System and method for creating cell processing protocols
Patent Information
- Application Number
- JP2024212227
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2018-09-11
- Filing Date
- 2024-12-05
- Publication Date
- 2025-03-11
Smart Images
Figure 2025032221000001_ABST
Abstract
Description
[Technical field]
[0001] This PCT patent application claims priority to U.S. Provisional Application No. 62 / 729,952, filed September 11, 2018, entitled “Cell Processing Protocol Generation System and Method,” assigned Attorney Docket No. 130670-09601 (formerly 1611 / C96), and named Seth Kasper as inventor, the disclosure of which is hereby incorporated by reference in its entirety.
[0002] The present invention relates to apheresis machines and cell processing devices, and more particularly to generating custom protocols for apheresis machines and cell processing devices. [Background technology]
[0003] In many applications, it is desirable to drain and collect blood and other fluids from wounds and surgical fields (e.g., during and / or after surgery). Removal of the fluids not only aids healing and reduces the risk of infection in the case of blood collection, but also provides an opportunity for hospitals to return collected blood to the patient. This, in turn, reduces the need for transfusions of blood that is not the patient's own (e.g., allogeneic blood).
[0004] Prior art systems typically have one or more sets of protocols that the device must follow. In some cases, the user may have the ability to select one of the protocols and change the process speed, wash volume, or start volume, but not customize the protocol beyond the workflow established for a given application and / or use. Thus, prior art systems have had limited application outside of their intended use. Summary of the Invention
[0005] In a first embodiment of the invention, a method for generating a custom cell processing protocol includes providing a cell processing apparatus having a display, a blood component separation device, and a pump. The method also includes using the display to select a first processing phase having a plurality of first processing phase parameters, and using the display to modify at least one of the first processing phase parameters. The method may then include using the display to select a second processing phase having a plurality of second processing phase parameters, and using the display to modify at least one of the second processing phase parameters. Once the phases have been selected and the parameters modified, the method may generate a custom protocol algorithm. The protocol algorithm may be based at least in part on the selected first and second processing phases and the modified first and second processing phase parameters.
[0006] The first and / or second process phase parameters may include flow direction, valve position, centrifugation speed, pump speed, end point criteria, button press time, outflow level, bowl optical value, target volume, phase time, and / or final volume. The first process phase may be a fill phase or a priming phase. The second process phase may be a wash phase, a drain phase, a rinse phase, and / or a cell addition phase.
[0007] In some embodiments, the method may also include selecting, using the display, a third processing phase having a plurality of third processing phase parameters. Additionally, the method may include modifying, using the display, at least one of the third processing phase parameters. The custom protocol algorithm may then be based at least in part on the selected third processing phase and the modified third processing phase parameters.
[0008] The method may include using the display to select a bowl size for the blood component separation device and / or verifying an algorithm for the protocol (e.g., by running a simulation of the protocol) before allowing a user to execute the protocol. Additionally or alternatively, the method may include selecting a preset application mode that adjusts at least one of the first or second processing phase parameters. For example, the preset applications may be a high quality mode, a default mode, and a fast mode. The pump may run at a high speed when in the fast mode and / or run at a low speed when in the high quality mode.
[0009] The method may also include selecting messages to be displayed to a user during operation of the cell processing device according to the custom protocol algorithm. Additionally or alternatively, the method may include optimizing the custom protocol algorithm by running the custom protocol algorithm on the cell processing device and using the display to select thresholds for the termination of given states.
[0010] According to further embodiments, a system for generating a custom cell processing protocol may include a cell processing device, an interface, and a processor. The cell processing device may process blood and / or blood products and may have a blood component separation device and a pump. The interface may be disposed on the cell processing device and may enable a user to select (1) a first processing phase having a plurality of first processing phase parameters, and (2) a second processing phase having a plurality of second processing phase parameters. Additionally, the interface may enable a user to modify at least one of the first processing phase parameters and / or at least one of the second processing phase parameters. The processor may generate a custom protocol algorithm based at least in part on the selected first and second processing phases and the modified first and second processing phase parameters.
[0011] The system may also include a controller disposed within the cell processing device. The controller may operate the cell processing device according to a custom protocol algorithm. For example, the controller may control the operation of the blood component separation device and the pump (e.g., according to the custom protocol algorithm). The first and second processing phase parameters may include flow direction, valve position, centrifugation speed, pump speed, end point criteria, button press time, outflow level, bowl optical value, target volume, phase time, and / or final volume. The first processing phase may be a fill phase or a priming phase. The second processing phase may be a wash phase, a drain phase, a rinse phase, and / or a cell addition phase.
[0012] In some embodiments, the interface may also allow a user to (1) select a third processing phase having third processing phase parameters, and (2) modify at least one of the third processing phase parameters. In such embodiments, the custom protocol algorithm may be based at least in part on the selected third processing phase and the modified third processing phase parameters. The interface may also allow a user to select a bowl size for the blood component separation device. The processor may validate the protocol algorithm before allowing a user to execute the protocol algorithm on the cell processing device. For example, the processor may run a simulation of the protocol to validate the protocol algorithm.
[0013] The system may also have a preset application mode that adjusts one of the first or second processing phase parameters. For example, the preset application modes may be a high quality mode, a default mode, and a fast mode. The pump may operate at a high speed in the fast mode and / or at a low speed in the high quality mode. The interface may include a display, and the blood processing device may include a centrifuge bowl. The interface may enable a user to select messages that are displayed to the user during operation of the cell processing device according to the custom protocol algorithm. Additionally or alternatively, the interface may enable a user to select an endpoint for at least one given condition during operation of the cell processing device according to the custom protocol algorithm and optimize the custom protocol algorithm.
