JPS5883247A - Measuring instrument for ionic activity - Google Patents

Abstract

PURPOSE:To prevent the position deviation between liquid spotting holes and electrodes by making the liquid spotting holes in areas relatively larger than the electrodes. CONSTITUTION:Sample spotting holes 28, 29 have areas that can enclose the entire surface of electrodes 10, and the liquid supplied through the holes 28, 29 contacts the entire surface of the electrodes 10 at all times as it fills the holes 28, 29, thus the areas contributing to measurement are regulated automatically by the areas of the electrodes 10. In other words, if the areas of the electrodes 10 are kept constant, the contact areas of the liquid and the electrodes 1 (wetting areas contributing to measurement) are always constant. If the measuring instrument for ionic activity having the spotting holes constituted as mentioned above is used, the ionic activity in solns. is measured easily with good accuracy.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to ion concentration or ion activity instruments. In particular, the present invention uses botensiometric K11 to measure ion concentration or ion activity in body fluids such as aqueous fluids, blood, and serum.
The present invention relates to an ion activity measuring device for determining ion activity.

Generally, Φ, Nae, Oa*e, and O1e are found in biological fluids.

Measuring the concentration of inorganic ions such as Hoo and θ is clinically important, and a wet method using an ion-selective electrode has already been implemented.

All of these are of the type that measure by immersing a needle-shaped O electrode in biological fluids, and the management of the electrodes is troublesome in terms of electrode maintenance, cleaning, conditioner cleaning, lifespan, damage, etc. Since it is necessary to sufficiently immerse the sample in the test sample liquid in the cup each time, an amount of sample liquid of several hundred microliters or more is required. In order to eliminate such inconvenience, an electrode film of the type in which the electrode is a dry film type and the test sample liquid is spotted on it was disclosed in Japanese Patent Application Laid-Open No. 52-142584.
In addition, a method of organizing electrodes into a thin wire-like dry type was disclosed in Japanese Patent Publication No. 52-47717 and Japanese Patent Application Laid-open No. 49-1287.
93. The ion selective electrode film disclosed in JP-A-52-142584 includes a metal layer on an insulating film, a water-insoluble salt layer of the same kind of metal as the metal of the metal layer, and a water-soluble salt layer having an anion common to the water-insoluble salt. It is a dry type in which a dried electrolyte layer consisting of a hydrophilic binder matrix containing dissolved salt and an ion selective membrane layer are laminated in this order. After forming a pair of these two electrode films, connecting them with a bridge, and connecting them to a potentiometric needle, a sample solution and a standard solution are respectively spotted on the pair of electrode films, and the potential difference is measured to determine the concentration of the sample solution. You can know. In addition, #i in %Opening No. 49-128793, a water-insoluble salt layer of the same kind of metal as the metal wire concentrically on the metal wire, an electrolyte layer containing an anion common to the water-insoluble salt,
Using a solid-state ion-selective electrode coated with an ion-selective membrane layer in this order, the electrode and the saturated electrode (
A method is described in which a control electrode (as a reference electrode) is connected to a potentiometer, and then the electrode is immersed in a sample solution to read the potential difference. These dry type ion selective electrodes.

By changing the type of ion-selective membrane on the top layer, it is possible to measure specific ions.

Therefore, there are many types such as Ki measurement, Nap"' measurement, S07θ measurement, and HOOI measurement.

Although these dry type electrode films have certainly improved in terms of cost, ethical strength, and reproducibility, which were problems with conventional wet methods, there is still a need to develop ion-selective electrodes that can provide highly accurate measurement results. It was wanted.

After investigating various factors thought to be involved in measurement accuracy, the present inventors found that the potential generated as a function of specific ions is caused by contact between the test liquid spotted on the ion-selective electrode and the ion-selective electrode. I learned that you can get a benefit depending on the area you cover.

