Abstract:
A fluid handling system is provided that includes a controller, a plurality of valves, a pump, and an interface in communication with the controller. The valves can be operatively connected with a conduit to along a flow path. Each of the valves is controlled by the controller for selective movement between a first position and a second position. The first position closes the flow path, while the second position opens the flow path. The pump can be operatively connected with the conduit and the is controlled by the controller for selective pumping of fluid through the flow path. The interface allows selective definition of the flow path through the valves.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. Provisional Application No. 62/365,409 filed on Jul. 22, 2016, the entire contents of which are incorporated herein by reference. 
     
    
     BACKGROUND 
     1. Field of the Invention 
       [0002]    The present disclosure is related to fluid handling systems for ultracentrifuges. More particularly, the present disclosure is related to a self-contained mobile work station that supports automated filling and fractionation of fluids to and from ultracentrifuges. 
       2. Description of Related Art 
       [0003]    The processing of many fluid products by ultracentrifuge is performed in a sterile environment and/or an aseptic environment to protect the product and/or the manufacturing personnel from contamination. Such fluid products can include, but are not limited to, pharmaceutical products (e.g., medicines and vaccines), food products, biological products, biochemical products, chemical products, nanoparticles, viral particles, viral vectors, and any combinations thereof. 
         [0004]    During such processing, it is known to fill the ultracentrifuge with the materials for processing and collection the fluid product during or after the processing. In some instances, the filling and/or collection can be performed during or after certain process steps and/or at certain time intervals. In other instances, the filling and/or collection can be performed after the processing is complete. Further, it is often necessary to clean and sterilize the flow paths in the system before and/or after processing, which can be accomplished by pumping certain fluids and/or gases through the system. The filling and/or collection and/or supply of cleaning fluids, as well as other fluid movement processes through the system, are individually and collectively referred to herein as “fluid handling”. 
         [0005]    Importantly, the fluid handling is a critical activity and creates a potential risk of contaminating the product and/or the sample, as well as potentially exposing the operator to hazardous conditions. 
         [0006]    Accordingly, it has been determined by the present disclosure that there is a need for systems and methods that can provide improved fluid handling. 
       SUMMARY 
       [0007]    A fluid handling system is provided that self-contained mobile work station that supports automated filling and fractionation of fluids to and from ultracentrifuges and other vessels, containers, or processing devices. 
         [0008]    In some embodiments, the system includes a plurality of pinch valves that allows for routing of fluid, pumps for flow and direction, an inline refractometer for fractionation/monitoring and disposable flow, pressure and temperature transducers for process monitoring. 
         [0009]    In other embodiments, the system includes one or more preprogrammed control programs and/or includes modifiable control structures that allow for the creation of customized methods for automation of various flow sequences such as sanitization, rinsing, filling, fractionation and other custom methods. The system can be easily integrated with a customer&#39;s network and/or industrial controllers (e.g., programmable logic controllers or PLC&#39;s) and can utilize upstream and downstream inputs and outputs via a software interface such as, but not limited to, Open Platform Communications (OPC). 
         [0010]    A fluid handling system is provided that includes a controller, a plurality of valves, a pump, and an interface in communication with the controller. The valves can be operatively connected with a conduit to along a flow path. Each of the valves is controlled by the controller for selective movement between a first position and a second position. The first position closes the flow path, while the second position opens the flow path. The pump can be operatively connected with the conduit and the is controlled by the controller for selective pumping of fluid through the flow path. The interface allows selective definition of the flow path through the valves. 
         [0011]    In some embodiments, the fluid handling system is a self-contained workstation. 
         [0012]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the conduit is flexible conduit, the valves are pinch valves, and the pump is a peristaltic pump. The pinch valves and the peristaltic pump are configured for operative connection to the flexible conduit. 
         [0013]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the fluid handling system further includes a sensor selected from the group consisting of a flow sensor, a pressure sensor, and a temperature sensor, a refractometer, and any combinations thereof, wherein the interface is configured to selectively define the flow path through the sensor. 
         [0014]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the fluid handling system further includes a refractometer controlled by the controller, the refractometer is an inline device that measures the state of the fluid through a transparent portion of the conduit, wherein the interface is configured to selectively define the flow path through the refractometer. 
         [0015]    In some embodiments, the state of the fluid measured by the refractometer is an index of refraction and/or a temperature. 
         [0016]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the fluid handling system further includes at least one additional device controlled by the controller, the at least one additional device being selected from the group consisting of a pressure sensor, a flow transducer, a scale, and any combinations thereof, wherein the interface is configured to selectively define the flow path through the at least one additional device. 
         [0017]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the controller is a programmable logic controller (PLC). 
         [0018]    In some embodiments, the interface is configured to allow visual programing of the PLC. 
