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

小型企业创新研究(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。目前测试一种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，许多动物毒性筛选往往发生在产品开发的后期阶段--在这一点上，已经花费了数百万美元的开发资金。重大财务损失是在不利的筛查结果之后发生的。具体地说，这项技术的开发意图不仅是为了在下游节省数百万美元，还将在跨行业的产品开发过程中维护动物福利和道德。与目前市场上已有的检测方法相比，这种新型的细胞毒性检测方法在时间和样本数量方面具有直观和易于管理的特点，同时还能提供快速、准确的评估。到2025年，全球毒物检测市场预计将达到144亿美元。这个小型企业创新研究(SBIR)第一阶段项目旨在开发一种利用细胞-电极界面生物打印技术的新型、可扩展的体外毒性测试技术。毒理学测试是在药物或消费品的产品开发接近尾声时进行的，在此之前，已投入数百万美元进行研发。这些体内筛查设备价格昂贵，对动物有害，而且经过多年的上市前开发，可能会杀死产品。生物印迹已经成为一种很有前途的新方法，用于体外毒理学筛选的生物软化模型和系统，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、产量低、成本高、缺乏灵活性)。这一建议旨在通过以下方式解决这些缺点：1)开发一种使用创新的生物打印技术来丰富组织的新方法；2)集成电极传感器，通过电信号输出相关性定量测量细胞的健康和活力。组织制造和电极-细胞测量的实验成功将取决于采用新的生物打印方法的细胞活性超过80%，以及电阻抗读数和典型分子毒性分析之间的相关值r 0.6。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.