Microfluidic chips and microfluidic devices

Abstract

The microfluidic chip is inserted into a slot extending in the horizontal direction and used as a microfluidic device. The microfluidic chip includes: an upper surface; a lower surface located on the opposite side of the upper surface; a flow path of the fluid arranged between the upper surface and the lower surface; and two connecting holes connected to the flow path and opening on the upper surface.

Description

Technical Field

[0001] The invention relates to a microfluidic chip and a microfluidic device. Background Art

[0002] A microfluidic device is a device having a tiny flow path through which liquid flows in order to analyze or synthesize a fluid. As one type of microfluidic chip constituting a microfluidic device, an organ-on-a-chip (Non-Patent Document 1) has been developed that cultures cells in a flow path by imitating an animal's internal organs or tissues.

[0003] Organ-on-a-chip is used as an alternative to animal experiments in the field of drug development, for example. Although animal experiments are useful in evaluating the effects and side effects of drugs, they are not desirable from the perspective of animal protection. In addition, even if animal experiments can be conducted to evaluate the effects of drugs on a certain animal, the evaluation may not be applicable to other types of animals. For example, for experiments on the administration of drugs to mice, it is impossible to fully grasp the effects and side effects of the drugs on humans. In order to investigate the effects of drugs on a certain animal, it is hoped to use organ-on-a-chips that culture cells from the animal.

[0004] Prior art literature

[0005] Patent Literature

[0006] Non-patent document 1: Julia Rogal, et al., "Integration concepts for multi-organc hips: how to maintain flexibility?!", Future Science OA, 2017, [online], [retrieved on September 10, 2017], Internet (URL: https: / / www.ncbi.nlm.nih.gov / pmc / articles / PMC5481865 / ) Summary of the invention

[0007] Technical problem to be solved by the invention

[0008] A microfluidic chip including an Organ-on-a-chip is combined with another component (e.g., a holder in which the microfluidic chip is inserted, a plate overlapping the microfluidic chip, or a microfluidic chip in which another type of cell is cultured) to be used as a microfluidic device. It is desirable to be able to simply manufacture such a microfluidic device.

[0009] To this end, the present invention provides a microfluidic chip capable of simply manufacturing a microfluidic device and a microfluidic device having the microfluidic chip.

[0010] Solutions for solving technical problems

[0011] A microfluidic chip in one embodiment of the present invention is a microfluidic chip inserted into a slot extending in a horizontal direction, and the microfluidic chip includes: an upper surface; a lower surface located on the opposite side of the upper surface; a fluid flow path arranged between the upper surface and the lower surface; and two connecting holes connected to the flow path and opening on the upper surface.

[0012] In this method, the microfluidic chip can be inserted into the slot in the horizontal direction, and the microfluidic device can be simply manufactured by a component with a slot and a microfluidic chip. For example, in order to use organ-on-a-chip to evaluate human drug metabolism, it is preferred to culture multiple different types of cells. In the case of culturing multiple cells on a chip, if even one type of cell culture fails, the overall function of the device will be lost. According to one example of the present invention, different types of cells are cultured on separate microfluidic chips, and only the microfluidic chips that have been successfully cultured are selected, and these microfluidic chips are assembled on a component with multiple slots, thereby making it possible to simply connect these microfluidic chips to each other. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 1 is a plan view showing a microfluidic device according to an embodiment of the present invention.

[0014] Figure 2 It shows the decomposition Figure 1 Top view of the various components of the microfluidic device.

[0015] Figure 3 It is shown Figure 1 Top view of the connected flow path chip of the microfluidic device.

[0016] Figure 4 yes Figure 3 A cross-sectional view of the connected flow path chip as viewed along line IV-IV.

[0017] Figure 5 It is shown Figure 1 Top view of the microfluidic chip of the microfluidic device.

[0018] Figure 6 yes Figure 1 Cross-sectional view of the microfluidic device taken along line VI-VI.

[0019] Figure 7 It is shown Figure 5 Rear view of the flow plate of the microfluidic chip.

[0020] Figure 8 is a side cross-sectional view showing a microfluidic device different from the embodiment.

[0021] Fig. 9 yes Figure 7 Enlarged cross-sectional view of the microfluidic chip taken along line IX-IX.

[0022] Fig.10 is an enlarged rear view showing a portion of a flow path plate of a microfluidic chip.

[0023] Fig.11 It is a perspective view showing the arrangement of elements of a microfluidic chip.

[0024] Fig.12 It is a side cross-sectional view showing a microfluidic device according to a modified example of the embodiment.

[0025] Fig.13 It is a side cross-sectional view of a microfluidic device showing another modified example of the embodiment.

[0026] Fig.14 This is an enlarged rear view of a part of a flow channel plate of a microfluidic chip showing another modified example of the embodiment.

[0027] Fig.15 This is an enlarged rear view of a part of a flow channel plate of a microfluidic chip showing another modified example of the embodiment.

[0028] Fig.16 It is a side cross-sectional view of a microfluidic device showing another modified example of the embodiment.

[0029] Fig.17 It is a side cross-sectional view of a microfluidic device showing another modified example of the embodiment.

[0030] Fig.18 This is a side cross-sectional view showing a stage before the microfluidic chip is inserted into the slot of the holder in the embodiment.

[0031] Fig.19 This is a side cross-sectional view showing an initial stage of inserting the microfluidic chip into the slot of the holder in the embodiment.

[0032] Fig. 20 It is shown Fig.19 A side cross-sectional view of the next stage.

[0033] Fig.21 It is shown Fig. 20 A side cross-sectional view of the next stage.

[0034] Fig. 22 It is shown Fig.21 A side cross-sectional view of the next stage.

[0035] Fig.23 It is shown Fig. 22 A side cross-sectional view of the next stage.

[0036] Fig.24 It is a side cross-sectional view showing the initial stage of inserting the microfluidic chip in the comparative example into the slot of the holder.

[0037] Fig.25 It is shown Fig.24 A side cross-sectional view of the subsequent stage.

[0038] Fig.26 It is a side cross-sectional view of a microfluidic device showing another modified example of the embodiment.

[0039] Fig. 27 It is a side cross-sectional view of a microfluidic device showing another modified example of the embodiment.

[0040] Fig.28 It is a top view of a microfluidic device showing another modified example of the embodiment. DETAILED DESCRIPTION

[0041] Below, while referring to the attached Figure 1 In the drawings, the scales do not necessarily accurately represent the products of the embodiments, and some dimensions may be exaggerated.

[0042] The microfluidic device of the embodiment is an organ-on-a-chip device. Figure 1 As shown, the microfluidic device includes a holder 1 , a plurality of (two in this embodiment) microfluidic chips 2 held on the holder 1 , and a connecting flow path chip 3 held on the holder 1 and connected to the microfluidic chips 2 .

[0043] Each microfluidic chip 2 is a rectangular plate. Figure 1 and Figure 2 As shown, the holder 1 is a roughly rectangular plate and has a plurality of slots 4 extending in the horizontal direction for inserting a plurality of microfluidic chips 2 in the horizontal direction. In addition, a rectangular long opening 5 is formed on the upper portion of the holder 1 for inserting a rectangular long connection flow path chip 3.

[0044] like Figure 3 and Figure 4 As shown, two second holes 28 are formed at both ends of the connecting flow path chip 3, and a connecting flow path 30 connected to the second holes 28 is formed in the central part of the connecting flow path chip 3. The connecting flow path 30 extends along the long side direction of the connecting flow path chip 3. The two second holes 28 do not penetrate the connecting flow path chip 3, but open on one side of the connecting flow path chip 3.

