The present invention relates to a cell culture apparatus, more particularly, to a cell culture apparatus capable of communicating the inside and outside of a thermostatic chamber through a tube.
In recent years, it has been demanded to cultivate cells, tissues, etc. in an artificial environment efficiently in fields including production of pharmaceutical products, gene therapy, regenerative medicine, immunotherapy and the like.
In such cell culture, a cell culture unit in which a culture container used for cell culture and a culture medium container for supplying a culture medium to a culture container are connected through a tube is used. Since this cell culture unit is closed, cell culture can be conducted while eliminating the risk of contamination.
The following Patent Document 1 discloses a cell culture apparatus in which this type of cell culture units are stored in multistage.
In the cell culture, since control of temperature, air environment or the like is required, a culture container of the cell culture unit is arranged in a thermostatic chamber (incubator). On the other hand, since a culture medium of the cell culture unit is required to be stored in a refrigerator, a culture medium container is arranged in a cold storage chamber. Then, a culture medium is transferred from a culture medium container to a culture container through a tube.
The opening parts of the thermostatic chamber and the cold storage chamber of the cell culture apparatus are sealed by a door with a packing element in order to maintain the temperature or the gas concentration in the rooms. At this time, the culture container arranged in the thermostatic room and the cell culture medium container arranged in the cold storage chamber are kept connected through a tube. When the tube is caught in the door, the tube is crushed and it becomes difficult to transfer the culture medium through the tube. In order to avoid crush of the tube, a communication groove (concave portion) into which the tube can be fitted is formed on the abutting surface which can be in contact with the packing element of the door around the openings of the thermostatic chamber and the cold storage chamber.
By forming the communication groove on the abutting surface of the partition wall, not forming a communication hole in the partition wall, between the thermostatic chamber and the cold storage chamber, the culture container and the culture medium container can be arranged in the thermostatic chamber and the cold storage chamber, respectively, while being connected by a tube.
If such a communication groove is formed in a cell culture apparatus, the inside and outside of the thermostatic chamber and the cold storage chamber are intercommunicated when a tube is not fitted to the communication groove. In particular, in the cell culture apparatus in which cell culture units can be stored in multiple stages, communication grooves of unused stages in each of which no cell culture unit is arranged are kept intercommunicated. As a result, a carbon dioxide gas filled in the thermostatic chamber and heat are escaped from the communication groove, and such escape is not preferable from the viewpoint of the control of the temperature and the air environment of the thermostatic chamber.
If a dummy member is attached to the communication groove in which no tube is fitted, the communication groove can be blocked. However, it is troublesome to attach dummy members to the communication grooves one by one, and there is a risk of forgetting to attach a dummy member.
The present invention has been attained in view of the above-mentioned circumstances, and is aimed at providing a cell culture apparatus in which communication between the inside and outside of the thermostatic chamber through a tube is maintained in a state where a door with a packing element is closed, and communication of the inside and outside of the thermostatic chamber can be automatically blocked when the tube is removed.
In order to solve the problems mentioned above, the cell culture apparatus of the present invention is a cell culture apparatus provided with a thermostatic chamber of which an opening part is opened and closed by a door with a packing element, and on an abutting surface around the opening part that abuts against the packing element when the door is closed, a communication groove into which a tube that communicates the inside and outside of the thermostatic chamber to be fitted is formed, wherein the cell culture apparatus comprises a shut-off mechanism for blocking communication between the inside and outside of the thermostatic chamber through the communication groove when the tube is removed from the communication groove.
According to the cell culture apparatus of the present invention, by forming a communication groove into which a tube that intercommunicates the inside and outside of the thermostatic chamber at an abutting surface around the opening of the thermostatic chamber to be fitted, not only communication of the inside and outside of the thermostatic chamber through a tube can be maintained in a state where a door with a packing element is closed, and by providing a shut-off mechanism, the communication of the inside and outside the thermostatic chamber through the communication groove can be automatically blocked when the tube is removed from the communication groove.
Herein below, the embodiment of the present invention will be explained with reference to the drawings.
The thermostatic chamber 3 is adjusted to have a temperature preferable for cell culture (e.g. 37° C.), and is adjusted to have a gas concentration that keeps a prescribed carbon dioxide concentration (e.g. 5%). The cold storage chamber 4 is adjusted to have a temperature preferable for storage of a culture medium (e.g. 4° C.).
Accommodation shells 32 and 42 are arranged for storing a plurality of cell culture units U in multistage in the thermostatic chamber 3 and the cold storage chamber 4. In order to facilitate the arrangement and removal of the cell culture units U, the accommodation shells 32 and 42 are configured such that they can be respectively drawn by slide rails 31 and 41.
Connection of the containers by the transfer tubes U40 and U42 is controlled by a blocking element U44 such as a pinch valve. The transfer tubes U40 and U42 are formed of a flexible material such as silicone rubber and a soft vinyl chloride resin.
When cell culture is conducted in the cell culture unit U, at first, a culture medium is transferred through the transfer tube U40 by means of the pump U41 from a port U11 in the culture medium container U10 to a port U21 of the first culture container U20 into which cells have been injected (see an arrow in a broken line (1) in
As mentioned above, the culture medium is transferred through the transfer tube U40 from the culture medium container U10 arranged in the cold storage chamber 4 to the first and second culture containers U20 and U30 arranged in the thermostatic chamber 3. Therefore, when the front doors 3a and 4a of the cell culture apparatus 1 are closed, it is required to maintain communication through the transfer tube U40 between the thermostatic chamber 3 and the cold storage chamber 4.
