JP4887886B2 - Reagent container - Google Patents

Description

  The present invention relates to a reagent container used for storing and storing a reagent.

Conventionally, in the fields of biotechnology and chemistry, reagent containers are used for storing and storing reagents. Examples of the reagent container include a test tube and a so-called chip in which a reagent storage portion called a well (concave portion) is formed.
The reagents contained in these reagent containers are sucked and separated by, for example, a pipette tip or a syringe needle, and the sorted reagents are dispensed to another container or a reaction unit arranged on the same chip. Is done.
By the way, when the reagent storage part of the reagent container is not sealed, the reagent may evaporate when left for a long time or heated.
Thus, for the purpose of preventing the reagent from evaporating, for example, Patent Document 1 discloses a container body having a reagent container and a covering film that is attached to the container body and covers the opening of the reagent container. A reagent container has been proposed. In the reagent container described in Patent Document 1, the reagent is dispensed by inserting the pipette tip or the tip of the injection needle into the coating film and penetrating it.
JP 09-099932 A

However, the reagent container described in Patent Document 1 has a problem that the absorbability when the reagent is sucked by a pipette tip or an injection needle penetrating the coating film is low, and the recoverability of the reagent is low.
Further, the coating film is required to have a high light-shielding property in order to prevent deterioration or deterioration of the reagent due to light, and to ensure a resistance to the reagent (hereinafter referred to as reagent resistance). Furthermore, the coating film is required to be able to pierce the tip of a pipette tip or an injection needle into a plurality of different places, that is, a film that ensures piercing property.
The present invention has been made in view of the above circumstances, and has both high reagent recovery and light shielding properties when recovering a reagent with a pipette tip or an injection needle penetrating a coating film, and has reagent resistance and piercing properties. An object of the present invention is to provide a reagent container secured together.

The present invention includes the following configurations.
[1] A reagent container comprising a container main body having a reagent containing portion for containing a reagent, and a covering film attached to the container main body and covering an opening of the reagent containing portion,
The covering film has an aluminum layer, a sealing layer adhered to the container body, and a protective layer made of a brittle material provided on the surface of the aluminum layer opposite to the sealing layer side, and embossed on the aluminum layer. And the protective layer is a layer for protecting the aluminum layer, and is made of a matte-like polyethylene terephthalate film or a foamed resin film whose surface is sandblasted .
[2] The embossed pattern of the aluminum layer is a checkered grid pattern in which a large number of linear first grooves and a plurality of second grooves orthogonal to the first grooves are formed. The reagent container according to [1], wherein the interval between the grooves and the interval between the second grooves are 2 mm or less.
[3] The reagent container according to [1] or [2], wherein the aluminum layer is made of a hard aluminum foil having a thickness of 10 μm or less.
[4] The reagent container according to any one of [1] to [3], wherein an intermediate layer is provided between the aluminum layer and the seal layer.

In the reagent container according to the first aspect of the present invention, the embossing is formed in the aluminum layer, so that when the tip of the pipette tip or the injection needle is pierced into the coating film, the coating film is cleaved substantially linearly. And a gap for allowing air to flow into the reagent container can be formed. As a result, when the reagent is sucked up with a pipette tip, an injection needle or the like, the inside of the reagent container is unlikely to become a negative pressure, and the sucking property is high, so the reagent recoverability is high. Furthermore, since the emboss is formed in the aluminum layer, the piercing property is ensured.
Moreover, in the reagent container of the invention according to claim 1 of the present application, since the coating film has an aluminum layer, the light shielding property is high. Moreover, the reagent resistance of the coating film is ensured.
In addition, oxidation and damage of the aluminum layer due to air can be prevented, and the handleability of the coated film can be improved. Moreover, since the coated film can be more easily cleaved in a substantially linear shape, the reagent recoverability can be further increased.

According to the invention of claim 2 of the present application and the invention of claim 3 of the present application, the coated film can be more easily cleaved in a substantially straight line, so that the reagent recoverability can be further increased.
According to the invention of claim 4 of the present application, the reagent resistance can be further increased because the reagent is difficult to directly contact the aluminum layer .

One embodiment of the reagent container of the present invention will be described.
1 and 2 show a reagent container according to this embodiment. The reagent container 1 has a substantially rectangular parallelepiped container main body 10 having wells 11, 11... That are reagent storage parts for storing the reagent S, and is attached to the container main body 10. Are provided with one covering film 20 that covers all of the openings 11a, 11a,.

