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Nanotech News
Simultaneous Synthesis and Screening in a Microfluidics Device In the quest for new methods to synthesize large numbers of drug leads, medicinal chemists are increasingly turning to microfluidics as a means of performing dozens of chemical reactions using minute quantities of chemical reagents. At the same time, drug developers are turning to microfluidics as a means of rapidly screening dozens if not hundreds of drug candidates for a desired biological activity. Now, investigators at the NanoSystems Biology Cancer Center (NBCC), one of eight Centers for Cancer Nanotechnology Excellence funded by the National Cancer Institute, have demonstrated that they can merge these two applications into a single microfluidics device. Hsian-Rong Tseng, Ph.D., Hartmuth Kolb, Ph.D., and Michael Phelps, Ph.D., all at the University of California, Los Angeles, and all members of the NBCC, led the team of investigators that is developing methods to drive down the time and cost of synthesizing and identifying new anticancer agents. This research is published in the journal Angewandte Chemie International Edition. The device that the researchers designed can synthesize and screen 32 compounds in parallel nanoscale reaction chambers. To synthesize these potential drug candidates, the investigators use a chemical reaction approach known as “click chemistry.” Click chemistry mimics some of the methods that nature relies on to join two molecules to make a single, larger molecule, using the target protein itself to guide the creation of molecules that might alter the biological function of that protein. A computer-controlled interface directs the flow of nanoliter volumes of chemical reactants though various metering pumps and mixers and into the appropriate reaction vessels. Using this device, the investigators can prepare a 32-compound library of potential drug candidates in 30 minutes and complete the screening for protein binding in 40 hours. For sake of comparison, the research team showed that their microfluidics device generated the same results as did traditional parallel chemical synthesis and screening methods that rely on larger 96-well microtitre plates. This work, which was supported in part by the National Cancer Institute’s Alliance for Nanotechnology in Cancer, is detailed in a paper titled, “Integrated microfluidics for parallel screening of an in situ click chemistry library.” Investigators from Siemens Medical Solutions USA also participated in this study. An abstract of this paper is available through PubMed. |
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