Selective holographic detection of glucose using tertiary amines.

Introducing tertiary amine monomers into holographic sensors containing phenylboronic acids gives greatly improved selectivity for glucose.

Initial clinical testing of a holographic non-invasive contact lens glucose sensor.

INTRODUCTION: The purpose of the present study was to determine the effectiveness of a new holographic contact lens glucose sensor for the non-invasive monitoring of blood glucose. METHODS: One fasting normal subject was given an oral challenge consisting of 44 g of glucose. The contact lens hologram signal and fingerstick blood glucose were measured over a 26- min period. RESULTS: The contact lens hologram signal appeared to track blood glucose well. The contact lens was comfortable and well tolerated. CONCLUSION: The holographic contact lens glucose sensor shows promise as a non-invasive home glucose monitor.

Crosslinking of phenylboronic acid receptors as a means of glucose selective holographic detection.

A holographic sensor for the detection of glucose has been developed that is based on a hydrogel film containing phenylboronic acid receptors. Changes to the replay wavelength of the hologram were used to characterise the swelling and de-swelling behaviour of the hydrogel matrix upon receptor-ligand binding. The effect of introducing a fixed positive charge into the polymer matrix by modification of the hydrogel with a quaternary amine group (3-acrylamidopropyl)trimethylammonium chloride (ATMA), was investigated for a range of sugars and the alpha-hydroxy acid, lactate, at physiological pH. The quaternary amine-modified hydrogel matrix was found to contract in the presence of glucose, whereas, it was minimally responsive to other saccharides. The selectivity of the sensor for glucose compared to lactate was also significantly improved compared to the unmodified film. A crosslinking mechanism is proposed to explain the enhanced selectivity to glucose.

Holographic glucose sensors.

A novel holographic sensor system capable of detecting dynamic changes in glucose concentration has been developed. The hologram is recorded within a bio-compatible hydrogel matrix containing phenylboronic acid derivatives. On binding glucose, the colour of the hologram red-shifts to longer wavelengths as the hydrogel expands and this colour change is used to quantify glucose concentration. However, phenylboronic acids are non-selective and bind a wide variety of cis-diols. In blood, glucose is the only sugar found free at high concentration, whilst other sugars are typically found as part of glycoproteins and macromolecular structures. Although glycoproteins have been shown to have no effect on the sensor, phenylboronic acids can bind lactate much more readily than glucose. We have designed two polymer hydrogel systems to increase the selectivity of the sensor for glucose over lactate. The first involved the use of high concentrations of 3-acrylamidophenylboronic acid (3-APB) whilst the second system utilised 2-acrylamido-5-fluorophenylboronic acid (5-F-2-MAPB). Both systems displayed an increased selectivity to glucose over lactate at physiological pH and ionic strength and could be deployed as selective holographic sensors for glucose detection in physiological fluids.

Glucose-sensitive holographic sensors for monitoring bacterial growth.

A glucose sensor comprising a reflection hologram incorporated into a thin, acrylamide hydrogel film bearing the cis-diol binding ligand, 3-acrylamidophenylboronic acid (3-APB), is described. The diffraction wavelength (color) of the hologram changes as the polymer swells upon binding cis-diols. The effect of various concentrations of glucose, a variety of mono- and disaccharides, and the alpha-hydroxy acid, lactate, on the holographic response was investigated. The sensor displayed reversible changes in diffraction wavelength as a function of cis-diol concentration, with the sensitivity of the system being dependent on the cis-diol tested. The effect of varying 3-APB concentration in the hydrogel on the holographic response to glucose was investigated, and maximum sensitivity was observed at a functional monomer concentration of 20 mol %. The potential for using this holographic sensor to detect real-time changes in bacterial cell metabolism was demonstrated by monitoring the germination and subsequent vegetative growth of Bacillus subtilis spores.

Metabolite-sensitive holographic biosensors.

A new type of biosensor that combines the inexpensiveness and mass-produceability of reflection holograms with the selectivity and specificity of enzymes is described. pH-sensitive holographic sensors were fabricated from ionizable monomers incorporated into thin, polymeric, hydrogel films which were transformed into volume holograms using a diffusion method coupled with holographic recording, using a frequency-doubled Nd:YAG laser (532 nm). These holograms were used as transducer systems to monitor the pH changes associated with specific enzymatic reactions to construct prototype urea- and penicillin-sensitive biosensors. The diffraction wavelength (color) of the holographic biosensors was used to characterize their shrinkage and swelling behavior as a function of analyte concentration. The potential of these sensors for the measurement of the clinically and industrially important metabolites urea and penicillin G is demonstrated.