         [0019]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the valves each include a light. The light is controlled by the controller to provide a visual indication of a state of each valve of the plurality of valves. The state is selected from the group consisting of whether the fluid path is open or closed, whether the conduit is to be installed in a particular valve, and combinations thereof. 
         [0020]    A pinch valve for opening and closing a fluid path in a conduit is also provided. The pinch valve includes a solenoid, a pinch valve head, and a light. The solenoid is moveable between a first position and a second position. The pinch valve head is operatively connected to the solenoid and configured to be operatively connected to the conduit so that that movement of the solenoid to the first position causes the pinch valve head to pinch the conduit closing the fluid path and so that movement of the solenoid to the second position causes the pinch valve head to release the conduit opening the fluid path. The light is secured to the pinch valve head to provide a visual indication of a state of the pinch valve. The state is selected from the group consisting of whether the fluid path is open or closed, whether the conduit is to be installed in the pinch valve head, and combinations thereof. 
         [0021]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the solenoid is selected from the group consisting of an electro-mechanical solenoid, a pneumatic solenoid, and any combinations thereof. 
         [0022]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the solenoid includes a first portion configured to be housed in a workstation and a second portion configured to extend from the workstation, the pinch valve head being operatively connected to the second portion. 
         [0023]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the pinch valve further includes a first seal configured to seal the solenoid to the workstation. 
         [0024]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the light is a light emitting diode (LED). 
         [0025]    In other embodiments alone or with one or more of the aforementioned or later mentioned embodiments, the light includes a cover secured to the pinch valve head by a second seal. 
         [0026]    The above-described and other features and advantages of the present disclosure will be appreciated and understood by those skilled in the art from the following detailed description, drawings, and appended claims. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0027]      FIG. 1  is a schematic view of a fluid handling system according to the present disclosure in use with an ultracentrifuge; 
           [0028]      FIG. 2  is a schematic depiction of a system architecture of the fluid handling system of  FIG. 1 ; 
           [0029]      FIG. 3  is a perspective view of the fluid handling system of  FIG. 1 ; 
           [0030]      FIG. 4  is a magnified view of the fluid handling system of  FIG. 1 ; 
           [0031]      FIG. 5  is an exploded view of a pinch valve according to the present disclosure; 
           [0032]      FIG. 6  is a schematic depiction of program interface illustrating a pre-programmed mode of operation; 
           [0033]      FIG. 7  is a flow diagram of a method programming interface process; 
           [0034]      FIG. 8  is a schematic depiction of program interface illustrating the method programming mode of operation; 
           [0035]      FIG. 9  is a schematic depiction of program interface illustrating the method programming mode of operation; and 
           [0036]      FIG. 10  is a schematic depiction of a state editing mode of operation. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0037]    Referring to the drawings and in particular to  FIGS. 1 and 2 , a fluid handling system according to the present disclosure is shown and is generally referred to by reference numeral  10 . 
         [0038]    Advantageously and as described in more detail herein, system  10  supports a plurality of pinch valves for routing of fluid, pumps for flow and direction, an inline refractometer for fractionation/monitoring and disposable flow, pressure and temperature transducers for process monitoring. System  10  includes software that includes pre-programmed operations and allows for the creation of customized methods for automation of various flow sequences such as sanitization, rinsing, filling, fractionation and other custom methods. Moreover, system  10  is configured to integrate with the customer&#39;s network and can utilize upstream and downstream inputs and outputs via OPC. 
         [0039]    System  10  is illustrated in use with an ultracentrifuge  12 , which includes a control cabinet  14  and a rotor/tank system  16 . System  10  is self-contained workstation  18  that supports automated filling and fractionation of fluids to and from ultracentrifuge  12  by, for example, communicating with control cabinet  14  of the ultracentrifuge  12 . It should be recognized that system  10  is illustrated by way of example only in use with ultracentrifuge  12 . Of course, it is contemplated by the present disclosure for system  10  to find use with any vessels, containers, or processing devices. 
         [0040]    Workstation  18  is compact and, preferably, configured to be mobile and/or configured for use in an industrial cleanroom environment. For example, workstation  18  can be made of stainless steel 303/304 and can be configured to meet or exceed standards such as, but not limited to, NEMA 4× an IP65. Workstation  18  can, in some embodiments, allow the position of the front panel to be adjusted with respect to the support legs. Thus, system  10  via the configuration of workstation  18  provides an ergonomic and compact design to fit even in a small clean room and to be able to pass through a commonly used egress doorway as small as 32 inches, is configured to easy cleaning by, for example, hand wiping, and provides all controls sufficient for activation via personnel wearing personal protective equipment (e.g., two Latex/Nitrile gloves). 
         [0041]    Thus, system  10  includes a computer  20  for communicating with ultracentrifuge  12  and/or any other customer network  22  in a wired and/or wireless manner. 
         [0042]    Systems  10  includes, resident on workstation  18 , computer  20  in communication with a programmable logic controller (PLC)  24 . Computer  20  includes an OPC communication software  26  resident thereon for wired and/or wireless communication with customer network  22 , PLC  24 , and one or more human-machine-interface (HMI)  28 . HMI  28  can be any interface such as, but not limited to, a keyboard, mouse, touchscreen, printer, display screen, speaker, notification device (e.g., lights, alarm, etc.), tablet, laptop, buttons, or any other interface. 
