JP2024066765A - Reaction device, method for sealing flow channel, and chip - Google Patents

Abstract

[Problem] To provide a reaction device that can improve the sealing performance inside a flow path without making the device large-scale. [Solution] A reaction device 10 comprising a chip body 2 having a flow path 3 with an opening 4 at at least one end, a sealing member 6 for sealing the opening 4, and a heat source 7, in which a heating region A in the chip body 2 that is heated by the heat source 7 includes a region B in which the opening 4 is provided, and the softening point Ts of the sealing member 6 is equal to or lower than the maximum temperature Tmax reached in the heating region A. [Selected Figure] Figure 1

Description

The present invention relates to a reaction device in which a thermal reaction takes place, a method for sealing a flow path, and a chip.

Conventionally, tests such as blood tests and genetic tests have been attempted by controlling the delivery and reaction of various specimens or samples using a chip provided with a flow path through which fluid is delivered. In a reaction device equipped with such a chip, a valve may be used as a flow path switching means for delivering multiple reagents to different locations. For example, in a reaction device used for PCR (Polymerase Chain Reaction), the thermal reaction section may be sealed with a valve to suppress the evaporation of the reaction liquid during the thermal reaction carried out in the final step.

The following Patent Document 1 discloses a method for opening and closing a flow path by rotating a rotary member to bring a diaphragm into contact with or away from a corresponding partition wall.

In addition, the following Patent Document 2 discloses a method of sealing the opening of a microinspection chip using an opening sealing member. In Patent Document 2, an opening sealing member is used that has a sealing lid for the opening and a first adhesive layer for adhering the sealing lid to the opening.

Patent No. 6981762 JP 2009-156741 A

However, in a reaction apparatus using a rotary valve as in Patent Document 1, in order to achieve highly reproducible airtightness while taking into account dimensional tolerances during molding of the valve, it is necessary to press the valve firmly against the chip. In this case, however, the torque during rotation increases, resulting in a problem of increased size of the apparatus. Another possible method is to apply a load from above the valve only during thermal reactions, but this also results in a problem of increased size of the apparatus. In addition, when an opening sealing member having an adhesive layer is used as in Patent Document 2, there is a problem that it is difficult to sufficiently increase the sealing property within the flow channel.

The object of the present invention is to provide a reaction device, a method for sealing a flow path, and a chip that can improve the sealing performance within the flow path without making the device large-scale.

This specification discloses the following reaction device, flow channel sealing method, and chip.

Item 1. A reaction device comprising a chip body having a flow path with an opening at at least one end, a sealing member for sealing the opening, and a heat source, wherein a heating region in the chip body that is heated by the heat source includes a region in which the opening is provided, and the softening point Ts of the sealing member is equal to or lower than the maximum temperature Tmax of the heating region.

Item 2. The reaction device according to item 1, wherein the chip body has a reaction chamber connected to the flow channel, and the heating region includes a region in which the reaction chamber is provided.

Item 3. The reaction device according to item 1 or 2, in which the difference between the maximum temperature Tmax of the heating region and the softening point Ts of the sealing member is 10°C or more and 70°C or less.

Item 4. The reaction device according to any one of items 1 to 3, having a portion where the opening and the heat source overlap in a plan view.

Item 5. The reaction device according to any one of items 1 to 4, wherein the thickness of the chip body is 0.5 mm or more and 10.0 mm or less.

Item 6. The reaction device according to any one of items 1 to 5, wherein the sealing member has a groove on the surface that contacts the chip body, and is arranged so that the sealing member can be in a state where the groove is connected to the opening and a state where the opening is sealed by a portion of the sealing member other than the groove, and the sealing member also serves as a valve.

Item 7. The reaction apparatus according to Item 6, in which the sealing member is arranged so that, by rotating around a rotation axis, the sealing member can assume a state in which the groove of the sealing member is connected to the opening and a state in which the opening is sealed by a portion of the sealing member other than the groove, and the sealing member also serves as a rotary valve.

