JPH0769291B2 - Anion selective electrode - Google Patents

Description

TECHNICAL FIELD The present invention relates to an anion-selective electrode, and particularly to a polymer-supporting membrane type suitable for use in measuring inorganic anions such as chloride ions in biological fluids. The anion-selective electrode of

[Conventional technology]

Conventionally, as anion-selective electrodes used for the analysis of anions in biological fluids, solid membrane electrodes composed of silver chloride and silver sulfide, or as a sensitive substance in a polymer supporting membrane such as polyvinyl chloride are used. A polymer-supported membrane-type electrode supporting an ion exchanger has been used. The former electrode has a problem that it is largely disturbed by halogen ions such as bromine ions and sulfide ions. On the other hand, the latter has a problem that it causes a measurement error due to interference of lipophilic ions and the like that are easily taken into the sensitive film of the electrode. Therefore, methods for improving the selectivity of the polymer-supported membrane type electrode have been tried. For example, according to the method described in JP-A-56-63246, tetraalkylammonium chloride, which is one of quaternary ammonium salts, is used as a sensitizer and a linear alcohol is used as a plasticizer. There is.

[Problems to be Solved by the Invention]

However, the anion-selective electrode according to the above-mentioned conventional technique has a problem that its performance may be deteriorated in a relatively short time by measuring a large number of control sera.

An object of the present invention is to provide an anion-selective electrode capable of maintaining the initial performance even after long-term use.

[Means for Solving the Problems]

The above object is to provide an anion-selective electrode having a sensitive membrane containing a quaternary ammonium salt or a quaternary phosphonium salt, which is an anion-sensitive substance, on a polymer support membrane, wherein the anion-sensitive substance is X ⁻ Anion is the following formula (1), where A is nitrogen or phosphorus. And R ₁ , R ₂ , R ₃ and R ₄ have the same carbon number n ₁ = 1 to 24
Group of compounds showing a normal or isoalkyl group, and R ₁ is a normal or isoalkyl group having a carbon number n ₂ = 1 to 20 and R ₂ , R ₃ and R ₄ have the same carbon number n ₃ = (n ₂ +1) ~ 24
And a mixture of at least one compound selected from the second group of compounds having a normal or isoalkyl group and having a low dielectric constant linear or branched aliphatic alcohol or a dielectric constant as a plasticizer. An anion-selective electrode having a sensitive membrane using an organic compound larger than a straight-chain or branched-chain aliphatic alcohol and optimizing their composition, and providing the anion-selective electrode is provided. This is accomplished by providing a biochemical component analyzer.

[Operation] The polymer-supporting membrane type anion-selective electrode is composed of a polymer material such as polyvinyl chloride as a base material, a plasticizer and a sensitive material. R ₁ in the formula (1) as a sensitive substance,
When a quaternary ammonium salt of the first group of compounds in which R ₂ , R ₃ , and R ₄ have the same carbon number n ₁ = 1 to 24 and an isoalkyl group is used, a long-chain alkyl group around a nitrogen atom is used. Since there are four groups, the nitrogen atom is less likely to be attacked by bulky anions such as hydrophilic hydrogen phosphate and hydrogen carbonate, and lipophilic hydrogen perchlorate. Therefore, when the quaternary ammonium salt of the first group of compounds is used as the sensitive substance, the anion-selective electrode has high selectivity without being disturbed by various bulky anions. However, the degree of dissociation of the quaternary ammonium salt of the first group of this compound is small,
Further, since the symmetry of the molecular structure is high, the surface activity is low and the orientation of the surface of the sensitive film to the oil-water interface is slightly low. Therefore, when the quaternary ammonium salt of the first group of the compounds is used alone, the function as the ion exchange site is contaminated with some component during the measurement and the performance is deteriorated.

The second group of compounds has a relatively large dissociation degree, has a low symmetry in the molecular structure, and thus has a high surface activity, and has a property that the orientation of the surface of the sensitive film with respect to the oil-water interface is relatively high. Therefore, the compound No. 2 which has the property of compensating for the defects of the compound No. 1
When the quaternary ammonium salt of the group coexists in the sensitive film,
It efficiently functions as an ion exchange site, promotes electrode response, increases slope sensitivity, reduces resistance, and maintains electrode performance for a long period of time.

