JP2001245957A - Apparatus and method for sealing double-chamber container for medical treatment - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an apparatus and a method in which the internal capacity of each chamber of a double-chamber container is controlled to be constant, and only a communication passage of the double-chamber container can be reliably sealed in one pressing operation. SOLUTION: In the sealing apparatus (1) for the communication passage of the double-chamber container having the communication passage to communicate the double chambers with each other and a connection portion, the sealing apparatus comprises a body (10) and a pressing means (20), the body (10) comprises a heating body (13) to bond only the communication passage with the communication passage and the connection portion placed thereon, an insulation body (14) to insulate the heating body from the body, a first capacity control unit (11) to control the capacity with the double-chamber container placed thereon and a second capacity control unit (12) to control the capacity with the other chamber of the double-chamber container placed thereon, the heating body (13) is provided between the first capacity control unit 11 and the second capacity control unit (12), and the pressing means (20) includes a pressing unit (21) to press the communication passage in the sealing apparatus (1) of the double-chamber container.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus and a sealing method for sealing a communication passage communicating each chamber of a multi-chamber container. More specifically, the present invention relates to a method and an apparatus for sealing a communication passage while controlling the internal volume of each chamber of a multi-chamber container to a fixed amount.

[0002]

2. Description of the Related Art Conventionally, red blood cells, platelets, white blood cells, bone marrow,
As a long-term storage method of a cell suspension such as hematopoietic stem cells, a method of immersing a cryopreservation container containing the cell suspension in liquid nitrogen and cryopreserving the same is adopted.

In recent years, it has become clear that the behavior of water crystals (ice) generated in cells during cryopreservation affects the damage to cell membranes and, as a result, the survival of cells. In order to enhance the survival of the cells, it is necessary to strictly adjust the cooling temperature from the start of freezing to a temperature at which the water in the cells stabilizes as crystals that do not damage the cell membrane. In order to rigorously adjust the cooling rate of the cell suspension, it is necessary to make the thickness of the cell suspension contained in the cryocontainer uniform over the entire surface of the cryocontainer.

Therefore, a flat type freezing container has been conventionally used. However, when a cell suspension is stored in a flat-type frozen container, the container shape after storage greatly changes from a plate shape to a sleeper shape according to the storage amount, so that the storage amount changes greatly. At this time, since the thickness of the container is small at the end of the container and large at the center, cooling of the cell suspension contained in the frozen container proceeds rapidly at the end of the container, and cooling is delayed at the center of the container. Tend. For this reason, it is difficult to freeze the contained cell suspension at a uniform speed in the flat-type freezing container, and this becomes a problem particularly as the accommodation amount of the cell suspension increases. In order to solve such a problem, a so-called three-dimensional freezing container having a flat rectangular chamber has been adopted. When the three-dimensional freezing container contains the cell suspension, the liquid thickness becomes uniform over the entire freezing container, so that the cell suspension can be frozen at a uniform speed. However, even when a three-dimensional freezing container is used, if the volume of the cell suspension to be stored exceeds the specified volume, water may expand during freezing and cause damage to the container. there were. For this reason, in recent years, a three-dimensional type freezing container has been replaced with a flat rectangular container (canister) so that the freezing container can be frozen at a uniform speed without being held in a horizontal state, and the freezing container can be prevented from being damaged. And the cell suspension is frozen while keeping the thickness of the cell suspension constant.

When the cell suspension is used in a clinical setting, the same cell suspension may be used a plurality of times, for example, by thawing only a part of the same cell suspension to proliferate the cells. Required. Therefore, a three-dimensional double-chamber freezing container that can be used by separating only a part of the cell suspension has been adopted. However, when the cell suspension is stored and frozen in such a three-dimensional multi-compartment freezing container, the smaller chamber of the multi-compartment freezing container is often damaged during freezing, and the valuable cell suspension is lost. was there.

