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The new DEAL A novel protein display technology captures DNA, proteins, and cells on the same microfluidic chip.
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of the University of Illinois Chicago. cause DNA is much more stable to the s modern science unravels the “[With] other types of arrays, scientists harsh PDMS casting process than promolecular basis of disease, cancer are still pioneering efforts, so this [tech- teins are, the chips can be imprinted diagnosis is rapidly moving from examnique] has the intriguing opportunity of with microfluidic channels; this shrinks ination of gross tissue pathology to marrying the challenging problem of the sample size and reagent volumes analyses of the proteins, mRNAs, and creating protein or cell arrays with the and shortens the time required to conindividual cells of a suspected tumor. mature technology of oligo deposition duct an assay. As an example, an ELISA Current multiparameter tissue analysis and hybridization.” typically involves multiple steps carried combines a range of techniques, includout over several hours, but in ing microarray technology, this work the researchers perimmunohistochemical stainform the assay in a single ing, and western blot analystep in 10 minutes. Heath sis, all of which are carried explains that “the timescales out separately on distinct tisCell separation are really limited by diffusue samples. James Heath sion, and so people think of and colleagues at the CaliforCells nia Institute of Technology ELISA assays as being intrinGenomic and and the University of Califorsically slow, but they’re not. proteomic nia Los Angeles have now Within a flowing microflusignatures developed a technology to idics environment only the DEAL platform streamline this process by kinetics of the analyte capmerging all of these analyses ture process are important. The DEAL method uses DNA displayed on the surface of a chip to onto a single microfluidic As a result, the assays only capture antibodies specific for cells, proteins, and cDNAs. chip ( J. Am. Chem. Soc. take a few minutes.” 2007, 129, 1959–1967). The researchers also show According to Heath, a major chalProtein and DNA arrays use very that the DEAL method can sort cells lenge in any surface display technology different and noncompatible surface and, in a proof-of-principle experiment, is nonspecific binding, or biofouling. In chemistries to display their respective that they can indeed detect proteins, macromolecules, so they are rarely com- the case of DEAL, the researchers had complementary DNAs (cDNAs), and to worry about two potential biofouling cells on a single chip. “It’s a very, very bined on the same chip. Heath and coissues: promiscuous protein adsorption workers circumvented this problem by important extension of traditional diagand hybridization of noncomplementary nostics to look at panels of proteins or moving exclusively to DNA array technology. In their method, a DNA-encod- DNAs. With proteins, the researchers other molecules at the same time quanwere lucky. “We were kind of surprised ed antibody library (DEAL) is created titatively,” says Mark Sullivan of the to see just how good DNA itself was at by spotting single strands of DNA on a University of Rochester. “I can imagine avoiding nonselective adsorption of pro- that other people that see this are going surface by conventional methods. Complementary strands of DNA are attached teins,” says Heath. Avoiding DNA bioto want to go try this pretty quickly.” fouling was a little trickier. “If you take to antibodies specific for the protein, Heath says that they are currently extwo random DNAs out of a hat, typical- panding the DEAL method to detect nucleotide, or cell type of interest. The ly they will hybridize. They may melt at antibodies are allowed to bind to their proteins and mRNAs related to brain 15 °C, but they will hybridize,” Heath targets in solution and are then capand prostate cancer and to detect more tured on the chip’s surface by their explains. To sidestep this problem, the analytes on a single chip. “Right now in complementary DNA strands. The reresearchers used in silico calculations to a given assay . . . we can look at about sult is a single surface with proteins, generate a set of six truly orthogonal half a dozen proteins if we have the cells, or nucleic acids bound in distinct 18-mer DNAs. “We were able to calcuright antibodies and such. We want to locations. late [that] using about a week of combe able to double that every year,” he “There are many person-years invest- puter time,” says Heath, but “you just says. “It’s a pretty enabling technique, ed in creating or generating oligo ardo that once.” and so we’ve been pushing quite hard rays, so there’s a lot of success and maThe researchers demonstrate that a on many different avenues.” a turity with DNA arrays,” says Brian Kay —Jennifer Griffiths major advantage of DEAL is that be© 2007 AMERICAN CHEMICAL SOCIETY
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