DISPOSABLE FILTRATION MODULE, DISPOSABLE CLEANING MODULE EACH USABLE IN A MODULAR FILTRATION SYSTEM

Description

[0001] The invention relates to a modular cross-flow filtration system for low-volume screening applications.

[0002] There is great interest in the biopharmaceutical industry in isolating and testing proteins for robustness and performance in ultrafiltration and diafiltration (UF and DF) processes, as well as buffers for protective or detrimental effects on proteins during such UF / DF processes. This interest is particularly evident in early development stages, where typically only small quantities of the biological product are available.

[0003] Current cross-flow filtration systems and their flow paths are not designed for low-volume testing procedures (screening applications). Even the smallest commercially available flat-membrane filtration devices have a membrane surface area of ​​approximately 50 cm². Due to their design, which is determined by other criteria, the known cross-flow filtration systems are also not suitable for conducting multiple low-volume screening processes in parallel. A further disadvantage with regard to the desired low-volume screening applications is that the known systems have a multitude of individual components (fluid connections, valves, sensors, etc.) that must be connected to one another using tubing, which is complex and error-free. Furthermore, the known large-scale systems have a correspondingly large dead volume, which is extremely inefficient in the aforementioned applications when only small amounts of protein solution are available.This means that only a limited number of process runs are possible. This leads to knowledge gaps, e.g., in determining cross-flow filtration process parameters or buffer conditions to create a stable target molecule environment.

[0004] EP 2 907 565 A1 describes an ultrafiltration unit for buffer exchange (diafiltration) for proteins in a sterile environment. Various disposable elements are used: filtration elements, valves, sensors (flow, pH, conductivity, UV, pressure), containers, and pumps. A recirculation loop may also be included.

[0005] DE 20 2009 003 680 U1 discloses a filtration system that essentially consists of a pre-sterilizable, single-use filtration system and reusable system components. The filtration system is based on a hose system and is delivered in sterile packaging as a closed, fully interconnected system. It includes valves, pumps, sensor points, recirculation tanks, fluid connections, and a filtration module. The system is removed from its outer packaging as a whole, and the disposable parts of the valves, pumps, and measuring points are connected to their counterparts in the filtration system.

[0006] EP 2 119 49 2A1 shows a UF tangential flow filtration system for the purification of proteins as a disposable system with various disposable elements such as pumps, sensors, pressure regulators, pressure gauges, containers, filters.

[0007] US 2008 / 0269468 A1 demonstrates an integrated protein purification process using various disposable elements: filters, containers, pressure transmitters, tube clamps that act as valves, and fluid connections. The filtration system is prefabricated and sterilized.

[0008] EP 2 255 865 A1 shows disposable filter membranes, liners and sensor ports for tangential flow filtration systems.

[0009] The object of the invention is to enable the most effective and efficient product and process development possible based on low-volume test procedures, taking the above aspects into account.

[0010] This object is achieved by a modular cross-flow filtration system having the features of claim 1. Advantageous and expedient embodiments of the filtration system according to the invention are specified in the subclaims.

[0011] The modular cross-flow filtration system according to the invention for low-volume screening applications comprises a prefabricated filtration module, wherein the filtration module has fluid connections and several components tailored to low-volume screening applications, which are permanently integrated into the filtration module. According to the invention, the entire filtration module is designed as a disposable filtration module. The modular cross-flow filtration system according to the invention further comprises a cleaning module for cleaning reusable components of the filtration system, wherein the entire cleaning module is designed as a disposable cleaning module and has a permanently integrated cleaning fluid container filled with a cleaning fluid. The filtration module and the cleaning module are designed with regard to their fluid connections and their mechanical connections such that they can alternatively be arranged and connected at the same location in the filtration system.

[0012] The invention is based on the realization that it is advantageous to design as many of the components used in a filtration process as possible as single-use components. Complete disposal of the pre-sterilized, disposable components not only reduces the cleaning effort itself and the associated loss of time, but also eliminates the risk that, for example, residues of toxins or antibodies remain in the components. Such residues would not only distort subsequent experiments but would also pose a health hazard to personnel and a general safety risk. In contrast, thanks to the invention, the majority of the contaminated components of a test setup can be replaced quickly and easily at once by simply replacing a used filtration module with a new one.

