KR100204410B1 - Composite for forming sensing membrane and solid ion sensor made of it - Google Patents

Abstract

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solid ion sensor, and in particular, a solid ion having an ion sensing membrane having an ion sensing characteristic almost equivalent to that of a conventional conventional electrode type ion sensor and having excellent adhesion to a metal electrode surface. Relates to a sensor.

The solid ion sensor of the present invention comprises a metal electrode; And an ion sensing membrane formed of a composition of 68.5 to 99.5% by weight of silicone rubber, 5 to 30% by weight of a plasticizer and 0.5 to 1.5% by weight of an ion-selective material. The present invention also provides a solid state ion sensor and a solid state integrated ion sensor composed of a transistor or an electronic circuit formed on the same solid substrate as the ion sensor and electrically coupled with the ion sensor. The ion sensor of the present invention can be used as a medical device for measuring the concentration of sodium, potassium, calcium or chloride ion in blood or serum for clinical examination.

Description

Solid ion sensor comprising a composition for forming an ion sensing membrane and an ion sensing membrane

1 is a cross-sectional view showing a conventional ion sensor.

1a is a cross-sectional view of an electrode type ion sensor,

1B is a cross-sectional view of a solid ion sensor. FIG. 2 is a block diagram of a system having a solid ion sensor of the present invention for measuring the concentration of ions in blood.

3 to 6 show the ion response characteristics of an ion selective polymer membrane formed from a composition according to the present invention as a function of output voltage (mV) over time (seconds) in comparison with conventional PVC type ion selective polymer membranes.

7A to 7D show correlations of sodium, potassium, calcium and chloride ion concentrations in serum measured using an ion sensor according to the present invention with those obtained using Ciba-Corning BGA 288. .

8a to 7d are graphs showing the change in the sensitivity gradient (mV / decade) with respect to the change in the addition ratio of the plasticizer in the sodium, potassium, calcium and chloride ion selective film formed of the composition according to the present invention.

* Explanation of symbols for main parts of the drawings

10 electrode body 20 ion sensing membrane fixture

30: internal reference electrode (Ag / AgC1) 30: internal reference solution

50: ion detection membrane 60: metal electrode

70: insulating film 80: substrate

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solid ion sensor, and more particularly, to an ion sensing membrane having an ion sensing characteristic almost equivalent to that of a conventional ion sensor and having an excellent adhesion to a solid electrode surface. A solid ion sensor having properties particularly suitable for use as a medical analyzer.

In general, ion sensing membranes are chemicals capable of selectively binding to specific ions (ionophores) and plasticizers to maintain a solid liquid structure for the polymer membranes, anions or cations in the polymer membranes. A lipophilic additive that provides a site and an appropriate polymer matrix are dissolved in an organic solvent in a proportion and then dried. An example of the use of such an ion sensing membrane is shown in FIG. 1, which is fixed to the electrode body as shown in FIG. 1a, and is referred to as a conventional electrode type ion sensor. do. In FIG. 1A, the ion sensing membrane is shown by a reference numeral 50, where 10 is an electrode body, 20 is an ion sensing membrane fixture, 30 is an internal electrode, and 40 is an internal reference electrode. Indicates. Further, in FIG. 1B showing a solid ion sensor, an ion sensing film is shown by reference numeral 50, where 60 is a metal electrode, 70 is an insulating film, and 80 is a semiconductor substrate. It is shown.

