JP3438842B2 - Method of making peelable test piece - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a peelable test piece which is a dry analytical tool for measuring a specific component in whole blood which is usually used in whole blood analysis in the field of clinical examination. .

[0002]

2. Description of the Related Art In the field of clinical examination, analysis of various components in whole blood is an index for objectively knowing the effects of diagnosis and treatment of many diseases. A method has been developed that requires no prior preparation of reagents, does not require stirring, and is capable of measuring many items with a small amount of sample. This method is used as an immediate examination method in hospital emergency laboratories, night nurses' offices, and practitioners. This method is called dry chemistry.

Among the dry analytical tools, it has a support,
A reagent layer is provided on the support, and a removable film layer having a sample weighing function is provided on the reagent layer. When used, the film layer is peeled off after application of the sample to color the reagent layer. There is also the case of using the "peeling test piece".

Specifically, the reagent reaches the reagent layer while filtering the blood cell components in whole blood above the reagent layer produced by impregnating the reagents with a matrix made of a thermoplastic resin or a non-thermoplastic substance. A film layer having the ability to measure an appropriate amount of the sample liquid to be used is arranged. When using, the sample blood (whole blood) is attached on the film layer of the test piece, and then the surface of the film layer is wiped to remove blood cells and excess blood, and then the film layer. Peel off to expose the reagent layer, and watch how the reagent layer is colored. of course,
It may be peeled off without wiping.

[0005]

In the method for producing the peelable test piece, the most commonly used method for fixing the support and the reagent layer and the reagent layer and the film layer is hot melt. The method of fixing is used.

However, in order to melt the thermoplastic resin, it is necessary to raise the temperature of the reagent layer to 100 to 110 ° C. for several seconds, and as a result, the substances (especially enzyme,
There was a risk of denaturing proteins such as antibodies and antigens. In addition, plasticizers, stabilizers, and the like are mixed in the hot melt to a considerable extent, and these components adversely affect the reagents and the measurement results.

[0007] Further, these peelable test pieces have a structure having at least three layers as described above, and when they are produced, the work of sticking the first and second layers and the work of sticking the second and third layers are performed. Two work steps are required, which is troublesome.

Further, in the peeling operation when the peelable test piece is used, it is necessary to peel it off between the reagent layer and the film layer, and there is no problem if the reagent layer and the support are peeled off. Therefore, in consideration of that point, the adhesive strength between the reagent layer and the support must be made stronger than the adhesive strength between the reagent layer and the film layer (hereinafter, sometimes referred to as interlayer bonding strength). No, it is complicated.

The problem of increasing and decreasing the bonding strength between the two layers while adhering three layers at a time and adhering at one time can be solved by using two kinds of adhesives, but the adhesive is mainly a polyacrylic resin. However, the polymerization initiator, the volatile monomer, the stabilizer, the plasticizer, and the wetting agent are mixed in a considerable amount, which may adversely affect the reagent in the reagent layer, and thus the use of the adhesive is not preferable. Therefore, there has been a demand for an ideal method for producing a peelable test piece, which can fix the three layers at a time and can increase or decrease the interlaminar bonding force without using an adhesive.

[0010]

Among dry analytical tools for measuring a specific component in a liquid sample, there is a support, and a reagent layer in which a porous matrix is impregnated with a reagent is provided on the support. In the production of a peelable test piece having a detachable film layer having a blood cell separating function on the reagent layer and peeling the film layer after applying a sample to see the coloration of the reagent layer when used. The above problems can be solved by adopting the following process sequence. That is, a step of arranging the reagent layer and the film layer on the support so as to be in contact with each other in this order, and applying vibration by ultrasonic waves from the support side. Process of integrating the surface material of the melted layer with the surface of the adjacent layer by applying pressure Process of releasing ultrasonic vibration and pressure

The so-called "ultrasonic fusing" method of melting plates or films made of a thermoplastic resin by ultrasonic waves and adhering them to each other as in the present invention has the following advantages. Rather than sticking the layers together with an adhesive, the thermoplastic resin that forms the layers is melted and fixed by the frictional heat of ultrasonic waves, so the influence of the plasticizer or solvent mixed in the adhesive on the reagent in the reagent layer Does not receive. Since heat is also generated instantaneously on the surface of the layer and quickly cooled, the reagent in the reagent layer is not denatured.

