Filtration system for cell removal system and method of using the same

Abstract

The filtration system may include a loading member configured to receive a plurality of filter members, which can be moved sequentially from an inactive position to an active position and to a discard position, wherein the corresponding filter members among the plurality of filter members are not connected to the sample flow path fluid of the cell removal system, the corresponding filter members are connected to the sample flow path fluid, and the discard position is where the corresponding filter members have been removed from the fluid connection with the sample flow path.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 978,770, filed on February 19, 2020, which is incorporated herein by reference in its entirety. Technical Field

[0003] The present disclosure relates to apparatus and processes for filtering materials, including filtering high solids content, cell-containing solutions to produce cell-free solutions and / or samples for further analysis. Background Art

[0004] Filtration systems that separate solid matter and fluids from a mixture via a filter medium are used in a variety of industries.

[0005] For example, it may be desirable to filter a cell solution generated by a bioreactor to obtain a cell-free sample for further laboratory testing and analysis, as well as to obtain online process control and feedback of conditions within the bioreactor so that adjustments can be made. Examples of such bioreactors are described in U.S. Pat. No. 5,015,585A, U.S. Pat. No. 6,582,955 B2, U.S. Pat. No. 6,616,912 B2, and an example of a filtration system that may be implemented is described in U.S. Pat. No. 7,172,696 B1.

[0006] However, such systems have many disadvantages, such as long setup and turnaround time between batches, low scale-up opportunities, quality control issues, and difficulty operating in an automated / continuous manner. Therefore, there is a need for systems and methods that overcome some or all of the deficiencies in the prior art. Summary of the invention

[0007] Disclosed herein are various embodiments of filtration systems and methods of using the same in connection with cell removal systems.

[0008] In one embodiment, a method for filtering a cell-containing solution is provided. The method includes: coupling a first filter member having a first filtration flow path to be fluidly connected to a sample flow path of a cell removal system; delivering the sample of the cell-containing solution to the sample flow path and the first filtration flow path; delivering the sample of the cell-containing solution to the sample flow path and the first filtration flow path; separating cellular material from the sample of the cell-containing solution by the first filtration member to obtain a permeate; removing the first filtration member from the fluid connection with the sample flow path; coupling a clean housing having a connecting flow path to be fluidly connected to the sample flow path of the cell removal system; delivering a disinfecting fluid through the sample flow path and the connecting flow path of the clean housing; removing the clean housing from the fluid connection with the sample flow path; and coupling a second filtration member having a second filtration flow path to be fluidly connected to the sample flow path of the cell removal system.

[0009] In another embodiment, a filtration system for use with a cell removal system is provided. The system includes a loading member configured to receive a plurality of filter members, each of the plurality of filter members including a filter inlet, a filter outlet, and a filter flow path extending from the filter inlet to the filter outlet. The system also includes at least one actuator, the at least one actuator being configured to move the plurality of filter members from an inactive position to an active position and to a discarded position in sequence, wherein the corresponding filter members in the plurality of filter members are not in fluid communication with the sample flow path of the cell removal system, in the active position, the corresponding filter members are in fluid communication with the sample flow path, and in the discarded position, the corresponding filter members have been removed from the fluid communication with the sample flow path.

[0010] In yet another embodiment, a cell removal system is provided. The system includes: a sample flow path having a sample inlet for receiving a sample containing a cell solution; a loading member configured to receive a plurality of filter members; and at least one actuator, the at least one actuator being configured to move the plurality of filter members sequentially from an inactive position to an active position and to a discard position, wherein the corresponding filter member of the plurality of filter members is not in fluid communication with the sample flow path of the cell removal system, the corresponding filter member is in fluid communication with the sample flow path, and the corresponding filter member has been removed from fluid communication with the sample flow path in the discard position.

[0011] The foregoing and other objects, features and advantages of the present invention will become more apparent from the following detailed description made with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 An exemplary filtration system that may be used with an exemplary cell removal system is illustrated.

[0013] Figure 2 Another exemplary filtration system that can be used with the exemplary cell removal system is illustrated.

[0014] Figure 3 Another exemplary filtration system that can be used with the exemplary cell removal system is illustrated.

[0015] Figure 4 Another exemplary filtration system that can be used with the exemplary cell removal system is illustrated.

