KR20040032429A - Composition for chloride-selective membrane and chloride-selective membrane electrode comprising the composition - Google Patents

Abstract

PURPOSE: Provided are composition for chloride-selective membrane and chloride-selective membrane electrode comprising the composition by which chloride sensors can be realized in compact size and produced in large volume, lowering production cost. CONSTITUTION: The composition for chloride-selective membrane consists of 50 to 94 wt.% of epoxy resin, and 6 to 50 wt.% of amine based hardener and diluent, wherein the epoxy resin includes bisphenol A group, bisphenol A brominated group, cycloaliphatic group, aliphatic polyglycidyl group, glycidyl amines group, and glycidyl esters group, and wherein the hardener includes aliphatic polyamine group, modified aliphatic polyamine group, aromatic amine group and amine group. The electrode comprises an alumina plate (70), a silver layer (60) on the alumina plate (70), an insulation layer (80) formed on the silver layer (60) while exposing a portion of the silver layer (60), a silver chloride layer (90) on exposed the silver layer (60), and a chlorine ion selective membrane (50) on the silver chloride layer (90) which is made of the chlorine ion selective membrane composition of this application.

Description

Chloride Ion Selective Membrane Composition and Chloride Ion Selective Electrode Using The Same TECHNICAL FIELD

The present invention relates to a chloride ion selective membrane composition, specifically, a chloride ion comprising an epoxy resin, an amine-based curing agent, a diluent, and a lipophilic additive, mounted on a conventional electrode and a solid-state electrode for measuring chloride ion activity in a solution. To selective membrane compositions.

Body fluids such as blood and urine; Household water and wastewater; Fast and accurate measurement of chloride ions in intermediate and final products, by-products, and industrial samples is very important in clinical, water and industrial analysis. In particular, chloride ions in serum, blood, etc. are the main anions of extracellular fluid, which help to control blood volume and blood pressure by maintaining osmotic pressure of blood through interaction with sodium ions, and also affect acid-base equilibrium. Therefore, quantitative analysis of chloride ion concentration in blood provides a great deal of information clinically.

Currently, mercury titration, argentimetric coulometry, and spectrophotometric method have been reported to quantify the concentration of chloride ions in the blood. Electrode contamination, difficult to analyze trace samples, inaccurate quantification, and above all, automated in clinical laboratories because it is an indirect method of separating blood cells from blood. Difficult to use for analyzing an assay or multisample.

On the other hand, unlike the above cases, an ion sensor is a representative example of chloride ion measurement using potentiometry. An ion-selective membrane electrode, a type of ion sensor, is used to measure the potential difference generated by a charge separation layer formed on the surface of a membrane when an ion-selective membrane attached to the electrode is bound to specific ions or molecules. By measuring, the ions contained in the sample can be quantified. In particular, ion-selective membrane electrodes have advantages such as excellent selectivity for specific ions, short analysis time, and low cost of analysis. It is used for process, environmental analysis, and ionic species in various fields such as hemodialysis, continuous automatic measurement of hematoma electrolytes, and clinical chemistry such as extracorporeal blood.

The ion-selective membrane electrode can be divided into two types. Conventional ion-selective membrane electrode having an inner reference filling solution between the ion-selective membrane and the inner reference metal electrode ( Conventional ion-selective membrane electrodes and solid-state ion-selective membrane electrodes that do not require internal reference solutions ( FIGS. 1A and 1B ). Advantages of the solid-state ion-selective membrane electrode are (1) it is advantageous for miniaturization since it does not require an internal reference solution; (2) it is easy to develop a multisensor capable of detecting several ions simultaneously on one chip; (3) Mass production is possible, so the price can be brought cheaply. In addition to the advantages of such an element itself (4) has the advantage that the use of a small amount of the sample according to the miniaturization of the sensitive portion. In the conventional ion selective membrane electrode, the ion selective membrane 50 may be fixed to the membrane fixture 20 in the electrode body to prevent the separation of the ion selective membrane 50, but in the case of a solid phase electrode, the ion selective membrane 50 Since the electrode surface is exposed without any fixture, the adhesion of the ion-selective membrane to the electrode surface is an important factor in determining the lifetime and electrochemical properties of the electrode.

The conventional ion-selective membrane electrode is also referred to as an organic solvent-polymer membrane electrode, a polymer material and a metal porphyrin compound such as poly (vinyl chloride), polyurethane (polyurethane), silicone rubber (silicone rubber), etc. , Ion selective materials such as neutral carriers such as organic mercury compounds, and anion exchangers such as quaternary ammonium salts, and plasticizers for the smooth operation of the added ion selective materials. And the like. Such a polymer chloride ion selective electrode has a disadvantage of serious interference with lipophilic anions such as thiocyanic acid (SCN ⁻ ) or salicylate ions.

Another type of solid-state ion-selective membrane electrode is AgCl, HgCl₂Using a poorly soluble metal salt layer, such as the ion-selective electrode membrane, has been used as a representative chloride ion selective electrode from the beginning of the ion-selective electrode research, Cases of use in clinical applications have also been reported. This solid ion selective membrane electrode is superior to the conventional ion selective membrane electrode because it does not require an internal reference solution, which is advantageous for miniaturizing the electrode, making it easy to manufacture various types of electrodes, and By simply polishing, a new electrode surface can be easily obtained, so that a stable electrode potential value can always be obtained.

However, such solid-state ion-selective membrane electrode binds more strongly with anions such as bromine and iodine which can form more soluble metal salts such as AgCl, HgCl ₂ , etc., and thus severely interfere with bromine ion when present in the sample. There is a drawback to receiving. In addition, low blood and biocompatibility, such as large molecules such as proteins are easily adsorbed on the surface of the electrode has been limited to applications in clinical analysis.

