CELL TREATMENT APPARATUS

Provided is a cell treatment apparatus that includes: an isolator that has an inner space maintained in aseptic conditions and is configured to treat cells in the inner space; trays and that are each configured to house plural kinds of articles, which include reagent containers with articles and reagents therein for use in treatment of cells in the inner space of the isolator, while positioning them; and pass boxes that are configured to respectively carry the trays with the plural kinds of articles housed therein into the isolator.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to Japanese Patent Application No. 2015-206193, the disclosure of which is incorporated herein by reference in its entirety.

FIELD

The present invention relates to a cell treatment apparatus for cell treatment.

BACKGROUND

In recent years, cell culture is performed using tissues and cells of various sites of human body, fertilized eggs, or the like, and the cultured cells have been put to practical use for regenerative medicine. In the cell culture, it is important to prevent contamination of cells by bacteria or the like during the culture. Therefore, a cell treatment apparatus that enables the culture of cells in an environment that can maintain thereinside in aseptic conditions has been already proposed.

The aforementioned cell treatment apparatus includes an equipment installing section with an operating robot arranged therein, and a conveying unit for conveying containers (articles) for use in treatment cells to the equipment installing section side. This conveying unit is constituted by a glovebox for temporal placement of the containers, and a communication section for connecting the glovebox with the equipment installing section.

Arranged inside the conveying unit are a carriage, on which containers put in the glovebox are mounted, and rails having a length extending between the glovebox and the communication section (for example, Patent Literature 1)

CITATION LIST

Patent Literature

SUMMARY

Technical Problem

Meanwhile, large kinds of containers are needed for containers such as reagent containers in which articles and reagents for use in cell treatment are contained. In this regard, Patent Literature 1 mentioned above is configured so that the same kind of containers are housed in a dedicated stand, and the stand with the plurality of containers housed therein is placed on the carriage to be conveyed toward the equipment installing section. Therefore, different kinds of containers cannot together be conveyed, which causes increase in the number of times that containers are conveyed by the carriage as the kinds of containers are increased. As a result, it take a long time to convey the containers, which poses a disadvantage of deteriorating the working efficiency.

In view of the above circumstances, it is an object of the present invention to provide a cell treatment apparatus that can shorten the time for conveying the articles.

Solution to Problem

A cell treatment apparatus according to the present invention includes: an isolator that has an inner space maintained in aseptic conditions and is configured to treat cells in the inner space; trays that are each configured to house plural kinds of articles for use in treatment of cells in the inner space of the isolator, while positioning them; and a pass box that is configured to carry the trays with the plural kinds of articles housed therein into the inner space of the isolator.

The cell treatment apparatus according to the present invention may be configured so that the isolator includes in the inner space a guide unit that guides the movement of the trays carried into the inner space of the isolator in a direction crossing the carrying-in direction.

The cell treatment apparatus according to the present invention may be configured so that the isolator includes in the inner space a robot for handling the articles housed inside of each of the trays carried into the isolator from the pass box, and the robot is configured to move the trays carried into the inner space in a direction crossing the carrying-in direction.

The cell treatment apparatus according to the present invention may be configured so that a plurality of pass boxes are provided.

DESCRIPTION OF EMBODIMENTS

Hereinafter, an apparatus to produce cultured cell products (hereinafter, referred to as production apparatus) that is an example of a cell treatment apparatus of the present invention will be described. In the following description on the front, rear, left, and right directions, the left and right directions correspond to the state shown inFIG. 1andFIG. 2, and the front and rear directions correspond to the state ofFIG. 2where the lower side corresponds to the “front” and the upper side corresponds to the “rear” (the directions are shown also inFIG. 2).

FIG. 1toFIG. 3show the production apparatus of this embodiment. The production apparatus includes a plurality of incubators2, a horizontally elongated isolator3, and a plurality (two inFIG. 2) of pass boxes4. An incubator2houses a cell culture vessel (hereinafter referred to a culture vessel)1that is an article. The isolator3is capable of having its inside maintained in aseptic conditions and treats the culture vessel1transferred from the incubator2. The pass boxes4are configured to be capable of carrying a reagent container into the isolator3, in which the reagent container contains an article and a reagent necessary for subdividing and putting-in of cells cultured in the culture vessel1. As the culture vessel1, a HYPERFlask (manufactured by Corning Incorporated) capable of culturing cells in multilayers, for example, can be used. Each part is controlled by a control device X schematically shown inFIG. 1. The control device X may be provided integrally with the production apparatus or may be a separate body (such as a personal computer) connected to the production apparatus in a wired or wireless manner. Further, it is also possible to provide the control device X integrally with the production apparatus and provide only an operation section of the control device X that is operated by an operator (such as a tablet terminal) as a separate body from the production apparatus.

