阅读说明：本技术 微流体器件 (Microfluidic device ) 是由 竹田昂司 小柳博 于 2021-06-04 设计创作，主要内容包括：本发明提供一种能够降低观察面的高度的偏差的微流体器件。具备：板,在内部形成有流路；以及保持体,保持所述板,所述保持体具有：第一保持部件,与所述板的第一主面的至少外周缘抵接；第二保持部件,与所述第一主面的相反侧的所述板的第二主面的至少外周缘抵接；以及固定部件,在将所述板夹在所述第一保持部件与所述第二保持部件之间的状态下,固定所述第一保持部件与所述第二保持部件。(The invention provides a microfluidic device capable of reducing the variation in height of an observation surface. The disclosed device is provided with: a plate having a flow path formed therein; and a holding body that holds the plate, the holding body having: a first holding member that abuts at least an outer peripheral edge of the first main surface of the plate; a second holding member that abuts at least an outer peripheral edge of a second main surface of the plate on an opposite side of the first main surface; and a fixing member that fixes the first holding member and the second holding member in a state where the plate is sandwiched between the first holding member and the second holding member.)

1. A microfluidic device is provided with:

a plate having a flow path formed therein; and

a holding body that holds the plate,

the holding body has: a first holding member that abuts at least an outer peripheral edge of the first main surface of the plate; a second holding member that abuts at least an outer peripheral edge of a second main surface of the plate on an opposite side of the first main surface; and a fixing member that fixes the first holding member and the second holding member in a state where the plate is sandwiched between the first holding member and the second holding member.

2. The microfluidic device of claim 1,

the plate and the first and second holding members are respectively made of resin, the water absorption rate of the resin constituting the first and second holding members is higher than the water absorption rate of the resin constituting the plate, and the hardness of the plate is harder than the hardness of the first and second holding members.

3. The microfluidic device of claim 1 or 2,

a plurality of openings for injecting a fluid into the flow path are formed in a central region of the first main surface of the plate, and the first holding member is in a frame shape abutting against an outer peripheral edge of the first main surface located around the central region.

4. The microfluidic device of claim 1 or 2,

the holding body has a rectangular shape having four sides in a plan view, and the plurality of fixing members are provided at equal intervals on one side.

5. The microfluidic device of claim 1 or 2,

the holding body has a rectangular shape having four sides in a plan view, and the fixing member is provided at the center of one side.

6. The microfluidic device of claim 1 or 2,

the second holding member has a support plate that abuts at least an outer peripheral edge of the second main surface of the plate, and a side wall that rises from the support plate and surrounds an outer side surface of the first holding member,

the fixing member is configured by a locking projection projecting from an outer side surface of the first holding member and a locking hole formed in a side wall of the second holding member into which the locking projection is inserted.

7. The microfluidic device of claim 1 or 2,

the second holding member is provided with a protruding portion that abuts against a side surface of the plate.

8. The microfluidic device of claim 1 or 2,

the second holding member is provided with a projection which engages with a recess provided in a side surface of the plate to position the plate with respect to the second holding member.

Technical Field

The present invention relates to microfluidic devices.

Background

Conventionally, cell and tissue culture has been performed using a culture dish or plate. Since the culture of cells and tissues using these culture dishes or plates is performed in a two-dimensional (planar) environment, the extracellular microenvironment cannot be reproduced. Therefore, in recent years, microfluidic devices (also referred to as "cell culture chips", "biochips", "microchips", and the like) having a micro flow path capable of creating a three-dimensional (three-dimensional) cell culture/experiment environment have been proposed, which have been difficult to realize by conventional methods.

For example, patent document 1 describes a microfluidic device in which two substrates are bonded to each other, and a flow path surrounded by a bonding portion of the two substrates to be bonded is formed by a flow path forming step formed on at least one of the substrates.

However, it is known to provide an analyzer with a module in which a plurality of analysis plates are housed in a holder (see patent document 2). The holder has a recess corresponding to a projection provided at an end of the analysis plate, and the analysis plate is fixed to the holder by fitting the projection into the recess.

