JP6917346B2 - Pre-freezing device and cryopreservation system - Google Patents

Description

The present invention relates to a preliminary freezing device and a cryopreservation system.

Biological samples such as blood, sperm of laboratory animals, fertilized eggs, and cells (sometimes referred to simply as "biological samples" or "samples") are used in the development of new drugs and basic medical research. Since biological samples deteriorate at room temperature due to biological action, they are generally cryopreserved by a cryopreservation device or the like. As the cryopreservation device, a cryopreservation device using liquid nitrogen is widely used because it can be stably stored for a long period of time.

By the way, it is known that when a biological sample is cryopreserved for a long period of time at a low temperature of −150 ° C. or lower, the cell viability decreases when the sample at room temperature is exposed to an environment of −150 ° C. and rapidly cooled. ing. Therefore, before cryopreservation, while controlling the cooling rate using a program freezer, dry ice or a mechanical refrigerator, the temperature at the time of cryopreservation or higher to a predetermined temperature, for example, -80 ° C. , Pre-cooled (this is called "pre-freezing").

Patent Document 1 discloses a cryopreservation device having such a pre-freezing function. The cryopreservation device disclosed in Patent Document 1 is a system that automatically performs pre-freezing and cryopreservation.

Japanese Patent Publication No. 2002-511626

By the way, in general, a cryopreservation device is required to be able to store a large amount of samples in a storage chamber adjusted to a temperature for cryopreservation. On the other hand, in the preliminary freezing, which is a preparation before cryopreservation, it is required to quickly cool a large amount of samples to a state where they can be cryopreserved.

However, in the cryopreservation apparatus disclosed in Patent Document 1, since pre-freezing and cryopreservation are performed in the same freezer, it is necessary to control the temperature in the freezer stepwise, and many of them reach the cryopreservation state. There is a problem that it takes time. In addition, since pre-freezing and cryopreservation are continuously performed in the same freezer, processing is performed in lot units (badge units), but since there is a limit to the amount of processing in one lot, processing of a large amount of sample is performed. There is a problem that it is not suitable for.

The present invention has been made in view of the above circumstances, and is a preliminary freezing device capable of cooling many biological samples to a required temperature in a short time before cryopreserving the biological samples. The challenge is to provide.

Another object of the present invention is to provide a cryopreservation system capable of cryopreserving many biological samples in a short time.

In order to solve the above problems, the present invention has the following configurations.
[1] A pre-freezing device that cools a biological sample to an arbitrary temperature before cryopreserving the biological sample in a box-shaped envelope.
An envelope holder for storing one or more of the envelopes,
A pre-freezing drawer that stores one or more envelope holders side by side in the vertical direction,
A pre-freezing device including one or more pre-freezing drawers, and a pre-freezing container having an opening for communicating with the outside on the upper surface.
[2] The envelope is a box-shaped storage member having a first surface and a second surface facing each other in the thickness direction.
The envelope holder has a mounting surface of the envelope and a plurality of partition plates erected in a direction perpendicular to the mounting surface described above.
The pre-freezing device according to [1], wherein the envelope is inserted into a space partitioned by the partition plate so that the first surface and the second surface face each other of the partition plate.
[3] The pre-freezing device according to [2], wherein the envelope holder is housed in the pre-freezing drawer with the above-mentioned placing surface facing in the vertical direction.
[4] The pre-freezing device according to [2] or [3], wherein the envelope holder has a large heat capacity depending on the material and thickness of the partition plate.
[5] The item according to any one of [2] to [4], wherein the envelope is inserted into the envelope holder so that the first surface and the second surface come into contact with the partition plate, respectively. Preliminary freezing device.
[6] The pre-freezing device according to any one of [2] to [5], wherein the pre-freezing container has an envelope holder and one or more fans for cooling the envelope by the cooling heat of liquid nitrogen.
[7] An elevating mechanism that raises and lowers the pre-freezing drawer in the vertical direction through the opening and maintains the pre-freezing drawer at an arbitrary height.
A waiting table above the pre-freezing container, which is provided so as to be adjacent to the opening when viewed in a plan view, and which can transfer the envelope holder to and from the pre-freezing drawer.
A first extrusion arm that moves the envelope holder placed on the waiting table to the pre-freezing drawer, and
The item according to any one of [2] to [6], comprising: The pre-freezing device described.
[8] The waiting table has a first mounting surface on which the envelope holder is placed in a state where the previously described mounting surface of the envelope holder is in the vertical direction when the envelope holder is delivered to and from the pre-freezing drawer. The pre-freezing device according to [7].
[9] Two or more of the openings are provided on the upper surface of the pre-freezing container so as to be adjacent to each other in another direction orthogonal to the direction from the pre-freezing drawer toward the waiting table.
The pre-freezing device according to [8], wherein the pre-freezing drawer is housed in each of the openings.
[10] The pre-freezing drawer has a heat insulating member at the upper part.
The pre-freezing device according to [9], wherein when the pre-freezing drawer is housed in the pre-freezing container, the heat insulating member closes each of the openings.
[11] The preliminary freezing device according to claim 9 or 10, wherein the waiting table is movable in the other direction.
[12] A transport table on which the envelope holder is placed is further provided.
The pre-freezing device according to any one of [9] to [11], wherein the transport table is movable in the other direction.
[13] The pre-freezing according to [12], wherein the transport table has a second mounting surface on which the envelope holder is mounted with the previously described mounting surface of the envelope holder in a horizontal direction when the envelope holder is transported. Device.
[14] The waiting table and the transport table are in a state where the first mounting surface and the second mounting surface are orthogonal to each other, and the first mounting surface and the second mounting surface are adjacent to each other. A rotating table with an L-shape integrated with
The rotating table is set so that either one of the first mounting surface and the second mounting surface is horizontal with the line where the first mounting surface and the second mounting surface intersect as an axis. A rotation mechanism that rotates 90 ° and
The pre-freezing device according to [13], further comprising a first transport mechanism for moving the swivel table in the other direction and transporting the swivel table to the inside and outside of the pre-freezing device.
[15] The pre-freezing device according to any one of the above [1] to [14] and the pre-freezing device.
A cryopreservation system comprising a cryopreservation device for cryopreserving the biological sample pre-frozen by the pre-freezing device in a state of being housed in the envelope.
[16] The cryopreservation system according to [15], further comprising an envelope holder holding mechanism capable of transferring the envelope holder accommodating one or more envelopes between the preliminary freezing device and the cryopreservation device. ..
[17] The cryopreservation device includes a cryopreservation drawer that stores the envelopes side by side, and a cryopreservation container having an opening that communicates with the outside on the upper surface.
With the first arm holding the cryopreservation drawer, the cryopreservation drawer is raised and lowered in the vertical direction through the opening, and the cryopreservation drawer is maintained at an arbitrary height. ,
A first stage above the cryopreservation container, which is provided so as to be adjacent to the opening when viewed in a plan view, and on which the envelope holder for accommodating the envelope can be placed.
A second arm that moves the envelope in the cryopreservation drawer located at a height adjacent to the first stage to the envelope holder mounted on the first stage.
The cryopreservation system according to [15] or [16], comprising a third arm for moving the envelope in the envelope holder placed on the first stage to the cryopreservation drawer.
[18] The cryopreservation device further includes a rotary table at the bottom of the cryopreservation container.
The cryopreservation drawer can be placed on the circumference of an arbitrary circle centered on the rotation axis of the rotary table, and the cryopreservation drawer can be placed.
The cryopreservation system according to [17], wherein the opening is located on the circumference of the circle when viewed in a plan view.
[19] Two or more of the openings are provided on the upper surface of the cryopreservation container so as to be adjacent to each other in another direction orthogonal to the direction from the cryopreservation drawer toward the first stage.
The rotary table allows the cryopreservation drawer to be placed on each circumference of any two or more concentric circles centered on the rotary axis of the rotary table.
The cryopreservation system according to [18], wherein the openings are located on each circumference of the concentric circles when viewed in a plan view.
[20] A plurality of pressing arms are provided at the tip of the third arm.
The cryopreservation system according to any one of [17] to [19], wherein the plurality of pressing arms are inserted into the space partitioned by the partition plate of the envelope holder.

The pre-freezing device of the present invention puts a biological sample in a flat storage bag and puts the biological sample up to an arbitrary temperature before cryopreserving the storage bag in a box-shaped envelope. It cools and houses an envelope holder that stores one or more envelopes, a pre-freezing drawer that stores one or more envelope holders side by side in the vertical direction, and one or more pre-freezing drawers inside and outside. It is configured to include a pre-freezing container provided on the upper surface with an opening communicating with the above.

As described above, since the storage means dedicated to pre-freezing capable of storing a large amount of biological samples is provided, a large amount of biological samples can be collectively pre-frozen in an envelope unit. Therefore, many biological samples can be cooled to the required temperature before cryopreservation in a short time.

Further, the cryopreservation system of the present invention is configured to include the above-mentioned pre-freezing device and a cryopreservation device for cryopreserving a biological sample pre-frozen by the pre-freezing device in a state of being stored in an envelope. There is. As described above, since the preliminary freezing and the cryopreservation are performed by separate devices, many biological samples can be cryopreserved in a short time.

It is a perspective view which shows the structure of the cryopreservation system which is one Embodiment to which this invention is applied. It is a front view which shows the structure of the cryopreservation system which is one Embodiment to which this invention is applied. It is a top view which shows the structure of the cryopreservation system which is one Embodiment to which this invention is applied. It is a side view which shows the structure of the preliminary freezing apparatus of this embodiment. It is a top view which shows the structure of the preliminary freezing apparatus of this embodiment. It is a perspective view which shows the structure of the envelope used for the cryopreservation system of this embodiment. It is a perspective view which shows the structure of the envelope holder used for the cryopreservation system of this embodiment. It is a front view which shows the structure of the envelope holder used for the cryopreservation system of this embodiment. It is a bottom view which shows the structure of the envelope holder used for the cryopreservation system of this embodiment. It is a top view for demonstrating the operation of the rotary table which comprises the preliminary freezing device of this embodiment. It is a side view for demonstrating the operation of the rotary table which comprises the preliminary freezing device of this embodiment. It is a top view which shows the structure of the envelope holder holding mechanism of this embodiment. It is a side view which shows the structure of the envelope holder holding mechanism of this embodiment. It is a side view which shows the structure of the envelope holder holding mechanism of this embodiment. It is a perspective schematic diagram which shows the drawer in the cryopreservation apparatus of this embodiment. It is sectional drawing which saw from the side of the cryopreservation container in the cryopreservation apparatus of this embodiment. It is sectional drawing which looked at the cryopreservation container in the cryopreservation apparatus of this embodiment from the top. It is a side schematic diagram which shows the operation of the drawer elevating device in the cryopreservation device of this embodiment. It is a plane schematic view which shows the 1st stage, the 2nd stage, the 1st pressing device, and the 2nd pressing device in the cryopreservation apparatus of this embodiment. FIG. 5 is a side schematic view showing a drawer elevating device, a drawer, a first drawer guide, a second drawer guide, a first stage, and a second stage in the cryopreservation device of the present embodiment. It is a top view which shows the drawer elevating device, the drawer, the 1st drawer guide, the 2nd drawer guide, the 1st stage and the 2nd stage in the cryopreservation apparatus of this embodiment.

Hereinafter, a preliminary freezing device according to an embodiment to which the present invention is applied will be described in detail together with a cryopreservation system using the same with reference to the drawings. In the drawings used in the following description, in order to make the features easier to understand, the featured parts may be enlarged for convenience, and the dimensional ratios of each component may not be the same as the actual ones. do not have.

