Microfluidic device

Abstract

Provided is a microfluidic device capable of effectively suppressing evaporation of a liquid injected into the microfluidic device. The microfluidic device includes a plate having a first main surface, a second main surface on the opposite side of the first main surface, and an outer side surface connecting the first main surface and the second main surface, the first main surface having an opening region in which a plurality of openings for injecting a fluid are formed, and an outer side reservoir including a bottomed opening erected toward a position higher than the first main surface on the outer side of the opening region and capable of being filled with a liquid.

Description

Technical Field

[0001] This invention relates to microfluidic devices. Background Technology

[0002] Previously, cell and tissue cultures used for analysis and other purposes were performed using culture dishes and plates. However, cell and tissue cultures using culture dishes and plates are conducted in a two-dimensional (planar) environment, making it impossible to reproduce the microenvironment outside the cells. Therefore, in recent years, a microfluidic device (also known as a "cell culture chip," "biochip," "microchip," or "microfluidic chip") has been proposed, which possesses microfluidic pathways capable of creating three-dimensional (stereoscopic) cell culture and experimental environments, a feature difficult to achieve with conventional methods. An example of such a microfluidic device is disclosed in Patent Document 1.

[0003] However, when a portion of the liquid injected into the culture plate evaporates, the concentration of the fluid changes, significantly impacting the processing and analysis results. Therefore, it is necessary to suppress the evaporation of the liquid injected into the culture plate and reduce changes in liquid concentration. Patent Document 2 discloses a method for suppressing the evaporation of liquid components injected into a conventional culture plate without microfluidic devices by arranging multiple groove-shaped liquid storage tanks around the holes of the culture plate, maintaining a high humidity atmosphere around the holes.

[0004] Existing technical documents

[0005] Patent documents

[0006] Patent Document 1: Japanese Patent Application Publication No. 2018-047614

[0007] Patent Document 2: US Patent No. 5,587,321 Summary of the Invention

[0008] The problem that the invention aims to solve

[0009] In microfluidic devices, it is desirable to reduce concentration changes associated with liquid evaporation. According to the inventors' investigation, since the volume of liquid injected into the microfluidic device is less than that injected into a conventional culture plate as disclosed in Patent Document 2, the concentration change of the liquid component accompanying the evaporation of a portion of the liquid component injected into the microfluidic device is greater than the concentration change of the conventional culture plate disclosed in Patent Document 1. Therefore, the inventors have found that evaporation suppression of the liquid component in microfluidic devices requires more precise control than that in conventional culture plates.

[0010] However, since the plate forming the microfluidic path is thinner and smaller than conventional culture plates, even if a liquid storage tank is set on the plate forming the microfluidic path as described in Patent Document 2, it is difficult to ensure a sufficient liquid volume and the evaporation is not adequately suppressed.

[0011] The purpose of this invention is to provide a microfluidic device that can effectively suppress the evaporation of liquid injected into the microfluidic device.

[0012] Methods used to solve problems

[0013] The microfluidic device of the present invention comprises: a plate having a first main surface, a second main surface opposite to the first main surface, and an outer surface, wherein the first main surface has an opening region having a plurality of openings for injecting fluid, and the outer surface connects the first main surface and the second main surface;

[0014] And a liquid storage tank, which includes a bottomed opening erected on the outer side of the opening area at a position above the first main surface and capable of being filled with liquid, including a liquid storage tank having a bottomed opening capable of being filled with liquid.

[0015] Although described in detail later, in the microfluidic device of the present invention, since the bottomed opening (bottomed opening) of the liquid reservoir is located higher than the first main surface of the plate, the liquid reservoir can be made deeper compared to the case where the liquid reservoir is provided inside a thinner plate. As a result, the liquid reservoir of the present invention can increase the amount of liquid that can be stored compared to a liquid reservoir provided inside a plate. Therefore, sufficient liquid volume can be ensured to maintain a high humidity atmosphere in the opening area. Thus, the evaporation of liquid components from the liquid injected through the opening can be effectively suppressed.

[0016] Furthermore, the microfluidic device may also include a retainer having an inner wall surface and a support surface, the inner wall surface being located outside the outer side of the plate, and the support surface supporting the second main surface side of the plate.

