JPWO2019189897A1 - Biological sample processing tool, pressing system and biological sample processing method - Google Patents

Abstract

Provided are a biological sample processing tool, a pressing system, and a biological sample processing method capable of easily processing a biological sample. The biological sample processing tool 100 includes a base body 10 and a flexible film 20. A first accommodating portion 30, a second accommodating portion 32, and a first communication passage 36a are provided between the base body 10 and the flexible film 20. The first communication passage 36a is for communicating the first storage portion 30 and the second storage portion 32, and is a first closing portion provided so as to block the first communication passage 36a. 36a1 is provided. The first storage unit 30 stores a liquid in which a biological sample or the like is dissolved, and the second storage unit stores a pretreatment liquid or the like. When the liquid is stored in the first storage portion 30 so as not to leak, when the liquid in the first storage portion 30 is pressed with a predetermined force, the blocked state by the first closing portion 36a1 is released. Then, the first accommodating portion 30 and the second accommodating portion 32 communicate with each other.

Description

The present invention relates to processing tools, pressing systems and processing methods used to process biological samples.

Microchannel chips have been proposed for inspecting minute amounts of biological samples such as proteins and nucleic acids (see Patent Document 1).

Patent No. 5986996

An object of the present invention is to provide a processing tool for a biological sample, a pressing system, and a method for processing a biological sample, which can easily process a biological sample.

1. 1. Processing tool for biological sample The processing tool for biological sample of the present invention is
With the base body
Flexible film and
A first accommodating portion provided between the base body and the flexible film,
One or more second accommodating portions provided between the base body and the flexible film, and
A first communication passage provided between the base body and the flexible film and for communicating the first accommodating portion and the second accommodating portion, and
The first communication passage includes a first closing portion provided so as to close the first communication passage.
The first accommodating portion is for accommodating the first liquid.
The second accommodating portion is for accommodating the second liquid.
When the first liquid in the first storage portion is stored so as not to leak, when the first liquid is pressed with a predetermined force, the blocked state by the first closed portion is released. The first accommodating portion and the second accommodating portion communicate with each other.

According to the present invention, the liquid in the first storage portion can be transferred to the second storage portion with a simple structure and without the liquid touching the hand. Therefore, the biological sample can be easily processed.

In the present invention, the first liquid is a liquid for dissolving a biological sample, and the second liquid can be a pretreatment liquid. According to this, the pretreatment of the biological sample can be processed in the processing tool for the biological sample.

In the present invention
The first closed portion is composed of a first adhesive portion.
The first adhesive portion is attached to the base body when the first liquid is stored in the first storage portion so as not to leak, and when the first liquid is pressed with a predetermined force. The adhesive strength can be such that it can be peeled off from the flexible film.

Since the first closed portion is composed of the first adhesive, the first closed portion can be easily provided.

In the present invention
When a plurality of the second accommodating portions are provided,
Adjacent second containments are communicated by a second communication passage.
The second communication passage is provided with a second closing portion that closes the second communication passage.
When the second liquid in the one second accommodating portion is accommodated so as not to leak, when the second liquid is pressed with a predetermined force, the obstructed state by the second obstructed portion is released. In addition, the one second accommodating portion and the other second accommodating portion communicate with each other.

According to the present invention, a plurality of treatments such as pretreatment can be realized in a processing tool for a biological sample.

In the present invention
The first accommodating portion is connected to a first passage for injecting the first liquid.
The second accommodating portion is connected to a second passage for injecting the second liquid.
In the first passage, the biological sample processing tool has a second adhesive portion that can block the first passage and a second adhesive portion.
The second passage includes a third adhesive portion that can block the second passage.
The first adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The second adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The third adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The second adhesive portion and the third adhesive portion may have a stronger adhesive force than the first adhesive portion.

According to the present invention, the liquid can be easily injected into the first accommodating portion and the second accommodating portion. In addition, it is not necessary to inject the liquid at the time of manufacturing the processing tool for the biological sample.

In the present invention
The base body and the flexible in at least a part of a region other than the first accommodating portion, the second accommodating portion, the first communication passage, the first passage, and the second passage. A fourth adhesive portion is provided between the sex film and the film to prevent liquid leakage.
The fourth adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The fourth adhesive portion can have a stronger adhesive force than the first adhesive portion.

According to the present invention, the base body and the flexible film can be easily joined.

In the present invention, the liquid accommodating amount of the first accommodating portion and the second accommodating portion can be 1.5 ml or less. The treatment tool for biological samples of the present invention is particularly useful when treating such a trace amount of liquid.

In the present invention
A reaction or interaction section provided between the base body and the flexible film and communicating with the second accommodating portion and the third communication passage is included.
The reaction or interaction unit is for at least reacting or interacting with the first liquid and the second liquid.
The third communication passage is blocked by the third blocking portion, and the third passage is blocked.
When the liquid is contained in the second accommodating portion so as not to leak, when the liquid is pressed against the second accommodating portion with a predetermined force, the obstructed state by the third obstructed portion is released, and the second accommodating portion The accommodating portion of 2 and the reaction or interacting portion may communicate with each other.

According to the present invention, interactions such as reaction and adsorption with a biological sample can be performed in a biological sample processing tool.

In the present invention, the reaction can be PCR, immune reaction, removal of red blood cells from blood, or reaction for extraction of serum. The processing tool for biological samples of the present invention is particularly useful for such processing.