The incubators2are provided while being vertically stacked in two stages as shown inFIG. 1. Six units of the incubators2are provided in total, at three points in total including one point at the left end of the isolator3and two points in the left end part behind the isolator3, as shown inFIG. 2. Two incubators2,2in the upper stage and the lower stage have the same configuration. Each of the incubators2is provided with racks (not shown) capable of housing a large number of the culture vessels1within a casing2A. The casing2A has a box shape with one lateral side opening so that the culture vessels1can be taken in and out through the lateral side. Two doors2B and2C configured to close the opening on the one lateral side of the casing2A are attached to the casing2A so as to be freely openable. The inside door2C is formed with a transparent material, so that the number of the culture vessels1housed therein and the state of the cell culture can be checked only by opening the outside door2B while the opening is closed by the inside door2C. Further, carbon dioxide gas for adjusting the culture atmosphere is configured to be supplied into the incubators2. Further, the culture vessels1housed on the racks inside the incubators2are configured to be delivered onto a plurality of mounting tables5provided in the isolator3by a delivery mechanism, which is not shown. Six units of the mounting tables5, which is the same number as the number of the incubators2, are arranged corresponding to the incubators2.

As described above, the isolator3is horizontally elongated (in this embodiment, it is rectangular in planer view), where one set (two units on the upper and lower sides) of incubators2is located on the short side of the isolator3(in this embodiment, the left side), and a plurality of sets (in this embodiment, two sets of incubators2) are located on the longitudinal side (in this embodiment, the rear side). This configuration can reduce the size of the production apparatus without decreasing the number of cultured cells.

The isolator3includes an observation section8, a processing section13, and an outlet14. The observation section8includes two first robot arms6and7configured to move the culture vessels1to an observation position so that the degree of growth in the culture vessels1taken out of the incubators2is checked. The processing section13is provided continuously with the observation section8. The processing section13includes three second robot arms10,11, and12. The second robot arms10,11, and12are configured to transfer cells in the culture vessels1that have a specified number of cells out of the culture vessels1observed in the observation section8into a large number of product containers9(such as vial containers, see the enlarged view ofFIG. 1), which have been carried in from the pass boxes4. The outlet14is configured to allow the large number of product containers9into which the cells have been transferred to be taken out therethrough. A large number of work gloves (not shown) that allow the operator to perform operations by putting their hands into the isolator3are attached onto the front and rear walls of the isolator3. As shown inFIG. 2, the five robot arms6,7,10,11, and12are aligned in a straight line extending in the left and right directions along the longitudinal direction of the isolator3.

With reference to the left and right directions, the first robot arm6on the left side corresponds to one set of incubators2located on the short side of the isolator3(in this embodiment, on the left side) and one set of incubators2on the left side out of the sets of incubators2located on the longitudinal side (in this embodiment, on the rear side). The first robot arm6on the left side can handle the culture vessels1that are housed in these incubators2(the range that can be reached by each robot arm (in planer view) is shown inFIG. 2with a dashed-double-dotted circle). Further, the first robot arm7on the right side corresponds to one set of incubators2on the right side out of the sets of incubators2located on the longitudinal side of the isolator3. The first robot arm7on the right side can handle the culture vessels1housed in the incubators2.

With reference to the left and right directions, the second robot arm10on the left side and the second robot arm11in the middle correspond to the pass box4on the left side out of the pass boxes4located on the longitudinal side of the isolator3(in this embodiment, on the rear side). The second robot arm10on the left side and the second robot arm11in the middle can handle reagent containers in which articles and reagents are contained, the reagent containers being to be housed (or having been housed) in the pass box4.

The second robot arm12on the right side corresponds to the pass box4on the right side out of the pass boxes4located on the longitudinal side of the isolator3(in this embodiment, on the rear side) and a box22for carrying out the product containers9. The second robot arm12on the right side can handle reagent containers in which articles and reagents are contained, the reagent containers being to be housed (or having been housed) in the pass box4, and the product containers9to be housed in the box22.

As seen from the overlapping of the dashed-double-dotted circles shown inFIG. 2, the five robot arms6,7,10,11, and12are arranged in a positional relationship so as to be capable of passing articles to each other.

In this way, the robot arms6,7,10,11, and12are located within the isolator3, thereby enabling each of the robot arms6,7,10,11, and12to act on the incubators2, the isolator3, the pass boxes4, and the box22according to the purpose. Thus, according to the production apparatus of this embodiment, it is possible to improve the working efficiency and contribute to mass production of cultured cell products.