<Cross storage system>
First, an example of the configuration of the cryopreservation system according to the embodiment to which the present invention is applied will be described with reference to FIGS. 1 to 3. Here, FIG. 1 is a perspective view showing a configuration of a cryopreservation system according to an embodiment to which the present invention is applied. FIG. 2 is a front view showing the configuration of a cryopreservation system according to an embodiment to which the present invention is applied. FIG. 3 is a top view showing the configuration of a cryopreservation system according to an embodiment to which the present invention is applied.

As shown in FIGS. 1 to 3, the cryopreservation system 100 of the present embodiment is roughly configured with a preliminary freezing device 200, a cryopreservation device 300, and an envelope holder holding mechanism 400. The cryopreservation system 100 is provided with a preliminary freezing device 200, a cryopreservation device 300, and an envelope holder holding mechanism 400 adjacent to each other. Hereinafter, the direction in which the cryopreservation device 300 and the envelope holder holding mechanism 400 are adjacent to each other is the "X direction", the direction in which the preliminary freezing device 200 and the envelope holder holding mechanism 400 are adjacent to each other is the "Y direction", and the vertical direction is the "Z axis". Sometimes called "direction".

The cryopreservation system 100 cools the biological sample to an arbitrary temperature by the pre-freezing device 200, pre-freezes the biological sample, and then freeze-preserves the biological sample by the cryopreservation device 300 at a temperature of, for example, −180 ° C. for a long period of time. It is a system to do.

Further, the cryopreservation system 100 of the present embodiment is a system in which the cryopreservation system 100 continuously and automatically performs pre-freezing by the pre-freezing device 200 and cryopreservation by the cryopreservation device 300.

As shown in FIG. 2, the cryopreservation system 100 of the present embodiment includes an envelope holder holding mechanism 400 capable of delivering an envelope holder (details will be described later) for accommodating one or more envelopes. As a result, the cryopreservation system 100 can collectively process pre-freezing and cryopreservation in units of envelope holders, so that a large amount of biological samples can be efficiently processed.

(Preliminary freezing device)
Next, an example of the configuration of the preliminary freezing device 200, which is an embodiment to which the present invention is applied, will be described. Here, FIG. 4 is a side view showing the configuration of the preliminary freezing device 200 of the present embodiment. FIG. 5 is a plan view showing the configuration of the preliminary freezing device 200 of the present embodiment.

As shown in FIGS. 1 to 5, the pre-freezing device 200 includes a pre-freezing drawer 2 for accommodating a pre-freezing target, a pre-freezing container 3 for accommodating the pre-freezing drawer 2, and a pre-freezing drawer. A rotating table 5 capable of passing the pre-freezing target between the pre-freezing drawer elevating device (elevating mechanism) 4 for moving 2 in the vertical direction and the pre-freezing drawer 2, and a rotating table 5 for pre-freezing the target. A first extrusion arm 6 for moving the pre-freezing target to the pre-freezing drawer 2 side, a second extrusion arm 7 for moving the pre-freezing target from the pre-freezing drawer 2 side to the rotary table 5, and a pre-freezing target. It is roughly configured with a first transport mechanism 27 for transporting inside and outside the freezing device 200.

The pre-freezing target of the pre-freezing device 200 is a biological sample such as blood, sperm of an experimental animal, a fertilized egg, or a cell, which is also a target of cryopreservation. That is, the pre-freezing device 200 controls the cooling rate before cryopreserving the biological sample to an arbitrary temperature equal to or higher than the temperature at the time of cryopreservation (for example, −180 ° C.). Specifically, it is a device for cooling to −80 ° C. and performing only preliminary freezing (also referred to as “slow freezing”).

Here, FIG. 6 is a perspective view showing the configuration of the envelope used in the cryopreservation system 100 of the present embodiment. FIG. 7 is a perspective view showing the configuration of the envelope holder used in the cryopreservation system 100 of the present embodiment. FIG. 8 is a front view showing the configuration of the envelope holder used in the cryopreservation system 100 of the present embodiment. FIG. 9 is a bottom view showing the configuration of the envelope holder used in the cryopreservation system 100 of the present embodiment.

As shown in FIGS. 6 and 8, the umbilical cord 8 is a box-shaped storage member having a first surface 8A and a second surface 8B facing each other in the thickness direction, and a blood bag or a blood bag or the like is contained therein. A protective device (protector) for storing a bag (storage bag) 9 such as a cord blood bag. In addition, a biological sample is contained in the bag 9. The bag 9 is a storage bag made of flat resin for storing an irregularly shaped biological sample. By using the envelope 8, even if the pre-freezing target has an indefinite shape, it can be easily taken out or stored, and at the same time, the pre-freezing target can be protected from impact or the like. In the pre-freezing device 200 of the present embodiment, since the pre-freezing is performed in a state where the biological sample that is also the target of cryopreservation is contained in the envelope 8, the envelope 8 can be said to be the target of pre-freezing.

The envelope 8 may be made of any material that can maintain its own shape. The envelope 8 may be formed of a resin or a metal having a high thermal conductivity, for example, aluminum. When pre-freezing, the envelope 8 is preferably made of aluminum from the viewpoint of heat conduction into the envelope 8.
Further, it is preferable that the envelope 8 is provided with an identification code.

As shown in FIGS. 7 to 9, the envelope holder 10 is a shelf-type storage tool for storing one or more envelopes 8. The envelope holder 10 has a bottom plate 11 and a plurality of partition plates 12. The bottom plate 11 has a mounting surface 11A of the envelope 8. The partition plates 12 are erected so as to be perpendicular to the mounting surface 11A. Further, each end portion 12a of the partition plate 12 is formed with a taper.

As shown in FIG. 8, in the envelope holder 10, the first surface 8A and the second surface 8B are paired in a space (also referred to as “storage space”) partitioned by the pair of partition plates 12 and 12. The envelope 8 is inserted so as to face the plates 12 and 12, respectively. In the preliminary freezing device 200 of the present embodiment, for example, 10 envelopes 8 can be stored in one envelope holder 10.

As shown in FIG. 9, a circular recess 11C is provided in the central portion of the bottom surface 11B of the envelope holder 10. Thereby, for example, the envelope holder 10 can be supported by using a member having a circular support portion having a shape matching the concave portion 11C and bringing the circular support portion into contact with the concave portion 11C from below the envelope holder 10. can.

The pre-freezing device 200 of the present embodiment performs pre-freezing with 10 units of envelope holders containing the envelope 8. That is, the pre-freezing device 200 performs pre-freezing for each of the envelope holders 10 containing the envelope 8.

Therefore, the envelope holder 10 preferably has a large heat capacity from the viewpoint of efficiently cooling the envelope 8. The bottom plate 11 and the partition plate 12 constituting the envelope holder 10 are preferably made of a metal having a high thermal conductivity, for example, aluminum. Further, the thickness of the bottom plate 11 and the partition plate 12 is preferably made thicker from the viewpoint of increasing the heat capacity. As for the thickness of each partition plate 12, when the envelope 8 is inserted into the storage space partitioned by the pair of partition plates 12 and 12, the first and second surfaces 8A and 8B of the envelope 8 are the partition plates 12 and 12. It is preferable that they come into contact with each other.

According to the pre-freezing device 200 of the present embodiment, when the envelope holder 10 containing the envelope 8 is pre-frozen, the envelope holder 10 has excellent thermal conductivity and each envelope 8 is brought into close contact with the envelope holder 10. Since it is retained, each sample can be cooled evenly. Further, since the envelope holder 10 having a large heat capacity is cooled, the temperature rise of each sample can be suppressed when the sample is transferred from the pre-freezing device 200 to the cryopreservation device 300 after the pre-freezing is completed.

As shown in FIGS. 1, 2 and 4, the pre-freezing drawer 2 is a member that stores one or more envelope holders 10 in a vertically arranged (stacked) state. As shown in FIG. 2, the preliminary freezing drawer 2 is composed of a pair of vertical plates 2A and 2A as side surfaces and a plurality of floor plates 2B provided between the vertical plates 2A and 2A. As a result, shelves (hereinafter, may be referred to as “storage space”) partitioned by vertical plates and floor plates are continuously provided in the Z-axis direction, and the envelope holder 10 can be stored in each shelf. Further, since at least one side surface orthogonal to the pair of vertical plates is open, the envelope holder 10 can be taken in and out.

Further, the preliminary freezing drawer 2 is provided with a heat insulating member 13 at the upper part of the partitioned storage space. The material of the heat insulating member 13 is not particularly limited as long as it has high heat insulating performance, but for example, urethane foam resin or the like can be used.

The pre-freezing drawer 2 can be raised and lowered in the Z-axis direction by the pre-freezing drawer elevating device 4 described later. The pre-freezing drawer 2 is not particularly limited as long as it can accommodate the envelope holder 10 and can be raised and lowered in the Z-axis direction by the pre-freezing drawer elevating device 4.

As shown in FIGS. 2 to 4, the pre-freezing container 3 is a container provided below the pre-freezing device 200 of the present embodiment. The pre-freezing container 3 has a function of a liquid nitrogen type program freezer in which the pre-freezing drawer 2 is housed inside the container, cooled to a required temperature, and pre-fused. As the preliminary freezing container 3, a vacuum double heat insulating container having a double structure formed of an inner tank and an outer tank made of stainless steel or the like and having a vacuum gap between the inner tank and the outer tank is used. be able to.

The pre-freezing container 3 includes an injection nozzle 14 that supplies liquid nitrogen into the container, an electric fan (fan) 15 that stirs the liquid nitrogen supplied into the container, and a temperature for measuring the temperature inside the container. A sensor (not shown) is provided. Here, as shown in FIG. 2, five injection nozzles 14 are provided inside the preliminary freezing container 3 at different heights along the Z-axis direction so as to form two rows thereof. .. Further, as shown in FIGS. 3 and 4, two electric fans 15 are provided so as to have different heights along the Z-axis direction. Therefore, by ejecting liquid nitrogen from the injection nozzle 14 into the inside of the preliminary freezing container 3 and stirring it with the electric fan 15, the inside of the container can be kept in a low temperature state by the cold heat of the liquid nitrogen. As a result, the envelope holder 10 housed in the pre-freezing drawer 2 is cooled and pre-frozen (slowly frozen) while being controlled from room temperature (1 to 30 ° C.) to an arbitrary temperature (for example, −80 ° C.). be able to.

As shown in FIGS. 3 and 5, a flat portion 16 is provided on the upper surface of the preliminary freezing container 3, and the flat portion 16 is provided with two openings 16A and 16B. Further, the two openings 16A and 16B are provided so as to be adjacent to each other in the Y-axis direction. Through the openings 16A and 16B, the internal space of the preliminary freezing container 3 and the work space (outside) 21 facing the flat portion 16 are communicated with each other.

The opening areas of the openings 16A and 16B are substantially the same as the area when the preliminary freezing drawer 2 is viewed in a plan view. Therefore, when the envelope holder 10 is conveyed from the pre-freezing drawer 2 in the work space 21, it is possible to prevent the envelope holder 10 from accidentally falling into the pre-freezing container 3 from the openings 16A and 16B. ..

As shown in FIGS. 2 to 5, a preliminary freezing drawer 2 is inserted into each of the openings 16A and 16B, respectively. At this time, by making the upper surface of the heat insulating member 13 provided on the upper part of the preliminary freezing drawer 2 and the upper surface of the flat portion 16 provided with the openings 16A and 16B at the same height, the openings 16A, Since 16B is closed, it is possible to suppress an increase in temperature inside the preliminary freezing container 3.

Further, when the pre-freezing drawer 2 is inserted into the openings 16A and 16B, the direction is adjusted so that the opening side of the pre-freezing drawer 2 is in the X-axis direction. By inserting the pre-freezing drawer 2 into the openings 16A and 16B in such a direction, the envelope holder 10 can be transferred to and from the rotating table 5 as described later.

