Polymers in Soft and Biological Matter2012

MICROFLUIDICS

Professor Eugenia Kumacheva

1. Fundamentals of microfludics2. Topics in microfluidics2. Topics in microfluidics

Microfluidics istheareaofscienceandtechnologythatisfocusedon

simple or complex mono or multiphasic flows that are circulating insimpleorcomplex,mono ormultiphasicflowsthatarecirculatingin

naturalorartificialmicro systemswithatleast,onedimensionof

below500m(sometimesbelow1000m)

MicrofluidicsystemsinnatureA b i i d i h l i l Atreebringingwaterandnutrientstotheleavesviaacomplexnetworkofcapillaries

A ill t k f h d d fAcapillarynetworkofhundredsofthousandsofmicrochannelswithdiametersbetween100m(inthetrunk)and10sof

(i th l f)nm(intheleaf).

Thehydrodynamicsofthesystem:theabilityofthecapillaries to deform under the effect of pressure), thecapillariestodeformundertheeffectofpressure),thesignificanceofcapillaryeffectsandredundancy (ifonecapillarydies,anothertakesitsplace).

Aspiderweb.Thespiderproducesalong,exceptionallystrongsilkenthreadafewdozenmin diameter. The silken thread is a protein that isindiameter.Thesilkenthreadisaproteinthatissynthesizedinagland

Oneofthesilkglandsofanephilaclavipes

Bloodcirculation

Vennermannetal.Exp.Fluids(2007)42,495

Manmadesystems.WhyMicro?

1. Uniquephysicalandchemicaleffects,massandheattransfercharacteristics

2.Smallvolumesofexpensiveand/ordangerousreagents

3 Parallel operation3.Paralleloperation

4.Portability,integration(reactions,separation,detection)

5.Implantingmicrofluidicdevicesinbiologicalsystems

6.Compatibilitywithothermicro/nanoscaledevices

Why Flow? Some of important features

FocusofMicrofluidicsf f

Phenomena Components Components Systems ApplicationsApplications

Cellbiology

MEMS and microfluidicsMi i i i i i h i l fl idiMiniaturizationmicrometersizemechanical,fluidic,

electromechanical,orthermalsystems.1980s Wheel Complex objectsWheelComplexobjects

1990s:birthofmicrofluidics

Dimensions:generally,below500m;300m

g y, ;sometimes1000m

ThisimagewasprovidedbytheKarlsruhegroup(Germany)

Microfluidics and high throughput screening/separation

Take a sample containingmany different objects

Microfluidic screening

A few words about nanofluidics

Interactions between adsorbed polymer layers

A Surface Forces Balance Technique

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 FlowThe fluid is pumped through the device via positive displacement pumps (syringe

microfluidic channels?

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 channelparabolic velocity profile within the channel.

V l it fil i i h l ith t ti 2 5 fVelocity profile in a microchannel with aspect ratio 2:5 for pressure driven flow (calculation using Coventorware software.

http://faculty.washington.edu/yagerp/microfluidicstutorial/basicconcepts/basicconcepts.htm

P1

P2

P

Hydrodynamic resistanceP1

P

Q is the volumetric flow rate of the liquid, P is pressure drop, Rh is the h d d i i t ( l t th l t ki ti l U IR)

P = RhQ P2hydrodynamic resistance (analogous to the electrokinetic law 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

Electrokinetic Flow

If the walls of a microchannel have a charge, an electric double layer of counter ionswill form at the walls. When an electric field is applied across the length of the channel, th i i th d bl l t d th l t d f it l it Thi tthe ions in the double layer move towards the electrode of opposite polarity. This creates 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 channelentire width of the channel.

Anode Cathode

For a closed channel, a recirculation pattern forms, in which a fluid along the center of the channel moves in a direction opposite to that ppat the walls.

Fluid mechanics of microfluidics

Navier-Stokes equation is the central relationship of fluid dynamics

Basic assumptionsBasic assumptionscontinuous mediacontinuum mechanics

For liquids:Assumptions made in macrofluidics, work for microfluidics (down to 10-100 nm)

How to describe the motion of a fluid? Velocity depends on space and time v = v(x(t) t)Velocitydependsonspaceandtimev =v(x(t),t) ConsiderNewtonslawforainfinitesimalvolumeV:

dVdVv(x(t),t)

fa and v are vectors!!

flowflow

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 tt=t2

flow

Accelerationalongastreamline

Increaseofthefluidvelocityduetomassconservation Fluid has to be accelerated along the streamlineFluidhastobeacceleratedalongthestreamline

v(x(t),t)

flow

The Navier-Stokes equation

for incompressible Newtonian fluids

lefthandside righthandside Changeinmomentum(Newton) duetochangeofvelocityovertime

atagivenlocation

Forcesactingonfluid pressuregradient frictionforces

duetoaccelerationoffluide.g.whenmovingintosmallerflowchannelcrosssections(alsoinstationary cases)

volumeforces

stationarycases)

Pressuregradient

p p+p

Bodyforce(=volumeforce)

