JP2018059916A - Micro flow passage chip - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a micro flow passage chip capable of inspecting an analyte simply and quickly, and further enabling precise liquid feeding control for stored liquid regent.SOLUTION: A micro flow passage chip 1 includes: a micro flow passage chip body 2 having a micro flow passage connected to a regent storage space A, a mixing and reaction space C connected to the micro flow passage and configured to make liquid regent 9 and an analyte mix or react with each other, and a retention space B provided between the regent storage space A and the mixing and reaction space C in the micro flow passage; and a regent storage body 7 having the liquid regent 9 and a sealing material 8 configured to seal the liquid regent 9 and be opened by pressing.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a microchannel chip for inspecting and analyzing a substance in a specimen or a reaction product of a substance in a liquid specimen.

  In recent years, a method of performing a blood test, a genetic test, and the like by providing a micro flow channel in one micro flow channel chip and controlling the liquid feeding and reaction of various specimens or samples has been studied. For example, in Patent Document 1 below, a substrate layer having a self-sealing property due to elastic deformation, a region formed including the substrate layer, and a puncture projecting on a surface facing the substrate layer in the region A microchannel chip provided with a structure has been proposed.

  However, in the above microchannel chip, the sample container for holding the liquid reagent is not integrated with the microchip. Therefore, for example, when a blood test or the like is performed using the microchannel chip, it is necessary to introduce a necessary reagent from outside the microchannel chip into the microchannel chip at the time of the test. In such a case, depending on the surrounding environment at the time of inspection, there is a possibility that foreign matter may be mixed in the microchannel chip and the inspection accuracy may be lowered.

  On the other hand, Patent Document 2 below discloses a microchannel chip in which a blister pack containing a liquid reagent is incorporated. In use, press and break the blister pack. Thereby, the liquid reagent flows into the mixing space with the specimen and other reagents.

JP 2013-145217 A Japanese Patent No. 5466745

  In the microchannel chip described in Patent Document 2, the liquid reagent directly flows into the mixing space by pressing the blister pack. Therefore, precise control of the inflow speed and mixing timing has been difficult. Further, in a complicated inspection / reaction system using a plurality of reagents, the inspection accuracy and reaction accuracy may be lowered.

  An object of the present invention is to provide a microchannel chip that can easily and quickly test a specimen and that can precisely control the liquid reagent contained therein.

  In order to solve the above problems, in the microchannel chip according to the present invention, the space in which the liquid reagent can stay in the liquid supply channel connected to the reagent storage space in which the reagent storage body filled with the liquid reagent is disposed. Is provided.

  That is, according to a wide aspect of the present invention, a reagent storage space, a microchannel connected to the reagent storage space, and a mixture of a liquid reagent and a sample or the liquid reagent connected to the microchannel A micro-channel chip body having a mixing / reaction space in which a reaction between the sample and the sample is performed, a retention space provided between the reagent storage space and the mixing / reaction space in the micro-channel There is provided a microchannel chip that is housed in the reagent housing space and includes a reagent container having a liquid reagent and a sealing material that seals the liquid reagent and is opened by pressing. .

  In a specific aspect of the microchannel chip according to the present invention, the microchannel includes a liquid supply channel that connects the reagent storage space and the retention space, and a liquid or gas in the retention space. It has an inlet flow path for inflow and an outlet flow path from the staying space to the mixing / reaction space.

  In another specific aspect of the microchannel chip according to the present invention, the volume of the residence space is equal to or larger than the volume of the liquid reagent filled in the reagent container. In this case, the liquid reagent can be retained more reliably in the retention space.

  In another specific aspect of the microchannel chip according to the present invention, the reagent storage space does not have an opening in the periphery other than the opening in which the liquid supply channel is opened in the staying space. In this case, the liquid reagent can be more reliably fed from the reagent storage space through the opening through the liquid feed channel.

  In another specific aspect of the microchannel chip according to the present invention, the reagent storage space is provided above the staying space, and the reagent storage body has an opening to the staying space of the liquid feeding channel. It is arranged on the part. In this case, by opening the reagent storage body in the reagent storage space, the liquid reagent can be quickly guided to the lower retention space.

  In still another specific aspect of the microchannel chip according to the present invention, the reagent storage space has a bottom surface having an opening in which the liquid supply channel is open, and the reagent storage body includes the bottom surface. In FIG. 5, it is bonded to the bottom surface in a region excluding the opening. In this case, the reagent container can be opened more reliably and stably.