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open publication No. 2019-78707

Patent document 2: japanese patent laid-open publication No. 2019-105528

Disclosure of Invention

Problems to be solved by the invention

A microfluidic device in which a plate having a microchannel is housed in a holder is required. If the microfluidic device in which the plate is housed in the holder can be placed on the stage of the dispensing apparatus, the ease of handling is improved.

However, when the plate is housed in the holder, for example, as in patent document 2, in order to fix the plate to the holder by fitting the projection and the recess, the recess needs to have a large size (both height and width) with respect to the projection. In this case, the plate rattles against the holding body. This fluctuation is not preferable because it is related to a variation in height of the observation surface for each timing of observation.

In addition, when the plate is made of resin, deformation such as warpage or undulation may occur in the manufacturing process or the use environment. This distortion is associated with a deviation in the height of the viewing surface of each microfluidic device and is not preferred.

In view of the above problems, an object of the present invention is to provide a microfluidic device capable of reducing variations in height of an observation surface.

Means for solving the problems

The microfluidic device of the present invention includes: a plate having a flow path formed therein; and a holding body that holds the plate, the holding body having: a first holding member that abuts at least an outer peripheral edge of the first main surface of the plate; a second holding member that abuts at least an outer peripheral edge of a second main surface of the plate on an opposite side of the first main surface; and a fixing member that fixes the first holding member and the second holding member in a state where the plate is sandwiched between the first holding member and the second holding member.

According to this configuration, since the holding body is held by the first holding member and the second holding member from the both-side nip plate, the play between the holding body and the plate can be suppressed, and the variation in height of the observation surface at each timing of observation can be reduced. Further, since the first holding member and the second holding member are fixed by the fixing member in a state where the plate is sandwiched between the first holding member and the second holding member, the first holding member, the second holding member, and the plate are integrated and corrected in shape as a whole, and variations in height of the observation surface of each microfluidic device can be reduced.

In the microfluidic device, the following configuration is also possible: the plate and the first and second holding members are respectively made of resin, the water absorption rate of the resin constituting the first and second holding members is higher than the water absorption rate of the resin constituting the plate, and the hardness of the plate is harder than the hardness of the first and second holding members.

According to this configuration, even if the first holding member and the second holding member deform more than the plate with moisture absorption, the plate harder than the first holding member and the second holding member can suppress deformation of the entire microfluidic device.

In the microfluidic device, the following configuration is also possible: a plurality of openings for injecting a fluid into the flow path are formed in a central region of the first main surface of the plate, and the first holding member is in a frame shape abutting against an outer peripheral edge of the first main surface located around the central region.

According to this configuration, since the opening is not covered with the first holding member, the fluid can be reliably injected from the opening into the flow path.

In the micro-fluid device, the holder may have a rectangular shape having four sides in a plan view, and the plurality of fixing members may be provided at equal intervals on one side.

By providing a plurality of fixing members at equal intervals, the first holding member and the second holding member can be reliably fixed in a well-balanced manner.

In the micro-fluid device, the holder may have a rectangular outer shape having four sides in a plan view, and the fixing member may be provided at the center of one side.

By providing the fixing member at the center of the side, the first holding member and the second holding member can be fixed with good balance.

Drawings

Fig. 1 is a perspective view of the microfluidic device of the present embodiment.

Fig. 2 is an exploded perspective view of the microfluidic device shown in fig. 1.

Fig. 3 is a cross-sectional view a-a of the microfluidic device shown in fig. 1.

Fig. 4 is a B-B cross-sectional view of the microfluidic device shown in fig. 1.

Fig. 5 is a top view of the plate.

Fig. 6 is a cross-sectional view C-C of the plate shown in fig. 5.

Fig. 7 is a diagram for explaining a method of evaluating the hardness of a plate.

Fig. 8 is a diagram for explaining a method of evaluating the hardness of the upper frame.

Fig. 9 is a sectional view showing a fixing member according to another embodiment.

Fig. 10 is a perspective view and a sectional view showing a fixing member according to another embodiment.