[Container body]
Although it does not restrict | limit especially as a material of the container main body 10, Since it is excellent in molding processability, it is preferable that it is resin. Examples of the resin constituting the container body 10 include polyvinyl chloride, polycarbonate (PC), polyethylene, polypropylene (PP), acrylic resin, ABS resin, polyethylene terephthalate, polybutylene terephthalate, cycloolefin polymer, fluororesin, and silicone. Examples thereof include resins.
The container body 10 may be formed by bonding two or more types of resin members, or may be formed by bonding a resin member and a metal member. These materials are preferably selected as appropriate in accordance with the properties of the reagent S and the mechanical properties required for the container body 10.
The thickness of the container main body 10 should just be a thickness which can ensure sufficient intensity | strength at the time of use.

Examples of the shape of the well 11 in the container body 10 include a hemispherical shape, a truncated cone shape, a truncated pyramid shape, a cylindrical shape, and a prism shape. These shapes may be appropriately selected according to processability, reagent S injection property, and the like.
The size of the well 11 is set according to the amount of the reagent S to be accommodated. From the viewpoint of convenience, it is preferable to set the diameter of the opening 11a to 5 to 10 mm and the depth to 5 mm or less. .

In addition, the surface of the inner wall of the well 11 may be provided with a silicone resin coating layer or a metal compound deposition layer in order to impart moisture resistance and gas barrier properties and to further improve reagent resistance.
Furthermore, in order to further improve the recovery efficiency of the reagent S accommodated in the well 11, the inner wall surface may be subjected to surface treatment such as plasma treatment or corona treatment.

  For example, when the container body 10 is made of a hard resin such as polycarbonate, the container body 10 is preferably manufactured by a method (cutting method) in which a well 11 is formed by cutting a predetermined position of a rectangular parallelepiped plate made of polycarbonate. . In the case of a soft resin such as polypropylene, it is manufactured by a method (melt molding method) in which a molten resin is filled in a mold having a shape capable of forming the well 11 and then cooled and molded. Is preferred.

[Coating film]
The covering film 20 includes an aluminum layer 21, a seal layer 22 attached to the container body 10, and an intermediate layer 23 provided therebetween. A protective layer 24 is provided on the surface of the aluminum layer 21 opposite to the seal layer 22 side.

In the aluminum layer 21 in this embodiment, as shown in FIG. 3, an emboss 21a is formed on the entire surface. The emboss 21a has a pattern in which a plurality of linear first grooves 21b, 21b... And a plurality of second grooves 21c, 21c... Orthogonal to the first grooves 21b, 21b. It is a checkered pattern.
The interval between the first grooves 21b and 21b and the interval between the second grooves 21c and 21c are preferably 2 mm or less. If the pattern of the emboss 21a is a grid pattern and the distance between the first grooves 21b and 21b and the distance between the second grooves 21c and 21c are 2 mm or less, the tip of the pipette tip or the injection needle is pierced At this time, the coating film 20 can be more easily cleaved in a substantially linear shape.
Here, the space | interval of grooves is the space | interval of the centers of the width direction of each groove | channel.

As a method of forming the emboss 21a on the aluminum layer 21, a method of pressing a plate (embossed plate) having an emboss formed on one side of a smooth aluminum layer, a roll having an emboss formed on one side of a smooth aluminum layer ( And a method of bringing it into contact with an embossing roll).
In the covering film 20, the surface with which the embossed plate or the embossing roll is in contact may be disposed on either the seal layer 22 side or the protective layer 24 side.

As the aluminum layer 21, for example, an aluminum foil, an aluminum vapor deposition film, or the like is used, and among these, a hard aluminum foil having a thickness of 10 μm or less is preferable. If the aluminum layer 21 is made of a hard aluminum foil having a thickness of 10 μm or less, the covering film 20 can be more easily cleaved substantially linearly when a pipette or injection needle is pierced.
The thickness of the hard aluminum foil is more preferably 8 μm or less.
Here, the hard aluminum foil is an aluminum foil having an elongation of 1% / 180 mm or less and a bursting degree of 0.5 kg / cm ² or less. The elongation in the present invention is a value measured at a tensile speed of 50 mm / min in a tensile test based on JIS C 2151, and the bursting degree is a value measured based on JIS P 8112.

