Ion selective electrode apparatus and method of producing ion selective electrode apparatus

An ion selective electrode of flowthrough type is used for electrochemical measurement of ion species contained in a biological fluid by the electrode method. In the electrode method, the reaction of an ion and a sensing substance contained in an ion-sensing membrane is electrochemically detected. plurality of holes are made on a part of the wall of a path for letting the biological fluid flow therethrough. An ion-sensing membrane is formed in the plurality of holes such that each membrane includes a different sensitive ion from the other and the inner surface of the path is kept smooth.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to an ion selective electrode of the 
flowthrough type for use in electrochemical measurement of ion species 
contained in a biological fluid. 
2. Description of the Related Art 
There are colorimetric method, flame method, atomic absorption method, 
coulometric-titration method, and electrode method, used as a measuring 
method of the electrolyte concentration in samples, such as a blood serum, 
plasma, and urine. Of these methods, the electrode method has come to be 
used broadly in recent sears. 
Especially, the electrode method is mainly used for concentration 
measurement of electrolytes such as sodium ion, potassium ion, and 
chlorine ion, in a clinical inspection field. 
The electrode method is a method of electrochemically detecting the 
reaction of an ion and a sensing substance using an ion-sensing membrane 
which confine the sensing material sensitive to an ion to be detected. A 
common method of detecting the electric signal from the sensing membrane 
is a detection with an Ag/AgCl electrode which is an internal electrode 
through an electrolyte solution. The method of producing the ion selective 
electrode used for the electrode method is that the ion-sensing membrane 
is beforehand made by methods such as casting and then a fragment of the 
membrane is stuck on an electrode main part. Moreover, when measuring 
electrolyte concentration in a sample in a clinical inspection, usually 
two or more ions, such as sodium, potassium, and chlorine, are 
simultaneously measured. For this reason, the ion selective electrode used 
in order to measure these ions is used as a complex electrode by 
combination, for example, unifying or glueing several ion-selective 
electrodes using packings, such as an O ring. 
Since an adhesion area for sticking the ion-sensing membrane is needed for 
an electrode main part according to the above-mentioned manufacturing 
method, in order to stick the ion-sensing membrane firmly, an electrode 
main part had to be large. Adhesion would be difficult if an adhesion side 
is small. Therefore, there is a limit in miniaturization of an electrode 
main part in such a method. 
On the other hand, a CWE system (which an ion-sensing membrane is) stuck on 
an Ag/AgCl electrode is also put to practical use. According to this 
method, since an electrolyte solution is not necessary, it is possible to 
miniaturize an electrode main part. However, the ion-sensing membrane 
needs to be formed directly the Ag/AgCl electrode surface by applying 
material which forms the ion-sensing membrane. In this case, the surface 
of the ion-sensing membrane is uneven, therefore even if the surface of an 
ion-sensing membrane is washed with calibration liquid after measurement 
in this case, a sample tends to remain on the surface of the ion-sensing 
membrane. 
Furthermore, according to the method of combining two or more ion selective 
electrodes, the path in an electrode through which a sample flows becomes 
long. Moreover, since the surface the junction side of the path in each 
electrode is not smooth and continuous, the sample often remains in the 
portion and an exact measurement result cannot be obtained. 
SUMMARY OF THE INVENTION 
It is an object of the present invention to provide an ion selective 
electrode and method of producing the ion selective electrode, wherein the 
ion selective electrode is small, is able to measure two or more ions in a 
sample simultaneously, and has few remains of a sample after washing. 
To accomplish the above object, an ion selective electrode apparatus 
according to the present invention comprises a holding portion having a 
plurality of tanks for containing an electrolyte solution and a path 
penetrating through a plurality of the tanks for letting a sample flow 
therethrough, an ion-sensing membrane formed in each of the tanks to 
enclose at least a portion of the path within the tank for contacting the 
ion-sensing membrane with an electrolyte solution when the sample flows in 
the path, the ion-sensing membrane being manufactured by a method 
comprising the step of making a plurality of holes on the holding portion 
therethrough to the path; inserting a pin all over the path; filling each 
of the plurality of holes with a sensing membrane solution having 
substantially the same ingredient as the holding portion and including a 
different sensitive ion from the other solution; drying the sensing 
membrane solutions removing the pin from the path, and an internal 
electrode dipped in each of the electrolyte solution. 
