Patent Publication Number: US-2023141350-A1

Title: Bioprocess System

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. application Ser. No. 16/757,804, filed Apr. 21, 2020, which claims the priority benefit of PCT/EP2018/079354 filed on Oct. 25, 2018, which claims priority benefit of Great Britain Patent Application No. 1717652.0 filed on Oct. 26, 2017, the entire contents of which are incorporated herein by reference. 
    
    
     TECHNICAL FIELD OF THE INVENTION 
     The present invention relates to a bioprocess system and to a base station of a bioprocess system. 
     BACKGROUND OF THE INVENTION 
     For large bioprocess systems such as chromatography or filtering systems flow paths within the system have traditionally been provided stationary in the system as metal or plastic pipes. These pipes need to be sanitized between different processes performed in the system. Especially in smaller bioprocess systems the flow paths are nowadays often instead provided as flexible, disposable tubing. Hereby the whole flow path can be exchanged between different processes. When exchanging the disposable tubing access is needed to valves into which the tubing need to be connected and pumps to which the tubing should be connected. A problem may be to get good access for an easy exchange of disposable tubing and another problem may be that the systems are bulky. 
     SUMMARY 
     An object of the invention is to provide an improved bioprocess system comprising a disposable tubing set where the disposable tubing set can be easily exchanged. 
     This is achieved in a base station and in a bioprocess system according to the independent claims. 
     According to one aspect of the invention there is provided a bioprocess system comprising: 
     a base station ( 1 ) including a frame or housing ( 5 ), wherein said frame or housing comprises plural valves ( 7   a - f ,  9   a - d ,  11   a - f ,  13   a - e ,  15   a - f ) for controlling fluid flow in the system and configured to be releasably fluidically connectable to a disposable tubing set ( 21 ); and a discrete movable pump holding device ( 35 ), at least partially containable within the frame or housing ( 5 ) and removable therefrom and which comprises at least one pump main body ( 37 ), said pump main body comprising a fluid connection ( 39 ) configured to be releasably connectable to a pump connection part ( 27 ) of the disposable tubing set ( 21 ). 
     Expressed in a different manner the invention provides a base station of a bioprocess system. Said base station comprises:
         a frame or housing, wherein said frame or housing comprises a number of valves into which a disposable tubing set during run of the system may be provided such that at least one inlet of the disposable tubing set is connected to at least one outlet of the disposable tubing set via a bioprocess separation device of the bioprocess system; and   a movable pump holding device, which can be provided in at least two different positions, whereof one is within the frame or housing and another is at least partly outside the frame or housing and which comprises at least one pump main body, said pump main body comprising a connection configured for connecting to a disposable pump connection part comprised in the disposable tubing set.       

     According to another aspect of the invention a bioprocess system is provided comprising a base station as defined above, a disposable tubing set and a bioprocess separation device. 
     Herby the pumps of the bioprocess system can be provided both inside the frame or housing and at least partly outside the frame or housing. Hereby the pumps can be easily accessed to change pump heads, for connection of tubing and for maintenance. The pumps can also be provided completely within the frame or housing during run of the system. Hereby a less bulky system is provided compared to if the pump heads always need to be provided outside the system and access for maintenance of the pumps is required. 
     In one embodiment of the invention said movable pump holding device comprises a trolley on wheels and said frame or housing comprises an empty space in a bottom part of the frame or housing for receiving said movable pump holding device. 
     In one embodiment of the invention said frame or housing comprises four walls constituting together with a roof of the frame or housing essentially a box, wherein the valves of the frame or housing are provided on at least three of said four walls and wherein a first wall of said four walls comprises an opening for receiving the movable pump holding device into an empty space of a bottom part of the frame or housing and wherein a second wall of said four walls comprises an inlet valve access opening through which access to at least one inlet valve positioned within the frame or housing is achieved. 
     In one embodiment of the invention said outlet valves of the frame or housing are provided on a third wall of said four walls. 
     In one embodiment of the invention at least five separation device valves are provided for receiving the disposable tubing set for controlling feeding of a fluid in the disposable tubing set either upflow or downflow through or bypass a bioprocess separation device connected to the disposable tubing set. 
     In one embodiment of the invention said at least five separation device valves are provided in the third wall of said four walls but at a lower position than the outlet valves. 
     In one embodiment of the invention said frame or housing comprises a holder for a disposable air trap of the disposable tubing set, wherein said holder for a disposable air trap is provided above said inlet valves. 
     In one embodiment of the invention said valves are pinch valves. 
