a skateboard bearsometimes because they dont know any better, he
gears, a stepper motor, a skateboard bearing, a ing and an old laser pointer,
Collin Ladd built his labs first
said with a laugh. In this case, I really didnt know if
bolt, and an old laser pointer.
prototype for the liquid-metal
this was going to work, and thats how a lot of
As luck would have it, the first time Ladd tried syringe pump. (Image courtesy
research is, but he made it work.
it out, a wire instantly formed. Dr. Dickey was of Michael Dickey.)
terms of its viscosity, so the challenge of patterning this material

was interesting.
The second motivation was to make connectionsakin to
wire bondsbetween electronic components. We knew from our
previous experience that you could inject liquid metal into microfluidic channels to make things like wires. Weve done that for a
while, Dickey said. The problem, however, is that you end up
with structures that are two dimensional. In other words, theyre
in plane. We needed to do them out of plane, which is important
for making more complex structures with 3-D printing.
To begin, they had to find the right material, and Dickey and
his lab settled on a liquid metal alloy of gallium and indium.
The alloy reacts with the oxygen in ambient room-temperature

air to form an external skin. That skin allows the liquid metal
to retain its structure. Two droplets dont coalesce into one.
Rather, the droplets can be made to connect to one another,
while retaining their own droplet shapes (Figure 6). The metal
spontaneously forms a thin oxide skin, and its strong enough to
hold these shapes that were patterning together, Dickey said.
Were just taking advantage of the properties of the material.
The resulting structure is similar to a water balloon in that
its solid on the outside but liquid on the inside. One big difference between the two is that if you puncture a water balloon, the
water is going to leak out of course, but if you puncture a bead
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want to have autonomous sensing capability using really lowcost sensors and distributed networks that can just transmit a
signal back. These types of uses do not require much power.
You only need power when you want to actually transmit a
signal, and at the same time, you may need a very small, very
low-mass battery because your entire sensor might be on the
FIGURE 6 Using a penny for comparison, this series of nesting dolls
order of a millimeter in size.
provides a demonstration of the small scales for which the liquidAlthough necessary to produce all-integrated devices, a battery
metal technology can be used. (Image courtesy of Collin Ladd.)
of that size scale simply was not commercially available. With a
request from the research group of Shen Dillon, UIUC assistant
of liquid metal, the skin reforms, Dickey described. The other
professor of materials science and engineering, Lewis collaborated
obvious difference is its a metal, so it has a lot of interesting propwith Dillon to build one. The result is a lithium-ion rechargeable
erties, such as electrical conductivity, thermal conductivity, and
battery that is about the size of a grain of sand [3]. They opted to
optical reflectivity. Between those properties and the way it flows
make a rechargeable battery because the small size precludes them
because its a liquid, we figured out that there were a number of
from having a large energy density (Figure 8).
cool and interesting things that we could do with it.
We developed this class of materials called printable electrode
One was to make wires (see Undergrad Turns Junk Parts into
inks for 3-D printing the anode and cathode, Lewis said, describing
New 3-D Printing Technology), which could be embedded into
her labs contribution to the project. The inks for the anode and cath3-D material, whether a polymer, ceramic, or some other material
ode are made with nanoparticles of different lithium metal oxide
(Figure 7). To illustrate the flexibility and conductive properties of the
compounds. We also custom-designed a 3-D printing platform in
liquid metal wire, Dickey and his lab embedded the wire in a rubbermy laboratory thats very high precision, and that has customized
like material and then stretched it from one light-emitting diode to
print heads to handle this variety of inks. The print head nozzles
another to switch on the light. Its perhaps a little hokey, but it does
are smaller than a human hair in diameter. The final battery includes
demonstrate the idea, he said.
layers of anodes and cathodes, all tightly stacked with a separator
Dickey hopes that engineers and researchers will see new posinto a tiny electrolyte-filled container (Figure 9).
sibilities for their own work. For me, the most obvious is printing
She readily admits that the task was not simple. The interconductors, interconnects, and things like that, and being able to
digitated battery design we used is well known, but the inks were
do it at room temperature. And beyond that, since the final strucdifficult, she said. Id love to say that we just whipped up a
ture you print is potentially deformable and flexible, you can start
batch, and a month later we were printing batteries, but it actuto think about printing a structure and then embedding it in a
ally took us about 12 months to create and refine the ink formupolymer to make a stretchable wire or stretchable antenna. He
lations that could be printed at such fine scales, that wouldnt
added, Because metals have so many nice properties, you can
crack, that would be able to maintain their shape, and that could
kind of let your imagination run wild.
then be filled with the liquid electrolyte.
With the battery completed, other projects loom. It should
Three-Dimensional Printed Microbatteries
be relatively straightforward to move to different types of battery
Another item that could advance 3-D printing in the biomedical
architectures and different materials for the battery, Lewis said.
industry and across the board is a printable microbattery, which
In this first rendition, we just printed the cathode and the anode,
could be used to power even the smallest of implanted medical
but wed love to be able to print the sepadevices. That work is well under way in
rator and everything all in one step.
the lab of Jennifer Lewis, S.D., Hansjrg
While they are tackling that project,
Wyss Professor of Biologically Inspired
they are also working on higher-capacity
Engineering at the Harvard University
electrode materials and envisioning appliSchool of Engineering and Applied Scications for 3-D printed batteries. You can
ences in Cambridge, Massachusetts.
really open up the design space if you can
Her research group at Harvard and her
3-D print the battery, because pretty much
previous lab at the University of Illinois
anything you can design by CAD, the
at Urbana-Champaign (UIUC) have
printers in theory will allow you to build
worked for about a decade on creating
and rapidly test, Lewis said. The idea is
3-D printable, functional materials.
that maybe these 3-D printed batteries can
We want to print both form plus
fill little cavities that are nonsimple polygfunction, so were interested in embedonal shapes in various devices.
ding things like 3-D integrated elecHearing aids come to mind when
tronics into plastics, Lewis said. And
thinking about possible implications for
batteries themselves are also critically
this technology. This may or may not be
enabling for those kinds of devices FIGURE 7 Liquid-metal wires (in the process
of extrusion at left and extruded at right)
the best example in the long run, but hearwhere you may just want to trans- show promise for use as conductive wires
ing aids seem like an obvious application.
mit wireless signals and know where and other structures in 3-D printed devices.
The reason is that right now something like
theyre located in space; or you may (Image courtesy of Collin Ladd.)
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(a)
(a)
(b)
(b)
FIGURE 8 A Harvard UniversityUniversity of Illinois at UrbanaChampaign team announced in June that it had developed a
3-D printable lithium-ion rechargeable battery. (a) This schematic details the battery, which is about the size of a grain of
sand. (b) The actual printed structure is shown in this scanning
electron microscope image. (Images courtesy of Jennifer Lewis.)
FIGURE 9 The microbattery inks, which Lewis team spent 12

months creating and refining, are made with nanoparticles of
different lithium metal oxide compounds. Shown here are (a) the
schematic and (b) the actual packaged battery. (Images courtesy
of Jennifer Lewis.)
98% of the plastic shells for hearing aids that go into your ear are
being 3-D printed, but then they have to take these plastic cavities
and hand-pot the electronics into them, which requires a three-day
assembly process, Lewis said. She continued, My dream would be
to 3-D print the entire hearing aid, including a rechargeable battery.
That means hearing aid users would no longer have to struggle to
replace the small coin battery in their devices every five to seven
days, she said. If you could take that hearing aid out at night, put it
on your bedstand, and have it recharge overnight, that would be a
huge plus. And since the shell is already being 3-D printed, it seems
like that is a nice example of an early potential product that could be
enabled by our concept of form plus function.
At least one biomedical company has contacted Lewis about
the microbatteries. They havent gone into a lot of detail about
what theyre looking for, but you can just imagine that a lot of
different designs are now possible, she said.
While the attention is a good thing, Lewis said, I do worry

about overhype and promising more than its going to be able to
deliver in the near term.
Summit agreed, commenting, Theres a lot of misunderstanding about what 3-D printing can do. Its a versatile and promising technology, but its not a panacea. Regardless of whether it
is based on fact or fiction, he said, the spotlight has one definite
benefit: It has brought in new players and new ideas, and thats
a good thing.
Lewis added, There are just so many different possibilities in
3-D printing. Its exciting. Its just a really exciting time.
Living Up to Its Potential

The 3-D printing world is big and getting bigger everyday, and
although the media might give the impression that 3-D printers are
comparable to the Star Trek replicators, the technology is not there yet.
For people like myself who have been working on this under
the radar for so long, we are stunned at the attention that 3-D
printing is getting now, Lewis said. For instance, she said she
just heard that the annual consumer electronics show in Las
Vegas, Nevada, was reporting that the floor space allocated for
3-D printing was the most popular space at the show, so much so
that the show organizers were expanding it.
__________ is a freelance science, medical, and

Leslie Mertz (lmertz@nasw.org)
technical writer, author, and educator living in northern Michigan.
References
[1] C. Ladd, J.-H. So, J. Muth, and M. D. Dickey. (2013, July 4). 3-D
printing of free standing liquid metal microstructures. Adv. Mater.
[Online]. Available: http://onlinelibrary.wiley.com/doi/10.1002/
adma.201301400/abstract
______________
[2] YouTube posting by M. Dickey, video by C. Ladd. (2013, July 8).
3-D printing of liquid metals at room temperature. [Online].
Available: https://www.youtube.com/watch?v=ql3pXn8-sHA
[3] K. Sun, T.-S. Wei, B. Y. Ahn, J. Y. Seo, S. J. Dillon, and J. A. Lewis.
(2013, June 17). 3-D printing of interdigitated li-ion microbattery
architectures. Adv. Mater. [Online]. Available: http://onlinelibrary.
wiley.com/doi/10.1002/adma.201301036/abstract
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Adding Value in
Additive Manufacturing
ISTOCKPHOTO.COM/KONDYUKANDREY
Researchers
in the United
Kingdom
and Europe
Look to 3-D
Printing for
Customization
By Jim Banks
aving already made a big impact in the medical sector, three-dimensional (3-D) printing technology continues to push the boundaries of cost efficiency, convenience, and
customization. It has transformed some aspects of medical device production. However,
expectations of the technology are often exaggerated in the media, so we spoke to leading
researchers in the field about its practical applications and what can be expected in the
near future.
There is no doubt that additive manufacturing, more commonly known as 3-D printing, is developing rapidly. However, the feeling among many of the proponents of 3-D printing techniques is that
developing applications for use in the medical industry is about incremental change and the steady
development of highly complex processes. While it is hard to resist the temptation to think outside the
box, it is also important to look at what is already in the box and appreciate the impressive practical
applications the technology has already delivered.
Three-dimensional printing is still in its infancy, but it is growing up fast. There is a lot of research
and development going on not only into new materials but also into improving reliability and

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2154-2287/13/$31.002013IEEE
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productivity. Clinicians are very enthusiastic about the technology

now despite being skeptical in the early years, says Peter Mercelis,
Ph.D., cofounder and managing director of LayerWise.
Based in Belgium, LayerWise focuses exclusively on additive
manufacturing processes for metal components, and founders Mercelis and Jonas Van Vaerenbergh were involved in the development
of selective laser melting (SLM) at the Catholic University of Leuven. Approximately 30% of the companys resources go directly
into research and development to extend the capabilities of 3-D
printing technology.
There is a lot of hype from the media and from governments,
and there is a tendency for people to exaggerate what can be done.
People have unrealistic expectations, especially about how soon
some of the exciting possibilitieslike printing living tissuewill
become a reality. This is not science fiction, and work is being done
in that area, but we must not expect it to happen soon. But what is
happening now is already spectacular, and there is no need to exaggerate it, Mercelis remarks.
Additive manufacturing has had a huge impact in the manufacture of hearing aids as well as dental, spinal, and hip implants. In
fact, around 99% of hearing aids that fit in the ear are made using
3-D printing techniques (Figure 1). This is in part because there are
fewer regulatory hoops to jump through for devices worn on the
body than for those placed inside the body.
Russell Harris, a professor of medical engineering at Loughborough University, Leicestershire, United Kingdom, has been
researching 3-D printing for over 15 years and has seen the technology move steadily into areas where the regulatory requirements
are more stringent.
Hearing aids were an immediately advantageous area in which
to use 3-D printing. Everyones ear canal is a different shape, and the
technology can produce customized devices with greater efficiency
and lower cost. Also, as they are mostly recognized as Class I
regulated medical devices, there are fewer regulations governing
the materials that are used. The technology is also used to create
titanium implants with a better fit by exploiting the ability to make
complex geometries. There is a lot of potential for producing direct
implants for use in the body, Harris says.
The manufacture of implants is a major area of focus for 3-D
printing in the medical sector and, beyond that, work is being done
(a)
FIGURE 1 Nearly all hearing aids today are manufactured using

3-D printing technology including these made by the Denmarkbased company Widex using their innovative CAMISHA method.
CAMISHA stands for Computer Aided Manufacturing of Individual
Shells for Hearing Aids, which uses laser technology to make an
impression of the hearing aid users ear canal and turns this data
into a 3-D computer model. (Image courtesy of Widex.)
on tissue engineering and enhanced processes for drug discovery.

Although the technology is still nascent, it is already changing the
way clinicians approach some complex treatments.
Looking Inside
Ex-vivo applications of 3-D printing techniques have become popular in part because they are relatively simple to bring to market,
but it is in the more complex and challenging areas of medicine
that the technology is likely to have the biggest impact, and
implants are the next obvious application.
Mercelis began working with 3-D printing during his Ph.D.
studies, when he was in close contact with the faculty of
medicine, and soon focused on producing implants. In 2004,
however, additive manufacturing was not ready to produce
titanium products with the necessary high density, so his team
initially worked with stainless steel. Now, LayerWise manufactures revolutionary orthopedic, maxillofacial, and dental
implants (Figure 2).
The most evident application of the technology was in
implants, where it has very clear advantages. The move to medical implants is a logical one and solves a clear problem in orthopedics, which is that standard implants are simply not sufficient
for some patient groups, particularly the most complex cases.
Surgeons had limited options and had to either modify standard
(b)
(c)
FIGURE 2 By subsequently melting thin metal layers, Layerwise produces maxillofacial implants with increased functionality, including lower jaw
implants such as the one rendered here [(a) the implant overlay, (b) its side view, and (c) its front view]. (Images courtesy of www.layerwise.com.)
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implants or do extra bone graft surgeries. We saw that 3-D printing

could be used to make implants from 3-D patient models, and the
digital data from scans was already available, Mercelis remarks.
Before implants could be used in clinical applications, they
needed a lot of validation, which took some time, but now we
make patient-specific implants as well as using the technology to
make standard implants more quickly, adds Mercelis.
Another Belgian company to spin off from the University of
Leuven is Materialise, which uses additive manufacturing in a
variety of applications and develops software to enable innovation
in biomedical research. The company, which developed the Mimics anatomical design software to interpret data from computed
tomography (CT) scans, has subsidiaries that specialize in manufacturing customized hip implants and cranial plates.
The orthopedics industry is maturing, and implants from different companies are not that different, so we looked at 3-D printing
to create fully adapted implants for individual patients or generic
implants that are porous to encourage bone ingrowth. Traditional
implants can be too strong, which can create problems because
bone is a living material, and if there is not enough stress on it, then
it goes away. Bone resorption can lead to the failure of an implant,
says Koen Engelborghs, director of biomedical software and solutions for engineering on anatomy at Materialise.
If there is significant bone loss in a patient receiving a hip
replacement, then it can be difficult to anchor the implant to
the remaining bone. Creating customized implants using 3-D
printing can help surgeons combat this problem and improve
the performance of implants elsewhere in the body.
In orthopedics, 3-D printing is making a big difference
to patients lives, not only through hip implants but through
other products too. Skulls have irregular shapes, so it is hard to
standardize a cranial implant and put it into a computer-aided
FIGURE 3 A porous titanium cranial plate was designed in 3-matic,

and the 3-D model of the skull with cranial defect was created
with Mimics design software developed by Materialise. (Image
courtesy of OBL, www.biomedical.materialise.com.)
design (CAD) package. So we have developed our own validated software to create customized plates, which builds on our
background in prototyping, says Engelborghs (Figure 3).
In many victims of head injury, the surgeon will have to
remove bone to give the brain room to swell, so when a cranial
plate is fitted it has to be the perfect fit. Some plates are milled, but
more and more are created using 3-D printing, which makes a big
difference. If you look at how implants are traditionally made, you
see a mold that is expensive to make but which can then make lots
of identical parts. With 3-D printing, it is much easier to customize
the design and make a one-off implant. It also gives you the freedom to look at things like the porosity of the implant or the use of
a material that can be reabsorbed by the body after a few years,
Engelborghs adds (Figure 4).
For the general public, the advantages of 3-D printing center
on its ability to produce items more quickly and cheaply than
traditional manufacturing methods. In its medical applications,
the technology can do just that in some applications, but the
true advantage it brings is in creating complex geometries and
bespoke (custom-made) products.
It depends on the type of implant. Some are made with 3-D
printing technology because it is cheaper, but this tends to be only
when a standard model is reproduced. But this does not utilize the
geometric freedom the technology gives you. That is why we focus
more on the customized implants. For some smaller implants,
there may be a cost advantagesuch as for spinal, dental, or craniofacial applicationsbut not for the bigger products. The important factor is that 3-D printed customized implants have higher
value for the patient and for the surgeon, notes Mercelis.
A New Chemistry Set

Beyond implants, there is a plethora of yet more advanced applications steadily progressing from theory toward practice. Although
these ideas, which include tissue engineering (see the related article The Body Printed, also in this issue) and home chemical fabricators that doctors or even patients could use to design and create
FIGURE 4 A skull implant generated by a 3-D printer.