In the present invention, the first accommodating portion, the one or more second accommodating portions, and the reaction or interacting portion can be arranged so as to be arranged in a straight line. According to the present invention, since a series of liquids are moved by moving the pressing portion in a straight line, it becomes easier to use the processing tool for a biological sample.

In the present invention, the first liquid in the first accommodating portion can be made movable through the second accommodating portion to the reaction or interacting portion while maintaining a closed system. This makes it possible to move the liquid without touching the air. It is especially useful for processing biological samples that are reluctant to come into contact with air.

In the present invention
A cleaning liquid accommodating portion provided between the base body and the flexible film and communicating with the reaction or interaction portion through a fourth communication passage is included.
The cleaning liquid accommodating portion is for cleaning the reaction or interacting portion.
The fourth passage is blocked by the fourth blockage, and is blocked.
When the liquid is stored in the cleaning liquid storage unit so as not to leak, when the liquid is pressed with a predetermined force, the blocked state by the fourth blocked portion is released, and the reaction or interaction with the cleaning liquid storage unit is released. It may communicate with the department.

In the present invention, the flexible film on the side portion of the first accommodating portion may be peelable from the base body up to the first accommodating portion. According to the present invention, the biological sample can be easily charged into the first storage portion.

In the present invention
The first liquid is contained in the first accommodating portion in a sealed state.
The second liquid can be contained in the second accommodating portion in a sealed state.

2. 2. Pressing system The pressing system of the present invention includes a pressing portion for pressing the processing tool for a biological sample of the present invention.
The pressing portion includes at least the first accommodating portion and a first roller capable of pressing the second accommodating portion.

In the present invention
The pressing part is
Including the first roller and the second roller
The first roller presses at least the first accommodating portion and the second accommodating portion.
The second roller supports the base body and
The biological sample processing tool can be made movable relative to the pressing portion between the first roller and the second roller.

The first roller can be moved up and down in the direction perpendicular to the biological sample processing tool. As a result, when pressing continuously, it is possible to skip a region that should not be pressed at that time.

In the present invention, a heating unit for heating the first liquid and the second liquid can be included. As a result, the liquid obtained by processing the biological sample can be heated.

3. 3. Biological sample processing method The biological sample processing method of the present invention is:
A method for processing a biological sample using the biological sample processing tool of the present invention.
The step (A) of injecting the first liquid into the first accommodating portion, and
The step (A) includes a step of pressing the first liquid of the first accommodating portion and moving the first liquid to the second accommodating portion.

FIG. 1 (A) is a plan view schematically showing a processing tool for a biological sample according to an embodiment, and FIG. 1 (B) schematically shows a cross section taken along the line AA of FIG. 1 (A). It is sectional drawing which shows. It is a figure which shows typically the processing tool for a biological sample which concerns on embodiment. It is a figure for demonstrating the principle of the processing tool for a biological sample which concerns on embodiment, FIG. 3A is a plan view which shows typically the processing tool for a biological sample, and FIG. 3B is FIG. It is sectional drawing which shows typically the cross section along the line BB of (A). FIG. 4 (A) is a diagram schematically showing a sample charging portion of the biological sample processing tool according to the embodiment, and FIG. 4 (B) is a cross section taken along the line CC of FIG. 4 (A). It is sectional drawing which shows typically. FIG. 5A is a side view of a specific example of a biological sample processing tool, and FIG. 5B is a plan view of a specific example of a biological sample processing tool. 6 (A) and 6 (B) are diagrams schematically showing a specific example of the pressing system. It is a figure for demonstrating the processing method of the processing tool for a biological sample which concerns on FIG. It is a figure for demonstrating the processing method of the processing tool for a biological sample which concerns on FIG. It is a figure for demonstrating the processing method of the processing tool for a biological sample which concerns on FIG. It is a figure for demonstrating the structural example of a PCR chamber, FIG. 10 (A) is a plan view of a PCR chamber, and FIG. 10 (B) shows the cross section along the line DD of FIG. 10 (A). It is a cross-sectional view, and FIG. 10 (C) is an enlarged view of the periphery of the through hole of FIG. 10 (B). It is a top view which shows typically the modification concrete example of the processing tool for a biological sample. It is a figure for demonstrating the processing method of the modification concrete example of the processing tool for a biological sample. It is a figure for demonstrating the processing method of the modification concrete example of the processing tool for a biological sample.

Hereinafter, preferred embodiments of the present invention will be described in detail.

1. 1. Biological sample processing tool The biological sample processing tool according to the embodiment will be described with reference to FIGS. 1 and 2.

The biological sample processing tool 100 according to the embodiment includes a base body 10 and a flexible film 20, and a first accommodating portion 30 and a first accommodating portion 30 are provided between the base body 10 and the flexible film 20. One or more second accommodating portions 32 and a first communication passage 36a are provided.

The base body 10 and the flexible film 20 are stuck together. This bonding may be performed by bonding with an adhesive or by fusion.

The base body 10 can be made of, for example, a chemically stable synthetic resin (for example, a polyester-based resin). The thickness of the base body 10 varies depending on the specific use of the biological sample processing tool 100, but for example, the thickness can be 0.05 to 2 mm. The amount of the liquid that can be stored in the first storage unit 30 varies depending on the specific use of the biological sample processing tool 100, but in the case of PCR processing, it can be, for example, 1.5 ml or less.

