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

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，以改进和降低针对人类肝脏的体外毒性筛选成本。这笔资金将直接导致一种产品的商业化，这种产品广泛应用于生物制药和化学安全行业，作为动物试验的体外替代品。MLA使用最先进的微加工技术来创建高密度的“微肝”组织阵列，其中填充了原代人肝细胞。我们独特的微流体设计模拟肝脏微血管系统，提供连续的灌注环境和3D细胞结构，证明可以增强肝脏的特定功能。MLA的设计符合标准的SBS（生物分子科学学会）标准，允许通过现有的筛选仪器和分析操作。此外，我们专有的制造工艺和减少细胞/试剂的使用将显著降低体外肝细胞毒性筛选的总体成本。为了使该技术商业化，有必要更充分地验证MLA培养的人肝细胞的长期生物学功能，并与目前最佳的体外和体内数据进行比较。为了促进这项任务，CellASIC与CellzDirect/Invitrogen公司合作，CellzDirect/Invitrogen公司是肝细胞相关筛查和研究的全球领导者。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。这项为期2.5年的SBIR快速通道拨款提案的目标是：与现有方法相比，评估MLA中人类肝脏特异性外源性代谢功能和途径的长期维持改进MLA平台以适应商业筛选应用

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.