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© Cambridge University Press 2010 Microfluidics. Microfluidics is the science of designing, manufacturing, and formulating devices and processes that.

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Presentation on theme: "© Cambridge University Press 2010 Microfluidics. Microfluidics is the science of designing, manufacturing, and formulating devices and processes that."— Presentation transcript:

1 © Cambridge University Press 2010 Microfluidics

2 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 liter) or picoliters (symbolized pl and representing units of liter).

3 Why use microfluidics?

4 Sample savings – nL of enzyme, not mL Faster analyses – can heat, cool small volumes quickly Integration – combine lots of steps onto a single device Novel physics – diffusion, surface tension, and surface effects dominate This can actually lead to faster reactions! Why use microfluidics?

5 Motivation for Microfluidics Test tubes Robotics Microfluidics Automation Integration Miniaturization Automation Integration Miniaturization Automation Integration Miniaturization

6 Timeline of the evolution of microfluidic technology

7 Microfluidics

8 Microfluidics field of application

9 © Cambridge University Press 2010 The behavior of fluids at the microscale Effects of micro domain lamniar flow surface tension electrowetting diffusion

10 Laminar flow Opposite to turbulent flow Low Reynold’s number (inertial to viscous forces) Flow follows certain paths Mixing typically does not occur Predict the position of a particle

11 Laminar flow

12 Many microfluidic systems create flows with no stirring. Physics of Mixing When 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

13 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

14 Molecules in the interiour of a liquid Molecules at the surface of a liquid Because of the increased number of interactions, molecules in the bulk of solution are at a lower energy state than those on the surface. Surface Tension Molecules in any medium experience an attractive force with other molecules. Mainly hydrogen bonds for polar molecules Van der Waals forces for other molecules Imbalance of this attractive force at an interface leads to surface tension

15 Capillary Action Capillary 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

16 Electrowetting Electrical modulation of the solid-liquid interfacial tension No Potential A droplet on a hydrophobic surface originally has a large contact angle. Applied Potential The droplet’s surface energy increases, which results in a reduced contact angle. The droplet now wets the surface.

17 Microfluidics Continuous-flow : Permanently etched microchannels, micropumps and microvalves Digital microfluidic : Manipulation of liquids as discrete droplets Biosensors : Optical: SPR, Fluorescence etc. Electrochemical: Amperometric, Potentiometric etc. Mixing: Static, Diffusion Limited Multiplexing

18 Material for the fabrication of microfluidic channels Silicon/ Si compounds Classical MEMS approach Etching involved Polymer/ plastics New methods Easy fabrication

19 Test 1 Test 2 Test 1 Test 2 Test 3 Test 4 Test 3 Test 4

20 Sample Chip Design We start with a chip design. Below is a simple sample design that we’ll be using as an example. Top View Side View Peristaltic Pump 70µm x 7µm Channel 70µm x 1µm Channel Hole-Punched Inlet

21 Fabrication by laser abalition Micromachining of silicon and glass

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

23 Polymers Inexpensive Flexible Easily molded Surface properties easily modified Improved biocompatibility

24 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 carcinogen

25 Polydimethylsiloxane (PDMS) Silicon-based organic polymer Non toxic Non flammable Gas permeable Most organic solvents can diffuse and cause it to swell

26 Teflon Polytetrafluoroethylene (PTFE) Synthetic fluoropolymer Non reactive Fluorinated Ethylene Propylene (FEP) Excellent electrical properties Flam resistant Excelent chemical resistance

27 Why Teflon Excellent chemical resistance High temperature tolerance Low gas permeability

28 Replica molding

29 Embossing

30 Injection Molding

31 Laser Ablation

32 Fabrication of nanofluidic with electrospun nanofibers

33 Nanofluidics is the study of the behavior, manipulation, and control of fluids that are confined to structures of nanometer (typically 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 wall May effect changes in thermodynamic properties and May also alter the chemical reactivity of species at the fluid-solid interface Nanofluidics

34 Flow behavior in nanofluidics

35 Nanocircuitries : Examples of NEMS

36 Micro Total Analysis system (uTAS)

37 Components Sample injection Puming Sepration Mixing Reaction Trasport Detection

38 Microfluidic flow

39 Pumps

40 Micromixer

41 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

42 Detection

43 Integrated microfluidic devices for DNA analysis Polymerase chain reaction (PCR) Integrated PCR and separation based detection Integrated DNA hybridization Devices for separation based detection General capillary electrophoresis Devices for cell handling, sorting and general analysis Cell handling and cytometry Devices for protein based applications Protein digestion, identification and synthesis Integrated devices for chemical analysis, detection and processing Integrated microreactors Chemical detection and monitoring devices Integrated microfluidic devices for immunoassay Microfluidic application

44 44 Devices for miniaturized PCR PCR the most widely used process in biotechnology for DNA fragments amplification Polymer devices for continuous-flow PCR

45 Summary of microfluidic motivation

46 Challenges with Lab-on-Chip

47

48 Application areas

49 What 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 the chip itself. These may include flow control, pumping, separations where necessary, and even detection.

50 LoC Microarray Microfluidics DNA Protein Cell Fluid handling Sample precondition Mixing Reaction Separation Pumping Concentration Dilution Extraction Active Mixer Passive Mixer Chemical Enzymatic Immunoassay Electrophoresis Biochips

51

52 Some companies

53 Lab-on-Chip for developping countries

54 Point of care (POC)

55 The Not-so-Distant Future PDA ?? Paramount

56


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