In conventionally known ion-selective electrodes, liquid is spotted at an appropriate location on the ion-selective electrode in order to correctly guide the test liquid or reference liquid (sometimes simply called liquid) onto the ion-selective electrode. Usually, holes are provided, and the wetting area of the electrode is determined by the area of these holes. Therefore, the area of the spotting hole is smaller than that of the electrode. It has been recognized in the prior art that configuring the liquid spotting holes to have such a small area is advantageous in order to properly guide the spotted liquid to the ion selective electrode. Thus, in order for a potential to develop as a function of ion concentration or activity, the deposited liquid must be properly guided onto the poles, but this requires minimal contact between the liquid and the electrodes. means you have to. In solid-liquid contact, if the amount of test liquid necessary for measurement is supplied, solid-liquid contact can be achieved by using plenty of test liquid without worrying about contact efficiency. In most cases, only a very small amount of test liquid can be used. This is the reason why, in known ion-selective electrodes, the spotting holes are designed to have a smaller area in order to minimize the loss of the sample liquid. On the other hand, the electrode that receives the test liquid is required to have an area with a sufficient tolerance so that unexpected accidents such as misalignment of the instrument can be dealt with as much as possible. For this reason, in known ion-selective electrodes, the liquid spotting holes are configured to have as small an area as possible, and the electrodes have a larger area, that is, the relationship between the spotting hole area and the electrode area is established. It is. However, even when an ion selective electrode configured in this manner is used, disturbances occur in the generated potential. According to the findings of the present inventors, as described above, there is a close relationship between the contact area between the liquid and the electrode and the generated potential. In known ion-selective electrodes in which the area of the spotting hole is equal to the area of the electrode, the spotting liquid reaches the electrode having an area larger than the spotting hole and then undergoes free diffusion on the surface. In this case, since the liquid p diffusion is not constant, the area where the liquid contacts the electrode is not constant.

In particular, in differential measurement methods that use both a test solution and a reference solution to measure the concentration or activity of a specific ion from their potential difference, the surface tensions are often different because the liquid compositions are not the same. It is virtually impossible to equalize the area of both liquids deposited at one point due to reasons such as the difficulty of supplying both liquids in exactly the same amount as a practical matter. .

In addition, in conventional ion activity measuring instruments, the primary purpose was to prevent misalignment between the liquid spotting hole and the electrode, so the periphery of the spotting hole was sealed with adhesive. fixed to the electrode. Most of the adhesive oozes out onto the electrode side surface by pressing the adhesive reservoir. The inventors' research has revealed that the adhesive that oozes out in this way is also a factor in making the area of the spotted liquid unstable. The present inventors have repeatedly studied how to eliminate the causes of potential fluctuations that affect measurement accuracy, and as a result, they have discovered an ion activity measuring instrument with a new structure based on an idea completely opposite to that of conventional technology.

Therefore, an object of the present invention is to provide an ion activity measuring instrument having a completely new structure.

A further object of the present invention is to provide an ion activity measuring instrument that eliminates various drawbacks observed in conventional electrodes, can be easily operated without requiring a high level of skill, and provides high accuracy. It's about doing.

In the present invention, an ``ion activity measuring device'' is a device consisting of an ion selection electrode as a minimum unit and at least one bridge connecting the electrodes. In order to carry out the measurement practically or conveniently when actually measuring ion activity, the ion activity measuring instrument of the present invention has, in addition to the above-mentioned basic structure, other known instrument components, for example.

It goes without saying that it may include bridge fixing means and the like.

The ion activity measuring device according to the present invention differs from conventional devices in that it has a structural feature in that the liquid spotting hole has a relatively larger area than the electrode.

More specifically, 1. The ion activity measuring instrument of the present invention basically consists of an ion selective electrode (also simply referred to as an electrode) containing at least a conductor and an ion selective layer or a protective layer, and a rumor bridge. The device component has a liquid spotting hole (simply referred to as a spotting hole), and the spotting hole is configured to have a relatively larger area than the area of the ion-selective electrode.

The liquid spotting holes 28 and 29 are as shown in FIG.
The entire surface of the electrode 10 can always be included. In this way, since the sample spotting holes 28.29 have an area that can cover the entire surface of the electrode IO, the sample spotting holes 28.
The liquid supplied through 29 always comes into contact with the entire surface of the electrode IO by filling the spotting holes 28,29. In other words, the area involved in the measurement is naturally defined by the area of the electrode IO.

In other words, if the area of the electrode 10 is kept constant in %1Jt, the contact area between the liquid and the electrode 10 (measured KfJ@applied wetting area)
is always constant.

In the present invention, when the liquid spotting hole is relatively larger than the area of the electrode, it means that the liquid spotting hole has a hole with an area that can cover the entire surface of the electrode. It may be of any shape as long as it satisfies the following relationship, and may be concentric or eccentric.

The shape of the spotting hole does not need to be a special shape as mentioned above;
For example, it may be a circle, an ellipse, a regular hexagon or other polygon, or any other shape. It is important that the dot holes are located so as to cover the entire surface of the electrode (that is, so as not to change the area of the electrode). There is no problem even if there is a discrepancy in the number of positions.

