Microchannel chip and liquid feeding method

Abstract

Provided is a microchannel chip through which it is possible to efficiently feed a liquid without having to use an external pump.　A microchannel chip 1, which is provided with a microchannel 2 for feeding a liquid, is provided with: an air-enclosing container 3 that encloses air for feeding the liquid in the microchannel 2; a reagent storage part 4 that stores the liquid containing a reagent; a chamber 5 to which the liquid containing the reagent is fed; and a reagent feeding channel 8 that connects the reagent storage part 4 and the chamber 5. The volume of the reagent storage part 4 is smaller than the sum of the volumes of the chamber 5 and the reagent feeding channel 8, and the volume of the liquid containing the reagent is larger than the volume of the chamber 5.

Description

Microchannel Chip and Liquid Delivery Method

[0001] The present invention relates to a microchannel chip provided with a microchannel through which a liquid is delivered, and a method for delivering a liquid using the microchannel chip.

[0002] Conventionally, by using a microchannel chip provided with a microchannel through which a liquid is delivered to control the delivery and reaction of various specimens or samples, tests such as blood tests and genetic tests, and biochemical analyses have been attempted. As a method for delivering a liquid such as a reagent in a microchannel chip, a method of connecting an external pump to the microchannel for delivery is known (for example, Patent Document 1).

[0003] Japanese Patent Application Laid-Open No. 2006-25661

[0004] However, when delivering a liquid such as a reagent in a microchannel chip, in the method of delivering the liquid using an external pump, contaminants may be mixed into the microchannel by the external pump, or conversely, contaminants in the microchannel may be mixed into the external pump. Further, although Patent Document 1 describes a method of installing a filter in the microchannel, it may be difficult to surely prevent the mixing of contaminants by the filter. Also, when the filter is wetted with a liquid, it may be difficult to efficiently deliver the liquid in the microchannel.

[0005] An object of the present invention is to provide a microchannel chip and a liquid delivery method using the microchannel chip that can efficiently deliver a liquid without using an external pump.

[0006] In this specification, the following microchannel chip and a liquid delivery method using the microchannel chip are disclosed.

[0007] Item 1. A microfluidic chip provided with a microchannel for delivering liquid, comprising: an air-enclosed container containing air for delivering liquid within the microchannel; a reagent storage section for storing a liquid containing a reagent; a chamber through which the liquid containing the reagent is delivered; and a reagent delivery channel connecting the reagent storage section and the chamber, wherein the volume of the reagent storage section is smaller than the sum of the volumes of the chamber and the reagent delivery channel, and the volume of the liquid containing the reagent is larger than the volume of the chamber.

[0008] Item 2. The microfluidic chip according to Item 1, wherein the ratio of the volume of the liquid containing the reagent to the volume of the reagent storage section is 0.1 or more and 1 or less.

[0009] Item 3. The microfluidic chip according to item 1 or 2, wherein the volume of the liquid containing the reagent is less than the sum of the volumes of the chamber and the reagent delivery channel.

[0010] Item 4. A microfluidic chip according to any one of items 1 to 3, wherein the volume of the liquid containing the reagent is 100 μL or less.

[0011] Item 5. The microfluidic chip according to any one of items 1 to 4, wherein the air-encapsulating container is a blister pack.

[0012] Item 6. The microfluidic chip according to item 5, wherein the microfluidic chip is provided with pins for pressing the blister pack to create a hole in the blister pack.

[0013] Item 7. The microfluidic chip according to any one of items 1 to 5, wherein the air-encapsulating container is provided with a hole that communicates with the microfluidic channel.

[0014] Item 8. The microfluidic chip according to any one of items 1 to 7, wherein a liquid reagent or solid reagent different from the liquid containing the reagent is disposed in the chamber.

[0015] Item 9. The microfluidic chip according to item 8, wherein a reaction chamber is further connected to the chamber.

[0016] Item 10. A microfluidic chip according to any one of items 1 to 9, wherein an external pump is not connected to the microfluidic channel.

[0017] Item 11. A method for delivering liquid using a microfluidic chip as described in any one of Items 1 to 10, comprising the steps of: placing a liquid containing the reagent in the microfluidic channel; and delivering the liquid containing the reagent to the chamber by pushing air in the air-encapsulated container into the microfluidic channel.

[0018] Item 12. The liquid delivery method according to item 11, wherein the rate at which the liquid containing the reagent is delivered is controlled by controlling the rate at which the volume of the air-filled container changes.

[0019] According to the present invention, it is possible to provide a microfluidic chip and a liquid delivery method using the microfluidic chip that can efficiently deliver liquid without using an external pump.

