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

血清或血浆中不规则量的特定微RNA（miRNA）分子是许多慢性疾病特别是癌症的有希望的生物标志物。已经发现不同类型的miRNA在不同癌症中过表达。本研究的目标是开发基于光纤的生物传感器，用于广泛的生物传感应用的miRNA分子生物标志物的即时（POC）测量。这项研究将利用该团队先前开发的用于从全血中提取miRNA的预处理技术。为了实现POC早期癌症筛查，这些预处理技术将与拟议的传感器集成，以实现极高的检测灵敏度。在这种传感器中，将使用附着在纳米颗粒上的特异性探针来提高灵敏度。在本项目的最后，我们将提供一个用于检测多种miRNAs的集成原型，并将进一步开发以检测更大的miRNAs生物标志物库。纳米锥阵列是基于圆锥/楔形几何形状的几种有趣且知之甚少的物理现象制造的。类似于金属尖端处的等离子体共振和电介质楔/锥处的散射，圆锥尖端处的倏逝波模式可以产生具有高光强的局部热点。这种尖端倏逝模耦合到经历多次内反射的特定光纤波导模。共振核壳纳米粒子，它允许进一步的等离子体共振增强，固定在尖端周围的独特的激光气泡接触线沉积技术。圆锥基底的极端曲率控制了圆锥尖端上的激光成核气泡的大小和随后的接触线后退速率。在楔形移动接触线的本体溶液中的纳米颗粒的沉积也由楔形接触线处的奇异加热和Marangoni效应控制。所有这些现象驱动的无限曲率的圆锥和楔形将仔细研究计算和实验相结合。在这个拟议的项目中，研究小组将设计这样一种纳米阵列，用于一组有前途的癌症生物标志物mi-RNAs，其在小体积患者血液样本（约10微升）中的单个拷贝数范围为10^2至10^6。利用他们过去的经验和行业联系，PI将为拟议的传感平台寻求商业化机会。该项目还将为来自代表性不足的本科生群体、当地社区学院和高中的学生提供研究机会。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.