SBIR Phase I: Single molecule detection of biomarkers using gold nanorods for in-vitro diagnostics

这项小企业创新研究（SBIR）项目的更广泛影响/商业潜力是开发一种新的诊断平台技术，与目前的诊断测试相比，该技术更快、更敏感、成本更低。更快的诊断结果将通过快速准确地隔离感染患者和预防合并感染来改善医院护理。目前的体外诊断测试要么非常敏感，需要大量的基础设施和技术专长才能执行，要么快速且易于使用，预测价值较差。这个SBIR项目将使一个处理复杂液体（如全血）的医疗诊断平台能够在快速的时间框架内区分多种病原体和临床生物标志物，而不会影响预测价值。将提高灵敏度的快速检测与简单的“从样本到答案”的操作方法相结合，从根本上颠覆了医疗诊断领域现有的两种独立的市场能力。此外，该平台正在开发中，以样本到答案的形式使用，以便在资源有限的环境中使用，并在医疗点附近使用；例如，在西非诊断埃博拉病毒。这项技术解决了一个重要的市场机会，目前正在经历快速增长。这个SBIR一期项目建议开发使用金纳米棒标签对干涉传感器表面的生物标志物进行单分子计数。使用具有极化增强的纳米棒将导致信号比使用球形颗粒增加10倍。这允许使用较低的数值孔径物镜，并减少成像限制，因为聚焦深度是微米而不是纳米。来自纳米棒的信号增加的另一个好处是，它允许传感器在较低的放大倍率下成像。视野的增加使整个分析成像不需要电动X-Y分期。这项工作可能会使诊断平台的成本显著降低，仪器尺寸显著减小，机械故障减少，采集速度显著提高。拟议的工作有两个主要目标。首先是优化利用金纳米棒检测蛋白质和核酸生物标志物。第二步是制作原型并展示一种低成本的基于纳米棒的仪器。目标的完成将为体外诊断技术的商业化铺平道路。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop a new diagnostic platform technology that is faster, more sensitive, and lower cost as compared with current diagnostic tests. Faster diagnostic results will improve hospital care by quickly and accurately isolating infectious patients and preventing co-infections. Current in-vitro diagnostic tests are, either, very sensitive, requiring significant infrastructure and technical expertise to perform, or, are quick and easy-to-use with poor predictive value. This SBIR project will enable a medical diagnostic platform that works with complex fluids (e.g., whole blood) to distinguish numerous pathogens and clinical biomarkers in a rapid time-frame without compromising on the predictive value. Combining a rapid test with improved sensitivity and an easy "sample-to-answer" method of operation fundamentally disrupts the two existing previously separate market capabilities for medical diagnostics. Additionally, the platform is being developed to be used in a sample-to-answer format so that it can be used in resource-limited settings, and near the point-of-care; for example, in West Africa for diagnosing Ebola virus. This technology addresses a significant market opportunity that is currently experiencing rapid growth.This SBIR Phase I project proposes to develop the use of gold nanorod tags for single molecule counting of biomarkers on an interferometric sensor surface. The use of nanorods with polarization enhancement will result in a 10-fold increase in signal over the use of spherical particles. This allows the use of a lower numerical aperture objective and reduces the imaging constraints because the depth of focus is in microns rather than nanometers. Another advantage as a result of increased signal from nanorods, is that it allows imaging of the sensor at lower magnification. The increase in the field of view enables imaging of entire assays without the need of motorized X-Y stages. The work potentially will result in a diagnostic platform with a significantly lower cost, dramatically reduced instrument size, fewer mechanical failures, and significantly improved acquisition speed. There are two primary objectives for the proposed work. The first is to optimize the use of gold nanorods for detection of protein and nucleic acid biomarkers. The second is to prototype and demonstrate a low-cost nanorod-based instrument. Completion of objectives will enable a path toward commercialization of the technology for in-vitro diagnostics.