Professional Documents
Culture Documents
EMBEDDED SYSTEMS
DONE BY,
C. ARAVIND,
S. NAGESWARAN,
MAHARAJA ENGG. COLLEGE,
AVINASHI.
Abstract such devices. And so, the brain–machine
Electrical recording from spinal cord interface restriction will indeed
vascular capillary bed has been achieved become one of the central issues of
demonstrating that the intravascular modern society. As this is being
space may be utilized as a means to considered, another quite different
address brain activity with out violating revolution is being enacted by the very
the brain parenchyma. While the initial rapid and exciting developments in the
demonstration was implemented using field of nanotechnology. Such
electrically insulated platinum electrodes developments deal with manufactured
in vitro, the possibility of using objects with characteristic dimensions of
conducting polymer filaments is now less than one micrometer. This issue is
being explored. This paper presents a set of high relevance here since the brain–
of highly possible future scenarios where machine impasse may ultimately be
the integration of electrophysiology and resolved through nanotechnology.
novel polymer technology using Obviously, what is required is a robust
embedded systems may serve as a new and noninvasive way to tap and address
approach towards basic and medical brain activity, that is an optimized
neuroscience. cognitive based command/control.
In addition to serving as a brain–
machine interface, such an approach
Introduction would be extraordinarily valuable in the
When considering the role of diagnosis and treatment of many
neuroscience in modern society the issue neurological and psychiatric conditions.
of the brain–machine interface is one of The technology to be described here will
the very relevant problems to be be vital in the diagnosis and treatment of
addressed in the next two decades. abnormal brain function. Such
Indeed, our ability to design and build technology would allow constant
new information analysis and storage monitoring and functional imaging as
systems that are light enough to be easily well as direct modulation of brain
carried, has advanced exponentially in activity. For instance, an advanced
the last few years. Ultimately, the brain– variation of present day deep brain
machine interface bottleneck will stimulation would be of excellent
become the major stumbling block to therapeutic value. Besides, interface with
robust and rapid communication ‘intelligent’ devices would significantly
with these devices. To date, the interface improve the lives of disabled individuals
improvements have not been as allowing them to be more fully involved
impressive as our progress in in everyday activity.
miniaturization or computational power
expansion. Indeed, the limiting factor
with most modern devices relates to Recording and stimulating brain
the human interface. Buttons must be activity in animals and humans
large enough to manipulate, screens Brain activity is mostly recorded with
wide enough to allow symbol electrodes placed on the surface of the
recognition, and so on. Clearly, the only skull. In the case of
way to proceed is to establish a more electroencephalography (EEG),
direct relationship between the brain and electrodes are placed on the skull and
record activity occurring on the surface and chemical etching have been used to
of the brain. In the case of successfully record neural activity in
magnetoencephalography (MEG), mouse brain. However, at present,
recording probes are also placed on the microelectrode arrays are inadequate for
surface, but through triangulation such long-term implantation. Implantation
activity can be mapped in three results in the migration of activated glial
dimensions. To record from within the cells and other inflammatory cells
brain the skull must be opened and (platelets, neutrophils, monocytes/
electrodes lowered into the brain mass. macrophages) to the array–tissue
Similarly, to stimulate the brain, as interface. Adherence to the array surface
is done therapeutically for some patients promotes glial scar formation and
with Parkinson’s disease, the skull must ultimately fibrous encapsulation. While
be opened and electrodes inserted. In the effectively sealing the site of injury,
last two decades there has been a serious encapsulation blocks neurite growth and
interest in multicellular recording from axonal regeneration. In an effort to
the central nervous system. This drive establish a more reliable, long term
resulted from the understanding that interface between microelectrode arrays
brain activity is, fundamentally, the and neural tissue, several investigators
resultant of coherent multicellular have used bioactive coatings to promote
activity to be understood only by biospecific cell adhesion for material
simultaneous recording of significant implant applications. While results are
number of neurons. Indeed, devices are encouraging, the use of potentially
routinely used to conduct biocompatible microelectrode arrays to
neuroscience research in monkeys and monitor/stimulate neural activity is
other animals. Mechanically, the devices extremely invasive.
must gather signals from a number of
recording sites, typically arranged in a
grid pattern. The need to record from Neurovascular approach
an increasing number of neurons led to One of the most attractive possibilities
the development of microelectrode that came to mind in trying to solve the
arrays. Many designs and manufacturing hardware problem concerns the
techniques have been development of a vascular approach.
developed to construct these arrays. The fact that a rich vascular bed
Use of a neuroprosthetic array requires permeates the nervous system
that it be both easily manufactured and parenchyma makes this space a
biocompatible. Electrical discharge very attractive candidate for our
machining (EDM) is a process that interface (Figure1).
makes use of computer aided design
(CAD), that runs under computer
numerical control (CNC), and that is
capable of batch processing. It can
generate intricate features with high
aspect ratios and is capable of machining
a large variety of conductive materials.
