Container, fluid handling device, and freeze-drying method

Abstract

To provide a container for use in producing a freeze-dried product, capable of more easily accelerating the freeze-drying.SOLUTION: The container for producing or storing a freeze-dried product, comprises a bottom wall, a side wall, a support that supports a fluid to be freeze-dried to prevent it from contacting the bottom wall, and at least one ventilation hole disposed on the bottom wall or at least on a part of the side wall positioned below the top of the support.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present invention relates to a container, a fluid handling device and a freeze-drying method. [Background technology]

[0002] Generally, biological materials such as blood, proteins, and DNA are analyzed by mixing them with reagents and performing processes such as heating, cooling, detection, etc. In recent years, microfluidic devices for performing multiple such processes consecutively have become known (see, for example, Patent Document 1).

[0003] Patent Document 1 describes a process in which a sample reacts with a reagent in a plurality of reaction chambers in a microfluidic device to perform an analysis.

[0004] In the microfluidic device described in Patent Document 1, the reagent is freeze-dried and placed in the reagent chamber. The solid reagent placed in the reagent chamber is mixed with a sample dilution solution at the time of analysis and prepared just before use. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] US Patent Application Publication No. 2010 / 0044918 Summary of the Invention [Problem to be solved by the invention]

[0006] When using a freeze-dried material in a microfluidic device for on-demand preparation as described above, the freeze-dried material must be placed in the reagent chamber of the microfluidic device. However, freeze-dried materials are very fragile and difficult to handle. Therefore, placing the freeze-dried material in the chamber can be difficult. Therefore, instead of placing the freeze-dried material in the chamber, it is possible to produce a freeze-dried material in a container by placing the reagent in a container and freeze-drying it, and then placing the freeze-dried material in the container and the container into the chamber.

[0007] However, when freeze-dried products are produced in containers in this manner, the solvent (for example, water) may not be sublimated sufficiently, resulting in insufficient drying.

[0008] An object of the present invention is to provide a container for producing a freeze-dried product in which drying is more easily accelerated. Another object of the present invention is to provide a fluid handling device having such a container. Another object of the present invention is to provide a freeze-drying method in which drying is more easily accelerated. [Means for solving the problem]

[0009] The container of the present invention is a container for producing or storing freeze-dried products, and has a bottom wall, a side wall, a support for supporting the fluid to be freeze-dried so that it does not come into contact with the bottom wall, and at least one air vent located in the bottom wall or in at least a portion of the side wall located below the top of the support.

[0010] The fluid handling device of the present invention comprises a container accommodating section for accommodating the container, and the container accommodated in the container accommodating section.

[0011] The freeze-drying method of the present invention includes the steps of providing a fluid to a container having a bottom wall and a side wall so as not to contact the bottom wall, and removing a solvent from the fluid provided in the container to freeze-dry the fluid. [Effects of the Invention]

[0012] According to the present invention, it is possible to provide a container (cartridge) for producing or storing a freeze-dried product in which drying is more easily accelerated. Also, according to the present invention, it is possible to provide a fluid handling device having such a container. Also, according to the present invention, it is possible to provide a freeze-drying method in which drying is more easily accelerated. [Brief explanation of the drawings]

[0013] [Figure 1] 1A and 1B are diagrams showing the configuration of a fluid handling device according to an embodiment. [Figure 2] 2A to 2C are diagrams showing the configuration of the container. [Figure 3] 3A to 3C are diagrams illustrating a method for dissolving a freeze-dried product. [Figure 4] 4A to 4C are diagrams showing the configurations of containers according to Modifications 1 to 3. FIG. [Figure 5] 5A to 5C are diagrams showing the configurations of containers according to Modifications 4 to 6. FIG. [Figure 6] 6A to 6C are diagrams showing a specific example of a method for producing a freeze-dried product. DETAILED DESCRIPTION OF THE INVENTION

[0014] A fluid handling device according to this embodiment will now be described with reference to the accompanying drawings.

[0015] (Configuration of fluid handling device) Figures 1A and 1B are diagrams showing the configuration of a fluid handling device 100. Figure 1A is a plan view of the fluid handling device 100, and Figure 1B is a cross-sectional view taken along line AA shown in Figure 1A.

[0016] The fluid handling apparatus 100 has a container accommodating section 120 and a container 130. In this embodiment, the fluid handling apparatus 100 further has a chamber, and the container accommodating section 120 is disposed within the chamber 121. The fluid handling apparatus 100 is a place where operations are performed on the freeze-dried material in the container 130 accommodated in the container accommodating section 120. The container 130 is detachable from the container accommodating section 120.

