I-Corps: Heat-stable binding proteins for diverse diagnostic applications

这个I-Corps项目的更广泛的影响/商业潜力将是能够快速开发准确、热稳定和负担得起的新型诊断测试，从而扩大服务不足的患者群体获得医疗服务的机会。诊断免疫测定传统上依赖于称为抗体的结合蛋白，用于捕获和检测患者样品中的疾病生物标志物。高质量诊断抗体的开发和生产缓慢且昂贵，并且这类试剂经常受到热不稳定性和脱靶结合的影响，导致测试结果不准确。该项目的重点是开发一种新型的低成本，热稳定的结合蛋白，可以快速开发，并容易整合到各种诊断格式。这些结合蛋白可以被工程化以靶向不同的疾病生物标志物，使得该平台适合于开发针对许多不同医疗条件的新型检测方法。该I-Corps项目将探索在广泛的诊断应用中使用结合蛋白的商业潜力。所提出的模块化结合蛋白已被验证用于一系列标准诊断形式和许多疾病靶标。用于开发这些新的结合蛋白的体外过程可以被精细地控制，以确保所选择的试剂是高度靶特异性的，并且以高亲和力结合感兴趣的生物标志物。此外，所选试剂可以进行进一步的工程改造，以产生多功能蛋白质构建体，从而实现简易的装置制造、高增益信号放大和高效的靶捕获。包含这些热稳定试剂的低成本诊断设备将能够在医疗点对疾病病例进行具有成本效益的检测，并且该平台所实现的新型诊断能力将解决未满足的公共卫生需求。该奖项反映了NSF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 I-Corps project will be to enable the rapid development of novel diagnostic tests that are accurate, thermally stable, and affordable, thereby expanding access to medical care within underserved patient populations. Diagnostic immunoassays have traditionally relied upon binding proteins called antibodies for the capture and detection of biomarkers of disease in patient samples. The development and production of high-quality diagnostic antibodies is slow and expensive, and this class of reagents is frequently subject to thermal instability and off-target binding, resulting in inaccurate test results. This project focuses on the development of a novel class of low-cost, heat-stable binding proteins that can be rapidly developed and readily integrated into various diagnostic formats. These binding proteins can be engineered to target diverse disease biomarkers, making this platform suitable for the development of novel assays addressing many different medical conditions.This I-Corps project will explore the commercial potential of using binding proteins in a broad range of diagnostic applications. The proposed modular binding proteins have been validated for a range of standard diagnostic formats and numerous disease targets. The in vitro processes used to develop these new binding proteins can be finely controlled in order to ensure that selected reagents are highly target-specific, and bind to the biomarker of interest with high affinity. In addition, selected reagents can be subjected to further engineering in order to produce multi-functional protein constructs, enabling facile device manufacturing, high-gain signal amplification, and highly efficient target capture. Low-cost diagnostic devices incorporating these heat-stable reagents will enable the cost-efficient detection of disease cases at the point-of-care, and novel diagnostic capabilities enabled by this platform will address unmet public health needs.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.