         [0043]    Additionally, computer  20  includes a fluid handling control software interface  30  resident thereon, which advantageously allows the operator to control PLC  24  to operate one or more devices  32  in a pre-programmed mode of operation, program system  10  using method programming process, operate system  10  using a state editing mode of operation, and any combinations thereof, which will be described in more detail below. Devices  32  can include sensors, pumps, valves, lights, data collection, and others. 
         [0044]    System  10  is illustrated in  FIG. 2  by way of example having specific communication protocols (e.g., Ethernet, USB, etc.) among computer  20 , customer network  22 , PLC  24 , HMI  28 , and devices  32 . Of course, it is contemplated by the present disclosure for system  10  to communicate among the various components in any desired manner. 
         [0045]    System  10 , by separating the control of devices  32  via PLC  24  from the communication with HMI  28  via computer  20  allows for redundancy within the system. For example, failure of HMI  28  during use will not cause failure or ceasing of operations by computer  20  or workstation  14 . Rather, a user can simply access computer  20  and PLC  24  via connection of another HMI. 
         [0046]    Referring now to  FIGS. 3 and 4 , system  10  will be described in more detail. 
         [0047]    System  10  is configured to fluidly communicate with ultracentrifuge  12  via conduit  40 . Conduit  40  can be disposable, reusable, and combinations thereof. System  10  includes, as one or more of devices  32 , an array of pinch valves  42  controlled by PLC  24  to selectively open and close conduit  40 . Here, conduit  40  at least in the portions acted upon by valves  42  is configured as resilient tubing. In the illustrated embodiment, system  10  includes thirteen normally closed pinch valves  42 , but of course it is contemplated by the present disclosure for system  10  to support any desired number or configuration of valves. 
         [0048]    System  10  further includes, as one or more of devices  32 , a pump  44  controlled by PLC  24  to pump fluid through conduit  40 . In some embodiments, pump  44  can be a peristaltic pump that acts on conduit  40  in a known manner. In this embodiment, conduit  40  at least in the portions acted upon by pump  44  is configured as resilient tubing. 
         [0049]    System  10  further includes, as one or more of devices  32 , a refractometer  46  controlled by PLC  24  to detect a state of fluid in conduit  40 . In some embodiments, refractometer  46  can be an inline device that senses the state of fluid in conduit  40 . Conduit  40  can be configured, at least in the region of refractometer  46 , to have transparency sufficient for measurement of the fluid. The state of fluid measured by refractometer  46  can include, but is not limited to, index of refraction and temperature. 
         [0050]    System  10  further includes, as one or more of devices  32 , one or more of a pressure sensor  48 , a flow transducer  50 , and a scale  52  controlled by PLC  24  to detect a state of fluid in conduit  40 . 
         [0051]    Of course, it should be recognized that devices  32  are described above as by way of example. However, it is contemplated by the present disclosure for system  10  to have any desired number or configuration of devices  32  controlled by PLC  24  as necessary for the particular use of the system. 
         [0052]    Accordingly, system  10  is configured for control of flow when loading rotor  16  with, for example, water for injection (WFI), gradient materials, analyte materials, process materials, sampling and/or unloading of the rotor materials during fraction collection, and others. In this manner, system  10  can be easily configured to allow the user to fill collection devices  54  in communication with conduit  40  such as, but not limited to, reservoirs, jars, bottles, bags, and the like. 
         [0053]    System  10  can load collection devices  54  according to variables such as, but not limited to, refractive index, volume, mass, time, a particular event or detected state of control cabinet  14 , rotor  16 , system  10 , fluid in conduit  40 , and others. 
         [0054]    In this manner, system  10 , having computer  20  resident thereon, operates independent from, but in communicating with ultracentrifuge  12  or a plurality of centrifuges. 
         [0055]    However, it is also contemplated by the present disclosure for system  10  to operate dependently with ultracentrifuge  12 . For example and referring again to  FIG. 2 , it is contemplated by the present disclosure for computer  20  and OPC communication software  26  resident thereon to be present in control cabinet  14  of ultracentrifuge  12  instead of workstation  18 . In this embodiment, computer  20  can be in wired and/or wireless communication with PLC  24  of workstation  18 . 
         [0056]    The construction and operation of each of the valves  42  is described in more detail with respect to  FIG. 5 . 
         [0057]    Valve  42  includes a solenoid  60  controlled by PLC  24 . Solenoid  60  can be an electro-mechanical solenoid, a pneumatic solenoid, or others. Solenoid  60  is housed partially within workstation  18  and extends through one or more openings  62  in the workstation for operative coupling with conduit  40 . 
         [0058]    Valve  42  further includes a pinch valve head  64  positioned outside of workstation  18  and operatively connected to solenoid  62  so that movement of the solenoid by PLC  24  causes the head to pinch conduit  40  to close the fluid path in a first position or to release the conduit to open the fluid path in a second position. Openings  62  in workstation  18  are sealed or otherwise closed by head  64  and, in some embodiments, first seal  66 . 
         [0059]    In embodiments where conduit  40  is disposable, the conduit is preferred to be made entirely of a soft resilient tubing. However, it is contemplated by the present disclosure for conduit  40 , even when disposable, to have one or more sections formed of rigid tubing—with the portions of the conduit at valves  42  and/or pump  44  having sufficient flexibility and resiliency to function in the intended manner. Moreover, it is contemplated by the present disclosure for conduit  40  to be rigid tubing with in communication with valves  42 , which can be any non-pinch valve design configured for operation by solenoid  60  such as, but not limited to ball valves, needle valves, cup valves, and the like. 
         [0060]    Valve  42  can further include one or more lights  68  (only one shown) in communication with PLC  24 . Light  68  can be a light emitting diode (LED) or any other light device. Light  68  can include a cover or protective lens  70  secured to head  64  by a second seal  72 . Light  68  can be controlled to provide a visual indication as to when the valve is open or closed. 
