Biosensors for antimicrobial optimisation
File(s)
Author(s)
McLeod, James
Type
Thesis
Abstract
1.3 million people a year die from antimicrobial resistant (AMR) infections, and without
improved stewardship of antimicrobials to reduce further development of AMR, the number
of deaths from AMR infections is likely to rise to 10 million deaths a year by 2050. One
contributing factor to the development of AMR is suboptimal dosing of antimicrobials.
Therapeutic drug monitoring offers a potential route to optimising dosing, however current
techniques generally rely on mass spectrometry which is prohibitively expensive and time
consuming to implement widely and is often unavailable in low resource settings.
Therapeutic drug monitoring is therefore rarely used for antimicrobials. Biosensors offer a
solution to this problem, providing inexpensive fast methods for monitoring antimicrobial
concentrations for optimisation of antimicrobial dosing. This thesis discusses three
biosensor technologies. Firstly, developing a point of care disposable electrochemical
biosensor for the detection of Cefiderocol and then expanding this technology into a
continuous microneedle sensor. Secondly developing a detailed model of enzymatic
biosensor and applying it to assessing the viability of beta lactamase sensors for monitoring
beta lactams. Lastly, producing a new method for the chronoamperometric interrogation of
aptamer sensors, with the aim of removing the need for individual calibration of aptamer
sensors.
improved stewardship of antimicrobials to reduce further development of AMR, the number
of deaths from AMR infections is likely to rise to 10 million deaths a year by 2050. One
contributing factor to the development of AMR is suboptimal dosing of antimicrobials.
Therapeutic drug monitoring offers a potential route to optimising dosing, however current
techniques generally rely on mass spectrometry which is prohibitively expensive and time
consuming to implement widely and is often unavailable in low resource settings.
Therapeutic drug monitoring is therefore rarely used for antimicrobials. Biosensors offer a
solution to this problem, providing inexpensive fast methods for monitoring antimicrobial
concentrations for optimisation of antimicrobial dosing. This thesis discusses three
biosensor technologies. Firstly, developing a point of care disposable electrochemical
biosensor for the detection of Cefiderocol and then expanding this technology into a
continuous microneedle sensor. Secondly developing a detailed model of enzymatic
biosensor and applying it to assessing the viability of beta lactamase sensors for monitoring
beta lactams. Lastly, producing a new method for the chronoamperometric interrogation of
aptamer sensors, with the aim of removing the need for individual calibration of aptamer
sensors.
Version
Open Access
Date Issued
2024-03
Date Awarded
2024-07
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Holmes, Alison
O'Hare, Danny
Sponsor
Medical Research Council (Great Britain)
Japan. Shionogi & Company, Limited
Publisher Department
Department of Infectious Disease
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)