PFI-TT: Interferometric Imaging for Multiplexed Molecular Kinetics

这项创新-技术转化伙伴关系（PFI-TT）项目的更广泛影响/商业潜力是推进当前最先进的生物检测技术。体外诊断和制药行业都依靠生物技术工具来发现和开发新的分子相互作用。由于所有的生物学途径都依赖于蛋白质- dna和蛋白质-蛋白质的相互作用，不仅这些相互作用的准确表征至关重要，而且它们是疾病治疗中小分子破坏的主要目标。新出现的疾病需要新的诊断测试，因此需要新的分子发现。这项技术转化（PFI-TT）项目将为基于光干涉的新技术的商业化铺平道路。通过实现更好的诊断和治疗，将产生直接的社会影响。此外，我们将在技术开发和创业方面培养几名女性工程博士研究生。拟议的项目建立在干涉反射成像传感器（IRIS）技术的创新基础上。潜在的测量原理是基于光学透明薄膜反射的光的干涉——同样的现象，当白光照射时，肥皂膜会呈现彩虹色。提出的创新使用了一种不同于通过复杂光学共振增强信号的传统方法的方法；相反，我们利用信号平均的功率在一个简单的仪器平台上实现非常高的灵敏度。通过设计，由于溶液的变化（称为“体效应”），IRIS技术对背景信号具有弹性。提出的新技术将进一步提高区分表面分子结合和体溶液变化的能力。IRIS平台在所有无标签光学生物传感器中是独一无二的，它可以在硅微流控芯片上作为低成本耗材进行分子结合动力学的多路检测。IRIS芯片上可以排列数百个捕获探针，并对目标分子进行并行测试。该仪器的预期低成本将允许集成并行传感器，以同时实现高吞吐量和多路复用。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 Partnerships for Innovation - Technology Translation (PFI-TT) project is to advance the current state-of-the-art biological detection technologies. Both in vitro diagnostics and the pharmaceutical industry rely on biotechnology tools to discover and develop new molecular interactions. Since all biological pathways rely on protein-DNA and protein-protein interactions, not only is accurate characterization of these interactions crucial, but they are prime targets for disruption with small molecules in disease treatment. Emerging diseases call for new diagnostic tests and thus new molecular discoveries. This Technology Translation (PFI-TT) project will pave the way to commercialization of a new technology based on light interference. There will be a direct societal impact by enabling better diagnostics and therapeutics. In addition, we will train several women engineering PhD students in technology development and entrepreneurship. The proposed project builds on innovations in Interferometric reflectance imaging sensor (IRIS) technology. The underlying measurement principle is based on the interference of light reflected from an optically transparent thin film—the same phenomenon that gives rainbow colors to a soap film when illuminated by white light. The proposed innovation uses a different approach than the conventional method of enhancing the signal through complex optical resonances; instead, we exploit the power of signal averaging to achieve very high sensitivity in a simple instrument platform. By design, the IRIS technique is resilient to the background signal due to variations in the solution (termed “bulk effect”). The proposed new technique will further improve the ability to distinguish molecular binding on the surface from the variations in the bulk solution. The proposed IRIS platform is unique among all label-free optical biosensors with multiplexed detection of molecular binding kinetics on Si microfludic chips as low-cost consumables. Hundreds of capture probes can be arrayed on the IRIS chip and tested against a target molecule in parallel. The expected low cost of the instrument will allow for integration of parallel sensors to achieve high throughput and multiplexing simultaneously.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.