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HIGH CONTENT IMAGING ASSAYS ON MICROARRAY CHIP BASED PLATFORM

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2016, Master of Science in Biomedical Engineering, Cleveland State University, Washkewicz College of Engineering.
Hepatotoxicity is a very common reason for drug withdrawal from the market. The conventional toxicology assessment models can lead to false negative and false positive outcomes due to lack of genetic relevance to humans (e.g., in vivo animal models) and poor cell-to-cell and cell-to-extracellular matrix (ECM) interactions (e.g., in vitro 2D cell models). Recent advances in “bioprinting” technology open up new possibilities for rapid and more reliable human cell-based toxicity assays. The present study aims at mechanistic toxicity assessment by using the Hep3B human hepatoma cell line encapsulated in two different hydrogel formulations via bioprinting on a micropillar/microwell chip platform and conducting high-content imaging (HCI) assays. The Hep3B cells grown into spheroids were exposed to six model compounds that are known to cause hepatotoxicity through different mechanisms, including mitochondrial dysfunction, DNA impairment, oxidative stress, and apoptosis/necrosis. The automated bioprinting technique we optimized on the chip platform provided robust data from HCI assays, with low coefficient of variation (CV) from the chips. The twenty four different dose response curves and IC50 values were obtained from the four different endpoints with the six compounds, and the results were compared with the previously published data. Altogether, the present study demonstrates that the Hep3B cells cultured in 3D on the chip platform can be used for rapid screening of compounds for their mechanistic hepatotoxicity via HCI assays.
Moo-Yeal Lee, PhD (Advisor)
Chandrasekhar Kothapalli, PhD (Committee Member)
Joanne Belovich, PhD (Committee Member)
105 p.

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Citations

  • Datar, A. (2016). HIGH CONTENT IMAGING ASSAYS ON MICROARRAY CHIP BASED PLATFORM [Master's thesis, Cleveland State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=csu1462795576

    APA Style (7th edition)

  • Datar, Akshata. HIGH CONTENT IMAGING ASSAYS ON MICROARRAY CHIP BASED PLATFORM . 2016. Cleveland State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=csu1462795576.

    MLA Style (8th edition)

  • Datar, Akshata. "HIGH CONTENT IMAGING ASSAYS ON MICROARRAY CHIP BASED PLATFORM ." Master's thesis, Cleveland State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1462795576

    Chicago Manual of Style (17th edition)