Electrochemical aptamer sensing of cortisol in saliva: mitigating matrix effects via interfacial and signal strategies
File(s)
Published version
Author(s)
Naeem, Nisha
Estrela, Pedro
Ghoreishizadeh, Sara S
Type
Journal Article
Abstract
Matrix effects in complex biological media present a significant challenge for electrochemical aptamer-based sensing and limit the reliable detection of analytes such as cortisol in saliva for non-invasive monitoring. In this work, we develop a cortisol electrochemical aptamer-based (E-AB) sensor and systematically investigate how salivary parameters, including pH, ionic strength, and divalent cation concentration, influence sensor performance. We observe distinct matrix-induced changes in sensor behaviour, with protein–aptamer interactions, salivary viscosity, and biofouling proposed as potential contributors to different modes of baseline drift. To address these effects, we implement complementary strategies comprising saliva enhancement to mitigate matrix interference, a mixed hydroxyl- and carboxylate-terminated self-assembled monolayer to enhance signal gain, and kinetic differential measurement to correct negative baseline drift. Together, these approaches improve the functional limit of detection from 111 to 2.4 ng/mL and enable sensor regeneration for at least five cycles in minimally processed saliva. The sensor further exhibits preferential response towards cortisol over the structurally related steroids cortisone and corticosterone and consistent responses to cortisol across saliva samples from five independent donors. These findings highlight the importance of characterising aptamer–matrix interactions and selecting mitigation strategies according to the resulting sensor behaviour when translating E-AB sensors to complex biological matrices.
Date Issued
2026-06-01
Date Acceptance
2026-09-17
Citation
Advanced Biosensors, 2026, 1
ISSN
3117-9339
Publisher
Elsevier BV
Journal / Book Title
Advanced Biosensors
Volume
1
Copyright Statement
© 2026 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Publication Status
Published
Article Number
100004
Date Publish Online
2026-09-17