JPS6293650A - Liquid specimen analyzing instrument - Google Patents

Abstract

PURPOSE:To make it possible to simultaneously handle the measuring item of anion selective electrode and that of a dry analytical element, by fixing the ion selective electrode and the dry analytical element to the same frame body. CONSTITUTION:Ion selective electrode pairs 111, 112 respectively consist of same ion selective electrodes 111a, 111b and 112a, 112b. Two spot-adhesion ports 151a, 151b for adhering a liquid specimen to the ion electrode pair 111 in a spotted state are provided in the depression 151 of an upper frame body 10a and the yarn bridge 161 passing through the two spot-adhesion ports is fixed to said frame body 10a. The other depression 152 is also constituted in the same way as the depression 151. A monolithic multilayered analytical element 12 is received in a frame body so that the position thereof is prescribed by the underside depression of the upper frame body 10 and the upside depression 143 of a lower frame body 10b. The specimen is adhered from the spot- adhesion port 153 and analyzed from a colorimetric analytical port 17. Notches 18a, 18b for contacting a connection terminal with each electrode are provided at two edge sides of the upper frame body.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of the Invention] The present invention relates to an analytical instrument for measuring specific components in liquid samples, particularly biological fluids (blood, urine, saliva, etc.).

[1V View of the Invention] In current medical care, clinical chemistry tests that perform determination and analysis of specific components in biological fluids are becoming increasingly important in order to perform accurate diagnosis and appropriate treatment. Measuring instruments frequently used in clinical chemistry tests include ion-selective electrodes and dry analysis elements.

An ion selective electrode is a measuring device for botensiometrically fixing a concentration of ions in a liquid sample.
It is disclosed in the official bulletin etc. That is, an ion-selective electrode includes a support, a conductive metal layer (eg, a deposited silver layer), and a water-insoluble salt of the metal (eg, a vapor-deposited silver layer).

a layer containing silver chloride), an anion and a common anion and a cation (e.g., potassium ion, sodium ion) with the anion of the water-insoluble salt (e.g., potassium chloride, sodium chloride) and a binder. It has a basic configuration in which an electrolyte layer and an ion selection layer are integrated in this order.

Furthermore, a dry analytical element is a measuring device having a structure consisting of a sheet-like single layer or a plurality of layers in which reagents necessary for wide detection are stored in a dry state. Dry analysis elements are spectroscopy based on the principle of colorimetric photometry of the absorbance or change in absorbance of a specific component to be measured (analyte) in a liquid sample or a product resulting from a chemical reaction of the analyte. Use objective measurements.

Among the dry analytical elements mentioned above, integrated multilayer analytical elements, in which the necessary reagents and components are designed so that the reactions proceed in a fixed order and are coated on a film, can be operated easily and quickly. It has high quantitative properties.

[Summary of the Invention] When the present inventor studied a liquid sample analysis method using an ion-selective electrode and a dry analysis element, it became clear that multiple test items F1 can be measured on the same sample in a practical stage such as clinical testing. It turns out that there are a couple of cases where it is necessary. For example, in diseases such as diabetes and chronic renal failure, an increase in blood sugar level and an increase in urea nitrogen, as well as an increase in nitrium ions, may be observed.

Furthermore, in chronic renal failure, potassium ion levels of 1.91 may be observed.

Based on the above facts, the unaccompanied suspect admitted that it is safe to measure these multiple test items simultaneously and easily.

An object of the present invention is to provide a liquid sample analyzer J↓ that can simultaneously and easily measure the electrolyte concentration and other component concentration J& or enzyme activity in a liquid sample.

The present invention provides (1) at least one ion-selective electrode pair consisting of two ion-selective electrodes of the same type that are electrically separated; (2) a liquid in the ion-selective electrode pair; A bridge that provides electrical continuity between the liquid sample and reference liquid when they are spotted on the spot to be spotted; (3) At least one dry analysis element; (4) Mount these. The present invention provides a liquid sample analysis instrument having a frame body that is fixed in place.