[0016] Figure 5 Another exemplary filtration system that can be used with the exemplary cell removal system is illustrated.

[0017] Figure 6 An exemplary filter replacement system is illustrated.

[0018] Figure 7 The diagram shows the Figure 6 An exemplary filter replacement system.

[0019] Figure 8 The diagram shows the Figure 6 An exemplary filter replacement system.

[0020] Fig. 9 The diagram shows the Figure 6 An exemplary filter replacement system.

[0021] Fig.10 The diagram shows the Figure 6 An exemplary filter replacement system.

[0022] Fig.11 Another exemplary filter replacement system is illustrated.

[0023] Fig.12 The diagram shows the Fig.11 An exemplary filter replacement system.

[0024] Fig.13 The diagram shows the Fig.11 An exemplary filter replacement system.

[0025] Fig.14 The diagram shows the Fig.11 An exemplary filter replacement system.

[0026] Fig.15The diagram shows the Fig.11 An exemplary filter replacement system.

[0027] Fig.16 Another exemplary filter replacement system is illustrated.

[0028] Fig.17 The diagram shows the Fig.16 An exemplary filter replacement system.

[0029] Fig.18 The diagram shows the Fig.16 An exemplary filter replacement system.

[0030] Fig.19 The diagram shows the Fig.16 An exemplary filter replacement system.

[0031] Fig. 20 The diagram shows the Fig.16 An exemplary filter replacement system.

[0032] Fig.21 The diagram shows the Fig.16 An exemplary filter replacement system. DETAILED DESCRIPTION

[0033] General Considerations

[0034] The present disclosure relates to equipment and processes for filtering materials (such as filtering cell-containing solutions to provide cell-free solutions). It should be understood that although the various embodiments described herein disclose the specific methods or materials used in specific embodiments, in view of these teachings, other methods, materials and embodiments similar or equivalent to those described herein are also possible. Therefore, the following description is exemplary in nature and is not intended to limit the scope, applicability or configuration of the present disclosure in any way. Without departing from the scope of the present disclosure, various changes can be made to the described embodiments, such as various changes in the function and arrangement of the elements described herein.

[0035] As used in this application, the singular forms "a", "an", and "the" include plural forms unless the context clearly dictates otherwise. In addition, the term "including" means "comprising". In addition, as used herein, the term "and / or" means any one item or combination of items in the phrase. In addition, the term "exemplary" means serving as a non-limiting example, instance, or illustration. As used herein, the terms "such as" and "for example" introduce a list of one or more non-limiting embodiments, examples, instances, and / or illustrations.

[0036] Unless otherwise stated, all the numbers used in the specification or claims representing the quantity of components, molecular weights, percentages, temperatures, times, etc. should be understood to be modified by the term "about". Therefore, unless otherwise implied or clearly stated, the numerical parameters set forth are approximate values, which may depend on the desired properties sought and / or the detection limits under standard test conditions / methods. When directly and clearly distinguishing an embodiment from the prior art discussed, the embodiment numbers are not approximate values, unless the word "about" is listed. In fact, the dimensions and values ​​disclosed herein should not be understood to be strictly limited to the exact values ​​listed. On the contrary, unless otherwise stated, each such dimension is intended to mean the listed values ​​and the functional equivalent range around the value. For example, the dimension disclosed as "40 mm" is intended to mean "about 40 mm" (that is, each value in the actual range close to 40 mm).

[0037] Although the operations of some disclosed methods are described in a particular sequential order for ease of presentation, it should be understood that this description encompasses rearrangement unless the specific language set forth below requires a particular order. For example, the operations described in sequence may in some cases be rearranged or performed simultaneously. In addition, for simplicity, the accompanying drawings may not show the various ways in which the disclosed things and methods can be used in conjunction with other things and methods. Additionally, the description sometimes uses terms such as "provide," "produce," "determine," and "select" to describe the disclosed methods. These terms are high-level descriptions of the actual operations performed. The actual operations corresponding to these terms will vary depending on the specific implementation and are readily discernible by those of ordinary skill in the art who benefit from the present disclosure.