Accordingly, the present inventors have been working to improve the disadvantages of the conventional conventional chloride ion selective membrane electrode and the solid-state chloride ion selective membrane electrode as described above, the ion selective membrane using a chloride ion selective membrane composition containing an epoxy resin and an amine-based curing agent The present invention was completed by finding that the electrode has excellent sensitivity to chloride ions and electrochemical properties, and exhibits long life and excellent biocompatibility.

An object of the present invention is to provide a chloride ion selective membrane composition provided in the chloride ion selective membrane electrode.

1A is a cross-sectional view of a conventional chloride ion selective electrode incorporating a chloride ion selective membrane using an epoxy resin and an amine curing agent of the present invention,

1B is a cross-sectional view of a solid-state chloride ion selective electrode incorporating a chloride ion selective membrane using an epoxy resin and an amine curing agent of the present invention.

Figure 2a is a graph comparing the ion response of a conventional electrode using a chloride ion selective membrane using the epoxy resin of the present invention and an amine curing agent,

(a) is a graph of response to chloride ions,

(b) is a graph of sensitivity to bromide ions,

(c) is a response graph for salicylate ion,

Figure 2b is a graph showing the calibration curve for the chloride ion of the conventional electrode using a chloride ion selective membrane using the epoxy resin and amine-based curing agent of the present invention,

3 is a graph comparing ion response of a conventional electrode using a chloride ion selective membrane using an epoxy resin and a non-amine curing agent.

(a) is a graph of response to chloride ions,

(b) is a response graph for salicylate ion,

Figure 4a is a graph comparing the ion response of a conventional electrode using a chloride ion selective membrane using the epoxy resin of the present invention and an amine curing agent,

(a) is a graph of response to chloride ions,

(b) is a graph of sensitivity to bromide ions,

(c) is a response graph for salicylate ion,

4B is a graph showing ion sensitivity of a conventional electrode using a chloride ion selective membrane in which DOA is added to an epoxy resin and an amine curing agent of the present invention.

(a) is a graph of response to chloride ions,

(b) is a graph of sensitivity to bromide ions,

(c) is a response graph for salicylate ion,

FIG. 5 is a graph showing ion response of a chloride ion selective membrane in which BGE is added to an epoxy resin and an amine curing agent of the present invention.

(a) is a graph of response to chloride ions,

(b) is a graph of sensitivity to bromide ions,

FIG. 6 is a graph of sensitivity to hydroxide ions in a universal buffer of a solid-state electrode equipped with a chloride ion selective membrane using an epoxy resin and an amine curing agent of the present invention.

(a) is a graph of the sensitivity to hydroxide ions of the chloride ion selective membrane using an epoxy resin and an amine curing agent,

(b) is a graph of the sensitivity to hydroxide ions of the chloride ion selective membrane added DOA to the epoxy resin and the amine curing agent,

(c) is a graph of the sensitivity to hydroxide ions of the chloride ion selective membrane in which BGE is added to an epoxy resin and an amine curing agent.

7 is a graph illustrating the sensitivity of hydroxide ions of membranes in which the amount of TDMACl is changed to a chloride ion selective membrane in which DOA is added to the epoxy resin and the amine curing agent of the present invention.

(a) is a sensitivity graph of the film to which 1.2 wt% of TDMACl is added,

(b) is a sensitivity graph of the film to which 20 wt% of TDMACl is added;

FIG. 8A is a graph of the sensitivity to chloride ion in a standard solution of a chloride ion selective electrode using a silver / silver chloride (Ag / AgCl) solid phase membrane.

(a) shows the response to chloride ion in 100 mM chloride ion.

(b) shows the response to chloride ion in standard solution 100mM chloride + 10mM bromine ion,

(c) shows the response to chloride ion in standard solution 100mM chloride + 20mM bromine ion,

8B is a graph illustrating the sensitivity of chloride ions to the standard solution of the chloride ion selective electrode using the epoxy resin of the present invention and an amine curing agent.

(a) shows the response to chloride ion in 100 mM chloride ion.

(b) shows the response to chloride ion in standard solution 100mM chloride + 10mM bromine ion,

(c) shows the response to chloride ion in standard solution 100mM chloride + 20mM bromine ion,

FIG. 9A is a graph of sensitivity to chloride ions in a standard solution of an electrode using a commercially available chloride ion selective material . FIG .

(a) shows the response to chloride ion in 100 mM chloride ion.

(b) shows the response to chloride ion in standard solution 100mM chloride + 1mM salicylate ion,

(c) shows the response to chloride ion in standard solution 100mM chloride + 2mM salicylate ion,

(d) shows the response to chloride ion in standard solution 100mM chloride + 3mM salicylate ion,

9B is a graph illustrating the sensitivity of chloride ions in the standard solution of the chloride ion selective electrode using the epoxy resin of the present invention and an amine curing agent.

(a) shows the response to chloride ion in 100 mM chloride ion.

(b) shows the response to chloride ion in standard solution 100mM chloride + 1mM salicylate ion,

(c) shows the response to chloride ion in standard solution 100mM chloride + 2mM salicylate ion,

(d) shows the response to chloride ion in standard solution 100mM chloride + salicylate ion 3mM,

10 is a graph showing the sensitivity of chloride ion in the standard solution, serum, and blood of the chloride ion selective electrode using the epoxy resin and the amine-based curing agent of the present invention. To quantify potential values by concentration)

(a) shows the response to chloride ion in standard solution,

(b) shows the response to chloride ions in serum,

(c) represents the response to chloride ions in the blood,

FIG. 11A is a graph of the sensitivity in a sulfide ion solution of a silver chloride selective electrode using a silver / silver chloride (Ag / AgCl) solid phase membrane;

(a) is the response at 10 mM sulfide ion,

(b) shows the basic potential in the electrode itself in the buffer solution,

11B is a graph of the sensitivity in the sulfide ion solution of the chloride ion selective electrode using the epoxy resin of the present invention and an amine curing agent.