[0017] Alternatively, the liquid storage tank may include: a bottom located outside the opening area of ​​the plate; an inner frame erected on the inner side away from the inner wall surface of the retainer, extending upward from the bottom towards a position above the first main surface; and an outer frame erected between the inner wall surface and the inner frame extending upward from the bottom.

[0018] Alternatively, the liquid storage tank and the retaining body can be separately constructed, with the bottom located above the first main surface. Compared to a liquid storage tank disposed on the same plane as the opening area, a larger bottom surface can be formed in the liquid storage tank, thus increasing the amount of liquid that can be stored. This ensures sufficient liquid volume to maintain a high humidity atmosphere in the opening area.

[0019] Alternatively, the liquid storage tank can be divided into multiple units by a partition plate, and the partition plate connects the inner frame and the outer frame.

[0020] Alternatively, the total area of ​​the inner bottom surface of the liquid storage tank may be more than twice the total area of ​​the openings of the plate.

[0021] Alternatively, a mark indicating the amount of liquid to be replenished may be provided on the inner side of the liquid storage tank.

[0022] Alternatively, at least a portion of the liquid storage tank may be provided with evaporation-promoting materials.

[0023] The microfluidic device of the present invention may also include a cover that covers the opening area and the liquid reservoir in such a way that a gap is formed between the cover and the upper end of the inner frame.

[0024] In the microfluidic device of the present invention, the plate may also be constructed by joining at least two plates, with a space between the joined plates for culturing cells or tissues.

[0025] Invention Effects

[0026] Therefore, it is possible to provide microfluidic devices that can effectively suppress the evaporation of liquid components. Attached Figure Description

[0027] Figure 1 This is a perspective view of the first embodiment of the microfluidic device.

[0028] Figure 2 yes Figure 1 A cross-sectional view of plane A1.

[0029] Figure 3 This is an exploded perspective view of the first embodiment of the microfluidic device.

[0030] Figure 4 This is a top view of the board.

[0031] Figure 5 yes Figure 4 A cross-sectional view along line A2-A2.

[0032] Figure 6 yes Figure 3 A cross-sectional view of the retainer on the A3 plane.

[0033] Figure 7 yes Figure 1 A cross-sectional view of a microfluidic device on the A4 plane.

[0034] Figure 8 This is a reference diagram of a microfluidic device without separators.

[0035] Figure 9 It is magnification Figure 3 The A5 area is shown, and a diagram with markings is added.

[0036] Figure 10 This is a three-dimensional view of a modified example of a microfluidic device.

[0037] Figure 11 yes Figure 10 A cross-sectional view of plane A6.

[0038] Figure 12 This is a cross-sectional view of a second embodiment of the microfluidic device.

[0039] Explanation of reference numerals in the attached figures

[0040] 1: Board

[0041] 1a: (of the board) the first main face

[0042] 1b: (of the board) the second main face

[0043] 1c: (of a board) outer surface

[0044] 3, 8: Storage tank

[0045] 4: Central Region

[0046] 5, 6: Maintain body

[0047] 7: Cover

[0048] 12: First substrate

[0049] 13: Second substrate

[0050] 21: Opening

[0051] 24: slot

[0052] 27: Slit-like opening

[0053] 31: Bottom

[0054] 32, 42: Inner frame

[0055] 32e, 42e: (upper edge of the inner frame)

[0056] 33: Outer frame

[0057] 35: Divider

[0058] 38: Liquid

[0059] 52: Inner wall surface

[0060] 53: Support surface

[0061] 100, 200, 300, 400: Microfluidic devices Detailed Implementation

[0062] Embodiments of the microfluidic device will be described with reference to the accompanying drawings. It should be noted that the drawings disclosed herein are schematic illustrations only. That is, the aspect ratios in the drawings may not necessarily match the actual aspect ratios, and the aspect ratios may not necessarily be consistent between different drawings.

[0063] The following explanation will refer to the XYZ coordinate system as appropriate. Furthermore, in this specification, when representing direction, positive and negative directions are distinguished, such as "+X direction" and "-X direction," using positive and negative signs. When representing direction without distinguishing positive and negative directions, it is simply referred to as "X direction." That is, in this specification, when only "X direction" is referred to, it includes both "+X direction" and "-X direction." The same applies to the Y and Z directions. In this embodiment, the horizontal plane is parallel to the XY plane, and the vertical direction is the -Z direction. The plate described later is shown parallel to the XY plane.

