Polymers in Soft and Biological Matter 2012
MICROFLUIDICS
Professor Eugenia Kumacheva
1. Fundamentals of microfludics 2. Topics in microfluidics
Microfluidics istheareaofscienceandtechnologythatisfocusedon
simpleorcomplex, complex mono ormultiphasicflowsthatarecirculatingin naturalorartificialmicro systemswithatleast,onedimensionof below500m(sometimesbelow1000m)
Microfluidicsystemsinnature
Atreebringing b i i waterand dnutrients i tothe h l leavesvia i acomplex l networkofcapillaries
Acapillary ill network t kof fhundreds h d d of f thousandsofmicrochannelswithdiameters between100m(inthetrunk)and10sof nm(in (i the th leaf). l f)
Thehydrodynamicsofthesystem:theabilityofthe capillariestodeformundertheeffectofpressure),the significanceofcapillaryeffectsandredundancy (ifone capillarydies,anothertakesitsplace).
[Link], exceptionallystrongsilkenthreadafewdozenm [Link] synthesizedinagland Oneofthesilkglandsofanephilaclavipes
Bloodcirculation
[Link](2007)42,495
[Link]?
1. Uniquephysicalandchemicaleffects,massandheattransfer characteristics [Link]/ordangerousreagents 3 Paralleloperation 3. [Link],integration(reactions,separation,detection) [Link] [Link]/nanoscaledevices
Why Flow? Some of important features
Focusof fMicrofluidics f
Phenomena Components Systems Applications
Cellbiology
MEMS and microfluidics
Mi i Miniaturization i i micrometer i size i mechanical, h i l fluidic, fl idi electromechanical,orthermalsystems. 1980s WheelComplexobjects
1990s:birthofmicrofluidics
300m
generally, y,below500m; ; Dimensions:g sometimes1000m
ThisimagewasprovidedbytheKarlsruhegroup(Germany)
Microfluidics and high throughput screening/separation
Take a sample containing many different objects
Microfluidic screening
A few words about nanofluidics
A Surface Forces Balance Technique
Interactions between adsorbed polymer layers
Forces in the presence of electrolyte (Debye layers)
(Expected) novel phenomena in nanochannelss
Experimental studies of flow in nanofluidic devices are just beginning
How to make liquid move through microfluidic channels?
Pressure Driven Flow
The fluid is pumped through the device via positive displacement pumps (syringe pumps) or using pressure gauges. One of the basic laws is the so-called no-slip boundary condition: the fluid velocity at the walls must be zero. This produces a parabolic velocity profile within the channel channel.
Velocity V l it profile fil i in a microchannel i h l with ith aspect t ratio ti 2 2:5 5f for pressure driven flow (calculation using Coventorware software.
[Link]
P1
P
P2
P1
Hydrodynamic resistance
P = RhQ
P2
Q is the volumetric flow rate of the liquid, P is pressure drop, Rh is the h d d hydrodynamic i resistance i t ( (analogous l t to th the electrokinetic l t ki ti l law U=IR U IR) Channel with a circular cross-section (total length L, radius R): Channel with a rectangular cross-section (width w and height h, h<w)
Rh increases as the system size decreases In a network of channels Rh can be computed as in electrokinetics: two channels in series have a resistance two channels in parallel have a resistance
Electrokinetic Flow If the walls of a microchannel have a charge, an electric double layer of counter ions will form at the walls. When an electric field is applied across the length of the channel, th ions the i in i the th double d bl layer l move towards t d the th electrode l t d of f opposite it polarity. l it Thi This creates t motion of the fluid near the walls and transfers via viscous forces into convective motion of the bulk fluid. Anode Cathode For the channel open at the electrodes, the velocity profile is uniform across the entire width of the channel channel. Anode Cathode
For a closed channel, a recirculation pattern forms, in which a fluid along the center of the pp to that channel moves in a direction opposite at the walls.
Fluid mechanics of microfluidics
Navier-Stokes equation is the central relationship of fluid dynamics Basic assumptions continuous media continuum mechanics For liquids: Assumptions made in macrofluidics, work for microfluidics (down to 10-100 nm)
How to describe the motion of a fluid?
Velocitydependsonspaceandtimev =v(x(t),t) (t) t) ConsiderNewtonslawforainfinitesimalvolumeV:
dV
v(x(t),t)
fa and v are vectors!!
flow
How to describe the motion of a fluid?