[0017] The configuration of fluid handling device 100 is not particularly limited as long as it has container-mounting section 120 and container 130, but it is preferable that it be configured to facilitate operations on freeze-dried materials. In fluid handling device 100, an operation to dissolve freeze-dried materials is performed, so it is preferable that it be configured to facilitate dissolution.

[0018] The chamber 121 is a compartment that can contain a liquid. The chamber 121 has a container holder 120 disposed therein.

[0019] The number of chambers 121 is not particularly limited. The number of chambers 121 may be one or more. In the present embodiment, the number of chambers 121 is one. When there are more than one chambers 121, some of the chambers 121 may not have a container accommodating section 120 arranged therein. Furthermore, a solvent for dissolving the freeze-dried product, a reagent, or the like may be accommodated in the chambers 121 in which the container accommodating section 120 is not arranged.

[0020] There are no particular limitations on the size and shape of chamber 121. The size and shape of chamber 121 may be set appropriately depending on the amount of fluid to be accommodated, the size of container accommodating portion 120, and the like.

[0021] In this embodiment, the shape of the chamber 121 is a rectangular parallelepiped.

[0022] The container accommodating portion 120 accommodates and holds the container 130. It is preferable that the container accommodating portion 120 can detachably accommodate the container. In this embodiment, the inner diameter of the container accommodating portion 120 is configured to be slightly smaller than the outer diameter of the container 130. This allows the container 130 to fit into the container accommodating portion 120, and the container accommodating portion 120 can detachably accommodate the container 130. The container accommodating portion 120 is fixed within the chamber 121.

[0023] The shape of the container accommodating portion 120 is not particularly limited and is set according to the container 130. In this embodiment, the shape of the container accommodating portion 120 is cylindrical. In addition, a notch that allows the fluid to pass through is provided at the bottom of the cylinder.

[0024] 2A to 2C are diagrams showing the configuration of container 130. FIG. 2A is a plan view of container 130, and the left view of FIG. 2B is a cross-sectional view taken along line AA shown in FIG. 2A. The right view of FIG. 2B shows a state in which freeze-dried material 139 is contained. FIG. 2C is a bottom view of container 130 and a partially enlarged view of the area indicated by the dashed dotted line. Note that in the left views of FIGS. 2A, 2B, and 2C, mesh 136 formed by first rib 137 and second rib 138 is shown shaded.

[0025] 2A to 2C, the container 130 has a bottom wall 131, a side wall 132, a protrusion 133, and an air vent 134. The container 130 may also have legs 135. The container 130 is for storing or producing a freeze-dried material. The container 130 may also be used to produce a freeze-dried material and then store the freeze-dried material as is. The container 130 is detachably stored in the container storage section 120.

[0026] The bottom wall 131 is a wall that forms the bottom of the container 130. In this embodiment, the bottom wall 131 includes a mesh 136, and the mesh 136 includes at least one ventilation hole 134.

[0027] The ventilation hole 134 may be disposed in at least a portion of the bottom wall 131, or in at least a portion of the side wall 132 located below the top of the protrusion 133. In addition, it is sufficient that at least one ventilation hole 134 is present.

[0028] When the container 130 is used to produce a freeze-dried product, the ventilation hole 134 functions as a hole through which gas sublimated from a frozen fluid passes. When the container 130 is used to store a freeze-dried product and a fluid (solvent) is supplied from below the ventilation hole 134, the ventilation hole 134 functions as a hole through which the fluid enters the container 130. When the container 130 is used to store a freeze-dried product and a fluid (solvent) is supplied from above the freeze-dried product, the ventilation hole 134 functions as a hole through which a dissolving solution (reagent) for the freeze-dried product exits the container 130.

[0029] There are no particular limitations on the ventilation hole 134 as long as it performs the above-mentioned function. The ventilation hole 134 may be formed by a mesh 136 or by a slit. Furthermore, as long as gas can pass in and out, a semipermeable membrane may be disposed in the ventilation hole. In this embodiment, the ventilation hole 134 is formed by a mesh. Furthermore, the mesh 136 is formed in the bottom wall 131.

[0030] The material of mesh 136 may be a resin such as polypropylene (PP), polyacetal (POM), or polyamide (PA), or a metal such as stainless steel, titanium, or aluminum. Mesh 136 may also be nonwoven fabric, paper, or cloth. In this embodiment, mesh 136 is made of resin and is integrally molded by injection molding.

[0031] Mesh 136 is formed by a plurality of ribs (a plurality of first ribs 137 and a plurality of second ribs 138). The plurality of first ribs 137 extend in a first direction, and the plurality of second ribs 138 extend in a second direction perpendicular to the first direction. As a result, a plurality of ventilation holes 134 are formed in the regions between the plurality of first ribs 137 and between the plurality of second ribs 138 in a plan view.

