Cargando…

E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum

The multiplexed, point-of-care measurement of specific antibodies could improve the speed with which diseases are diagnosed and their treatment initiated. To this end, we are developing E-DNA scaffold sensors, which consist of a rigid, nucleic acid “scaffold” attached on one end to an electrode and...

Descripción completa

Detalles Bibliográficos
Autores principales: Parolo, Claudio, Greenwood, Ava S., Ogden, Nathan E., Kang, Di, Hawes, Chase, Ortega, Gabriel, Arroyo-Currás, Netzahualcóyotl, Plaxco, Kevin W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433188/
https://www.ncbi.nlm.nih.gov/pubmed/34567628
http://dx.doi.org/10.1038/s41378-019-0119-5
_version_ 1783751325602807808
author Parolo, Claudio
Greenwood, Ava S.
Ogden, Nathan E.
Kang, Di
Hawes, Chase
Ortega, Gabriel
Arroyo-Currás, Netzahualcóyotl
Plaxco, Kevin W.
author_facet Parolo, Claudio
Greenwood, Ava S.
Ogden, Nathan E.
Kang, Di
Hawes, Chase
Ortega, Gabriel
Arroyo-Currás, Netzahualcóyotl
Plaxco, Kevin W.
author_sort Parolo, Claudio
collection PubMed
description The multiplexed, point-of-care measurement of specific antibodies could improve the speed with which diseases are diagnosed and their treatment initiated. To this end, we are developing E-DNA scaffold sensors, which consist of a rigid, nucleic acid “scaffold” attached on one end to an electrode and presenting both a redox reporter and an epitope on the other. In the absence of antibody, the reporter efficiently transfers electrons when interrogated electrochemically. Binding-induced steric hindrance limits movement, reducing electron transfer in a manner that is both easily measured and quantitatively related to target concentration. Previously we have used monoclonal antibodies to explore the analytical performance of E-DNA sensors, showing that they support the rapid, single-step, quantitative detection of multiple antibodies in small volume samples. Here, in contrast, we employ authentic human samples to better explore the platform’s clinical potential. Specifically, we developed E-DNA sensors targeting three HIV-specific antibodies and then compared the analytical and clinical performance of these against those of gold standard serological techniques. Doing so we find that, although the multistep amplification of an ELISA leads to a lower detection limits, the clinical sensitivity of ELISAs, E-DNA sensors and lateral-flow dipsticks are indistinguishable across our test set. It thus appears that, by merging the quantitation and multiplexing of ELISAs with the convenience and speed of dipsticks, E-DNA scaffold sensors could significantly improve on current serological practice.
format Online
Article
Text
id pubmed-8433188
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-84331882021-09-24 E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum Parolo, Claudio Greenwood, Ava S. Ogden, Nathan E. Kang, Di Hawes, Chase Ortega, Gabriel Arroyo-Currás, Netzahualcóyotl Plaxco, Kevin W. Microsyst Nanoeng Article The multiplexed, point-of-care measurement of specific antibodies could improve the speed with which diseases are diagnosed and their treatment initiated. To this end, we are developing E-DNA scaffold sensors, which consist of a rigid, nucleic acid “scaffold” attached on one end to an electrode and presenting both a redox reporter and an epitope on the other. In the absence of antibody, the reporter efficiently transfers electrons when interrogated electrochemically. Binding-induced steric hindrance limits movement, reducing electron transfer in a manner that is both easily measured and quantitatively related to target concentration. Previously we have used monoclonal antibodies to explore the analytical performance of E-DNA sensors, showing that they support the rapid, single-step, quantitative detection of multiple antibodies in small volume samples. Here, in contrast, we employ authentic human samples to better explore the platform’s clinical potential. Specifically, we developed E-DNA sensors targeting three HIV-specific antibodies and then compared the analytical and clinical performance of these against those of gold standard serological techniques. Doing so we find that, although the multistep amplification of an ELISA leads to a lower detection limits, the clinical sensitivity of ELISAs, E-DNA sensors and lateral-flow dipsticks are indistinguishable across our test set. It thus appears that, by merging the quantitation and multiplexing of ELISAs with the convenience and speed of dipsticks, E-DNA scaffold sensors could significantly improve on current serological practice. Nature Publishing Group UK 2020-03-23 /pmc/articles/PMC8433188/ /pubmed/34567628 http://dx.doi.org/10.1038/s41378-019-0119-5 Text en © The Author(s) 2020 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
Parolo, Claudio
Greenwood, Ava S.
Ogden, Nathan E.
Kang, Di
Hawes, Chase
Ortega, Gabriel
Arroyo-Currás, Netzahualcóyotl
Plaxco, Kevin W.
E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum
title E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum
title_full E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum
title_fullStr E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum
title_full_unstemmed E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum
title_short E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum
title_sort e-dna scaffold sensors and the reagentless, single-step, measurement of hiv-diagnostic antibodies in human serum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433188/
https://www.ncbi.nlm.nih.gov/pubmed/34567628
http://dx.doi.org/10.1038/s41378-019-0119-5
work_keys_str_mv AT paroloclaudio ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum
AT greenwoodavas ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum
AT ogdennathane ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum
AT kangdi ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum
AT haweschase ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum
AT ortegagabriel ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum
AT arroyocurrasnetzahualcoyotl ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum
AT plaxcokevinw ednascaffoldsensorsandthereagentlesssinglestepmeasurementofhivdiagnosticantibodiesinhumanserum