Glucose Biosensor Based on Oxygen Electrode Part IV: In Vivo Evaluation of the Rechargeable Glucose Sensor

Abstract

A glucose monitoring system consisting of a pair of amperometric sensors: a glucose biosensor based on oxygen electrode and an oxygen sensor, two miniature potentiostats, an instrumentation amplifier and a data logger has been developed. The glucose sensor has linear response to the glucose concentration in vitro at 37°C up to 26 mM (480 mg/dL) in the phosphate buffer solution (pH 7.4), and linear range up to 21 mM (380 mg/dL) in undiluted bovine plasma. The system was evaluated in vivo with the sensors subcutaneously implanted in healthy mongrel dogs. During the implantation the system output was continuously recorded. The results of short-term subcutaneous implantation of the integrated system demonstrated good agreement between the glucose concentration measured by the biosensor and that obtained using standard glucose determination methods. The delay-time between the tissue glucose level (measured by the biosensor) and the blood glucose level (obtained by standard methodology) was 3 to 10 minutes. During the chronic implantation the biosensor was refilled in vivo. Rejuvenation of the sensor response after refilling was observed demonstrating the potential of such sensors for long-term implantation.     

Oxygen isotope exchange in praseodymium nickelate

Oxygen surface exchange kinetics and diffusion were studied in Pr₂NiO_4?+?δ (PNO) by the isotope exchange method with gas phase equilibration in the temperature range of 600–800 °C and oxygen pressure range of 0.33–1.62 kPa. The oxygen heterogeneous exchange rate (r_H), oxygen diffusion coefficient (D), rates of oxygen dissociative adsorption (r_a), and oxygen incorporation (r_i) were calculated along with the apparent activation energies of oxygen surface exchange and diffusion processes. The temperature dependence of r_H was found to benon-linear in Arrhenius coordinates. The apparent activation energy changed from 1.4?±?0.2 eV at T?>?700 °C to 2.0?±?0.1 eV. This might be attributed to the change in the rate-determining stage of oxygen exchange for Pr₂NiO_4?+?δ at T ~?700 °C, because of a shift in the ratio between r_a and r_i caused by the difference in their activation energies. Possible reasons for the observed changes in the rate-determining stage are discussed.     

Polyurethane cationomers III: Oxygen permeation

Dynamic oxygen permeation measurements at 20–70°C on films cast from solutions and emulsions of three series of polyurethane (PU) cationomers based on MDI, HDI, and TDI that are the subject of Parts I and II of this series were made by Barrer's vacuum technique. For the MDI system, films cast from solutions of ionized PU exhibit permeation coefficients P that are higher at 20–40°C (below the glass transition temperature T_gh of the hard domains) than at 50–70°C (above T_gh) by factors of about 5 and 40. This is the opposite of what is observed for normal homopolymers and un-ionized PU. This phenomenon is attributed to the continuous/dispersed morphology of these films. At the low temperature, oxygen molecules diffuse through the continuous phase (soft domains) only. But at the high temperature, oxygen molecules diffuse through soft domains and subsequently through hard domains, leading to an increase in diffusion pathlength. For films cast from the PU emulsions, such a drop in P was not observed because the hard domains were partially inverted from the dispersed phase to a continuous phase that gives an interwoven morphology. Such morphology allows oxygen molecules to diffuse through soft and phase-inverted hard domains simultaneously. For the HDI and TDI systems, P and D vs. 1/T plots show no zone of discontinuity. This is attributed to a T_gh that is lower than or close to the permeation temperature. © 1995 John Wiley & Sons, Inc.     