As shown in FIGS. 1 to 5, the work space 21 is provided above the pre-freezing container 3 and communicates with the pre-freezing container 3 through the openings 16A and 16B. The pre-freezing device 200 of the present embodiment is surrounded by a housing, and the working space 21 has a dew point of −40 ° C. or lower, preferably a dew point of −50 ° C. or lower due to nitrogen gas evaporated from the pre-freezing container 3 or the like. It is maintained in a dry environment. By covering the work space 21 including the openings 16A and 16B of the pre-freezing container 3 with a housing, frostbite caused by the operator directly touching the pre-freezing drawer 2 and liquid nitrogen, and from the openings 16A and 16B The risk of oxygen deficiency due to evaporating nitrogen gas can be eliminated. Further, by maintaining the inside of the housing in a dry environment, it is possible to prevent dew condensation in the work space 21.

As shown in FIGS. 2 to 5, the pre-freezing drawer elevating device 4 closes the openings 16A and 16B and raises and lowers the pre-freezing drawer 2 housed in the pre-freezing container 3 in the vertical direction. It is a member for allowing the member to maintain the height at an arbitrary height, and is provided in the work space 21. The preliminary freezing drawer elevating device 4 is composed of a support column 17, a movable portion 18, and a connecting member 20.

As shown in FIGS. 2 and 4, the support pillar 17 is a columnar member for pulling up the pre-freezing drawer 2 upward along the Z-axis direction, and closes the openings 16A and 16B and is a pre-freezing container. The pre-freezing drawers 2 housed in each of the three can be pulled upward along the Z-axis direction.

The support column 17 is provided with a movable portion 18 that can be moved in the Z-axis direction along the support column 17 by a ball screw type actuator or the like (not shown). Further, the movable portion 18 is provided with a connecting member 20 so as to hang downward along the Z-axis direction.

The connecting member 20 is a member that connects the movable portion 18 and the pre-freezing drawer 2 so that a predetermined distance (clearance) is provided between the movable portion 18 and the upper end of the pre-freezing drawer 2. There is no particular limitation as long as it can exhibit the function of holding the preliminary freezing drawer 2.

Further, the pre-freezing drawer elevating device 4 closes the openings 16A and 16B, respectively, and is provided with one for each pre-freezing drawer 2 housed in the pre-freezing container 3. As a result, the pre-freezing drawer 2 stored in the pre-freezing container 3 can be independently loaded and unloaded through the plurality of openings 16A and 16B.

Further, by stopping the driving of the actuator, the movable portion 18 can be maintained at an arbitrary height in the Z-axis direction. That is, the preliminary freezing drawer 2 can be maintained at an arbitrary height.

As shown in FIG. 5, a plate 22 extending to the vicinity of the envelope holder holding mechanism 400 is provided below the work space 21 along the Y-axis direction. A first Y-axis rail 23 is provided on the plate 22 along the extending direction (that is, the Y-axis direction) of the plate 22. The first Y-axis rail 23 is provided with a transport stage 24, and is movable to an arbitrary position in the Y-axis direction by the drive device 25. Further, a rotating table 5 and a rotating mechanism 26 for rotating the rotating table 5 are provided on the transport stage 24.

In the preliminary freezing device 200 of the present embodiment, the first transport mechanism 27 is configured by the transport stage 24 and the drive device 25. The first transfer mechanism 27 moves the transfer stage 24 in the Y-axis direction to move the envelope holder 10 mounted on the rotating table 5 at positions adjacent to the openings 16A and 16B in a plan view. Can be transported. Further, the first transport mechanism 27 can transport the envelope holder 10 mounted on the rotary table 5 inside and outside the preliminary freezing device 200 by moving the transport stage 24 in the Y-axis direction.

When the rotating table 5 is adjacent to either of the openings 16A and 16B in a plan view, the envelope holder 10 is stored in a storage space of an arbitrary height of the pre-freezing drawer 2, or the pre-freezing drawer is stored. When taking out the desired envelope holder 10 housed at an arbitrary height from 2, it is not necessary to take out the entire pre-freezing drawer 2 from the pre-freezing container 3. As a result, the preliminary freezing drawer 2 is raised until the bottom surface of the storage space in which the desired envelope holder 10 is housed and the rotating table 5 are at the same height, whereby the first extrusion arm 6 described later is used. The envelope holder 10 before the pre-freezing process can be stored in the storage space at a desired height of the pre-freezing drawer 2. Similarly, the second extrusion arm 7 allows only the desired envelope holder 10 for which the prefreezing process has been completed to be taken out onto the rotary table 5. Therefore, it is possible to prevent the temperature of samples other than the target sample from rising. Further, since it is not necessary to pull up the entire pre-freezing drawer 2, the height direction of the device can be miniaturized.

Here, FIG. 10 is a plan view for explaining the operation of the rotary table constituting the preliminary freezing device 200 of the present embodiment. FIG. 11 is a side view for explaining the operation of the rotary table constituting the preliminary freezing device 200 of the present embodiment.
As shown in FIGS. 10 and 11, the rotating table 5 moves so as to be adjacent to the openings 16A and 16B when viewed in a plan view while holding the envelope holder 10 above the preliminary freezing container 3. It is a movable table that is possible and can transfer the envelope holder 10 to and from the preliminary freezing drawer 2.

The rotary table 5 is a standby table unit (standby table) used when the envelope holder 10 is transferred between the transfer table unit (convey table) 28 used when transporting the envelope holder 10 and the preliminary freezing drawer 2. ) 29 is combined (joined) and integrated. Therefore, when the rotary table 5 moves in the Y-axis direction, the transport table portion 28 and the standby table portion 29 move together.

Specifically, the transport table portion 28 mounts the envelope holder 10 when the transport stage 24 is moved in the Y-axis direction and the envelope holder 10 is transported to positions adjacent to the openings 16A and 16B in a plan view. This is the part to put. The transport table portion 28 supports the bottom surface 11B so that the bottom plate 11 is horizontal when the envelope holder 10 is transported. That is, the transport table portion 28 has a mounting surface (second mounting surface) 28A on which the envelope holder 10 is mounted in a state where the mounting surface 11A of the envelope holder 10 is in the horizontal direction.

The mounting surface 28A is provided with an opening 30. The opening 30 is composed of a circular portion 30A penetrating the central portion of the mounting surface 28A and a slit portion 30B provided from the circular portion 30A in a plan view toward the side surface facing the envelope holder holding mechanism 400. Has been done. As a result, the envelope holder 10 placed on the rotating table 5 can be pushed out or pushed up from the bottom surface 11B side of the bottom plate 11 through the opening 30.

The shape of the opening 30 is not particularly limited as long as the bottom plate 11 of the envelope holder 10 can be pushed out or pushed up. For example, it may be a polygon instead of a circle.

A holder guide 31 is provided on the outer peripheral portion of the mounting surface 28A. The holder guide 31 can regulate the position of the envelope holder 10 so that it is placed at a predetermined position on the mounting surface 28A when the rotating table 5 described later rotates. As a result, the envelope holder 10 can be safely conveyed by the rotating table 5.

The standby table portion 29 is a portion used when the rotating table 5 is moved to a position adjacent to each of the openings 16A and 16B in a plan view and then the envelope holder 10 is handed over to and from the preliminary freezing drawer 2. .. The standby table portion 29 is provided on one end side of the partition plates 12 at both ends so that the bottom plate 11 (in other words, the mounting surface 11A) is vertical when the envelope holder 10 is transferred to and from the preliminary freezing drawer 2. Supports the partition plate 12 of. That is, the standby table portion 29 has a mounting surface (first mounting surface) 29A on which the envelope holder 10 is mounted in a state where the mounting surface 11A of the envelope holder 10 is in the vertical direction.

A holder guide 32 is provided on the outer peripheral portion of the mounting surface 29A. The holder guide 32 is composed of a pair of rails extending in the X-axis direction on the mounting surface 29A. When the envelope holder 10 is delivered to and from the preliminary freezing drawer 2 by the holder guide 32, the envelope holder 10 moves between the pair of rails on the mounting surface 29A, so that the envelope holder 10 moves in the Y-axis direction. Can be regulated. As a result, the envelope holder 10 can be reliably delivered to and from the preliminary freezing drawer 2.

The rotating table 5 is a transport table in a state where the mounting surface 28A of the transport table portion 28 and the mounting surface 29A of the standby table portion 29 are orthogonal to each other, and the mounting surface 28A and the mounting surface 29A are adjacent to each other. The unit 28 and the standby table unit 29 are integrated in an L shape. When the envelope holder 10 is placed on the rotating table 5, the bottom plate 11 is placed on the mounting surface 28A of the transport table portion 28, and one of the partition plates 12 at both ends is placed on the mounting surface of the standby table portion 29. Each of them is in contact with 29A.

The rotation mechanism 26 has either the mounting surface 28A or the mounting surface 29A with the line where the mounting surface 28A of the transport table portion 28 and the mounting surface 29A of the standby table portion 29 intersect as the rotation shaft (axis) 33. This is a device that rotates the rotary table 5 at a right angle (90 °) so that one of them is horizontal.

The rotation mechanism 26 is provided on the rotation shaft 33 and the transfer stage 24, and is pivotally supported by the rotation shaft 33 and the support portions 34 that support both ends of the rotation shaft 33 at both ends of the rotation table 5. The rotating plate 35, the rotor unit 36 that comes into contact with the rotating plate 35 to transmit power, the drive unit 37 provided on the transport stage 24, and the rotational movement of the drive unit 37 are transmitted to the rotor unit 36. It is roughly configured with a belt 38. Further, the rotating plate 35 is a disk-shaped member having a size of a quarter of the circumference, and is connected to the rotating shaft 33 at the central portion of the circle and the rotor portion 36 at the circumferential portion. Is in contact with. Therefore, when the drive unit 37 is rotated clockwise or counterclockwise, the rotational motion is transmitted to the rotor unit 36 via the belt 38. Then, when the rotor portion 36 rotates while being in contact with the circumferential portion of the rotating plate 35, the rotating plate 35 also rotates by a quarter of the circumference (that is, 90 °). As a result, the rotation shaft 33 connected to the central portion of the rotation plate 35 rotates by a quarter of the circumference (that is, 90 °), so that the rotation table 5 can be rotated by 90 °. can.

The transport stage 24 is provided with a support member 39 that supports the rotary table 5 (that is, the transport table portion 28) in a state where the mounting surface 28A of the transport table portion 28 is horizontal. Further, the plate 22 is provided with a support member 40 that supports the rotating table 5 (that is, the standby table portion 29) in a state where the mounting surface 29A of the standby table portion 29 is horizontal. With these support members 39 and 40, the rotary table 5 can be stably supported in two states.

As shown in FIG. 4, a plate 41 is provided in the work space 21 above the plate 22. A pair of rails 42, 42 extending in the Y-axis direction are provided on the bottom surface of the plate 41. The transfer stage 43 is mounted on a pair of rails 42, 42, and is movable in the Y-axis direction above the transfer stage 24 and the rotary table 5. Therefore, the transport stage 43 can be moved to a position adjacent to each of the openings 16A and 16B in a plan view.

Further, a plate 44 is provided below the work space 21 and on the opposite side of the plate 22 with the openings 16A and 16B interposed therebetween. A pair of rails 45, 45 extending in the Y-axis direction are provided on the plate 44. The transport stage 46 is mounted on a pair of rails 45, 45 and is movable in the Y-axis direction. Therefore, the transport stage 46 can be moved to a position adjacent to each of the openings 16A and 16B in a plan view.

As described above, the transfer stage 43 and the transfer stage 46 can move in the Y-axis direction, and can move in a pair in the Y-axis direction. As a result, as shown in FIGS. 4 and 5, for example, when the pre-freezing drawer 2 on the opening 16A side is taken in and out of the pre-freezing container 3, the transport stage 43 and the rotating table 5 (standby table portion) are used. 29), the opening 16A, and the transport stage 46 can be arranged adjacent to each other in this order in the X-axis direction. The transfer stage 43 and the transfer stage 46 can be operated not only as a pair at the same time but also individually.

