Fast and Accurate Tools for Measuring Fluorescence in Living Cells

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43MH096670-01A1
Agency Tracking Number: R43MH096670
Amount: $348,182.00
Phase: Phase I
Program: SBIR
Awards Year: 2011
Solicitation Year: 2011
Solicitation Topic Code: NIMH
Solicitation Number: PA08-071
Small Business Information
2155 Analysis Drive, Suite B, BOZEMAN, MT, 59718-
DUNS: 145280157
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 (406) 539-7399
Business Contact
Phone: (406) 539-7399
Research Institution
DESCRIPTION (provided by applicant): Project Summary/Abstract Drug discovery depends crucially upon reliable assays for biological activity. Live cell assays provide a rich environment for measuring biological activity. Coupled with genetically encodedfluorescent biosensors, live cell assays have the potential to provide read-outs with unprecedented specificity for particular signaling pathways. Although widely used for basic research applications in living cells, genetically encoded fluorescent biosensors have had little impact on drug discovery because of difficulties in measuring and interpreting fluorescence intensity read-outs, including poor signal to noise ratios, variability in cell expression, and interference from fluorescence emitted by compounds. This Phase 1 project will demonstrate the feasibility of a new strategy that combines highly specific biosensors with extremely fast fluorescence lifetime measurements to produce the speed, sensitivity and specificity needed for high throughput screening applications. This approach employs an alternative fluorescence measurement based on fluorescence lifetime that is much faster than time-correlated single photon counting (TCSPC), yet also more precise. It operates in non-imaging mode which makes forsimple data interpretation and minimizes background fluorescence. It goes far beyond the expected incremental improvements to image-based technologies. Our preliminary data demonstrates the tremendous potential for robust live cell assays when lifetime methodology is applied to measuring genetically encoded fluorescent sensors. Our specific aims will accomplish the vital proof of principle steps and set the direction for our long term objectives of producing a robust live cell drug discovery platform within5 years. PUBLIC HEALTH RELEVANCE: New assays for biological activity are urgently needed to develop safe and effective drugs that provide better treatment outcomes and improved human health. This proposal addresses the technical challenges associated with using fluorescent live-cell assays and has strong potential to reduce the cost and improve the reliability of drug discovery processes.

* information listed above is at the time of submission.

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