The flexible film 20 can be made of, for example, a polymer film. The thickness of the flexible film 20 is not particularly limited as long as the film itself is not torn and leaks, and can be, for example, 50 to 100 μm or less. The amount of the liquid that can be stored in the second storage unit 32 varies depending on the specific use of the biological sample processing tool 100, but in the case of PCR processing, it can be, for example, 1.5 ml or less.

The first accommodating portion 30 is for accommodating the first liquid. As the first liquid, for example, a liquid for dissolving a biological sample can be mentioned.

The second accommodating portion 32 is for accommodating the second liquid, and may include, for example, a pretreatment liquid, for example, a liquid for treating a liquid in which a biological sample is dissolved. Can be done. When there are a plurality of second accommodating portions 32, different liquids may be accommodated or the same liquid may be accommodated. The number of the second accommodating portion 32 and the liquid to be injected are determined according to the required processing of the biological sample.

The first communication passage 36a is provided between the base body 10 and the flexible film 20, and is provided so as to communicate the first accommodating portion 30 and the second accommodating portion 32.

The first closing portion 36a1 is provided so as to close the first communication passage 36a in the first communication passage 36a. When the first liquid of the first storage portion 30 is stored so as not to leak, when the first liquid is pressed with a predetermined force, the blocked state by the first closed portion 36a1 is released. It is composed.

The first closed portion 36a1 can be configured by the first adhesive portion. The first adhesive portion 36a1 can be made of a thermosetting or ultraviolet curable adhesive, and known ones can be applied. The first adhesive portion 36a1 is flexible with the base body 10 when the first liquid is stored in the first storage portion 30 so as not to leak, and when the first liquid is pressed with a predetermined force. The adhesive strength can be such that it can be peeled off from the sex film 20. The first closing portion 36a1 is not limited to bonding with an adhesive, and is not particularly limited as long as it can withstand the pressure from a predetermined liquid and is opened when the pressure from the liquid is higher than the predetermined pressure.

When a plurality of second accommodating portions 32 are provided, the adjacent second accommodating portions 32 are communicated with each other by the second communication passage 36b. The second communication passage 36b is provided with a second closing portion 36b1 that closes the second communication passage 36b. The second communication passage 36b has a second blockage when the second liquid of one of the second storage portions 32 is stored so as not to leak, and when the second liquid is pressed with a predetermined force. The blocked state by the portion 36b1 is released.

The first accommodating portion 30 is connected to a first passage 38a for injecting the first liquid. In the first passage 38a, a second adhesive portion capable of closing the first passage 38a is provided. The second adhesive portion is composed of a thermosetting or ultraviolet curable adhesive, and known ones can be applied. When the second adhesive portion blocks the first passage 38a and the first liquid of the first storage portion 30 is stored so as not to leak, the first liquid is stored with a predetermined force. When the closed state by the first closed portion 36a1 is released when pressed, the closed state of the first passage 38a by the second adhesive portion is not released. The adhesive strength of the second adhesive portion is determined in relation to the adhesive strength of the first adhesive portion 36a1, and for the second adhesive portion, an adhesive stronger than the adhesive strength of the first adhesive portion 36a1 is selected. To.

The second accommodating portion 32 is connected to a second passage 38b for injecting the second liquid. In the second passage 38b, a third adhesive portion 38b1 capable of closing the second passage 38b is provided. The third adhesive portion 38b1 is composed of a thermosetting or ultraviolet curable adhesive, and known ones can be applied. When the third adhesive portion 38b1 blocks the second passage 38b and the second liquid of the second accommodating portion 32 is accommodated so as not to leak, the second liquid is subjected to a predetermined force. When the closed state due to the closed portion existing in the communication passage with the adjacent second accommodating portion 32 or the reaction or interacting portion 34 is released when pressed with, the second by the third adhesive portion 38b1. Prevent the passage 38b from being unblocked. The adhesive strength of the second adhesive portion 38a1 is determined in relation to the adhesive strength of the first adhesive portion 36a1, and the second adhesive portion 38a1 has an adhesive stronger than the adhesive strength of the first adhesive portion 36a1. Be selected.

When the base body 10 and the flexible film 20 are bonded together by an adhesive, the first accommodating portion 30, the second accommodating portion 32, the first communication passage 36a, the first passage 38a, And, in at least a part of the region other than the second passage 38b, the base body 10 and the flexible film 20 are made flexible by the fourth adhesive portion 40 for preventing liquid leakage between the base body 10 and the flexible film 20. It can be bonded to the film 20. The fourth adhesive portion 40 is composed of a thermosetting or ultraviolet curable adhesive, and the fourth adhesive portion 40 can be configured to have a stronger adhesive force than the first adhesive portion 36a1. An adhesive seal 42 may be provided on the side of the fourth adhesive portion 40. A tab 22 for peeling from the base body 10 may be provided at the end of the flexible film 20. The tab 22 of the flexible film 20 can be provided so as to project from the base body 10.