As shown in FIG. 4, the first extrusion arm 6 is a member for moving the envelope holder 10 placed on the standby table portion 29 to a predetermined storage space of the preliminary freezing drawer 2. The first extrusion arm 6 is provided on the transfer stage 43. The first extrusion arm 6 is composed of a first support portion 47 and a first pressing portion 48.

The first support portion 47 is below the transport stage 43, and is provided with a base end on a side surface opposite to the side surface facing the openings 16A and 16B. The tip of the first support portion 47 is movably attached in the X-axis direction.

The first pressing portion 48 is provided at the tip of the first supporting portion 47. The first pressing portion 48 can press the envelope holder 10 on the standby table portion 29 in the X-axis direction.

As described above, since the mounting surface 28A of the transport table portion 28 constituting the rotating table 5 is provided with an opening 30, the first pressing portion 48 is enveloped through the opening 30. The holder 10 can be pressed.

Further, the first extrusion arm 6 can retract the first pressing portion 48 to any position in the X-axis direction when the rotary table 5 rotates. Therefore, it is possible to avoid interference between the rotary table 5 and the first extrusion arm 6.

According to the first extrusion arm 6 configured in this way, the envelope holder 10 mounted on the mounting surface 29A of the standby table portion 29 is pressed toward the pre-freezing drawer 2 side, whereby the envelope holder 10 is pressed. Can be stored in a predetermined storage space of the preliminary freezing drawer 2.

According to the preliminary freezing device 200 of the present embodiment, the envelope holder 10 mounted on the mounting surface 29A of the standby table portion 29 has a vertical mounting surface 11A of the bottom plate 11 as shown in FIG. It is stored in the preliminary freezing drawer 2 in the direction facing the direction. Therefore, each of the envelopes 8 housed in the envelope holder 10 is pre-frozen in a direction in which the first surface 8A and the second surface 8B facing each other in the thickness direction are horizontal. In this way, since each envelope 8 is pre-frozen (slowly frozen) in a so-called laid state, there is no possibility that the biological sample will be biased in the flat bag 9 housed in the envelope 8. Therefore, pre-freezing (slow freezing) can be performed while keeping the temperature of the biological sample uniform.

As shown in FIGS. 4 and 5, the second extrusion arm 7 is housed in the storage space of the preliminary freezing drawer 2 maintained at a height adjacent to the standby table portion 29 by the preliminary freezing drawer elevating device 4. It is a member that moves the envelope holder 10 to the standby table portion 29 side by pressing the envelope holder 10 toward the standby table portion 29 side. The second extrusion arm 7 is provided on the transfer stage 46. The second extrusion arm 7 is composed of a second support portion 49 and a second pressing portion 50.

The second support portion 49 is on the transport stage 46, and is provided with a base end on a side surface opposite to the side surface facing the openings 16A and 16B. The tip of the second support portion 49 is movably attached in the X-axis direction.

The second pressing portion 50 is provided at the tip of the second supporting portion 49. The second pressing portion 50 pushes up to a predetermined height, and the predetermined envelope holder 10 in the preliminary freezing drawer 2 maintained at that height can be pressed in the X-axis direction.

According to the second extrusion arm 7 configured in this way, the envelope holder 10 housed in the storage space located at the height adjacent to the waiting table portion 29 in the preliminary freezing drawer 2 is placed on the waiting table. By pressing the portion 29 side, the envelope holder 10 can be placed on the mounting surface 29A of the standby table portion 29.

The preliminary freezing drawer elevating device 4, the rotating table 5, the first extrusion arm 6, and the second extrusion arm 7 are placed on the standby table portion 29 by operating in cooperation with each other. The envelope holder 10 can be stored in the pre-freezing drawer 2 that has been delivered from the pre-freezing container 3 by the pre-freezing drawer elevating device 4. Further, the pre-freezing drawer elevating device 4 allows the envelope holder 10 to be placed on the standby table portion 29 from the pre-freezing drawer 2 delivered from the pre-freezing container 3.

For example, as shown in FIGS. 4, 5, 10, and 11, when the envelope holder 10 is placed on the standby table portion 29 from the preliminary freezing drawer 2, first, the rotating table 5 and the transport stage 46 are moved. It moves to a position facing each other across the opening 16A in a plan view. Next, the rotating table 5 rotates so that the mounting surface 29A of the standby table portion 29 is horizontal. As a result, the mounting surface 29A and the opening 16A are in a state of being adjacent to each other in the X-axis direction.

Next, the pre-freezing drawer elevating device 4 is used to eject the pre-freezing drawer 2 from the pre-freezing container 3 through the opening 16A, and the bottom surface of the storage space and the standby table in which the target envelope holder 10 is stored. The pre-freezing drawer 2 is raised until the mounting surface 29A of the portion 29 is at the same height.

Next, while the preliminary freezing drawer 2 is maintained at a required height, the desired envelope holder 10 is spared by pressing the target envelope holder 10 in the X-axis direction with the second extrusion arm 7. It is moved from the freezing drawer 2 to the mounting surface 29A of the waiting table unit 29. By the above operation, the desired envelope holder 10 can be placed on the standby table unit 29.

Next, the rotating table 5 is rotated by 90 ° in a state where the bottom plate 11 of the envelope holder 10 mounted on the mounting surface 29A of the standby table portion 29 is in contact with the mounting surface 28A of the transport table portion 28. do. As a result, the envelope holder 10 is placed on the mounting surface 28A of the horizontal transport table portion 28.

Next, as shown in FIG. 5, the envelope holder 10 taken out on the transport table portion 28 is the housing of the preliminary freezing device 200 of the present embodiment by the first transport mechanism 27 provided in the work space 21. Is transported to the outside of the take-out port 51.

The input / output device (operation panel) (not shown) is, for example, a personal computer provided outside the housing and having a display unit and an input unit. The operator can perform various operations for storing and removing the envelope holder 10 by operating the input / output device and issuing an instruction to the control device 52 built in the preliminary freezing device 200. For example, when the operator places the envelope holder 10 on the rotating table 5 outside the housing and instructs the envelope holder 10 to be stored, the first transport mechanism 27 automatically causes the opening 16A or the opening 16B. The envelope holder 10 can be stored in the pre-freezing drawer 2 and pre-frozen in the pre-freezing container 3. In addition, the storage unit provided in the external input / output device can store the information of the envelope holder 10 that is pre-frozen in the pre-freezing device 200.

Further, as shown in FIGS. 2 to 4, the control device 52 in the preliminary freezing device 200 includes a preliminary freezing drawer elevating device 4, a first transfer mechanism 27, a rotary table 5, a transfer stage 43, and a transfer stage 46. , A control program for instructing the operation of the first extrusion arm 6, the second extrusion arm 7, and the like is incorporated. As a result, for example, after the envelope holder 10 is placed on the mounting surface 29A of the standby table portion 29 by the second extrusion arm 7, the preliminary freezing drawer 2 is lowered by the preliminary freezing drawer elevating device 4 to prepare the preliminary freezing drawer 2. It is possible to give an operation instruction such as moving it into the freezing container 3. As a result, it is possible to prevent the temperature of the other envelope holder 10 (biological sample) housed in the preliminary freezing drawer 2 from rising.

Next, a method of operating the pre-freezing device 200 of the present embodiment, that is, a method of pre-freezing a biological sample before cryopreservation using the above-mentioned pre-freezing device 200 will be described.

First, as shown in FIG. 6, a plurality (for example, 10) envelopes 8 containing the bags 9 in advance are stored in the envelope holder 10.

Next, as shown in FIGS. 1, 2 and 5, the rotating table 5 is arranged so that the mounting surface 11A of the envelope holder 10 is horizontal on the outside of the take-out port 51 of the housing of the preliminary freezing device 200. The envelope holder 10 is placed on the mounting surface 28A of the transport table portion 28 constituting the above. Then, the input / output device executes the start of operation. As a result, the transport stage 24 to which the rotary table 5 is attached by the first transport mechanism 27 moves inside the housing along the Y-axis direction, and the envelope holder 10 reaches a position adjacent to, for example, the opening 16A in a plan view. To carry. Further, above the transport stage 24, the transport stage 43 moves along the Y-axis direction so as to be at the same position as the rotary table 5.

Next, as shown in FIGS. 4, 5, 10 and 11, after confirming that the first pressing portion 48 is retracted, the rotating table 5 is 90 clockwise by the rotating mechanism 26. By rotating by °, the mounting surface 29A of the standby table portion 29 becomes horizontal. Then, the envelope holder 10 is placed on the mounting surface 29A so that the mounting surface 11A of the envelope holder 10 is vertical.

On the other hand, the pre-freezing drawer elevating device 4 pulls the pre-freezing drawer 2 that closes the opening 16A upward along the Z-axis direction, and stands by with the bottom surface of the desired storage space in the pre-freezing drawer 2. It is maintained at a height at which the mounting surface 29A of the table portion 29 is flush with the mounting surface 29A.

Next, the bottom surface 11B of the bottom plate 11 of the envelope holder 10 is pressed by the first pressing portion 48 constituting the first extrusion arm 6 through the opening 30 provided in the mounting surface 28A of the transport table portion 28. By pressing the pre-freezing drawer 2 side, the envelope holder 10 is automatically stored in the predetermined storage space of the pre-freezing drawer 2.

Next, when the envelope holder 10 is stored in the pre-freezing drawer 2, the pre-freezing drawer elevating device 4 pushes the pre-freezing drawer 2 downward along the Z-axis direction, and the pre-freezing drawer 2 is pushed downward along the Z-axis direction. The opening 16A is closed by 2.

On the other hand, after confirming that the first pressing portion 48 is retracted, the rotating table 5 is rotated 90 ° counterclockwise by the rotating mechanism 26, so that the mounting surface 28A of the transport table portion 28 Becomes horizontal. Next, the transport stage 24 to which the rotary table 5 is attached is moved along the Y-axis direction by the first transport mechanism 27, and the mounting surface 28A of the transport table portion 28 is automatically moved outward from the take-out port 51 of the housing. Come back to.

For example, when 100 envelopes 8 are stored in 10 envelope holders 10, the above operation is repeated 10 times. Next, when the pre-freezing device 200 detects that all the envelopes 8 are housed in the pre-freezing container 3, the liquid nitrogen type program freezer automatically starts cooling. According to the preliminary freezing device 200 of the present embodiment, a large amount (up to 100 sheets) of bags 9 can be cooled from room temperature to −80 ° C. within 1 hour to complete the preliminary freezing (slow freezing). ..

Next, when the pre-freezing device 200 detects the signal of the completion of pre-freezing, it pulls up the pre-freezing drawer 2 from the inside of the pre-freezing container 3, and takes out the stored envelope holder 10 from the housing of the pre-freezing device 200. It is carried out one after another to the outside of the mouth 51.

Specifically, first, the transport stage 24 to which the rotary table 5 is attached by the first transport mechanism 27 moves inside the housing along the Y-axis direction to a position adjacent to, for example, the opening 16A in a plan view. do.

Next, as shown in FIGS. 4, 5, 10 and 11, after confirming that the first pressing portion 48 is retracted, the rotating table 5 is rotated by 90 ° by the rotating mechanism 26. By doing so, the mounting surface 29A of the standby table portion 29 becomes horizontal.

On the other hand, the transport stage 46 moves along the Y-axis direction, and moves to a position opposite to the mounting surface 29A of the standby table portion 29 with the opening 16A in the plan view.

