Page 419 - Handbook of Biomechatronics

414 Graham Brooker

antibodies, nucleic acids, microorganisms, and lectins. There are five major
transducer classes including electrochemical, optical, thermometric, piezo-
electric, and magnetic, with most of the current glucose biosensors of the
electrochemical type because of their good sensitivity, reproducibility,
and easy maintenance (Yoo and Lee, 2010).
Electrochemical sensors can use current, voltage, or conductivity to
measure concentration, with devices that measure current generated when
electrons are exchanged between the biological system and the electrode
being the most common for glucose monitoring. Transducers used for glu-
cose measurements are based on interactions with one of three enzymes:
hexokinase, GOx, or glucose-1-dehydrogenase (GDH), with GOx being
the most common as it has a reasonably high affinity for glucose and can
withstand more extreme conditions than the other transducer types. The
process starts with the immobilized GOx catalyzing the oxidation of β-D-
glucose by molecular oxygen to produce gluconic acid and H 2 O 2 . The
H 2 O 2 is in turn oxidized at a catalytic, platinum anode where electron flow
(current) is proportional to the number of glucose molecules present in the
blood sample (Yoo and Lee, 2010).
The basic principles for this technology were introduced in 1956 by
Leland Clark Jr. in a paper on the oxygen (later Clarke) electrode. In
1962, he and Ann Lyons from the Cincinnati Children’s Hospital developed
the first glucose enzyme electrode. This glucose biosensor consisted of an
oxygen electrode, an inner oxygen semipermeable membrane, a thin layer
of GOx, and an outer dialysis membrane. Enzymes were immobilized on an
electrochemical detector to form an enzyme electrode. A decrease in the
measured oxygen concentration was proportional to the glucose concentra-
tion. This process was greatly simplified by Updike and Hicks who bound
the GOx in a polyacrylamide gel on an oxygen electrode and showed for the
first time that it was possible to measure the glucose concentration of bio-
logical fluids (Updike and Hicks, 1967).
This technology was first used commercially in 1975 in the Model 23A
YSI analyzer developed by the Yellow Springs Instrument Company. It
measured current flow in a platinum electrode. The 1980s saw significant
efforts to reduce interference by other reactive molecules including uric
and ascorbic acid as well as certain drugs. A further problem was the limited
solubility of oxygen in biological fluids that resulted in fluctuations in the
oxygen tension, known as the “oxygen deficit” (Yoo and Lee, 2010).
Mediator-based glucose biosensors overcame the oxygen deficit problem
and allowed for the introduction of commercial screen-printed strips in the