The seal layer 22 is preferably formed from a heat sealable resin. Examples of the heat-sealable resin include polyethylene, polypropylene (including acid-modified products such as maleic acid), ethylene-vinyl acetate copolymer, and acid component-modified polyethylene terephthalate which is a copolyester resin. Among these, acid-modified polyethylene terephthalate and maleic acid-modified polypropylene are preferable from the viewpoint of seal strength.
Further, the sealing layer 22 has a thickness of 15 μm or less because the coating film 20 can be more easily cleaved substantially linearly when the pipette tip or the tip of the injection needle is pierced. Is preferably 1 kg / cm ² or less.

  The sealing layer 22 is formed by, for example, a method of directly molding a molten resin into a layer shape (for example, an extrusion molding method or an inflation molding method), a method of forming a coating solution by dissolving a resin in a solvent, or the like. The

The intermediate layer 23 is a layer provided for the purpose of improving adhesion between the aluminum layer 21 and the seal layer 22, improving gas barrier properties, preventing the reagent S from contacting the aluminum layer 21, and the like. Examples of the resin constituting the intermediate layer 23 include polyamides, polyethylene, polypropylene, polyesters such as polyethylene terephthalate and polybutylene terephthalate, cellulosic resins, polyurethane, and polyvinyl chloride. Among these, polyester is preferable. Polyester is excellent in processability and heat resistance, and has high hardness. Therefore, it is possible to prevent the pipette tip and the tip of the syringe from coming into close contact with the intermediate layer 23 when a pipette tip or an injection needle is pierced.
The thickness of the intermediate layer 23 is preferably 10 μm or less from the viewpoint that the coating film 20 can be more easily cleaved substantially linearly when the tip of a pipette tip or injection needle is pierced.

The protective layer 24 protects the aluminum layer 21. As resin which comprises the protective layer 24, an acrylic resin, polyester, etc. are mentioned, for example.
Further, the protective layer 24 is preferably made of a brittle material because the coating film 20 can be more easily cleaved in a substantially straight line when the tip of a pipette tip or injection needle is pierced. Examples of the brittle material include a matte polyethylene terephthalate film whose surface is matte-like by sandblasting or the like, a foamed resin film, and the like.
The protective layer 24 preferably has a thickness of 15 μm or less, an elongation of 30% / 180 mm or less, and a rupture degree of 2 kg / cm ² or less. Even when the protective layer 24 has such physical properties, the covering film 20 can be more easily cleaved in a substantially straight line when the tip of a pipette tip or injection needle is pierced.

[Production method]
The reagent container 1 is heated, for example, after the covering film 20 is stacked so as to cover the opening 11 a of the well 11 in the container body 10, and then the portion of the covering film 20 positioned around the opening 11 a of the well 11 is heated. It is obtained by pressing the sealed bar.

[Usage]
The above-described reagent container 1 is suitably used for the μ-Total Analysis System technology and the Lab-on-Chip technology for detecting a chemical reaction, an antigen-antibody reaction, a DNA reaction, a protein reaction and the like on a chip.
For example, in the detection of the antigen-antibody reaction, the antibody as the reagent S is accommodated in the well 11 of the container body 10 in advance, and the well 11 is sealed with the coating film 20. Next, the tip of the pipette tip is pierced and penetrated into the coating film 20, the antibody is separated by the pipette tip, and the separated antibody is used as an antigen placed in the reaction part of the same reagent container or another member. Dripping. At that time, the presence or absence of the antigen-antibody reaction can be detected by attaching a labeling substance to the antigen or antibody. As the labeling substance, a luminescent substance such as a fluorescent substance can be used. When a luminescent substance is used as the labeling substance, light can be emitted when an antigen-antibody reaction occurs.

In the detection of the DNA reaction, the sample DNA as the reagent S is accommodated in the well 11 of the container body 10 in advance, and the well 11 is sealed with the coating film 20. Next, the tip of the pipette tip is pierced and penetrated through the coating film 20, the sample DNA is separated by the pipette tip, and the collected sample DNA is arranged in the reaction part of the same reagent container or another member. Dripping into. At this time, the presence or absence of a DNA reaction can be detected by attaching a labeling substance to the sample DNA.
Such a DNA reaction using the reagent container 1 can be applied to single nucleotide polymorphism (SNP) analysis. In the case of SNP analysis, there may be a plurality of nucleic acid probes and other reagents S used for detection. As an analysis of SNP, an invader method developed by Third Wave Technologies, Inc. (Madison, Wisconsin, USA) can be employed.