[0013] Another significant advantage of the invention is that the provision of the majority of the components required for a filtration experiment in a prefabricated module allows for an extremely compact design. Instead of conventional reusable "universal components" that must be used for a variety of different experiments and / or large-scale applications and laboriously connected to one another, the invention provides a set of pre-connected components that are specifically designed for a specific application. The elimination of connecting components such as sterile connectors or Luer, screw, and TRI-Clamp connectors, etc., not only allows for a space-optimized design of the filtration module provided according to the invention but also reduces dead space.For example, a special filtration module with appropriately small-sized components, especially a filter with a reasonably small surface area, can be provided for a low-volume screening process. The use of such specially designed prefabricated filtration modules is extremely simple for the user and largely eliminates errors in test setup.

[0014] A disposable cross-flow filtration device with a filter is provided for the actual filtration process.

[0015] According to a first variant of the invention, the filtration device is permanently integrated into the filtration module, i.e., the filtration device is an integral part of the filtration module. With this variant, the filtration device cannot be connected incorrectly, and no additional installation effort is required.

[0016] According to a second variant of the invention, the filtration device is a separate disposable filtration device that can be plugged into or onto the filtration module as a unit. This variant allows for maximum flexibility in selecting a suitable filtration device (filter properties, filter size, etc.) without significantly increasing the installation effort. Ideally, all required fluid connections are automatically established simultaneously when the filtration device is plugged in or connected.

[0017] The effort required to connect the components required for a specific experiment is reduced the more these components are already pre-assembled in the filtration module. Therefore, a filtration module with a one-way flow path, into which a recirculation tank for process fluid and / or at least one sensor and / or at least one flow valve and / or a pump are at least partially integrated, proves advantageous. A reservoir for diafiltration medium can also be provided in the filtration module. Furthermore, the filtration module can have ports that allow media (e.g., diafiltration medium) to be supplied from external sources.

[0018] A flow path is understood here to mean those components of the filtration system with which the process fluid comes into contact and which determine at least a portion of the process fluid's path through the filtration system. Several flow paths can be provided in the filtration system, even within a filtration module or cleaning module (as explained in more detail later). These can be alternatively selected depending on the selected process sequence or can be flowed through in parallel or sequentially. Here, the focus will primarily be on the flow path(s) within a filtration module.

[0019] In the previously explained variants of the invention, the filtration device can be permanently integrated into a one-way flow path or integrated as a separate unit into a one-way flow path that is itself permanently integrated into the filtration module. However, the one-way flow path can also, in principle, be integrated into the filtration module as a complete unit.

[0020] A further development of the invention provides temperature control for the filtration module. For certain experiments, it is important that the temperature of the process fluid be kept constant at a certain value during filtration; or the same experiment should be conducted at different temperatures in order to document the temperature dependence of the results. In such cases, it is advantageous if the temperature of the entire filtration module can be controlled. A simple but effective temperature control can be achieved, for example, by coupling an outer wall of the filtration module to a temperature-controlled surface, in particular that of a Peltier element.

[0021] A modular cross-flow filtration system according to the invention also includes a special cleaning module. Such a cleaning module is intended to be used for cleaning reusable components of the filtration system. The entire cleaning module is designed as a disposable cleaning module, significantly reducing the effort required for cleaning: Firstly, the assembly and connection of the components required for cleaning are simplified; secondly, the required components can be disposed of quickly and easily all at once.

[0022] According to a particular aspect of the invention, the filtration module and / or the cleaning module has a plurality of one-way flow paths. The plurality of flow paths within the same module can be used in different ways depending on the selected process sequence: For example, the flow path intended for the desired process can be selected or set, while the other flow path(s) remain unused initially and can possibly be used for later experiments. Another possibility is to use two or more flow paths simultaneously in an experiment or during a cleaning run. The different flow paths can then be flowed through either in parallel or sequentially. The provision of multiple flow paths, each of which can optionally be used as a separate unit in the filtration module or cleaning module, thus creates even greater flexibility and efficiency.

[0023] The integration of certain components into a disposable filtration module or a disposable cleaning module is not readily possible, for example because the drive, control, or signal transmission must be provided externally, or because the exclusive use of disposable components for such components is not technically or economically viable. It is therefore a particular challenge to integrate such components, especially pumps, valves, or sensors, at least partially into the disposable modules.

[0024] In the case of a fluid pump, a pump mechanism may be provided which is at least partially formed from disposable components which are firmly integrated into the filtration module, in particular into the filtration device, or the cleaning module.

[0025] For example, the pump mechanism can comprise a disposable pump tube and a reusable drive, in particular with a rotor and an attached roller unit for deforming the disposable pump tube. This allows for the realization of a peristaltic pump in which the pump tube is permanently integrated into the filtration module or cleaning module as a disposable component. Since the complex drive mechanism with rotor and roller unit does not come into contact with the process or cleaning fluid in the pump tube, it is advantageous to implement it as an external, reusable sub-unit of the pump mechanism.

