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).
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! Why use microfluidics?
Motivation for Microfluidics Test tubes Robotics Microfluidics Automation Integration Miniaturization Automation Integration Miniaturization Automation Integration Miniaturization
Timeline of the evolution of microfluidic technology
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
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
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 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
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 Biosensors : Optical: SPR, Fluorescence etc. Electrochemical: Amperometric, Potentiometric etc. Mixing: Static, Diffusion Limited Multiplexing
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 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
Fabrication 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 Mask Positive Resist Negative Resist Photolithography
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
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 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
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
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 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
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.
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