Microfluidics – A Primer BITS Embryo Chemical Engineering Lecture Ketan “Kittu” Bhatt (97 A1) Post Doc, Material Science & Engineering University of Illinois at Urbana-Champaign Ph. D., Chemical & Biomolecular Engineering North Carolina State University

Outline What are microfluidics & lab-on-a-chip systems? Why microfluidics? Some concepts Applications Wikipedia: ( 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 Photoresist Glass 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/NH 4 F, 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 L = Length scale, Diameter V avg = Average fluid velocity  = Density  = viscosity Typical values: Channel width, L = 1 mm Average fluid velocity = 1 mm/s Density = 1000 kg/m 3 Viscosity = 0.001Ns/m 2 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: Separations Chemical analysis Chemical sensing Microscale synthesis Combinatorial synthesis Drug screening Genetic fingerprinting Genetic research Cell screening Clinical diagnostics Materials research Catalysis research Microfabrication Photonics Electronics (Slide courtesy: Orlin Velev)

DNA Arrays

DNA pairing basics (Slide courtesy: Orlin Velev)

 Human genome contains ~ genes which encode more than 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 fragments Match 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 diagnostics Genetic fingerprinting Drug screening Genetic research Cell 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 nanoparticles 2% white polystyrene latex 2% pink fluorescent latex 0.2% white latex V DC 0.2% white polystyrene latex 0.2% pink fluorescent latex

On-chip microdroplet engineering Separation at the top Separation at the bottom Synthesis of supraparticles Mixing Reaction Microbioassays

Mixing of droplets of aqueous suspension and encapsulation inside oil droplet gold nanoparticles latex in water  dodecane  

Chemical reactions and precipitations 3 CaCl K 2 HPO 4  Ca 3 (PO 4 ) KCl + 2 HCl FeSO NaOH  Fe(OH) 2 + Na 2 SO 4

Simultaneous “eyeballs” syntheses in multiple on-chip droplet microreactors Massive parallelization possible Gold – latex anisotropic assemblies 1 min 7 min 11 min 18 min50 min Time

Acknowledgements Orlin Velev Jennifer Lewis BITS Embryo Team Nitish Korula Velev Group members Lewis Group members Contact information