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).

Aspiderweb.Thespiderproducesalong, exceptionallystrongsilkenthreadafewdozenm indiameter.Thesilkenthreadisaproteinthatis synthesizedinagland Oneofthesilkglandsofanephilaclavipes

Bloodcirculation

Vennermannetal.Exp.Fluids(2007)42,495

Manmadesystems.WhyMicro?
1. Uniquephysicalandchemicaleffects,massandheattransfer characteristics 2.Smallvolumesofexpensiveand/ordangerousreagents 3 Paralleloperation 3. 4.Portability,integration(reactions,separation,detection) 5.Implantingmicrofluidicdevicesinbiologicalsystems 6.Compatibilitywithothermicro/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.
http://faculty.washington.edu/yagerp/microfluidicstutorial/basicconcepts/basicconcepts.htm

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

http://strc.herts.ac.uk/mm/micromixers.html http://alcheme.tamu.edu/?page_id=6720

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
http://www.zzz.com.ru/data/users/arhines/mf3.jpg http://www.smalltimes.com/images/ microfluidics_inside_1.jpg

http://www.epigem.co.uk/images/fluidics -intro3 intro3.jpg jpg

http://www.micronit.com/images/Cust_chips.jpg

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 - J.Berthier P.Silberzan Micro and NanoFlows (2-nd edition of Karnadiakiss book) Reviews: -H.Stone, A.Stroock, A.Ajdari, Ann.Rev.Fluid Mech, 36, 381(2004) - S.Quake, T.Squire, Microfluidics : Fluid Physics at the microscale(2005) -Analytical A l ti l Chemistry, Ch i t L Lab b on a Chip Chi - P.A.Auroux, D.Iossifids, D.Reyes, A.Manz, Anal.Chem,74, 2637 (2002) - Huck et al. Angew. Chem. Int. Ed., 49, 5846-5868 (2010)