Jack Pevenstein
Technology Partnership Office
301-975-5519
nisttech@nist.gov
100 Bureau Drive, M/S 2200
Gaithersburg, MD, 20899
Study Biological Processes at the Cellular Level Using Microfluidics
Generates multiple chemical gradients simultaneously within a microfluidic chamber. Enables the study of simultaneous diffusion and mixing of drugs or chemicals in applications where molecular gradients play an important role. With more than three ports to introduce fluids, this device eliminates convection in chemical/molecular transport to allow controlled and stable diffusion patterns to be examined. Diffusion gradients permit chemical molecules to move in and out of the cells naturally and eliminate the risk of shear stresses, commonly produced by currents, which could cause the cells to rupture or behave abnormally. An independent gradient forms for each substance that remains constant as long as flow into the system does not change. A blend of concentrations occurs where the gradients meet, and the combination in any single location within the blend is distinctly different from all other locations.
The mixing area is the pin-sized chamber bordered by three holes in the center of the top layer. (Credit: G. Cooksey, NIST)
For each of the three dyes injected into the NIST microfluidic palette, an independent gradient forms that remains constant as long as flow into the system does not change. Overlapping the three gradients results in a blend of dye concentrations, but the combination of colors in any single location is distinctly different from all others location. (Credit: J. Atencia, NIST)
Credit: NIST
The invention consists in a microfluidic device that generates multiple chemical gradients simultaneously within a microfluidic chamber. The chemical gradients are generated without convection, only by diffusion, and they can be maintained over long periods of time, or be modified dynamically.
Description of the microfluidic device:
The device consists of a main microfluidic chamber where there is no convection (no flow movement) and where mixing is done by diffusion. The chamber is accessed by "convection-diffusion units". A convection-diffusion unit consists of a microchannel that has matched flow at its inlet and outlet; thus, even if the microchannel has an opening to the microfluidic chamber, all the liquid that is introduced through the inlet has to come out through the outlet (conservation of mass) making it impossible to get into the chamber except by diffusion. If the inlet and outlet of each convection-diffusion unit were not exactly matched, difference in pressure among microchannels would generate convection through the chamber ruining the diffusion-only premise inside the microfluidic chamber.
The convection-diffusion units decouple convection in the microchannels from diffusion in the chamber. Therefore, if a solution of a drug is introduced through inlet 1 and retrieved through outlet 1, the concentration of this drug at the opening 1 to the chamber will be the same as at the channel. If only buffer flows through channels 2 and 3, the concentration of the drug at the openings 2 and 3 necessarily will be zero. Thus, in the microfluidic chamber, opening 1 works as a diffusive source of the drug, while opening 2 and 3 work as sinks, and all the space in between (after some transient time) will have a static gradient in concentration of the drug.
J. Atencia, J. Morrow and L.E. Locascio. The microfluidic palette: A diffusive gradient generator with spatio-temporal control. Lab on a Chip. Posted online June 22, 2009.
Files are in Portable Document Format (PDF). You may download a reader at http://get.adobe.com/reader/