  In another specific aspect of the microchannel chip according to the present invention, a substrate having first and second main surfaces facing each other, and having a recess opening in the first main surface; It is provided so that the said recessed part may be sealed, and it has the sealing film which has elasticity, The said reagent storage space is provided by the said recessed part and the said sealing film. In this case, the reagent container can be easily opened by pressing the sealing film.

  More preferably, the inner surface of the sealing film is provided with a protrusion that protrudes toward the reagent container. In this case, the sealing film can be pressed and the reagent container can be opened more easily and reliably by the convex portion.

  ADVANTAGE OF THE INVENTION According to this invention, it becomes possible to provide the microchannel chip | tip which can test | inspect a sample simply and rapidly and can perform precise liquid feeding control of the liquid reagent accommodated.

It is front sectional drawing which shows the principal part of the microchannel chip concerning the 1st Embodiment of this invention. It is front sectional drawing which shows the principal part of the microchannel chip concerning the 2nd Embodiment of this invention. It is a partial notch front sectional drawing for demonstrating the principal part of the microchannel chip concerning the 3rd Embodiment of this invention. It is front sectional drawing which shows the principal part of the microchannel chip concerning 4th Embodiment. It is a top view for demonstrating the modification of a reagent storage body. It is front sectional drawing which shows the principal part of the microchannel chip concerning the 4th Embodiment of this invention.

  Hereinafter, the present invention will be clarified by describing specific embodiments of the present invention with reference to the drawings.

  FIG. 1 is a front cross-sectional view showing the main part of the microchannel chip according to the first embodiment of the present invention.

  The microchannel chip 1 includes a microchannel chip body 2 and a reagent storage body 7. In the first embodiment, the microchannel chip body 2 includes a substrate 3, a sealing film 4, and a cover member 5.

  The substrate 3 has first and second main surfaces 3a and 3b facing each other. A recess 3 c is provided so as to open to the first main surface 3 a of the substrate 3. The sealing film 4 is bonded to the first main surface 3a so as to close the recess 3c. Thereby, reagent storage space A is provided. A reagent storage body 7 is stored in the reagent storage space A.

  The reagent container 7 includes a liquid reagent 9 and a sealing material 8 that seals the liquid reagent 9 and is opened by pressing. The sealing material 8 includes a sheet 8b and a film 8a bonded to the sheet 8b. The film 8a partially swells away from the sheet 8b. The bulging portion is a closed space, and the liquid reagent 9 is sealed in the closed space. Such a reagent container 7 is generally called a blister pack. In the reagent container 7, the film 8a is broken by pressing the film 8a. Thereby, the liquid reagent 9 is released.

  The substrate 3 is preferably made of a synthetic resin molded body. However, the substrate 3 may be formed by laminating a plurality of synthetic resin sheets.

  A micro flow path is provided in the substrate 3. The micro flow path is a fine flow path in which a so-called micro effect is generated when a fluid is conveyed. In such a microchannel, the liquid is strongly influenced by the surface tension and the capillary phenomenon, and behaves differently from the liquid flowing in a normal large-sized channel.

  The cross-sectional shape and size of the micro flow path are not particularly limited as long as the micro flow effect is generated. For example, when using a pump or gravity when flowing a fluid through a microchannel, the cross-sectional shape of the microchannel is generally small (including a square) from the viewpoint of reducing the channel resistance. The side dimension 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 miniaturization of the microfluidic device, 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.

  Further, when the cross-sectional shape of the microchannel is generally circular, the diameter (in the case of an ellipse, the short diameter) 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 miniaturization of the microfluidic device, the diameter (in the case of an ellipse, the short diameter) 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 the capillary phenomenon is effectively used when flowing a fluid through the microchannel, the dimension of the smaller side is used when the cross-sectional shape of the microchannel is generally rectangular (including a square). It is preferably 5 μm or more, more preferably 10 μm or more, and further preferably 20 μm or more. The smaller side dimension is preferably 200 μm or less, and more preferably 100 μm or less.

  The microchannel has a liquid feeding channel 6a, an inlet channel 6b, an outlet channel 6c, and a discharge channel 6d.

  The liquid feeding flow path 6a is open to the reagent storage space A. In the present embodiment, a retention space B is provided below the reagent storage space A. The liquid feeding flow path 6a connects the reagent storage space A and the retention space B. In the staying space B, the aforementioned inlet channel 6b and the outlet channel 6c are opened. The downstream end of the outlet channel 6 c is open to the mixing / reaction space C. One end of the discharge channel 6d is opened in the mixing / reaction space C.