The inventors of the present invention have applied a plurality of layers of a thermoplastic resin (or a combination of a thermoplastic resin and a porous non-thermoplastic substance) to one another, and apply ultrasonic oscillation from one side to ultrasonic fusion. Comparing the strength of the inter-layer bonding force when adhesion occurred, it was found that the inter-layer bonding force was stronger in the layer closer to the side to which the ultrasonic waves were applied. The present invention applies this principle to the production of a peelable test piece.

When the three layers are fused at one time by using a device that directly generates and sends heat, even if the layers on the front side of the side to which the heat is applied can be fixed, the layers between the inner layers may be separated due to the heat conduction. It is difficult to fix, and even if the inner layers can be fixed, the layers already in front are destroyed by the high heat, and the reagents completely lose their activity.

However, since the present invention does not directly conduct heat but conducts ultrasonic vibration and indirectly conducts heat (friction heat caused by vibration), the above-mentioned problems do not occur at all. Absent.

As described above, the present invention does not have the drawbacks of the conventional method for producing a peelable test piece, and can utilize all the advantages of ultrasonic fusion effectively, and is a completely new method for producing a peelable test piece. Is.

【Constitution】

As is apparent from the claims, the present invention has a support, a reagent layer on the support, and a detachable film layer having a sample measuring function on the reagent layer. Although it is a method for producing a test piece, the material of each layer is defined separately.

According to the present invention, the thermoplastic resin on the surface of the layer is melted by ultrasonic waves, and the melted resin is soaked into the pores of the adjacent layer if the adjacent layer is a non-thermoplastic porous matrix. It is an essential requirement to fix by "the tack effect", or if the adjacent layers are also thermoplastic resin and their surfaces are also melted, the melted resins are integrally fixed.

Therefore, among the basic three layers constituting the peelable test piece using the porous matrix as the reagent layer, (1) all three layers are thermoplastic resin, or (2) two layers are thermoplastic. Whether one layer of resin is a non-thermoplastic matrix,
(3) It should be noted that the middle layer of the three layers is a thermoplastic resin and the upper and lower two layers are non-thermoplastic matrices, in other words, the non-thermoplastic matrices must not be adjacent to each other. is there.

Specifically, when the materials of the support, the reagent layer and the film layer are all thermoplastic resins, the materials of the support and the film layer are thermoplastic resins,
When the material of the reagent layer is a non-thermoplastic matrix, the material of the support and the film layer is a non-thermoplastic resin, and when the material of the reagent layer is a thermoplastic matrix, the material of the support and the reagent layer is a thermoplastic material. When it is a resin and the material of the film layer is a non-thermoplastic matrix,
There are cases. It is also conceivable that the material of the film layer and the reagent layer is a thermoplastic resin and the material of the support is a non-thermoplastic matrix, but the binding force between the thermoplastic resins and the thermoplastic resin and the non-thermoplastic Comparing the bonding strength with the matrix, the latter is somewhat weak, so in this case it is desirable to avoid it.

The thermoplastic resin may be a thermoplastic resin among those usually used in dry analytical tools of this type, and examples thereof include polyethylene terephthalate, polycarbonate, polystyrene and cellulose ester.

As the non-thermoplastic material, those usually used in this field may be used, and examples thereof include a three-dimensional lattice structure composed of filter paper, non-woven fabric, woven fabric, knitted fabric, glass fiber filter paper, membrane filter and polymer microbeads. A thing etc. are illustrated. However, it is an essential condition that it does not melt by heat.

The thickness of the support is sufficient as long as it can sufficiently support the reagent layer to be fixed later. This may be the same as a normal dry analytical tool.

The film layer may be in the form of a matrix having a plurality of pores in order to have a blood filtering ability and a liquid retaining ability, or the film layer itself does not have pores and a sample is weighed in a part of the layer. It only has to have the ability to hold and hold.

