Functional Layer-By-Layer Design of Xerogel-Based First-Generation Amperometric Glucose Biosensors

Abstract

Xerogel-based first-generation amperometric glucose biosensors, constructed through specific layer-by-layer assembly of films featuring glucose oxidase doped xerogel, a diffusion-limiting xerogel layer, and capped with both electropolymerized polyphenol and blended polyurethane semipermeable membranes, are presented. The specific combination of xerogels formed from specific silane precursors, including propyl-trimethoxysilane, isobutyl-trimethoxysilane, octyl-trimethoxysilane, and hydroxymethyl-triethoxysilane, exhibit impressive dynamic and linear ranges of detection (e.g., ≥24-28 mM glucose) and low response times, as well as significant discrimination against common interferent species such as acetaminophen, ascorbic acid, sodium nitrite, oxalic acid, and uric acid as determined by selectivity coefficients. Additionally, systematic electrochemical and contact angle studies of different xerogel silane precursors, varying in structure, chain length, and/or functional group, reveal that sensor performance is more dependent on the tunable porosity/permeability of the layered interfaces rather than the hydrophobic character or functional groups within the films. While the sensing performance largely exceeds that of existing electrochemical glucose sensing schemes in the literature, the presented layered approach establishes the specific functionality of each layer working in concert with each other and suggests that the strategy may be readily adaptable to other clinically relevant targets and is amenable to miniaturization for eventual in situ or in vivo sensing.

Layer-by-layer design and optimization of xerogel-based amperometric first generation biosensors for uric acid

“…Xerogel layering and construction of the biosensing components was performed with an adaptation to prior procedures [5]. Typically, the process, performed inside a humidity-controlled chamber (Cole-Parmer, 50% RH), involved separate mixtures of 4 mg of UOx in 75 μL of UP water and 25 μL of silane in 100 μL of tetrahydrofuran (THF) being agitated (Vortex) for 10 min.…”

“…The sol-gels were aged at 50% RH for 48 h to form xerogels. Note: The environment during aging is of crucial importance, since sensor performance has been shown to vary drastically depending on time and RH [5,35]. SEM and electrochemical characterization of the xerogel layers has been either previously presented [5,35] or is included in Supplementary material herein.…”

“…Note: The environment during aging is of crucial importance, since sensor performance has been shown to vary drastically depending on time and RH [5,35]. SEM and electrochemical characterization of the xerogel layers has been either previously presented [5,35] or is included in Supplementary material herein. Additionally, prior work in the lab evaluated the porosity and surface area of drop-cast xerogel films, including films from silane precursors used in this report, using electrochemistry, spectroscopy, and contact angle goniometry [5].…”

“…Over the past two decades, many of these reports have focused specifically on the development of glucose biosensing schemes where a number of excellent reviews are available [1][2][3][4]. The large amount of research activity focused on glucose biosensor development can be attributed to the increasing need for improved diabetes management as well as the idea that glucose represents a well-understood, relatively inexpensive model system for fundamental studies [5]. Within the biosensor research, however, it is relatively rare that the strategies, materials, and constructs shown to be effective for glucose biosensing prove robust and versatile enough to be readily adapted to a dramatically different target molecule.…”

Electrochemical Biosensor Based on Bienzyme and Carbon Nanotubes Incorporated into an Os‐complex Thin Film for Continuous Glucose Detection in Human Saliva

“…Os-complex as the electrons mediator is immobilized by covalent linking for avoiding the leakage [32]. The semipermeable membrane of polyphenol is used for rejection of potential interferences and protection of the biosensor surface [33]. The biosensor shows good characterization by extremely low-potential detection and the exclusion of electroactive constituents of whole saliva and provides noninvasive, highly reproducible, and continuous salivary glucose monitoring for personal and point-ofcare use.…”