Date of Award

5-10-2026

Date Published

June 2026

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Zhen Ma

Keywords

AI;Bioengineering;Cardiomyocyte;Deep Learning;Machine Learning;Stem Cell

Abstract

Recent advances in human induced pluripotent stem cell (hiPSC) technology have enabled the development of high-throughput platforms for cardiotoxicity screening. However, conventional analytical approaches remain limited by time-intensive processing, manual annotation requirements, and reduced scalability for large datasets. To address these challenges, calcium fluorescence signals from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC CMs) were analyzed using a high-throughput imaging platform and complementary machine learning frameworks. First, a feature-based supervised learning approach using engineered waveform descriptors and low-dimensional signal embeddings enabled rapid and interpretable screening of large chemical datasets, with combined features improving predictive performance relative to engineered features alone. Second, an unsupervised autoencoder-based multi-donor voting platform was developed to quantify drug-induced cardiotoxicity directly from raw waveforms without manual labeling. Application of this framework revealed donor-specific variability in drug responses across multiple hiPSC lines, while aggregation of donor predictions enabled population-level IC50 estimation, safety margin analysis, and consensus toxicity assessment. Together, these findings demonstrate a scalable computational strategy for cardiotoxicity screening that integrates rapid classification, waveform-level toxicity detection, and biologically meaningful donor variability.

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Open Access

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