[0026] In another embodiment of the pump mechanism, it comprises a disposable piston-cylinder unit or a disposable pusher and a reusable drive for actuating the piston or pusher. Here, the piston-cylinder unit or pusher that comes into contact with the process or cleaning fluid can be permanently integrated into the filtration module, in particular into the filtration device, or the cleaning module as a disposable unit, while the drive can be implemented independently as an external, reusable subunit of the pump mechanism. In this way, a partially integrated piston pump or a partially integrated pump based on the principle of a manually operated soap dispenser or a manually operated spray pump can be realized, but which is mechanically driven.

[0027] The integration concept can be implemented for externally driven or controlled valves by providing the filtration module, in particular the filtration device, or the cleaning module with at least one valve connection. A valve mechanism partially formed from disposable components is arranged at the at least one valve connection of the filtration module, the filtration device, or the cleaning module, wherein these disposable components are permanently integrated into the filtration module, in particular the filtration device, or the cleaning module. The other components required for valve operation can be designed as external, reusable components, especially if they do not come into direct contact with the process or cleaning fluid.These reusable components are preferably critical components that must be particularly precise, resilient and / or reliable and that would result in disproportionately high costs if used as disposable components only once.

[0028] According to a first variant, the valve mechanism comprises a flexible disposable hose and a reusable guided plunger. The flow cross-section of the disposable hose, which is permanently integrated into the filtration module, in particular the filtration device, or the cleaning module, can be changed using the externally actuated plunger, thus allowing the flow rate to be adjusted.

[0029] According to a second variant of the valve mechanism, a one-way plunger is guided in a one-way seal. With appropriate deflection, the plunger can penetrate a flow channel of the filtration module, in particular a flow channel of the filtration device or the cleaning module, and thus specifically influence the flow rate.

[0030] A third variant of the valve mechanism is based on an elastic membrane which, as a disposable component firmly integrated into the filtration module, in particular into the filtration device, or the cleaning module, can be pressed into a flow channel of the filtration module, in particular into a flow channel of the filtration device, or the cleaning module by means of a reusable plunger.

[0031] In principle, with the first and third variants of the valve mechanism, it is also possible to provide a compressed gas source for pressurizing the disposable hose or the disposable membrane instead of the reusable plunger.

[0032] According to the principles described above, more complex control components can also be implemented, such as 3-way valves for modules with multiple flow paths that can be operated or driven from outside the module. In any case, such a control component is partly made up of disposable components that are permanently integrated into the filtration or cleaning module, while the other components can be designed as external, reusable components, especially if they do not come into direct contact with the process or cleaning fluid.

[0033] Appropriate sensors are required to detect specific process parameters. To enable the use of a sensor with a disposable filtration module and / or a disposable cleaning module, it is proposed to arrange a sensor device, in particular a pressure sensor device, partially formed from disposable components at a sensor connection of the filtration module, in particular at a sensor connection of its filtration device or of the cleaning module. These disposable components are permanently integrated into the filtration module, in particular into the filtration device, or the cleaning module.

[0034] According to an advantageous concept, a disposable membrane, in particular a pressure membrane, can be stretched over an opening of the sensor connection, which interacts with a reusable sensor device, in particular a pressure sensor, arranged at the opening. The flexible membrane is thus part of the disposable components, while the typically expensive sensor device can be reused. In the case of a deflectable but impermeable pressure membrane, the pressure sensor on the side opposite the fluid does not come into contact with the fluid and does not require cleaning. However, the membrane can also be deliberately chosen to be permeable in order to divert samples for external analysis of specific parameters such as electrical conductivity, pH value, viscosity, or protein concentration.

[0035] As already mentioned, the invention also includes a special cleaning module, which is designed as a disposable module and, together with the filtration module, forms part of a modular cross-flow filtration system according to the invention. The cleaning module has a permanently integrated cleaning fluid container. This container can either be pre-filled with a cleaning fluid or serve to temporarily store an externally supplied cleaning fluid.

[0036] The invention provides that the cleaning module and the filtration module are designed with regard to their fluid connections and mechanical connections so that they can be alternatively arranged and connected at the same location in a filtration system, in particular a cross-flow filtration system, for low-volume screening applications. This allows the used filtration module to be removed and disposed of after an experiment, and a cleaning module to be inserted in the same location without great effort. After the cleaning run, the removed and disposed cleaning module is simply replaced with the new filtration module intended for the next experiment. In this way, a large number of experiments can be carried out extremely efficiently in a short period of time.