[0014] According to a further embodiment, a method for generating a custom cell processing protocol includes providing a cell processing apparatus having a display, a blood component separation device, a plurality of valves, and a pump. The method may also include performing a cell processing procedure on the cell processing apparatus and manually controlling operation of the cell processing apparatus during the cell processing procedure. The processor may monitor the manual control of the operation of the cell processing apparatus during the cell processing procedure, and the method may generate a custom protocol algorithm based at least in part on the monitored manual control of the operation of the cell processing apparatus. Manually controlling the operation of the cell processing apparatus may include manual operation of at least one of the plurality of valves, manual operation of a pump speed, manual operation of a processing volume, manual operation of a current state of the cell processing apparatus, and / or manual operation of a system parameter. The method may also include saving the custom protocol algorithm to a data storage device and / or modifying the custom protocol algorithm.
[0015] In an additional embodiment, a system for generating a custom cell processing protocol includes a cell processing device for processing blood and / or blood products. The cell processing device may include a blood component separation device, a plurality of valves, and a pump. The system may also include an interface disposed on the cell processing device that allows a user to place the cell processing device in a learn mode in which the user may manually control operation of the cell processing device during a cell processing procedure. When in the learn mode, the processor may monitor the manual control of operation of the cell processing device during the cell processing procedure and may generate a custom protocol algorithm. The custom protocol algorithm may be based at least in part on the monitored manual control of operation of the cell processing device.
[0016] Manual control of the operation of the cell processing device may include manual operation of one of the valves, manual operation of the pump speed, manual operation of the processing volume, manual operation of the current state of the cell processing device, and / or manual operation of a system parameter. The system may have a data storage device that stores the custom protocol algorithm and / or the interface may allow a user to modify the custom protocol algorithm. The cell processing device may have a controller that operates the cell processing device according to the custom protocol algorithm. For example, the controller may control a pump, a blood component separation device, and / or one or more valves. [Brief description of the drawings]
[0017] The features of the above described embodiments will be more readily understood by reference to the following detailed description taken in conjunction with the accompanying drawings, in which:
[0018] 1A to 1C show a schematic diagram of a processing apparatus according to an embodiment of the present invention.
[0019] FIG. 2 is a flow chart illustrating a method for generating a custom protocol according to an embodiment of the present invention.
[0020] 3A to 3J show schematic screenshots representative of a user interface at different stages of the method shown in FIG. 2 according to an embodiment of the present invention.
[0021] FIG. 4 is a flow chart illustrating a method for generating a second custom protocol according to an embodiment of the present invention.
[0022] 5A to 5F show schematic screenshots representative of a user interface at different stages of the method shown in FIG. 4 according to an embodiment of the present invention.
[0023] FIG. 6 shows diagrammatically a screenshot representative of a protocol generated as shown in FIGS. 2 and 4 according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0024] In the illustrated embodiment, the system and method may generate a custom cell processing protocol for the cell processing device. A user may use a display on the cell processing device to select one or more processing phases for the protocol and modify some of the phase parameters. Based on the selected processing phases and the modified parameters, the system / method may generate a custom protocol algorithm that runs on the cell processing device.
[0025] 1A-1C show schematic diagrams of a blood / cell processing system 100 according to some embodiments of the present invention. The system 100 includes a blood component separation device (e.g., centrifuge bowl 110) that separates whole blood into its individual components. For example, in some embodiments, anticoagulant may be added to the blood / cells as they are transported to the processing system 100 (from an anticoagulant bag suspended from a pole 120 coupled to the processing system 100). The blood is then introduced (e.g., via a container / reservoir suspended from a pole 130 or directly from the patient) into the blood component separation device 110, which separates the blood into its individual components (e.g., red blood cells, plasma, platelets, etc.). Once the blood is separated, the platelets and / or plasma may be transported to a waste bag for disposal, and the processing system 100 may introduce a wash solution into the separation device to wash the red blood cells. After washing the red blood cells, the processing system 100 may return the red blood cells to the patient. System 100 includes a display 140 (e.g., a touch screen display) that allows a user to interact with system 100 before, during, and after processing. In addition, system 100 may display information regarding the current procedure on display 140 during processing.
[0026] For example, as shown in FIG. 1C, in a blood salvage application, the system 100 may include an aspiration line 26 for aspirating blood lost from a wound site 12a (or surgical site) of the patient 12. The aspiration line 26 is in fluid communication with the collection reservoir 16 via a port 16a (e.g., an inlet port). An anticoagulant container is in fluid communication with the aspiration line 26 via a supply line 28. A vacuum source 19 is coupled to a port 16b (e.g., a vacuum port) of the reservoir 16 via a vacuum line 21. The vacuum source 19 creates a vacuum within the aspiration line 26 such that the aspiration line 26 can aspirate blood from the wound / surgical site 12a into the reservoir 16. A reservoir level sensor 17 detects the level of fluid within the reservoir 16, as described in more detail below.
[0027] Reservoir 16 is in fluid communication with centrifuge bowl 110 via line 30, valve V1, and inlet port PT1. As described above, centrifuge 100 separates and washes collected blood received from reservoir 16 and is rotated by motor 23. An optical sensor 20a directed / aimed at bowl 110 detects the hematocrit level within centrifuge bowl 110 by directing a light beam into the interior of centrifuge bowl 110 that reflects back to sensor 20a. If the light beam does not reflect back to sensor 20a, centrifuge bowl 110 is deemed full of red blood cells.
