Abstract
Small molecules identified through high-throughput screens are an essential element 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 α-chymotrypsin assay. 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.
| Original language | English (US) |
|---|---|
| Title of host publication | Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society |
| Subtitle of host publication | Engineering the Future of Biomedicine, EMBC 2009 |
| Publisher | IEEE Computer Society |
| Pages | 788-791 |
| Number of pages | 4 |
| ISBN (Print) | 9781424432967 |
| DOIs | |
| State | Published - Jan 1 2009 |
| Event | 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009 - Minneapolis, MN, United States Duration: Sep 2 2009 → Sep 6 2009 |
Publication series
| Name | Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009 |
|---|
Other
| Other | 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009 |
|---|---|
| Country | United States |
| City | Minneapolis, MN |
| Period | 9/2/09 → 9/6/09 |
Fingerprint
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Biomedical Engineering
- Medicine(all)
Cite this
A method for identifying small molecule aggregators using photonic crystal biosensor microplates. / Chan, Leo L.; Lidstone, Erich A.; Finch, Kristin E.; Heeres, James T.; Hergenrother, Paul J.; Cunningham, Brian T.
Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009. IEEE Computer Society, 2009. p. 788-791 5333796 (Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009).Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - A method for identifying small molecule aggregators using photonic crystal biosensor microplates
AU - Chan, Leo L.
AU - Lidstone, Erich A.
AU - Finch, Kristin E.
AU - Heeres, James T.
AU - Hergenrother, Paul J.
AU - Cunningham, Brian T.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Small molecules identified through high-throughput screens are an essential element 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 α-chymotrypsin assay. 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.
AB - Small molecules identified through high-throughput screens are an essential element 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 α-chymotrypsin assay. 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=77951021548&partnerID=8YFLogxK
U2 - 10.1109/IEMBS.2009.5333796
DO - 10.1109/IEMBS.2009.5333796
M3 - Conference contribution
C2 - 19964243
AN - SCOPUS:77951021548
SN - 9781424432967
T3 - Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009
SP - 788
EP - 791
BT - Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society
PB - IEEE Computer Society
ER -