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

此PFI：空气技术转换项目专注于转换基于表面声波(SAW)的生物传感和非特异性结合去除技术，以满足直接从体液(如血液和尿液)定量护理点(POC)生物标记物的需求。这种SAW生物传感器很重要，因为血液和尿液中的蛋白质水平为pg/ml，是癌症等疾病的预后和诊断标记物。这项技术能够在POC环境中(例如在临床医生的办公室)快速、定量地确定生物标记物；这可以为患者带来更快的诊断。该项目将产生用于POC应用的SAW生物传感器原型所需的概念验证。这种SAW生物传感器具有以下独特功能：在pg/ml范围内具有临床相关的低检测下限，疾病生物标志物的快速量化，从真实基质(如血液)进行POC检测，以及与现有技术相比减少了错误确定。与市场上任何一种基于光学、声学或电学传感原理的领先竞争技术相比，这些特性提供了以下优势：精度、体积小、成本节约和易用性。该项目在从研究发现转化为商业应用的过程中解决了以下技术差距(S)：(1)通过使用Rayleigh SAW产生的声流技术去除非特异结合(NSB)蛋白质，直接从复杂基质中操作；(2)通过通过声流诱导混合改进孵育时间，实现临床环境中必要的快速检测；(3)通过结合使用声子结构和功能化纳米探针，操纵剪切水平锯，将检测极限降低至临床相关水平；以及(4)将这些功能整合到用于POC应用的小型传感器平台上。利用压电衬底ST石英在垂直方向上支撑剪切-水平和剪切-垂直极化的锯片，在单个传感区域上实现了传感、NSB去除和混合功能。这使得可以制造小型、快速、无标记的传感器微阵列来量化多个生物标记物，从而能够在临床相关浓度下对疾病生物标记物面板进行POC监测。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，本项目展示了癌症生物标记物在pg/ml水平的检测极限。利用声流技术去除和混合NSB，并将这些现象与传感相结合，将改变POC生物传感器技术。这种声表面波生物传感器也适用于食品安全和环境监测中的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，他们将通过每周与商业合作伙伴和导师的互动、参加Venture Well的BMEdea等技术竞赛、与成功的科技型小企业企业家互动，以及参加位于南佛罗里达大学的i-Corps训练营，获得创新、创业和技术翻译经验。该项目聘请了商业导师Victor Poirier(NAE成员和植入式心脏辅助设备领域的先驱)、商业合作伙伴(Qorvo和AW传感器)和合作者(莫菲特癌症中心的Santo Nicosia和托莱多大学的Brent Cameron)，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努力。

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.