After confirming that the standby table portion 29 and the transport stage 46 have moved to a position adjacent to the opening 16A in a plan view, the preliminary freezing drawer 2 that closes the opening 16A is moved by the preliminary freezing drawer elevating device 4. It is pulled upward along the Z-axis direction and maintained at a height at which the bottom surface of the desired storage space in the preliminary freezing drawer 2 and the mounting surface 29A of the standby table portion 29 are flush with each other.

Next, the second pressing portion 50 constituting the second extrusion arm 7 waits for the envelope holder 10 housed in the storage space of the preliminary freezing drawer 2 maintained at a height adjacent to the waiting table portion 29. Press toward the table portion 29 side. As a result, the envelope holder 10 is moved to the standby table portion 29 side.

Next, when the movement of the envelope holder 10 from the inside of the pre-freezing drawer 2 to the mounting surface 29A of the standby table portion 29 is completed, the pre-freezing drawer elevating device 4 causes the pre-freezing drawer 2 to move along the Z-axis direction. The opening 16A is closed by the preliminary freezing drawer 2.

On the other hand, after confirming that the first pressing portion 48 is retracted, the rotating table 5 is rotated 90 ° counterclockwise by the rotating mechanism 26, so that the mounting surface 28A of the transport table portion 28 Becomes horizontal. Then, the envelope holder 10 is placed on the mounting surface 28A so that the mounting surface 11A of the envelope holder 10 is horizontal.

Next, the transport stage 24 to which the rotary table 5 is attached is moved along the Y-axis direction by the first transport mechanism 27, and the envelope holder 10 is automatically carried out from the take-out port 51 of the housing.

The envelope holder 10 mounted on the mounting surface 28A of the transport table portion 28 is automatically stored in the cryopreservation device 300 described later, or is taken out by an operator. After that, the remaining envelope holder 10 is also automatically carried out in the same manner.

As described above, according to the preliminary freezing device 200 of the present embodiment, the biological sample is placed in a flat bag (storage bag) 9, and the bag 9 is stored in a box-shaped envelope 8. Before cryopreservation in, the biological sample is cooled to an arbitrary temperature (for example, -80 ° C) equal to or higher than the temperature at which the biological sample is cryopreserved (for example, −180 ° C.). The envelope holder 10 for storing the above envelope 8, the pre-freezing drawer 2 for storing one or more envelope holders 10 in the vertical direction, and one or more pre-freezing drawer 2 are housed inside and communicated with the outside. The openings 16A and 16B are provided with a preliminary freezing container 3 provided on the upper surface.

In this way, since the pre-freezing container 3 dedicated to pre-freezing capable of accommodating a large amount of biological samples is provided, it is possible to collectively perform pre-freezing treatment on a large amount of biological samples in envelope units. can. Therefore, many biological samples can be cooled to the required temperature before cryopreservation in a short time.

Further, according to the preliminary freezing device 200 of the present embodiment, when the envelope holder 10 containing the envelope 8 is pre-frozen, the envelope holder 10 has excellent thermal conductivity and each envelope 8 is brought into close contact with the envelope holder 10. Since it is held in such a manner, each sample can be cooled evenly. Further, since the envelope holder 10 having a large heat capacity is cooled, the temperature rise of each sample can be suppressed when the sample is transferred from the pre-freezing device 200 to the cryopreservation device 300 after the pre-freezing is completed.

Further, according to the preliminary freezing device 200 of the present embodiment, the envelope holder 10 mounted on the mounting surface 29A of the standby table portion 29 is pre-frozen in a state where the mounting surface 11A of the bottom plate 11 is in the vertical direction. It is stored in the drawer 2. Therefore, each of the envelopes 8 housed in the envelope holder 10 is pre-frozen in a direction in which the first surface 8A and the second surface 8B facing each other in the thickness direction are horizontal. In this way, since each envelope 8 is pre-frozen (slowly frozen) in a so-called laid state, there is no possibility that the biological sample will be biased in the flat bag 9 housed in the envelope 8. Therefore, pre-freezing (slow freezing) can be performed while keeping the temperature of the biological sample uniform.

Further, according to the preliminary freezing device 200 of the present embodiment, the configuration is provided with a rotating table 5 that rotates so that the mounting surface 11A of the envelope holder 10 is horizontal or vertical while the envelope holder 10 is mounted. It has become. Therefore, the orientation of the envelope holder 10 can be changed automatically.

Further, according to the pre-freezing device 200 of the present embodiment, the envelope holder 10 can be automatically stored and carried out in the pre-freezing drawer 2 and the pre-freezing container 3, so that a large number of bags 9 can be collectively stored. Even in the case of pre-freezing, a huge amount of time and labor is not required.

According to the cryopreservation system 100 of the present embodiment, the pre-freezing device 200 dedicated to the pre-freezing described above and the biological sample pre-frozen by the pre-freezing device 200 are cryopreserved in a state of being housed in the envelope 8. It is configured to include a cryopreservation device 300 dedicated to cryopreservation. As described above, since the preliminary freezing and the cryopreservation are performed by separate devices, many biological samples can be cryopreserved in a short time.

Although the preliminary freezing device 200, which is an embodiment of the invention, has been described in detail with reference to the drawings, the specific configuration is not limited to this embodiment, and the design does not deviate from the gist of the present invention. Etc. are also included. For example, in the above-mentioned pre-freezing device 200, an example in which two pre-freezing drawers 2 are arranged so as to be adjacent to each other in the pre-freezing container 3 and provided with two openings 16A and 16B has been described. It is not limited to. For example, one pre-freezing drawer 2 may be housed in the pre-freezing container 3 and may have one opening, or three or more pre-freezing drawers 2 may be adjacent to each other in the pre-freezing container 3. They may be arranged in such a manner and have three or more openings.

Further, in the above-mentioned preliminary freezing device 200, an example in which an input / output device (not shown) is provided outside the housing has been described, but the present invention is not limited to this embodiment. For example, one or both of the input unit and the display unit of the input / output device may be provided on the outer wall of the housing so as to be integrally configured with the preliminary freezing device 200.

Further, in the pre-freezing device 200 described above, the control device 52 includes a pre-freezing drawer elevating device 4, a first transport mechanism 27, a rotary table 5, a transport stage 43, a transport stage 46, a first extrusion arm 6, and a first. An example in which a control program for instructing an operation is incorporated in the extrusion arm 7 or the like of 2 and an operator operates an input / output device connected to the outside to give various instructions to the control unit has been described. It is not limited. For example, the operator may operate the control device 52 without going through the input / output device to directly instruct each operating unit such as the preliminary freezing drawer elevating device 4.

Further, in the above-mentioned preliminary freezing device 200, the case where the flat bag 9 is housed in the envelope 8 has been described, but the case is not particularly limited as long as it can be stored in the envelope 8 such as a tube shape.

(Envelope holder holding mechanism)
Next, an example of the configuration of the envelope holder holding mechanism 400, which is an embodiment to which the present invention is applied, will be described.
As shown in FIGS. It is provided at a position adjacent to each of the freezing device 200 and the cryopreservation device 300. The envelope holder holding mechanism 400 is a device for temporarily holding the envelope holder 10 when the envelope holder 10 accommodating one or more envelopes 8 is transferred between the preliminary freezing device 200 and the cryopreservation device 300. Is.

Here, FIG. 12 is a plan view showing the configuration of the envelope holder holding mechanism 400 according to the embodiment of the present invention. FIG. 13 is a side view showing the configuration of the envelope holder holding mechanism 400 according to the embodiment of the present invention. FIG. 14 is a side view showing the configuration of the envelope holder holding mechanism 400 according to the embodiment of the present invention.

As shown in FIGS. 12 to 14, the envelope holder holding mechanism 400 according to the embodiment to which the present invention is applied is roughly composed of a shaft member 453, a support portion 454, and a drive portion 455.

The shaft member 453 is a rod-shaped member extending vertically in the vertical direction. The shaft member 453 is attached so as to be movable up and down in the Z-axis direction by a drive unit 455. Further, the shaft member 453 is narrower than the width of the slit portion 30B extending in the Y-axis direction among the openings 30 provided in the mounting surface 28A of the transport table portion 28 constituting the rotating table 5 described above. It is the width. Further, the shaft member 453 has a width narrower than the width of the slit portion 352B extending in the X-axis direction among the openings 352 provided in the mounting surface 305A of the first stage 305 of the cryopreservation device 300, which will be described later. It has become.

The support portion 454 is a disk-shaped member provided at the upper end of the shaft member 453. The upper surface of the support portion 454 has a shape that matches the circular recess 11C provided in the central portion of the bottom surface 11B of the envelope holder 10. The envelope holder 10 can be supported by bringing the upper surface of the circular support portion 454 into contact with the recess 11C from below the envelope holder 10.

Further, the support portion 454 is larger than the circular portion 30A penetrating the central portion of the mounting surface 28A among the openings 30 provided in the mounting surface 28A of the transport table portion 28 constituting the rotating table 5 described above. It has a small area. Further, the support portion 454 is smaller than the circular portion 352A penetrating the central portion of the mounting surface 305A among the openings 352 provided in the mounting surface 305A of the first stage 305 of the cryopreservation device 300 described later. It is an area.

The drive unit 455 can move the shaft member 453 up and down in the Z-axis direction and maintain the shaft member 453 at a predetermined height. As a result, the envelope holder 10 supported by the support portion 454 can be pushed up to a predetermined height, and the envelope holder 10 can be maintained at a predetermined height.

Next, an example of the operation method of the envelope holder holding mechanism 400 of the present embodiment will be described.
When passing the envelope holder 10 to and from the pre-freezing device 200, first, the envelope holder 10 before pre-freezing is placed on the upper surface of the support portion 454. At this time, since the shapes of the circular recess 11C provided in the central portion of the bottom surface 11B of the envelope holder 10 and the upper surface of the support portion 454 match, positioning can be easily performed.

Next, the drive unit 455 is driven to move the shaft member 453 upward in the Z-axis direction, and then the shaft member 453 is maintained at a predetermined height. As a result, the envelope holder 10 supported by the support portion 454 is retracted upward in the Z-axis direction.

Next, the transfer stage 24 is moved in the Y-axis direction by the first transfer mechanism 27 of the preliminary freezing device 200, and the rotary table 5 is moved from the take-out port 51 to the outside of the housing (not shown) of the preliminary freezing device 200. send out. The rotating table 5 is below the envelope holder 10 supported by the support portion 454, and moves to a position where the envelope holder 10 and the mounting surface 28A of the transport table portion 28 overlap in a plan view. Since the mounting surface 28A of the transport table portion 28 is provided with the slit portion 30B extending in the Y-axis direction, the shaft member 453 is inside the opening 30 without interfering with the rotating table 5. You can move.

Next, the drive unit 455 is driven to move the shaft member 453 downward in the Z-axis direction. As a result, the envelope holder 10 is placed on the mounting surface 28A of the transport table portion 28 of the rotating table 5. The support portion 454 descends together with the shaft member 453 and is retracted below the rotary table 5 through the opening 30 provided in the mounting surface 28A.

Next, the transfer stage 24 is moved in the Y-axis direction by the first transfer mechanism 27 of the preliminary freezing device 200, and the rotary table 5 is housed inside the housing (not shown) of the preliminary freezing device 200 from the take-out port 51. do. As described above, the envelope holder 10 before the preliminary freezing is delivered from the envelope holder holding mechanism 400 to the preliminary freezing device 200.

When the pre-frozen envelope holder 10 is delivered from the pre-freezing device 200 to the envelope holder holding mechanism 400, the procedure opposite to the above-described procedure is performed.

Similarly, when passing the envelope holder 10 to and from the cryopreservation device 300 described later, first, the envelope holder 10 is placed on the upper surface of the support portion 454. Next, the drive unit 455 is driven to move the shaft member 453 upward in the Z-axis direction, and then the shaft member 453 is maintained at a predetermined height. As a result, the envelope holder 10 supported by the support portion 454 is retracted upward in the Z-axis direction.