[0020] Figure 1 is a schematic perspective view showing the external appearance of a microfluidic chip according to one embodiment of the present invention. Figure 2 is a schematic plan view illustrating the flow channel structure of a microfluidic chip according to one embodiment of the present invention. Figure 3 is a schematic cross-sectional view of the portion along line A-A in Figure 2. Figure 4 is a schematic cross-sectional view showing a modified example of the portion of the microfluidic chip according to one embodiment of the present invention where an air-encapsulating container is provided. Figure 5 is a schematic cross-sectional view showing a first modified example of the portion of the microfluidic chip according to one embodiment of the present invention where a reagent storage section is provided. Figure 6 is a schematic cross-sectional view showing a second modified example of the portion of the microfluidic chip according to one embodiment of the present invention where a reagent storage section is provided. Figure 7 is a schematic plan view illustrating a modified example of the flow channel structure of a microfluidic chip according to one embodiment of the present invention. Figure 8 is a graph showing the liquid delivery rate until the target chamber is filled with liquid reagent in Examples 3 to 8.

[0021] The details of the present invention will be described below.

[0022] [Microfluidic Chip] Figure 1 is a schematic perspective view showing the external appearance of a microfluidic chip according to one embodiment of the present invention. Figure 2 is a schematic plan view illustrating the channel structure of the microfluidic chip according to one embodiment of the present invention. Figure 3 is a schematic cross-sectional view of the portion along line A-A in Figure 2.

[0023] As shown in Figure 1, the microfluidic chip 1 has a rectangular plate shape. However, in the present invention, the microfluidic chip 1 may have a shape such as a disc shape, and the shape of the microfluidic chip 1 is not particularly limited.

[0024] The microfluidic chip 1 has a first main surface 1a and a second main surface 1b that are opposite each other. The microfluidic chip 1 also has first to fourth side surfaces 1c to 1f that connect the first main surface 1a and the second main surface 1b. The first side surface 1c and the second side surface 1d are opposite each other. The third side surface 1e and the fourth side surface 1f are also opposite each other.

[0025] The microfluidic chip 1 is made of synthetic resin. The microfluidic chip 1 can be formed, for example, by molding synthetic resin using a molding method such as injection molding. The microfluidic chip 1 may also be made by laminating multiple sheets of synthetic resin.

[0026] The microfluidic chip 1 may consist of a substrate and a cover member provided on the substrate. In this case, both the substrate and the cover member can be made of synthetic resin. The cover member may be made of elastomer.

[0027] The microfluidic chip 1 may be made of a material other than synthetic resin.

[0028] The microfluidic chip 1 contains a microfluidic channel 2 for transporting liquid. The microfluidic channel 2 is a fine channel that produces micro-effects during fluid transport. In such a microfluidic channel 2, the fluid is strongly affected by surface tension and behaves differently from fluids flowing in normal, large-sized channels.

[0029] The cross-sectional shape and size of the microchannel 2 are not particularly limited as long as the microchannel produces the above-mentioned micro-effects. For example, when flowing fluid through the microchannel 2, from the viewpoint of reducing flow resistance, if the cross-sectional shape of the microchannel 2 is roughly rectangular (including square), the dimension of the smaller side (one side in the case of a square) 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 microchannel chip 1, 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.

[0030] Furthermore, when the cross-sectional shape of the microchannel 2 is generally circular, the diameter (or 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 microchannel chip 1, the diameter (or 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.

[0031] On the other hand, for example, when flowing fluid through the microchannel 2 and effectively utilizing capillary action, if the cross-sectional shape of the microchannel 2 is roughly rectangular (including a square), the dimension of the smaller side (one side in the case of a square) is preferably 5 μm or more, more preferably 10 μm or more, even more preferably 20 μm or more, preferably 200 μm or less, and more preferably 100 μm or less.

[0032] The microfluidic chip 1 is a chip that can perform tests such as blood tests and genetic tests, as well as analyses such as biochemical analyses. In this embodiment, the microfluidic chip 1 has a channel structure as shown in Figure 2.

[0033] As shown in Figure 2, the microfluidic chip 1 comprises an air-encapsulated container 3, a reagent storage section 4, a chamber 5, a reaction chamber 6, and a waste liquid channel 7. The air-encapsulated container 3, the reagent storage section 4, the chamber 5, the reaction chamber 6, and the waste liquid channel 7 are connected by a microfluidic channel 2.

[0034] The air-filled container 3 is a container that contains air for transporting liquid within the microchannel 2. In this embodiment, the air-filled container 3 is a blister pack.

[0035] The reagent storage section 4 is a part that stores the liquid containing the reagent that is delivered in the microchannel 2. In this embodiment, the liquid containing the reagent is a liquid reagent. However, the liquid containing the reagent may be a solid reagent dispersed in a solvent or the like.