Item 8. A method for sealing a flow channel in a reaction device comprising a chip body having a flow channel with an opening at at least one end and a sealing member for sealing the opening, the method comprising the steps of heating an area of the chip body where the opening is provided, and sealing the flow channel by allowing a portion of the sealing member melted by the heating to flow into the opening.

Item 9. A chip comprising a chip body having a flow path with an opening at at least one end, and a sealing member for sealing the opening, the softening point Ts of the sealing member being 100°C or lower.

The present invention provides a reaction device, a method for sealing a flow channel, and a chip that can improve the sealing performance within the flow channel without making the device large-scale.

FIG. 1 is a schematic cross-sectional view showing a reaction apparatus according to a first embodiment of the present invention. FIG. 2 is a schematic cross-sectional view showing a state in which the inside of the flow channel is sealed by a sealing member in the reaction apparatus of FIG. FIG. 3 is a schematic cross-sectional view showing a chip according to the first embodiment of the present invention. FIG. 4 is a schematic cross-sectional view showing a state in which an opening of a flow channel is connected to a groove portion of a sealing member in a reaction device according to a second embodiment of the present invention. FIG. 5 is a schematic cross-sectional view showing a state in which the opening of the flow channel is closed by a portion of the sealing member other than the groove in the reaction device of FIG. FIG. 6 is a schematic cross-sectional view showing a state in which the inside of the flow channel is sealed by a sealing member in the reaction device of FIG.

The present invention will be clarified below by explaining specific embodiments of the present invention with reference to the drawings.

[First embodiment]
(Reaction Apparatus)
FIG. 1 is a schematic cross-sectional view showing a reaction apparatus according to a first embodiment of the present invention.

As shown in FIG. 1, the reaction device 10 includes a chip 1 and a heat source 7. The chip 1 is an inspection chip that can perform various reaction tests and inspections. The chip 1 also includes a chip body 2 and a sealing member 6.

The chip body 2 has a rectangular plate-like shape. The chip body 2 has a first main surface 2a and a second main surface 2b that face each other. Note that the shape of the chip body is not limited to a rectangular plate-like shape, and may have other shapes.

A flow channel 3 is provided inside the chip body 2. One end of the flow channel 3 opens to the first main surface 2a, and an opening 4 is formed in the first main surface 2a. The other end of the flow channel 3 is connected to a reaction chamber 5.

A sealing member 6 is provided on the first main surface 2a of the chip body 2. The sealing member 6 is a member for sealing the opening 4 of the flow channel 3. Note that FIG. 1 shows the state before the opening 4 of the flow channel 3 is sealed by the sealing member 6.

A heat source 7 is provided on the second main surface 2b of the chip body 2. The heating area A in the chip body 2 that is heated by the heat source 7 includes an area B in which the opening 4 is provided and an area C in which the reaction chamber 5 is provided. Therefore, the heat source 7 can heat the area B in which the opening 4 is provided and the area C in which the reaction chamber 5 is provided.

In this embodiment, the softening point Ts of the sealing member 6 is equal to or lower than the maximum temperature Tmax of the heating region A. In addition, the portion of the sealing member 6 in contact with the opening 4 is included in the region B in which the opening 4 is provided, so when the heating region A is heated by the heat source 7, the portion of the sealing member 6 in contact with the opening 4 is also heated. At this time, since the softening point Ts of the sealing member 6 is equal to or lower than the maximum temperature Tmax of the heating region A, when the portion of the sealing member 6 in contact with the opening 4 is heated, a portion of the sealing member 6 melts. As a result, as shown in FIG. 2, a portion of the sealing member 6 melted by heating can flow from the opening 4 into the flow path 3, sealing the inside of the flow path 3.

In addition, since the region C in which the reaction chamber 5 is provided is also included in the heating region A, the reaction chamber 5 can also be heated by heating the heating region A with the heat source 7. This allows a reaction involving heating, such as PCR, to be carried out in the reaction chamber 5.