[0064] <First Implementation>

[0065] A first embodiment of the microfluidic device will be described. Figure 1 This is a three-dimensional view of the microfluidic device 100. Figure 2 yes Figure 1 A cross-sectional view of plane A1 (the plane parallel to plane YZ). Figure 3 This is an exploded perspective view of the microfluidic device 100. The microfluidic device 100 includes a plate 1 for culturing and analyzing cells or tissues, a reservoir 3, and a holder 5 supporting the plate 1 from below. (Refer to...) Figure 2 as well as Figure 3 The microfluidic device 100 is formed by embedding a plate 1 into the inner side of the holder 5 from the upper side (+Z side) of the holder 5, and embedding a liquid storage tank 3 into the inner side of the holder 5 from the upper side of the embedded plate 1.

[0066] [plate]

[0067] Explanation of board 1. Figure 4 This is a top view of plate 1. Plate 1 is rectangular, shown with its edges extending along the X and Y directions. Figure 5 yes Figure 4 A cross-sectional view along line A2-A2. (Refer to...) Figure 4 as well as Figure 5The plate 1 has: a first main surface 1a having an opening region B1 with multiple openings 21 and slit-like openings 27 for injecting fluid containing cells or tissues; a second main surface 1b opposite to the first main surface 1a; and an outer surface 1c connecting the first main surface 1a and the second main surface 1b. The plate 1 is formed by joining a first substrate 12 and a second substrate 13. The openings 21 are provided in the first substrate 12 on the surface not joined to the second substrate 13. The surface of the first substrate 12 joined to the second substrate 13 has a groove 24 for culturing and analyzing cells or tissues. In this embodiment, one groove 24 is connected to two openings 21.

[0068] The second substrate 13 is joined to the first substrate 12 by covering a groove 24 connected to the two openings 21. The groove 24 functions as a hollow flow path sandwiched between the two substrates (12, 13) through the main surfaces of the first substrate 12 and the second substrate 13 joining each other. This hollow flow path is a microfluidic path with a width and depth on the micrometer scale. In the microfluidic path, a small volume of fluid can be injected from the two connected openings 21, or fluid can be discharged from the microfluidic path through the openings 21. The microfluidic path is used as a culture medium or analytical site for cells and tissues. When fluid is present in the microfluidic path, it is not necessarily in a state where the fluid is flowing. For example, for culturing cells or tissues, there may be a state without fluid flow, such as a state where fluid containing cells is stored.

[0069] The bonding of the first substrate 12 and the second substrate 13 is performed, for example, by irradiating the bonding surfaces of the first substrate 12 and the second substrate 13 with 172 nm ultraviolet light to activate the bonding surfaces and achieve adhesion. Furthermore, in this embodiment, the thickness (dimension in the Z direction) of the second substrate 13 is thinner than the thickness (dimension in the Z direction) of the first substrate 12. When viewed from the +Z direction, the second substrate 13 is the same size as the first substrate 12 or smaller than the first substrate 12.

[0070] Examples of materials constituting the first substrate 12 or the second substrate 13 include polymethyl methacrylate (PMMA), polycarbonate (PC), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polystyrene (PS), and silicone resins. In this embodiment, COP, which has high heat resistance and transparency and low self-fluorescence during fluorescence detection for analysis, is used in both the first substrate 12 and the second substrate 13. Alternatively, materials combining two or more of the aforementioned resin materials may be used in both the first substrate 12 and the second substrate 13. Furthermore, the materials used in the first substrate 12 and the second substrate 13 may be different.

[0071] The shape of plate 1 is not particularly limited, and it may not be rectangular. The thickness of plate 1 (dimension in the Z direction) is 10 mm or less, preferably 7 mm, and more preferably 5 mm or less. In addition, plate 1 can be formed by joining three or more substrates, or it can be formed by a single substrate.