As mentioned above, the single-point deposition hole only needs to have a relatively large area compared to the electrode, and is not required to have a specific size, but considering the amount of sample liquid usually used for measurement,
In the circular case, the diameter is generally #? Those with 72 to 6 cranes are preferred.

In this case, the electrode is also circular, with a diameter of 1 to 5
Cotton is preferred. Furthermore, if the electrode and the spotting hole are concentric, the above relative relationship between the two is such that, as a rough guide, the spotting hole should have a diameter approximately 0.5 to zIllll larger than the outer circumference of the electrode. Satisfied by composing.

In the present invention, as described above, the liquid spotting hole is configured to have a relatively large area compared to the electrode, and the area of the liquid is defined by the area of the electrode. Even in the case of using adhesive that spreads, the constant area defining function of the electrodes is not impaired by the adhesive that oozes out. However, the currently available adhesives, without exception, bleed to some extent due to the crimping operation. Immobilization can be easily achieved without using.

In order to make the liquid spotting hole larger in area than the electrode in the *polar device of the present invention, it is better to configure the electrode to have a smaller area than conventionally known ones, from the viewpoint of minimizing the amount of liquid sample. It is also convenient from the viewpoint of resource saving.

The liquid spotting hole may be provided in any component constituting the ion activity measuring device of the present invention, but in order to realize the function of supplying the test liquid and the reference liquid, it is necessary to provide the liquid spotting hole at both ends of the bridge. Alternatively, it is preferable to provide it in the instrument frame (particularly the upper slide frame) provided as necessary, or in the case where the upper slide frame and the bridge are integrated, in common.

In the ion activity measuring device of the present invention, the ion selective electrode includes at least a conductive layer and an ion selective layer or a tumor layer. The ion-selective electrode is further coated with an electrolyte layer (
provided between the conductor layer and the ion selective layer).

An example of the layer structure of a typical ion selective electrode is as follows.

All are laminated and integrated in the order listed.

fi+ Conductive metal layer and ion selective layer (2) Conductive metal oxide layer and ion selective layer (3) Conductive metal layer, water-insoluble salt layer of the same metal as the metal, and ion selective layer (or protective layer) 141 Conductive metal layer, water-insoluble salt layer of the same metal as the metal, electrolyte layer, and ion selective layer +61 Conductive metal oxide layer, electrode layer, ion selective layer, etc.

In any of the above cases, if the conductive layer has self-supporting properties, it can be formed as a layer on a suitable support if it does not have self-supporting properties.

As the conductive metal and metal oxide constituting the electrode, metals used in known electrodes can be used, and examples thereof include silver, copper, platinum, gold, etc., and oxides thereof.

Examples of water-insoluble salts of conductive metals include genides (for example, Ago/, AgBr, AgI) and sulfides (for example, Ag*8.0us8, etc.) of the above metals.

The electrolyte layer is a layer of an electrolyte having an anion common to the anion of the above-mentioned water-insoluble salt.
O/, NaOl, Ks 8, etc.). The electrolyte layer may be of a water-using type or a dry type.

The ion selective layer can select specific ions,
Preferably, it is sufficient that it is electrically insulating in a dry state before coming into contact with the reference liquid or test liquid. "Being able to select a specific ion" does not only mean that only a specific ion is selectively permeable or sensitive, but also that a specific ion can be detected by other substances that are not the target of measurement with a sufficient time difference for measurement. This also includes cases where it is selected from. Additionally, depending on the material used in the ion-selective layer, the botensiometric response corresponding to changes in ion activity in the liquid may be measured through ion exchange, resulting in a function equivalent to selecting a specific ion. [Specific ions can be selected, called phrases.

Since both the test liquid measured in the present invention and the reference liquid used as necessary are aqueous liquids, the ion selective layer must be water-insoluble. It may be hydrophilic or hydrophobic as long as it is water-insoluble, but hydrophobic is preferable. A typical example of ion selection 1 is an ion carrier, an ion carrier solvent, and a hydrophobic organic binder (or a matrix consisting of a hydrophobic organic binder).
It consists of Ion carriers include palinomycin, cyclic polyether, tetralactone, macrolidoactin, enninatine group, monensins, gramicins, nonactin group, tetraphenylborate,
There are cyclic polypeptides, etc.

As an ion carrier solvent, bromophenyl-%3
-methoxyphenyl- and 4-methoxyphenyl-phenyl ether, etc. -dimethyl-, diptyl-, dioctyl-phthalate, etc. -1-digtyl sebacate, etc.

Hydrophobic organic binders include hydrophobic natural or synthetic polymers that can form thin films (for example).

cellulose esters, polyvinyl chloride, polyurethane, etc.).

