Page 115 - Glucose Monitoring Devices

116 CHAPTER 6 CGM sensor technology

Transduction technologies in development
Transduction technologies and CGM systems under development have been exten-
sively reviewed elsewhere [46,52,66,67,68]. This section highlights some of the
technologies that have progressed from academic to corporate development
programs.
The third generation of glucose oxidase-based CGM sensors is being developed
by DirectSens GmbH (Klosterneuburg, Austria), in which a genetically modified
enzyme is covalently and electrochemically linked directly to the working electrode,
thus eliminating the need for oxygen or redox-active mediators [7].
A glucose oxidase, electrochemical CGM sensor that is designed to be fully
implanted into subcutaneous tissue is under development by researchers at the Uni-
versity of Connecticut in collaboration with Biorais, Inc. (Storrs, CT, USA) [53]. In
contrast to the current, commercial CGM sensors that use an electrochemical
glucose oxidase sensor that protrudes through the skin during use, the Biorais sensor
is fully implanted into the subcutaneous tissue and wirelessly sends data and power
through the skin via light. The sensor incudes a drug-eluting coating to suppress the
foreign body response and thereby enable long (at least 3 months) implant life.
A fully implantable sensor that uses a combination of two immobilized enzymes,
glucose oxidase, and catalase, immobilized in contact with an electrochemical
oxygen sensor, is under development by Glysens, Inc (San Diego, CA) using tech-
nology developed by David Gough of the University of California, San Diego [54].
The combination of enzymes catalyzes the reaction:
Glucose þ ½O 2 ¼ gluconic acid
The sensor measures glucose based on differential electrochemical oxygen
detection. Oxygen remaining (i.e., not consumed by the enzymatic process) is
measured by one enzyme-coated oxygen sensor and compared to a similar oxygen
sensor that does not contain enzymes; the differential signal is used to determine
glucose concentration. The sensor is designed to allow for a sufficient supply of ox-
ygen to the enzyme region to avoid a stoichiometric oxygen deficit and to account
for variations in oxygen concentration and local perfusion [54]. Another potential
advantage of the dual enzyme configuration is that the immobilized catalase may
prolong the in vivo lifetime of the glucose oxidase by preventing build of up of
hydrogen peroxide, a potential source of enzyme inactivation and tissue inflamma-
tion [55]. This also allows for use of an excess of glucose oxidase to extend sensor
life, as the overproduction of hydrogen peroxide is minimized by the catalase.
Several groups have applied enzymatic, electrochemical sensor technology onto
microneedle-array sensors that are designed to penetrate and reside in the skin layers
(dermis or epidermis) rather than in the subcutaneous tissue [56]. Two different
approaches to microneedle sensor designs have been reported. In one approach,
under development by Cass and coworkers (Imperial College of London, UK) and
independently under development by Sano Intelligence (San Francisco, CA), the
microneedles are designed to function as electrodes that measure current from the