JPS63100369A - Ion sensor - Google Patents

Abstract

PURPOSE:To enhance selectivity to interfering ion and to increase response speed by providing an isolating layer having the function to hinder the transfer of the constituting layer of an oxidation reduction function layer and ion selective layer and to transmit the potential difference by contact with the ion from the selective layer to the function layer between the above-mentioned function layer and selective layer. CONSTITUTION:A lead 2 consisting of a coated copper wire is adhered and fixed to the base 1a of a conductive substrate 1 of an ion sensor. The oxidation reduction function layer 5 is formed to the top end of the substrate 1 exposed by polishing. An iron sensitive part of the sensor is constituted of such function layer 5 and the ion selective layer 7. The isolating layer 6 is provided between the function layer 5 and the selective layer 7. The surface of the function layer 5 is coated with the isolating layer 6 to prevent the transfer of the materials constituting the selective layer 7 and the function layer 5 between the respective layers and to transmit the potential difference generated in the selective layer 7 by the contact with the ions from the selective layer 7 to the function layer 5. The change in the inclination of the ion characteristics is prevented for a long period of time and the selectivity to the ions is improved.

Description

Detailed Description of the Invention 10 Background of the Invention (Field of Industrial Application) The present invention relates to an electrode potential responsive ion sensor, more specifically a solid-state ion sensor having no internal (standard) solution, and more preferably This invention relates to an ion sensor that can also perform measurements in living organisms.

(Prior art and its problems) Conventionally, the ion sensor in which the ion concentration in a solution is measured by electrode potential response, and which can be made small and solid-state, is made by depositing a redox film on a conductive substrate and further measuring the ion concentration. There are electrode potential responsive ion sensors coated with a carrier film.

However, since the electrode was composed of a conductive substrate/redox membrane/ion-selective membrane, dissolution of the redox membrane composition into the ion-selective membrane or dissolution of the ion-selective membrane composition into the redox membrane was difficult. Therefore, there was a drawback that the ionic characteristics (especially the sensitivity) of the electrode began to deteriorate after one month had passed.

■0 Purpose of the Invention Therefore, the present invention provides a structure in which the substance constituting the redox functional layer and the substance constituting the ion-selective layer do not mutually dissolve and elute, the ionic properties are stable for a long period of time, and the selectivity to interfering ions is maintained. The purpose of the present invention is to provide an ion sensor with high ion response speed.

The above object is an ion sensor that includes an ion-sensing part and measures the ion concentration in a solution by electrode potential response, wherein the ion-sensing part includes a conductive substrate and a redox functional layer covering the surface of the conductive substrate. , comprising a partition layer covering the surface of the redox functional layer and an ion selective layer covering the surface of the partition layer, the partition layer having a function of transmitting information to the ion selective layer and the redox functional layer. This is achieved by an ion sensor characterized by the following. Further, the above object is achieved by the above ion sensor in which the thickness of the barrier layer is 0.2141 to 1.0 mm.

IIl. Detailed Description of the Invention Hereinafter, the present invention will be specifically explained based on Examples.

The features of the present invention can be more clearly understood by referring to FIG. 1 and Tables 1 and 2.

FIG. 1 is a block diagram of an embodiment of an ion sensor according to the present invention. Conductive substrate 1 (diameter 1.1 m × length 3
, Omm) on the bottom surface 1a of the Teflon-coated copper wire (0,2
+nφ) lead vA2 is fixed with conductive adhesive 8,
Furthermore, the outer periphery of the conductive substrate 1 is covered and insulated with a heat shrink tube 4 so that 1.5 mm is exposed. Furthermore, the exposed tip of the conductive substrate 1 is polished into a hemispherical shape, and the surface area of the exposed portion is 0.064. ff1 (average), and a redox functional layer 5 is formed on the exposed surface of the m-conductive substrate 1 by electrolytic oxidative polymerization.