(a) is the response at 10 mM sulfide ion,

(b) shows the response at 20 mM sulfide ion,

(c) is the response at 30 mM sulfide ion,

(d) indicates the response at 40 mM sulfide ion,

(e) shows the response at 50 mM sulfide ion,

(f) represents the basic potential in the electrode itself in the buffer solution,

12A is a graph illustrating a long time response gradient of the solid chloride ion selective electrode using the epoxy resin and the amine curing agent of the present invention with respect to chloride ion;

12B is a graph illustrating a long time response gradient of the solid-state chloride-ion-selective electrode added with DOA to the chloride-ion-selective electrode using the epoxy resin and the amine-based curing agent of the present invention.

Explanation of symbols on the main parts of the drawings

10: plastic electrode body 20: membrane fixture

30: silver / silver chloride wire 40: internal solution

50: chloride ion selective membrane 60: silver layer

70: alumina plate 80: insulating film

90: silver chloride layer

In order to achieve the above object, the present invention provides a chloride ion selective membrane composition provided in the chloride ion selective membrane electrode.

Hereinafter, the present invention will be described in detail.

In the present invention, an epoxy resin, an amine provided in a solid chloride ion selective membrane electrode composed of a conventional chloride ion selective membrane electrode having an internal reference solution between the ion selective membrane and the internal reference electrode, a poorly soluble metal salt layer, and an ion selective membrane. And a chloride ion selective membrane composition comprising a system curing agent.

Specifically, the epoxy resin is to act as a support of the adhesive film composition by reacting with the curing agent in the membrane electrode, the epoxy resin of the present invention to control the degree of epoxidation (epoxidization) bisphenol A diglycidyl ether bisphenol A system such as (bisphenol A diglycidyl ether); Bisphenol A brominated series such as tetrabromo bisphenol A diglycidyl ether; Cycloaliphatic systems such as tetraphenylene ethane tetraglycidyl ether, triglycidyl ether of trihydroxybiphenyl, and the like; Polyglycidyl ether of hydroxypolyphenyls, phenol formaldehyde noblock polyglycidyl ether of phenol formaldehyde novlac, o-cresolformaldehyde noblock polyglycidyl ether of aliphatic polyglycidyl systems such as o-cresolformaldehyde novlac); Glycidyl amines such as 4,4-diamino-diphenylmethane; And diglycidyl isophthalate, diglycidyl terephthalate, diglycidyl hexahydroterephalate, diglycidyl phthalate, diglycidyl phthalate 3,5-dichloroterephthalate, diglycidyl diphenoate, triglycidyl trimesoate, triglycidyl trimelliate, tetraglycidyl trimelliate, tetraglycidyl trimelliate Glycidyl groups in the glycidyl esters family such as glycidyl pyromellitate and the like. Preferably it is an epoxy resin series containing glycidyl group, More preferably, it is a bisphenol A series glycidyl epoxy resin series, For example, it is bisphenol A diglycidyl ether. In the present invention, the epoxy resin contains 50 to 94% by weight, preferably 50 to 80% by weight based on the total composition. If it is less than the above range or exceeds the above range, epoxidation will not occur, and even if a film is not formed or a film is formed, the adhesive strength in the film itself will be lowered and the flexibility in the film itself will appear.

In addition, the amine-based curing agent is to react with the epoxy resin in the membrane electrode to cure a three-dimensional thermosetting material, diethylene triamine (triethylene triamine), triethylene tetramine (triethylene tetramine), methane diamine ( aliphatic polyamines such as methane diamine, meta-xylene diamine and the like; Epoxy polyamine adducts, ethylene polyamine adducts, propylene oxide polyamine adducts, cyanoethyl polyamine adducts, ketone-blocked polyamine adducts ( modified aliphatic polyamines such as ketimine adduct); Aromatic amines such as m-phenylene diamine, dimethyl aniline, and the like; Secondary amines and tertiary amines such as dimethyl aminomethyl phenol and benzyl dimethyl amine. Preferably, ethylenediamine, trimethylhexamethylenediamine, diethylenetriamine, dipropylenetriamine, dipropylenetriamine, triethylenetetramine, tetraethylenepentaamine , 2-hydroxyethyldiethylenetriamine, diethylaminopropylamine, N-aminoethylenepiperazine, m-xylylenediamine, benzyl Selected from an amine group consisting of benzyldimethylamine, n-buthylimidazole, 1-methylimidazole and boron trifluoride monoethylamine Use it. In the present invention, the amine-based curing agent includes 6 to 50% by weight, preferably 20 to 50% by weight based on the total composition. If it is less than the above range, the epoxidation (epoxilation) is not formed or the film is formed even if the film is sticky, the curing temperature is high, or takes a long time to cure, the drawback, the pot life and curing time is too short When the film is formed, the adhesive strength in the film itself is reduced, and the film is too hard, so that not only the flexibility in the film itself is reduced, but also the hydration time is long and the sensitivity to chloride ions is decreased.

The present invention further adds amine curing accelerators such as tertiary amines and imidazols to acid anhydrides. If only the acid anhydride is used without mixing the amine-based curing agent as the curing agent, the prepared film does not show a sensitivity to chloride ions. This is due to the hydrogen bond between nitrogen atoms and chloride ions formed by mixing the epoxy resins containing glycidyl groups with amine curing agents to form secondary or tertiary amine groups in the membrane. Or due to non-covalent bonding due to the positive charge of the quaternary ammonium salt.

