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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...

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Autores principales: 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
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
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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.
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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
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