Next, the first stage 305 is moved in the X-axis direction by the second transport mechanism 361 described later of the cryopreservation device 300, and the first stage 305 is moved from the take-out port 362 to the housing of the cryopreservation device 300 (illustrated). Send out to the outside of). The first stage 305 is below the envelope holder 10 supported by the support portion 454, and moves to a position where the envelope holder 10 and the mounting surface 305A of the first stage 305 overlap in a plan view. Since the mounting surface 305A of the first stage 305 is provided with the slit portion 352B extending in the X-axis direction, the shaft member 453 of the opening 352 does not interfere with the first stage 305. Can move inward.

Next, the drive unit 455 is driven to move the shaft member 453 downward in the Z-axis direction. As a result, the envelope holder 10 is placed on the mounting surface 305A of the first stage 305. The support portion 454 descends together with the shaft member 453 and is retracted below the first stage 305 via the opening 352 provided in the mounting surface 305A.

Next, the first stage 305 is moved in the X-axis direction by the second transport mechanism 361 of the cryopreservation device 300, and the first stage 305 is moved from the take-out port 362 to the housing (not shown) of the cryopreservation device 300. Contain inside. As described above, the envelope holder 10 is delivered from the envelope holder holding mechanism 400 to the cryopreservation device 300.

When the envelope holder 10 is delivered from the cryopreservation device 300 to the envelope holder holding mechanism 400, the procedure opposite to the above procedure is performed.

Further, the envelope holder holding mechanism 400 may be one whose operation can be controlled by the control device 52 in the preliminary freezing device 200.

As described above, according to the envelope holder holding mechanism 400 of the present embodiment, when the envelope holder 10 accommodating one or more envelopes 8 is transferred between the preliminary freezing device 200 and the cryopreservation device 300, The envelope holder 10 can be temporarily held. At that time, by interlocking with the pre-freezing device 200 and the cryopreservation device 300, the envelope holder 10 before the pre-freezing can be automatically carried into the pre-freezing device 200, and the pre-frozen envelope holder 10 can be pre-frozen. After being automatically taken out from the device 200, it can be directly carried into the cryopreservation device 300. Therefore, even when a large amount of envelope 8 is pre-frozen or cryopreserved in a batch, it is safe without requiring a huge amount of time and labor.

(Croze storage device)
Next, the configuration of the cryopreservation device according to the embodiment to which the present invention is applied will be described with reference to FIGS. 1 to 3. As shown in FIGS. 1 to 3, the cryopreservation device 300 of the present embodiment includes a cryopreservation container 302, a drawer elevating device (first arm) 304 in the work space 303, a first stage 305, and a first stage. A second stage 306, a first pressing device (third arm) 307, and a second pressing device (second arm) 308 are roughly configured.

The cryopreservation device 300 of the present embodiment is provided in the cryopreservation container 302 by independently driving the drawer elevating device 304 and the second pressing device 308 by the control device 52 provided in the preliminary freezing device 200 described above. It automatically takes out the stored biological sample of interest and reduces the temperature rise of the biological sample other than the intended one.

As shown in FIG. 15, the drawer (freeze storage drawer) 313 is composed of a pair of vertical plates 331 and 331 as side surfaces and a plurality of floor plates 332 provided between the vertical plates 331 and 331. .. As a result, shelves are continuously provided in the Z-axis direction. In the cryopreservation device 300 of the present embodiment, the envelope 8 containing the biological sample is cryopreserved. The envelope 8 is housed at regular intervals on the shelves of the drawer 313 provided perpendicular to the Z-axis direction. In FIG. 15, 10 envelopes 8 are housed upright on each of the four shelves. In order to regulate the position and orientation of the envelope 8, it is preferable that the shelf of the drawer 313 is provided with a partition plate. A groove for erecting the envelope 8 may be provided instead of the partition plate. Further, since at least one side surface orthogonal to the pair of vertical plates is open, the envelope 8 can be taken in and out.

As shown in FIGS. 1 and 2, the cryopreservation container 302 is provided below the cryopreservation device 300 of the present embodiment. The cryopreservation container 302 is a container for accommodating the drawer 313 and cryopreserving it.

FIG. 16 is a schematic cross-sectional view of the cryopreservation container 302 in the cryopreservation apparatus 300 according to the embodiment to which the present invention is applied, as viewed from the side surface.
As shown in FIG. 16, the cryopreservation container 302 has a double structure formed of an inner tank 321 and an outer tank 322 made of stainless steel or the like, and the gap between the inner tank 321 and the outer tank 322 is a vacuum. It is a vacuum double insulation container. Therefore, by filling the inside of the inner tank 321 with a low-temperature liquefied gas such as liquid nitrogen, the inside can be kept in a low temperature state. For example, by filling liquid nitrogen up to the vicinity of the bottom of the inner tank 321, specifically under the drawer table (rotary table) 324 described later, the gas phase part inside the inner tank 321 is kept at −150 ° C. or lower. be able to.

Two openings 323a and 323b are provided on the upper surface of the cryopreservation container 302. The internal space of the cryopreservation container 302 and the work space 303 are communicated with each other through the openings 323a and 323b.
The two openings 323a and 323b are provided so as to be adjacent to each other in the radial direction of the drawer table 324 described later.

The opening area of each of the openings 323a and 323b is substantially the same as the area when the drawer 313 is viewed in a plan view. Therefore, when the envelope 8 is conveyed from the drawer 313 in the work space 303, it is possible to prevent the envelope 8 from accidentally falling from the openings 323a and 323b into the cryopreservation container 302.

Caps 325 that close the openings can be installed in the openings 323a and 323b. Here, in FIG. 16, a case where the opening 323a is provided with the cap 325 and closed, and the opening 323b is not provided with the cap 325 will be described as an example. By providing the cap 325 in each of the openings 323a and 323b, the opening is closed, so that the temperature rise in the cryopreservation container 302 can be suppressed.

The material of the cap 325 is not particularly limited as long as it has high heat insulating performance, and examples thereof include urethane foam resin.

A grip portion 326 is provided on the upper surface of the cap 325. The shape of the grip portion 326 is not particularly limited as long as it is easy to grip when the cap 325 is attached to and detached from the openings 323a and 323b, but it can be gripped by the drawer elevating device 304 described later. Shape is preferable. If the gripping portion 326 can be gripped by the drawer elevating device 304, the cap 325 can be automatically attached to and detached from the openings 323a and 323b by raising and lowering the drawer elevating device 304 in the Z-axis direction. ..

As shown in FIGS. 16 and 17, a drawer table 324 for mounting the drawer 313 is provided at the bottom of the cryopreservation container 302. The drawer table 324 is configured so that it can be rotated about the rotation shaft 328 by a motor 327 provided on the outside of the cryopreservation container 302 and coupled to the rotation shaft 328 of the drawer table 324.

Further, as shown in FIG. 17, on the drawer table 324, a plurality of drawers 313 can be placed on each circumference of any two concentric circles centered on the rotation axis 328. The openings and the concentric circles are aligned so that the openings 323a and 323b are on the circumferences of the concentric circles when viewed in a plan view.

Thereby, when taking out the arbitrary drawer 313, by rotating the drawer table 324, the arbitrary drawer 313 can be moved so as to be located directly under the opening 323a or the opening 323b.

Further, as shown in FIG. 16, a drawer guide 329 having a tapered shape with an extended upper end portion is provided on the drawer table 324 so as to correspond to a position where each drawer 313 is placed. By providing the drawer guide 329, each drawer 313 can be fixed so as to be placed in a predetermined position. This makes it possible to prevent the positions of the drawers 313 from shifting on the drawer table 324 when the drawer table 324 is rotated. Further, the tapered portion of the drawer guide 329 can correct the misalignment when the drawer 313 is lowered.

When each drawer 313 is placed on the drawer table 324, when the drawer 313 is raised by the drawer elevating device 304 described later, the drawer 313 is placed so that the open side surface faces the first stage 305 side.

A grip portion 333 is provided on the upper surface of the drawer 313. The shape of the grip portion 333 is not particularly limited as long as the drawer 313 can be raised and lowered in the Z-axis direction, but a shape that can be gripped by the drawer elevating device 304 described later is used. preferable. If the gripping portion 333 can be gripped by the drawer lifting device 304, the drawer 313 can be automatically loaded and unloaded from the openings 323a and 323b by raising and lowering the drawer lifting device 304 in the Z-axis direction. can.

As shown in FIGS. 1 and 2, the work space 303 is provided above the cryopreservation container 302 and communicates with the cryopreservation container 302 via the openings 323a and 323b. The cryopreservation device 300 of the present embodiment is surrounded by a housing (not shown), and the work space 303 is moved to an envelope 8 or the like taken out from the cryopreservation container 302 by nitrogen gas or the like evaporated from the inside of the cryopreservation container 302. It is maintained in a dry environment (for example, -20 ° C or lower) that can reduce frost formation. By covering the work space including the openings 323a and 323b of the cryopreservation container 302 with a housing, frostbite caused by the worker's direct contact with the drawer 313 and liquid nitrogen, and nitrogen gas evaporating from the openings 323a and 323b are caused. The risk of oxygen deficiency can be eliminated. Further, by maintaining the inside of the housing in a dry environment, it is possible to prevent dew condensation in the work space 303.

As shown in FIG. 18, the drawer elevating device 304 is for raising and lowering the drawer 313 in the Z-axis direction through either one of the openings 323a and 323b while holding the drawer 313 by gripping or the like. It is a member and is provided in the work space 303. The drawer elevating device 304 includes a support rail 341, an elevating device driving unit 342, a spindle unit 343, and a hook 344.

The support rail 341 is provided above the work space 303 in the X-axis direction. An elevating device drive unit 342 is attached to the support rail 341 so as to be movable in the X-axis direction.

The elevating device drive unit 342 is provided so that the spindle unit 343 hangs down. Further, a hook 344 is provided at the lower end of the spindle portion 343. The shape of the hook 344 is not particularly limited as long as it can grip the drawer 313. For example, it can be uncinus. As a result, the grip portion 333 provided on the upper part of the drawer 313 can be gripped.

According to the drawer elevating device 304 configured in this way, by moving the drawer elevating device 304 on the support rail 341 in the X-axis direction, the opening 323a and the opening 323b corresponding to the position of the drawer 313 in which the target sample is stored are provided. The hook 344 can be moved above either.

Further, when the drawer elevating device 304 is lowered into the cryopreservation container 302 to grip the grip portion 333 provided on the upper part of the drawer 313, the position of the hook 344 is moved by moving on the support rail 341 in the X-axis direction. Can be easily adjusted. As a result, even if there is only one drawer elevating device 304, the drawer 313 can be loaded and unloaded from the plurality of openings 323a and 323b.

Further, by driving the elevating device drive unit 342, the hook 344 can be raised and lowered in the Z-axis direction via the main shaft portion 343. That is, while holding the drawer 313, the drawer 313 can be raised and lowered in the Z-axis direction through either of the openings 323a and 323b. As a result, the drawer 313 can be taken in and out of the cryopreservation container 302.

Further, by stopping the driving of the elevating device driving unit 342, the hook 344 can be maintained at an arbitrary height in the Z-axis direction. That is, the drawer 313 can be maintained at an arbitrary height while the drawer 313 is being gripped.

As shown in FIGS. 3 and 19, a first X-axis rail 351 is provided below the work space 303 in the X-axis direction. The first stage 305 is attached to the first X-axis rail 351 and is movable in the X-axis direction. Therefore, the first stage 305 can move to a position adjacent to each of the opening 323a and the opening 323b when viewed in a plan view (particularly, see FIG. 3).

