A Layer-by-Layer Approach To Retain a Fluorescent Glucose Sensing Assay within the Cavity of a Hydrogel Membrane

Abstract

A continuous glucose monitoring device that resides fully in the subcutaneous tissue has the potential to greatly improve the management of diabetes. Toward this goal, we have developed a competitive binding glucose sensing assay based on fluorescently labeled PEGylated concanavalin-A (PEGylated-TRITC-ConA) and mannotetraose (APTS-MT). In the present work, we sought to contain this assay within the hollow central cavity of a cylindrical hydrogel membrane, permitting eventual subcutaneous implantation and optical probing through the skin. A “self-cleaning” hydrogel was utilized because of its ability to cyclically deswell/reswell in vivo, which is expected to reduce biofouling and therefore extend the sensor lifetime. Thus, we prepared a hollow, cylindrical hydrogel based on a thermoresponsive electrostatic double network design composed of N-isopropylacrylamide and 2-acrylamido-2-methylpropanesulfonic acid. Next, a layer-by-layer (LbL) coating was applied to the inner wall of the central cavity of the cylindrical membrane. It consisted of 5, 10, 15, 30, or 40 alternating bilayers of positively charged poly(diallyldimethylammonium chloride) and negatively charged poly(sodium 4-styrenesulfonate). With 30 bilayers, the leaching of the smaller-sized component of the assay (APTS-MT) from the membrane cavity was substantially reduced. Moreover, this LbL coating maintained glucose diffusion across the hydrogel membrane. In terms of sensor functionality, the assay housed in the hydrogel membrane cavity tracked changes in glucose concentration (0 to 600 mg/dL) with a mean absolute relative difference of ∼11%.

Facile Non-Enzymatic Electrochemical Sensing for Glucose Based on Cu2O–BSA Nanoparticles Modified GCE

“…Many methods have been used for glucose sensing, including electrochemical [2,3,4,5,6,7,8,9,10], chemiluminescence [11,12,13], colorimetry [2,14], Raman spectra [15,16], and fluorescence spectrometry [17,18,19,20,21]. In these methods, electrochemical glucose sensors are very important, because this method is simple and selective, along with having low detection limit, fast response time, good stability and low cost [2,3,4,5,6,7,8,9,10].…”

A Glucose Biosensor Based on Phosphorescence Lifetime Sensing and a Thermoresponsive Membrane

“…[10,11] Specifically, detection of a subcutaneous optical glucose sensor could be accomplished via an LED and photodiode pair on a smartwatch. Optical glucose sensors based on fluorescence intensity measurements have been widely studied, such as with Förster resonance energy transfer (FRET) assays, [20,21] or phenylboronic acid assays. [22,23] However, the fluorescence intensity values, and thus apparent glucose levels, may be significantly affected by factors influencing the fluorophores, the excitation efficiency, or measured light intensity.…”

Comb Architecture to Control the Selective Diffusivity of a Double Network Hydrogel

“…48,49 Indeed, this selective diffusion behavior was confirmed for DN-25%. 42 Herein, a comb architecture was used to precisely control and reduce the mesh size of this thermoresponsive, electrostatic DN hydrogel (Scheme 1). The mobility of combs, characterized by grafts tethered to backbones, has been leveraged to create polymer electrolytes and antifouling coatings.…”