The invention further comprises a diluent. The diluent is to reduce the viscosity in order to facilitate the production of the electrode film with the epoxy resin and the amine-based curing agent, to prevent the deterioration of physical properties, to improve the flowability and defoaming during use, tetrahydrofuran (" THF ”, organic / inorganic solvents such as acetone, methanol, cyclohexanone, dichloromethane, xylene or butyl glycidyl ether, phenyl glycid Phenyl glycidyl ether, 2-ethylhexthyl glycidyl ether, and also bis (2-ethylhexyl) adipate (DOA), diisooctyl phthalate (DOP), Plasticizers composed of ether or epoxy-based compounds such as 2-ethylhexyl epoxytalate (EHE) and 2-nitrophenyloctyl ether (NPOE) are selected as diluents. The content of the diluent is 13 to 65 parts by weight with respect to 100 parts by weight of the membrane composition, if outside the above range is not epoxidation (epoxilation) does not form a film or sticky even if the film is formed and the curing temperature is high. In addition, the pot life and curing time is too short or long, the adhesion of the film itself is reduced when the film is formed, not only the flexibility in the film itself, but also the hydration time is prolonged and the degree of sensitivity to chloride ions appears. Occasionally, the addition of excess diluent may increase the hindrance of lipophilic anions.

In addition, the lipophilic additive increases the conductivity of the membrane and helps the chloride ion selective material to facilitate the exchange of chloride ions in the membrane itself, thereby increasing the response to the chloride ion, tridodecylmethylammonium chloride (TDMACl ), Tetradodecylammonium chloride (TDACl), tridodecylmethylammonium nitrate (TDMANO ₃ ), tetradodecylammonium nitrate (TDANO ₃ ), tetraoctylammonium bromide, methyltrioctadecylammonium bromide ( Methyltrioctadecylammonium bromide, dimethyl distearylammonium chloride, dimethyl distearylammonium bromide, tetraoctadecylammonium bromide, tetraoctadecylammonium bromide, tetraoctadecyl ammonium chloride, tetraoctadecylammonium phenyl chloride Force Lilly include Dean) ammonium chloride (bis (triphenylphosphoranylidene) ammonium chloride), and use the quaternary ammonium salt is selected from the series, such as, from 0.5 to 30 parts by weight based on 100 parts by weight of the film composition of the invention section. If the content is out of the above range, the adhesive strength in the membrane itself is weakened, and the flexibility of the membrane is reduced, so it has a disadvantage of being easily broken. In the severe case, a uniform membrane is not formed, so a fine gap is formed in the membrane, and the internal reference solution leaks when mounted on the conventional electrode. Come out. In addition, the excessive lipophilic additive has a disadvantage in that the interference with the lipophilic anions increases.

The chloride ion selective membrane composition of the present invention can be mounted on a solid-state electrode and a conventional electrode of a chloride ion sensor.

Specifically, the prepared chloride-ion selective membrane composition was mixed with a diluent to prepare an ion-selective membrane of a conventional electrode, poured into a glass ring on Teflon, dried by molding at 25 to 100 ° C. for one to two days, and formed into 5.5 mm It is cut in a circle and attached to a conventional ion-selective electrode body.

In the solid phase chloride-ion selective electrode of the present invention, as the poorly soluble metal salt layer, a metal chloride such as AgCl, HgCl _2, and the like, or a mixture thereof, or a mixture of silver sulfide (Ag ₂ S) and the like may be used.

The chloride ion selective membrane electrode is manufactured by thinly applying a mixed solution of a composition dispersed in a diluent to the surface of a solid electrode using a pneumatic dispenser or the like.

Conventional electrode or solid-state electrode made of the membrane composition of the present invention is used for the determination of chloride ions in solution, macromolecules such as halide ions such as bromine and iodine or interfering ionic species such as salicylate ions in biological samples and proteins. The effect of adsorption can be reduced to obtain accurate measured values of chloride ions. Especially for solid-state electrodes, excellent adhesion and electrochemical properties to the surface of solid-state electrodes prevent the reduction of sensitivity to chloride ions and prolong the lifetime. Excellent electrochemical properties facilitate the miniaturization and mass production of chloride ion sensors.

The present invention will be described in more detail with reference to the following examples.

However, the following examples are only for exemplifying the present invention, and the present invention is not limited by the examples.

Example 1 Preparation of Chloride-ion Selective Membrane Electrode Using Chloride-ion-selective Membrane of the Present Invention

(1) Preparation of an Ion Selective Membrane with a Conventional Chloride Ion Selective Membrane Electrode

In order to prepare the ion-selective membrane provided in the conventional chloride ion-selective membrane electrode, the composition of Table 1 was diluted in tetrahydrofuran solvent and poured on a glass ring on Teflon and dried at room temperature for about 2 days. Or molded for 1 day in an oven controlled at 45 ° C. The prepared ion-selective membrane was cut out using a punch and mounted on a conventional electrode to prepare a chloride-ion selective membrane electrode (see FIG. 1A ).

(2) Preparation of an Ion Selective Membrane in a Solid Phase Chloride Ion Selective Membrane

In order to form a chloride ion selective membrane provided in the solid phase chloride selective membrane, the composition of Table 1 is diluted in a tetrahydrofuran solvent, and then the solution is applied thinly on the silver chloride layer of the solid phase electrode using a microsyringe. Then, the chloride ion selective electrode was manufactured by drying in the same manner as the conventional electrode film (see FIG. 1B ). The solid phase electrode is formed by screen printing method of silver paste on the alumina, polyester, or polycarbonate substrate by the screen printing method of silver paste, and the egg on the silver electrode. A soluble silver chloride layer was formed by immersion in 0.1 M iron chloride (FeCl ₃ ) solution for about 10 minutes.