The first robot arms6and7and the second robot arms10,11, and12in this embodiment have the same configuration. Therefore, the description for the first robot arm6located at the left end will be applied to the description for each of the first robot arm7, and the second robot arms10,11, and12. The first robot arm6is constituted by articulated robot arm. The first robot arm6includes a fixed part6A fixed to a base member15of the isolator3, a base part6B that is pivotable about the vertical axis at the distal end part of the fixed part6A, a first arm6C that is swingable about the horizontal axis at the distal end part of the base part6B, a second arm6D that is swingable about the horizontal axis at the distal end part of the first arm6C, a third arm6E that is swingable about the horizontal axis at the distal end part of the second arm6D, and a pair of grips6F,6F that are attached to the distal end of the third arm6E so as to be opposed thereto. The pair of grips6F,6F are configured to be capable of moving close to and away from each other. The articulated first robot arms6and7can hold the culture vessels1delivered from the incubators2using the pair of grips6F (seeFIG. 1) and move them to a microscope16at the observation position. The second robot arms10,11, and12are configured to hold such as a centrifuge tube17and a preparation tank18shown inFIG. 1in addition to the culture vessels1so as to be capable of performing various processes.

The microscope16located at an observation position is arranged between the two first robot arms6and7. According to such an arrangement, it is possible to move the culture vessels1to the microscope16using the first robot arm6on the left side so as to observe the cells, and as a result of the observation, it is possible to hold the culture vessels1that have been determined to have a specified number of cells so as to rapidly move them to the processing section13side, using the first robot arm7on the right side. That is, the first robot arm6on the left side mainly performs the operation to move the culture vessels1to the microscope16, and the first robot arm7on the right side performs the operation to move the culture vessels1that have been determined to have a specified number of cells toward the processing section13side. These operations by the first robot arms6and7can accelerate the operation speed. The determination on whether the culture vessels1have a specified number of cells may be made by counting the number of cells by visual inspection of the operator (human) of the production apparatus or may be made automatically by the control device based on the number of cells calculated by analyzing an image captured by a camera so as to automatically calculate the number of cells. The culture vessels1that are delivered from the incubator2located opposed to the first robot arm7on the right side are held by the first robot arm7on the right side to be moved to the microscope16. Further, a microscope25is provided also in the processing section13. The object observed by the microscope25is held by the second robot arm12on the right end to be moved.

The culture vessels1after the observation are conveyed not only by being directly passed from the first robot arm7on the right side to the second robot arms10arranged at the left end of the processing section13. For example, in the case where the second robot arm10is in an operation, the culture vessels1are conveyed by a conveying apparatus19to a position where the second robot arm10at the left end of the processing section13or the second robot arm11arranged at horizontal center of the processing section13can grip them. The conveying apparatus19is provided along the front sidewall of the isolator3and is set to a length that allows the conveying apparatus19to convey them from the right end part of the observation section8of the isolator3to the horizontal center of the processing section13. Accordingly, when the first robot arm7on the right side passes the culture vessels1after the observation to the conveyance starting end part of the conveying apparatus19, the conveying apparatus19conveys the culture vessels1to the position where one of the two second robot arms10and11can grip them.

The conveying apparatus19is provided corresponding to at least one robot arm (in this embodiment, the first robot arm7) located in the observation section8and a plurality of robot arms (in this embodiment, the two second robot arms10and11) located in the processing section13. The first robot arm7can directly deliver the articles to the second robot arm10. The conveying apparatus19can deliver the articles to the first robot arm7and the third robot arm11between which direct delivery of the articles is impossible. Therefore, even in the case where the articles cannot be delivered from the first robot arm7to the third robot arm11via the second robot arm10due to the second robot arm10being in operation, the articles can be delivered from the first robot arm7to the third robot arm11via the conveying apparatus19. Therefore, the articles can be conveyed in parallel (via a plurality of routes) within the isolator3. Accordingly, the working efficiency within the isolator3can be improved, and thus the productivity can be improved.

In the processing section13, three units of the second robot arms10,11, and12are arranged at equal intervals, and the intervals are set to be smaller than the interval between the two first robot arms6and7, so that the speed of various processes performed between the second robot arms10and11or11and12is higher. As shown inFIG. 4, an immovable fixed auxiliary arm20is provided at a position in the vicinity of each of the second robot arms10,11, and12and below each of the second robot arms10,11, and12. The auxiliary arm20includes a fixed part20A fixed to a fixing member21, and a pair of grips20B,20B (inFIG. 4, only the grip20B on the front side is shown) attached so as to be capable of moving close to and away from the fixed part20A.FIG. 4shows the state where, for example, after the upper end part of the preparation tank18is held by the second robot arm10,11, or12, so as to be moved to a position where it can be gripped by the pair of grips20B,20B of the auxiliary arm20, the lower end part of the preparation tank18is gripped by the pair of grips20B of the auxiliary arm20. In this way, a cap18A of the preparation tank18can be opened or closed by the single second robot arm10,11, or12. Further, a program to open and close screw caps that are provided on a plurality of types of containers is stored in the second robot arms10,11, and12, so that the second robot arms10,11, and12can open and close the screw caps provided on the plurality of types of containers. Therefore, it is not necessary to unify the types of containers into the same type, and thus the production apparatus of cultured cell products can be easily achieved. Also in the first robot arms6and7, such a program may be stored.