(Photo courtesy of Stratasys.)
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medicine at home, are at the leading edge of what 3-D printing is

thought to be capable of, their proponents are among those most
keen to calm the hype about additive manufacturing and focus on
the science. Among them is Prof. Lee Cronin, Gardiner Chair of
Chemistry at the University of Glasgow.
I became engaged in 3-D printing four years ago when
I heard people saying that it was just a gimmick for printing
plastic items. I saw the possibility of getting some chemistry in
there. A 3-D printer is just a cheap robot that can print with
three axes instead of two. Chemists do operations by moving
liquids around, and you have a technology that prints out plastic objects; so if you combine those two things, you are coupling the process of reaction configuration and chemistry, which
allows you to look at tissue engineering. You can manipulate
chemistry, tissue, and cells, Cronin says.
In his research, Cronin is using tools to modify the local
chemistry of items to change the way cells adhere to structures
using positional control capability to grow tissue and chemistry
to control stem cell differentiation. Potential applications include
the ability to grow complete human organs that can be used for
drug discovery. Using stem cells to create an organ could allow for
the screening of treatments to gauge their efficacy for a specific
patient, which, in turn, could reduce the need for animal testing.
However, Cronin is keen to stress that there is much to be done
before this process is either practical or commonplace.
Some people are doing small facets of what is possible, manufacturing small items or specialized tools for tissue engineering, but
no one is manipulating cells at the moment. The ultimate aim is to
use tissue engineering to do new science, but people get distracted
by the ability to 3-D print single products. I want to take some steps
towards the larger goals the technology promises, but we cant put
the cart before the horse. We must understand the obstacles and the
science, Cronin notes.
A paper by Cronin, Integrated 3-D Printed Reactionware for
Chemical Synthesis and Analysis, published in Nature Chemistry,
outlines a process in which a 3-D printer can be used to create
reactionware, which refers to vessels for chemical reactions that are
made from a polymer gel. By adding more chemicals to these vessels with the printer, Cronins team has triggered chemical reactions
in which the vessels play an active part.
We may be able to standardize the chemistry of drug manufacturing by using 3-D printing to handle complex processes more
simply and more viably. In biology, for instance, it is relatively easy
to manipulate DNA, but in chemistry the tool kit is much bigger.
We could find a way to assemble protein chemistry elements from
the various jigsaw pieces to make a universal set of parts that can
be repurposed using chemical fabricators. The potential for drug
discovery is huge. There is no science fiction here, but we have to
remember that a lot of research and development still needs to be
done, Cronin says.
Building the Ultimate Training Tool

A challenging strand of research that could take the practical
applications of additive manufacturing to another level is being
undertaken at Loughborough University, where Prof. Harris and a
European consortium, through the ArtiVasc 3-D project, are seeking to combine different techniques of 3-D printing; jetting and
multiphoton polymerization along with electrospinning into a

single hybrid.
All additive manufacturing processes have different advantages and disadvantages. There is no single process that solves
every problem. There are significant technological and engineering
challenges in combining these three types into a single process, not
least getting the right file format for this hybrid technology, but the
potential capabilities are exciting, says Harris.
Implants are great, but Ive spent enough time in hospital
wards to know that we are just touching the surface of what 3-D
printing can do for the medical industry. Training models could
have a huge impact over the career of a surgeon, but we are looking at ten years at least before we see the outcome and benefit of
our research, he added.
The models Harris is creating are for training surgeons in complex procedures and, ultimately, preparing them to operate on specific individuals.
The technology has evolved over time, and it is well used
in producing one-off components. Nowhere is this needed more
than in the human body. From MRI and CT scan data, you can
get a representation of what is inside the body, and this allows us
to make maxillofacial models, for example, that help a surgeon to
explore the structure of a specific patient, Harris says.
Creating high-fidelity artificial phantom models for training
surgeons could be a big breakthrough. The gold standard is to train
on cadavers, but there are problems with cost and availability, and
they are not necessarily the best representation of a patient as they
have no pathology and no clinical objective, which means practicing on them is primarily a lesson in anatomy. We are working on
specialized forms of 3-D printing to make it feasible and economic
to create anatomical representations that behave in the same way
as a real subject would, Harris adds.
Such models have a natural home in the ear, nose, and throat
area, but last year, the team began a pilot program to develop tools
for training in gastrointestinal surgery. With bowel cancer, the
third most common cancer in the United Kingdom, it is vital to
have high-quality training techniques for colonoscopy, and Harris
believes 3-D printed models of anatomy with the right pathology
could be the answer.
Funding the Future

Although many groundbreaking uses of additive manufacturing
lie a decade or more in the future, there is a strong belief that
some innovations can be commercialized much sooner. That is
certainly the view of the United Kingdoms Technology Strategy
Board (TSB), a public body that reports to the Department for
Business, Innovation, and Skills. In December 2012, the TSB
put 7 million on the table and ran a competitive process for
proposals using 3-D printing that could lead relatively quickly
to a marketable product. Of the 18 projects chosen for funding,
five were in the medical field.
There is a lot of promise in the technology and a lot of
research going on in the United Kingdom. Our strategy for
high-value manufacturing identifies additive manufacturing as
one of 22 national competencies into which we can be expected
to put money. We want to take in the full spectrum of innovation and talent that the country has to offer to get the right
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critical mass because there is a lot of demand

tangible applications for the technology. Nevfor what 3-D printing can offer, says Robin
ertheless, the pace of development is such that
Wilson, the TSBs lead technologist for highit is hard not to imagine what it will bring in
value manufacturing (Figure 5).
the future.
We had proposals for printing stem cells for
Three-dimensional printing is evolving
the growing of human organs, but we felt that
fast compared to traditional methods of makit was too early and the process was too innoing implants, such as milling or forging. Provative for this particular competition, though
ductivity is increasing in terms of the number
the TSB is very interested in the technology.
of cubic centimeters you can build in an hour,
We ruled them out because we had a stringent
and there is also better resolution, accuracy,
and tight focus on applications that can come to
reliability, and repeatability, notes Mercelis.
market relatively soon, Wilson adds.
Transistors were invented 70 years ago,
One of the funded projects is for addiso back then it was theoretically possible to
tive manufacturing for design-led effective
build computers with the same functionality as
patient treatment (ADEPT), which will cre- FIGURE 5 Robin Wilson is the lead
today, but it was in no sense practical to do so.
ate craniofacial implantable medical devices technologist, High Value ManuBut there has been a revolution over the years
with reduced cost and shorter lead times. The facturing, with the Technology
in size and power consumption, so now the
Strategy Board, United Kingdom.
three-year project, run by Cardiff Metropoli- (Photo courtesy of Robin Wilson.)
theory has become a reality. We could see the
tan University working with LPW Technology
same revolution in 3-D printing, adds Cronin.
Ltd. and Renishaw, capitalizes on the potential for 3-D printing
The work now being done on robotics and 3-D printing, includto make medical devices more cost effective and accessible.
ing the nascent area of tissue engineering, could herald a revolution
The second project chosen aims to transform high-value joint
in personalized medicine. Yet it is important to accept that this is still
replacement in the next two years. Likened to a pizza box deliva long way off.
ery to the operating room, Embody Orthopaedic and London
Sometimes expectations can be too high, but new applications
Universitys Imperial College are working on a way to disrupt the
are coming out all the time. 3-D printing faces a lot of challenges,
current supply chain model for orthopedic surgery with an innoand it is still hard to make a repeatable manufacturing process,
vative automated supply system that provides sterile customized
notes Engelborghs.
instruments for the surgeon and correctly sized implants that are
Harris agrees that development will not happen overnight,
personalized to the patient using CT scan data.
commenting that In the medical sector, incremental steps must
The TSB has also contributed money to a project run by FDM
be made and what is produced must complement current medical
Digital Solutions and a team from Salford University to accelpractice. We have to use 3-D printing to augment what clinicians
erate the production of bespoke orthotics within 24 h, which
are already doing, so we need to have engineers who have a deep
would enable customized insoles that can be locally manufacunderstanding of the medical industry as well as clinicians who
tured. It is also funding the development of a novel 3-D printed
will champion the technology. You cant force the technology into
coating for bioactive glass and metallic elements in hip implants
applications; it has to evolve.
run by JRI Composites.
For Cronin, it is vital that innovators allow their imaginations
The final project to be awarded money in the competition is
to drive them forward without glossing over the many challenges
known as Ticle (titanium cleaning) and is led by Corin Group.
they face.
Rather than producing a medical device, this innovation seeks
What we need is vision, money, and time. There must be
to improve the process by which 3-D printed medical implants
cross-disciplinary teams of tissue engineers, software developers,
are created.
and roboticists working together to not only push the science forThere is a lot of excitement about 3-D printing, but there is a lot
ward but also to manage expectations. The technology could be
of work to do before and after the printing process. A lot of work is
very important in the development of personalized medicine. In
required on the CAD files to create the geometry, and a temporary
the future, we could be taking stem cells from milk teeth at birth to
scaffold has to be created for the printed item. After printing, there
build a tool kit for growing and developing tissues. But we have to
is often a rough finish, so metal components may need to be heat
separate the fact from the fiction and get away from the gimmicky
treated, for example, says Wilson.
ideas about what 3-D printing could be used for. We have to differThe dirty secret of 3-D printing is that you dont just press a
entiate between useful speculation and hype so that we dont skew
button and get the finished item. We have brought that fact into the
the scientific process, Cronin says.
open, and the Ticle project addresses it directly. It is about mechaIt is certain that the biomedical sector will be one of the most
nizing the process of cleaning the product that has been printed
fertile for innovation in 3-D printing, but it is important to marand adding techniques like scanning for residue and removing the
vel at what has already been achieved without expecting the most
scaffolding, Wilson adds.
advanced ideas to become a reality overnight.
Jim Banks is a freelance writer based in the United Kingdom.
Daring to Dream
The scientists and engineers driving innovation in 3-D printing for
biomedical applications have stressed the importance of focusing on
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The Body Printed

By Shannon Fischer
t takes only a few minutes for the

NovoGen MMX to print out a
chunk of human liver cells. Its a
small chunk, only 4-mm wide and
20 cell layers thick, which wouldnt
do much good in a human patient.
But at a cellular level, this tiny swatch
of machine-made flesh has all the
essential ingredients of an original
organ: tight hexagons of hepatocytes
and fatty stellate cells and endothelial
cells gathered into nascent capillaries.
It produces cholesterol, albumin, and
detoxifying P450 enzymes. After it is
printed, the ensemble can survive for
almost an entire weeknearly triple
the endurance of classic two-dimensional (2-D) liver cultures.
Although it sounds like science
fiction, this liver and its creatorthe
seven-year-old San Diego, California, startup company Organovo
are at the forefront of what has
become one of the most daring frontiers in tissue engineering: threedimensional (3-D) bioprinting. The
end goal? Printed organs.
As you read this, multidisciplinary teams of scientists from
Osaka, Japan, to Iowa City, Iowa, are tinkering
with nozzles and lasers, polymer gels, and stem
cells. Some groups work with printers they have
built from the ground up; others have jury-rigged
existing machines to accommodate living cells.
During the last ten years, research output in the
field has nearly tripled, and the breakthroughs
have come fast. In 2008, University of Missouri
researchers printed a blood vessel. In 2011,
laser-printed heart patches restored cardiac functions in rats that had heart attacks. Right now,
researchers are in the process of using bioprinters
to assemble miniature kidneys built from the ground up.
ISTOCKPHOTO.COM/SHUMPC
Its a heady time to be in bioprintingenthusiasm runs high,

and it is easy to see why. The potential impact here could be enormous. Currently, 119,000 patients languish on
the organ donor list in the United States alone,
dying at a steady clip of 18 per day. If all a person
needed to do to make a new liver was press the
print button, it would revolutionize medicine.
However, there is reason to be cautious.
The bioprinting niche is still in its infancy, and
its foundation rests largely on proofs of concept and technological troubleshooting. Like
Organovos liver construct, most of the tissues
that have been printed so far have yet to exceed
more than a few millimeters in size. Enormous
hurdles in sciences understanding of biological functioning will
have to be overcome before the field can progress.
It has a long way to go, says Michael Renard, Organovos
executive vice president of commercial operations. Weve got
How 3-D Printing

Could Change the
Face of Modern
MedicineAnd
Why That Future Is
Still So Far Away

2154-2287/13/$31.002013IEEE
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ten years of history, but significant work remains to get us to the

ultimate solution. But, he adds, I do think it is going to a place
where well be able to do the kind of things that people today
dream about in tissue engineering.
From the Ground Up

Twenty-five years ago, Texas cell biologist Robert Klebe drained
the ink from the cartridges of his Hewlett Packard (HP) 2225C
Think Jet ink-jet printer and replaced it with fibronectin. On his
computer, he typed out the word fibronectin in lowercase letters, filled the printer tray with a thin sheet of plastic, and hit
print. He called the act cytoscribing, but it is better known now as
bioprintingand this was the worlds first instance of it.
But Klebe was ahead of his time. Computers had only really
become commonplace a few years prior, and the idea of printing
anything but ink was still relatively novel. His report, published
in Experimental Cell Research, went largely unnoticed.
The same year of Klebes printing experiment, a great deal
was afoot in the nearby field of tissue engineering. A team of
researchers led by Joseph Vacanti of Boston Childrens Hospital
and Robert Langer of the Massachusetts Institute of Technology (MIT) had just published a seminal report in the Journal
of Pediatric Surgery detailing how they had seeded 3-D polymer
structuresscaffoldswith cells from livers, intestines, and
pancreases, and then implanted them into rats. Within three
days, they reported that they had seen blood vessels creeping into
the embedded materials, and at seven days, three each of the liver
and intestinal grafts had begun to settle in and set up shop.
At heart this was a simple idea: the scaffold provided a starter
home for cells by mimicking the natural architecture of the target
organ. Then, as the cells grew and spread around it, the structure
degraded away, leaving only lab-grown tissue in its wake. Simple
or not, this revolutionized tissue engineering.
Over the next few decades, scaffolds became more sophisticated as fabrication techniques moved from molds and mesh
to nanoscale electrospinning and decellularizationa method
in which a donated organs preexisting cells are washed away,
leaving a perfect, nature-made skeleton of connective tissue
to repopulate. Around the turn of the century, as 3-D printing
emerged as a manufacturing force, researchers seized on that as
well and folded it into their repertoire, using it to turn out even
FIGURE 1 Anthony Atala, director of the Wake Forest Institute for

Regenerative Medicine, at work in his lab. (Photo courtesy of the
Wake Forest Institute for Regenerative Medicine.)
more elaborately crafted sculptures. In time, scaffold-grown tracheae and bladders began finding their way into patients.
The next frontier is the solid organs, says Anthony Atala,
director of the Wake Forest Institute for Regenerative Medicine and
a pioneer in tissue engineering (Figure 1). But thats also where traditional scaffolding starts to falter. On the scale of complexity, Atala
explains, body parts such as tracheas and bladders are frankly not
that difficult. A trachea is essentially a simple tube of tissues, but a
kidney has more than 30 different types of cells, all fed by an exquisite network of vascular channels. Even with the most meticulously
fashioned scaffold, manually seeding that level of cellular organization with any hope of accuracy poses a Herculean task.
In 2003, bioengineer Thomas Boland of Clemson University and his colleagues retraced Klebes early steps with an HP
660C printer, but Boland did not stop at two dimensions. He
also printed out a scaffoldlike layer of gel, let it set, then went
back and printed a layer of endothelial cell aggregates on top of the
already-printed gel. Automated precision cell placement in three
dimensionsthis time, people noticed.
Location, Location, Location

The simple beauty of 3-D bioprinting is that it allows tissue engineers to place their cells exactly where they need to be throughout construction. The best analogy is to think in terms of color
printing, says Brian Derby, a materials scientist at the University
of Manchester. A conventional printer uses four ink cartridges:
black plus three colors. From those, it can create any number
of complex designs just by mixing and positioning the droplets
of ink. Translate that into a palette of printable cell types, and
suddenly, a scientist can craft complicated cellular patterns and
textures. Before, they were coating a premade scaffold with ink
and hoping the cells found their niche.
As researchers seized on this newfound freedom, the years following Bolands discovery became a frenzy of collaborative trial
and error. Tissue engineers shifted through industrial 3-D printing technologies, discarding what would not translate and adapting what would. High-temperature laser sintering was obviously
outit would fry the cells. The same went for any technique that
relied on powdered or granulated material; living matter needed
an aqueous form. Early on, more than a few desktop printers
were gutted for the cause. I just took HP cartridges, admits Marc
FIGURE 2 Marc in het Panhuis at work in the University of

Wollongong lab with the 3-D printer he constructed. (Photo by
Grant Reynolds.)
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FIGURE 3 The NovoGen MMX Bioprinter is small and compact enough

to fit easily into a biosafety cabinet. (Photo courtesy of Organovo.)
in het Panhuis, head of the Soft Materials Group at the University

of Wollongong, Australia, where he studies bioinks. I actually
used to nick them off people when they threw their printers out.
It was literally a matter of opening them up and refilling them.
But then we realized we needed something more sophisticated.
Like many of his colleagues, in het Panhuis experimented with a
few other printer types before finally building his own (Figure 2).
Now a decade out, three primary printing techniques have
risen to dominance: extrusion, ink-jet and laser forward transfer.
Fundamentally, they operate on the same basic premise. Start
with a computer-aided design (CAD) model sliced into horizontal layers. The information goes to the printing apparatus, which
proceeds to fabricate the shape layer by layer from the ground up.
Most versions of these printers use bioinks made of a combination of cells mixed into a hydrogel solution, which serves to both
protect the living cargo and act as a coprinted scaffold.
However, each method comes with its own pros and cons.
In extrusion printing, filaments of thick bioink paste are pressed
from a nozzle. Its pretty much like pushing out toothpaste, in
het Panhuis describes. Of the three techniques, its by far the fastest, although it also tends to have the lowest resolution when it
comes to cell placement. Ink-jet printing, which drops tiny volumes of bioinks, can achieve a much finer scale, but it can also
be hard on the cells unless an appropriate soft gel substrate is
used. Laser forward transfer is the most precise of all. In some
versions, cells can be placed within 5.6 m of the planned coordinates. Here, a laser pulse focuses on a bioink-coated plate (often
quartz), causing a quick shock wave or heat spike that forces
bioink onto the final surface below. Unfortunately, the sheer
number of technological bells and whistles that laser printing
demands also makes it the least accessible of the three methods.
For its part, Organovo prints with a two-headed printer based
on research by pioneering Missouri bioengineer Gabor Forgacs
(Figure 3). Its based on extrusion technology, but with a twist.
Where most 3-D bioprinting still relies on hydrogel-cell inks,
Organovo uses straight-up cells cultured into discrete spheroids,
each containing between 10,000 and 30,000 cells of various types
that are able to finish the job themselves (Figure 4). In printing liver
tissue, for example, spheroid-based filaments are laid down by the
printer, but then the cells self-organize into their final positions
hepatic cells clustering over here and endothelial cells gathering
FIGURE 4 One of Organovos tissue engineers oversees the

construction of a vascular tissue construct on the Novogen MMX
Bioprinter. (Photo courtesy of Organovo.)
there to form nascent capillary channels (Figures 5 and 6). Its a

sort of nature knows best approach that sidesteps the resolution
issues by leaving the final steps to the tissues themselves.
Theres no real one answer, in het Panhuis says. He believes
that the next wave of technology will include hybrid printers
that combine the best of each technology to print across sizes
and speeds. Indeed, signs of such a shift have already begun to
emerge: Anthony Atala, for instance, recently combined the multinozzle printer built in his Wake Forest lab with different bioinks to print micro- and macrotissue architecture (Figure 7). Its
like laying down a painting on a canvas using a wide brush or a
narrow brush, Atala explains. He is now using the machine to
create tiny kidney organoids in an organized fashion (Figure 8).
FIGURE 5 Living human liver tissue built with multiple cell types.
(Photo courtesy of Organovo.)
FIGURE 6 A histology stain showing multiple cell types, alive and

in a native orientation. (Photo courtesy of Organovo.)
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FIGURE 7 An integrated 3-D printing at work. (Photo courtesy of

the Wake Forest Institute for Regenerative Medicine.)
FIGURE 8 A kidney prototype and ear and finger bone scaffolds

were printed on a 3-D bioprinter in Atalas lab. (Photo courtesy
of the Wake Forest Institute for Regenerative Medicine.)
kindthat he uses to coprint hollow hydrogel channels alongside his tissue of choice (Figure 9).
But what then? Would a fully vascularized organ with all the
key cells in all the key places actually work? Maybe. But maybe
not. In many ways, the more researchers achieve in bioprinting,
the less they find they understand. Much of what science knows
about cell biology comes from work in two dimensionsbut that
is not a natural environment. For our endothelial cells, when
we seed them in a petri dish with a hydrogel at the bottom, they
proliferate at a certain rate. When we encapsulate (in 3-D) the
exact same cells in the exact same gel, they behave completely
different, says Bertassoni. So all the answers we had, we have
to ask them again in a different way.
Most bioprinting work so far has relied on a handful of
hydrogel scaffolds to guide and structure cells, such as alginate,
gelatin, chitosan, or, on the synthetic side, poly(ethylene glycol).
The natural gels make excellent chemical homes full of growthpromoting signals, but they vary from one batch to another, complicating matters not just now but almost certainly down the line
when regulatory agencies will push exacting reproducibility standards. (The same goes double for all those patient-personalized
cells and stem cells that will eventually be printed, a fact already
causing headaches for manufacturing and regulatory scientists
watching the field.) Synthetic gels are more reliable but need to
have tailored signals added in, and a gel must fit within the very
narrow window of being just viscous enough to print without
hurting the cells but not so liquid that it cannot hold them in place.
Current tissue printing can achieve some function already, but
to scale it up enough for humans, researchers will need a better
understanding of how cells interact with their surroundings and
how to capitalize on that knowledge. A lot of the 3-D printing is
getting better and better, Derby says. But at the moment, we can
just make a higher-resolution nonfunctional model of the object.
We havent got the understanding of how the whole thing works.
Going Forward
The Catch
This all sounds impressive, but even miniature kidneys and functional liver patches are a far cry from human organs on demand.
There is a fine balance between the size of the structures you
print and the viability of the cells that are included in the structure, explains Luiz Bertassoni, a researcher working with Harvard Medical School tissue engineer Ali Khademhosseini.
Any tissue thicker than a few hundred micrometers must
have a working vascular system to transport nutrients and oxygen or it will quickly die. This has been a rate-limiting step for
bioprinting from the start and remains its most immediate challenge today. After all, without a system in place to support cells
during construction, a printed organ of any serious size could be
half-dead before it was even fully built.
In his research, Bertassoni is experimenting with different types of hydrogels that he uses to create vascular channels
during the printing process. Similar work is at play elsewhere
too. At the University of Pennsylvania, researchers have printed
sugar-glass channels that wash away. At the University of Iowa,
mechanical engineer Ibrahim Ozbolat has built an extrusion
printer with two independently operating armsthe first of its
Next year, Organovos microlivers will go on the market, not for