[0038] As described above, the systems and methods described herein and their individual components should not be construed as being limited in any way to the specific uses or systems described herein. Instead, the present disclosure is directed to all novel and non-obvious features and aspects of the various disclosed embodiments, both individually and in various combinations and sub-combinations with each other. For example, any feature or aspect of the disclosed embodiments may be used in various combinations and sub-combinations with each other, as would be recognized by a person of ordinary skill in the relevant art in view of the information disclosed herein. In addition, the disclosed systems, methods, and components thereof are not limited to any particular aspect or feature or combination thereof, nor do the disclosed things and methods require the existence of any one or more specific advantages or the resolution of any one or more specific problems.

[0039] As used herein, the term "wetted parts" means parts that are in direct contact with fluids (gas and / or liquids) and are typically selected from the group consisting of reservoirs, conduits, filters, and combinations thereof.

[0040] As used herein, the term "fluid coupling" or "fluid communication" means that two or more components have a structural connection between them that allows fluid to be transferred from one part to another via the fluid coupling. The term "fluid coupling" or "fluid communication" does not require that fluid transfer occur, only that a fluid pathway has been established so that the fluid can flow when the device is used to cause such fluid transfer.

[0041] As used herein, the term "filtration member" refers to a filter suitable for separating a high solids cell-containing solution from a cell-free solution, such as a hollow fiber filtration member. As used herein, a "hollow fiber module" is a filtration member comprising a plurality of hollow fibers.

[0042] As used herein, the term "using" means the process of filtering the same solution (eg, a solution of equivalent formulation) before changing to another different solution (eg, a solution of different formulation).

[0043] As used herein, the term "single use (disposable)" means that the element referred to as "single use" can be discarded after a single use.

[0044] As used herein, the term "cell-containing" refers to a solution or sample, or a portion thereof, that contains cellular material. The term "cell-free" refers to a solution or sample, or a portion thereof, that has been filtered to reduce or eliminate cellular material from the cell-containing solution or sample.

[0045] As used herein, the term "permeate" refers to material separated from a cell-containing solution or sample (such as a cell-free solution or sample) by a filtration member.

[0046] As used herein, the term "bioreactor" refers to any manufactured or engineered device or system that supports a biologically active environment, such as a device or system in which cells or tissues can be grown, for example in a rigid reusable container (e.g., stainless steel) or a single-use container (e.g., a flexible bag).

[0047] Filter components and usage

[0048] The present disclosure relates to equipment and processes for filtering high solids cell-containing solutions to produce cell-free solutions and / or samples for further analysis. Such equipment and processes can be used in conjunction with, for example, bioreactor sampling systems. In particular, product quality attribute testing of samples from bioreactors can desirably include analyzing one or more cell-free samples. In order to provide cell-free samples, a cell removal system (CRS) can separate cells from permeate to be transferred to instruments such as high performance liquid chromatography (HPLC), ultra-high performance liquid chromatography (UPLC), mass spectrometers, and other devices for analysis.

[0049] Figure 1 A cell removal system 100 is illustrated that uses tangential flow filtration in conjunction with a filtration system 102, such as a hollow fiber module, to separate cells from the permeate. Figure 1 As shown, the filtration system 102 can include a plurality of filtration members 102a, 102b, 102c, which can be received in the cell removal system 100 for filtration.

[0050] The filter member can be fluidly coupled to the sample flow path of the cell removal system 100 by loading the filter member in the cell removal system 100 and coupling the filter member at both ends so that the filter flow path of the filter member forms part of the flow path of the cell removal system (i.e., the filter member is in fluid communication with the cell removal system). In addition, the filter member can be fluidly coupled to additional devices, such as coupling the filter system sample outlet 114 to a reservoir or liquid handling system 118 to further process the permeate separated from the cells.

[0051] Figure 1 The sample flow paths (and other flow paths) are schematically illustrated. It will be appreciated that these flow paths may be formed by any conduits, tubes or internal passages suitable for providing a fluid pathway that allows material to flow within and / or outside of the cell removal system as shown.

[0052] The coupling of the filter member to the cell removal system may be automated, such as by one or more actuators, which move to engage the cell removal system with the respective ends of the filter member and / or the filter system sample outlet. Alternatively, coupling of these components may be accomplished manually.