[0036] Chamber 5 is the target chamber through which the liquid containing the reagent is delivered. In this embodiment, a liquid reagent or solid reagent different from the liquid reagent stored in the reagent storage unit 4 is placed inside Chamber 5.

[0037] The reagent storage unit 4 and the chamber 5 are connected by a reagent delivery channel 8. The reagent delivery channel 8 is a part of the microchannel 2. The reagent delivery channel 8 is the channel portion in the microchannel 2 that connects the reagent storage unit 4 and the chamber 5.

[0038] The volume of the reagent storage section 4 is smaller than the sum of the volumes of the chamber 5 and the reagent delivery channel 8. Furthermore, the volume of the liquid containing the reagent is larger than the volume of the chamber 5.

[0039] Note that the volume of the reagent storage section 4 and the volume of the liquid containing the reagent may be the same. In this case, it is preferable that the volume of the liquid containing the reagent is smaller than the sum of the volumes of the chamber 5 and the reagent delivery channel 8.

[0040] In this embodiment, the reaction chamber 6 and the waste liquid channel 7 are connected to the downstream side of the chamber 5. More specifically, the microchannel 2 is branched downstream of the chamber 5, and the reaction chamber 6 is connected to one end of the branched microchannel 2. The waste liquid channel 7 is connected to the other end of the branched microchannel 2.

[0041] A flow path switching valve may be provided in the downstream flow path of chamber 5 to switch between the flow path on the reaction chamber 6 side and the flow path on the waste liquid flow path 7 side. Alternatively, the downstream flow path of reaction chamber 6 may be connected to the waste liquid flow path 7.

[0042] In the microchannel chip 1 of the present embodiment, the air extruded from the air-containing container 3 can be used to send the liquid containing the reagent. Further, in the microchannel chip 1 of the present embodiment, since the volume of the reagent storage unit 4 is smaller than the total volume of the chamber 5 and the reagent liquid feed channel 8, the amount of the liquid containing the reagent included in the reagent storage unit 4 can be reduced, and the liquid containing the reagent can be efficiently sent. Therefore, according to the microchannel chip 1 of the present embodiment, the liquid can be efficiently sent without using an external pump. Thus, in the microchannel chip 1 of the present embodiment, the contamination of contaminants into the microchannel 2 can be prevented, and the occurrence of contamination can be made difficult.

[0043] Hereinafter, each member constituting the microchannel chip 1 will be described.

[0044] (Air-containing container) The air-containing container 3 is a container that can extrude air by pressing. In the present embodiment, the air-containing container 3 is a blister pack. The air-containing container 3 may be, for example, a syringe, and is not particularly limited as long as it is a container that can extrude air by pressing.

[0045] As shown in FIG. 3, in the present embodiment, the air-containing container 3 is arranged so as to seal the end 2a of the microchannel 2. As shown in FIG. 3, the air-containing container 3 is a blister pack.

[0046] The microchannel chip 1 is provided with a pin 9A for making a hole in the air-containing container 3 by pressing the air-containing container 3.

[0047] Specifically, the air-containing container 3 is provided so as to face the end portion 2a of the microchannel 2 with the space 10A therebetween. Further, a pin 9A is provided so as to face the space 10A. Then, by pressing the air-containing container 3 toward the space 10A and bringing it into contact with the pin 9A, a hole can be formed in the air-containing container 3. Starting from the hole in the air-containing container 3, the air extruded from the air-containing container 3 is sent into the microchannel 2, and the liquid is fed in the microchannel 2. Note that the pin 9A for forming a hole in the air-containing container 3 by pressing may be provided in the air-containing container 3.

[0048] When the air-containing container 3 is a blister pack, examples of the material of the air-containing container 3 include plastics such as PET (polyethylene terephthalate), PVC (polyvinyl chloride), PP (polypropylene), and PE (polyethylene), plastics with silica vapor deposition or aluminum vapor deposition applied thereto, aluminum foil, or those obtained by laminating them.

[0049] When the air-containing container 3 is a syringe, examples of the material of the air-containing container 3 include plastics such as glass, PP, PE, PS (polystyrene), cyclic olefin polymer, or polyisoprene rubber.

[0050] The volume of the air contained in the air-containing container 3 can be appropriately determined according to the amount required for liquid feeding in the microchannel 2. The volume of the air-containing container 3 can be, for example, 0.1 mL or more and 10 mL or less. Further, the volume of the air contained in the air-containing container 3 can be, for example, 0.1 mL or more and 10 mL or less.