The biological sample processing tool 100 may include a reaction or interaction unit 34 provided between the base body 10 and the flexible film 20 and communicating through a second accommodating portion 32 and a third communication passage 36c. it can. The reaction or interaction unit 34 is for at least reacting or interacting with the first liquid and the second liquid. Reaction or interaction The reaction or interaction in the interaction unit 34 is a concept including, for example, a chemical reaction or an interaction due to a force based on an electromagnetic factor (Couron force), and more specifically, an antigen-antibody reaction. It is a concept that includes ion exchange reaction, intermolecular interaction, ion-ion interaction, hydrogen-bonding interaction, protein-protein interaction, and the like. Specific examples of the reaction include PCR, immune reaction, removal of red blood cells from blood, and reaction for extraction of serum.

The third communication passage 36c is closed by the third closing portion 36c1. When the liquid is stored in the second storage portion 32 so that the liquid does not leak, when the liquid is pressed against the second storage portion 32 with a predetermined force, the third closing portion 36c1 causes the third closing portion 36c1. The configuration is such that the blocked state is released.

The first containment section 30, one or more second containment sections 32 and the reaction or interaction section 34 can be arranged in a straight line. As a result, the processing can be performed by linearly moving the pressing portion 50 such as a roller.

The biological sample processing tool 100 can include a cleaning liquid accommodating portion (68a, 68b in FIG. 5). The cleaning liquid accommodating portion is provided between the base body 10 and the flexible film 20, and can communicate with the reaction or interaction portion 34 through a communication passage. The cleaning liquid storage unit is for cleaning the reaction or interaction unit 34. The fourth communication passage between the cleaning liquid accommodating portion and the reaction or interaction portion is blocked by the fourth closing portion (76d, 76e in FIG. 5). When the liquid is stored in the cleaning liquid storage portion so that the liquid does not leak, the fourth closed portion releases the blocked state due to the fourth closed portion when the liquid is pressed against the reaction or interaction unit 34 side with a predetermined force. It is structured so that it can be taken.

The flexible film 20 on the side of the first accommodating portion 30 can be peeled off to the first accommodating portion 30. As a result, a cotton swab or the like to which the biological sample is attached can be easily inserted into the first accommodating portion 30.

The flexible film 20 also includes a film obtained by coating a liquid that is a material of the flexible film 10 and then curing the liquid. That is, in the biological sample processing tool 100, the entire surface of the base body is coated with a thermoplastic resin, and a heated mold (for example, an iron) is pressed against the heat to apply heat, thereby providing a space or flow for accommodating the solution. Including those that form a road.

As the adhesive constituting any of the above-mentioned adhesive portions, an adhesive made of a thermoplastic resin that is thermally cured at a relatively high temperature is preferable.

In any of the above-mentioned closed portions, the closed portion pressure can be adjusted by adjusting the width or cross-sectional area of the closed portion.

By using a blood component separation filter or a support utilizing the adsorption principle for the first accommodating portion 30, the second accommodating portion 32 and the reaction or interaction portion 34, a biological sample is processed from blood in a closed system. A PCR reaction, an immune reaction, etc. can be performed.

2. 2. Liquid injection method A method of injecting liquid into the first accommodating portion 30 will be described with reference to FIGS. 1 and 2.

An injection means such as an injection needle or a thin pipe is inserted into the first passage 38a to inject the solution. When the liquid is run into the first accommodating portion 30, the first accommodating portion 30 swells. Although the inside of the first accommodating portion 30 has a slight positive pressure, the bond or adhesive between the base body 10 and the flexible film 20 does not come off, and the obstruction of the first obstruction portion 36a1 is not released. , Make sure that the liquid stays in the first accommodating portion 30.

After the injection of the liquid is completed, the injection means is pulled out, the first passage 38a is held down, and heat is applied to close the first passage 38a. Specifically, heat is applied to the second adhesive portion 38a1 of the first passage 38a to cure it, and the first passage 38a is closed. The closing force by the second adhesive portion withstands the pressure of the liquid in the first accommodating portion 30 so that the closing force is stronger than that of the first closing portion 36a1. That is, even when a pressure is applied to the liquid in the first accommodating portion 30 to release the first closed portion 36a1, the obstruction by the second adhesive portion 38a1 is not released. To do.

As a method for injecting the liquid into the second accommodating portion 32, the same method as the method for injecting the liquid into the first accommodating portion 30 can be applied.

3. 3. An example of the principle of releasing the blockage When the first blockage portion 36a1 is composed of an adhesive and the first storage portion 30 is filled with the first liquid as shown in FIGS. 3 (B) and 3 (1). think of. As shown in FIGS. 3B and 3B, the pressing portion 50 such as a roller is advanced in the traveling direction so as to crush the first liquid. Although the pressure of the first liquid in the first accommodating portion 30 rises, the first closing portion 36a1 is in a state of withstanding the pressure.

When the pressing portion 52 is further advanced, as shown in FIGS. 3B and 3B, the pressure of the first liquid in the first accommodating portion 30 further increases, and the first closing portion 36a1 is gradually peeled off. ..

As shown in FIGS. 3 (B) and 3 (4), the first closed portion 36a1 is completely peeled off, the closed state is released, and the first accommodating portion 30 and the second accommodating portion 32 are communicated with each other. The first liquid begins to move to the second accommodating section 32.

As shown in FIGS. 3B and 5), at the stage where the pressing portion 52 crushes all the first accommodating portions 30, almost the entire amount of the first liquid is transferred to the second accommodating portion 32. When the second liquid is injected into the second accommodating portion 32, the first liquid and the second liquid are mixed.