[0023]

EXAMPLE An example of a method for producing a peelable test piece in which each layer is fixed by the method according to the present invention will be described below with reference to the accompanying drawings. Although the size ratio is different from the actual one,
This is to make the drawings easy to understand, and these do not limit the content of the present invention.

As an example, a peelable test piece was prepared by the following method. Substrate base serving as a support; white polyethylene terephthalate having a thickness of 0.3 mm (Teijin) (Fig. 1) Porous matrix serving as a reagent layer; filter paper having a thickness of 0.3 m (Whatman, 3MMChr) (Fig. 1) Medium) Film layer: Nylon mesh having a thickness of 0.3 mm (Teijin Co., Ltd.) (in FIG. 1) 70 mm × 360 mm base material base, as shown in FIG.
A tape-shaped reagent layer with a width of 7 mm and a tape-shaped film layer with a width of 10 mm are arranged, and the frequency is 20 kHz from the base material base side.
Ultrasonic vibration of z and a pressure of 70 kg / cm ² were applied. 0.
Keep this state for 2 seconds, then stop the ultrasonic vibration,
The pressure was released after being held for 0.2 seconds in the pressure only state. The fixing form at that time is made streak, and the fixing points are shown in the figure (in FIG. 1). After this, as shown in FIG.
It was cut into a predetermined size of mm width to obtain a peelable test piece.

Test 20 prepared test pieces were prepared, 10 μl of blue ink (water-based ink for fountain pen) was spotted on each film layer, wiped off immediately after spotting, and after 60 seconds, sample The measuring layer was peeled off.

[Results] The reagent layers of the 20 test pieces were all colored in blue, and when the film layer was peeled off, the film layer and the reagent layer were not peeled from each other, and There was no one that came off.

[0027]

As described in detail, according to the present invention, the three layers can be fixed at one time without using an adhesive, and the peelable test piece can be manufactured while increasing or decreasing the interlayer bonding strength. That is,
This is a completely new method for producing a peelable test piece, which does not have the drawbacks of the conventional method for producing a peelable test piece and effectively utilizes all the advantages of ultrasonic fusion.

[0028]

[Brief description of drawings]

FIG. 1 is a plan view and a sectional view of a test piece according to the present invention before cutting. -FIG. 2 is a plan view after cutting the test piece of FIG. 1 into a width of 7 mm. (The cross-sectional view is the same as in Fig. 1, so it is omitted.)

[Explanation of symbols] ; Support (base material) ; Reagent layer (porous matrix) ; Film layer ; Ultrasonic fusion point (streak)

Claims (5)

(57) [Claims] 1. A dry analytical tool for measuring a specific component in a liquid sample, which has a support, and a reagent layer in which a porous matrix is impregnated with reagents on the support,
A method for producing a peelable test piece which has a removable film layer having a blood cell filtration function on the reagent layer, and when the sample layer is applied, peels off the film layer to observe the coloration of the reagent layer when used. And a manufacturing method comprising the following steps. A step of arranging the reagent layer and the film layer on the support so as to be in contact with each other in this order, and applying vibration by ultrasonic waves from the support side. Process of integrating the surface material of the melted layer with the surface of the adjacent layer by applying pressure Process of releasing ultrasonic vibration and pressure 2. The material of the support, the reagent layer and the film layer is selected from either a thermoplastic resin or a non-thermoplastic porous matrix, wherein the non-thermoplastic porous matrix layer is used. The method according to claim 1, characterized in that the two are not adjacent. 3. The film layer according to claim 1, wherein the film layer has a plurality of pores and has a metering capacity by itself, or has a sample metering portion consisting of a portion attached to the film layer. The method described in any one of. 4. The thermoplastic resin according to claim 1, wherein the thermoplastic resin is a material selected from polyethylene terephthalate, polypropylene, polyethylene, polystyrene, polycarbonate, polyvinyl acetate, and polyvinyl chloride. the method of. 5. The non-thermoplastic porous matrix comprises:
Patents selected from paper, wood, glass, ceramics, metal cloth, non-woven cloth (membrane filter, uniaxially stretched porous film, biaxially stretched porous film, radiation irradiated porous film), sintered body, porous ceramic sheet, patent The method according to any one of claims 1 to 4.