[0051] The air-encapsulating container 3 can be formed by attaching it to the microfluidic chip body, for example, using double-sided tape. Examples of adhesives that make up the double-sided tape include acrylic adhesives, silicone adhesives, urethane adhesives, or rubber adhesives. In this embodiment, a hole for supplying air to the microfluidic chip body is provided near the center of the air-encapsulating container 3 on the microfluidic chip mounting surface. Therefore, in this case, it is desirable that the adhesive making up the double-sided tape has a frame-like shape, such as a donut shape. However, the double-sided tape only needs to be provided in the area where the air-encapsulating container 3 and the microfluidic chip body are in contact.

[0052] In this embodiment, when pressing the air-encapsulated container 3, the air-encapsulated container 3 is pressed by a pressing member. For example, plastic, metal, or ceramic can be used as such a pressing member. However, the pressing member is not particularly limited as long as it is a member that can press the air-encapsulated container 3 toward the space 10A.

[0053] The material of pin 9A is not particularly limited, as long as it can create a hole in the air-enclosed container 3. The material of pin 9A may be the same as the material of the microfluidic chip body. In this case, it is desirable that pin 9A be formed by integral molding with other components during the manufacturing of the microfluidic chip 1.

[0054] Figure 4 is a schematic cross-sectional view showing a modified example of a portion of a microfluidic chip according to one embodiment of the present invention, in which an air-encapsulated container is provided. As shown in the modified example of the air-encapsulated container 3A in Figure 4, a hole 3a (a hole communicating with the microfluidic channel 2) may be provided in advance in the air-encapsulated container 3A.

[0055] Furthermore, when the air-encapsulated container 3 is pressed, it is not necessary to have a pin 9A for creating a hole in the air-encapsulated container 3 or a hole 3a such as the air-encapsulated container 3A. In this case, pressing the air-encapsulated container 3 may cause it to rupture, and the air that is pushed out thereafter may be used to deliver liquid through the microchannel 2.

[0056] (Reagent Storage Section) In this embodiment, the reagent storage section 4 is a reagent container. In this embodiment, the reagent container is a blister pack.

[0057] As shown in Figure 3, in this embodiment, the reagent storage unit 4 is connected to the downstream side of the air-encapsulated container 3. More specifically, the microchannel 2 is branched downstream of the air-encapsulated container 3, and the reagent storage unit 4 is connected to the end 2b of the branched microchannel 2.

[0058] As shown in Figure 3, in this embodiment, the reagent storage unit 4 is positioned to seal the end 2b of the branched microchannel 2. As shown in Figure 3, the reagent storage unit 4 is a blister pack.

[0059] The microfluidic chip 1 is provided with a pin 9B for pressing the reagent storage section 4 to create a hole in the reagent storage section 4.

[0060] Specifically, the reagent storage section 4 is positioned opposite the end 2b of the branched microchannel 2, separated by a space 10B. A pin 9B is also provided facing the space 10B. By pressing the reagent storage section 4 toward the space 10B and bringing it into contact with the pin 9B, a hole can be made in the reagent storage section 4. Starting from this hole in the reagent storage section 4, the liquid containing the reagent is pushed out of the reagent storage section 4 and delivered into the microchannel 2.

[0061] Figure 5 is a schematic cross-sectional view showing a first modified example of a portion of a microfluidic chip according to one embodiment of the present invention, in which a reagent storage section is provided. Note that only the portion necessary for explaining the microfluidic chip body is shown in Figure 5. In the first modified example shown in Figure 5, the reagent storage section 4A has a reagent storage body 4Aa and a cavity 4Ab. The reagent storage body 4Aa is a portion for storing liquid containing reagents and is not directly connected to the microfluidic chip body. The reagent storage body 4Aa is connected to the microfluidic chip body across the cavity 4Ab.

[0062] In the first modification, a hole can be made in the cavity 4Ab by pressing it toward the pin 9B of the microfluidic chip body. Then, starting from the hole in the cavity 4Ab, the liquid containing the reagent pushed out from the reagent storage body 4Aa can be sent to the microfluidic chip body. As in the first modification, in the reagent storage 4A, the reagent storage body 4Aa, which stores the liquid containing the reagent, may be connected to the microfluidic chip body across the cavity 4Ab.

[0063] Figure 6 is a schematic cross-sectional view showing a second modified example of a portion of a microfluidic chip according to one embodiment of the present invention, in which a reagent storage section is provided. Note that only the portion necessary for explaining the microfluidic chip body is shown in Figure 6. In the second modified example shown in Figure 6, similar to the first modified example, the reagent storage section 4B has a reagent storage body 4Ba and a cavity 4Bb. In the second modified example, a pin 9Ba is provided in the cavity 4Bb. On the other hand, the microfluidic chip body side does not have a pin 9B.

