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

基本信息

项目摘要

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.
该项目将开发高灵敏度的方法,用于同时检测血液中许多与疾病相关的分子,称为“生物标志物”。这些生物标志物将通过结合到称为量子点(QD)的发光纳米颗粒上来检测,这些纳米颗粒可作为明亮的标签。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种不同的生物标志物。生物标志物检测将在被称为“光子晶体”(PC)的工程表面上进行,这些表面能够将QD亮度放大数千倍,从而允许单独计数QD。PC还用于在特定方向上引导QD光输出,所述特定方向被测量以区分每种类型的QD之间的差异。此外,将开发新的方法,可以快速将每个生物标志物分子转化为PC表面上的许多QD。通过结合PC和QD,传感器可以简单,快速和廉价,使生物标志物测试能够在诊所和医院等场所进行。该团队将开发一门广泛接受的短期课程,题为“你的血液中有什么?”基因组学测试和你,”将通过Osher终身学习研究所提供。 该课程的各个方面将适用于通过Woese基因组生物学研究所提供的面向公众的项目,以及每年在大型科学博物馆举办的“基因组学世界”活动中的互动展示。对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朝着前所未有的检测极限发展,但受到复杂程序、热循环和严格样品制备的阻碍。光子超材料表面基本上放大从半导体量子点收集的光子输出的能力的最新进展使得具有与小型低成本仪器兼容的数字分子精度的测定。应用具有光子晶体荧光放大的QD标签使得可以对目标分子进行数字计数,并通过其外耦合发射模式区分QD发射波长的能力来执行多路复用。因此,可以实现具有阿摩尔水平检测限和6 log(10)数量级动态范围的microRNA的单步、室温、无酶测定,并且具有进一步扩展的潜力。在这个项目中,坎宁安和史密斯实验室将设计和合成新的量子点标签,将工程多光谱亮度,可编码的发射饱和度,和可编码的PC增强因子。量子点将专门与光子超材料表面耦合,以增强它们的激发,调制它们的寿命,并提取它们的发射,以区分多达45个不同的量子点标签,用于分子复用。最后,该团队将介绍一种新的生物分子检测模式,其中每个目标分子都可以产生多个下游数字分辨率QD检测事件,从而通过简单快速的方法实现超灵敏的检测限。该奖项反映了NSF的法定使命,并通过使用基金会的知识价值和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

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Brian Cunningham其他文献

Silicon Electrolyte Interface Stabilization (SEISta), Quarter 2, FY20
硅电解质界面稳定 (SEISta),2020 财年第 2 季度
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Anthony Burrell;Brian Cunningham
  • 通讯作者:
    Brian Cunningham
Immediate weight-bearing as tolerated has improved outcomes compared to non–weight-bearing after surgical stabilisation of midshaft clavicle fractures in polytrauma patients
  • DOI:
    10.1016/j.jotr.2017.08.004
  • 发表时间:
    2018-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Brian Cunningham;Jennifer Tangtiphaiboontana;Hrayr Basmajian;Ryan Mclemore;Brian Miller;Anthony Rhorer;Gilbert Ortega
  • 通讯作者:
    Gilbert Ortega
Swimming Anatomy and Lower Back Injuries in Competitive Swimmers: A Narrative Review.
游泳解剖学和竞技游泳运动员的下背部损伤:叙事回顾。
  • DOI:
    10.1177/19417381231225213
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    3.3
  • 作者:
    Connie Hsu;Brian Krabak;Brian Cunningham;Joanne Borg
  • 通讯作者:
    Joanne Borg
Induction of tolerance in composite-tissue allografts
复合组织同种异体移植物耐受的诱导
  • DOI:
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    6.2
  • 作者:
    M. Siemionow;T. Ortak;D. Iżycki;Ramadan Oke;Brian Cunningham;Rita Prajapati;J. Zins
  • 通讯作者:
    J. Zins
How Does the Cost Effectiveness of Posterior Spinal Fusion Compare to Arthroplasty for Osteoarthritis of the Hip or Knee?
  • DOI:
    10.1016/j.spinee.2012.08.365
  • 发表时间:
    2012-09-01
  • 期刊:
  • 影响因子:
  • 作者:
    Dennis G. Crandall;Brian Cunningham;Ryan McLemore
  • 通讯作者:
    Ryan McLemore

Brian Cunningham的其他文献

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{{ truncateString('Brian Cunningham', 18)}}的其他基金