transplant but for drug development. Thats where the immediate future lies. After all, the very fact that 3-D cultures do act
FIGURE 9 A multiarmed bioprinter allows University of Iowa

researcher Ibrahim Ozbolat to develop ways to coprint vasculature and tissue simultaneously. (Photo courtesy of the Biomanufacturing Laboratory at the University of Iowa.)
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FIGURE 10 Rosalie Sears, a researcher at the Oregon Health

and Science University Knight Cancer Institute, is working
with Organovo to develop 3-D printed tumor models. (Photo
courtesy of Carl Pelz.)
FIGURE 11 Sears oversees Ellen Langer, a senior postdoctoral

fellow, who pipettes cells and media into tissue culture plates
to grow for future studies, including bioprinting and drug
treatment. (Photo courtesy of Carl Pelz.)
differentlymore realisticallythan 2-D already makes them

an invaluable stand-in for tests and models. Part of the reason
for so many billions being wasted in current pharmaceutical creation is that the current preclinical models such as dish culture
and mice make poor substitutes for humans. Theres a way to
test drugs on human liver cells, but theres no way to test drugs
on a human liver, Organovos Mike Renard says. He believes
3-D printing can close that gap, and hes not alone. Organovo
has already landed partnerships with various pharmaceutical
companies, including Pfizer and United Therapeutics.
Its the same for cancer research. This January, the Knight
Cancer Institute at Oregon Health and Science University also
inked a deal of its own with Organovo and began building 3-D
models of breast and pancreatic cancers. Here again, printed
cultures are more lifelike: tumor cells are more resistant to
therapy, they migrate extensively, and they communicate more
accurately with cells around them. Its really amazing, the
cells are behaving like aggressive cancer tissue, says Knight
researcher Rosalie Sears (Figure 10). Her team is already talking about a clinical trial with pancreatic cancer patients to see
if they can use this technology to predict a better course of
treatment based on how printed models of the patients tumors
respond in vitro (Figure 11). I am really excited, Sears says. I
think this is transformative. Itll allow us to learn things weve
never learned before about tumor cell interactions.
Printers can craft diseased tissue just as well as healthy, and
that too will most likely be more realistic than a petri dish or a
mouse. Last year at MIT and Harvard Medical School, researchers printed blocks of neurons that extended their axons and
bore traces of key neurotransmittersa proof-of-concept the
researchers there hope could become models for normal and disordered processes in the brain.
And yes, organs too will eventually emerge. Even the pragmatists who worry over the fields inevitable clash with regulatory bodies and clinical standards are confident in this. Well
see movement on that within a decade, says David Williams, a
manufacturing and regulatory scientist at Loughborough University, United Kingdom, who has been tracking the bioprinting
industrys emergence with an eye for its future hurdles. It wont
be the livers or the kidneys, he says, but it will be the simpler
things, parts that dont require a lot of vascularization or different types of tissuesbone, for instance. Others, like Derby, predict
that cartilage and skin will emerge as early players on the scene
as well and for the same reasons. Then most likely will come partial organs that sidestep complexity, like faux pancreases made of
membranes, basic insulin-producing cells, and very little else.
Its something that well have happen in the next generation,
Williams says. The energy of the community will make it happen.
Shannon Fischer is a freelance science writer living in Boston, Massachusetts.
For Further Reading

T. Boland, V. Mironov, A. Gutowska, E. A. Roth, and R. R. Markwald,
Cell and organ printing 2: Fusion of cell aggregates in three-dimensional gels, Anat. Rec. A, vol. 272A, no. 2, pp. 497502, June 2003.
B. Derby, Printing and prototyping of tissues and scaffolds, Science, vol. 338, no. 6109, pp. 921926, Nov. 2012.
C. J. Ferris, K. G. Gilmore, G. G. Wallace, and M. in het Panhuis,
Biofabrication: An overview of the approaches used for printing of living
cells, Appl. Microbiol. Biotechnol., vol. 97, no. 10, pp. 42434258, 2013.
K. Jakab, C. Norotte, F. Marga, K. Murphy, G. Vunjak-Novakovic,
and G. Forgacs, Tissue engineering by self-assembly and bio-printing
of living cells, Biofabrication, vol. 2, no. 2, p. 022001, 2010.
R. J. Klebe, Cytoscribing: A method for micropositioning cells
and the construction of two- and three-dimensional synthetic tissues, Exp. Cell Res., vol. 179, no. 2, pp. 362373, Dec. 1988.
F. P. W. Melchels, M. A. N. Domingos, T. J. Klein, J. Malda, P. J.
Bartolo, and D. W. Hutmacher, Additive manufacturing of tissues and
organs, Prog. Polym. Sci., vol. 37, no. 8, pp. 10791104, Aug. 2012.
I. T. Ozbolat and Y. Yu, Bioprinting towards organ fabrication:
Challenges and future trends, IEEE Trans. Biomed. Eng., vol. 60,
no. 3, pp. 19, 2013.
J. P. Vacanti, M. A. Morse, W. M. Saltzman, A. J. Domb, A. PerezAtayde, and R. Langer, Selective cell transplantation using bioabsorbable artificial polymers as matrices, J. Pediatr. Surg., vol. 123, no. 1,
pp. 39, 1988.
W. C. Wilson and T. Boland, Cell and organ printing 1: Protein and
cell printers, Anat. Rec. A, vol. 272A, no. 2, pp. 491496, June 2003.
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Moving the Science

of Behavioral Change
into the 21st Century: Part 2
By Niilo Saranummi, Donna Spruijt-Metz,
Stephen S. Intille, Ilkka Korhonen,
Wendy J. Nilsen, and Misha Pavel
hat follows is the second part of a twopart special series of articles that illustrate
through examples the breadth and depth
of the field of behavioral-change science
and highlight the challenges in moving
it in to the 21st century. The first part
appeared in the September/October issue of IEEE Pulse
(see [1][3]).
In this issue, the article by Spring et al. addresses
the potential of continuous observation of behavior. The highly granular continuous information
afforded by new wearable, wireless, and digital
technologies is revolutionizing the way that
we monitor, model, motivate, and modify
health-related behaviors. The interdisciplinary collaborations among behavioral scientists, engineers, and computer scientists that
generated these intervention technologies
should propel behavioral-change theory to
catch up with new intervention capabilities. The second article,
The motivation
by Rivera
and Jimison,
behind this series
illustrates the
is the fact that
application of
chronic diseases are
systems and comgaining
in prevalence
putational modeling
and consuming
for predicting behavan
increasing part
ior change and optimizing interventions through
of health budgets
the presentation of two disglobally.
tinct examples: an intervention for
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2012 WWW.ALL-FREE-DOWNLOAD.COM

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2154-2287/13/$31.002013IEEE
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To move the science

of behavioral change
to the 21st century,
we need to build a
transdisciplinary
community of
stakeholders in
research, industry,
and health.
managing weight gain during pregnancy and a health-coaching

platform for elderly patients.
The motivation behind this series is the fact that chronic
diseases are gaining in prevalence and consuming an increasing part of health budgets globally. We know that the best prevention (and the best care) against chronic diseases is a healthy
lifestyle. Furthermore, we know that public health measures
aimed at creating awareness and setting up policies that guide
citizens toward healthier lifestyles are not effective enough to
motivate people to lead healthier lifestyles. What we need is a
personalized approach that provides citizens with the ability to
manage their health and well-being, thereby preventing the
development of chronic diseases. We have the technology for
this (smartphones, mHealth apps, and cloud computing) but
we do not have the knowledge to support behavior change of
citizens in their everyday lives.
To move the science of behavioral change to the 21st
century, we need to build a transdisciplinary community of
stakeholders in research, industry, and health; we need to
deploy advances in computerized measurement and Internet-connected devices to make data accessible at scales not
previously possible; and we need to make intelligent use of
such data to create model-based smart applications that will
longitudinally assist us in the difficult task of managing our
health behavior choices.
This knowledge gap was the focus of the International
Workshop on New Computationally Enabled Theoretical Models to Support Health Behavior Change and Maintenance (www.behaviorchange.be) that we organized in
mid-October 2012 in Brussels, Belgium. This workshop was
sponsored by the National Science Foundation; the European Commission Directorate for Communications Networks, Content and Technology Health and Well-Being Unit;
and the National Institutes of Health Office of Behavioral

and Social Sciences Research. Altogether, 30 experts from
the United States and Europe representing a mix of scientific
disciplines were invited to participate. The final outcome of
the workshop is a white paper that has been submitted to the
sponsoring organizations for consideration in their respective
upcoming research agendas and is currently under review
for wider publication.
Niilo Saranummi (niilo.saranummi@vtt.fi)
is with the
_______________
VTT Technical Research Centre of Finland, Tampere. Donna
Spruijt-Metz (dmetz@usc.edu)
__________ is with the University of South___________ is with
ern California. Stephen S. Intille (S.Intille@neu.edu)
___________
Northeastern University. Ilkka Korhonen (ilkka.korhonen@
tut.fi)
____ is with the Tampere University of Technology, Finland.
Wendy J. Nilsen (nilsenwj@od.nih.gov)
_____________ is with the Office of
Behavioral and Social Sciences Research, U.S. National Institutes
of Health. Misha Pavel (mpavel@nsf.gov)
__________ is with the Computer, Informational Systems, and Engineering Department, U.S.
National Science Foundation and Northeastern University.
References
[1] N. Saranummi, D. Spruijt-Metz, S. S. Intille, I. Korhonen, W. J.
Nilsen, and M. Pavel, Moving the science of behavioral change
into the 21st century, IEEE Pulse, vol. 4, no. 5, pp. 2224, 2013.
[2] E. B. Hekler, P. Klasnja, V. Traver, and M. Hendriks, Realizing
effective behavioral management of health, IEEE Pulse, vol. 4,
no. 5, pp. 2934, 2013.
[3] W. J. Nilsen and M. Pavel, Moving behavioral theories into the
21st century, IEEE Pulse, vol. 4, no. 5, pp. 2528, 2013.
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Healthy Apps
By Bonnie Spring, Marientina Gotsis, Ana Paiva, and Donna Spruijt-Metz
t is now known that nearly half of the toll that

illness takes in developed countries is linked to
four unhealthy behaviors: smoking, excess alcohol intake, poor diet, and physical inactivity.
These common risk behaviors cause preventable,
delayed illness that then manifests as chronic
disease, requiring extended medical care with
associated financial costs. Chronic disease already
accounts for 75% of U.S. health-care costs,
foreshadowing an unsustainable financial burden for the aging population [1]. We are facing an urgent need to re-engineer health systems to improve public health through behavior change, and
technology-supported behavioral change interventions will be
a part of 21st-century health care. As new technical capabilities to observe behavior continuously in context make it
possible to tailor interventions in real time, the way we
understand and try to influence behavior will change
fundamentally.
Mobile Devices
for Continuous
Monitoring and
Intervention
Health Behavioral Change

Intervention Theory
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The goals of health behavioral interventions are

to spark and sustain health-enhancing activities,
such as exercising and using sunscreen, and stop
health-compromising behaviors, such as tobacco
use and excessive alcohol intake. Similarly, preventive interventions are designed to discourage unhealthy habits before they start. Applying
theory is useful because it is well established that
interventions based on theory are more effective at
modifying behavior than those not based on theory
[2]. Most behavioral interventions derive from social
science theories that posit how different individual,
community, and environmental factors influence behavior and the mechanisms whereby altering these factors will
bring about behavior change. Each theory specifies a set of
abstract concepts (constructs), related measurable variables, and
a set of propositions that systematically explain how these concepts
are interrelated. Thus, health behavioral theories predict how applying
an intervention (input) will drive change in underlying behavioral mechanisms or determinants (mediating constructs) that will in turn drive health behavioral change (output).
For example, the health belief theory proposes that a persons odds of discontinuing an unhealthy behavior are jointly determined by his expectations about
perceived susceptibility to illness, perceived severity of illness, and perceived value
(benefits and barriers) of giving up the behavior. Since the 1950s, this theory has
guided most behavior change counseling performed in general medical practice.
2154-2287/13/$31.002013IEEE
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Motivation is the engine that drives the entire

Social cognitive theory, the health behavioral
behavior change undertaking because it is the
theory most extensively applied in behavioral
Motivation is the
energizing force that catalyzes and sustains
research today, posits that a persons odds of iniengine that drives
an organisms goal-directed behavior. Motivatiating a behavior are determined predominantly
the entire behavior
tion plays a critically important double role in
by his confidence about being able to perform
change undertaking
behavioral change intervention. First, motithe behavior (self-efficacy) and beliefs about the
because it is the
vation influences a persons willingness to
probability and value of the behaviors conseenergizing force that
engage with self-monitoring his own behavior
quences (outcome expectancies).
or being monitored by someone else. Privacy
These theories have done a good job at guidcatalyzes and sustains
concerns, burden, personal temperament, and
ing behavioral change approaches that made use
an organisms goalthe extrinsically rewarding or persuasive feaof conventional assessment and interventional
directed behavior.
tures of a technology all enter the equation
technologies. Their cause-and-effect models are
here. Unless this initial motivational engagelargely static, assuming a single set of mediating
ment challenge can be overcome, the behavior
causal pathways, rather than dynamic feedback
change game is over because it will not be possible for ubiquiloops or evolution of changing determinants over time. Most
tous technologies to monitor behavior to determine whether
theories make some mention of environmental determinants
a change has occurred. Second, motivation enters our con(e.g., the health beliefs theory includes cues to action; the social
ceptual model at a later point. There, motivation reflects
cognitive theory posits reciprocal determinism, whereby people
the persons volition to cooperate with the intervention and
both choose and are acted upon by their environments). Howmodify the targeted behavior as intended, rather than pushever, the vast majority of causal constructs in these theories are
ing back to resist change.
intrapsychic, conscious, somewhat vaguely specified processes
whose quantitative relationship to health behavioral change is
only imprecisely specified.
Monitoring
Because intervention has been predictable, fixed, and protocol
Until now, our understanding of human behaviors has been
driven rather than response dependent, assessment of mediabased on snapshots in time, such as a questionnaire completed
tors has only needed to be done infrequently (e.g., baseline and
once (or even several times), direct observation for short periods
follow-up). For example, a smoking cessation treatment that is
of time, or an interview. The models we built from such data did
based on the social cognitive theory will be implemented based
not reflect how behaviors were elicited by circumstances or time,
on the fixed sequence of sessions specified by the treatment
or how they changed throughout the day. For the most part, they
manual, rather than changing dose or technique in response to
were based on self-reported measures that are subject to several
fluctuations in a clients self-efficacy to quit. Indeed, the main
forms of bias, including the fact that people forget answers to
reason why mediators have been assessed in the past has been
some questions, such as: how many hours of television have you
to determine, after the fact, whether any change in the targeted
watched this week? They may not know the answers to other
health behavior could be accounted for statistically by change in
questions, such as: how many minutes did you spend in modthe mediator.
erate-to-vigorous physical activity yesterday? Sometimes people
Fast-forward now to the current era of mobile technologies
are hesitant to answer questions (for example, about drug usage),
that allows continuous recording of both objective and subjective
and sometimes they answer dishonestly to portray themselves in
data. These tools, and the engineers and computer scientists who
a positive light.
developed them, introduced behavioral scientists to new interNew technologies, such as the smartphone and wearable,
ventional capabilities and a different approach to causal modelimplantable, and environmental sensors have revolutioning. From our professional vantage points in psychology, design,
ized our ability to monitor peoples behavior and the ability
and engineering, we discuss how the interjection of continuous
of people to monitor their own behavior in real time. These
monitoring technologies is likely to disrupt health behavioral
technologies allow us to reduce participant bias by objectively
change theory and treatmentfor the better, we think.
measuring such behaviors as physical activity, smoking, place,
Changing a deeply ingrained health risk behavior requires
addressing what we conceptualize as the 4 Ms: monitoring,
modeling, motivating, and modifying (Figure 1). Monitoring
Model
(measuring) is needed to track if and how behavior changes in
response to an intervention and whether the theorized mediators change in parallel. The highly granular information afforded
Modify
Monitor
by new wearable, wireless, and digital technologies (sensors,
beacons, and smartphones) can help build a model of how the
Motivate
behavior truly works in real timewhat prompts it; when,
where, and with whom it occurs; and what the person is feeling
and thinking before and after the behavior.
FIGURE 1 Changing a long-standing health risk behavior requires
To collect the rich data needed to launch into modeling
addressing the 4 Ms: monitoring, modeling, motivating, and
and then intervention, we must first address motivation.
modifying.
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the weight of a formerly obese patient starts to

time spent in various activities, and so forth.
creep back up during weight-loss maintenance,
Data can be collected through combinations
Technologies that
we can prompt the patient to make small adjustof ubiquitous mobile, body, and environmensupply data storms
ments in sleep, diet, and exercise behaviors to
tally embedded devices that people wear, use,
from large numbers
preempt the return of obesity.
and otherwise encounter throughout their day
of individuals make
It may seem odd to suggest that data from
and night. People leave a broad swath of digiit feasible to create
entertainment usage be combined with that
tal footprints: through Internet use, credit card
snapshots of the
from medical records to model information about
purchases, entrance and exit scanners, and the
health behaviors. Yet it makes perfect sense.
like. These traces let us measure things that
behavior of entire
Digital data about the type of entertainment we
we never thought to measure (and thus never
populations.
choose and how we consume it is abundantly
included in our earlier models of behavior).
available and greatly underutilized. Through
This deluge of data tells us more about peoback-end technologies, we know much about
ples behavior than we ever imagined we could
the games people play, when, and with whom. Our selections of
know a decade ago. Although we still rely on self-reported meastreaming video and music convey information about our frame
sures for some things (for instance, there is no objective meaof mind and our emotional and cognitive well-being. Whether
sure of toothache), we now can elicit self-reported measures
we choose to watch a comedy, a horror flick, religious programat designated times, in prespecified locations, or in reaction to
ming, or a documentary says something about our mood at the
key events using a combination of sensors and cell phone techtime of making the choice. Moreover, our pattern of media connologies. The ability to collect such a rich array of objective and
sumption and the behaviors we pair with being entertained can
subjective measures in real time and context provides unprecefeed back to influence affective tone. For example, binge watchdented opportunity to develop more sophisticated causal models
ing several films in a row while sitting on the couch consumof what, how, who, when, where, and, ultimately, why behaviors
ing pizza, beer, and chocolates suggests the onset of a downward
occur and shift.
spiral that involves a cascade of health-compromising behaviors.
For instance, if global positioning system (GPS) sensors in
Being able to capture and model such sequences of health-comyour phone or fitness device let us know that you are enterpromising behaviors opens the possibility of being able to disrupt
ing a fast food restaurant, we can make this time-and-locationthe pattern to interject healthier habits.
stamped data quickly available for analysis on a smartphone,
the cloud, or a back-end secure server. That enables us to apply
the method of ecological momentary assessment, whereby your
Modeling
smartphone pings you to ask if you are hungry or stressed, or
Our new access to data about sequences of cues and behavioral
what you plan on buying. Through this combination of techresponse patterns that recur throughout the day permits the
nologies and methods, we can begin to form a rich and detailed
development of dynamic relational computational models. Such
picture of how your feelings, thoughts, and behaviors affect
data-driven models depict how behaviors link dynamically to
each other that is accurately placed in time, and in social- and
events in the persons physiology, psychological state, and surbuilt-environmental context. As discussed later in this article,
rounding social and physical contexts. Extracting patterns from
we can apply analytical and simulation techniques to these data
the obtained data allows behaviors, emotions, and urges to be
to develop dynamic models of health behavior determinants
inferred and classified, offering a high-level interpretation of
that help us adapt to intervention strategies in real time.
the data. Recording behaviors together with time and location
Two other types of life recordhealth and entertainment
stamps adds contextual data that enriches the model sufficiently
afford additional opportunities to monitor very diverse data on
to allow intelligent prediction of the precise moment and place
human behavior. Many health systems have already implein the socialemotionalphysical space when intervention can
mented electronic health records (EHRs) that can be tapped to
optimally be delivered.
guide intervention both at the point of care and beyond it. For
At this point, we can apply control systems engineering prinexample, by depicting information about food stores in a patients
ciples [3] to design and implement a behavior change system that
neighborhood, some EHRs equip providers to deliver contextis optimized to deploy finely tailored, properly dosed, just-in-time
sensitive counseling about how to make healthier eating choices.
bouts of intervention at the precise moment and context when
Other EHRs offer patients a special portal to transmit data continthey will be maximally effective at influencing your behavually about their glucose level, weight, physical activity, and diet.
ior. Consider, for example, the scenario of a recovering cocaine
Giving health professionals access to these digital data and letting
user whose voice samplings indicate that he had an argument
patients know that caring staff are looped in creates a technologywith his employer earlier in the day and whose respiratory and
supported behavior change system that can be highly effective.
heart rate patterns suggest lingering signs of stress. The GPS on
Knowing that a coach is monitoring and supporting their behavhis phone now shows him to be driving toward a part of town
ior change efforts keeps patients accountable and reinforced for
where he has previously purchased drugs. Our model predicts
staying on track to meet their goals. Mining the data generated by
that the precipitating conditions are present to trigger an urge
such a system makes it possible to derive algorithms that detect
to use cocaine, and, moreover, that a facilitating environment
periods of risk so that an intervention can be triggered before
of drug access is about to be present. Armed with such a model,
an unhealthy behavior pattern can take hold. For example, if
a human coach, an avatar, or the technology itself can apply an
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engineering models of behavior change. Conassortment of prompts, nudges, or back-pats to