     In one embodiment of the invention said disposable tubing set comprises:
         at least one inlet tubing;   at least one outlet tubing;   at least one disposable pump connection part connected to the inlet tubing and configured for being connected to a pump main body;   at least one disposable air trap; and   two separation device connection points for connection to a bioprocess separation device,   wherein said at least one outlet tubing is connected to said at least one inlet tubing via the other components of the disposable tubing set.       

     In one embodiment of the invention said disposable air trap is a disposable swirl type air trap. 
     In one embodiment of the invention said disposable tubing set further comprises one or more of a disposable UV sensor, a disposable flow sensor, a disposable air sensor, a disposable pH meter, a disposable conductivity meter and a disposable pressure meter. 
     In one embodiment of the invention all the components of the disposable tubing set are connected and the disposable tubing set can be removed from the base station in one piece. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS.  1   a  and  1   b    show two different perspective views of a base station of a bioprocess system according to one embodiment of the invention. Disposable tubing is connected to the base station. 
         FIGS.  2   a  and  2   b    show two different perspective views of a bioprocess system according to one embodiment of the invention. 
         FIGS.  3   a  and  3   b    show two different perspective views of a base station according to one embodiment of the invention. A movable pump holding device of the base station is here provided outside a frame or housing of the base station. 
     
    
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       FIGS.  1   a  and  1   b    show two different perspective views of a base station  1  of a bioprocess system according to one embodiment of the invention.  FIGS.  2   a  and  2   b    show the same base station as shown in  FIGS.  1   a  and  1   b    but also connected to a bioprocess separation device  31 . Hereby  FIGS.  2   a  and  2   b    show two different perspective views of a bioprocess system  3  according to one embodiment of the invention.  FIGS.  3   a  and  3   b    show two different perspective views of the same base station as shown in  FIGS.  1   a  and  1   b    but without a disposable tubing set connected. 
     The invention relates to a base station  1  of a bioprocess system  3  and to a bioprocess system  3  comprising such a base station  1 . A bioprocess system according to the invention comprises a base station  1 , a disposable tubing set  21  connected to the base station and a separation device  31 , such as for example a chromatography column or a filter which is connected to the disposable tubing set. A separation device  31  is not shown in  FIGS.  1   a  and  1   b    but in  FIGS.  2   a  and  2   b   . The base station  1  comprises valves and pumps (further described and numbered below) to which the disposable tubing set will be connected. Furthermore the base station  1  suitably comprises some type of controlling capability for controlling the valves and pumps during run of the bioprocess system. This control will not be described further. 
     The base station  1  according to the invention comprises a frame or housing  5 , wherein said frame or housing comprises a number of valves  7   a - f ,  9   a - d ,  11   a - f ,  13   a - e ,  15   a - f  into which a disposable tubing set  21  during run of the system is provided such that at least one valve inlet  23   a - j  is connected to at least one outlet  25   a - f  of the disposable tubing set via a bioprocess separation device  31  of the bioprocess system  3 . In this embodiment of the invention  10  separate inlets  23   a - j  are provided. Of course the number of inlets can be varied. In this embodiment of the invention the inlets  23   a - j  are separated into two groups. A first group comprises four inlets  23   a - d , called first inlets  23   a - d , which are provided above a second group comprising six inlets  23   e - j , called second inlets  23   e - j . All the inlets  23   a - j  can be used for feeding of for example buffer and sample into the system. Of course the number of first and second inlets  23   a - j  can be varied. Each of the inlets  23   a - j  are during run of the bioprocess system connected to a valve  7   a - f ,  9   a - d  provided on the base station  1 . The valves  7   a - f  to which the second inlets  23   e - j  are connected are called second inlet valves  7   a - f  and the valves  9   a - d  to which the first inlets  23   a - d  are connected are called first inlet valves  9   a - d . Of course the number of first and second inlet valves  9   a - d ,  7   a - f  can vary in the base station. In this embodiment of the invention furthermore six different outlets  25   a - f  of the disposable tubing set  21  are provided. Of course the number of outlets  25   a - f  can vary within the scope of the invention. Accordingly in this embodiment of the invention six outlet valves  11   a - f  are provided in the base station  1 . During run of the system the outlets  25   a - f  of the disposable tubing set  21  are provided connected one to each of these outlet valves  11   a - f . Of course also the number of outlet valves  11   a - f  can be varied. 
