Microfluidic Bioreactor for High Throughput Cell-based

用于高通量细胞的微流控生物反应器

• 批准号: 7157415
• 负责人: PAUL JUSUNG HUNG
• 金额: $ 19.97万
• 依托单位: CELLASIC CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157415
• 关键词: alternatives to animals in research; bioengineering /biomedical engineering; biomedical equipment development; bioreactors; biotechnology; cell membrane; cytotoxicity; drug adverse effect; drug discovery /isolation; drug screening /evaluation; hepatotoxin; high throughput technology; liver cells; microfluidics; semiconduction; tissue /cell culture

DESCRIPTION (provided by applicant): Project Summary/Abstract: 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. Project Narrative: 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.

描述（由申请人提供）： 项目摘要/摘要：拨款申请建议开发 SBS 标准热塑性塑料 (PMMA) 微流体生物反应器，用于制药和生物技术行业的高通量连续灌注细胞筛选。更具体地说，为期一年的一期项目将重点开发用于连续灌注人肝细胞筛选的核心微流控板，以在药物发现过程的早期阶段更好地预测药物毒性。利用最先进的塑料和半导体制造工艺，我们将创建一个强大的金属半导体模板，以可靠地复制数千个微流体生物反应器。在塑料铸造厂的支持下，我们将在市场上提供生理高通量毒性分析。该项目的主要目标是开发高产量、低成本的SBS标准微流控生物反应器，并获得连续灌注培养7天的人肝细胞模型化合物的IC50曲线。该项目的完成将提高我们对连续灌注稳态培养条件下肝细胞长期药物毒性的理解。该板将为稳态细胞筛选提供最高的通量。细胞和试剂的节省将使最终用户能够将仪器纳入药物开发过程的早期阶段。此外，它可以在药物发现过程的早期阶段提供更好的药物毒性预测能力。通过持续的二期资助，我们将能够为高通量早期稳态肝毒性筛查提供完整的解决方案。项目叙述：该提案是对计划公告 PA-06-019 分子库筛选仪器 SBIR (R43/R44) 的回应，更具体地说，是对旨在开发高通量微流体生物反应器以评估化合物对人类肝细胞毒性的研究活动/代谢筛查。该项目的成功完成将为制药和生物技术行业提供一个更好、更具成本效益的HTS平台，重点关注预测毒理学和DMPK（药物代谢和药代动力学）分析。