In the reaction device 10 of this embodiment, the heat for heating the reaction chamber 5 can be used to melt a part of the sealing member 6, thereby sealing the inside of the reaction chamber 5 connected to the flow path 3. In this way, in the reaction device 10, the reaction chamber 5 can be sealed simply by providing the sealing member 6 on the opening 4 provided at one end of the flow path 3, so no large-scale device is required for sealing. In addition, in the reaction device 10, the opening 4 is sealed by causing a part of the sealing member 6 melted by heating to flow from the opening 4 into the flow path 3, so that the sealing property in the flow path 3 can be improved. Therefore, according to the reaction device 10, the sealing property in the flow path 3 can be improved without making the device large-scale.

In this embodiment, the difference (Tmax-Ts) between the maximum temperature Tmax reached in the heating area A and the softening point Ts of the sealing member 6 is preferably 10°C or more, more preferably 15°C or more, even more preferably 30°C or more, and is preferably 70°C or less, more preferably 50°C or less. When the difference (Tmax-Ts) is equal to or greater than the lower limit, the inside of the flow path 3 can be sealed more reliably. When the difference (Tmax-Ts) is equal to or less than the upper limit, the molten sealing member 6 can be more reliably prevented from entering the reaction chamber 5.

The maximum temperature Tmax of the heating area A is not particularly limited, but is preferably 90°C or higher, more preferably 95°C or higher, and preferably 110°C or lower, more preferably 100°C or lower. When the maximum temperature Tmax of the heating area A is equal to or higher than the lower limit, the inside of the flow path 3 can be sealed more reliably. When the maximum temperature Tmax of the heating area A is equal to or lower than the upper limit, the melted sealing member 6 can be more reliably prevented from being mixed into the reaction chamber 5. However, the maximum temperature Tmax of the heating area A can be appropriately set depending on the type of reaction to be performed in the reaction chamber 5.

The temperature of region B where the opening 4 is provided when heated by the heat source 7 is not particularly limited, but is preferably 75°C or higher, more preferably 80°C or higher, and preferably 110°C or lower, more preferably 95°C or lower. When the temperature of region B is equal to or higher than the lower limit, the inside of the flow path 3 can be sealed more reliably. When the temperature of region B is equal to or lower than the upper limit, the melted sealing member 6 can be more reliably prevented from entering the reaction chamber 5.

The softening point Ts of the sealing member 6 is preferably 40°C or higher, more preferably 50°C or higher, and preferably 100°C or lower, more preferably 80°C or lower, and even more preferably 70°C or lower. When the softening point Ts of the sealing member 6 is equal to or higher than the lower limit, the molten sealing member 6 can be more reliably prevented from being mixed into the reaction chamber 5. When the softening point Ts of the sealing member 6 is equal to or lower than the upper limit, the flow path 3 can be more reliably sealed.

In this embodiment, the opening 4 and the heat source 7 overlap in a plan view. As in this embodiment, it is preferable that the opening 4 and the heat source 7 at least partially overlap in a plan view, and it is more preferable that the opening 4 completely overlaps the heat source 7. In this case, the region B in which the opening 4 is provided can be more reliably included within the heating region A.

The thickness of the chip body 2 is preferably 0.5 mm or more, more preferably 1.0 mm or more, and is preferably 10.0 mm or less, more preferably 5.0 mm or less. Even in this case, the region B in which the opening 4 is provided can be more reliably included within the heating region A.

The following describes in detail each component that makes up the reaction device 10.

(Chip body)
The material of the chip body 2 is not particularly limited, and may be, for example, a synthetic resin, rubber, metal, etc. The synthetic resin is not particularly limited, but is preferably a thermoplastic resin. Among them, the thermoplastic resin may be, for example, a cycloolefin polymer, a cycloolefin copolymer, polycarbonate, polymethyl methacrylate, or polypropylene.

