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

• 批准号: 1847324
• 负责人: Chao Wang
• 金额: $ 50万
• 依托单位: Arizona State University
• 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: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1847324&HistoricalAwards=false
• 关键词: CAREER; Integrated; Optofluidic; Chips; towards

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.

癌症是发病率和死亡率的全球主要原因。随着癌症中观察到的异质性和复杂性的增加，对疾病进展的准确诊断和分子监测的需求变得比以往任何时候都变得更加重要。从人体流体循环的细胞中的微观囊泡的液体活检是一种有前途，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，已成为早期诊断的有前途的策略。但是，此类技术的现有诊断工具缺乏在临床上可行的必要灵敏度，特异性，速度和成本效益。这项职业建议完全利用了小型技术的尖端开发，例如纳米素养化学，纳米荧光学和生物传感，以从具有提高敏感性，减少样品体积和减少分析时间的临床样品中检测诊断核酸的新颖解决方案。拟议技术的成功将对早期诊断以及疾病的预后和治疗产生重大影响，包括心血管疾病，自身免疫性综合症，神经退行性疾病和感染性疾病。通过整合研究和教育，该项目将促进公众对纳米生物技术在卫生保健中重要性的认识，并培养纳米技术领域的科学家和工程师的下一代，并生物启动以应对负担得起和便携式疾病诊断中的巨大挑战。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）的参与。 这项职业建议的研究目标是验证以下假设：综合和多重的光氟水平台可以准确检测外泌体miRNA。为了实现这一目标，将设计纳米流体芯片（Exomirchip），以便在功能上整合无标签的外泌体纯化，芯片外泌体miRNA提取和等离子miRNA感应。将合并理论和实验，以应对实现高分辨率和高通量外部纳米颗粒排序，高敏性和高特异性miRNA检测以及纳米富集系统的多功能整合的基本挑战。该项目将在纳米尺度上探索外泌体纳米颗粒流体动力学中的科学未知数，并旨在全面阐明芯片外泌体纯化中的限制因素。该项目将通过序列特异性锁定核酸（LNA）探针进行光学耦合的超敏度等离激敏纳米传感器，并使用它们来确定影响外泌体miRNA的关键因素，包括血浆式传感器设计，包括纳米结构，纳米结构，miRNA MoiRNA浓缩，mirna Solecular浓度和miRNA选择性。在exomirchip上成功的纳米流体整合将显着减少诊断样品体积（从毫升到微量流量），最大程度地减少偏见和污染，提高诊断速度（估计数量/周至小时），并有可能启用多路复用生物标志物检测。我们希望该项目在未来的生物传感中具有变革性，并适用于各种生物分子。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估标准来评估值得支持的。

项目成果

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: ACS Sensors
• 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: Biosensors and Bioelectronics
• 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: Nano Research
• 影响因子: 9.9
• 作者: Zhi Zhao;Xiahui Chen;Jiawei Zuo;A. Basiri;Shinhyuk Choi;Yu Yao;Yan Liu;Chao Wang