Integrated Acoustofluidic Plasmonic Molecular Diagnostic System for Detecting MicroRNA Biomarkers

用于检测 MicroRNA 生物标志物的集成声流控等离子体分子诊断系统

基本信息

批准号：
10580345
负责人：
Tuan Vo-Dinh
金额：
$ 3.44万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10580345
关键词：
Acoustics Adopted Area Benchmarking Biological Assay Biological Markers Biological Models Biomedical Research Blood Circulation Blood specimen Cancer Diagnostics Cardiovascular Diseases Cardiovascular system Centrifugation Chylomicrons Clinical Colorectal Cancer Communicable Diseases Detection Development Devices Disease Early Diagnosis Early treatment Evaluation Goals Human Human Resources In Situ Investigation Knowledge Lipoprotein (a)Lipoproteins Low-Density Lipoproteins Malignant Neoplasms Measures Messenger RNA Methods MicroRNAs Molecular Molecular Analysis Monitor Output Pathology Performance Phase Preparation Proteins Quantitative Reverse Transcriptase PCR Research Sampling Sentinel Specificity Specimen Speed Statistical Data Interpretation Surface Symptoms System Systems Analysis Techniques Technology Testing Training Translations Validation Whole Blood accurate diagnosis base biobank biological research cancer diagnosis cancer type clinical application clinical diagnosis clinical practice clinical translation clinically relevant colon cancer patients cost effective density design diagnostic platform diagnostic screening diagnostic technologies disease diagnostic early detection biomarkers early screening exosome improved innovation interactive feedback microRNA biomarkers molecular diagnostics molecular marker mortality multiplex detection nanoprobe neoplastic cell new technology novel performance tests physical property plasmonics point of care point-of-care diagnostics rapid diagnosis small molecule

项目摘要

ABSTRACT The goal of this project is to develop an Integrated acoustofluidic plasmonic molecular diagnostic system designed for rapid isolation, detection and multiplexed identification of circulating exosomal microRNA (miRNA) biomarkers in human clinical samples for early detection of diseases. Dysregulation of miRNAs is often observed in various diseases including cancer, cardiovascular illnesses, and infectious diseases. For instance, recent studies have also demonstrated that miRNAs can be secreted from tumor cells into bloodstream via exosomes, and their expression profiles can be used to classify cancer types. Therefore, circulating exosomal miRNAs are considered promising biomarkers for early detection and diagnosis of cancer. However, these small molecules have not been adopted into clinical practice because of the technical difficulties involved in the isolation of exosomes and the analysis of exosomal miRNAs. Thus, there is a need to develop alternative analyzing strategies that could offer more advantages over conventional methods. In this regard, we propose an integrated acoustofluidic plasmonic molecular diagnostic system designed for rapid isolation and multiplexed detection of exosomal miRNA biomarkers. The cross-disciplinary approach will provide new capabilities to advance the precise clinical diagnosis of cancer. This system integrates two unique but proven technologies: (1) the acoustofluidic technology that can rapidly isolate exosomes with high yield and purity, and (2) surface-enhanced Raman scattering (SERS)-based “Inverse Molecular Sentinel” (iMS) nanoprobes for direct miRNA detection. Although miRNAs related to colorectal cancer (CRC) will be used as the model system, the proposed project will lead to the development of a generally applicable point-of-care diagnostic technology for other types of diseases. The specific aims are: (1) Develop and integrate an acoustofluidic system for exosomal miRNA isolation; (2) Develop iMS nanoprobes for multiplexed detection of exosomal miRNA biomarkers; and (3) Technical Evaluation of the SERS-acoustofluidic system. We will build upon the combined knowledge of our interdisciplinary team and establish the technical validation required to ready this integrated technology for use in clinical settings. Throughout this project, an integrated acoustofluidic plasmonic system will be developed and validated for in-situ analysis of multiple exosomal miRNAs from clinical samples without the need for miRNA extraction and amplification. In the technical validation phase, the result will be compared to that obtained using conventional assays (e.g. qRT-PCR). The proposed system will lead to a no-sample preparation and “sample- to-answer” analysis approach that is based on the integration of existing sub-components, many of which have already been separately tested in similar applications. This new integrated molecular diagnostic system is capable of enhancing research and translation in the areas of early detection and screening of various cancers beyond CRC, and is ultimately well suited for point-of-care. The proposed molecular analysis system represents a major innovation that has a transformative potential in biomedical research, diagnostics and screening.

