RESUMO
BACKGROUND: Current methods of glucose monitoring rely predominantly on enzymes such as glucose oxidase for detection. Phenylboronic acid receptors have been proposed as alternative glucose binders. A unique property of these molecules is their ability to bind glucose in a fully reversible covalent manner that facilitates direct continuous measurements. We examined (1) the ability of a phenylboronic-based sensor to measure glucose in blood and blood plasma and (2) the effect on measurement accuracy of a range of potential interferents. We also showed that the sensor is able to track glucose fluctuations occurring at rates mimicking those experienced in vivo. METHOD: In vitro static measurements of glucose in blood and blood plasma were conducted using holographic sensors containing acrylamide, N,N'-methylenebisacrylamide, 3-acrylamidophenylboronic acid, and (3-acrylamidopropyl) trimethylammonium chloride. The same sensors were also used for in vitro measurements performed under flow conditions. RESULTS: The opacity of the liquid had no affect on the ability of the optical sensor to measure glucose in blood or blood plasma. The presence of common antibiotics, diabetic drugs, pain killers, and endogenous substances did not affect the measurement accuracy, as shown by error grid analysis. Ex vivo flow experiments showed that the sensor is able to track changes accurately in concentration occurring in real time without lag or evidence of hysteresis. CONCLUSIONS: The ability of phenylboronic acid sensors to measure glucose in whole blood was demonstrated for the first time. Holographic sensors are ideally suited to continuous blood glucose measurements, being physically and chemically robust and potentially calibration free.
RESUMO
BACKGROUND: We recently described a holographic optical sensor with improved selectivity for glucose over fructose that was based on a thin-film polymer hydrogel containing phenylboronic acid receptors. The aim of the present work was to measure glucose in human blood plasma as opposed to simple buffers and track changes in concentration at a rate mimicking glucose changes in vivo. METHODS: We used holographic sensors containing acrylamide, N,N'-methylenebisacrylamide, 3-acrylamidophenylboronic acid, and (3-acrylamidopropyl)trimethylammonium chloride to measure 7 human blood plasma samples at different glucose concentrations (3-33 mmol/L) in static mode. Separately, using a flow cell, the glucose concentration was varied at approximately 0.17-0.28 mmol(-1) x L(-1) x min(-1), and the sensor's ability to continuously monitor glucose was investigated over an extended period. RESULTS: We subjected the results of the ex vivo static measurements to error grid analysis. Of 46 measurements, 42 (91.3%) fell in zone A of a Clarke error grid, and the remainder (8.7%) fell in zone B. The ex vivo flow experiments showed that the sensor is able to accurately track changes in concentration occurring in real time without lag or evidence of hysteresis. CONCLUSIONS: We demonstrate the ability of a phenylboronic acid-based sensor to measure glucose in human blood plasma for the 1st time in vitro. Holographic glucose sensors can be used without recourse to recalibration. Their robust nature, coupled with their format flexibility, makes them an attractive alternative to conventional electrochemical enzyme-based methods of glucose monitoring for people with diabetes.
