Backgroundi 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 Berthierp 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

Folch’s groupUW di f i i

Caliper, lab on chipUW, gradient generator for mixing

Shen’s lab, UW20 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 donephysics 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 fapproach 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 technologicalby exploiting an important accumulation of technological knowledge, and taking advantage of the availability of sophisticated equipment.p q p

Airbag SensorAirbag Sensor -- Analog DeviceAnalog DeviceAirbag SensorAirbag Sensor Analog DeviceAnalog Device

m

3 mm

Commercial Inkjet using MEMS technologyCommercial Inkjet using MEMS technologyj g gyj g gy

22 mm

Perhaps, everything started with a talk given by R. Feynman….

There's Plenty of Room at the Bottom

Perhaps, everything started with a talk given by R. Feynman….

There s Plenty of Room at the Bottom

An Invitation to Enter a New Field of Physicsy

R Feynman, CALTECH, Dec 1959

I would like to describe a field, in which little has been done, but inwhich an enormous amount can be done in principle. This field is not quiteh h h i h i ill ll h f f d l

R Feynman, CALTECH, Dec 1959

the same as the others in that it will not tell us much of fundamentalphysics (in the sense of, ``What are the strange particles?'') but it ismore like solid-state physics in the sense that it might tell us much ofgreat interest about the strange phenomena that occur in complexit tisituations.

Furthermore, a point that is most important is that it would have anenormous number of technical applications.

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 sebeam. 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 flowsMicrofluidics Realization and study of flows and transfers in (artificial) microsystems

A few milestones1970 - 1990 : Essentially nothing (apart from the Stanford gas

A few milestones1970 - 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 (micromixers1990 -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 ifostered the domain. All sorts of microfluidic systems with various levels of complexity are made, using different technologies

MOTIVATIONMOTIVATION

• Macro scale = laminar, random, and turbulent flow

• Micro scale = laminar flow• Laminar flow allows controlledLaminar 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

Thermalsensor

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 llresolution, 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

DIAGNOSESHEART ATTACKWITHIN 10 MN

4

Length scales

1021 105 101 10-4

Metere e

108 104 100 10-5

107 103 10 1 10-7107 103 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 peeledtimes, 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 stretch orPDMS 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 surfacesystems 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 tito 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 stampsas small rubber contact stamps

The chemical ink covers all surfaces butThe 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 thiolsmonolayers based on silanes or thiols

Micro Contact Printing (CP)

Alkane thiols with tailored headgroups provide versatile and

powerful chemical control over subsequent patterning such assubsequent 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 bmany 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 it’s 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 layerThe 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 FabricationDeposition 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)

ExposePost-exposure Develop Exposebake (PEB)Develop

Post-bake(Hard bake)

Etch thin film Strip PR

Process (3)

DevelopmentDevelopment Etching

Most common procedure to make pmicrochannels

• Utilize soft lithographytechniquesS i ti i d t• Spin coating is used to cover silicon wafers with a viscous photoresistphotoresist.

• The photoresist is baked, covered with a mask and then exposed to UV light.

• The unexposed areas can then pbe washed away, leaving patterned ridges.

•PDMS is then poured over the pattern curedover the pattern, cured and removed.

•The PDMS slab exposed to oxygen plasma, giving it p , g ghydrophilic surface propertiesproperties.

•After 24 hrs of contact•After 24 hrs. of contact the two surfaces covalently bond.

Physical aspects of microfluidicsPhysical aspects of microfluidics

Mean free path in gases

Bubble nucleation barrier

Thermal capillarity length There exists interactions betweenmicroscopic and macroscopic scalesi i fl idi

Fl t ti f

Debye layer thicknessin microfluidic systems

VdW force range

Fluctuation forces range

Nanofluidics

1nm 10m100nm km10nm 1m 100m10m100nm km10nm 1m 100m

MicrofluidicsSinglegMoleculestudies

RECENT NUMERICAL SIMULATIONSINDICATE THAT ORDINARY HYDRODYNAMICSHYDRODYNAMICSIS RECOVERED IN THE SUBMICRON RANGE

The fluid mechanics of microfluidicsThe fluid mechanics of microfluidics

(B d T b li ’ t tb k)(Based on Tabeling’s textbook)

Navier-Stokes equationsq

DuDt

ut

(u)u 1P u

Dt t

t

divu 0t

Reynolds numbers are small in microsystems

Re = Ul/ ~ l2Re = Ul/ ~ l

One thus may think in the framework of Stokes equations

Microhydrodynamics

2

Stokes regime : inertial terms are neglected

0 p

2ui

xi xjxj

Acceptable approximation in most case. Exceptions are Micro-heat pipes and drop dispensers

L t ULet us reverse U

U-U

If it is a Stokes solution, arrows must be invertedeverywhere

This solution cannot be StokesThis solution cannot be Stokes

UU

B if UBecause if we reverse U

U-U

We obtain a non plausible streamline patternWe obtain a non plausible streamline pattern

Experiment Performed byPerformed byO Stern (2001)

