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要求对化学品的毒性进行全生命周期的监测。然而，目前的测试系统不能模拟与每个步骤相关的暴露条件，并且与硅分析中的下游不兼容。需要一套新的仪器，使模块化测试能力与集成的数据桥接和电子模型开发系统中的渐进式测试能力相结合。TOXBOX将提供一种基于在H2020项目PANBioRA中开发的原型的设备，具有灵活的微流控和仪器架构，以提供即插即用测试平台，从而简化可访问性和实验室间验证。该系统将包括以下测试，并针对生命周期的每个步骤进行修改：自动化细胞毒性和遗传毒性测试，具有细胞因子和实时电化学读数的连接屏障/代谢组织偶，具有模拟环境条件的流动循环模块，基于机械刺激的斑马鱼胚胎测试模块。该系统将使用金属2D结构和纳米颗粒、杀生剂和已知的内分泌干扰物进行验证。定制的功能多肽(新型杀生剂)将用于覆盖设计阶段。将反复开发用于长期影响的渐进式计算机模型，并用于预测每一组要测试的新组，直到通过新的化学配方实现良好的可预测性(全面风险评估)。将开发一个能够与现有数据库对接的数据管理平台。在4个合作伙伴对该装置进行实验室间验证后，将准备一个标准化文件夹，使不同的利益攸关方能够在材料生命周期评估的所有阶段使用该装置进行测试。TOXBOX渴望推出一种仪器，在相关条件下为每种化学品提供可靠的毒性数据，并使可靠的硅胶模型开发成为可能。

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.