[Effects of the Invention] In the liquid sample analysis instrument of the present invention, since the ion-selective electrode pair and the dry analysis element are fixed to the same frame, the liquid sample spotting operation, processing after sample spotting, and measurement operation are easy. etc., the measurement items of the ion selective electrode and the measurement items of the dry analysis element can be handled simultaneously and easily.

In addition, since the liquid sample analysis instrument of the present invention has colorimetric measurement items and electrode measurement items on the same slide, it is possible to compare the correspondence between the two measurement values to detect diabetes, chronic renal failure, etc. The pathology of a disease can be easily and accurately grasped.

Furthermore, the flame method is currently used as a standard method for measuring electrolytes for alkali metal ions such as sodium ions and potassium ions. Since this flame method and the measurement method using the ion-selective electrode have different measurement principles, the measured values for the same liquid sample may differ. This difference in measured values poses a problem in measurement accuracy, and may also cause confusion in the processing and judgment of these measured values. In the above case, the analytical instrument of the present invention uses the standard method to determine the electrolyte concentration such as alkali metal ions measured using the ion-selective electrode with reference to the lipid concentration, protein concentration, etc. measured using the dry analytical element. This has the effect that it is possible to easily perform numerical corrections to comply with the Flame Light Law.

[9, Detailed Description of Akira J The ion selective electrode constituting the liquid sample analysis instrument of the present invention is already known as described above. Various types of ion-selective electrodes can be used in the liquid sample analysis device of the present invention. The ion-selective electrodes that can be used in the liquid sample analysis device of the present invention include a support, a conductive gold layer,
A basic configuration in which a layer containing a water-insoluble salt of the metal, an electrolyte layer containing an anion of the water-insoluble salt, an electrolyte salt of a common anion and a cation, and a binder, and an ion selective layer are integrated in this order. However, there are no particular restrictions on other details.

Specific examples of ion selective electrodes that can be used in the liquid sample analysis instrument of the present invention include
In addition to the ion selective electrode described in Japanese Patent Application Laid-Open No. 156848/1984.

No. 49-128793, No. 57-17851, No. 5
No. 7-17852, No. 55-89741 and No. 56
-92442 and other publications and patent application No. 59-93774
No. 59-93775, No. 59-100317,
Ion-selective electrodes and ion-selective electrodes described in JP-A No. 59-128240 and JP-A No. 59-128241 can be mentioned.

When these ion selective electrodes are used in the liquid sample analysis instrument of the present invention, there are no particular limitations on the measurement items. That is, the liquid sample analysis instrument of the present invention can measure items that can generally be measured using an ion-selective electrode (eg, potassium ions, sodium ions, chloride ions, carbonate ions, etc.). Note that the liquid sample analysis instrument of the present invention is as follows.

This is particularly advantageous in measuring the concentration of alkali metal ions such as sodium ions and potassium ions (details will be described later).

In the liquid sample analysis instrument of the present invention, the ion selective electrode is
Two ion selective electrodes A consisting of the basic configuration as described above.
(for reference solution) and B (for sample solution) are used as an ion selection electrode pair. In actual ion concentration measurement, the potential difference between each ion selective layer A and B is measured, and the concentration of the electrolyte contained in the liquid sample is calculated from this potential difference and a calibration curve prepared in advance. can be used.

In this specification, the liquid spotting portion of the ion-selective electrode pair generally means the ion-selective layer. However, it is also possible to provide a porous liquid transfer member or the like on the ion selective layer and to spot the liquid onto this member, and in this case, the portion where the liquid is to be spotted is included in the above member.

The ion-selective electrode pair is generally provided with a bridge made of a porous material that connects the liquid spotting portions of the ion-selective electrodes A and B. However, in the liquid sample analysis instrument of the present invention, the bridge described in No. 1 can be installed directly on the ion-selective electrode pair or on a frame described later.