Description of the reference numerals

1: board

1 a: first main surface

1 b: second main surface

1 c: side part

2: holding body

4: liquid storage tank

10 a: outer peripheral edge of first main surface

10 b: outer peripheral edge of the second main surface

11: first substrate

12: second substrate

13: flow path

14: opening of the container

21: upper frame

22: lower frame

31: locking protrusion

32: locking hole

34: locking claw

35: screw nail

100: microfluidic device

Detailed Description

Embodiments of the microfluidic device of the present invention will be explained. In addition, the drawings are schematically illustrated below, and the dimensional ratio in the drawings does not necessarily coincide with the actual dimensional ratio, and the dimensional ratio does not necessarily coincide between the drawings.

Fig. 1 is a perspective view of the microfluidic device 100, and fig. 2 is an exploded perspective view of the microfluidic device 100. Fig. 3 is a cross-sectional view a-a of the microfluidic device 100 shown in fig. 1. Fig. 4 is a B-B cross-sectional view of the microfluidic device 100 shown in fig. 1. As shown in fig. 1, the microfluidic device 100 has a plate 1 and a holder 2 holding the plate 1.

Hereinafter, the description will be made with reference to the XYZ coordinate system as appropriate. In the present specification, when directions are expressed, positive and negative directions are distinguished, and the directions are described with positive and negative symbols as "+ X direction" and "— X direction". In addition, when the expression direction of the positive and negative directions is not distinguished, only the direction "X" is described. That is, in the present specification, when only "X direction" is described, both "+ X direction" and "— X direction" are included. The same applies to the Y direction and the Z direction. In the present embodiment, the horizontal plane is parallel to the XY plane, and the vertical direction is the-Z direction. The main surface of the plate 1 is parallel to the XY plane.

[ plate ]

Fig. 5 is a plan view of the plate 1. As shown in fig. 2, the board 1 includes a first substrate 11 and a second substrate 12. The second substrate 12 is bonded to the lower surface of the first substrate 11. The first substrate 11 and the second substrate 12 are both substantially rectangular plate-shaped, and the entire panel 1 is substantially rectangular plate-shaped. As shown in fig. 5, the second substrate 12 is smaller than the first substrate 11, and the side surface constituting the second substrate 12 is located inward of the side surface constituting the first substrate 11.

The plate 1 has a first main surface 1a, a second main surface 1b which is a surface opposite to the first main surface 1a, and four side portions 1c connecting the first main surface 1a and the second main surface 1 b. The first main surface 1a is an upper surface of the first substrate 11, and the second main surface 1b is a lower surface of the second substrate 12. The side portions 1c extend in parallel in the X direction or the Y direction, respectively.

Fig. 6 is a cross-sectional view C-C of the plate 1 shown in fig. 5. A flow path 13 is formed inside the plate 1. Specifically, a groove is formed in the lower surface of the first substrate 11, and the second substrate 12 is bonded to the first substrate 11 so as to cover the groove, thereby forming a hollow flow channel 13 sandwiched between the two substrates (11, 12). The hollow flow path is a micro flow path (minute flow path) having a width and a depth of the order of micrometers to millimeters.

A plurality of openings 14 are formed in the central region of the first main surface 1 a. Two openings 14 are connected to one flow path 13. The fluid can be injected into the channel 13 from the two connected openings 14, or can be discharged from the channel 13 through the openings 14. When a fluid is present in the flow path 13, the flow path 13 is not limited to a state in which the fluid flows. For example, the state where no fluid flows, such as a state where a fluid containing cells is stored, is included for the purpose of culturing the cells.

The first substrate 11 has a slit-like gap 15 extending in the Y direction. The voids 15 are formed at a plurality of locations separated in the X direction. Voids 15 are formed between adjacent openings 14. Both ends of the gap 15 are located inside the side portion 1 c. By forming a plurality of slit-like voids 15 in the first substrate 11, warpage and undulation can be easily corrected when the plate 1 is pressed from both sides.

Further, a recess 16 is provided in the side portion 1c of the plate 1 (the side surface of the first substrate 11). As will be described in detail later, the protrusion 223 of the holder 2 is inserted into the recess 16, and the tip of the protrusion 223 contacts the bottom of the recess 16.