On the other hand, in recent years, according to the development of semiconductor technology and the demand for miniaturization and low cost of the ion sensor, interest in the solid-state ion sensor as shown in FIG. There is an urgent need for an ion sensing membrane. Generally widely used as a support for an ion sensing membrane for forming on a metal electrode of a solid ion sensor is a PVC material having excellent electrical response properties. However, when the ion-sensing membrane with PVC as a support is applied to a solid-state sensor, the adhesion of PVC to the solid surface is extremely weak, which causes problems in sensing characteristics, lifespan, and productivity due to instability of the adhesive surface, especially in aqueous solution. When used, there was a problem that it is difficult to endure several hours. In order to overcome this problem of PVC ion sensing membranes, attempts have been made to form ion sensing membranes on metal electrodes using adhesive polymers such as silicone rubber and polyurethane. It was inferior to the results obtained at all. Among them, in particular, silicone rubber (SR) has a high electrical resistivity, so the noise appeared in the detection characteristics, and its practicality was questioned. In addition, although 10% by weight of CN (Cyanide) -induced SR was mixed in order to lower the electrical resistivity, the sensing characteristics thereof were also far less than the ion sensing characteristics of the PVC ion sensing membrane.

In order to solve such a conventional problem, the inventor of the present invention has conducted a number of studies and experiments, through which a certain amount of plasticizer is mixed with silicone rubber and used as a support for a solid ion sensing membrane, The present invention has been accomplished by discovering that the adhesive property is excellent while the sensing property is almost equivalent to that of the PVC ion detecting film.

Accordingly, the primary object of the present invention, which is devised to solve the conventional problems as described above, is, when formed on an ion sensing film and used on a metal electrode surface, while maintaining the sensing characteristics of a conventional ion sensor at least intact. Provides a composition for forming an ion sensing membrane of a solid-type ion sensor that is excellent in adhesion to the surface of the metal electrode to improve the life and reliability of the sensor, and also to meet the demand for improved productivity and cost reduction due to miniaturization It's there.

Further, another object of the present invention is to provide a solid ion sensor having an ion sensing membrane formed as the composition on a metal electrode surface. In order to achieve the above object, the present invention in the first embodiment, dealcohol and deacetic acid-type silicone rubber 68.5% by weight to 94.5% by weight; It provides a composition for forming an ion sensing film of a solid ion sensor, characterized in that consisting of 5 to 30% by weight of a plasticizer and 0.5 to 1.5% by weight of an ion selective material.

On the other hand, in the second embodiment, the present invention is a metal electrode; Provided is a solid ion sensor comprising an ion sensing membrane made of a composition of dealcohol and deacetic acid type silicone rubber 68.5 to 99.5% by weight, a plasticizer 5 to 30% by weight, and an ion-selective material 0.5 to 1.5% by weight on the metal electrode.

Further, the present invention, in the third embodiment, the metal electrode; An ion sensing membrane composed of a composition of dealcohol and deacetic acid-type silicone rubber 68.5 to 99.5% by weight, plasticizer 5 to 30% by weight, and 0.5 to 1.5% by weight of an ion-selective material, arranged to adhere to the working site of the metal electrode; It provides a solid ion sensor consisting of an insulating film arranged so that portions other than the working portion of the metal electrode can be electrically insulated from the solution to be measured. And, as a fourth embodiment, the present invention provides an electrically insulating support member; A metal electrode supported by the insulating support member; Dealcohol and deacetic acid-type silicone rubber 68.5 ~ 99.5% by weight of a portion surrounding the metal electrode in an adhesive state; An ion sensing membrane comprising a composition of 5 to 30% by weight of a plasticizer and 0.5 to 1.5% by weight of an ion selective material; In order to separate the other part of the metal electrode from the solution to be measured, a solid ion sensor including an insulating film coated on the other part of the metal electrode is provided.

In a fifth embodiment of the present invention, there is provided an electrode comprising an ion sensing field effect transistor (ISFET); It is arranged to adhere to the surface of the gate insulating film of the ion-sensing field effect transistor, the ion consisting of the composition of the de-alcohol and deacetic acid silicone rubber 68.5 ~ 99.5% by weight, the plasticizer 5-30% by weight and the ion-selective material 0.5-1.5% by weight Provided is an ion sensor composed of a sensing membrane.