Dry analysis elements constituting the liquid sample analysis instrument of the present invention are also already known, and various types of dry analysis elements can be used in the liquid sample analysis instrument of the present invention. A specific example of a dry analytical element that can be used is an integrated multilayer analytical element. Regarding this integrated multilayer analytical element,
They are described in Japanese Patent Application No. 677, Japanese Patent Application Laid-Open No. 164356/1982, and Japanese Patent Application No. 179158/1984. Regarding dry analytical elements other than integrated multilayer analytical elements such as test paper type, please refer to Japanese Patent Publication Nos. 58-19220, 56-18904, 59-6900, 57
-53661 and 57-187656, etc. By referring to various documents such as patent publications regarding the above-mentioned dry analysis elements, it is also possible to prepare analysis conditions according to spirituality.

Even when these dry analysis elements are used in the liquid sample analysis instrument of the present invention, there is no particular restriction on the measuring element 11. That is, the liquid sample analysis instrument of the present invention generally measures items that can be measured using dry analytical elements (e.g., concentrations of glucose, urea nitrogen, bilirubin, etc., and amylase,
Measurement of enzyme activity such as alkaline) 1-sphatase is effective. Various dry analytical elements related to these various measurement items are already commercially available. The measurement +1 of the dry analytical element used in the liquid sample analysis material of the present invention is determined by taking into account the necessity of the clinical chemistry test scale and the measurement items of the ion selective electrode mentioned above.

When the measurement item of the aforementioned ion-selective electrode is the concentration of alkali metal ions such as sodium ions and potassium ions, it is preferable to add the lipid concentration or protein concentration in the liquid sample to [1] for the measurement of the dry analytical element. That is, the difference between the measured value using an ion-selective electrode for a liquid sample and the measured value using the standard flame method is mainly due to the influence of lipids or proteins contained in the liquid sample. There is a correlation between the difference in the measured values of the two Kitami species and the fat content or protein concentration in the liquid sample. Therefore, by measuring the lipid concentration or protein concentration using a dry analytical element at the same time as electrolyte measurement using an ion-selective electrode, it is possible to calculate the electrolyte concentration value using the lipid concentration or protein concentration measurement value as a reference. Numerical corrections can be easily made to comply with the flame law.

As a dry analysis element capable of measuring lipid concentration, there may be mentioned a body type multilayer analysis element for lipid analysis described in JP-A-53-2893. In addition, as a dry analysis element capable of measuring protein concentration, Japanese Patent Application Laid-Open Nos. 54-101398, 58-85163 and 59-51356 and Japanese Patent Application No. 1987-1
An integrated multilayer analytical element for total protein analysis described in No. 32057.

JP-A-60-97274 and patent application 1986-'
16625 B V) Integrated multilayer analysis element 22 for albumin analysis described in Mei 1B Zhu.

In this specification, the liquid spotting area of a dry analytical element generally means the developing layer in the case of an integrated multilayer analytical element, and the spotting photometric surface in the case of a test strip type analytical element.

However, it is also a rotation to provide a porous liquid transfer member on top of these and to spot the liquid on this member, and in this case, the portion where the liquid is to be spotted is included in the above member.

The frame for mounting and fixing the ion-selective electrode pair and the dry analysis element constituting the liquid sample analysis material of the present invention can be manufactured from a desired shape-retaining material, but it is water-impermeable and electrically insulating. It is preferable to use a material having More moldability.

In consideration of various properties such as impact resistance, it is preferable to use a plastic material, for example.

Known methods such as a method of putting a plastic material into a desired mold and molding it, and a drawing method using a sheet-like plastic material can be used.

The frame body can be configured in various shapes including a flat plate, a sheet, etc. as long as it has a part for fixing the ion selection electrode pair and the dry analysis element in a position. However, in general, it is preferable to have a shape that accommodates the ion-selective electrode pair and the dry analysis element.When using a frame that accommodates the ion-selective electrode pair and the dry analysis element, the frame An opening for spotting a liquid sample and a reference solution on the liquid spotting area of the ion-selective electrode pair.

