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

血清或血浆中不规则数量的微小RNA(MiRNA)是许多慢性疾病，特别是癌症的生物标志物。不同类型的miRNAs被发现在不同的癌症中过度表达。这项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中的miRNA分子生物标记物的POC测量。这项研究将利用该团队之前开发的从全血中提取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所提出的传感器集成，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定探针来提高灵敏度。一个用于测量多个miRNAs的集成原型将在这个项目结束时交付使用，并将在未来进一步开发以检测更大的miRNAs生物标志物文库。纳米锥阵列基于几种有趣且鲜为人知的锥形/楔形几何物理现象并制造而成。与金属尖端的等离子体共振和介质楔体/锥体的散射一样，圆锥尖端的逝去波模可以产生高光强的局域热点。这种尖端消逝模式耦合到经历多次内反射的特定光纤波导模式。通过一种独特的激光气泡接触线沉积技术，可以进一步增强等离子体共振的共振核-壳纳米颗粒被固定在尖端周围。锥形衬底的极端曲率控制着锥形尖端上激光成核气泡的大小和随后的接触线退缩速率。在楔形移动接触线的本体溶液中，纳米粒子的沉积还受楔形接触线处的奇异加热和Marangoni效应的控制。所有这些现象都是由锥体和楔体的无限曲率驱动的，我们将结合计算和实验对这些现象进行仔细的研究。在这项拟议的项目中，该团队将为一组有前景的癌症生物标记物mi-RNAs设计这样的纳米阵列，其在小容量患者血液样本(~10微升)中的单个拷贝数从10^2到10^6不等。私人投资督察会利用他们过往的经验和业界关系，为拟议的感测平台寻找商业化机会。该项目还将为来自未被充分代表的本科生群体、当地社区大学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优势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.