Momentumequation(acceleration)inxdirection:
Momentumequationin3D(vectornotation):
Nabla operator
Accelerationovertime
v(x,t1)
t=t1
v(x,t2) t=t t t2
flow
Accelerationalongastreamline
Increaseofthefluidvelocityduetomassconservation Fluidhastobeacceleratedalongthestreamline
v(x(t),t)
flow
The Navier-Stokes equation
for incompressible Newtonian fluids
lefthandside Changeinmomentum(Newton)
duetochangeofvelocityovertime atagivenlocation duetoaccelerationoffluide.g. whenmovingintosmallerflow channelcrosssections(alsoin stationarycases)
righthandside Forcesactingonfluid
pressuregradient frictionforces volumeforces
Pressuregradient
p+p
Bodyforce(=volumeforce)
Actuation of fluid by the body force: force fvolume acts in the volume itself Body forces: centrifugal forces gravity forces electrostatic forces
fvolume
Example1:staticpressureundergravity
OnlygravityisconsideredinNSequation
Stationaryflow(v=const (v=const.): ):
frictioniszero(nomotion) accelerationiszero(dv/dt=0)
Result:
dp p = g dy
Example1:forwaterinamicrochannel:
= 1000kg/m3 g = 9.81m/s2 h = 100m
pmax = 0.981Pa = 9.81106 bar
Gravitationaleffectsarenegligibleinmicrofluidics
Friction
Frictionaffectsthemotion(velocity)ofthefluid
vz(x) z x
The h motionisdamped d dby b the h friction f force f
Reynoldsnumber(Re)
Approximatefrictionenergy Approximatekineticenergy
E friction F friction
v v l = Al = V l l
E kin m v 2
Ekin mv l lv = = = Re E friction vV
2
Reynolds number is the ratio of work spent on acceleration to energy dissipated by friction (A more general definition: Re a dimensionless number that gives the ratio of inertial forces (characterizing how much a particular fluid resists to motion) to viscous forces.
theRenumberisthemostimportantdimensionlessnumberinmicrofluidics lowRenumbers, numbers i i.e. e viscousforcesdominate dominate,aretypicalformicrofluidics l isacharacteristiclengthscale
Simplificationsinmicrofluidics
v + ( v ) v = p + 2 v + f volum e , g t
Gravityisneglected Influenceofconvectionissmall, , (v )v 0, i.e. weassumethatthereisnoconvective momentumtransport Ifadditionallyastationaryflowisconsidered
Poissonequation(drivingpressureandfrictionarebalancedinastationarylaminarflow):
v + ( v ) v = p + 2 v + g t
Flow Regimes Re R <1 1(Stokes (St k regime) i )
No lateral convection
Adjacent layers (lamellae) do not interfere (lamellae do not mix) inertial terms are neglected 1 < Re < Re * (Intermediate) Lateral convection becomes increasingly important Re>Re * (Turbulent) Perturbations are amplified Curling g of field lines Unpredictable" development of field of velocity vectors over time
Re > Re * turbulent fow Re < Re * laminar flow a a
Re* ~ 2300
CriticalReynoldsnumber
Critical Re* corresponds to a critical velocity v*
v = Re l
* *
Typically Re* is in the range of 2300 For a microdevice v* is hardly reached (l = 100 m v* 25 m/s) As Re increases further, the turbulent character of flow increases
Examples of laminar flow
[Link] [Link]
Laminar flow means that diffusion is the only mechanism to achieve mixing between parallel fluid streams. This is a slow process.
Other dimensionless numbers
C ill Capillary phenomena h are extremely l i important i in microsystems i
Laplace law
Droplet
Pressure drops caused by capillarity are ~ l-1 while those due to viscosity scale as l0
The capillary number, Ca, represents the relative effect of viscous forces versus surface tension acting g across an interface between a liquid q and a g gas, , or between two immiscible liquids
is the viscosity of the liquid, U is a characteristic velocity and is the surface or
interfacial tension between the two fluid phases Microfluidics: Ca 10-1 - 10-3
Summary
NSequation ti i isd derived i db byamomentum t b balance l f fora continuumelement ForNewtonian,incompressible fluidstheNSequationis
Momentumchange(righthandside)canbecausedby: Pressuregradients Viscouslosses d f B Body forces Re numbercharacterizesthedampingofdisturbances laminarand ) turbulentflow)
Summary(cont)
For Re < Re * the flow is laminar For Re > Re * the flow is turbulent In microfluidics we (usually) assume No gravity Incompressibility Dominance D i of f viscous i f forces Capillarity plays an important role in microfluidics microfluidics, as represented nu small Capillary numbers
How to make a microfluidic device?
Thermoembossing Wet and dry etching Moulding Laser ablation Photolithography Soft lithography . other clever methods
[Link] [Link] microfluidics_inside_1.jpg
[Link] -intro3 [Link] jpg
[Link]
Speed matters!