In this way, the compound 2 group having an excellent function as an ion exchange site is mixed at an appropriate ratio with the compound 1 group having an excellent selectivity as a sensitive substance,
High selectivity and long-term electrode life can be obtained.

〔Example〕

 Examples of the present invention will be described below.

FIG. 1 is a vertical sectional view of an anion-selective electrode to which the present invention is applied. The electrode cylinder 1 contains an internal solution 2 containing 10 mmol / sodium chloride, and the internal solution 2 contains Ag.
The internal electrode 3 made of / AgCl is immersed. Electrode tube 1
An ion sensitive film 4 is formed at the end of the. The ion-sensitive membrane 4 contains a polymer material such as polyvinyl chloride,
The anion-sensitive substance and the plasticizer are blended so as to have appropriate weight concentrations.

In the present invention, a tetraalkylammonium salt is used as the quaternary ammonium salt belonging to the first group of compounds which are anion sensitive substances. As such a quaternary ammonium salt, a tetraalkylammonium salt having four alkyl groups having 10 to 24 carbon atoms such as a tetradodecyl ammonium salt, a tetracetyl ammonium salt, and a tetraoctadecyl ammonium salt is used. Further, as the quaternary ammonium salt belonging to the second group of compounds, hexadecyltrioctadecyammonium salt, butyltrioctadecylammonium salt, methyltrioctadecylammonium salt, ethyltrihexadecylammonium salt, methyltritetradecylammonium salt, etc. An ammonium salt having one alkyl group having 1 to 20 carbon atoms and three alkyl groups having more carbon atoms than those is used.

In the first embodiment of the present invention, chlorine ion is a target ion,
A chloride ion selective electrode was obtained by using tetraoctedecyl ammonium chloride as a quaternary ammonium salt belonging to the first group of compounds and hexadecyltrioctadecyl ammonium chloride as a quaternary ammonium salt belonging to a second group of compounds. 12 wt% of each of the above-mentioned sensitive materials,
3wt%, 25w of n-tetradecyl alcohol as a plasticizer
t%, n-tridecyl alcohol 5% by weight, o-nitrophenyl octyl ether 10% by weight, polyvinyl chloride as a polymer substance is weighed to be 45% by weight, and tetrahydrofuran as a solvent is added and mixed, if necessary. Accordingly, after heating and melting, the solvent was removed by evaporation to produce the ion sensitive film 4. This was punched out to an appropriate size according to the size of the electrode cylinder 1 in FIG. 1 and adhered to the end of the electrode cylinder 1.

Although the combination of n-tetradecyl alcohol and n-tridecyl alcohol, which are aliphatic alcohols having a low dielectric constant, is used as the plasticizer in the above-mentioned embodiments, the plasticizer is not limited to this. Among aliphatic alcohols having 10 to 40 carbon atoms, the carbon number is different by 1 or the melting point is 13
Combinations of two fatty alcohols that are within ° C give good results. From the viewpoint of responsiveness and selectivity as a chloride ion-selective electrode, it is appropriate that the total content of the two types of aliphatic alcohols having a low dielectric constant in the sensitive film is 15 to 50 wt%.

As the organic compound having a high dielectric constant, not only o-nitrophenyl octyl ether but also nitrobenzene and its derivatives (o, m, p-nitrotoluene, etc.) and acetophenone and its derivatives can be used. 15 wt% or less is appropriate.

The total content of the quaternary ammonium salt dispersed in the sensitive film is preferably 5 to 30 wt% in terms of responsiveness, selectivity and reduction of membrane impedance. Also, when another quaternary ammonium salt based on the present invention is used as a sensitive substance, the total content thereof is preferably 5 to 30 wt% for the above reason.