[0045] The connecting flow path chip 3 is formed of a transparent elastomer, such as silicone rubber or acrylic rubber with polydimethylsiloxane (PDMS) as the main component. The method for manufacturing the connecting flow path chip 3 is not limited, for example, the connecting flow path chip 3 can be manufactured by 3D printing. Specifically, around the supporting material (core) that forms the second hole 28 and the connecting flow path 30, for example, using a photomolding method, after the outer shape of the connecting flow path chip 3 is formed using ultraviolet-cured PDMS, the supporting material is dissolved and removed using an alkaline solution, thereby enabling the second hole 28 to be opened with the connecting flow path 30. However, the connecting flow path chip 3 can also be manufactured by joining parts formed using a mold formed using photolithography or 3D printing.

[0046] like Figure 5 and Figure 6 As shown, each microfluidic chip 2 has: a flat plate 6, which is rectangular and has a uniform thickness; and a flow path plate 8, which is a rectangular flat plate with a uniform thickness overlapping the flat plate 6. The flat plate 6 has a flat first upper surface 6a and a flat first lower surface 6b parallel to the first upper surface 6a. The flow path plate 8 has a flat second upper surface 8a and a flat second lower surface 8b parallel to the second upper surface 8a. The flat plate 6 and the flow path plate 8 are arranged horizontally, and the flow path plate 8 is arranged above the flat plate 6. The first upper surface 6a of the flat plate 6 is bonded to the second lower surface 8b of the flow path plate 8. Therefore, the second upper surface 8a of the flow path plate 8 is the upper surface of the microfluidic chip 2, and the first lower surface 6b of the flat plate 6 is the lower surface of the microfluidic chip 2.

[0047] The flat plate 6 is formed of a transparent material such as glass or acrylic resin. The flow path plate 8 is formed of a transparent elastomer, such as silicone rubber or acrylic rubber with PDMS as the main component. The thickness of the flat plate 6 is, for example, 1 mm, the thickness of the flow path plate 8 is, for example, 2 mm, and the thickness of the entire microfluidic chip 2 is, for example, 3 mm.

[0048] like Figure 1 As shown, the flat plate 6 has a greater length than the flow path plate 8. When the microfluidic chip 2 is inserted into the slot 4, the entire flow path plate 8 and a portion of the flat plate 6 are arranged inside the slot 4, and the end of the flat plate 6 is exposed.

[0049] like Figure 5 and Figure 7 As shown, a concave portion that serves as a flow path for a liquid is formed on the second lower surface 8b of the flow path plate 8. The concave portion includes a culture chamber concave portion 14h and a first passage concave portion 16h and a second passage concave portion 18h that communicate with both ends of the culture chamber concave portion 14h, respectively. A first communication hole 10 that communicates with the first passage concave portion 16h and a second communication hole 12 that communicates with the second passage concave portion 18h are formed on the flow path plate 8, and the first communication hole 10 and the second communication hole 12 open on the second upper surface 8a.

[0050] The flat plate 6 is joined to the flow path plate 8 and covers the recessed portion, thereby defining the flow path in cooperation with the flow path plate 8. In the present embodiment, the flow path includes a culture chamber 14 in which cells of an animal (including a human) are cultured, a first passage 16 between the first communicating hole 10 and the culture chamber 14, and a second passage 18 between the second communicating hole 12 and the culture chamber 14. The first passage 16 and the second passage 18 have a smaller width than the culture chamber 14. The first passage 16 and the second passage 18 have the same width and length as each other.

[0051] The culture chamber 14 is a long space extending along a straight line, and the first passage 16 and the second passage 18 extend along the same straight line. Since the flow path having the culture chamber 14 and the first passage 16 and the second passage 18 extends linearly from one connecting hole toward another connecting hole (without bending or curving), the structure of the flow path is simple. However, the culture chamber 14 and the first passage 16 and the second passage 18 can also be bent or curved. In the present embodiment, in each microfluidic chip 2, the line segment connecting the two first connecting holes 10 and the second connecting holes 12 arranged at both ends of the flow path is inclined relative to the insertion direction of the microfluidic chip 2 inserted into the slot 4, and the culture chamber 14 and the first passage 16 and the second passage 18 extend linearly along the line segment. However, the line segment connecting the two first connecting holes 10 and the second connecting holes 12 can also extend along the insertion direction.

[0052] Thus, the microfluidic chip 2 has: a fluid flow path disposed between the second upper surface 8a and the first lower surface 6b; and two first communication holes 10 and a second communication hole 12 communicating with the flow path and opening at the second upper surface 8a.

[0053] like Figure 6 As shown, the holder 1 has a stacked upper wall 20, a middle wall 22 and a lower wall 24. The top surface of the slot 4 is the lower surface of the upper wall 20, and the bottom surface of the slot 4 is the upper surface of the lower wall 24. When the microfluidic chip 2 is inserted into the slot 4, the upper wall 20 is opposite to the second upper surface 8a of the flow path plate 8 of the plurality of microfluidic chips 2, and the lower wall 24 is opposite to the first lower surface 6b of the flat plate 6 of the plurality of microfluidic chips 2. The middle wall 22 is disposed between the upper wall 20 and the lower wall 24, and defines the side of the slot 4.

[0054] The upper wall 20, the middle wall 22 and the lower wall 24 are fixed to each other. These fixings can be, for example, Figure 1 As shown, a plurality of locking members 25 are used. Each locking member 25 may include, for example, a through hole 25A (see FIG. 25A ) inserted through the upper wall 20, the middle wall 22 and the lower wall 24. Figure 2) and a nut threaded with the screw. Alternatively, each fixing member 25 may also be a clamping mechanism. Alternatively, the upper wall 20, the middle wall 22 and the lower wall 24 may also be formed in one piece. Alternatively, the upper wall 20, the middle wall 22 and the lower wall 24 may also be joined using an adhesive, chemical reaction or thermal reaction.

[0055] The upper wall 20 , the middle wall 22 , and the lower wall 24 are formed of, for example, an opaque resin material, but may also be formed of a transparent material.

[0056] like Figure 1 , Figure 2 and Figure 6 As shown, a plurality of first holes 26 are formed in the upper wall 20. The plurality of first holes 26 penetrate through the upper wall 20 and are used as an inlet or outlet for liquid or an outlet for air that flows under pressure from the liquid.

[0057] In addition, an opening 5 is formed in the upper wall 20. The opening 5 passes through the upper wall 20, and the connection flow path chip 3 is embedded and fixed in the opening 5. A plurality of second holes 28 formed in the connection flow path chip 3 embedded in the opening 5 open in the slot 4. Although not shown in the figure, a fixing member for fixing the connection flow path chip 3 to the opening 5 may also be used.

[0058] The connecting flow path chip 3 can be considered as a part of the holder 1. That is, the holder 1 can be considered to include an upper wall structure 19 having an upper wall 20 and the connecting flow path chip 3, a middle wall 22, and a lower wall 24. The top surface of the slot 4 is the lower surface of the upper wall structure 19, and the bottom surface of the slot 4 is the upper surface of the lower wall 24.

[0059] Furthermore, a plurality of observation windows 29 are formed on the upper wall 20. The observation windows 29 pass through the upper wall 20. After the microfluidic chip 2 is inserted into the slot 4, each observation window 29 overlaps with the culture chamber 14 of the microfluidic chip 2. Through the observation windows 29, the cells in the culture chamber 14 can be observed. For cell observation, a microscope can be used, for example. In order to increase the brightness for cell observation, a lighting window passing through the lower wall 24 can also be formed on the lower wall 24. In the present embodiment, although the upper wall 20 is formed of an opaque material, even when the upper wall 20 is formed of a transparent material, in order to perform good cell observation based on a microscope, it is preferred to form an observation window 29 passing through the upper wall 20.