Furthermore, to accomplish the above object, a method of producing an ion 
selective electrode apparatus according to the present invention comprises 
the step of preparing a holding portion, having a tank to store an 
electrolyte solution in the lover part, and that the upper part is open; 
making a path which penetrates the holding portion; making a plurality 
holes on the holding portion therethrough to the path; inserting a pin all 
over the path; filling each of the plurality of holes with a sensing 
membrane solution having substantially the same ingredient as the holding 
portion and including a different sensitive ion from the other solution; 
drying the sensing membrane solution; removing the pin from the path; 
closing the upper part of the holding portion with a lid which has a 
pouring hole; and pouring a electrolyte solution from the pouring hole 
into the holding portion. 
According to the present invention, by forming directly an ion sensing 
membrane on the path which penetrates through holding portion which 
contains an electrolyte solution using a sensing solution to two or more 
ions which differ, a miniaturization of an electrode main part is enable, 
and two or more ions in a sample can be measured simultaneously, and the 
sample remainder after washing also be made few.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
An embodiment of the present invention will be described, with reference to 
the accompanying drawings. 
FIG. 1 is an exploded perspective view showing the structure of the ion 
selective electrode according to all embodiment of the present invention. 
In the figure, an example in which two ion detection electrodes are 
combined is shown. A holding portion 1 has a half-cylindrical shape and 
two hollow portions each forming a part of an internal solution tank 1b, 
1e. At the center of each hollow portion, a projection portion is provided 
along the center axis of the half-cylinder. A path 1a penetrates through 
the projecting portions along the center axis of the half-cylinder. A 
sensing membrane 4 (K-membrane) and a sensing membrane 7 (Na-membrane) are 
formed in membrane holes 1c and 1f, respectively each of which is provided 
on the projecting portion and connected to the path. An electrode main 
part with a cylindrical shape is constituted by closing the hollow 
portions of the holding portion 1 with lids 2 and 5 of half-cylinder type. 
The electrode main part has two cells each of the cells (1 unit electrode) 
is separated by a wall 1d, and includes an internal solution tank 1b and 
1e. The electrode main part is mainly polyvinyl chloride (PVC). An 
electrolyte solution is held in each of the tanks 1b, 1e of the electrode 
main part. Ag/AgCl electrodes 3 and 6 are used as internal electrodes and 
penetrate through and are fixed to the lids 2 and 5, respectively, and are 
dipped in the electrolyte solution. Moreover, air extraction holes 2a and 
5a for extracting air and pouring holes 2b and 5b for pouring in the 
electrolyte solution are formed in the lids 2 and 5, respectively. 
FIG. 2 is a cross-sectional view showing the structure of the ion selective 
electrode of the present invention. The cells A, B, and C for measuring 
different ions are united in the direction of an axis of the electrode 
main part. The inside of the electrode main part is separated by walls 1d 
and 1g. 
FIG. 3 shows the flowchart representing an outline of the method of 
producing the ion selective electrode apparatus of this invention. 
A metal pin, such as a pin of the stainless-steel (SUS) which fits the 
inner diameter of the path 1a, is inserted in the path 1a of the electrode 
main part which is beforehand made from PVC. Although a SUS pin is used in 
this embodiment, the material of the pin can be anything as long as it 
does not react with ion sensing substances. 
After inserting the SUS pin, each of the membrane holes 1c and 1f, which 
beforehand are prepared in the path 1a, is filled with a sensing membrane 
solution. The sensing membrane solutions in the holes do not leak into the 
path since the pin is inserted in the path. The solution is made from PVC 
dissolved in organic solvent (for example, tetrahydrofuran) to which an 
ion sensing substance, a plasticizer, etc. is added. Several different 
types of solutions are made with several ion sensing substances to detect 
several ions, such as Na.sup.+ and K.sup.+. Each of the sensing membrane 
solution is applied in the hole several times using a dispenser, etc. to 
form a uniform and film sensing membrane. The thickness of the membrane is 
determined by the amount of the solution applied at a time and the number 
of applications. 
Then, the solution is dried in a dry air flow and the SUS pin is removed 
from the path. Due to the pin fitted to the inner wall of the path, a 
membrane facing the path with a smooth and continuous boundary is formed. 
In addition to the above, a sensing membrane may be made by the method that 
after dripping 1 or several drops of the sensing solution in the sensing 
membrane hole, the SUS pin, which is inserted, may be moved, for example, 
rotated about its axis (see FIG. 4). The movement produces a layer of the 
sensing material on the inner surface of the path. Due to the pin fitted 
to the path, the layer can be thin enough such that the inner surface of 
the path is substantially smooth and continuous. The layer makes a large 
surface area of the sensing material, which improves the sensitivity. 
