A hydrogel-based glucose affinity microsensor

Abstract

We present a hydrogel-based affinity microsensor for continuous glucose measurements. The microsensor is based on microelectromechanical systems (MEMS) technology, and incorporates a synthetic hydrogel that is attached to the device surface via in situ polymerization. Glucose molecules that diffuses into and out of the device binds reversibly with boronic acid groups in the hydrogel via affinity binding, and causes changes in the dielectric properties of the hydrogel, which can be measured using a MEMS capacitive transducer to determine the glucose concentration. The use of the in situ polymerized hydrogel eliminates mechanical moving parts found in other types of affinity microsensors, as well as mechanical barriers such as semipermeable membranes that are otherwise required to hold the glucose-sensitive material. This facilitates the miniaturization and robust operation of the microsensor, and can potentially improve the tolerance of the device, when implanted subcutaneously, to biofouling. Experimental results demonstrate that in a glucose concentration range of 0–500 mg/dL and with a resolution of 0.35 mg/dL or better, the microsensor exhibits a repeatable and reversible response, and can potentially be useful for continuous glucose monitoring in diabetes care.

A dielectric affinity glucose microsensor using hydrogel-functionalized coplanar electrodes

“…These time constants are a substantial reduction from that (16 min) calculated for our previously reported device (Shang et al 2016) and are comparable to those (0.65–1.30 min) estimated for the commercially available electrochemical continuous glucose sensors (Keenan et al 2009). To understand the physical significance of these time constants, we consider the transport of glucose molecules to the sensor surface.…”

“…Affinity glucose sensors based on microelectromechanical systems (MEMS) technology are promising in achieving miniaturized subcutaneous implantable CGM devices. MEMS has been applied to affinity glucose sensors using proteins (Kuenzi et al 2010), synthetic polymers (Li et al 2008), and hydrogel receptors (Shibata et al 2010; Shang et al 2016; Lei et al 2006; Guenther et al 2014), based on measurements of glucose-induced changes in physical properties of the sensing material such as the fluorescence intensity (Shibata et al 2010), viscosity (Zhao et al 2007), or volume (Lei et al 2006; Guenther et al 2014). Unfortunately, these methods are not well suited to implanted operation due to issues such as requirements of optical access or mechanical moving parts.…”

“…In contrast, dielectric affinity sensors that detect changes in the glucose-dependent permittivity of the sensing material can alleviate these limitations and are hence highly attractive. Our group previously reported our preliminary work exploring hydrogel-based affinity glucose sensors (Shang et al 2016). That work demonstrated the potential of hydrogels for affinity glucose sensing, but was limited by a very slow time response (~16 min) due to the use of a thick hydrogel layer (~250 μm), which required long diffusion times between the sensor surface and surroundings.…”

“…Key to the rapid responsiveness and robust construction of the device is the adoption of a substantially thinner hydrogel (~10 μm), achieved by the innovative use of in situ gelation, to speed up the time response (potentially down to 1.2 s). Additionally, the device adopts a coplanar capacitive transducer, which, compared with the parallel-plate based configuration used in our preliminary work (Shang et al 2016), is considerably more robust and easier to fabricate, is amenable to in situ hydrogel preparation, and fully avails the hydrogel layer to glucose exchange. The device has been tested in phosphate-buffered saline (PBS) solution at pH 7.4 and 37 °C.…”

Control of Volume‐Responsive Properties of Hydrogels through Molybdenum Disulfide Nanosheet Incorporation

“…[17,18] Recently, low dimensional nanomaterials with a large specific surface area such as carbon nanotubes and graphene oxide have been incorporated to hydrophilic polymers such as PNIPAM, chitosan, and polyacrylic acid hydrogels to enhance the adsorption of substances and chemical storage capacity. [17,18] Recently, low dimensional nanomaterials with a large specific surface area such as carbon nanotubes and graphene oxide have been incorporated to hydrophilic polymers such as PNIPAM, chitosan, and polyacrylic acid hydrogels to enhance the adsorption of substances and chemical storage capacity.…”