Actuation of fluid by the body force:force fvolume acts in the volume itself

Body forces: centrifugal forces gravity forces

fvolumeelectrostatic forces

Example1:staticpressureundergravity

OnlygravityisconsideredinNSequation

Stationary flow (v=const ): Stationaryflow(v=const.): frictioniszero(nomotion) accelerationiszero(dv/dt=0)

dp Result:

p gdy

=

Example1:forwaterinamicrochannel:= 1000kg/m3g= 9.81m/s2h= 100m

6max 0.981 9.81 10 barp Pa

= =

Gravitationaleffectsarenegligibleinmicrofluidics

Friction

Frictionaffectsthemotion(velocity)ofthefluid

v (x)vz(x)

z

h d d b h f f

x

Themotionisdampedbythefrictionforce

Reynoldsnumber(Re) Approximate friction energy v vl A l Approximatefrictionenergy

Approximatekineticenergy

friction frictionv vE l A l Vl l

= =F2

kinE mv

2kinE mv l lv Re

Reynolds number is the ratio of work spent on acceleration to energy dissipated by friction

kin

friction

ReE vV

= = =

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 low Renumbers i e viscous forces dominate are typical for microfluidicslowRenumbers,i.e.viscousforcesdominate,aretypicalformicrofluidics l isacharacteristiclengthscale

Simplificationsinmicrofluidics

2,( ) volume gpt

+ = + + v v v v f

Gravityisneglected Influenceofconvectionissmall, (v )v 0, i.e. weassumethatthereisnoconvective

t

, (v )v 0,momentumtransport

Ifadditionallyastationaryflowisconsidered

Poissonequation(drivingpressureandfrictionarebalancedinastationarylaminarflow):

2( ) p + + + v v v v g( ) pt + = + + v v v v g

Flow Regimes

R 1 (St k i ) ReRe * (Turbulent) Re>Re (Turbulent) Perturbations are amplified Curling of field lines

Re> Re *turbulent fowg

Unpredictable" development of field of velocity vectors over time

fow

Re* ~ 2300

CriticalReynoldsnumber

Critical Re* corresponds to a critical velocity v*

* *v Re = Typically Re* is in the range of 2300

v Rel=

Typically Re is in the range of 2300

For a microdevice v* is hardly reached (l = 100 m v* 25 m/s)(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 numbersC ill h l i i iCapillary phenomena are extremely important in microsystems

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 across an interface between a liquid and a gas, or between two g q g ,

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

SummaryNS ti i d i d b t b l f NSequationisderivedbyamomentumbalanceforacontinuumelement

For Newtonian incompressible fluids the NS equation is ForNewtonian,incompressible fluidstheNSequationis

Momentumchange(righthandside)canbecausedby: Pressuregradients ViscouslossesB d f Bodyforces

Re numbercharacterizesthedampingofdisturbances laminarandturbulentflow))

Summary(cont)

For Re < Re * the flow is laminar For Re > Re * the flow is turbulent

In microfluidics we (usually) assume No gravity Incompressibility

D i f i f Dominance of viscous forces

Capillarity plays an important role in microfluidics as Capillarity plays an important role in microfluidics, as represented nu small Capillary numbers

How to make a microfluidic device?

Thermoembossing Thermoembossing

Wet and dry etching

Moulding

Laser ablation

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

Soft lithography

. other clever methods

http://www.micronit.com/images/Cust_chips.jpghttp://www.epigem.co.uk/images/fluidics-intro3 jpgintro3.jpg

Speed matters!

Fabrication of Microfluidic Device: Soft Lithography

1) Spincoat photoresist

2) UV Exposure

3) Develop photoresist

4) Prepare mold4) Prepare mold

5) Seal to substrateChannel

5) Sea to subst ate

Si WaferSU-8 Photomask PDMS prepolymer

Y. Xia, G. M. Whitesides, Angew. Chemie Int. Ed. 1998, 37, 550

MIXING IN MICROFLUIDICS

Mixinginmicrofluidics No turbulence in microfluidics Mixing occurs by diffusion Little or no mixing No turbulence in microfluidics. Mixing occurs by diffusion. Little or no mixing.

A dimensionless number, analogous to the Reynolds number, is Peclet number

advectionPe = Ul/D ~ advectiondiffusion

Diffusion time for a 100 m wide channel (for a molecule such as fluorescein):

Mixingbydiffusion

CleversolutionsPosts The distributive micromixerThe distributive micromixer

N

Hydrodynamic focusing

From A. Manz (2004)From A. Manz (2004)

Mixing in tens of microsecondsAustin et al, PRL (2002)

Chaoticmixerformicrochannels

Whitesides et al. Science, 295, 647 (2002)

To generate transverse flows in i h l id l dmicrochannels, ridges were placed on

the floor of the channel at an oblique angle, with respect to the long axis (y) of the channel

Crosschannelmixer

D l t i fl idiDroplet microfluidics

Generationofdroplets

A and B are two immiscible liquids

Narrow size distributionHigh frequency of droplet generationControl of droplet morphology (double emulsions)

