Background

i i Prerequisites:
Calculus, tensor and vector analysis, ODEs, PDEs
Fluid Mechanics (Reynolds transport theorem, Navier Stokes equations, Stokes ( y p , q ,
flow, etc)
General physics and chemistry
Useful reference books: Useful reference books:
Theoretical Microfluidics by Henrik Bruus, Oxford (theory based)
Introduction to Microfluidics by Tabeling, Oxford
Fundamentals and Applications of Microfluidics by Nam-Trung Nguyen
and Steve Wereley
Microdrops and digital microfluidics by Jean Berthier p g y
The Structure and Rheology of Complex Fluids by R. Larson
Transport phenomena by Bird, Stewart and Lightfoot
Literature search: Web of Science, electronic journals
Topics to cover
Lecture 1: Introduction to microfluidics; History;
Microfabrication; Scaling Analysis in microfluidics ; g y
Lecture 2: Wettability and hydrophobicity in
microfluidics; Interfaces, droplets and multiphase flows in
microfluidics
Lecture 3: Micromixing; Rheology effects in microfluidics
Lecture 4: Perspectives and microfluidics related applications in
biotechnology and nanotechnology
Lecture 1: Introduction to microfluidics and nanofluidics
Folchs group
UW di f i i
Caliper, lab on chip
UW, gradient generator for mixing
Shens lab, UW
20 microns LC droplets
Microfluidics
Microfluidics (associated with MEMS and lab-on-a-chip)
studies the behavior of fluids on microscopic levels.
Mi fl idi i i di i li d i d i b Microfluidics is an interdisciplinary domain, driven by
applications (existing or potential), in which interesting
physics can be done physics can be done.
The control of tiny amounts of gases or liquids in a
miniaturized system of channels, pumps, valves, and sensors. miniaturized system of channels, pumps, valves, and sensors.
Most of the phenomena taking place in microsystems can be
described in a macroscopic framework; however, for a number p ; ,
of systems (gases, macromolecules...), the microscopic scales
interfere directly with the microsystem size.
Balances of forces are modified as we go from the ordinary to
the micro world. Reasoning on scaling laws is a powerful
h t ti i t th h t f approach to anticipate the changes one may expect from
miniaturizing a given system.
MEMS= MEMS=
MICRO ELECTROMECHANICHAL SYTEMS
Systems whose sizes lie in the range 1 -300 microns
A new situation arose in the seventies, further to the tremendous
development of microelectronics: it became possible to fabricate
all sorts of miniaturized objects: microcondensators, microvalves,
micropumps, microresonators, microdispenser...
by exploiting an important accumulation of technological by exploiting an important accumulation of technological
knowledge, and taking advantage of the availability of
sophisticated equipment. p q p
Airbag Sensor Airbag Sensor -- Analog Device Analog Device Airbag Sensor Airbag Sensor Analog Device Analog Device
300 m
3 mm
Commercial Inkjet using MEMS technology Commercial Inkjet using MEMS technology j g gy j g gy
22 mm
Perhaps, everything started with a talk given by R. Feynman.
There's Plenty of Roomat the Bottom
Perhaps, everything started with a talk given by R. Feynman.
Theres Plenty of Room at the Bottom
An Invitation to Enter a New Field of Physics y
R Feynman, CALTECH, Dec 1959
I woul d l i ke t o descr i be a f i el d, i n whi ch l i t t l e has been done, but i n
whi ch an enor mous amount can be done i n pr i nci pl e. Thi s f i el d i s not qui t e
h h h i h i i l l l l h f f d l
R Feynman, CALTECH, Dec 1959
t he same as t he ot her s i n t hat i t wi l l not t el l us much of f undament al
physi cs ( i n t he sense of , ``What ar e t he st r ange par t i cl es?' ' ) but i t i s
mor e l i ke sol i d- st at e physi cs i n t he sense t hat i t mi ght t el l us much of
gr eat i nt er est about t he st r ange phenomena t hat occur i n compl ex
i t t i si t uat i ons.
Fur t her mor e, a poi nt t hat i s most i mpor t ant i s t hat i t woul d have an
enor mous number of t echni cal appl i cat i ons.
Craighead (Cornell)
The nanoguitar is played by hitting the strings with a focused laser e ogu s p yed by g e s gs w ocused se
beam. When the strings vibrate they create interference patterns in
the light reflected back, which can be detected and electronically
converted down to audible notes. The device can play only simple
tones..
Microfluidics = Realization and study of flows Microfluidics Realization and study of flows
and transfers in (artificial) microsystems
Afew milestones
1970 - 1990 : Essentially nothing (apart from the Stanford gas
A few milestones
1970 - 1990 : Essentially nothing (apart from the Stanford gas
chromatographer)
1990 : First liquid chromatograph (Manz et al)
TAS concept (Manz, Graber, Widmer, Sens.Actuator, 1991)
1990 -1998 : First elementary microfluidic systems (micromixers 1990 -1998 : First elementary microfluidic systems (micromixers,
microreactors, separation systems,..)
1998-2004 : Appearance of soft lithography technology, which
f t d th d i All t f i fl idi t ith i fostered the domain. All sorts of microfluidic systems with various
levels of complexity are made, using different technologies
MOTIVATION MOTIVATION
Macro scale = laminar, random, and
turbulent flow
Micro scale = laminar flow
Laminar flow allows controlled Laminar flow allows controlled
mixing
Low thermal mass
Efficient mass transport Efficient mass transport
Good (large) ratio of channel surface
area: channel volume