When the first stage 305 is adjacent to either of the openings 323a and 323b when viewed in a plan view, the drawer 313 is taken out from the drawer 313 with a desired envelope 8 housed at an arbitrary height. It is no longer necessary to remove the entire product from the cryopreservation container 302. As a result, the drawer 313 is raised until the bottom surface of the storage space in which the desired envelope 8 is stored and the first stage 305 are at the same height, whereby the second pressing device 308 (second arm) described later is used. ) Allows only the desired envelope 8 to be removed onto the first stage 305. Therefore, it is possible to suppress the temperature rise of samples other than the target sample. Further, since it is not necessary to pull up the entire drawer 313, the height direction of the device can be miniaturized.

As shown in FIG. 19, the first stage 305 has a mounting surface 305A, and the envelope holder 10 can be mounted on the mounting surface 305A.
Further, as shown in FIG. 12, an opening 352 is provided in a part of the mounting surface 305A. The opening 352 has a circular portion 352A penetrating the central portion of the mounting surface 305A and a slit portion 352B communicating with the circular portion 352A and extending in the X-axis direction.

Further, as shown in FIGS. 3 and 19, a second X-axis rail 354 is located below the work space 303 and on the opposite side of the first X-axis rail 351 with the openings 323a and 323b interposed therebetween. It is provided along the axial direction. The second stage 306 is attached to the second X-axis rail 354 and is movable in the X-axis direction. Therefore, the second stage 306 can move to a position adjacent to each of the opening 323a and the opening 323b when viewed in a plan view (particularly, see FIG. 3).

The first stage 305 and the second stage 306 are movable in the X-axis direction as described above, and are movable in the X-axis direction in pairs. As a result, for example, as shown in FIG. 19, when the drawer 313 is loaded and unloaded from the opening 323a, the first stage 305, the opening 323a, and the second stage 306 are arranged adjacent to each other in this order. Can be done. The first stage 305 and the second stage 306 can be operated not only as a pair at the same time but also individually.

The first pressing device 307 is for storing the envelope 8 in the drawer 313 by pressing the envelope 8 stored in the envelope holder 10 placed on the first stage 305 toward the drawer 313. It is a member. As shown in FIG. 3, the first pressing devices 307 and 307 are provided on the sides of the first stage 305 facing the openings 323a and 323b, respectively. As shown in FIG. 19, the first pressing device 307 includes a first supporting portion 356 and a first pressing portion 357.

The tip of the first support portion 356 is movably attached in the Y-axis direction.
The first pressing portion 357 is provided at the tip of the first supporting portion 356. Further, the first pressing portion 357 is provided with a plurality of pressing arms 157 ... As shown in FIGS. 3 and 19, in the cryopreservation device 300 of the present embodiment, the first pressing device 307 has 10 pieces so as to correspond to the number of envelopes 8 housed in the envelope holder 10. Pressing arms 157 are provided respectively. Each of the envelopes 8 housed in the envelope holder 10 can be pressed in the Y-axis direction by the plurality of pressing arms 157 provided on the first pressing portion 357.

According to the first pressing device 307 configured in this way, each envelope 8 is pressed toward the drawer 313 by pressing each envelope 8 housed in the envelope holder 10 placed on the first stage 305. 8 can be stored in the drawer 313.

The second pressing device 308 presses the envelope 8 housed in the drawer 313 maintained at a height adjacent to the first stage 305 by the drawer elevating device 304 toward the first stage 305 side. It is a member that moves the envelope 8 into the envelope holder 10 placed on the first stage 305. The second pressing device 308 is provided on the second stage 306. As shown in FIG. 19, the second pressing device 308 includes a moving table 358 and a second pressing portion 359.

The moving table 358 is provided so as to be movable in the X-axis direction on the second stage 306. Further, the second pressing portion 359 is mounted on the moving table 358 so as to be movable in the Y-axis direction. Further, one pressing arm 159 is provided at the tip of the second pressing portion 359.

The second pressing device 308 moves in the X-axis direction on the second stage 306, and the second pressing portion 359 moves in the Y-axis direction on the moving table 358, so that the second pressing portion 359 A pressing arm 159 provided at the tip presses a specific envelope 8 in the drawer 313 located at a height adjacent to the first stage 305 toward the first stage 305. As a result, the pressed envelope 8 can be stored in the envelope holder 10 placed on the first stage 305 from the drawer 313. The pressing arm 159 is preferably large enough to push out one envelope 8.
In the present embodiment, the configuration in which one pressing arm 159 is provided has been described as an example, but a plurality of pressing arms 159 can be provided. In this case, a plurality of envelopes 8 can be extruded at the same time.

As described above, the first pressing portions 357 of the first pressing devices 307 and 307 are each provided with a plurality of pressing arms 157. As a result, no matter which part of the envelope holder 10 the envelope 8 is housed in, the envelope 8 in the envelope holder 10 is pushed out toward the drawer 313 without considering the position of the envelope 8. It can be accommodated in the drawer 313. Further, even if there are a plurality of envelopes 8 in the envelope holder 10, they can be accommodated in the drawer 313 at one time.

In the cryopreservation device 300 of the present embodiment, a configuration in which two first pressing devices 307 are provided so as to face the openings 323a and 323b has been described as an example, but the first pressing device 307 is described. , As with the second pressing device 308, only one may be provided. In that case, the first pressing device 307 can move in the X-axis direction.

As shown in FIG. 20, the first and second drawer guides 155 and 255 are provided up and down in the Z-axis direction in which the drawer 313 moves. By providing guides at two locations along the Z-axis direction in this way, it is possible to regulate the displacement of the drawer 313 when the drawer 313 moves up and down, and therefore, the drawer 313 can be moved up and down in a more accurate position. This can be done in a more accurate posture.

The first drawer guide 155 is preferably provided on the support rail 341 which is a part of the drawer elevating device 304. As a result, when pulling up the drawer 313, it is possible to regulate the displacement of the upper part of the drawer 313 in particular.

The second drawer guide 255 is provided below the first drawer guide 155. As a result, when pulling up the drawer 313, it is possible to regulate the displacement of the lower part of the drawer 313 in particular. The second drawer guide 255 is attached to the second stage 306.

As shown in FIG. 21, the first and second drawer guides 155 and 255 are provided so as to surround the drawer 313 when viewed in a plan view. Thereby, the positional deviation in the two directions of the X-axis and the Y-axis can be regulated. If the shape of the drawer 313 is a quadrangular prism, the shapes of the first and second drawer guides 155 and 255 are preferably square frames.

As shown in FIG. 3, the cryopreservation device 300 of the present embodiment is provided with an outlet 362 in a housing covering the work space 303. Further, an automatic door may be used as the take-out port 362, and the first stage 305 may be moved on the X-axis in conjunction with the automatic door to serve as an automatic sliding door. In this case, the operator can carry the envelope holder 10 inside and outside the cryopreservation device 300 without putting his / her hand inside the housing.

The input / output device (operation panel) and the control device 52 can be used in common with the preliminary freezing device 200 according to the above-described embodiment.
The operator can perform various operations for taking out and storing the envelope 8 by operating the input / output device and giving an instruction to the control device 52. For example, the operator can select a sample to be taken out from the inventory information and instruct to take out the envelope 8, so that the envelope holder 10 containing the desired envelope 8 can be automatically moved to the outside of the take-out port 362. .. In addition, the storage unit included in the input / output device can store the information of the envelope 8 managed by the cryopreservation device 300.

Further, the control device 52 incorporates a control program that instructs the drawer elevating device 304, the first stage 305, the second stage 306, the first pressing device 307, the second pressing device 308, and the like to operate. There is. As a result, for example, after the envelope 8 is stored in the envelope holder 10 placed on the first stage 305 by the second pressing device 308, the drawer 313 is lowered by the drawer elevating device 304 and inside the cryopreservation container 302. It is possible to give an operation instruction such as moving to. As a result, it is possible to prevent the temperature of other samples housed in the drawer 313 from rising.

Next, a method of taking out the desired envelope 8 by ejecting the drawer 313 through the opening 323b using the above-mentioned cryopreservation device 300 will be described.

First, the operator operates an input / output device (not shown) to instruct the control device 52 to take out the desired envelope 8. As a result, the drawer 313 is raised through the opening 323b until the bottom surface of the storage space in which the desired envelope 8 is stored and the first stage 305 are at the same height. At this time, since the first and second drawer guides 155 and 255 are provided up and down in the Z-axis direction in which the drawer 313 moves, the drawer 313 can be moved to a predetermined position and in a predetermined posture. ..

Next, the pressing arm 159 of the second pressing device 308 moves in the X-axis direction and faces the desired envelope 8. The pressing arm 159 then presses the desired envelope 8 in the Y-axis direction to move only the desired envelope 8 from the drawer 313 to the envelope holder 10 on the first stage 305. By the above operation, the desired envelope 8 is placed on the envelope holder 10.

Next, the first stage 305 on which the envelope holder 10 on which the envelope 8 is placed is moved in the X-axis direction to the outside of the take-out port 362 of the housing that covers the work space 303. At this time, the envelope holder 10 is held on the support portion 454 of the envelope holder holding mechanism 400 by interlocking the envelope holder holding mechanism 400 described above. In this case, the operator can take out the envelope 8 without putting his / her hand in the housing of the cryopreservation device 300. By the above operation, the desired operation of taking out the envelope 8 is completed.

Hereinafter, a method of accommodating the envelope 8 in the cryopreservation device 300 will be described.
First, the envelope holder 10 is held on the support portion 454 of the envelope holder holding mechanism 400. The operator then accommodates the envelope 8 at a designated location on the envelope holder 10. This designated location is instructed by the input / output device based on the warehousing / delivery status. Next, the input / output device (not shown) is operated to move the first stage 305 in the X-axis direction, the envelope holder 10 is handed over from the envelope holder holding mechanism 400 to the first stage 305, and then the take-out port 362. The first stage 305 is carried into the cryopreservation device 300.

Next, the first stage 305 on which the envelope holder 10 is placed is moved in the X-axis direction so as to be adjacent to the opening 323b. At this time, the drawer 313 is moved so that the first stage 305 and the bottom surface of the drawer shelf to be accommodated are at the same height.

Next, the pressing arm 157 of the first pressing device 307 is moved in the Y-axis direction and abutted against the envelope 8 housed in the envelope holder 10. After that, the envelope 8 is further extruded, and when the entire envelope 8 is accommodated in the drawer 313, the movement is stopped. As a result, the envelope 8 is accommodated in the drawer 313.
At this time, since the first pressing device 307 has a plurality of pressing arms 157, the envelope 8 can be reliably accommodated in the drawer by one extrusion regardless of where the envelope holder 10 is accommodated. Further, even a plurality of envelopes 8 can be accommodated by one extrusion. The drawer 313 is then housed in the cryopreservation container 302.

According to the cryopreservation device 300 of the present embodiment, a drawer 313 that stores the envelopes 8 in several stages by arranging them in the vertical direction is housed inside, and openings 323a and 323b that communicate with the work space 303 are provided on the upper surface. While holding the cryopreservation container 302 and the drawer 313, the drawer elevating device 304 that raises and lowers the drawer 313 in the vertical direction through the openings 323a and 323b and maintains the drawer 313 at an arbitrary height. The first stage 305 and the envelope 8 are provided above the cryopreservation container 302 and adjacent to the openings 323a and 323b when viewed in a plan view, and on which an envelope holder 10 capable of accommodating the envelope 8 is placed. Is provided with a second pressing device 308 that presses and moves the container to the envelope holder 10 on the first stage 305.

As described above, since the first stage 305 is provided so as to be adjacent to the openings 323a and 323b when viewed in a plan view, when the target envelope 8 is taken out from the cryopreservation container 302 by the drawer elevating device 304, Only the target envelope 8 can be taken out by the second pressing device 308 to the envelope holder 10 placed on the first stage 305 without pulling the entire drawer 313 out of the cryopreservation container 302. Therefore, the target envelope 8 can be automatically taken out, and the temperature rise of other than the target envelope 8 can be suppressed.

