Microfluidic Biotool to Accurately Model Corrosive Chemical Exposures for Human

微流控生物工具可准确模拟人体腐蚀性化学品暴露

• 批准号: 9341643
• 负责人: Randall Edwin McClelland
• 金额: $ 22.5万
• 依托单位: SCIKON INNOVATION, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9341643
• 关键词: Agriculture; Agrochemicals; Animals; Biochemical; Biological; Biological Assay; Caustics; Cell Culture Techniques; Cell Line; Cell Survival; Cell physiology; Cells; Characteristics; Chemical Exposure; Chemicals; Chloroform; Complement; Corrosives; Culture Media; Data; Deterioration; Development; Dose; Environment; Equipment and supply inventories; Ethers; Ethics; Evaluation; Excretory function; Exposure to; Glass; Goals; Grant; Health; Human; Human Biology; Human Cell Line; Image; Impact evaluation; In Vitro; Industry; Injection of therapeutic agent; Kinetics; Laboratories; Liquid substance; Measures; Metabolism; Microfluidics; Modeling; Molds; Monitor; Morphology; Optics; Outcome; Pathway interactions; Phase; Physiological; Physiology; Plasticizers; Poison; Polymers; Production; Property; Pump; Reaction; Reader; Research Personnel; Resistance; Safety; Small Business Innovation Research Grant; Structure; Surface; System; Techniques; Technology; Testing; Time; TimeLine; Toluene; Toxic effect; Toxicity Tests; Toxicology; United States Environmental Protection Agency; Work; absorption; airway epithelium; authority; base; bronchial epithelium; cell type; chemical property; chemical stability; consumer product; cost effective; culture plates; cytotoxic; design; environmental chemical; exposed human population; human tissue; improved; in vitro testing; in vivo; innovation; instrumentation; manufacturing process; novel; oxidation; prevent; prototype; response; tissue culture; tool

Project Summary There is a critical gap between the need to evaluate the effect of chemicals on human physiology and the availability of in vivo and in vitro testing systems that provide the necessary predictive data. This need is especially pronounced for corrosive and caustic chemicals that are not compatible with current in vitro and in vivo testing systems. For example, the Toxic Substances Control Act (TSCA) requires that the EPA inventory all currently manufactured, processed, and imported chemical compounds. This list currently contains 85,000 chemicals, many with no toxicity data evaluated in a biologically relevant manner. The scope of this SBIR project is to develop a first-in-class corrosive resistant fluidic culture system that will enable industries, including environmental, regulatory, agricultural, chemical and consumer products, to evaluate thousands of corrosive and caustic chemicals for their effects on human tissues and cell lines, under physiologically relevant conditions. SciKon, Inc has previously introduced a disruptive technology to the scientific tools market that enables toxicity testing under non-linear flow conditions in a microfluidic environment. The corrosive resistant SciFlow system to be developed in this work will provide three major advances over current toxicological testing options: 1) dramatically improved biological relevance due to the fluidic and non-linear exposure gradients of the core SciFlow technology; 2) ability to test corrosive chemicals at higher doses for longer periods of time without degradation of the tissue culture plate and exposure of the cells to the plastic breakdown products; 3) compatibility with high content imagers and plate readers due to the optical properties of the glass-like plastic polymers and SBS compliant plate format. In Phase I, we will complete the following Specific Aims: Aim 1: Characterize glass-like polymers that can withstand corrosive environments, are able to be injection molded for mass production, and are inert for cell culture. Aim 2: Generate a glass-like SciFlowTM System prototype for corrosive exposure kinetics and bioassay evaluation. Upon completion of the Phase I aims, our Phase II work will focus on validating the system and scaling the unit for production. Successful completion of this project will result in development of the SciFlow corrosive-resistant system, which will provide the first in vitro system with a chemically inert environment suitable for repeated dosing in long-term corrosive culture environments.

项目摘要 评估化学品对人类的影响的需要与 生理学以及体内和体外测试系统的可用性， 预测数据这种需求对于腐蚀性和腐蚀性化学品尤其明显， 与目前的体外和体内测试系统不兼容。例如，有毒 物质控制法（TSCA）要求EPA库存所有目前生产的， 加工和进口化学化合物。该清单目前包含85，000种化学品， 许多没有以生物学相关方式评价的毒性数据。 该SBIR项目的范围是开发一流的耐腐蚀流体培养 该系统将使包括环境、监管、农业、化学 和消费品，以评估数以千计的腐蚀性和腐蚀性化学品， 在生理相关条件下对人体组织和细胞系的影响。SciKon，Inc 此前曾向科学工具市场推出了一项颠覆性技术， 在微流体环境中的非线性流动条件下的毒性测试。腐蚀性 在这项工作中开发的耐SciFlow系统将提供三个主要进展， 目前的毒理学测试选项：1）由于 核心SciFlow技术的流体和非线性曝光梯度; 2）测试 腐蚀性化学品在较高剂量下持续较长时间，而不会使组织降解 培养板和细胞暴露于塑料分解产物; 3）与 由于玻璃状塑料的光学特性， 聚合物和SBS兼容板格式。 在第一阶段，我们将完成以下具体目标：目标1：表征玻璃状 可以承受腐蚀性环境的聚合物，能够被注塑成型， 大规模生产，并且对细胞培养是惰性的。目标2：生成玻璃状SciFlowTM 腐蚀暴露动力学和生物测定评价系统原型。 在完成第一阶段的目标后，我们的第二阶段工作将集中于验证系统， 将该装置按比例放大以用于生产。该项目的成功完成将导致发展 SciFlow耐腐蚀系统，这将提供第一个体外系统， 化学惰性环境，适合在长期腐蚀性培养中重复给药 环境.