JPH08134024A - Anion selective electrode - Google Patents

Abstract

PURPOSE: To provide an anion selective electrode excellent in selectivities to bulky anions and having a high accuracy in measuring actual specimens. CONSTITUTION: This anion selective electrode is provided with a sensitive membrane containing at least an aliphatic alcohol as a plasticizer and a quanternary ammonium salt or a quaternary phosphonium salt of the fomula (X<-> is an anion; A is N or P; at least one of R1 to R4 is an α,α-disubstituted type or an α,α,α-trisubstituted-type substituting group having 2 or 3 alkyl substituting groups on an α-carbon next to N or P) as a sensitive material in a supporting membrane consisting of a high molecular substance. As the plasticizer, two kinds of linear aliphatic alcohols having different carbon numbers each other (preferably n-tetradecylalcohol and n-tridecylalcohol) or further adding thereto an organic compound having a larger dielectric constant than those of the aliphatic alcohols (preferably orthonitorphenyl octyl ether) are preferable.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an anion-selective electrode, and more particularly, to a polymer-supported membrane-type anion-selective electrode suitable for measurement of monatomic anions such as chloride ions in biological fluids. Regarding electrodes.

[0002]

2. Description of the Related Art Conventionally, as anion-selective electrodes used for analysis of chlorine ions in biological fluids, solid membrane electrodes made of silver chloride and silver sulfide, or polymers such as polyvinyl chloride are used. A polymer-supported membrane type electrode in which a quaternary ammonium salt or the like is carried as a sensitive substance in the support membrane 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 electrode is widely used for the analysis of anions in biological fluids. For example, according to the method described in JP-A-3-41352, three alkyl groups having 17 or more carbon atoms and an alkyl group having 9 or less carbon atoms, such as methyltrioctadecyl ammonium salt, are used as sensitive substances. The selectivity is improved by using a quaternary ammonium salt having one and an aliphatic alcohol as a plasticizer.

[0003]

However, the anion-selective electrode according to the prior art has insufficient selectivity for a bulky anion in measuring chloride ion in a biological fluid, particularly blood, and thus the measurement is difficult. There was a problem that the accuracy was a little low.

An object of the present invention is to provide an anion-selective electrode which is excellent in selectivity for bulky anions and has high accuracy in actual sample measurement.

[0005]

In order to achieve the above object, the present invention comprises a support film made of the above-mentioned polymeric substance containing a quaternary ammonium salt or a quaternary phosphonium salt as an anion-sensitive substance, In an anion-selective electrode provided with a sensitive membrane containing an aliphatic alcohol as an agent,
The sensitizer is represented by the general formula 2, R1, R2, R
Α, α-2 substituted or α, α, α-3 in which at least one of the four substituents of 3, R4 has two or three alkyl substituents on the α carbon adjacent to nitrogen or phosphorus
It is achieved by containing a compound which is a substitution type substituent as the sensitizer, or by further containing an organic compound having a higher dielectric constant than the aliphatic alcohol as a plasticizer and optimizing the composition thereof. .

[0006]

Embedded image

[0007]

As a sensitizer of a polymer-supported membrane type anion-selective electrode, at least one of the four substituents R1, R2, R3 and R4 in the general formula 2 is on the α-carbon adjacent to nitrogen or phosphorus. When a compound which is an α, α-2 substituted type or an α, α, α-3 substituted type substituent having two or three alkyl substituents is used, a very bulky compound is formed adjacent to the nitrogen or phosphorus atom. Due to the high alkyl groups attached, the steric hindrance around the nitrogen or phosphorus atom, which is the reaction center of this sensitizer, becomes very large. Therefore, various bulky interfering ions are less likely to interact with this sensitive substance, so that the anion-selective electrode using this sensitive substance has high selectivity for various bulky anions and can improve the measurement accuracy.

[0008]

1 is an example of a cross-sectional view of an anion-selective electrode to which the present invention is applied. 10 mmol / L for electrode cylinder 1
The internal liquid 2 containing sodium chloride is stored therein, and the internal electrode 3 made of Ag / AgCl is immersed in the internal liquid 2. An ion sensitive film 4 is formed at the end of the electrode cylinder 1. The ion-sensitive film 4 contains a polymer substance such as polyvinyl chloride, and an anion-sensitive substance and a plasticizer are dispersed so that the weight concentration is appropriate.