[0053] exist Figure 1 In the illustrated embodiment, filter member 102a has been used for tangential flow filtration operation and has been stopped (e.g., abandoned), filter member 102b is currently configured for tangential flow filtration operation (e.g., active filter member), and filter member 102c can be used for deployment and use after filter member 102b is stopped. In certain embodiments, the exchange of a filter member with another filter member can occur after a single use of the active filter member.

[0054] like Figure 1 As shown, in one embodiment, a sample of a cell-containing solution may be withdrawn from a sample source 104. The sample may be provided using any device suitable for removing one or more samples from a bioreactor in a generally sterile manner.

[0055] The sample can be caused to flow in a first direction 106 toward and through the filtration system 102 by a first pump member 108. After moving through the filtration system 102, the sample can be redirected back through the filtration system 102 in a second direction 110 opposite to the first direction by a second pump member 112. Figure 1 When filtering by the movable filter element 102b in the active filter element, the cell-free solution (ie, the cell-free sample) can leave the filtration system through the filtration system sample outlet 114 in the movable filter element.

[0056] exist Figure 1 In the illustrated embodiment, the first pump member 108 and the second pump member 112 are syringe pumps. However, other pump configurations are possible, as described and shown in other embodiments herein.

[0057] like Figure 1 As shown, multiple valves 116 can be provided throughout the cell removal system to facilitate sampling and filtering, as well as cleaning portions of the cell removal system. In some embodiments, when the corresponding valve 116 is in an open position, the filtered cell-free solution exiting the outlet 114 can be delivered to a sample reservoir and / or liquid handling system 118 for further processing and / or analysis.

[0058] Thus, to achieve filtration of the sample, the active filter member is positioned so that its filtration system inlet 120 and filtration system outlet 122 are in fluid communication with the sample flow path. This allows the sample to be drawn from the sample source 104 and transported through the filtration flow path of the active filter member to separate cells from permeate. The fluid coupling of the cell removal system to the filtration system (i.e., the coupling at the filtration system inlet and outlet) can be achieved by any suitable fluid coupling device of the cell removal system (such as those disclosed in more detail below).

[0059] After the cell-free solution is removed from the sample and / or the filtration event is complete, the active filter member (i.e., Figure 1 The filter element 102b in the cell removal system 100 is removed so that the filter system inlet 120 and the filter system outlet 122 of the filter element are no longer in fluid communication with the sample flow path of the cell removal system 100.

[0060] After removing the active filter element (e.g., filter element 102b), a new filter element (e.g., filter element 102c) can be moved so that the filtration system inlet 120 and the filtration system outlet 122 of the new filter element are in fluid communication with the sample flow path of the cell removal system 100 (e.g., the filtration flow path of the new filter element is in fluid communication with the sample flow path of the cell removal system).

[0061] In some embodiments, after removal and / or discarding of a filter member, the sample flow path in the cell removal system 100 may be sanitized before a new filter member is moved into fluid communication with the sample flow path of the cell removal system 100 .

[0062] In some embodiments, disinfection is provided for all wetted parts of the cell removal system so that parts that come into direct contact with the sample (e.g., reservoirs, conduits) can be disinfected. To achieve this disinfection, a fluid coupling member (e.g., a cleaning housing) can establish a connecting flow path across the inlet and outlet portions of the cell removal system that will be connected to the filtration member during the filtration process.

[0063] like Figure 2 As shown, the cell removal system 100 includes a sterilizing fluid inlet 124, a water inlet 126, and a gas inlet 128, respectively coupled to a sterilizing fluid source 130, a water source 132, and a gas source 134. Each of these can be arranged to be in fluid communication with at least a portion of a sample flow path of the cell removal system 100. Although this embodiment illustrates a system using sterilizing fluid, water, and gas, it should be understood that other systems can use any combination of these fluids (e.g., sterilizing fluid only, sterilizing fluid and gas only, etc.).

[0064] The valves 116 associated with the sterilizing fluid inlet 124, the water inlet 126, and the gas inlet 128 are independently operable between a closed position that restricts flow and an open position that allows flow of the respective materials.

[0065] As described above, the flow path across the portion of the cell removal system provided during filtration can be provided during disinfection by another fluid coupling member (e.g., a cleaning housing). The cleaning housing 136 has an inlet and an outlet that are configured to be positioned in fluid communication with the sample flow path of the cell removal system (in the same or similar manner as the filter member) to allow disinfection of the upstream portion of the sample flow path (i.e., the inlet side of the filter member) and the downstream portion of the sample flow path (i.e., the outlet side of the filter member).