As shown in FIGS. 3B and 6B, some of the liquid may return to the first accommodating portion 30.

4. Method of charging a biological sample A method of charging a biological sample will be described with reference to FIG. The flexible film 20 on the side portion of the first accommodating portion 30 can be peeled off from the base body 10 up to the first accommodating portion 30 (see FIGS. 4 (B) (1) to (3)). .. In this case, as shown in FIGS. 4 (B) and 4 (3), the flexible film 20 is peeled off from the base body 10 to the first accommodating portion 30, and a sample rod (cotton swab or the like) to which the biological sample is attached is attached. The biological sample is dissolved in the first liquid by putting it in the liquid of the storage portion 30 of 1. Here, the biological sample processing tool 100 may be vibrated. The sample rod is pulled out, and as shown in FIGS. 4 (B) and 4 (4), the flexible film 20 is attached to the base body 10 by the fourth adhesive portion 40 so that the first accommodating portion 30 is sealed. match. After that, as shown in FIGS. 4 (B) and 4 (5), the liquid contained in the first accommodating portion 30 is pressed by the pressing portion 52.

A tab 22 for peeling from the base body 10 may be provided at the end of the flexible film 20. The tab 22 of the flexible film 20 can be provided so as to project from the base body 10.

5. Pressing system A specific configuration of the pressing system 50 will be described.

The pressing system 50 includes a pressing portion 50 for pressing the biological sample processing tool 100. The pressing portion 50 can press at least the first accommodating portion 30 and the second accommodating portion 32. The pressing portion 50 can be composed of, for example, one or a plurality of rollers.

As shown in FIG. 6A, when the pressing portion 52 is composed of one roller, the biological sample processing tool 100 is placed on the pedestal 58, and the biological sample processing tool 100 is pressed by the roller. can do. The optical device 54 and the heating means 56 may be provided on the side, the end portion, or the vicinity of the end portion of the pedestal 58. The rollers of the pressing system 50 can be moved in the vertical direction and can be moved in the horizontal direction.

As shown in FIG. 6B, when the pressing portion 52 is composed of a plurality of rollers, the pressing portion 52 can include the first roller 52a and the second roller 52b, and the first roller The 52a can press at least the first accommodating portion 30 and the second accommodating portion 32, and the second roller 52b can support the base body 10. The biological sample processing tool 100 can be made movable relative to the pressing portion 52 between the first roller 52a and the second roller 52b. The first roller 52a can move in the vertical direction. The pressing system 50 itself is moved horizontally, and the biological sample processing tool 100 moves relatively horizontally between the first roller 52a and the second roller 52b in relation to the pressing portion 52. Can be done.

The optical device 54 is composed of optical system components such as a lens in order to magnify and visually recognize the substance in the processing liquid. The pressing system 50 can be provided with a heating means 56 for heating the treatment liquid. As the heating means 56, for example, a heating means using a Peltier element can be mentioned.

6. Specific Example of First Biological Sample Processing Tool (1) Specific Configuration When the biological sample processing tool 100 is used as a PCR reaction system, as shown in FIG. 5, the first storage unit 30 is used. For example, the sample chamber 60 can be used. As the second accommodating portion 32, for example, a lysis liquid chamber 62, a bind liquid chamber 64, and a propanol liquid chamber 66 can be used. The biological sample processing tool 100 may be provided with a first cleaning liquid storage unit, a second cleaning liquid storage unit 68b, and an extract chamber 68c. As the reaction or interaction unit 34, for example, a reaction chamber can be provided. The reaction or interaction unit 34 is connected to the PCR chamber 74 through a communication passage. A closed portion can be provided in the communication passage between the reaction or interaction portion 34 and the PCR chamber 74.

As shown in FIGS. 10A and 10B, the PCR chamber 74 is guided to the container 90 by a flow path 12 provided in the base body 10 and a through hole 94 connected to the flow path 12. As shown in FIG. 10C, the surface of the container 90 side (back surface side of the base body 10) around the through hole 94 of the base body 10 may be hydrophobically processed to provide the hydrophobically processed portion 24. A glass plate 92 is installed in the container 90. Examples of this hydrophobic processing method include a paraffin coating process. By performing the hydrophobic treatment, the water droplets can be made smaller, and the water droplets can be easily dropped into the container 90.

(2) Example of Use The method of use when the biological sample processing tool 100 is used as a PCR reaction system will be described. The biological sample contains nucleic acid.

Corresponds to each of the sample chamber 60, the lysis liquid chamber 62, the bind liquid chamber 64, the propanol liquid chamber 66, the first cleaning liquid storage unit 68a, the second cleaning liquid storage unit 68b, and the extract liquid chamber 68c of the biological sample processing tool 100. Inject the liquid to be used. The liquid can be injected by the method described in the above-mentioned injection method section.

The sample is dissolved in the sample chamber 60.

The biological sample processing tool 100 is set in the pressing system 50. Specifically, the biological sample processing tool 100 is set in the pressing system 50.

The sample chamber 60 is pressed by the pressing portion 50, and as shown in FIGS. 7 and 9 (A) and (B), the obstruction portion 76a between the sample chamber 60 and the lysis liquid chamber 62 is released to release the lysis. The liquid is sent to the liquid chamber 62.