I-Corps: Blood analyzer to detect Bovine Respiratory Disease by using blood cell counts and morphology
I-Corps:利用血细胞计数和形态检测牛呼吸道疾病的血液分析仪
  • 批准号:
    2143132
  • 财政年份:
    2022
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
RAPID: A rapid and ultrasensitive technology for sensing intact SARS-CoV-2 using designer DNA nanostructure capture probes and photonic resonator interference scattering microscopy
RAPID:一种快速、超灵敏的技术,使用设计的 DNA 纳米结构捕获探针和光子谐振器干涉散射显微镜来感测完整的 SARS-CoV-2
  • 批准号:
    2027778
  • 财政年份:
    2020
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
Photonic resonator hybrids for ultrasensitive biosensing
用于超灵敏生物传感的光子谐振器混合体
  • 批准号:
    1900277
  • 财政年份:
    2019
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
PFI-TT: Clip-On Smartphone Biosensor for Mobile Health Diagnostics
PFI-TT:用于移动健康诊断的夹式智能手机生物传感器
  • 批准号:
    1919015
  • 财政年份:
    2019
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
UNS:Multiresonator Photonic Crystal Enhanced Fluorescence and SERS
UNS:多谐振器光子晶体增强荧光和 SERS
  • 批准号:
    1512043
  • 财政年份:
    2015
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
PFI:BIC - Pathtracker: A smartphone-based system for mobile infectious disease detection and epidemiology
PFI:BIC - Pathtracker:基于智能手机的移动传染病检测和流行病学系统
  • 批准号:
    1534126
  • 财政年份:
    2015
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
EAGER: Lab-in-a-Smartphone
EAGER:智能手机实验室
  • 批准号:
    1447893
  • 财政年份:
    2014
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
2014 National Science Foundation Workshop on Food Safety-Global Supply Chain Research Needs
2014年美国国家科学基金会食品安全研讨会——全球供应链研究需求
  • 批准号:
    1448172
  • 财政年份:
    2014
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
Multimode Smartphone Biosensor
多模式智能手机生物传感器
  • 批准号:
    1264377
  • 财政年份:
    2013
  • 资助金额:
    $ 60万
  • 项目类别:
    Standard Grant
I/UCRC: Center for Innovation Instrumentation Technology (CIIT)
I/UCRC:创新仪器技术中心 (CIIT)
  • 批准号:
    1067943
  • 财政年份:
    2011
  • 资助金额:
    $ 60万
  • 项目类别:
    Continuing Grant

相似国自然基金

Research on Quantum Field Theory without a Lagrangian Description
  • 批准号:
    24ZR1403900
  • 批准年份:
    2024
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
Simulation and certification of the ground state of many-body systems on quantum simulators
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    2020
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Mapping Quantum Chromodynamics by Nuclear Collisions at High and Moderate Energies
  • 批准号:
    11875153
  • 批准年份:
    2018
  • 资助金额:
    60.0 万元
  • 项目类别:
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相似海外基金

CAREER: Controlling the Deformability of Quantum Dots Solids for Wearable NIR Optoelectronics
职业:控制可穿戴近红外光电器件的量子点固体的变形能力
  • 批准号:
    2337974
  • 财政年份:
    2024
  • 资助金额:
    $ 60万
  • 项目类别:
    Continuing Grant
STTR Phase I: High-Sensitivity Flexible Quantum Dots/Graphene X-Ray Detectors and Imaging Systems
STTR 第一阶段:高灵敏度柔性量子点/石墨烯 X 射线探测器和成像系统
  • 批准号:
    2322053
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    2024
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    $ 60万
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Mid-infrared quantum dots for room temperature photodetectors and emitters
用于室温光电探测器和发射器的中红外量子点
  • 批准号:
    DP240101309
  • 财政年份:
    2024
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    $ 60万
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    Discovery Projects
Infra-Plas: Colloidal Quantum Dots for Short-Wave Infrared Plasmonic Lasers
Infra-Plas:用于短波红外等离子激光器的胶体量子点
  • 批准号:
    EP/Z000912/1
  • 财政年份:
    2024
  • 资助金额:
    $ 60万
  • 项目类别:
    Fellowship
RII Track-4:NSF: In-vitro Cytotoxicity Assessment of Synthesized Quantum Dots for Enhanced Cell Imaging
RII Track-4:NSF:用于增强细胞成像的合成量子点的体外细胞毒性评估
  • 批准号:
    2327429
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    $ 60万
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Memory-Enhanced Entanglement Distribution with Gallium ARsenide quantum Dots
砷化镓量子点的记忆增强纠缠分布
  • 批准号:
    EP/Z000556/1
  • 财政年份:
    2024
  • 资助金额:
    $ 60万
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High color purity and multicolor luminescence based on precise synthesis and electronic structure design of multinary quantum dots
基于多元量子点的精确合成和电子结构设计的高色纯度和多色发光
  • 批准号:
    23H01786
  • 财政年份:
    2023
  • 资助金额:
    $ 60万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Structure-Optoelectronic Property Relationships in Homogeneous and Heterogeneous/Gradient Alloyed Colloidal I-(II)-III-VI Quantum Dots
均质和异质/梯度合金胶体 I-(II)-III-VI 量子点的结构-光电性质关系
  • 批准号:
    2304949
  • 财政年份:
    2023
  • 资助金额:
    $ 60万
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    Standard Grant
NSF-NSERC: Building a two-qubit controlled phase gate using laterally coupled semiconductor quantum dots
NSF-NSERC:使用横向耦合半导体量子点构建两个量子位控制的相位门
  • 批准号:
    2317047
  • 财政年份:
    2023
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    $ 60万
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    Standard Grant
Nanoscale Interaction of Engineered Quantum Dots with Cephem Skeleton
工程量子点与头孢烯骨架的纳米级相互作用
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    2313252
  • 财政年份:
    2023
  • 资助金额:
    $ 60万
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