Abstract:
The present invention relates to systems and methods for optimising the usage of laboratory and cell culturing space for cell culture and biomanufacturing. The invention provides a system and method that can be used to provide a plurality of workstations and/or storage bays for bioreactors in cell culturing and/or biomanufacturing facilities.

Description:
FIELD OF INVENTION 
       [0001]    Embodiments of the present invention relate to the field of cell culture and biomanufacturing. In particular, embodiments of the present invention relate to systems and methods for optimising the usage of laboratory and cell culturing space for cell culture and biomanufacturing. 
       BACKGROUND OF THE INVENTION 
       [0002]    Cell culture, for example the culture of mammalian, bacterial or fungal cells, may be carried out to harvest the living cells for therapeutic purposes and/or to harvest biomolecules, such as proteins or chemicals (e.g. pharmaceuticals) produced by the cells. The cells are generally grown in bioreactors which are sterilizable vessels designed to provide the necessary nutrients and environmental conditions required for cell growth and expansion. Conventional bioreactors have glass or metal growth chambers which can be sterilized and then inoculated with selected cells for subsequent culture and expansion. Media within the growth chambers are often agitated or stirred by the use of mechanical or magnetic impellers to improve aeration, nutrient dispersal and waste removal. 
         [0003]    In recent years, there has been a move towards ‘single use’ bioreactors which offer greater production flexibility, ease of use, reduced capital cost investment and reduced risk of cross-contamination. These systems can also improve the efficiency of aeration, feeding and waste removal to increase cell densities and product yields. Examples include WAVE™ bags (GE Healthcare) mounted on rocking platforms for mixing, to the introduction of stirred-tank single-use vessels such as those available from Xcellerex (GE Healthcare). 
         [0004]    Manufacturing facilities, such as tissue culture laboratories, for the production of cells and biomolecules, have traditionally been custom designed and carried out in clean environments to reduce the risk of contamination. Such facilities are costly to run and maintain and also to modify if priorities or work demands change. Work stations for maintaining or harvesting the cells within the bioreactors require a specific ‘footprint’ which occupies a significant floorspace in the culture laboratory. As the workstations spend much of their time unattended, while the cells are growing in the bioreactors, the laboratory space is not efficiently or effectively used. 
         [0005]    There is therefore a need to optimise the usage of cell culture and laboratory space which grow cells in bioreactors for cell culture and biomanufacturing. The present invention addresses this problem and provides systems and methods that can be used to provide a plurality of workstations and/or storage bays for bioreactors. 
       SUMMARY OF THE INVENTION 
       [0006]    According to a first aspect of the present invention, there is provide a system for cell culture and/or biomanufacturing comprising
       i. a base unit comprising:
           a frame supporting walls, and   a movable platform to define a chamber therein;   
           ii. a stacking unit comprising:
           a frame supporting side walls, a back wall, a ceiling and a movable platform to define an upper and a lower chamber therein,   said lower chamber being dimensioned to receive said base unit therein;   
           iii. a guard unit comprising:
           a frame supporting side walls, a movable platform and an openable front wall to define an upper and a lower chamber therein, said lower chamber being dimensioned to partially receive said stacking unit therein; and   legs supporting said frame and dimensioned to receive the movable base unit therebetween;   
           wherein the base unit, the stacking unit and the guard unit interconnect to provide a plurality of workstations and/or storage bays for a bioreactor.       
 
         [0017]    As used herein, the term “biomolecule” can mean any molecule, such as a protein, peptide, nucleic acid, metabolite, chemical or biopharmaceutical that is produced by a cell. 
         [0018]    In one aspect, the base unit and/or the stacking unit and/or the guard unit are movable. 
         [0019]    In another aspect, the base unit and/or the stacking unit and/or the guard unit comprise wheels. In an embodiment, the wheels are reversibly lockable. 
         [0020]    In a further aspect, the system further comprising a connection to utilities selected from the group consisting of electricity, water, nitrogen, oxygen, air and carbon dioxide. Optionally, the system further comprises a connection to a waste disposal outlet. 
         [0021]    In an embodiment, the connections are reversibly connectable. 
