Soya Gamsey

Optical glucose detection across the visible spectrum using anionic fluorescent dyes and a viologen quencher in a two-component saccharide sensing system

A very general system is described in which anionic fluorescent dyes possessing a wide range of absorbance and emission wavelengths are used in combination with a boronic acid-modified viologen quencher to sense glucose at pH 7.4 in buffered aqueous solution. The present study demonstrates this capability with the use of eleven anionic fluorescent dyes of various structural types. Signal modulation occurs as the monosaccharide binds to the viologen quencher and alters its efficiency in quenching the fluorescence of the anionic dyes. The degree of quenching and the magnitude of the glucose signal were found to correlate roughly with the number of anionic groups on the dye. Optimal quencher : dye ratios were determined for each dye to provide a fairly linear signal in response to changes in glucose concentration across the physiological range.

Use of a Novel Fluorescent Glucose Sensor in Volunteer Subjects with Type 1 Diabetes Mellitus

Background: Stress hyperglycemia in the critically ill has been found to be associated with increased morbidity and mortality. Studies have found significant improvements in morbidity and mortality in postsurgical patients whose glucose levels were closely maintained in the euglycemic range. However, subsequent studies, in particular the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study, found no improvement in subjects with tight glycemic control. In addition to differences in protocol design, patients in the tight glycemic control arm of the NICE-SUGAR study experienced high rates of hypoglycemia compared with other studies. One interpretation of the NICE-SUGAR study results is that it is difficult to achieve normal glycemia in critically ill patients with existing glucose monitoring technology. The purpose of the study reported here was to evaluate the safety and performance of a continuous intravascular glucose sensor that could be used in the future in critically ill patients. Methods: A first-generation prototype of an intravascular continuous glucose sensor was evaluated in 29 volunteer subjects with type 1 diabetes mellitus. The sensor operates on the principle of quenched fluorescence. The fluorescent emission from the sensor chemistry is nonlinear, resulting in improved accuracy in the hypoglycemic range. The duration of each study was 8 hours. Sensor output was compared with temporally correlated reference measurements made from venous samples on a laboratory glucose analyzer. Results: Data were obtained from 18 of the 29 subjects in the study. Data were analyzed retrospectively using a factory calibration plus a one-point in vivo calibration. The mean absolute relative difference was 7.97%, and 95.1% of all the points were in zone A of the Clarke error grid. Conclusions: This pilot study was the first use in human subjects of a prototype of the GluCath Intravascular Continuous Glucose Monitoring System (GluCath System). The GluCath System is based on a novel fluorescent sensor chemistry. The study found the GluCath System had a high level of accuracy as compared with a laboratory reference analyzer.

Preclinical Evaluation of Poly(HEMA-co-acrylamide) Hydrogels Encapsulating Glucose Oxidase and Palladium Benzoporphyrin as Fully Implantable Glucose Sensors.

Background: Continuous glucose monitors (CGMs) require percutaneous wire probes to monitor glucose. Sensors based on luminescent hydrogels are being explored as fully implantable alternatives to traditional CGMs. Our previous work investigated hydrogel matrices functionalized with enzymes and oxygen-quenched phosphors, demonstrating sensitivity to glucose, range of response, and biofouling strongly depend on the matrix material. Here, we further investigate the effect of matrix composition on overall performance in vitro and in vivo. Methods: Sensors based on three hydrogels, a poly(2-hydroxyethyl methacrylate) (pHEMA) homopolymer and 2 poly(2-hydroxyethyl methacrylate-co-acrylamide) (pHEMA-co-AAm) copolymers, were compared. These were used to entrap glucose oxidase (GOx), catalase, and an oxygen-sensitive benzoporphyrin phosphor. All sensor formulations were evaluated for glucose response and stability at physiological temperatures. Selected sensors were then evaluated as implanted sensors in a porcine model challenged with glucose and insulin. The animal protocol used in this study was approved by an IACUC committee at Texas A&M University. Results: PHEMA-co-AAm copolymer hydrogels (75:25 HEMA:AAm) yielded the most even GOx and dye dispersion throughout the hydrogel matrix and best preserved GOx apparent activity. In response to in vitro glucose challenges, this formulation exhibited a dynamic range of 12-167 mg/dL, a sensitivity of 1.44 ± 0.46 µs/(mg/dL), and tracked closely with reference capillary blood glucose values in vivo. Conclusions: The hydrogel-based sensors exhibited excellent sensitivity and sufficiently rapid response to the glucose levels achieved in vivo, proving feasibility of these materials for use in real-time glucose tracking. Extending the dynamic range and assessing long-term effects in vivo are ongoing efforts.

Three chiral vinyldioxazaborocanes.

The structures of three chiral vinyldioxazaborocanes are reported, namely (2E)- and (2Z)-6-benzyl-2-buten-2-yl-1,3,6,2-dioxazaborocane, C27H30BNO2, (II) and (III), respectively, and (2Z)-2-buten-2-yl-6-isobutyl-1,3,6,2-dioxazaborocane, C24H32BNO2, (IV). These compounds may be useful in asymmetric reactions. In the structures reported here, the N-B donor-acceptor bond is longer than in any previously reported analogous compounds.