[0006] In order to solve the above problems, the present applicant has already proposed a method and a sealing device for sealing a communication passage which communicates a plurality of chambers of a multi-chamber freezing container (Japanese Patent Laid-Open No. Hei 11-1999). -3
No. 42179). This is a device that can mount a large room and a small room of a double-compartment freezing container composed of two large and small rooms, and seals a communication passage between the large room and the small room while controlling the capacity of the small room.
As a result, the small chamber container is no longer damaged, but since only the capacity of the small chamber is controlled, the capacity of the small chamber tends to be small, and the capacity of the large chamber tends to be large. Is desired. In addition, not only the communication path of the multi-chamber container but also the cutting guide cut portion provided for separation is welded during the sealing operation. For this reason, the cutting distance becomes long, and there is a possibility that the frozen container may be cut off accidentally, causing liquid leakage. Furthermore, in order to completely weld the communication passage of the freezing container, it is necessary to perform an average of five pressing operations per container, and the operation is complicated. In addition, during the pressing operation, the temperature of the sealing device itself also increases, and there is a concern that the viability of the cell suspension in the cryocontainer may be affected during the sealing operation.

[0007]

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned circumstances, and it has been proposed to seal a communication passage while controlling the volume of a cell suspension contained in each chamber of a multi-chamber container to a fixed amount. It is possible to securely seal only the communication path by a single pressing operation without welding the cutting guide cut portion provided for separating the respective chambers of the multi-chamber container, Moreover, an object of the present invention is to provide a sealing device and a sealing method in which the temperature of the sealing device does not increase during a pressing operation. The present inventor has conducted various studies in order to achieve the above object, and as a result of adopting a deformed heater for the sealing device, it is possible to reliably weld only the communication path without increasing the temperature of the sealing device. I found that. Further, they have found that the capacity can be controlled to a fixed amount by providing a capacity control unit for controlling the capacity of each chamber of the multi-chamber container in the sealing device, and arrived at the present invention.

[0008]

That is, the present invention provides a method of
A sealing device for a communication passage of a multi-chamber container having two multi-chambers, a communication passage connecting the multi-chambers, and a connecting portion connecting the multi-chambers, wherein the sealing device has a main body and a pressurizing means. Become
The main body mounts one of the chambers of the multi-chamber container, and controls the capacity of the first chamber and the second chamber of the multi-chamber container, and controls the capacity of the second chamber. A heating element for mounting the communication path and the connecting portion of the multi-chamber container and welding only the communication path, and an insulator for insulating the heating element and the main body. It is provided between the first capacity control section and the second capacity control section, and the pressurizing means includes a pressurizing section for pressurizing the communication path and the connecting section on the heating element. It is a sealing device for a multi-chamber container.

[0009] The present invention also relates to a cell suspension containing a cell suspension.
A multi-chamber container having two multi-chambers, a communication passage connecting the multi-chambers, and a connecting portion connecting the multi-chambers is placed on the main body of the sealing device, and the cell suspension of each chamber is removed. After controlling the capacity, the communication path is pressurized using the pressurizing means of the sealing device, and the multi-chamber container is sealed by welding the communication path by the heat generated by the heating element of the sealing device. Is the way.

[0010]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The multi-chamber container according to the present invention may have various shapes depending on the cell suspension to be contained.
Preferably, it comprises two flat rectangular double chambers, a communication passage communicating the multiple chambers, and a connecting portion having a cutting guide cut for connecting the multiple chambers and separating the multiple chambers. It is a multi-chamber container. The cell suspension contained in the multi-chamber container of the present invention includes hematopoietic stem / progenitor cells contained in red blood cells, platelets, white blood cells, bone marrow, peripheral blood and cord blood.
The material of the double-chamber container of the present invention preferably has a melting point of 150 ° C. or less, and includes, for example, a polyolefin resin. In particular, when the multi-chamber container is used for freezing, ultra-high molecular weight polyethylene resin, ethylene-vinyl acetate copolymer resin, fluorine resin, cold-resistant synthetic resin such as polyimide resin are preferably mentioned, and liquid nitrogen is preferably used. Those that can withstand temperature are good.