The lysis chamber is pressed by the pressing portion 50, and as shown in FIGS. 7 and 9 (B) and (C), the closure portion 76b between the lysis liquid chamber 62 and the binding liquid chamber 64 is released and bound. The liquid is sent to the liquid chamber 64.

The bind liquid chamber 64 is pressed by the pressing portion 50, and as shown in FIGS. 7 and 9 (C) and 9 (D), the obstruction portion 76c between the bind liquid chamber 64 and the propanol liquid chamber 66 is released. The liquid is sent to the propanol liquid chamber 66.

The propanol liquid chamber 66 is pressed by the pressing portion 50, and as shown in FIGS. 7 and 9 (D) and (E), the blockage portion 76d between the propanol liquid chamber 66 and the adsorption chamber 70 is released. The liquid is sent to the suction chamber 70.

As shown in FIGS. 7 and 9 (E) and (F), the liquid in the adsorption chamber 70 is agitated. An adsorbent that traps nucleic acids such as glass beads and an adsorbent is enclosed in the adsorption chamber 70, and the nucleic acids in the liquid of the adsorption chamber 70 are trapped.

The liquid is pressed into the suction chamber 70 by the pressing portion 50, and the liquid is returned to the propanol liquid chamber 66 as shown in (G) of FIGS. 7 and 9.

As shown in FIGS. 7 and 9 (H) and 9 (I), the liquid of the first cleaning liquid accommodating portion 68a is pressed by the pressing portion 50, and the liquid between the first cleaning liquid accommodating portion 68a and the suction chamber 70 is pressed. The blockage of the blockage portion 76e is released, and the liquid is sent to the suction chamber 70.

As shown in FIGS. 7 and 9 (I), the pressing portion 50 is moved to the downstream side of the suction chamber 70, and as shown in FIGS. 7 and 9 (J) and (K), the inside of the suction chamber 70. Is pressed by the pressing portion 50 and returned to the first cleaning liquid accommodating portion 68a to clean the suction chamber 70.

As shown in FIGS. 8 and 9 (K), the pressing portion 50 is moved between the first cleaning liquid accommodating portion 68a and the second cleaning liquid accommodating portion 68b. As shown in FIGS. 8 and 9 (L) and (M), the liquid of the second cleaning liquid accommodating portion 68b is pressed, and the closing portion 76f between the second cleaning liquid accommodating portion 68b and the suction chamber 70 The blockage is released and the mixture is sent to the suction chamber 70.

As shown in (M) of FIGS. 8 and 9, the pressing portion 50 is moved to the downstream side of the suction chamber 70, and as shown in (N) and (O) of FIGS. 8 and 9, inside the suction chamber 70. Is pressed by the pressing portion 50 and returned to the second cleaning liquid accommodating portion 68b to clean the suction chamber 70.

As shown in (O) of FIGS. 8 and 9, the pressing portion 50 is moved to the downstream side of the extract chamber 68c, and as shown in (P) and (Q) of FIGS. 8 and 9, the extract chamber is used. The liquid of 68c is pressed to release the blockage of the closing portion 76g between the extract chamber 68c and the suction chamber 70, and the liquid is sent to the suction chamber 70. The presence of the extract in the adsorption chamber 70 extracts the nucleic acid trapped in the adsorption chamber 70.

As shown in (Q) of FIGS. 8 and 9, the pressing portion 50 is moved to the upstream side of the small chamber of the suction chamber 70. As shown in FIGS. 8 and 9 (R), the liquid in the suction chamber 70 is pressed to release the blockage 76h between the suction chamber 70 and the PCR chamber 74, and (S) in FIGS. 8 and 9 ), The liquid is sent to the PCR chamber 74.

PCR is performed in the PCR chamber 74. When performing PCR, the liquid can be heated by the heating means 56 of the pressing system 50. When observing the PCR, the observation can be performed by the optical device 54 of the pressing system 50.

7. Specific Example of Second Biological Sample Processing Tool (1) Specific Configuration When the biological sample processing tool 100 is used as a PCR reaction system, as shown in FIG. 11, the first storage unit 30 is used. For example, the sample chamber 60 can be used. As the second accommodating portion 32, for example, a lysis liquid chamber 62, a bind liquid chamber 64, and a propanol liquid chamber 66 can be used. The biological sample processing tool 100 may be provided with a first cleaning liquid storage unit, a second cleaning liquid storage unit 68b, and an extract chamber 68c. As the reaction or interaction unit 34, for example, a reaction chamber can be provided. The reaction or interaction unit 34 is connected to the PCR chamber 74 through a communication passage. A closed portion can be provided in the communication passage between the reaction or interaction portion 34 and the PCR chamber 74. The biological sample processing tool 100 may be provided with a NaOAc liquid chamber 78, a PCR liquid chamber 82, an oil chamber 84, and a waste liquid passage 98.

(2) Example of Use The method of use when the biological sample processing tool 100 is used as a PCR reaction system will be described. The biological sample contains nucleic acid.

As shown in FIG. 12A, the roller 52 is installed in front of the sample chamber 60.

As shown in FIG. 12B, the roller 52 is moved to press the sample liquid in the sample chamber 60 to release the blockage of the closed portion 96a, and the sample liquid is sent to the lysis liquid chamber 62 to separate the sample liquid and the lysis liquid. Mix.

