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Sci. Adv., Sep 22 2023, 9 (38) eadh4978 | https://doi.org/10.1126/sciadv.adh4978
An antibody-based molecular switch for continuous small-molecule biosensing.
Ian A P Thompson 1, Jason Saunders 1, Liwei Zheng 2, Amani A Hariri 2, Nicolò Maganzini 1, Alyssa P Cartwright 1, Jing Pan 3, Steven Yee 1, Constantin Dory 1, Michael Eisenstein 1 2, Jelena Vuckovic 1, Hyongsok Tom Soh 1 2 *
1Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
2Department of Radiology, Stanford University, Stanford, CA 94305, USA.
3Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL 32611, USA.
*Corresponding author: correspondence to Hyongsok Tom Soh
Abstract
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.
논문정보
- Research article
- 2023년 09월 (BRIC 등록일 2023-10-26)
- 국외 연구진
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