  The residence space B and the mixing / reaction space C are provided by covering the opening opened on the second main surface 3 b of the substrate 3 with the cover member 5. Further, the inlet channel 6 b, the outlet channel 6 c, and the discharge channel 6 d are provided by covering a groove opened on the second main surface 3 b of the substrate 3 with the cover member 5.

  The reagent storage space A has a bottom surface 3d. That is, the bottom surface 3d of the recess 3c is the bottom surface of the reagent storage space A. A reagent storage body 7 is provided on the bottom surface 3d. In the present embodiment, the reagent container 7 is provided so as to cover the opening of the liquid feeding flow path 6a.

  Next, the characteristics of the microchannel chip 1 will be clarified by explaining the usage method.

  The microchannel chip 1 is characterized in that the reagent storage space A in which the reagent storage body 7 is arranged is connected to the staying space B by the liquid supply channel 6a. That is, the retention space B is provided in the middle of the microchannel.

  In the microchannel chip 1, the reagent container 7 is opened by pressing the reagent container 7. Thereby, the liquid reagent 9 can be caused to flow into the microchannel in the microchannel chip 1. At this time, since the reagent storage space A and the retention space B are connected, the liquid reagent 9 released from the reagent storage body 7 can be prevented from flowing directly into the mixing / reaction space C. Thereby, it is possible to prevent mixing and reaction at unintended timing due to variations in the pressing force and the opening of the reagent container 7.

  Further, even when the liquid reagent 9 is ejected or ejected when the reagent container 7 is opened by pressing, the influence can be reset by providing the staying space B, and the liquid feeding of the liquid reagent 9 can be easily controlled.

  The location of the retention space B is not particularly limited as long as it is connected to the reagent storage space A. It may be provided directly under the reagent storage space A as in this embodiment. Moreover, the residence space B may be provided so as to be adjacent to the reagent storage space A as in the microchannel chip 41 of the fourth embodiment shown in FIG.

  The method of opening the reagent container 7 by pressing and the inflow of the liquid reagent 9 into the microchannel chip associated therewith are not particularly limited. For example, as illustrated in FIG. 4, a protrusion 42 as a protrusion protruding toward the reagent storage space A may be provided. In this case, since the protrusion 42 is pushed into the reagent container 7 by pressing, the opening can be performed more easily and reliably.

  Note that the microchannel chip 41 of the fourth embodiment is different from the microchannel chip 1 of the first embodiment except that the position of the staying space B is different and the protrusions 42 are provided. It is constituted similarly.

  Further, as in the modified example of the reagent container 7 shown in FIG. 5, the reagent container 7 is provided with an easily peelable seal portion 7a, and the easily peelable seal portion 7a is selectively opened when pressed. Good.

  The staying space B preferably has a liquid or gas inlet F and an outlet G in addition to the liquid supply passage 6a connected to the reagent storage space A in which the reagent storage body 7 is disposed. Here, the inlet F is a portion where the inlet channel 6b is open to the staying space B. The outlet G is a portion where the outlet channel 6c opens into the stay space B. Since it has the inflow port F and the outflow port G, the reagent storage body 7 is opened by pressing the reagent storage body 7, the inflow process of the liquid reagent 9, and the liquid reagent 9 held in the retention space B is mixed and reacted. The step of feeding liquid to C can be a separate step. Therefore, the liquid feeding timing and speed can be easily controlled. The staying space B may have a plurality of inflow ports F.

  The method for feeding the liquid reagent 9 held in the staying space B to the mixing / reaction space C is not particularly limited. For example, a method of sending a gas such as liquid or air from the inflow port F using a pump or the like installed outside the microchannel chip may be used. A member that generates gas by an external stimulus such as light or heat is disposed in a space connected from the inlet F, and gas is generated by applying an external force to the gas generating member at a predetermined timing. Good.

  The shapes of the inflow port F and the outflow port G in the staying space B are not particularly limited, and a circular shape, an elliptical shape, a square shape, a rectangular shape, or other shapes that match the shape of the liquid supply flow path can be used.

  Moreover, the arrangement | positioning location of the inflow port F and the outflow port G in the said retention space B is not specifically limited, It can arrange | position according to the shape of a microchannel chip, and the shape of a liquid feeding channel.

