Cargando…

Digital immunoassay for biomarker concentration quantification using solid-state nanopores

Single-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores—fully electronic sensors with single-molecule...

Descripción completa

Detalles Bibliográficos
Autores principales: He, Liqun, Tessier, Daniel R., Briggs, Kyle, Tsangaris, Matthaios, Charron, Martin, McConnell, Erin M., Lomovtsev, Dmytro, Tabard-Cossa, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429538/
https://www.ncbi.nlm.nih.gov/pubmed/34504071
http://dx.doi.org/10.1038/s41467-021-25566-8
_version_ 1783750549805465600
author He, Liqun
Tessier, Daniel R.
Briggs, Kyle
Tsangaris, Matthaios
Charron, Martin
McConnell, Erin M.
Lomovtsev, Dmytro
Tabard-Cossa, Vincent
author_facet He, Liqun
Tessier, Daniel R.
Briggs, Kyle
Tsangaris, Matthaios
Charron, Martin
McConnell, Erin M.
Lomovtsev, Dmytro
Tabard-Cossa, Vincent
author_sort He, Liqun
collection PubMed
description Single-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores—fully electronic sensors with single-molecule sensitivity—are well suited to the task. Here we present a digital immunoassay scheme capable of reliably quantifying the concentration of a target protein in complex biofluids that overcomes specificity, sensitivity, and consistency challenges associated with the use of solid-state nanopores for protein sensing. This is achieved by employing easily-identifiable DNA nanostructures as proxies for the presence (“1”) or absence (“0”) of the target protein captured via a magnetic bead-based sandwich immunoassay. As a proof-of-concept, we demonstrate quantification of the concentration of thyroid-stimulating hormone from human serum samples down to the high femtomolar range. Further optimization to the method will push sensitivity and dynamic range, allowing for development of precision diagnostic tools compatible with point-of-care format.
format Online
Article
Text
id pubmed-8429538
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-84295382021-09-24 Digital immunoassay for biomarker concentration quantification using solid-state nanopores He, Liqun Tessier, Daniel R. Briggs, Kyle Tsangaris, Matthaios Charron, Martin McConnell, Erin M. Lomovtsev, Dmytro Tabard-Cossa, Vincent Nat Commun Article Single-molecule counting is the most accurate and precise method for determining the concentration of a biomarker in solution and is leading to the emergence of digital diagnostic platforms enabling precision medicine. In principle, solid-state nanopores—fully electronic sensors with single-molecule sensitivity—are well suited to the task. Here we present a digital immunoassay scheme capable of reliably quantifying the concentration of a target protein in complex biofluids that overcomes specificity, sensitivity, and consistency challenges associated with the use of solid-state nanopores for protein sensing. This is achieved by employing easily-identifiable DNA nanostructures as proxies for the presence (“1”) or absence (“0”) of the target protein captured via a magnetic bead-based sandwich immunoassay. As a proof-of-concept, we demonstrate quantification of the concentration of thyroid-stimulating hormone from human serum samples down to the high femtomolar range. Further optimization to the method will push sensitivity and dynamic range, allowing for development of precision diagnostic tools compatible with point-of-care format. Nature Publishing Group UK 2021-09-09 /pmc/articles/PMC8429538/ /pubmed/34504071 http://dx.doi.org/10.1038/s41467-021-25566-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
He, Liqun
Tessier, Daniel R.
Briggs, Kyle
Tsangaris, Matthaios
Charron, Martin
McConnell, Erin M.
Lomovtsev, Dmytro
Tabard-Cossa, Vincent
Digital immunoassay for biomarker concentration quantification using solid-state nanopores
title Digital immunoassay for biomarker concentration quantification using solid-state nanopores
title_full Digital immunoassay for biomarker concentration quantification using solid-state nanopores
title_fullStr Digital immunoassay for biomarker concentration quantification using solid-state nanopores
title_full_unstemmed Digital immunoassay for biomarker concentration quantification using solid-state nanopores
title_short Digital immunoassay for biomarker concentration quantification using solid-state nanopores
title_sort digital immunoassay for biomarker concentration quantification using solid-state nanopores
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429538/
https://www.ncbi.nlm.nih.gov/pubmed/34504071
http://dx.doi.org/10.1038/s41467-021-25566-8
work_keys_str_mv AT heliqun digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores
AT tessierdanielr digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores
AT briggskyle digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores
AT tsangarismatthaios digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores
AT charronmartin digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores
AT mcconnellerinm digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores
AT lomovtsevdmytro digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores
AT tabardcossavincent digitalimmunoassayforbiomarkerconcentrationquantificationusingsolidstatenanopores