Page 113 - Glucose Monitoring Devices

114 CHAPTER 6 CGM sensor technology

mediator) at the working electrode is measured, rather than the current generated by
oxidation of hydrogen peroxide. Such CGM transduction systems are called as
“wired enzymes.”
The longevity of GOx-based CGM sensors may be limited by the in vivo stability
of the enzyme. Loss of enzyme activity over time has been attributed to the presence
of low molecular weight materials or build-up of hydrogen peroxide concentrations
in the fluid surrounding the implanted sensor [51]. Incorporation of stabilizing addi-
tives into the sensor formulation is the most common means of increasing enzyme
in vivo life, although molecular engineering of glucose oxidase to improve its stabil-
ity has also been reported [51]. As all of the commercial GOx-based CGMs are
based on needles that protrude through the skin during their usage lifetime, it is
also possible that the irritation created by the movement of the needle with and
prevention of wound closure does not allow for resolution of tissue inflammation
that creates the enzyme inactivating species. In fact, an enzymatic and fully implant-
able CGM sensor under development by Glysens, Inc. (San Diego, CA) has been
reported to function for up to 180 days in a human clinical trial, suggesting full
implantation may be important to longevity [27].
Performance limitations frequently associated with enzymatic, electrochemical-
based glucose sensors include sensitivity to fouling of the electrode surface by bio-
molecules (e.g., proteins, cells) over time resulting in loss of functionality, transient
loss of glucose sensitivity upon physical compression at the sensor implant site
(which typically occurs during sleeping), and chemical interferences from
commonly used electroactive compounds such as ascorbic acid (vitamin C) and
acetaminophen [65].

Nonenzymatic, optical-based sensors
Various CGM sensor technologies that do not require enzymes for glucose recogni-
tion or that use optical rather than electrochemical means of detection are reported in
the literature [66,67]. However, the CGM system from Senseonics is the only such
system commercially available in the United States and in Europe. Glucose concen-
tration is measured by means of fluorescence from an abiotic (i.e., nonenzyme
based), glucose-binding polymer that coats the surface of a sensor that is fully
implanted into the dermal subcutaneous tissue (Fig. 6.3). Intensity of light emitted
by the polymer changes in response to the glucose concentration in the ISF that sur-
rounds the sensor. Fluorescence is measured by an optical system contained within
the implanted sensor comprises a light-emitting diode, which serves as the excitation
source for the fluorescent polymer, and spectrally filtered photodiodes that measure
the glucose-dependent fluorescence intensity. As the sensor is fully implanted, it
contains an internal antenna that wirelessly receives power from and communicates
with an externally worn transmitter.
Glucose reversibly binds to the indicator boronic acid groups (which act as
glucose receptors) in an equilibrium-binding reaction as shown in Fig. 6.3 [45].