CAREER: Ultrasensitive Multiplex Nanopore Biosensing for Point-of-Care Testing of Infectious Diseases

职业:用于传染病即时检测的超灵敏多重纳米孔生物传感

基本信息

  • 批准号:
    2047503
  • 负责人:
  • 金额:
    $ 50万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-05-01 至 2026-04-30
  • 项目状态:
    未结题

项目摘要

The ongoing global pandemic of COVID-19 has reminded us the importance of diagnostic testing technologies. Current point-of-care testing (POCT) technologies are inexpensive and easy to use, store, and transport. However, their simplicity causes a significant loss of sensitivity and specificity comparing to lab based diagnostic tests. The major goal of this NSF CAREER research program is to develop a new nanopore testing technology to enable ultrasensitive detection of infectious diseases at a reasonably low cost. Upon the successful completion of this project, the proposed nanopore test will meet the urgent need for a POCT technology with accuracy that exceeds current POCTs or even lab-based testing technologies. This platform technology presents great potential for changing the current paradigm of POCT for existing infectious diseases. Also, it can be readily modified with minimal optimization as soon as new diseases and biomarkers are identified for rapid deployment in clinics and at the point of care. This project also includes education and outreach activities, such as organizing a summer research workshop and internship for high school students on the fundamentals of Biomedical Engineering and Nanotechnology, broadly presenting our research to local communities, and starting an infectious disease research symposium that brings an additional synergy among local clinicians, biomedical engineers, and scientists. Special attention will be given to students from underrepresented groups and first-generation college students, who constitute a significant part of our student population. This CAREER program should result in achievement awards and authorships on research publications for undergraduate and high school students.In the era of personalized medicine, rapid and accurate quantification of multiple biomarkers at the point-of-care is fundamental to a successful control and management of infectious disease outbreaks. Classical point-of-care testing (POCT) technologies are inexpensive and easy to use, store, and transport. But their simplicity causes a significant loss of sensitivity and specificity comparing to lab based in vitro diagnostics. The nanopore technology is a promising alternative because of its single-molecule analysis capacity, portability, and low cost. However, existing nanopore technologies are not suitable for detecting analytes in complex human samples, can only analyze charged biomarkers of certain sizes, and are not device compatible. The major goal of this CAREER program is to develop a next generation nanopore biosensor to enable ultrasensitive detection and quantification of multiple infectious disease biomarkers from human blood at the point of care. The program has three research objectives: (1) Develop and optimize a nanopore biosensor with unprecedented sensitivity, robustness, and reproducibility for various purposes; (2) Enable sensitive and specific biomarker detection by automated immunoprecipitation and novel signal transduction mechanisms; (3) Demonstrate ultrasensitive multiplex quantification of circulating proteomics biomarkers and its applications in infectious disease diagnosis and prognosis. Proposed approach has several innovative elements: several amplification methods are employed to achieve the sub-femtomolar level detection limit; special single strand DNA structures are used as detection surrogates for biomarkers, so that the readout signal can be easily differentiated from other biomolecules to prevent false-positives; an integrated microfluidic automatic immunoprecipitation module can reduce sample-to-answer time and human errors in the assay protocol.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.
正在进行的新冠肺炎全球大流行提醒我们诊断检测技术的重要性。目前的护理点检测(POCT)技术价格低廉,易于使用、存储和运输。然而,与基于实验室的诊断测试相比,它们的简单性会导致灵敏度和特异度的显著下降。NSF职业研究计划的主要目标是开发一种新的纳米孔测试技术,以合理的低成本实现对传染病的超灵敏检测。在该项目成功完成后,拟议的纳米孔测试将满足对POCT技术的迫切需求,其精度超过目前的POCT,甚至超过基于实验室的测试技术。这一平台技术为改变现有传染病的POCT模式提供了巨大的潜力。此外,一旦新的疾病和生物标记物被确定用于临床和护理点的快速部署,它可以很容易地进行最小优化修改。该项目还包括教育和外展活动,例如为高中生组织一个关于生物医学工程和纳米技术基础的暑期研究研讨会和实习,向当地社区广泛展示我们的研究,并开始一个传染病研究研讨会,在当地临床医生、生物医学工程师和科学家之间带来额外的协同效应。将特别关注代表不足群体的学生和第一代大学生,他们是我国学生总数的重要组成部分。这一职业计划应该为本科生和高中生带来成就奖和研究出版物上的作者。在个性化医学时代,在护理地点快速准确地量化多个生物标志物是成功控制和管理传染病爆发的基础。传统的护理点检测(POCT)技术价格低廉,易于使用、存储和运输。但与基于实验室的体外诊断相比,它们的简单性导致敏感性和特异性的显著丧失。纳米孔技术由于其单分子分析能力、可移植性和低成本,是一种很有前途的替代技术。然而,现有的纳米孔技术不适合检测复杂人体样本中的分析物,只能分析某些大小的带电生物标志物,并且不能与设备兼容。这项职业计划的主要目标是开发下一代纳米孔生物传感器,以便能够在护理点对人类血液中的多种传染病生物标志物进行超灵敏检测和量化。该计划有三个研究目标:(1)开发和优化具有前所未有的灵敏度、稳定性和重复性的纳米孔生物传感器,以满足各种目的;(2)通过自动免疫沉淀和新的信号转导机制实现灵敏和特异的生物标记物检测;(3)展示循环蛋白质组学生物标记物的超灵敏多重定量及其在传染病诊断和预后中的应用。建议的方法有几个创新之处:使用几种扩增方法来达到亚毫微摩尔水平的检测极限;使用特殊的单链DNA结构作为生物标志物的检测替代品,以便读出的信号可以很容易地与其他生物分子区分开来,防止假阳性;集成的微流控自动免疫沉淀模块可以减少分析协议中的样本到答案的时间和人为错误。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。

