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

• 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
• 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

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.

摘要

项目成果

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)
• 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

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.

• DOI: 10.1021/acsnano.9b08349
• 发表时间: 2020-03
• 期刊: ACS nano
• 影响因子: 17.1
• 作者: Liying Zhang;Zhenhua Tian;Hunter Bachman;Peiran Zhang;T. Huang

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