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.

该项目将开发高度敏感的方法，用于同时在血液中检测许多称为“生物标志物”的分子。这些生物标志物将通过与发光纳米颗粒（称为量子点（QD））结合来检测，该纳米颗粒用作明亮的标签。通过设计QD可以轻松区分彼此，研究小组设想了在单滴中检测多达45种不同生物标志物的能力。生物标志物检测将在称为“光子晶体”（PCS）的工程表面上进行，这些表面能够将QD亮度放大数千倍，从而可以单独计数QD。 PC还用于将QD光输出引导到特定方向，这些方向可确定每种QD之间的差异。此外，将开发出可以快速将每个生物标志物分子转换为PC表面上许多QD的新方法。通过组合PC和QD，传感器可以简单，快速且廉价，从而可以在诊所和医院等地方进行生物标志物测试。该团队将开发一门题为“您的血液中的内容？基因组学测试和您”的广泛访问的短期课程，将通过Osher终身学习学院提供。该课程的各个方面将适用于WOESE基因组生物学研究所提供的公共面向公共计划，并在“基因组学世界”事件中进行互动显示，该活动每年在大型科学博物馆中每年提供。超构敏感，超级优化和高度多重的生物分子发现复杂媒体的疾病诊断型疾病诊断和环境科学研究中的核心是生物分类的核心。新的“数字分辨率”生物分子检测方法导致了前所未有的检测极限，但由于复杂的程序，热循环和严格的样品准备而受到阻碍。光子超材料表面的能力的最新进展实质上扩大了半导体量子点收集的光子输出，这使数字分子精度与小，低成本仪器兼容。用光子晶体荧光扩增应用QD标签，可以通过数字计数目标分子进行数字计数，并通过通过其超过耦合的发射模式来区分QD发射波长的能力。结果，可以实现具有大气压级检测极限和6 log（10）动态范围的单步，室温，无酶测定，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颖的QD标签，这些QD标签结合了工程的多光谱亮度，可编码的发射饱和度和可编码的PC增强因子。 QD将专门与光子超材料表面相结合，以增强其兴奋，调节其寿命，并提取其发射以区分多达45个不同的QD标签，以进行分子多路复用。 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 honestly of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.