[0060] A plurality of first grooves 32 and second grooves 34 are formed on the lower surface of the upper wall 20. The first grooves 32 and second grooves 34 extend linearly along the long side direction of the slot 4 (the insertion direction of the microfluidic chip 2 into the slot 4). Figure 1 and Figure 2As shown, there is a first hole 26 on the extension line of the first groove 32, and a second hole 28 on the extension line of the second groove 34. When the microfluidic chip 2 is inserted into the slot 4, the first connecting hole 10 of each microfluidic chip 2 moves in the slot 4 while overlapping with the first groove 32, and the second connecting hole 12 of each microfluidic chip 2 moves in the slot 4 while overlapping with the second groove 34. The second groove 34, which has the second hole 28 arranged on the deep side of the slot 4 on the extension line, extends across the observation window 29.

[0061] After the microfluidic chip 2 is inserted into the slot 4, the multiple first holes 26 formed on the upper wall 20 of the upper wall structure 19 are respectively configured to be approximately coaxial with the first connecting holes 10 of the flow path plates 8 of the multiple microfluidic chips 2, and are respectively communicated with the first connecting holes 10, and the multiple second holes 28 formed on the upper wall structure 19 connecting the flow path chip 3 are respectively configured to be approximately coaxial with the second connecting holes 12 of the flow path plates 8 of the microfluidic chip 2, and are respectively communicated with the second connecting holes 12.

[0062] like Figure 1 As shown, the two second holes 28 are connected by a connecting flow path 30. The connecting flow path 30 extends horizontally across the two slots 4. Through the connecting flow path 30, liquid can be transferred from a flow path of one microfluidic chip 2 to a flow path of another microfluidic chip 2.

[0063] A plurality of first annular seals 36 and second annular seals 38 formed of an elastomer are arranged on the second upper surface 8a of the flow path plate 8 having the first connecting hole 10 and the second connecting hole 12. In the present embodiment, the first annular seals 36 and the second annular seals 38 are O-rings, but they may also be rings having other cross-sectional shapes such as D-rings. The material of the first annular seals 36 and the second annular seals 38 is, for example, silicone rubber, or other elastomers. In the present embodiment, the first annular seals 36 and the second annular seals 38 have the same size, but they may also have different sizes.

[0064] like Figure 6 As shown, in this embodiment, a groove for embedding the first annular seal 36 and the second annular seal 38 is formed on the second upper surface 8a of the flow path plate 8, and the first annular seal 36 and the second annular seal 38 are fixed to the second upper surface 8a by embedding the first annular seal 36 or the second annular seal 38 in each groove. The first annular seal 36 and the second annular seal 38 may also be bonded to the second upper surface 8a. As a bonding method, for example, bonding based on an adhesive may be used, or two components may be chemically bonded by irradiating oxygen plasma or irradiating ultraviolet rays in a vacuum to activate the surface of the components.

[0065] The first annular seal 36 is arranged substantially coaxially with the first communication hole 10 formed in the flow path plate 8 and surrounds the first communication hole 10, and the second annular seal 38 is arranged substantially coaxially with the second communication hole 12 formed in the flow path plate 8 and surrounds the second communication hole 12. A portion of the first annular seal 36 overlaps with the first passage 16, and a portion of the second annular seal 38 overlaps with the second passage 18.

[0066] After the microfluidic chip 2 is inserted into the slot 4, the first annular seal 36 is configured to be substantially coaxial with the first hole 26 formed in the upper wall 20 and surround the first hole 26, and the second annular seal 38 is configured to be substantially coaxial with the second hole 28 formed in the connecting flow path chip 3 and surround the second hole 28. Therefore, the first annular seal 36 surrounds the first hole 26 formed in the upper wall 20 and the first communicating hole 10 formed in the flow path plate 8, and the second annular seal 38 surrounds the second hole 28 formed in the connecting flow path chip 3 and the second communicating hole 12 formed in the flow path plate 8.

[0067] When the microfluidic chip 2 is inserted into the slot 4, the first lower surface 6b of the flat plate 6 of the microfluidic chip 2 slides on the lower wall 24 of the holder 1, and the first annular seal 36 and the second annular seal 38 fixed to the second upper surface 8a of the flow path plate 8 slide on the upper wall 20 of the holder 1. After the microfluidic chip 2 is inserted into the slot 4, the lower wall 24 continues to contact the flat plate 6 of the plurality of microfluidic chips 2. After the microfluidic chip 2 is inserted into the slot 4, the upper wall 20 of the holder 1 is opposite to the second upper surface 8a of the flow path plate 8 connecting the flow path chip 3 and the plurality of microfluidic chips 2, and continues to compress the first annular seal 36 and the second annular seal 38 toward the flow path plate 8.

[0068] In this way, the first annular seal 36 or the second annular seal 38 is used to surround the first hole 26 or the second hole 28 formed on the upper wall 20 or the connecting flow path chip 3 and the first connecting hole 10 or the second connecting hole 12 formed on the flow path plate 8, and is compressed, thereby being able to seal the liquid flowing from the first hole 26 or the second hole 28 to the first connecting hole 10 or the second connecting hole 12, or the liquid flowing from the first connecting hole 10 or the second connecting hole 12 to the first hole 26 or the second hole 28.

[0069] As the first annular seal 36 and the second annular seal 38 are compressed, the flow path plate 8 receives a reaction force from the first annular seal 36 and the second annular seal 38. Figure 8 As shown, when there is nothing in the first passage 16 and the second passage 18 , the flow channel plate 8 is elastically deformed, and there is a possibility that the first passage 16 and the second passage 18 are blocked. Figure 8The state in which the blocked portion 16A is generated in the first passage 16 is shown as the flow path plate 8 is elastically deformed by the force received from the first annular seal 36. Although not shown, similarly to the second passage 18, a blocked portion may be generated as the flow path plate 8 is elastically deformed by the force received from the second annular seal 38.

[0070] In this regard, in this embodiment, if Figures 9 to 11 As shown, a first support structure 40 is fixed at a position overlapping with the first annular seal 36 in the interior of the first passage 16, and the first support structure 40 ensures the height of the first passage 16 to prevent the first passage 16 from being blocked. In addition, a second support structure 42 is fixed at a position overlapping with the second annular seal 38 in the interior of the second passage 18, and the second support structure 42 ensures the height of the second passage 18 to prevent the second passage 18 from being blocked. Figures 9 to 11 Although the first support structure 40 is shown to be disposed in the first passage 16, Figures 9 to 11 In the embodiment, the first passage 16 , the first passage recess 16 h , the first support structure 40 , the first communicating hole 10 and the first hole 26 may be renamed as the second passage 18 , the second passage recess 18 h , the second support structure 42 , the second communicating hole 12 and the second hole 28 .

[0071] The first support structure 40 and the second support structure 42 are elongated substantially rectangular parallelepiped protrusions, and are formed on the flow path plate 8. The first support structure 40 is arranged at the center of the width direction of the elongated first passage recess 16h constituting the first passage 16, and extends along the long side direction of the first passage recess 16h. The second support structure 42 is also arranged at the center of the width direction of the elongated second passage recess 18h constituting the second passage 18, and extends along the long side direction of the second passage recess 18h.

[0072] The depth D of the first passage recess 16h and the second passage recess 18h (the depth of the culture chamber recess 14h ) is, for example, 0.1 mm, and the height of the first support structure 40 and the second support structure 42 may be the same as the depth D.

[0073] The ratio w / W of the width w of the first support structure 40 and the second support structure 42 to the width W of the first passage recess 16h and the second passage recess 18h is not limited, but is preferably 0.2 to 0.5, for example. If w / W is too large, the flow of the liquid in the first passage 16 and the second passage 18 is hindered, and the pressure loss is large. For example, the width W of the first passage recess 16h and the second passage recess 18h can be 1 mm, and the width w of the first support structure 40 and the second support structure 42 can be 0.4 mm. In this case, the ratio w / W is 0.4.