  The volume of the retention space B is not particularly limited as long as it is at least the volume of the liquid reagent 9. However, it is preferable to have a volume of 100% to 120% of the volume of the liquid reagent 9. In that case, it is possible to prevent unintentional outflow to the mixing / reaction space C. Further, at the time of liquid feeding, it is possible to prevent bubbles from being entrained in the liquid feeding flow path 6a and to lose liquid continuity, and to easily control the liquid feeding timing and speed.

  In the microchannel chip of the present embodiment, it is preferable that the reagent storage space A in which the reagent storage body 7 is arranged does not have an opening other than the opening H of the liquid feeding flow path 6a connected to the staying space B. . In that case, when the liquid reagent 9 is discharged from the reagent container 7, liquid leakage to the outside of the microchannel chip 1 is unlikely to occur. In addition, the liquid reagent 9 can be selectively introduced from the opening H into the staying space B.

  As a method of creating a structure in which the reagent storage space A has no opening other than the opening H as described above, for example, an opening for arranging the reagent storage body 7 in the reagent storage space A is used as a reagent storage body. The method of sealing after arranging 7 is mentioned. The sealing method is not particularly limited. For example, there are a method of bonding a resin plate, a resin film or the like by heat fusion, a method of bonding by an adhesive, or a method of pressure-sensitive adhesion using a pressure-sensitive adhesive tape. Especially, it is preferable to seal with a flexible film such as an elastomer film so that the reagent container 7 can be pressed by an external force.

  The reagent storage body 7 is preferably disposed on the opening H of the liquid feeding flow path 6a that connects the reagent storage space A and the retention space B. By arranging the reagent storage body 7 on the opening H, even when the reagent storage space A has an opening other than the opening H, the liquid reagent 9 is selectively introduced from the opening H into the staying space B. can do.

  Furthermore, it is preferable that the reagent storage body 7 is bonded to a surface of the bottom surface 3d of the reagent storage space A except at least the opening H. By adhering to the bottom surface 3d, liquid leakage and the like can be prevented, and the liquid reagent 9 can be introduced into the staying space B from the opening H more selectively.

  In addition, when bonding the reagent storage body 7 and the bottom surface 3d of the reagent storage space A, it is preferable to avoid the opening H and bond the region in the region surrounding the opening H. In that case, when the reagent container 7 is opened, in the space between the opening of the reagent container 7 and the opening H, the openings other than the opening and the opening H of the reagent container 7 are sealed. . Therefore, the liquid reagent 9 can be more selectively introduced into the retention space B.

  However, the reagent container 7 may be provided at a position where it does not overlap the opening H, like the microchannel chip 31 of the third embodiment shown in FIG.

  The reagent storage space A may have no opening other than the opening H, and the reagent storage body 7 may be bonded to at least the surface of the bottom surface 3d of the reagent storage space A excluding the opening H. In that case, liquid leakage to the outside of the microchannel chip can be suppressed. Furthermore, the liquid residue in the reagent storage space A can be suppressed, and the liquid reagent 9 can be more selectively introduced into the retention space B.

  A material constituting the microchannel chip 1 is not particularly limited. For example, a configuration in which the cover member 5 is bonded to the substrate 3 on which a concave portion serving as a micro flow path in accordance with a target inspection and reaction can be used. That is, a structure like the microchannel chip 21 of the second embodiment shown in FIG. 2 may be used. Here, the cover member 5 is bonded to the second main surface 3 b of the substrate 3. Therefore, the sealing film 4 may not be laminated on the first main surface 3a side. In this case, the reagent storage space A is opened upward. The reagent container 7 is fixed to the bottom surface 3d of the recess 3c with an adhesive 10.

  The microchannel chip 21 is configured in the same manner as the microchannel chip 1 except that it does not have the sealing film 4.

  The material of the substrate 3 is not particularly limited, and various moldable materials such as synthetic resin, rubber, or metal can be used. For example, the substrate layer can be formed by injection molding a resin having high moldability such as polyolefin.

  The material of the cover member 5 is not particularly limited, and a pressure sensitive adhesive using a method of bonding a plate or film of the same material as the substrate layer by thermal fusion, a method of bonding by an adhesive, or a pressure sensitive adhesive tape. Or the like can be used.