In the present invention, as the anion-sensitive substance, at least one of the four substituents R1, R2, R3, and R4 in the general formula has two or three substituents on the α carbon adjacent to nitrogen or phosphorus. Compounds having α, α-2 substituted or α, α, α-3 substituents with are used. Such compounds include iso-propyl-tri (octadecyl) ammonium salt, (1-methylpropyl) -tri (hexadecyl) ammonium salt, (1-ethylpropyl) -tri (pentadecyl) ammonium salt, (1-methylputyl). -Tri (tetradecyl) ammonium salt, (1-ethylbutyl) -tri (tridecyl) ammonium salt,
(1-Propylbutyl) -tri (dodecyl) phosphonium salt, tert-butyl-tri (hexadecyl) ammonium salt, (1,1-dimethylpropyl) -tri (pentadecyl) ammonium salt, (1-methyl-1-ethylpropyl) ) -Tri (tetradecyl) ammonium salt, (1,1
-Diethylpropyl) -tri (tridecyl) ammonium salt, (1,1-dimethylbutyl) -tri (dodecyl)
Ammonium salt, (1-methyl-1-ethylbutyl)-
Tri (undecyl) ammonium salt, (1,1-diethylbutyl) -tri (decyl) phosphonium salt and the like, α, α-2 substituted or α, α, α-3 having 1 to 10 carbon atoms.
A quaternary onium salt having one substituted alkyl group and three alkyl groups having 10 to 24 carbon atoms is preferably used.

Further, in the present invention, at least one aliphatic alcohol is used as a plasticizer. As such compounds, linear aliphatic alcohols such as n-tetradecyl alcohol, n-tridecyl alcohol, n-dodecyl alcohol, n-pentadecyl alcohol and n-hexadecyl alcohol are preferably used.

Example 1 In the first example of the present invention, a chloride ion-selective electrode was obtained by using chloride ions as the target ions and iso-propyl-tri (hexadecyl) ammonium chloride as the sensitive substance. 15wt of sensitive material
%, N-tetradecyl alcohol as a plasticizer 30 w
t%, 10 wt% of o-nitrophenyl octyl ether
%, Polyvinyl chloride as a polymer substance is weighed so as to be 45 wt%, a solvent (tetrahydrofuran) is added and mixed, and if necessary heated and dissolved, the solvent is removed by evaporation to remove the ion sensitive film 4 Was produced. This is punched out into an appropriate size according to the size of the electrode cylinder 1 in FIG.
Glued to the edges.

The content of the sensitive substance dispersed in the sensitive film is 5 in terms of responsiveness, selectivity, membrane impedance and the like.
To 30 wt% is appropriate. Further, when another quaternary ammonium salt based on the present invention is used as a sensitive substance,
For the above reasons, the total content is 5 to 30 wt%
Is preferred.

Although n-tetradecyl alcohol was used as the plasticizer for the aliphatic alcohol in the above-mentioned examples, the invention is not limited to this. When the sensitizer used has a low solubility or dissociation property, the number of carbon atoms differs by 1 among the aliphatic alcohols having 10 to 40 carbon atoms, such as a combination of n-tetradecyl alcohol and n-tridecyl alcohol. Alternatively, a combination of two aliphatic alcohols with melting point differences within 13 ° C. gives good results. From the viewpoint of responsiveness and selectivity as a chloride ion-selective electrode, the content of the aliphatic alcohol in the sensitive film is 15 to 50 in total.
wt% is suitable.

As the organic compound having a higher dielectric constant than the aliphatic alcohol, 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. The content in the sensitive film is preferably 0 to 15 wt%.

Polyvinyl chloride was used in this embodiment as the polymer substance carrying the sensitive substance or the plasticizer, but other substances such as polycarbonate, silicone rubber, epoxy resin, polyurethane and the like can be used. By the way, when the content of the polymer substance in the sensitive film is 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 increases,
It becomes difficult to obtain stable electrode performance. Therefore, the content of the polymer substance is preferably 35 to 60 wt%.

<Embodiment 2> In the second embodiment of the present invention,
Iso-propyl-tri (octadecyl) as a sensitive substance
A chloride-selective electrode was obtained using ammonium chloride. 15 wt% each of the above-mentioned sensitive materials, 28 wt% of n-tetradecyl alcohol as a plasticizer, 2 wt% of n-tridecyl alcohol, 10 wt% of o-nitrophenyl octyl ether, and 45 wt% of polyvinyl chloride as a polymer substance. I was there. The method of manufacturing the sensitive film and the like are the same as those in the first embodiment.

In this example, as the sensitizer, the length of the three alkyl groups having no substituents on the α-carbon adjacent to the nitrogen was slightly longer than that used in the first example. Was used. When using a sensitive substance having such a slightly low solubility, by adding about 2 wt% of n-tridecyl alcohol having 1 carbon number smaller than that of n-tetradecyl alcohol as a second plasticizer, Solubility in the sensitive membrane is enhanced, and stability is enhanced.

