Biomedical Engineering Reference
In-Depth Information
sensing system. We have successfully developed components that can detect
biologically relevant levels of glucose with the required sensitivity and selectivity
in a physiologically relevant matrix solution. The materials are physically and
chemically stable in aqueous media at physiological pH. Scalability is also an
advantage of these reagents in that they are reproducible on a large scale with the
capability to meet commercial demand.
The novel approach to glucose sensor design devised by our group involves
two main components: a synthetically optimized boronic acid terminated dendrimer
scaffold and a surface immobilized monosaccharide mimic. When these components
are exposed to glucose, they competitively interact to produce a detectable and
reproducible signal that is responsive to fluctuating levels of glucose. The magnitude
of sensitivity and selectivity is tunable through the use of appropriate boronic acid
and dihydroxy (diol) analogues and the degree of sensitivity and selectivity can be
optimized based on a system specific binding affinity model and database. Reported
herein is an overview of the development of our synthetic glucose sensing system.
This description includes a discussion of our strategy, along with an overview of the
in-depth considerations we used to select system components for optimal detection
performance in a physiologically relevant environment.
3 Self-Contained and Closed-Cycle Stable Glucose
Sensing System
The design of our device is based on the creation of an integrated, self-contained
sensing system that produces an RFID readout, which provides two pieces of
information: milligrams per deciliter (mg/dL) glucose values and an indication of
whether the physiological glucose concentration is increasing or decreasing. This
combination of information can be used by the diabetic patient to determine
whether their glucose levels are currently low, safe, or high (Fig. 3 ). Demonstration
of the closed-cycle chemical sensing system required the interaction of two
components. These components are (1) the competitive agent/signaling component,
which is based on a dendrimer-boronic acid (DBA) construct (Fig. 3 ) and (2) the
glucose-competitive DBA binding environment, which consists of an immobilized
monosaccharide mimic (iDIOL, Fig. 3 ). Our unique detection approach functions
through reversible competitive binding between glucose and the iDIOL for the
DBA. The amount of DBA that is bound to the iDIOL binding environment on the
mass-sensitive transduction interface fluctuates in response to changing levels of
glucose. The change in free versus bound DBA is measured via a change in the
resonance frequency of the MEMS microcantilever. This signal transduction event
gives a measurement of glucose concentration that can be calibrated to bloodstream
glucose levels (Fig. 3 ). The function of this type of sensor relies on the relative
affinity of glucose and the iDIOL for the DBA. Consequently, optimization of the
glucose sensing system was based on our evaluation of the binding affinities of the
DBA for both glucose and the iDIOL. More broadly, our approach for constructing
and optimizing component materials was also based on an in-depth consideration of
how these materials related to the sensing system and the device as a whole.
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