Flowfocusing

B

B

A

Stone, APL, 2002

Liquid C

Liquid B

Liquid A

Liquid C

Liquid B

42

48

m

)

m

)

d = [(4/) (Qdrop/vx, cont)]1/220 30 40 50

30

36

d

(

d

o

(

m

d is the average diameter of the coaxial jet

20 30 40 50 Qw (ml/h)

112

Qw (mL/h)

d0 = (1.5 breakup d2)1/364

80

96

d

0

(

m

)

d

o

(

m

)

d0 is the average diameter of droplets 20 30 40 5064

Qw(ml/h)Qw (mL/h)Z. Nie et al. J. Am. Chem. Soc. 127, 8058 (2005)

100

150

s

i

o

n

(

m

)

a) Water

16 24 32 40 480

50

D

i

m

e

n

Q (ml/h)b)30

40

Core-shell

Core

CORE-SHELL

CORES

50

100

150

e

n

s

i

o

n

(

m

)

Qw(ml/h)b)

Oil 1

10

20

%

0.16 0.24 0.32 0.40 0.48 0.560

50

D

i

m

e

Qm(ml/h)c)30 40 50 60 70 80 90 100 110

0

10

Diameter ( m)

50

100

150

m

e

n

s

i

o

n

(

m

) Oil 2 Diameter ( m)

0.04 0.05 0.06 0.07 0.08 0.090D

i

m

Qo (ml/h)

Multicore Capsules: Hypothesism0m0m0mo

d029Interfacial wavelength

jetd02.92/1)/(~ di QQ )/( contdisp QQ

n/ om n is the number of monodisperseoil cores per capsulen/1-n om

Stable breakup of coaxial jet

Z. Nie et al. J. Am. Chem. Soc. 127, 8058 (2005)

/1 n/1-n om

0

0

0

0

0

0

Synthesis of Polymer Capsules

8

1.0

0 0.2

8

1.0

0 0.2

8

1.0

0 0.2

06

0.

8 0.4 tota

l Q

D0

6

0.8 0.4 to

tal Q

D0

6

0.8 0.4 to

tal Q

DD

4

0.6 0.6Q

w / Q

to

Q m ' / Q tota4

0.6 0.6Q

w / Q

to

Q m ' / Q tota4

0.6 0.6Q

w / Q

to

Q m ' / Q tota

0 2

0.

4 6 0.8 al

A

F HI

0 2

0.

4 6 0.8 al

A

F HI

0 2

0.

4 6 0.8 al

A

F HI

A

FI H

0

0.2 1.0B C

EG

0

0.2 1.0B C

EG

0

0.2 1.0B C

EG

E

B

G

C

1.0 0.8 0.6 0.4 0.2 0

Q o' / Q total1.0 0.8 0.6 0.4 0.2 0

Q o' / Q total1.0 0.8 0.6 0.4 0.2 0

Q o' / Q total

Continuous Microfludic Reactors

WATERMicrofluidic Flow-Focusing Device

MONOMER

UV irradiationUV-irradiation

WATER

H. A. Stone et al. Appl. Phys. Lett. 361, 51-515 (2001)

Poly(tripropylene glycole diacrylate)

0 5 % < CV < 3 %

PolyacrylatesPolystyrenePolyurethaneBiopolymer gels 0.5 % < CV < 3 %Biopolymer gels

S. Xu et al. Angew. Chem. Intnl. Ed. 44, 724 (2005)

Nanoparticle-loaded beads

Polymermicrobeads

Liquid Crystal-polymer particles

Porousmicrobeads

FITC-BSA-conjugated beads

(d)(d) (e)(e)(d)(d) (e)(e)

SShape andmorphologycontrol

(f)(f)

100 m 58

Synthesis of Janus particles

A

W

B

W

A: MAOP-DMS + dyeB: PETA-3/AA

100 m

h1

h2R

h1

h2

h1

h2R

h1

h2R

h1

h2

h1

h2

)3( 12

11 hRhQ V ~ (Qm1+ Qm2)/ Qw)

1/2 1/1 2/1Qm1/Qm2

)3()3(

22

2

11

2

1

hRhhRh

QQ

m

m

=

Exploratory droplet microfluidics

Optimization of chemical reactions

High-throughput generation of cellularmicroenvironments

Ismagilov, 2005

Microenvironments for cell co-culture

Directandindirectcellcellinteractions:

Agarose solutionR G

proliferation,selfrenewal,deathordifferentiation 37 oC

A li tiApplications: woundhealingi i i

MicrogelsSoy bean oil tissueengineering inhibitionofcancerspreading

61

Qtor =QG+QR=constChangetheratioQG/QR 61

Microenvironments for cell co-cultureMurine embryonic stem (mES) cells labelled with Vybrant Cell y ( ) yTracer ( green ) and CellTracker Orange (red)

1 day 2 day

Embryoidbodies(YC5 Mouse

4 day

(YC5 Mouse Embryonic Stem cells) Scalebaris100mCellcoculture

62

Microfluidics and single molecule studies

Books

P Tabeling Introduction to MicrofluidicsP. Tabeling. Introduction to 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)A l ti l Ch i t L b Chi-Analytical Chemistry, Lab on a Chip

- 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)