The conductive substrate 1 used in the ion sensor of the present invention is, for example, basal plane pyrolytic. Graphite (basal plane pyrolyt)
icgraphite (hereinafter referred to as BPG), conductive carbon materials such as glassy carbon; gold, platinum, copper, silver9
Examples include metals such as palladium, nickel, and iron, particularly noble metals, and those whose surfaces are coated with semiconductors such as indium oxide and tin oxide. Among these, conductive carbon materials are preferred, BPG is particularly preferred, and the shape is preferably cylindrical.

In addition, the layer 5 having a redox function (hereinafter sometimes referred to as a redox functional layer) means that an electrode formed by depositing this layer on the surface of a conductive substrate generates a constant potential on the conductive substrate through a redox reaction. In the present invention, it is particularly preferable to use a material whose potential does not vary depending on the oxygen gas partial pressure. Such a redox functional layer 5 is, for example, (2) quinone-hydrochloride. In addition, in the case of a polymer, the quinone-hydroquinone type redox reaction herein refers to, for example, one represented by the following reaction formula.

(In the formula, Rt and Rz represent, for example, a compound with an aromatic-containing structure.) In addition, the amine-quinoid type redox reaction is expressed by the following reaction formula, for example, in the case of a polymer as described above. refers to what is done.

(In the formula, R3, R,) represents, for example, a compound having an aromatic-containing structure. Examples of compounds that can form the layer 5 having such a redox function include the following la) to (C). Examples include compounds.

(al (OH)mt・length r,→Rs)nz (wherein, Ar is an aromatic nucleus, each R3 is a substituent, m2 is an effective valence number of 1 to Ar1, and n2 is an effective atom of O to Ar) A hydroxy aromatic compound represented by (having a valence of -1). The aromatic nucleus of Ar may be a monocyclic one such as a benzene nucleus, or a polycyclic one such as an anthracene nucleus, a pyrene nucleus, a chrysene nucleus, a perylene nucleus, a coronene nucleus, etc. Moreover, not only a benzene bone core but also a heterocyclic bone core may be used.

Substituted MR5 includes, for example, an alkyl group such as a methyl group,
Examples include aryl groups such as phenyl groups, and halogen atoms. Specifically, for example, dimethylphenol, phenol, hydroxypyridine, 0- or m-benzyl alcohol, 0-lm- or p-hydroxybenzaldehyde, 0- or m-hydroxyacetophenone, 0-lm- or p-hydroxypropyl alcohol, Fenon,
o-lm- or p-hydroxybenzophenone, o-l
m- or p-carboxyphenol, diphenylphenol, 2-methyl-8-hydroxyquinoline, 5-hydroxy-1,4-naphthoquinone, 4-(p-hydroxyphenyl)2-butanone, 1,5-dihydroxy-
1,2,3,4-tetrahydronaphthalene, bisphenol A1 salicylanilide, 5-hydroxyquinoline,
Examples include 8-hydroxyquinoline, 1,8-dihydroxyanthraquinone, 5-hydroxy-1,4-naphthoquinone, and the like. Among these, dimethylphenol is particularly preferred.

(In the formula, Arz is an aromatic nucleus, each R6 is a substituent, m3 is 1 to the effective valence number of Ar2, and n3 is 1 to the effective valence number of Arz - 1).

As the aromatic nucleus of Arz and the substituent R5, the same ones as Arl and the substituent R3 in compound (a) are used, respectively. Specific examples of amino aromatic compounds include aniline,
1,2-diaminobenzene, aminopyrene, diaminopyrene, aminochrysene, diaminochrysene, 1-aminophenanthrene, 9-aminophenanthrene, 9.10
-diaminophenanthrene, 1-aminoanthraquinone, p-phenoxyaniline, 0-phenylenediamine,
p-chloroaniline, 3.5-'; chloroaniline, 2
, 4.6-drichloroaniline, N-methylaniline,
N-phenyl-p-phenylenediamine and the like.

(C) 1.6-pyrenequinone, 1.2,5.8-tetrahydroxynarizarin, phenanthrenequinone, 1
-aminoanthraquinone, purpurin, 1-amino-4
-Quinones such as hydroxyanthraquinone and anthralphine.

