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freeing them back into solution. Whichever way the students charge their LGNs, ion exchange removes a few but not all of the extraneous proteins.


The third step is gel filtration, in which a high-pressure liq- uid chromatograph pushes a sample through a two- or three- foot column containing beads of gel that sieve the various mol- ecules by their sizes. As long as the machine works well, the method works well. Temperature, pressure, electrical charge, and other variables limit or enhance each method’s effectiveness. And that can only be checked after the fact, by running an electrophoresis gel. An ideal gel would be a nearly clear sheet, with bars showing only the LGN molecules. The team didn’t achieve that perfect purity, of course, but Hyde says they got close to their 95 percent target. And they honed the three-step protocol for getting there. When they get a pure enough sample, they’ll move on to


crystallization, suspending a drop of LGN solution over a pool of liquid and letting vapor exchange gradually superconcentrate


Perfect, since the team is researching research—that is, seek- ing ways to make lab work faster, easier, and cheaper. Imagine a doctor in a remote or devastated region, needing to test pa- tients’ blood for infections or toxins but without access to the glassware, reagents and solvents, and big, high-tech machinery of a good laboratory. That doctor’s best hope is the very new but quickly evolving “lab on a chip” technology: A plastic wafer no bigger than a Triscuit is etched with tiny channels and reser- voirs; when an infinitesimal drop of fluid is injected, the chip operates as an automated lab, moving the fluid from one “sta- tion” to the next for processing and analysis. Frederick says electrophoresis, a multistep process to separate various protein molecules, can already be done on such a chip. And she’s work- ing hard to make advances, experimenting simultaneously with different plastics, microcoatings, and channel depths, as well as ways of moving and filtering fluids.


Leland Martin ’14 is making chips from plexiglass, while Brenda Olivo ’14 works with thinner plastic—old overhead- transparency film, to be exact. They use the lab’s commercial laser etcher to cut a tiny channel and two wells, then they fuse on another chip as a cover. For a while Martin tries “slight- ly melting the surface of the chip and letting it cool before finishing the fus- ing, which has been shown to prevent tiny air bubbles from forming.” He tests the chip by zapping a drop of ionized fluid with electricity and checking its flow to the other end of the chip’s channel. “If we get no cur- rent there, or if we see it spike, we know the fluid has leaked out some- where, possibly due to these bubbles,” he says.


PROTEIN PURIFIERS ALEX ZANETTI ’13, PROF. BRANDY SREENILAYAM, AND MICHAEL HYDE ’13


the drop, over days or weeks, until the LGN molecules form 3D structures that they can see and chart with x-ray crystallography. It’s painstaking, but the students agree, “It’s cool to be real scientists. And it’s nice to think that, down the line, our work might contribute to cancer research.”


HONEY, I SHRUNK THE LAB


Last spring three promising freshmen, just finishing Skidmore’s introductory chemistry course, accepted their professor’s invita- tion to do summer research in an innovative field. Their inex- perience wasn’t a concern, because “our curriculum never specifically covers this kind of work anyway,” says chemist Kim Frederick. “I started them with take-home readings, and we did a daylong ‘research boot camp.’”


16 SCOPE WINTER 2012


Through many trials, he and Olivo learn that etching smaller-di- ameter tubes and larger wells works the best. They also determine which combination of settings—for laser


power, speed, and number of passes—tends to create the smoothest channels. To measure depth and width, they in- spect the chips under a scanning electron microscope. As fine as lasers are, the huge magnification of the SEM shows the inte- rior surfaces of the channels to be surprisingly rough. Seeking the best lamination and sealing protocols for the thin chips, Olivo (with high-schooler Denise Croote for four weeks) is testing them with Schweppes tonic water—handy, she explains, because “quinine fluoresces in ultraviolet light, so we can easily see any leaks.” After concentrating the tonic water, she uses a micropipette to inject a drop of it into the chip. To pressure-test it, she epoxies a nozzle from a nitrogen-gas tank to the chip’s port, cures the epoxy in an oven, and then opens the gas valve. At first, she says, “what fails when we apply pressure is the


GARY GOLD


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