journal article·2025-08-12Open access

Extracellular Vesicles for Clinical Diagnostics: From Bulk Measurements to Single-Vesicle Analysis

Hai Linh Tran, Wenshu Zheng, David A. Issadore, Hyungsoon Im, Yoon-Kyoung Cho, Yuanqing Zhang, Dingbin Liu, Yang Liu, Bo Li, Fei Liu, David Tai Wai Wong, Jiashu Sun, Kun Qian, Mei He, Meihua Wan, Yong Zeng, Ke Cheng, Tony Jun Huang, Daniel T. Chiu, Luke P. Lee, Lei Zheng, Andrew K. Godwin, Raghu Kalluri, Steven A. Soper, Tony Y. Hu

ACS Nano· Volume 19· Issue 31

Abstract

Extracellular vesicles (EVs) play a crucial role in intercellular communication, signaling pathways, and disease pathogenesis by transporting biomolecules such as DNA, RNA, proteins, and lipids derived from their cells of origin, and they have demonstrated substantial potential in clinical applications. Their clinical significance underscores the need for sensitive methods to fully harness their diagnostic potential. In this comprehensive review, we explore EV heterogeneity related to biogenesis, structure, content, origin, sample type, and function roles; the use of EVs as disease biomarkers; and the evolving landscape of EV measurement for clinical diagnostics, highlighting the progression from bulk measurement to single vesicle analysis. This review covers emerging technologies such as single-particle tracking microscopy, single-vesicle RNA sequencing, and various nanopore-, nanoplasmonic-, immuno-digital droplet-, microfluidic-, and nanomaterial-based techniques. Unlike traditional bulk analysis methods, these methods contribute uniquely to EV characterization. Techniques like droplet-based single EV-counting enzyme-linked immunosorbent assays (ELISA), proximity-dependent barcoding assays, and surface-enhanced Raman spectroscopy further enhance our ability to precisely identify biomarkers, detect diseases earlier, and significantly improve clinical outcomes. These innovations provide access to intricate molecular details that expand our understanding of EV composition, with profound diagnostic implications. This review also examines key research challenges in the field, including the complexities of sample analysis, technique sensitivity and specificity, the level of detail provided by analytical methods, and practical applications, and we identify directions for future research. This review underscores the value of advanced EV analysis methods, which contribute to deep insights into EV-mediated pathological diversity and enhanced clinical diagnostics.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Extracellular vesicles in disease · Cell Adhesion Molecules Research · MicroRNA in disease regulation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Center for Cellular and Molecular Diagnostics and Department of Biochemistry and Molecular Biology

Tulane University School of Medicine

Department of Bioengineering

University of Pennsylvania

Department of Radiology, Massachusetts General Hospital

Harvard Medical School

Department of Biomedical Engineering

Ulsan National Institute of Science and Technology (UNIST)

School of Pharmaceutical Sciences

Sun Yat-Sen University

State Key Laboratory of Medicinal Chemical Biology, Research Center for Analytical Sciences, Tianjin Key Laboratory of Molecular Recognition and Biosensing, College of Chemistry

Nankai University

Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy

Tianjin’s Clinical Research Center for Cancer

Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Nanfang Hospital

Southern Medical University

Department of Medicine, Brigham and Women’s Hospital

School of Dentistry

University of California

Beijing Engineering Research Center for BioNanotechnology, CAS Key Laboratory of Standardization and Measurement for Nanotechnology

National Center for Nanoscience and Technology

School of Future Technology

University of Chinese Academy of Sciences

State Key Laboratory of Systems Medicine for Cancer, School of Biomedical Engineering and Institute of Medical Robotics, Division of Cardiology, Renji Hospital, School of Medicine

Shanghai Jiao Tong University

Funding

National Cancer Institute · National Institute of Neurological Disorders and Stroke · National Institute of Allergy and Infectious Diseases · U.S. Department of Defense · Eunice Kennedy Shriver National Institute of Child Health and Human Development

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