The chip body 2 can be made of, for example, an injection-molded synthetic resin. The chip body 2 may also be made by laminating multiple synthetic resin sheets, and there are no particular limitations on its structure or material.

A flow channel 3 is provided inside the chip body 2. The flow channel 3 may be a micro flow channel. A micro flow channel is a minute flow channel in which a micro effect occurs when transporting a fluid. In such a micro flow channel, the fluid is strongly affected by surface tension and behaves differently from a fluid flowing through a normal large-dimension flow channel.

The cross-sectional shape and size of the microchannel are not particularly limited as long as the micro-effect occurs. For example, from the viewpoint of reducing flow resistance when a pump or gravity is used to pass a fluid through the microchannel, if the cross-sectional shape of the microchannel is roughly rectangular (including square), the dimension of the smaller side is preferably 20 μm or more, more preferably 50 μm or more, and even more preferably 100 μm or more. From the viewpoint of further miniaturizing the reaction device 10, the dimension of the smaller side is preferably 5 mm or less, more preferably 1 mm or less, and even more preferably 500 μm or less.

When the cross-sectional shape of the microchannel is approximately circular, the diameter (minor axis in the case of an ellipse) is preferably 20 μm or more, more preferably 50 μm or more, and even more preferably 100 μm or more. From the viewpoint of further miniaturizing the reaction device 10, the diameter (minor axis in the case of an ellipse) is preferably 5 mm or less, more preferably 1 mm or less, and even more preferably 500 μm or less.

On the other hand, for example, when flowing a fluid through a microchannel, in order to effectively utilize the capillary phenomenon, if the cross-sectional shape of the microchannel is roughly rectangular (including square), the dimension of the smaller side is preferably 5 μm or more, more preferably 10 μm or more, and even more preferably 20 μm or more. Also, the dimension of the smaller side is preferably 200 μm or less, and more preferably 100 μm or less.

A reaction chamber 5 is provided inside the chip body 2. The dimensions of the reaction chamber 5 are not particularly limited, but can be, for example, 3 mm to 30 mm in length, 0.5 mm to 5 mm in width, and 0.05 mm to 2.0 mm in height.

A mixture of a recovery liquid containing nucleic acid extracted from a sample and a reaction reagent such as a PCR reaction reagent is sent to the reaction chamber 5, and a reaction involving heating such as PCR can be carried out in the reaction chamber 5.

(Sealing member)
The material of the sealing member 6 is not particularly limited, but may be, for example, an elastomer such as an olefin-based elastomer, a polyester-based elastomer, a styrene-based elastomer, or a urethane-based elastomer. These elastomer materials may be used alone or in combination.

The shape of the sealing member 6 is not particularly limited as long as it can seal the opening 4. The shape of the sealing member 6 can be, for example, a rectangular plate or a disk. The thickness of the sealing member 6 is also not particularly limited, and can be, for example, 1 mm or more and 10 mm or less.

(Heat source)
For example, a Peltier heater, a lamp heater, etc. can be used as the heat source 7. Also, a plurality of heaters with different temperatures may be sequentially brought into contact with the substrate.

(Method of sealing the flow path)
In the method for sealing the flow channel 3 of this embodiment, first, the above-mentioned reaction device 10 is prepared. Next, the region B in which the opening 4 is provided in the chip body 2 constituting the reaction device 10 is heated. Next, by heating the region B in which the opening 4 is provided, a part of the molten sealing member 6 is caused to flow into the opening 4, thereby sealing the opening 4. This makes it possible to seal the inside of the flow channel 3.

In the method for sealing the flow path 3 of this embodiment, the reaction chamber 5 can be sealed simply by providing a sealing member 6 over the opening 4 at one end of the flow path 3, so no large-scale device is required for sealing. In addition, in the method for sealing the flow path 3, a part of the sealing member 6 melted by heating is caused to flow from the opening 4 into the flow path 3, thereby sealing the opening 4, so that the sealing ability within the flow path 3 can be improved. Therefore, according to the method for sealing the flow path 3 of this embodiment, the sealing ability within the flow path 3 can be improved without using a large-scale device.