In the reagent container 1 described above, since the emboss 21a is formed on the aluminum layer 21 of the covering film 20, when the pipette tip or the tip of the injection needle is pierced into the covering film 20 in order to collect the reagent S, A hole is not opened only in the pierced part, but the covering film 20 can be cleaved substantially linearly. Specifically, as shown in FIG. 4, a linear tear 25 can be formed. As a result, a gap for allowing air to flow into the well 11 can be formed, and when the reagent S is sucked by a syringe attached to a pipette tip or a syringe needle, the inside of the well 11 is unlikely to become negative pressure, The reagent S can be sucked up easily, and the recoverability of the reagent S can be improved.
In the reagent container 1, since the coating film 20 is cleaved substantially linearly when the pipette tip or the tip of the injection needle is pierced, the pipette tip or the tip of the injection needle is pierced into the coating film 20 even after the cleavage. The part which can do is left and the piercing property is secured.
Moreover, since the light shielding property can be enhanced by the aluminum layer 21 of the coating film 20, the alteration and deterioration of the reagent S can be prevented.
Furthermore, as a result of investigation by the present inventor, it was found that the coating film 20 has secured reagent resistance.

In the reagent container 1, since the intermediate layer 23 is provided between the aluminum layer 21 and the seal layer 22 of the coating film 20, a part of the seal layer 22 is formed by the reagent S accommodated in the well 11. Even if it is attacked, the aluminum layer 21 and the reagent S can be prevented from coming into direct contact. As a result, the reagent resistance of the coating film 20 can be further improved.
Further, since the protective layer 24 is provided on the surface of the aluminum layer 21 opposite to the seal layer 22 side, the aluminum layer 21 can be prevented from being oxidized and damaged by air, and the handleability of the covering film 20 is improved. Can be made.

The reagent container of the present invention is not limited to the above-described embodiment example. For example, the reagent container of the above-described exemplary embodiment includes a container main body having a well and a covering film that covers the opening of the well. It may be a bottle and the opening of the reagent container may be covered with a coating film.
In the embodiment described above, the openings of the plurality of wells are covered with one cover film, but one cover film may be covered with respect to one opening.
Moreover, the embossed pattern of the aluminum layer is not limited to a grid pattern, and may be, for example, a dot pattern or a wavy pattern. The emboss may not be formed on the entire surface, but only on a part thereof.
Furthermore, as long as the coating film has an aluminum layer and a seal layer, the intermediate layer and / or the protective layer may not necessarily be provided.

Example 1
First, an embossed plate having an embossed pattern formed on one side of a 10 μm thick hard aluminum foil (rupture degree 0.05 kg / cm ² , elongation 1% / 180 mm) is pressure-bonded at a temperature of 200 ° C. and a linear pressure of 100 kg / cm. The emboss was formed on the entire surface of the hard aluminum foil. The embossed plate used at this time is a grid-like lattice pattern in which a large number of linear first grooves and a plurality of second grooves orthogonal to the first grooves are formed. And the interval between the second grooves is 4 mm. Thereby, an emboss having a grid lattice pattern was formed, and an aluminum layer made of a hard aluminum foil having a distance between the first grooves and a distance between the second grooves of 4 mm was obtained.
Next, a protective layer made of a matte-like polyethylene terephthalate film (burst degree 2 kg / cm ² , elongation 6% / 180 mm) having a thickness of 15 μm and subjected to sandblasting on the surface of the aluminum layer on which the emboss is formed, It laminated | stacked through the polyester urethane type adhesive agent (thickness 2 micrometers).
Next, a heat seal lacquer mainly composed of maleic acid-modified polypropylene was applied at a thickness of 3 μm on the other surface of the aluminum layer to form a seal layer, thereby obtaining a coated film.
Moreover, the container main body in which four hemispherical wells which are reagent storage parts were formed was produced by injection molding polypropylene.
Then, after each of the wells contains a pH 4 aqueous solution or a pH 11 aqueous solution (reagent), the container is formed so that all four wells containing the aqueous solution are covered and the seal layer is in contact with the container body. A coating film was stacked on the main body. Then, a seal bar was pressed at 200 ° C. for 3 seconds at 20 N / cm ² at a portion located around the well opening in the coated film, and heat sealed to obtain a reagent container.

