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

用于护理点泛癌症筛查的高灵敏度多重纳米锥阵列

• 批准号: 1931850
• 负责人: Tengfei Luo
• 金额: $ 38.14万
• 依托单位: University of Notre Dame
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1931850&HistoricalAwards=false
• 关键词: Highly; Sensitive; Multiplexed; Nanocone; Array

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.

对于许多慢性疾病，尤其是癌症，血清或血浆中微-RNA（miRNA）的特异性分子（miRNA）是有希望的生物标志物。已发现不同类型的miRNA对于不同的癌症而过表达。这项研究的目的是开发基于光纤的生物传感器，以测量miRNA分子生物标志物（POC），以用于广泛的生物传感应用。这项研究将利用该团队先前开发的预处理技术，用于从全血中提取miRNA。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。在该传感器中，将使用附着在纳米颗粒上的特定探针来提高灵敏度。该项目结束时将传递一个用于测量多个miRNA的集成原型，将来将进一步开发以检测更大的miRNA生物标志物库。纳米阵列基于并制造了几种有趣且在圆锥形/婚礼的GeoMetries中引人入胜且鲜为人知的物理现象。像在金属尖端处的等离子共振和介电楔/锥体处的散射一样，圆锥尖端的evanescent波模式可以产生具有高光学强度的局部热点。此尖端evanevanscent模式与经历多种内部反射的特定光纤波浪旋化模式结合在一起。允许进一步的等离子谐振增强的谐振核壳纳米颗粒通过独特的激光气泡接触线沉积技术固定在尖端周围。圆锥底物的极端曲率控制锥形尖端上激光核泡的气泡的大小和随后的接触线后退速率。纳米颗粒在块状式移动接触线中的大量解决方案中的沉积也受到楔形式接触线的奇异加热和Marangoni效应的控制。所有这些由锥和楔形的无限曲线驱动的现象将仔细研究结合计算和实验。在这个拟议的项目中，该团队将为一组有希望的癌症生物标志物MI-RNA设计这样的纳米阵列，其单个拷贝数在小型患者血液样本（〜10微级）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工业联系，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的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来提供支持。

项目成果

Molecular-Level Understanding of Efficient Thermal Transport across the Silica–Water Interface

• DOI: 10.1021/acs.jpcc.1c06571
• 发表时间: 2021-10
• 期刊: The Journal of Physical Chemistry C
• 作者: Zhihao Xu;Dezhao Huang;T. Luo

Biocompatible Direct Deposition of Functionalized Nanoparticles Using Shrinking Surface Plasmonic Bubble

• DOI: 10.1002/admi.202000597
• 发表时间: 2020-06-01
• 期刊: ADVANCED MATERIALS INTERFACES
• 影响因子: 5.4
• 作者: Moon, Seunghyun;Zhang, Qiushi;Luo, Tengfei
• 通讯作者: Luo, Tengfei