<Embodiment 3> In the third embodiment of the present invention,
Chloride-selective electrodes were obtained using tert-butyl-tri (hexadecyl) ammonium chloride as the sensitive material. 15wt% of each sensitive material, n as plasticizer
25% by weight of tetradecyl alcohol, 5% by weight of n-tridecyl alcohol, 10% by weight of o-nitrophenyl octyl ether, and 45% by weight 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 example, as the sensitizer, a compound having an α, α, α-3 substituent having three substituents on the α carbon adjacent to the nitrogen and having considerably large steric hindrance was used. When such a sensitive substance having a slightly low solubility is used, as in the second embodiment, by adding n-tridecyl alcohol, the solubility of the sensitive substance in the sensitive film is enhanced and the stability is enhanced. .

<Embodiment 4> Next, a chloride ion selective field effect transistor according to a fourth embodiment of the present invention will be described with reference to FIG. FIG. 2 is an example of a cross-sectional view of a chloride ion selective field effect transistor to which the present invention is applied. n
The source 5 and the drain 6 of the shape are formed on the Si substrate 7, and the SiO ₂ film 8 and the Si ₃ N ₄ insulating film 9 are covered thereover. Next, a film component having the same composition as that of the sensitive film in the first example of the present invention was dissolved in THF, and then dropped directly onto 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 that of the sensitive film in the first embodiment is used, but it goes without saying that an ion sensitive film having another composition according to the present invention may be used.

<Embodiment 5> Next, a biochemical component analyzer according to a fifth embodiment of the present invention will be described with reference to FIG. FIG. 3 is an example of a schematic configuration 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, and a liquid delivery device 13 is provided.
And valves 14 and 15, sampling mechanism 16, measurement control device 17, reference electrode solution 18, internal standard solution 19, external standard solution 20, measurement sample solution 21, and electrode 22 of another kind.
Etc.

By the functions of the liquid feeding device 13 and the valves 14 and 15, the reference electrode liquid 18 causes the reference electrode liquid 18 in the flow cell 12 to flow.
, And the internal standard solution 19 as a sample solution is sent to the anion-selective electrode 10 and merges in the flow cell to form a liquid junction. Then, an electromotive force corresponding to the activity of the target ion in the internal standard solution 19 is generated between the reference electrode 11 and the anion-selective electrode 10, and this is measured.

Next, the sampling mechanism is operated to measure the external standard solution 20 or the measurement sample solution 21 as a sample solution 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 output such as display and printing is performed. 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.
Of course, a similar biochemical component analyzer can be formed by using another anion-selective electrode or anion-selective field effect transistor according to the present invention.

Next, the effect of each of the above embodiments will be described.

Here, a conventional example is shown for comparison with the present invention. As this conventional example, the one described as the first embodiment in Japanese Patent Laid-Open No. 41352/1993 is cited. This contains 15 wt% of methyltrioctadecyl ammonium salt as a sensitive substance, 30 wt% of n-tetradecyl alcohol and 10 wt% of o-nitrophenyl octyl ether as a plasticizer in the sensitive film. That is,
In this conventional example, all of the substituents bonded to the nitrogen of the quaternary ammonium salt used as a sensitizer are α adjacent to the nitrogen.
The present invention differs from the present invention in that it does not have a plurality of alkyl substituents on carbon and has little steric hindrance around the nitrogen atom which is the reaction center.

FIG. 4 shows the results of measuring the selection coefficients for various anions with reference to chlorine ions, for the chloride ion selective electrodes of the first to third embodiments of the present invention and the above-mentioned conventional example. Was shown logarithmically. In the figure, a is the result of the conventional example, and b, c and d are the results of the first to third embodiments based on the present invention. As is clear from FIG. 4, the chloride ion-selective electrode according to the present invention is superior in selectivity to bulky anions such as sulfate ion and bicarbonate ion as compared with the conventional example.

Example 6 In FIG. 5, the chlorine ion concentration in 18 kinds of commercially available controlled serum was measured by the biochemical component analyzer based on the sixth example, and the coulometric titration method (coulometry) which is a standard method was measured. 2) shows the result of examining the correlation with the measured value by a chloride counter based on the method). 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 method and has a small measurement error.
That is, it is understood that the accuracy is high. Further, as compared with the conventional example, that is, JP-A-3-41352, it can be seen that the deviation from the regression line and Syx are small and the measurement accuracy is improved.