[0066] Thus, in order to sterilize the sample flow path between uses of the first filter member and the second filter member, the first filter member (e.g., Figure 2 The cleaning housing 136 can be positioned in the location of the filter component 102a in the cell removal system 100.

[0067] The valve 116 associated with the disinfection fluid can be moved to an open position, and the disinfection fluid can be delivered to the sample flow path of the cell removal system and the connecting flow path of the cleaning housing. A pump 138 can be provided to facilitate the delivery of the disinfection fluid from the disinfection fluid inlet 124 through the sample flow path and the connecting flow path.

[0068] The disinfecting fluid can be any suitable fluid that can disinfect, sterilize or sterilize the sample flow path. The disinfecting fluid can be a liquid, a gas or a combination thereof. The disinfecting fluid comprises steam, ethylene oxide, glutaraldehyde, formaldehyde, formalin, chlorine, hypochlorite, bromine, hypobromite, iodine, hypoiodite, bromine chloride, chlorine dioxide, ozone, hydrogen peroxide, monochloramine, dichloramine, trichloramine, quaternary ammonium salt, ethanol, 70% ethanol / water, isopropanol, 70% isopropanol / water, peracetic acid and peracetic acid. In one embodiment, the disinfecting fluid is steam. In another embodiment, the disinfecting fluid is ethylene oxide. In another embodiment, the disinfecting fluid is glutaraldehyde.

[0069] like Figure 2 As shown, the gas inlet 128 can be disposed upstream of the disinfection fluid inlet 124 to deliver gas through the sample flow path and the connecting flow path. After the sample flow path is exposed to the disinfection fluid, the gas can eliminate and / or reduce the amount of disinfection fluid remaining in the sample flow path. Thus, the gas can clean the path and / or remove any material from the previous sample in the area in contact with the disinfection fluid. In one embodiment, the gas includes compressed air.

[0070] In some embodiments, water can also be provided alone or in combination with a disinfecting fluid and / or gas to clean the sample flow path. For example, after the sample flow path is disinfected with a disinfecting fluid, water can be introduced into the sample flow path to at least partially remove residual disinfecting fluid from the sample flow path.

[0071] like Figure 2 As shown, at least some portions of the gas path overlap with the sterilization fluid path, which in turn at least partially overlaps with the sample flow path to allow the gas to purge the sterilization fluid from the sample path.

[0072] like Figure 2 As shown, pump 138 can be used to facilitate delivery of one or more of a disinfecting fluid, water, and / or gas associated with a cleaning operation. In some embodiments, pump 138 can include a peristaltic pump.

[0073] like Figure 1 and Figure 2 As shown, one or more valves in the cell removal system can be opened to allow material (e.g., sample, sterilizing fluid, gas, water, etc.) to be delivered to the waste reservoir 140. For example, as shown in FIG. Figure 2As shown, valve 116 associated with downstream waste reservoir 140 may be opened to allow the sanitizing fluid, water, and / or gas to be discharged from the cleaning operation.

[0074] Figure 3 Another embodiment of a cell removal system 200 is illustrated in which a first filter member (e.g., 102a) is used with a first sampling procedure and then replaced with a second filter member (e.g., 102b) to provide a new filter member for use with a second sampling procedure. Figure 2 As shown in the described and depicted embodiments, a cleaning housing 136 can be provided after the first filter member is used and before the second filter member is positioned in fluid communication with the sample flow path of the cell removal system 200. As described in more detail below, the same cleaning housing 136 can be used for each disinfection operation. Alternatively, more than one cleaning housing can be provided, and different cleaning housings can be used between two or more filtration procedures.

[0075] Figure 3 The operation of the cell removal system 100 is similar to Figure 2 The cell removal system 100. However, in Figure 3 , the sample flow path and the filtration flow path can together form a closed loop system that allows sample to be introduced into the filtration system 102 in one or both directions 106, 110 through operation of the first pump member 108 (e.g., a syringe pump) and / or an additional pump member 142 downstream of the first pump member 108. In some embodiments, the additional pump member 142 can include a peristaltic pump.