  The configuration of the reagent container 7 is not particularly limited. For example, various configurations are possible as long as the container can contain the liquid reagent 9, such as a blister type container in which a pocket portion and a lid portion are bonded, a bag-like film pack, a capsule, or the like. Can be used. Among these, a blister type container is preferable. In the case of a blister container, opening control by pressing is easy and molding is easy.

  When using a blister type container, various materials such as various plastic materials such as polyethylene, polypropylene, vinyl chloride, metal films such as aluminum films, and laminates thereof can be used as the material for the pocket portion. It is preferable to include one or more aluminum layers. By including the aluminum layer, the load required when pressing the container can be reduced. In addition, the storage stability of the filled reagent can be increased. Therefore, the period from the creation of the microchannel chip to the use thereof can be extended.

  Although it does not specifically limit as a material of a cover part, It is preferable to use an aluminum film. In the case of an aluminum film, opening control is easy due to the arrangement of protrusions and the like, and molding is easy.

  FIG. 6 is a front cross-sectional view of a microchannel chip according to a fourth embodiment of the present invention. In the microchannel chip 51, the reagent container 7 is formed of a bag-shaped film pack. The reagent container 7 is placed on the bottom surface 3d of the recess 3c constituting the reagent storage space. The liquid feeding flow path 6a is arranged close to one side of the reagent storage space. Except for these, it is configured in the same manner as the microchannel chips 1 and 31. Therefore, the same parts are denoted by the same reference numerals, and the description thereof is omitted.

  A bag-shaped film pack may be used as the reagent container 7 as in the microchannel chip 51. Here, the reagent container 7 is configured by laminating a flexible synthetic resin film 7A and a synthetic resin film 7B at the outer peripheral edge portion. A liquid reagent 9 is stored inside the reagent storage body 7. In addition, as a flexible film, you may use not only a synthetic resin film but metal foil etc. which have flexibility.

  Even when the reagent container 7 made of the bag-shaped film pack is used, the reagent container 7 can be pierced by being pressed from the sealing film 4 side. Thereby, the liquid reagent 9 can be promptly supplied to the liquid supply channel 6a side.

DESCRIPTION OF SYMBOLS 1 ... Microchannel chip 2 ... Microchannel chip body 3 ... Board | substrate 3a, 3b ... 1st, 2nd main surface 3c ... Recess 3d ... Bottom surface 4 ... Sealing film 5 ... Cover member 6a ... Liquid sending channel 6b ... Inlet channel 6c ... Outlet channel 6d ... Drain channel 7 ... Reagent container 7a ... Easily peelable seals 7A, 7B ... Synthetic resin film 8 ... Sealing material 8a ... Film 8b ... Sheet 9 ... Liquid reagent 10 ... Adhesives 21, 31, 41, 51 ... microchannel chip 42 ... protrusion

Claims (8)

A reagent storage space, a microchannel connected to the reagent storage space, and a mixture / reaction that is connected to the microchannel and in which the liquid reagent and the sample are mixed or the liquid reagent and the sample are reacted A microchannel chip body having a space and a retention space provided between the reagent storage space and the mixing / reaction space in the microchannel;
A microchannel chip that is stored in the reagent storage space, and includes a reagent storage body that includes a liquid reagent and a sealing material that seals the liquid reagent and is opened by pressing.   The microchannel includes a liquid supply channel that connects the reagent storage space and the retention space, an inlet channel that allows liquid or gas to flow into the retention space, and the mixing / reaction from the retention space. The microchannel chip according to claim 1, further comprising an outlet channel reaching the space.   The microchannel chip according to claim 1 or 2, wherein a volume of the staying space is equal to or larger than a volume of a liquid reagent filled in the reagent container.   The microchannel chip according to any one of claims 1 to 3, wherein the reagent storage space does not have an opening in the periphery other than the opening in which the liquid supply channel is open in the staying space. .   The reagent storage space is provided above the retention space, and the reagent storage body is disposed on an opening portion of the liquid supply channel to the retention space. The microchannel chip according to one item.   The reagent storage space has a bottom surface having an opening in which the liquid supply channel is open, and the reagent storage body is bonded to the bottom surface in a region excluding the opening on the bottom surface. The microchannel chip according to claim 5.   A substrate having first and second main surfaces facing each other and having a recess opening in the first main surface, and provided to seal the recess of the substrate. The microchannel chip according to claim 1, wherein the reagent storage space is provided by the recess and the sealing film. The microchannel chip according to claim 7, wherein a convex portion that protrudes toward the reagent storage body is provided on an inner surface of the sealing film.

Images