抽象的该项目的目标是开发集成声流控等离子体分子诊断系统设计用于循环外泌体 microRNA (miRNA) 的快速分离、检测和多重鉴定人类临床样本中用于疾病早期检测的生物标志物经常被观察到 miRNA 的失调。例如，最近发生的各种疾病，包括癌症、心血管疾病和传染病。研究还表明，miRNA 可以通过外泌体从肿瘤细胞分泌到血液中，其表达谱可用于对癌症类型进行分类，因此，循环外泌体 miRNA 是重要的。被认为是用于癌症早期检测和诊断的有前途的生物标志物。由于分离技术困难，尚未应用于临床实践因此，需要开发替代分析方法。与传统方法相比，我们提出了一种综合策略。声流控等离子体分子诊断系统，设计用于快速分离和多重检测外泌体 miRNA 生物标志物的跨学科方法将提供新的能力来推进该系统集成了两种独特但经过验证的技术：（1）癌症的精确临床诊断。声流控技术可以快速分离高产量和高纯度的外泌体，以及（2）表面增强基于拉曼散射 (SERS) 的“反向分子哨兵”(iMS) 纳米探针，用于直接 miRNA 检测。虽然与结直肠癌（CRC）相关的 miRNA 将被用作模型系统，但拟议的项目将导致开发出适用于其他类型疾病的普遍适用的护理点诊断技术。具体目标是：（1）开发并集成用于外泌体miRNA分离的声流系统； (2) 开发用于外泌体 miRNA 生物标志物多重检测的 iMS 纳米探针；以及 (3) 技术我们将基于我们的综合知识对 SERS 声流系统进行评估。跨学科团队并建立准备使用该集成技术所需的技术验证在整个项目中，将开发和应用集成的声流体等离子体系统。经验证可对临床样本中的多种外泌体 miRNA 进行原位分析，无需 miRNA 在技术验证阶段，结果将与使用获得的结果进行比较。传统的检测方法（例如 qRT-PCR）将实现无样品制备和“样品-PCR”。 to-answer”分析方法基于现有子组件的集成，其中许多子组件具有这种新的集成分子诊断系统已经在类似的应用中进行了单独测试。能够加强各种癌症早期检测和筛查领域的研究和转化超越 CRC，并且最终非常适合现场护理。所提出的分子分析系统代表了这一点。这是一项在生物医学研究、诊断和筛查领域具有变革潜力的重大创新。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Smartphone-Based Device for Colorimetric Detection of MicroRNA Biomarkers Using Nanoparticle-Based Assay.

DOI：
10.3390/s21238044
发表时间：
2021-12-01
期刊：
Sensors (Basel, Switzerland)
影响因子：
0
作者：
Krishnan T;Wang HN;Vo-Dinh T
通讯作者：
Vo-Dinh T

A sound approach to advancing healthcare systems: the future of biomedical acoustics.

DOI：
10.1038/s41467-022-31014-y
发表时间：
2022-06-16
期刊：
Nature communications
影响因子：
16.6
作者：
通讯作者：

Acoustofluidics for simultaneous nanoparticle-based drug loading and exosome encapsulation.

DOI：
10.1038/s41378-022-00374-2
发表时间：
2022
期刊：
MICROSYSTEMS & NANOENGINEERING
影响因子：
7.9
作者：
Wang, Zeyu;Rich, Joseph;Hao, Nanjing;Gu, Yuyang;Chen, Chuyi;Yang, Shujie;Zhang, Peiran;Huang, Tony Jun
通讯作者：
Huang, Tony Jun

Acoustofluidic Holography for Micro- to Nanoscale Particle Manipulation.

DOI：
10.1021/acsnano.0c03754
发表时间：
2020-11-24
期刊：
ACS nano
影响因子：
17.1
作者：
Gu Y;Chen C;Rufo J;Shen C;Wang Z;Huang PH;Fu H;Zhang P;Cummer SA;Tian Z;Huang TJ
通讯作者：
Huang TJ

A Cell-Phone-Based Acoustofluidic Platform for Quantitative Point-of-Care Testing.