[0011] The capacity control section of the present invention controls the capacity of each chamber of the multi-chamber container to a constant capacity. In order to control the volume in the multi-chamber container to be constant, it is necessary to control the thickness of the cell suspension contained in the multi-chamber container to a certain thickness. Such a capacity control unit includes a mounting table on which each chamber of the multi-chamber container is mounted, an openable and closable lid member for controlling the capacity of the contents in the multi-chamber container to a constant value, and a lid member that does not float. And a fixing device for fixing the fixing member. It is preferable that the capacitance control section is formed of a material such as a metal that has a small deformation. In addition, the capacity control unit and the multi-chamber container are provided so that heat from the main body is transmitted to the multi-chamber container via the capacity control unit and does not affect the cell suspension contained in the multi-chamber container. A resin plate may be provided on the contact surface with the resin. Examples of the material for forming the resin plate include a polypropylene resin, a polycarbonate resin, a polyethylene resin, and a polyoxymethylene resin.

The heating element of the present invention is provided between the capacity control sections, places the communication path and the connection section of the multi-chamber container, and welds only the communication path. Such a heating element is preferably a modified heater comprising a portion (A) for welding the communication passage and a portion (B) for not welding the communication passage. The irregular heater is
Part where the communication passage is welded (A) and part where the communication passage is not welded (B)
Have different widths. Specifically, the portion where the communication passage is welded (A)
Is 1 / compared to the width of the part (B) where the communication passage is not welded.
It is preferably 5/3/5. More preferably, 1 /
2. If it is less than 1/5, the welding width becomes too small, and the bag may be cut at the time of cutting, causing liquid leakage. If it is larger than 3/5, the heat generation temperature of the non-welded portion (B) rises, and the cut-inducing notch may be welded. Further, in the deformed heater, the heat generation temperature of the portion where the communication passage is welded (A) is higher than the melting point of the material of the multi-chamber container, and the heat generation temperature of the portion where the communication passage is not welded (B) is higher than the melting point of the material. Is also low. Preferably, the heating temperature of the portion (A) where the communication path of the irregular shaped heater is welded is 30 ° C.
0 to 400 ° C., and the heat generation temperature of the portion (B) where the communication passage is not welded is 25 to 100 ° C. Examples of such a heating element include a thin strip of a nichrome alloy, inconel, or the like, which is formed in a ribbon shape. The linear heater in the present invention refers to a heating element having a constant width.

[0013] The insulator of the present invention is provided between the heating element and the main body to prevent the current from leaking to the main body when the current flows through the heating element. As such an insulator,
An electrically insulating resin is preferable, and examples thereof include a polytetrafluoroethylene resin, a silicone resin, and a fluorine resin.

[0014] The pressurizing means of the present invention comprises a pressurizing section for pressurizing the communication path and the connecting portion of the multi-chamber container mounted on the heating element. The pressing means is formed from a thermoplastic resin such as a polypropylene resin. It is preferable that the pressurizing portion has flexibility to uniformly press the communicating portion of the multi-chamber container against the heating element and has heat resistance. For example, a heat-resistant resin such as a silicone resin and a fluoro rubber is used.

Next, an embodiment of the present invention will be described with reference to the drawings. 1 is a diagram showing an embodiment of a sealing device for a multi-chamber container, FIG. 2 is a plan view of a capacity control unit of the sealing device shown in FIG. 1, and FIG. 3 is a capacity control unit shown in FIG. FIG. 4 is a plan view showing a state in which a multi-chamber container is placed in FIG. 4, and FIG. 4 is a plan view showing an example of the multi-chamber container.

The multi-chamber container (2) according to the present invention has, for example, two flat rectangular multi-chambers (21) and (22) as shown in FIG. 4, and a communication passage (23) ( 24) and a connecting portion (25) for connecting the multiple chambers. The connecting portion (25) is provided with a cutting guide notch (251) capable of easily separating each chamber.

