TY - JOUR
T1 - In vivo application of an implantable tri-anchored methylene blue-based electrochemical pH sensor
AU - González-fernández, Eva
AU - Staderini, Matteo
AU - Marland, Jamie R.k.
AU - Gray, Mark E.
AU - Uçar, Ahmet
AU - Dunare, Camelia
AU - Blair, Ewen O.
AU - Sullivan, Paul
AU - Tsiamis, Andreas
AU - Greenhalgh, Stephen N.
AU - Gregson, Rachael
AU - Clutton, Richard Eddie
AU - Smith, Stewart
AU - Terry, Jonathan G.
AU - Argyle, David J.
AU - Walton, Anthony J.
AU - Mount, Andrew R.
AU - Bradley, Mark
AU - Murray, Alan F.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
U2 - 10.1016/j.bios.2021.113728
DO - 10.1016/j.bios.2021.113728
M3 - Article
SN - 0956-5663
SP - 113728
JO - Biosensors and Bioelectronics
JF - Biosensors and Bioelectronics
ER -