basic microfluidic concepts

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Basic Microfluidic Concepts A microfluidic device can be identified by the fact that it has one or more channels with at least one dimension less than 1 mm. Common fluids used in microfluidic devices include whole blood samples, bacterial cell suspensions, protein or antibody solutions and various buffers. Microfluidic devices can be used to obtain a variety of interesting measurements including molecular diffusion coefficients, fluid viscosity, pH, chemical binding coefficients and enzyme reaction kinetics. Other applications for microfluidic devices include capillary electrophoresis, isoelectric focusing, immunoassays, flow cytometry, sample injection of proteins for analysis via mass spectrometry, PCR amplification, DNA analysis, cell manipulation, cell separation, cell patterning and chemical gradient formation. Many of these applications have utility for clinical diagnostics. The use of microfluidic devices to conduct biomedical research and create clinically useful technologies has a number of significant advantages. First, because the volume of fluids within these channels is very small, usually several nanoliters, the amount of reagents and analytes used is quite small. This is especially significant for expensive reagents. The fabrications techniques used to construct microfluidic devices, discussed in more depth later, are relatively inexpensive and are very amenable both to highly elaborate, multiplexed devices and also to mass production. In a manner similar to that for microelectronics, microfluidic technologies enable the fabrication of highly integrated devices for performing several different functions on the same substrate chip. One of the long term goals in the field of microfluidics is to create integrated, portable clinical diagnostic devices for home and bedside use, thereby eliminating time consuming laboratory analysis procedures.

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Page 1: Basic Microfluidic Concepts

Basic Microfluidic ConceptsA microfluidic device can be identified by the fact that it has one or more channels with at least one dimension less than 1 mm. Common fluids used in microfluidic devices include whole blood samples, bacterial cell suspensions, protein or antibody solutions and various buffers. Microfluidic devices can be used to obtain a variety of interesting measurements including molecular diffusion coefficients, fluid viscosity, pH, chemical binding coefficients and enzyme reaction kinetics. Other applications for microfluidic devices include capillary electrophoresis, isoelectric focusing, immunoassays, flow cytometry, sample injection of proteins for analysis via mass spectrometry, PCR amplification, DNA analysis, cell manipulation, cell separation, cell patterning and chemical gradient formation. Many of these applications have utility for clinical diagnostics.

The use of microfluidic devices to conduct biomedical research and create clinically useful technologies has a number of significant advantages. First, because the volume of fluids within these channels is very small, usually several nanoliters, the amount of reagents and analytes used is quite small. This is especially significant for expensive reagents. The fabrications techniques used to construct microfluidic devices, discussed in more depth later, are relatively inexpensive and are very amenable both to highly elaborate, multiplexed devices and also to mass production. In a manner similar to that for microelectronics, microfluidic technologies enable the fabrication of highly integrated devices for performing several different functions on the same substrate chip. One of the long term goals in the field of microfluidics is to create integrated, portable clinical diagnostic devices for home and bedside use, thereby eliminating time consuming laboratory analysis procedures.

Basic Principles of Microfluidics

The flow of a fluid through a microfluidic channel can be characterized by the Reynolds number, defined as -

where L is the most relevant length scale, µ is the viscosity, is the fluid density, and Vavg is the average velocity of the flow. For many microchannels, L is equal to 4A/P where A is the cross sectional area of the channel and P is the wetted perimeter of the channel. Due to the small dimensions of microchannels, the Re is usually much less than 100, often less than 1.0. In this Reynolds number regime, flow is completely laminar and no turbulence occurs. The transition to turbulent flow generally occurs in the range of Reynolds number 2000. Laminar flow provides a means by which molecules can be transported in a relatively predictable manner through microchannels. Note, however,

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that even at Reynolds numbers below 100, it is possible to have momentum-based phenomena such as as flow separation. There are two common methods by which fluid actuation through microchannels can be achieved.

Pressure Driven Flow

In pressure driven flow, in which the fluid is pumped through the device via positive displacement pumps, such as syringe pumps. One of the basic laws of fluid mechanics for pressure driven laminar flow, the so-called no-slip boundary condition, states that the fluid velocity at the walls must be zero. This produces a parabolic velocity profile within the channel. Pressure driven flow can be a relative inexpensive and quite reproducible approach to pumping fluids through microdevices. With the increasing efforts at developing functional micropumps, pressure driven flow is also amenable to miniaturization.

Electrokinetic Flow

Another common technique for pumping fluids is that of electro-ösmotic pumping. If the walls of a microchannel have an electric charge, as most surfaces do, an electric double layer of counter ions will form at the walls. When an electric field is applied across the channel, the ions in the double layer move towards the electrode of opposite polarity. This creates motion of the fluid near the walls and transfers via viscous forces into convective motion of the bulk fluid. If the channel is open at the electrodes, as is most often the case, the velocity profile is uniform across the entire width of the channel. However, if the electric field is applied across a closed channel (or a back pressure exists that just counters that produced by the pump), a recirculation pattern forms in which fluid along the center of the channel moves in a direction opposite to that at the walls. In closed channels, the velocity along the centerline of the channel is 50% of the velocity at the walls.

Advantages: Microfluidics will truly revolutionize many critical aspects of our lives:

Allow quantitative measurement of small molecules, large proteins and nucleic acids at low concentrations in biological fluids rapidly and by anyone. 

Allow minimally trained personnel to perform chemical and biochemical analyses when and where they are needed.

o Medical practice for patient diagnosiso Epidemiology and biological threat surveillanceo Environmental monitoringo Agricultural (plants and animal) testingo Food safety

Reduce the cost of healthcare in the developed world by commoditizing a wide range of diagnostic tests  (as has been done for blood glucose testing) to the point

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where early and frequent screening for disease is economical, voluntary and ubiquitous

Bring sophisticated medical and agricultural diagnostics to low-resource settings—e.g., places in the developing world without the funds or infrastructure.