Electrochemical glucose biosensors - Electrochemical Sensors, Biosensors and Their Biomedical Applications - page 61

Gluconic acid Go x (OX) Mediator (OX)

Glucose Go x (Red) Mediator (Red)

FIGURE 3.2 Sequence of events that occur in “second-generation” (mediator-based) glucose biosensor
mediated systems.

3.4.2 Use of artifi cial mediators
Particularly useful have been the artifi cial mediators that shuttle electrons between the
FAD center and the surface by the following scheme:

Glucose GOx (ox) → Gluconic acid GOx (red) (4)

2H GOx (red) 2 M (ox) → GOx (ox) 2 M (red) (5)

2e

2 M (red) → 2 M (ox) (6)

where M (ox) and M (red) are the oxidized and reduced forms of the mediator. Such a
mediation cycle produces a current dependent on the glucose concentration (Fig. 3.2).
Diffusional electron mediators, such as ferrocene derivatives, ferricyanide, conducting
organic salts (particularly tetrathiafulvalene-tetracyanoquinodimethane, TTF-TCNQ),
phenothiazine and phenoxazine compounds, or quinone compounds have thus been
widely used to electrically contact GOx [7, 8]. As a result of using these electron-
carrying mediators, measurements become largely independent of oxygen partial
pressure and can be carried out at lower potentials that do not provoke interfering reac-
tions from coexisting electroactive species [Eq. (6)]. In order to function effectively,
the mediator should react rapidly with the reduced enzyme (to minimize competition
with oxygen), possess good electrochemical properties (such as a low redox poten-
tial), have low solubility in aqueous medium, and must be non-toxic and chemically
stable (in both reduced and oxidized forms). Commercial blood glucose self-testing
meters, described in the following section, commonly rely on the use of ferricyanide or
ferrocene mediators. Most in-vivo devices, however, are mediatorless due to potential
leaching and toxicity of the mediator.

3.4.3 Attachment of electron-transfer relays
Heller's group [12] developed an elegant non-diffusional route for establishing a com-
munication link between GOx and electrodes based on “wiring” the enzyme to the
surface with a long fl exible poly-pyridine polymer having a dense array of osmium-
complex electron relays (Fig. 3.3). The resulting three-dimensional redox-polymer/
enzyme networks offer high current outputs and stabilize the mediator to electrode
surfaces.