Electrochemical glucose biosensors - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 57

Since Clark and Lyons fi rst proposed the initial concept of glucose enzyme elec-
trodes in 1962 [3] we have witnessed tremendous activity towards the development of
reliable devices for diabetes control. A variety of approaches have been explored in the
operation of glucose enzyme electrodes. In addition to diabetes control, such devices
offer great promise for other important applications, ranging from food analysis to
bioprocess monitoring. The great importance of glucose has generated an enormous
number of publications, the fl ow of which shows no sign of diminishing. Yet, despite
impressive advances in glucose biosensors, there are still many challenges related to
the achievement of clinically accurate tight glycemic monitoring.
The goal of this chapter is to examine the history and current status of electrochem-
ical glucose biosensors, and discuss their principles of operation along with future
challenges.

3.2 FORTY YEARS OF PROGRESS

The history of glucose enzyme electrodes starts with the fi rst device developed in 1962
by Clark and Lyons from the Children Hospital in Cincinnati [3]. Their fi rst device
relied on a thin layer of GOx entrapped over an oxygen electrode (via a semipermeable
dialysis membrane), and monitoring the oxygen consumed by the enzyme-catalyzed
reaction:

Gox
⎯→

Glucose Oxygen ⎯⎯⎯ Gluconic acid Hydrogen peroxide (1)

Clark's original patent [4] covers the use of one or more enzymes for converting
electroinactive substrates to electroactive products. The effect of interferences was cor-
rected by using two electrodes (one covered with GOx) and measuring the differential
current. Clark's technology was subsequently transferred to Yellow Spring Instrument
Company, which launched in 1975 the fi rst dedicated glucose analyzer (the Model 23
YSI analyzer) for the direct measurement of glucose in 25 L samples of whole blood.

Updike and Hicks [5] developed further this principle by using two oxygen working
electrodes (one covered with the enzyme) and measuring the differential current for
correcting the oxygen background variation in samples. In 1973, Guilbault and Lubrano
[6] described an enzyme electrode for the determination of blood glucose based on
amperometric (anodic) monitoring of the liberated hydrogen peroxide:

µ

2H 2e H 2 O 2 → O 2 (2)

Good accuracy and precision were obtained in connection to 100 L blood samples. A

wide range of amperometric enzyme electrodes, differing in the electrode design or mate-
rial, membrane composition, or immobilization approach have since been described.
During the 1980s biosensors became a “hot” topic, refl ecting the growing emphasis
on biotechnology. Considerable efforts during this decade focused on the development
of mediator-based “second-generation” glucose biosensors [7, 8], the introduction of
commercial strips for self-monitoring of blood glucose [9, 10], and the use of modifi ed
electrodes for enhancing the sensor performance [11]. In the 1990s we witnessed intense

µ