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)

基本信息

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
项目类别：
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

项目摘要

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.

用于多器官药物测试的流体可编程重力迷宫阵列 (FPGA) 抽象的器官芯片系统与多个器官相互作用，使用来自实验动物模型的细胞，重现体内组织样的真实细胞行为，并提供定量、时间依赖性的信息与药代动力学建模方法相结合时出现的现象。提高临床前的准确性使用这些相互作用的器官进行药物筛选将节省大量成本和时间，并且可以提供动物试验的替代方案。这些增值的、更复杂的非人类动物衍生的微生理学检测可以在现有的动物体内毒性数据和基于人体细胞的毒性数据之间架起一座桥梁体外数据有望降低人类安全风险。这些器官型培养模型可用于建立临床前药物开发有助于当前减少、精炼并最终替代动物的努力模型。然而，将这些体外器官系统推进临床前药物存在一些挑战毒性研究，评估器官功能并改进对药物及其药物暴露的预测代谢物。此外，目前还没有被动的、可扩展的、可灌注的多重多器官器官型培养平台可用于推进毒理学分析。因此，Biopico 系统公司提议为基于多个器官的药物开发流体可编程重力迷宫阵列（FPGA）筛选。这使得在插入物上发育的多个器官能够在特定方向上串行或并行地相互作用彼此之间使用重力驱动的单向再循环以阵列形式进行。这样的另类动物 FPGA 系统中的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。在第一阶段，Biopico 将开发 24 孔流体平台格式化并验证模拟生理现象的肝脏和心脏之间的代谢相互作用准确的药品安全检测。具体目标如下。目标1：优化FPGA芯片设计通过串联-并联 transwell-插入器官进行再循环。目标 2：在 FPGA 中开发血管化器官药物测试和测量系统。目标 3：表征 FPGA 系统以研究毒理学效应肝-心器官相互作用。该平台允许设计独立的集成脉管系统和与其他剪切应力敏感的器官系统相比，其构建和维护起来容易且具有成本效益对动物。 Biopico 预计 FPGA 将被药理学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来产生更安全的化合物。