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：AIR 技术翻译项目专注于翻译基于表面声波 (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护理点 (POC) 生物标志物定量的需求。这种 SAW 生物传感器非常重要，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。该技术能够在 POC 环境（例如临床医生办公室）中快速定量测定生物标志物；这可以加快患者的诊断速度。该项目将为 POC 应用的 SAW 生物传感器原型设计提供必要的概念验证。该 SAW 生物传感器具有以下独特功能：临床相关检测限低（pg/ml 范围内）、疾病生物标志物快速定量、从血液等真实基质中进行 POC 检测，以及与现有技术相比减少错误测定。与该市场领域中任何基于光学、声学或电气传感原理的领先竞争技术相比，这些功能具有以下优势：精确、尺寸小、节省成本和易于使用。该项目在从研究发现转向商业应用时解决了以下技术差距：(1) 通过使用瑞利声表面波产生的声流去除非特异性结合 (NSB) 蛋白质，直接从复杂基质中进行操作，(2) 快速通过声流诱导混合来改善孵育时间，从而在临床环境中进行必要的测定，（3）通过使用声子结构结合使用功能化的剪切水平声表面波操作，将检测限降低到临床相关水平纳米探针，(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，压电基板可支持正交方向剪切水平和剪切垂直极化的 SAW、传感、NSB 去除和混合功能，可在单个传感区域上发挥作用。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种生物标志物，从而能够在临床相关浓度下对疾病生物标志物组进行 POC 监测。此外，在传感器配置中加入微腔阵列将提高灵敏度并降低检测限。结合使用金纳米粒子构建的纳米探针，该项目证明了癌症生物标志物的 pg/ml 水平的检测限。使用声流去除和混合 NSB 以及通过传感配置这些现象将改变 POC 生物传感器技术。该 SAW 生物传感器也适用于食品安全和环境监测感兴趣的其他复杂基质的检测。参与该项目的人员，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Venture Well的BMEidea等技术竞赛、与成功人士的互动，获得创新、创业和技术转化的经验。技术小型企业企业家，并参加位于南佛罗里达大学 I-Corps 训练基地的 I-Corps 训练营。该项目聘请了商业导师 Victor Poirier（NAE 成员和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 和托莱多大学的 Brent Cameron）增强研究能力，提供测试环境，并指导该技术转化工作从研究发现到商业现实的商业化方面。