[0074] As the first annular seal 36 and the second annular seal 38 are compressed, the flow path plate 8 receives a reaction force from the first annular seal 36 and the second annular seal 38, but the first support structure 40 and the second support structure 42 fixed to the inside of the first passage 16 and the second passage 18 at a position overlapping with the first annular seal 36 and the second annular seal 38 ensure the height of the first passage 16 and the second passage 18 to prevent the first passage 16 and the second passage 18 from being blocked. In the present embodiment, the two first annular seals 36 and the second annular seals 38 are used to seal at two locations, and the two first support structures 40 and the second support structures 42 prevent the flow path from being blocked at these two locations.

[0075] The flow path plate 8 having the first supporting structure 40 and the second supporting structure 42 in the first passage recess 16h and the second passage recess 18h can be manufactured, for example, by soft lithography. For example, a mold for molding the flow path plate 8 can also be manufactured by forming a protrusion on a substrate. Alternatively, a mold for molding the flow path plate 8 can also be manufactured by 3D printing. Alternatively, the flow path plate 8 itself can also be manufactured by 3D printing. In these cases, the first supporting structure 40 and the second supporting structure 42 in the first passage recess 16h and the second passage recess 18h are manufactured integrally with the flow path plate 8 as part of the flow path plate 8. However, the first supporting structure 40 and the second supporting structure 42 can also be bonded to the flow path plate 8 formed with the first passage recess 16h and the second passage recess 18h using an adhesive, a chemical reaction, or a thermal reaction.

[0076] The flow path plate 8 can be bonded to the flat plate 6 using an adhesive, chemical reaction, or thermal reaction. For example, when the flow path plate 8 is formed of silicone rubber containing PDMS as a main component and the flat plate 6 is formed of glass, the flow path plate 8 can be bonded to the flat plate 6 through a siloxane bond.

[0077] In the embodiment, the height of the first support structure 40 and the second support structure 42 may be the same as the depth of the first passage recess 16h and the second passage recess 18h. Fig.12 As shown, the height of the first support structure 40 may be smaller than the depth of the first passage recess 16h, and the height of the second support structure 42 may be smaller than the depth of the second passage recess 18h.

[0078] In the embodiment, the first support structure 40 and the second support structure 42 are formed on the flow path plate 8. However, Fig.13As shown, the support structure 43 protruding toward the first passage recess 16h may be formed or fixed to the flat plate 6, and the support structure protruding toward the second passage recess 18h may be formed or fixed to the flat plate 6. Although not shown, the support structure may be formed or fixed to both the flow path plate 8 and the flat plate 6.

[0079] In the embodiment, a first support structure 40 is disposed in the first passage 16, and a second support structure 42 is also disposed in the second passage 18. Fig.14 As shown, a plurality of first supporting structures 40 may be arranged in the first passage 16, and a plurality of second supporting structures 42 may be arranged in the second passage 18. When a plurality of linear first supporting structures 40 and second supporting structures 42 are arranged in the first passage recess 16h and the second passage recess 18h, the ratio w / W of the width w of the first supporting structure 40 and the second supporting structure 42 to the width W of the first passage recess 16h and the second passage recess 18h is not limited, but in order to make the flow of the liquid in the first passage 16 and the second passage 18 smooth, it is desirable to be 0.2 / n to 0.5 / n, for example. n is the number of linear supporting structures arranged in one passage recess. For example, the width W of the first passage recess 16h and the second passage recess 18h may be 1 mm, and the width w of the first supporting structure 40 and the second supporting structure 42 may be 0.2 mm. In this case, n·w / W is 0.4.

[0080] In addition, the shapes of the first support structure 40 and the second support structure 42 are not limited to those in the embodiment. Fig.15 As shown in FIG. 1 , a cylindrical support structure 44 may be disposed in the first passage 16 and the second passage 18. Fig.15 In the figure, the support structures 44 are arranged in three rows, two rows are aligned in the long side direction of the passage, and the central row is offset from the other two rows. When a plurality of cylindrical support structures 44 are arranged in the first passage recess 16h and the second passage recess 18h, the ratio D / W of the diameter D of the support structure 44 to the width W of the first passage recess 16h and the second passage recess 18h is not limited, but in order to make the flow of the liquid in the first passage 16 and the second passage 18 smooth, it is desired to be 0.2 / n to 0.5 / n, for example. n is the number of rows aligned in the long side direction of the support structures 44 arranged in one passage recess, Fig.15 For example, the width W of the first passage recess 16h and the second passage recess 18h may be 1 mm, and the diameter D of the first support structure 40 and the second support structure 42 may be 0.2 mm. In this case, n·D / W is 0.4.

[0081] In the embodiment, the first annular seal 36 and the second annular seal 38 are rings separated from the flow path plate 8 and fixed to the outer surface (upper surface) of the flow path plate 8. Fig.16 As shown, the third annular seal 46 may be formed as a part of the flow path plate 8 from the same material as the flow path plate 8 to surround the first communication hole 10, and the annular seal may be formed as a part of the flow path plate 8 from the same material as the flow path plate 8 to surround the second communication hole 12. That is, the third annular seal 46 may also be a bump or lip protruding from the flow path plate 8. In such a case, it is preferred that the annular seal is manufactured as a part of the flow path plate 8 and is integrally manufactured with the flow path plate 8, for example, by soft lithography.

[0082] Or, if Fig.17 As shown, the fourth annular seal 48 may be formed of a material different from that of the flow path plate 8 to surround the first communication hole 10, and the annular seal may be formed of a material different from that of the flow path plate 8 to surround the second communication hole 12. In such a case, the annular seal may be bonded to the outer surface (upper surface) of the flow path plate 8 using an adhesive, chemical reaction, or thermal reaction.

[0083] Next, an example of using a microfluidic device of an organ-on-a-chip device of an embodiment is described. In the organ-on-a-chip device, one microfluidic chip 2 simulates an internal organ of an animal (e.g., a liver), and another microfluidic chip 2 simulates another internal organ of the animal (e.g., a lung). For example, a culture chamber 14 of one microfluidic chip 2 is equipped with cells and a drug (e.g., an anticancer agent) from the liver, and a culture chamber 14 of another microfluidic chip 2 is equipped with cells from the lungs. In the former culture chamber 14, some substances are generated by cells from the liver as a reaction of the drug. After sufficient time, the substance generated in the former culture chamber 14 is transferred to the latter culture chamber 14, and the above-mentioned observation window 29 can be used to observe the effects or side effects of the substance on the cells from the lungs.

[0084] In this embodiment, after the flow path (culture chamber 14 and first passage 16, second passage 18) of the microfluidic chip 2 and the first connecting hole 10, second connecting hole 12 are filled with culture fluid (containing cells or cells and drugs), the microfluidic chip 2 can be easily inserted into the slot 4 in the horizontal direction while suppressing the mixing of bubbles into the culture fluid. Fig.18 4 is a side cross-sectional view showing the stage before the microfluidic chip 2 is inserted into the slot 4 of the holder. Fig.18As shown, before the microfluidic chip 2 is inserted into the slot 4, the culture solution 50 is stored not only in the flow path and the first connecting hole 10 and the second connecting hole 12, but also in the first annular seal 36 and the second annular seal 38 surrounding the first connecting hole 10 and the second connecting hole 12. The upper surface of the culture solution 50 bulges under the action of surface tension. Fig.18 The upper surface of the culture solution 50 in the second annular seal 38 surrounding the second communicating hole 12 is shown to be raised, and the upper surface of the culture solution 50 in the first annular seal 36 surrounding the first communicating hole 10 is also raised. In the case where the amount of the culture solution 50 stored in the microfluidic chip 2 is small, bubbles may be mixed into the culture solution 50 when the microfluidic chip 2 is inserted into the slot 4. If the cells of animals are exposed to the air, their growth is hindered or they die, so it is preferred that the cells in the culture solution 50 do not touch the bubbles. In this embodiment, by using the first annular seal 36 and the second annular seal 38 to store a large amount of culture solution 50, it is possible to suppress the mixing of bubbles into the culture solution 50 when the microfluidic chip 2 is inserted into the slot 4.