In the present invention, polyvinyl chloride was used as the polymer substance supporting the sensitive substance or the plasticizer, but it is not limited thereto, and other substances such as polycarbonate,
Silicon rubber and epoxy resin can also be used. By the way, when the content of the polymer substance in the sensitive film becomes 35 wt% or less due to the relationship with other compositions, the mechanical strength of the sensitive film becomes extremely weak. On the other hand, when the content of the polymer substance is 60 wt% or more, the membrane impedance becomes high and it becomes difficult to obtain stable electrode performance. Therefore, the content of the polymer substance is preferably 35 to 60 wt%.

In a second embodiment of the present invention, the fourth compound belonging to the first group of compounds
A chloride ion-selective electrode was obtained by using tetraoctedecyl ammonium chloride as a quaternary ammonium salt and butyltrioctadecyl ammonium chloride as a quaternary ammonium salt belonging to the second group of compounds. 12 wt% and 3 wt% of the above-mentioned sensitive substances, 28 wt% of n-tetradecyl alcohol and 2 w of n-tridecyl alcohol as plasticizers, respectively.
t%, 10 wt% of o-nitrophenyl octyl ether,
Polyvinyl chloride 45 wt% was used as the polymer substance. The method of manufacturing the sensitive film and the like are the same as those in the first embodiment. In this example, as the quaternary ammonium salt of the second group of compounds, one in which one of the carbon chains was a little shorter than butyl was used. In the case of using a sensitive substance having such a dissociation property and a slightly high surface activity, stable electrode characteristics can be obtained by adding about 2 wt% of n-tridecyl alcohol.

In the third embodiment of the present invention, the fourth compound belonging to the first group of compounds
A chloride ion selective electrode was obtained by using tetraoctadecyl ammonium chloride as a primary ammonium salt and methyltrioctadecyl ammonium chloride as a quaternary ammonium salt belonging to the second group of compounds. The above-mentioned sensitive substances are 12 wt% and 3 wt%, n-tetradecyl alcohol is 30 wt% as a plasticizer, o-nitrophenyl octyl ether is 10 wt%, and polyvinyl chloride is a polymer substance.
45 wt% was used. The method of manufacturing the sensitive film and the like are the same as those in the first embodiment. In this example, as the quaternary ammonium salt of the second group of compounds, one in which one of the carbon chains was extremely short was methyl was used. When such a sensitive substance having higher dissociation and surface activity is used, stable electrode characteristics can be obtained without adding n-tridecyl alcohol.

In a fourth embodiment of the present invention, a fourth compound belonging to the first group of compounds
A chloride ion selective electrode was obtained by using tetraoctadecyl ammonium chloride as the primary ammonium salt and ethyltrihexadecyl ammonium chloride as the quaternary ammonium salt belonging to the second group of compounds. 12 wt% and 3 wt% of the above-mentioned sensitive materials, 30 wt% of n-tetradecyl alcohol as a plasticizer, 10 wt% of o-nitrophenyl octyl ether, and 45 wt% of polyvinyl chloride as a polymer substance were used. The method of manufacturing the sensitive film and the like are the same as those in the first embodiment. This example is the fourth compound belonging to the second compound group.
The third embodiment differs from the third embodiment in that the length of the longer carbon chain of the primary ammonium salt is shortened from 18 to 16, and conversely the length of the shorter carbon chain is increased from 1 to 2.

In the fifth embodiment of the present invention, nitrate ions are the target ions,
Tetraoctadecyl ammonium nitrate was used as the quaternary ammonium salt belonging to the first group of compounds, and methyltritetradecyl ammonium nitrate was used as the quaternary ammonium salt belonging to the second group of compounds to obtain a nitrate ion-selective electrode. 5wt% of the above-mentioned sensitive materials, 1
0w%, 28w of n-tetradecyl alcohol as a plasticizer
t%, 2 wt% of n-tridecyl alcohol, 10 wt% of o-nitrophenyl octyl ether, and 45 wt% of polyvinyl chloride as a polymer substance. The method of manufacturing the sensitive film and the like are the same as those in the first embodiment. In this embodiment, the above formula (1) is used.
By using nitrate ion as the anion X ⁻ in the compound and increasing the content of the quaternary ammonium salt of the compound 2 group as compared with the quaternary ammonium salt of the compound 1 group,
An anion-selective electrode having high selectivity for nitrate ions can be obtained.