versely, like the computer scientist depicted
preempt risk behaviors and reinforce healthier
Personalization
in Figure 2, team members from engineering
responses. We can monitor the behavioral outis the key to
express frustration about how to specify compucomes of this experiment to determine if positive
maintaining diverse
tational relationships among the numerous fuzzchange occurred and build what we learn into
participants in the
ily defined concepts in behavioral science theory.
the next version of our predictive model. Then,
cycle of continuous
Like the health beliefs, social cognitive and
we can continue to test and modify our model
observation and realother theories used by behavioral scientists, the
linking risk behaviors to their triggering cues and
computational models that engineers derive
contexts until we can predict and preempt risk
time adaptation.
(from analysis of continuous observations) depict
behaviors with great precision.
an understanding of the web of influences that
The information derived from continuous
surround a health behavior. The difference is that computaobservation and modeling also can be used at the macrolevel by
tional modeling is driven descriptively from the bottom up by
health institutions and policy makers. Technologies that supply
the obtained data, consistent with methodological tradition in
data storms from large numbers of individuals make it feasible
engineering science, rather than top down by a set of constructs
to create snapshots of the behavior of entire populations. Recent
and propositions that predicts a priori how the data should look,
advances in systems science [4] and social simulation now allow
consistent with methodological tradition in behavioral science.
us to connect these temporally dense snapshots, coming from
Studies of team science suggest that this type of challenging diathe observed data, into predictive models that simulate populogue across different scientific disciplines can produce transforlations as dynamical networks whose shapes change as new
mative change and scientific breakthroughs so long as diverse
behavior patterns emerge and shift. At a pragmatic level, the
collaborators persist in trying to develop a shared mental model
ability to perform data-based simulations of complex systems
of their work.
enables decision makers to try out and adjust potential poliA fruitful and needed outcome of such interdisciplinary
cies and interventions in simulated reality before implementing
cross-talk should be to bring 20th-century behavioral theories
programmatic change in the real world. That capability helps
up to the task of guiding intervention delivery in the age of
decision makers envision both the intended positive consemobile technologies and mobile-enabled interventions. Existquences and any unintended adverse ones they should anticiing behavioral change theories have in many respects become
pate from applying a contemplated health promotion strategy
ossified, failing to be revised or refuted by the emergence of
to a population.
data that contradict them. We can now construct new, more
Thus far, we have discussed modeling as if the process
dynamic descriptive models of how behavior works using techcould be reduced to a series of programming operations that
nology-enabled denser, richer, continuous storms of data than
occurs quasi-magically under the hood of a computer. It is
have previously been available. For these developed, ground-up
easy to forget that the programming operations that translate
descriptive models to achieve generalized utility beyond a spedata into models are crafted by human beings who select and
cific local context; however, we have to restore the appropriate
interpret data through the lens of their prior experiences and
iterative relationship among data, modeling, and theory. As the
beliefs. Increasingly, public opinion holds that health promoengineer in Figure 2 is attempting to do, a scientist ought to be
tion is everybodys business. That is, the responsibility for
able to express behavioral science theory quantitatively in cominculcating and sustaining healthy lifestyles extends beyond
putational models that can be tested through simulation and
the individual or the doctorpatient dyad to include families,
communities, social institutions, and the government. Hence,
there are more stakeholders whose insights and purviews on
data about behavioral determinants add value and need to be
taken into account.
The need to determine which data should be presented to
which user, when, and how has made data visualization and
visual analytics a ripe area for design and development. The dialectical relationship between viewers and data presents many
nuances in how audiences differing in demographic attributes
and expertise perceive and interpret information. To engage
these diverse and important audiences in filtering, curating,
interpreting, and using data displays is a challenge that 21stcentury model building still needs to address.
Two groups of stakeholders that collaborate to develop technology supported behavioral change interventions are behavFIGURE 2 A computer scientist tries to grasp a behavioral
scientists approach to modeling. Behavioral science theories
ioral scientists and computer science engineers. The approach
are models that are specified in advance to guide the design of
to modeling in these two disciplines reflects divergent methodan intervention. Even though the theory usually lacks quantitaological traditions. Behavioral scientists on the team are usually
tive details, behavioral interventions based on theory are more
puzzled by the absence of theorized mediating mechanisms in
effective at changing behavior than those not based on theory.
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real-world application. The results of such testing

need to iterate back to inform revision of not only
the computational model but also ultimately the
theory so that behavioral science theories remain
viable and useful.
Motivating
to change their behavior, and motivating them

to maintain positive behavior change. Because
different people are motivated differently, personalization is the key to maintaining diverse
participants in the cycle of continuous observation and real-time adaptation.
The self-monitoring required by behavioral
change techniques traditionally has been highly
burdensome. Until passive sensing technologies
became available, self-monitoring necessitated
keeping detailed paper records of target behaviors (eating, activity, or substance use) throughout the day and
also noting the antecedents and consequences of each bout of
behavior. Getting feedback about behavior change required analyzing and manually plotting the data, or waiting for an appointment with a specialist who did so. It was the rare individual who
enjoyed doing this kind of self-monitoring. Recent developments
in technology have, however, made it easier to motivate people
to engage actively in self-monitoring. Indeed, those who affiliate
with the quantified self movement find it inherently reinforcing to use self-tracking tools. Many say that self-tracking helps
them attain self-knowledge through numbers. Self-measuring
clearly can become intrinsically motivating by leveraging peoples inherent desires for competence and competition.
Although engaging design features embedded within a technology help facilitate uptake, it is not solely the physical attributes of the technology that heighten peoples desire to engage
but rather the way these features interact with users psychological predispositions. For example, a successful system might
combine several new technological capabilities and incorporate
a menu of assets such as a playful interface and microeconomies,
or a compelling story that leverages peoples intrinsic desires to
be entertained, to participate in narrative, and to generate or be
told a story. Intuitive interaction, appealing user interfaces, variety in incentives, scripted storytelling or user-generated narrative, characters that empathize with users, characters that users
can empathize with, fantasy worlds that can be explored, or real
worlds that can be augmentedthese are all ingredients that
can influence the success of a designed experience [5].
The self-determination theory of motivation posits that
human beings have three innate developmental needs: competence, autonomy, and relatedness. The need for competence is
reinforced by feelings of mastery that result from experiences
that increase our knowledge and skills. The need for autonomy
is grounded in the desire to act of our own free will without
the direct intervention of others. We all have a desire to be
causal agents of our own lives, acting with a feeling that we are
in full volitional control [6]. Indeed, for some individuals, the
perception of being controlled by others is sufficient to provoke
reactance [7], an aversive feeling of being externally controlled
that motivates the person to push back and resist intervention.
Interventions that neglect this principle are likely to face serious problems with continuing usage (compliance). For example,
having your mobile telephone always tell you as you walk into
an ice cream shop that you should not indulge might be a nice
gimmick initially but may ultimately lead to irritation and a
smashed smartphone rather than behavior modification. Less
The need for

competence is
reinforced by feelings
of mastery that result
from experiences
that increase our
knowledge and skills.
As the force that drives goal-directed behavior,

motivation is integral to the entire endeavor
of understanding, changing, and maintaining
health behavior. Three main challenges need to
be addressed: motivating people to self-monitor their behavior
(or be monitored by someone else), motivating them actually
FIGURE 3 The smartphone display for the ENGAGED weight loss

app [9]. Fans coded in traffic light colors show how much you
have already eaten today relative to your daily allowances for
calories and fat. The green fan signifies that you can still eat 327
more calories today. However, if you enter the steak that you are
thinking about ordering, the fan will turn bright red. You can
top up the green physical activity thermometer by accumulating more minutes of moderate intensity exercise until you reach
your weekly goal. Wearing the study accelerometer lets your
minutes of activity accumulate automatically, but if you forget
to wear it, you can get credit (in lighter green) by entering your
exercise manually.
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commanding messages that suggest options and ask what you

prefer are likely to be better received and more effective.
Importantly, the needs to experience competence and autonomy do not suggest needs to be independent of others. Quite
the contrary, a third fundamental need is to feel meaningfully
connected with others. Current technologies allow people to
share data about their health behaviors almost in real time with
others in an extended social network. Social media, including
blogs, tweets, and virtual social networks, let us share information about our actions with a large population of friends, family, health-care providers, and even strangers. Broadcasting our
behavioral data serves many different motivational functions.
For example, social sharing allows us to elicit encouragement
and emotional support from peers, who may also help by holding us accountable for meeting our goals. The ability to perform
social comparisons against others is informative and can spur
competitive motivation to surpass the performance of networked
others, potentially energizing the entire group.
Modifying
Since the goal of health behavioral intervention is to effectively
modify health-compromising actions, we conclude by discussing how technology-supported interventions produce positive
behavior change. In the language of behavioral science theory,
which mechanisms mediate improvement? Despite all the novel,
exciting features offered by new technologies, we do not believe
that widgets, in and of themselves, magically modify behavior.
Technologies merely offer affordances [8] that allow people to
perform an action in relation to a device. A pedometer affords
walking and receiving feedback about step counts. A pedometer purchased and kept in a drawer will not increase walking
because the device is not magical. However, a worn pedometer
may increase walking because wearing the device allows walking to trigger feedback, which reinforces more walking. As the
example illustrates, the sensors and devices incorporated into
effective technology-supported treatments largely serve as channels to deploy the validated behavior change principles set forth
in health behavioral theories. Technologies work to modify
behavior when they afford the user a relationship with a system
that activates effective behavior change mechanisms.
Consider the ENGAGED weight loss app [9], shown in
Figure3, an enhanced Android version of an effective mHealth
program for weight loss [10]. The app is part of a technologysupported system that the first author and her colleagues developed to deliver the Diabetes Prevention Program (DPP), a gold
standard intensive lifestyle intervention to treat obesity. The
DPP applies a number of effective behavior change techniques
drawn from social cognitive theory. The first, self-monitoring (of
food intake and exercise), is a staple of behavior change techniques. Doing this kind of monitoring, usually in and of itself,
improves problematic behaviors, probably by heightening
awareness of them.
The second technique, goal setting, specifies the target behaviors needed to achieve the valued health outcome: for DPP, the
targets are daily calorie and fat intake allowances and physical
activity goals. Participating in the DPP traditionally requires people to use paper and pencil to write down everything they eat.
FIGURE 4 Color-coded information about team members in the

ENGAGED weight loss competition. The left-most flag tab shows
each persons self-reported status. Mark seems to need help.
He posted his status as red (danger). His middle (knife and fork)
tab is also red, indicating that he has not yet entered any meals
today, and his right-most (accelerometer) tab is red, showing
that he has not put on his accelerometer. Everyone else on the
team has already recorded two meals, but no one has turned the
knife and fork tab green by entering three meals. Two people
(June and BlueFoxyz) have turned the physical activity tab
green by wearing the accelerometer for two-thirds of the day.
Everyone else besides Mark has accumulated one-third of a day
of accelerometer wear.
Only later when they look up and tally the calories and fat grams
in those foods can they get delayed feedback on whether they
met their goals. In contrast, using an app like ENGAGED to enter
food intake creates a simple control system [2] that immediately
detects and visualizes discrepancy between current behavior
and goal as color-coded positive (green) or negative (red) feedback (Figure 3). Additionally, the app gives the user more accurate and motivating exercise feedback than paper and pencil by
having them fill up a goal thermometer on the smartphone by
accumulating physical activity counts that are Bluetoothed in
real time from an accelerometer.
In addition to building self-efficacy about the ability to
meet diet and activity goals, the ENGAGED system applies
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two further principles of the social cognitive theory. By being

embedded in a smartphone that is ever present for most users,
the app creates a facilitating physical environment to support
weight self-management. The ENGAGED system also establishes a facilitating social environment by transmitting behavioral data to others who provide support and accountability
for self-monitoring and healthy change. Complete data are
sent to an interventionist who monitors recording compliance
and behavior and then provides personalized coaching by telephone. Additionally, as shown in Figure 4, data on one anothers
recording adherence are sent to a group of eight participants who
have been incentivized as a team in a weight loss competition
against other teams. The purpose of the incentive is to align team
members financial interests so that they are motivated to care
about and support one anothers weight loss efforts. Color-coded
icons on the smartphone convert from red to yellow to green as
participants enter more meals and wear the accelerometer for longer portions of the day. Armed with these data about their teammates compliance with self-monitoring, team members use a
private message board to communicate and support each other.
Many unknowns remain about how technology can best
facilitate healthy lifestyle change. One important gap in knowledge concerns how easy to make self-monitoring. Will behavioral tracking be as effective in reducing problematic responses
when it can be done passively by sensors, or is the burdensome
conscious reflection implicit in written recording necessary for
benefit to occur? Can technological systems function as effectively to shape healthy new behaviors as to disrupt problematic ones? Finally, and very importantly, how will 21st-century
interventions incorporate and use continuous observational
data about behavior?
Technologies such as the ENGAGED app currently collapse
minute-by-minute data into cumulative aggregate scores, discarding tremendous amounts of real-time information. Now
that behavioral change technologies are capable of processing responses to learn in real time and change their treatment
algorithms accordingly, interventions can be personalized and
adaptive so that doses and even modalities and messages are tailored on the fly. How shall we use these capabilities to optimize
behavioral treatment? Will an ability to perform single-case
experiments in real time replace the need to perform randomized controlled trials? Will we now abandon the underlying
premise of evidence-based treatment guidelines that effective
interventions produce generalized benefit for many individuals? Will our new default assumption be that a unique personalized treatment algorithm needs to be learned for each person
and relearned as time, circumstance, and context change? How
will the needs for technology redesign and reprogramming keep
up with the pace of intervention refinement for individuals
over time? And how practical is any of this for a cash-strapped
health-care delivery system?
Fewer than 20 years ago, personal digital assistants were cutting-edge intervention technology. Yet, despite massive changes
in the operating systems, sensors, and design of contemporary

mobile technologies, the theory-derived change principles
implemented for behavioral intervention remain largely the
same today. Interest in doing real-time intervention refinement
based on continuously observed behavioral response data is
inspired as much by new interdisciplinary collaboration among
behavioral scientists, engineers, and computer scientists as it is
by new technological capabilities. As these new collaborations,
technologies, and computational modeling capabilities create
new intervention capabilities over the next several decades, we
look forward to seeing our behavioral change theories catch up.
Bonnie Spring (bspring@northwestern.edu)
________________ is with Northwestern
University Feinberg School of Medicine, Chicago, Illinois. Marientina
Gotsis is with the University of Southern California, Los Angeles. Ana
Paiva is with GAIPS, INESC-ID and Instituto Superior Tcnico, Lisboa, Portugal. Donna Spruijt-Metz is with the University of Southern
California, Los Angeles.
References
[1] World Health Organization, 20082013 Action Plan for the Global
Strategy for the Prevention and Control of Noncommunicable Diseases,
vol. 36. Geneva: WHO, 2008.
[2] K. Glanz and D. B. Bishop, The role of behavioral science theory
in development and implementation of public health interventions, Annu. Rev. Pub. Health, vol. 31, pp. 399418, 2010.
[3] D. E. Rivera, Optimized behavioral interventions: What does
system identification and control engineering have to offer?, in
Proc. 16th Int. Federation of Automatic Control (IFAC) Workshop on System Identification (SYSID 2012), pp. 882893.
[4] R. A. Hammond, Complex systems modeling for obesity
research, Prev. Chronic Dis., vol. 6, p. A97, July 2009.
[5] J. Vassileva, Motivating participation in social computing
applications: A user modeling perspective, User Model. UserAdapt. Interact., vol. 22, pp. 177201, Mar. 2012.
[6] E. L. Deci and R. M. Ryan, Overview of self-determination theory, in The Oxford Handbook of Human Motivation, R. M. Ryan, Ed.
London, U.K.: Oxford Univ. Press, 2012, pp. 85107.
[7] S. S. Brehm and J. W. Brehm, Psychological Reactance: A Theory of
Freedom and Control. New York: Academic Press, 1981.
[8] D. A. Norman, The Design of Everyday Things. New York: Basic
Books, 2002.
[9] C. A. Pellegrini, J. M. Duncan, A. C. Moller, J. Buscemi, A. Sularz,
A. DeMott, A. Pictor, S. Pagoto, J. Siddique, and B. Spring,
A smartphone-supported weight loss program: Design of the
ENGAGED randomized controlled trial, BMC Pub. Health,
vol. 12, p. 1041, 2012.
[10] B. Spring, J. M. Duncan, E. A. Janke, A. T. Kozak, H. G. McFadden,
A. DeMott, A. Pictor, L. H. Epstein, J. Siddique, and C. A. Pellegrini,
Integrating technology into standard weight loss treatment:
A randomized controlled trial, JAMA Intern. Med., vol. 173(2),
no. 2, p. 105, Jan. 2013.
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Systems Modeling
of Behavior Change
By Daniel E. Rivera and Holly B. Jimison
PUSHPIN
ystems science techniques are becoming

increasingly important
as tools for modeling
behavior change and
as enablers for delivering more effective tailored
interventions [1], [2]. Systems
approaches offer a fresh perspective on the understanding
of behavior change, providing a means for better capturing
complexity, exposing gaps in the existing body of knowledge, enhancing the predictive capability of models, and
ultimately enabling optimal decision making in behavioral intervention settings.
The approaches that have been applied to model
behavior change are diverse in nature; these include
computational/mathematical modeling, agentbased modeling, dynamical systems modeling, and
network analysis. Powerful computational environments as well as the increasing ability to gather large
amounts of behavioral data (in the field through
ecological momentary assessment or otherwise)
facilitate the use of systems modeling approaches in
behavior change.
There are many challenges to using data
from sensors in the home and environment to
infer robust and meaningful estimates of clinically meaningful behaviors. Health monitoring and
interventions in natural settings typically make use
of inexpensive and unobtrusive sensors. For example,
data collection techniques may be based on computer or
mobile phone interactions, motion sensors, or global positioning system (GPS) information. Sophisticated models and
analysis techniques are required to address issues of noise, bias,
and context effects and to classify behaviors in real time. The
constraints of making inferences with systems that emphasize
low cost and scalability require careful modeling and analysis
techniques to reap the benefits of obtaining information from
Two Illustrations
from Optimized
Interventions for
Improved Health
Outcomes

2154-2287/13/$31.002013IEEE
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Using Sensor Data and Model Inference to Tailor Home

