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A Method for Identifying Small-Molecule Aggregators Using Photonic Crystal Biosensor Microplates.

Leo L Chan1, Erich A Lidstone, Kristin E Finch

  • 1Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL.

JALA (Charlottesville, Va.)
|October 9, 2010
PubMed
Summary
This summary is machine-generated.

Photonic crystal (PC) biosensors can identify and quantify small-molecule aggregation, a common issue in drug discovery. This technology offers a reliable method to filter out problematic compounds early in the screening process.

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Area of Science:

  • Biotechnology
  • Pharmaceutical Sciences
  • Materials Science

Background:

  • Small molecules are crucial in pharmaceutical discovery, but aggregation can cause false positives in screening assays.
  • Identifying aggregating compounds early streamlines drug discovery by removing unsuitable molecules.

Purpose of the Study:

  • To demonstrate the utility of photonic crystal (PC) optical biosensor microplate technology for identifying and quantifying small-molecule aggregation.
  • To compare the PC biosensor method with established techniques like dynamic light scattering (DLS), colorimetric assays, and scanning electron microscopy (SEM).

Main Methods:

  • Utilized PC optical biosensor microplate technology to detect and measure small-molecule aggregation.
  • Tested known aggregators and non-aggregators using the PC biosensor.
  • Compared PC biosensor results with DLS, an α-chymotrypsin colorimetric assay, and SEM.

Main Results:

  • PC biosensor measurements accurately identified and quantified small-molecule aggregation.
  • PC biosensor results were consistent with SEM visual confirmation and generally agreed with the α-chymotrypsin assay.
  • DLS provided inconsistent readings for many compounds, likely due to non-spherical aggregate shapes not accounted for in DLS modeling.

Conclusions:

  • PC biosensor microplate technology is an effective, label-free method for detecting small-molecule aggregation in a high-throughput screening compatible format.
  • This approach provides quantitative mass density measurements and streamlines pharmaceutical screening by enabling early identification of aggregating compounds.