As shown in FIG. 1, the sealing device 1 of the present invention comprises an aluminum alloy main body (10) and a pressurizing means (20). The main body (10) includes a first capacity control section (11) and a second capacity control section (12) made of an aluminum alloy. FIG.
As shown in (1), the first capacity control unit (11) includes a first mounting table (111) for mounting one of the chambers of the multi-chamber container, and an openable and closable second control unit for controlling the capacity in the container to a fixed amount. One lid member (112) and a first fixture for fixing the first lid member (112) to the first mounting table (111)
(113). The second capacity control unit (12) includes a second mounting table (121) for mounting the other chamber of the multi-chamber container, and an openable / closable second lid member (122) for controlling the capacity of the container to a constant capacity. And a second fixing member (123) for fixing the second lid member (122) to the second mounting table (121). The first mounting table (111) and the second mounting table (12
Between 1), a heating element (1
An insulator (14) made of 3) and Teflon (registered trademark) is provided. The pressing means (20) has a pressing portion (21) made of a silicone resin.

Next, a method of using the sealing device of the present invention is shown in FIG.
This will be described with reference to FIGS. First, place the cell suspension in a multi-chamber container.
As shown in FIG. 3, the thin part of the heating element (13) composed of a deformed heater is connected to the communication passage (23) (2) of the multi-chamber container (2).
4) Place the multi-chamber container (2) underneath. And
Closing the first lid member (112) and the second lid member (122),
The fixing device (113) and the second fixing device (123) are connected to the first lid member (112).
And it is inserted and fixed to the second lid member (122). Next, when the pressurizing means (20) is depressed, a current flows through the electrodes in the main body (10) and the heating element (13) generates heat, the communication passages (23) and (24) are welded, and the connecting portion is welded. Not to be.

[0019]

The present invention will be described below in more detail with reference to examples. Example 1 A container having a thickness of 8 mm and a capacity of 20 shown in FIG.
Three multi-chamber containers (2) each having a total capacity of 25 ml having a large chamber of 5 ml and a small chamber of 5 ml are prepared. 10% DMSO + in each container
1% Dextran aqueous solution was filled in 25 ml each, and FIG.
The capacity control units (11) and (12) of the sealing device (1) shown in
Is placed as shown in FIG. The first and second lid members (1
12) (122) is closed, and the cover members (112) and (122) are inserted into the first and second fixtures (113) and (123), and the first and second mounting tables are inserted.
Fixed to (111) and (121) (with large and small room control). Next, the pressurizing means (20) was pushed down, and the communication paths (23) and (24) were welded. After that, the large room (21) and small room (22) were separated, and the large room (21) and small room (2
Each capacity of 2) was measured. Table 1 shows the results.

[Comparative Example 1] A double-chamber container as in Example 1.
Prepare three (2), capacity control unit of the sealing device (1) shown in FIG.
(11) The multi-chamber container (2) is placed on the (12) as shown in FIG. 3, and the first and second lid members (112) and (122) are not closed (no large / small chamber control), and the pressure is applied. The part (21) was pressed to weld the communication paths (23) and (24). After that, the large room (21) and the small room (22) were separated, and the large room
Each volume of (21) and small chamber (22) was measured. Table 1 shows the results.

[Comparative Example 2] A double-chamber container as in Example 1.
Prepare three (2), capacity control unit of the sealing device (1) shown in FIG.
(11) Place the multi-chamber container (2) on the (12) as shown in FIG. 3, close the first lid member (112), and do not close the second lid member (122) (only the small chamber is controlled. ), Press the pressurizing part (21),
(23) and (24) were welded. Thereafter, the large room (21) and the small room (22) were separated, and the capacities of the large room (21) and the small room (22) were measured. Table 1 shows the results.

[Comparative Example 3] A double-chamber container as in Example 1.
Prepare three (2), capacity control unit of the sealing device (1) shown in FIG.
(11) Place the multi-chamber container (2) on the (12) as shown in FIG. 3, close the second lid member (122), and do not close the first lid member (112) (only the large room is controlled). Yes), pressing the pressurizing part (21)
(23) and (24) were welded. Thereafter, the large room (21) and the small room (22) were separated, and the capacities of the large room (21) and the small room (22) were measured. Table 1 shows the results.

[0023]

[Table 1]

As is apparent from Table 1, when the communication path of the multi-chamber container is sealed by using the sealing device of the present invention, welding can be performed by controlling the capacity of the large chamber and the small chamber to a fixed amount. Was. On the other hand, when the welding was performed without performing the capacity control, the accommodation amount was varied.