In the above embodiments according to the present invention, the components and amounts of the plasticizer used to form the ion sensing membrane are very important for the present invention. Plasticizers that can be used in the present invention are preferably alkyl adipates and alkyl sebacates and more preferably bis (2-ethylhexyl) adipate, bis- (1-butyl pentyl) adipate, bis (2-ethylhexyl ) Sebacate, and dibutyl sebacate. In addition, the plasticizer should be used in the range of 5 to 30% by weight, which is less than 5% by weight of the electrical conductivity of the formed ion-sensing membrane is not sufficient, when used in excess of 30% by weight of the metal electrode of the ion-sensing membrane This is because the adhesion to the surface becomes poor.

The solid ion sensor according to the present invention can be used as a medical device for measuring the concentration of sodium ions, potassium ions, calcium ions or chloride ions in blood or serum, especially for clinical examination. Examples of calcium ion selective materials that may be added to the ion-sensing film-forming composition for measuring calcium ion concentration in blood or serum include (-)-(R, R) -N, N '-[bis (11-e). Oxycarbonyl) undecyl] -N / N ',-4,5-detramethyl-3,6-dioctane diamide; N, N, N ', N'-tetracyclohexyl-3-oxapentanediamide; And N, N'-dicyclohexyl-N, N'-dioctadecyl-3-oxapentanediamide. Further, 5,10,15,20-tetrapentyl-21H, 23H-porphine manganese (III) chloride is preferable for use as a chloride ion selective material, and ballinomycin (PV) is preferred for use as a potassium ion selective material. Valinomycin; Molecular Formula: C ₅₄ H ₉₀ N ₆ O ₁₈ ). As the sodium ion selective material, N, N ', N-triheptyl-N, N', N-triethyl-4,4'4-propylidinetris (3-oxabutylamide) may be preferably used. ; N, N'-dibenzyl-N, N'-diphenyl-1,2-phenylenedioxydiacetamide; N, N, N ', N'-tetracyclohexyl-1,2-phenylenedioxydiacetamide; 4-octadecanoyloxymethyl-N, N, N'N'-tetracyclohexyl- (1,2-phenylenedioxydiacetamide; and bis [(12-crown-4) methyl] dodecyl methylmalonate In the second embodiment of the present invention, the metal electrode is preferably a structure called CWE (Coated Wire Electrode), or a plate type electrode, on which an ion sensing film is coated.

It is preferable that the insulating film with respect to the metal electrode in the said 3rd, 4th and 5th embodiment which concerns on this invention is an oxide film or a nitride film normally formed at the time of manufacture of a semiconductor element.

The solid state ion sensor in the second, third, fourth, and fifth embodiments described above is preferably provided on a semiconductor substrate such as a silicon chip.

On the other hand, forming the ion sensing film on the metal electrode using the composition for forming an ion sensing film according to the present invention can be achieved according to a conventional method. For example, first dissolve the silicone rubber in a tetrahydrofuran (THF) solvent in a container and dissolve the ion-selective material for each measured ion in a tetrahydrofuran solvent in another separate container. Thereafter, the silicone rubber solution and the ion-selective material solution are mixed and stirred for about 30 minutes, and then a plasticizer or other additive is added thereto, mixed and stirred for about 1 hour. Subsequently, the mixture is cast on a metal electrode and molded, and then dried at room temperature for about 72 hours to prepare a solid-state ion sensor.

The solid state ion sensor of the present invention can be installed in a conventional system as shown in FIG. 2 to measure the electrolyte concentration in blood.

2 is a block diagram of a system for measuring ion concentration in blood.

In FIG. 2, the detection unit 17 for detecting the change amount of K, Na, Ca, and C1 ions in the blood and the temperature change in the blood first performs two-point calibration (standardization of measurement points) for accurate detection. This is to determine the change in voltage which is proportional to the change in molarity of the K, Na, Ca and C1 ions per liter.