[0072] [Maintaining Body]

[0073] Reference Figure 3 The retainer in this embodiment will be described. In this embodiment, the retainer 5 is a frame shape with a central region 4 extending through it. Because the central region 4 of the retainer 5 is through, light can be irradiated from the upper side (+Z side) of the microfluidic device 100, and the light passing through the groove 24 of the plate 1 can be analyzed from the lower side (-Z side) of the microfluidic device 100. Alternatively, light can be irradiated from the lower side of the microfluidic device 100, and the light reflected or scattered inside the groove 24 of the plate 1 can be analyzed from the lower side of the microfluidic device 100.

[0074] The holder 5 can also be a shape in which the central region 4 of the holder 5 is not penetrated, i.e., a bottomed shape. When the holder 5 is a bottomed shape and is difficult to transmit light, light can be irradiated from the top of the microfluidic device 100, and the light reflected or scattered inside the groove 24 of the plate 1 can be received on the top of the holder 5 for analysis.

[0075] Figure 6 yes Figure 3 A cross-sectional view of the retainer 5 on the A3 plane (the plane parallel to the XZ plane). When referring to... Figure 2 as well as Figure 6 In this embodiment, the retaining body 5 has an inner wall surface 52 located outside the outer surface 1c of the plate 1 in the XY plane and a support surface 53 on the side of the second main surface 1b on which the plate 1 is mounted. The inner wall surface 52 is disposed opposite to the outer surface 1c of the plate 1. The support surface 53 contacts the second main surface 1b of the plate 1. In this embodiment, the retaining body 5 is formed to surround the outer surface 1c of the plate 1. Moreover, the inner wall surface 52 surrounds all the outer surfaces 1c of the plate 1, and the support surface 53 supports the area of ​​the second main surface 1b except for the opening region B1 of the plate 1.

[0076] The material of the retainer 5 may include, for example, polymethyl methacrylate (PMMA), polycarbonate (PC), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polystyrene (PS), silicone, or other resin materials, or metal materials. In this embodiment, PS is used in the retainer 5.

[0077] [Liquid Storage Tank]

[0078] Reference Figure 2 as well as Figure 3The storage tank 3 will be described below. The storage tank 3 is a container with a bottom opening, configured to store liquid. When liquid containing cells or tissue is injected into the plate 1 for culture, analysis, or storage, it is necessary to suppress the evaporation of the liquid injected into the plate 1. To suppress liquid evaporation, a liquid is stored in the storage tank 3 to maintain a high humidity atmosphere in the plate 1. The evaporation of the liquid stored in the storage tank 3 can suppress the decrease in humidity of the atmosphere in the plate 1.

[0079] Here, it is assumed that even if a liquid storage tank is provided inside the plate 1, it is impossible to provide a liquid storage tank deeper than the thickness of the plate 1. However, as in this invention, by providing a liquid storage tank 3 outside the plate 1, a liquid storage tank deeper than the thickness of the plate 1 can be provided. Therefore, compared to the case where a liquid storage tank is provided inside the plate 1, the present invention, which provides a liquid storage tank 3 outside the plate 1, can increase the amount of liquid that can be stored. Thus, sufficient liquid volume can be ensured, and therefore the atmosphere of the plate 1 can be maintained at a high humidity. In addition, the liquid stored in the liquid storage tank 3 decreases with evaporation, so it is necessary to replenish the liquid periodically. The liquid storage tank 3 of this invention has a larger capacity than the liquid storage tank provided inside the plate 1, so the replenishment frequency can be reduced to, for example, once every 1 to 3 days. In addition, the liquid storage tank of this embodiment can store 3 ml or more.

[0080] In this embodiment, the liquid storage tank 3 has a frame shape with the central region 4 extending through it (see reference). Figure 3 The liquid storage tank 3 has a bottom opening positioned above the first main surface 1a of the plate 1. The liquid storage tank 3 with the bottom opening includes a bottom 31, an inner frame 32 extending upwards (in the +Z direction) from the bottom 31, and an outer frame 33 (see reference). Figure 2 The bottom 31 is located outside the opening area B1 of the plate 1. The inner frame 32 is located on the inner side away from the inner wall surface 52 of the retainer 5. The outer frame 33 is located between the inner wall surface 52 and the inner frame 32. In this embodiment, the outer frame 33 is in contact with the inner wall surface 52 at least in a portion. The liquid storage tank 3 is configured to store liquid in a space that is formed by the bottom 31, the inner frame 32 and the outer frame 33, thus having a bottom cylindrical shape.