[0032] The shape of the mesh 136 in a plan view is not particularly limited. In this embodiment, the shape of the mesh 136 in a plan view is circular. The shape of the plurality of vent holes 134 in the mesh 136 in a plan view is not particularly limited. The shape of the vent holes 134 in a plan view may be circular or polygonal. In this embodiment, the plurality of first ribs 137 and the plurality of second ribs 138 form the plurality of vent holes 134 in a square shape in a plan view. The length of one side of the vent holes 134 is appropriately set depending on the viscosity of the reagent in a liquid state, the type of reagent, and the like. The length of one side of the vent holes 134 (opening of the mesh 136) is preferably in the range of 0.1 μm to 500 μm, and more preferably in the range of 0.2 to 300 μm. If the length of one side of the vent holes 134 (opening of the mesh 136) is within the above range, the mesh 136 can be easily manufactured by injection molding.

[0033] The protrusions 133 protrude from the bottom wall 131. When the container 130 is used to produce a freeze-dried product, the protrusions 133 support the fluid to be freeze-dried so that it does not come into contact with the bottom wall 131. It is believed that the fluid is supported by the protrusions 133 due to surface tension. The support of the fluid by the protrusions 133 increases the area over which gas can sublimate from the bottom of the frozen fluid, facilitating freeze-drying. The gas sublimated from the bottom of the frozen fluid is discharged to the outside of the container 130 through at least one vent hole 134 located in at least a portion of the bottom wall or at least a portion of the side wall located below the top of the protrusions.

[0034] Since the freeze-dried product is produced as described above, the freeze-dried product is usually contained in the container 130 while being supported by the protrusion 133, as shown in the right diagram of FIG. 2B.

[0035] The shape of the protrusion 133 is not particularly limited as long as it can support the fluid without contacting the bottom wall 131. Examples of the shape of the protrusion 133 include a columnar shape, a cylindrical shape, a plate shape, etc. In this embodiment, the protrusion 133 is columnar.

[0036] The shape of the top of the convex portion 133 in a plan view is not particularly limited as long as it can exhibit the above-mentioned functions. Examples of the shape of the top of the convex portion 133 in a plan view include a circle, a cross, a rectangle, a polygon, etc. In this embodiment, the shape of the top of the convex portion in a plan view is a circle.

[0037] The size of the top of the protrusion 133 when viewed in plan is not particularly limited as long as it can perform the above-mentioned function. The area of ​​the top of the protrusion 133 when viewed in plan is, for example, 0.07 mm 2 ~0.80mm 2 In this embodiment, the shape of the top of the convex portion is circular, and the diameter of the circle is 0.5 mm.

[0038] The number of protrusions 133 is not particularly limited as long as they can perform the above functions. The number of protrusions 133 may be, for example, one, two, or three. In this embodiment, the number of protrusions 133 is one.

[0039] The side wall 132 is disposed so as to surround the bottom wall 131 and defines the outer shape of the container 130. When the fluid to be freeze-dried is supported by the protrusions 133, the inner surface of the side wall 132 may come into contact with the fluid.

[0040] When side wall 132 comes into contact with the fluid, side wall 132, together with convex portion 133, contributes to supporting the fluid to be freeze-dried so that it does not come into contact with bottom wall 131. From this perspective, the shape of the space defined by the inner surface of side wall 132 is preferably a shape that can easily support the fluid. In this embodiment, this shape is circular, as shown in FIG. 2A.

[0041] The area of ​​the space defined by the inner surface of the side wall 132 in plan view is 8.0 mm 2 ~16.0mm 2 It is preferable that the range is within this range.

[0042] The legs 135 are disposed at the bottom of the container. The legs 135 position the container 130 at an elevated position, creating a space between the bottom of the container 130 and the bottom of the container accommodating portion 120. This space is a portion that receives a fluid (solvent) or a solution (reagent) of a lyophilized product provided to the container accommodating portion 120. When a fluid is supplied from below the vent hole 134, the fluid first fills the space and then enters the container 130 through the vent hole 134. When a fluid is supplied from above the lyophilized product, the solution of the lyophilized product enters the space through the vent hole 134.

[0043] The shape, number, etc. of leg portions 135 are not particularly limited as long as they can perform the above-mentioned functions. In this embodiment, the length of leg portions 135 is such that the bottom of container 130 can be positioned close to the bottom of container storage portion 120, as shown in Fig. 1B. In this embodiment, the number of leg portions 135 is three.