http://www.spie.org/web/oer/august/aug00/microfluidics.html
First microfluidic system : Terry (1975) (Stanford)
Injection valve
channel 1.5 m long
Thermal
sensor
Reyes et al, Anal Chem, 74, 2623 (2002)
A microfluidic system for DNA separation
From Agilent-
y p
From Agilent-
Caliper
Allow to characterize DNA
Fragments with excellent
l ti d i ll resolution, and in a small
time
A system which will probably have an impact in biology
(Quake et al, Science 2002)
An elementary
Lab-on-a-chip
LAB-ON A CHIP BIOSITE
DIAGNOSES
HEART ATTACK
WITHIN 10 MN
4
Length scales
10
21
10
5
10
1
10
-4
Meter e e
10
8
10
4
10
0
10
-5
10
7
10
3
10
1
10
-7
10
7
10
3
10
-1
10
-7
Single hair strand: ~ 50 microns, 1 micron = 10
-6
m
Microfabrication
There are many fabrication techniques
Etching MEMs devices (glass/glass devices, glass/Si wafer
d i ) devices)
Soft lithography techniques (glass/PDMS or PDMS/PDMS
de ices) devices)
Replica Molding (REM)
The original master can be used many
times with PDMS poured and peeled times, with PDMS poured and peeled
off repeatedly, with good stability
This PDMS negative can then act as
mask to reproduce the original, with a
high Tg polymer such as poly(methyl
methacrylate) PMMA, or polyurethane
Replica Molding (REM)
The elastomeric properties of the
PDMS can also be used to stretchor PDMS can also be used to stretch or
compress the sizescale, from 180nm of
a waveguide to 40nm (Xia, U. Wash.)
The drawbacks of this compression are
introducing more fabrication steps
(reproducible compression limit ~25%)
also liftoff surface energies in small
systems can exceed the PDMS surface systems can exceed the PDMS surface
energy (~22 dyn/cm), which increases
wear, limiting number of reproductions
Replica Molding (REM)
One clever side application
however is to use slight expansion
and compression for mechanically
switchable elastic optics
Here, optical elements are formed
INSIDE the PDMS using liquid
metals (Hg or Ga) which conform
t th it d t d ti to the cavity and act as adaptive
optics for beam steering and focus
Micro Contact Printing (CP)
The PDMS masks can also be applied
as flexible stamps, inked with adsorbing
or assembling molecules, and then used
as small rubber contact stamps as small rubber contact stamps
The chemical ink covers all surfaces but The chemical ink covers all surfaces, but
Surface relief patterns transfer only
molecules in direct contact. 5nm is
sufficient, with 200nm spaces.
Inks can be adsorbing polymers,
reactant compounds, or self assembling
monolayers based on silanes or thiols monolayers based on silanes or thiols
Micro Contact Printing (CP)
Alkane thiols with tailored
headgroups provide versatile and
powerful chemical control over
subsequent patterning such as subsequent patterning, such as
polymer adsorption, photoresists,
vapour deposition of inorganics,
etching, electroplating of metals
PDMS Stamps can deposit
controlled patterns within 10nm over
d h b many square cm, and have been
demonstrated for features down to
35nm(etching of grooves on gold) 35nm (etching of grooves on gold)
Micro Contact Printing (CP)
Complex architectures are possible from any master, as long as its limited
to a single layer to be deposited on a Au or Si coated flat surface
The Limitation: This produces one layer well but only a single layer The Limitation: This produces one layer well, but only a single layer.
CURVED surfaces are also amenable to micro-contact printing, opening the
way to the third dimension through unfolding complex topologies
Micro Contact Molding
Here, liquid pre-polymer flows into channels by capilliary action, hardens
over time and with mask removal the desired structures are left behind : over time, and with mask removal the desired structures are left behind :
Mask-Free Fabrication
Deposition of a trail of liquids from an AFM tip represents a small ink pen
Bottom Up Fabrication
Lithography process
Circuit design CAD layout & simulation
Process sequence
Substrate cleaning Spin coat
Pre-bake
(soft bake)
Expose
Post-exposure
Develop
Expose
bake (PEB)
Develop
Post-bake
(Hard bake)
Etch thin film Strip PR
Process (3)
Development Development
Etching
Most common procedure to make p
microchannels
Utilize soft lithography
techniques
S i ti i d t Spin coating is used to cover
silicon wafers with a viscous
photoresist photoresist.
The photoresist is baked,
covered with a mask and then
exposed to UV light.
The unexposed areas can then p
be washed away, leaving
patterned ridges.
PDMS is then poured
over the pattern cured over the pattern, cured
and removed.
The PDMS slab
exposed to oxygen
plasma, giving it p , g g
hydrophilic surface
properties properties.
After 24 hrs of contact After 24 hrs. of contact
the two surfaces
covalently bond.
Physical aspects of microfluidics Physical aspects of microfluidics
Mean free path in gases
Bubble nucleation barrier
Thermal capillarity length
There exists interactions between
microscopic and macroscopic scales
i i fl idi
Fl t ti f
Debye layer thickness
in microfluidic systems
VdW force range
Fluctuation forces range
Nanofluidics
1nm
10m
100nm 1km 10nm
1m 100m 10m
100nm 1km 10nm
1m 100m
Microfluidics
Single g
Molecule
studies
RECENT NUMERICAL SIMULATIONS
INDICATE THAT ORDINARY
HYDRODYNAMICS HYDRODYNAMICS
IS RECOVERED IN THE SUBMICRON RANGE
The fluid mechanics of microfluidics The fluid mechanics of microfluidics
(B d T b li t tb k) (Based on Tabelings textbook)
Navier-Stokes equations q
Du
Dt
=
cu
ct
+ (uV)u =
1

