An Integrated Magneto-Electrochemical Device for the Rapid Profiling of Tumour Extracellular Vesicles from Blood Plasma

Authors

Jongmin Park, Harvard Medical School
Jun Seok Park, Harvard Medical School
Chen Han Huang, Harvard Medical School
Ala Jo, Harvard Medical School
Kaitlyn Cook, Harvard T.H. Chan School of Public HealthFollow
Rui Wang, Harvard T.H. Chan School of Public Health
Hsing Ying Lin, Harvard Medical School
Jan Van Deun, Harvard Medical School
Huiyan Li, Harvard Medical School
Jouha Min, Harvard Medical School
Lan Wang, Harvard Medical School
Ghilsuk Yoon, Kyungpook National University School of Medicine
Bob S. Carter, Harvard Medical School
Leonora Balaj, Harvard Medical School
Gyu Seog Choi, Kyungpook National University Hospital
Cesar M. Castro, Harvard Medical School
Ralph Weissleder, Harvard Medical School
Hakho Lee, Harvard Medical School

Document Type

Article

Publication Date

7-1-2021

Publication Title

Nature Biomedical Engineering

Publication Title

Nature Biomedical Engineering

Volume

5

Issue

7

Abstract

Assays for cancer diagnosis via the analysis of biomarkers on circulating extracellular vesicles (EVs) typically have lengthy sample workups, limited throughput or insufficient sensitivity, or do not use clinically validated biomarkers. Here we report the development and performance of a 96-well assay that integrates the enrichment of EVs by antibody-coated magnetic beads and the electrochemical detection, in less than one hour of total assay time, of EV-bound proteins after enzymatic amplification. By using the assay with a combination of antibodies for clinically relevant tumour biomarkers (EGFR, EpCAM, CD24 and GPA33) of colorectal cancer (CRC), we classified plasma samples from 102 patients with CRC and 40 non-CRC controls with accuracies of more than 96%, prospectively assessed a cohort of 90 patients, for whom the burden of tumour EVs was predictive of five-year disease-free survival, and longitudinally analysed plasma from 11 patients, for whom the EV burden declined after surgery and increased on relapse. Rapid assays for the detection of combinations of tumour biomarkers in plasma EVs may aid cancer detection and patient monitoring.

Comments

Peer reviewed accepted manuscript.

Original title: A high-throughput magneto-electrochemical array for the integrated isolation and profiling of extracellular vesicles from plasma

First Page

678

Last Page

689

Recommended Citation

Park, Jongmin; Park, Jun Seok; Huang, Chen Han; Jo, Ala; Cook, Kaitlyn; Wang, Rui; Lin, Hsing Ying; Van Deun, Jan; Li, Huiyan; Min, Jouha; Wang, Lan; Yoon, Ghilsuk; Carter, Bob S.; Balaj, Leonora; Choi, Gyu Seog; Castro, Cesar M.; Weissleder, Ralph; and Lee, Hakho, "An Integrated Magneto-Electrochemical Device for the Rapid Profiling of Tumour Extracellular Vesicles from Blood Plasma" (2021). Statistical and Data Sciences: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/sds_facpubs/65

Digital Object Identifier (DOI)

10.1038/s41551-021-00752-7