As shown in
The communication groove 51 is formed so as to permit the thermostatic chamber 3 to communicate with the cold storage chamber 4, and the transfer tube U40 of the cell culture unit U is fitted into the communication groove 51. Therefore, as shown in
If the thermostatic chamber 3 and the cold storage chamber 4 are kept communicated with the outside through the communication groove 51 when the transfer tube U40 is not fitted into the communication groove 51, heat and carbon dioxide gas are escaped from the thermostatic chamber 3 through the communication groove 51, and such escapes are not preferable in view of control of the temperature and air environment in the thermostatic chamber 3. Further, since external heat enters the cold storage chamber 4 through the communication groove 51, it is not preferable in view of temperature control in the cold storage chamber 4.
The cell culture apparatus 1 of the present embodiment is provided with a shut-off mechanism 5 for blocking communication of the thermostatic chamber 3 and the cold storage chamber 4 with the outside through the communication groove 51 when the transfer tube U40 is removed from the communication groove 51.
An upper surface 50a of the block 50 on which the communication groove 51 is formed serves as the abutting surface 2a on which the packing elements 3b and 4b abut. Two guide holes 52 are formed in the block 50 so that each guide holes 52 opens on the upper surface 50a and crosses the communication groove 51. Each guide hole 52 is opened at a position in the abutting surface 2a where the position is covered by the packing elements 3b and 4b when the front doors 3a and 4a are closed. The guide hole 52 has larger depth than the communication groove 51. In the present embodiment, the guide hole 52 penetrates a bottom surface 50b of the block 50. The guide hole 52 may or may not necessarily penetrate.
A plate-like shutter member 53 that is bent in an L-shape and a coil-like spring member 54 are inserted in the guide hole 52. The shutter member 53 can move between a blocking position that blocks the communication groove 51 shown in
The upper part of the shutter member 53 blocks the communication groove 51 at the blocking position. On the other hand, the lower part 53b of the shutter member 53 is bent at right angle with respect to the upper part of the shutter member 53. The lower surface 53b of the lower part serves as a receiving part 53b receiving one end of the spring member 54. The other end of the spring member 54 abuts on the abutting surface 20a of a notched part of the center pillar 20. The spring member 54 serves as a press spring, and energizes the shutter member 53 to the blocking position.
The upper surface 53c of the lower part of the shutter member 53 serves as an abutting part 53c abutting on the inner surface 52a of the guide hole 52 when the shutter member 53 is energized to the blocking position. Due to the abutting of the abutting part 53c on the inner surface of the guide hole 52, the shutter member 53 is prevented from flying out of the opening part of the guide hole 52, and the upper end surface 53a of the shutter member 53 is flushed with the abutting surface 2a when the shutter member 53 is positioned at the blocking position.
As shown in
As shown in
In
As mentioned above, according to the cell culture apparatus of the present embodiment, communication between the thermostatic chamber 3 and the cold storage chamber 4 can be maintained with the front doors 3a and 4a provided with the packing elements 3b and 4b being closed, and when the transfer tube U40 is not attached to the communication groove 51, the communication groove 51 can be automatically blocked by the shutter member 53.
Hereinabove, the embodiment of the present invention was explained. The present invention is not restricted to the above-mentioned embodiment, and various modifications are possible within the scope of the present invention. For example, in the above-mentioned embodiment, an example is given in which the communication groove 51 is formed between the thermostatic chamber 3 and the cold storage chamber 4. The cell culture apparatus of the present invention is not restricted to one having a two-chamber structure of a thermostatic chamber and a cold storage chamber, and one which is not provided with a cold storage chamber can be applied. Further, a communication groove may be formed at any part of the abutting surfaces around the opening of the thermostatic chamber.
In the above-mentioned embodiment, an explanation was made on an example in which a linear communication groove 51 is formed. In the present invention, the shape of the communication groove is not limited thereto, and a winding communication groove, or a communication groove of which the width or the depth partially changes, may be formed.
In the above-mentioned embodiment, an explanation was made on an example in which the shutter member 53 is moved in a direction perpendicular to an abutting surface between the blocking position and the opening position. In the present invention, the shutter member may be moved in an oblique direction relative to the abutting surface or rotated. Further, in the above-mentioned embodiment, an explanation is made on an example in which the plate-like shutter member 53 is used. In the present invention, the shape of the shutter member is not restricted to this, and a shutter member having various shapes (e.g. cylindrical, prismatic, truncated cone, truncated pyramid, etc.) can be used.
In the above-mentioned embodiment, an explanation is made on an example in which a coil-like spring member 54 is provided. In the present invention, a spring member is not limited thereto. An appropriate and preferable energizing member such as a plate spring or various elastic bodies may be used.
In the above-mentioned embodiment, an explanation was made on an example in which, in the resin-made block 50 that can be processed easily, the communication groove 51 and the guide hole 52 are formed, and the shutter member 53 and the spring member 54 are incorporated into the block 50. In the present invention, the resin-made block may not necessarily be used, and a communication groove, etc. may be directly formed on the abutting surface of the center pillar or the housing, and a shutter member, etc. may be incorporated into the center pillar or the housing. The block may be made from resin or metal such as aluminum.
The present invention can preferably be used in regenerative medicine, immunotherapy, production of antibody medicine, etc. in which a large amount of cells is cultured in a closed system.
The documents described in the specification and the specification of the Japanese application on the basis of which the present application claims Paris convention priority are incorporated herein by reference in its entirety.
Number | Date | Country | Kind |
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2015-090633 | Apr 2015 | JP | national |
Filing Document | Filing Date | Country | Kind |
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PCT/JP2016/002061 | 4/15/2016 | WO | 00 |