An opening for spotting a liquid sample or a reference liquid is provided in the liquid spotting portion of the dry analysis element, and an opening that functions as a passage for incident light and reflected light for colorimetric analysis.

The liquid sample analysis instrument in which the ion-selective electrode pair and the dry analysis element are housed inside the frame as described above has the ion-selective electrode and the dry analysis element housed in the frame having an opening necessary for analysis operation. In addition to analytical operations,
It also has the advantage of being easy to process, such as packaging, transporting, and storing, and at the same time being advantageous in terms of protecting the ion-selective electrode and dry analysis element.

The frame that constitutes the liquid sample analysis material of the present invention has an opening (hereinafter sometimes referred to as a spotting port) for spotting a liquid sample or a reference liquid on the ion-selective electrode pair and the dry analysis element. The 0 point inlet is provided at a position corresponding to the liquid spotting area of the ion selection electrode and the dry analysis element.The 0 point inlet may be provided at a position corresponding to the liquid spotting area of the ion selection electrode and the dry analysis element. The size, shape, etc. of the 0-point port, which can be made to correspond to multiple liquid spotting locations with one spotting port, depend on the configuration of the ion selection electrode and the liquid spotting location of the dry analysis element; Determine by taking into account spotting instruments such as pipettes and other analytical devices.

Roughly speaking, the above-mentioned frame constitutes the liquid sample analysis material of the present invention, which has an opening (hereinafter sometimes referred to as a colorimetric analysis port) that functions as a passage for incident light and reflected light for colorimetric analysis. If the dry analytical element to be used is an integrated multilayer analytical element,
The colorimetric analysis port is provided on the opposite side (lower side) to the above-mentioned spotting port side (upper side) via the integrated multilayer analysis element. Furthermore, when using a test paper type dry analysis element constituting the liquid sample analysis material of the present invention, the colorimetric analysis port is provided on the same side as the spotting port.

The same opening can function as a spotting port and a colorimetric port. The present invention also includes an embodiment in which the spotting port and the colorimetric analysis port are common.

Further, the frame constituting the liquid sample analysis material of the present invention may be integrated into a single frame or may be formed by combining a plurality of frames. As shown, the frame consists of an upper frame having an opening for spotting a liquid sample and a lower frame having an opening that functions as a passage for incident light and reflected light for colorimetric analysis. I can do it.

Furthermore, the frame body made up of a plurality of elements can be integrated after the liquid sample analysis instrument of the present invention is completed. Further, by providing a hinge-like joint between the plurality of frame elements to enable opening and closing of the frame, it is also possible to replace the ion selection electrode and the colorimetric analysis element.

By enabling the frame to be opened and closed as described above, the liquid sample analysis device of the present invention can also be used mainly as a device for spotting a liquid sample onto an ion selective electrode and a colorimetric analysis element. .

Embodiments of the present invention will be described below with reference to one drawing.

FIG. 1 is a schematic perspective view of a liquid sample analysis instrument that is an embodiment of the present invention, and FIG. 2 is a schematic exploded perspective view of the liquid sample analysis instrument shown in FIG.

As shown in FIG. 2, one of the ion-selective electrode pairs 111 consists of a first ion-selective electrode 111a and a second ion-selective electrode 111b, and the electrodes ttia and 1llb are the same ion-selective electrode. The other ion-selective electrode pair 112
The same applies to 111. The two ion-selective electrode pairs l11 and 112 are different ion-selective electrode pairs. These two pairs of ion selection electrodes are formed by grooves 131 and 132 provided on the lower side of the upper frame 10a.
and a groove 141 provided on the upper side of the lower frame body tob.
and 142, the position is defined and housed.