Examples of the material constituting the first substrate 11 or the second substrate 12 include resin materials such as polymethyl methacrylate (PMMA), Polycarbonate (PC), cycloolefin copolymer (COC), cycloolefin polymer (COP), Polystyrene (PS), and silicone. In the present embodiment, COP is used for the first substrate 11 and the second substrate 12. In addition, 2 or more of these resin materials may be combined. The materials used for the first substrate 11 and the second substrate 12 may be different from each other.

[ holding body ]

The holder 2 includes an upper frame 21 (an example of a first holding member) and a lower frame 22 (an example of a second holding member). The outer shape of the holding body 2 is rectangular in plan view. As shown in fig. 3, the upper frame 21 and the lower frame 22 are fixed to each other with the plate 1 sandwiched therebetween from above and below.

The upper frame 21 is a rectangular frame as a whole. The frame portion of the upper frame 21 has a rectangular cross section elongated in the Z direction, and has an upper surface 21a, a bottom surface 21b, an inner surface 21c, and an outer surface 21 d. The inner surface 21c is located inward of the side portion 1c of the plate 1 (see fig. 4). That is, the through-hole 21e formed by the four inner side surfaces 21c is smaller than the outer shape of the plate 1. The inner side surface 21c is located horizontally outward of the plurality of openings 14 of the plate 1 (see fig. 1). On the other hand, the outer side surface 21d is located horizontally outward of the side portion 1c of the plate 1 (see fig. 4). Thereby, the bottom surface 21b of the upper frame 21 can be brought into contact with the outer peripheral edge 10a of the first main surface 1a located around the central region in which the plurality of openings 14 are formed.

The thickness of the upper frame 21 in the Z direction is larger than the thickness of the plate 1 in the Z direction. The thickness of the upper frame 21 in the Z direction is larger than the thickness of a support plate 221 (described later) of the lower frame 22 in the Z direction.

The reservoir 4 is formed in the upper frame 21. The reservoir 4 is divided into a plurality of tanks. As shown in fig. 4, the reservoir 4 is a recess formed from the upper surface 21a toward the lower surface 21 b. The purpose of the reservoir 4 is to suppress the variation in concentration of the liquid injected into the plate 1. Since the amount of liquid injected into the plate 1 is very small, the injected liquid may evaporate with time. When the liquid evaporates, the concentration of the liquid remaining in the channel 13 changes, which is not preferable for culturing and observing cells. Therefore, a liquid (for example, water) for controlling the humidity of the atmosphere of the panel 1 is poured into the reservoir 4, and the liquid is stored. This prevents the humidity of the atmosphere in the plate 1 from decreasing, and prevents the liquid injected into the plate 1 from evaporating.

An engagement projection 31 projecting outward is formed on the outer side surface 21d of the upper frame 21. Three locking projections 31 are provided on the outer surface 21d parallel to the X direction at equal intervals in the X direction. The middle locking projection 31 of the three locking projections 31 is provided in the X-direction center portion of the outer side surface 21 d. One locking projection 31 is provided on the outer surface 21d parallel to the Y direction at the center in the Y direction. The number of the locking projections 31 provided on the one outer side surface 21d is not particularly limited, and at least one locking projection may be provided.

As shown in fig. 4, the locking projection 31 has a substantially triangular cross section. The upper portion 31a of the locking projection 31 is a flat surface substantially parallel to the XY plane. The lower portion 31b of the locking projection 31 is an inclined surface extending in a direction away from the outer surface 21d of the upper frame 21 as it goes in the + Z direction.

The lower frame 22 has a rectangular frame shape as a whole. That is, the holder 2 having the lower frame 22 and the upper frame 21 has a rectangular frame shape having a central region penetrating therethrough, and can irradiate light from the upper side (+ Z side) of the microfluidic device 100 and analyze light transmitted through the flow path 13 of the plate 1 at the lower side (-Z side) of the microfluidic device 100. The lower frame 22 includes a support plate 221 and a side wall 222 rising from the outer peripheral edge of the support plate 221 in the Z direction.