The two pass boxes4,4are provided to be continuous with the rear wall of the processing section13. One (on the left side) of the pass boxes4is arranged so that the articles can be carried therein passing through between the second robot arm10located at the left end and the second robot arm11located at the center. Examples of the articles include a plurality of types of containers including the product containers9, the culture vessels1, and the centrifuge tube17, and the preparation tank18that is a container in which drugs are put. The other (on the right side) of the pass boxes4is arranged so that the articles are carried to the second robot arm12located at the right end. The articles (various kinds of containers) carried from the pass box4on the left side are handled by the second robot arm10located at the left end and the second robot arm11located at the horizontal center, while the articles (containers) carried from the pass box4on the right side are handled by the second robot arm12located at the right end.

As described above, the isolator3is horizontally elongated, in which the plurality (in this embodiment, two) of pass boxes4are located on the longitudinal side of the isolator3(in this embodiment, on the rear side). This configuration can reduce the size of the production apparatus without limiting the amount of articles to be carried into the isolator3.

The opening of the outlet14is configured to have a size such that the second robot arm12located at the right end can easily enter therethrough. The outlet14is provided with a freely openable electric shutter (not shown) and is provided continuously with the box22that forms a space in which the product containers9moved through the outlet14to the outside of the isolator3are kept for a while.

The processing section13includes a first transfer processing unit, a separation processing unit, and a second transfer unit. The first transfer processing unit is configured to transfer a cell-containing liquid housed in the culture vessels1received from the first robot arm7into the centrifuge tube17using the second robot arm10. The separation processing unit is configured to separate the cells and a liquid portion by subjecting the centrifuge tube17to a centrifuge26using the second robot arm10. The second transfer unit is configured to transfer a specified number of cells within the centrifuge tube17into a large number of the product containers9while a preservative solution (cryopreservation solution) is put into the centrifuge tube17after removing at least part of the liquid portion separated in the separation processing unit from the centrifuge tube17, using the second robot arm10. In the description of this embodiment, the term “cell-containing liquid” simply means a “liquid containing cells” and is not limited to a liquid in a specific state.

The processing section13includes a medium-replacing unit configured to replace the culture medium within the culture vessels1taken out of the incubators2using the first robot arm7. The medium-replacing unit is configured to open the caps of the culture vessels1received by the second robot arm10from the first robot arm7, to dispose of the culture medium within the culture vessels1, to supply another culture medium into the cell culture vessels1, to put the caps thereon, and to return them to the first robot arm7.

The processing section13configured as above is capable of performing a first process of thawing frozen cells and seeding them, a second process (passage process) of collecting the cells and seeding them on a large number of culture vessels, and a third process of collecting the cultured cells in the culture vessels after the passage process, subdividing the collected cells, transferring them into the product containers9, and carrying them out through the outlet14.

Provided at a position close to the processing section13within the observation section8is a first disposal part23for disposal of waste products, which can be lid-closed, such as the centrifuge tube17and the preparation tank18(mainly those having a large size), in addition to the cell culture vessels1, which become unnecessary during the aforementioned processes. Provided at a position close to the box22within the processing section13is a second disposal part24for disposal of waste products (mainly those having a small size, but even for tips, there are large tips such as disposable tips), which cannot be lid-closed and therefore may cause dripping, such as pipette tips (suction openings mounted to pipettes, not shown).

The two pass boxes4have the same configuration. Each of the pass boxes4includes a first box27that constitutes a clean bench chamber for carrying containers from outside thereinto, and a second box28that constitutes a decontamination chamber for carrying containers from the clean bench chamber into the isolator3. As shown inFIG. 5, each of inner side surfaces respectively opposed to the second boxes28,28(only one of them are shown inFIG. 5) has a large number of (four inFIG. 5) glove ports G1and G2to enable operation by putting the hand in the decontamination chamber R2.

As shown inFIG. 5, shutters34of sliding type (only one of them is shown inFIG. 5) that can slide in the vertical direction are each provided on one lateral side of each of the two opposed clean bench chambers. Each of the shutters34is configured to change the opening degree of an opening34K formed on a lower side. Herein, the opening34K is set to be substantially one fourth of an area when the shutter34is in the fully opened position. Containers are manually passed through the opening34K from the outside of the clean bench chamber R1into the clean bench chamber, where containers are subjected to decontamination with alcohol or other treatments.