[Embodiment 2] A double-chamber container similar to that of Embodiment 1
Prepare 10 pieces of (2). 10% DMSO + 1% in each container
Each 25 ml of Dextran aqueous solution is filled, and the heating element (13) of the sealing device (1) shown in FIG. 1 is a modified heater, and the communication paths (23) and (24) of the multi-chamber container (2) are completely filled. Welded. At this time, the number of presses by the pressurizing means (20) and the welding state of the cutting induction cutout (251) were observed. Further, the welding portions after sealing the communication passages (23) and (24) were cut with scissors, and it was confirmed whether or not there was a liquid leak in the large chamber (21) and the small chamber (22). Table 2 shows the results.

Comparative Example 4 A double-chamber container similar to that of Example 1
Prepare 10 pieces of (2). 10% DMSO + 1% in each container
A Dextran aqueous solution is filled by 25 ml each, and the heating device (13) of the sealing device (1) shown in FIG. 1 is replaced with a linear heater, and the communication passages (23) (24) of the multi-chamber container (2) are The number of presses by the pressurizing means (20) until completely welded, and the welding state of the cutting-induction notch (251) were observed. Also,
After sealing the communication passage, cut off the welding point with scissors, and
It was confirmed that there was a liquid leak in the small chamber (22). Table 2 shows the results.

[0027]

[Table 2]

As is clear from Table 2, the sealing device using the deformed heater can completely weld the communication passage by one pressing operation, and the cutting guide cut portion provided at the connecting portion is not welded. It was still. For this reason, no liquid leakage was observed when the large and small chambers were cut with scissors. on the other hand,
The sealing device using the linear heater required five pressing operations to completely seal the communication path, and the cutting induction cut portion was welded. For this reason, when the large room and the small room were cut with scissors, liquid leakage was observed.

[Embodiment 3] A double-chamber container similar to that of Embodiment 1
Prepare 10 pieces of (2). 10% DMSO + 1% in each container
Each 25 ml of Dextran aqueous solution was filled, and the heating element (13) of the sealing device (1) shown in FIG. It was completely welded by the pressing operation twice. Then, the temperature of the main body (10) and the temperatures of the capacity control units (11) and (12) when the ten containers were continuously sealed were measured. Table 3 shows the results.

Comparative Example 5 A double-chamber container similar to that of Example 1
Prepare 10 pieces of (2). 10% DMSO + 1% in each container
Using a sealing device (1) in which the Dextran aqueous solution was filled in 25 ml each and the heating element (13) of the sealing device (1) shown in FIG. 1 was replaced with a linear heater, the communication path ( 23) (24) to 5
It was completely welded by the pressing operation twice. Then, the temperature of the main body (10) and the capacity control unit (11) when the ten containers are continuously sealed.
The temperature of (12) was measured. Table 3 shows the results.

[0031]

[Table 3]

As is evident from Table 3, in the example using the deformed heater, there was no rise in the main body temperature and the temperature of the capacity control section. For this reason, there was no concern about raising the temperature of the multi-chamber container, and there was no possibility of affecting the viability of the contained cell suspension. On the other hand, in the sealing device using the conventional linear heater, the temperature of the main body and the temperature of the capacity control unit increased greatly. For this reason, there is a possibility that the temperature of the multi-chamber container may be increased to affect the cell suspension.

[0033]

According to the sealing device of the present invention, the communication path can be sealed while controlling the volume of the cell suspension to a constant amount. For this reason, there is no possibility that the container will be damaged during freezing.
Further, since the temperature of the heating element can be partially increased, only the communication path can be welded. Further, since the temperature of the main body hardly increases during the sealing operation, there is no possibility that the survival rate of the cell suspension in the multi-chamber container is affected.

[Brief description of the drawings]

FIG. 1 is a perspective view showing a sealing device of the present invention.

FIG. 2 is a plan view illustrating an example of a capacity control unit according to the present invention.

FIG. 3 is a plan view showing a state where a multi-chamber container is placed on the capacity control unit of the present invention.