[0076] The disinfection process can also be similar to the above Figure 2 Operations are described wherein sterilizing fluid and other fluids (eg, gas, water) are delivered partially or, more preferably, entirely through the sample flow path.

[0077] Figure 4 Another embodiment of a cell removal system 300 is illustrated in which a first filter member (e.g., 102a) is used with a first sampling procedure and then replaced with a second filter member (e.g., 102b) to provide a new filter member for use with a second sampling procedure. The operation of the cell removal system 300 can be similar to that described above with respect to Figure 3 In addition, the cell removal system 300 also includes a collapsible bladder 144 in the sample flow path.

[0078] The collapsible pouch 144 can be a variable volume reservoir that can receive different volumes of fluid (e.g., sample) in the sample flow path, thereby increasing the available volume of the fluid flow path for receiving the fluid. Thus, during a sampling procedure, a larger volume of sample can be received in the fluid flow path, and as permeate is removed, the volume of the collapsible pouch 144 can be reduced, thereby adjusting to the amount of remaining sample volume in the sample flow path.

[0079] Sterilization of the cell removal system 300 may be accomplished as described in other embodiments, such that a portion of the sample flow path, or more preferably the entire sample flow path (including the collapsible bladder 144), may be sterilized for subsequent sampling procedures.

[0080] Figure 5 Yet another embodiment of a cell removal system 400 is illustrated in which a first filter member (eg, 102a) is used with a first sampling procedure and then replaced with a second filter member (eg, 102b) to provide a new filter member for use with a second sampling procedure.

[0081] The cell removal system 400 includes a first pump member 146 configured to deliver samples and other fluids (e.g., disinfecting fluids, gases, water) through sample flow paths, filtration flow paths, and / or connecting flow paths as described herein. The first pump member 146 may include a peristaltic pump that moves the sample and other fluids through a closed-loop sample flow path. In addition, another pump member 148 may be provided in communication with the permeate fluid separated from the cells to facilitate separation of the permeate and delivery of the permeate to a downstream reservoir or liquid handling station 118.

[0082] Figure 6-10 An exemplary filter replacement system 500 is illustrated that is configured to receive a plurality of filter components. For example, Figure 6 There is shown a filtration system 102 comprising a cartridge of a plurality of filter members 102a, 102b, 102c, 102d, 102e, etc. The filter members are arranged to be dropped from above into position to engage a sample flow path.

[0083] like Figure 6 As shown, each filter member has a filter system inlet 120 and a filter system outlet 122. The inlet 120 and the outlet 122 are configured to engage with a coupling device that places the filter member in fluid communication with a sample flow path of a cell removal system (e.g., an inlet portion of the CRS adjacent to the filter system inlet and an outlet portion of the CRS adjacent to the filter system outlet).

[0084] Figure 7A coupling device 150 is shown on each side of the filter replacement system 500, and the coupling device 150 engages with the filter member to fluidly couple the coupling device 150 with the filter member 102a, such as Figure 8 Once engaged, the sample can be received in the sample flow path and transported through the filter member 102, as described in the above embodiments. For convenience, the filter system sample outlet 114 (such as Figure 1-5 However, the connection with the filtration system sample outlet 114 can be achieved in the same manner as shown with respect to the filtration system inlet 120 and the filtration system outlet 122.

[0085] refer to Fig. 9 After filtering is complete, the coupling device 150 can be separated from the previously active filter member (e.g., 102a) and engaged with the cleaning housing 536. The cleaning housing 536 can be any shape or structure that allows a sterilization process to occur by allowing a sterilizing and cleaning fluid (e.g., sterilizing fluid, gas, water) to be transferred from an upstream portion of the sample flow path to a downstream portion of the sample flow path to sterilize and clean the sample flow path between sampling procedures. Fig. 9 As shown, in some embodiments, the coupling device 150 of the cell removal system can be engaged with the cleaning housing in the same manner as the filter member.

[0086] refer to Fig.10 After sterilization, the filter replacement system 500 can index to the next filter component (e.g., 102b) in the bin to perform another sampling process with the next filter component.

