In vivo application of an implantable tri-anchored methylene blue-based electrochemical pH sensor

Eva González-fernández, Matteo Staderini, Jamie R.k. Marland, Mark E. Gray, Ahmet Uçar, Camelia Dunare, Ewen O. Blair, Paul Sullivan, Andreas Tsiamis, Stephen N. Greenhalgh, Rachael Gregson, Richard Eddie Clutton, Stewart Smith, Jonathan G. Terry, David J. Argyle, Anthony J. Walton, Andrew R. Mount, Mark Bradley, Alan F. Murray

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The development of robust implantable sensors is important in the successful advancement of personalised medicine as they have the potential to provide in situ real-time data regarding the status of health and disease and the effectiveness of treatment. Tissue pH is a key physiological parameter and herein, we report the design, fabrication, functionalisation, encapsulation and protection of a miniaturised self-contained electrochemical pH sensor system and characterisation of sensor performance. Notably for the first time in this environment the pH sensor was based on a methylene blue redox reporter which showed remarkable robustness and accuracy and sensitivity. This was achieved by encapsulation of a self-assembled monolayer containing methylene blue entrapped within a Nafion layer. Another powerful feature was the incorporation, within the same implanted device, of a fabricated on-chip Ag/AgCl reference electrode – vital in any electrochemical sensor, but often ignored. When utilised in vivo, the sensor allowed accurate tracking of externally induced pH changes within a naturally occurring ovine lung cancer model, and correlated well with single point laboratory measurements made on extracted arterial blood, whilst enabling in vivo time-dependent measurements. The sensors functioned robustly whilst implanted, and maintained in vitro function once extracted and together, these results demonstrate proof-of-concept of the ability to sense real-time intratumoral tissue pH changes in vivo.
Original languageEnglish
Pages (from-to)113728
JournalBiosensors and Bioelectronics
Early online date1 Nov 2021
Publication statusE-pub ahead of print - 1 Nov 2021


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