Yuji Miyahara

An integrated chemical sensor with multiple ion and gas sensors

Abstract An integrated chemical sensor with multiple ion and gas sensors, composed of four ISFETs (pH, Na + , K + and Cl − ) and two gas sensors ( P O 2 and P CO 2 ) on a 4 mm × 4 mm chip, is realized using semiconductor processing. The ISFETs are based on an Si 3 N 4 -gate ISFET, and use polymeric membrane except for the pH ISFET. The P O 2 sensor is a miniaturized Clark-type sensor, consisting of a Pt cathode and Ag/AgCl anode patterned by the lift-off process. The P CO 2 sensor is a miniaturized Severinghaus-type sensor using a pH ISFET. All of the ISFETs show sensitivities over 50 mV/decade, and a linear range between 1 × 10 −4 and 5 × 10 −1 mol/l. The sensitivities of the P O 2 and P CO 2 sensors are 0.35 nA/mmHg and 42 mV/decade, respectively, and their response times are 30 s and 1 min, respectively. The integrated chemical sensor with multiple ion and gas sensors could be used for clinical analysis.

The Suitability of Ta2O5 as a Solid State Ion-Sensitive Membrane

Ta2O5 films were used as ion-sensitive membranes of a solid state H+ ion sensor. The responses of the Ta2O5 films to H+ ions were characterized by utilizing 2 kinds of solid state devices: a LIS cell and an n-channel ISFET. Ta2O5 with different electrical and optical properties and crystalline structures were applied to both devices for an inspection of the relation between those properties and ion-sensitive properties. No substantial influence of the electrical properties of the films was found on the ion-sensitive properties. A crystalline transformation of the Ta2O5 film from an amorphous to a polycrystalline state by thermal annealing did not immediately effect the ion-sensitive properties however, aging tests showed it drastically reduced the film lifetime.

Urea sensor based on an ammonium-ion-sensitive field-effect transistor

Abstract A urea sensor based on an ammonium-ion-sensitive field-effect transistor has been realized in combination with an immobilized urease membrane. The effect of buffer concentrations on the response characteristics of the sensor is investigated. The lower detection limit, as given by the calibration curve, is strongly affected by the concentrations of potassium and sodium ions, while its slope in the appropriate buffer solution is independent of the buffer concentration in a limited urea concentration range. Although the slope in physiological saline solution is only 18 mV/dec, the dynamic range of the sensor covers the physiological range of urea in blood. The small slope and the narrow dynamic range are found to be due to poor selectivity of the ammonium-ion-selective membrane over sodium and potassium ions. It is, therefore, possible to improve the sensor response characteristics by improving the selectivity of the ammonium-ion-selective membrane.

Infrared ATR spectroscopy of substrates in aqueous solution using cryoenrichment and its application in enzyme-activity assays

Assays of enzyme activity in aqueous solutions were carried out with the use of the cryoenrichment method for infrared spectroscopy. A calibration method that used partial least-squares (PLS) for the measurement of enzyme activity was investigated. In this method, the enzyme activity was estimated by measuring the change in the concentration of a substrate or a product based on enzyme catalysis using the cryoenrichment method for infrared spectroscopy. The correlation coefficients between the activity levels of lactate dehydrogenase, amylase, and creatine kinase and the concentration changes of the substrate or the product were over 0.93. However, the correlation coefficient for alkaline phosphatase was only 0.78. Our findings from this study confirm that enzyme activity can be measured by infrared spectroscopy.

Shift and drift of electromotive forces of solid-state electrodes with ion-selective liquid membranes

The behavior of electromotive forces (EMFs) of solid-state ion sensors, in which the interface between the ion-selective liquid membrane and the silver-silver chloride electrode is modified with a hydrophilic intermediate layer containing various concentrations and various kinds of electrolyte salts, are described in this study. The EMF of this sensor is significantly dependent on the concentrations and kinds of electrolyte salts in the intermediate layer. The solid-state ion sensor shows a stable EMF only when the intermediate layer contains the primary ions and chloride ions. This indicates that an efficient ion exchange process is necessary at all interfaces involved, including a thin water layer, for a stable EMF of the solid-state ion sensor. The resistance measurement shows that mechanical deterioration of the ion-selective membranes in the solid-state ion sensor with the optimized intermediate layer does not take place due to the osmolality difference as long as the ion-selective membrane adheres to the sensor body tightly. The long term stability of the solid-state ion sensor with the optimized intermediate layer was found to be sufficient for practical use.

