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Microfluidics Cambridge University Press 2010Microfluidics Microfluidics is the science of designing, manufacturing, and formulating devices and processes that deal with volumes of fluid on the order of nanoliters (symbolized nl and representing units of 10 -9 liter) or picoliters (symbolized pl and representing units of 10 -12 liter).

Why use microfluidics?

Sample savings nL of enzyme, not mLFaster analyses can heat, cool small volumes quicklyIntegration combine lots of steps onto a single deviceNovel physics diffusion, surface tension, and surface effects dominateThis can actually lead to faster reactions!Why use microfluidics?Motivation for Microfluidics

Test tubesRoboticsMicrofluidicsAutomationIntegrationMiniaturizationAutomationIntegrationMiniaturizationAutomationIntegrationMiniaturization

Timeline of the evolution of microfluidic technology

Microfluidics Microfluidicsfield of application

The behavior of fluids at the microscale Effects of micro domainlamniar flowsurface tensionelectrowettingdiffusion

Cambridge University Press 2010Laminar flow

Opposite to turbulent flow Low Reynolds number (inertial to viscous forces) Flow follows certain pathsMixing typically does not occurPredict the position of a particle Laminar flow

Many microfluidic systems create flows with no stirring.

Physics of MixingWhen there is very little mixing, multiple streams of fluid can be used to pattern the chemical species inside a microchannel

The widths of the fluid streams are algebraic functions of the flow rates

Low mixing enables patterning, but high mixing is required for chemical assays

Mixing is enhanced by stirring, or increasing the interfacial area between regions of different scalar concentration, i.e., shortening diffusion length scales

Microfluidic Mixing

Molecules in the interiour of a liquidMolecules at the surface of a liquidBecause of the increased number of interactions, molecules in the bulk of solution are at a lower energy state than those on the surface.Surface TensionMolecules in any medium experience an attractive force with other molecules.Mainly hydrogen bonds for polar moleculesVan der Waals forces for other molecules

Imbalance of this attractive force at an interface leads to surface tension

Capillary ActionCapillary action refers to the movement of liquid through thin tubes, not a specific force.Several effects can contribute to capillary action, all of which relate to surface tension

ElectrowettingElectrical modulation of the solid-liquid interfacial tension

No PotentialA droplet on a hydrophobic surface originally has a large contact angle.

Applied PotentialThe droplets surface energy increases, which results in a reduced contact angle. The droplet now wets the surface.16MicrofluidicsContinuous-flow : Permanently etched microchannels, micropumps and microvalvesDigital microfluidic : Manipulation of liquids as discrete droplets

Biosensors: Optical: SPR, Fluorescence etc. Electrochemical: Amperometric, Potentiometric etc.

Mixing: Static, Diffusion LimitedMultiplexing

17Material for the fabrication of microfluidic channels

Silicon/ Si compoundsClassical MEMS approachEtching involvedPolymer/ plasticsNew methodsEasy fabricationTest 1Test 2Test 1Test 2Test 3Test 4Test 3Test 4

Sample Chip DesignWe start with a chip design. Below is a simple sample design that well be using as an example.Top ViewSide ViewPeristaltic Pump70m x 7m Channel70m x 1m ChannelHole-Punched Inlet20Fabrication by laser abalition Micromachining of silicon and glass

There are two types of photoresist: Positive: Exposure to UV light removes resist Negative: Exposure to UV light maintains resist

MaskPositive ResistNegative ResistPhotolithography22PolymersInexpensiveFlexibleEasily moldedSurface properties easily modifiedImproved biocompatibility

Polymethyl methacrylate (PMMA) Often use as an alternative to glass Easily scratched Not malleable It can come in the form of a powder mixed with liquid methyl methacrylate, which is an irritand and possible carcinogenPolydimethylsiloxane (PDMS)

Silicon-based organic polymer Non toxic Non flammable Gas permeable Most organic solvents can diffuse and cause it to swell

TeflonPolytetrafluoroethylene (PTFE)Synthetic fluoropolymerNon reactive

Fluorinated Ethylene Propylene (FEP)Excellent electrical propertiesFlam resistant Excelent chemical resistance

Why Teflon

Excellent chemical resistance

High temperature tolerance

Low gas permeability

Replica molding

Embossing

Injection Molding

Laser Ablation

Fabrication of nanofluidic with electrospun nanofibers Nanofluidics is the study of the behavior, manipulation, and control of fluids that are confined to structures of nanometer (typically 1-100nm) characteristic dimensions (1nm = 109 m). Exhibit physical behaviors not observed in larger structures, such as those of micrometer dimensions and above, Increased viscosity near the pore wall May effect changes in thermodynamic properties and May also alter the chemical reactivity of species at the fluid-solid interface Nanofluidics Flow behavior in nanofluidics

Nanocircuitries :Examples of NEMS

Micro Total Analysis system (uTAS)Components Sample injection Puming Sepration Mixing Reaction Trasport Detection

Microfluidic flow

Pumps

Micromixer

Flow (electroosmotic and pressure driven)

Electroosmotic flow is developed in a capillary when the capillary has electrical charges, the fluids are electrolytes and external electric fields are applied

Detection Integrated microfluidic devices for DNA analysis Polymerase chain reaction (PCR) Integrated PCR and separation based detection Integrated DNA hybridization Devices for separation based detectionGeneral capillary electrophoresis Devices for cell handling, sorting and general analysisCell handling and cytometry Devices for protein based applicationsProtein digestion, identification and synthesis Integrated devices for chemical analysis, detection and processingIntegrated microreactorsChemical detection and monitoring devices Integrated microfluidic devices for immunoassayMicrofluidic application 44

Devices for miniaturized PCR PCR the most widely used process in biotechnology for DNA fragments amplification

Polymer devices for continuous-flow PCR

Summary of microfluidic motivation

Challenges with Lab-on-Chip

Application areasWhat are the main types of biochips?Passive (array):all liquid handling functions are performed by the instrument. The disposable is simply a patterned substrate.

Active (lab-on-chip, m-TAS):some active functions are performed by thechip itself. These may include flow control, pumping, separations where necessary, andeven detection.

49LoCMicroarrayMicrofluidicsDNAProteinCellFluid handling

Sample precondition

Mixing

Reaction

SeparationPumpingConcentrationDilutionExtractionActive MixerPassive MixerChemicalEnzymaticImmunoassayElectrophoresisBiochips

Some companies

Lab-on-Chip for developping countriesPoint of care (POC)

The Not-so-Distant Future

PDA2008

2308??Paramount