Microfluidic Biotool to Accurately Model Corrosive Chemical Exposures for Human

项目摘要 在评估化学物质对人类的影响的需要之间存在着严重的差距 生理学和体内和体外测试系统的可用性，提供必要的 预测性数据。这一需求对于腐蚀性和腐蚀性化学品来说尤其明显 与目前的体外和体内测试系统不兼容。例如，有毒的 物质控制法(TSCA)要求EPA库存所有当前生产的， 加工和进口的化合物。这份清单目前包含8.5万种化学物质， 许多没有毒性数据，以生物相关的方式进行评估。 该SBIR项目的范围是开发一流的耐腐蚀性流体培养物 这一系统将使环境、监管、农业、化工等行业 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公司 之前向科学工具市场引入了一项颠覆性技术，使 微流控环境中非线性流动条件下的毒性试验。腐蚀性 这项工作将开发的抗性SciFlow系统将在以下三个方面提供主要进展 目前的毒理学测试选项：1)大大提高了生物相关性，因为 核心SciFlow技术的流体和非线性曝光梯度；2)测试能力 较高剂量的腐蚀性化学物质可持续更长时间，而不会使组织退化 培养板和细胞暴露在塑料分解产品中；3)与 由于类玻璃塑料的光学特性，高含量成像器和平板阅读器 聚合物和SBS兼容的板材格式。 在第一阶段，我们将完成以下具体目标：目标1：表征玻璃样 可耐受腐蚀性环境的聚合物，可用于注塑 大量生产，并对细胞培养具有惰性。目标2：生成类似玻璃的SciFlowTM 腐蚀暴露动力学和生物测定评估的系统原型。 在第一阶段目标完成后，我们第二阶段的工作将集中于验证系统和 按比例调整该装置以进行生产。这个项目的成功完成将导致开发 这将为第一个体外系统提供 适合长期腐蚀培养中反复给药的化学惰性环境 环境。

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.