A method for identifying small molecule aggregators using photonic crystal biosensor microplates

Leo L. Chan, Erich A. Lidstone, Kristin E. Finch, James T. Heeres, Paul J. Hergenrother, Brian T. Cunningham

Research output: Chapter in Book/Report/Conference proceedingConference contribution

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 languageEnglish (US)
Title of host publicationProceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Subtitle of host publicationEngineering the Future of Biomedicine, EMBC 2009
PublisherIEEE Computer Society
Pages788-791
Number of pages4
ISBN (Print)9781424432967
DOIs
StatePublished - Jan 1 2009
Event31st 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 2009Sep 6 2009

Publication series

NameProceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009

Other

Other31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009
CountryUnited States
CityMinneapolis, MN
Period9/2/099/6/09

Fingerprint

Optics and Photonics
Biosensing Techniques
Photonic crystals
Biosensors
Assays
Screening
Molecules
Agglomeration
Chymotrypsin
Electron Scanning Microscopy
Drug products
Throughput
Technology
Scanning electron microscopy
Dynamic light scattering
Transducers
Pharmaceutical Preparations
Libraries
Labels
Observation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Biomedical Engineering
  • Medicine(all)

Cite this

Chan, L. L., Lidstone, E. A., Finch, K. E., Heeres, J. T., Hergenrother, P. J., & Cunningham, B. T. (2009). A method for identifying small molecule aggregators using photonic crystal biosensor microplates. In Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009 (pp. 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). IEEE Computer Society. https://doi.org/10.1109/IEMBS.2009.5333796

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 proceedingConference contribution

Chan, LL, Lidstone, EA, Finch, KE, Heeres, JT, Hergenrother, PJ & Cunningham, BT 2009, A method for identifying small molecule aggregators using photonic crystal biosensor microplates. in Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009., 5333796, 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, pp. 788-791, 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009, Minneapolis, MN, United States, 9/2/09. https://doi.org/10.1109/IEMBS.2009.5333796
Chan LL, Lidstone EA, Finch KE, Heeres JT, Hergenrother PJ, Cunningham BT. A method for identifying small molecule aggregators using photonic crystal biosensor microplates. In 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). https://doi.org/10.1109/IEMBS.2009.5333796
Chan, Leo L. ; Lidstone, Erich A. ; Finch, Kristin E. ; Heeres, James T. ; Hergenrother, Paul J. ; Cunningham, Brian T. / A method for identifying small molecule aggregators using photonic crystal biosensor microplates. 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. pp. 788-791 (Proceedings of the 31st Annual International Conference of the IEEE Engineering in Medicine and Biology Society: Engineering the Future of Biomedicine, EMBC 2009).
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