Since the variation of the variation range is different for each sensor, the correlation between the variation of the measured ion and the output voltage is set before the measurement of the sample to be measured. Prior to the two-point calibration, the pipe and the detector 17 are cleaned, which is a motor for supplying the cleaning liquid of the wash valve while the wash valve 21d is opened and the bubble valve 21e is turned on and off every two seconds. To drive. This method is to improve the cleaning power by blowing air between the cleaning solution supplied to clean the pipe and the detection unit 17. In the calibration process, the voltage minimum is supplied to the detection unit 17 at a predetermined pressure at a predetermined pressure in a state in which only the first buffer valve 21b of the valve unit 21 is opened and the rest is locked, thereby verifying the voltage at that time. do. This verification adjusts and corrects the PC 12 so that the lowest voltage becomes 1.2V when supplying the concentration of the feed solution at 2.0mmo1 / L.

At this time, the bubble detection unit 18 judges the presence or absence of a solution, turns on when there is a solution, and stops driving the pump. After adjusting the minimum voltage, the first buffer valve 21b is locked, and the wash valve 21d is opened to wash and discharge the first calibration solution remaining in the pipe. The washing operation at this time is the same as the washing operation of the previous step. When the cleaning is completed in the above process, the wash valve 21e is closed, and the second buffer valve 21c is opened to supply a second calibration solution having a concentration of 4.80 mmol / L to the detection unit 17 to detect the voltage. Is corrected by adjusting it to 2V on the PC 12. At this time, the adjustment process is turned on after the second buffer valve 21C and the driving motor of the second buffer valve are turned on, and the bubble amplification unit is operated for 3 seconds. After the above process, the same cleaning process as in the previous step is performed, and then the first buffer valve 21A is opened to repeat the first buffer valve operation once, and then the same cleaning process as described above is performed once. .

After adjusting the sensitivity of the sensor to the above process, the operation for detecting the ion change of the blood is performed, this process by opening the sampling valve 21a, by driving a motor for supplying a sample solution of blood Blood is sent to the detection unit 17. In this case, the bubble component in the solution is also detected and the bubble amplification unit for amplifying the detected signal is turned on for 3 seconds and then stopped.

The detection unit that detects the ion change amount and the temperature change of the specimen solution by the sampling process outputs the result to the analog amplifier 16. The analog amplifier amplifies the input detection analog signal to a predetermined size and outputs it to the multiplexer 15. The multiplexer selects a terminal corresponding to the input signal and outputs the signal input from the analog amplifier 16 to the analog / digital converter 14. The analog / digital converter converts the input analog signal into a digital signal and outputs the digital signal to the PC 12. The PC 12 outputs the input result to the display unit 13 as an image displayable signal. Shows the result of detection according to this signal as a numerical value on the screen. The process of displaying the above-described detection result on the display unit is similarly applied to the two-point calibration process mentioned above, and the adjustment is performed as the key input unit 11 as an input device. In addition, by selectively opening and closing the valve of the valve unit and supplying the corresponding solution through the selection valve, the PC 12 displays the image displayed on the display unit and inputs the adjustment contents to the PC 12 from the key input unit 11. The control signal is output to the analog / digital conversion screw 14, and the analog / digital conversion section converts the input value into a digital signal and outputs it to the multiplexer 15 to select a terminal to be adjusted, and then selects the selection line. Input to the adjusting unit 19 through. The controller 19 opens the valve corresponding to the selected line and adjusts the driving time of the motor, so as to perform the adjustment for detecting the required solution.

In addition, the control unit 19 controls the valve unit 21 and the peristaltic pump 22, and also the signal received from the bubble detector 23, the bubble amplifier 18 for detecting the bubble component in the solution PC ( 12) acts to deliver.

Hereinafter, the present invention will be described in more detail based on the following examples.

Example 1

Adhesion Test of Ion Sensing Membrane to Metal Electrode Surface

87.0 wt% of dealcohol and deacetic acid type silicone rubber, 12.0 wt% of bis (2-ethylhexyl) adipate as a plasticizer and 1 wt% of N, N ', N-triheptyl-N, N' as an ion-selective material The composition according to the present invention consisting of, N-trimethyl-4,4 ', 4-propylidinetris (3-oxabutylamide) was cast on each of 30 Ag / AgC1 metal electrode surfaces and cured to form an ion sensing film. did. Likewise, for comparison, PVC was cast on each of 30 Ag / AgC1 metal electrode surfaces and then cured to form an ion sensing film.

