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Cells are seeded on top of these discs, and compounds slowly diffuse out, affecting proximal cells. In contrast with microtiter-based screening, this system does not involve the use of wells or walls between each compound-treated group of cells. We demonstrate detection of the effects of a single compound in a large microarray, that diverse compounds can be released in this format, and that extended release over several days is feasible. We performed a small synthetic lethal screen and identified a compound (macbecin II) that has reduced activity in cells with RNA interference-mediated decrease in the expression of tuberous sclerosis 2. Thus, we have developed a microarray-based screening system for testing the effects of small molecules on mammalian cells by using an imaging-based readout. This method will be useful to those performing small-molecule screens to discover new chemical tools and potential therapeutic agents.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0404425101","type":"journal-article","created":{"date-parts":[[2004,11,8]],"date-time":"2004-11-08T20:25:16Z","timestamp":1099945516000},"page":"16144-16149","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":123,"title":["Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens"],"prefix":"10.1073","volume":"101","author":[{"given":"Steve N.","family":"Bailey","sequence":"first","affiliation":[{"name":"Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142; and Departments of Biological Sciences and Chemistry, Columbia University, Fairchild Center MC2406, 1212 Amsterdam Avenue, New York, NY 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Sabatini","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142; and Departments of Biological Sciences and Chemistry, Columbia University, Fairchild Center MC2406, 1212 Amsterdam Avenue, New York, NY 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent R.","family":"Stockwell","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142; and Departments of Biological Sciences and Chemistry, Columbia University, Fairchild Center MC2406, 1212 Amsterdam Avenue, New York, NY 10027"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,11,8]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"355","volume":"5","year":"2002","unstructured":"Root, D. 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