Side wall 222 is located outward of side portion 1c of plate 1 and outer side surface 21d of upper frame 21, and an upper end of side wall 222 is higher than upper surface 21a of upper frame 21. Thereby, the side wall 222 laterally surrounds the plate 1 and the upper frame 21. The board 1 and the upper frame 21 are fitted into the side wall 222 from above the lower frame 22.

The support plate 221 has a rectangular frame shape having a through hole 22e smaller than the outer shape of the plate 1 at the center. Thereby, the support plate 221 can support the plate 1 from below by abutting on the outer peripheral edge 10b of the second main surface 1b of the plate 1.

The side wall 222 has a lower wall 222a and an upper wall 222b thinner than the lower wall 222 a. The outer surface of the upper wall 222b is offset inward from the outer surface of the lower wall 222 a. A side panel that covers a cover (not shown) of the microfluidic device 100 from above can be disposed outside the upper wall 222b and above the lower wall 222 a.

A protrusion 223 is provided at a corner formed by the lower wall 222a and the support plate 221 (see fig. 2). The projection 223 is inserted into the recess 16 provided in the plate 1 and is configured to be able to contact the bottom surface of the recess 16. Thus, when fitting the plate 1 into the lower frame 22, the plate 1 can be positioned with respect to the lower frame 22 by pressing the bottom of the recess 16 of the plate 1 so as to contact the protrusion 223.

The upper wall 222b is formed with a plurality of locking holes 32 penetrating the upper wall 222 b. Three locking holes 32 are provided in the upper wall 222b parallel to the X direction at equal intervals in the X direction. The central locking hole 32 of the three locking holes 32 is provided in the X-direction center portion of the upper wall 222 b. One locking hole 32 is provided in the upper wall 222b parallel to the Y direction at the center in the Y direction.

The locking hole 32 is provided at a position corresponding to the locking projection 31 of the upper frame 21, and into which the locking projection 31 is inserted. Slits 33 are formed on both sides of the locking hole 32. By providing the slit 33, the upper wall 222b of the portion where the locking hole 32 is formed is easily bent outward, and therefore, the locking projection 31 is easily inserted into the locking hole 32.

By inserting the locking projection 31 into the locking hole 32, the upper frame 21 and the lower frame 22 can be fixed in a state where the panel 1 is sandwiched between the upper frame 21 and the lower frame 22. That is, in the present embodiment, the locking projection 31 and the locking hole 32 correspond to a fixing member.

The locking hole 32 is formed such that the height from the upper surface of the support plate 221 to the upper edge portion 32a of the locking hole 32 is substantially the same as the height from the upper surface of the support plate 221 to the upper portion 31a of the locking projection 31 in a state where the plate 1 is sandwiched between the upper frame 21 and the lower frame 22. Thus, the outer peripheral edge 10a of the first main surface 1a of the plate 1 can be pressed by the upper frame 21, and the outer peripheral edge 10b of the second main surface 1b of the plate 1 can be pressed by the lower frame 22, so that the upper frame 21, the lower frame 22, and the plate 1 are integrated and the shape of the whole can be corrected.

Examples of the material of the upper frame 21 or the lower frame 22 include resin materials such as polymethyl methacrylate (PMMA), Polycarbonate (PC), cycloolefin copolymer (COC), cycloolefin polymer (COP), Polystyrene (PS), and silicone. In the present embodiment, PS is used for the upper frame 21 and the lower frame 22.

The water absorption of the resin constituting the upper frame 21 and the lower frame 22 is preferably higher than the water absorption of the resin constituting the plate 1, and the hardness of the plate 1 is preferably higher than the hardness of the upper frame 21 and the lower frame 22. Thus, even if the upper frame 21 and the lower frame 22 deform more than the plate 1 due to moisture absorption, the plate 1 is harder than the upper frame 21 and the lower frame 22, and therefore, when the plate 1 is sandwiched between the upper frame 21 and the lower frame 22, the upper frame 21 and the lower frame 22 deform so as to follow the shape of the plate 1, and as a result, deformation of the entire microfluidic device 100 can be suppressed.