Thereafter, the scotch tape was pressed onto the surface of the cured ion sensing membrane, and then the scotch tape was pulled from the membranes. In this test, all 30 ion sensing membranes formed of the composition according to the present invention consisting of silicone rubber and plasticizer were all preserved on the metal electrode surface, while the ion sensing membrane formed of PVC material was completely removed from the metal electrode surface. .

On the other hand, in order to test the life of the ion sensor when used in an aqueous solution, the composition and the PVC composition according to the present invention were coated on each of 24 silver electrode surfaces and cured, and then the silver electrodes were placed in water for 6 hours. I soaked it. Thereafter, the silver electrodes were washed with running water, and the silver electrode coated with the composition of the present invention retained the sensing film as it was, whereas the PVC coated silver electrode was removed from 18 PVC sensing films.

Although the results of these tests are not quantitatively rigorous test results, it is said that the superiority of the sensing film prepared according to the present invention is revealed in terms of the adhesion property of the sensing film which is known to have the most important effect on the life of the solid-state chemical sensor. Can be.

The test results are summarized in Table 1 below.

Example 2

Response test for sodium ions

To test the ion sensing properties of the ion sensing membrane formed from the composition according to the invention, 87% by weight of silicone rubber as support, 12% by weight of bis (2-ethylhexyl) adipate as plasticizer and 1% as sodium ion selective material % Of N, N, N ', N-tetracyclohexyl-1,2-phenylenedioxyacetamide (composition of the present invention) was dissolved in tetrahydrofuran organic solvent according to a conventional ion sensing membrane formation method. It is mixed, molded and cured to form an ion sensing membrane. Thereafter, the formed ion sensing membrane was provided in an electrode type ion sensor as shown in FIG. 1A of the accompanying drawings. Further, for comparison, an electrode type ion sensor having a PVC membrane was prepared as conventionally used.

Na in the same blood sample using the above two electrode type ion sensors The sensitivity to ions was measured in a conventional manner. At this time, for every 100 seconds, the concentration of sodium is Increased by M.

Sensing characteristics obtained by an electrode type sensor with an ion sensing membrane formed from the composition according to the present invention are shown graphically in FIG. 3A as potential difference (mV) over time (seconds) and applied to an electrode type sensor with a PVC ion sensing membrane. The detection characteristic obtained is shown in b. As can be seen from the two graphs of FIGS. 3A and 3B, the ion sensing membrane formed of the composition of the present invention has almost the same sensitivity as the PVC ion sensing membrane conventionally recognized as having excellent sensitivity. Thus, this is a groundbreaking reversal of the conventional view that the ion sensing membrane based on the silicone rubber having excellent adhesion as demonstrated in Example 1 above cannot be used as an ion sensing membrane of the ion sensor because of its poor sensitivity. It is a discovery. Thus, the ion sensing membrane formed from the composition of the present invention based on silicone rubber is Na as demonstrated in this example. Although the ion-sensitization properties are almost equivalent to the PVC membranes used as conventional ion-sensing membranes, the adhesion is so excellent that it does not degrade the wjsrl chemical properties of the sensor. It is implied that the practical use of the solid state ion sensor is possible when it is provided in the metal electrode of the solid state ion sensor for measuring the ion concentration.