Composition of Epoxy Chloride Selective Membrane (wt%) Composition 1 Composition 2 Composition 3 Composition 4 Composition 5 Composition 6 Composition 7 Composition 8 Epoxy resin ^a 50 ^a 40.5 ^a 40.1 ^a 30 ^a 50 ^b 50 ^b 40.5 ^a 50 Hardener ^c 50 ^c 40.5 ^c 40.1 ^c 30 ^d 50 ^e 50 ^e 40.5 ^f 50 DOA ^g - 19 18.6 - - - 19 TDMACl ^h - - 1.2 - - - - Thinner ⁱ - - - 40 - - - a: bisphenol A diglycidyl ether> 60%, b: bisphenol A proxilate diglycidyl ether, c: 2,4,6-tri (dimethylaminomethyl) phenol 10-20% / mercaptoamine 80-90% mixture, d: tetraethylenepentaamine, e: meta-phenylene diamine, f: methyl nadic anhydride, g: bis (2-ethylhexyl) adipate, h: tridodecylmethylammonium chloride i: butyl Glycidyl ether

Experimental Example 1 Sensitivity of Chloride-ion Selective Membrane Formed from Epoxy Resin and Amine Curing Agent

(1) A membrane prepared using the composition shown in Composition 1 of Table 1 was mounted on a conventional electrode body, and N- [2-hydroxyethyl] piperazine- N ' -[3-propanesulfonic acid] was dissolved in sodium hydroxide solution. The sensitivity of chloride, bromine and salicylate ions in the buffer solution adjusted to pH 7.4 was investigated. The results are shown in Figure 2a , and also the calibration curve for the response to chloride ions of the present invention is shown in Figure 2b .

As shown in Figure 2a , a is a response to the chloride ion, b is a response to the bromide ion, c is a response to the salicylate ion.

In general, in the case of chloride ion selective membrane electrodes, the reaction of halide ions such as bromine ions is greater than that of chloride ions, and the hindrance to lipophilic anions such as salicylate is also greater. Thus, even if these interfering species are present in the sample at low concentrations, they will affect the accurate quantification of chloride ions. In the chloride ion sensor using quaternary ammonium salts, manganese, or indium porphyrin-based chloride ion selective materials, the bromine ion selection coefficient is approximately 0.6 to 1.2 for chloride ion, and the salicylate ion selection coefficient is The disturbance is large about 1.5 ~ 3.8. In addition, the sensor using a poorly soluble metal salt layer such as silver chloride (AgCl) or mercury chloride (HgCl ₂ ) as an ion-selective electrode membrane does not interfere with salicylate ions, whereas halide ions such as bromine or iodine There is a disadvantage in that severe substitution occurs even in the presence of a small amount in the sample by the substitution action.

On the other hand, the chloride ion selective membrane prepared using the epoxy resin and the amine curing agent of the present invention has a selection coefficient of bromine ion of 0.45 and a salicylate ion of 0.62 with respect to chloride ions. The selectivity was greatly improved.

In addition, as shown in Figure 2b , the slope in the section from 10 ^-4 M to 10 ^-1 M chloride ion -57.7mV / decade showed good response even in the low concentration range.

(2) The membrane prepared using the composition of Composition 5 in Table 1 was placed on a solid-state electrode, and N- [2-hydroxyethyl] piperazine- N ' -[3-propanesulfonic acid] was titrated with sodium hydroxide solution. The sensitivity of chloride, bromide, and salicylate ions in the buffer solution adjusted to pH 7.4 was compared.

As a result, compared with the membrane of composition 1, the slope of response was -51mV / decade, but the selectivity coefficient of salicylate ion to chloride ion was -0.69.

Comparative Example 1 Sensitization Characteristics of Chloride-ion Selective Membrane Formed from Epoxy Resin and Non-amine Curing Agent

The membrane prepared using the composition shown in Composition 8 of Table 1 was placed on a solid-state electrode, and N- [2-hydroxyethyl] piperazine- N ' -[3-propanesulfonic acid] was titrated with sodium hydroxide solution to adjust the pH. The sensitivity of chloride and salicylate ions in the buffer solution adjusted to 7.4 were compared. The result is shown in Fig.

As shown in Figure 3 , a is a chloride ion, b represents a salicylate ion. Compared to FIG . 2 of the composition 1 using the amine-based curing agent, it can be seen that in FIG. 3 , the response to the salicylate ion, which is the interference ion species, is not observed for the chloride ion, which is the main ion. This makes it possible to know that the amine-based curing agent is a major factor showing the property of chloride ion selective in the composition of the chloride ion selective electrode film.

Experimental Example 2 Comparison of Sensing Characteristics of Chloride-ion Selective Membranes Added with Plasticizer

The membranes prepared using the compositions 1, 2, 3, 6, and 7 of Table 1 were mounted on conventional electrode bodies or placed on solid-state electrodes, and then N- [2-hydroxyethyl] piperazine- N ' -[3. -Propanesulfate] was titrated with sodium hydroxide solution to compare the sensitivity to chloride, bromide and salicylate ions in a buffer solution adjusted to pH 7.4.

Results of membranes prepared using compositions 6 and 74aWow4bIndicated through. The tendency of response such as the degree of response and the speed of response for each ion4aof Membrane with DOA4bof The unused membranes were similar, and the sensitivity gradients showed that the DOA-based membranes had a slope of -55 mV / decade, slightly better than the slope of the non-DOA-side membranes -54 mV / decade.