[0028] As also shown in FIG. 1C, waste container 22 for collecting waste material washed out from the collected blood is fluidly connected to centrifuge bowl 110 via outlet port PT2 and outlet line 36. Outlet line 36 passes through optical line sensor 7, which detects the turbidity of the fluid flowing through outlet line 36. Optical line sensor 7 may also control the speed of pump P, the number of wash steps, and the volume of wash solution used to wash the blood components. To facilitate the washing process, system 100 may have bag 18 containing wash solution. Wash solution container 18 may be fluidly connected to centrifuge bowl 110 via wash line 34, valve V2, line 30, and inlet port PT1.
[0029] To collect the final / washed blood components (e.g., red blood cells), the system 100 also includes a collection bag 24, which is then fluidly connected to the centrifuge bowl 110 via inlet port PT1, line 30, valve V3, and line 32. In some embodiments, the system 100 has a line 38 connected to the outlet of the collection bag 24. This line 38 allows the fluid collected in the collection bag 24 to be transferred into a secondary infusion bag (not shown) where air is removed and pressure infused to the patient 2 via a venous needle. Alternatively, the fluid collected in the collection bag 24 may be gravity fed to the patient 2 via the venous needle and line 38. Valves V1, V2, and V3 are remotely operated to control the flow direction of the fluid pumped by pump P within the device 100. Pump P may be a peristaltic pump, pumping fluid into and out of the centrifuge bowl 110. Optionally, a clamp C may be included to clamp the outflow line 36.
[0030] Generally, in operation, blood from the wound 12a (or surgical site) is aspirated from the patient 2 via the suction line 26. The aspirated blood is anticoagulated with anticoagulant dripped from the anticoagulant bag 14 via the supply line 28 and retained in the reservoir 16. As noted above, the reservoir 16 may include a level sensor 17, which detects the level of collected blood in the reservoir 16. Once a predetermined amount of collected blood has been retained / collected in the reservoir 16, the level sensor 17 (or controller) activates the pump P to begin what is referred to as a fill mode by pumping the collected blood from the reservoir 16 through line 30, valve V1 and inlet port PT1 into the centrifuge bowl 110, with valve V1 open and valves V2 and V3 closed. The speed of the pump P is controlled by the optical line sensor 7 and / or the controller.
[0031] Blood enters separation chamber 76 of centrifuge bowl 110, and as centrifuge bowl 110 fills with blood, centrifuge bowl 110 is spun by motor 23, separating the blood inside separation chamber 76 into different fractions according to the density of the components. Once inside bowl 110, centrifugal force separates the blood into a high density component (mainly red blood cells (RBCs)), a medium density component (mainly white blood cells and platelets), and a low density component (mainly plasma). The RBCs are forced against the outer wall of centrifuge bowl 110, while the plasma remains near the core of centrifuge bowl 110. A "buffy coat" forms between the plasma and the RBCs. This "buffy coat" is composed of an inner layer of platelets and an outer layer of white blood cells (WBCs).
[0032] As the bowl 110 fills with blood, the RBC layer moves radially inward, resulting in the border lifting upward. The optical sensor 20a is positioned relative to the centrifuge bowl 110 such that when the bowl 110 is filled (e.g., to approximately 50% hematocrit), the upwardly lifting RBC layer scatters the light beam generated by the optical sensor 20a. As a result, the optical sensor 20a does not receive a reflected beam of light, and the optical sensor 20a determines that the centrifuge bowl 110 is filled. Once the optical sensor 20a determines that the bowl 110 is filled (e.g., to approximately 50% hematocrit), the pump P stops pumping, and the filling of the centrifuge bowl 110 is terminated. As described above, once the blood has been separated, the platelets and / or plasma may be transferred to a waste bag for disposal, and the processing system 100 may introduce a wash solution into the separation device to wash the red blood cells. After washing the red blood cells, the processing system 100 may return the red blood cells to the patient.
[0033] It should be noted that conventional processing systems are "state machines" with predefined protocols that define the system's behavior. For example, the system stays in a current (and predefined) state until a decision point is reached, and then the protocol moves the system to the next state until a subsequent decision point is reached. In such systems, the user has little flexibility over the states or decision points (e.g., the user cannot significantly modify the protocol). However, in many applications, especially in academic and cell therapy applications, it may be useful for the user to modify the protocol or even create entirely new protocols. To that end, some embodiments of the present invention have a "flex mode," which allows the user to define both the states (selected critical parameters) and the decision points.
[0034] As described in more detail below, Flex Mode allows a user to create custom protocols and groups of settings (e.g., wash volume, fill rate, drain rate, etc.) for, for example, locked state behaviors fill, wash, drain. The user may also define each of the critical parameters and states for the protocol. Examples of critical parameters include, but are not limited to, pump speed, valve position, and centrifuge speed. Examples of decision points include simple points such as a button press to more complex system feedback such as effluent reaching a clean level, bowl optics reaching an RBC detection gradient value, target volume reaching, time in state, centrifuge speed reaching, etc.
[0035] Additionally, in some embodiments, the system 100 may allow the user to select and customize additional options to further optimize the protocol and customize the protocol for a particular application. For example, the user may select the messages to be displayed on the display 140. These messages may include types of warning messages, process information (e.g., flow rates, pressures, volumes, current process stages, etc.), and / or instructions for the user (e.g., connecting various components, performing manual tasks, etc.). Additionally or alternatively, the user may input volumes for certain conditions that may vary from step to step, such as fill volumes (or other volumes that determine the start or end of a process step). As described in more detail below, once a protocol has been created, the user may save the custom protocol for later use (e.g., in a data storage / database) and may password protect each saved protocol to ensure that it is not inadvertently edited. Such workflows / protocols may be created through visual drag-and-drop of predefined conditions on a touch screen or through menus with add / remove buttons.