[0081] Water can be used as the liquid stored in the storage tank 3. In addition, antibiotics or other agents can be added to the liquid stored in the storage tank 3 to prevent the growth of mold and other microorganisms in the culture medium.

[0082] The liquid storage tank 3 has a larger volume as its depth increases. Here, the upper end 32e of the inner frame 32 is located at a position higher than the first main surface 1a of the plate 1 (on the +Z side) (refer to...). Figure 2 This means that, compared to having a liquid storage tank inside plate 1, a deeper liquid storage tank can be designed, increasing the amount of liquid that can be stored.

[0083] like Figure 1 as well as Figure 3 As shown, in this embodiment, the liquid reservoir 3 and the retainer 5 are separately constructed. As described above, the microfluidic device 100 is formed by embedding the liquid reservoir 3 inside the retainer 5 after the plate 1 is embedded in it. Here, the bottom 31 of the embedded liquid reservoir 3 is located above the first main surface 1a in such a way that it covers the outer periphery of the plate 1 (the outer region of the opening region B1) (see reference). Figure 2 Because the storage tank 3 can be stacked on the plate 1, the area of ​​the bottom 31 of the storage tank 3 can be made larger compared to the storage tank located on the outer side of the same plane as the plate 1. This increases the liquid volume of the storage tank 3. The storage tank 3 itself is designed not to cover the size and shape of the opening area B1, allowing fluid to be injected into the opening 21 while the storage tank 3 is embedded in the retainer 5.

[0084] In this embodiment, the liquid storage tank 3 is divided into multiple units by a partition plate 35 connecting the inner frame 32 and the outer frame 33 (see reference). Figure 3 In this embodiment, the liquid storage tank 3 has 24 units, but the number of units is not particularly limited. (See reference...) Figure 7 as well as Figure 8 The effect of dividing the space into multiple units will be explained. Figure 7 In Figure 1 When the microfluidic device 100 is tilted at a specified angle (here, 45 degrees around the X-axis) and Figure 1 The cross-sectional view corresponds to the A4 plane (the plane parallel to the YZ plane). Additionally, in Figure 7 The diagram illustrates the state in which liquid 38 is injected into each unit of the liquid reservoir 3 of the microfluidic device 100.

[0085] In order to analyze or observe cells or tissues contained within the microfluidic device 100 (especially within the groove 24), the microfluidic device 100 is sometimes tilted. In addition, during the handling of the microfluidic device 100, the microfluidic device 100 may sometimes tilt unintentionally or unavoidably. Figure 7 The attached diagram simulates this state.

[0086] Figure 8 and Figure 7 The attached images are different, imitating Figure 7 The figure shows a cross-sectional view of the microfluidic device 200 when the liquid reservoir 3 is not divided into multiple units. (See figure) Figure 8 As shown, when the microfluidic device 200 is tilted at a specified angle (45 degrees around the X-axis), the liquid 38 is biased towards the bottom of the reservoir 3 and accumulates, and the liquid 38 overflows from the reservoir 3 and flows out.

[0087] In contrast, in the case where the liquid storage tank 3 is divided into units by the partition plate 35 (refer to...) Figure 7Even if the microfluidic device 100 is tilted, the liquid 38 will not easily flow over the individual units. That is, if... Figure 7 The structure shown is the same as Figure 8 Compared to the configuration shown, even when the microfluidic device is tilted, the liquid is less likely to flow out of the reservoir 3.

[0088] As shown above, by providing a partition plate 35 in the liquid storage tank 3, the liquid in the liquid storage tank 3 is less likely to flow out even when the microfluidic device 100 is tilted at a predetermined angle. Furthermore, during the handling of the microfluidic device 100, the liquid in the liquid storage tank 3 with the partition plate 35 is less likely to flow out. The partition plate 35 can be integrally formed with the base 31, inner frame 32, and outer frame 33, or it can be configured for later installation.