Health Interventions for the Elderly
Across the world, many societies are experiencing a health-care
crisis as their aging demographic grows and overall health-care
expenditures escalate. The societal challenge to providing quality
care for the elderly needs to be addressed with changes in practice
on several fronts, including reimbursement policies, clinical
workflow, and a move toward more proactive and out-of-hospital
continuous care. Technology and model-based approaches for
home monitoring and home-based health interventions can play a
large role in this transformation.
There are several important approaches to using computational
modeling to augment the effectiveness of technology-based health
interventions in the home (see [S1] and [S2]). First, we need
computational models to make inferences about behaviors and
health states based on streaming sensor data from the home and
environment. This is a new area of research where behavioral
markers of health states based on unobtrusive sensor data provide
clinically useful metrics for the early detection of conditions and for
monitoring that is useful for providing input and evaluation of the
effectiveness of ongoing health interventions.
Second, it is important to use sensor data to monitor
adherence to action plan activities associated with health
interventions. These data inform model estimates of an individuals
readiness to change, motivations, and barriers. Finally,
computational models are necessary in taking the estimates of
health states, motivations, barriers, readiness to change, and
preferences to inform a dynamic user model of an individual. The

computational inferences from this user model can then be used
to tailor just-in-time messages for encouragement and feedback to
better enable a persons ability to change.
An example of a system that uses unobtrusive sensor data along
with computational models to infer health states and features of
behavior change to tailor messaging in health interventions is
shown in Figure S1. This diagram represents the information flow in
the Health Coaching Platform used for interventions with seniors in
the Oregon Center for Aging and Technologys (ORCATECH) Living
Lab. The participants using this system are typically around 85 years
of age with multiple chronic conditions. They live independently in
their homes and have consented to try a variety of new
technologies. Each home has motion sensors for inferring activities
of daily living, walking speed, and sleep quality; contact switches
(e.g., for the exterior door used to infer time out of the home or
apartment); and all participants have computers that they use to
play our adaptive cognitive computer games, specifically designed
to monitor metrics of working memory, executive function, divided
attention, and verbal fluency.
The monitoring of computer interactions also includes typing
speed and linguistic complexity measures from written materials. In
addition, some participants have Bluetooth-enabled medication
dispensers for intelligent medication reminding, phone monitors, and a
Kinect camera for our interactive video exercise intervention. Various
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FIGURE S1 A variety of sensors used in the ORCATECH participants homes. These include passive IR motion sensors for activity monitoring, reduced field-of-view motion sensors for measuring walking speed, computers with software for measuring
cognitive function and motor speed, door switches, phone sensors, and Bluetooth-enabled medication monitoring [S2].
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computational modeling techniques are used in first describing robust

behavior inference metrics such as walking speed, socialization
behaviors, or a description of sleep. These estimates require a careful
understanding of optimal sampling methods, a model and
representation of noise versus the inherent variability in behaviors, and
a careful model that takes indirect data from a variety of inputs to infer
an individuals behavior in real time.
The classified and quantified behavior measures can then inform
models of health states. For example, repeated measures of walking
speeds can serve as an early indicator of cognitive decline. Similarly,
typing speed, the linguistic complexity of typed text, and cognitive
measures derived from computer game interactions also inform
estimates of cognitive health. Our measures of balance, flexibility, and
strength derived from the skeletal representation from the Kinect
camera during use of the interactive physical exercise module are an
example of using computational modeling to infer an individuals
physical health state.
Figure S2 describes how the home-based unobtrusive sensor
technology is used as input to computational modeling components of
the system to derive measures of behaviors and health states, shown in
the Inference box. These estimates, along with assessments of
Initial Assessments:
3%,",,-+
3(%+
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3
**#*+
3#'++,("'!
3* *'+
Coach Discussions;
Self-Report
Semiautomated
Tailored Action Plan
Family Interface
preferences, motivations, barriers, and readiness to change, are then

used as part of a dynamic user model. The diagram shows information
flow from a message database and the dynamic user model to
automatically create tailored messages for the user. Our semiautomated
messages contain the following:
greeting: a randomly selected greeting phrase using the
participants preferred name
review of the past weeks activities: based on comparing action
plan activities with sensor data monitoring, e.g., You came
close to completing your goal of three chair exercise sessions
this week and did a great job in achieving your memory
game goals
plan for next week: e.g., progress to the next phase of the
physical exercise program, with the content automatically
tailored based on previous performance and estimated
readiness to change
complementary closure: randomly selected closure using the
health coachs name.
The knowledge representation and computational technique for
the tailored message generation is based on active methods, where
active components in the dynamic user model database trigger the
Inference:
3
".#(*+
3 "*',((%+
3%,",,+
3%)-%#,1
3(!'#,#.-',#('
3(,(*)
3(#%#2,#('.%
3"1+#% ,#.#,1
3Trend Detection
'+(*+#',"(&
3(,#('
3(&)-,*',*,#('+
(!'#,#.&+
#'!-#+,#(&)%0#,1
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&#%+!
- Typing Speed
3#,#('+
3"('+!
3(',,/#,"+
(e.g., Door)
Dynamic User Model:

3-**',(%+
3-**',(,#.,#('+
3-**',
**#*+
3-**',%,",,
3(!'#,#..%
Message Database:
3*,#'!+
3 -,#('%(',',
3$++!+
3(&&',#('+
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Automated Tailored
Messages
Patient Interface
Coach Interface
FIGURE S2 Information flow diagram for the ORCATECH Health Coaching Platform, highlighting the components using computational modeling algorithms to tailor a health intervention.
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concatenation of a sequence of message phrases from the

message database. This modeling approach serves as a
framework for tailoring health interventions.
Thus far, 33 elderly participants (average age 80.3 9.4 years)
have participated in the health coaching study and have tested
the feasibility of modules on cognitive training, sleep
management, socialization, and physical exercise. For each of
these modules, we first use an in-home visit or Skype
conferencing to assess current activity levels, health behavior
goal selection, readiness to change, motivations, and barriers
(when appropriate). For example, with our sleep intervention, we
assess sleep hygiene behaviors anxiety, and circadian rhythm
patterns before recommending changes to the environment or
relaxation exercises. A tailored action plan is created and
updated each week.
Although we make use of a human health coach for face-toface training and assessments, the computational modeling
and analysis described earlier offers a mechanism for
facilitating this health coach in keeping the intervention
personal and tailored to each individuals needs and
preferences while enabling the coach to manage a large group
of clients simultaneously. This approach of using computational
analysis for inferring behaviors and health states and
incorporating models of health behavior change provides a
method for improving the effectiveness of health interventions
through tailoring and for improving the scalability through
automated message generation.
References
[S1] H. B. Jimison and M. Pavel, Integrating computer-based health
coaching into elder home care, in Proc. 2007 Int. Conf. Technology and Aging (FICCDAT), 2008.
[S2] M. Pavel, H. B. Jimison, H. D. Wactlar, T. L. Hayes, W. Barkis, J.
Skapik, and J. Kaye, The role of technology and engineering
models in transforming healthcare, IEEE Rev. Biomed. Eng. vol. 6,
pp. 156177, 2013.
[S3] J. A. Kaye, S. A. Maxwell, N. Mattek, T. L. Hayes, H. Dodge,
M. Pavel, H. Jimison, K. Wild, L. Boise, and T. Zitzelberger,
Intelligent systems for assessing aging changes: Homebased, unobtrusive and continuous assessment of aging,
J. Gerontol.: Psychol. Sci., vol. 66B (suppl 1), pp. i180i190,
2011.
[S4] H. B. Jimison, M. Pavel, J. McKanna, and J. Pavel,Unobtrusive monitoring of computer interactions to detect cognitive status in elders, IEEE Trans. Inform. Technol. Biomed., vol. 8, no. 3, pp. 248252,
Sept. 2004.
[S5] H. B. Jimison, M. Pavel, P. Bissell, and J. McKanna, A framework
for cognitive monitoring using computer game interactions, in
Medinfo 2007: Proceedings of the 12th World Congress on Health
(Medical) Informatics; Building Sustainable Health Systems, K. A.
Kuhn, J. R. Warren, and T. Y. Leong, Eds. Amsterdam, The Netherlands: IOS Press, 2007.
[S6] H. B. Jimison, J. McKanna, K. Ambert, S. Hagler, W. J. Hatt, and
M. Pavel, Models of cognitive performance based on home
monitoring data, in Proc. IEEE Engineering in Medicine and Biology Conf., Buenos Aires, Argentina, Sept. 2010.
Dynamical Systems Modeling of a Gestational

Weight Gain Intervention
Dynamical systems modeling has the potential to improve
behavioral theories and, by extension, improve health
interventions. However, there is still much debate among
behavioral scientists regarding the best theoretical models of
behaviors, and the best methods for studying and developing
behavioral theories. One illustration of how dynamical systems,
concepts, and behavioral theories can inform the modeling of
behavior change is a model of an intervention to prevent
excessive weight gain during pregnancy. This is part of the
activities of a recently funded National Institutes of Health
grant between Penn State and Arizona State (Grant
R01HL119245: Control systems engineering for optimizing a
prenatal weight intervention, Downs, PI; Rivera, consortium PI).
High prepregnancy body mass index (BMI) and excessive
gestational weight gain (GWG) are serious health concerns.
Research shows that excessive weight gain during pregnancy is
often associated with many adverse maternal and neonatal
outcomes, including gestational diabetes, pregnancy-related
hypertension, complications through labor and delivery, infant
macrosomia, and childhood obesity. Pregnancy thus represents
an opportune moment in a womans life to promote healthy
lifestyle behaviors and learn effective techniques for proper
weight management.
A dynamical model for a gestational weight intervention is
developed through the integration of a mechanistic energy
balance model for gestational weight gain and a fluid analogy of
the theory of planned behavior (TPB), augmented with selfregulation. TPB is a broad-based psychological theory that can be
understood conceptually through the path diagram shown in
Figure S3(a) [S7].
While there are many different and competing theoretical
models about behavior and behavioral change, a path diagram such
as the one describing the TPB provides a solid starting framework for
expressing behavioral change as a dynamical system represented
via a fluid analogy. In TPB, behavior (h 5) is determined by intention
(h 4) and perceived behavioral control (PBC; h 3) . Intention,
meanwhile, is influenced by attitude toward the behavior (h 1),
subjective norm (h 2), and PBC (h 3) . Navarro et al. [S8] show that
the path diagram associated with TPB represents a steady-state
association between these variables. Each block in the TPB path
diagram can be viewed as an inventory, as depicted in Figure S3(b),
with inflows corresponding to exogenous variables reflecting the
strength of beliefs (e.g., p 1, p 2, and p 3) or (for intention and
behavior) the outflows from other inventories in the network. The
levels of the various inventories accumulate or deplete over time
based on the magnitude and changes occurring in the exogenous
variables as well as the corresponding changes in the outflows of
the other interconnected tanks.
To generate the dynamical system equations, the concept of
conservation of mass is applied to each inventory, from which a
system of differential equations is obtained. An illustration for the
equation describing intention (h 4) is
x4
dh 4
= b 41 h 1 (t - i 4) + b 42 h 2 (t - i 5)
dt
+ b 43 h 3 (t - i 6) - h 4 (t) + g 4 (t) .
(S1)
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Behavioral
Belief
Evaluation
of Outcome
(1 = b1 e1)
Normative
Belief
Motivation
to Comply
(2 = n1 m1)
11
Attitude
Toward the
Behavior
(1)
41
2
22
Subjective
Norm
(2)
42
54
Intention
(4)
Behavior
(5)
43
53
Control
Belief
Power of
Control Belief
(3 = c1 p1)
33
Perceived
Behavioral
Control
(3)
3
(a)
222(t 2)
2(t )
2(t )
100%
1(t )
111(t 1)
1(t )
100%
Subjective
Norm
(2)
0%
0%
(1 42)2
PBC
(3)
4(t )
433(t 6)
411(t 4)
(1 41)1
3(t )
100%
422(t 5)
Attitude
(1)
333(t 3)
3(t )
0%
100%
(1 43 53)3
Intention
(4)
0%
(1 54)4
533(t 8)
544(t 7)
5(t )
100%
0%
Behavior
(5)
5(t )
(b)
FIGURE S3 (a) A path diagram representing the TPB and (b) a corresponding fluid analogy.
In (S1), the parameters b i j and c i j represent gains of the

system, while variables xi and ii are time constants and delays,
respectively, which dictate the speed of response of the system. gi
corresponds to disturbances.
Self-regulation, as depicted in Figure S4, is an important
aspect of behavior change that forms part of this model. The selfregulation theory in psychology has been largely influenced by
the work of Carver and Scheier [S9] who proposed that human
behavior is goal directed and regulated by feedback control

processes. Self-regulation reflects the capacity of individuals to
alter their behavior, enabling individuals to adjust their actions to
a broad range of social and situational demands. Repeated
measurement of behavioral outcomes provides a major stimulus
to self-regulation.
The collective integration of self-regulation, the TPB, and energy
balance in the form of a fluid analogy is depicted in Figure S5 for the
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energy intake portion of the gestational weight gain intervention.

The energy balance model can predict changes in fat mass and fatfree mass as functions of energy intake and characteristics of the
mother. Daily weight measurement and dietary records of energy
intake generate the signals that drive two self-regulation loops that
influence perceived behavioral control along with other
components of the behavioral intervention. Intervention
components I 1 through I n represent structured intervention
programs such as healthy eating education, active learning, and
goal setting, which, through the TPB model, ultimately influence
healthy eating behavior and, consequently, meeting gestational
weight gain targets.
The usefulness of a dynamic model for a behavioral
intervention comes in many forms, from simulation, evaluation of
decision policies, and, most importantly, the opportunity to
optimize an intervention through an adaptive, just-in-time
approach. Adaptive just-in-time interventions represent feedback
or combined feedbackfeedforward control systems that make
decisions on the magnitude and sequencing of intervention
components by relying on assessments of tailoring variables that
Dosages of
Intervention Components
I1(t ) In (t )
d (Outside Influences)
r (Goal) +
Behavior
Self-Regulator
u
+
Effect on
Environment
Perception of the
Effects of Behavior
FIGURE S4 Behavior and perception as elements of a feedback

loop guiding human action per the self-regulation theory of
Carver and Scheier [S9].
reflect outcomes, adherence to treatment, or other important
measures of participant response during the course of an
intervention. Decision policies for this class of interventions can
range from simple IF-THEN decision rules [S10] to model-based
Optimized
Intervention
Algorithm
Intervention Delivery Dynamics
I1(t )
In (t )
GWG
Self-Regulator
in
in
in
1 (t )
1(t )
out
1 (t )
1(t ) out(t )
2
2 (t )
1(t )
ATT
(1)
w
3 (t )
Diet
Self-Regulator
EI
3 (t )
3(t )
2(t )
2(t ) out(t )
3
SN
(2)
Energy Intake
Goal r EI (t )
Dietary
Record
3(t )
4(t )
PBC
(3)
Gestational
Weight Gain
Measurement
In +2(t )
In +1(t )
Intention
(
4)
I20
Energy Intake
Theory of Planned Behavior
GWG Goal r W(t )
3(t )
2(t ) 3(t )
2(t )
1(t )
3 (t )
5(t )
Behavior
5(t )
5(t )
EI (t )
+
+
d EI (t )
Energy
Balance
Fat-Free
Mass
PAL(t )
GWG
Consumed
by PA
Fat
Mass
GWG
FIGURE S5 A fluid analogy for the energy intake portion of a comprehensive dynamical systems model for an optimized gestational weight gain intervention.
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control-theoretic formulations that fully incorporate the dynamical

behavior model, such as model predictive control (MPC) [S11].
Since adaptive interventions mirror clinical decision-making, these
individualized, tailored forms of treatment delivery can serve as
helpful aids to clinicians by improving effectiveness over a larger
participant population, lowering costs, and overall resulting in
much greater intervention potency.
Our work to date [S12], [S13] has shown proof of concept for the
use of dynamical modeling in a gestational weight gain intervention
and the benefits that enhancing behavioral theory with a systems
perspective can have in providing useful predictive models of
behavior. Behavioral theories and energy balance provide an initial
structure for the dynamical model; however, data-driven tasks
involving experimental design, parameter estimation, and model
validation need to be accomplished to reach at a final model. These
are problems that fall within the realm of semiphysical system
identification [S14]. The increasing availability of intensive
longitudinal data from repeated measurement and assessment of
behavioral variables enhances the feasibility of obtaining these
kinds of dynamical system behavioral change models.
References
[S7] I. Ajzen, Attitude, Personality, and Behavior. Milton Keynes, U.K.:
Open University Press, 1998.
[S8] J. E. Navarro-Barrientos, D. E. Rivera, and L. M. Collins, A dynamical
model for describing behavioral interventions for weight loss and
many forms of ubiquitous but noisy or indirect data for inferring

health behaviors.
Here, we illustrate how systems and computational modeling approaches can impact behavior change and optimize
interventions for health involving behavioral outcomes with
two examples. The first, in Using Sensor Data and Model
Inference to Tailor Home Health Interventions for the Elderly,
is an example of integrating health behavior change variables
with computational inference about behaviors and health
states for tailoring interventions. The second, Dynamical Systems Modeling of a Gestational Weight Gain Intervention,
demonstrates how behavioral theories from psychology come
into play in developing a comprehensive dynamical model for
an intervention to manage gestational weight gain.
body composition change, Math. Comput. Model. Dynam. Syst.,

vol. 17, no. 2, pp. 183203, 2011.
[S9] C. S. Carver and M. F. Scheier, On the Self-Regulation of Behavior.
Cambridge, U.K.: Cambridge Univ. Press, 1998.
[S10] D. E. Rivera, M. D. Pew, and L. M. Collins, Using engineering control principles to inform the design of adaptive interventions:
A conceptual introduction, Drug Alcohol Depend., vol. 88, no. 2,
pp. S31S40, 2007.
[S11] N. N. Nandola and D. E. Rivera, An improved formulation of hybrid
model predictive control with application to production-inventory
systems, IEEE Trans. Control Syst. Technol., vol. 21, no. 1, pp. 121135,
2013.
[S12] Y. Dong, D. E. Rivera, D. M. Thomas, J. E Navarro-Barrientos, D. S.
Downs, J. S. Savage, and L. M. Collins, A dynamical systems model
for improving gestational weight gain behavioral interventions,
in Proc. 2012 American Control Conf., Montreal, Canada, 2012, pp.
40594064.
[S13] Y. Dong, D. E. Rivera, D. S. Downs, J. S. Savage, D. M. Thomas, and L.
M. Collins, Hybrid model predictive control for optimizing gestational weight gain behavioral interventions, in Proc. 2013 American
Control Conf., Washington DC, 2013, pp. 19731978.
[S14] D. E. Rivera, Optimized behavioral interventions: What does system identification and control engineering have to offer?, in Proc.
16th IFAC Symp. System Identification (SYSID 2012), Brussels, Belgium,
July 1113, 2012, pp. 882893.
Daniel E. Rivera (daniel.rivera@asu.edu)

______________ is with the School for
Engineering of Matter, Transport, and Energy, Ira A. Fulton Schools
of Engineering, Arizona State University, Tempe. Holly B. Jimison
____________ is with the College of Computer and Informa(h.jimison@neu.edu)
tion Science and the School of Nursing, Bouv College of Health Sciences, Northeastern University, Boston, Massachusetts.
References
[1] P. L. Mabry, S. E. Marcus, P. I. Clark, S. J. Leischow, and D. Mendez,
Systems science: A revolution in public health policy research, Amer.
J. Pub. Health, vol. 100, no. 7, pp. 11611163, July 2010.
[2] K. Hassmiller Lich, E. M. Ginexi, N. D. Osgood, and P. L. Mabry,
A call to address complexity in prevention science research,
Prev. Sci., vol. 14, no. 3, pp. 279289, June 2013.
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STATE OF THE ART
Is It Really Personalized Medicine?