As described above, the anion-selective electrode according to the present invention is superior in selectivity to bulky interfering ions as compared with the conventional example, and as a result, accuracy in measuring a serum sample is high.

[0031]

EFFECTS OF THE INVENTION According to the present invention, a sensitizer containing a quaternary ammonium salt or a quaternary phosphonium salt as an anion-sensitive substance and a fatty alcohol as a plasticizer in a support film made of a polymer substance. In the anion-selective electrode provided with a membrane, the sensitizer is represented by the general formula 2, and at least one of the four substituents R1, R2, R3, and R4 is an α-carbon adjacent to nitrogen or phosphorus. A compound which is an α, α-2 substituted type or an α, α, α-3 substituted type substituent having 2 or 3 alkyl substituents above is contained as a sensitizer, or higher than an aliphatic alcohol An anion-selective electrode with excellent selectivity for bulky anions and high accuracy when measuring actual samples by including an organic compound having a dielectric constant as a plasticizer and optimizing the composition of them. It can be provided.

[Brief description of drawings]

1 is a cross-sectional view of an anion selective electrode according to the present invention.

FIG. 2 is a cross-sectional view of an anion selective field effect transistor according to the present invention.

FIG. 3 is an explanatory diagram of a biochemical component analyzer for measuring anion concentration according to a fourth embodiment of the present invention.

FIG. 4 is a characteristic diagram showing selectivity coefficients (logarithms) for various interfering anions of a chloride ion selective electrode according to the present invention and a chloride ion selective electrode according to a conventional example.

FIG. 5 shows a coulometric titration method when a commercially available control serum is measured using the chloride ion-selective electrode according to the first embodiment of the present invention in the biochemical component analyzer according to the fourth embodiment of the present invention. The characteristic view which shows correlation.

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Electrode cylinder, 2 ... Internal liquid, 3 ... Internal electrode, 4 ... Ion sensitive membrane.

Claims (9)

[Claims] 1. An anion-selective sensitive substance, wherein the sensitive substance has a molecular structure of a quaternary ammonium salt or a quaternary phosphonium salt represented by the general formula 1, wherein R1 and R
At least one of the four substituents of R2, R3, R4 has two or three alkyl substituents on the alpha carbon adjacent to the nitrogen or phosphorus alpha, alpha-2 substituted or alpha,
A sensitive substance which is an α, α-3 substitution type substituent. Embedded image 2. The molecular structure of the sensitizer according to claim 1, wherein the molecular structure of the sensitizer is represented by Chemical Formula 1, and R1 is one of four substituents R1, R2, R3, and R4 on the α-carbon adjacent to nitrogen or phosphorus. An α, α-2 substituted or α, α, α-3 substituted substituent having two or three alkyl substituents on R,
A sensitive substance in which 2, R3 and R4 are linear alkyl groups having 10 to 24 carbon atoms. 3. Anion selection having a sensitive membrane containing a quaternary ammonium salt or a quaternary phosphonium salt as a sensitive material in a support membrane made of a polymeric material and at least an aliphatic alcohol as a plasticizer. An anion-selective electrode comprising the sensitive material according to claim 1 or 2 in a positive electrode. 4. The sensitive film according to claim 3, wherein the plasticizer contains two kinds of linear aliphatic alcohols having different carbon numbers, preferably n-tetradecyl alcohol and n-tridecyl alcohol. Anion selective electrode. 5. The plasticizer according to claim 3, wherein an organic compound having a dielectric constant larger than that of the aliphatic alcohol, preferably orthonitrophenyl octyl ether, is added to the aliphatic alcohol in the sensitive film. Anion-selective electrode containing. 6. The support film according to claim 3, 4 or 5, wherein the anion-sensitive substance is contained in the support film in an amount of 5 to 30% by weight, and two kinds of aliphatic alcohols are used as the plasticizer in an amount of 15 to 4 respectively.
0 wt% and 0 to 10 wt%, 0 to 15 wt% of the high dielectric constant organic compound, 35 to 60 wt% of polymeric substance
Anion-selective electrode containing. 7. An anion-selective field-effect transistor comprising a sensitive film containing the sensitive material according to claim 1. 8. A biochemical component equipped with an anion-selective electrode or an anion sensor such as an anion-selective field-effect transistor equipped with a sensitive film containing the sensitive substance according to claim 1. Analysis equipment. 9. Anions using an anion-selective electrode or an anion-selective field-effect transistor such as an anion-selective field-effect transistor equipped with a sensitive film containing the sensitive substance according to claim 1. Anion concentration measuring method for measuring concentration.