VP +vAu
Dt ct
c
ct
+ divu = 0
ct
Reynolds numbers are small in microsystems
Re = Ul/v ~ l
2
Re = Ul/v ~ l
One thus may think in the framework of Stokes equations
Microhydrodynamics
2
Stokes regime : inertial terms are neglected
0 =
p
+
2
u
i
x
i
x
j
x
j
Acceptable approximation in most case. Exceptions are
Micro-heat pipes and drop dispensers
L t U Let us reverse U
U -U
If it is a Stokes solution, arrows must be inverted
everywhere
This solution cannot be Stokes This solution cannot be Stokes
UU
B if U Because if we reverse U
U -U
We obtain a non plausible streamline pattern We obtain a non plausible streamline pattern
Experiment
Performed by Performed by
O Stern (2001)
Flows in cavities at low Reynolds numbers
Hele Shaw flows
Darcy law governs Hele Shaw cells Darcy law governs Hele Shaw cells
V =
b
2
12
Vp
12
In a Hele Shaw cell, flows are potential e e S w ce , ows e po e
An important notion : the hydrodynamic resistance
AP = RQ
m
Q
m
12 L
R =
12v
b
2
L
S
~ l
3
Increases as the system size decreases
A PDMS t t b d M lti l A PDMS actuator, based on Multi-layer
Soft Lithography
Actuation channel Actuation channel
Glass slide
Working channel
PDMS
Working channel
PDMS
A U H P Ch T Th A S h t S R Q k S i 288 113 (2000) A. Unger, H-P. Chou, T. Thorsen, A . Scherer et S. R. Quake, Science, 288, 113, (2000).
From the electrical point of view, pneumatic actuators are
represented by a capacitance/non linear resistance system. represented by a capacitance/non linear resistance system .
They are not just diodes
V
C
R
R
Non linear
R=f(V )
Non linear
resistances
R=f(V
C
)
J .Goulpeau, A. Ajdari
P. Tabeling,J. Appl.Phys.
May 2005
No actuation :
Large localized Large localized
gradient
Actuation : Producing different
Concentration gradients
b h i th t ti by changing the actuaction
parameters
Mechanical actuators dedicated to the generation of
concentration gradients g
Passive concentration
gradient generator
(1)
The same, using mechanical
actuators
(1)
J eon et al, Nature Techn., 20, 826 (2002))
The boundary conditions The boundary conditions
for liquids
The slip length
z
The slip length
z
u
c
| |
Navier Boundary Conditions
u = L
s
cu
cz
|
\

|
.
|
Slip length (or extrapolation length) p g ( p g )
Pressure drop with a slip length
AP
Pressure drop with a slip length
Flow rate Q
AP
12LQ 1
Depth b
AP =
12LQ
wb
3