About the obtained reagent container, the piercing property, recovery rate, and reagent resistance of the coated film were evaluated. The evaluation results are shown in Table 1.
[Puncture of coated film]
A polypropylene pipette tip (200 μl) was pierced into the coating film, and the piercing property was evaluated according to the following criteria.
A: It was possible to pierce five times or more.
○: It was possible to pierce 3 times or more and less than 5 times.
[Recovery rate]
With the goal of collecting 100 μl of reagent, the reagent contained in the well was collected with a pipette tip, and the actual amount collected was measured. Then, the recovery rate was determined by the formula (actual recovery amount) / 100 μl × 100%. Generally, if the recovery rate is 85% or more, it is considered practical.
[Reagent resistance of coated film]
A reagent container containing a pH 4 aqueous solution or a pH 11 aqueous solution (reagent) in a well was prepared, and then allowed to stand in an environment of 40 ° C. and a relative humidity of 90% for 72 hours. And the coating film was peeled, the surface was observed visually, and the following references | standards evaluated.
○: No change.
X: The aluminum layer of the coating film was discolored.

(Example 2)
As the embossed plate, an emboss having a grid-like lattice pattern is formed using an interval between the first grooves and an interval between the second grooves of 2 mm, and the interval between the first grooves and the second interval. A reagent container was obtained in the same manner as in Example 1 except that an aluminum layer having an interval between the grooves of 2 mm was obtained. And it evaluated similarly to Example 1. FIG. The evaluation results are shown in Table 1.

(Example 3)
A reagent container was obtained in the same manner as in Example 2 except that a hard aluminum foil having a thickness of 7 μm was used. And it evaluated similarly to Example 1. FIG. The evaluation results are shown in Table 1.

(Comparative Example 1)
A reagent container was obtained in the same manner as in Example 1 except that no emboss was formed on the hard aluminum foil. And it evaluated similarly to Example 1. FIG. The evaluation results are shown in Table 1.

(Comparative Example 2)
A reagent container was obtained in the same manner as in Example 3 except that no emboss was formed on the hard aluminum foil. And it evaluated similarly to Example 1. FIG. The evaluation results are shown in Table 1.

(Comparative Example 3)
Emboss is not formed on the hard aluminum foil, and grid-like ridges are formed on the pressing surface, the interval between the parallel ridges is 2 mm, and the area of the pressing surface is approximately equal to the area of the coating film A reagent container was obtained in the same manner as in Example 1 except that the coating film was heat-sealed to the container body using a bar and embossed was formed only on the protective layer of the coating film. And it evaluated similarly to Example 1. FIG. The evaluation results are shown in Table 1.

In the reagent containers of Examples 1 to 3 provided with a coating film in which an emboss is formed on an aluminum layer, the piercing property was ensured and the reagent recoverability was excellent. Furthermore, the coating film was also ensured reagent resistance. And since the coating film has an aluminum layer, it was excellent in light-shielding property.
On the other hand, in the reagent containers of Comparative Examples 1 and 2 having a coating film in which no emboss is formed on the aluminum layer, the reagent recoverability was low.
Further, in the reagent container of Comparative Example 3 in which the embossing was not formed on the hard aluminum foil and the embossing was formed on the protective layer, the aluminum layer was altered, and the reagent resistance was low.

It is a perspective view which shows one embodiment of the container for reagents of this invention. It is A-A 'sectional drawing of FIG. It is the figure which expanded the surface of the aluminum layer which comprises the coating film of the container for reagents of FIG. FIG. 2 is a top view showing a state in which the coating film is cleaved substantially linearly in the reagent container of FIG. 1.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Reagent container, 10 Container main body, 11 Well (reagent accommodating part), 11a Opening part, 20 Cover film, 21 Aluminum layer, 21a Embossing, 21b 1st groove | channel, 21c 2nd groove | channel, 22 Seal layer, 23 Middle Layer, 24 protective layer, 25 fissure, S reagent

Claims (4)

A reagent container comprising a container main body having a reagent containing portion for containing a reagent, and a covering film attached to the container main body and covering an opening of the reagent containing portion,
The covering film has an aluminum layer, a sealing layer adhered to the container body, and a protective layer made of a brittle material provided on the surface of the aluminum layer opposite to the sealing layer side, and embossed on the aluminum layer. And the protective layer is a layer for protecting the aluminum layer, and is made of a matte-like polyethylene terephthalate film or a foamed resin film whose surface is sandblasted .   The embossed pattern of the aluminum layer is a checkered grid pattern in which a large number of linear first grooves and a plurality of second grooves orthogonal to the first grooves are formed. The reagent container according to claim 1, wherein the interval and the interval between the second grooves are 2 mm or less.   The reagent container according to claim 1 or 2, wherein the aluminum layer comprises a hard aluminum foil having a thickness of 10 µm or less.   The reagent container according to any one of claims 1 to 3, wherein an intermediate layer is provided between the aluminum layer and the seal layer.

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