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

doi:10.1016/j.sbsr.2020.100375

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 UnderwoodAnthony J. Walton, David J. Argyle, Alan F. Murray

^*Corresponding author for this work

Biomedical Engineering

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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.

Original language	English
Article number	100375
Journal	Sensing and Bio-Sensing Research
Volume	30
Early online date	11 Aug 2020
DOIs	https://doi.org/10.1016/j.sbsr.2020.100375
Publication status	Published - 1 Dec 2020

Keywords

implantable
microfabrication
oxygen sensor
tumour hypoxia

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10.1016/j.sbsr.2020.100375Licence: CC BY 4.0

Marland-etal-SBR-2020-Real-time-measurement-of-tumour-hypoxia-using-an-implantable-microfabricated-oxygen-sensorFinal published version, 2.9 MBLicence: CC BY 4.0

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Marland, J. R. K., Gray, M. E., Dunare, C., Blair, E. O., Tsiamis, A., Sullivan, P., González-Fernández, E., Greenhalgh, S. N., Gregson, R., Clutton, R. E., Parys, M. M., Dyson, A., Singer, M., Kunkler, I. H., Potter, M. A., Mitra, S., Terry, J. G., Smith, S., Mount, A. R., ... Murray, A. F. (2020). Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor. Sensing and Bio-Sensing Research, 30, Article 100375. https://doi.org/10.1016/j.sbsr.2020.100375

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title = "Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor",

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.",

keywords = "implantable, microfabrication, oxygen sensor, tumour hypoxia",

author = "Marland, {Jamie R.K.} and Gray, {Mark E.} and Camelia Dunare and Blair, {Ewen O.} and Andreas Tsiamis and Paul Sullivan and Eva Gonz{\'a}lez-Fern{\'a}ndez and Greenhalgh, {Stephen N.} and Rachael Gregson and Clutton, {R. Eddie} and Parys, {Magdalena M.} and Alex Dyson and Mervyn Singer and Kunkler, {Ian H.} and Potter, {Mark A.} and Srinjoy Mitra and Terry, {Jonathan G.} and Stewart Smith and Mount, {Andrew R.} and Ian Underwood and Walton, {Anthony J.} and Argyle, {David J.} and Murray, {Alan F.}",

year = "2020",

month = dec,

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doi = "10.1016/j.sbsr.2020.100375",

language = "English",

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Marland, JRK, Gray, ME, Dunare, C, Blair, EO, Tsiamis, A, Sullivan, P, González-Fernández, E, Greenhalgh, SN, Gregson, R, Clutton, RE, Parys, MM, Dyson, A, Singer, M, Kunkler, IH, Potter, MA, Mitra, S, Terry, JG, Smith, S, Mount, AR, Underwood, I, Walton, AJ, Argyle, DJ & Murray, AF 2020, 'Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor', Sensing and Bio-Sensing Research, vol. 30, 100375. https://doi.org/10.1016/j.sbsr.2020.100375

TY - JOUR

T1 - Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor

AU - Marland, Jamie R.K.

AU - Gray, Mark E.

AU - Dunare, Camelia

AU - Blair, Ewen O.

AU - Tsiamis, Andreas

AU - Sullivan, Paul

AU - González-Fernández, Eva

AU - Greenhalgh, Stephen N.

AU - Gregson, Rachael

AU - Clutton, R. Eddie

AU - Parys, Magdalena M.

AU - Dyson, Alex

AU - Singer, Mervyn

AU - Kunkler, Ian H.

AU - Potter, Mark A.

AU - Mitra, Srinjoy

AU - Terry, Jonathan G.

AU - Smith, Stewart

AU - Mount, Andrew R.

AU - Underwood, Ian

AU - Walton, Anthony J.

AU - Argyle, David J.

AU - Murray, Alan F.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

KW - implantable

KW - microfabrication

KW - oxygen sensor

KW - tumour hypoxia

U2 - 10.1016/j.sbsr.2020.100375

DO - 10.1016/j.sbsr.2020.100375

M3 - Article

AN - SCOPUS:85090130457

VL - 30

JO - Sensing and Bio-Sensing Research

JF - Sensing and Bio-Sensing Research

M1 - 100375

ER -

Real-time measurement of tumour hypoxia using an implantable microfabricated oxygen sensor

Abstract

Keywords

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