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Drug Discovery example. But MScreen can also accomplish other jobs, such as making and handling mixture plates for screening multiple com- pounds simultaneously. It shows you views of each well and the compounds contained within the well, with thumbnails of each compound's structure, to which is linked the complete information on the individual compounds. An MScreen author Richard Neubig, M.D., Ph.D., professor of pharmacology, and co-director of the Center for Chemical Genomics at the University of Michigan, says that MScreen also has a unique ability to handle compounds and extracts. "[This is useful] if you have an unknown mixture," said Dr. Neubig. "MScreen has a large collection of natural extracts. We can also link those to the constituents [of your mixture] once you've identified what the chemical constituents are. So we've got sub- stances and compounds, and you can link a compound well, or a compound structure, to a particular substance so that you can see how those fit." Mscreen also helps you keep track of chemicals' sources, using different sets of daughter plates made with different concen- trations, or made at different times. "If you order in a new stock of some- thing, we can keep good track of which lot it was, and we also can keep track of the different daughter plates," said Dr. Neubig. "We make sure that when we do a screen, we know exactly which daughter plate the com- pound came from. So if we see discrepancies between two assays on a single compound, we can track those easily to make sure there wasn't a difference in the two daughter plates that were used." MScreen also features a specially designed infrastructure for managing nucleic acid re- agents. "We have a very specific structure set up for the siRNAs, where we have links to sequences of the siRNAs in the collection, and links to the genes that are targeted by the siRNAs," continued Dr. Neubig. This framework within MScreen is also easily adaptable to work for shRNAs or mi- cro RNAs as well, he added. Errors and Quality Control Though automation is meant to prevent human error, it can also inadvertently result in more errors—which could have potential- ly profound effects on compound manage- ment. For example, even increases in sample throughput and plate densities in HTS can increase the frequency of errors. "[In addition to error frequency,] these technologies also introduce opportunities for [entirely] new types of errors, some of which may not be obvious until the technology is used routinely," said Pierre Baillargeon, compound manager at Scripps Florida. "At the same time, new technologies of- ten allow tighter integration between soft- ware and hardware automation, leading to reduced potential for human error." He recommended that tools for quality control and quality assurance be in place to One size fits few. check for errors that might originate from new technologies. "This means identifying bottle- necks and weaknesses in existing laboratory practices, and finding ways to mitigate error without negating the efficiency gains from the technology being used," said Baillargeon. For example, his group uses an automat- ed volume checking device to verify that the amount of solubilized sample in a container matches the electronic record of that sample. This eliminates the potential error that might result from discrepancies between actual sample amounts, and those recorded in the management system. To help prevent further errors, Baillargeon's group also developed a novel machine vision based instrument called the Plate Auditor, which automatically inspects plates for insuf- ficient volume, precipitate, and sample color. "By integrating this new instrument into our existing workflows, we have enabled er- rors to be detected and corrected much ear- lier in the sample lifecycle," said Baillargeon. "Detecting problems earlier in the sample lifecycle simultaneously reduces the cost of errors and increases the quality of data pro- duced downstream." The Plate Auditor was recently licensed by Brooks Life Science Sys- tems (www.brooks.com). Monitoring for Aggregates The issue of precipitates or aggregates in solutions is one that vexes nearly every lab. The Plate Auditor, cameras to look for pre- cipitates in samples, and devices to measure the amount of water in a DMSO solvent, are some solutions that researchers use. Robert Damoiseaux, scientific director of the Molecular Screening Shared Resource at UCLA's Jonsson Comprehensive Cancer Center, uses dynamic light scattering to look for particles or aggregates in solutions using 384 and 1,536 well plates. Wells containing particles are flagged for further inspection. "We use this for nanoformulations quite a bit," said Damoiseaux. "For example, the compound Abraxane® is nanoparticles made of Taxol particles with an albumin shell. It's a great concept, because Taxol is very hydro- phobic and precipitates out really easily." The albumin shell renders it less hydro- phobic, making it more potent and easier to infuse into patients. "The vasculature around cancers actually actively recruits albumin because it's bound to many nutrients," explained Damoiseaux. See Compound Management on page 22 /HDUQ KRZ &KDUOHV; 5LYHU FDQ WDLORU ELRSKDUPDFHXWLFDO WHVWLQJ VHUYLFHV WR ILW \RXU QHHGV flexibility. innovation. people who care. &5,9(5 • ZZZ FULYHU FRP IOH[LELOLW\ Genetic Engineering & Biotechnology News | genengnews.com | October 1, 2012 | 21