Method for the determination of the solubility of gases in liquids

A rapid and experimentally simple method for the determination of the solubilities of oxygen or hydrogen in liquids is presented The method employs a membrane-enclosed amperometric detector of the well known Clark type to measure the partial pressure of the gas when distributed at equilibrium between the liquid and a gas space for a series of internal volumes of the system. The amounts of all substances and the temperature are maintained constant throughout the series although the internal pressure changes as a result of the volume changes. The glass apparatus is water jacketed for temperature control, has inlet and outlet ports for gas, and the amperometric sensor is mounted in a gas-tight sliding fitting for effecting the volume changes. The liquid content is vigorously stirred by a magnetic bar during measurements. Equations for the interpretation of results at different internal volumes take into account the conservation of the solvent and of the gas, the dependence of the volume of the liquid on the concentration of dissolved gas and Henry's law describing the distribution of the gas between gas and liquid phases at equilibrium. The solution of these equations yields an equation for the dependence of the measured partial pressure on volume, which includes the Henry's law constant H as a parameter. Conditions can usually be arranged to give a straight line dependence of volume on the reciprocal of partial pressure. The method has been applied to several common liquids, and has been shown to produce results which agree with literature solubilities to within about ±5%. Examples which have been studied include oxygen in water (H=4.039 × 10⁶ kPa at 20°C), in acetone (1.25 × 10⁵ kPa at 20°C), in ethanol (1.758 × 10⁵ kPa at 20°C) and in toluene (1.05 × 10⁵ kPa at 20°C) as well as hydrogen in water (6.89 × 10⁶ kPa at 20°C).     

The NTB phase in an achiral asymmetrical bent-core liquid crystal terminated with symmetric alkyl chains

ABSTRACT

The characteristics of the twist-bend nematic (N_TB) phase of an achiral asymmetrical rigid bent-core liquid crystal (LC), the ends of which are terminated by symmetric alkyl chains, are reported. The nematic–nematic phase transition and its properties are studied by differential scanning calorimetry (DSC), polarising microscopy and the electro-optic techniques. Large domains of opposite handedness are observed in the absence of the external field in the N_TB phase. Another set of periodic striped pattern consisting of domains with sharp boundaries is formed when a high-frequency electric field with a magnitude above its threshold is applied across a planarly aligned cell. The neighbouring domains are of opposite chirality. The temperature dependence of the heliconical angle θ₀ is determined from the birefringence measurements using Haller’s extrapolation technique. This material shows lower values of the heliconical angle (~9.3° at a temperature of 155°C within the N_TB phase) when compared with the previously reported dimer-based twist-bend nematic LCs (31°±3°).     

The solubility and isotopic fractionation of gases in dilute aqueous solution. I. Oxygen

A very precise and accurate new method is described for determination of the Henry coefficient k and the isotopic fractionation of gases dissolved in liquids. It yields fully corrected values for k at essentially infinite dilution. For oxygen the random error for k is less than 0.02%, which is an order of magnitude better than the best previous measurements on that or any other gas. Extensive tests and comparison with other work indicate that systematic errors probably are negligible and that the accuracy is determined by the precision of the measurements. In the virial correction factor (1+λP_t), where P_t is the total pressure of the vapor phase, the coefficient λ for oxygen empirically is a linear decreasing function of the temperature over the range 0–60°C. The simple three-term power series in 1/T proposed by Benson and Krause, $$\ln k = a_0 + a_1 /T + a_2 /T^2 $$ provides a much better form for the variation of k with temperature than any previous expression. With a₀=3.71814, a₁=5596.17, and a₂=?1049668, the precision of fit to it of 37 data points for oxygen from 0–60°C is 0.018% (one standard deviation). The three-term series in 1/T also yields the best fit for the most accurate data on equilibrium constants for other types of systems, which suggests that the function may have broader applications. The oxygen results support the idea that when the function is rewritten as $$\ln k = - (A_1 + A_2 ) + A_1 \left( {\frac{{T_1 }}{T}} \right) + A_2 \left( {\frac{{T_1 }}{T}} \right)^2 $$ it becomes a universal solubility equation in the sense that A₂ is common to all gases, with T₁ and A₁ characteristic of the specific gas. Accurate values are presented for the partial molal thermodynamic function changes for the solution of oxygen in water between the usual standard states for the liquid and vapor phases. These include the change in heat capacity, which varies inversely with the square of the absolute temperature and for which the random error is 0.15%. Analysis of the high-temperature data of Stephan et al., in combination with our values from 0–60°C, shows that for oxygen the fourterm series in 1/T, $$\ln k = - 4.1741 + 1.3104 \times 10^4 /T - 3.4170 \times 10^6 /T^2 + 2.4749 \times 10^8 /T^3 $$ where p=kx and p is the partial pressure in atmospheres of the gas, probably provides the best and easiest way presently available to calculate values for k in the range 100–288°C, but more precise measurements at elevated temperatures are needed. The new method permits direct mass spectrometric comparison of the isotopic ratio³⁴O₂/³²O₂ in the dissolved gas to that in the gas above the solution. The fractionation factor α=³²k/³⁴k varies from approximately 1.00085 (±0.00002) at 0°C to 1.00055 (±0.00002) at 60°C. Although the results provide the first quantitative determination of α vs. temperature for oxygen, it is not possible from these data to choose among several functions for the variation ofInα with temperature. If the isotopic fractionation is assumed to be due to a difference in the zero-point energy of the two species of oxygen molecules, the size of the solvent cage is calculated to be approximately 2.5 Å. The isotopic measurements indicate that substitution of a³⁴O₂ molecule for a³²O₂ molecule in solution involves a change in enthalpy with a relatively small change in entropy.     