Next, a sixth embodiment of the present invention will be described. FIG. 2 is an example of a sectional view of the structure of a chloride ion selective field effect transistor to which the sensitive film of the present invention is applied. An n-type source 5 and a drain 6 are formed on a Si substrate 7, and a SiO ₂ film 8 and a Si ₃ N ₄ insulating film 9 are formed on the Si substrate 7. Next, the first of the present invention
After dissolving the film component having the same composition as that of the sensitive film in Example 1 in THF, it was dropped directly on the Si ₃ N ₄ film to evaporate THF to form the ion sensitive film 4. In this way, an anion-selective field effect transistor is formed. In this embodiment, the same composition as the sensitive film in the first embodiment is used, but of course, an ion sensitive film having another composition according to the present invention may be used.

Next, a biochemical component analyzer according to a seventh embodiment of the present invention will be described with reference to FIG. FIG. 3 is a block diagram of a biochemical component analyzer to which the present invention is applied. In this biochemical component analyzer, the anion-selective electrode 10 and the reference electrode 11 shown in the first embodiment of the present invention are held in a flow cell 12, a liquid sending device 13 and valves 14 and 15, a sampling mechanism. 16,
It comprises a measurement control device 17, a reference electrode solution 18, an internal standard solution 19, an external standard solution 20, a measurement sample solution 21, an electrode 22 of another kind, and the like. Next, an outline of the operation of this device will be described. The reference electrode liquid 18 is operated by the functions of the liquid sending device 13 and the valves 14 and 15.
Are sent to the reference electrode 11 in the flow cell 12, and the internal standard solution 19 as a sample solution is sent to the anion-selective electrode 10 to merge in the flow cell 12 to form a liquid junction. Then, the internal standard solution 19 is placed between the reference electrode 11 and the anion selective electrode 10.
Since an electromotive force is generated according to the activity of the target ions inside,
Measure it. Next, the sampling mechanism 16 is operated to use the external standard solution 20 or the measurement sample solution 21 as a sample solution.
Is measured by the same procedure. Based on the calibration curve created using the measured values of the external standard solution 20, the activity of the target ions contained in the measurement sample solution 21 is calculated, and the display and the printing are output. The above measurement and control are automatically performed by the measurement control device 17 based on the instruction of the measurer. In this embodiment, the chloride ion-selective electrode according to the first embodiment of the present invention was used as a component. However, a similar biochemical component analyzer can be formed by using another anion-selective electrode according to the present invention. it can.

Next, the effect of the embodiment based on the present invention will be described.

Here, a conventional example will be shown for comparison with the present invention. Japanese Patent Application
In the chloride ion selective electrode disclosed in JP-A-63-103935 (JP-A-1-276060), 15 wt% of tetraoctadecyl ammonium chloride is used as a sensitive substance, 25 wt% of n-tetradecyl alcohol is used as a plasticizer, and n-tridecyl alcohol is used as a plasticizer. 5 wt% decyl alcohol, 10 wt% o-nitrophenyl octyl ether, 45 wt% polyvinyl chloride as a polymer
% Included. That is, it differs from the present invention in that it does not contain a quaternary ammonium salt belonging to the second group of compounds.

FIG. 4 shows the results of measuring the selection coefficients for various anions when chlorine ions are used as a reference for the chloride ion selective electrodes of the first to fourth embodiments of the present invention and the above-mentioned conventional example. . In the figure, a is a conventional example, b to e
Are results of the first to fourth embodiments according to the present invention. As is clear from FIG. 4, the chloride ion selective electrode according to the present invention has substantially the same selectivity as the conventional chloride ion selective electrode.

In FIG. 5, chlorides in 23 types of commercially available controlled sera were measured by the biochemical component analyzer based on the seventh embodiment, and the coulometric titration method (coulometry method), which is the standard measurement method, was adopted. The result of having investigated the correlation with the measured value by a counter is shown. As is clear from FIG. 5, the biochemical component analyzer based on the present invention has excellent correlation with the device based on the standard measurement method and has a small measurement error, that is, high accuracy.