Next, the Ag/AgCl electrodes 3 and 6, which are coated with silver chloride 
on the surfaces by electrolitic deposition, are penetrated and fixed in 
the lids 2 and 5, respectively. The lids 2 and 5 are glued on the holding 
portion 1 in which the sensing membranes 4 (K membrane) and 7 (Na 
membrane) are formed, using adhesives. Then, electrolyte solution is 
poured into internal solution tanks 1b and 1e from pouring holes 2b and 5b 
prepared in the lids 2 and 5. The air in the internal solution tanks 1b 
and 1e are extracted from air extraction holes 2a and 5a as the tanks are 
filled with the electrolyte solution. After pouring the electrolyte 
solution, the pouring holes 2b and 5b and the extraction holes 2a and 5a 
ale closed by adhesive or the like. This completes the process of 
manufacturing an ion selective electrode of the invention. 
The ion selectivity electrodes, assembled as mentioned above, are tested 
repeatedly and the results are shown in FIG. 5 and FIG. 6. 
FIG. 5 shows the result of measurements on sodium ion performed 20 times. 
This result shows that a maximum value is 140.9 mmol/l, a minimum value is 
139.9 mmol/l, and the range between the maximum and minimum values is 1.0 
mmol/l. In the case of sodium ion, if this range is 2.0 mmol/l or less, it 
can be considered that the measurement result is stable. Therefore, the 
measurement result on sodium ion shows that the ion selective electrode of 
this invention can be considered to be stable enough. 
FIG.6 shows the result of measurements on sodium ion performed 20 times. 
This result shows that a maximum value is 4.20 mmol/l, a minimum value is 
4.15 mmol/l, and the range between the maximum and minimum values is 0.05 
mmol/l. In the case of sodium ion, if this range is 0.2 or less, it can be 
considered that the measurement result is stable. Therefore, the 
measurement result on sodium ion shows that the ion selective electrode of 
the present invention can be considered to be stable enough. 
The following Table 1 shows the results of evaluation of ion-selective 
electrode units according to the present invention. Two types of 
multi-cell electrode units (as shown in FIG. 2) are used in the 
evaluation. One has a Na-membrane in cell A and a K-membrane in cell B, 
and the other has a K-membrane in cell A and a Na-membrane in cell B: 
TABLE 1 
______________________________________ 
membrane potential 
sensitivity 
reproducibility 
(mV) (%) R 
Electrode 
Na K Na K Na K 
______________________________________ 
A 229.9 236.5 90.3 94.5 1.0 0.05 
B 216.7 226.1 93.9 98.6 1.2 0.09 
______________________________________ 
In the evaluation especially membrane potential, sensitivity, and 
reproducibility (same as "range" as above-mentioned). According to this 
result, With respect to membrane potential, it is almost the same level as 
the conventional ion selectivity electrode, with respect to sensitivity, 
since it can be considered to be sufficient for practical use if it 
generally is 85% or more, it can be considered to be quite good from this 
result. Moreover, with respect to reproducibility, in the case of sodium 
ion, if the result is 2.0 mmol/l or less, it can be considered to be 
stable and, in the case of potassium ion, if the result is 0.2 mmol/l or 
less, it can he considered to be stable. Therefore, it can be considered 
that measurement results both on sodium ion and potassium ion are stable 
enough. As explained above, an ion selective electrode unit can be made to 
include two or more cells separated by a wall, while conventional cells 
had to be made independently. These cells correspond to conventional ion 
selectivity electrode unit. Thus, by making in the unified form, the 
distance between cells can be minimized and the path through which a 
sample flows in the electrode unit can be shortened. Therefore, the 
quantity of a required sample for the measurement can be reduced. 
Furthermore, since the packing or the adhesives for combining electrode 
units are unnecessary and excess membrane material does not exist in the 
path, the inner surface of the path can be kept smooth and continuous, and 
no sample remains in the path after washing. 
As mentioned above, according to the present invention, since the structure 
includes two or more cells, one, two or more kinds of ions in a sample can 
be simultaneously measured by a small ion selective electrode unit with a 
short path, and measurement of ion concentration can be efficiently 
performed even if the quantity of a sample for measurement is small. 
Moreover, the uniform and stable ion-sensing membrane with a sufficient 
ion detection performance can be formed, securing a smooth path.