Cytotoxicity testing with cell-based assays is critical for the development of pharmaceutical compounds, nanoparticles, and other materials that may be introduced into the human body by direct or indirect methods. Despite the wide use of cell-based assays for toxicology screens, it remains a challenge to generate reliable toxicology data that are relevant to more sophisticated whole-animal and human tissue models. Introducing highly quantitative and multiparametic measurement approaches into cell-based cytotoxicity assays may aid in elucidating the issues involved in developing reliable cell-based toxicology assays. This project involves the development of automated microscopy and high-content image analysis procedures that can quantify several biomarkers on a cell-by-cell basis from a population of cells in a cytotoxic dose-response study. The use of multiparametric population data and appropriate data analysis techniques will allow improved evaluation of biomarker or a combination of biomarkers in measuring cytotoxicity and possibly define conditions where current toxicity assays fail. Specific aspects of the project may include the development and use of novel cytoxicity assays, automated microscopy sampling procedures, assessment and use of several image analysis routines for data extraction, and investigating methods to evaluate how multiparameter biomarker measurement can improve prediction ability of a cytotoxic assay.
Biomarker; Cytotoxicity; Fluorescence microscopy; Multiparametric analysis; Quantitative cell biology;