The clean bench chamber includes a decontamination chamber opening35A that is openable and closable for carrying containers into the decontamination chamber. As shown inFIG. 7, this decontamination chamber opening35A can be opened and closed by moving up and down a first cover35using an air cylinder36. The first cover35is formed by a plate-shaped member having a substantially square shape, and is vertically movably supported to a rear wall28A of the second box28by a guide mechanism (not shown). The air cylinder36has a cylinder tube36B that is fixed to the rear wall28A of the second box28with a proximal end of the cylinder tube36B upwardly oriented, and has a piston rod36A that is connected to a lower end of the first cover35with a distal end of the piston rod36A oriented downwardly. The piston rod36A of the air cylinder36is retracted to slide the first cover35upwardly so that the decontamination chamber opening35A is brought into an opened state, and the piston rod36A of the air cylinder36in the retracted state is extended to slide the first cover35downwardly, which has been slid upwardly, so that the decontamination chamber opening35A is brought into a closed state.

The decontamination chamber includes an isolator opening37A that can be opened and closed, through which containers carried from the clean bench chamber into the decontamination chamber is carried into the isolator3. As shown inFIG. 9andFIG. 10, the isolator opening37A can be opened and closed by sliding a second cover37in the lateral direction. The second cover37is formed by a plate-shaped member having a substantially square shape, and includes handles37H,37H for opening and closing operation at both ends in the slide direction. The second cover37is configured so as to be able to move in the lateral direction while having its upper and lower ends supported by a pair of upper and lower guide rails38and39. The upper guide rail38and the lower guide rail39are arranged to oppose to each other in the vertical direction, and are formed respectively by L-shaped members fixed over a front wall28B and a left side wall28C that are two adjacent side walls of the second box28constituting the decontamination chamber. The upper guide rail38includes a top plate part38A fixed to four (only three are shown inFIGS. 11) brackets40fixed to the two side walls28B and28C, a pair of vertical plate parts38B,38B extending downward from both ends in the width direction of the top plate part38A, and a pair of horizontal plate parts38C,38C that respectively extend from lower ends of the pair of vertical plate parts38B,38B to be close to each other. A pair of moving bodies41,41are movably provided inside the upper guide rail38, and an upper end of the second cover37is connected to the pair of moving bodies41,41. Each of the moving bodies41includes a pair of bearings43,43that are mounted on the pair of horizontal plate parts38C,38C and coupled to each other through lateral shafts42, a spacing member44for holding a space between the bearings43,43and having the lateral shafts42extending therethrough, and a pin45that is attached to the spacing member44while extending therethrough movably around a vertical axis. In each of the moving bodies41, an upper frame body46having a reversed L-shape, which is fixed to an upper end of the second cover37with screws, is fastened and fixed to the spacing member44by the pin45. Accordingly, the second cover37can smoothly change its moving direction without deflecting during moving through a curved portion of the upper guide rail38since the second cover37can smoothly move along the upper guide rail38by the rotation of the pair of bearings43, while rotating around the axis of the pin45. The lower guide rail39has a substantially U-shape with its upper end opening, and a pair of left and right rollers47,47, which are rotatable around the vertical axis, are provided within the lower guide rail39. The pair of left and right rollers47,47are coupled, rotatably around the vertical axis, to a lower frame body48that has a L-shape and is fixed to a lower end of the second cover37with screws. Accordingly, the second cover37can smoothly change its moving direction without deflecting during moving through a curved portion of the lower guide rail39since the second cover37can smoothly move along the lower guide rail39by the rotation of the pair of left and right rollers47,47.

The reference numeral49shown inFIG. 10represents a stopper member, to which the second cover37abuts when it is located at the closing position, and the reference numeral50represents a stopper member, to which the second cover37abuts when it is located at the opening position.

The culture vessel1, the centrifuge tube17, the preparation tank18and the like, which are various kinds of containers for use in the isolator3, are placed in the pass box4on the left side, then housed in a first tray29shown inFIG. 11aandFIG. 11b, and then the first tray29is carried into the isolator3through a carrying-in device31. The first tray29is constituted by a housing body29A of a box type having a rectangular shape in planer view with its upper side opening, a partitioning plate29B that is configured to house various kinds of containers while positioning them within the housing body29A, and pairs of front and rear rotating rollers29C,29C and29D,29D that are mounted at both ends in the front-rear direction (carrying-in direction) of the housing body29A with a certain interval in the width direction. Specifically, Fig. lla shows the case where one centrifuge tube17, one waste liquid tank32, two culture vessels1,1, and one PBS (phosphate buffered saline) solution tank33are housed in the first tray29. Holes matching in shape with these various kinds of containers (holes capable of receiving various kinds of containers and positioning the same) are formed in the partitioning plate29B. InFIG. 11b, one centrifuge tube17, one waste liquid tank32, and two culture vessels1,1are housed in the first tray29. Holes matching in shape with these various kinds of containers (holes capable of receiving various kinds of containers and positioning the same) are formed in the partitioning plate29B. The first tray29ofFIG. 11aand the first tray29ofFIG. 11bhave the same configuration for the housing body29A and the pairs of the front and rear rotating rollers29C,29C and29D,29D, while having a slight difference in those holes formed in the partitioning plate29B. The first trays29are carried into the isolator3from the pass box4on the left side. A second tray30to be carried from the pass box4on the right side is smaller in width than the first tray29to be carried from the pass box4on the left side into the isolator3(FIG. 15shows the second tray30), and houses containers, which mainly have a smaller size than the containers housed in the first tray29. The second tray30houses, for example, a cell counter, a microplate, a pipette tip, and the like.