         [0061]    For example, light  68  can be controlled to be on (i.e., illuminate) when valve  42  is in the first position and can be controlled to be off (i.e., not illuminated) when the valve is in the second position. Of course, this operation can be reversed in some embodiments. 
         [0062]    In other embodiments, light  68  can illuminate in two different colors representative of the first and second positions, respectively. In still other embodiments, light  68  can include two different lighting elements that illuminate in different colors representative of the first and second positions, respectively. 
         [0063]    It should be recognized that valve  42  is described as using light  68  to indicate only first and second positions of the valve, namely where the on and off state of the light corresponds to the open and closed states of the valve. Of course, it is contemplated by the present disclosure for valve  42  to be configured so that light  68  illuminates proportionally with respect to the state of the valve, namely with an intensity or number of lights corresponding the proportion of openness of the valve. 
         [0064]    In some embodiments, light  68  can be controlled directly by the position of solenoid  60 , while in other embodiments the light can be controlled by PLC  24 . 
         [0065]    In this manner, system  10  is configured to provide the user with a visual indication—viewable from a distance such as from outside the clean room— of the flow path through the system during use. 
         [0066]    Additionally, and in some embodiments where it is necessary to install disposable conduit  40 , system  10  can be controlled to illuminate the valves  42  into which the conduit is to be installed. Furthermore, PLC  24  can be controlled so that the view of the flow path on HMI  28  mirrors that of lights  68 . 
         [0067]    In some embodiments, head  64  includes a conduit receiving opening  74  into which conduit  40  can be removably received. 
         [0068]    System  10  can be configured to operate in a pre-programmed or main mode  80 , which is illustrated with reference to  FIG. 6 . Here, system  10  can include one or more pre-programmed control schemes resident on computer  20  and/or PLC  24 . In the illustrated example, a user can select—via HMI  28 —the use of pre-programmed mode  80  and once selected can select a particular program  82  shown as a “load buffer/gradient” program from among a plurality of different the pre-programmed control schemes. 
         [0069]    In response, to selection of program  82 , HMI  28  can illustrate to the user the operation of system  10  and PLC  24  can control devices  32  according to the program. When lights  68  are present, PLC  24  can also provide the visual indication of the state of valves  42 . 
         [0070]    In this way, the normal operation of system  10  can be selected by the user during the pre-programmed mode  80 . Here, the user can, for example, enter via HMI  28  unique batch identifying information, which system  10  can compare to information present on customer network  22  related to the batch, and can either load program  82  based on information from the customer network or allow the operator to continue upon verification of proper batch information. Once the desired program  82  has been selected and commenced, system  10  can—where installation of conduit  40  is required—will open valves  42  and/or light lights  68  to prompt the operator to install the conduit. After confirmation of proper setup, system  10  as controlled by PLC  24  will control devices  32  according to program  82 . 
         [0071]    System  10  can also be configured to operate in a method programming mode  84 , which is illustrated with reference to  FIGS. 7-9 . Without wishing to be bound by any particular theory, it has been determined by the present disclosure that the language necessary for PLC  24  to operate devices  32  can be difficult to understand and/or program. Thus, method programming mode  84  advantageously provides a way for the operator to program PLC  24  using software  26  resident on computer  20  and, not, via the PLC language. Mode  84  provides a visual method of programming tasks into system  10 . 
         [0072]    Here, the method editor of programming mode  84  allows the user to list sequential operations or steps of a particular desired program  86 . This is a dynamic method editor the user can change, and is not hard coded so that the operator can define the control steps of devices  32 . Programming mode  84  allows the operator to create, edit and disable programs  86 . While working on a method, system  10  allows the operator to add, insert, delete or reorder the steps  88  of program  86  while providing a visual indication via HMI  28  of the various device  32  and their states of operation. Upon completion of programming mode  84 , computer  20  will store the program  86  and control PLC  24  to execute the program to control devices  32  as desired. 
         [0073]    System  10  can also be configured to operate in a state editing mode  90 , which is illustrated with reference to  FIG. 10 . Here, the operator can select the state editing mode  90  from the main sequence editor ( FIG. 6 ). Here, any programs  82  that were selected or programs  86  that were designed can be manually overridden by the operator. For example,  FIG. 10  illustrates manual overrides via state editing mode  90  of pump  44 . Although illustrated with respect to pump  44 , it is contemplated by the present disclosure for editing mode  90  to find use with the control of any device  32  within system  10 . 
         [0074]    It should also be noted that the terms “first”, “second”, “third”, “upper”, “lower”, and the like may be used herein to modify various elements. These modifiers do not imply a spatial, sequential, or hierarchical order to the modified elements unless specifically stated. 
         [0075]    While the present disclosure has been described with reference to one or more exemplary embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the present disclosure. In addition, many modifications may be made to adapt a particular situation or material to the teachings of the disclosure without departing from the scope thereof. Therefore, it is intended that the present disclosure not be limited to the particular embodiment(s) disclosed as the best mode contemplated, but that the disclosure will include all embodiments falling within the scope of the present invention. 
         [0000]    
       