Arthur T. Johnson
coming in and (we hope) cured patients

going out.
Truly personalized medicine will
come about when primary care physicians become the central core of medical
care. Especially if a long-term relationship
has been developed between the physician and the patient, the primary care
IMAGE LICENSED BY INGRAM PUBLISHING
and the phenotype of a

hey call it personalized medicine
person. Each living organthe genetic testing of the patient to
ism is a product not only
determine the predicted efficacies
of its genetics but also its
of an array of pharmaceuticals. Some of
physical, chemical, and
these medicines may be more effective,
biological environments.
and some may be metabolized differently.
The present outcome for
The choice of medicine to administer for
all living things is a chaotic
all diseases, from cancer to depression, is
(in the mathematical sense)
improved if we are aware in advance of
result of the entire sum of
the presence of indicative genetic markers.
all of our past experiences
Knowing that each persons health his(recently called the expotory depends only partially on the genetic
some) and, given what we
blueprint carried by that person, I wonder
know about epigenetics,
where all this is going. Certainly, improvesome past experiences of
ments in medical treatments can be made
those who predate us.
possible as more information about the
Personalized medicine
patient becomes known. But the presence
certainly is a great catchof certain genes tells only a part of the
phrase that captures a lot
story. Whether those genes are expressed
of attention. However, it
or not is important and so are the many
seems that patients are only
environmental factors that make life so
being distributed among
unpredictable. If Uncle John stepped into
smaller queues. Instead of
a vat of acetone, I think he would probably
blindly prescribing a few
be treated to counteract
standard drugs to everyits toxic effects no matter
The choice of medicine
one and monitoring the
what his genome said.
results to see if they have
In the 1970s and
to administer for all
the desired effect, prior
1980s, there was a group
diseases, from cancer
genetic testing can now be
of researchers who placed
to depression, is
used to make this less of a
a lot of faith in the physimproved if we are
trial-and-error medical
iome project. The hope
aware in advance
adventure. This in itself is
of this work was that
of the presence of
good. However, is it really
knowing the full genetic
personalized medicine?
complement of a person
indicative genetic
I think not.
would completely determarkers.
My experience in hosmine her or his characpitals, both as a biomedical
teristics. However, there
engineer working there
is a differencesomeand as a husband of a trauma patient, is
times very largebetween the genotype
that there is little personalized anything
in a hospital setting. A hospital is largely
a get-em-well factory with sick patients
physician knows much more about the

patient, including lifestyle, occupation,
health history, and medical preferences,
than is likely to be known by doctors and
nurses in the get-em-well factory. This
intimate knowledge needs to be incorporated into the factory routine.
More detail about a patients genome
is useful but does not, by itself, lead to
personalized treatment. Only recognition of the patient as a human being
worthy of respect will do this. I have suggested that this respect can come from
enhanced involvement by primary care
physicians, and this may be a heavy burden for them to bear. What personalized
medicine really needs are more primary
care physicians and fewer specialists.
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Call For Papers

Discovering, Innovating and Engineering Future Biomedicine
The 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC14) will
take place 27-31 August 2014, at the Sheraton Chicago Hotel & Towers.
The conference will cover diverse topics such as biomedical engineering, healthcare technologies, and medical and
clinical applications. The conference program will consist of invited plenary lectures, symposia, workshops, invited
sessions and oral and poster sessions of unsolicited contributions. All papers will be peer reviewed; accepted papers of
up to four pages will appear in the Conference Proceedings and be indexed by IEEE Xplore and Medline/PubMed.
All are welcome to participate in this exciting conference as an author, attendee and/or exhibitor; Proposals for
organizing special sessions on emerging topics in the following themes are also encourage:
*
*
*
*
*
*
*
*
*
*
*
Biomedical Signal Processing

Biomedical Imaging and Image Processing
Bioinstrumentation, Biosensors, and Bio-Micro/Nano Technologies
Bioinformatics & Computational Biology, Systems Biology, and Modeling Methodologies
Cardiovascular and Respiratory Systems Engineering
Neural and Rehabilitation Engineering
Tissue Engineering and Biomaterials
Biomechanics and Biorobotics
Therapeutic Systems, Devices & Technologies, and Clinical Engineering
Healthcare Information Systems and Telemedicine
Biomedical Engineering Education
Key Dates:
Proposal Submission: 14 October 2013 14 January 2014
4 Page Paper Submission: 3 February 2014 - 17 March 2014
1 Page Paper Submission Deadline: 31 March 2014 26 May 2014
For more information, please visit the EMBC14 website: http://embs.embs.org/2014

Conference Chair: Zhi-Pei Liang, University of Illinois at Urbana-Champaign
Conference Co-Chair: Xiaochuan Pan, University of Chicago
Program Chairs: Jeff Duerk, Case Western Reserve University & Jim Ji, Texas A&M University
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RETROSPECTROSCOPE
Cardiac Output:
Since When, Who, and How?
By Max E. Valentinuzzi and Ron S. Leder
No doubt at all, arterial blood pressure is absolutely necessary, but if there is no flow or if it is
hindered, the whole system faces deep trouble.
Thus, you had better have a good pumping
action. Ocassionally, people forget this truth.
Max E. Valentunuzzi
ncient Rome had a rather complex

hydraulic network formed by aqueducts for its water supply and for
waste. The system provided a constant
stream to central areas, in contrast to
modern systems, which deliver water on
demand to individual connections. It certainly was a marvel of engineering accomplishment. The date of the first aqueduct
is estimated to be 312 BC, and it had nine
channels. Whenever possible, these aqueducts followed a steady downhill course.
The amount of delivered water has been
estimated to have been within the ample
range of 322,0001,010,623 m3/day, or
about 67 L/day per capita. In comparison,
todays residents of the United States use
approximately 250 L per person per day,
that is, roughly four times more [1].
It is philosophically interesting to
pose one question: did the Romans have
the concepts of pressure and flow? Obviously, in practical terms they did, but as
we understand them today, it is doubtful.
Not everybody knows that Palenque,
in the Mayan region of southern Mexico,
also has one of the best-preserved systems of aqueducts, a unique architectural
example. Most of the visible monuments
in the plaza date to the period in which
the great king Pakal ruled (ca. 700 AD),
about 1,000 years after the Romans.

The aqueduct is still visible and contains water from the Otulum River [2].
Around 1400 AD, that is, about 400 centuries later, the Incan Empire in Per,
South America, constructed another
hydraulic system fed with water that
came mostly from nearby rivers and
from fresh-water springs on the mountains. Machu Picchu, the most famous of
Incan archeological sites, contains a complex aqueduct system. The Incas demonstrated in these works a high degree of
engineering skill in the careful gradation
of the ducts [3].
The same question and comment
come up: did the Mayas and the Incas
have the concepts of pressure and flow?
Obviously, while perhaps some communication between these two cultures could
have occurred, no connection at all with
the Romans appears as even thinkable.
did not refer to volume displacement per

unit time, although he reported some
volume values (as ventricular volume or
total blood volume in horses) and carried out the first experiment on hemorrhaging [7]. Almost another century had
passed when, in 1828, Jean Louis Marie
Poiseuille (17991869) reported in his
doctoral dissertation a series of blood
pressure values in a few mammals, better expressed this time in millimeters of
mercury. He came just a step away from
the concept of flow by giving a value of
390 ft/min for blood velocity at the aortic root based on data from an author
named Keill (no information could be
found about him; the reference in Poiseuilles dissertation is incomplete) [8].
This figure is equivalent to 168 cm/s;
the actual average value is in the range
of 4050 cm/s, i.e., roughly one-third of
the former or, better, at 45 cm/s, a 1.8-cm
diameter aorta would pass (45 3.14
0.81 60)/1,000 = 6.87 L/min, which is
a rather typical output flow for a normal
young male adult at rest. Why didnt
Poiseuille take into account the aortas
cross section in his calculations to obtain
Blood Flow in Modern Times

Galen (129ca. 216 AD), the famous
Greek physician, failed to recognize the
hearts role as a pump. Did he understand what hydraulic pressure or blood
pressure were in physical terms? It took
15 centuries for Western science to discover the blood circulation [4]. Why
did it take such a long time? This is a
good question that some historians have
tried to answer [5]. William Harvey
(15781657) proved the circular motion
of blood in the body in 1628, but he did
not describe it in terms of pressure and
flow [6]. Is that possible? Stephan Hales
(16771761), slightly over 100 years
later, in 1733, actually measured arterial pressure in inches of blood, but he
FIGURE 1 Fick, shown here in 1897,

developed a method to measure mean
cardiac output in the 19th century.
(Image courtesy of www.wikipedia.org.)
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Members share fascinating rst-person stories

of technological innovations. Come read and
contribute your story.
IEEE Global History Network

www.ieeeghn.org
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in the horse, reporting the results in a very

long agricultural yearbook (Figure 4) [18].
The Direct Fick Method
FIGURE 2 Ficks communication to the Wrburgs society described his new method
(see [9].)
flow? It is difficult to understand, at least

looking back now, from the 21st century.
Forty-two more years elapsed until
Adolph Fick (Figure 1) described a method
in 1870 to measure mean cardiac output.
The method was described in a very short
communication to the Society of Physics
and Medicine in the city of Wrzburg,
Germany [9], [10]. An English translation was published many years ago by
Hoff and Scott [11]. The method was also
discussed in an article by Edward Shapiro
[12]. Fick was the first to clearly introduce the concept of flow coming out of
the cardiac pump (Figure 2). However, he
never actually put it into practice because
he lacked the means to do so. Human
cardiac catheterization (to sample blood

gas) was still many years away, even
though Claude Bernard, on one hand
and Jean Baptiste Auguste Chauveau and
Etinne Jules Marey, on the other hand,
(all three in France) performed it for
many years almost routinely in animals;
Bernard started as early as 1844 [13], [16].
Ficks idea was first tested in dogs by
Nestor Grhant and Charles Eugene
Quinquaud in 1886. They reported values
of 5912,614 mL/min for body weights
ranging from 7 to 18 kg (Figure 3) [17].
This short communication clearly explains
the procedure using CO2 as physiological marker. Twelve years later, in 1898,
Nathan Zuntz and Oskar Hagemann did it
Let us read what Fick said, reproduced from

the translation given in [12], although the
version given by Hoff and Scott in 1948
[11] is more literal. Those readers with
some knowledge of German may compare
the following paragraph against the original text shown in Figure 2:
It is astonishing that no one has
arrived at the following obvious
method by which [the amount of
blood ejected by the ventricle of
the heart with each systole] may
be determined directly, at least
in animals. One measures how
much oxygen an animal absorbs
from the air in a given time, and
how much carbon dioxide it gives
off. During the experiment one
obtains a sample of arterial and
venous blood; in both the oxygen
and carbon dioxide content are
measured. The difference in oxygen content tells how much oxygen each cubic centimeter of blood
takes up in its passage through
the lungs. As one knows the total
quantity of oxygen absorbed in a
given time one can calculate how
many cubic centimeters of blood
passed through the lungs in this
time. Or if one divides by the number of heart beats during this time
one can calculate how many cubic
centimeters of blood are ejected
with each beat of the heart. The
corresponding calculation with the
quantities of carbon dioxide gives
a determination of the same value,
which controls the first.
For a long time, Ficks method was a
reference (actually, the reference), and it
is called the direct Fick method. The total
flow or cardiac output, CO = Ft , exits
the left ventricle at high pressure, enters
the right heart via the vena cava at very
low pressure, is also expelled by the right
ventricle at moderately low pressure, and
finally, after circulating the body, returns
to the right atrium at very low pressure
again. If the lungs are considered a node
(Figure 5), the continuity principle applied
to blood (as the carrier, in mL blood/min)
and oxygen (as the transported substance,
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5IJTQVCMJDBUJPOPFSTPQFOBDDFTTPQUJPOTGPSBVUIPST
*&&&0QFO"DDFTT1VCMJTIJOH
What does IEEE Open Access mean to an author?
t5PQRVBMJUZQVCMJTIJOHXJUIFTUBCMJTIFEJNQBDUGBDUPST
t*ODSFBTFEFYQPTVSFBOESFDPHOJUJPOBTBUIPVHIUMFBEFS
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Learn more about IEEE Open Access Publishing:
www.ieee.org/open-access
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another, they were active contributors to

the essential concepts of blood flow and
cardiac output. The Internet has several
sites where more details can be found.
Adolph Fick
FIGURE 3 The title and first paragraph of the communication presented by Grhant
and Quinquaud in 1886 to the Societ de Biologie. It says: The procedure we have
followed consists of taking with a sound (a probe, a catheter) simultaneously from
the right heart and from the carotid artery of a dog two equal volumes of blood that
are injected in a container emptied of air by a mercury pump. Extraction of gas was
made at a temperature of 60; we have dosed exactly the carbon dioxide acid there
contained. As has always been frequently demonstrated, the volume of carbonic acid
given by the venous blood was larger than that contained in arterial blood.
in mL O2/mL blood) establishes in the

steady state condition that
Ft [V] + Fox = Ft [A] [mL O 2 / min],
(1)
where [V] and [A] stand for the concentration of oxygen in venous and in arterial
blood, respectively, while Fox represents
the net oxygen uptake in [mL O 2 / min]
via the respiratory system. Solving for Ft
results in
Ft = Fox / {[A] - [V]} [mL blood/ min],
(2)
which is the famous and well-known
Ficks formula. Instead of oxygen, carbon dioxide can be used, as Grhant and
Quinquaud used in 1886. Those familiar
with electric circuits will find this similar to the total current converging to
and diverging from a node (Kirchhoffs
current law) [19]. After all, recall that
current is nothing but the amount of
electric charge per unit of time (1 amp =
1 coulomb/s), and in (1), we have the
amount of oxygen also per unit of time.
The numerator in (2) is usually obtained
from a metabolimeter (a relatively easy
measurement; Grhant and Quinquaud
probably used a water-sealed spirometer
in 1886 to collect exhaled CO2). A normal adult at rest may take up about 250
mL O2/min. A sample of blood from any
artery (the method, thus, requires arterial
puncture) and, subsequent determination
in the biochemistry lab, gives the arterial

concentration of oxygen. The venous concentration of oxygen is not easy. Samples
from a peripheral vein are not acceptable
because the oxygen consumption varies
greatly from tissue to tissue. A representative sample has to be a mixture coming
from all tissues. Only the right atrium,
or better, the right ventricle, or the best,
the pulmonary artery carry venous blood
meeting such a requirement. Hence, a
probing catheter must be introduced to
any of these vascular places to withdraw a
few milliliters of blood to be tested in the
lab for oxygen content (or carbon dioxide,
should this gas be employed as marker).
Typical expected normal values are
20 mL O2/100 mL blood, for the oxygenated blood, and about 15 mL O2/100 mL
blood, for the mixture of venous blood.
Thus, the arteriovenous difference is
about five. These units are many times
referred to by physiologists as so many
milliliters of substance percent. When
the above figures are replaced in (2), the
result is a mean, steady-state value of
5 L/min. The latter is the typical normal
figure for a resting adult male. However,
the heart was untouchable, and it took
60 yearsfrom 1870 to 1930to actually run the measurement in humans.
Pioneers in Physiology
Let us say something about these peoples
lives, all of whom were important figures in physiology, even though some,
perhaps, are less known; one way or
Adolph Fick (18291901) was born in Cassel, Germany. Very early on, he showed a
remarkable talent for mathematics and
physics, and when he enrolled at the
University of Marburg, he manifestly
wanted to acquire credentials in these
disciplines. However, influenced by
his brother Heinrich (a lawyer), young
Adolph matriculated in medicine. Fick
turned his attention to physiology, taking a prosectorship with Carl Ludwig
in Zurich in 1852, when he was 23,
remaining with him for 16 years [20].
Thereafter, Adolph moved to Wrzburg
as professor of physiology. Throughout
his time in Zurich, Fick made several
remarkable contributions, also showing
interest in philosophy and literature. For
example, his is the concept that diffusion
is proportional to concentration gradient.
Throughout his more than three decades
in Wrzburg, Fick produced a steady
stream of papers [21], [22].
Claude Bernard
Claude Bernard (18131878) received his
early education in the Jesuit school of
his native town, Saint Julien, in France,
continuing later in Lyon and becoming an assistant in a druggists shop. He
attempted without success to be a comedy
and drama author. At the age of 21, in
1834, he went to Paris and decided to go
medical school, coming in contact with
the great physiologist Franois Magendie,
whom he succeeded in 1855. Bernards
marriage to Marie Franoise Fanny
Martin, arranged by a colleague for convenience, was unhappy and brought him
many problems. However, physiology and
medicine were enriched and significantly
advanced by his outstanding contributions. In 1868, Bernard was incorporated
into the Academie Franaise and to the
Royal Swedish Academy of Sciences.
Louis Napoleon helped him by building a laboratory at the Musum National
dHistoire Naturelle in 1864. Upon his
death, the nation honored him with a
public funeral. His tomb is in Paris, at the
famous Pre Lachaise Cemetery (Figure 6),
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Are you keeping up

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where many distinguished people rest in

peace, for example, the musician Frdric
Chopin. Bernard liked philosophy, and
many memorable thoughts can be found
in his musings, for example, Le chercheur
devrait prendre des prcautions extrmes
pour ne pas trouver ce que lon cherche (the
researcher should take extreme precaution not to find what he or she is looking
for)good advice indeed. For years, he
wrote his ideas and thoughts in a notebookle cahier rouge, or the red notebook,
because the cover was red [23].
Jean Baptiste Auguste Chauveau

Jean Baptiste Auguste Chauveau
(18271917) was born in Villeneuvela-Guyard, France. He was educated
at cole Nationale Vtrinaire dAlfort
and then cole Nationale Vtrinaire
de Lyon, where, at the age of 21, he
became part of the staff and became
the schools director in 1875. Later, in
1886, he was appointed to the position
of professor at the Musum National
dHistoire Naturelle in Paris. With
tienne-Jules Marey (18301904), he
studied different phases of the cardiac cycle and intracardiac pressures
and played a significant role in cardiac
catheterization. He was a master experimenter. As with Claude Bernard, the
ire of many antivivisectionists became
a deeply disturbing headache for him
due to his experiments on animals [24].
Etinne-Jules Marey
Etinne-Jules Marey was a native of
Beaune, France, and died in Paris. In
1849, he enrolled at the Parisian Medical School, qualifying as a medical doctor in 1859. A few years later, in 1864,
he set up in a small laboratory to study
the circulation of the blood, publishing Le Mouvement dans les Fonctions de la
Vie in 1868. From 1863 on, Marey perfected his methode graphique. By means
of polygraphs and similar recording
instruments, he analyzed the human
and equine gait and the flight of birds
and insects. His works were significant
in the development of cardiology, physiology, physical instrumentation at large,
photography, and cinema. For example,
he developed the sphygmograph to
measure arterial pulse. In 1890, Marey
produced the book Le Vol des Oiseaux
FIGURE 4 The Zuntz and Hageman publication, Investigations on the Exchange of Substances in the Horse Under Resting and Working Conditions, has contributions from Curt
Lehmann and Johannes Frentzel. It was published in Berlin by the editorial house Paul
Parey in 1898.
(The Flight of Birds). The Internet abounds

with sites full of details about his highly
productive scientific life.
Louis Franois Nestor Grhant

Louis Franois Nestor Grhant (1838
1910) is less known. The information
given here was taken from a publication
with no clear-cut identification, but it
was quite complete and written by MarieThrse Cousin [25]. Grhant was born in
Laon, France, where he started secondary studies, which he finished later in
Paris at the Napoleon Lyceum (now Louis
le Grand). Thereafter, Grhant studied
physics, ending up in medical school with

a doctoral thesis combining both fields
(1864). However, he never went into clinical practice. He assisted Claude Bernard
from 1865 to 1868, collecting invaluable laboratory experience. In addition,
he completed a second dissertation in
natural sciences in 1870. In 1893, he was
appointed professor of physiology, having
produced several outstanding papers in
several subjects.
Charles Eugene Quinquaud

Charles Eugene Quinquaud (18411894)
was a physician born in Lafat, Creuse, a
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IEEE Biomedical Engineering Award

RECOGNIZING THE EXTRAORDINARY
Nomination Deadline:
For outstanding contributions to the

field of biomedical engineering.
31 January (Annually)
The IEEE Biomedical Engineering Award was established

Selection criteria
include:
(a) Impact on the
profession and/or
society
(b) Succession of
significant technical or
other contributions
(c) Leadership in
accomplishing
worthwhile goal(s)
(d) Achievements as
evidenced by
publications or patents or
other evidence
in November 2010. The first presentation is scheduled

for 2013.
PRESENTED TO - An individual, a team, or multiple

recipients up to three in number
PRIZE - Recipient will receive a bronze medal,
certificate, and US$10,000 honorarium.
SPONSORS IEEE Engineering in Medicine and Biology
Society, IEEE Circuits and Systems Society, and IEEE
Computational Intelligence Society
Nomination guidelines and forms can be downloaded

from the IEEE Awards Web site at:
http://www.ieee.org/about/awards/tfas/biomed_eng.html
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commune in the Creuse department in the Limousin region in

central France. He entered medical school in Limoges in 1864 and,
in 1868, moved to Paris, where he
obtained his doctorate in 1873. He
was elected member of the Acadmie de Mdecine in 1892. Quinquaud contributed in many areas
of medicinebeing a skilled bacteriologist as well as a clinician
and alongside Nestor Grhant
(18381910), they became very
active in the scientific community.
In 1880, 1885, and 1887, Quinquaud won academic prizes for his
works. He was editor of the journal
La Mdecine Scientifique [26].
Continuity Equation:
The load that goes in
(the two entering arrows)
is equal to the load that
comes out (exiting arrow).
Blood Flow from

Lungs to Left Heart
Carrying a High
Level of Oxygen
Oxygen
Input
in mL/min
Lungs
Blood Flow from Right