(Tip)
3 is a schematic cross-sectional view showing a chip according to the first embodiment of the present invention. The chip 1 shown in FIG. 3 can be used as, for example, an inspection chip capable of performing various reaction tests and inspections.

The chip 1 comprises a chip body 2 and a sealing member 6 provided on the first main surface 2a of the chip body 2. The chip body 2 and the sealing member 6 may be the same as those described in the section on the reaction device 10.

In the chip 1 of this embodiment, the softening point Ts of the sealing member 6 is 100° C. or less. Therefore, by heating the chip 1 with the heat source 7 of the reaction device 10, a part of the sealing member 6 can be melted, and the inside of the reaction chamber 5 connected to the flow path 3 can be sealed. In this way, in the chip 1, the inside of the reaction chamber 5 can be sealed simply by providing the sealing member 6 on the opening 4 provided at one end of the flow path 3, so that a large-scale device is not required for sealing. In addition, in the chip 1, the opening 4 is sealed by causing a part of the sealing member 6 melted by heating to flow from the opening 4 into the flow path 3, so that the sealing property in the flow path 3 can be improved. Therefore, according to the chip 1, the sealing property in the flow path 3 can be improved without making the device large-scale.

Second Embodiment
Fig. 4 is a schematic cross-sectional view showing a state where an opening of a flow channel is connected to a groove of a sealing member in a reaction device according to a second embodiment of the present invention. Fig. 5 is a schematic cross-sectional view showing a state where an opening of a flow channel is closed by a part other than the groove of the sealing member in the reaction device of Fig. 4. Fig. 6 is a schematic cross-sectional view showing a state where the inside of a flow channel is sealed by a sealing member in the reaction device of Fig. 4.

As shown in FIG. 4, the reaction device 20 includes a chip 21 and a heat source 7. The chip 21 includes a chip body 22 and a sealing member 26. The sealing member 26 is provided on the first main surface 22a of the chip body 22. The heat source 7 is provided on the second main surface 22b of the chip body 22.

In this embodiment, the sealing member 26 also serves as a rotary valve. The sealing member 26 has a disk-like shape and is attached to the chip body 22 so as to be rotatable around the rotation axis X. A groove 28 is provided on the surface 26a of the sealing member 26 that contacts the chip body 22. The chip body 22 is also provided with another flow path 23 different from the flow path 3. In this embodiment, the other flow path 23 is provided so as to include the rotation axis X. In this case, it is preferable that the central axis of the other flow path 23 coincides with the rotation axis X. The shape of the sealing member 26 is not particularly limited, and may be a rectangular plate shape, etc.

As shown in FIG. 4, when the groove 28 of the sealing member 26 is connected to the opening 4, the groove 28 forms a connecting flow path that connects the flow path 3 and the other flow path 23. The groove 28 extends from the rotation axis X of the sealing member 26 to the radial outside of the sealing member 26. Note that in this embodiment, the groove 28 is linear, but it may have other planar shapes such as a curved shape, a meandering shape, or an L-shape.

In the state shown in FIG. 4, by rotating the sealing member 26 around the rotation axis X, the opening 4 of the flow path 3 can be closed by the portion of the sealing member 26 other than the groove portion, as shown in FIG. 5. In this state, the flow path 3 and the other flow paths 23 are not connected via the groove portion 28. However, the other flow paths 23 may be connected to other flow paths (not shown) via the groove portion 28. Other points are the same as those of the first embodiment.

