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

PFI:AIR - TT：基于表面声波对体液中生物标志物进行定量的护理点生物传感器

基本信息

批准号：
1640668
负责人：
Venkat Bhethanabotla
金额：
$ 20万
依托单位：
University of South Florida
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-01 至 2021-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1640668&HistoricalAwards=false
关键词：
PFI AIR TT Point Care

项目摘要

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.

该PFI：空气技术翻译项目的重点是基于表面声波（SAW）的生物传感和非特异性结合去除技术，以填补直接从血液和尿液等体液的护理点（POC）生物标志物定量。这看到生物传感器很重要，因为PG/ML水平的血液和尿液中的蛋白质是癌症等疾病的预后和诊断标记。该技术可以快速，定量地确定POC环境中的生物标志物，例如在临床医生办公室中；这可能会导致患者更快的诊断。该项目将导致对POC应用的SAW生物传感器进行原型型概念验证。这看到生物传感器具有以下独特的特征：PG/ML范围内的低临床检测极限，疾病生物标志物的快速定量，与现有技术相比，实际基质（如血液）的POC检测以及虚假确定的降低。这些功能提供了以下优势：与基于该市场领域的光学，声学或电气感应原理的任何领先的竞争技术相比，准确性，尺寸较小，成本节省和易用性。该项目解决了以下技术差距，因为它从研究发现转化为商业应用：（1）通过使用Rayleigh Saws产生的声流删除非特异性结合（NSB）蛋白质直接从复杂矩阵进行操作，（2）通过在临床上进行临床频率限制（3）在临床上的临床频率（3）（3）临床频率限制（3）（3）（2）降低临床型号（3），（3使用语音结构与功能化纳米探针结合使用的剪切 - 锯齿锯，以及（4）在小型传感器平台上集成这些特征以用于POC应用。基于ST Quartz的利用，在正交方向上，将剪切 - 摩托底和剪切垂直极化的锯显示出来的压电基底物，传感，NSB去除和混合功能被带到单个感应区域上。这允许制造小型，快速，无标签的传感器微阵列来定量多种生物标志物，从而在临床上相关的浓度下对POC监测疾病生物标志物面板。另外，将微腔阵列掺入传感器构型将提高灵敏度，并将检测的限制提高。结合使用金纳米颗粒构建的纳米探针，在该项目中证明了癌症生物标志物的PG/ML水平的检测极限。使用声学流以及这些现象与传感的构型进行NSB去除和混合将改变POC生物传感器技术。该SAW生物传感器适合从其他感兴趣的复杂矩阵中检测到食品安全和环境监测。参与该项目的人员，2名本科生，1名研究生和1名专业学生，将通过每周与商业伙伴和导师的互动，参与Venture Well的BMEIDEA，与成功的技术小型业务企业培训I-CORP在I-COUCK Instoration互动中，通过每周与商业伙伴和导师的互动来获得创新，企业家和技术翻译经验佛罗里达。该项目与商业导师Victor Poirier（NAE成员兼植入室辅助设备领域的先驱），商业合作伙伴（Qorvo和AW传感器）以及合作者（Moffitt Cancer Center的Santo Nicosia和U. Toledo的Brent Cameron），以增强研究能力，为测试环境提供了研究，并为商业化的方面提供了研究。