Example 3

Responsiveness test for potassium ion

Same procedure as described in Example 2, except that 12.0% by weight of bis (2-ethylhexyl) sebacate is used as the plasticizer and 1% by weight of valinomyclin is used as the potassium ion-selective material. Repeat K in the blood The data obtained by measuring the sensitivity to ions is shown graphically in FIG. In FIG. 4a, a graph of the response characteristics measured using an electrode sensor having an ion sensing membrane formed of the composition according to the present invention, and FIG. 4b is the sensitivity characteristic measured using an electrode sensor having a PVC ion sensing membrane. Is the graph for. As can be seen from Figures 4a and b, the potential difference (mV) over time (seconds) shown as two graphs is similar to each other, so It can be seen that the ion-sensing membrane formed from the composition of the present invention and the conventional PVC ion-sensing membrane are comparable in sensitizing properties to ions. Thus, this means that the ion sensing membrane formed of the composition according to the invention is K Responsiveness to ions K almost equal to PVC membrane When formed on the metal electrode of the solid-state ion sensor for measuring the ion concentration, the adhesion of the solid-state ion sensor with the ion sensing membrane of the present invention is excellent because the adhesion is superior to that of the PVC membrane and does not degrade the electrochemical properties of the ion sensor. It suggests that practical use is possible.

Example 4

Responsiveness test for calcium ions

0.87% by weight of N, N, N ', N-tetracyclohexyl-3-oxapentanediamide is used as the calcium ion selective material and 0.43% by weight of a mixture of tetrakis (4-chlorophenyl) borate as an additive thereto. Ca in the blood was repeated by repeating the same procedure as described in Example 2 except that Data obtained by measuring the sensitivity to ions is shown graphically in FIG. Figure 5a is a graph of the response characteristics obtained by using an electrode-type ion sensor with an ion sensing membrane formed as a seed of the present invention, Figure b is a response characteristic obtained by using an electrode-type ion sensor having an ion sensing membrane of PVC material Is the graph for. As can be seen from FIGS. 5a and b, since the potential difference with time and concentration change of the two graphs is similar to each other, Ca It is evident that the ion-sensing membrane formed from the composition of the present invention and the conventional ion-sensing membrane made of PVC material are comparable in ion-sensitive properties. Therefore, this means that the ion sensing membrane formed of the composition of the present invention is Ca Ca in the blood while the sensitization characteristics of ions are almost equal to that of PVC When formed on the metal electrode of the solid-type ion sensor for measuring the ion concentration, its adhesion is significantly superior to that of the PVC membrane and does not degrade the electrochemical properties of the ion sensor. It suggests that the practical use of the solid state ion sensor is possible.

Example 5

Sensitivity test for chloride ion

Except that 1% by weight of 5,10,15,20-tetraphenyl-21H, 23H-phosphine manganese (III) chloride was used as the chloride ion selective material and 12.0% by weight of ortho-nitrophenyloctyl ether was used as the plasticizer. Then, repeat the same procedure as described in Example 2 to repeat C1 in the blood. The data obtained by measuring the sensitivity to ions is shown graphically in FIG. Figure 6a is a graph of the response characteristics obtained using an electrode type ion sensor with an ion sensing membrane formed of the composition of the present invention, Figure b is a response to the characteristics obtained using an electrode type ion sensor having a PVC ion selective polymer membrane It is a graph.

As can be seen from FIGS. 6a and b, the potential difference with time and concentration change in the two graphs is similar, so C1 It is evident that the ion-sensing membrane formed from the composition of the present invention and the conventional PVC ion-sensing membrane in terms of sensitization to ions are comparable to each other.

Therefore, this means that the ion sensing membrane formed of the composition of the present invention is C1. Ion-responsiveness is nearly equal to that of PVC membranes, while C1 It does not deteriorate the electrochemical properties of the solid-state ion sensor for measuring ions, suggesting that miniaturization of the solid-state ion sensor is practical.

Example 6

Electrolyte ions present in human blood, eg Na , K , Ca , C1 Data obtained by detecting the concentration of is essential for the diagnosis and treatment of patients. However, although the analysis of the electrolyte using an extremely expensive electrode type ion sensor, the present invention has developed a very low-cost solid-type ion sensor for detecting the concentration of the electrolyte ions. Therefore, in this embodiment, an experiment was performed to confirm the practicality of the solid-type ion sensor of the present invention by evaluating the clinical test analysis ability of the solid-type ion sensor according to the present invention in comparison with the electrode-type ion sensor.

Experimental conditions are as follows.