The carrying-in device31includes a first carrying-in unit51installed in the pass box4on the left side shown inFIG. 12aandFIG. 12b, and a second carrying-in unit52installed in the pass box4on the right side shown inFIG. 13aandFIG. 13b. These two carrying-in units51and52differ from each other only in that they have widths adjusted to the widths of the two kinds of trays29and30having different widths, while basically having the same configuration. As shown inFIG. 12aandFIG. 12b, the first carrying-in unit51includes a first movable member53that can move the first tray29, which is placed on the first movable member53in the pass box4, toward the isolator3side, and a first support member54that movably supports the first movable member53.

The first movable member53includes a first mounting member53A that is a plate like member having a rectangular shape in planer view and allows substantially all the area of the first tray29excepting a rear end part to be mounted thereon, and a first interlocking member53B that is a plate like member having a rectangular shape in planer view extending from one end of the first mounting member53A, allows the rear end part of the first tray29to be mounted thereon, and is interlocked with the first support member54side. The first mounting member53A and the first interlocking member53B respectively have a large number of holes53aand a large number of holes53b, through which air flows pass. The first interlocking member53B has a width slightly larger than the width of the first mounting member53A. Provided at a portion of the first interlocking member53B close to the first mounting member53A side is a first vertical plate53C that is provided upstanding to abut a rear end in the carrying-in direction of the first tray29to block the movement of the first tray29rearward in the carrying-in direction of the first tray29. A first handle53D is attached to an upper part of a rear surface in the front-rear direction (carrying-in direction) of the first vertical plate53C. A plate55is arranged at a position just beneath the first movable member53when the first movable member53has moved into the isolator3, and has a large number of holes55A through which air flows pass.

The first support member54includes a pair of first side plates54A,54A provided upstanding with an interval therebetween in the left-right direction (width direction) on a base plate56of the pass box4, an L-shaped first cover member54B that is configured to cover an area including a rear half in the front-rear direction of an upper side between the first side plates54A,54A and a rear end in the front-rear direction between the first side plates54A,54A, a pair of rod-shaped first guide members54C,54C that are supported at a certain height from the base plate56of the pass box4and arranged with a certain interval therebetween in the left-right direction, and a pair of left and right first rotating rollers54D,54D that contact a lower surface of the first movable member53to support the same during movement of the first movable member53. First tubular bodies53E,53E, through which the pair of first guide members54C,54C extend so as to be movable therealong, are connected to a lower surface of a rear end part in the front-rear direction of the first movable member53. The first side plates54A,54A and the first cover member54B respectively have a large number of holes54aand a large number of holes54b,through which air flows pass.

The second carrying-in unit52also includes a second movable member57that can move the second tray30, which is placed on the second movable member57in the pass box4, toward the isolator3side, and a second support member58that movably supports the second movable member53.

The second movable member57includes a second mounting member57A that is a plate like member having a rectangular shape in planer view and allows substantially all the area of the second tray30excepting a rear end part to be mounted thereon, and a second interlocking member57B that is a plate like member having a rectangular shape in planer view extending from one end of the second mounting member57A, allows the rear end part of the second tray30to be mounted thereon, and is interlocked with the second support member58side. The second mounting member57A and the second interlocking member57B respectively have a large number of holes57aand a large number of holes57b, through which air flows pass. The second interlocking member57B has a width in the left-right direction slightly larger than the second mounting member57A. Provided at a portion of the second interlocking member57B close to the second mounting member57A side is a second vertical plate57C that is provided upstanding to abut a rear end in the front-rear direction of the second tray30to block the movement of the second tray30rearward in the front-rear direction of the second tray30. A second handle57D is attached to an upper part of a rear surface in the front-rear direction of the second vertical plate57C. A plate59is arranged at a position just beneath the second movable member57when the second movable member57has moved into the isolator3, and has a large number of holes59A (seeFIG. 14) through which air flows pass.

The second support member58includes a pair of left and right second side plates58A,58A provided upstanding with an interval therebetween in the left-right direction (width direction) on the base plate56of the pass box4, an L-shaped second cover member58B that is configured to cover an area including a rear half in the front-rear direction of an upper side between the second side plates58A,58A and a rear end in the carrying-in direction between the second side plates58A,58A, a pair of rod-shaped second guide members58C,58C that are supported at a certain height from the base plate56of the pass box4and arranged with a certain interval therebetween in the left-right direction, and a pair of left and right second rotating rollers58D,58D that contact a lower surface of the second movable member57to support the same during movement of the second movable member57. Second tubular bodies57E,57E, through which the pair of second guide members58C,58C extend so as to be movable therealong, are connected to a lower surface of a rear end part in the front-rear direction of the second movable member57. The second side plates58A,58A and the second cover member58B respectively have a large number of holes58aand a large number of holes58b, through which air flows pass.

