Microfluidic Liver Array for Long Term In Vitro Hepatocyte Culture and Screening

用于长期体外肝细胞培养和筛选的微流控肝脏阵列

• 批准号: 8214518
• 负责人: Philip J Lee
• 金额: $ 35.33万
• 依托单位: CELLASIC CORPORATION
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-24 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8214518
• 关键词: ABCB1 gene; Animal Testing; Applications Grants; Architecture; Automation; Benchmarking; Biological; Biological Assay; Biological Preservation; Biological Products; CYP1A2 gene; CYP2B6 gene; CYP2C19 gene; CYP2C9 gene; CYP3A4 gene; Cell Culture Techniques; Cell Survival; Cells; Chemicals; Cytochrome P450; Data; Databases; Dependence; Development; Devices; Dose; Drug Compounding; Drug Interactions; Engineering; Ensure; Environment; Enzymes; Funding; Goals; Gold; Government; Health; Hepatocyte; Hepatotoxicity; Hour; Human; Human body; In Vitro; Industry; Lead; Life; Liver; Maintenance; Measurement; Metabolic; Methods; Microfabrication; Microfluidics; Modeling; Monitor; National Toxicology Program; Organ; Pathway interactions; Perfusion; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Physiological; Proteins; Publishing; Reagent; Reliance; Research; Risk; Safety; Science; Screening procedure; Shipping; Ships; Simulate; Small Business Innovation Research Grant; Societies; System; Technology; Temperature; Testing; Time; Tissues; Toxic effect; Toxicity Tests; UGT1A1 gene; Xenobiotics; commercialization; cost; culture plates; density; design; environmental chemical; exposed human population; improved; in vivo; instrumentation; mRNA Expression; manufacturing process; matrigel; new technology; operation

DESCRIPTION (provided by applicant): The goal of this proposal is to complete development of a Microfluidic Liver Array (MLA) platform for improved and lower cost in vitro toxicity screening targeting the human liver. This funding will directly lead to the commercialization of a product with widespread application in the biopharmaceutical and chemical safety industry as an in vitro alternative to animal testing. The MLA uses state-of-the-art microfabrication technology to create high density arrays of "micro- liver" tissue populated with primary human hepatocytes. Our unique microfluidic design mimics the liver micro-vasculature, providing a continuous perfusion environment and 3D cellular architecture proven to enhance liver specific functions. The MLA is designed to conform to standard SBS (Society for Biomolecular Sciences) standards, allowing operation by existing screening instrumentation and assays. Moreover, our proprietary manufacturing process and reduction in cell/reagent usage will significantly reduce the overall cost of in vitro hepatocyte toxicity screening. In order to commercialize this technology, it is necessary to more fully validate the long term biologic functions of human hepatocytes cultured in the MLA, and compare with the best current in vitro and in vivo data. To facilitate this task, CellASIC has partnered with CellzDirect/Invitrogen Corporation, the global leader in hepatocyte related screening and research. This partnership will ensure that the MLA is rigorously tested against industry relevant benchmarks to maximize the commercial utility of the novel technology. The objective of this 2.5-year SBIR Fast Track grant proposal are: 1. Evaluate the long-term maintenance of human liver-specific xenobiotic metabolizing functions and pathways in the MLA compared with existing methods 2. Improve the MLA platform to suit commercial screening applications PUBLIC HEALTH RELEVANCE: There is a high demand both from regulatory agencies and pharmaceutical/chemical development companies for improved in vitro toxicity screening technologies that are predictive of human exposure risks while reducing the reliance on animal testing. CellASIC's Microfluidic Liver Array platform uses state-of-the-art microfluidics technology to recreate the liver tissue microenvironment in a high throughput array, resulting in more accurate chemical toxicity assessment at significantly reduced cost.

描述（由申请人提供）：本提案的目标是完成微流控肝脏阵列（MLA）平台的开发，以改进和降低靶向人类肝脏的体外毒性筛选成本。这笔资金将直接导致产品的商业化，该产品在生物制药和化学安全行业中广泛应用，作为动物试验的体外替代品。MLA使用最先进的微制造技术来创建填充有原代人肝细胞的“微肝”组织的高密度阵列。我们独特的微流体设计模仿肝脏微血管系统，提供连续灌注环境和3D细胞结构，证明可增强肝脏特异性功能。MLA的设计符合标准SBS（生物分子科学协会）标准，允许通过现有的筛选仪器和测定进行操作。此外，我们专有的生产工艺和细胞/试剂用量的减少将显著降低体外肝细胞毒性筛选的总体成本。 为了将该技术商业化，有必要更充分地验证在MLA中培养的人肝细胞的长期生物学功能，并与目前最好的体外和体内数据进行比较。为了促进这项任务，CellASIC与肝细胞相关筛选和研究的全球领导者CellzDirect/Invitrogen公司合作。这种伙伴关系将确保MLA根据行业相关基准进行严格测试，以最大限度地发挥新技术的商业效用。 这个2.5年SBIR快速通道赠款提案的目标是：1。与现有方法相比，评价MLA中人类肝脏特异性异生物质代谢功能和途径的长期维持2。改进MLA平台，以适应商业筛选应用 公共卫生相关性：监管机构和制药/化学品开发公司都非常需要改进体外毒性筛选技术，以预测人类接触风险，同时减少对动物试验的依赖。CellASIC的Microfluidic Liver Array平台使用最先进的微流体技术在高通量阵列中重建肝脏组织微环境，从而以显著降低的成本进行更准确的化学毒性评估。