As shown in FIG. 12C, the roller 52 is moved to press the liquid in the lysis liquid chamber 62 to release the blockage of the closed portion 96b, and the mixed liquid of the sample liquid and the lysis liquid is sent to the bind liquid chamber 64. The mixture of the sample solution and the lysis solution and the binding solution are mixed.

As shown in FIG. 12D, the liquid in the bind liquid chamber 64 is pressed to release the blockage of the closed portion 96c, and the liquid is sent to the propanol liquid chamber 66.

As shown in FIG. 12 (E), the roller 52 is moved to press the liquid in the propanol liquid chamber 66 to release the blockage of the closed portion 96d, and the liquid in the propanol liquid chamber 66 is adsorbed in the adsorption chamber (glass beads or the like) 70. Send to. At this time, the liquid in the NaOAc chamber 78 is simultaneously pressed to release the blockage of the closed portion 96e, and the liquid in the NaOAc chamber 78 is sent to the adsorption chamber 70. In the adsorption chamber 70, at least a part of the nucleic acid in the liquid is adsorbed by an adsorbent (not shown). The liquid that has passed through the suction chamber 70 is discarded through the waste liquid passage 98. A waste liquid absorbing portion (not shown) such as a sponge may be provided in the waste liquid passage 98, and the waste liquid may be absorbed by the waste liquid absorbing portion.

As shown in FIG. 12F, the cleaning liquid of the first cleaning liquid accommodating portion 68a is pressed to release the obstruction of the closed portion 96f and sent to the suction chamber 70 to clean the suction chamber 70. The liquid that has passed through the suction chamber 70 is discarded through the waste liquid passage 98. A waste liquid absorbing portion (not shown) such as a sponge may be provided in the waste liquid passage 98, and the waste liquid may be absorbed by the waste liquid absorbing portion.

As shown in FIG. 13 (G), the cleaning liquid of the second cleaning liquid storage portion 68b is pressed to release the blockage of the blocked portion 96 g and sent to the suction chamber 70 to clean the suction chamber 70. The liquid that has passed through the suction chamber 70 is discarded through the waste liquid passage 98. A waste liquid absorbing portion (not shown) such as a sponge may be provided in the waste liquid passage 98, and the waste liquid may be absorbed by the waste liquid absorbing portion.

As shown in FIG. 13 (H), the extract in the extract chamber 68c is pressed to release the blockage of the blocked portion 96h, sent to the adsorption chamber 70, and the nucleic acid adsorbed in the adsorption chamber 70 is extracted. At this time, the roller 52 presses the waste liquid passage 98 to block the waste liquid passage 98 to prevent the liquid from leaking or suppress the liquid leakage.

As shown in FIG. 13 (I), the liquid in the suction chamber 70 is pressed to release the blockage of the closed portion 96i, and the liquid is sent to the liquid storage chamber (temporary reservoir) 72.

As shown in FIG. 13 (J), the liquid in the liquid storage chamber 72 is pressed to send the liquid to the PCR chamber.

As shown in FIG. 13 (K), the liquid in the PCR liquid chamber 82 is pressed to release the blockage of the closed portion 96j, and the liquid is sent to the PCR chamber 74.

As shown in FIG. 13 (L), the liquid in the oil chamber 84 is pressed to release the blockage of the closed portion 96k, and the liquid is sent to the PCR chamber 74.

8. Action effect According to the biological sample processing tool according to the present embodiment, it is possible to separate and store the liquid necessary for processing the biological sample. When processing the biological sample, the first liquid in the first containment 30 can move through the second containment 32 to the reaction or interaction 34 while maintaining a closed system. The biological sample can be processed without touching the air and without touching the hands.

According to the biological sample processing tool 100 according to the present embodiment, the biological sample can be easily processed in a closed system by a small device.

The present embodiment can be modified in various ways within the scope of the present invention.

The processing tool for a biological sample of the present invention is useful, for example, when extracting a biological sample or performing a chemical treatment or a molecular biological treatment on a biological sample.

10 Base body 20 Flexible film 22 Tab 24 Hydrophobic processed part 30 First accommodating part 32 Second accommodating part 34 Reaction or interaction part 36a First communication passage 36b Second communication passage 36c Third communication passage 36a1 First obstruction part (first adhesive part)
36b1 Second obstruction part 36c1 Third obstruction part 38a First passage 38b Second passage 38a1 Second adhesive part 38b1 Third adhesive part 40 Fourth adhesive part 42 Adhesive seal 50 Pressing system 52 Pressing part ( roller)
52a First roller 52b Second roller 54 Optical device 56 Heating means 60 Sample chamber 62 Lysis liquid chamber 64 Bind liquid chamber 66 Propanol liquid chamber 68a First cleaning liquid storage 68b Second cleaning liquid storage 68c Extraction chamber 70 Adsorption chamber 72 Liquid storage chamber 74 PCR chamber 76a to 76g Closure 78 NaOAc liquid chamber 82 PCR liquid chamber 84 Oil chamber 90 Container 92 Glass plate 94 Through hole 96a to 96k Closure 98 Waste liquid passage 100 Treatment tool for biological samples

Claims (19)