         [0022]    In one aspect, the system additionally comprises a connection to a refrigeration unit. 
         [0023]    In another aspect, the platform within the base unit is movable in a vertical plane. 
         [0024]    In a further aspect, the lower platform in the stacking unit is movable in a horizontal and/or a vertical plane. 
         [0025]    In a further aspect, the platform in the guard unit is movable in a horizontal and/or a vertical plane. 
         [0026]    In one aspect, the openable front wall of the guard unit is a sliding wall. It will be understood that the front wall may optionally be removable to provide user access to the unit. 
         [0027]    In another aspect, the chamber of the base unit, the stacking unit and the guard unit comprise internal sterilizable surfaces to reduce the risk of contamination. 
         [0028]    In a further aspect, the base unit, the stacking unit and the guard unit have a cuboid configuration. 
         [0029]    In one aspect, the platform in the base unit and the stacking unit can support at least one bioreactor. 
         [0030]    In another aspect, the bioreactor is a movement based bioreactor such as a WAVE bioreactor. 
         [0031]    In a further aspect, the bioreactor is a stir tank bioreactor, such as an Xcellerex bioreactor. 
         [0032]    In one aspect, the platforms are movable by electronic or pneumatic means. 
         [0033]    In another aspect, the base unit and/or the guard unit are movable by electronic or pneumatic means. 
         [0034]    In a further aspect, the system additionally comprises one or more bioreactor, such as a WAVE bioreactor. 
         [0035]    According to a second aspect of the present invention, there is provided a use of a system as hereinbefore described as a workstation and/or a storage bay for a plurality of bioreactors. 
         [0036]    In accordance with a third aspect of the present invention, there is provided a use of a system as hereinbefore described for cell culture and/or biomanufacturing. 
         [0037]    According to a fourth aspect of the present invention, there is provided a method for cell culture comprising growing a cell culture in at least one bioreactor in a system as hereinbefore described to produce a plurality of cells. 
         [0038]    In accordance with a fifth aspect of the present invention, there is provided a method for biomanufacturing comprising harvesting a biomolecule from a plurality of cells produced by the method of the fourth aspect. 
         [0039]    According to a sixth aspect of the present invention, there is provide a system for cell culture and/or biomanufacturing comprising
       i. a housing comprising a plurality of vertically stacked workstations;   ii. a mechanism for rotating said plurality of workstations; and   iii. a port for providing user access to one of the workstations.       
 
         [0043]    In accordance with a seventh aspect of the present invention, there is provided a use of a system according to the sixth aspect as a workstation and/or a storage bay for a plurality of bioreactors. 
         [0044]    According to an eighth aspect of the present invention, there is provided a use of a system according to the sixth aspect for cell culture and/or biomanufacturing. 
         [0045]    In accordance with a ninth aspect of the present invention, there is provided a method for cell culture comprising growing a cell culture in at least one bioreactor in a system according to the sixth aspect to produce a plurality of cells. 
