2026-09-21T15:48:41Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/18539 2023-07-10 col_2142_5131 col_2142_5163 com_2142_5130 com_2142_5162 com_2142_234

Item released from any restrictions by Sarah Shreeves (sshreeve@illinois.edu) on 2013-01-22T11:00:23Z http://hdl.handle.net/2142/18539 en Licenses have been obtained from Elsevier, Inc. for copyrighted work presented in this thesis. Cunningham, Brian T. Lidstone, Erich A. 2011-01-21T22:45:12Z 2011-01-21T22:45:12Z 2013-01-22T11:00:23Z 2011-01-21T22:45:12Z 2010-12 Small molecules identified through high-throughput screens are essential elements in pharmaceutical discovery programs. It is now recognized that a substantial fraction of small molecules exhibit aggregating behavior leading to false positive results in many screening assays, typically due to nonspecific attachment to target proteins. Therefore, the ability to efficiently identify compounds within a screening library that aggregate can streamline the screening process by eliminating unsuitable molecules from further consideration. In this work we show that photonic crystal (PC) optical biosensor microplate technology can be utilized to identify and quantify small molecule aggregation. A group of aggregators and nonaggregators were tested using the PC technology, and measurements were compared with those gathered by three alternative methods: dynamic light scattering (DLS), an α-chymotrypsin colorimetric assay, and scanning electron microscopy (SEM). The PC biosensor measurements of aggregation were confirmed by visual observation using SEM, and were in general agreement with the -chymotrypsin assay. DLS measurements, in contrast, demonstrated inconsistent readings for many compounds that are found to form aggregates in shapes very different from the classical spherical particles assumed in DLS modeling. As a label-free detection method, the PC biosensor aggregation assay is simple to implement and provides a quantitative direct measurement of the mass density of material adsorbed to the transducer surface, while the microplate-based sensor format enables compatibility with high-throughput automated liquid handling methods used in pharmaceutical screening. Item withdrawn by Mark Zulauf (zulauf@illinois.edu) on 2010-12-09T21:16:30Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Lidstone MS Thesis_12_6_10_FORMATTEDb.docx: 2787646 bytes, checksum: 599876aa353beb6105897bf7072ddffa (MD5) Lidstone MS Thesis_12_6_10_FORMATTEDb.pdf: 3104445 bytes, checksum: 9c06509e5d3dd01c64e7d5fca539e1a8 (MD5) Made available in DSpace on 2011-01-21T22:45:12Z (GMT). No. of bitstreams: 3 Lidstone_Erich.pdf: 3098906 bytes, checksum: ea1ba07f3e62c0c95718a3512672615c (MD5) license.txt: 4063 bytes, checksum: 09c7357c66fc27a8c824a9a2111970d7 (MD5) Lidstone_Erich.docx: 2791018 bytes, checksum: c86538e11be6328b910756f2559f3909 (MD5) Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by William Ingram (wingram2@illinois.edu) on 2011-01-21T22:48:07Z Item is restricted until 2013-01-21T22:47:37Z Item reinstated by Sarah Shreeves (sshreeve@illinois.edu) on 2013-01-22T11:00:23Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Theses and Dissertations - Bioengineering (ID: 225) No. of bitstreams: 3 Lidstone_Erich.pdf: 3098906 bytes, checksum: ea1ba07f3e62c0c95718a3512672615c (MD5) license.txt: 4063 bytes, checksum: 09c7357c66fc27a8c824a9a2111970d7 (MD5) Lidstone_Erich.docx: 2791018 bytes, checksum: c86538e11be6328b910756f2559f3909 (MD5) Biosensors Photonic crystals pharmaceutical screening small molecule screening drug screening Identifying small molecule aggregators with photonic crystal biosensor microplates Bioengineering 1343 Bioengineering 0408 University of Illinois at Urbana-Champaign Thesis M.S. PHD: Bioengineering-UIUC 10KS0408PHD