Engineering Quantum Dots and Photonic Metamaterials for Ultrasensitive and Multiplexed Digital Resolution Biomolecule Detection

用于超灵敏和多重数字分辨率生物分子检测的工程量子点和光子超材料

• 批准号: 2232681
• 负责人: Brian Cunningham
• 金额: $ 60万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2232681&HistoricalAwards=false
• 关键词: Engineering; Quantum; Dots; Photonic; Metamaterials

This project will develop highly sensitive approaches for detecting many disease-related molecules, called “biomarkers,” in blood at the same time. These biomarkers will be detected by binding to light-emitting nanoparticles, called Quantum Dots (QDs), that serve as a bright tag. By designing QDs to be easily distinguished from each other, the research team envisions the capability to detect as many as 45 different biomarkers in a single blood droplet. Biomarker detection will be performed on engineered surfaces called “photonic crystals” (PCs) that are able to amplify the QD brightness by several thousand-fold, allowing QDs to be counted individually. The PCs also serve to direct the QD light output in specific directions that are measured to tell the difference between each type of QD. In addition, new approaches will be developed that can rapidly convert each biomarker molecule into many QDs on the PC surface. By combining PCs and QDs, the sensor can be simple, fast, and inexpensive, enabling biomarker tests to be performed in places like clinics and hospitals. The Team will develop a broadly accessible short course entitled “What’s in Your Blood? Genomics Testing and You,” to be offered through the Osher Lifelong Learning Institute. Aspects of the course will be adapted for public-facing programs offered through the Woese Institute for Genomic Biology and an interactive display at “World of Genomics” events that are offered annually at large science museums.Ultrasensitive, ultraselective, and highly multiplexed detection of biomolecules within complex media is a central component of disease diagnostics, life science research, and environmental monitoring. New “digital resolution” biomolecular detection methods are leading toward unprecedented detection limits, but are hindered by complex procedures, thermal cycling, and stringent sample preparation. Recent advances in the capability for photonic metamaterial surfaces to substantially amplify the collected photon output from semiconductor quantum dots are making assays with digital molecule precision compatible with small, low cost instruments. Applying QD tags with photonic crystal fluorescence amplification makes it possible to digitally count target molecules and to perform multiplexing through the ability to distinguish QD emission wavelengths by their outcoupled emission pattern. As a result, single-step, room temperature, enzyme-free assays for microRNA with attomolar-level detection limits and 6 log(10) orders of dynamic range can be achieved, with the potential to extend even further. In this project, the Cunningham and Smith labs will design and synthesize novel QD tags that incorporate engineered multispectral brightness, encodable emission saturation, and encodable PC enhancement factor. The QDs will specifically couple with photonic metamaterial surfaces to enhance their excitation, to modulate their lifetime, and to extract their emission to differentiate up to 45 distinct QD labels for molecular multiplexing. Finally, the team will introduce a new paradigm for biomolecule detection in which each target molecule can generate multiple downstream digital-resolution QD detection events to achieve ultrasensitive detection limits with simple and rapid methods.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.

该项目将开发高度灵敏的方法，同时检测血液中许多与疾病相关的分子（称为“生物标记物”）。这些生物标记物将通过与发光纳米颗粒（称为量子点（QD））结合来检测。通过设计易于区分的量子点，研究小组设想能够在单个血滴中检测多达 45 种不同的生物标记物。被称为“光子晶体”（PC）的量子点亮度可以放大数千倍，从而可以对量子点进行单独计数。这些PC还可以将量子点光输出引导到特定方向，通过测量来区分不同方向。此外，还将开发新的方法，可以将每种生物标记分子快速转化为 PC 表面上的许多 QD。通过将 PC 和 QD 结合起来，传感器可以变得简单、快速且廉价，从而使生物标记测试变得更加容易。该团队将开发一门广泛普及的短期课程，题为“你的血液中有什么？基因组学测试和你”，该课程将通过奥舍尔终身学习研究所提供。面向沃斯基因组生物学研究所提供的项目以及每年在大型科学博物馆举办的“基因组世界”活动中的互动展示。复杂介质中生物分子的超灵敏、超选择性和高度多重检测是疾病诊断、生命科学研究和环境监测的核心组成部分新的“数字分辨率”生物分子检测方法正在实现前所未有的检测极限，但受到复杂的程序、热循环和严格的样品制备的最新进展的阻碍。光子超材料表面能够大幅放大从半导体量子点收集的光子输出，使得数字分子精度测定与小型、低成本仪器兼容，应用具有光子晶体荧光放大功能的量子点标签使得数字计数成为可能。目标分子，并通过其耦合发射模式区分 QD 发射波长的能力进行多重分析，从而实现对 microRNA 的单步、室温、无酶检测，检测限为阿摩尔级，且达到 6 log(10) 级。的动态范围可以实现，并有可能进一步扩展。在这个项目中，坎宁安和史密斯实验室将设计和合成新型量子点标签，其中包含工程多光谱亮度、可编码发射饱和度和量子点将专门与光子超材料表面耦合，以增强其激发，调节其寿命，并提取其发射以区分多达 45 个不同的量子点标签，以进行分子复用。用于生物分子检测，其中每个目标分子可以生成多个下游数字分辨率量子点检测事件，以通过简单快速的方法实现超灵敏的检测极限。该奖项授予 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。