Glucose electrodes

Scale of Operation Voltammetry is routinely used to analyze samples at the parts-per-million level and, in some cases, can be used to detect analytes at the parts-per-billion or parts-per-trillion level. Most analyses are carried out in conventional electrochemical cells using macro samples however, microcells are available that require as little as 50 pL of sample. Microelectrodes, with diameters as small as 2 pm, allow voltammetric measurements to be made on even smaller samples. For example, the concentration of glucose in 200-pm pond snail neurons has been successfully monitored using a 2-pm amperometric glucose electrode. ... 

The potentialities offered by chemical processes catalyzed by enzymes immobilized in a polymeric matrix are obvious and are now successfully utilized in various ways [6, 13, 16, 17, 40, 43,44, 50, 58, 61], This idea was introduced into electroanalytical chemistry by Clark and Lyons [9], who proposed a glucose electrode, with glucose oxidase immobilized between cuprophane membranes and with amperometric determination of the hydrogen peroxide formed by the reaction... 

Figure 17-11 Response of an cmperometric glucose electrode with dissolved 02 concentration corresponding to an oxygen pressure of 0.027 bar, which is 20% lower than the typical concentration in subcutaneous tissue. [Data from S.-K. Jung and G. W. Wilson, "Polymeric Mercaptosilane-MocMed Platinum Electrodes lor Elimination of Interfer-ants in Glucose Biosensors," Anal. Chem. 1996,68.591.]...

Selected Commercial Glucose Analyzer Based on Glucose Electrode (59, 92)... 

The enzyme can be incorporated into an amperometric sensor in a thick gel layer, in which case the depletion region due to the electrochemical reaction is usually confined within this layer. Alternatively, enzyme can be immobilized at the surface of the electrode or even within the electrode material itself, in which case the depletion region extends into the solution in the same way as it would for an unmodified electrode. In the latter case, the enzyme can then be seen as a true electrocatalyst that facilitates the interfacial electron transfer, which would otherwise be too slow. The general principles of the design and operation of these biosensors is illustrated on the example of the most studied enzymatic sensor, the glucose electrode (Fig. 2.14, Section 2.3.1). 

There are several species in this reaction that can be used for electrochemical sensing. Detection of proton released from the gluconic acid was used in the poten-tiometric glucose electrode (Section 6.2.1). The amperometric sensor can be based on oxidation of hydrogen peroxide, on reduction of oxygen, or on the oxidation of the reduced form of glucose oxidase itself. 

The earliest design of the glucose electrode (which is generally applicable to any oxidase and uses oxygen as the ultimate electron acceptor) is based on the differential measurement of oxygen deficiency at the oxygen electrode, caused by the... 

The three types of glucose electrode discussed here illustrate the major facets of design and operation of enzymatic amperometric sensors. Examples of amperometric enzyme electrodes for other substrates are shown in Table 7.3. The actual design details of these sensors depend on the enzyme kinetics involved and on the operating conditions under which they are used. 

In the previous papers(12,13), we reported on the vessel access type, i.e. tubular type, glucose sensor. It consisted of a glucose electrode system with a GOX enzyme immobilized Nylon membrane and a glucose semipermeable membrane, and a reference oxygen electrode system. The sensor could directly measure up to 700 mg/dl of BGL in an arterial blood stream when it was placed into an external A-V shunt. This sensor, however, has some problems such as thrombus during in vivo testing without heparin and clinical complexity associated with implanting the sensor in a blood stream. 

Csoregi E, Quinn CP, Schmidtke DW, Lindquist SE, Pishko MV, Ye L, Katakis I, Hubbell JA, Heller A. Design, characterization, and one-point in vivo calibration of a subcutaneously implanted glucose electrode. Analytical Chemistry 1994,66, 3131-3138. 

Kemer W, Kiwit M, Linke B, Keck FS, Zier H, Pfeiffer EF. The function of hydrogen-peroxide-detecting electroenzymatic glucose electrode is markedly impaired in human subcutaneous tissue and plasma. Biosensors Bioelectronics 1993, 8, 473. 

Csoregi E, Schmidtke D, Heller A. Design and optimization of a selective subcutaneously implantable glucose electrode based on wired glucose oxidase. Analytical Chemistry 1995, 67, 1240-1244. 

Thus, glucose oxidase can be randomly immobilised on the modified nylon mesh (I). The resultant enzyme membrane (II) when held tautly over a platinun anode disc provides a high performance, long life glucose electrode which can be housed in a Stelte cell adapted for flow injection analysis (4). 

On-wafer membrane deposition and patterning is an important aspect of the fabrication of planar, silicon based (bio)chemical sensors. Three examples are presented in this paper amperometric glucose and free chlorine sensors and a potentiometric ISRET based calcium sensitive device. For the membrane modified ISFET, photolithographic definition of both inner hydrogel-type membrane (polyHEMA) and outer siloxane-based ion sensitive membrane, of total thickness of 80 pm, has been performed. An identical approach has been used for the polyHEMA deposition on the free chlorine sensor. On the other hand, the enzymatic membrane deposition for a glucose electrode has been performed by either a lift-off technique or by an on-chip casting. 

In our earlier work we have studied the realization of an amperometric transducer using thin film and photolithography techniques (7) as well as that of an AI2O3 type pH-ISFET (2). The use of the former in an enzymatic glucose electrode (3) and of the latter in for example a K+ sensitive device (4) has been reported. In both cases the control of membrane thicknesses and adhesion was the most critical parameter of the sensor realization. In this paper we will focus on different on-wafer and on-chip... 

In order to maintain the advantage of the microfabrication approach which is intended for a reproducible production of multiple devices, parallel development of membrane deposition technology is of importance. Using modified on-wafer membrane deposition techniques and commercially available compounds an improvement of the membrane thickness control as well as the membrane adhesion can be achieved. This has been presented here for three electrochemical sensors - an enzymatic glucose electrode, an amperometric free chlorine sensor and a potentiometric Ca + sensitive device based on a membrane modified ISFET. Unfortunately, the on-wafer membrane deposition technique could not yet be applied in the preparation of the glucose sensors for in vivo applications, since this particular application requires relatively thick enzymatic membranes, whilst the lift-off technique is usable only for the patterning of relatively thin membranes. 

Third-Generation Glucose Electrodes Potentiometric Urea Elearode... 

The so-called first generation of glucose electrodes relies on monitoring either the consumption of oxygen or the formation of hydrogen peroxide ... 

Fig. 5. Schematic illustration of the three generations of glucose electrodes (A) first generation, (B) second generation, (C) third generation. E, enzyme.

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