Recesses 151 and 152 are provided on the upper side of the upper frame 10a. In one recess 151, there are two spots 15 for spotting a liquid sample on the ion selective electrode pair 111.
1a and 151b are provided, and a bridge 161 (hereinafter referred to as a yarn bridge) made of polyethylene terephthalate fiber heating yarn (spun yarn) passing through the two dots is attached at both ends by heat fusion or adhesive near the recess. Fixed location. The same is true for the other recess 152 as well. The recesses 151 and 152 are functionally not necessary, but are preferable in order to protect the bridge.
A small protrusion area is provided around b to prevent the liquid sample to be spotted and supplied from overflowing onto the surface of the recess, and to serve as a guide for easily and reliably spotting the liquid sample.

Alternatively, the recesses 151 and 152 may be provided on the lower surface of the upper frame 10a, and the thread bridges 161 and 162 may be disposed within the recesses on the lower surface of the upper frame.

The integrated multilayer analysis element 12 is housed with its position defined by a recess (not shown) provided on the do side of the two-part frame 10a and a recess 143 provided on the upper side of the lower frame 10b. ing. As an integrated multilayer analysis element, it is also possible to use one in the form of a slide frame.

Separately, an integrated multilayer analysis element 1 is provided above the upper frame 10a.
2 is also provided with a spot 11153 for spotting a liquid sample.

Two opposing edges of the upper frame are provided with notches 18a and 18b for electrically contacting the contact bA terminal of the potential' measuring mechanism with the electrical connection terminal portion of each electrode. The notch may be a single cutout that spans the width of the entire electrode or a cutout that is separated for each electrode, and instead of a cutout, an opening for inserting a connection terminal may be provided.

A colorimetric analysis port 17 that functions as a passage for incident light and reflected light for colorimetric analysis is provided in a recess 143 provided on the upper side of the f-section frame lOb.

By joining and fixing the upper frame 10a and the lower frame 10b so that their edges match (for example, by heat fusion), a liquid sample, which is an embodiment of the present invention, having the appearance shown in FIG. 1 is obtained. Analytical instruments are obtained.

FIG. 3 is a schematic perspective view of a liquid sample analysis instrument according to another embodiment of the present invention, and FIG. 4 is a schematic exploded perspective view of the liquid sample analysis instrument shown in FIG. 3. The differences between this instrument and the instruments shown in FIGS. 1 and 2 will be mainly explained below.

The dot 251 provided on the upper frame 20a is a horizontally long opening with a width that includes the thread bridge 26 directly provided on the ion selection electrode pair 21. Part 251a corresponding to the planned liquid spotting part
and 251b are expanded in width.

The upper frame 20a is also provided with openings 28a and 28b for electrically contacting the connection terminal of the potential measuring mechanism with the electrical connection terminal portion of each electrode.

Integrated multi-layer analysis element 22. a and 22b are the same integrated multilayer analytical element, and 22a and 22b form a dry analytical element pair. In this embodiment having at least one pair of dry analysis elements, fluctuations in the measured values of the dry analysis elements for liquid samples due to variations during manufacturing or over time can be easily corrected using the dry analysis elements for the reference liquid. It has the advantage of being able to It should be noted that it is also possible for the integrated multilayer analysis elements 22a and 22b to be of different types and is included in the embodiments of the present invention. Multiple dry analysis elements of different types 1. In such cases, each analytical element should be spotted and used for liquid samples.

The interval between the scheduled liquid spotting parts of the integrated multilayer analysis elements 22a and 22b is set so that the liquid spotting of the ion selective electrodes 21a and 21b is equal to the interval between the legs.

As in this embodiment, the spotting points on the liquid spotting portions of the two ion selective electrodes constituting each ion selective electrode pair and the two dry analytical elements constituting each dry analytical element pair. A liquid sample is applied to an analysis instrument in which a pair of ion-selective electrodes and a pair of dry analysis elements are arranged so that the distances connecting each pair of the liquid sample points on the liquid-spot area are substantially equal. In the case where the application is made by the present applicant, Japanese Patent Application No. 60-14765 and No.
By using the dual pipette described in the specification of the publication, which is capable of inhaling and discharging two types of liquids, it is possible to easily apply the two types of liquids at the same time.

