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

描述(由申请人提供)：这项提案的目标是完成微流控肝阵列(MLA)平台的开发，以改进和降低成本，针对人体肝脏进行体外毒性筛选。这笔资金将直接导致一种在生物制药和化学安全行业广泛应用的产品商业化，作为动物实验的体外替代品。MLA使用最先进的微制造技术来制造高密度的“微型肝”组织阵列，其中填充了原始人类肝细胞。我们独特的微流体设计模拟了肝脏微血管系统，提供了一个连续的灌流环境和3D细胞结构，事实证明，它可以增强肝脏的特定功能。MLA的设计符合标准SBS(生物分子科学学会)标准，允许通过现有的筛查仪器和分析进行操作。此外，我们的专利制造工艺和细胞/试剂使用量的减少将显著降低体外肝细胞毒性筛选的总体成本。为了将这项技术商业化，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。为了促进这一任务，Cellasic与肝细胞相关筛选和研究的全球领先企业CellzDirect/Invitgen Corporation建立了合作伙伴关系。这一伙伴关系将确保MLA经过严格的行业相关基准测试，以最大限度地发挥这项新技术的商业效用。这项为期2.5年的SBIR快速通道资助计划的目标是：1.与现有方法相比，评估在MLA中长期维持人类肝脏特异性异物代谢功能和途径的情况2.改进MLA平台以适应商业筛查应用 与公共健康相关：监管机构和制药/化学品开发公司都对改进的体外毒性筛选技术提出了很高的要求，这些技术可以预测人类暴露的风险，同时减少对动物试验的依赖。Cellasic的微流体肝脏阵列平台使用最先进的微流体技术，以高通量阵列重建肝脏组织微环境，从而在显著降低成本的情况下进行更准确的化学毒性评估。

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.