Oxygen diffusion in poly(dimethyl siloxane) using fluorescence quenching. I. Measurement technique and analysis

The transport properties of oxygen in poly(dimethyl siloxane) have been measured using the method of quenching of fluorescence. This paper discusses the uniqueness of this method and its use in measuring the diffusion coefficient of oxygen in unfilled PDMS. The results show (1) a large value for the diffusion coefficient of oxygen in pure PDMS at 25°C, D = 3.55 × 10^?5 cm²/s, (2) a low value of the acitivation energy, E_D = 4.77 kcal/mole, which was not temperature dependent in the ranges evaluated, and (3) a large value of the preexponential term, D₀ = 0.115 cm²/s. The diffusion coefficient was found to be independent of both the oxygen concentration and fluorophor concentration in the pressure and temperature ranges used in these experiments. The import of these experiments lies in their application to a unique biomedical oxygen sensor which is fast, sensitive, and does not consume oxygen.     

Sensitivity of Semiconductor Gas Sensors to Hydrogen and Oxygen in an Inert Gas Atmosphere

Semiconductor gas sensors with nine types of gas-sensing films were prepared and their sensitivity for hydrogen and oxygen in binary and ternary gas mixtures containing nitrogen in concentrations of 0–4 and 0–8 vol %, respectively was studied. The sensor temperature was varied from 200 to 500°C. Sensors based on an In₂O₃+ Al₂O₃(30 : 70) composite with platinum contact areas exhibited the best metrological and performance characteristics. The resistance of sensors heated to an optimum temperature of 400°C was measured as a function of the test gas concentration. In principle, the concentrations of the components in nitrogen can be determined to within 5 rel % with the use of the above functions.     

A Highly Sensitive Enzymatic Assay Method for Hypoxanthine Estimation Based on the Use of an Oxygen Electrode

Abstract

Using a Clark-type oxygen electrode as sensor, a highly sensitive enzymatic assay method for hypoxanthine was developed, based on xanthine oxidase. The sensitivity of the assay is comparable to that of standard chemiluminescent techniques. The incorporation of sulfite, 0 to 150 mM, allowed hypoxanthine determination over the range of 5 nM to 100 μM. The response time was 4 min or less at 30°C.     

Glucose Biosensor Based on Oxygen Electrode. Part II: Long-Term Operational Stability of the Rechargeable Glucose Biosensor

Abstract

A potentially implantable glucose biosensor for measuring blood or tissue glucose levels in diabetic patients has been developed. The glucose biosensor is based on an amperometric oxygen electrode and immobilized glucose oxidase enzyme, in which the immobilized enzyme can be replaced (the sensor recharged) without surgical removal of the sensor from the patient. Recharging of the sensor is achieved by injecting fresh immobilized enzyme into the sensor using a septum. A special technique for immobilization of the enzyme on Ultra-Low Temperature Isotropic (ULTI) carbon powder held in a liquid suspension has been developed.