Experimental Example 3 Sensitivity Comparison of Chloride-ion Selective Membranes Added with Diluent

Hydroxide of N- [2-hydroxyethyl] piperazine-N '-[3-propanesulfonic acid] by mounting the membrane prepared using the compositions shown in Compositions 1 and 4 of Table 1 on a conventional electrode body or on a solid phase electrode The sensitivity to chloride and bromide was compared in a buffer solution adjusted to pH 7.4 by titration with sodium solution.

The results are shown in Fig. Sensitivity tendency, such as the degree of sensitivity and sensitivity for each ion was found to be similar to the membrane ( Fig. 2a ) without the use of a butyl glycidyl ether (BGE) as a diluent. The slope of the response is -52mV / decade, with the membrane using butyl glycidyl ether (BGE) slightly reduced than the membrane without butyl glycidyl ether (BGE).

Experimental Example 4 Comparison of Sensitization Characteristics of Hydroxide by Selective Chloride Ion Membranes According to Various Compositions

(1) The membrane made by using the composition shown in the composition of Table 1 was mounted on a conventional electrode body or placed on a solid-state electrode.Universal buffer: boric acid 11.4mM, citric acid 6.7mM, Comparison of the sensitivity to hydroxide ions in dihydrogen phosphate (sodium phosphate, dibasic) 10 mM mixed solution) is shown in FIG. 6 .

As a result, as shown in FIG. 6 , the membrane without the DOA (compositions 1,5,6) showed a response of 0.4 to 1.4 mV at pH 7-8, the pH range of the biological sample, and the membrane using DOA or TDMACl. Compositions 2, 3, and 7 showed 1.2 to 2.1 mV response in the same section, and diluent-added membranes (composition 4) showed 1.8 to 3 mV response in the same section. Membranes using DOA or TDMACl (compositions 2, 3, 7) showed a relatively gentle slope in the pH range of 8-10.

(2) The reaction characteristics of hydroxide ions in the membrane formed by increasing the ratio of TDMACl to 5, 10, 15, and 20 wt% in the composition 3 were also investigated. The results are shown in Fig.

As shown in Figure 7 , it can be seen that as the ratio of TDMACl increases, the response decreases to ± 1.5 to 2mV in the interval of pH 8 ~ 10.5.

Experimental Example 5 Comparison of Sensitivity Time and Sensitivity of Samples Containing Chloride and Interfering Ions

In fact, the clinical samples to be analyzed were examined for the effects of chloride and interfering ions together.

Raising a film made with a composition shown in Composition 1 in Table 1 in the solid electrode concentration of chloride ions is a concentration of 100 mM present in normal serum, interfering ion in the case of the bromide ions greater concentration than the concentration ranges present in the actual human 10 mM and 20 mM salicylate ions were tested at 1,2,3 mM.

For ease of comparison, FIG. 8 illustrates the interference effects on 10 mM and 20 mM bromine ions, and FIG. 9 illustrates the interference effects on 1,2,3 mM salicylate ions. In Tables 2 and 3 , the potentials of all the tested solutions were converted to concentrations, and are shown for each electrode.

Chloride ion concentration values determined using different types of chloride ion selective electrodes Sample type Composition of the sample (or reference value attached at the time of reagent purchase) Quantitative value of chloride ion (mM) Electrode with silver / silver chloride (Ag / AgCl) solid phase membrane Electrode Using Epoxy Chloride Selective Membrane Solvent-Polymer Electrode (Commercial Analyzer ^a ) Standard solution Cl ^- 100mM 100 100 99 Cl ^- 100mM + Br ^- 10mM - 102 124 Cl ^- 100mM + Br ^- 20mM - 98 - ^a Blood analyzer (Nova Stat Profile Ultra M; Waltham, MA, USA).

As shown in FIG. 8A , the chloride-ion-selective electrode using the silver / silver chloride (Ag / AgCl) solid-phase membrane was about 30 mV in the solution containing 10 mM bromide than in the presence of only 100 mM chloride. The larger the response, the larger the actual concentration value and the error. After experimenting with a solution containing bromide, it can be seen that the Ag / AgCl of the electrode is replaced with Ag / AgBr, so that the basic potential value of the electrode itself fluctuates a lot. have. In FIG. 8B , the response of the chloride-ion-selective electrode to the 100 mM chloride ion using the epoxy resin and the amine curing agent showed similar response (within 1 to 1.5 mV) regardless of the presence or absence of 10 mM and 20 mM bromide ions. Quantitative values are also within the error range of 102mM and 98mM. In addition, commercially available analyzers (eg Nova Stat Profile Plus 5) using solvent / polymeric chloride-ion selective membrane electrodes showed 124 mM values that deviated significantly from actual concentrations in the presence of 10 mM bromide and the presence of 20 mM bromide The measurement was not possible due to the error range of the machine.

