Microfluidics – A Primer

BITS EmbryoChemical Engineering Lecture

Ketan “Kittu” Bhatt(97 A1)

Post Doc, Material Science & Engineering University of Illinois at Urbana-Champaign

Ph. D., Chemical & Biomolecular EngineeringNorth Carolina State University

Outline• What are microfluidics & lab-on-a-chip systems?

• Why microfluidics?

• Some concepts

• Applications

Wikipedia: (www.wikipedia.org)• Microfluidics deals with the behavior, precise control and manipulation of microliter and nanoliter volumes of fluids• Lab on Chip - Devices that integrate (multiple) laboratory functions on a single chip of only millimeters to a few square centimeters in size that are capable of handling extremely small fluid volumes down to less than picoliters

Fluidics & Lab-on-chip systems

Advantages:- Low cost - Reduced sample & reagent- High throughput consumption- Faster analysis - Extensive parallel architectures- Compact design - Reliability- Ease-of-use

Entirely new techniques might become available opening up possibilities for new experiments and innovations not possible by traditional

methods

Mask

Photolithography: Fabrication of fluidic channels

PhotoresistGlass

Glass is coated with a layer of photoresist

After the remaining photoresist surface have been removed, the top plate can be attached eg. by thermal bonding

An appropriate etchant, eg. HF/NH4F, is used to etch the channel pattern

The exposed photoresist is removed

The channel pattern is transferred via a mask and radiation source eg. UV light

UV Light

Soft lithography: Stamp Fabrication

Xia & Whitesides, Annu. Rev. Mater. Sci. 28, 153 (1998)

Schematics of the procedure for fabricating PDMS stamps from a master having relief

structures on its surface

Press on a surface, connect tubing

(Slide courtesy: Orlin Velev)

Liquid transport: Pressure driven Laminar flow

avgLV

ReL = Length scale, Diameter

Vavg = Average fluid velocity

= Density = viscosity

Typical values:Channel width, L = 1 mmAverage fluid velocity = 1 mm/sDensity = 1000 kg/m3

Viscosity = 0.001Ns/m2

Re = 1

(strc.herts.ac.uk/mm/)

Liquid transport: Electroosmotic pumping

The counterions next to the wall move with the field: plug flow

(Slide courtesy: Orlin Velev)

Fluidics: What principles are used to make liquids and particles move?

Comparison of fluid- and particle-propulsion methods in microfluidics

Huang et al., Anal. Bioanal. Chem. 372, 49 (2002)

(Slide courtesy: Orlin Velev)

Microfluidic chips & devices: examples

Uses include:

SeparationsChemical analysisChemical sensingMicroscale synthesisCombinatorial synthesisDrug screening Genetic fingerprintingGenetic researchCell screeningClinical diagnosticsMaterials researchCatalysis researchMicrofabricationPhotonicsElectronics

(Slide courtesy: Orlin Velev)

DNA Arrays

DNA pairing basics

(Slide courtesy: Orlin Velev)

Human genome contains ~ 30000 genes which encode more than 90000 RNA species and basic proteins. The possible mutations increase this number multiple fold.

Many genes work in combination with others, so understanding and using their function requires characterization of multiple genes.

Massively parallel detection and analysis is required.

The amount of reagents and samples is small and they are very expensive so it all needs to be done on a miniature scale.

DNA array chips – Basic principles

Fluorophore

Immobilized fragmentsMatch

Hybridization(Slide courtesy: Orlin Velev)

Basics of what’s on the surface of a DNA chip

DNA array chips – Basics

(Slide courtesy: Orlin Velev)

Bioarrays: Future of bioresearch and medicine

Thousands of genes checked on chip

Clinical diagnosticsGenetic fingerprinting Drug screening Genetic researchCell research

(Slide courtesy: Orlin Velev)

Droplet – Based Microfluidics

Dielectrophoretic chips with suspended microdroplets: Principle of operation

Liquid – liquid chip system without walls or channels

Velev, Prevo and Bhatt, Nature 426, 515 (2003)

Droplet equilibrium positions

Droplet-chip geometry to scale.Finite element electrostatic calculations using conformal triangles (Femlab)

High intensity regions

Controlled parallel transport of multiple droplets

300 V, 300 Hz

gold nanoparticles2% white polystyrene latex2% pink fluorescent latex

0.2% white latex

- 500 V DC

0.2% white polystyrene latex0.2% pink fluorescent latex

On-chip microdroplet engineering

Separationat the top

Separationat the bottom

Synthesisof supraparticles

Mixing Reaction

Microbioassays

Mixing of droplets of aqueous suspension and encapsulation inside oil

droplet

gold nanoparticles

latex in water

dodecane

DodecaneFoilWaterDodecaneWaterFoil ///

Chemical reactions and precipitations

3 CaCl2 + 2 K2HPO4 Ca3(PO4)2 + 4 KCl + 2 HCl

FeSO4 + 2 NaOH Fe(OH)2 + Na2SO4

Simultaneous “eyeballs” syntheses in multiple on-chip droplet microreactors

Massive parallelization possible

Gold – latex anisotropic assemblies

1 min 7 min 11 min 18 min 50 min

Time

Acknowledgements

Orlin VelevJennifer Lewis

BITS Embryo TeamNitish Korula

Velev Group membersLewis Group members

Contact informationketan.bhatt@gmail.com