Heart, mL/min,
Carrying Oxygen,
mL Oxygen/mL Blood
to Pflger in Bonn. He came to

my lab one day and finding me
at work precisely in that subject
he said, Well, but you have not
asked my permission to do this.
Either you stop these experiments or leave my laboratory.
Since I was not in a position to
leave the laboratory, I stopped
the project.
Oskar Hagemann
Oskar Hagemann (18621926) was

a well-reputed and active veterinarian (Figure 7) [30] who obtained
his degrees (medical veterinary and
FIGURE 5 In the Fick principle or continuity equation, the
doctorate) in Berlin (Hochschule and
lungs are considered a node. The amount of material
University, respectively). He was a
(oxygen, in this case) that goes into the node in the
steady state equals the amount that comes out, always
veterinarian for the German Army
per unit of time. See (2) and the text for unit details.
and was involved in World War I as
Nathan Zuntz
a veterinarian, even occupying leadNathan Zuntz (18471920) was
research problems (a good bioengineering responsibilities. (Recall that horses were
born in Bonn, Germany. His father was
ing philosophy). Younger investigators
important components of armies in those
a merchant and a scholar of Hebrew hiswere attracted to this laboratory not only
days.) Hagemann reached the high pository. Nathan, the eldest of 11 children,
from Germany but from other countries.
tions of rector to the Landwirtschaftlichen
was recognized early as possessing a sciThey found Zuntz to be a man of keen
Hochschule Bonn-Poppelsdorf (Agriculentific inclination. Yet, his first job was
understanding and wisdom and a helptural High School) and director of the Instias an apprentice in a Bonn bank. An
ful and kind person. Zuntzs talent in
tut fr Anatomie, Physiologie, und Hygiene
apt scholar, he was able to read the Bible
devising methods and constructing appader Haussugetier (Institute of Anatomy,
in Hebrew at an early age. After finishratuses was superb, with an extraordiPhysiology, and Hygiene of Domestic Maming the gymnasium (an advanced high
nary knowledge of the literature of the
mals). For a considerable time, he was a
school in Germany) at 17, Nathan entered
times. In 1908, he spent the summer at
close collaborator of Zuntz, with whom he
medical school at the University of Bonn,
the School of Agriculture of Cornell Unipublished several papers.
where he studied chemistry under Friedversity in Ithaca, New York. His major
rich August Kekul (18291896), physics
investigations were on the subjects of
under Rudolf Julius Emanuel Clausius
blood and blood gases, blood circulation,
(18221888), and physiology under Edumechanics and chemistry of respiration,
ard Friedrich Wilhelm Pflger (1829
general metabolism, and nutrition. Over
1910), all three magnificent researchers
29 years, he measured his own basal
and highly respected professors. Pflger
metabolism. The two most complete
supervised Zuntzs doctoral thesis,
accounts of Zuntzs career are found in
Beitrage zur Physiologie des Blutes (Con[27] and [28]. However, most of this
tributions to the Physiology of Blood), in
information was taken from [29], where
1868. In 1870, Zuntz became an assistant
we found the following striking story:
to Pflger while being appointed also as
Joseph Barcroft (18721947),
privatdozent in physiology at Bonn. In
British physiologist, gives an insight
1874, he became an extraordinary prointo the academic environment in
fessor of anatomy at the Medical Faculty
those days in Germany. Barcroft
of Bonn University, where he remained
was puzzled for the incomplete
for six more years. In 1880, Zuntz moved
studies of the effect of innervato Berlin to occupy the chair of animal
tion on muscle metabolism that
physiology at the Landwirtschaftliche
had been done by Zuntz, certainly
Hochschule, giving up his medical pracnot well fit to his personality, and
tice. Soon, Prof. Oskar Hagemann, who
FIGURE 6 Unfortunately, Claude Bernards
Barcroft asked Zuntz why, during
was already famous for his research on
tomb in Paris at Pre Lachaise Cemetery,
a meeting in Teneriffe. To which
horses, joined the group. It was Zuntzs
seen here in 1997, is not well kept and is
Zuntz replied: When I started
idea that there should be intermingling
rather hidden. (Photo courtesy of Max E.
those experiments, I was assistant
of the specialties in the attack on larger
Valentinuzzi.)
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Translating Key Health Challenges through Advances in Biomedical

and Health Informatics

HealthInformaticsisidentiedasoneofthe14GrandChallengesofThe21stCenturyby
theUSANationalAcademyofEngineering.BiomedicalandHealthInformatics(BHI)is
theinterdisciplinaryeldthatstudiesandpursuestheeectiveusesofbiomedicaldata,
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Informaticstoimprovehealthcareoutcomesandeciencieswhilstloweringcosts.

ThemaintopicsofBHI2014willbe,butnotlimitedto:

InformationTechnologiesforHealthcareDeliveryandManagement

HealthDataAcquisition,ManagementandVisualization

HealthcareKnowledgeManagementandDecisionSupport

HealthcareModelingandSimulation
x DataAnalytics,DataMiningandMachineLearning
x HealthInformationSystems
x HealthcareCommunicationNetworksandEnvironments
x InteractionswithHealthInformationTechnologies
x Bioinformatics
x ImagingInformatics

Key Dates:
Special Session Proposals: 25 September9 October 2013
4 Page Paper Submission deadline: 18 November 2013
1 Page Paper Submission: 2 December 201310 February 2014

Thisisacongressnottobemissed.Wearelookingforwardtoseeingyouin
Valencia!

BHI2014ConferenceChairs

BHI2014TechnicalProgramChairs
SergioGuillenandVicenteTraver

DimitrisFotiadisandAndrewLaine
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FIGURE 7 Oskar Hagemann in his lab in

Bonn, Germany, 1910. The appliances and
hardware seen would be compatible with
large animal experimentation. (Image courtesy of the National Library of Medicine.)
Cardiac Output in the 20th Century

It is quite amazing, but after the concept
was clearly established in 1870, the new
century began with scientists having determined the average cardiac output only in
canine and equine hearts. Still, 30 more
years had to pass before the human heart
was reached with a catheter. The many
tests and measurements made in animals
had not been enough to convince physiologists and physicians that, indeed, the procedure was harmless if properly carried out,
and the heart was considered forbidden
territory, which is difficult to understand,
at least with a 21st-century mind-set. A
detailed account of the history of right
heart catheterization is found in [31].
In 1929, Werner Theodor Otto Forssmann was the first to introduce a catheter
in his own right heart via the brachial
vein, so demonstrating the feasibility of
the procedure in the human being and
paving the way to cardiac output determinations. In 1956, he shared the Nobel
Prize with Andr Frdric Cournand
(18951988) and Dickinson Woodruff
Richards (18951973), although he was
severely reprimanded by his superior
medical chief for breaking hospital rules
at the time. The two latter researchers had
started their studies at Bellevue Hospital
in New York, resulting in the development
of a technique for catheterization of the
heart carried out in a series of tests during the 1940s (see the two Nobel lectures
by Cournand and Richards from December 1956, which are freely available on
the Web with all the scientific references,
some of which are also given herein) [32],
[33]. Richards own words say, as quoted
from his Nobel lecture:
FIGURE 8 The first paragraphs of Kleins communication clearly show a simple mathematical expression and its description, either by oxygen or carbon dioxide determinations.
The first sentence says: To determine the heart minute-volume via Ficks Principle in the
human being, it was essential to measure the gas content of mixed venous blood entering the lungs (see [36]).
We were aware of the earlier

experiment of Forssmann and
had followed closely its isolated
uses in Germany, Portugal, South
America, and France. It suffices
for me to say that late in 1940,
Cournand and Ranges took up the
catheterization technique, showing in their initial studies that consistent values for blood gases could
be obtained from the right atrium,
that with this, cardiac output could
be reliably and fairly accurately
determined by the Fick principle,
and furthermore that the catheter
could be left in place for considerable periods without harm.
However, in 1930, Otto Klein
(18811968) measured cardiac output
in humans by the direct Fick method,
obtaining venous samples with a cardiac catheter (Figure 8) [34]. In 1938,
because of his Jewish origin, Dr. Klein

had to resign his academic post, and soon
after in 1939, he left Germany, going to
Argentina. There, Dr. Klein worked at
FIGURE 9 Otto Klein worked for many years

at the Durand Hospital, in Buenos Aires.
This photo was taken in 1980. Currently,
it is one of the citys big health centers.
(Image courtesy of www.wikipedia.com.)
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FIGURE 10 Baumanns communication

does not refer too much to Ficks idea. It
begins by saying: For the determination
of the minute-volume of the heart, there
are today a large number of methods,
however, no one meets the necessary
conditions nor offers satisfactory results.
He does not seem to be aware of the
previous contributions of Grhant and
Quinquaud and Zuntz and Hageman.
the Durand Hospital [35] in Buenos Aires

(Figure 9). He retired in 1951 because
of severe health problems. Very little is
known about his life afterward other
than he traveled to Vienna and did some
studies on the composer Brahms. Apparently, he returned to Argentina, where he
died in Buenos Aires in 1968, survived by
his wife.
H. Baumann, another German physician, for all that we could find out,
independently produced a paper on
cardiac output in 1930 [36]; it is more
or less a brief review displaying many
doubts, while offering a comparative
numerical table of results (Figure 10).

Unfortunately, no biographical details
about the author could be located. Did
the Nobel Prize Committee know about
these previous contributions? It is not
fair when recalling Otto Kleins contributions [37]. [An irrelevant coincidence: the Durand Hospital in Buenos
Aires is over 100 years old; it serves
the neighborhood where coauthor Max
E. Valentinuzzi was born and lived for
many years, the Almagro Quartier.]
Forssmann was raised under traditional, strict Prussian values: honesty,
respect for the law, and surrender of
self-interest to the common good. The
experiments by the French physiologists convinced him that inserting a catheter into the human heart was as safe for
humans as it was for animals. Cautiously,
Schneider, his boss, encouraged Forssmann to run experiments on animals
to test the safety of the procedurebut
for what reason? Forssmann strongly
believed in the experiment and without
a shred of doubt performed the catheterization on himself [38]. After all, it had
been done so many times before in mammals. With the help of a coworker, he
punctured his left cubital vein, inserted a
well-lubricated ureteral catheter into the
vein, and pushed the catheter up. A week
later, Forssmann repeated the experiment
by himself and experienced a sensation
of warmth on the wall of the vein when
he moved the catheter. With the catheter
in his heart, he walked from the operating room downstairs to the X-ray room,
where he proceeded while moving the
catheter with the help of a nurse. After his
report, a number of papers were published
over approximately three years using
catheterization for cardiac studies. There
was some opposition, and the method
was discredited by some people, which
led to another ten years passing before
TABLE 1. TYPICAL CARDIAC HEMODYNAMIC PARAMETERS

Measure
End diastolic volume (EDV)
End systolic volume (ESV)
Stroke volume (SV)
Ejection fraction (Ef )
Heart rate (HR)
Cardiac output (CO)
Typical Value
120 mL
50 mL
70 mL
58%
75
5.25
Normal Range
65240 mL
16143 mL
55100 mL
5570%
60100 beats/min
4.08.0 L/min
Cournand and his coworkers proved that

heart catheterization was not merely a
clinical curiosity but a safe and sound procedure to study cardiac physiology. Meanwhile, Forssmann catheterized himself
nine more times, hoping to get a publishable angiograph of himself, but to no avail.
As before, the response of the academic
community ranged from laughter and disbelief to admiration, as in [39], which was
authored by Forssmanns daughter, who
was also a physician. It is a touching narrative full of personal details that tell the
inside face of scientific activities.
Discussion and Conclusions

The why not? questions brought up do
not have definite answers beyond mere
conjectures. Why did it take 60 years
(18701930) to reach the human application of Ficks idea, especially when
cardiac catheterization had been practiced in animals since 1840? Insufficient
technology was obviously a factor, but a
lack of basic knowledge was undoubtedly
another. A third factor may have been the
relative slowness of communications (as
compared to what we enjoy today) plus
many mere human weaknesses, prejudices, or even sheer envy [40], [41]. We
might also add the psychological aspects
often influencing human decisions to
accept or reject a given concept.
The whole development was unfortunately stained by disbelief, lack of
information if not sheer ignorance,
prejudices, and even perhaps a competitive spirit; it was significantly delayed,
and recognition injustices took place. In
the meantime, other techniques were
introduced. The measurement of blood
flow as a local parameter has its own
history, and we do not want to overload this article with excessive words
and more references, especially because
herein the objective was to give a historical birds-eye view of the output of the
heart as a simple pump, in a somewhat
reductionistic approach.
After all, errare humanum est while
divinum ignoscere, and so the world keeps
moving. Today, one can walk into a
clinic, have a noninvasive Doppler study
or other imaging method and, in fewer
than 60 min, walk out with hemodynamic data like those displayed in Table 1,
which are relevant to evaluate heart
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performance. We should be glad to live

during these times.
Max E. Valentinuzzi (maxvalentinuzzi@
___________
ieee.org) is with the Universidad Buenos
Aires, Instituto Ingeniera Biomdica. Ron S.
Leder (rleder@ieee.org)
_________ is with the Universidad Nacional Autnoma Mxico, Facultad
Ingeniera.
References
[1] R. D. Hansen. (2013). Water and wastewater systems in Imperial Rome. [Online].
Available: http://www.waterhistory.org/
histories/rome
________
[2] L. J. Lucero and B. W. Fash. (2006). Precolumbian Water Management, University
of Arizona Press, Tucson, USA [Online].
Available: http://archaeology.about.com/
od/pathroughpd/a/palenque_aqueducts.
______________________
htm
__
[3] Wikipedia. (2013 Mar.). Incan aqueducts
[Online]. Available: http://en.wikipedia.
org/wiki/Incan_aqueducts
[4] C. R. S. Harris, The Heart and the Vascular
System in Ancient Greek Medicine. Oxford:
Clarendon Press, 1973.
[5] M. Megill. (19982000). Galen & Circulation. [Online]. Available: http://ablemedia.
com/ctcweb/showcase/megill2.html
[6] W. Harvey, Exercitatio Anatomica de Motu
Cordis et Sanguinis in Animalibus (in Latin,
Anatomical Exercises on the Movement of
the Heart and Blood in Animals). Frankfurt, Germany: William Fitzer, 1628.
[7] S. Hales, Statical Essays: Containing Haemastaticks, vol. 2. London, United Kingdom:
Innys, Manby & Woodward, 1733.
[8] J. L. M. Poiseuille, Rcherches sur la
force du coeur aortique, (in French, Investigations on the force of the aortic
heart), Ph.D. dissertation, No. 166, Facult de Mdicine de Paris, Imprimerie
Didot Le Jeune, 1828.
[9] A. Fick, ber die Messung des Blutquantums in den Herzventrikeln (in German,
On the measurement of the amount of
blood in ventricles), Sitzungsberichte der
Physikalisch-Medizinische Gesellschaft Wrzburg, July 9, 1870.
[10]F. Schenk, Adolf Fick Gesammelte
Abhandlungen (in German, Ficks Collected Publications), 4 vols. Wrzburg,
Germany: 19031905.
[11] H. E. Hoff and H. J. Scott, Physiology
(Part 2), New Engl. J Med., vol. 239,
no. 4, pp. 120126, 1948.
[12]E. Shapiro, Adolf FickForgotten genius of cardiology, Amer. J. Cardiol., vol.

30, pp. 662665, Nov. 1972.
[13] C. Bernard, Leons de Physiologie Exprimentale Applique a la Mdicine. Faites au College
de France (in French, Lessons of Experimental
Physiology Applied to Medicine Made at the College of France). Paris, France: Baillire, 1855.
[14]C. D. Lawrence. (1995). The history of
cardiac catheterization, in The Virtual
Cardiac Catheterization Laboratory [Online]. Available: http://user.gru.net/
clawrence/vccl/cath.HTM
______________
[15]J. B. A. Chauveau, C. Bertolus, and F.
Laroyenne, Mmoire sur la vitesse de
la circulation dans les artres du cheval
(in French, Memoir on the velocity of
the circulation in the horse arteries), J.
Physiologie de lHomme et Animaux, vol. 3,
pp. 695711, 1860.
[16]E. J. Marey, Physiologie Medicale de la Circulation du Sang (in French, Medical Physiology of the Blood Circulation). Paris,
France: Adrien Delahaye, 1863.
[17]N. Grhant and C. E. Quinquaud, Recherches exprimentales sur la mesure
du volume du sang qui traverse le poumon en un temps donn (in French,
Experimental investigations on the measurement of the blood volume traversing
the lungs in a given time), Comptes Rendus
Sances Societ Biologie Paris, vol. 38, no. 5,
ser. 8, pp. 159173, 1886.
[18]N. Zuntz and O. Hagemann, Untersuchungen ber den stoffwechsel des
pferdes bei ruhe und arbeit (in German,
Investigations on the exchange of substances in the horse at rest and at work),
Landwirtschaftlich Jahrbuch (Agricultural
Yearbook), vol. 27, suppl. 3, pp. 1438,
1898.
[19]M. E. Valentinuzzi, L. A. Geddes, L. E.
Baker, and H. E. Hoff, The node equation
and its applications in physiology, Med.
Biol. Eng., vol. 6, no. 4, pp. 387397, 1968.
[20]M. E. Valentinuzzi, B. Klaus, and E.
Gonzlez Germn, Ludwig: The teacher,
IEEE Pulse, vol. 3, no. 6, pp. 6471, 2012.
[21] Corrosion Doctors. (2013, Apr.). [Online]. Available: http://www.corrosiondoctors.org/Biographies/FickBio.htm
[22] R. Bezel, Der physiologe Adolf Fick,
18291901: Seine Zrcher jahre, 1852
1868 (in German, The physiologist Adolph
Fick, 18291901: His years at Zrich,
18521868), Zrcher Medizingeschichtliche
Abhandlungen (Transactions of the Zrich
History of Medicine), vol iii. Zrich: JurisVerlag, 85 pp., 1979.

[23]C. Bernard, The Cahier Rouge of Claude
Bernard (Transl.: H. E. Hoff, L. Guillemin,
and R. Guillemin). Cambridge, Massachusetts: Schekman, 1967.
[24]H. E. Hoff, M. E. Valentinuzzi, L. A. Geddes,
and A. G. Moore, A modern version of
J.B.A. Chauveaus Demonstration Laboratory, Southwestern Veterinarian, vol. 23,
no. 4, pp. 313322, 1970.
[25] M. T. Cousin (2006). Nestor Grhant,
18381910; Un Physiologiste Trop Oubli (in
French, A Too Forgotten Physiologist). Paris,
France: S.I. 14 pp. Available: http://www.
editions-harmattan.fr/auteurs/article_pop.
______________________
asp?no=8244&no_artiste=11500. Also
___________________
available: http://www.sudoc.abes.fr/
DB=2.1/SRCH?IKT=12&TRM=159500826
______________________
[26]Ole Daniel Enersen. Whonamedit? A Dictionary of Medical Eponyms. [Online]. Available:
http://www.whonamedit.com/
doctor.cfm/1105.html
____________
[27]A. Loewy, Dem andenken an Nathan
Zuntz (in German, To the memory of
Nathan Zuntz), Archiv Gesamtes Physiologie,
[Arch. Gen. Physiol.], vol. 194, pp. 119,
1922.
[28]K. von der Heide, Nathan Zuntz, Landwirtschaftliche Jahrbucher, vol. 51, pp.
329362, 1918.
[29]R. M. Forbes. (1955, Sept.) Nathan
Zuntz: Biography. J. Nutrition [Online].
Available: jn.nutrition.org
[30]G. Pfeiffer and E. Ohl, Oskar Hagemann,
Obituary Note, Zeitschrift fr angewandte
Chemie, vol. 39, pp. 207208.
[31]B. D. Nossaman, B. A. Scruggs, V. E.
Nossaman, S. N. Murthy, and P. J. Kadowitz.
(2010, Mar.Apr.). History of right heart
catheterization: 100 years of experimentation and methodology development.
Cardiol. Rev. [Online]. 18(2), pp. 94101.
Available: http://www.ncbi.nlm.nih.gov/
pmc/articles/PMC2857603/
_______________
[32] A. Cournand and H. A. Ranges, Catheterization of the right auricle in man, Proc.
Soc. Exp. Biol. Med., vol. 46, no. 462, 1941.
[33]D. W. Richards, Cardiac output by the
catheterization technique in various
clinical conditions, Feder. Proc., vol. 4,
no. 215, 1945.
[34]O. Klein, Zur Bestimmung des zirkulatorischen minutenvolumens beim menschen
nach dem Fickschen Prinzip. (Gewinnung
des gemischten vensen blutes mittels herzsondierung) [in German, Determination
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October 8-10, 2014

Seattle, Washington
SAVE THE DATE
,((((0%66SHFLDO7RSLF&RQIHUHQFHRQ
+HDOWKFDUH,QQRYDWLRQV 3RLQWRI&DUH
3OHDVH MRLQ XV DW The ,((( (0%6 6SHFLDO 7RSLF &RQIHUHQFH RQ +HDOWKFDUH
,QQRYDWLRQV 3RLQWRI&DUH 7HFKQRORJLHV which will be held at the 5HQDLV
VDQFHH6HDWWOH+RWHO:DVKLQJWRQ6WDWHIURP2FWREHU. This is special
topic conference focused on healthcare innovations and point-of-care technologies
is proposed to address challenges in healthcare delivery across different environments, global healthcare and translational engineering in medicine. The conference
will provide an international forum with clinicians, healthcare providers, industry
experts, innovators, researchers and students to define clinical needs and technology solutions towards commercialization and translation to clinical applications.
Panel discussions and open forum sessions along with research presentations will
focus on the development, commercialization, implementation and usercompliance of innovative healthcare and point-of-care technologies in clinical
(hospital, emergency, acute, chronic and primary care), non-traditional (consumer)
and under-resourced settings.