Finally, FIG. 6 shows the change over time in the slope sensitivity when used for serum measurement, using the chloride ion selective electrode according to the first embodiment of the present invention and the chloride ion selective electrode according to the conventional example. The results are shown below. The chloride sensitivity of the chloride ion selective electrode a based on the conventional example decreases in a relatively short time, while the slope sensitivity of the chloride ion selective electrode b according to the first embodiment of the present invention is twice as high as that of the conventional example. The high value was maintained over the above long term. Similar results were obtained for the other conventional electrodes. This is because the electrode of the conventional example consisting only of a quaternary ammonium salt belonging to the first group of compounds, which has low surface activity and does not necessarily have sufficient ion exchange function, is further difficult to respond because the ion exchange function is further deteriorated by contact with blood. On the other hand, the electrode according to the present invention to which a quaternary ammonium salt belonging to the second group of compounds having a high surface activity and a high ion exchange function is added has a high responsiveness because the ion exchange ability is maintained for a long period of time even when contacted with blood. Is maintained.

In this way, the chloride ion-selective electrode according to the present invention has a long-lasting electrode performance as compared with the conventional example.

〔The invention's effect〕

According to the present invention, the first group of compounds having excellent selectivity and the second group of compounds having excellent functions as an ion exchange site are mixed at an appropriate ratio to be used as an anion-sensitive substance in the sensitive membrane to achieve high selectivity. It is possible to provide an anion-selective electrode having excellent properties and long-term electrode life, and a biochemical component analyzer using the anion-selective electrode.

[Brief description of drawings]

1 is a vertical cross-sectional view of an anion-selective electrode, FIG. 2 is a cross-sectional view of an anion-selective electrode field effect transistor, and FIG. 3 is a view of a biochemical component analyzer for measuring anion concentration. FIG. 4 is a diagram showing selectivity coefficients for various anions of the chloride ion-selective electrode according to the present invention and the chloride ion-selective electrode according to the conventional example, and FIG.
The figure showing the correlation with the coulometric titration method when measuring commercially available controlled serum using a chloride ion selective electrode based on the example of
FIG. 6 is a diagram showing changes with time in slope sensitivity of a chloride ion selective electrode according to the present invention and a conventional example. 1 ... Electrode cylinder, 2 ... Internal liquid, 3 ... Internal electrode, 4 ...
Ion-sensitive membrane, 5 ... Source, 6 ... Drain, 7 ...
Si substrate, 8 ... SiO ₂ film, 9 ... Si ₄ N ₃ insulating film, 10 ... Anion selective electrode, 11 ... Reference electrode, 12 ... Flow cell, 13 ... Liquid transfer device, 14 and 15 …… Valve, 16 …… Sampling mechanism, 17 …… Measurement control device, 18 …… Reference electrode liquid, 19
...... Internal standard solution, 20 …… External standard solution, 21 …… Measurement sample solution, 22 …… Other types of electrodes, a …… Conventional example, b …… First
Embodiment, c ... second embodiment, d ... third embodiment,
e ... Fourth embodiment.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Hiroyuki Miyagi, Inventor Hiroyuki Miyagi 1-280, Higashi Koikekubo, Kokubunji, Tokyo (56) References Japanese Patent Laid-Open No. 59-137851 (JP, A)

Claims (9)