Sample type Composition of the sample (or reference value attached at the time of reagent purchase) Quantitative value of chloride ion (mM) Electrode Using Epoxy Chloride Selective Membrane Solvent-Polymer Electrodes (Commercialized Ion-Selective Materials ^a ) Solvent-polymer electrode (commercialized ion selective material ^b ) Standard solution Cl ^- 100mM 100 100 100 Cl ^- 100mM + Sal ^- 1mM 100 - 102 Cl ^- 100mM + Sal ^- 2mM 99 - 115 Cl ^- 100mM + Sal ^- 3mM 98 - 136 a: Chloride Ionophore I (5,10,15,20-tetraphenyl-21H, 23H-polpine manganese (III) chloride) b: Chloride Ionophore II ([4,5-dimethyl-3,6-dioctyl-1 , 2-phenylene] -bis- (mercury-trifluoroacetate))

According to the sensitivity to salicylate ion, Fluka chloride ion selective material I (Chloride Ionophore I: 5,10,15,20) is a chloride ion selective material commercially available without using an epoxy resin and an amine curing agent in Table 3 . -Tetraphenyl-21H, 23H-polpine manganese (III) chloride), Chloride Ionophore II: [4,5-dimethyl-3,6-dioctyl-1,2-phenylene] -bis- (mercury-trifluor Loacetate)) was prepared in the following composition-33% by weight of poly (vinyl chloride), 1% by weight of Chloride Ionophore, 66% by weight of DOA, 0.5% by weight of TDMACl-to prepare a solvent-type polymeric chloride ion electrode. We compared the sensitivity of chloride ion selective electrode with amine curing agent and 100 mM chloride ion and salicylate ion.The chloride ion selective material I was shown in Table 3 and Figure 9a to 1 mM salicylate ion. Is also severely disturbed and its potential value For not been able to represent the chloride ion quantitative values chloride ion ion selective material Ⅱ also 1mM In exhibit a similar chloride ion quantitative value 2, it shows for the salicylate ion of 3mM Severe disturbance effects to 115mM, 136mM. Fig. 9b is a chloride ion selective electrode using an epoxy resin and an amine curing agent, unlike in FIG. 9a , there is no difference in the potential value even in the presence of 3 mM salicylate ion, and thus does not affect the quantification of chloride ion. Through the use of epoxy, the chloride ion selective electrode is unlikely to be affected by the determination of the concentration value of chloride ion even when bromine or salicylate ion coexists with the chloride ion, unlike other electrodes.

Experimental Example 6 Application to Actual Clinical Sample Analysis

Whether the use of chloride ion selective membranes formed of glycidyl epoxy resins and amine curing agents can reduce the effects of contamination of electrode surfaces by adsorption of macromolecules such as proteins and can be used for clinical analysis. An experiment was performed to see if there was any. The result is shown in Fig.

The tested 106 mM and 53 mM chloride ions were tested to quantify the potential value of chloride ion. In the standard solution, the three types of chloride ion-selective electrodes show similar values and can be used in samples without protein. Here blood and serum are used to determine the effect on protein. When the electrodes were exposed to the sample, the electrode without the epoxy membrane showed a greater response than the membrane using the epoxy membrane due to protein adsorption, which was converted to a concentration value of about 100 mM in serum and about 111 mM in blood. Was higher than the reference value of 94.4 (± 4) mM attached at the time of reagent purchase, and blood was actually 11 mM larger than the commercialized analyzer (eg Nova Stat Profile Plus 5). However, the chloride-ion-selective electrode formed of glycidyl-based epoxy resin and amine-based curing agent showed accurate quantitative value of 98.4 mM in serum and 101.2 mM in blood. These quantitative values are shown in Table 4 below.

Chloride ion concentration values determined using different types of chloride ion selective electrodes Sample type Composition of the sample (or reference value attached at the time of reagent purchase) Quantitative value of chloride ion (mM) Electrode without Epoxy Chloride Selective Membrane Electrode Using Epoxy Chloride Selective Membrane Solvent-Polymer Electrode (Commercial Analyzer ^a ) Standard solution ^b Cl ^- 80 ± 5 mM 80.0 79.0 79.0 Serum ^c Cl ^- 94.4 ± 4 mM 100.0 98.4 97.0 Blood ^d Cl ^- 99 ± 4 mM 111.1 101.2 100 a: Blood analyzer (Nova Stat Profile Ultra M; Waltham, MA, USA) .b: ALKO Diagnostic Corporation-Hollistonc: Nissui Pharmaceutical Co. (Tokyo, Japan) d: Received from a blood source.

<Experiment 7> Study on the feasibility of applying it to actual industrial sample analysis

The use of a chloride ion selective membrane formed of a glycidyl epoxy resin and an amine curing agent is used for the surface of electrodes by sulfides containing sulfide ions, sulfate ions, sulfite ions, or sulfide ions in industrial samples. An experiment was conducted on the effects of contamination. The result is shown in Fig.

The concentration of chloride ion was examined from 10 ^-5 M to 10 ^-1 M for the performance test of the electrode by placing the membrane made using the composition shown in the composition 1 of Table 1 for the electrode performance test. Up to 50 mM.

Referring to FIG. 11A , a chloride-ion selective electrode using a silver / silver chloride (Ag / AgCl) solid-phase membrane has an inclination of -55 mV / decade in a range from 10 ^-3 M to 10 ^-1 M chloride ion using an epoxy resin and an amine curing agent. It showed a sensitive characteristic in which the slope was slightly lower than that of the chloride ion selective electrode. It can be seen from the experiment that the solution mixed with 10 mM sulfide ion flows negatively and the electrode is broken. After experimenting with a solution containing sulfide ions, the same Ag / AgCl as Ag / Ag ₂ S was substituted for N- [2-hydroxyethyl] piperazine-N '-[3 as in the case of bromide ions. -Propanesulfonic acid] was titrated with sodium hydroxide solution and the pH of the buffer was adjusted to 7.4. On the other hand, in FIG. 11B , the slope of the chloride ion selective electrode using the epoxy resin and the amine curing agent was 10 ⁻³ M to 10 ⁻¹ M in the range of −58 mV / decade, and the silver / silver chloride (Ag / AgCl) solid phase membrane was used. Its slope is superior to that of chloride-ion-selective electrodes and maintains the performance of N- [2-hydroxy, regardless of the presence of high concentrations of sulfide ions, even if there is a slight interference with sulfide ions from 10 mM to 50 mM. Ethyl] piperazine-N '-[3-propanesulfonic acid] was titrated with sodium hydroxide solution and returned to a constant value when looking at the basic potential value of the electrode in a buffer solution adjusted to pH 7.4.