项目成果

期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Narrowing Signal Distribution by Adamantane Derivatization for Amino Acid Identification Using an α-Hemolysin Nanopore
  • DOI:
    10.1021/acs.nanolett.3c03593
  • 发表时间:
    2024-01-24
  • 期刊:
  • 影响因子:
    10.8
  • 作者:
    Wei,Xiaojun;Ma,Dumei;Liu,Chang
  • 通讯作者:
    Liu,Chang
Translocation Behaviors of Synthetic Polyelectrolytes through Alpha-Hemolysin (α-HL) and Mycobacterium smegmatis Porin A (MspA) Nanopores
合成聚电解质通过α-溶血素 (α-HL) 和耻垢分枝杆菌孔蛋白 A (MspA) 纳米孔的易位行为
  • DOI:
    10.1149/1945-7111/ac6c55
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    3.9
  • 作者:
    Wang, Xiaoqin;Stevens, Kaden C.;Ting, Jeffrey M.;Marras, Alexander E.;Rezvan, Gelareh;Wei, Xiaojun;Taheri-Qazvini, Nader;Tirrell, Matthew V.;Liu, Chang
  • 通讯作者:
    Liu, Chang
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Chang Liu其他文献

Graphene oxide coated capillary for chiral separation by CE
用于 CE 手性分离的氧化石墨烯涂层毛细管
  • DOI:
    10.1002/elps.201200516
  • 发表时间:
    2013-03
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Nengsheng Ye;Jian Li;Yali Xie;Chang Liu
  • 通讯作者:
    Chang Liu
Unconventional Inner-TL Electric Polarization in TL-LaOBiS2 with Ultrahigh Carrier Mobility
具有超高载流子迁移率的 TL-LaOBiS2 中的非常规内 TL 电极化
  • DOI:
    10.1039/c9nr05282h
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Chao He;Jiajun Zhu;Yong-Hong Zhao;Chang Liu;Botao Fu
  • 通讯作者:
    Botao Fu
Anthropogenic and Climatic Factors Differentially Affect Waterbody Area and Connectivity in an Urbanizing Landscape: A Case Study in Zhengzhou, China
人为和气候因素对城市化景观中水体面积和连通性的影响不同:以中国郑州为例
  • DOI:
    10.3390/land10101070
  • 发表时间:
    2021-10
  • 期刊:
  • 影响因子:
    3.9
  • 作者:
    Chang Liu;Emily S. Minor;Megan B. Garfinkel;Bo Mu;Guohang Tian
  • 通讯作者:
    Guohang Tian
Electrostatic tuning of block copolymer morphologies by inorganic macroions
无机大离子对嵌段共聚物形态的静电调节
  • DOI:
    10.1016/j.polymer.2016.10.057
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Liying Zhang;Chang Liu;Hongyu Shang;Xiao Cao;Shengchao Chai;Quan Chen;Lixin Wu;Haolong Li
  • 通讯作者:
    Haolong Li
Visual Tracking by Structurally Optimizing Pre-Trained CNN
通过结构优化预训练的 CNN 进行视觉跟踪

Chang Liu的其他文献

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{{ truncateString('Chang Liu', 18)}}的其他基金