[0064] In the second modification, the cavity 4Bb can be pressed toward the microfluidic chip body, and the pin 9Ba can be brought into contact with the center of the microfluidic chip mounting surface of the cavity 4Bb, thereby creating a hole in the cavity 4Bb. Then, starting from the hole in the cavity 4Bb, the liquid containing the reagent pushed out from the reagent storage body 4Ba can be transferred toward the microfluidic chip body. As in the second modification, the pin 9Ba may be provided in the reagent storage body 4B.

[0065] Alternatively, in yet another modification, the reagent storage section 4 may have pre-formed holes. In this case, the pin 9B does not need to be provided in either the microfluidic chip body or the reagent storage section 4.

[0066] In this embodiment, when the reagent storage section 4 is a blister pack, the material of the reagent storage section 4 can be, for example, plastics such as PET (polyethylene terephthalate), PVC (polyvinyl chloride), PP (polypropylene), PE (polyethylene), plastics coated with silica or aluminum vapor deposition, aluminum foil, or laminates thereof.

[0067] The volume of the reagent storage section 4 is smaller than the sum of the volumes of the chamber 5 and the reagent delivery channel 8. In this embodiment, if the reagent storage section 4 is a reagent storage container such as a blister pack, the volume of the reagent delivery channel 8 refers to the sum of the volume of the branch channel and the volume of the channel extending from the branch channel towards the chamber 5 (the volume of the channel from the dashed line X in Figure 3 to the chamber 5). Therefore, the portion where the branch channel and the chamber 5 overlap in a plan view is included in the reagent delivery channel 8.

[0068] The volume ratio of the reagent storage section 4 to the sum of the volumes of the chamber 5 and the reagent delivery channel 8 (reagent storage section 4 / chamber 5 and reagent delivery channel 8) is preferably 0.05 or more, more preferably 0.1 or more, preferably 0.9 or less, and more preferably 0.75 or less. In this case, the liquid containing the reagent can be delivered more efficiently within the microfluidic chip 1.

[0069] The volume of the reagent storage section 4 can be, for example, 10 μL or more and 5 mL or less. The volume of the chamber 5 can be, for example, 10 μL or more and 4.9 mL or less. The volume of the reagent delivery channel 8 can be, for example, 10 μL or more and 5 mL or less.

[0070] In this embodiment, when the reagent storage section 4 is a reagent storage container such as a blister pack, the ratio of the volume of the liquid containing the reagent contained in the reagent storage section 4 to the volume of the reagent storage section 4 (volume of the liquid containing the reagent / volume of the reagent storage section 4) is preferably 0.1 or more, more preferably 0.3 or more, even more preferably 0.5 or more, preferably 1 or less, and more preferably 0.95 or less. Therefore, the volume of the liquid containing the reagent stored in the reagent storage section 4 and the volume of the reagent storage section 4 may be the same. The volume of the liquid containing the reagent is preferably 10 μL or more, more preferably 20 μL or more, preferably 100 μL or less, and more preferably 90 μL or less. The volume of the reagent storage section 4 is preferably 10 μL or more, more preferably 20 μL or more, preferably 333 μL or less, and more preferably 200 μL or less. The upper limit of the volume of the reagent storage section 4 may be, for example, 100 μL or 90 μL, depending on the material of the reagent storage section 4.

[0071] If the reagent storage section 4 is a reagent storage container such as a blister pack, the reagent storage container can be formed by attaching it to the microfluidic chip body, for example, with double-sided tape. Examples of adhesives that make up the double-sided tape include acrylic adhesives, silicone adhesives, urethane adhesives, or rubber adhesives. In this embodiment, a hole is provided near the center of the microfluidic chip mounting surface of the reagent storage container for supplying liquid containing reagents to the microfluidic chip body. Therefore, in this case, it is desirable that the adhesive making up the double-sided tape has a frame-like shape, such as a donut shape. However, the double-sided tape only needs to be provided in the area where the reagent storage container and the microfluidic chip body are in contact.

[0072] In this embodiment, when pressing the reagent storage container, the reagent storage container is pressed by a pressing member. For example, plastic, metal, or ceramic can be used as such a pressing member. However, the pressing member is not particularly limited as long as it is a member that can press the reagent storage container toward the space 10B.

[0073] The materials of pins 9B and 9Ba are not particularly limited, as long as they can create holes in the reagent storage container. The material of pin 9B may be the same as the material of the microfluidic chip body. In this case, it is desirable that pin 9B be formed by integral molding with other components during the manufacturing of the microfluidic chip 1.

[0074] Figure 7 is a schematic plan view illustrating a modified example of the channel structure of a microfluidic chip according to one embodiment of the present invention.

