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Modelling microelectrode biosensors : free-flow calibration can substantially underestimate tissue concentrations
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Newton, Adam J. H., Wall, Mark J. and Richardson, Magnus J. E. (2017) Modelling microelectrode biosensors : free-flow calibration can substantially underestimate tissue concentrations. Journal of Neurophysiology, 117 (3). pp. 937-949. doi:10.1152/jn.00788.2016 ISSN 0022-3077.
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Official URL: http://dx.doi.org/10.1152/jn.00788.2016
Abstract
Microelectrode amperometric biosensors are widely used to measure concentrations of analytes in solution and tissue including acetylcholine, adenosine, glucose and glutamate. A great deal of experimental and modelling effort has been directed at quantifying the response of the biosensors themselves; however, the influence that the macroscopic tissue environment has on biosensor response has not been subjected to the same level of scrutiny. Here we identify an important issue in the way microelectrode biosensors are calibrated that is likely to have led to underestimations of analyte tissue concentrations. Concentration in tissue is typically determined by comparing the biosensor signal to that measured in free-flow calibration conditions. In a free-flow environment the concentration of the analyte at the outer surface of the biosensor can be considered constant. However, in tissue the analyte reaches the biosensor surface by diffusion through the extracellular space. Because the enzymes in the biosensor break down the analyte, a density gradient is set up resulting in a significantly lower concentration of analyte near the biosensor surface. This effect is compounded by the diminished volume fraction (porosity) and reduction in the diffusion coefficient due to obstructions (tortuosity) in tissue. We demonstrate this effect through modelling and experimentally verify our predictions in diffusive environments.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QP Physiology R Medicine > R Medicine (General) |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Physics | ||||||||
Library of Congress Subject Headings (LCSH): | Biosensors -- Mathematical models, Acetylcholine, Adenosine, Glucose, Glutamic acid | ||||||||
Journal or Publication Title: | Journal of Neurophysiology | ||||||||
Publisher: | American Physiological Society | ||||||||
ISSN: | 0022-3077 | ||||||||
Official Date: | 1 March 2017 | ||||||||
Dates: |
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Volume: | 117 | ||||||||
Number: | 3 | ||||||||
Page Range: | pp. 937-949 | ||||||||
DOI: | 10.1152/jn.00788.2016 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 2 March 2017 | ||||||||
Date of first compliant Open Access: | 2 March 2017 | ||||||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) | ||||||||
Grant number: | BB/J0153691/1 |
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