Toxicology-testing platform integrating immunocompetent in vitro/ex vivo modules with real-time sensing and machine learning based in silico models for life cycle assessment and SSbD

安全和可持续的设计方法需要对化学品的毒性进行整个生命周期的监测。然而，目前的测试系统无法模拟与每个步骤相关的暴露条件，并且与下游计算机模拟分析不兼容。需要新的成套仪器，使模块化测试能力与集成的数据桥接和渐进的计算机模型开发系统。TOXBOX将提供一种基于H2020项目PANBioRA中开发的原型的设备，该设备具有灵活的微流体和仪器架构，可提供即插即用的测试平台，以方便访问和实验室间验证。该系统将纳入以下测试，并对生命周期的每个步骤进行修改：自动细胞毒性和遗传毒性测试，连接屏障/代谢组织与细胞因子和实时电化学读数的耦合，模拟环境条件的流动循环模块，基于斑马鱼胚胎的机械刺激测试模块。该系统将使用金属2D结构和纳米颗粒，杀菌剂和已知的内分泌干扰物进行验证。定制的功能性多肽（新型杀生物剂）将用于覆盖设计阶段。将迭代开发用于长期效应的渐进式计算机模拟模型，并用于预测待测试的每个新组，直到使用新化学制剂实现良好的可预测性（综合风险评估）。将开发一个数据管理平台，以便与现有数据库进行接口。在4个合作伙伴对器械进行实验室间确认后，将准备一个标准化文件夹，以便在材料生命周期评估的所有阶段对不同的利益相关者进行测试。TOXBOX希望推出一种仪器，为每种化学品提供相关条件下的可靠毒性数据，并实现可靠的计算机模型开发。

Safe and Sustainable by Design approach requires an entire life cycle monitoring of toxicity of chemicals. However, current testing systems cannot mimic the exposure conditions related to each step and are not compatible with downstream in silico analyses. New sets of instrumentation that enables modular testing capacities with integrated data bridging and progressive in silico model development systems are needed. TOXBOX will provide a device based on a prototype developed in a H2020 project, PANBioRA, with a flexible microfluidic and instrument architecture to provide a plug and play testing platform to ease accessibility and interlaboratory validation. The system will incorporate the following tests, with modifications for each step of life cycle: automated cytotoxicity and genotoxicity tests, connected barrier/metabolic tissue couples with cytokine and real-time electro-chemical read-outs, flow cycle modules with environment mimicking conditions, a testing module based on zebrafish embryo with mechanical stimuli. The system will be validated using metallic 2D structures and nanoparticles, biocides, and known endocrine disruptors. Custom made functional polypeptides (novel biocides) will be used to cover the design phase. Progressive in silico models for long term effects will be iteratively developed and used to predict each new group to be tested until good predictability is achieved with new chemical formulations (comprehensive risk assessment). A data management platform that enables interfacing with the available databases will be developed. After interlaboratory validation of the device by 4 partners, a standardization folder will be prepared, to make the device available for testing with accessibility at all stages of material life cycle assessment to different stakeholders. TOXBOX aspires to bring forth an instrument that will provide reliable toxicity data in relevant conditions for each chemical and enable reliable in silico model development.