ERA SynBio: Orthogonal Replication as the Platform for an Episome
ERA SynBio:正交复制作为附加体的平台
  • 批准号:
    1545158
  • 财政年份:
    2015
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant
New GK-12: The Boat-of Knowledge in the Science Classroom (BooKS in Classroom)
新GK-12:科学课堂上的知识之船(课堂上的书)
  • 批准号:
    0947813
  • 财政年份:
    2010
  • 资助金额:
    $ 50万
  • 项目类别:
    Continuing Grant
EFRI-BSBA:Bio-Inspired Arrays of Haircell Sensors for Artificial Glabrous and Hairy Skin
EFRI-BSBA:用于人造无毛和多毛皮肤的仿生毛细胞传感器阵列
  • 批准号:
    0938007
  • 财政年份:
    2009
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant
NSWP: Magnetic Reconnection and Distribution of Accelerated Electrons in Solar Flares
NSWP:太阳耀斑中加速电子的磁重联和分布
  • 批准号:
    0819662
  • 财政年份:
    2009
  • 资助金额:
    $ 50万
  • 项目类别:
    Continuing Grant
Track 1, GK-12: Science and Technology Enrichment for Appalachian Middle-schoolers (STEAM)
第 1 轨,GK-12:阿巴拉契亚中学生科学技术强化课程 (STEAM)
  • 批准号:
    0538588
  • 财政年份:
    2006
  • 资助金额:
    $ 50万
  • 项目类别:
    Continuing grant
CCLI-A&I: Sustained Service Learning Projects in Software Engineering Project Courses
CCLI-A
  • 批准号:
    0510198
  • 财政年份:
    2005
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant
Integrated Sensing: Biomimetic Sensors for Autonomous Underwater Vehicles
集成传感:用于自主水下航行器的仿生传感器
  • 批准号:
    0225519
  • 财政年份:
    2002
  • 资助金额:
    $ 50万
  • 项目类别:
    Standard Grant
CAREER: Biologically-Inspired Integrated Sensors for Robotics Applications
职业:用于机器人应用的仿生集成传感器
  • 批准号:
    9984954
  • 财政年份:
    2000
  • 资助金额:
    $ 50万
  • 项目类别:
    Continuing Grant
Integrated Sensitive Skin with Advanced Data Architecture
将敏感皮肤与先进的数据架构集成
  • 批准号:
    0080639
  • 财政年份:
    2000
  • 资助金额:
    $ 50万
  • 项目类别:
    Continuing Grant

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I-Corps:生物结合事件的实时、超灵敏电转导在病原体和疾病检测中的转化潜力
  • 批准号:
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Quantum microscopy facility for ultrasensitive nanoscale magnetic imaging
用于超灵敏纳米级磁成像的量子显微镜设备
  • 批准号:
    LE240100092
  • 财政年份:
    2024
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Bioinspired Multiplexed Ultrasensitive Biosensing
仿生多重超灵敏生物传感
  • 批准号:
    EP/Z000130/1
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    2024
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I-Corps: Rapid Ultrasensitive Biodetection Chip for Early Lung Cancer Diagnosis
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  • 批准号:
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  • 财政年份:
    2023
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Elucidating the mechanism of hydrogen entry into metals under corrosive environment using an ultrasensitive hydrogen visualization system
使用超灵敏氢可视化系统阐明腐蚀环境下氢进入金属的机制
  • 批准号:
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  • 财政年份:
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Ultrasensitive, Rapid, Amplification-Free RNA Virus Detection Using Nanodimer-Based Nucleic Acid Target Sequence Recognition
使用基于纳米二聚体的核酸靶序列识别进行超灵敏、快速、无扩增的 RNA 病毒检测
  • 批准号:
    2232940
  • 财政年份:
    2023
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Ultrasensitive mass sensing utilizing weakly-coupled micro resonators' mode localization, with nonlinear feedback control
利用弱耦合微谐振器的模式定位和非线性反馈控制的超灵敏质量传感
  • 批准号:
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Ultrasensitive multiomic platform using epitope-targeted DNA methylation mapping
使用表位靶向 DNA 甲基化作图的超灵敏多组学平台
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Towards Ultrasensitive Detection of Bacterial Extracellular Electron Transfer in Human Gut by Novel Functionalized Carbon Nanotube Electrode Interfaces and Organic Microbial Electrochemical Transistor
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Solute-driven Online Preconcentration in Lateral Flow Assay (SOP-LFA) devices for ultrasensitive biochemical testing
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    $ 50万
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