High-throughput detection of small molecules and post translational protein modifications that involve small molecule biochemical reactions are critical for understanding the mechanisms underlying cancer initiation and progression, for discovering proper biomarkers that enable early cancer detection, and for screening drug candidates for effective cancer treatment. The most widely used technology uses fluorescence labels, which is problematic for small molecules whose sizes are comparable to those of the fluorescent dyes. Various label- free techniques have been developed, but their sensitivity diminishes with the size of the molecules, making it extremely challenging to detect small molecules. To address the need, a charge sensitive optical detection will be developed in this project. The technology is particularly suitable for the detection of small molecules, and biochemical interactions that involve small mass changes. The detection method uses optical probes that compatible with the standard microplate technology, making it attractive for high-throughput detection. The success of the project will lead to a new detection technology to measure small molecule interactions, such as drug-target interactions, membrane protein signaling, protein phosphorylation and other post translational modifications, oxidative and reduction reactions that involves charge transfer. Many of these processes are highly important for the research, diagnostic and treatment of cancer.

Public Health Relevance

A new charge sensitive optical detection technology will be developed for label-free measurement of small molecule interactions. The success of the project will lead to a new high-throughput screening tool for research, diagnostic and treatment of diseases including cancer.

National Institute of Health (NIH)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZCA1)
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Knowlton, John R
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Arizona State University-Tempe Campus
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United States
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Ma, Guangzhong; Guan, Yan; Wang, Shaopeng et al. (2016) Study of Small-Molecule-Membrane Protein Binding Kinetics with Nanodisc and Charge-Sensitive Optical Detection. Anal Chem 88:2375-9
Guan, Yan; Shan, Xiaonan; Wang, Shaopeng et al. (2014) Detection of molecular binding via charge-induced mechanical response of optical fibers. Chem Sci 5:4375-4381