[0036] FIG. 2 is a flow chart depicting an exemplary process for generating a custom protocol according to an embodiment of the present invention. FIGS. 3A-3J show exemplary screenshots of the display 140 as a user progresses through the protocol generation process. It should be noted (and as will be described in more detail below) that while FIG. 2 shows a protocol generation for a fill-wash-drain-rinse-drain workflow, other protocols / workflows can be generated. In general, the protocol generated in FIG. 2 is similar to the default protocol for a standard 70 mL bowl, except that the fill phase is automatically run to a set volume instead of performing air detection, a small rinse step of 20 mL is added after the first drain step, and a second drain step is added after the rinse step. However, other protocols may be generated that differ significantly from those shown in FIG. 2.
[0037] When the system 100 is launched, the display / interface 140 may display a "Main Screen" 305 with a number of options / buttons for the user to select, such as "Cell Harvesting" 302 and / or "Sorting" 303 (FIG. 3A). As described in more detail below, this main screen 305 may also include a list of all custom algorithms / protocols that have been created so far. The user may select "Flex Protocol" 310 on the display 140 to begin the generation of a customized protocol (FIG. 3A). To allow the user to name the custom protocol (step 210), the display / touch screen 140 may provide the user with an on-screen keyboard, and the user may enter the protocol name using the touch screen 140. Alternatively, the system 100 may include a separate keyboard, which the user may use to enter the protocol name. Once the name has been entered, the system 100 displays a "Bowl Selection Screen" 320. Using this screen, the user can select the bowl type and size 322A / B / C they want to use for the custom protocol (step 215). For example, the user may select a 70 mL bowl 322A, a 125 mL bowl 322B, or a 225 mL bowl 322C.
[0038] After the user selects the desired bowl, the system 100 may return to the main screen 305 (FIG. 3A). Alternatively, the user may manually return to the main screen using the navigation buttons 324 located on the side of the bowl selection screen 320. For example, the navigation buttons may include a "Cell Harvest" button 324A, a "Sorting" button 324B, a "Settings" button 324C, a "Record" button 324D, a "System" button 324E, a "Help" button 324F, and a "Flex Protocol" button 324G. The user may press the "Flex Protocol" button 324G to return to the main Flex Protocol screen 305. In the main screen 305, the user may add a phase by pressing the "+" button 312 and selecting a phase, such as the fill phase (step 220). The system then displays a "Build Fill Phase" screen 330 to allow the user to customize the settings for the fill phase. For example, the user may use up and down buttons 331A / B to scroll through the various details of the fill phase and customize the settings for each (step 225) (FIG. 3C). For example, the user may set the flow direction to inflow, the valve position to fill, the centrifuge speed to 7000, the pump speed to 150, the end condition to volume, and the final volume to 500. After the desired settings have been entered, the user may press done 332 to complete the fill phase. At any point, if the user wishes to use the default settings, the user may simply press default button 333 and system 100 will automatically set each setting to the default parameters.
[0039] The system 100 then navigates to the Flex Protocol page 338 of FIG. 3D, which shows that the fill phase 334 has been built and added to the protocol. To add the next phase, in this case the wash phase (step 230), the user may press the Add button 312 again and select the wash phase. In a similar manner to the fill phase, the user may edit / customize the wash phase of the protocol (step 235) by navigating through various details / aspects of the wash phase using the up / down buttons 331A / B on the wash phase screen 340. For example, as shown in FIG. 3E, the user may set the flow direction to inflow, the valve position to wash, the centrifuge speed to 7000, the pump speed to 150, the end state to volume, and the final volume to 1000. Once the user has completed building the wash phase, they may press the Done button 332 to complete the wash phase and add the customized wash phase to the protocol.
[0040] The user may continue this process to add and edit any additional phases. For example, the user may add and edit a drain phase (steps 240 and 245), a rinse phase (steps 250 and 255), and a second drain phase (steps 260 and 265). As shown in FIGS. 3F-3H, and in a manner similar to that described above (e.g., using the up / down buttons 331A / B, etc.), the user may customize various parameters of each of those drain and rinse phases on respective screens 350, 360, 370 to customize the overall processing protocol. Once the user has added and edited each of the desired phases (e.g., the fill phase, the wash phase, the drain phase, the rinse phase), each phase will be displayed on the Flex Protocol page 338 (FIG. 3I), and the user may press the Done button 335 to complete / establish the protocol. At this point, the system 100 will generate the algorithms necessary for the system 100 to execute the protocol when the user is ready. For example, the system 100 may include a processor that generates a protocol based on the selected phases and the edited parameters in each of the selected phases. Once the system 100 has generated an algorithm / protocol, the system 100 may store the algorithm / protocol for later use (e.g., in a database and / or data storage device) and may add the protocol to a list 306 of available protocols on the main screen 305 (FIG. 3J). To subsequently execute the generated protocol (e.g., to execute the protocol using a blood component separation device), the user may return to the main screen 305, select the desired protocol from the list (FIG. 3J), and press the activate button 336 (step 270). The system then begins executing the protocol.