Among these compounds, especially 2,6-xylenol, 1
-Ami/pyrene is preferred.

Furthermore, as a compound that can form the redox functional layer 5 according to the example, (d) poly(N-methylaniline) [Onuki, Matsuda,
Koyama, Journal of the Chemical Society of Japan, 1801-1809 (1984)
), poly(2,6-dimethyl-1,4-phenylene ether), poly(O-phenylenediamine), poly(phenol), poly2,6 xylenol; polymers of pyrazoquinone vinyl monomers, polymers of isoalloxazine vinyl monomers An organic compound containing the compounds (a) to (C) such as a quinone-based vinyl polymer condensation compound, a low polymerization degree polymer compound (oligomer) of the compound (a) to (C), or ( Examples include those having the redox reactivity, such as those in which al~(C) is fixed to a polymer compound such as a polyvinyl compound or a polyamide compound.Among these, poly(2,6 xylenol) is particularly preferred.

Note that in this specification, the term polymer includes both homopolymers and interpolymers such as copolymers.

In order for the compound capable of forming the redox functional layer 5 on the ridges to be deposited on the surface of the conductive substrate 1, an amino aromatic compound, a hydroxy aromatic compound, etc. are applied by an electrolytic oxidation polymerization method or an electrolytic deposition method. Direct polymerization on the substrate surface or electron beam irradiation.

A method of fixing to the substrate surface by drying or a method of directly fixing the polymer film to the substrate surface by chemical treatment, physical treatment, or irradiation treatment can be adopted. Among these methods, electrolytic oxidative polymerization is particularly preferred.

The electrolytic oxidation polymerization method uses an amino aromatic compound in the presence of a suitable supporting electrolyte in a solvent, hydroxy aromatic conditions are -20°C, and an electrode potential of 0.0 to 1.5 V (vs. saturated sodium chloride calomel electrode; 5SCE). It is preferable to carry out an electrolytic reaction at 1.5 cm for 10 minutes after 3 regressions (sweep rate: 50 mV/5 ec). Examples of the solvent include acetonitrile, water, dimethylformamide, dimethyl sulfoxide, propylene carbonate, and among these, acetonitrile is particularly preferred. Supporting electrolytes include, for example, sodium perchlorate, sulfuric acid, disodium sulfate, phosphoric acid, boric acid, tetrafluoroborate,
Preferred examples include potassium tetrafluorophosphate and quaternary ammonium salts, and among these, even a thin film can block oxygen permeation. However, in order to be usable in the present invention, the redox functional layer 5 is not particularly limited as long as it has the redox reactivity, and it does not matter how dense the layer is.

The thickness of the redox functional layer 5 is preferably 0.1 μm to 0.5 μm. If it is thinner than 0.1 μm, it is not preferable.

Further, the redox functional layer 5 can be used by impregnating it with an electrolyte. Examples of the electrolyte include dipotassium hydrogen phosphate, sodium perchlorate, sulfuric acid, tetrafluoroborate, and tetraphenylborate. Among these, sodium perchlorate is particularly preferred. A method of immersion in a redox solution is simple.

The partition layer 6 is further coated on the surface of the electrode in which the redox functional layer 5 is coated on the conductive substrate 1 in a ridge-like manner.
It prevents the movement of substances constituting each layer between the redox functional layer 5 and the ion-selective layer 7, and transmits the potential difference and ions generated in the ion-selective layer 7 due to contact with ions to the redox functional layer 5. It has the function of Examples of the layer having such a function include a polymer layer containing an electrolyte solution or an aqueous solution, a cellulose derivative layer, a water-soluble polymer layer, etc. Among these, a polyvinyl alcohol (hereinafter abbreviated as PVA) layer is particularly suitable. It is mentioned as something. In order to cover the redox functional layer 5 with the partition layer 6, for example, a 10% aqueous solution of PVA or P containing an electrolytic solution is used.
The desired thickness is obtained by preparing a 0% VAl aqueous solution, thoroughly immersing the redox electrode in this solution, pulling it up, air drying, and repeating the steps of drying at 150° C. to obtain the desired thickness. As the electrolytic solution, a pH buffer solution is preferred, and for hydrogen ions, citrate and phosphate solutions are preferred. The pH range is 4.8 to 7.4, which is almost the same as the pH range in living organisms.
is preferable, and (6.0 to 7.4 is preferable. PVA
The thickness of the zero layer is 0.2 μm to 10 m (preferably 200 μm to 800 μm, particularly preferably 40 m).
It is 0 μm to 600 μm. As the ion-selective layer 7 further coated on the surface of the partition layer 6, there is used a layer in which a polymer compound supports an ion carrier substance for the analyte ions and, if necessary, an electrolyte salt. For example, the following ion carrier substances are used depending on the ion to be detected.