Fabrication of Microfluidic Device: Soft Lithography
1) Spincoat photoresist 2) UV Exposure 3) Develop photoresist 4) Prepare mold
Channel
5) Seal Sea to substrate subst ate SU-8 Si Wafer Photomask PDMS prepolymer
Y. Xia, G. M. Whitesides, Angew. Chemie Int. Ed. 1998, 37, 550
MIXING IN MICROFLUIDICS
Mixinginmicrofluidics
No turbulence in microfluidics microfluidics. Mixing occurs by diffusion diffusion. Little or no mixing mixing. A dimensionless number, analogous to the Reynolds number, is Peclet number
Pe = Ul/D ~
advection diffusion
Diffusion time for a 100 m wide channel (for a molecule such as fluorescein):
Mixingbydiffusion
Cleversolutions
Posts The distributive micromixer N
Hydrodynamic focusing
From A. Manz (2004)
Mixing in tens of microseconds Austin et al, PRL (2002)
Chaoticmixerformicrochannels
Whitesides et al. Science, 295, 647 (2002)
To generate transverse flows in microchannels, i h l ridges id were placed l d on the floor of the channel at an oblique angle, with respect to the long axis (y) of the channel
Crosschannelmixer
D Droplet l t microfluidics i fl idi
Generationofdroplets
A and B are two immiscible liquids Narrow size distribution High frequency of droplet generation Control of droplet morphology (double emulsions)
Flowfocusing
Stone, APL, 2002
Liquid C Liquid B Liquid A Liquid B Liquid C
48 42 36 30 20 30 40 Q w (ml/h) 50
d = [(4/) (Qdrop/vx, cont)]1/2
dm (m) do ( m)
Qw (mL/h)
d is the average diameter of the coaxial jet d0 = (1.5 breakup d2)1/3
112 (m) m) do d(
0
96 80 64
d0 is the average diameter of droplets Z. Nie et al. J. Am. Chem. Soc. 127, 8058 (2005)
20
Qw (mL/h)
30 40 Q w(ml/h)
50
a) Dimension (m) 150 100 50 0 16 b) Dime ension (m) 150 100 50 0 0.16 c) Dim mension (m) 150 100 50 0 0.04
Water
40
CORES
Core
24
32 Qw(ml/h)
40
48
30
CORE-SHELL
Core-shell
Oil 1
%
0.32 0.40 0.48 0.56
20
10
0.24
0 30 40 50 60 70 80 90 100 110
Qm(ml/h)
Oil 2
Diameter (
m)
0.05
0.06 0.07 Qo (ml/h)
0.08
0.09
Multicore Capsules: Hypothesis
m
o 0
m
Interfacial wavelength
9.02d jet
1/ 2 ~ (Qdisp / Q ) di cont
m / o n
n - 1 < m / o < n
n is the number of monodisperse oil cores per capsule n is the number of polydisperse oil cores per capsule
m is breakup wavelength of monomer jet
o is breakup wavelength of oil jet;
Stable breakup of coaxial jet
Z. Nie et al. J. Am. Chem. Soc. 127, 8058 (2005)
n - 1 < m / o < n
M
Synthesis of Polymer Capsules
0 0.2 1.0 0.8
D D
tot al
0.4
/Q
0.6
'/
Q 0.6
al tot
0. 4
A A
0.2
F F
I I
H H
0.8
G G
E E
B B
0.6 0.4
C C
0.2
1.0
1.0
0.8
Q o' / Q total
Continuous Microfludic Reactors
WATER
MONOMER
Microfluidic Flow-Focusing Device
WATER
UV irradiation UV-irradiation
H. A. Stone et al. Appl. Phys. Lett. 361, 51-515 (2001)
Poly(tripropylene glycole diacrylate) Polyacrylates Polystyrene Polyurethane Biopolymer gels
0 5 % < CV < 3 % 0.5
S. Xu et al. Angew. Chem. Intnl. Ed. 44, 724 (2005)
Polymer microbeads
Nanoparticle- Liquid Crystalloaded beads polymer particles
Porous FITC-BSAmicrobeads conjugated beads
(d)
(e)
SShape andmorphologycontrol
(f)
100 m
58
Synthesis of Janus particles
W
A B
W A: MAOP-DMS + dye B: PETA-3/AA
h1 R h2
100 m
V ~ (Qm1+ Qm2)/ Qw)
Qm1/Qm2
1/2
1/1
2/1
Qm1 h1 (3R h1 ) = 2 Qm 2 h2 (3R h2 )
2
Exploratory droplet microfluidics
Optimization of chemical reactions High-throughput generation of cellular microenvironments
Ismagilov, 2005
Microenvironments for cell co-culture
Directandindirect cellcellinteractions:
proliferation,selfrenewal, deathordifferentiation
Agarose solution
R G
37 oC
A li ti Applications:
woundhealing tissue i engineering i i inhibitionofcancerspreading Qtor =QG+QR =const ChangetheratioQG/QR
Soy bean oil
Microgels
61 61
Microenvironments for cell co-culture
Murine embryonic y stem ( (mES) ) cells labelled with Vybrant y Cell Tracer ( green ) and CellTracker Orange (red)
1 day 2 day
4 day
Embryoidbodies Cellcoculture
(YC5 Mouse Embryonic Stem cells) Scalebaris100m
62
Microfluidics and single molecule studies
Books P Tabeling. P. Tabeling Introduction to Microfluidics. Microfluidics Microfluidics for Biotechnology - [Link] [Link] Micro and NanoFlows (2-nd edition of Karnadiakiss book) Reviews: -[Link], [Link], [Link], [Link] Mech, 36, 381(2004) - [Link], [Link], Microfluidics : Fluid Physics at the microscale(2005) -Analytical A l ti l Chemistry, Ch i t L Lab b on a Chip Chi - [Link], [Link], [Link], [Link], [Link],74, 2637 (2002) - Huck et al. Angew. Chem. Int. Ed., 49, 5846-5868 (2010)