         [0046]    According to a tenth aspect of the present invention, there is provided a method for biomanufacturing comprising harvesting a biomolecule from a plurality of cells produced by the method of the ninth aspect. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0047]    The features and advantages of the invention will become apparent from the following description taken in connection with the accompanying drawings in which: 
           [0048]      FIG. 1  depicts a perspective view of one embodiment of a system according to the invention housing or storing a plurality of bioreactors; 
           [0049]      FIG. 2  illustrates a perspective view of a base unit of the system of  FIG. 1  (but does not show the bioreactor); 
           [0050]      FIG. 3  shows a perspective view of a stacking unit of the system of  FIG. 1  (but does not show the bioreactor); 
           [0051]      FIG. 4  presents a perspective view of a guard unit of the system of  FIG. 1  (but does not show the movable platform supporting the bioreactor); 
           [0052]      FIG. 5  illustrates a side view of the system of  FIG. 1 ; 
           [0053]      FIG. 6  provides another perspective view of one embodiment of a system according to the invention housing or storing a series of bioreactors; 
           [0054]      FIG. 7  illustrates a perspective view of the system of  FIG. 1  or  6  in which the front wall of the guard unit is in an open configuration to allow user access to the base unit; 
           [0055]      FIG. 8  shows a perspective view of the system of  FIG. 7  in which the base unit has been moved away from the lower chamber of the stacking unit; 
           [0056]      FIG. 9  depicts a perspective view of the system of  FIG. 8  in which the movable platform within the base unit has been raised to provide user access to the bioreactor housed or stored within the chamber; 
           [0057]      FIG. 10  depicts a perspective view of the system of  FIG. 9  in which the movable platform of the base unit has been lowered to return the bioreactor to a housing or storage position; 
           [0058]      FIG. 11  shows a perspective view of the system of  FIG. 10  in which the base unit has been moved back or returned to the lower chamber of the stacking unit; 
           [0059]      FIG. 12  is a perspective view of the system of  FIG. 11  in which the lower platform of the stacking unit has been moved or pulled out from the stacking unit to allow user access to the bioreactor; 
           [0060]      FIG. 13  depicts a perspective view of the system of  FIG. 12  in which the lower platform of the stacking unit has been moved or returned to the stacking unit and the wall of the guard unit closed; 
           [0061]      FIG. 14  shows a perspective view of the system of  FIG. 13  in which the guard unit housing or storing a bioreactor has been moved or pulled away from the base unit and the stacking unit; 
           [0062]      FIG. 15  illustrates a perspective view of the system of  FIG. 14  in which the movable platform of the guard unit supporting a bioreactor has been lowered; 
           [0063]      FIG. 16  depicts a perspective view of the system of  FIG. 15  in which the front wall of the guard unit is in an open configuration to allow user access to the bioreactor; 
           [0064]      FIG. 17  is a perspective view of the system of  FIG. 16  in which the front wall of the guard unit is in a closed configuration; 
           [0065]      FIG. 18  provides a perspective view of the system of  FIG. 17  in which the movable platform of the guard unit has been raised; and 
           [0066]      FIG. 19  is a perspective view of the system of  FIG. 18  in which the guard unit has been moved back into position to enclose the stacking unit. 
           [0067]      FIG. 20  is a schematic diagram showing a system  2000  for cell culture and/or biomanufacturing. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0068]    Embodiments of the present invention relate to a system for cell culture and/or biomanufacturing. In particular, embodiments of the present invention relate to a system for providing a plurality of workstations and/or storage bays for bioreactors.  FIG. 1  is a schematic perspective view of a system  100  in accordance with an embodiment of the invention. The system  100  consists of a base unit  120 , a stacking unit  140  and a guard unit  160 . The system  100  shown in  FIG. 1  is in a resting or storage position or configuration and is shown in use housing or storing bioreactors (e.g.  180   a, b, c ) in a series of chambers ( 123 ,  146 ,  164 ) or storage bays. 
         [0069]      FIG. 2  shows a schematic perspective view of a base unit  220  of the system in accordance with an embodiment of the invention. The base unit  220  consists of a frame  221  supporting walls ( 222   a, b, c, d ) and a movable platform  224  which forms a base and thereby defines a chamber  223  within the unit. One of the walls  222   d  may optionally be reinforced and act as a spacer and/or support when the system is in a closed or storage configuration ( FIG. 1 ). The movable platform  224  is designed to provide a support for a bioreactor (not shown in the figure). Control panels ( 226   a,b ) may be used to automatically raise or lower the movable platform  224  within the base unit  220 . The base unit  220  may also have wheels (e.g.  225 ) or coasters or be on a trolley or rail system to facilitate movement of the base unit into and out of the system  100  and so provide user access to the interior chamber  223  of the unit. The interior chamber  223  may also serve as a storage bay for one or more bioreactors. Handles (e.g.  227 ) may be provided to assist the user in moving the base unit  220 . The wheels (e.g.  220 ) may optionally be reversibly lockable to increase the stability of the unit  220 . 