1. Sample: human serum

2. Comparator: Ciba-Corning BGA 288

3. Measurement Item: Na , K , C1 , Ca

4. Experimental method: Correlation analysis according to NCCLS (National Committe for Clinical Latoratory Standards, USA)

5. Basic specification of ion sensor according to the present invention

① Electrode type: Solid state sensor (Equipped with ion sensing membrane of the component and composition described in Example 2, 3, 4, and 5, respectively.

② Calibrator: specific ion concentration control solution based on HEPES buffer

③ Reference electrode: Ordinary double junction electrode (Orion A; / AgC1 electrode)

④ Sensor Cartridge: Single Flow Type

⑤ Acquisition of data: solid state ion sensor ⇒ noise filter ⇒ solid state ion sensor detection circuit ⇒ LCD display. Continuous detection, no average, more than 95% of end-point

First of all, the conventional sensor used for comparison is a precision test for repeatedly measuring ten samples of three different concentrations every 30 minutes in order to determine the reliability and suitability of the Ciba-Corning BGA 288. ) Was performed. The reagents used in this test were Seronorm and Pathonorm from Nycomed. As a result. Na of Ciba-Corning BGA 288 , K , Ca , C1 The accuracy of the sensor was satisfactory in the CLLA specification. Therefore, the measurement result of Ciba-Corning BGA 288 was used as the reference value of the sample in the following correlation test.

For the correlation test, the specimens were supplied once every three days from the Seoul National University Hospital's Clinical Pathology Department and Emergency Laboratory.

Each specimen had already been supplied with the entire test tube centrifuged for measurement in the hospital, covered with parafilm for transport and stored in an ice box for transportation. The pH distribution range of the specimens reached was higher than pH7.7. ~ PH8, and the distribution range of the specimens used in each experiment is shown in Table 2 below.

The results measured by calibration with the above solution are shown graphically in Figs. 6A to 6B. At the bottom of each graph, each analysis value is shown. The statistical program used to calculate this analysis used SAS, which is widely used in hospitals, for clinical data statistics.

6a to d show a high correlation with the existing system for any of the ions, and the dispersion of the measured values is also good. Therefore, the clinical test analysis capability of the solid-state ion sensor having an ion sensing membrane formed from the composition according to the present invention is equivalent to that of the Ciba Corning BGA 288 satisfying the CLLA regulations, and thus the practicality of the solid-state ion sensor of the present invention. This proves to be excellent. This experiment was performed continuously by repeating the cleaning and calibration of the sensor every time a sample was measured, and there was no deterioration of the sensor at 50 to 60 blood measurements with one sensor. Therefore, this result shows that the solid ion sensor according to the present invention is an excellent sensor that can withstand a long time blood measurement. The results also show that ionic interference, another important sign of ion selective membranes, is small enough not to be a problem in the clinical domain.

Example 7

This example is presented to determine the preferred addition ratio of the plasticizer by measuring the potential difference sensitive slope (mV / decade) according to the change of the plasticizer addition ratio in the ion sensing membrane formed from the silicone rubber-based composition of the present invention. The experiment was carried out for 7 days on an aqueous solution with a metal electrode with ion sensing membranes formed by varying the amount of plasticizer, i.e., bis (2-ethylhexyl) adipate, in the range of 0 to 60% by weight. The measurements of potentiometric response were performed on the first day, two days, four days and seven days, respectively, and the results are shown graphically. The attached figures 7a to d show the above measurement results, and (a) is a graph showing the potential difference response slope according to the change of the addition ratio of the bis (2-ethylhexyl) adipate plasticizer in the sodium ion selective membrane. will be. In the a diagram, sodium formed by varying the addition ratio of the plasticizer within the range of 0 to 60% by weight on the first day (○), after 2 days (▽), after 4 days (*) and after 7 days (□), respectively. The potential difference response of the ion-selective membrane was measured and shown as a graph. On the first day, the linearity remained almost unchanged from the addition ratio of 5 wt% to 60 wt%, but from about 5 wt% to about 30 wt% after 2 days The slope of the response (mV / decade) is significantly reduced except for the range of plasticizer addition ratio. Therefore, it is implied that it is preferable to add the plasticizer in the range of 5% by weight to 30% by weight in view of the lifetime. In addition, the potentiometric response slopes (mV / decade) according to the change of the bis (2-ethylhexyl) adipate plasticizer addition ratio in the potassium, calcium and chloride ion selective films are shown in a, c and d degrees, respectively. Similarly in b, c, and d, there was almost no decrease in the response slope on the first day, but there was a sharp decrease in the response slope when it was outside the range of 5% by weight to 30% by weight. Therefore, it is proved that even in the case of potassium, calcium and chloride ion selective membranes, the plasticizer addition ratio of 5 to 30% by weight is preferable in consideration of the lifetime of the ion sensor.