[Claims] 1. In an anion-selective electrode having a sensitive membrane containing a quaternary ammonium salt or a quaternary phosphonium salt, which is an anion-sensitive substance, on a polymer support membrane, the anion-sensitive substance is X ^−. Is an anion and A is nitrogen or phosphorus. And R ₁ , R ₂ , R ₃ and R ₄ have the same carbon number n ₁ = 10 to 24
Group of compounds showing a normal or isoalkyl group, and R ₁ is a normal or isoalkyl group having a carbon number n ₂ = 1 to 20 and R ₂ , R ₃ and R ₄ have the same carbon number n ₃ = (n ₂ +1) ~ 24
2. An anion-selective electrode, characterized in that at least one kind is selected from each group of the second group of compounds showing a normal or isoalkyl group of 1. 2. An anion-selective electrode having a sensitive membrane containing a quaternary ammonium salt or a quaternary phosphonium salt, which is an anion-sensitive substance, on a polymer support membrane, wherein the anion-sensitive substance is X ^−. Is an anion and A is nitrogen or phosphorus. And R ₁ , R ₂ , R ₃ and R ₄ have the same carbon number n ₁ = 10 to 24
A first group of compounds showing normal or isoalkyl groups, and R ₁ represents a normal or isoalkyl group having carbon numbers n ₂ = 1 to 9 and R ₂ , R ₃ and R ₄ have the same carbon number n ₁ = 10 to 24 2. An anion-selective electrode, characterized in that at least one kind is selected from each group of the second group of compounds showing a normal or isoalkyl group of 1. 3. The anion-selective electrode according to claim 1, wherein a linear or branched aliphatic alcohol is dispersed in the sensitive film. 4. The anion-selective electrode according to claim 1 or 2, wherein a plurality of linear or branched aliphatic alcohols having different carbon numbers are dispersed in the sensitive film. 5. The ortho-nitrophenyl octyl ether, which is an organic compound having a dielectric constant larger than that of a linear or branched chain aliphatic alcohol, is dispersed in the sensitive film, according to claim 1 or 2. Anion selective electrode. 6. The anionic sensitizer of the first group is contained in the sensitive film in an amount of 5 to 20% by weight, and the anionic sensitizer of the second group is contained in the sensitive film.
0.2 to 10% by weight, 15 to 40% by weight and 0 to 10% by weight of the above two kinds of aliphatic alcohols, 0 to 15% by weight of the high dielectric constant organic compound, and 35 to 60% by weight of the polymer substance. %
The anion-selective electrode according to any one of claims 1 to 5, further comprising: 7. An anion-selective electrode having a sensitive membrane containing a quaternary ammonium salt or a quaternary phosphonium salt, which is an anion-sensitive substance, on a polymer support membrane, wherein the anion-sensitive substance is X ^−. Is an anion and A is nitrogen or phosphorus. Wherein R ₁ , R ₂ , R ₃ and R ₄ represent a normal or isoalkyl group having a molecular weight m ₁ = 140 to 340, and R ₁ is a normal or isoalkyl group having a molecular weight m ₂ = 15 to 281. Shows that R ₂ , R ₃ and R ₄ have the same molecular weight m ₃ = (m ₂ +14) to 34
A second group of compounds having a normal or isoalkyl group of 0,
An anion-selective electrode, characterized in that at least one kind is selected from each group to be a mixture. 8. X ⁻ is an anion, A is nitrogen or phosphorus, and is represented by the following formula (1): Or a quaternary ammonium salt represented by the structure:
Primary phosphonium salt, wherein R ₁ , R ₂ , R ₃ and R ₄ represent a normal or isoalkyl group having the same carbon number n ₁ = 10 to 24, and R ₁ has a carbon number n ₂ = 1 to 20 normal or isoalkyl groups and R ₂ , R ₃ and R ₄ have the same carbon number n ₃ =
An anion-selective sensitizer, which is a mixture of at least one selected from each group of (n ₂ +1) to 24 compounds having a normal or isoalkyl group. 9. A biochemical component analyzer for measuring anion concentration, wherein X ⁻ is an anion and A is nitrogen or phosphorus as an anion selective sensitizer. And R ₁ , R ₂ , R ₃ and R ₄ have the same carbon number n ₁ = 10 to 24
Group of compounds showing a normal or isoalkyl group, and R ₁ is a normal or isoalkyl group having a carbon number n ₂ = 1 to 20 and R ₂ , R ₃ and R ₄ have the same carbon number n ₃ = (n ₂ +1) ~ 24
, A second group of compounds showing normal or isoalkyl groups, and a biochemical component analysis comprising an anion-selective electrode having a sensitive membrane containing at least one selected from each group as a mixture apparatus.