PFI:AIR - TT: Point of Care Biosensor for Quantification of Biomarkers in Bodily Fluids Based on Surface Acoustic Waves

这个PFI: AIR技术翻译项目的重点是翻译基于表面声波（SAW）的生物传感和非特异性结合去除技术，以满足直接从血液和尿液等体液中进行生物标志物定量的需求。这种SAW生物传感器很重要，因为血液和尿液中pg/ml水平的蛋白质是癌症等疾病的预后和诊断标志物。该技术可以在临床医生办公室等POC环境中快速定量测定生物标志物；这可能会使患者得到更快的诊断。该项目将为POC应用的SAW生物传感器的原型设计提供必要的概念验证。这种SAW生物传感器具有以下独特的特点：在pg/ml范围内具有较低的临床相关检测限，疾病生物标志物的快速定量，从真实基质（如血液）中检测POC，以及与现有技术相比减少错误测定。这些特性提供了以下优势：与该市场中基于光学、声学或电传感原理的任何领先竞争技术相比，精确、体积小、节省成本和易于使用。该项目解决了从研究发现到商业应用的以下技术差距：(1)利用瑞利saw产生的声流去除非特异性结合（NSB）蛋白，直接从复杂基质中进行操作；(2)通过声流诱导混合，提高培养时间，在临床环境中进行必要的快速检测；(3)利用声子结构结合功能化纳米探针操作剪切水平saw，将检测限降低到临床相关水平。(4)将这些功能集成到用于POC应用的小型传感器平台上。基于ST石英的利用，压电衬底在正交方向上支持剪切-水平和剪切-垂直极化的saw，在单个传感区域上实现了传感、NSB去除和混合功能。这允许制造小型、快速、无标记的传感器微阵列，用于定量多种生物标志物，从而实现POC监测临床相关浓度的疾病生物标志物。此外，在传感器配置中加入微腔阵列将提高灵敏度，降低检测极限。结合使用金纳米颗粒构建的纳米探针，该项目证明了癌症生物标志物在pg/ml水平上的检测限。利用声流去除和混合NSB以及将这些现象配置为传感将改变POC生物传感器技术。这种SAW生物传感器也适用于食品安全和环境监测中其他复杂基质的检测。参与该项目的人员，包括2名本科生、1名研究生和1名博士后，将通过每周与商业伙伴和导师的互动、参加科技竞赛（如Venture Well的BMEidea）、与成功的科技小企业企业家的互动，获得创新、创业和技术翻译经验。并参加位于南佛罗里达大学的I-Corps训练营。该项目由商业导师Victor Poirier （NAE成员，植入式心室辅助装置领域的先驱）、商业合作伙伴（Qorvo和AW Sensors）和合作者（莫菲特癌症中心的Santo Nicosia和U. Toledo的Brent Cameron）共同参与，以增强研究能力，提供测试环境，并指导这项技术从研究发现到商业现实的商业化方面的工作。

This PFI: AIR Technology Translation project focuses on translating surface acoustic wave (SAW) based biosensing and non-specific binding removal technology to fill the need for point of care (POC) biomarker quantification directly from bodily fluids such as blood and urine. This SAW biosensor is important because proteins in blood and urine in pg/ml levels are prognostic and diagnostic markers for diseases such as cancer. This technology enables rapid, quantitative determinations of biomarkers in POC settings such as in a clinician's office; this could lead to faster diagnoses for patients. The project will result in proof-of-concepts necessary for prototyping the SAW biosensor for POC applications. This SAW biosensor has the following unique features: low, clinically-relevant detection limits in the pg/ml range, rapid quantification of disease biomarkers, POC detection from real matrices such as blood, and reduction in false determinations compared to existing technologies. These features provide the following advantages: accuracy, small size, cost savings, and ease of use when compared to any of the leading competing technologies based on optical, acoustic or electrical sensing principles in this market space. This project addresses the following technology gap(s) as it translates from research discovery toward commercial application: (1) operation directly from complex matrices by removing non-specifically bound (NSB) proteins using acoustic streaming generated by Rayleigh SAWs, (2) rapid determinations necessary in clinical settings by improving incubation times via acoustic streaming induced mixing, (3) lowered detection limits to clinically-relevant levels by manipulation of shear-horizontal SAWs using phononic structures combined with the use of functionalized nanoprobes, and (4) integration of these features on a small sensor platform for POC applications. Based on the utilization of ST quartz, a piezoelectric substrate that is shown to support SAWs of shear-horizontal and shear-vertical polarizations in orthogonal directions, sensing, NSB removal and mixing functions are brought to bear on a single sensing area. This allows for small, rapid, label-free sensor micro-arrays to be fabricated for quantification of multiple biomarkers, thus enabling POC monitoring of disease biomarker panels at clinically-relevant concentrations. Additionally, incorporation of microcavity arrays in the sensor configuration will push sensitivity higher and limits of detection lower. Combined with nanoprobes constructed using gold nanoparticles, detection limits in the pg/ml level for cancer biomarkers are demonstrated in this project. NSB removal and mixing using acoustic streaming and configuration of these phenomena with sensing will transform POC biosensor technology. This SAW biosensor is suitable for detection from other complex matrices of interest to food safety and environmental monitoring as well. Personnel involved in this project, 2 undergraduate, 1 graduate and 1 post-doctoral students, will receive innovation, entrepreneurship, and technology translation experiences through weekly interactions with business partners and mentors, participation in technology competitions such as Venture Well's BMEidea, interactions with successful technology small-business entrepreneurs, and participation in the I-Corps training camp at the I-Corps training site located here at the University of South Florida. The project engages a business mentor Victor Poirier (NAE member and pioneer in the field of implantable ventricular assist devices), commercial partners (Qorvo and AW Sensors), and collaborators (Santo Nicosia of Moffitt Cancer Center and Brent Cameron at U. Toledo) to augment research capability, provide test environment, and guide commercialization aspects in this technology translation effort from research discovery toward commercial reality.