Ion exchange resins can also be used as materials for the ion selective layer. When an ion exchange resin is used, the ion exchange causes a change in ion activity in the ion-containing solution, and the resulting potential difference response is measured.

The ion exchange resin may be either cationic or anionic; for example, quaternary alkysphonium, alkyl,
Polydialkyldithiocarbamates such as sonium, stibonium or sulfonium ions, Q-diketoy
Class 1 includes sulfonated polystyrene, etc.

Father, regarding the ion-selective layer, the ion to be measured is
, Nae, 0. In the case of me, HOOse (7), KU is essential, but the ion to be measured is Ole.

When the conductor layer is made of scissors and the water-insoluble salt is silver chloride, the ion selective layer is not necessary. Cellulose esters described in JP-A-55-89741, JP-A-53-72622 and JP-A-54-138
A layer formed from the latex or the like described in 4 is provided as a storage layer permeable to ions to be detected.

Each constituent material of the ion selective electrode used in the present invention is known, and a known method can be applied to layer formation. In particular, regarding conductive metal oxides and metal oxides, JP-A-52-1425
84. 49-128793, % Kosho 52-47717
and Per Kofstad “No11-No11-
5toicbio.

D eye fusion and gl*'ctrical
Conductivity in Binary Met
Al αwidesJ, published by Wiley Interscience Co., Ltd., published in 1972, for information on the materials and formation of the i-electrolyte, see US Pat. JP 52-142585゜U.S. Patent Nos. 4053381, 4171246, 4
No. 214968 and “Research Disclosure”
It is detailed in the magazine Hobun-16113 (September 1977 issue).

In the ion activity measuring instrument of the present invention, a bridge is formed in order to cause and promote ion movement between the test liquid and the reference liquid required for potentiometric measurement. Known materials can be used as bridge materials, such as porous paper (F paper/blotting paper), binder, membrane filter, cotton material (cotton cloth), and mixtures of thickeners and polycarbonate or polyamide. It is made of porous materials such as

When using a plastic frame as a bridge, a coating film can be applied to the plastic using a surfactant that can promote ion migration (e.g., octylphenoxyethanol, nonylphenoxyethanol, etc.) or the porous material mentioned above. may be formed.

In addition, a preferable example of the bridge is 1% 1425
No. 84 (U.S. Patent No. 4.05 381°4, z1+, t
ASA and 4171.246), 55-593
No. 26, No. 55-71942, No. 55-20499 (corresponding to U.S. Pat. No. 414 to 936), Utility Model Application No. 55-6
It is described in No. 4759, etc.

The above-mentioned prickle is preferably fixed on the electrode so that the spotted liquid connection can be accurately communicated. As the means for fixing the bridge, the means described in the above-mentioned published publication or the known literature by Hiro can be applied, but a typical method is to fix the bridge using an adhesive.

Protrusions are provided at both ends of the cover sheet that protects the ion selection' electrodes. It has a recess that can receive a bridge extending away from the center and means for physically engaging the bridge with the recess.

The present invention will be explained in more detail below with reference to one drawing.

FIG. 2 (4) is a conceptual diagram showing the case where the electrode used in the ion-selective electrode device of the present invention is manufactured on an industrial scale.

That is, the first opening having the shape shown in FIG. 2 Φ)K and (Q
An electrode having this shape is produced by stacking patterns having a large number of second openings as shown in FIG. In the second −, the electrode is numbered 10
18 indicates an electrical connection terminal, and electrode 1G
The diameter (, ) is 3 mm, and the portion connected to the connecting terminal 18 has a width (B) i g * and a length C) 4 m 1 m. The length d) of the connecting terminal 18 is 5, and the width (,) is 6.
It's a crane. A first opening (B) having such size
A plurality of openings are provided at a spacing of 4B (f), and two openings of the same size are vertically spaced apart from each other by a distance of 7 mm from the circular part of the opening, and are connected so that the circular parts form both ends. The second opening (d of the drain opening is 2d) shown in Figure (0) is arranged so that the first opening and the circular portions face each other.

A high-purity conductive metal (for example, silver) is placed in a tungsten basket evaporation source, the above pattern is superimposed on a polyethylene terephthalate film (about 100 μm thick), and the above pattern is placed in a vacuum evaporation apparatus at a distance of about 30 cm from the evaporation source. do. Operate the vacuum evaporator to achieve a vacuum level of approximately 5X.
For example, the amount of silver deposited at 10-5 Torr is 4 g/
Conductive metal (transfer) layer 1 is deposited until it reaches m”.
1. Next, after pasting vinyl chloride adhesive tape at the positions and widths indicated by i and 2h in FIG. A layer 12 of the conductive metal salt (silver chloride) is formed by treatment with a solution consisting of 5 g of 7g% 36% hydrochloric acid and 11 of water. Itl12 may be formed by vacuum deposition of the conductive metal salt.

