An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma

Jongmin Park; Jun Seok Park; Chen Han Huang; Ala Jo; Kaitlyn Cook; Rui Wang; Hsing Ying Lin; Jan Van Deun; Huiyan Li; Jouha Min; Lan Wang; Ghilsuk Yoon; Bob S. Carter; Leonora Balaj; Gyu Seog Choi; Cesar M. Castro; Ralph Weissleder; Hakho Lee

doi:10.1038/s41551-021-00752-7

An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma

Jongmin Park, Jun Seok Park, Chen Han Huang, Ala Jo, Kaitlyn Cook, Rui Wang, Hsing Ying Lin, Jan Van Deun, Huiyan Li, Jouha Min, Lan Wang, Ghilsuk Yoon, Bob S. Carter, Leonora Balaj, Gyu Seog Choi, Cesar M. Castro, Ralph Weissleder, Hakho Lee

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103 Scopus citations

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.

Original language	English
Pages (from-to)	678-689
Number of pages	12
Journal	Nature Biomedical Engineering
Volume	5
Issue number	7
DOIs	https://doi.org/10.1038/s41551-021-00752-7
State	Published - Jul 2021

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Park, J., Park, J. S., Huang, C. H., Jo, A., Cook, K., Wang, R., Lin, H. Y., Van Deun, J., Li, H., Min, J., Wang, L., Yoon, G., Carter, B. S., Balaj, L., Choi, G. S., Castro, C. M., Weissleder, R., & Lee, H. (2021). An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma. Nature Biomedical Engineering, 5(7), 678-689. https://doi.org/10.1038/s41551-021-00752-7

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title = "An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma",

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.",

author = "Jongmin Park and Park, {Jun Seok} and Huang, {Chen Han} and Ala Jo and Kaitlyn Cook and Rui Wang and Lin, {Hsing Ying} and {Van Deun}, Jan and Huiyan Li and Jouha Min and Lan Wang and Ghilsuk Yoon and Carter, {Bob S.} and Leonora Balaj and Choi, {Gyu Seog} and Castro, {Cesar M.} and Ralph Weissleder and Hakho Lee",

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doi = "10.1038/s41551-021-00752-7",

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Park, J, Park, JS, Huang, CH, Jo, A, Cook, K, Wang, R, Lin, HY, Van Deun, J, Li, H, Min, J, Wang, L, Yoon, G, Carter, BS, Balaj, L, Choi, GS, Castro, CM, Weissleder, R & Lee, H 2021, 'An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma', Nature Biomedical Engineering, vol. 5, no. 7, pp. 678-689. https://doi.org/10.1038/s41551-021-00752-7

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AU - Park, Jongmin

AU - Park, Jun Seok

AU - Huang, Chen Han

AU - Jo, Ala

AU - Cook, Kaitlyn

AU - Wang, Rui

AU - Lin, Hsing Ying

AU - Van Deun, Jan

AU - Li, Huiyan

AU - Min, Jouha

AU - Wang, Lan

AU - Yoon, Ghilsuk

AU - Carter, Bob S.

AU - Balaj, Leonora

AU - Choi, Gyu Seog

AU - Castro, Cesar M.

AU - Weissleder, Ralph

AU - Lee, Hakho

PY - 2021/7

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AB - 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.

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JO - Nature Biomedical Engineering

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An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma

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