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

用于多器官药物测试的流体可编程重力迷宫阵列 (FPGA)

• 批准号: 10080010
• 负责人: John Collins
• 金额: $ 25.08万
• 依托单位: BIOPICO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-21 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080010
• 关键词: 3-Dimensional; Address; Albumins; Algorithms; Animal Model; Animal Testing; Animal Testing Alternatives; Animals; Automobile Driving; Biological Assay; Biomimetics; Blood Circulation; Blood Vessels; Cardiac; Cardiac Myocytes; Cardiotoxicity; Cell model; Cells; Clinical Research; Closure by clamp; Coculture Techniques; Collaborations; Complement; Complex; Computer software; Custom; Cyclophosphamide; Data; Development; Dose; Doxorubicin; Drug Kinetics; Drug Screening; Drug toxicity; Drug usage; Early identification; Electrodes; Evaluation; Experimental Animal Model; Exposure to; Feasibility Studies; Force of Gravity; Frequencies; Gases; Geometry; Glass; Heart; Hepatocyte; Human; Image; In Vitro; Industry; Investigation; Legal patent; Liquid substance; Liver; Measurement; Measures; Metabolic; Microscope; Modeling; Motor; Nutrient; Organ; Organ Culture Techniques; Organ Model; Organ Size; Performance; Perfusion; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Physiologic pulse; Physiological; Preclinical Drug Development; Property; Pump; Quantitative Reverse Transcriptase PCR; Research Personnel; Risk; Running; Safety; Sampling; Savings; Series; System; Terfenadine; Time; Tissues; Toxic effect; Toxicology; Translations; Urea; Valproic Acid; Vascular Endothelial Cell; Video Recording; base; body system; cell behavior; cost; cost effective; design; dosage; drug candidate; drug development; drug efficacy; drug metabolism; drug testing; drug use screening; electric field; improved; in vitro Model; in vivo; innovation; medication safety; novel; optical imaging; organ on a chip; pharmacokinetic model; pre-clinical; preclinical study; preclinical trial; programs; residence; response; safety testing; seal; shear stress; specific biomarkers

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.

用于多器官药物检测的Fluorescent可编程重力迷宫阵列（FPGA） 摘要 具有多个器官相互作用的芯片上器官系统，使用来自实验动物模型的细胞， 概括体内组织样的真实细胞行为，并提供关于定量的、时间依赖的 当与药代动力学建模方法相结合时的现象。提高临床前诊断的准确性 使用这些器官型相互作用器官的药物筛选将产生显著的成本和时间节省， 提供动物实验的替代品。这些，增值，更复杂的非人类动物源性 微生理学测定可以在现有的体内动物毒性数据和基于人类细胞的毒性数据之间建立桥梁。 在体外数据设置的希望，以降低风险的人类安全。这些器官型培养模型可用于 临床前药物开发，促进目前的努力，以减少，完善，并最终可以取代动物 模型然而，将这些体外器官系统推进到临床前药物存在几个挑战 毒性研究，评价器官功能和改善对药物暴露及其 代谢物。此外，目前，没有被动的、可扩展的和可灌注的多路复用多器官 可用于推进毒理学分析的器官型培养平台。因此，Biopico Systems Inc 提出开发一种用于多器官药物治疗的Fluorescent可编程重力迷宫阵列（FPGA） 筛选这允许在插入物上发育的多个器官在特定方向上串行或并行地相互作用 彼此使用阵列形式的重力驱动的单向再循环。这种另类动物 FPGA系统中的分析能够早期识别脱靶毒性，这将有助于重新设计 预测毒理学和安全性测试中的药物。在第一阶段，Biopico将开发24孔的流体平台， 格式和验证肝脏和心脏之间的代谢相互作用，模拟生理现象， 准确的药物安全检测。具体目标如下。目标1：优化FPGA芯片的设计， 通过串并联transwell-Insert器官进行再循环。目标2：在FPGA中开发血管化器官 用于药物测试和测量的系统。目的3：表征FPGA系统以研究毒理学效应 相互作用的肝脏和心脏器官。该平台允许设计独立的集成脉管系统， 与其它剪切应力敏感器官系统相比， 动物。Biopico设想FPGA将被制药行业和研究人员采用， 一种动物替代品，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， 更安全的化合物。