The microfluidic device 100 is used, for example, at a temperature of 37 degrees and a humidity of 90%. The water absorption of PS used in the present embodiment is higher than the water absorption of COP used in the present embodiment.

The "hardness" in the present invention is evaluated by the magnitude of the deformation amount δ when the side facing one side of the fixing member is pressed against the member perpendicularly with a constant force while the one side is gripped. In the case of the plate 1, as shown in fig. 7, the deformation δ when one of a pair of sides parallel to the Y direction is held and fixed, and the other side is pressed with a constant force perpendicularly to the plate 1 (-Z direction) is measured. At this time, the pressed region is the entire region of the side (region Ar1 shown in fig. 7 a) or the end portion of the side (Ar 2 shown in fig. 7 a). When the "hardness" is evaluated by pressing the area Ar1, the correction of the warpage in the height direction (Z direction) of the plate 1 can be evaluated as shown in fig. 7 (b). On the other hand, when the "hardness" is evaluated in the pressing region Ar2, the correction of the undulation of the bottom surface of the plate 1 can be evaluated as shown in fig. 7 (c).

In the case of the upper frame 21, as shown in fig. 8, the deformation amount δ when one of the pair of sides parallel to the Y direction is held and fixed and the other side is pressed with a constant force perpendicularly to the upper frame 21 (-Z direction) is measured. The lower frame 22 can also be evaluated for "hardness" in the same manner as the upper frame 21.

While the embodiments of the present invention have been described above with reference to the drawings, the specific configurations are not to be considered as being limited to these embodiments. The scope of the present invention is defined by the claims, not only by the description of the above embodiments, but also by all modifications equivalent in meaning and scope to the claims.

The configuration adopted in each of the above embodiments can be adopted in any other embodiment. The specific configuration of each portion is not limited to the above-described embodiment, and various modifications can be made without departing from the scope of the present invention.

(1) In the microfluidic device 100 of the above embodiment, the combination of the locking projection 31 and the locking hole 32 is shown as the fixing member for fixing the upper frame 21 and the lower frame 22, but the present invention is not limited thereto. As shown in fig. 9, for example, the fixing member may be a locking claw 34 formed at the upper end of the side wall 222 of the lower frame 22. The upper frame 21 and the lower frame 22 can be fixed by engaging the engaging claws 34 with the upper surface 21a of the upper frame 21.

(2) Further, as a fixing member for fixing the upper frame 21 and the lower frame 22, a screw 35 as shown in fig. 10 may be used. Fig. 10 (a) is a perspective view of the microfluidic device 100 as viewed from below, and fig. 10 (b) is a sectional view including the screw 35. The upper frame 21 may be drawn toward the lower frame 22 by screws 35 provided to the lower frame 22. Thereby, the upper frame 21 and the lower frame 22 are fixed to each other with the plate 1 sandwiched from above and below.

(3) In the microfluidic device 100 according to the above-described embodiment, the lower frame 22 is shown as the second holding member that abuts at least the outer peripheral edge 10b of the second main surface 1b of the plate 1, but the present invention is not limited thereto. The second holding member may be a rectangular plate-shaped holding member having a central region that does not penetrate therethrough. In this case, the microfluidic device 100 may be irradiated with light from above, and the cells and tissues may be analyzed using light reflected or scattered inside the flow channel 13 of the plate 1.

(4) In the microfluidic device 100 according to the above-described embodiment, the opening 14 is connected to each end of the linear flow path 13 with respect to one flow path 13, but the present invention is not limited to this. The flow paths 13 may be Y-shaped, for example, and in this case, the openings 14 are connected to the ends of the Y-shaped flow paths 13 with respect to one flow path 13. The shape, number, and the like of the flow channel 13 and the opening 14 can be appropriately set.

(5) The use of microfluidic devices for culturing and analyzing cells and tissues is described above. However, the microfluidic device of the present invention can also be used for other than culture and analysis of cells and tissues. For example, the microfluidic device of the present invention can be used for various purposes such as mixing, separation, reaction, synthesis, extraction, or analysis of chemicals.