Glucose-sensitive systems

Major developments have been reported in the utilization of environmentally responsive hydrogels as glucose-sensitive systems that... 

An early example of an MIP-QCM sensor was a glucose monitoring system by Malitesta et al. (1999). A glucose imprinted poly(o-phenylenediamine) polymer was electrosynthesized on the sensor surface. This QCM sensor showed selectivity for glucose over other compounds such as ascorbic acid, paracetamol, cysteine, and fructose at physiologically relevant millimolar concentrations. A unique QCM sensor for detection of yeast was reported by Dickert and coworkers (Dickert et al. 2001 Dickert and Hayden 2002). Yeast cells were imprinted in a sol-gel matrix on the surface of the transducer. The MIP-coated sensor was able to measure yeast cell concentrations in situ and in complex media. A QCM sensor coated with a thin permeable MIP film was developed for the determination of L-menthol in the liquid phase (Percival et al. 2001). The MIP-QCM sensor displayed good selectivity and good sensitivity with a detection limit of 200 ppb (Fig. 15.7). The sensor also displayed excellent enantioselectivity and was able to easily differentiate the l- and D-enantiomers of menthol. 

Fig. 16. Concept of glucose sensitive insulin release system using PVA/poly (NVP-10-PBA) complex system, (polymer capsule type)...

The most desired outcome of a glucose sensor system is to prevent the occurrence of hyper- and hypoglycemia or, at least, reduce the severity of hypoglycemia. For a stand-alone monitor system, all it needs to do is to sound an alarm accurately and in a timely fashion. This, in concept, is an open-loop system. It requires the patient to decide how to manage the monitoring process. In reality, however, this seemingly simple task has been very difficult. Sensitivity and specificity are usually used to evaluate the effectiveness of the alarm methodology as well as the usefulness of the device. 

Glucose sensitive neurons are present in the hypothalamus. They depend on glucokinase and act in many ways similar to beta cells [51]. They influence both insulin secretion and glucose uptake, and there appear to be neural connections between all glucose sensing cells [15]. The output may be part of the hepato-portal system, but also conditioned reflexes may participate in the neural stimulation of insulin release and glucose uptake [52]. In this sense the CNS also participates in predictive control. 

Any sol-gel phase reversible system described above can be used as an erodible matrix system. All the components of the system in the sol state are essentially in the dissolved state, and thus they can be released to the environment in the absence of protecting membranes. During the process of gel to sol transition by the addition of glucose, the incorporated insulin can be released as a function of glucose concentration. There are of course other polymeric systems which can be used in glucose-sensitive erodible insulin delivery. 

Fig. 24. Experimental setup of a blood glucose monitoring system. ISFET, ion-sensitive FET. (Reproduced from Ito et al. (52), with permission.)...

Other minor enzyme systems can be used, such as P-galactosidase (5). This system works well. However, it can lead to some false-positive problems resulting from endogenous enzymes which have a similar reactivity (6). Another enzyme not commonly used is glucose oxidase. A glucose oxidase system can provide a sensitive and specific assay if other endogenous enzyme activity is a problem. 

Taylor Ml, Tanna S, Cockshott S, and Vaitha R. A self-regulated delivery system using unmodified solutes in glucose-sensitive gel membranes. Journal of Pharmacy and Pharmacology 1994 46 (Suppl. 2) 1051a. 

Podual K, Doyle F, and Peppas NA. Modeling of water transport in and release from glucose-sensitive swelling-controlled release systems based on poly(diethylaminoethyl methacrylate-g-ethylene glycol). Industrial engineering chemistry research 2004 43 7500-7512. 

Less sensitive systems are obtained when enzyme reactions are used, in which ATP is one of the cofactors. For example, the phosphorylation of glucose by hexokinase requires ATP as cosubstrate (Eq. (11.9)). Thus, a glucose electrode was combined with hexokinase and signal reduction was observed when ATP was present [120]. 

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