Abstract
Electrochemical sensing plays a vital role in the ever-evolving diagnostics landscape. At a basiclevel, electrochemical sensors rely upon interaction of an electrode with an analyte to create an
electrochemical signal. Electrochemical sensors are at the forefront of point-of-care sensing
due to low cost, accuracy, practicality and efficiency considerations. The field of
electrochemical diagnostics originated with the development of amperometric glucose sensing,
which revolutionised diabetes management by replacing colorimetric urine testing with an
accurate point – of – need blood test. Continuous electrochemical glucose sensors are now in
the process of completely replacing blood glucose test strips, but the impact of this technology
upon diabetes healthcare was profound. The next generation of glucose sensors will begin to
phase out enzymatic recognition elements as the move towards implantable or wearable smart
technology is realised.
Chemo-sensing relies upon the interaction of a chemical receptor with the target analyte. A
multitude of chemo-sensors have been reported employing different functional groups as the
basis for interaction between receptor and analyte, including boronic acids. Boronic acids are
a versatile receptor capable of reversibly binding with nucleophilic species to form covalent
ester complexes. These receptors are attractive due to the reversibility of the interaction, which
makes sensors reusable (advantageous for continuous type sensing) and the range of other
chemical groups that can be incorporated into boronic acid receptor designs to affect key
properties. Boronic acids have been exploited for glucose sensing, with which they form 5 –
membered covalent ring complexes. Most reported glucose sensors based on boronic acids rely
upon fluorescence transduction. A key aim of this thesis is to demonstrate how boronic acids
can be the lynchpin for novel electrochemical sensors for glucose.
In this thesis, the key objectives in sensor design are to i) develop proof - of - principle
electrochemical chemo-sensors for glucose or other biologically relevant analytes based on
boronic acids, ii) show how graphene foam electrodes can host new electrochemical sensor
designs, iii) develop accurate chemo-sensing methods in ‘realistic’ media such as serum. Other
objectives included developing an understanding of the graphene foam electrode provided by
Integrated Graphene in terms of surface morphology, deposition pattern for the boronic acid
and elucidating characteristic properties of the electrode including conductivity and
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electrochemical surface area. Optimisation of boronic acid design to enhance i) selectivity and
ii) sensing at physiological pH was also considered desirable for practical sensor development.
To realise this, several challenges had to be overcome. Initially, a sensor concept employing a
pyrene – derivatised boronic acid attached to graphene foam was conceived. A redox indicator
species was introduced to allow electrochemical ‘visualisation’ of the boronic acid. Indirect
glucose detection was enabled through shifting of voltammetric peak magnitude due to glucose
binding to the boronic acid. This was termed the ‘polymer indicator displacement assay’. The
sensor was shown to function in serum, but accuracy was limited and improved sensor design
was necessary to enable accurate serum testing.
Next, the polymer indicator displacement assay is applied to lactic acid sensing, with new
amperometric and, importantly, impedimetric assays developed. The challenge for this sensor
design is improving the dynamic pH range for detection, which currently at pH < 6 means
sensing at physiological pH remains unfulfilled. This sensor was shown to selectively recruit
lactic acid against a range of interferants in serum/buffer/sweat solutions, although the low
limit of detection (~ 7 mM) means this method requires optimisation.
Finally, a quantum capacitive methodology with no redox element enabled sensitive lactic acid
detection through a novel mechanism. The finding that charged receptors can boost capacitance
may impact not just the field of electrochemical sensing but also energy storage (capacitors).
The capacitance change was exploited in this instance for electrochemical lactic acid sensing
via impedance spectroscopy. Low limits of detection (< 2mM) are achieved for lactic acid.
Throughout the studies presented in this thesis, efforts are made to characterise in detail the
electrochemical sensor components including the graphene foam electrode, boronic acid
receptor and redox polymer using a range of techniques (electron microscopy, XPS, NMR,
Raman and more) to optimise and fundamentally understand the sensor.
Overall, this thesis presents the conception of novel electrochemical sensing methods and
subsequent application to the detection of biologically – relevant analytes. New proof-of-
concept sensors are developed using electrochemistry and applied to complex analytical
solutions to realise new routes to sense biological targets.
| Date of Award | 13 Nov 2024 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Tony James (Supervisor), Steven Bull (Supervisor) & Frank Marken (Supervisor) |