         
               
             
               
               
             
           
               
                   
               
               
                 PARTS LIST 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 system 10 
               
               
                   
                 ultracentrifuge 12 
               
               
                   
                 control cabinet 14 
               
               
                   
                 rotor/tank system 16 
               
               
                   
                 self-contained workstation 18 
               
               
                   
                 computer 20 
               
               
                   
                 customer network 22 
               
               
                   
                 programmable logic controller (PLC) 24 
               
               
                   
                 communication software 26 
               
               
                   
                 human-machine-interface (HMI) 28 
               
               
                   
                 fluid handling control software interface 30 
               
               
                   
                 devices 32 
               
               
                   
                 conduit 40 
               
               
                   
                 pinch valves 42 
               
               
                   
                 pump 44 
               
               
                   
                 refractometer 46 
               
               
                   
                 pressure sensor 48 
               
               
                   
                 flow transducer 50 
               
               
                   
                 scale 52 
               
               
                   
                 collection devices 54 
               
               
                   
                 solenoid 60 
               
               
                   
                 openings 62 
               
               
                   
                 pinch valve head 64 
               
               
                   
                 first seal 66 
               
               
                   
                 light 68 
               
               
                   
                 cover or protective lens 70 
               
               
                   
                 second seal 72 
               
               
                   
                 conduit opening 74 
               
               
                   
                 pre-programmed or main mode 80 
               
               
                   
                 particular program 82 
               
               
                   
                 method programming mode 84 
               
               
                   
                 particular desired program 86 
               
               
                   
                 steps 88 
               
               
                   
                 state editing mode 90