Electrochemical Detection of Tumor-Derived Extracellular Vesicles on Nanointerdigitated Electrodes

Dilu G. Mathew, Pepijn Beekman, Serge G. Lemay, Han Zuilhof, Severine le Gac, Wilfred G. van der Wiel*

*Corresponding author for this work

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Abstract

Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their essential function in intercellular communication and their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. Moreover, the presence of particles in blood with a similar size as that of tdEVs makes their selective and sensitive detection further challenging. Therefore, highly sensitive and specific biosensors are required for unambiguous tdEV detection in complex biological environments, especially for decentralized point-of-care analysis. Here, we report an electrochemical sensing scheme for tdEV detection, with two-level selectivity provided by a sandwich immunoassay and two-level amplification through the combination of an enzymatic assay and redox cycling on nanointerdigitated electrodes to respectively enhance the specificity and sensitivity of the assay. Analysis of prostate cancer cell line tdEV samples at various concentrations revealed an estimated limit of detection for our assay as low as 5 tdEVs/μL, as well as an excellent linear sensor response spreading over 6 orders of magnitude (10–106 tdEVs/μL), which importantly covers the clinically relevant range for tdEV detection in blood. This novel nanosensor and associated sensing scheme opens new opportunities to detect tdEVs at clinically relevant concentrations from a single blood finger prick.
Original languageEnglish
JournalNano letters
Publication statusAccepted/In press - 19 Sep 2019

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Tumors
tumors
Blood
blood
Electrodes
electrodes
Assays
Tumor Biomarkers
biomarkers
cancer
Nanosensors
immunoassay
Biosensors
Amplification
bioinstrumentation
cultured cells
Cells
selectivity
communication
Communication

Keywords

  • UT-Hybrid-D
  • Redox Cycling
  • Enzymatic amplification
  • Tumor-derived Extracellular Vesicles (tdEVs)
  • Nanoelectrodes

Cite this

@article{2387407448d1498aae11d207203e0961,
title = "Electrochemical Detection of Tumor-Derived Extracellular Vesicles on Nanointerdigitated Electrodes",
abstract = "Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their essential function in intercellular communication and their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. Moreover, the presence of particles in blood with a similar size as that of tdEVs makes their selective and sensitive detection further challenging. Therefore, highly sensitive and specific biosensors are required for unambiguous tdEV detection in complex biological environments, especially for decentralized point-of-care analysis. Here, we report an electrochemical sensing scheme for tdEV detection, with two-level selectivity provided by a sandwich immunoassay and two-level amplification through the combination of an enzymatic assay and redox cycling on nanointerdigitated electrodes to respectively enhance the specificity and sensitivity of the assay. Analysis of prostate cancer cell line tdEV samples at various concentrations revealed an estimated limit of detection for our assay as low as 5 tdEVs/μL, as well as an excellent linear sensor response spreading over 6 orders of magnitude (10–106 tdEVs/μL), which importantly covers the clinically relevant range for tdEV detection in blood. This novel nanosensor and associated sensing scheme opens new opportunities to detect tdEVs at clinically relevant concentrations from a single blood finger prick.",
keywords = "UT-Hybrid-D, Redox Cycling, Enzymatic amplification, Tumor-derived Extracellular Vesicles (tdEVs), Nanoelectrodes",
author = "Mathew, {Dilu G.} and Pepijn Beekman and Lemay, {Serge G.} and Han Zuilhof and {le Gac}, Severine and {van der Wiel}, {Wilfred G.}",
note = "ACS deal",
year = "2019",
month = "9",
day = "19",
language = "English",
journal = "Nano letters",
issn = "1530-6984",
publisher = "American Chemical Society",

}

TY - JOUR

T1 - Electrochemical Detection of Tumor-Derived Extracellular Vesicles on Nanointerdigitated Electrodes

AU - Mathew, Dilu G.

AU - Beekman, Pepijn

AU - Lemay, Serge G.

AU - Zuilhof, Han

AU - le Gac, Severine

AU - van der Wiel, Wilfred G.

N1 - ACS deal

PY - 2019/9/19

Y1 - 2019/9/19

N2 - Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their essential function in intercellular communication and their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. Moreover, the presence of particles in blood with a similar size as that of tdEVs makes their selective and sensitive detection further challenging. Therefore, highly sensitive and specific biosensors are required for unambiguous tdEV detection in complex biological environments, especially for decentralized point-of-care analysis. Here, we report an electrochemical sensing scheme for tdEV detection, with two-level selectivity provided by a sandwich immunoassay and two-level amplification through the combination of an enzymatic assay and redox cycling on nanointerdigitated electrodes to respectively enhance the specificity and sensitivity of the assay. Analysis of prostate cancer cell line tdEV samples at various concentrations revealed an estimated limit of detection for our assay as low as 5 tdEVs/μL, as well as an excellent linear sensor response spreading over 6 orders of magnitude (10–106 tdEVs/μL), which importantly covers the clinically relevant range for tdEV detection in blood. This novel nanosensor and associated sensing scheme opens new opportunities to detect tdEVs at clinically relevant concentrations from a single blood finger prick.

AB - Tumor-derived extracellular vesicles (tdEVs) are attracting much attention due to their essential function in intercellular communication and their potential as cancer biomarkers. Although tdEVs are significantly more abundant in blood than other cancer biomarkers, their concentration compared to other blood components remains relatively low. Moreover, the presence of particles in blood with a similar size as that of tdEVs makes their selective and sensitive detection further challenging. Therefore, highly sensitive and specific biosensors are required for unambiguous tdEV detection in complex biological environments, especially for decentralized point-of-care analysis. Here, we report an electrochemical sensing scheme for tdEV detection, with two-level selectivity provided by a sandwich immunoassay and two-level amplification through the combination of an enzymatic assay and redox cycling on nanointerdigitated electrodes to respectively enhance the specificity and sensitivity of the assay. Analysis of prostate cancer cell line tdEV samples at various concentrations revealed an estimated limit of detection for our assay as low as 5 tdEVs/μL, as well as an excellent linear sensor response spreading over 6 orders of magnitude (10–106 tdEVs/μL), which importantly covers the clinically relevant range for tdEV detection in blood. This novel nanosensor and associated sensing scheme opens new opportunities to detect tdEVs at clinically relevant concentrations from a single blood finger prick.

KW - UT-Hybrid-D

KW - Redox Cycling

KW - Enzymatic amplification

KW - Tumor-derived Extracellular Vesicles (tdEVs)

KW - Nanoelectrodes

M3 - Article

JO - Nano letters

JF - Nano letters

SN - 1530-6984

ER -