[0085] Before the microfluidic chip 2 is inserted into the slot 4, the connecting channel chip 3 is fixed to the opening 5 of the holder 1. Therefore, the holder 1 has two first holes 26 and second holes 28 for each microfluidic chip 2, which are connected to the two first connecting holes 10 and the second connecting holes 12, respectively. Figure 2 As shown by the arrow, the microfluidic chip 2 moves toward the deep part of the slot 4 and in the horizontal direction. After the microfluidic chip 2 is inserted into the slot 4, each first connecting hole 10 or second connecting hole 12 communicates with a desired first hole 26 or second hole 28 of the retaining frame 1. When the microfluidic chip 2 is inserted into the slot 4, if the second connecting hole 12 arranged on the deep side of the slot 4 moves while passing through the undesired first hole 26, bubbles may be mixed into the culture solution 50. This will occur if the line segment connecting the first connecting hole 10 and the second connecting hole 12 and the line segment connecting the first hole 26 and the second hole 28 extend along the insertion direction of the microfluidic chip 2.

[0086] However, in the present embodiment, the line segment connecting the two first communicating holes 10 and the second communicating holes 12 is inclined relative to the insertion direction, and the line segment connecting the two first holes 26 and the second holes 28 of the holder 1 is also inclined relative to the insertion direction. Therefore, when the microfluidic chip 2 is inserted into the slot 4, the second communicating hole 12 arranged on the deep side of the slot 4 will not pass through an undesired hole, thereby preventing bubbles from mixing into the culture solution 50. The inclination angle of the line segment connecting the first communicating hole 10 and the second communicating hole 12 relative to the insertion direction is not limited, and is, for example, 15° to 35°.

[0087] In addition, a plurality of first grooves 32 and second grooves 34 extending along the insertion direction of the slot 4 are formed on the lower surface of the upper wall 20 of the holder 1. When the microfluidic chip 2 is inserted into the slot 4, the first connecting hole 10 of each microfluidic chip 2 overlaps with the first groove 32 while moving in the slot 4 and finally reaching the desired first hole 26, and the second connecting hole 12 of each microfluidic chip 2 overlaps with the second groove 34 while moving in the slot 4 and finally reaching the desired second hole 28 (see Fig.19 ). When the microfluidic chip 2 is inserted into the slot 4, when the culture solution 50 filled and raised by the first communicating hole 10, the second communicating hole 12 and the first annular seal 36, the second annular seal 38 contacts the lower surface of the upper wall structure 19, because the culture solution 50 moves in the slot 4 while continuously receiving shear force from the lower surface, a part of the culture solution 50 continues to overflow from the first annular seal 36, the second annular seal 38, and when the first communicating hole 10, the second communicating hole 12 reaches the desired first hole 26, the second hole 28, the amount of the culture solution 50 in the first communicating hole 10, the second communicating hole 12 is greatly reduced, and bubbles may be mixed into the culture solution 50. In this embodiment, the first communicating hole 10, the second communicating hole 12 moves in the slot 4 while overlapping with the first groove 32, the second groove 34 formed on the lower surface of the upper wall structure 19, thereby minimizing the time that the culture solution 50 contacts the lower surface of the upper wall structure 19 and suppressing the mixing of bubbles into the culture solution 50.

[0088] The width of the first groove 32 is preferably larger than the diameter of the culture solution 50 stored in the first annular seal 36. In addition, the width of the first groove 32 is preferably larger than the outer diameter of the first annular seal 36 so as not to give an impact to the first annular seal 36 from the lower surface of the upper wall structure 19 during the movement of the microfluidic chip 2. The width of the second groove 34 is preferably larger than the diameter of the culture solution 50 stored in the second annular seal 38. In addition, the width of the second groove 34 is preferably larger than the outer diameter of the second annular seal 38 so as not to give an impact to the second annular seal 38 from the lower surface of the upper wall structure 19 during the movement of the microfluidic chip 2.

[0089] like Figure 1 As shown, the first groove 32 is separated from the first hole 26, and the second groove 34 is separated from the second hole 28. This is to allow the lower surface of the upper wall structure 19 to apply uniform force to the first annular seal 36 and the second annular seal 38 disposed around the first hole 26 and the second hole 28 throughout the circumference.

[0090] Reference Figure 19 to Figure 23 The state of the culture solution 50 stored in the second communication hole 12 and the second annular seal 38 disposed on the deep side of the slot 4 while the microfluidic chip 2 is inserted into the slot 4 will be described. Fig.19As shown, in the initial stage of the microfluidic chip 2 being inserted into the slot 4, the upper surface of the raised culture solution 50 does not contact the lower surface of the upper wall 20 due to the second groove 34. Fig. 20 As shown, the second communicating hole 12 and the second annular seal 38 reach the observation window 29. The observation window 29 penetrates through the upper wall 20, so when the second communicating hole 12 and the second annular seal 38 pass through the observation window 29, the culture solution 50 filled in the second communicating hole 12 and the second annular seal 38 does not face the lower surface of the upper wall 20 due to the observation window 29. Next, as Fig.21 As shown, the second communicating hole 12 and the second annular seal 38 are opposite to the lower surface of the upper wall 20 again through the edge of the observation window 29, but because the second groove 34 extends across the observation window 29, the upper surface of the raised culture solution 50 still does not contact the lower surface of the upper wall 20. Figure 19 to Figure 21 In the stage shown, the upper surface of the culture solution 50 continues to move away from the lower surface of the upper wall structure 19.

[0091] Next, if Fig. 22 As shown, the second connecting hole 12 and the second annular seal 38 reach the connecting flow path chip 3. At this time, due to the lower edge of the connecting flow path chip 3, the culture solution 50 stored in the second connecting hole 12 and the second annular seal 38 is subjected to shear force, so that part of the culture solution 50 overflows from the second annular seal 38, but immediately thereafter, it is covered by the lower surface of the connecting flow path chip 3, and the possibility of mixing with bubbles is small. Next, as Fig.23 As shown, the second communication hole 12 and the second annular seal 38 reach the desired second hole 28 .

[0092] The upper wall structure 19 of the holder 1 includes a connecting flow path chip 3 fixed to the holder 1, and the connecting flow path 30 and the second hole 28 are formed in the connecting flow path 30. Fig.23 It is obvious that after the connecting flow path 30 and the second hole 28 are filled with the culture solution 50 (for example, the culture solution containing neither cells nor drugs), the connecting flow path chip 3 can be fixed to the holder 1. Preferably, before the microfluidic chip 2 is inserted into the slot 4, the connecting flow path chip 3 filled with the culture solution 50 in the connecting flow path 30 and the second hole 28 is fixed to the holder 1. Under the effect of the interfacial tension, the culture solution 50 does not flow down from the connecting flow path chip 3. Then, while the microfluidic chip 2 is moved horizontally, as shown in FIG. Fig.23 As shown, the culture solution 50 filled in the second communicating hole 12 and the second annular seal 38 is connected to the culture solution 50 filled in the connecting channel 30 and the second hole 28 of the connecting channel chip 3. On the contrary, after the microfluidic chip 2 is inserted into the slot 4, when the connecting channel chip 3 is fixed to the holder 1, bubbles may be mixed into the culture solution 50 when the connecting channel chip 3 is moved downward.