Long-life planar oxygen sensor

Abstract A planar amperometric oxygen sensor has been developed using a printing method for an Ag anode and a four-layered structure for an electrolyte solution. The sensor consists of four glass substrates stuck together by epoxy resin. A Pt cathode and an Ag anode are deposited on one of these glass substrates by r.f. sputtering and by printing, respectively. An internal electrolyte solution is enclosed in the structure and sealed off by an oxygen-permeable membrane. A linear relationship is obtained between the reduction current and the partial pressure of oxygen in the range 0–600 mmHg. The current at an oxygen pressure of 100 mmHg is stable for more than 2000 h. The amount of Ag anode patterned by the printing method is found to be sufficient for continuous long-term use. Based on methods and structures similar to those described in this paper, it should be possible to fabricate miniaturized oxygen sensors and biosensors.

Highly Sensitive Biochemical Analysis Using Low-Temperature Infrared Spectroscopy Measurements

A sensitive infrared spectroscopic analysis of biochemical components in an aqueous solution is described. The infrared spectrum of an aqueous solution containing glucose, urea, and creatinine was measured at −4.7 °C by Fourier transform infrared spectroscopy (FT-IR) with an attenuated total reflection (ATR) crystal. The infrared absorption bands of these components increased by about 100 times at −4.7 °C as compared with those measured at 22 °C. This increase in the infrared absorption bands was found to occur because of segregation of the components toward the surface of the ATR crystal caused by solidification of the sample solution. The creatinine concentration in an aqueous solution, prepared in the physiological range of human blood, was also estimated at −4.7 and 22 °C by using the partial least-squares (PLS) method. The correlation coefficient between the predicted concentrations by PLS and the prepared concentrations was 0.95 at −4.7 °C, but was 0.07 at 22 °C. Thus, the precision of the determination of creatinine was remarkably improved by using the low-temperature measurement. Index Headings: Biochemical analysis; Low-temperature infrared spectroscopy; Solidification.

Surface Modification and Hybridization on a Thermal Gradient DNA Chip

We developed a method for attaching oligonucleotide (ON) probes to the silicon nitride surface of a thermal gradient DNA chip. We verified that aminosilane and poly-lysine were effective in generating reactive surface amino groups, and phenyl-diisothiocyanate (PDC) was effective to link amino modified ON to the chip surface. We used the chip to detect single-base changes by allele-specific ON hybridization.

Thermal Gradient DNA Chip

We have developed a new DNA chip that allows the temperature of each DNA probe to be controlled independently and set to an optimum value. By simulation, a thermal gradient is found to be established in the SiO2 membrane on the chip. We fabricated the prototype chip and evaluated the fundamental characteristics of the chip. The temperature-sensing characteristic is almost linear, so the Si-islands’ temperatures can be detected and controlled by using the simple function of the pi-junction’s voltage. With the proposed structure, an Si-island can effectively be thermally isolated from the neighboring islands. Using this new DNA chip, we can arrange the appropriate DNA probes depending on the melting temperature and hybridization between a target DNA and carry it out in the optimum condition.

Highly Sensitive Measurement Of Biochemical Substances Based On ATR/FT-IR Technique

Low temperature measurement of infrared spectra was proposed in the present study for highly sensitive determination of biochemical substances in aqueous solutions. Infrared absorption by glucose was enhanced more than tenfold compared with that at room temperature by lowering the temperature to about -20 OC. The proposed method offers a possibility for quantitative analyses of biochemical substances with high sensitivity based on the ATR/FT-IR technique.