[0041] It should be noted that while the embodiments described above generate a protocol that includes a fill phase (e.g., bowl 110 is filled with blood / blood components), a wash phase (e.g., a wash solution is introduced into the bowl to wash red blood cells), a drain phase (e.g., a portion of the contents of bowl 110 is drained), a rinse phase (e.g., a small amount of solution is introduced into bowl 110 to rinse the contents), and a second drain phase (e.g., bowl 110 is emptied), other embodiments can generate different protocols with different phases. For example, FIG. 4 is a flow chart illustrating an exemplary process for generating different custom protocols according to additional embodiments of the present invention. FIGS. 5A-5F show exemplary screenshots of display 140 as a user progresses through the protocol generation process. It should be noted that FIG. 4 illustrates the protocol generation of a workflow of prime-add cells-wash-drain (described in more detail below). This protocol uses a 225 mL bowl, and the bowl is first primed (e.g., with anticoagulant or wash solution) from wash line 34. The protocol then fills the bowl with a predetermined variable volume, set by the user during the procedure based on the variable volume of cells (in mL). The system 100 then performs a wash step and a standard drain step / phase.
[0042] In a similar manner as described above, and to generate this protocol upon system startup, the user may select the Flex Protocol option to begin generating a custom protocol. The user may then name the protocol (e.g., "Flex Protocol Test 2" in FIG. 4) (step 410) and select the desired bowl size (e.g., 225 mL) (step 415). Once the bowl size is selected, the user may then press the Add button 312 to add a custom priming phase (step 420). Note that since this is not a standard phase, the user may use the keyboard 505 to name the phase (e.g., "Priming" in FIG. 5A) and then edit / customize each of the parameters as needed on the priming phase screen 510 (step 425). For example, the user may set the flow direction to inflow, the valve position to wash, the centrifuge speed to 5000, the pump speed to 250, and the endpoint to a volume of 300 mL. After editing the priming phase, the user may press the Done button 335 to add the phase to the protocol.
[0043] The user may then continue to add and edit additional phases for the protocol in a similar manner. To generate the protocol shown in FIG. 4, the user may add and edit an "Add Cells" phase on the Add Cells screen 520 (steps 430 and 435; FIG. 5C), add and edit a wash phase on the Wash Phase screen 530 (steps 440 and 445; FIG. 5D), and add and edit a drain phase on the Drain Phase screen 540 (steps 450 and 455; process 5E). It should be noted that while FIGS. 4 and 5A-5E show specific parameters that are selected, embodiments of the present invention allow the user to customize each of the phases, and thus the user may modify any of the parameters shown in the figures. To finalize and generate the protocol (and the algorithms required by the system 100 to execute the protocol), the user may select Done 335 on the Protocol screen 550, which will then add the newly generated protocol (e.g., Flex Protocol 2) to the list of protocols available on the Launch / Main screen 305 (FIG. 6).
[0044] When the user is ready to begin a blood or cell processing procedure, the user may select the desired protocol from the list (e.g., "Flex Protocol 2") and press the start button 336 (step 460). This will start the selected protocol and load the parameters for that protocol. Once the protocol is loaded and the user has configured the system 100 / device, the user may then press the "Start Procedure" button 337 to begin the procedure.
[0045] It is important to note that by allowing users to customize and create any number of protocols, embodiments of the present invention allow the system 100 to be used in academic research settings. Additionally, embodiments of the present invention may be used in applications where workflows other than the standard fill-wash-drain phases are used and may provide a more targeted solution for cell therapy customers / applications. For cell therapy, GMP processes typically utilize custom workflows that require the execution of a combination of manual steps. This is prone to user error and has inherent variability in the endpoints of each phase. Various embodiments of the present invention allow users to develop customizable, reproducible protocols that provide the level of automation necessary to reduce variability in the process. Additionally, the system 100 may keep records of procedures that provide traceability and objective evidence of the procedure, including date, time, processing volume, product volume, and more.
[0046] In addition to the cell recovery procedures described above, in some embodiments, the cells may be harvested using a number of processing systems (e.g., the Cell Saver™ available from Haemonetics, Inc., Braintree, Massachusetts, USA). 登録商標 Elite 登録商標 and / or Cell Saver 登録商標 This may allow customization of the preparative algorithm available on the Ficoll 5+ system, where the effluent is split into two bags (e.g., platelet-rich plasma and platelet-poor plasma). Tuning of this algorithm may be beneficial to achieve automation and standardization across Ficoll separation programs that use the preparative algorithm. Various embodiments of the Flex Protocol may be utilized across academic research applications to build experimental designs in a controlled manner, reducing the variability inherent in manually running the instrument.
[0047] It must be noted that it is important to ensure the safety of the patient / donor and also the safety of the system. Current cell processing / recovery systems include monitoring systems that monitor various aspects of the process, such as centrifuge speed, manifold pressure / vacuum detection, predicted fluid detection window for bowl type, volume counting / monitoring through air detector, predicted detection of bleed air / plasma fluid, air / plasma fluid detection system in bowl optics, fluid spill detection in centrifuge, and cover locking. An embodiment of the present invention may utilize similar / identical state behaviors as the proven cell recovery mode. Thus, the same safeguards exist for implementing safeguards. For example, if the drain line is manually clamped by the operator when pumping the bowl contents to the drain destination, a warning is generated that there is excessive pressure in the blue line. Similarly, if the protocol has the system 100 pump fluid from the wash line to the bowl 110 and the line is pinched, a message is generated that the saline is empty.
[0048] Some embodiments of the invention may also validate the generated protocol, for example, to ensure that the protocol works as expected and to ensure that there are no safety issues. In such embodiments, the system 100 may include a custom validation program that validates the generated protocol using a simulation mode or through standard regression-type verification and validation ("V&V") testing. If the system 100 determines that the generated protocol has a problem (e.g., is dangerous to the system 100 or the patient, or generates an error message), the system 110 may alert the user so that the user may modify the protocol and / or parameters as necessary prior to running the protocol.