Other structures, such as recesses 231 and 241 in the upper and lower frames, respectively, to define the position of the ion-selective electrodes, and in the lower frame to define the position of the integrated multilayer analytical element. recess 242a
and 242b, etc., are the same as in the embodiment shown in FIGS. 1 and 2.

Note that the number of ion-selective electrode pairs and dry analysis elements that can be used in the liquid sample analysis instrument of the present invention is not limited to the above two embodiments, and it is possible to arrange as many as are practically required. is possible.

[Brief explanation of drawings]

FIG. 1 is a schematic perspective view of a liquid sample analysis instrument that is an embodiment of the present invention. FIG. 2 is a perspective exploded schematic diagram of the liquid sample analysis instrument of FIG. 1. FIG. 3 is a schematic perspective view of a liquid sample analysis instrument according to another embodiment of the present invention. FIG. 4 is a perspective exploded schematic diagram of the liquid sample analysis instrument of FIG. 3. 10a, 20a; Upper frame 10b, 20b; Lower frame 111.112.21; Ion selection electrode pair 12.22a
, 22b; Integrated multilayer analysis element 151a, 151b, 152a, 152b; , spotting ports 161, 162, 26 to integrated multilayer analytical element: bridge 17; colorimetric analysis ports 27a, 27b; colorimetric analysis ports 18a, 18b; cutouts 28a, 28b; for electrical connection 1) f4a patent Applicant Fuji Photo Film Co., Ltd. Representative Patent Attorney
Yasushi Yanagawa C

Claims (1)

[Claims] 1. (1) At least one ion-selective electrode pair composed of two ion-selective electrodes of the same type that are electrically isolated from each other; (2) A schedule for liquid spotting of the ion-selective electrode pair; a bridge for electrically conducting between the liquid sample and reference liquid when they are spotted on the part; (3) at least one dry analysis element; (4) having a frame for mounting and fixing these. Liquid sample analysis equipment. 2. The analysis instrument according to claim 1, characterized in that a dry analysis element pair is constituted by two dry analysis elements of the same type, and has at least one dry analysis element pair. 3. Spotting points on the liquid spotting areas of each of the two ion selective electrodes constituting each ion selective electrode pair and liquid spotting areas of each of the two dry analysis elements forming each dry analysis element pair. The ion-selective electrode pair and the dry analysis element pair are arranged so that the distances connecting each pair of the above spotting points are substantially equal. Analytical instruments. 4. The analysis instrument according to claim 1, wherein the dry analysis element is an integrated multilayer analysis element. 5. The frame body accommodates the ion-selective electrode pair and the dry analysis element therein, and has an opening for spotting the liquid sample and the reference liquid in the liquid spotting portion of the ion-selective electrode pair;
A frame body having an opening for spotting a liquid sample or a reference liquid on the liquid application area of a dry analysis element, and an opening that functions as a passage for incident light and reflected light for colorimetric analysis. Claims 1 to 4 are characterized in that
Analytical instruments described in any of the sections. 6. An upper frame in which the ion-selective electrode pair and the integrated multilayer analysis element each have an opening at a position corresponding to the intended liquid spotting area, and an opening at a position corresponding to the reflective photometric surface of the integrated multilayer analysis element. A patent characterized in that the container is provided with a lower frame body having a portion, and the bridge is fixed to the upper frame body so as to cross an opening at a position corresponding to the liquid spotting portion of the ion-selective electrode pair. An analysis instrument according to claim 5. 7. The ion-selective electrode pair and the integrated multilayer analytical element each have an upper frame having an opening at a position corresponding to the intended liquid spotting area, and an opening at a position corresponding to the reflective photometric surface of the integrated multilayer analytical element. Claim 5, characterized in that the bridge is fixed to the ion-selective electrode pair so as to cross the liquid spotting area of the ion-selective electrode pair. Analytical instruments as described in section. 8. The analytical instrument according to claim 1, wherein the ion-selective electrode pair is for measuring alkali metal ions, and the dry analysis element is for measuring lipid concentration.