[0075] As shown in Figure 7, the reagent storage section 4C may be a reagent storage chamber located in the middle of the microchannel 2. In this case, the volume of the reagent storage section 4C is the volume of the reagent storage chamber. The reagent delivery channel 8 is a channel connecting the reagent storage section 4C and the chamber 5.

[0076] Furthermore, as in this modified example, if the reagent storage section 4C is a reagent storage chamber, the volume of the liquid containing the reagent stored in the reagent storage section 4C only needs to be less than or equal to the volume of the reagent storage section 4C.

[0077] (Chamber) In this embodiment, a liquid reagent or solid reagent different from the reagent stored in the reagent storage unit 4 is placed inside the chamber 5. In the chamber 5, the reagent stored in the reagent storage unit 4 and the reagent placed inside the chamber 5 merge.

[0078] In this case, examples of reagents stored in the reagent storage section 4 include extraction solutions, washing solutions, or elution solutions. Examples of reagents placed in the chamber 5 include internal standard reagents, extraction efficiency enhancers, washing efficiency enhancers, elution efficiency enhancers, enzymes, primers, probes, or detection efficiency enhancers.

[0079] The reagent storage chamber (reagent storage section 4C in Figure 7) or chamber 5 may be provided with caps or the like for placing reagents, etc., inside the reagent storage chamber or chamber 5, respectively.

[0080] Reagents do not necessarily need to be placed inside chamber 5. Chamber 5 may be a chamber where reagents are weighed, or it may be a chamber where reagents stored in the reagent storage unit 4 and reagents placed inside chamber 5 are mixed. Chamber 5 may be equipped with filters, beads, etc., for capturing specific substances in the liquid. Alternatively, chamber 5 may also serve as a reaction chamber.

[0081] (Reaction Chamber) In reaction chamber 6, reactions involving heating, such as PCR (Polymerase Chain Reaction), can be carried out. However, reaction chamber 6 is not required, and in this case, reactions involving heating, such as PCR, may be carried out in chamber 5.

[0082] A chamber for weighing reagents may be provided between chamber 5 and reaction chamber 6. Furthermore, a mixing channel may be provided between chamber 5 and reaction chamber 6 for mixing reagents stored in reagent storage unit 4 with reagents placed in chamber 5.

[0083] The downstream channel of the reaction chamber 6 is an outlet channel connected to the outside. A filter may be provided in the outlet channel to prevent contamination from the outside. A reagent absorbent may also be provided in the outlet channel.

[0084] (Waste liquid channel) The waste liquid channel 7 is a channel through which unwanted liquid from the microchannel 2 is delivered.

[0085] The downstream channel of the wastewater channel 7 is an outlet channel connected to the outside. A filter may be provided in the outlet channel to prevent contamination from external contaminants. A reagent absorbent may also be provided in the outlet channel.

[0086] The following describes an example of a liquid delivery method using the microfluidic chip 1.

[0087] [Liquid delivery method] The liquid delivery method in this embodiment is a liquid delivery method using the microfluidic chip 1.

[0088] In the liquid delivery method of this embodiment, first, the reagent storage container, which is the reagent storage section 4, is pressed by a pressing member. This breaks the blister pack, which is the reagent storage section 4, and places the liquid containing the reagent stored in the reagent storage section 4 into the microchannel 2.

[0089] Next, the air-encapsulated container 3 is pressed with the pressing member. This breaks the blister pack, which is the air-encapsulated container 3, and pushes the air contained within the air-encapsulated container 3 into the microchannel 2. This delivers the liquid containing the reagent to the chamber 5. If necessary, the liquid may also be delivered to the reaction chamber 6 and the waste liquid channel 7 by further pushing out the air contained within the air-encapsulated container 3.

[0090] The air-filled container 3 may contain a large amount of air to enable repeated liquid delivery. The volume of the air-filled container 3 can be appropriately determined according to the amount of liquid to be delivered and the distance to be delivered.

[0091] The liquid delivery rate within the microchannel 2 may be controlled by controlling the rate of volume change of the air-encapsulated container 3. The rate of volume change of the air-encapsulated container 3 can be controlled, for example, by the pressing rate of the air-encapsulated container 3 by the pressing member.

[0092] In the liquid delivery method of this embodiment, the liquid containing the reagent can be delivered by air pushed out from the air-encapsulated container 3. Furthermore, in the liquid delivery method of this embodiment, a microfluidic chip 1 is used in which the volume of the reagent storage section 4 is smaller than the sum of the volumes of the chamber 5 and the reagent delivery channel 8. Therefore, the amount of liquid containing the reagent stored in the reagent storage section 4 can be reduced, and the liquid containing the reagent can be delivered efficiently. Accordingly, according to the liquid delivery method of this embodiment, liquid can be delivered efficiently without using an external pump. Thus, in the liquid delivery method of this embodiment, the entry of contaminants into the microfluidic channel 2 can be prevented, and contamination can be made less likely to occur.

