Highly Sensitive Multiplexed Nanocone Array for Point-of-Care Pan-Cancer Screening

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Irregular amounts of specific molecules of micro-RNA (miRNA) in serum or plasma are promising biomarkers for many chronic diseases, particularly cancers. Different types of miRNAs have been found to be over-expressed for different cancers. The goal of this research is to develop optical fiber-based biosensors for point-of-care (POC) measurement of miRNA molecular biomarkers for a wide of range of bio-sensing applications. This research will leverage the team's previously developed pretreatment technologies for miRNA extraction from whole blood. To achieve POC early cancer screening, these pretreatment technologies will be integrated with the proposed sensor to achieve extremely high sensitivity of detection. In this sensor, specific probes attached to nanoparticles will be used to increase sensitivity. An integrated prototype for measuring multiple miRNAs will be delivered at end of this project, and this will be further developed to detect much larger libraries of miRNAs biomarkers in the future.The nanocone array is based on and fabricated with several intriguing and poorly understood physical phenomena at conic/wedge geometries. Like plasmonic resonance at metallic tips and scattering at dielectric wedges/cones, evanescent wave mode at a conic tip can produce a localized hotspot with high optical intensity. This tip evanescent mode is coupled to specific optical fiber wave-guide modes that undergoes multiple internal reflections. The resonant core-shell nanoparticles, which allows further plasmonic resonant enhancement, are immobilized around the tip by a unique laser bubble contact line deposition technique. The extreme curvature of the conic substrate controls the size of the laser-nucleated bubble on the cone tip and the subsequent contact-line receding rate. The deposition of the nanoparticle in the bulk solution to the wedge-like moving contact line is also controlled by singular heating and Marangoni effects at the wedge-like contact line. All these phenomena driven by the infinite curvatures of cones and wedges will be carefully studied combining computation and experiments. Within this proposed project, the team will design such a nanoarray for a promising set of cancer biomarkers, mi-RNAs, whose individual copy number ranges from 10^2 to 10^6 in a small-volume patient blood sample (~10 microliter). Leveraging their past experience and industrial connections, the PIs will seek commercialization opportunities for the proposed sensing platform. This project will also provide research opportunities to students from under-represented undergraduate groups, local community college and high school.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.