Fluidic Programmable Gravi-maze Array (FPGA) for Multi-organs Drug Testing

用于多器官药物检测的可编程重力迷宫阵列 摘要 芯片上的器官系统具有多个器官的相互作用，使用来自实验动物模型的细胞， 概括了体内类似组织的真实细胞行为，并提供了与时间相关的定量信息 当与药代动力学建模方法相结合时，这些现象。提高临床前诊断的准确性 使用这些器官类型相互作用的器官进行药物筛选将大大节省成本和时间，并可以 提供动物试验的替代方案。这些附加值更高、更复杂的非人类动物来源 微生理学分析可以在现有的活体动物毒性数据和基于人类细胞的数据之间架起一座桥梁 体外数据设定了降低人类安全风险的希望。这些器官类型的培养模型可以为 临床前药物开发，促进当前减少、提炼并最终可能取代动物的努力 模特们。然而，将这些体外器官系统发展为临床前药物面临着几个挑战。 毒性研究，在评估器官功能和改进对暴露于药物和他们的 代谢物。而且，目前还没有被动的、可扩展的、可灌流的多器官多器官 可用于推进毒物分析的有机类型培养平台。因此，Biopico Systems Inc. 提出了一种用于多器官药物的射流可编程重力迷宫阵列 放映。这允许在插入物上形成的多个器官以串联或并行的方式在特定方向上相互作用 其中彼此以阵列形式使用重力驱动的单向再循环。这种交替动物 通过在现场可编程门阵列系统中进行分析，能够及早识别脱靶毒性，这将有助于重新设计 一种用于预测毒理学和安全性测试的药物。在一期工程中，Biopico将开发24口井的流体平台 建立和验证肝脏和心脏之间的代谢相互作用，以模拟以下生理现象 准确的药品安全检测。具体目标如下。目标1：优化设计现场可编程门阵列芯片 通过串并跨井插入器官的再循环。目标2：在现场可编程门阵列中开发血管器官 药品检测和计量系统。目的3：表征现场可编程门阵列系统，研究其毒理学效应 相互作用的肝脏和心脏器官。该平台允许设计独立的集成血管系统和 其他易于构建和维护的剪应力敏感器官系统相比较 对动物来说。Biopico预计，现场可编程门阵列将被制药行业和研究人员采用为 一种动物替代方案，用于测试具有未知代谢特性的药物，同时获得更广泛的用途以产生 更安全的化合物。

Fluidic Programmable Gravi-maze Array (FPGA) for Multi-organs Drug Testing Abstract Organ on a chip systems with the interaction of multiple organs, using cells from experimental animal models, recapitulate in-vivo tissue-like realistic cellular behavior and provide information on quantitative, time-dependent phenomena when combined with a pharmacokinetic modeling approach. Improving the accuracy of preclinical drug screening using these organotypic interacting-organs will generate dramatic cost and time savings and can provide alternatives to animal testing. These, value-added, more complex non-human animal-derived microphysiological assays can build a bridge between existing in vivo animal toxicity data and human cell-based in vitro data to set the hope to de-risk human safety. These organotypic culture models can be established for preclinical drug development that facilitates current efforts to reduce, refine, and ultimately could replace animal models. However, there are several challenges to advance these in-vitro organ systems to preclinical drug toxicity studies, in the evaluation of organ function and improved prediction upon exposure to drugs and their metabolites. Moreover, currently, there is no passive, scalable and perfusable multiplexed multi-organs organotypic culture platform available to advance toxicological profiling. Therefore, Biopico Systems Inc proposes to develop a Fluidic Programmable Gravi-maze Array (FPGA) for multiple organs based drug screening. This allows multiple organs developed on inserts to interact in a specific direction in serial or parallel with one another using gravity-driven unidirectional recirculation in an array format. Such alternate animal profiling in the FPGA system enables early identification of off-target toxicities that would help in the redesign of a drug in predictive toxicology and safety testing. In Phase I, Biopico will develop the fluidic platform in 24-well format and validate the metabolic interaction between liver and heart that mimic physiological phenomena for accurate drug safety testing. The specific aims are as follows. Aim 1: optimize the design of FPGA Chip for recirculations through series-parallel transwell-Insert organs. Aim 2: develop vascularized organs in FPGA system for drug testing and measurement. Aim 3: characterize FPGA system to study the toxicological effects of interacting liver-heart organs. This platform allows the design of self-contained integrated vasculature and other shear stress-sensitive organ systems that are easy and cost-effective to construct and maintain compared to animals. Biopico envisions that FPGA will be adapted by the pharmacological industries and researchers as an animal alternative for testing drugs with the unknown metabolic property while gaining broader use to generate safer compounds.