(i) Hydrogen ion hydrogen ion toner substances may, for example, be expressed by the following formula (wherein R?, R, and R1 represent the same or different alkyl groups, at least two of which have 8 carbon atoms.
Preferred examples include amines represented by the following formula (in which RIG represents an alkyl group having 8 to 1 carbon atoms): Examples include tri-n-dodecylamine.

Among these, tridodecylamine is particularly preferred.

(ii) Potassium ion palinomycin; nonactin, monactin; crown ether compounds such as dicyclohexyl-18-crown-6, naphtho-15-crown-5, bis(15-crown-5); Medium, palinomycin, bis(
15-crown-5) is preferred. Among these, palinomycin is particularly preferred.

(iii) Sodium ion aromatic amides or diamides, aliphatic amides or diamides, crown compounds such as bis[(1
2-crown-4) methyl] dodecyl malonate, N
, N, N, N-tetrapropyl-3,6-thioxanetodiamide, N, N, N', N'-tetrabenzyl-1,2-ethylenedioxydiacetamide, N, N''
-dibenzyl-N,N'-diphenyl-1,2-phenylene diacetamide, NIN',N''-trihebutyl-
N,N',N"-trimethyl-4,4',4"-propyridine tris(3-oxbutylamide), 3-methoxy-N,N,N,N-tetrapropyl-1,2-phenylenedi Oxydiacetamide, (-)-(R,R)-4
,5-dimethyl-N, N, N, N=tetrapropyl-3,6-thioxaoctanediamide, 4-methyl-
N,N,N,N-tetrapropyl-3,6-thioxaoctane-diamide, N,N,N.

N-tetrapropyl-1,2-phenylenedioxydiacetamide, N,N,N,N-tetrapropyl-2,
3-Naphthalenedioxydiacetamide, 4-t-butyl-N,N,N,N-tetrapropyl-1,2-cyclohexanedioxy-diacetamide, cis-N,N,N
, N-tetrapropyl-1,2-cyclohexanedioxydiacetamide, trans-N.

Examples include N, N, N-tetrapropyl-1,2 cyclohexanedioxydiacetamide, and among these, bis[(12-crown-4)methyl]dodecylmalonate is particularly preferred.

(iv) Chlorine ion A quaternary ammonium salt represented by the following formula (where R1° represents hydrogen or an alkyl group having 1 to 8 carbon atoms) and a quaternary ammonium salt represented by the following formula: Examples include triphenyltin chloride. Among these, triphenyltin chloride is particularly preferred.

(V) Calcium ion Calcium-bis[di(n-octylphenyl)phosphate)), (-1~(R,R)-N,N'-bis(
(11-ethoxycarbonyl)undecyl) -N.

Preferred examples include N', 4,5-tetramethyl-3,6-thioxaoctanediamide, calcium bis[di(n-decyl)phosphate], and the like. Among these, calcium bis[di(n-octylphenyl)phosphate] is particularly preferred.

(vi) Hydrogen carbonate ion The following formula (in the formula, R111R121R13 are the same or different and each represents an alkyl group having 8 to 18 carbon atoms, R14 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and X- is a C1- , Br-
or OH-); a quaternary ammonium salt represented by the following formula (wherein, RIS represents a phenyl group, a hydrogen atom, or a methyl group; RIS represents a hydrogen atom or a methyl group; R1? represents a hydrogen atom, a methyl group; or an octadecyl group); furthermore, compounds represented by the following formula 8 and the like can be mentioned. Among these, tri(n-dodecyl)ammonium chloride is particularly preferred.