In vitro studies of the sensors show stable performance during several recharge cycles over a period of 3 months of continuous operation.

Diffusion membranes which ensure linear dependence of the sensor response on glucose concentration have been developed. These membranes comprise silastic latex-rubber coatings over a microporous polycarbonate membrane. Calibration curves of the amperometric signal show linearity over a wide range of glucose concentrations (up to 16 mM), covering hypoglycemic, normoglycemic and hyperglycemic conditions.

The experimental results confirm the suitability of the sensors for in vitro measurements in undiluted human sera.     

Gas–liquid equilibrium data for mixture gas of carbon dioxide + nitrogen in 1,2-ethanediamine + triethylene glycol aqueous solution

Isothermal gas–liquid equilibrium (GLE) data were measured for the system of 1,2-ethanediamine (EDA) + triethylene glycol (TEG) + H₂O + carbon dioxide (CO₂) + N₂ at T = 293.15, 298.15, 303.15 and 308.15 K and p = 121.74, 126.94 and 129.87 kPa with CO₂ partial pressure ranging from 0 to 13.0 kPa. Measurements were carried out using a saturation method in a glass absorption apparatus, which was controlled at the constant temperature by a thermostatic circulation bath with a Beckmann thermometer. The measurement uncertainties for temperature, total pressure, CO₂ concentration in the gas phase and CO₂ concentration in the liquid phase were less than ±0.02 K, ±0.15 kPa, ±2.5% and ±0.6, respectively. The results indicate that the addition of TEG into the aqueous EDA solution could significantly improve the stability of EDA in CO₂ absorption process, thus enhancing the performance of aqueous amine-based CO₂ scrubbing.     

Synthesis and properties of mesogenic laterally fluorinated compounds containing benzoxazole unit

Series of mesogenic laterally fluorinated compounds, 2-(2′,3′-difluoro-4′-alkoxybiphenyl-4-yl)-benzoxazole derivatives (nB-Fx) bearing different substituents (H, CH₃, Cl, NO₂, coded as nB-FH, nB-FM, nB-FC and nB-FN, respectively) at 5-position, were prepared and characterised. Their phase transition behaviour was investigated by differential scanning calorimetry and polarising optical microscopy. nB-Fx with alkoxy chain lengths of 2 to 10 carbons exhibited enantiotropic mesophases, for which the mesophase ranges were 0°C–58°C and 0°C–71°C on heating and cooling for nB-FH, 41°C–93°C and 66°C–140°C for nB-FM, 44°C–133°C and 87°C–155°C for nB-FC, and 0°C–76°C and 0°C–95°C for nB-FN, respectively. Compared to non-fluorinated analogues, with the exception of nB-FC, fluorinated nB-Fx mainly exhibited nematic mesophase both in heating and cooling, which were attributed to the disruption of the side-to-side intermolecular packing caused by the two ortho-lateral fluoro substituents. For nB-Fx series, nB-FM, nB-FC and nB-FN exhibited a much wider mesophase range than the corresponding nB-FH series, which indicated that the substituent at benzoxazole moiety was helpful in increasing the mesophase stability. With the exception of nB-FN, the nB-Fx series displayed intense photoluminescence emission at 379–383 nm in methylene chloride solution, when it was excited at its absorption maxima.     

Phase equilibriums, oxygen exchange kinetics and diffusion in oxides CaZr1 ? x Sc x O3 ? x/2 ? δ

Oxides CaZr_{1 ? x} Sc _x O_{3 ? x/2 - ??} (x = 0.00?C0.20) were synthesized according to the ceramic technology. The solubility boundary of scandium with formation of solid solutions on the basis of calcium zirconate CaZrO_{3 ? ??} corresponds to x = 0.07?C0.08. The second phase of CaSc₂O₄ is present in the samples with scandium content of x = 0.10, 0.15, 0.20. Its fraction grows at an increase in x. The method of full-profile Rietveld analysis was used to calculate the structure parameters for oxides CaZr_0.99Sc_0.01O_{2.995 ? ??} and CaZr_0.95Sc_0.05O_{2.975 ? ??}. The method of isotopic exchange with gas phase analysis was used to study the kinetics of gas-phase oxygen interaction with the CaZr_0.95Sc_0.05O_{2.975 ? ??} oxide in the temperature range of 700?C850°C and at oxygen pressures of 0.13?C6.67 kPa. The values of effective activation energies of the oxygen exchange and diffusion processes were 1.36 ± 0.32 and 1.92 ± 0.21 eV, accordingly. The dependence of the interphase exchange rate on the pressure of oxygen corresponds to the power law with the exponent of 0.31 ± 0.04 at the temperature of 750°C.     