As demonstrated through Examples 1 to 7 above, the solid ion sensor according to the present invention has excellent adhesion to the metal electrode surface of the ion sensing membrane while maintaining the detection characteristics of the conventional ion sensor, and thus, the solid ion sensor By fundamentally solving the problem that has hampered the practical use of the present invention, it has the effect of enabling the industrial use of the solid-state ion sensor. And, if the conventional electrode type ion sensor, which has the disadvantage of being bulky and expensive, is replaced by the solid-state ion sensor according to the present invention, the volume is about the size of a semiconductor chip and the price is incomparable with that of the conventional sensor due to the inherent mass productivity of the semiconductor. It is inexpensive enough. The miniaturization and inexpensiveness of the ion sensor thus enables the miniaturization and inexpensiveness of the ion measurement system, and also has the effect of imparting economic realities to applications that were not conceivable with conventional sensors, for example, disposable sensors.

In addition, in accordance with the present invention, the solid-state ion sensor using an ion-sensing membrane based on silicone rubber has excellent suitability for clinical and pathological applications, especially blood analysis, thereby miniaturizing and reducing the cost of medical examination devices including blood analyzers. It has the effect of enabling medical diagnosis.

Claims (7)

A composition for forming an ion-sensing membrane of a solid ion sensor, comprising 68.5 to 99.5% by weight of dealcohol and deacetic acid type silicone rubber, 5 to 30% by weight of a plasticizer, and 0.5 to 1.5% by weight of an ion selective material. The composition of claim 1 wherein the plasticizer is an alkyl adduct or alkyl sebacate. The plasticizer of claim 2 wherein the plasticizer is selected from the group consisting of bis (2-ethylhexyl) adipate, bis-1 (1-butylpentyl) adipate, bis (2-ethylhexyl) sebacate and dibutyl sebacate A composition, characterized in that. The ion-selective material of claim 1, wherein the ion-selective material is for selecting sodium ions, wherein N, N ', N-triheptyl-N, N', N-triheptyl-4,4'4-propylidinethiris (3-oxa Butylamide); TT, TT'-dibenzyl- tt, TT'-diphenyl-1,2-phenylenedioxydiacetamide; N, N, N'N'-tetracyclohexyl-1,2-phenylenedioxyacetamide; 4-octadecanoyloxymethyl-N, N, N'N'-terracyclohexyl-1,2-phenylenedioxydiacetamide; And bis [(12-crown-4) methyl] dodecyl methylmalonate. The composition of claim 1, wherein the ion selective material is ballinomycin for selecting potassium ions. The method of claim 1, wherein the ion-selective material is used to select calcium ions and is selected from (2-)-(R, R) -N, N '-[bis (11-ethoxycarbonyl) undecyl-N, N' -4.5 tetramethyl-3,6-dioctanediamide; N, N, N ', N'-tetracyclohexyl-3-oxapentanediamide; And N, N'-dicyclohexyl-N, N'-dioctadecyl-3-oxapentanediamide. The composition of claim 1, wherein the ion selective material is 5,10,15,20-tetrapentyl-21H, 23H-phosphine manganese (III) chloride for selecting chloride ions.