Page 117 - Glucose Monitoring Devices

118 CHAPTER 6 CGM sensor technology

chemical attack from cellular-generated reactive oxygen species (ROS); additional
chronic effects include collagen encapsulation of the sensor that reduces access to
glucose from the surrounding tissue and results in an increase in lag time between
blood and sensor glucose responses [47,67,69]. Common strategies to reduce these
effects include a selection of sensor materials that induce a minimal FBR, the addi-
tion of coatings that reduce protein absorption or elicit a favorable (healing) tissue
response, and minimizing the size of the sensor. Nonetheless, the FBR is typically
the predominant factor that limits the in vivo lifetime of implanted CGMs.
To reduce the chronic foreign body response and enable sensor longevity extend-
ing beyond a few weeks, several different medicinal agents have been incorporated
into CGM sensors. The Senseonics implantable sensor contains a silicone polymer
that releases micrograms of dexamethasone per day. The dexamethasone reduces
inflammation in the local tissue surrounding the sensor thus reducing the generation
of reactive oxygen species (ROS) that can oxidize the glucose-binding polymer.
Similarly, Biorasis has shown that dexamethasone release from an erodible (i.e., dis-
solving) coating on their fully implantable CGM sensor reduces local inflammation
over several months of implant time [25]. Vascular endothelial growth factor
(VEGF) has been used to increase the density of blood vessels (and thus increase
access to glucose) around an implantation site [38]. Klueh and coworkers demon-
strate that VEGF enhances glucose sensor performance via increased vascularization
while also having an antiinflammatory effect [23]. Nitric oxide has also been used to
improve the tissue interface around an implanted glucose sensor. Nitric oxide serves
as an inhibitor of bacterial cell proliferation and biofilm formation and prevents
platelet activation and adhesion, infection, and subsequent thrombosis [6]. Nitric-
oxide-releasing polymers developed by Mark Schoenfisch of the University of North
Carolina at Chapel Hill have been demonstrated to enhance the performance of
implanted glucose sensors [29] and that technology is in use by Clinical Sensors,
Inc. (Research Triangle Park, NC).

Noninvasive technologies
Noninvasive (i.e., without implantation of a device or a chemical) CGMs are being
developed using devices that clip onto the ear, that shine light through the skin, and
that measure glucose sensing “smart” tattoos, and with glucose sensing contact
lenses.
The ability of infrared light to penetrate the skin allows for the noninvasive mea-
surement of glucose via Ramen spectroscopy [42]. One such CGM was developed
by C8 Medisensors (San Jose, CA). A sensor worn on the skin shined near infrared
light (NIR) light through the skin and measured the glucose Ramen signal that was
reflected to the sensor. The sensor received CE mark approval but manufacturing and
user to user variability reportedly prevented commercialization [34].
Dyes that change color or fluorescence intensity with changes in glucose concen-
tration can be tattooed onto the skin and glucose measured using an optical measure-
ment device applied over the tattoo [32]. Researchers at Harvard University and MIT