[0093] The present invention will be clarified below by providing specific examples and comparative examples of the present invention. However, the present invention is not limited to the following examples.

[0094] (Example 1) In Example 1, a microfluidic chip 1 (hereinafter referred to as a microfluidic chip) having the flow channel structure shown in Figure 2 was prepared. As the air-encapsulated container 3, an empty blister pack (Air blister pack) with a volume of 750 μL was prepared and attached to the predetermined position using double-sided tape (manufactured by 3M, part number "SPR-19R").

[0095] For the reagent storage section 4, a blister pack containing a liquid reagent with a volume of 50 μL (reagent blister pack) was prepared and attached to the designated position using double-sided tape (3M, part number "SPR-19R"). The volume of the liquid reagent contained in the reagent blister pack was 40 μL.

[0096] In the microfluidic chip, the volume of the reagent delivery channel 8 was set to 70 μL. The volume of the chamber 5 was set to 25 μL.

[0097] (Example 2) A microfluidic chip was prepared in the same manner as in Example 1, except that a reagent blister pack with a volume of 90 μL was prepared. The volume of the liquid reagent contained in the reagent blister pack was 80 μL.

[0098] (Comparative Example 1) A microfluidic chip was prepared in the same manner as in Example 1, except that a reagent blister pack with a volume of 150 μL was prepared. The volume of the liquid reagent contained in the reagent blister pack was 140 μL.

[0099] (Comparative Example 2) A microfluidic chip was prepared in the same manner as in Example 1, except that a reagent blister pack with a volume of 400 μL was prepared. The volume of the liquid reagent contained in the reagent blister pack was 350 μL.

[0100] [Evaluation] For each example and comparative example, the microfluidic chips prepared were subjected to a reagent blister pack using a vertical electric measuring stand (IMADA, part number "EMX-1000N-FA") and a digital force gauge (IMADA, part number "ZTA-1000N") at a pressing speed of 15 mm / min. This broke the reagent blister pack and placed the liquid reagent into the microfluidic channel. The pressing of the reagent blister pack was continued until the load on the load testing machine reached 100 N. A video was recorded at this time to confirm whether the target chamber was filled with the liquid reagent. The test was performed five times, and samples in which the target chamber was filled with the liquid reagent were evaluated as A, while samples in which the target chamber was not filled with the liquid reagent were evaluated as B.

[0101] Next, for samples where the target chamber was not sufficiently filled with the liquid reagent in the evaluation described above, an Air blister pack was pressed using a vertical electric measuring stand (IMADA, model number "EMX-1000N-FA") and a digital force gauge (IMADA, model number "ZTA-1000N") at a pressing speed of 15 mm / min. This ruptured the Air blister pack and pushed out the air contained within it, thereby transferring the liquid reagent to the chamber. The Air blister pack was pressed until the load on the load testing machine reached 100 N. A video was recorded during this process to confirm whether the target chamber was filled with the liquid reagent. The test was performed five times, and samples where the target chamber was filled with the liquid reagent were evaluated as A, while samples where the target chamber was not filled were evaluated as B.

[0102] The results are shown in Table 1 below.

[0103]

[0104] Table 1 shows that in the samples of Examples 1 and 2, where the volume of the reagent blister pack was smaller than the sum of the volumes of the chamber and the reagent delivery channel, and the volume of the liquid reagent was larger than the volume of the target chamber, it was confirmed that the target chamber was filled with the liquid reagent by pushing out the air contained in the Air blister pack.

[0105] On the other hand, in the samples of Comparative Examples 1 and 2, where the volume of the reagent blister pack was larger than the sum of the volumes of the chamber and the reagent delivery channel, the target chamber was filled with liquid reagent due to the pressure of the reagent blister pack, and excess liquid reagent was introduced. As a result, a large amount of liquid reagent was wasted, and the liquid reagent could not be used efficiently.

[0106] (Example 3) In Example 3, a microfluidic chip 1 (hereinafter referred to as a microfluidic chip) was prepared, comprising an air-encapsulated container 3 with a flow channel structure as shown in Figure 7, a reagent storage section 4C, and a chamber 5. As the air-encapsulated container 3, an empty blister pack (Air blister pack) with a volume of 750 μL was prepared and attached to the predetermined position using double-sided tape (3M, part number "SPR-19R"). A hole was made in the center of the Air blister pack facing the flow channel using tweezers. In addition, a 50 μL liquid reagent was introduced into the reagent chamber with a volume of 90 μL, which is the reagent storage section 4C.