[0049] While the above-described embodiments allow the user to fully customize the protocol, some embodiments may include modes based on preset application. For example, the system 100 may include an option to have modes to switch / adjust the operation of the entire algorithm based on the selected mode. For example, some embodiments may have a high quality mode, a default mode, and / or a fast mode. These modes may change the pump speed accordingly to achieve the desired result (e.g., to obtain a higher quality product, to speed up the procedure time, etc.). The high quality mode may run the pump speed at a very slow speed (based on the size of the bowl). For example, under the high quality mode using a 70 mL bowl, the system may run the pump at a slow speed of 25 mL / min. Conversely, for the fast mode, the system may run the pump at a fast speed of 200 mL / min for a 70 mL bowl. For a 225 mL bowl, the system 100 may run the pump at a speed of 100 mL / min to 1000 mL / min, respectively.
[0050] In some cases, it may be beneficial / necessary for the user to manually control the operation of the system 100 to determine the required parameters and how the protocol / algorithm should be generated. To obtain and generate the protocol / algorithm from this manual mode, some embodiments may include a learn mode. When in this learn mode, the system 100 (e.g., processor or controller) tracks the device / system 100 status, valve positions, pump speeds, processing volumes, other system parameters, and manual operations. Once the procedure is completed, the user may exit the learn mode, and the system may generate a protocol / algorithm based on the status and parameters at which the device was operated (e.g., when learn / listen was on) during the manual mode. Once the protocol is generated, the user may save and / or edit the process steps as needed. This then allows the user to reproducibly repeat the manual process just performed, and allows the user to capture variable / lengthy processes with minimal button presses.
[0051] Some embodiments may also provide for process optimization, which in turn allows for more detailed customization. For example, by utilizing the device's monitoring equipment and sensors (e.g., spill and bowl optics sensors), the system 100 may display the acquired spill signals (max, min) during the states after the actual formulation is run. This allows the user to use these signal detection values to change states. To optimize a given protocol, the user may first generate / build the protocol as described above and then run the protocol (e.g., for the actual formulation). The system 100 may then display on the display 140 the bowl optics signal and the spill signal over each state. The user may then select a threshold for the end of the given state. If the user wishes to fill the bowl 110 until a decrease occurs in the line sensor signal (e.g., from a signal of 1800 A / D counts to a target of 500 A / D counts), the user may select "Flush at 500" to change from the fill cycle to the next subsequent cycle.
[0052] While the embodiments described above have generated custom protocols directly on the cell processing device 100, in other embodiments the protocols may be generated remotely. For example, in some embodiments, the user generating the protocol may be located at a remote system (e.g., a remote server or computer system) that communicates with one or more cell processing devices via a global data communications net such as the Internet. Once generated in the remote system, the remote system can transmit / communicate the generated protocol to one or more of the cell processing devices with which it is in communication.
[0053] It should also be noted that terms such as "controller", "processor" and "server" may be used herein to describe devices that may be used in certain embodiments of the invention and should not be construed to limit the invention to any particular type of device or system unless the context requires otherwise. Thus, without limitation, a system may include a client, a server, a computer, an appliance, or other types of devices. Such devices typically include one or more network interfaces for communicating over a communications network, and a processor (e.g., a microprocessor with memory and other peripherals, and / or application-specific hardware) appropriately configured to perform the functions of the device and / or system. Communications networks generally may include public and / or private networks; may include local area, wide area, metropolitan area, storage, and / or other types of networks; and may use communications technologies, including, without being limited in any way, analog, digital, optical, wireless, network, and inter-network technologies.
[0054] The various components of the control program may be implemented individually or in combination, for example, each component may be implemented on a dedicated server or on a collection of servers arranged in a distributed manner.
[0055] It should also be noted that devices may use communication protocols and messages (e.g., messages generated, transmitted, received, stored, and / or processed by the system), and such messages may be conveyed by a communication network or medium. Unless the context requires otherwise, the present invention should not be construed as being constrained to any particular communication message type, communication message format, or communication protocol. Thus, communication messages may generally include, but are not limited to, frames, packets, datagrams, user datagrams, cells, or other types of communication messages. Unless the context requires otherwise, it should be understood that references to particular communication protocols are exemplary, and that alternative embodiments may employ variations of such communication protocols (e.g., modifications or extensions to protocols that may be made from time to time), or other protocols now known or developed in the future, as appropriate.
[0056] It should also be noted that logic flows may be described herein to illustrate various aspects of the invention and should not be construed as limiting the invention to any particular logic flow or logic implementation. The described logic may be partitioned into different logic blocks (e.g., programs, modules, interfaces, functions, or subroutines) without changing the overall result or otherwise departing from the true scope of the invention. In many cases, logic elements may be added, modified, omitted, implemented in a different order, or implemented using different logic constructs (e.g., logic gates, loop primitives, conditional logic, and other logic constructs) without changing the overall result or otherwise departing from the true scope of the invention.
[0057] The present invention may be embodied in many different forms, including, but not limited to, in any way, computer program logic for use with a processor (e.g., a microprocessor, microcontroller, digital signal processor, or general purpose computer), programmable logic for use with a programmable logic device (e.g., a field programmable gate array (FPGA) or other programmable logic device (PLD)), discrete components, integrated circuits (e.g., application specific integrated circuits (ASICs)), or any other means including any combination thereof. In some embodiments of the present invention, all logic described above is primarily embodied as a set of computer program instructions that are converted into a computer executable form, stored as such on a computer readable medium, and executed by a microprocessor under the control of an operating system.