[0044] (Erase preparation method) Next, a method for preparing a reagent just before use (a method for dissolving the freeze-dried material 139) will be described.

[0045] 3A, a container 130 containing a freeze-dried material 139 is prepared. The container 130 is housed in the container housing portion 120 of the fluid handling device 100.

[0046] Next, a solvent is supplied to the container 130. The method of supplying the solvent is not particularly limited as long as the solvent is supplied to the container 130. The direction of supplying the solvent is also not particularly limited and can be selected arbitrarily. The solvent may be supplied from the top or bottom of the container 130, as indicated by the arrows in FIG. 3B . Specifically, the solvent may be supplied from the top of the container 130 using a pipette or the like, or may be supplied using a syringe inserted into a through-hole (notch) disposed in the bottom of the container accommodating section 120. Furthermore, if the container has a mesh 136 (vent hole 134) in the sidewall 132, as in the container 330 of a modified example described below, the solvent may be supplied from the side of the container 330 so as to be supplied through the mesh 136 (vent hole 134) (see FIG. 3C ). The solvent that comes into contact with the freeze-dried material 139 dissolves the freeze-dried material and becomes a reagent.

[0047] Next, the obtained reagent is removed. There is no particular limitation on the method for removing the reagent. For example, the reagent may be removed from the top of the container 130 using a pipette or the like, or the reagent may be removed using a syringe inserted into the through-hole.

[0048] (Variation) 4A to 5C show containers according to Modifications 1 to 6, respectively. In each of Figs. 4A to 5C, the left drawing shows a state without freeze-dried material 139, and the right drawing shows a state with freeze-dried material 139 contained therein. The containers according to Modifications 1 to 6 will be described below. In addition, in the containers according to Modifications 1 to 6, the same components as those in the container according to embodiment 1 are denoted by the same reference numerals, and description thereof will be omitted.

[0049] <Variation 1> 4A shows a container 230 according to Modification 1. Container 230 differs from container 130 according to Embodiment 1 in that mesh 136 (vent holes 134) is arranged not only on bottom wall 131 but also on side wall 132 located below the top of protrusion 133.

[0050] <Variation 2> 4B shows a container 330 according to Modification 2. In container 330, similar to container 230, mesh 136 (vent holes 134) is arranged not only on bottom wall 131 but also on side wall 132. However, mesh 136 (vent holes 134) is arranged not only below but also above the top of protrusion 133.

[0051] <Variation 3> 4C shows a container 430 according to Modification 3. Container 430 differs from the containers according to Embodiment 1 and Modifications 1 and 2 in that mesh 136 (vent holes 134) is arranged only on side wall 132 located below the top of protrusion 133.

[0052] <Variation 4> 5A shows a container 530 according to Modification 4. Container 530 differs from the containers according to Embodiment 1 and Modifications 1, 2, and 3 in that mesh 136 (vent holes 134) is arranged over the entire bottom wall 131 and side wall 132.

[0053] <Variation 5> 5B shows a container 630 according to Modification 5. Container 630 differs from the other containers described above in that it has a plurality (two) of protrusions 133. Container 630 also differs from the other containers in that it has a holding protrusion 140 for holding a freeze-dried material 139. Holding protrusion 140 protrudes from bottom wall 131.

[0054] The holding convex portion 140 is a convex portion for holding the freeze-dried material 139. The holding convex portion 140 can hold the freeze-dried material 139 by inserting its tip into the freeze-dried material 139.

[0055] For example, by the holding convex portion 140 holding the freeze-dried material 139, the freeze-dried material is prevented from floating on the surface of the solvent when the freeze-dried material is dissolved in the solvent, and dissolution is promoted. The size, arrangement, shape, etc. of the holding convex portion 140 are not particularly limited as long as they can hold the freeze-dried material 139. When the convex portion 133 protrudes from the bottom wall 131, the holding convex portion 140 is preferably longer than the convex portion 133. Furthermore, in order to hold the freeze-dried material 139 more reliably, the holding convex portion 140 preferably has an inverse tapered shape in which the outer shape becomes larger or thicker as it gets further away from the bottom wall 131.

[0056] Variation 6 5C shows a container 730 according to Modification 6. Container 730 differs from the other containers described above in that it has a protrusion 133 protruding from side wall 132. Like the protrusion 133 protruding from bottom wall 131 described above, protrusion 133 protruding from side wall 132 is intended to support the fluid so that it does not come into contact with bottom wall 131.