[0087] Figure 11-15 Another exemplary embodiment of a filter replacement system 600 is shown. Fig.11 As shown, the arrangement of system 600 is similar to the arrangement of system 500 ( Figure 6-10 ).For example, Fig.11 A filter system 102 is illustrated that includes a plurality of bins of filter members 102a, 102b, 102c, 102d, 102e, etc., and that are arranged to drop from above into position to engage with a sample flow path. As in the previous embodiments, each filter member has a filter system inlet 120 and a filter system outlet 122 that are configured to engage with a coupling device 150 to place the corresponding filter member in fluid communication with the sample flow path of the cell removal system.

[0088] Fig.12 The first filter member 102a is shown in a position for engagement with the coupling device 150, Fig.13The first filter member 102a is shown engaged with the coupling device 150 so that the first filter member 102a is in fluid communication with the sample flow path of the cell removal system.

[0089] refer to Fig.14 After filtering is completed, the coupling device 150 is separated from the previous active filter member (e.g., 102a) and the filter member is removed (e.g., discarded). Before engaging with a new filter member, the coupling device 150 can be engaged with the cleaning housing 636. In this embodiment, the cleaning housing 636 is included in the embodiment of Fig.15 The inner cavity in a portion of one of the clamping structures 652 shown. As with other cleaning housings disclosed herein, this structure allows a sterilization process to occur by allowing a sterilization and cleaning fluid (e.g., sterilization fluid, gas, water) to be transferred from an upstream portion of the sample flow path to a downstream portion of the sample flow path to sterilize and clean the sample flow path between sampling procedures. After sterilization, the filter replacement system 600 can index to the next filter component (e.g., 102b) in the bin to perform another sampling process with the next filter component.

[0090] Figure 16-21 Another exemplary embodiment of a filter replacement system 700 is shown. Fig.16 As shown, the arrangement of system 700 uses a rotary conveyor system for replacing the filter element after use. For example, Fig.16 A filtration system 102 is shown, which includes a plurality of filter members 102a, 102b, 102c, 102d, 102e, etc., and these filter members are arranged to rotate into a position to engage with a sample flow path. In addition, as in the previous embodiments, each filter member has a filter system inlet and a filter system outlet, which are configured to engage with a coupling device that places the filter member in fluid communication with the sample flow path of the cell removal system.

[0091] Fig.17 The first filter member 102a is shown to be received in the rotary loading device 754, and Fig.18 It is shown received in slot 756 of rotary loading device 754. Fig.19 The filter element 102a is shown in FIG. 1 . Fig.18 150. As shown, the first filter member 102a after the top of the rotating loading device 754 is moved to its operating position engaged with the coupling device 150. In this embodiment, the rotating device is indexed 180 degrees, and the first filter member 102a is lowered to a position engaged with the coupling device 150.

[0092] After the first filter member 102a is engaged with the coupling device 150, as shown in FIG. Fig.19 As shown, a sample may be drawn into the filter member and filtration may commence. A second coupling device 757 may be provided to engage with the filtration system sample outlet 114 to receive the permeate after it has been separated from the cells.

[0093] refer to Fig. 20 After filtering is completed, the coupling device 150 is separated from the previous active filter member (e.g., 102a), and the filter member is removed (e.g., discarded) through the waste tank 758. Before engaging with a new filter member, the coupling device 150 can be engaged with the cleaning housing 736, such as Fig.21 shown.

[0094] like Fig.21 As shown, the cleaning housing 736 can be secured in a slot directly opposite the slot that receives the filter element (or otherwise secured to the loading device). Fig.16 As shown, when a new filter element is rotated into position for filtration, the cleaning housing 736 is rotated away from the sample flow path of the cell removal system, and when the filter element is discarded, the cleaning housing is rotated back into fluid connection with the sample flow path of the cell removal system, thereby providing a connected flow path that allows disinfection and cleaning as disclosed herein.

[0095] The above-described systems and methods offer a number of potential advantages over conventional CRS techniques that reuse sample contacting portions including filtration systems. In particular, the reuse of filtration systems introduces a number of potential problems and disadvantages. For example, the cleaning procedures required to reuse components increase turnaround time and increase the likelihood that residual material from previous samples will remain in the reused components, which may result in sample contamination. In addition, continued use of a filtration system (e.g., a hollow fiber member) over multiple sampling procedures can result in reduced separation efficiency and require additional procedures to monitor the number of uses and applications in which the filtration system has been used.