     The disposable tubing set  21  will be connected to a bioprocess separation device  31  during run of the system. The disposable tubing set  21  comprises two separation device connection points  71 ,  73  which can be seen in  FIG.  1     a.  The disposable tubing is branched such that one branch  75   a  of the tubing comprises one of the separation device connection points  71  and another branch  75   b  comprises the other separation device connection point  73 . Furthermore, in this embodiment also a bypass branch  75   c  of the tubing is provided in between the other two branches  75   a,b . The three branches are collected into one tubing before and after the separation device connection points  71 ,  73 . The base station  1  comprises separation device valves  13   a - e  to which said branches  75   a,b,c  of the disposable tubing are connected during run. One separation device valve is provided on each side of each separation device connection point  71 ,  73  and one separation device valve is also provided to the bypass branch. By this arrangement of separation device valves  13   a - e  and the branching of the disposable tubing set  21  for the connection of the separation device  31 , the separation device  31  can be connected for both upflow separation (liquid flow upwardly through the device  31 ) and downflow separation (liquid flow downwardly through the device) without the need of any rearranging of the tubing but only by control of the separation device valves  13   a - e . Furthermore the separation device  31  can also be bypassed. However, also a simpler arrangement of separation device valves without this possibility of switching between upflow and downflow separation is covered by the invention. In such a system no branching of the disposable tubing around the separation device connection points  71 ,  73  is needed and furthermore only three separation device valves would be needed. 
     Furthermore in the base station  1  as shown in  FIG.  1   a  and  1   b    six more valves  15   a - f  are provided. These are provided for allowing bypass or connection of separate components of the disposable tubing set  21  and are also called component bypass valves  15   a - f . In this embodiment of the invention an air trap  63  and a filter cartridge  64  of the disposable tubing set  21  are connected to these component bypass valves  15   a - f . If no bypass of these components is needed these valves can be omitted in the base station  1 . An additional air vent valve  65  is in this embodiment also provided on the frame or housing  5  to which an air vent tube from the air trap  63  can be connected. 
     The valves  7   a - f ,  9   a - d ,  11   a - f ,  13   a - e ,  15   a - f ,  65  connected to the frame or housing  5  of the base station  1  can for example be pinch valves or membrane valves. 
     According to the invention the base station  1  comprises further a movable pump holding device  35 . The movable pump holding device  35  can be provided in at least two different positions, whereof one is within the frame or housing  5  and another is at least partly outside the frame or housing  5 . The movable pump holding device  35  comprises at least one pump main body  37 . In the embodiment shown in  FIGS.  1  and  3    the movable pump holding device  35  comprises two pump main bodies  37  however the number of pump main bodies can be varied within the scope of the invention. Each pump main body  37  comprises a pump connection  38  configured for connecting to a disposable pump connection part  27 , for example a disposable pump head, comprised in the disposable tubing set  21 . 
     In the embodiment of the invention as shown in  FIGS.  1 - 3    the movable pump holding device  35  comprises a trolley on wheels  39 . Furthermore the frame or housing  5  comprises an empty space  41  in a bottom part  43  of the frame or housing  5  for receiving said movable pump holding device  35 . An alternative to a trolley on wheels  39  for the movable pump holding device  35  can be to provide rails to the frame or housing  5  such that the movable pump holding device  35  can be mounted to the rails and moved along the rails to a position within and at least partly outside the frame or housing. However an advantage with providing the movable pump holding device separately on a trolley on wheels  39  is that vibrations from the pumps when they are running are not transferred to the rest of the system. This may be a problem in traditional systems where the pumps are mounted in the system. Another advantage with providing the pump main bodies  37  on a movable pump holding device  35  according to the invention is that both a less bulky system with pumps completely hidden within the system can be achieved while at the same time good access to the pumps easily can be achieved by moving the movable pump holding device  35  outside the frame or housing  5 . Access to the pumps is for example needed when the disposable tubing set should be exchanged and when maintenance of the pumps is needed. In a traditional system where the pumps are fixedly mounted to the system they need to be mounted such that they both are accessible for connection and for maintenance. This probably requires access from more than one side of the pumps. Hereby the systems are often bulky and parts of the pumps are protruding out from the system. This requires more space in the room. 