For example, when the first movable member57is to be moved into the isolator3, the first handle53D is grabbed through a given one of the glove ports G1to G2and pulled manually toward the isolator3side.FIG. 13aandFIG. 13bshow the state where the second movable member57has been moved to the isolator3side. At this moment, as described above, the second tubular bodies57E,57E are moved while being guided by the pair of left and right second guide members58C,58C, with the lower surface of the second movable member57being supported by the pair of left and right second rotating rollers58D,58D, so that the second movable member57is smoothly moved toward the isolator3side while maintaining the horizontal direction thereof. Although the second cover37is not shown inFIG. 12a,FIG. 12b,FIG. 13a, andFIG. 13b, the handle37H of the second cover37is grabbed to thereby slide the second cover37in the lateral direction to the opening position in an actual operation, so that the first movable member53or the second movable member57can be moved through the thus opened isolator opening37A.

As shown inFIG. 11aandFIG. 11b, it is possible to efficiently house the containers in the tray by housing a plural kinds of containers in a tray (the first tray29in Figures). As a result, it is possible to reduce the number of times that the containers are carried into the isolator3, and shorten the time for carrying in the containers corresponding to such reduction. In addition, it is possible to suppress contamination inside of the isolator3due to the large amount of air entering the isolator3from the pass box4, because the tray can be instantly carried into the isolator3through the small isolator opening37A which is opened with the second cover37moved at the opening position.

The thus configured isolator3includes guide units60,60located therein, which are configured to move the first tray29or the second tray30carried into the isolator3by the first movable member53or the second movable member57while guiding them in a direction (left-right direction) orthogonal to (or crossing) the carrying-in direction (front-rear direction). As shown inFIG. 14a,FIG. 14b, andFIG. 15, each of the guide units60is constituted by a pair of front-rear rod shaped members61and62that extend in the left-right direction with an interval therebetween in the front-rear direction in the isolator3, and the pair of left and right rotating rollers29C,29C and29D,29D at the front and rear ends of the first tray29or the pair of rotating rollers30C,30C and30D,30D at the front and rear ends of the second tray30in order to engage with the pair of front-rear rod-shaped members61and62.

The rod shaped member61on the front side is formed by a single rod-shaped member extending in the left-right direction from a portion corresponding to the isolator opening37A so that when, for example, the first tray29is carried into the isolator3by the first carrying-in unit51, the rod shaped member61on the front side can engage with the pair of left and right rotating rollers29C,29C at the front end of the first tray29. A portion corresponding to the isolator opening37A of the rod shaped member62on the rear side is omitted so as to allow passing of the first tray29, for example, when the first tray29is carried into the isolator3by the first carrying-in unit51. The rod shaped member62on the rear side is constituted by a left-side rod-shaped member62A extending from a portion in proximity to the left end of the isolator opening37A toward the left side, and a right-side rod-shaped member62B extending from a portion in proximity to the right end of the isolator opening37A toward the right side. Accordingly, inFIG. 15, when the second tray30is carried into the isolator3from the pass box4on the right side, the pair of left and right rotating rollers30C,30C at the front end of the second tray30come into engagement with the rod shaped member61on the front side from above. In this engaging state, the second robot arm12holds the second tray30and moves the same toward one side in the left-right direction to thereby allow the pair of left and right rotating rollers30D,30D at the rear end of the second tray30to come into engagement with the rod shaped member62A on the rear left side or the rod shaped member62B on the rear right side. Whereby, the second tray30can be smoothly moved to a certain position in the left-right direction while the rotating rollers30C,30C and30D,30D at the front and rear ends are being rotated along the rod shaped members61and62on the front and rear sides. When the second tray30is to be moved to a far position from the isolator opening37A, for example, to the left end, the second tray30can be moved thereto by transferring of the second tray30from the second robot arm12at the right end to the second robot arm11at the center.FIG. 15shows the state where the first trays29are sequentially carried into the isolator3from the pass box4on the left side, and five first trays29in total (in this embodiment, five trays are provided, but two or more numbers of trays may be provided) are arranged in certain positions in the left-right direction. The second trays30from the pass box4on the right side can be also arranged with five second trays30being aligned in the left-right direction. The rod shaped members61and62respectively have a pair of grooves61M and a pair of grooves62M at each of five places with the same pitch as the rotating rollers. The rotating rollers29C,20C or30C,30C fit into the front grooves61M, and the rotating rollers29D,29D or30D,30D fit into the rear grooves62M, so that each of the first trays29and each of the second trays30can be positioned while not being unintentionally moved in the left-right direction.FIG. 15shows the five first trays29respectively fitting into the grooves61M and62M. In this arrangement, no rod shaped members are provided on the rear side for the first tray29and the second tray30positioned at the center. Therefore, the rotating rollers29D,29D and30D,30D on the rear side cannot fit into the grooves. The pair of grooves61M,61M on the front side formed at the center thus have a depth larger than the remaining four pairs of grooves61M,61M so as to increase the fitting engagement force to securely prevent unintentional movement of the trays in the left-right direction. InFIG. 15, the containers and the partitioning plates to be housed in the first tray29and the second tray30are omitted.

