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

González-Fernández E., Staderini M., Marland J. R. , Gray M. E. , Uçar A. , Dunare C., ...More

Biosensors and Bioelectronics, vol.197, 2022 (Journal Indexed in SCI Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 197
  • Publication Date: 2022
  • Doi Number: 10.1016/j.bios.2021.113728
  • Title of Journal : Biosensors and Bioelectronics
  • Keywords: Implantable, Methylene blue, Microfabrication, pH, Sensor, Tumour


© 2021 Elsevier B.V.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, 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.