CAREER: Integrated Optofluidic Chips towards Label-Free Detection of Exosomal MicroRNA Biomarkers
职业:集成光流控芯片实现外泌体 MicroRNA 生物标志物的无标记检测
基本信息
- 批准号:1847324
- 负责人:
- 金额:$ 50万
- 依托单位:
- 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:2019-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Cancer is a major global cause of morbidity and mortality. With the increasing heterogeneity and complexity observed in cancers, the need for accurate diagnosis and molecular monitoring of disease progression has become more important than ever. Liquid biopsy of microscopic vesicles from our cells circulating in human bodily fluids is a promising, inexpensive, and minimally invasive approach for cancer diagnosis and personalized medical treatment. Particularly, detecting the biomolecules carried by these vesicles, including nucleic acids encoding genetic information, has emerged as a promising strategy for early diagnosis. However, the existing diagnostic tools for such technologies lack the needed sensitivity, specificity, speed, and cost-effectiveness necessary to become clinically viable. This CAREER proposal fully exploits the cutting-edge development in small-scale technologies such as nanophotonics, nanofluidics, and biosensing to provide novel solutions for the detection of diagnostic nucleic acids from clinical samples with an improved sensitivity, reduced sample volume, and decreased analysis time. The success of the proposed technology will have significant impact on early-stage diagnosis as well as prognosis and management of diseases, including cardiovascular diseases, autoimmune syndromes, neurodegenerative disorders, and infectious diseases. By integrating research and education, the project will promote public awareness of the importance of nanobiotechnology in health care, and to cultivate the next-generation of scientists and engineers in nanotechnology and biosensing to address grand challenges in affordable and portable disease diagnosis. Further, this project aims to attract the participation of K-12 students and underrepresented individuals (e.g., female and Native American students) in STEM careers. The research objective of this CAREER proposal is to validate the hypothesis that an integrated and multiplexed optofluidic platform can accurately detect exosomal miRNAs. In pursuit of this goal, a nanofluidic chip (ExoMiRChip) will be designed to functionally integrate label-free exosome purification, on-chip exosomal miRNA extraction, and plasmonic miRNA sensing. Theories and experiments will be combined to address fundamental challenges in achieving high-resolution and high-throughput exosome nanoparticle sorting, high-sensitivity and high-specificity miRNA detection, and multi-functional integration of nanofluidic systems. This project will explore scientific unknowns in exosome nanoparticle fluidic dynamics at the nanometer scale, and aim to comprehensively elucidate the limiting factors in on-chip exosome purification. The project will innovate optically coupled ultrasensitive plasmonic nanosensors functionalized with sequence-specific locked nucleic acid (LNA) probes, and use them to identify the critical factors affecting accurate detection of exosomal miRNA, including the plasmonic sensor design, nanostructure fabrication, miRNA molecular concentration, and the miRNA selectivity. Successful nanofluidic integration on the ExoMiRChip will significantly reduce sample volume in diagnosis (from milliliters to microliters), minimize bias and contamination, improve diagnosis speed (estimated from days/weeks to hours), and potentially enable multiplexed biomarker detection. We expect the project to be transformative in future biosensing and applicable to a wide variety of biomolecules.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.