     In the embodiment of the invention as shown in  FIGS.  1 - 3    the frame or housing  5  comprises four walls  45   a,b,c,d  constituting together with a roof  47  of the frame or housing  5  essentially a box  48 . Hereby a compact design of the base station is achieved. The valves  7   a - f ,  9   a - d ,  11   a - f ,  13   a - e ,  15   a - f  of the frame or housing  5  are in this embodiment of the invention provided on two of these walls  45   a,    45   c  and within an opening  51  of another one of the walls  45   b  which will be further described below. A first wall  45   a  of said four walls comprises an opening  49  for receiving the movable pump holding device  35  into the empty space  41  of the bottom part  43  of the frame or housing  5 . In the embodiment shown in  FIGS.  1 - 3   , but not necessarily, a second wall  45   b  of said four walls comprises an inlet valve access opening  51  through which access to the inlet valves  7   a - f ,  9   a - d  of the frame or housing is achieved. Alternatively the inlet valves  7   a - f ,  9   a - d  are provided mounted to one of the walls  45   a,b,c,d . However an advantage of providing the inlet valves  7   a - f ,  9   a - d  within an opening  51  of one of the walls  45   b  as shown in  FIGS.  1 - 3    is that the base station will be less bulky and access to the inlets is convenient when the disposable tubing set  21  is provided to the base station  1 . Furthermore tubing can be made shorter and be kept inside the system in an efficient way. A minimum of tubing length in the disposable tubing set  21  is advantageous for process efficiency, saving of sample and overall performance and measuring accuracy. Hereby the opening  51  is suitably provided in a bottom part  43  of the frame or housing  5  close to the movable pump holding device  35  when the movable pump holding device  35  is provided inside the frame or housing  5 . In the embodiment as shown in  FIGS.  1 - 3    the second inlet valves  7   a - f  are provided on a lower surface  101  of the frame or housing  5  surrounding the opening  51  and the first inlet valves  9   a - d  are provided on an upper surface  103  of the frame or housing surrounding the opening  51 . 
     The lower surface  101  is shown to be inclined and the upper surface is shown to be flat however both the surfaces can be either flat or inclined. These are only design alternatives for providing good access. 
     In the embodiment as shown in  FIGS.  1 - 3    the first wall  45   a  also comprises the component bypass valves  15   a - f  and a third wall  45   c  comprises both the outlet valves  25   a - f  and the separation device valves  13   a - e . The third wall  45   c  is opposite the second wall  45   b  in the box  48 . Furthermore the outlet valves  25   a - f  are provided above the separation device valves  13   a - e  on the third wall  45   c  referring to directions in the drawings and how the base station will be provided onto a floor. The outlet valves  25   a - f  are positioned above the connection points  71 ,  73  to the separation device  31  to ensure that all instruments are fully filled with liquid during operation even at low flow rates. 
     Three of the component bypass valves  15   a - c  may be for connection of an air trap  63  of the disposable tubing set  21  and the other three of the component bypass valves  15   d - f  may be for connection of a filter cartridge  64 . An air trap holder  61  and a filter cartridge holder  66  can be provided on the first wall  45   a.  The air trap holder  61  can be provided on the first wall  45   a  of the frame or housing  5  at a higher position than the pumps. Hereby a raising flow from inlet to the air trap  63  is provided which is suitable for allowing air to get out from the system through the air trap. 
     The disposable tubing set  21  of the bioprocess system  3  comprises as mentioned above at least one inlet tubing  23   a - j , at least one outlet tubing  25   a - f , at least one disposable pump connection part  27 , for example a pump head, which is connected to the inlet tubing  23   a - j  and configured for being connected to a pump main body  37 . The disposable tubing set  21  comprises further according to one embodiment of the invention at least one disposable air trap  63  and two separation device connection points  71 ,  73  for connection to a bioprocess separation device  31 . Said at least one outlet tubing  25   a - f  is connected to said at least one inlet tubing  23   a - j  via the other components  27 ,  63 ,  71 ,  73  of the disposable tubing set  21 . 
     The disposable air trap  63  is in one embodiment of the invention a swirl type air trap. Such an air trap requires less volume than a traditional air trap where inlet and outlet both are provided in a bottom of the air trap. In the swirl type air trap a housing in a cylindrical form is provided with an inner central rod around which the fluid is circling. An inlet to the cylindrical housing is provided through a wall of the housing and in a direction such that the fluid provided into the housing is provided along a wall of the housing. Hereby the fluid will swirl around the inner central rod. An outlet from the air trap is provided in a bottom of the cylindrical housing, i.e. below the inlet. Furthermore a venting opening for letting gas out is provided in the top of the air trap. The whole air trap  63  is made from plastic and is thus disposable together with the rest of the disposable tubing set  21 . 
     The disposable tubing set  21  may further comprise one or more of the following disposable components: a disposable UV sensor, a disposable flow sensor, a disposable air sensor, a disposable pH meter, a disposable conductivity meter and a disposable pressure meter. According to the invention the complete tubing set with components as specified above, such as pump heads, air trap, UV sensors etc. is provided in materials suitable for being disposable, i.e. low cost and suitable for being gamma irradiated or sanitized in another way. Furthermore the whole disposable tubing set  21  with its connected components can be removed in one piece, i.e. all parts connected. Hereby an easy handling of the product is achieved.