A Telemetry-Instrumentation System for Long-Term Implantable Glucose and Oxygen Sensors

Abstract

This paper describes the development of a compact, low power, implantable system for in vivo monitoring of oxygen and glucose concentrations. The telemetry-instrumentation system consists of two amperometric sensors: one oxygen and one glucose biosensor and two potentiostats for biasing the sensors, an instrumentation amplifier to subtract and amplify sensor output signals, and a signal transmitter subunit to convert and transmit glucose dependent signal from the sensors to a remote data acquisition system. The system produces a unipolar glucose dependent voltage in the range of 1 to 3.6 V which is converted to a frequency and then transmitted using a frequency-modulated (FM) oscillator. Initial tests were performed on an open model electronic circuit using resistors to simulate sensor outputs in the 10 to 1000 nA range. Further in vitro evaluation of the system was conducted with a compact printed circuit board embedded in silicone elastomer, entirely submerged in buffer solution using actual sensors. The test results indicated satisfactory operation of the system in simulated implantation conditions for seven days. Response curve of transmitted signal vs glucose concentration was obtained. The results of the in vitro evaluation of the telemetry system permits its subcutaneous implantation in an animal model.     

Oxygen ionosorption on compressed semiconducting powders of zinc and germanium oxynitrides

Oxygen ionosorption on zinc and germanium oxynitrides, Zn_xGeO_yN_z, is observed through the electrical resistance variation of pellets of these materials. In vacuum the resistance versus temperature characteristics log R₀(1/T)_are nearly straight; they show good reproducibility and are used as references for isothermal adsorption and desorption experiments and for temperature programmed desorptions (TPD). Ionosorbed oxygen acts as an electron acceptor trap at the surface of an n-type semiconductor. That leads to a resistance increase, which depends on the adsorption temperature and on the conditions of preparing the material: several ionosorption energetic levels exist in the temperature range 40 – 300 °C. This study shows that temperatures higher than 150 °C should be preferred if zinc and germanium oxynitrides are to be used and reducing gas sensor materials.     

Mercury selenide stoichiometry and phase relations in the mercury-selenium system

The phase relations in the 0–65 at% Hg portion of the condensed mercury-selenium system were determined from liquidus temperatures to 250°C by evacuated silica tube experiments in which vapor is always a phase. Stoichiometric HgSe melts at 795 ± 2°C whereas Hg_0.51Se_0.49 melts at 797 ± 2°C and Hg_0.49Se_0.51 melts at 793 ± 2°C. In the HgSeSe portion of the system a monotectic exists at 683 ± 3°C and 71.5 at% Se and a liquid immiscibility field at this temperature extends from 71.5 to 85.5 at% Se. The presence of HgSe depresses the melting temperature of Se by about 8°C. An eutectic exists between HgSe and Se at 208°C and a composition of more than 99.95 at% Se. In the HgHgSe portion of the system a monotectic exists at 708 ± 3°C and about 25 at% Se. The solubility of Hg in HgSe was found to exceed stoichiometry by 1.11 ± 0.25 at% at 650°C whereas the solubility of Se in HgSe exceeds stoichiometry by 0.75 ± 0.25 at% Se at the same temperature. All synthetic mercury selenides show the sphalerite type structure. The unit cell dimension of stoichiometric HgSe is a₀ = 6.080 ± 0.001 Å. Mercury selenide synthesized in equilibrium with liquid Se gives a₀ = 6.082 ± 0.001 Å and mercury selenide synthesized in equilibrium with Hg gives a₀ = 6.078 ± 0.001 Å.     

