SBIR Phase I: Fully Screen Printed Electric Cell-Substrate Impedance Sensing Toxicity Assay

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力是开发一种新的产品测试工具，以评估开发中产品的潜在人体毒性。目前测试产品对人类影响的做法包括冗长、昂贵和有害的动物研究。考虑到成本，许多动物毒性筛选通常发生在产品开发的后期阶段——此时已经花费了数百万美元的开发资金。不利的筛选结果导致重大经济损失。具体来说，这项技术的开发不仅旨在为下游节省数百万美元，而且还将在各行业的产品开发过程中维护动物福利和道德规范。与目前市场上的其他产品相比，这种新型细胞毒性测定方法直观，易于管理，涉及时间和样品数量，同时提供快速，准确的评估。到2025年，全球毒理学检测市场预计将达到144亿美元。这个小企业创新研究（SBIR）第一阶段项目旨在开发一种新颖的、可扩展的体外毒性试验，利用细胞电极界面生物打印技术。毒理学测试发生在药品或消费品的产品开发的最后阶段，在数百万美元已经投入研发之后。这些体内筛选昂贵，对动物有害，并且在经过多年的上市前开发后有可能杀死产品。生物打印已经成为一种有前途的新方法，用于体外毒理学筛选的生物制造模型和系统，试图解决上述伦理和经济负担。然而，尽管具有革命性的潜力，传统的生物打印在技术和商业上都存在缺陷（例如细胞损伤、低通量、高成本、不灵活）。本提案旨在通过开发1)一种使用创新生物打印技术的生物制造组织的新方法和2)电极传感器的集成来通过电信号输出相关性定量测量细胞健康和活力来解决这些缺点。组织制造和电极细胞测量的实验成功将取决于采用新型生物打印方法后细胞存活率的80%以上，以及电阻抗读数与典型分子毒性分析之间的相关值为0.6。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop a new product testing tool to evaluate potential human toxicity of products in development. Current practices that test a product’s effects on humans consist of lengthy, expensive, and harmful animal studies. Given the cost, many animal toxicity screenings often happen in later product development stages – at which point millions of development dollars have already been spent. Major financial losses follow unfavorable screening results. Specifically, this technology will be developed with the intention to not only save millions of dollars downstream, but also maintain animal welfare and ethics in the product development process across industries. Compared to the current market offerings by others, this novel cell toxicity assay is intuitive and easy to manage with respect to time and the number of samples, while providing a rapid, accurate assessment. The global toxicology testing market is projected to reach $14.4 billion by 2025. This Small Business Innovation Research (SBIR) Phase I project is aimed at developing a novel, scalable in vitro toxicity assay that leverages a cellular-electrode interface bioprinting technology. Toxicological testing occurs toward the end of product development of a drug or consumer product after millions of dollars have already been poured into R&D. These in vivo screens are expensive, harmful to animals, and have the potential to kill products after years of pre-market development. Bioprinting has emerged as a promising new approach for biofabricating models and systems for in vitro toxicology screening in an attempt to address the ethical and financial burden aforementioned. Yet, despite revolutionary potential, traditional bioprinting has technical and commercial drawbacks (e.g. cell damage, low throughput, high cost, inflexible). This proposal is designed to address those drawbacks by developing 1) a novel method to biofabricate tissues using an innovative bioprinting technique and 2) an integration of electrode sensors to quantitatively measure cell health and viability via electrical signal output correlations. Experimental success of tissue fabrication and electrode-cellular measurements will be determined by greater than 80% of cellular viability following novel bioprinting method and a correlation value of r 0.6 between electrical impedance readings and canonical molecular toxicity analyses.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.