2MicrofluidicsMicrofluidics 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 liter) or picoliters (symbolized pl and representing units of liter).
4Why use microfluidics? Sample savings – nL of enzyme, not mL Faster 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!
5Motivation for Microfluidics AutomationIntegrationMiniaturizationTest tubesAutomationIntegrationMiniaturizationRoboticsAutomationIntegrationMiniaturizationMicrofluidics
6Timeline of the evolution of microfluidic technology
12Physics of MixingMany microfluidic systems create flows with no stirring.When there is very little mixing, multiple streams of fluid can be used to pattern the chemical species inside a microchannelThe widths of the fluid streams are algebraic functions of the flow rates
13Microfluidic MixingLow mixing enables patterning, but high mixing is required for chemical assaysMixing is enhanced by “stirring”, or increasing the interfacial area between regions of different scalar concentration, i.e., shortening diffusion length scales
14Surface TensionBecause of the increased number of interactions, molecules in the bulk of solution are at a lower energy state than those on the surface.Molecules in any medium experience an attractive force with other molecules.Mainly hydrogen bonds for polar moleculesVan der Waals forces for other moleculesMolecules in the interiour of a liquidMolecules at the surface of a liquidImbalance of this attractive force at an interface leads to surface tension
15Capillary 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
16ElectrowettingElectrical modulation of the solid-liquid interfacial tensionNo PotentialA droplet on a hydrophobic surface originally has a large contact angle.Applied PotentialThe droplet’s surface energy increases, which results in a reduced contact angle. The droplet now wets the surface.
17MicrofluidicsContinuous-flow : Permanently etched microchannels, micropumps and microvalvesDigital microfluidic : Manipulation of liquids as discrete dropletsMultiplexingMixing: Static, Diffusion LimitedBiosensors:Optical: SPR, Fluorescence etc.Electrochemical: Amperometric, Potentiometric etc.
18Material for the fabrication of microfluidic channels Silicon/ Si compoundsClassical MEMS approachEtching involvedPolymer/ plasticsNew methodsEasy fabrication
20Sample Chip Design Top View Side View We start with a chip design. Below is a simple sample design that we’ll be using as an example.Top View70µm x 7µm Channel70µm x 1µm ChannelPeristaltic PumpSide ViewHole-Punched Inlet
21Fabrication by laser abalition Micromachining of silicon and glass
22Photolithography Mask Positive Resist Negative Resist There are two types of photoresist:Positive: Exposure to UV light removes resistNegative: Exposure to UV light maintains resistMaskPositive ResistNegative Resist
24Polymethyl methacrylate (PMMA) Often use as an alternative to glassEasily scratchedNot malleableIt can come in the form of a powder mixedwith liquid methyl methacrylate, which is anirritand and possible carcinogen
25Polydimethylsiloxane (PDMS) Silicon-based organic polymerNon toxicNon flammableGas permeableMost organic solvents can diffuse andcause it to swell
26Teflon Polytetrafluoroethylene (PTFE) Synthetic fluoropolymer Non reactiveFluorinated Ethylene Propylene (FEP)Excellent electrical propertiesFlam resistantExcelent chemical resistance
27Why Teflon Excellent chemical resistance High temperature tolerance Low gas permeability
32Fabrication of nanofluidic with electrospun nanofibers
33NanofluidicsNanofluidics is the study of the behavior, manipulation, and control of fluids that are confined to structures of nanometer (typically 1-100 nm) characteristic dimensions (1 nm = 10−9 m).Exhibit physical behaviors not observed in larger structures, such as those of micrometer dimensions and above,Increased viscosity near the pore wallMay effect changes in thermodynamic properties andMay also alter the chemical reactivity of species at the fluid-solid interface
41Flow (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
43Microfluidic application Integrated microfluidic devices for DNA analysisPolymerase chain reaction (PCR)Integrated PCR and separation based detectionIntegrated DNA hybridizationDevices for separation based detectionGeneral capillary electrophoresisDevices for cell handling, sorting and general analysisCell handling and cytometryDevices for protein based applicationsProtein digestion, identification and synthesisIntegrated devices for chemical analysis, detection and processingIntegrated microreactorsChemical detection and monitoring devicesIntegrated microfluidic devices for immunoassay
44Devices for miniaturized PCR PCR the most widely used process in biotechnology for DNA fragments amplificationPolymer devices for continuous-flow PCR
49What are the main types of biochips? Passive (array):all liquid handling functions are performed bythe instrument. The disposable is simply apatterned 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.
50Biochips DNA Protein Microarray Cell Fluid handling Pumping LoC MicrofluidicsDNAProteinCellFluid handlingSample preconditionMixingReactionSeparationPumpingConcentrationDilutionExtractionActive MixerPassive MixerChemicalEnzymaticImmunoassayElectrophoresis