[0096] In view of the many possible embodiments to which the principles of the disclosed invention may be applied, it should be appreciated that the illustrated embodiments are merely preferred examples of the invention and should not be considered to limit the scope of the invention. Instead, the scope of the invention is defined by the following claims. Therefore, we regard all that fall within the scope and spirit of these claims as our invention.

Claims

1. A filtration system for use with a cell removal system, the filtration system comprising: a loading member configured to receive a plurality of filter members, each of the plurality of filter members comprising a filter inlet, a filter outlet, and a filter flow path extending from the filter inlet to the filter outlet; at least one actuator configured to sequentially move the plurality of filter members from an inactive position, in which a corresponding filter member of the plurality of filter members is not in fluid communication with a sample flow path of the cell removal system, to an active position, in which a corresponding filter member is in fluid communication with the sample flow path, and to a discard position, in which the corresponding filter member has been removed from fluid communication with the sample flow path, Wherein, the loading component is a rotary indexing bin.

2. The filtration system according to claim 1, wherein: The plurality of filter members are vertically arranged on the loading member.

3. The filtration system according to claim 1, wherein: The rotary indexing station is configured to receive a corresponding filter member in the inactive position and rotate 180 degrees to move the corresponding filter member to the active position.

4. The filtration system of any one of claims 1-3, further comprising a cleaning housing having a connecting flow path, wherein the at least one actuator is configured to move the cleaning housing into and out of fluid connection with the sample flow path of the cell removal system.

5. The filtration system according to claim 4, wherein: The cleaning housing is a linear member extending from a first portion of the sample flow path to a second portion of the sample flow path.

6. The filtration system according to claim 4, wherein: The clean housing is a non-linear member extending from a first portion of the sample flow path to a second portion of the sample flow path.

7. The filtration system according to any one of claims 1 to 3, wherein: Each of the plurality of filter members also includes a permeate outlet.

8. A cell removal system comprising: a sample flow path having a sample inlet for receiving a sample containing a cell solution; a loading member configured to receive a plurality of filter members, each of the plurality of filter members comprising a filter inlet, a filter outlet, and a filter flow path extending from the filter inlet to the filter outlet; at least one actuator configured to sequentially move the plurality of filter members from an inactive position, in which a corresponding filter member of the plurality of filter members is not in fluid communication with a sample flow path of the cell removal system, to an active position, in which a corresponding filter member is in fluid communication with the sample flow path, and to a discard position, in which the corresponding filter member has been removed from fluid communication with the sample flow path, Wherein, the loading component is a rotary indexing bin.

9. The cell removal system of claim 8, further comprising: A first coupling device is configured to engage with a filter inlet of a corresponding filter member of the plurality of filter members, and a second coupling device is configured to engage with a filter outlet of a corresponding filter member of the plurality of filter members.

10. The cell removal system according to any one of claims 8-9, further comprising: One or more pump systems are configured to transport the sample of the cell-containing solution through the sample flow path and the filter flow path of a corresponding filter member of the plurality of filter members.

11. The cell removal system according to claim 10, wherein: The one or more pump systems include at least one syringe pump.

12. The cell removal system according to claim 10, wherein: The one or more pump systems include at least one peristaltic pump.

13. The cell removal system according to any one of claims 8-9, further comprising: One or more variable volume reservoirs in the sample flow path.

14. The cell removal system according to any one of claims 8-9, wherein: The plurality of filter members are vertically arranged on the loading member.

15. The cell removal system according to claim 8, wherein: The rotary indexing station is configured to receive a corresponding filter member in the inactive position and rotate 180 degrees to move the corresponding filter member to the active position.

16. The cell removal system of any one of claims 8-9, further comprising a cleaning housing having a connecting flow path, wherein the at least one actuator is configured to move the cleaning housing into and out of fluid connection with the sample flow path of the cell removal system.

17. The cell removal system according to claim 16, wherein: The cleaning housing is a linear member extending from a first portion of the sample flow path to a second portion of the sample flow path.

18. The cell removal system according to claim 16, wherein: The clean housing is a non-linear member extending from a first portion of the sample flow path to a second portion of the sample flow path.

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