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

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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.