Sensing and Bio-Sensing Research (Dec 2020)
Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor
- Jamie R.K. Marland,
- Mark E. Gray,
- Camelia Dunare,
- Ewen O. Blair,
- Andreas Tsiamis,
- Paul Sullivan,
- Eva González-Fernández,
- Stephen N. Greenhalgh,
- Rachael Gregson,
- R. Eddie Clutton,
- Magdalena M. Parys,
- Alex Dyson,
- Mervyn Singer,
- Ian H. Kunkler,
- Mark A. Potter,
- Srinjoy Mitra,
- Jonathan G. Terry,
- Stewart Smith,
- Andrew R. Mount,
- Ian Underwood,
- Anthony J. Walton,
- David J. Argyle,
- Alan F. Murray
Affiliations
- Jamie R.K. Marland
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK; Corresponding author.
- Mark E. Gray
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK
- Camelia Dunare
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK
- Ewen O. Blair
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK
- Andreas Tsiamis
- School of Engineering, Institute for Bioengineering, The University of Edinburgh, Faraday Building, Edinburgh EH9 3DW, UK
- Paul Sullivan
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK
- Eva González-Fernández
- School of Chemistry, University of Edinburgh, Joseph Black Building, Edinburgh EH9 3FJ, UK
- Stephen N. Greenhalgh
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK
- Rachael Gregson
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK
- R. Eddie Clutton
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK
- Magdalena M. Parys
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK
- Alex Dyson
- Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK
- Mervyn Singer
- Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London WC1E 6BT, UK
- Ian H. Kunkler
- Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK
- Mark A. Potter
- Department of Surgery, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
- Srinjoy Mitra
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK
- Jonathan G. Terry
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK
- Stewart Smith
- School of Engineering, Institute for Bioengineering, The University of Edinburgh, Faraday Building, Edinburgh EH9 3DW, UK
- Andrew R. Mount
- School of Chemistry, University of Edinburgh, Joseph Black Building, Edinburgh EH9 3FJ, UK
- Ian Underwood
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK
- Anthony J. Walton
- School of Engineering, Institute for Integrated Micro and Nano Systems, The University of Edinburgh, Scottish Microelectronics Centre, Edinburgh EH9 3FF, UK
- David J. Argyle
- The Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, Roslin, Midlothian EH25 9RG, UK
- Alan F. Murray
- School of Engineering, Institute for Bioengineering, The University of Edinburgh, Faraday Building, Edinburgh EH9 3DW, UK
- Journal volume & issue
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Vol. 30
p. 100375
Abstract
Hypoxia commonly occurs within tumours and is a major cause of radiotherapy resistance. Clinical outcomes could be improved by locating and selectively increasing the dose delivered to hypoxic regions. Here we describe a miniature implantable sensor for real-time monitoring of tissue oxygenation that could enable this novel treatment approach to be implemented. The sensor uses a solid-state electrochemical cell that was microfabricated at wafer level on a silicon substrate, and includes an integrated reference electrode and electrolyte membrane. It gave a linear response to oxygen concentration, and was unaffected by sterilisation and irradiation, but showed susceptibility to biofouling. Oxygen selectivity was also evaluated against various clinically relevant electroactive compounds. We investigated its robustness and functionality under realistic clinical conditions using a sheep model of lung cancer. The sensor remained functional following CT-guided tumour implantation, and was sufficiently sensitive to track acute changes in oxygenation within tumour tissue.