[0093] Assuming that the second groove 34 is not formed on the lower surface of the upper wall 20, Fig.24 (and Fig.19 As shown in the figure, in the initial stage of the microfluidic chip 2 being inserted into the slot 4, the upper surface of the culture solution 50 stored in the second connecting hole 12 and the second annular seal 38 is subjected to shear force due to the lower edge of the upper wall 20, so that a part of the culture solution 50 overflows from the second annular seal 38. Afterwards, because the culture solution 50 continues to be subjected to shear force from the lower surface while moving in the slot 4, a part of the culture solution 50 continues to overflow from the second annular seal 38. Further, as shown in FIG. Fig.25 (and Fig.21 As shown in the figure, when the second communicating hole 12 and the second annular seal 38 pass through the observation window 29, the culture solution 50 filled in the second communicating hole 12 and the second annular seal 38 temporarily touches the air due to the observation window 29, and passes through the lower edge of the upper wall 20 again, and the culture solution 50 stored in the second communicating hole 12 and the second annular seal 38 is subjected to shear force, so that part of the culture solution 50 overflows from the second annular seal 38. In this way, when the second groove 34 is not formed on the lower surface of the upper wall 20, the culture solution 50 is greatly reduced, and bubbles may be mixed into the culture solution 50.

[0094] In contrast, in the embodiment, the second groove 34 extends across the observation window 29 , so that when the culture solution 50 stored in the second communication hole 12 and the second annular seal 38 passes through the observation window 29 , the amount of the culture solution 50 is reduced and mixed with bubbles.

[0095] In the use of the organ-on-a-chip device, when a substance generated in a culture chamber 14 of a microfluidic chip 2 (e.g., a microfluidic chip simulating a liver) is transferred to a culture chamber 14 of another microfluidic chip 2 (e.g., a microfluidic chip simulating a lung), a new culture solution is injected into the first through hole 26 communicating with the first communicating hole 10 of the former microfluidic chip 2. A syringe (e.g., a syringe pump) can be used for injecting the new culture solution. By injecting the new culture solution into the through hole 26 and the first communicating hole 10, the culture solution 50 containing the substance generated in the culture chamber 14 simulating the liver is pushed by the new culture solution to flow toward the second communicating hole 12 and the second hole 28, and further flows into the culture chamber 14 simulating the lung through the connecting flow path 30, through another second hole 28 and the second communicating hole 12. The excess amount of the culture solution 50 in the culture chamber 14 simulating the lung is discharged from the first communicating hole 10 communicating with the culture chamber 14 and the through hole 26. The compressed first annular seal 36 and the second annular seal 38 can seal the liquid. In addition, after the culture solution 50 is filled into the connecting flow path 30 and the second hole 28, the culture solution 50 is transferred from the flow path of one microfluidic chip 2 to the flow path of another microfluidic chip 2, so that air can be prevented from mixing into the culture solution 50.

[0096] Other variations

[0097] Although the embodiments of the present invention have been described above, the above description does not limit the present invention, and various modifications including deletion, addition, and replacement of constituent elements are conceivable within the technical scope of the present invention.

[0098] For example, in the embodiment, the upper wall structure 19 of the holder 1 includes, in addition to the upper wall 20, a connecting flow path chip 3 fixed to the holder 1, and the connecting flow path 30 and the second hole 28 are formed in the connecting flow path 30. However, the connecting flow path chip 3 may be removed. Fig.26 In the modified example shown, the upper wall structure 19 has only the upper wall 20, and the connecting flow path 30 and the second hole 28 are formed on the upper wall 20. In this modified example, the second hole 28 is a through hole, and before the microfluidic chip 2 is inserted into the slot 4, the culture solution 50 is filled into the connecting flow path 30 and the second hole 28 from the upper side of the upper wall 20 through the second hole 28. Under the action of interfacial tension, the culture solution 50 does not flow down from the second hole 28. Thereafter, the culture solution 50 filled in the second connecting hole 12 and the second annular seal 38 is connected to the culture solution 50 filled in the connecting flow path 30 and the second hole 28 while the microfluidic chip 2 is moved horizontally. When the culture solution 50 is transferred from the microfluidic chip 2 to another microfluidic chip 2, the upper part of the second hole 28 is blocked by a plug or a blocking plate (not shown) to prevent the culture solution 50 from flowing out of the second hole 28 opened at the top.

[0099] exist Fig. 27 In the modified example shown, the upper wall structure 19 has only the upper wall 20, and the connecting flow path 30 and the second hole 28 are formed on the upper wall 20. In this modified example, the second hole 28 opens on the lower surface of the upper wall 20. A through hole 24a is formed on the lower wall 24, and a syringe 52 is inserted into the through hole 24a. Before the microfluidic chip 2 is inserted into the slot 4, the connecting flow path 30 and the second hole 28 are filled with a culture solution 50 by the syringe 52. Even if the pressure formed by the syringe 52 is released, the culture solution 50 does not flow down from the second hole 28 due to the effect of interfacial tension. Thereafter, the syringe 52 is removed from the microfluidic device, and the culture solution 50 filled in the second connecting hole 12 and the second annular seal 38 is connected to the culture solution 50 filled in the connecting flow path 30 and the second hole 28 while the microfluidic chip 2 is moved horizontally.

[0100] In the embodiment and the modified example, the connecting flow path 30 and the second hole 28 are formed in the same member (connecting flow path chip 3 or upper wall 20). However, the connecting flow path 30 may be formed in a member different from the member in which the second hole 28 is formed, and these members may be joined.

[0101] In the embodiment, two microfluidic chips 2 are inserted into the holder 1. However, three or more microfluidic chips 2 may be inserted into the holder 1. Fig.28 A microfluidic device having three microfluidic chips 2 is shown. In this modification, a long opening 55 is formed at the upper portion of the holder 1, and a connecting flow path chip 53 spanning the three microfluidic chips 2 is embedded in the opening 55. The connecting flow path chip 53 has three second holes 28 respectively connected to the second connecting holes 12 of the three microfluidic chips 2 and a connecting flow path 30 connected to the three second holes 28. Therefore, in this modification, for example, the culture medium can be transferred from the central microfluidic chip 2 (simulating one internal organ) to the other two microfluidic chips 2 (simulating the other two internal organs).

[0102] The microfluidic device of the embodiment is an organ-on-a-chip device. However, the present invention may also be applied to other microfluidic devices, such as other devices for analyzing body fluids or other fluids of animals.

[0103] In the embodiment, a plurality of microfluidic chips 2 are horizontally inserted into a plurality of slots 4 of the holder 1 to form a microfluidic device. However, a single microfluidic chip 2 may be horizontally inserted into a single slot 4 of the holder 1 to form a microfluidic device.

[0104] In the embodiment, the first groove 32 and the second groove 34 are formed in the upper wall structure 19 of the retainer 1. However, the first groove 32 and the second groove 34 are not necessarily indispensable.

[0105] In the embodiment, an annular seal is provided on the upper part of each microfluidic chip 2, and a supporting structure is arranged in the flow path. However, the supporting structure is not indispensable. In addition, the annular seal is not indispensable. In particular, when the upper wall structure 19 of the retaining frame 1 is formed with the first groove 32 and the second groove 34, it can be considered that even without the annular seal, when the microfluidic chip 2 is inserted into the slot 4, the amount of liquid filled in the first connecting holes 10 and 12 is reduced.

[0106] The above-mentioned modifications may be combined as long as there is no contradiction.

[0107] The aspects of the present invention can also be described in the following numbered items.

[0108] Item 1. A microfluidic chip inserted into a slot extending in a horizontal direction, characterized in that it comprises:

[0109] upper surface;

[0110] a lower surface located on the opposite side of the upper surface;

[0111] a flow path of a fluid, arranged between the upper surface and the lower surface; and

[0112] Two communication holes are communicated with the flow path and open on the upper surface.

