A technology that can detect and quantify the kinetics of small molecule binding and biochemical reactions, such as post-translational protein modifications, is critical for understanding the mechanisms underlying cancer initiation and progression, for discovering cancer biomarkers, and for screening cancer drug candidates. Currently, the most widely used technology uses fluorescence labels, which is difficult for small molecules with sizes comparable to the fluorescent dyes, especially for quantitative kinetic information. Various label-free techniques have been developed, but their sensitivity diminishes with the molecular mass, making it extremely challenging to detect small molecules and biochemical reactions that involve small mass changes. To address this need, a charge sensitive optical detection (CSOD) technology will be developed in this project. CSOD is compatible with the standard microplate technology, making it attractive for high-throughput screening and analysis of molecular interactions and reactions. The basic principle was established with the support of an IMAT (Innovative Molecular Analysis Technologies for cancer research) R21 grant. In the present R33 project, the team will work closely with collaborators in academic research labs and pharmaceutical companies, and a bioanalytical instrument company to develop and validate the technology for the unmet need. The success of the project will lead to a new label-free high-throughput screening technology for measuring molecular interactions, particularly small molecule interactions and post-translational modifications. These processes are highly important for the research, diagnosis and treatment of cancer.

Public Health Relevance

A charge sensitive optical detection technology will be developed for label-free detection and quantification of small molecule interactions, and biochemical reactions. This capability will have a large impact on biomedical research of cellular processes, discovery of biomarkers, and screening of drug candidates related to the understanding, diagnosis and treatment of cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA202834-02
Application #
9316572
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Sorg, Brian S
Project Start
2016-08-01
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Miscellaneous
Type
Organized Research Units
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Ma, Guangzhong; Syu, Guan-Da; Shan, Xiaonan et al. (2018) Measuring Ligand Binding Kinetics to Membrane Proteins Using Virion Nano-oscillators. J Am Chem Soc 140:11495-11501