Determination of Glucose Levels Using a Functionalized Hydrogel−Optical Fiber Biosensor: Toward Continuous Monitoring of Blood Glucose in Vivo

Abstract

Glucose-selective optical sensors were fabricated by incorporating 3-phenylboronic acid and a tertiary amine, dimethylaminopropylacrylamide, into a hydrogel matrix. Determination of glucose in solution is based on the glucose-induced contraction of the hydrogel. The gel was fabricated on the end of an optical fiber, and the optical length was measured by an interferometric technique. Previously it was found the gel could be tuned for enhanced glucose sensitivity and selectivity by varying the 3-phenylboronic acid/tertiary amine ratio. The properties of the responsive hydrogel as a glucose sensor were determined in more detail with respect to swelling kinetics and equilibrium swelling degree. Temperature effects, size variation, molecular interference, and reversibility were addressed. Results showed there was a good degree of reversibility, both for equilibrium swelling and swelling kinetics. Fabricated hydrogel sensors with slight differences in size yielded an overlapping relative response indicating an excellent degree of sensor reproducibility. The sensor proved to be temperature-dependent; by increasing the temperature from 25 to 37 degrees C, the swelling was about 4-fold more rapid, and a concomitant decrease in equilibrium swelling was seen. Identified interference from other analytes with determination of glucose was used a basis for selecting ethylenediaminetetraacetic acid (EDTA) as an anticoagulant for in vitro determination of glucose concentration in blood plasma. Glucose measurements performed in blood plasma were promising, showing that the sensor is capable of measuring physiological glucose levels in blood with a minimal effect from interfering molecules. The obtained results indicate that the developed sensor is a candidate for continuous monitoring of glucose in blood.

High resolution interferometry as a tool for characterization of swelling of weakly charged hydrogels subjected to amphiphile and cyclodextrin exposure

“…Additionally, kinetics constants of 100 seconds and larger for swelling of phenylboronic acid incorporated hydrogels associated with changes in glucose have been reported [3]. These data indicated that the swelling kinetics associated with changes in ionic strength reflected the limit due to the diffusion of the network chains, while the others were limited by the rate of interactions among the involved species.…”

“…The three solutions were mixed together yielding 10 wt% of AAM, 0.22, 0.44 and 0.88 mol% AMPSA relative to AAM, 3, 6 or 12 mol% Bis relative to AAM, and 0.15 mol% of initiator relative to AAM in the pregel solutions. Aliquots of the pre-gel solutions were deposited on the tip of the functionalized fiber and polymerized as described [1][2][3][4]45].…”

“…It has already proved its potential in sensing such analytes as glucose [2,3] and oligonucleotides [4][5][6]. Herein we present the technique as a useful tool for label-free monitoring of swelling phenomena occurring in various hydrogelamphiphile and hydrogel-amphiphile-macrocycle cases.…”

A viscosity-dependent affinity sensor for continuous monitoring of glucose in biological fluids

“…For these reasons, investigation on affinity binding sensors has been undertaken using various technologies, such as fluorescence (Ballerstadt et al, 2004(Ballerstadt et al, , 2006(Ballerstadt et al, , 2007Ballerstadt and Schultz, 2000) or viscosity-based (Beyer et al, 2001;Diem et al, 2004;Huang et al, 2009;Kuenzi et al, 2011;Zhao et al, 2007) principle. Recently, hydrogel-based sensors have emerged as promising tools for affinity sensing (Tierney et al, 2009a(Tierney et al, , 2009b. However, the development of biosensors for medical and biological applications that allows for long-term reversibility and stability remains a challenge.…”

MULTI-ANALYTE DETECTION FOR BIOLOGICAL FLUIDS - Towards Continous Monitoring of Glucose, Ionized Calcium and pH using a Viscometric Affinity Biosensor

“…For these reasons, intensive investigations on affinity binding sensors have been carried out using different technics such as fluorescence (Ballerstadt, 2004) or viscosity measurements . Recently, hydrogelbased sensors have emerged as promising materials 295 for affinity sensing (Tierney, 2009). Despite many efforts towards the development of continuous biosensors for medical and biological applications, long term reversibility and stability remains a challenge.…”