[0089] In order to inject an appropriate amount of liquid into the storage tank 3, a mark indicating the amount of liquid to be added can also be set on the storage tank 3. Figure 9 yes Figure 3 An enlarged view of area A5 is provided, in which an example of such marking is additionally shown. In the reservoir 3, a protrusion 36, indicating the maximum liquid level, is provided on the inner surface of the outer frame 33. The operator or replenishing device replenishes liquid to the reservoir 3 until the liquid level reaches the protrusion 36.

[0090] The shape of the protrusion 36 is not particularly limited. It can also be a recess, a printed mark, or a mark other than the protrusion 36. The mark can be provided on the outer surface or on the inner frame 32. The mark can be provided in all units or only in some units. The height position of the mark can also be changed for each unit constituting the liquid storage tank 3, and an appropriate liquid volume can be set for each unit.

[0091] The bottom 31, inner frame 32, outer frame 33, and partition plate 35 of the liquid storage tank 3 can be made of materials such as polymethyl methacrylate (PMMA), polycarbonate (PC), cyclic olefin copolymer (COC), cyclic olefin polymer (COP), polystyrene (PS), silicone, or other resin materials, or metal materials. In this embodiment, PS is used in the liquid storage tank 3. An evaporation-promoting material (e.g., a hygroscopic gel, a sponge-like absorbent material, or a heat sink, etc., that increases the area of ​​the gas-liquid interface) can also be disposed inside at least a portion of the liquid storage tank 3. If an evaporation-promoting material is disposed in the liquid storage tank 3, the atmosphere can be maintained at a high humidity, thus easily suppressing the evaporation of liquid from the plate 1.

[0092] However, the ease of evaporation of the liquid from plate 1 and storage tank 3 is related to the area of ​​the gas-liquid interface. In plate 1, when the number of openings 21 is large, or when the area of ​​each opening 21 is large, the total area of ​​the openings 21 in plate 1 becomes larger. If the total area of ​​the openings 21 becomes larger, the area of ​​the gas-liquid interface in the openings 21 becomes larger, and the liquid becomes easier to evaporate. Similarly, the ease of evaporation of the liquid from storage tank 3 also increases as the area of ​​the gas-liquid interface in storage tank 3 increases.

[0093] To suppress the evaporation of liquid from opening 21, the area of ​​the gas-liquid interface in the storage tank 3 can be designed to be the same size as the total area of ​​opening 21. The size of the gas-liquid interface area in the storage tank 3 varies significantly depending on the size of the inner bottom surface of the storage tank. Therefore, it is preferable that the total area of ​​the inner bottom surface of the storage tank 3 is more than twice the total area of ​​opening 21, and even better if it is more than ten times. By setting it to more than twice, and even more than ten times, the evaporation rate from the entire storage tank 3 is greater than the evaporation rate from the entire opening 21, which can suppress the evaporation of liquid from opening 21. To control the evaporation rate from the storage tank 3, a heat source or a heat-conducting component from an external heat source can also be placed near the storage tank 3.

[0094] If the microfluidic device 100 is stored in a storage chamber (also called an incubator) with a high humidity environment (e.g., humidity above 95%), water vapor in the storage chamber forms the atmosphere of the microfluidic device 100, making it easy to control the humidity of the atmosphere of the microfluidic device 100. This further suppresses the evaporation of liquid components from the opening 21 of the microfluidic device 100. However, due to the opening and closing of the storage chamber door, the humidity may not be strictly maintained. Therefore, even when the plate 1 is stored in the storage chamber, the liquid storage tank 3 helps to control the humidity of the atmosphere around the plate 1.

[0095] Reference Figure 10 as well as Figure 11 A modified example of a microfluidic device is shown. Figure 10 This is a perspective view of the microfluidic device 300. In addition to the plate 1, the reservoir 3, and the holder 5, the microfluidic device 300 also includes a cover 7. Figure 10 In the middle, the plate 1 and the liquid storage tank 3 are embedded in the retainer 5, and the cover 7 is removed from the retainer 5. Figure 11 yes Figure 10 A cross-sectional view of plane A6 (the plane parallel to plane YZ). However, it is shown with the cover 7 installed on the retainer 5.