[0058] Computer program logic implementing all or part of the functionality described hereinbefore may be embodied in various forms, including but not limited to in any way to source code, computer executable forms, and various intermediate forms (e.g., forms generated by an assembler, compiler, linker, or locator). Source code may include a series of computer program instructions embodied in any of a variety of programming languages (e.g., object code, assembly language, or high level languages such as FORTRAN, C, C++, JAVA, or HTML) for use with various operating systems or operating environments. Source code may define and use various data structures and communication messages. Source code may be in a computer executable form (e.g., via an interpreter) or the source code may be converted (e.g., via a translator, assembler, or compiler) into a computer executable form.
[0059] The computer program may be fixed in any form (e.g., in the form of source code, computer executable form, or intermediate form) either permanently or temporarily in a tangible storage medium such as a semiconductor memory device (e.g., RAM, ROM, PROM, EEPROM, or flash programmable RAM), a magnetic memory device (e.g., diskette or fixed disk), an optical memory device (e.g., CD-ROM), a PC card (e.g., PCMCIA card), or other memory device. The computer program may be fixed in any form in a signal that can be transmitted to a computer using any of a variety of communication technologies, including but not limited to analog, digital, optical, wireless, network, and inter-network technologies. The computer program may be distributed in any form, such as a removable storage medium (e.g., shrink-wrapped commercial software) with accompanying printed or electronic documentation, may be preloaded into a computer system (e.g., on a system ROM or fixed disk), or may be distributed from a server or electronic bulletin board via a communication system (e.g., the Internet or the World Wide Web).
[0060] Hardware logic (including programmable logic for use with a programmable logic device) implementing all or a portion of the functionality described hereinabove may be designed using conventional manual methods, or may be designed, captured, simulated, or electronically documented using a variety of tools, such as computer-aided design (CAD), hardware description languages (e.g., VHDL or AHDL), or PLD programming languages (e.g., PALASM, ABEL, or CUPL).
[0061] The programmable logic may be fixed, either permanently or temporarily, in a tangible storage medium such as a semiconductor memory device (e.g., RAM, ROM, PROM, EEPROM, or flash programmable RAM), a magnetic memory device (e.g., diskette or fixed disk), an optical memory device (e.g., CD-ROM), or other memory device. The programmable logic may be fixed in a signal that can be transmitted to a computer using any of a variety of communication technologies, including, but not limited to, analog, digital, optical, wireless (e.g., Bluetooth), network, and inter-network technologies. The programmable logic may be distributed as a removable storage medium (e.g., shrink-wrapped commercial software) with accompanying printed or electronic documentation, may be preloaded into a computer system (e.g., on a system ROM or fixed disk), or may be distributed from a server or electronic bulletin board via a communication system (e.g., the Internet or World Wide Web). In practice, some embodiments may be implemented in a Software as a Service ("SAAS") model or in a cloud computing model. Of course, some embodiments of the invention may be implemented as a combination of both software (e.g., a computer program product) and hardware, while still other embodiments of the invention are implemented entirely in hardware or entirely in software.
[0062] The embodiments of the invention described above are intended to be merely illustrative; numerous variations and modifications will be apparent to those skilled in the art. All such variations and modifications are intended to be included within the scope of the invention as defined in the appended claims.
Claims
1. 1. A method for generating a custom cell processing protocol, comprising: (a) providing a cell processing apparatus, the cell processing apparatus having a display, a blood component separation device, and a pump; (b) selecting a first processing phase using the display, the first processing phase having a plurality of first processing phase parameters; (c) varying at least one of the plurality of first processing phase parameters using the display; (d) selecting a second processing phase using the display, the second processing phase having a plurality of second processing phase parameters; (e) varying at least one of the plurality of second processing phase parameters using the display; and (f) generating a custom protocol algorithm based at least in part on the selected first and second processing phases and the modified first and second processing phase parameters.
2. 2. The method of claim 1, wherein the first processing phase parameters include at least one selected from the group consisting of flow direction, valve position, centrifugation speed, pump speed, endpoint criterion, button press time, outflow level, bowl optical value, target volume, phase time, and final volume.
3. 2. The method of claim 1, wherein the second processing phase parameters include at least one selected from the group consisting of flow direction, valve position, centrifugation speed, pump speed, endpoint criterion, button press time, outflow level, bowl optical value, target volume, phase time, and final volume.
4. The method of claim 1 , wherein the first processing phase is a filling phase or a priming phase.
5. 2. The method of claim 1, wherein the second processing phase is at least one selected from the group consisting of a washing phase, a draining phase, a rinsing phase, and a cell adding phase.
6. moreover: (g) selecting a third processing phase using the display, the third processing phase having a plurality of third processing phase parameters; and 13. The method of claim 1, further comprising: (h) modifying at least one of a plurality of third processing phase parameters using the display, wherein the custom protocol algorithm is based at least in part on the selected third processing phase and the modified third processing phase parameters.
7. moreover:
10. The method of claim 1, comprising using the display to select a bowl size for the blood component separation device.
8. The method of claim 1 , further comprising validating the protocol algorithm prior to allowing a user to execute the protocol.
9. The method of claim 8 , wherein the verifying comprises running a simulation of the protocol.
10. The method of claim 1 , further comprising selecting a preset application mode using the display, the preset application mode adjusting at least one of the first or second processing phase parameters.
11. The method of claim 10 , wherein the preset application mode is selected from the group consisting of a high quality mode, a default mode, and a fast mode.
12. 12. The method of claim 11, wherein the pump is operated at a high speed when in the rapid mode.
13. The method of claim 11 , wherein the pump is operated at a slow speed when in the high quality mode.
14. moreover:
10. The method of claim 1, further comprising using the display to select messages to be displayed to a user during operation of the cell processing device in accordance with the custom protocol algorithm.