Microelectrode arrays fabricated in our
MIT BioInstrumentation Lab by EDM
Figure 3. Branching of artery showing
branching points.
Figure 2. Close-up view of brain arterial Figure 4. Left: Purkinje cell showing
system showing graduate decrease in spaces occupied by capillaries (c). Right:
vessel size. Electron micrograph through Purkinje
cell dendrite including capillary. Dot
placed in capillary is 500 nm in
diameter.
Electrode visualization
In these experiments, nanoelectrodes are
inserted into mesentery vessels near a
nerve bundle or plexus. The electrodes
are introduced into the vessel through a
catheter that is tied in place. The
electrode is then advanced and carried
into the vessel by an infusion of Ringer’s Figure 11. Intravascular recording in the
solution. This preparation is transparent spinal cord.
and progress of the electrode in the
vessel can be followed using a video
camera. This allows evaluation
of the mechanical properties of the
electrodes and their behavior at vessel
branch points.
Figure 19. Conducting polymer. Figure 21. The current density flowing
through our conducting polymer
microwire as a function of electric field
Electrical properties of over a large range of current densities.
conducting polymers
By comparison the usual upper working
Our conducting polymer wires exhibit
limit of copper wire in a high
metallic-like conductivity. Figure 20
performance electric motor is 10
below shows the highly linear
MA/m2. The conductivity of the
relationship (i.e. Ohm’s law) between
conducting polymer grown for this
voltage and current which is typical of
experiment was 37 kS/m (i.e. the slope
our conducting polymer wires.
of the current density verses electric
field plot below). A conducting polymer
wire does not need to have sub-
micrometer diameters until near its tip.
Consider a wire having a diameter which
is progressively stepped from 100 lm
down to 200 nm. If the 200 nm diameter
tip region extends for 100 lm then such a
wire if made from a conducting polymer
having a conductivity of 37 kS/m would
Figure 20. Current–voltage relationship
have an overall resistance of less than 10
in conducting polymer microwires.
k and could carry currents in the order
The slope of this linear relationship
of 500 nA. We expect that the This instrument will be used to
conductivities of our conducting determine if the polymer nanowires are
polymers will increase considerably more robust than comparably sized
as we learn to improve their method of metal wires. The fiber to be tested is
manufacture. It is expected that these attached between a computer controlled
nanowires will have superior resistance micro-actuator and a highly sensitive
to fracture in the brain nanowire force sensor. A software interface allows
application. Malleable materials such as the user to impose a wide variety of
gold or platinum will require minimal mechanical length perturbations to the
forces to permanently deform the wires fiber while measuring the force
with very small diameters. Conducting developed in the fiber. The micro-
polymers are not malleable, and should actuator consists of a compound linear
therefore be more resistant to motor and piezoelectric transducer that
deformation due to impact with together allow a wide range of strain
particulates in the blood. Conducting states to be imposed upon the fiber or
polymers are typically tested at low nanowire that is being tested. The linear
voltages (e.g., <10 V). However if they motor (Aerotech, MX80) allows
are to be used for brain stimulation (as the imposition of large scale
well as recording) it is essential that they displacements of up to 50 mm at speeds
survive high voltages (e.g., 100 V). We of up to 1.5 m/s, while resolving the
have recently shown that our conducting position of the linear motor stage to 20
polymer wires do degrade when subject nm resolution. Simultaneously, the
to 160 V pulses. piezoelectric motor (PhysikInstrumente
P-841.10) can impose small
displacements (15 micrometer, measured
Mechanical and electrical testing to sub-nm resolution) over a bandwidth
apparatus of 1 kHz. The capability of these two
We have built a nanoscale .ber motors allows a wide variety of
mechanical and electrical testing mechanical tests to be performed, from
apparatus (Figure 22) that is capable of very slow stretching over large
performing a variety of 1D mechanical displacements to high frequency
measurements on fibers ranging from 50 dynamic stiffness measurements at small
nm to 20 micrometer in diameter. displacement. The other end of the fiber
is attached to custom force transducer
consisting of a silvered quartz cantilever
with high resonant frequency (>1 kHz.)
The displacement of the cantilever is
measured to about 1 nm resolution using
a twin-wavelength laser interferometer
(Hewlett-Packard). Different micro-
machined beams (i.e. having differing
beam deflection stiffnesses) are used for
to cover different force ranges.
As an example consider a 200 nm
Figure 22. Nanoscale fiber testing diameter nanowire fabricated out of a
apparatus. conducting polymer having an elastic
modulus of 800 MPa (which is typical). Conducting polymer
A force of 2.5 nN is required to stretch biocompatibility and
this wire by 0.01%. Such forces are
biodegradation
readily measured using our apparatus.
