Microfluidics

Microfluidics 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?

Why use microfluidics? 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!

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

Timeline of the evolution of microfluidic technology

Microfluidics

Microfluidics field of application

The behavior of fluids at the microscale Effects of micro domain lamniar flow surface tension electrowetting diffusion

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

Laminar flow

Physics of Mixing Many 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 microchannel The widths of the fluid streams are algebraic functions of the flow rates

Microfluidic Mixing 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

Surface Tension Because 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 molecules Van der Waals forces for other molecules Molecules in the interiour of a liquid Molecules at the surface of a liquid Imbalance of this attractive force at an interface leads to surface tension

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

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.

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

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

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

Sample 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 View 70µm x 7µm Channel 70µm x 1µm Channel Peristaltic Pump Side View Hole-Punched Inlet

Fabrication by laser abalition Micromachining of silicon and glass

Photolithography Mask Positive Resist Negative Resist 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

Polymers Inexpensive Flexible Easily molded Surface properties easily modified Improved 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 carcinogen

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

Teflon Polytetrafluoroethylene (PTFE) Synthetic fluoropolymer Non reactive Fluorinated Ethylene Propylene (FEP) Excellent electrical properties Flam 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 Nanofluidics 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 wall May effect changes in thermodynamic properties and May also alter the chemical reactivity of species at the fluid-solid interface

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

Microfluidic application 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

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 areas

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.

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

Some companies

Lab-on-Chip for developping countries

Point of care (POC)

The Not-so-Distant Future 2008 PDA 2308?? Paramount