Each of the isolator opening37A and the decontamination chamber opening35A has such a height as to allow a container having a largest dimension (herein HYPERFlask manufactured by Corning Incorporated) capable of culturing cells to pass therethrough. It is preferable that the isolator opening37A and the decontamination chamber opening35A have a width in the left-right direction being slightly larger than the width in the left-right direction of the first tray29and the second tray30, so that the first tray29and the second tray30can be passed therethrough. The opening34K of the clean bench chamber R1also has such a height as to allow a container having a largest dimension (herein HYPERFlask manufactured by Corning Incorporated) capable of culturing cells to pass therethrough. Such height setting enables the size of each opening to be minimized and air flows to be desirably controlled, while enabling all the kinds of handled container to be carried into the respective chambers. As a result, it is possible to more securely avoid occurrence of troubles such as contamination.

The cell treatment apparatus according to the present invention is not limited to the aforementioned embodiment, and various modifications can be made without departing from the gist of the present invention.

The aforementioned embodiment was described by taking, for example, the case where the two robot arms6and7are provided in the observation section8, and the three robot arms10,11, and12are provided in the processing section13. However, it is also possible to apply, to the present invention, the configuration of providing at least one robot arm in the observation section8and providing at least one robot arm in the processing section13.

In the aforementioned embodiment, the isolator3is configured to have a horizontally elongated shape as an example, but may be configured to have a square shape or a circular shape. Further, it may be configured to have a bent shape.

The aforementioned embodiment was described by taking, for example, the case where the first cover35is configured to be movable in the vertical direction and the second cover37is configured to be movable in the lateral direction. However, the moving direction of each of the first cover35and the second cover37may be set to any direction.

The description of the aforementioned embodiment was made for the apparatus to produce cultured cell products, which is configured to culture cells and subdivide cultured cells into products. However, the present invention is also applicable to an apparatus to culture cells, which is configured to perform only cell culturing, or applicable to a product manufacturing apparatus, which is configured to subdivide cultured cells into products.

The aforementioned embodiment was described by taking, for example, the case where the two pass boxes4,4are provided. However, the present invention is also applicable to the case where one pass box, or three or more pass boxes are provided.

The aforementioned embodiment was described by taking, for example, the case where each of the trays29and30has a rectangular shape in planer view. However, the trays29and30may have any shape, such as a square shape, a polygonal shape, a circular shape or an elliptical shape.

The configuration and action of the aforementioned embodiment will be summarized below. The cell treatment apparatus according to the present embodiment includes: an isolator3that has an inner space maintained in aseptic conditions and is configured to treat cells in the inner space; trays29and30that are each configured to house plural kinds of articles for use in treatment of cells in the inner space of the isolator3, while positioning them; and pass boxes4,4that are configured to respectively carry the trays29and30with the plural kinds of containers housed therein into the isolator3.

According to the above configuration, the plural kinds of containers are housed in each of the trays29and30while being positioned therein, so that the containers can be efficiently housed in the inner part of each of the trays29and30. As a result, it is possible to reduce the number of times that the containers are carried into the isolator3, and shorten the time for carrying in the containers corresponding to such reduction.

The isolator3may include in the inner space a guide unit60that guides the movement of the trays29and30carried into the inner space of the isolator3in a direction crossing the carrying-in direction.

According to such a configuration, the guide unit60guides the movements of the trays29and30carried into the inner space of the isolator3in a direction crossing the carrying-in direction, so that a plurality of trays29and30can be arranged in the inner space of the isolator3while being aligned and thereby a large number of cells can be treated.

The isolator3may include in the inner space a robot for handling the containers housed in the trays29and30, and the robot is configured to move the trays29and30carried into the inner space in a direction crossing the carrying-in direction.

According to such a configuration, only carrying-in of the trays29and30suffices since the robot moves the trays29and30carried inside in a direction crossing the carrying-in direction.

A plurality of the pass boxes4,4may be provided. With such a configuration including the plurality of pass boxes4,4, it is possible to complete carrying-in operations of the trays29and30in a short time and hence further shorten the time required for carrying in the containers.

REFERENCE SIGNS LIST