         [0070]      FIG. 3  is a schematic perspective view of a stacking unit  340  of a system in accordance with an embodiment of the invention. The stacking unit  340  consists of a frame  341  supporting side walls  342   a, b , an optional back wall  343 , a ceiling or roof  344  and a movable platform  345  which define an upper  346  and a lower  347  chamber. The lower chamber  347  is dimensioned such that it can receive the base unit ( FIG. 2 ) within it. The platform  345  is designed to provide a support for a bioreactor (not shown) within the upper chamber  346  which may also serve as a storage bay for a bioreactor. The base of the frame  341  may optionally have feet (e.g.  348 ) to provide stability for the unit. In other embodiments, the frame  341  may have lockable wheels rather than feet  348  to provide mobility and stability. In yet other embodiments, the stackable unit  340  may be secured into place, for example by bolting against a wall and/or to the floor to provide stability. 
         [0071]      FIG. 4  is a schematic perspective view of a guard unit  460  of a system in accordance with an embodiment of the invention. The guard unit  460  consists of a frame  461  supporting side walls  462   a, b , an openable front wall  463   a,b , and a movable platform  470  which define an upper chamber  464   a  and a lower chamber  464   b  which is dimensioned to partially receive the stacking unit ( FIG. 3 ). The guard unit  460  is supported on legs  465   a,b  which may also have wheels (e.g.  446 ) or coasters or be on a trolley or rail system to facilitate movement of the guard unit away from the base unit  120  and stacking unit  140  ( FIG. 1 ) and provide user access to the interior of chamber  464 . Handles  468  are provided to assist the user in moving the guard unit  460  away from/towards the base unit  120  and stacking unit  140 . As shown in the figure, optionally there may be a rear wall  467  opposing wall  463  which may be reinforced to act as a spacer and/or support when the system is in a closed or storage configuration ( FIG. 1 ). In the embodiment shown, the interior chamber  464  is accessible via the openable wall  463   a,b  by means of sliding panel  463   b.  The movable platform  470  is used to support a bioreactor, as seen in  FIG. 1 . Control panels  469   a,b,c  are used to raise and/or lower the movable platform  470 . 
         [0072]    In embodiments of the invention, movable platform  470  is replaced with a movable ceiling or roof of the stacking unit. 
         [0073]      FIG. 5  is a side view of the system  500  of  FIG. 1 . For illustrative purposes, a schematic user  501  is shown facing the front of the system  500 . As with  FIG. 1 , the system  500  is shown in a closed or storage configuration housing or storing bioreactors. The component parts of the system  500  can be seen to be the base unit  52 , the stacking unit  540  and the guard unit  560 . From this perspective, it can be seen that the base unit  520  is accommodated within the lower chamber of the stacking unit  540  which is itself partially surrounded by or received within the chamber of the guard unit  560 . 
         [0074]    Use of the system of embodiments of the invention as depicted in  FIGS. 1 to 5  will be described with reference to  FIGS. 6 to 19  below. It is expected that the system will be maintained in a clean area such as a tissue culture suite or biomanufacturing facility to minimise the risk of microbial contamination. Bioreactors will be housed or stored in the system until such time as it is necessary to carry out work on them and the growing cultures, such as sub-culturing or harvesting cells, media and/or biomolecules. 
         [0075]      FIG. 6  is a schematic perspective view of a system  600  in accordance with an embodiment of the invention as shown in  FIG. 1 . For illustrative purposes a user  601  in depicted in front of the system  600  which comprises a base unit  620 , a stacking unit  640  and a guard unit  660 . Again for illustrative purposes, the system  600  is shown housing or storing bioreactors  680   a, b, c . in a closed or storage configuration. It will be understood, that while the embodiment shown houses or stores one bioreactor  680  in each of the three units ( 620 ,  640  and  660 ), other embodiments of the system are capable of storing or housing more than one bioreactor in each unit; thus, for example, the system can house or store a total of six, or nine, or twelve, or more bioreactors depending upon the size of the respective units. 
         [0076]    To use the system  600  the user, in the interests of safety, would first turn off and disconnect the supply of utilities (such as electricity, water, nitrogen, oxygen, air and carbon dioxide) to the system. The user may also disconnect any waste removal or outlet conduits from the system. 