1
1+ 6L
S
/ b
Slip length L
S
Microfluidics and capillarity
A few important things
to know in microfluidics
Laplaces law Laplace s law
S
oE = poV + oS
R
V =
4
3
tR
3
oV = 4tR
3
oR
V
S = 4tR
2
oS = 8tRoR
Bubble
At mechanical equilibrium : oE=0
Bubble
q
p =
2
p =
R
THE PATTERNS WHICH DEVELOP IN ORDINARY TWO PHASE FLOWS
OFTEN PRODUCE COMPLEX MORPHOLOGIES; THIS IS DUE
TO HYDRODYNAMIC TURBULENCE TO HYDRODYNAMIC TURBULENCE
IN MICROFLUIDIC SYSTEMS, WE OBTAIN MUCH SIMPLER
MORPHOLOGIES : ESSENTIALLY DROPLETS
Wetting are exceedingly important in
microsytems
3 cases
Complete wetting
Partial wetting
D i Desorption
S di t Spreading parameter
S = S =
SG SL
When S is non homogeneous droplets spontaneously When S is non homogeneous, droplets spontaneously
move on the surfaces
u
A
<u
B
u
A
u
B
Poor wetting (S <0)
Good wetting (S 0)
In liquid, one may easily change S by adding surfactants
oil
water

SO

SW
= cosu
SO

SW
cosu
Wetting properties of the walls are g p p
important in microfluidic multiphase flows
Water
Oil with or without
surfactant (Span 80) surfactant (Span 80)
Water
R Dreyfus, P.Tabeling, H Willaime, Phys Rev Lett, 90, 144505 (2003))
NICE DROPS CAN BE PRODUCED NICE DROPS CAN BE PRODUCED
IN MINIATURIZED SYSTEMS IN COMPLETE WETTING CONDITIONS
When oil fully wets the surface
100
Oil flow rate
(L/min)
Stratified regime Isolated water drops
10 10
kl
1
Pear necklace
Coalescence
Pears
Large-pearl necklace
0.1
Coalescence
Pearl necklace
0.1 1 10 100
Water flow rate (L/min)
WHEN THE FLUIDS PARTIALLY WET THE WALLS
m
n
)

(

L
/
m
w
-
r
a
t
e
O
i
l

f
l
o
w
O
Water flow-rate (L/mn)
(R Dreyfus, P.Tabeling, H Willaime, Phys Rev Lett (2003))
Rayleigh instability is the most
important instability to be aware of
d
E
C
= 2tRL =
2tV
R
Surface energy of a column
d C

R
Surface energy of N spherical droplets

E = 4tR'
2
N =
3V
'
gy p p

R'
R' >
3
2t
R
UNSTABLE
Applications: Digital microfluidics
- Liquid liquid flows are used in microsystems, in
several circumstances.
Producing drops of one liquid into another liquid Producing drops of one liquid into another liquid
so as to generate emulsions, or perform screening
Producing bubbles in a microchannel flow so as
to increase heat exchange, or simply because the
li id b il liquid boils.
Digital microfluidics Digital microfluidics
1 - In air
The drop moves in air The drop moves in air
over a flat surface
2 - In a liquid
The drop moves in a liquid
in a microchannel in a microchannel
Digital microfluidics is interesting for chemical
analysis, protein cristallization, elaborating novel emulsions,
I il l Ismagilov et al
(Chicago University)
AN EXAMPLE OF AN INTERESTING PROBLEM : REDUCING THE DROP
SIZE OF AN EMULSION BY USING DIGITAL MICROFLUIDICS
TECHNOLOGY TECHNOLOGY
10m
Suppose we are willing to reduce the drop Suppose we are willing to reduce the drop
size of an emulsion
One possibility is to cut the drops one by one
in a microfluidic system y
Water drop Water drop
10m
U
L
0
u
l = L
0
u
U
DIFFERENT REGIMES, FOR INCREASING SIDE FLOWS
WHITE = WATER DROP, BLACK (IN THE CHANNEL) = HEXADECANE
We would like also to
control the drop break-up
L
f
V
L
f
V
S
Finger ge
Curve
suggested by
To break or not to break
suggested by
the theory
(Navot, 1999)
BREAKING
V
S
( / ) (m/s)
NON
BREAKING
L ( )
BREAKING
0 1 2 3 4 5 x10
2
L
f
(m)
Laure MENETRIER, 2004
Liquid-liquid flows in microsystems may be used to produce Liquid-liquid flows in microsystems may be used to produce
well controlled drops, emulsions,
provided the wetting properties of the exposed surfaces,
with respect to the working fluids, are appropriately chosen.