[0113] In this embodiment, the microfluidic chip can be inserted into the slot in the horizontal direction, and a microfluidic device can be easily manufactured using a member having a slot and the microfluidic chip.

[0114] Item 2. The microfluidic chip according to Item 1, characterized in that a line segment connecting the two connecting holes is inclined relative to an insertion direction of the microfluidic chip into the slot.

[0115] In such a case, after the liquid is filled with the flow path and the communicating hole, it is easy to insert the microfluidic chip into the slot while suppressing the bubbles from mixing into the liquid. The component with the slot has two holes that are respectively connected to the two communicating holes. After the microfluidic chip is inserted into the slot, each communicating hole communicates with a desired hole of the component with the slot. For example, in the case where the liquid equipped in the flow path is the culture fluid of animal cells, it is hoped that the liquid is not in contact with the air as much as possible. In the case where the liquid that should not be in contact with the air is filled with the flow path and the communicating hole, when the microfluidic chip is inserted into the slot, if the communicating hole on the deep side of the slot moves through an unexpected hole, the liquid may be mixed with bubbles. However, the line segment connecting the two communicating holes is inclined relative to the insertion direction, and the line segment connecting the two holes of the component with the slot is also inclined relative to the insertion direction, so when the microfluidic chip is inserted into the slot, the communicating hole configured on the deep side of the slot does not pass through an unexpected hole, thereby being able to suppress the bubbles from mixing into the liquid.

[0116] Item 3. The microfluidic chip according to Item 2, characterized in that:

[0117] The two communicating holes are arranged at both ends of the flow path,

[0118] The flow path extends linearly along a line segment connecting the two communicating holes.

[0119] In such a case, the flow path extends from one communicating hole toward the other communicating hole, so the structure of the flow path is simple.

[0120] Item 4. The microfluidic chip according to any one of Items 1 to 3, characterized in that:

[0121] The microfluidic chip further includes two annular seals formed of an elastic body, the two annular seals are fixed to the upper surface or formed on the upper surface and respectively surround the communicating holes.

[0122] In this case, after the microfluidic chip is inserted into the slot, the annular seal is compressed between the member with the slot and the upper surface while connecting the connecting hole and the hole of the member with the slot. Before the microfluidic chip is inserted into the slot, liquid is stored not only in the flow path and the connecting hole but also in the annular seal surrounding the connecting hole, thereby preventing bubbles from mixing into the liquid when the microfluidic chip is inserted into the slot. In addition, the annular seal is compressed, so that the liquid flowing from the hole to the connecting hole or the liquid flowing from the connecting hole to the hole can be sealed.

[0123] Item 5. The microfluidic chip according to Item 4, characterized in that:

[0124] The microfluidic chip further includes at least two supporting structures, which are fixed inside the flow path at positions overlapping the annular seal to ensure the height of the flow path to prevent the flow path from being blocked.

[0125] In such a case, the microfluidic chip receives a reaction force from the annular seal as the annular seal is compressed, but the support structure fixed inside the flow path at a position overlapping the annular seal ensures the height of the flow path to prevent the flow path from being blocked.

[0126] Item 6. A microfluidic device, comprising:

[0127] At least one of the microfluidic chips described in item 1; and

[0128] a holder for holding the microfluidic chip,

[0129] The retaining frame has:

[0130] At least one slot for inserting the microfluidic chip and extending in a horizontal direction;

[0131] an upper wall structure, which is opposite to the upper surface of the microfluidic chip when the microfluidic chip is inserted into the slot;

[0132] a lower wall, which contacts the lower surface of the microfluidic chip when the microfluidic chip is inserted into the slot; and

[0133] Two holes are formed in the upper wall structure, and when the microfluidic chip is inserted into the slot, the two holes are respectively communicated with the two communicating holes of the microfluidic chip.

[0134] In this case, the microfluidic chip can be inserted into the slot in the horizontal direction, and the microfluidic device can be easily manufactured using the holder and the microfluidic chip.

[0135] Item 7. A microfluidic device, comprising:

[0136] At least one of the microfluidic chips described in item 2 or 3; and

[0137] a holder for holding the microfluidic chip,

[0138] The retaining frame has:

[0139] At least one slot for inserting the microfluidic chip and extending in a horizontal direction;

[0140] an upper wall structure, which is opposite to the upper surface of the microfluidic chip when the microfluidic chip is inserted into the slot;

[0141] a lower wall, which contacts the lower surface of the microfluidic chip when the microfluidic chip is inserted into the slot; and

[0142] Two holes are formed in the upper wall structure, and when the microfluidic chip is inserted into the slot, they are respectively connected to the two communicating holes of the microfluidic chip,

[0143] A line segment connecting the two holes communicating with the two communicating holes of the microfluidic chip is inclined relative to an insertion direction of the microfluidic chip into the slot.

[0144] In this case, the microfluidic chip can be inserted into the slot in the horizontal direction, and the microfluidic device can be simply manufactured by the holder and the microfluidic chip. The line segment connecting the two connecting holes of the microfluidic chip is inclined relative to the insertion direction, and the line segment connecting the two holes of the holder is also inclined relative to the insertion direction. Therefore, when the microfluidic chip is inserted into the slot, the connecting hole arranged on the deep side of the slot does not pass through the undesired hole, thereby suppressing the mixing of bubbles into the liquid.

[0145] Item 8. A microfluidic device, comprising:

[0146] At least one of the microfluidic chips described in item 4 or 5; and

[0147] a holder for holding the microfluidic chip,

[0148] The retaining frame has:

[0149] At least one slot for inserting the microfluidic chip and extending in a horizontal direction;

[0150] an upper wall structure, which, when the microfluidic chip is inserted into the slot, is opposite to the upper surface of the microfluidic chip and compresses the annular seal toward the upper surface;

[0151] a lower wall, which contacts the lower surface of the microfluidic chip when the microfluidic chip is inserted into the slot; and

[0152] Two holes are formed in the upper wall structure, and when the microfluidic chip is inserted into the slot, the two holes are respectively communicated with the two communicating holes of the microfluidic chip.

[0153] In such a case, the microfluidic chip provided with an annular seal on the top can be inserted into the slot in the horizontal direction, and the microfluidic device can be simply manufactured by a retainer and a microfluidic chip. After the microfluidic chip is inserted into the slot, the annular seal is compressed between the upper wall structure of the retainer and the upper surface of the microfluidic chip while connecting the hole of the communicating hole and the retainer. Before the microfluidic chip is inserted into the slot, not only the flow path and the communicating hole but also the annular seal surrounding the communicating hole also stores liquid, thus when the microfluidic chip is inserted into the slot, bubbles can be suppressed from mixing with the liquid. In addition, the annular seal is compressed, so that the liquid flowing from the hole to the communicating hole or the liquid flowing from the communicating hole to the hole can be sealed.

[0154] Item 9. The microfluidic chip according to any one of Items 6 to 8, characterized in that

[0155] At least two grooves are formed on the lower surface of the upper wall structure of the holder. The grooves extend linearly along the insertion direction of the microfluidic chip into the slot, and the two holes are respectively located on the extension lines of the grooves.

[0156] In such a case, when the microfluidic chip is inserted into the slot, the two communicating holes of the microfluidic chip overlap with the two grooves formed on the lower surface of the upper wall structure respectively while moving in the slot, and finally reach the desired hole. Therefore, after the flow path and the communicating holes are filled with liquid, the microfluidic chip is easily inserted into the slot while suppressing bubbles from mixing with the liquid. When the microfluidic chip is inserted into the slot, when the liquid filled with the communicating holes contacts the lower surface of the upper wall structure, the liquid moves in the slot while being continuously subjected to shear force from the lower surface, so when the communicating holes reach the desired hole, the amount of liquid in the communicating holes is reduced, and bubbles may be mixed into the liquid. The communicating holes overlap with the grooves formed on the lower surface of the upper wall structure while moving in the slot, thereby minimizing the time that the liquid contacts the lower surface of the upper wall structure, and suppressing bubbles from mixing with the liquid.