For brain interface applications it is
In addition to being quite robust,
advantageous for the wires to be
conducting polymers are an attractive
biocompatible and biodegradable.
alternative to precious metals for a
The use of conducting polymers as
variety of reasons. Alternatively,
biomaterials is attractive because it
platinum foil of similar dimensions cost
allows the coupling of electrical
approximately $30,000/ kg (VWR
stimulation and cell growth/modulation.
international). While there is some cost
Biocompatibility is influenced by several
increase in the technology development
factors including the free energy at the
to make very small wires, the cost
solid–liquid interface, the hydrophobic/
advantage of using organic material
hydrophilic character of the surface, and
instead of metals remains. Conducting
the surface chemistry/charge density.
polymers have a density similar to brain
Neutral polymers and polyanions appear
tissue which is about 20 times less than
to be less cytotoxic than polycations.
platinum.
Polymer flexibility, surface roughness,
and molecular weight have also been
shown to influence biocompatibility.
Conducting polymer actuators Low molecular weight polymers absorb
In a particular form, conducting less protein and display less platelet
polymers can be used as actuators. Such adhesion.
actuators feature muscle-like contractile
properties at very low drive voltages (-1 Contact between blood and a biomaterial
V), while being capable of generating results in a rapid activation of the
high stresses up to 40 MPa in its linear coagulation and complement systems.
form (cf. 0.35 MPa mammalian skeletal Within a millisecond of contact, a layer
muscle). Figure 23 below shows a of protein adsorbs to the material.
trilayer actuator constructed in our Fibrinogen, which in the presence of
laboratory, capable of generating large thrombin, forms the fibrin scaffold, also
displacements. acts as an adhesive, causing platelets
(PTLs) to attach to the surface. Otto et al
have demonstrated that PTL adherence
is influenced not only by protein pre
adsorption but also by blood flow
conditions.
This would allow us to steer the While thrombin and other activated
nanowire-probe selectively into desired clotting factors may be diluted under
blood vessels, thus creating the first true high blood flow conditions, insertion of
steerable nano-endoscope. a nano wire may alter blood flow and/or
cause turbulence that could promote
adhesion of PTL. This is currently of
little consequence in our initial studies as
the blood contact time is minimal.
However, it does require consideration conductivity. Polymers began
for any long-term studies. Although to degrade, as measured by tissue
many polymers are considered to be infiltration, 14 to 29 days after sub-
biocompatible, not all are degradable. cutaneous implantation in rats. The
Degradation or dissolution changes the oligomers remaining after polymer
shape, size, or mass of a polymer – the degradation should be consumed by
polymer erodes. Erosion in a macrophages. More recently, Wang et al.
physiological environment (bio erosion) have shown in vitro that a
can be due to solubilization of intact PPy/poly(D,L-lactide)(PDLLA)
polymer or chemical degradation. The composite is capable of acting as a
most common cause of bioerosion is bioconductor. This biodegradable
chemical degradation, primarily electrically conductive composite
hydrolytic cleavage of the polymer delivered continuous current within 0.6
backbone. While hydrolysis is the most to lA in a simulated biological solution
common mode by which polymers for up to 8 weeks. It is expected that the
degrade, oxidation of polymers (by the acidic microenvironment created by
host or by the device or external hydrolysis of the PDLLA should
environment) can also occur as can increase the conductivity of the PPy with
degradation due to enzymatic significant loss of conductivity being
mechanisms. Enzymatic, cellular, or restricted to the final stage of
microbial degradation of polymer is degradation. Increased acidity may be
referred to as biodegradation. Several problematic in vivo. Finally, the
factors have been shown to affect mechanical properties of such materials
bioerosion rate. Understanding the have not yet been fully explored, but
behavior of degradable polymers will these polymer composites are promising
facilitate successful manipulation due to their biological significance.
through better design. The use of
conducting polymers as biomaterials Conclusion
is attractive because it allows the Thus this technology using embedded
coupling of electrical stimulation and proves to be worthful in the treatment of
cell growth/modulation. For the most neuro-vascular central nervous system
part, attempts to copolymerize have with the help of nano probes.
resulted in non conducting copolymers.
However, Rivers et al. synthesized a
biodegradable electrically conducting
polymer by ‘tethering conductive
pyrrole–thiophene oligomers with
degradable ester linkages using an
aliphatic linker’. The ester linkages can
be cleaved by cholesterol esterase, an
enzyme secreted by cells during normal
wound repair processes and the
aliphatic linker provides flexibility in
between the rigid pyrrole-thiophene
oligomers. The pyrrole–thiophene
oligomers appear to be suffcient for