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Lab making miniaturized plumbing system by Dick Peterson Public Relations It’s not the sort of thing likely to be found at a medical school. But MUSC’s microfabrication lab is here and actively developing methods to produce microfluidic devices for proteomic analysis.   “That’s miniaturized plumbing,” said Department of Pharmacology’s Dan Knapp, Ph.D. His explanation caters to a layman’s focus until it’s understood that he’s referring to tubing so fine that it looks more like a strand of hair than a tube.   Dr. Dan Knapp, in front of his lab's clean room module, displays a silicon  chip which was fashioned into a mold to make a prototype of a microfluidic device. Microfluidic devices developed in the clean room will allow the use of smaller samples in proteomic analysis. Described as microscopic plumbing, the devices are developed in an absolutely clean environment to avoid clogs from foreign material in the channels. “Everyone knows about microelectronics,” Knapp said. “There’s a new field of microfluidics which is using a lot of the same technology that is used for electronic microchips but basically making miniaturized plumbing systems.   Among the driving forces in development of microfluidic devices are ink jet printers and miniaturized analytical chemistry systems—sometimes called “a lab on a chip,” which promise point-of-care diagnostics.   But Knapp, who heads the NIH-funded proteomics center at MUSC, has other plans for microfluidic devices. “What we want to do is take advantage of some of these microfluidic devices to improve the analytical methodology for proteomics and allow us to use smaller and smaller samples. This has always been the quest in the biological and analysis areas.”   Knapp explained that one of the big problems in proteomics analysis “is that the stuff you’re looking to see are really small amounts of proteins that are present in very complex mixtures.” So small and so complex, in fact, that Knapp compares them to a few blades of grass in a forest.   “The big challenge there is to take these very complex mixtures and separate them, spread them out enough so that you can see the little things unobstructed by the big things,” Knapp said. “By making these separation systems in a microfluidic format, we can do things that are not practical to do in conventional hardware.”   Knapp’s proteomics lab currently uses comparatively large liquid chromatography columns in its conventional hardware. These columns cost several hundred dollars apiece, and if they become clogged, they have to be replaced at several hundred dollars apiece. By making them on a microchip format, a hundred columns can be manufactured as easily as one.   “It’s a simple process. What we’re doing is actually making chromatography columns on chips by a lithography process whereby we polymerize a porous monolith in a channel rather than individually pack channels with small particles as is done in conventional column production.” Knapp said that although the microfabrication lab is working on only two, three or four columns to a chip, their effort is to work out the methodology. Eventually 100 columns will go onto one chip, “where to try to plumb up 100 columns in conventional hardware would be totally impractical.”    To make microfluidic devices, “We print patterns and then we either mold plastic over these patterns or take these patterns and emboss them with heat into a plastic device. So we make the master with lithography and use that to produce the devices with a hot embossing press.” The wafer of plastic with a pattern of grooves in it is then sealed with another piece of plastic on top of it to create closed channels. The fine tubing is used in conventional capillary plumbing systems. It is largely replaced by the fine channels in the microchip, but sometimes used to make connections to the chip.   Microfabrication laboratories are the domain of engineering schools where the focus is microelectronics with clean rooms and all the equipment. “We didn’t have any of that, so we had to build from scratch.”   Knapp’s solution was initially to build a homemade clean room, which served to get started in the area. He later bought a modular clean room that could be purchased and installed at a fraction of the cost of permanent clean room construction. A bonus, Knapp said, will come when the university begins renovating the third-floor Basic Science space where the module is now located. It will be dismantled and re-installed elsewhere at a fraction of the cost of demolishing and rebuilding a permanent clean room.   The microfabrication clean room facility is also being used by a Clemson researcher to build devices where he moves cells with a laser beam in microfluidic channels.       Friday, April 22, 2005 Catalyst Online is published weekly, updated as needed and improved from time to time by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. Catalyst Online editor, Kim Draughn, can be reached at 792-4107 or by email, catalyst@musc.edu. Editorial copy can be submitted to Catalyst Online and to The Catalyst in print by fax, 792-6723, or by email to petersnd@musc.edu or catalyst@musc.edu. To place an ad in The Catalyst hardcopy, call Community Press at 849-1778.