15. moreover: optimizing the custom protocol algorithm, where optimizing the custom protocol algorithm includes running the custom protocol algorithm on the cell processing device and using the display to select thresholds for endpoints of given states;
16. 1. A system for generating a custom cell processing protocol, comprising: a cell processing apparatus configured to process blood and / or blood products, the cell processing apparatus having a blood component separation device and a pump; an interface disposed on the cell processing device and configured to enable a user to select a first processing phase having a plurality of first processing phase parameters and a second processing phase having a plurality of second processing phase parameters, the interface further configured to enable a user to modify at least one of the plurality of first processing phase parameters and / or at least one of the plurality of second processing phase parameters; and A system comprising: a processor configured to generate a custom protocol algorithm based at least in part on the selected first and second processing phases and the modified first and second processing phase parameters.
17. moreover:
20. The system of claim 16, further comprising a controller disposed within the cell processing device, the controller configured to operate the cell processing device according to the custom protocol algorithm.
18. The system of claim 17 , wherein the controller is configured to control operation of the blood component separation device and the pump.
19. 17. The system of claim 16, wherein the first processing phase parameters include at least one selected from the group consisting of flow direction, valve position, centrifuge speed, pump speed, endpoint criterion, and final volume.
20. 17. The system of claim 16, wherein the second processing phase parameters include at least one selected from the group consisting of flow direction, valve position, centrifuge speed, pump speed, endpoint criterion, and final volume.
21. 17. The system of claim 16, wherein the first processing phase is a filling phase or a priming phase.
22. 17. The system of claim 16, wherein the second processing phase is at least one selected from the group consisting of a washing phase, a draining phase, a rinsing phase, and a cell adding phase.
23. 17. The system of claim 16, wherein the interface is further configured to enable a user to select a third processing phase having a plurality of third processing phase parameters and to modify at least one of the plurality of third processing phase parameters, wherein the custom protocol algorithm is based at least in part on the selected third processing phase and the modified third processing phase parameters.
24. 20. The system of claim 16, wherein the interface is further configured to allow a user to select a bowl size for the blood component separation device.
25. 20. The system of claim 16, wherein the processor is further configured to validate the protocol algorithm prior to allowing a user to execute the protocol algorithm.
26. 26. The system of claim 25, wherein the processor is configured to run a simulation of the protocol to verify the protocol algorithm.
27. 20. The system of claim 16, further comprising a preset application mode, the preset application mode adjusting at least one of the first or second processing phase parameters.
28. 28. The system of claim 27, wherein the preset application mode is selected from the group consisting of a high quality mode, a default mode, and a fast mode.
29. 30. The system of claim 28, wherein the pump is operated at a high speed when in the rapid mode.
30. 30. The system of claim 28, wherein the pump is operated at a slower speed when in the high quality mode.
31. The system of claim 16 , wherein the interface includes a display.
32. The system of claim 16 , wherein the blood component separation device comprises a centrifuge bowl.
33. 17. The system of claim 16, wherein the interface is further configured to allow a user to select messages that are displayed to the user during operation of the cell processing device according to the custom protocol algorithm.
34. The system of claim 16, wherein the interface is further configured to allow a user to select an end point for at least one processing state during operation of the cell processing device according to the custom protocol algorithm, thereby optimizing the custom protocol algorithm.
35. 1. A method for generating a custom cell processing protocol, comprising: (a) providing a cell processing apparatus, the cell processing apparatus having a display, a blood component separation device, a plurality of valves, and a pump; (b) performing a cell processing procedure on the cell processing device; (c) manually controlling the operation of the cell processing device during the cell processing procedure; (d) using a processor within the cell processing device to monitor manual control of the operation of the cell processing device during the cell processing procedure; and (e) generating a custom protocol algorithm based at least in part on the monitored manual control of operation of the cell processing device.
36. The method of claim 35, wherein manually controlling the operation of the cell processing device includes at least one selected from the group consisting of manual operation of at least one of a plurality of valves, manual operation of a pump speed, manual operation of a processing volume, manual operation of a current state of the cell processing device, and manual operation of a system parameter.
37. 36. The method of claim 35, further comprising storing the custom protocol algorithm in a data storage device.
38. 36. The method of claim 35, further comprising modifying the custom protocol algorithm.
39. 1. A system for generating a custom cell processing protocol, comprising: a cell processing apparatus configured to process blood and / or blood products, the cell processing apparatus having a blood component separation device, a plurality of valves, and a pump; an interface disposed on the cell processing device and configured to enable a user to place the cell processing device in a learn mode, and when in the learn mode, the user manually controls operation of the cell processing device during a cell processing procedure; and and a processor configured to monitor manual control of operation of the cell processing device during a cell processing procedure when in a learning mode, and generate a custom protocol algorithm based at least in part on the monitored manual control of operation of the cell processing device.
40. The system of claim 39, wherein manual control of the operation of the cell processing device includes at least one selected from the group consisting of manual operation of at least one of a plurality of valves, manual operation of a pump speed, manual operation of a processing volume, manual operation of a current state of the cell processing device, and manual operation of a system parameter.
41. 40. The system of claim 39, further comprising a data storage device configured to store the custom protocol algorithm.
42. 40. The system of claim 39, wherein the interface is further configured to allow a user to modify the custom protocol algorithm.
43. 40. The system of claim 39, wherein the cell processing device includes a controller, the controller configured to operate the cell processing device according to the custom protocol algorithm.
44. 44. The system of claim 43, wherein the controller is configured to control at least one selected from at least one of a pump, a blood component separation device, and a plurality of valves.