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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：
10322659
负责人：
Tuan Vo-Dinh
金额：
$ 42.01万
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/10322659
关键词：
Acoustics Adopted Area Benchmarking Biological Biological Assay Biological Markers Biological Models Biomedical Research Blood Circulation Blood specimen Cancer Diagnostics Cardiovascular Diseases Cardiovascular system Cells Centrifugation Characteristics Chylomicrons Clinical Colorectal Cancer Communicable Diseases Consumption Detection Development Devices Disease Early Diagnosis Early treatment Encapsulated Evaluation Future Gastrointestinal tract structure Gene Expression Genetic Transcription Goals Gold Human Human Resources In Situ Infection Investigation Knowledge Lead Lipoprotein (a)Lipoproteins Liquid substance Low-Density Lipoproteins Malignant Neoplasms Measures Messenger RNA Metaplasia Methods MicroRNAs Microfluidics Molecular Molecular Analysis Molecular Biology Monitor Neurodegenerative Disorders Northern Blotting Output Pathology Performance Phase Preparation Procedures Process Proteins Quantitative Reverse Transcriptase PCR Research Research Personnel Sampling Sentinel Small RNA Sorting - Cell Movement Specificity Specimen Speed Statistical Data Interpretation Surface Symptoms System Systems Analysis Techniques Technology Testing Time Training Translations Tumor-Derived Ultracentrifugation Untranslated RNA Validation Vesicle Whole Blood accurate diagnosis base biobank biological research biomaterial compatibility 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 diagnosis disease diagnostic early detection biomarkers early screening exosome improved innovation interactive feedback interdisciplinary collaboration microRNA biomarkers molecular diagnostics molecular marker mortality multiplex detection nanobiosensor nanoprobe nanoscale neoplastic cell new technology novel novel diagnostics performance tests physical property plasmonics point of care point of care testing point-of-care diagnostics rapid diagnosis small molecule

项目摘要

The goal of this project is to develop an integrated 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 infection. Recent studies have also demonstrated that miRNAs can be secreted from tumor cells into bloodstream via exosomes; 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, because of technical difficulties arising from exosome isolation and miRNA analysis, detection of these small molecules has not been adopted into clinical practice. Thus, there is a need to develop alternative analysis strategies that could offer more advantages over conventional methods. In this project, 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 diseases. This system integrates two unique technologies: (1) 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 also 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 establishing the technical validation required to ready this integrated technology for future use in clinical settings. Throughout this project, an integrated 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 results will be compared to those obtained using conventional assays (e.g. qRT-PCR). The system will lead to a no-sample preparation and “sample-to- answer” analysis approach that is based on the integration of existing and tested sub-components. This new diagnostic system is capable of enhancing research and translation in the areas of early detection and screening of various diseases beyond CRC; it is exceedingly well suited for point-of-care testing. The proposed system represents a major innovation with transformative potential in biomedical research, diagnostics, and screening.

该项目的目标是开发一种用于快速隔离的综合诊断系统，