Examples of electrolyte salts include sodium tetrakis (p-
chlorophenyl)borate, potassium tetrakis(p-
chlorophenyl) borate, and the following formula % formula % (wherein R111 is an alkyl group, preferably having 2 to 2 carbon atoms)
(6) shows the alkyl group. Among them, potassium tetrakis(p-chlorophenyl)borate is used for hydrogen ions, potassium ions, sodium ions, and hydrogen carbonate ions, tetrachloroborate is used for chlorine ions, and di(n- Particularly preferred is octylphenyl) phosphate.

Further, for the layer material supporting the ion carrier substance, examples of the polymer compound include vinyl chloride resin and vinyl chloride-ethylene copolymer.

Examples include organic polymer compounds such as polyester, polyacrylamide, and polyurethane, and inorganic polymer compounds such as silicone resins. Among these, vinyl chloride is particularly preferred. The plasticizer used is one that is difficult to dissolve. Examples of such plasticizers include dioctyl sebacate, dioctyl adipate, dioctyl maleate, di-n-octylphenylphosphonate, and the like.

Among these, dioctyl sebacate (DOS) and di(2-ethylhexyl sebacate) are preferred.

Moreover, as a solvent, tetrahydrofuran (THF) is particularly preferable. The ion-selective layer 7 can be coated, for example, by adjusting a polymer compound, a plasticizer, and an ion carrier substance in a solvent such as tetrahydrofuran. The thickness of the ion selective layer 7 is 0.1 μm to 10 μm.
1, especially 0.4 to 2 Osm.

For the hydrogen ion sensor prepared as described above, which includes a barrier layer between the redox functional layer and the ion selective layer, the hydrogen ion sensor is used as a working electrode.

Using a saturated sodium chloride calomel electrode (SSCE) as a reference electrode, the electromotive force for 5SCE is plotted against pH, and the dependence of the slope of the Nernst plot over time is investigated to determine the ion-selective layer of the substance that constitutes the redox functional layer. The presence or absence of elution was investigated.

Oxygen gas dependence was investigated by comparing the difference between the potential measured after bubbling nitrogen gas into the pH 7.4 phosphate buffer for 1 hour and the potential measured after bubbling oxygen gas for 1 hour. Carbon dioxide dependence was examined by dissolving carbon dioxide gas in a pH 7,4 phosphate buffer and checking for the presence or absence of a change in potential. Also, 20℃, 30℃, 37℃, 45℃
The relationship between pH and electromotive force was determined, and the slope of the Nernst plot was examined.

In addition, the presence or absence of elution of the constituent substances of the redox functional layer into the hydrogen ion selective layer and the presence or absence of elution of the constituent substances of hydrogen ion selectivity into the redox functional layer were also investigated. The results are shown in Table 1.
Shown in Table 2.

(Left below) It can be seen that after a day has passed, it agrees well with the theoretical value of 61.55, and moreover, the slope of the Nernst plot has hardly changed for three months, showing a stable value.

It can also be seen that there is no elution of the substance constituting the redox functional layer into the hydrogen ion selective layer, and no elution of the substance constituting the hydrogen ion selective layer into the redox functional layer. Also, 95%
It was confirmed that the response speed was within 5 seconds.

When the ion sensor of the present invention peels off the ion-selective layer after 90 days and observes it, the color change of the layer is due to the elution of the quinoid compound (reddish brown) in the redox functional layer into the ion-selective layer. was not observed at all. on the other hand,
In the conventional case, the ion-selective layer was observed to turn yellow around 20 days after production. In addition to the visual inspection described above, spectral analysis (absorption photometry, etc.), gas chromatography, liquid chromatography, and the like can be used to check for elution. Furthermore, it can be seen that it is not affected by oxygen gas and carbon dioxide. It should be noted that this embodiment is an example of the present invention and is not limited thereto, and the composition of the constituent materials forming each layer is not limited thereto either.

potassium ion sensor, sodium ion sensor,
Regarding chloride ion sensors and calcium ion sensors, the characteristics of the slope of the Nernst plot, the presence or absence of elution of substances constituting the redox functional layer into the ion-selective layer,
Results similar to those of the hydrogen ion sensor were confirmed regarding the presence or absence of elution of the substance constituting the ion-selective layer into the redox functional layer and the dependence on oxygen gas and carbon dioxide.

