Development of plasmon-enhanced biosensing for multiplexed profiling of extracellular vesicles

用于细胞外囊泡多重分析的等离子体增强生物传感的发展

• 批准号: 10468868
• 负责人: Hyungsoon Im
• 金额: $ 35.7万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10468868
• 关键词: Address; Basic Science; Biological; Biological Assay; Biological Markers; Biological Models; Biosensing Techniques; Blood; Cancer cell line; Cardiovascular Diseases; Cells; Cerebrospinal Fluid; Clinical; Clinical Research; Color; Cytolysis; Detection; Development; Disease; Emerging Technologies; Fluorescence; Generations; Genetic Materials; Goals; Gold; Heterogeneity; Human; Individual; Integral Membrane Protein; Label; Lipids; Liquid substance; Malignant Neoplasms; Malignant neoplasm of ovary; Membrane; Methods; Modeling; Molecular; Molecular Probes; Monitor; Names; Neurodegenerative Disorders; Performance; Periodicity; Phospholipids; Plasma; Procedures; Process; Production; Proteins; RNA; RNA marker; Reproducibility; Saliva; Sampling; Signal Transduction; Structure; Surface Plasmon Resonance; System; Technology; Testing; Tumor-Derived; Urine; Variant; Vesicle; base; cancer diagnosis; cell type; circulating biomarkers; clinical application; clinically relevant; design; detection assay; detection platform; detection sensitivity; exosome; experimental study; extracellular vesicles; improved; innovation; insight; liquid biopsy; minimally invasive; molecular diagnostics; molecular marker; nanoplasmonic; nanopore; nanoscale; new technology; next generation; noninvasive diagnosis; pre-clinical; protein biomarkers; prototype; sensor; sensor technology; tool; transmission process; treatment response; tumor

Extracellular vesicles (EVs) present new opportunities for molecular diagnostics from non-invasive liquid biopsies. These cell-derived membrane-bound vesicles are abundantly present in biological fluids. EVs carry cell-specific cargos (e.g., lipids, proteins, and genetic materials), which can be harnessed to probe the molecular status of their cellular origins. EV analyses, however, pose unique technical challenges due to EVs' nanometer-sizes and presence in a vast biological background. EV analyses, however, pose unique technical challenges due to EVs' nanometer-sizes and presence in a vast biological background. While new technologies for EV analysis have been developed, fundamental limitations still remain, including i) low sensitivity limited to bulk analyses; ii) necessities of EV lysis for detecting markers inside of EVs; iii) lack of multiplexed analysis on protein and RNA markers; and iv) a separate EV isolation process required prior to the assay. The overall goal of this application is to overcome these technical challenges and develop a new platform that enables multiplexed analyses of EV protein and RNA markers in individual EVs. We previously developed a nanoplasmonic EV sensing platform based on transmission surface plasmon resonance through periodic nanohole gratings. We showed that the nanoplasmonic sensors could rapidly and sensitively detect disease-specific EVs directly from clinical samples. In this project, we will further advance the technology for robust multiplexed EV analysis and implement on-chip EV isolation to achieve simple assay procedures and good reproducibility. We will validate the system using well-established preclinical and clinical samples to demonstrate the feasibility and potential of the new technology for clinical applications. Successful completion of the project will produce a highly sensitive sensing platform for multiplexed EV analysis. The development of such a technology could offer additional insight into understanding subtypes, heterogeneity, and production dynamics of EVs during disease development and progression. The gained insights will pave the way for expanding EV studies to various diseases, further broadening the scope of EV applications in clinical settings.

细胞外囊泡（EVs）为非侵入性液体分子诊断提供了新的机会