Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor
Jamie R. K. Marland, Mark Gray, Camelia Dunare, Ewen O. Blair, Andreas Tsiamis, P. J. Sullivan, Eva González‐Fernández, Stephen N. Greenhalgh, Rachael Gregson, R. Eddie Clutton, Magdalena Parys, Alex Dyson, Mervyn Singer, Ian Kunkler, Mark A. Potter, Srinjoy Mitra, Jonathan G. Terry, Stewart Smith, Andrew R. Mount, Ian Underwood, A.J. Walton, David J. Argyle, Alan F. Murray
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.