With the base body
Flexible film and
A first accommodating portion provided between the base body and the flexible film,
One or more second accommodating portions provided between the base body and the flexible film, and
A first communication passage provided between the base body and the flexible film and for communicating the first accommodating portion and the second accommodating portion, and
The first communication passage includes a first closing portion provided so as to close the first communication passage.
The first accommodating portion is for accommodating the first liquid.
The second accommodating portion is for accommodating the second liquid.
When the first liquid in the first accommodating portion is accommodated so as not to leak, when the first liquid is pressed with a predetermined force, the obstructed state by the first obstructed portion is released. A processing tool for a biological sample in which the first accommodating portion and the second accommodating portion communicate with each other. In claim 1,
The first liquid is a liquid for dissolving a biological sample, and is
The second liquid is a treatment tool for a biological sample which is a pretreatment liquid. In claim 1 or 2,
The first closed portion is composed of a first adhesive portion.
The first adhesive portion is attached to the base body when the first liquid is stored in the first storage portion with a predetermined force when the first liquid is stored so as not to leak. A processing tool for a biological sample having an adhesive strength that can be peeled off from the flexible film. In claim 1 or 2,
When a plurality of the second accommodating portions are provided,
Adjacent second containments are communicated by a second communication passage.
The second communication passage is provided with a second closing portion that closes the second communication passage.
When the second liquid in the one second accommodating portion is accommodated so as not to leak, when the second liquid is pressed with a predetermined force, the obstructed state by the second obstructed portion is released. A biological sample processing tool in which the one second accommodating portion and the other second accommodating portion communicate with each other. In claim 1 or 2,
The first accommodating portion is connected to a first passage for injecting the first liquid.
The second accommodating portion is connected to a second passage for injecting the second liquid.
In the first passage, the biological sample processing tool has a second adhesive portion that can block the first passage and a second adhesive portion.
The second passage includes a third adhesive portion that can block the second passage.
The first adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The second adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The third adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The second adhesive portion and the third adhesive portion are processing tools for biological samples having stronger adhesive strength than the first adhesive portion. In claim 5,
The base body and the flexible in at least a part of a region other than the first accommodating portion, the second accommodating portion, the first communication passage, the first passage, and the second passage. A fourth adhesive portion is provided between the sex film and the film to prevent liquid leakage.
The fourth adhesive portion is composed of a thermosetting or ultraviolet curable adhesive.
The fourth adhesive portion is a processing tool for a biological sample having a stronger adhesive force than the first adhesive portion. In claim 1 or 2,
A biological sample processing tool having a liquid capacity of 1.5 ml or less in the first storage portion and the second storage portion. In claim 1 or 2,
A reaction or interaction section provided between the base body and the flexible film and communicating with the second accommodating portion and the third communication passage is included.
The reaction or interaction unit is for at least reacting or interacting with the first liquid and the second liquid.
The third communication passage is blocked by the third blocking portion, and the third passage is blocked.
When the liquid is contained in the second accommodating portion so as not to leak, when the liquid is pressed against the second accommodating portion with a predetermined force, the obstructed state by the third obstructed portion is released and the second accommodating portion is released. A processing tool for a biological sample in which the accommodating portion of 2 and the reaction or interacting portion communicate with each other. In claim 8.
The reaction is a processing tool for a biological sample, which is a reaction for PCR, immune reaction, removal of red blood cells from blood, or extraction of serum. In claim 8.
A biological sample processing tool in which the first accommodating portion, the one or more second accommodating portions, and the reaction or interacting portion are arranged in a straight line. In claim 8.
A processing tool for a biological sample, in which the first liquid in the first storage portion can be moved through the second storage portion to the reaction or interaction portion while maintaining a closed system. In claim 8.
A cleaning liquid accommodating portion provided between the base body and the flexible film and communicating with the reaction or interaction portion through a fourth communication passage is included.
The cleaning liquid accommodating portion is for cleaning the reaction or interacting portion.
The fourth passage is blocked by the fourth blockage, and is blocked.
When the liquid is stored in the cleaning liquid storage unit so as not to leak, when the liquid is pressed with a predetermined force, the blocked state by the fourth blocked portion is released, and the reaction or interaction with the cleaning liquid storage unit is released. A processing tool for biological samples that communicates with the unit. In claim 1 or 2,
A processing tool for a biological sample in which the flexible film on the side portion of the first accommodating portion can be peeled off from the base body up to the first accommodating portion. In claim 1 or 2,
The first liquid is contained in the first accommodating portion in a sealed state.
A processing tool for a biological sample in which a second liquid is stored in a state of being sealed in the second storage portion. A pressing portion for pressing the biological sample processing tool according to claim 1 or 2 is included.
The pressing portion is a pressing system including at least a first accommodating portion and a first roller capable of pressing the second accommodating portion. 15.
The pressing part is
Including the first roller and the second roller
The first roller presses at least the first accommodating portion and the second accommodating portion.
The second roller supports the base body and
A pressing system in which the processing tool for a biological sample can move relative to the pressing portion between the first roller and the second roller. 15.
The first roller is a pressing system that can move up and down in the direction perpendicular to the biological sample processing tool. 15.
A pressing system including a heating unit for heating the first liquid and the second liquid. A method for processing a biological sample using the biological sample processing tool according to claim 1 or 2.
The step (A) of injecting the first liquid into the first accommodating portion, and
A method for processing a biological sample, which comprises, after the step (A), a step of pressing the first liquid in the first storage portion and moving the first liquid to the second storage portion.

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