Thermally induced polymerization of isobutylene in the presence of SnCl4: Kinetic study of the polymerization and NMR structural investigation of low molecular weight products

The polymerization reactivity of isobutylene/SnCl₄ mixtures in the absence of polar solvent, was investigated in a temperature interval from −78 to 60 °C. The mixture is nonreactive below −20 °C but slow polymerization proceeds from −20 to 20 °C with the initial rate r₀ of the order 10⁻⁵ mol · l⁻¹ · s⁻¹. The rate of the process increases with increasing temperature up to ∼10⁻² mol · l⁻¹ · s⁻¹ at 60 °C. Logarithmic plots of r₀ and M̄_n versus 1/T exhibit a break in the range from 20 to 35 °C. Activation energy is positive with values E = 21.7 ± 4.2 kJ/mol in the temperature interval from −20 to 35 °C and E = 159.5 ± 4.2 kJ/mol in the interval from 35 to 60 °C. The values of activation enthalpy difference of molecular weights in these temperature intervals are ΔH_Mn = −12.7 ± 4.2 kJ/mol and −38.3 ± 4.2 kJ/mol, respectively. The polymerization proceeds quantitatively, the molecular weights of products are relatively high, M̄_n = 1500–2500 at 35 °C and about 600 at 60 °C. It is assumed that initiation proceeds via [isobutylene · SnCl₄] charge transfer complex which is thermally excited and gives isobutylene radical‐cations. Oxygen inhibits the polymerization from −20 to 20 °C. Possible role of traces of water at temperatures above 20 °C is discussed. It was verified by NMR analysis that only low molecular weight polyisobutylenes are formed with high contents of exo‐ terminal unsaturated structures. In addition to standard unsaturated groups, new structures were detected in the products. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1568–1579, 2000     

Dilatometry and high temperature x-ray diffractometry study of LaCrO<Subscript>3</Subscript> prepared using microwave heating

The phase transitions in the LaCrO₃ were studied using bulk dilatometry and high temperature X-ray diffractometry from room temperature to 1050 and 1200°C, respectively. LaCrO₃ was prepared at 500°C from oxalate precursor employing microwave heating technique. Bulk shrinkage measurements on LaCrO₃ pellets were carried out using dilatometer designed and fabricated in our own laboratory. Dilatometric curves of LaCrO₃ showed two peaks in ΔL/L vs. temperature curves in the range 200–400 and 800–1000°C, respectively. These phase transitions have been confirmed using high temperature X-ray diffractometry. The role of simple technique like bulk dilatometry in detecting and monitoring the polymorphic transformations in solids is discussed for lanthanum chromates.     

Experimental Evidence for a Calix[4]arene-Proton Complex

From extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium H⁺(aq) + 1 ·Na⁺(nb) ⇆ 1 ·H⁺(nb) + Na⁺(aq) taking place in the two-phase water-nitrobenzene system (1 = p-tert-butylcalix[4]arene-tetrakis(N, N-diethylacetamide); aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log K _ex(H⁺, 1 ·Na⁺) = −1.4 ± 0.1. Further, the stability constant of the p-tert-butylcalix[4]arene-tetrakis(N,N-diethylacetamide)-H⁺ complex in water saturated nitrobenzene was calculated for a temperature of 25°C as log β_nb(1 · H⁺) = 8.1 ± 0.1.     

Experimental Evidence for a Calix[4]arene-Proton Complex

Summary. From extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium H⁺(aq) + 1 ·Na⁺(nb) ⇆ 1 ·H⁺(nb) + Na⁺(aq) taking place in the two-phase water-nitrobenzene system (1 = p-tert-butylcalix[4]arene-tetrakis(N, N-diethylacetamide); aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log K _ex(H⁺, 1 ·Na⁺) = −1.4 ± 0.1. Further, the stability constant of the p-tert-butylcalix[4]arene-tetrakis(N,N-diethylacetamide)-H⁺ complex in water saturated nitrobenzene was calculated for a temperature of 25°C as log β_nb(1 · H⁺) = 8.1 ± 0.1.