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Title:Identifying small molecule aggregators with photonic crystal biosensor microplates
Author(s):Lidstone, Erich A.
Advisor(s):Cunningham, Brian T.
Department / Program:Bioengineering
Degree Granting Institution:University of Illinois at Urbana-Champaign
Photonic crystals
pharmaceutical screening
small molecule screening
drug screening
Abstract: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.
Issue Date:2011-01-21
Rights Information:Licenses have been obtained from Elsevier, Inc. for copyrighted work presented in this thesis.
Date Available in IDEALS:2011-01-21
Date Deposited:2010-12

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