[0057] The configuration of the convex portions 133 protruding from the side wall 132 is not particularly limited as long as it can support the fluid without contacting the bottom wall 131. In this embodiment, there are two (a pair of) convex portions 133 protruding from the side wall 132, and they are arranged to face each other across the center of the bottom wall 131 when viewed from above.

[0058] Other Modifications In the above embodiment and variations 1 to 6, the container has been described as having a structure (e.g., protrusion 133) as a support portion for supporting the fluid. However, the container of the present invention is not particularly limited as long as it can support the fluid without contacting bottom wall 131, and the container does not need to have a structure as a support portion. For example, the container of the present invention also includes a container having side wall 132 as a support portion, the roughness and wettability of the surface that comes into contact with the fluid being appropriately adjusted so that the fluid can be supported without contacting bottom wall 131.

[0059] (Method of producing freeze-dried product) Next, a method for producing the freeze-dried product will be described.

[0060] First, a fluid is supplied to the container without contacting the bottom wall 131. A possible method for supplying a fluid in this manner is to use a container according to the above-described embodiment or modified example. Specifically, for example, the fluid may be supplied so as to be supported by a protrusion 133 protruding from the bottom wall 131 or side wall 132 of the container.

[0061] Next, the solvent (e.g., water) is removed from the top and bottom of the fluid supplied to the container to freeze-dry the fluid. Specifically, after the fluid is frozen, the solvent is removed by reducing the pressure. The solvent is then removed by sublimation.

[0062] When the solvent is removed, the frozen fluid is prone to sublimation from the bottom because it is not in contact with the bottom wall 131. The gas sublimated from the bottom of the frozen fluid is discharged from at least one vent hole 134 located on at least a portion of the bottom wall 131 or on at least a portion of the side wall 132 located below the top of the protrusion 133. This promotes drying.

[0063] A specific example of a method for producing a freeze-dried product will be described below using the container according to the other modified example described above.

[0064] 6A to 6C are diagrams showing how a freeze-dried product is produced using the container 830 according to the other modified example.

[0065] First, as shown in Fig. 6A, a container 830 is prepared. As can be seen from Fig. 6A, the container 830 does not have a structure (for example, a protrusion 133) as a support portion.

[0066] 6B, a fluid 139′ to be freeze-dried is placed in a container 830. Here, the side wall 132 of the container 830 has an adjusted roughness and wettability of the surface that comes into contact with the fluid 139′, so that the fluid 139′ can be supported without coming into contact with the bottom wall 131.

[0067] Next, the fluid 139' is freeze-dried. The sublimated gas is mainly discharged from the top of the container 830 and the vent hole 134. In this way, a container containing the freeze-dried material 139 can be obtained, as shown in FIG. 6C.

[0068] (effect) According to the present invention, it is possible to provide a container in which drying is more easily promoted, a fluid handling device having such a container, and a freeze-drying method. [Industrial Applicability]

[0069] The container, fluid handling device, and freeze-drying method of the present invention can be applied to, for example, the analysis of minute amounts of biological samples. [Explanation of symbols]

[0070] 100 Fluid handling device 120 Container storage section 121 Chamber 130, 230, 330, 430, 530, 630, 730, 830 containers 131 Bottom wall 132 Side wall 133 Convex 134 Ventilation hole 135 Legs 136 mesh 137 First Rib 138 Second Rib 139 Freeze-dried products 139' fluid 140 Retaining protrusion

Claims

1. A container for producing or storing a freeze-dried product, The bottom wall and A side wall; a support for supporting the fluid to be freeze-dried so that it does not come into contact with the bottom wall; at least one vent hole disposed in the bottom wall or at least a portion of the side wall located below the top of the support; and A container for being contained in a fluid handling device that performs an operation to dissolve the freeze-dried product.

2. The container according to claim 1 , wherein the support portion is a protrusion protruding from the bottom wall or the side wall.

3. 3. The container of claim 1, wherein at least a portion of the bottom wall or the side wall has a mesh that includes the at least one vent hole.

4. The container according to any one of claims 1 to 3, further comprising the freeze-dried material supported by the support.

5. a container receiving portion for receiving the container; The container according to any one of claims 1 to 4 housed in the container housing portion; and A fluid handling device for carrying out the operation of dissolving the freeze-dried product.

6. providing a fluid to a container having a bottom wall and a side wall without contacting the bottom wall; removing a solvent from the fluid provided in the container to freeze-dry the fluid; and A freeze-drying method, wherein the container is a container to be housed in a fluid handling device that performs an operation of dissolving the freeze-dried product.

7. The freeze-drying method according to claim 6 , wherein in the step of providing the fluid, the fluid is supported on a protrusion protruding from the bottom wall or the side wall of the container.

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