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Glucose-sensitive nanofiber scaffolds with an improved sensing design for physiological conditions.

ABSTRACT: Continuous physiological monitoring of electrolytes and small molecules such as glucose, creatinine, and urea is currently unavailable but achieving such a capability would be a major milestone for personalized medicine. Optode-based nanosensors are an appealing analytical platform for designing in vivo monitoring systems. In addition to the necessary analytical performance, such nanosensors must also be biocompatible and remain immobile at the implantation site. Blood glucose in particular remains a difficult but high-value analyte to monitor continuously. Previously, we developed glucose-sensitive nanosensors that measure glucose by a competitive binding mechanism between glucose and a fluorescent dye to 4-carboxy-3-fluorophenyl boronic acid. To improve the sensitivity and residency time of our reported sensors, we present here a series of new derivatives of 4-carboxy-3-fluorophenyl boronic acid that we screened in a macrosensor format before translating into a nanofiber format with electrospinning. The lead candidate was then implanted subdermally and its residency time was compared to spherical nanosensor analogues. The nanofiber scaffolds were markedly more stable at the implantation site whereas spherical nanosensors diffused away within three hours. Based on the enhanced sensitivity of the new boronic acids and the residency time of nanofibers, this sensor configuration is an important step towards continuous monitoring of glucose and other analytes.

SUBMITTER: Balaconis MK

PROVIDER: S-EPMC4356171 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Glucose-sensitive nanofiber scaffolds with an improved sensing design for physiological conditions.

Balaconis Mary K MK Luo Yi Y Clark Heather A HA

The Analyst 20150201 3

Continuous physiological monitoring of electrolytes and small molecules such as glucose, creatinine, and urea is currently unavailable but achieving such a capability would be a major milestone for personalized medicine. Optode-based nanosensors are an appealing analytical platform for designing in vivo monitoring systems. In addition to the necessary analytical performance, such nanosensors must also be biocompatible and remain immobile at the implantation site. Blood glucose in particular rema ...[more]

PMID: 25426497

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Project description:The chemical exchange of labile protons of the hydroxyl groups can be exploited in a variety of magnetic resonance experiments to gain information about the groups and their physicochemical environment. The exchangeable -OH protons provide important contributions to the T2 of water signals thus contributing to the T2-weighted contrast of MRI images. This exchange can be exploited more specifically and sensitively in chemical exchange saturation transfer (CEST) or longitudinal rotating frame relaxation (T1,ρ) experiments. Since glucose is omnipresent in living organisms, it may be seen as a rather universal probe. Even though the potential was first recognized many years ago, practical use has remained scarce due to numerous challenges. The major limitation is the rather low glucose concentration in most tissues. The other obstacles are related to multiple dependencies of the exchange parameters, such as temperature, pH, and concentration of various ions that are not known in sufficient detail for glucose. Thus, we embarked on evaluating the exchange parameters of a model that included every relevant chemical site for all -OH protons in both dominant enantiomers of glucose. We have (1) obtained conventional one-dimensional proton NMR spectra of glucose solutions in suitable temperature ranges, (2) we have iterated through several exchange models with various degrees of freedom determined by the number of distinguishable -OH proton sites and compared their performance, (3) we extrapolated the parameters of the best model of physiological temperature and (4) we demonstrated the use of the parameters in virtual experiments. As the main results, (1) we have obtained the temperature dependence of exchange parameters with reliable confidence intervals in three different pH values, with two of them reaching physiological temperature, and (2) we show how the parameters can be used in virtual experiments, helping to develop new applications for glucose as an NMR/MRI probe.

Dataset Information

Glucose-sensitive nanofiber scaffolds with an improved sensing design for physiological conditions.

Publications

Glucose-sensitive nanofiber scaffolds with an improved sensing design for physiological conditions.

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