An ion-selective layer or an ion-permeable film-holding layer 14 is formed on the conductive metal salt layer 12 thus obtained. In this case, the same composition may be used (to obtain an electrode for testing two or three items) or different compositions may be used (an electrode assembly for two or three items may be obtained depending on the cutting section). ). Finally, the polyvinyl chloride adhesive tape is removed and the ion selective electrode 10 is removed.

FIG. 2(b) shows the electrode obtained by cutting along the line 1000 in FIG. 2(4). The pair of electrodes 10 are connected by a bridge 20 (made of Catan thread, for example).

This bridge 20 has point holes 28 and 29 having a larger area than the entire surface of the electrode 10, and constitutes an ion activity measuring instrument of the present invention.

FIG. 2(G) shows an electrode assembly cut along the line 2000 in FIG. This shows an ion activity measuring instrument in which the bridge 2° is #t to connect the electrodes.

Conventionally known methods can be applied to perform potentiometric analysis of a liquid using the ion activity measuring instrument of the present invention.

That is, when measuring ion activity using the above-mentioned ion activity measurement device, when a test sample solution and a standard solution are spotted on each pair of electrode films, the test solution and standard solution are , the liquid in the test liquid penetrates through the bridge due to capillary action, and the two liquids come into contact almost at the center of the bridge, and the potential difference between the electrode fills that occurs when ion communication is achieved is measured with a potentiometer. The concentration or ion activity of the analyte ions contained in the sample can be measured.

The results of measuring the potassium ion activity in the test liquid as described above using the ion-selective electrode device of the present invention are shown below.

For comparison, the results obtained using a conventional ion activity measurement device (liquid spotting hole 1) are also shown.

The compositions of the spotted test solution and reference solution are as follows.

Reference solution; Na1l 142 mmol//
4゜KOI 3 mmo+// Test solution; Na1l 142 mmol//KO
I 6 mmol// Amount of each liquid applied; 20s1 Invention 40 19 98.5 &91
Conventional method 40 5.5 97.5 5.8
51) Standard deviation/average value x 100 2) Actual value/true value The coefficient of variation is smaller and higher accuracy values can be obtained than in the case of

are doing.

By using the ion active lid measuring instrument of the present invention configured as described above, the ion activity in a solution can be easily and accurately measured.

[Brief explanation of drawings]

Fig. 1 is a conceptual diagram showing an example of the ion activity measurement device of the present invention, and Fig. 2 (4) shows the large-scale production of an ion selective electrode with a preferred shape used to realize the present invention. It is a top view showing an example. Figure 2 (B) and (Q is an enlarged view of the -th and second openings,
) and (g) in FIG. 2 are preferred embodiments of the ion activity measuring instrument of the present invention, in which the ion-selective electrode pairs obtained by cutting along the lines 1000 and 2000 in FIG. 2 (4) are connected by a bridge, respectively. FIG. The main symbols in the figure are shown below. IO solid electrode 11 Conductive metal (silver) layer 12 Metal salt (chlorinated steel) layer 14 Ion selective layer or ion permeable storage layer 18 Connection terminal 19 Support 20 Bridge 28 Test liquid spotting hole 29 Reference liquid spotting Patent Applicant: Fuji Photo Film Co., Ltd. Agent: Gobe Sunakawa (and 1 other person) Figure 1 2nd, f Figure 2 (A) Figure 2 (B) Figure 2 (C) 19. 14 19 Figure 2 (DJ Figure 2 (E) Procedural amendment (spontaneous) January 21, 1980 Director-General of the License Office Mr. Shunto Shimada, following the case, 1982 Patent Application No. 182477 2, Name of the invention: Ion activity measuring device 3, relationship with the case of the Ministry of Health, Labor and Welfare: Patent applicant address: 210 Nakanuma, Minamiashigara City, Kanagawa Prefecture Site name (520
) Fuji Photo Film Co., Ltd. Representative Dai fj
i Tei 4, Agent

Claims (1)

[Claims] In an ion activity measurement device having a liquid spotting hole consisting of an ion selective electrode and at least one bridge communicating between the electrodes, the liquid spotting hole has an area relatively larger than the area of the electrode. Characteristic ion activity measuring instrument.