Self-Correction of pH-Induced Signal Variations in Methylene Blue-Labeled Aptamer Electrochemical Biosensors: Wearable Cortisol Detection in Sweat

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Not specified in abstract

• Primary Outcome: Accurate cortisol quantification with pH self-correction across pH 5.5-7.5 range

• Nnt Or Sensitivity: Excellent correlation reported but specific sensitivity/specificity values not provided

• Confidence Interval: Not reported

Clinical Application

High feasibility for non-invasive continuous monitoring, though requires technical expertise for implementation Relevant for TGA medical device approval pathway, potential applications in sports medicine and endocrinology practices, alignment with digital health initiatives Individuals requiring continuous cortisol monitoring, particularly for stress assessment, endocrine disorders, or athletic performance monitoring

Abstract

Common electrochemical aptamer-based (E-AB) biosensors employing methylene blue (MB) redox reporters suffer from significant pH-induced signal variations. Consequently, dynamic pH fluctuations in biofluids, such as in sweat, can greatly distort the measured signal and lead to inaccurate target quantification. Here, we introduce a self-correction strategy that enables accurate analyte quantification by compensating for pH-induced signal variations in MB-based aptasensors using the Nernstian shift of the MB peak potential. The highly reproducible reversible pH dependence of the MB peak potential enables real-time monitoring of the sample pH that provides a continuously synchronized built-in compensation of the pH interference, thereby eliminating the need for external pH sensors or additional measurement steps. This precise yet simple and effective self-correction of pH effects ensures that the Square Wave Voltammetry (SWV) signal reliably reflects real-time analyte variations, as demonstrated using a cortisol MB-labeled E-AB biosensor in both in vitro and on-body settings. In vitro measurements in artificial sweat across pH 5.5-7.5 showed excellent correlation with real-time pH and cortisol changes, confirming the reliability of the peak potential-based correction. On-body measurements using an epidermal wearable patch showed cortisol changes in sweat that would have been missed without this signal-correction method. This approach is broadly applicable to other MB-labeled E-AB biosensors and biofluids, providing a robust strategy for continuous on-body monitoring.

References

1. 1.Sabbagh, B., Khan, M. I., Kim, G., Nandhakumar, P., Chiu, L., Zheng, H., Jakasania, A., Perez, V., Saha, T., Park, M., & Wang, J. (2026). Self-correction of pH-induced signal variations in methylene blue-labeled aptamer electrochemical biosensors: Wearable cortisol detection in sweat. ACS Sensors. https://doi.org/10.1021/acssensors.6c00737