癌症是全球发病和死亡的主要原因。随着癌症的异质性和复杂性不断增加,对疾病进展进行准确诊断和分子监测的需求变得比以往任何时候都更加重要。对人体体液中循环的细胞的微小囊泡进行液体活检是一种有前景、廉价且微创的癌症诊断和个性化医疗方法。特别是,检测这些囊泡携带的生物分子,包括编码遗传信息的核酸,已成为一种有前景的早期诊断策略。然而,此类技术的现有诊断工具缺乏临床可行性所需的灵敏度、特异性、速度和成本效益。该职业提案充分利用纳米光子学、纳米流体学和生物传感等小规模技术的前沿发展,为从临床样本中检测诊断核酸提供新颖的解决方案,提高灵敏度、减少样本量并缩短分析时间。该技术的成功将对疾病的早期诊断以及预后和管理产生重大影响,包括心血管疾病、自身免疫综合征、神经退行性疾病和传染病。通过整合研究和教育,该项目将提高公众对纳米生物技术在医疗保健中重要性的认识,并培养下一代纳米技术和生物传感领域的科学家和工程师,以应对负担得起和便携式疾病诊断的巨大挑战。此外,该项目旨在吸引 K-12 学生和代表性不足的个人(例如女性和美国原住民学生)参与 STEM 职业。 本 CAREER 提案的研究目标是验证集成和多重光流控平台可以准确检测外泌体 miRNA 的假设。为了实现这一目标,纳米流体芯片(ExoMiRChip)将被设计为在功能上集成无标记外泌体纯化、芯片上外泌体 miRNA 提取和等离子体 miRNA 传感。将理论和实验相结合,解决实现高分辨率和高通量外泌体纳米颗粒分选、高灵敏度和高特异性miRNA检测以及纳米流体系统多功能集成的基本挑战。该项目将探索纳米尺度外泌体纳米颗粒流体动力学的科学未知数,旨在全面阐明芯片上外泌体纯化的限制因素。该项目将创新以序列特异性锁核酸(LNA)探针为功能的光耦合超灵敏等离子体纳米传感器,并利用它们来识别影响外泌体miRNA准确检测的关键因素,包括等离子体传感器设计、纳米结构制造、miRNA分子浓度、和 miRNA 选择性。 ExoMiRChip 上成功的纳米流体集成将显着减少诊断中的样本量(从毫升到微升),最大限度地减少偏差和污染,提高诊断速度(估计从几天/几周到几小时),并有可能实现多重生物标志物检测。我们期望该项目能够在未来的生物传感领域带来变革,并适用于多种生物分子。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(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Picomolar-Level Sensing of Cannabidiol by Metal Nanoparticles Functionalized with Chemically Induced Dimerization Binders
通过化学诱导二聚化粘合剂功能化的金属纳米颗粒对大麻二酚进行皮摩尔水平传感
- DOI:10.1021/acssensors.3c01758
- 发表时间:2023
- 期刊:
- 影响因子:8.9
- 作者:Ikbal, M. D.;Kang, Shoukai;Chen, Xiahui;Gu, Liangcai;Wang, Chao
- 通讯作者:Wang, Chao
Sapphire-supported nanopores for low-noise DNA sensing
用于低噪声 DNA 传感的蓝宝石支撑纳米孔
- DOI:10.1016/j.bios.2020.112829
- 发表时间:2021
- 期刊:
- 影响因子:12.6
- 作者:Xia, Pengkun;Zuo, Jiawei;Paudel, Pravin;Choi, Shinhyuk;Chen, Xiahui;Rahman Laskar, Md Ashiqur;Bai, Jing;Song, Weisi;Im, JongOne;Wang, Chao
- 通讯作者:Wang, Chao
Deterministic assembly of single emitters in sub-5 nanometer optical cavity formed by gold nanorod dimers on three-dimensional DNA origami
- DOI:10.1007/s12274-021-3661-z
- 发表时间:2021-04
- 期刊:
- 影响因子:9.9
- 作者:Zhi Zhao;Xiahui Chen;Jiawei Zuo;A. Basiri;Shinhyuk Choi;Yu Yao;Yan Liu;Chao Wang
- 通讯作者:Zhi Zhao;Xiahui Chen;Jiawei Zuo;A. Basiri;Shinhyuk Choi;Yu Yao;Yan Liu;Chao Wang
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Chao Wang其他文献
A new decomposition method based on the coherency matrix
一种基于相干矩阵的新分解方法
- DOI:
10.1109/apsar.2015.7306255 - 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
Jianbo Wang;Chao Wang;Hong Zhang;Fan Wu;Bo Zhang - 通讯作者:
Bo Zhang
The mechanical behavior and collapse of graphene-assembled hollow nanospheres under compression
石墨烯组装空心纳米球在压缩下的机械行为和塌陷
- DOI:
10.1016/j.carbon.2020.11.040 - 发表时间:
2021-03 - 期刊:
- 影响因子:10.9
- 作者:
Yifan Zhao;Yushun Zhao;Fan Wu;Yue Zhao;Yaming Wang;Chao Sui;Xiaodong He;Chao Wang;Huifeng Tan;Chao Wang - 通讯作者:
Chao Wang
Understanding of the Effect of Climate Change on Tropical Cyclone Intensity: A Review
了解气候变化对热带气旋强度的影响:回顾
- DOI:
10.1007/s00376-021-1026-x - 发表时间:
2022-01 - 期刊:
- 影响因子:5.8
- 作者:
Liguang Wu;Haikun Zhao;Chao Wang;Jian Cao;Jia Liang - 通讯作者:
Jia Liang
Evolution and Removal of Surface Scratches by magnetorheological finishing(MRF)
磁流变精加工(MRF)表面划痕的演变和去除
- DOI:
10.1117/1.oe.58.5.055102 - 发表时间:
2019 - 期刊:
- 影响因子:1.3
- 作者:
Jianwei Ji;Wei Gao;Chao Wang;Yunfei Zhang;Wei Fan;Min Xu;Fang Ji - 通讯作者:
Fang Ji
Design and optimization of electromagnetic tomography and electrical resistance tomography dual-modality sensor
电磁层析成像和电阻层析成像双模态传感器的设计与优化
- DOI:
10.1088/1361-6501/ac8146 - 发表时间:
2022-07 - 期刊:
- 影响因子:0
- 作者:
Chao Wang;Ruichang Wang;Xiao Liang;Jiamin Ye;Xueyong Chen - 通讯作者:
Xueyong Chen
Chao Wang的其他文献
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{{ truncateString('Chao Wang', 18)}}的其他基金
Collaborative Research: FW-HTF-R: Wearable Safety Sensing and Assistive Robot-Worker Collaboration for an Augmented Workforce in Construction
合作研究:FW-HTF-R:可穿戴安全传感和辅助机器人工人协作,增强建筑劳动力
- 批准号:
2222881 - 财政年份:2022
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
Collaborative Research: FMitF: Track I: A Principled Approach to Modeling and Analysis of Hardware Fault Attacks on Embedded Software
合作研究:FMitF:第一轨:嵌入式软件硬件故障攻击建模和分析的原则方法
- 批准号:
2220345 - 财政年份:2022
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
NSF-BSF: Synchronous electro-optical DNA detection using low-noise dielectric nanopores on sapphire
NSF-BSF:使用蓝宝石上的低噪声介电纳米孔进行同步电光 DNA 检测
- 批准号:
2020464 - 财政年份:2020
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
FW-HTF-P: Collaborative Research: Wearable Safety and Health Assistive Robot Collaboration for Skilled Construction Workers
FW-HTF-P:合作研究:为熟练建筑工人提供可穿戴安全与健康辅助机器人协作
- 批准号:
2026575 - 财政年份:2020
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
Photochemically Induced, Polymer-Assisted Deposition for 3D Printing of Micrometer-Wide and Nanometer-Thin Silver Structures
用于微米宽和纳米薄银结构 3D 打印的光化学诱导聚合物辅助沉积
- 批准号:
1947753 - 财政年份:2020
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
Low-Profile Ultra-Wideband Wide-Scanning Multi-Function Beam-Steerable Array Antennas
薄型超宽带宽扫描多功能波束可控阵列天线
- 批准号:
EP/S005625/1 - 财政年份:2019
- 资助金额:
$ 50万 - 项目类别:
Research Grant
Enhancing CO2 Reduction by Controlling the Ensemble of Active Sites
通过控制活动站点的整体来加强二氧化碳减排
- 批准号:
1930013 - 财政年份:2019
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
Interplay of Mass Transport and Chemical Kinetics in the Electroreduction CO2
电还原 CO2 中传质与化学动力学的相互作用
- 批准号:
1803482 - 财政年份:2018
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
CSR: Small: Collaborative Research: Safety Guard: A Formal Approach to Safety Enforcement in Embedded Control Systems
CSR:小型:协作研究:安全卫士:嵌入式控制系统中安全执行的正式方法
- 批准号:
1813117 - 财政年份:2018
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
INFEWS N/P/H2O: Collaborative Research: Catalytic Dephosphorylation Using Ceria Nanocrystals
INFEWS N/P/H2O:合作研究:使用二氧化铈纳米晶体催化脱磷酸
- 批准号:
1664967 - 财政年份:2017
- 资助金额:
$ 50万 - 项目类别:
Standard Grant
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