Further, according to the cryopreservation device 300 of the present embodiment, at least the drawer elevating device 304 and the second pressing device 308 are controlled. Therefore, after the envelope 8 is placed on the envelope holder 10 on the first stage 305 by the second pressing device 308, the drawer 313 is lowered by the drawer elevating device 304 and housed in the cryopreservation container 302. Can be done automatically. As a result, it is possible to further suppress the temperature rise of other than the target envelope 8.

Further, according to the cryopreservation device 300 of the present embodiment, the first and second drawer guides 155 and 255 are provided at two locations above and below the drawer 313 in the Z-axis direction. Therefore, the misalignment of the drawer 313 in the X-axis and Y-axis directions can be regulated. In the present invention, since only a predetermined envelope 8 among the plurality of envelopes 8 placed on the shelves of the drawer 313 is taken out, high accuracy is required for the position of the envelope 8. It is preferable that the first and second drawer guides 155 and 255 are provided because the misalignment of the drawer 313 in the X-axis and Y-axis directions can be further regulated. Further, it is preferable that the first and second drawer guides 155 and 255 are provided vertically in the Z-axis direction because the inclination and sway that may occur when the drawer 313 is moved up and down can be regulated.

Further, according to the cryopreservation device 300 of the present embodiment, the first pressing portion 357 has a plurality of pressing arms 157, and the second pressing portion 359 includes one pressing arm 159. The pressing arm 159 can move on the second stage 306 in the X-axis direction and push only the desired envelope 8 in the direction of the first stage 305. The drawer 313 is provided with a storage space for a plurality of envelopes 8 having a width corresponding to the storage space for the envelope holder 10. Further, the envelope holder 10 is arranged so that the storage space thereof and the storage space of the drawer 313 coincide with each other in the Y-axis direction. Therefore, by pushing the pressing arm 159 in the Y-axis direction, the envelope 8 housed in the drawer 313 can be housed in the envelope holder 10 on the first stage 305.

Although the cryopreservation device 300 of the present embodiment has been described in detail with reference to the drawings, the specific configuration is not limited to this embodiment, and includes a design and the like within a range that does not deviate from the gist of the present invention. Is done. For example, in the above-mentioned cryopreservation device 300, an example in which drawers 313 are concentrically arranged in two stages in a cryopreservation container 302 and provided with two openings 323a and 323b has been described, but the present invention is limited to this embodiment. is not it. For example, the drawers 313 may be arranged in one arbitrary circle in the cryopreservation container 302 and have one opening, or the drawer 313 may be arranged in three or more arbitrary concentric circles in the cryopreservation container 302. It may be arranged in a row and have three or more openings.

Further, in the cryopreservation device 300 of the above-described embodiment, the configuration in which the drawer 313 is provided with a storage space for accommodating a plurality of envelopes 8 has been described as an example, but the present invention is not limited to this. For example, the drawer 313 may be provided with a shelf for storing the envelope holders 10 side by side in the Z-axis direction. In this case, the first pressing device 307 is composed of the first supporting portion 356 and the first pressing portion 357, and a plurality of pressing arms 157 are unnecessary. Further, the second pressing device 308 is composed of the second pressing portion 359, and one pressing arm 159 becomes unnecessary.

The pre-freezing device, cryopreservation device and cryopreservation system of the present invention can be used as a device for cryopreserving biological samples such as blood, sperm of laboratory animals, fertilized eggs, and cells.

2 ... Preliminary freezing drawer, 3 ... Preliminary freezing container, 4 ... Preliminary freezing drawer elevating device (elevating mechanism), 5 ... Rotating table, 6 ... First extrusion arm, 7 ... Second extrusion arm, 8 ... envelope, 9 ... bag (storage bag), 10 ... envelope holder, 11 ... bottom plate, 11A ... mounting surface, 11B ... bottom surface, 11C ... recess, 12 ... partition plate, 13 ... heat insulating member, 14 ... injection nozzle, 15 ... electric fan (fan), 16 ... flat part, 16A, 16B ... opening, 17 ... support pillar, 18 ... movable part, 20 ... connecting member, 21 ... work space (outside), 22 ... plate, 23 ... first Y-axis rail, 24 ... transport stage, 25 ... drive device, 26 ... rotation mechanism, 27 ... first transport mechanism, 28 ... transport table section (convey table), 28A ... mounting surface (second mounting surface) , 29 ... Standby table part (standby table), 29A ... Mounting surface (first mounting surface), 30 ... Opening, 30A ... Circular part, 30B ... Slit part, 31, 32 ... Holder guide, 33 ... Rotation Shaft (axis), 34 ... Support part, 35 ... Rotating plate, 36 ... Rotor part, 37 ... Drive part, 38 ... Belt, 39,40 ... Support member, 41,44 ... Plate, 42,45 ... Rail, 43 , 46 ... Conveying stage, 47 ... 1st support, 48 ... 1st pressing, 49 ... 2nd support, 50 ... 2nd pressing, 51 ... Extraction port, 52 ... Control device, 100 ... Cryopreservation system, 155 ... first drawer guide, 157 ... pressing arm, 159 ... pressing arm, 200 ... preliminary freezing device, 255 ... second drawer guide, 300 ... cryopreservation device, 302 ... cryopreservation container, 303 ... Work space, 304 ... Drawer lifting device (first arm), 305 ... first stage, 306 ... second stage, 307 ... first pressing device (third arm), 308 ... second pressing device (Second arm), 313 ... Drawer (drawer for cryopreservation), 321 ... Inner tank, 322 ... Outer tank, 323a, 323b ... Opening, 324 ... Drawer table (rotary table), 325 ... Cap, 326 ... Gripping 327 ... Motor, 328 ... Rotating shaft, 329 ... Drawer guide, 331 ... Vertical plate, 332 ... Floor plate, 333 ... Grip part, 341 ... Support rail, 342 ... Lifting device drive unit, 343 ... Main shaft part, 344 ... Hook , 351 ... 1st X-axis rail, 352 ... Opening, 353 ... Box guide, 354 ... 2nd X-axis rail, 356 ... 1st support, 357 ... 1st pressing, 358 ... Moving Table, 359 ... Second pressing part, 36 1 ... 2nd transport mechanism, 362 ... Take-out port, 400 ... Envelope holder holding mechanism, 453 ... Shaft member, 454 ... Support part, 455 ... Drive part

Claims (17)

A pre-freezing device that cools the biological sample to an arbitrary temperature before cryopreserving the biological sample in a box-shaped envelope.
An envelope holder that stores one or more of the envelopes side by side,
A pre-freezing drawer that stores one or more envelope holders side by side in the vertical direction,
A pre-freezing container for accommodating one or more of the pre-freezing drawers inside and having an opening for communicating with the outside on the upper surface is provided .
The envelope is a box-shaped storage member having a first surface and a second surface facing each other in the thickness direction.
The envelope holder has a mounting surface of the envelope and a plurality of partition plates erected in a direction perpendicular to the mounting surface described above.
A pre-freezing device in which the envelope is inserted into a space partitioned by the partition plate so that the first surface and the second surface are in close contact with the partition plate. The pre-freezing device according to claim 1 , wherein the envelope holder is housed in the pre-freezing drawer with the above-mentioned placing surface facing in the vertical direction. The pre-freezing device according to claim 1 or 2 , wherein the pre-freezing container has an envelope holder and one or more fans for cooling the envelope by the cooling heat of liquid nitrogen. An elevating mechanism that raises and lowers the pre-freezing drawer in the vertical direction through the opening and maintains the pre-freezing drawer at an arbitrary height.
A waiting table above the pre-freezing container, which is provided so as to be adjacent to the opening when viewed in a plan view, and which can transfer the envelope holder to and from the pre-freezing drawer.
A first extrusion arm that moves the envelope holder placed on the waiting table to the pre-freezing drawer, and
The invention according to any one of claims 1 to 3 , further comprising a second extrusion arm for moving an envelope holder located at a height adjacent to the waiting table from the pre-freezing drawer to the waiting table. Pre-freezing device. The waiting table has a first mounting surface on which the envelope holder is placed in a vertical direction when the envelope holder is delivered to and from the pre-freezing drawer. Item 4. The preliminary freezing device according to item 4. Two or more of the openings are provided on the upper surface of the pre-freezing container so as to be adjacent to each other in another direction orthogonal to the direction from the pre-freezing drawer toward the waiting table.
The pre-freezing device according to claim 5 , wherein each of the pre-freezing drawers is housed in the opening. The pre-freezing drawer has a heat insulating member at the top.
The pre-freezing device according to claim 6 , wherein when the pre-freezing drawer is housed in the pre-freezing container, the heat insulating member closes each of the openings. The pre-freezing device according to claim 6 or 7 , wherein the waiting table is movable in the other direction. Further provided with a transport table on which the envelope holder is placed,
The pre-freezing device according to any one of claims 6 to 8 , wherein the transport table is movable in the other direction. The preliminary freezing device according to claim 9 , wherein the transport table has a second mounting surface on which the envelope holder is mounted in a state where the previously described mounting surface of the envelope holder is horizontally oriented when the envelope holder is transported. The waiting table and the transport table are L in a state where the first mounting surface and the second mounting surface are orthogonal to each other and the first mounting surface and the second mounting surface are adjacent to each other. A rotating table integrated in a shape and
The rotating table is set so that either one of the first mounting surface and the second mounting surface is horizontal with the line where the first mounting surface and the second mounting surface intersect as an axis. A rotation mechanism that rotates 90 ° and
The pre-freezing device according to claim 10 , further comprising a first transport mechanism for moving the swivel table in the other direction and transporting the swivel table to the inside and outside of the pre-freezing device. The pre-freezing device according to any one of claims 1 to 11.
A cryopreservation system comprising a cryopreservation device for cryopreserving the biological sample pre-frozen by the pre-freezing device in a state of being housed in the envelope. The cryopreservation system according to claim 12 , further comprising an envelope holder holding mechanism capable of transferring the envelope holder accommodating one or more envelopes between the preliminary freezing device and the cryopreservation device. The cryopreservation device includes a cryopreservation drawer that stores the envelopes side by side, and a cryopreservation container having an opening that communicates with the outside on the upper surface.
With the first arm holding the cryopreservation drawer, the cryopreservation drawer is raised and lowered in the vertical direction through the opening, and the cryopreservation drawer is maintained at an arbitrary height. ,
A first stage above the cryopreservation container, which is provided so as to be adjacent to the opening when viewed in a plan view, and on which the envelope holder for accommodating the envelope can be placed.
A second arm that moves the envelope in the cryopreservation drawer located at a height adjacent to the first stage to the envelope holder mounted on the first stage.
The cryopreservation system according to claim 12 or 13 , further comprising a third arm for moving the envelope in the envelope holder placed on the first stage to the cryopreservation drawer. The cryopreservation device further comprises a rotary table at the bottom of the cryopreservation container.
The cryopreservation drawer can be placed on the circumference of an arbitrary circle centered on the rotation axis of the rotary table, and the cryopreservation drawer can be placed.
The cryopreservation system according to claim 14 , wherein the opening is located on the circumference of the circle when viewed in a plan view. Two or more openings are provided on the upper surface of the cryopreservation container so as to be adjacent to each other in a direction orthogonal to the direction from the cryopreservation drawer toward the first stage.
The rotary table allows the cryopreservation drawer to be placed on each circumference of any two or more concentric circles centered on the rotary axis of the rotary table.
The cryopreservation system according to claim 15 , wherein the openings are located on each circumference of the concentric circles when viewed in a plan view. A plurality of pressing arms are provided at the tip of the third arm.
The cryopreservation system according to any one of claims 14 to 16 , wherein the plurality of pressing arms are inserted into a space partitioned by a partition plate of the envelope holder.

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