[0096] like Figure 11As shown, the cover 7 is installed on the retainer 5 to cover the opening area B1 and the liquid storage tank 3. This confines the atmosphere in the opening area B1 to a small space, making humidity control easier. Furthermore, a gap d1 is formed between the cover 7 and the upper end 32e of the inner frame 32 of the liquid storage tank 3. Therefore, even when the cover 7 is installed on the retainer 5, the liquid stored in the liquid storage tank 3 will evaporate and flow into the opening area B1.

[0097] Figure 11 The cover 7 and the holder 5 shown have a tiny, ventilated gap (not shown). Even when the cover 7 is installed on the holder 5, if the microfluidic device 300 is configured to allow ventilation between the inside and outside, the high-humidity atmosphere inside the storage tank can flow into the microfluidic device 300. Furthermore, in a ventilated microfluidic device 300, when gas flows in from the outside, the flowing gas passes near the liquid surface of the storage tank 3, thus promoting the evaporation of the liquid in the storage tank 3. In addition, to maintain the acidity of the liquid injected into the microfluidic device, CO2 is sometimes added at a concentration higher than atmospheric level, but the tiny gap between the cover 7 and the holder 5 also functions as an inlet for CO2.

[0098] The cover 7 can be made of a light-transmitting material. Analysis can be performed while the cover 7 is covering the plate 1. In addition, a port for injecting liquid into the liquid storage tank 3 can be provided on the cover 7.

[0099] <Second Implementation>

[0100] Reference Figure 12 A second embodiment of the microfluidic device will be described. Figure 12 The microfluidic device 400 shown has a reservoir 8 including a holder 6. That is, the holder 6 and the reservoir 8 are integrated. In this embodiment, the upper end 42e of the inner frame 42 is also located higher than the first main surface 1a of the plate 1. That is, it is erected with a bottom opening facing upwards from the first main surface.

[0101] The first embodiment, its variations, and the second embodiment have been described above. However, the present invention is not limited to any of the above embodiments, and various changes or improvements can be made to the embodiments without departing from the spirit of the present invention.

[0102] Industrial availability

[0103] The applications of microfluidic devices described above include cell and tissue culture and analysis. However, the microfluidic devices of the present invention can also be applied beyond cell and tissue culture and analysis. For example, the microfluidic devices of the present invention can also be used for mixing, separating, reacting, synthesizing, extracting, or analyzing chemical reagents.

Claims

1. A microfluidic device, characterized in that, have: The plate has a first main surface, a second main surface opposite to the first main surface, and an outer surface. The first main surface has an opening region with a plurality of openings for injecting fluid. The outer surface connects the first main surface and the second main surface. The liquid storage tank includes a bottomed opening on the outer side of the opening area, which is positioned above the first main surface, and is capable of being filled with liquid. as well as The retainer has an inner wall surface and a supporting surface, the inner wall surface being located outside the outer side of the outer side of the plate, and the supporting surface supporting the second main surface side of the plate. The liquid storage tank includes: a bottom located outside the opening area of ​​the plate; and an inner frame located inside the inner wall surface of the retainer, erected from the bottom towards a position above the first main surface. And an outer frame, which is erected from the bottom upwards between the inner wall surface and the inner frame. The liquid storage tank and the retaining body are separately constructed, and the bottom is located above the first main surface.

2. The microfluidic device as described in claim 1, characterized in that, The liquid storage tank is divided into multiple units by a partition plate, which connects the inner frame and the outer frame.

3. The microfluidic device as described in claim 1 or 2, characterized in that, The total area of ​​the inner bottom surface of the liquid storage tank is more than twice the total area of ​​the openings of the plate.

4. The microfluidic device as described in claim 1 or 2, characterized in that, The inner side of the liquid storage tank is marked with a mark indicating the amount of liquid to be replenished.

5. The microfluidic device as described in claim 1 or 2, characterized in that, At least a portion of the liquid storage tank is provided with evaporation-promoting material.

6. The microfluidic device as described in claim 1 or 2, characterized in that, The microfluidic device includes a cover that covers the opening area and the reservoir in such a way that a gap is formed between the cover and the upper end of the reservoir.

7. The microfluidic device as described in claim 1 or 2, characterized in that, The plate is constructed by joining at least two plates together. There is space between the joined plates that is capable of culturing cells or tissues.

Images