In Examples 4 to 7, at 20°C to 45°C, the slope of the Nernst plot (+*V/pH) closely approximates the theoretical value, and the isothermal point exists in the range of p) 15 to 6. It can be seen that the temperature dependence is extremely small in the pH range of 6.0 to 8.0, which is approximately the same as the pH range in living organisms.

Although not listed in Table 2, the presence or absence of elution of the substance constituting the redox functional layer into the hydrogen ion selective layer and the presence or absence of elution of the substance constituting the hydrogen ion selective layer into the redox functional layer are as follows from Examples 1 to 2. Results similar to those in Example 3 were obtained. This is because when the aqueous solution permeates the partition layer and causes it to swell, the partition layer acts as an internal reference liquid as an internal liquid layer of a conventional liquid film type ion electrode, such as a glass electrode. When the partition layer is 78 m or less, the above results are not obtained.

potassium ion sensor, sodium ion sensor,
The same results as in Examples 4 to 6 were obtained for the chloride ion sensor and the calcium ion sensor.

By changing the ion concentration of the partition layer, an isothermal point can be set in any ion concentration region, and temperature dependence in the measurement range can be reduced.

■0 Effects of the invention The present invention prevents the mutual movement of substances constituting each layer between the redox functional layer and the ion-selective layer, and selects ions by reducing the potential difference that occurs in the ion-selective layer due to contact with ions. By providing the partition layer that has the function of transmitting information from the selective layer to the redox functional layer, mutual dissolution and elution of the redox functional layer constituent material and the constituent material of the ion selective layer do not occur, and the ionic characteristics, that is, the Nernst plot. The slope does not change over a long period of time, resulting in high selectivity to interfering ions and fast ion response speed.

By setting the thickness of the partition layer to 0.2 μm to 1.0 mm, at 20° C. to 45° C., the pl+ range is 6.0 to 8.0, which is almost the same as the in-vivo range, and there is no temperature dependence. It exhibits similar temperature characteristics to a conventional glass electrode with an internal liquid chamber.

In addition, since it is a solid-state sensor, unlike glass-type electrodes that have a liquid chamber inside, it is easy to handle and can be miniaturized.Moreover, unlike glass electrodes, it is difficult to break, so it can be combined with guide wires, catheters, etc. It can be used as a medical ion sensor to measure test ions in vivo.

[Brief explanation of the drawing]

FIG. 1 is a block diagram of the ion sensor of the present invention. 1... Conductive substrate, 1a... Bottom surface of conductive substrate, 2.
... Lead wire, 3 ... Teflon coating part, 4 ... Heat shrinkable tube, 5 ... Redox functional layer, 6 ... Partition layer, 7 ... Ion selective layer, 8 ... conductive adhesive, 9
···Insulator. The King/Figure 1

Claims (2)

[Claims] (1) In a solid-state ion sensor that is equipped with an ion-sensing part and measures the ion concentration in a solution by electrode potential response,
The ion sensitive section includes a conductive substrate, a redox functional layer covering the surface of the conductive substrate, a partition layer covering the surface of the redox functional layer, and an ion selective layer covering the surface of the partition layer. The partition layer prevents the movement of substances constituting each layer between the ion-selective layer and the redox functional layer, and reduces the potential difference generated in the ion-selective layer by contact with ions. An ion sensor characterized by having a function of transmitting information from a selective layer to a redox functional layer. (2) The ion sensor according to claim 1, wherein the partition layer has a thickness of 0.2 μm to 1.0 mm.