Cargando…
An antibody-based molecular switch for continuous small-molecule biosensing
We present a generalizable approach for designing biosensors that can continuously detect small-molecule biomarkers in real time and without sample preparation. This is achieved by converting existing antibodies into target-responsive “antibody-switches” that enable continuous optical biosensing. To...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516488/ https://www.ncbi.nlm.nih.gov/pubmed/37738337 http://dx.doi.org/10.1126/sciadv.adh4978 |
_version_ | 1785109137989828608 |
---|---|
author | Thompson, Ian A.P. Saunders, Jason Zheng, Liwei Hariri, Amani A. Maganzini, Nicolò Cartwright, Alyssa P. Pan, Jing Yee, Steven Dory, Constantin Eisenstein, Michael Vuckovic, Jelena Soh, Hyongsok Tom |
author_facet | Thompson, Ian A.P. Saunders, Jason Zheng, Liwei Hariri, Amani A. Maganzini, Nicolò Cartwright, Alyssa P. Pan, Jing Yee, Steven Dory, Constantin Eisenstein, Michael Vuckovic, Jelena Soh, Hyongsok Tom |
author_sort | Thompson, Ian A.P. |
collection | PubMed |
description | We present a generalizable approach for designing biosensors that can continuously detect small-molecule biomarkers in real time and without sample preparation. This is achieved by converting existing antibodies into target-responsive “antibody-switches” that enable continuous optical biosensing. To engineer these switches, antibodies are linked to a molecular competitor through a DNA scaffold, such that competitive target binding induces scaffold switching and fluorescent signaling of changing target concentrations. As a demonstration, we designed antibody-switches that achieve rapid, sample preparation–free sensing of digoxigenin and cortisol in undiluted plasma. We showed that, by substituting the molecular competitor, we can further modulate the sensitivity of our cortisol switch to achieve detection at concentrations spanning 3.3 nanomolar to 3.3 millimolar. Last, we integrated this switch with a fiber optic sensor to achieve continuous sensing of cortisol in a buffer and blood with <5-min time resolution. We believe that this modular sensor design can enable continuous biosensor development for many biomarkers. |
format | Online Article Text |
id | pubmed-10516488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105164882023-09-23 An antibody-based molecular switch for continuous small-molecule biosensing Thompson, Ian A.P. Saunders, Jason Zheng, Liwei Hariri, Amani A. Maganzini, Nicolò Cartwright, Alyssa P. Pan, Jing Yee, Steven Dory, Constantin Eisenstein, Michael Vuckovic, Jelena Soh, Hyongsok Tom Sci Adv Physical and Materials Sciences We present a generalizable approach for designing biosensors that can continuously detect small-molecule biomarkers in real time and without sample preparation. This is achieved by converting existing antibodies into target-responsive “antibody-switches” that enable continuous optical biosensing. To engineer these switches, antibodies are linked to a molecular competitor through a DNA scaffold, such that competitive target binding induces scaffold switching and fluorescent signaling of changing target concentrations. As a demonstration, we designed antibody-switches that achieve rapid, sample preparation–free sensing of digoxigenin and cortisol in undiluted plasma. We showed that, by substituting the molecular competitor, we can further modulate the sensitivity of our cortisol switch to achieve detection at concentrations spanning 3.3 nanomolar to 3.3 millimolar. Last, we integrated this switch with a fiber optic sensor to achieve continuous sensing of cortisol in a buffer and blood with <5-min time resolution. We believe that this modular sensor design can enable continuous biosensor development for many biomarkers. American Association for the Advancement of Science 2023-09-22 /pmc/articles/PMC10516488/ /pubmed/37738337 http://dx.doi.org/10.1126/sciadv.adh4978 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Physical and Materials Sciences Thompson, Ian A.P. Saunders, Jason Zheng, Liwei Hariri, Amani A. Maganzini, Nicolò Cartwright, Alyssa P. Pan, Jing Yee, Steven Dory, Constantin Eisenstein, Michael Vuckovic, Jelena Soh, Hyongsok Tom An antibody-based molecular switch for continuous small-molecule biosensing |
title | An antibody-based molecular switch for continuous small-molecule biosensing |
title_full | An antibody-based molecular switch for continuous small-molecule biosensing |
title_fullStr | An antibody-based molecular switch for continuous small-molecule biosensing |
title_full_unstemmed | An antibody-based molecular switch for continuous small-molecule biosensing |
title_short | An antibody-based molecular switch for continuous small-molecule biosensing |
title_sort | antibody-based molecular switch for continuous small-molecule biosensing |
topic | Physical and Materials Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516488/ https://www.ncbi.nlm.nih.gov/pubmed/37738337 http://dx.doi.org/10.1126/sciadv.adh4978 |
work_keys_str_mv | AT thompsonianap anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT saundersjason anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT zhengliwei anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT haririamania anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT maganzininicolo anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT cartwrightalyssap anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT panjing anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT yeesteven anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT doryconstantin anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT eisensteinmichael anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT vuckovicjelena anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT sohhyongsoktom anantibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT thompsonianap antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT saundersjason antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT zhengliwei antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT haririamania antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT maganzininicolo antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT cartwrightalyssap antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT panjing antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT yeesteven antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT doryconstantin antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT eisensteinmichael antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT vuckovicjelena antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing AT sohhyongsoktom antibodybasedmolecularswitchforcontinuoussmallmoleculebiosensing |