This proposal is to apply for a supplement grant to support a talented, minority Ph.D. student, Frank DeLuna, to develop a new label-free imaging system for drug toxicity assays in Dr. Jing Yong Ye?s laboratory at the University of Texas at San Antonio. Accurate analysis of drug toxicities is in urgent demand as failures of newly discovered drug candidates due to toxic side effects have resulted in about 30% of clinical attrition, leading to enormous economic losses for the pharmaceutical industry. One of the main reasons for these failures can be attributed to the fact that most animal models fail to accurately reflect human physiology. Therefore, there is a significant interest in constructing human organ models for drug toxicity assays before proceeding with clinical trials. For that, it is critically important not only to construct small tissue chips that can well mimic the architecture and functionality of human tissues, but also to continuously monitor the dynamic behaviors of human organ-on-a-chip models in response to drugs in situ over an extended period. The overarching goal of the parent R01 project (1R01GM126571) is to address the challenging issues of drug toxicity assays by using a human organ-on-a-chip model monitored with an automated, label-free, optical biosensor system that allows for real-time, long-term, sensitive, and kinetic analyses of human cardiac tissue models in response to various drugs in their microenvironments. The proposed research activities for the student under this supplement grant is to develop a new label-free imaging system by utilizing a photonic crystal biosensor in a unique detection mode for accurate quantification of biomarkers due to drug toxicities. The proposed work is related to Aim 2 in the parent project, and it will also create a new capability for directly imaging samples in the evanescent field of the sensor for simultaneously monitoring reflective index changes in each sample well due to binding events of biomarkers secreted by a heart-on-a-chip model with biorecognition probes on the sensor surface. This new design will offer a good alternative approach for multiplex detection of biomarkers in drug toxicity assays. This supplement grant will offer an excellent training opportunity for the minority student to gain deep knowledge and necessary research skills in biophotonics as well as to improve his other capabilities, such as writing and networking skills, preparing him for a successful academic career.

Public Health Relevance

This is a statement of work to be fulfilled by the University of Texas at San Antonio (UTSA) as a subcontract of NIH proposal entitled ?Supplement grant: Development of a new label-free imaging system for drug toxicity assays? to be submitted by Terasaki Research Institute. Dr. Jing Yong Ye at UTSA will be in charge of training the minority student, Frank DeLuna, to be funded by the supplement grant for the development of a new label-free imaging system by utilizing a photonic crystal biosensor in a unique detection mode for accurate quantification of biomarkers due to drug toxicities. It is understood by both parties that this is a research/traingin project and that the work will be conducted on a best effort basis to achieve the objectives of this proposal.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Gindhart, Joseph G
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Terasaki Institute for Biomedical Innovation
Los Angeles
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