Flows in cavities at low Reynolds numbers

Hele Shaw flows

Darcy law governs Hele Shaw cellsDarcy law governs Hele Shaw cells

V b2

12p

12

In a Hele Shaw cell, flows are potentiale e S w ce , ows e po e

An important notion : the hydrodynamic resistance

P RQmQm12 LR 12b2

LS

~ l3

Increases as the system size decreases

A PDMS t t b d M lti lA PDMS actuator, based on Multi-layer Soft Lithography

Actuation channelActuation channel

Glass slideWorking channelPDMS Working channelPDMS

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 arerepresented by a capacitance/non linear resistance system .represented by a capacitance/non linear resistance system . They are not just diodes

VCR

R

Non linear R=f(V )Non linearresistances

R=f(VC)

J.Goulpeau, A. AjdariP. Tabeling,J. Appl.Phys.May 2005

No actuation : Large localizedLarge localized gradient

Actuation : Producing different Concentration gradients b h i th t tiby changing the actuaction parameters

Mechanical actuators dedicated to the generation of concentration gradientsg

Passive concentrationgradient generator (1)

The same, using mechanicalactuators

(1)Jeon et al, Nature Techn., 20, 826 (2002))

The boundary conditionsThe boundary conditions for liquids

The slip length

z

The slip length

z

u

Navier Boundary Conditions

u Lsuz

Slip length (or extrapolation length)p g ( p g )

Pressure drop with a slip length

P

Pressure drop with a slip length

Flow rate QP

12LQ 1Depth b

P 12LQ

wb3 1

1 6LS / b

Slip length LS

Microfluidics and capillarity

A few important thingsto know in microfluidics

Laplace’s lawLaplace s law

SE pV S

RV 4

3R3 V 4R3R

V S 4R2 S 8RR

Bubble At mechanical equilibrium : E=0 Bubble q

p 2

p R

THE PATTERNS WHICH DEVELOP IN “ORDINARY” TWO PHASE FLOWS

…OFTEN PRODUCE COMPLEX MORPHOLOGIES; THIS IS DUETO HYDRODYNAMIC TURBULENCETO 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 iDesorption

S di tSpreading parameter

S S SG SL

When S is non homogeneous droplets spontaneouslyWhen S is non homogeneous, droplets spontaneouslymove on the surfaces

A<BA B

Poor wetting (S <0)Good wetting (S ≈ 0)

In liquid, one may easily change S by adding surfactants

oil water

SO SW cos SO SW cos

Wetting properties of the walls are g p pimportant in microfluidic multiphase flows

WaterOil 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 PRODUCEDNICE DROPS CAN BE PRODUCEDIN MINIATURIZED SYSTEMS IN COMPLETE WETTING CONDITIONS

When oil fully wets the surface100

Oil flow rate(L/min) Stratified regimeIsolated water drops

1010

kl

1

Pear necklace

CoalescencePearsLarge-pearl necklace

0.1

Coalescence

Pearl necklace

0.1 1 10 100

Water flow rate (L/min)

WHEN THE FLUIDS PARTIALLY WET THE WALLS

mn)

(L/

mw

-rat

eO

il flo

wO

Water flow-rate (L/mn)(R Dreyfus, P.Tabeling, H Willaime, Phys Rev Lett (2003))

Rayleigh instability is the mostimportant instability to be aware of

d EC 2RL 2V

R

Surface energy of a column

d C R

Surface energy of N spherical droplets

E 4R' 2 N 3V

'

gy p p

R'

R' 3

2R UNSTABLE

Applications: Digital microfluidics

- Liquid liquid flows are used in microsystems, in several circumstances.

Producing drops of one liquid into another liquidProducing drops of one liquid into another liquidso as to generate emulsions, or perform screening

Producing bubbles in a microchannel flow so asto increase heat exchange, or simply because theli id b illiquid boils.

Digital microfluidicsDigital microfluidics

1 - In airThe drop moves in airThe drop moves in air over a flat surface

2 - In a liquidThe drop moves in a liquidin a microchannelin a microchannel

Digital microfluidics is interesting for chemical analysis, protein cristallization, elaborating novel emulsions,…

I il lIsmagilov et al(Chicago University)

AN EXAMPLE OF AN INTERESTING PROBLEM : REDUCING THE DROP SIZE OF AN EMULSION BY USING DIGITAL MICROFLUIDICS TECHNOLOGYTECHNOLOGY

10m

Suppose we are willing to reduce the dropSuppose we are willing to reduce the drop size of an emulsion

One possibility is to cut the drops one by onein a microfluidic systemy

Water dropWater drop

10m

U

L0

u l L0uU

DIFFERENT REGIMES, FOR INCREASING SIDE FLOWS

WHITE = WATER DROP, BLACK (IN THE CHANNEL) = HEXADECANE

We would like also to control the drop break-up

Lf VLf VS

Fingerge

Curve suggested by

To break or not to breaksuggested bythe theory (Navot, 1999)

BREAKING

VS( / )(m/s)

NONBREAKING

L ( )

BREAKING0 1 2 3 4 5 x102

Lf (m) Laure MENETRIER, 2004

Liquid-liquid flows in microsystems may be used to produceLiquid-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.