Experimental Example 8 Electrode Life Study of Chloride Ion Selective Electrode Formed with Glycidyl Epoxy Resin and Amine Curing Agent

Membranes made using the compositions shown in Compositions 1,2,6,7 in Table 1 were placed on a solid-state electrode, and N- [2-hydroxyethyl] piperazine- N ' -[3-propanesulfonic acid] was dissolved in sodium hydroxide solution. The sensitivity of chloride ions, bromide ions, and salicylate ions in the buffer solution adjusted to pH 7.4 was compared. Then, titrate N- [2-hydroxyethyl] piperazine- N ' -[3-propanesulfonic acid] with sodium hydroxide solution, soak the electrode in a buffer solution adjusted to pH 7.4 The response to ions, bromide and salicylate ions was observed. 12a and 12b look at the usable period of the composition 1 and composition up to about 320 days.

For an electrode using the electrode film of composition 1, the average response slope was approximately 250 days for the electrode using the electrode film of composition 2, and the former was -52 mV / decade for the former and -55 mV / decade for the latter. Indicated. Similarly, the electrodes of Compositions 6 and 7 exhibited an average slope of -55 mV / decade for a similar period, confirming that the life of the electrodes was improved.

As described above, the conventional electrode or the solid-state electrode to which the chloride ion selective membrane formed of the composition of the present invention is applied is exemplified by bromine ion or salicylate ion in the quantitative analysis of chloride ion in a biological material using a chloride ion sensor provided therewith. The effect of the adsorption of interfering ionic species such as proteins and macromolecules such as proteins is reduced, so that accurate measurement of chloride ion can be obtained, and it is measured by not being inhibited by hydroxide ion in biological materials in the pH range of 5.5 to 10.5. It is effective to further improve the reliability of, and in particular, the chloride ion selective membrane formed on the surface of the solid phase electrode by the composition according to the present invention has excellent adhesion and electrochemical properties to the surface of the solid phase electrode, which is a problem of sensitivity to chloride ion. Of the chloride ion sensor It enables the type forming.

Claims (9)

An epoxy resin and an amine curing agent provided in a conventional ion selective membrane electrode composed of a conventional chloride ion selective membrane electrode having an internal reference solution between the ion selective membrane and the internal reference electrode, and a poorly soluble metal salt layer and an ion selective membrane. Chloride ion selective membrane composition comprising. The method of claim 1, wherein the epoxy resin is bisphenol A diglycidyl ether; Tetrabromo bisphenol A diglycidyl ether; Tetraphenylene ethane tetraglycidyl ether, trihydroxybiphenyl triglycidyl ether; Hydroxypolyphenyl polyglycidyl ether, phenol formaldehyde noblock polyglycidyl ether, o-cresolformaldehyde noblock polyglycidyl ether; 4,4-diamino-diphenylmethane; And diglycidyl isophthalate, diglycidyl terephthalate, diglycidyl hexahydroterephthalate, diglycidyl phthalate, diglycidyl 3,5 dichloroterephthalate, diglycidyl diphenoate, triglycidyl Chloride ion selective membrane composition, characterized in that the epoxy resin containing glycidyl groups (glycidyl groups) in cydyl trimethoate, triglycidyl trimellitate, tetraglycidyl pyromellitate. The method of claim 1, wherein the amine curing agent is ethylenediamine, trimethylhexamethylenediamine, diethylenetriamine, dipropylenetriamine, triethylenetetraamine, tetraethylenepentaamine, 2-hydroxyethyldiethylenetriamine Amine consisting of diethylaminopropylamine, N-aminoethylenepiperazine, m-xylenediamine, benzyldimethylamine, n-butylimidazole, 1-methylimidazole and boron trifluoride monoethylamine Is selected from a family group; A chloride ion selective membrane composition, characterized in that it is a mixture of a tertiary amine and an amine curing accelerator of an imidazole group in an acid anhydride. The chloride ion selective membrane composition according to claim 1, wherein the epoxy resin and the amine curing agent are mixed at 50 to 94: 6 to 50 wt%. The chloride ion selective membrane composition according to claim 1, further comprising 13 to 65 parts by weight of diluent based on 100 parts by weight of the membrane composition. The method of claim 5, wherein the diluent is tetrahydrofuran, acetone, methanol, cyclohexanone, dichloromethane, xylene; Butyl glycidyl ether, phenyl glycidyl ether, 2-ethylhexyl glycidyl ether; Or bis (2-ethylhexyl) adipate (DOA), diisooctyl phthalate (DOP), 2-ethylhexyl epoxytalate (EHE), 2-nitrophenyloctyl ether (NPOE) Ion Selective Membrane Compositions. The chloride ion selective membrane composition according to claim 1, wherein the lipophilic additive further comprises 0.5 to 30 parts by weight based on 100 parts by weight of the membrane composition. 8. The method of claim 7, wherein the lipophilic additive is tridodecylmethylammonium chloride, tetradodecylammonium chloride, tridodecylmethylammonium nitrate, tetradodecylammonium nitrate, tetraoctylammonium bromide, methyltrioctadecylammonium bromide , Dimethyl distyrylammonium chloride, dimethyl distyrylammonium bromide, tetraoctadecylammonium bromide, tetraoctadecylammonium chloride and bis (triphenylphosphoryldine) ammonium chloride Selective membrane composition. A chloride ion selective membrane electrode comprising the chloride ion selective membrane composition of claim 1.