&RQIHUHQFHWKHPHVZRXOGLQFOXGHDWRSLFDOFRYHUDJHRIEXWQRWOLPLWHGWR
x Healthcare Innovations: Devices, Systems and Services with applications to
monitoring, diagnosis, therapeutic, surgical, emergency care and interventional
protocols
x Point-Of-Care Technologies
x Lab-on-a-chip
x Compliance and Acceptance of POC Technologies
x Evidence-based Medicine
x Personalized, Preventive and Precision Medicine including omics
x Other issues such as Critical Care; Data Communication, Security, Privacy
x Infrastructure Independent Care
x Integration of innovations and point of care diagnostic devices into systems of
healthcare
Regulatory challenges (US and International)
Conference Chair: Atam P. Dhawan

Conference Co-Chair: Clifford Dacso
More information:
D.bernstein@ieee.org
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of the circulatory cardiac output in the human being by Ficks Principle (Sampling of
mixed venous blood by means of cardiac
catheterization)], Mnchener Medizinische
Wochenschrift, vol. 77, pp. 13111312,
1930.
[35]J. L. Francella and L. Cubellun. (2013
Apr.). Historia del Hospital Durand (in
Spanish, History of the Durand Hospital), Sociedad Argentina de Historia de la
Medicina. [Online]. Available: http://
___
www.durand.org.ar/pagina_n.htm
[36]H. Baumann, ber die verwertbarkeit
der verschiedenen methoden zur minutenvolumenbestimmung (in German,
On the usefulness of different methods

to determine cardiac output), Zeitschrift
Kreislaufforschung, vol. 22, pp. 610615,
1930.
[37]S. Stern. (2005). A note on the history of cardiology: Dr. Otto Klein, 1881
to 1968. J. Amer. Coll. Cardiol. [Online]. 45(3), pp. 446447. Available:
http://content.onlinejacc.org/article.
aspx?articleid=1136258.
_____________
[38]W. Forssmann, Die sondierung des
rechten herzens (in German, Catheterization of the right heart], Klinische
Wochenschrift, vol. 8, pp. 20852087
[addendum in p. 2287], 1929.
PERSPECTIVES ON GRADUATE LIFE

This is a really frustrating problem when
your effort does not necessarily correlate
with your generated data and forward
progress on your project. Having said all
that, while it is frustrating that you have to
work even more when your experiments
are not progressing, you really do not have
many other options. Sadly, I guess it is just
part of the training process and something
with which every graduate student has to
[39]R. Forssmann-Falck, Werner Forssmann:

A pioneer of cardiology, Amer. J. Cardiol.,
vol. 79, pp. 651660, 1997.
[40]R. A. Lange, S. Bailey, and L. D. Hillis,
Cardiovascular Catheterization and Intervention. A Textbook of Coronary, Peripheral and
Structural Heart Disease, D. Mukherjee,
E. R. Bates, M. Roffi, and D. J. Moliterno,
Eds. Boca Raton, FL: CRC, 2010, pp. 112.
[41] E. Neil. (2011, Jan.). Peripheral circulation:
Historical aspects. Supplement 8, Handbook of Physiology, The Cardiovascular System,
Peripheral Circulation and Organ Blood Flow.
[Online]. Originally published 1983.
(continued from page 11)
deal. Therefore, in terms of maintaining a

worklife balance in the lab, it seems that
you must hope for some luck so that your
experiments work with at least some frequency to maintain both progress on your
project and in your personal life.
I am not sure how to solve the work
life balance problem. Maybe just start the
conversation about it earlier? Set expectations for number of hours worked?
Attempt to assess what you want your life

to be like in five, ten, or 20 years? I guess
there is no clear answer. It varies from
individual to individual, but I hope to figure it out for myself someday.
Matthew C. Canver is currently an M.D./
Ph.D. candidate at Harvard Medical School in
Boston, Massachusetts.
YO U K N O W YO U R S T U D E N T S N E E D I E E E I N F O R M AT I O N .
N O W T H E Y C A N H AV E I T . A N D Y O U C A N A F F O R D I T .
IEEE RECOGNIZES THE SPECIAL NEEDS OF SMALLER COLLEGES,
and wants students to have access to the information that will

put them on the path to career success. Now, smaller colleges can
subscribe to the same IEEE collections that large universities
receive, but at a lower price, based on your full-time enrollment
and degree programs.
Find out morevisit www.ieee.org/learning
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CONTINUING EDUCATION
E-Learning with EMBS: Employing

Medical Imaging in Drug Development
By Mats Bergstroem and Cristian A. Linte
he development of novel drugs is a

lengthy process that requires years of
preclinical and clinical research and
many steps to ensure that the developed
compound can be administered with
minimal risk to patients. Drug effectiveness was traditionally assessed based
on well-established clinical end points.
However, secondary surrogate end points
can also be assessed on the basis of biological markers quantified using imaging that serve as direct indicators of the
drugs therapeutic efficiency. Compared
to primary end points, biomarkers are
expected to provide a shorter evaluation
process without compromising the safety
and efficiency of the developed drug.
Modern imaging technologies enable
multidimensional and multiparameter data
visualization. As the spatial and temporal
resolution has improved with newer imaging technologies, various modalities have
been used to monitor substrate and protein dynamics and study the progression of
therapy delivery in real time. For example,
imaging data can provide the basis for the
mathematical modeling of protein kinetics
and biochemical signaling networks.
While imaging modalities are now
applied to provide secondary end points
in some therapeutic areas, it is desirable to
include imaging for end-point assessment
in preclinical investigations by exploring
models designed to report the activity of
selected biomarkers that are detectable
by certain imaging modalities. Moreover,
with the advent of molecular probes,
imaging will aid in not only visualizing gross anatomical structures but also
visualizing cellular substructures and

monitoring molecular dynamics.
To complement the available knowledge on the scientific and operational use
of medical imaging in drug development,
the IEEE Engineering in Medicine and
Biological Society (EMBS) has launched
a recent education initiative to convey a
series of tutorials on this topic to cater to
specialists in the field as well as others
interested in the concepts, methodologies, and applications.
The educational material consists of
slide presentations narrated by Prof. Mats
Bergstroem. He has more than 30 years of
experience in medical imaging and more
than ten years of experience in the pharmaceutical industry.
The first module, Including Medical Imaging in Drug DevelopmentTo
Answer the Relevant Question, covers the
conceptual aspects of using medical imaging in drug development. The key message
emphasizes that the inclusion of imaging in
drug development needs prospective planning. The questions to be answered during
the clinical and preclinical phases must be
considered very early in the development
stage of a specific compound. A questionbased priority list that follows the mechanistic sequence from drug administration
to drug effect forms the basis for the suggested inclusion of medical imaging. Adaptive designs are, in most cases, effective
means to obtain the best results at a lower
cost and with the exposure and engagement of a limited number of patients.
The presentation covers several aspects
of the utilization of medical imaging,
including recording drug distribution,
target interaction, and cellular or organ
consequences of the drug. The lecture
also indicates best practices on how this

information can be used in selecting the
right patient population, determining
the optimal dose to be administered, and
considering early termination.
The second module, Applying Medical
Imaging in Drug DevelopmentTo Certify Confidence in Conclusions, addresses
some of the challenges centered on generating the highest-quality data and best
interpreting the available information. For
example, positron emission tomography
(PET) measures radioactivity concentration, but in the context of in vivo human
studies, this imaging modality cannot differentiate whether the radioactive label
stays with the drug molecules originally
labeled or is transferred on to the metabolites of the drug. As such, different ways to
certify that the PET signal is correctly interpreted and converted to drug concentrations in the targeted organs are discussed.
Using techniques such as pharmacokinetic
(PK) and PK/pharmacodynamic modeling, the PET readings can be analyzed and
exploited to provide critical information on
the processes of drug entry and distribution in the organs. Moreover, specifically
designed studies enable high-precision
quantification of the degree of drug interaction with the targeted site, which, in
turn, provides insight on optimal dosing
and scheduling of drug therapy.
Another key feature of employing medical imaging in the development and evaluation of new drugs is the recording of drug
effects, which are identified by changes in
cellular or organ function or changes in
structure and topography of the disease
expression. The preclinical study design
and relevance of the preclinical models are
critical for determining whether the use of
a particular imaging modality qualifies as
an appropriate surrogate before the initiation of human studies.
These e-modules are primarily targeted
to scientists within the pharmaceutical
sector and academia who are engaged in
drug development and want to learn more
about the utility and practices of including
medical imaging as a biomarker indicative
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of a particular disease or the effect of a particular drug. These lectures also cater to
the medical imaging community and those
interested in learning more about various
applications of medical imaging in drug
development.
Both modules can be accessed via
IEEE Xplore:
Including Medical Imaging in Drug
DevelopmentTo Answer the Relevant
Question: http://ieeexplore.ieee.org/
xpl/modulesabstract.jsp?mdnumber=
______________________
EW1361
_____
Applying medical imaging in drug
developmentTo certify confidence in
conclusions: http://ieeexplore.ieee.org/
xpl/modulesabstract.jsp?mdnumber=
_______________________
EW1362.
_____
Since these modules constitute a first
attempt at developing materials to better
educate our members and collaborators
on some of the latest cutting-edge scientific topics, we very much appreciate your
feedback to help us improve the contents
of future e-library modules. We welcome
your comments, impressions, and suggestions via e-mail: ______________
linte.cristian@mayo.edu.
CLASSIFIED EMPLOYMENT
To conform to the Age Discrimination
in Employment Act, and to discourage
age discrimination, IEEE may reject any
advertisement containing any of these
phrases, or similar ones: recent college
grad, 14 years maximum experience,
up to 5 years experience, or 10 years
maximum experience. IEEE reserves
the right to append to any advertisement,
without specific notices to the advertiser,
Experience ranges are suggested minimum requirements, not maximums.
IEEE assumes that, since advertisers have
been notified of this policy in advance,
they agree that any experience requirements, whether stated as ranges or otherwise, will be construed by the reader as
minimum requirements only. While IEEE
does not ban the use of the term entry
level its use is discouraged since, to some,
it connotes an age rather than experience
designation.
To place an ad in the
IEEE PULSE
Employment Opportunities
section, call:
Susan E. Schneiderman
Business Development Manager
+1 732 562 3946
IEEE PULSE
Thank you, and we hope you enjoy your

e-learning experience!
Mats Bergstroem recently retired from his
position as distinguished scientist in the Clinical Imaging Group at F. HoffmanLaRoche
and currently upholds consultancy on medical imaging for a few pharmaceutical and
___
biotech companies. Cristian A. Linte (linte.
cristian@mayo.edu)
___________
is an assistant professor
of biomedical engineering at the Mayo Clinic
Graduate School and College of Medicine and
a research scientist at the Biomedical Imaging
Resource at the Mayo Clinic in Rochester, Minnesota. He also serves as the EMBS Education
Committee chair as well as the chair of the
Southern Minnesota EMBS Chapter.
2014-2015 CLINICAL ENGINEERING INTERNSHIPS

UNIVERSITY OF CONNECTICUT
The Biomedical Engineering Program is pleased to announce the availability
of Clinical Engineering Internship opportunities at the University of Connecticut
beginning the Fall 2014 semester. Students accepted into this program earn a
M.S. in Biomedical Engineering, which requires a minimum of 15 credit hours
of course work and a Thesis or 24 credit hours of course work without a Thesis.
Institutions currently participating in the program include: Hartford Hospital, John
Dempsey Hospital, West Haven VA Hospital, Boston VA Hospital, Providence VA
Hospital, Baystate Medical Center, Middlesex Memorial Hospital, Massachusetts
General Hospital, UMass Medical Center, Brigham & Womens Hospital, Rhode
Island Hospital and ABM Health Incorporated. Activity at these major medical
institutions involves an in-depth exposure to all clinical engineering activities.
The two-year Clinical Engineering Internship program offers an in-depth,
rigorous, clinical experience that matches the engineering expertise gained in
the classroom. The primary objectives of this intense internship program are as
follows:
R Provide exposure to hospital organization and administrative
functions.
R Permit hospital experience of clinical engineering; that is, provide an
opportunity to apply engineering techniques to patient care and hospital-based
research.
R Provide substantial experience working with hospital personnel, including
administrators, nurses, technicians and medical staff.
The internship includes a stipend for each academic year and a full tuition
scholarship. Summer support is also available. Information about this program
is contained in the Biomedical Engineering Handbook at:
http://www.bme.uconn.edu/program-handbook.php.
A graduate application is available for download at:
http://grad.uconn.edu/prospective/apply.html.
For details contact:
Dr. John Enderle
260 Glenbrook Road
University of Connecticut
Storrs, CT 06269-3247
Tel (860) 486-5521
Fax (860) 486-2500
Email: _________________
jenderle@bme.uconn.edu
For full consideration, applicants should have their graduate applications
received by January 1, 2014. Interviews will be conducted during February and
March of 2014. Final selections will be made in April 2014.
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CHAPTER NEWS
Joint Action of the IEEE EMBS

and EMCS Romanian Chapters
t the end of May, a joint scientific

event brought together members of
the IEEE Engineering in Medicine
and Biology Society (EMBS) and the IEEE
Electromagnetic Compatibility Society
(EMCS) Romanian Chapters. The International Symposium on Advanced Topics in
Electrical Engineering (ATEE), organized
since 1996 by the Electrical Engineering
Faculty of the University Politehnica of
Bucharest, held its Eighth annual conference on 2325 May 2013 in Bucharest.
A special session on EMB and EMC was
held on 23 May in the afternoon. Eight
papers were presented during the oral
joint session, and 19 others were included

in poster sessions.
A common Chapters meeting took
place after the scientific session, where
brief reports and activity programs were
presented by EMBS Romanian Chapter
President Prof. Alexandru Mihail Morega

and EMCS Romanian Chapter President Prof. Andrei Marinescu, following
an established tradition for joint actions.
Prof. Costantinos Pattichis, from Cyprus,
also attended the meeting, where he was
recognized for his remarkable scientific
achievements, and served as an invited
IEEE distinguished lecturer. His lecture
An Overview of M-Health Medical
Video Communication Systems was
presented in the morning plenary session
the same day.
Attendees gather at the 2013 Advanced Topics in Electrical Engineering Conference in

Bucharest. (Photo courtesy of Alexandru Morega.)
_____________________
___________
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_______________
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CALENDAR
SAN DIEGO, CALIFORNIA
IASI, ROMANIA
VALENCIA, SPAIN
Presymposium on Problems
at the Neural Interface
2013 IEEE E-Health and Bioengineering

Conference (EHB)
International Conference on Biomedical

and Health Informatics (BHI)
6th International IEEE EMBS

Conference onNeural Engineering
Contact: Hariton Costin

Web: http://www.ehbconference.ro/
E-mail: ___________
hcostin@gmail.com
Contact: Jessica Lotito

E-mail: emb-conferences@ieee.org
______________
HANGZHOU, CHINA
2014 5th IEEE International

Conference on Biomedical Robotics
and Biomechatronics (BioRob)
56 NOVEMBER 2013
68 NOVEMBER 2013
Contact: Dana Lynn Bernstein

Phone: +1 732 981 3451
Fax: +1 732 465 6435
Web: http://neuro.embs.org/2013
E-mail: d.bernstein@ieee.org
___________
CHANIA, GREECE
2013 IEEE 13th International
Conference on Bioinformatics
and Bioengineering (BIBE)
1113 NOVEMBER 2013

Contact: Themis Exarchos
E-mail: __________
exarchos@cc.uoi.gr
HOUSTON, TEXAS
GENSIPS 2013
1719 NOVEMBER 2013

Web: www.gensips2013.org
E-mail: datta@ece.tamu.edu
___________
2123 NOVEMBER 2013
31 MAY3 JUNE 2014
SO PAULO, BRAZIL
BMEI and CISP 2013
1618 DECEMBER 2013

Contact: Lipo Wang
E-mail: elpwang@ntu.edu.sg
___________
cispbmei2013.hznu.edu.cn
______________
12 AUGUST 2014
ANGERS, LOIRE VALLEY, FRANCE
2014 36th Annual International

Conference of the IEEE Engineering in
Medicine and Biology Society (EMBC)
Web: www.biorob2014.org
CHICAGO, ILLINOIS
International Joint Conference on
Biomedical Engineering Systems and
Technologies (BIOSTEC 2014)
36 MARCH 2014
Contact: Ana Margarida Guerreiro

Web: http://www.biostec.org/
E-mail: aguerreiro@insticc.org
____________
2014 IEEE International Symposium
on Bioelectronics and Bioinformatics
(ISBB 2014)
1114 APRIL 2014
Contact: Shuenn-Yuh Lee

E-mail: _____________
ieesyl@mail.ncku.edu.tw
2630 AUGUST 2014
Web: http://embc2014.embs.org
E-mail: emb-conferences@ieee.org
______________
SEATTLE, WASHINGTON
HIC and POCT
810 OCTOBER 2014

Contact: Dana Bernstein
E-mail: ___________
d.bernstein@ieee.org
OAHU, HAWAII
BEIJING, CHINA
2014 IEEE 11th International
Symposium on Biomedical Imaging
(ISBI 2014)
29 APRIL2 MAY 2014

2014 IEEE Micro- and Nanoengineering

in Medicine Conference (MNMC)
812 DECEMBER 2014
Contact: Jessica Lotito

E-mail: ______________
emb-conferences@ieee.org
___________
Contact: d.bernstein@ieee.org
Web: http://biomedicalimaging.org/2014/
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CALL FOR NOMINATIONS

IEEE EMBS Technical Achievement Awards

Nominations are being sought for the IEEE Engineering in Medicine and Biology Society
Technical Achievement Awards for 2014.
Each award recipient will receive a
plaque/certificate, an honorarium, and reimbursement in travel expenses associated
with attending the EMBS Awards Presentation at the 36th Annual International
Conference of the Society. The 2014 conference will be held in Chicago, Illinois, USA,
27-31 August 2014 (http://embc.embs.org/2014/).
For outstanding achievements, contributions, or innovations in any area of bioengineering by
an individual or group of individuals. Up to five awards will be selected each year.
Qualifications for the award include, but are not limited to, new technologies or significant
extensions of existing technologies, research results that extend domain knowledge, and
design of new hardware or software having a significant impact in any area of bioengineering.
Examples of eligible Bioengineering Technologies (additional areas will also be considered)
x
x
x
x
Biosignal Processing
Bioinstrumentation
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A MAGAZINE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY

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Highest quality products More than 3000 grades

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A MAGAZINE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY

New World of 3-D Printing Offers

Dream It, Design It, Print It in 3-D

Adding Value in Additive

The Body Printed

Moving the Science of Behavioral

by Niilo Saranummi, Donna Spruijt-Metz,

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by Daniel E. Rivera and Holly B. Jimison

COLUMNS & DEPARTMENTS

4 FROM THE EDITOR

48 STATE OF THE ART

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SENIOR ART DIRECTOR

State of the Art

IEEE prohibits discrimination, harassment,

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2 IEEE PULSE NOVEMBER/DECEMBER 2013

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FROM THE EDITOR

ngineering is involved with many

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4 IEEE PULSE NOVEMBER/DECEMBER 2013

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IEEE Medal for Innovations in Healthcare