The grant application proposes the development of an SBS standard thermoplastic (PMMA) microfluidic bioreactor for high throughput continuously perfused cell-based screening for the pharmaceutical and biotechnology industry. More specifically, the 1- year Phase I project will focus on developing the core microfluidic plate for continuously perfused human hepatocyte screening to better predict drug toxicity at the early stage of the drug discovery processes. Taking advantage of the state-of-the-art plastic and semiconductor manufacturing processes, we will create a robust metal-on-semiconductor template to reliably copy thousands of microfluidic bioreactors. With the support from a plastic foundry, we will make physiologic high throughput toxicity analysis readily available in the market. The primary targets of this project are to develop high yield and low cost SBS standard microfluidic bioreactors and obtain the IC50 curves of model compounds for human hepatocytes cultured under continuous perfusion for time scale up 7 days. The completion of this project will improve our understanding of long-term drug toxicity on hepatocytes under continuously perfused steady-state culture conditions. The plate will offer the highest throughput for steady-state cell-based screening. The savings on cells and reagents will allow end users to incorporate the instrumentation into earlier stage of drug development processes. In addition, it may provide better predictive power of drug toxicity at early stage of the drug discovery processes. With a continuing Phase II grant, we will be able to provide a complete solution to high throughput early-stage steady-state hepatotoxicity screening. The proposal is in response to the program announcement PA-06-019 Molecular Libraries Screening Instrumentation SBIR (R43/R44), more specifically, to the research activities aiming at developing high throughput microfluidic bioreactor to assess compound toxicity for human hepatocyte toxicity/metabolism screening. The successful completion of the project will provide the pharmaceutical and biotechnology industry a better and more cost-effective HTS platform focusing on predictive toxicology and DMPK (drug metabolism and pharmacokinetics) profiling.
Thesaurus Terms: biomedical equipment development, bioreactor, cytotoxicity, drug adverse effect, drug discovery /isolation, drug screening /evaluation, hepatotoxin, high throughput technology, liver cell, microfluidics alternatives to animals in research, cell membrane, semiconduction bioengineering /biomedical engineering, biotechnology, tissue /cell culture