         [0077]    The user can then open the sliding panel  763   b  of the guard unit  760  which provides the user  701  access to the base unit  720  ( FIG. 7 ). The base unit  820  can then be pulled or moved away from the stacking unit  840  and guard unit  860  ( FIG. 8 ). The user  901  would then raise the movable platform  924  supporting the bioreactor  980  by means of the control panel  926  to provide a workstation which is at a convenient height and is easily accessible. Work, such as culture maintenance or harvesting, can now be carried out on the cultures within the bioreactor  980  ( FIG. 9 ). Once work has been completed on the bioreactor  1080  and/or the cultures therein, the user  1001  lowers the movable platform  1024  by means of the control panel  1026  ( FIG. 10 ). The user  1101  now pushes the base unit  1120  back into position, utilising handles  1127 , within the stacking unit  1140  and guard unit of the system  1100  ( FIG. 11 ). The bioreactor  1180  is now in its resting or storage position within the base unit  1120  of the system  1100  and the wheels  1125  of the base unit  1120  locked to secure it in position. 
         [0078]    To work on the bioreactor  1280  within the stacking unit  1240 , the user  1201  pulls the movable platform  1245  from the upper chamber  1246  of the stacking unit  1240  ( FIG. 12 ). This creates a work station for the user  1201  who can now readily access the bioreactor  1280 . Maintenance work, such as sub-culturing, cell harvesting or biomolecule harvesting, can now be carried out on the cultures within the bioreactor  1280 . Once work has been completed the platform  1245  is pushed back into chamber  1246  of the stacking unit  1240  ( FIG. 12 ) and the sliding panel  1363   b  is closed to return the system  1300  into its resting or storage position ( FIG. 13 ). 
         [0079]    To access the bioreactor  1480  in the chamber  1464  of guard unit  1460  in system  1400 , the user  1401  first pulls the guard unit  1460  away from the stacking unit  1440  using handles  1468  as shown in  FIG. 14 . The movable platform  1570  supporting the bioreactor  1580  in the chamber  1564  is lowered by means of the control panel  1569  to user  1501  level ( FIG. 15 ). The sliding panel  1663   b  may then be opened to provide user  1601  access to the bioreactor  1680  within the chamber  1664  of the guard unit  1660  ( FIG. 16 ) and thus a workstation. The user  1601  can then carry out work, such as maintenance or cell/biomolecule harvesting on the culture within the bioreactor  1680 . Once work has been completed, the user  1701  can close the sliding panel  1663   b  of the guard unit ( FIG. 17 ) and raise the movable platform  1870  using the control panel  1869  to its return the bioreactor  1880  to its resting or storage position within the chamber  1864  of the guard unit  1860  of the system  1800 . The guard unit  1960  can then be pushed back to partially surround or enclose the stacking unit  1940  and the wheels  1966  locked to secure it into position ( FIG. 19 ). The system  1900  is now in a resting or storage position and, once reconnected to utilities and waste outlets, can be left in this position or configuration until further work is required on the cultures within the bioreactors. 
         [0080]      FIG. 20  is a schematic diagram showing a system  2000  for cell culture and/or biomanufacturing comprising a housing  2090  comprising a plurality of vertically stacked workstations  2020 , a mechanism  2092  for rotating said plurality of workstations; and a port  2095  for providing user  2001  access to one of the workstations  2020 . The system  2000  allows multiple workstations to be held per floor of space area (e.g. two, three, four, five, six or seven). The workstations  2020  are presented in an ergonomically suitable form for the user  2001 . The rotating mechanism  2092  allows full rotation to each of the workstations  2020  either continuously or in a single rotation format (arrows A and B depict the direction of rotation). Each workstation  2020  has a suitable identification (e.g. bar code or RFID tag) so that the user  2001  can dial up or retrieve and access the workstation  2020  of interest. Moreover, each bioreactor  2080  is uniquely identified by, for example, a bar code or RFID tag). 
         [0081]    While illustrative embodiments of the present invention are described, one skilled in the art will appreciate that the present invention can be practiced by other than the described embodiments, which are presented for purposes of illustration only and not by way of limitation. The present invention is limited only by the claims that follow.