[0107] For the prepared sample, an Air blister pack was pressed using a vertical electric measuring stand (IMADA Corporation, model number "EMX-1000N-FA") and a digital force gauge (IMADA Corporation, model number "ZTA-1000N") at a pressing speed of 10 mm / min. This ruptured the Air blister pack and pushed out the air contained within it, thereby delivering the liquid reagent to the target chamber.

[0108] (Example 4) The liquid reagent was delivered to the target chamber in the same manner as in Example 3, except that a hole was not made with tweezers in the center of the Air blister pack facing the flow path.

[0109] (Example 5) Except for the pressing speed of the Air blister pack being set to 20 mm / min, the liquid reagent was delivered to the target chamber in the same manner as in Example 3.

[0110] (Example 6) The liquid reagent was delivered to the target chamber in the same manner as in Example 5, except that a hole was not made with tweezers in the center of the Air blister pack facing the flow path.

[0111] (Example 7) Except for the pressing speed of the Air blister pack being set to 30 mm / min, the liquid reagent was delivered to the target chamber in the same manner as in Example 3.

[0112] (Example 8) The liquid reagent was delivered to the target chamber in the same manner as in Example 7, except that a hole was not made with tweezers in the center of the Air blister pack facing the flow path.

[0113] [Evaluation] In Examples 3 to 8, the delivery of the liquid reagent was recorded on video, and the delivery rate until the target chamber was filled with the liquid reagent was measured. Each sample was evaluated five times. The results are shown in Figure 8.

[0114] As shown in Figure 8, in the samples of Examples 3, 5, and 7, in which a hole was made with tweezers in the center of the Air blister pack facing the flow path, it was confirmed that the rate at which the liquid reagent was filled into the target chamber was more stable compared to the samples of Examples 4, 6, and 8, in which no hole was made in the Air blister pack.

[0115] 1...Microfluidic chip 1a...First main surface 1b...Second main surface 1c...First side surface 1d...Second side surface 1e...Third side surface 1f...Fourth side surface 2...Microfluidic channel 2a, 2b...Ends 3, 3A...Air-enclosed container 3a...Hole 4, 4A, 4B, 4C...Reagent storage section 4Aa, 4Ba...Reagent storage main body section 4Ab, 4Bb...Cavity section 5...Chamber 6...Reaction chamber 7...Waste liquid channel 8...Reagent delivery channel 9A, 9B, 9Ba...Pins 10A, 10B...Space

Claims

1. A microfluidic chip provided with a microchannel for transporting liquid, comprising: an air-enclosed container containing air for transporting liquid within the microchannel; a reagent storage section for storing a liquid containing a reagent; a chamber through which the liquid containing the reagent is transported; and a reagent transport channel connecting the reagent storage section and the chamber, wherein the volume of the reagent storage section is smaller than the sum of the volumes of the chamber and the reagent transport channel, and the volume of the liquid containing the reagent is larger than the volume of the chamber.

2. The microfluidic chip according to claim 1, wherein the ratio of the volume of the liquid containing the reagent to the volume of the reagent storage section is 0.1 or more and 1 or less.

3. The microfluidic chip according to claim 1 or 2, wherein the volume of the liquid containing the reagent is smaller than the sum of the volumes of the chamber and the reagent delivery channel.

4. The microfluidic chip according to claim 1 or 2, wherein the volume of the liquid containing the reagent is 100 μL or less.

5. The microfluidic chip according to claim 1 or 2, wherein the air-encapsulating container is a blister pack.

6. The microfluidic chip according to claim 5, wherein the microfluidic chip is provided with pins for pressing the blister pack to create a hole in the blister pack.

7. The microfluidic chip according to claim 1 or 2, wherein the air-encapsulating container is provided with a hole that communicates with the microfluidic channel.

8. The microfluidic chip according to claim 1 or 2, wherein a liquid reagent or solid reagent different from the liquid containing the reagent is disposed in the chamber.

9. The microfluidic chip according to claim 8, wherein a reaction chamber is further connected to the chamber.

10. The microfluidic chip according to claim 1 or 2, wherein an external pump is not connected to the microfluidic channel.

11. A method for delivering liquid using a microfluidic chip according to claim 1 or 2, comprising the steps of: placing a liquid containing the reagent in the microfluidic channel; and delivering the liquid containing the reagent to the chamber by pushing air in the air-encapsulated container into the microfluidic channel.

12. The liquid delivery method according to claim 11, wherein the rate at which the liquid containing the reagent is delivered is controlled by controlling the rate at which the volume of the air-filled container changes.

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