In the second embodiment, the softening point Ts of the sealing member 26 is also equal to or lower than the maximum temperature Tmax of the heating region A by the heat source 7. In addition, the portion of the sealing member 26 that contacts the opening 4 is included in the region B in which the opening 4 is provided, so when the heating region A is heated by the heat source 7, the portion of the sealing member 26 that contacts the opening 4 is also heated. At this time, since the softening point Ts of the sealing member 26 is equal to or lower than the maximum temperature Tmax of the heating region A, when the portion of the sealing member 26 that contacts the opening 4 is also heated, a part of the sealing member 26 melts. As a result, as shown in FIG. 6, a part of the sealing member 26 that melts due to heating can flow from the opening 4 into the flow path 3, sealing the inside of the flow path 3.

As in the second embodiment, the sealing member 26 may be arranged so that it can assume a state in which the groove portion 28 of the sealing member 26 is connected to the opening 4 and a state in which the opening 4 is sealed by the portion of the sealing member 26 other than the groove portion, and the sealing member 26 may also function as a valve. However, as in the second embodiment, it is preferable that the sealing member 26 also functions as a rotary valve.

In the reaction device 20 of the second embodiment, the heat for heating the reaction chamber 5 can be used to melt a part of the sealing member 26, thereby sealing the reaction chamber 5 connected to the flow path 3. In this way, in the reaction device 20, the reaction chamber 5 can be sealed simply by providing the sealing member 26 on the opening 4 provided at one end of the flow path 3, so no large-scale device is required for sealing. In addition, in the reaction device 20, the opening 4 is sealed by causing a part of the sealing member 26 melted by heating to flow from the opening 4 into the flow path 3, so that the sealing property in the flow path 3 can be improved. Therefore, according to the reaction device 20, the sealing property in the flow path 3 can be improved without making the device large-scale.

Reference Signs List 1, 21: Chip 2, 22: Chip body 2a, 22a: First main surface 2b, 22b: Second main surface 3: Flow path 4: Opening 5: Reaction chamber 6, 26: Sealing member 7: Heat source 10, 20: Reaction device 23: Another flow path 26a: Surface 28: Groove

Claims (9)

A chip body having a flow channel with an opening at at least one end;
a sealing member for sealing the opening;
A heat source;
Equipped with
a heating region of the tip body that is heated by the heat source includes a region in which the opening is provided;
A reaction apparatus, wherein the softening point Ts of the sealing member is equal to or lower than the maximum temperature Tmax of the heating region. the chip body has a reaction chamber connected to the flow channel;
2. The reactor of claim 1, wherein the heating region comprises a region in which the reaction chamber is located. The reaction device according to claim 1 or 2, wherein the difference between the maximum temperature Tmax of the heating region and the softening point Ts of the sealing member is 10°C or more and 70°C or less. The reaction device according to claim 1 or 2, wherein the opening and the heat source overlap in a plan view. The reaction device according to claim 1 or 2, wherein the thickness of the chip body is 0.5 mm or more and 10.0 mm or less. the sealing member has a groove on a surface that contacts the chip body, and is disposed so as to be capable of assuming a state in which the groove of the sealing member is connected to the opening and a state in which the opening is sealed by a portion of the sealing member other than the groove;
The reaction apparatus according to claim 1 or 2, wherein the sealing member also serves as a valve. the sealing member is disposed such that, by rotating about a rotation axis, the sealing member can assume a state in which a groove portion of the sealing member is connected to the opening portion and a state in which the opening portion is sealed by a portion of the sealing member other than the groove portion;
7. The reaction apparatus according to claim 6, wherein the sealing member also serves as a rotary valve. 1. A sealing method for sealing a flow channel in a reaction device, the method comprising: a chip body having a flow channel with an opening at at least one end; and a sealing member for sealing the opening, the method comprising the steps of:
heating a region of the chip body where the opening is provided;
a step of causing a part of the sealing member melted by the heating to flow into the opening, thereby sealing the inside of the flow path;
A method for sealing a flow path comprising: A chip body having a flow channel with an opening at at least one end;
a sealing member for sealing the opening;
Equipped with
The softening point Ts of the sealing member is 100° C. or lower.

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