FIG. 4 is a plan view showing an example of a multi-chamber container.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Sealing device 10 Main body 11 1st capacity control part 111 1st mounting table 112 1st lid member 113 1st fixture 12 2nd capacity control part 121 2nd mounting table 122 2nd lid member 123 2nd fixture 13 Heat generation Body 14 Insulator 20 Pressurizing means 21 Pressurizing section 2 Multi-chamber container 21 Large chamber 22 Small chamber 23, 24 Communication passage 25 Connecting section 251 Cutting guide cut section

Claims (15)

[Claims] 1. A sealing device for a communication passage of a multi-chamber container having two multi-chambers, a communication passage connecting the multi-chambers, and a connecting portion connecting the multi-chambers, wherein the sealing device includes a main body and a main body. The main body has one chamber of the multi-chamber container mounted thereon, a first capacity control section for controlling the capacity thereof, and the other chamber of the multi-chamber container mounted thereon, A second capacity control unit that controls the communication path and the connection part of the multi-chamber container,
A heating element that welds only the communication path; and an insulator that insulates the heating element from the main body. The heating element is provided between the first capacity control section and the second capacity control section. Become
The pressurizing means includes a pressurizing portion for pressurizing the communication path and the connecting portion on the heating element. 2. The heating element on which the communication path and the connecting portion are placed and only the communication path is welded generates heat by pressing a pressing means for pressing the communication path. The sealing device for a multi-chamber container according to claim 1. 3. The heating element, on which the communication path and the connecting portion are placed and which welds only the communication path, is a deformed heater comprising a part where the communication path is welded and a part where the communication path is not welded. The sealing device for a multi-chamber container according to claim 1. 4. The sealing device for a multi-chamber container according to claim 3, wherein the deformed heater has a different size (width) between a portion where the communication passage is welded and a portion where the communication passage is not welded. 5. The double chamber according to claim 3, wherein a portion (width) of the deformed heater where the communication passage is welded is 1/5 to ３ of a portion (width) where the communication passage is not welded. Container sealing device. 6. The modified heater, wherein a heating temperature of a portion where a communication passage is welded is higher than a melting point of a material of the multi-chamber container.
The sealing device for a multi-chamber container according to claim 3, wherein a heat generation temperature of a portion where the communication passage is not welded is lower than a melting point of the material. 7. The sealing device for a multi-chamber container according to claim 6, wherein the material of the multi-chamber container is polyolefin. 8. The heat generation temperature of a portion where the communication passage of the deformed heater is welded is 300 to 400 ° C., and the heat generation temperature of a portion where the communication passage of the deformed heater is not welded is:
The sealing device for a multi-chamber container according to claim 7, which is at 25 to 100C. 9. The sealing device for a multi-chamber container according to claim 1, wherein the insulator that insulates the heating element from the main body is an electrically insulating resin. 10. The sealed multi-chamber container according to claim 1, wherein the first capacity control unit and the second capacity control unit each have a resin plate on a contact surface with each chamber of the multi-chamber container. Stop device. 11. The first capacity control section and the second capacity control section each include a mounting table for mounting each of the multiple chambers and an openable and closable lid for controlling the capacity of the contents in the multiple chambers to be constant. The sealing device for a multi-chamber container according to claim 1, comprising a member. 12. The multi-chamber container includes at least two flat rectangular multi-chambers containing a cell suspension, a communication passage communicating the multi-chambers, communicating the multi-chambers, and separating the multi-chambers. The sealing device for a multi-chamber container according to claim 1, comprising a connecting portion having a cutting guide cut portion for cutting. 13. The multi-chamber container sealing device according to claim 1, wherein the multi-chamber container is a multi-chamber freezing container. 14. The sealing device according to claim 1, further comprising a multi-chamber container having two multi-chambers accommodating the cell suspension, a communication passage connecting the multi-chambers, and a connecting portion connecting the multi-chambers. After being placed on the main body and controlling the volume of the cell suspension in each chamber, the communication path is pressurized by using the pressurizing means of the sealing device to generate heat from the heating element of the sealing device. And fusing the communication passage. 15. The method for sealing a multi-chamber container according to claim 14, wherein the multi-chamber container is placed on the main body of the sealing device, and the volume of the cell suspension in each chamber is simultaneously controlled.