[0157] Item 10. The microfluidic chip according to Item 9, characterized in that:

[0158] At least one observation window is formed on the upper wall structure of the retaining frame and passes through the upper wall structure.

[0159] The groove extends across the observation window, with the hole disposed on the deep side of the slot being present on an extension line.

[0160] In such a case, the liquid in the flow path of the microfluidic chip can be observed through the observation window that passes through the upper wall structure. Since the observation window passes through the upper wall structure, when the microfluidic chip is inserted into the slot and the connecting hole of the microfluidic chip passes through the observation window, the liquid filled in the connecting hole arranged on the deep side of the slot is temporarily not opposite to the lower surface of the upper wall structure, and then, it is opposite to the lower surface of the upper wall structure again. In the case where there is no groove on the lower surface of the upper wall structure, when the liquid filled in the connecting hole is opposite to the lower surface of the upper wall structure again, the liquid is subjected to a large shear force from the lower surface of the upper wall structure, and the amount of liquid in the connecting hole is greatly reduced, and bubbles may be mixed into the liquid. By extending the groove across the observation window, it is possible to suppress the amount of liquid in the connecting hole from being reduced and bubbles from being mixed in when the liquid filled in the connecting hole passes through the observation window.

[0161] Item 11. The microfluidic device according to any one of Items 6 to 10, characterized in that

[0162] The microfluidic device comprises a plurality of microfluidic chips.

[0163] The retaining frame has:

[0164] A plurality of slots for inserting a plurality of the microfluidic chips and extending in a horizontal direction;

[0165] A plurality of holes communicating with a plurality of communicating holes of a plurality of the microfluidic chips; and

[0166] The connecting flow path is formed in the upper wall structure and connects the plurality of holes arranged on the deep side of the slot.

[0167] In such a case, the liquid can be transferred from the flow path of one microfluidic chip to the flow path of another microfluidic chip via the connecting flow path provided in the upper wall structure of the holder.

[0168] Item 12. The microfluidic device according to claim 11, characterized in that

[0169] The upper wall structure includes a connection flow path chip fixed to the holder, and the connection flow path is formed in the connection flow path chip.

[0170] In such a case, after the liquid is filled into the connecting flow path, the connecting flow path chip can be fixed to the holder. In the use of the microfluidic device, after the liquid is filled into the connecting flow path, the liquid can be transferred from the flow path of one microfluidic chip to the flow path of another microfluidic chip to suppress the mixing of air into the liquid.

[0171] Description of Reference Numerals

[0172] 1 Cage

[0173] 2 Microfluidic Chip

[0174] 3 Connect the flow chip

[0175] 4 Slots

[0176] 5 Opening

[0177] 6 Tablet

[0178] 6a First upper surface

[0179] 6b First lower surface

[0180] 8 Manifold board

[0181] 8a Second upper surface

[0182] 8b Second lower surface

[0183] 10 First communication hole

[0184] 12 Second communication hole

[0185] 14 Culture chamber

[0186] 16 First Access

[0187] 18 Second Path

[0188] 19 Upper wall structure

[0189] 20 upper wall

[0190] 22 Middle Wall

[0191] 24 lower wall

[0192] 26 First Hole

[0193] 28 Second hole

[0194] 29 Observation window

[0195] 30 Connecting the flow path

[0196] 32 first slot

[0197] 34 Second slot

[0198] 36 First annular seal

[0199] 38 Second annular seal

[0200] 46 Third annular seal

[0201] 48 Fourth annular seal

[0202] 40 first supporting structure

[0203] 42 Second support structure

[0204] 50 culture medium

Claims

1. A microfluidic chip, inserted into a slot extending in a horizontal direction, characterized in that: include: upper surface; a lower surface located on the opposite side of the upper surface; a flow path of the fluid, arranged between the upper surface and the lower surface; and two communicating holes, communicating with the flow path and opening on the upper surface, The line segment connecting the two communicating holes is inclined relative to the insertion direction of the microfluidic chip into the slot.

2. The microfluidic chip according to claim 1, characterized in that: The two communicating holes are arranged at both ends of the flow path, The flow path extends linearly along a line segment connecting the two communicating holes.

3. The microfluidic chip according to claim 1, characterized in that: The microfluidic chip further comprises two annular seals formed of an elastic body, the two annular seals are fixed to the upper surface or formed on the upper surface and respectively surround the communicating holes.

4. The microfluidic chip according to claim 3, characterized in that: The microfluidic chip further includes at least two supporting structures, which are fixed at positions inside the flow path overlapping with the annular seal to ensure the height of the flow path to prevent the flow path from being blocked.

5. A microfluidic device, characterized in that: include: At least one microfluidic chip according to claim 1; and a holder for holding the microfluidic chip, The retaining frame has: At least one slot for inserting the microfluidic chip and extending in a horizontal direction; an upper wall structure, which is opposite to the upper surface of the microfluidic chip when the microfluidic chip is inserted into the slot; a lower wall, which contacts the lower surface of the microfluidic chip when the microfluidic chip is inserted into the slot; and Two holes are formed in the upper wall structure, and when the microfluidic chip is inserted into the slot, the two holes are respectively communicated with the two communicating holes of the microfluidic chip.

6. A microfluidic device, characterized in that: include: At least one microfluidic chip according to claim 2 or 3; and a holder for holding the microfluidic chip, The retaining frame has: At least one slot for inserting the microfluidic chip and extending in a horizontal direction; an upper wall structure, which is opposite to the upper surface of the microfluidic chip when the microfluidic chip is inserted into the slot; a lower wall, which contacts the lower surface of the microfluidic chip when the microfluidic chip is inserted into the slot; and Two holes are formed in the upper wall structure, and when the microfluidic chip is inserted into the slot, the two holes are respectively communicated with the two communicating holes of the microfluidic chip.

7. A microfluidic device, characterized in that: include: At least one microfluidic chip according to claim 4; and a holder for holding the microfluidic chip, The retaining frame has: At least one slot for inserting the microfluidic chip and extending in a horizontal direction; an upper wall structure, which, when the microfluidic chip is inserted into the slot, is opposite to the upper surface of the microfluidic chip and compresses the annular seal toward the upper surface; a lower wall, which contacts the lower surface of the microfluidic chip when the microfluidic chip is inserted into the slot; and Two holes are formed in the upper wall structure, and when the microfluidic chip is inserted into the slot, the two holes are respectively communicated with the two communicating holes of the microfluidic chip.

8. The microfluidic device according to any one of claims 5 to 7, characterized in that: At least two grooves are formed on the lower surface of the upper wall structure of the holder. The grooves extend linearly along the insertion direction of the microfluidic chip into the slot, and the two holes are respectively located on the extension lines of the grooves.

9. The microfluidic device according to claim 8, characterized in that: At least one observation window is formed on the upper wall structure of the retaining frame and passes through the upper wall structure. The groove having the two holes on an extension line extends across the observation window, and the two holes are arranged on the deep side of the slot.

10. The microfluidic device according to any one of claims 5 to 7, characterized in that: The microfluidic device comprises a plurality of microfluidic chips. The retaining frame has: A plurality of slots for inserting a plurality of the microfluidic chips and extending in a horizontal direction; A plurality of holes communicating with a plurality of communicating holes of a plurality of the microfluidic chips; and The connecting flow path is formed in the upper wall structure and connects the plurality of holes arranged on the deep side of the slot.

11. The microfluidic device according to claim 10, characterized in that: The upper wall structure includes a connection flow path chip fixed to the holder, and the connection flow path is formed in the connection flow path chip.

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