[0037] Further features and advantages of the invention will become apparent from the following description and the accompanying drawings, to which reference is made. In the drawings: Figure 1 a filtration module with a permanently integrated cross-flow filtration device for a modular filtration system; Figure 2 a filtration module with an insertable cross-flow filtration device; Figure 3 a cleaning module for a modular filtration system; Figure 4 a cross-flow filtration device with a partially integrated pumping mechanism; Figure 5a a first variant of the pump mechanism for the cross-flow filtration device from Figure 4 ; Figure 5b a second variant of the pump mechanism for the cross-flow filtration device from Figure 4 ; Figure 5c a third variant of the pump mechanism for the cross-flow filtration device from Figure 4 ; Figure 6aa side sectional view of a cross-flow filtration device with various connections; Figure 6b a bottom view of the cross-flow filtration device from Figure 6a ; Figure 6c a top view of the cross-flow filtration device from Figure 6a ; and Figure 7a a first variant of a partially integrated valve mechanism of a cross-flow filtration device; Figure 7b a second variant of a partially integrated valve mechanism of a cross-flow filtration device; Figure 7c a third variant of an integrated valve mechanism of a cross-flow filtration device; Figure 8a a first variant of a partially integrated pressure sensor mechanism of a cross-flow filtration device; and Figure 8b a second variant of a partially integrated pressure sensor mechanism of a cross-flow filtration device.

[0038] The following describes individual modules of a cross-flow filtration system, which can be used individually or in combination with each other, as well as certain components of these modules.

[0039] In Figure 1 A filtration module (cartridge) 10 with a permanently integrated filtration device, in this case a cross-flow filtration device 12, is shown schematically. The filtration module 10 is intended for use in a modular filtration system. The filtration system can form an automated filtration system to which the filtration module 10 can be plugged as a prefabricated unit. Suitable connectors 14 are provided on the module housing for this purpose. Since the complete filtration module 10 is designed as a disposable module, it can be disposed of as a whole after use and replaced with a new filtration module 10 for the next application.

[0040] The filtration module 10, which in the present case is intended for ultrafiltration or diafiltration, contains at least one one-way flow path into which a recirculation tank 16 for process fluid, at least part of one or more sensor devices 18, at least one externally driven flow valve 20, and at least part of a pump 22 are integrated. The filtration module 10 also has a cross-flow filtration device 12, which is also permanently integrated into the one-way flow path. Furthermore, various connections are provided on the filtration module 10, in particular the fluid connections 24 necessary for supply and discharge. Further connections can also be provided, for example, fluid connections for an external pump or further connections for sensors. Of course, other components can also be integrated into the one-way flow path.

[0041] The outer wall 26 of the filtration module 10 is in contact with a temperature-controlled surface of the filtration system, for example, a Peltier element. This allows all components of the filtration module 10 to be brought to a desired temperature, and the temperature can be maintained constant throughout an experiment.

[0042] In Figure 2A filtration module 10 is shown that differs from the previously described module in particular in that the cross-flow filtration device 12 is designed as a separate disposable unit that can be inserted into the filtration module 10. For this purpose, the cross-flow filtration device 12 has suitable connectors 28 that are matched to complementary connectors of the filtration module 10, creating, for example, a snap-in connection. When the cross-flow filtration device 12 is plugged in, all necessary fluid connections are automatically established at the same time.

[0043] The cross-flow filtration device 12 is therefore not permanently integrated into the filtration module 10. Rather, a device 12 suitable for the respective experiment can be selected from a variety of different compatible cross-flow filtration devices 12 and inserted into the filtration module 10.

[0044] In another embodiment, the flow path of the filtration module 10 is designed as a separate unit, which—as described above in connection with the cross-flow filtration device 12—can be inserted into the filtration module 10. The cross-flow filtration device 12 is then either permanently integrated into the flow path or, again as a separate unit, can be plugged into the flow path. In these cases, too, snap-in connections are preferably provided, and all necessary fluid connections are automatically established simultaneously upon plugging in.

[0045] In Figure 3A cleaning module 30 for a modular filtration system is shown schematically. The cleaning module 30 is designed so that it can be used in the filtration system instead of a filtration module 10, in particular instead of one of the filtration modules 10 described above. This means that, thanks to appropriate connectors 14, the cleaning module 30 can be connected to an automated filtration system as a prefabricated unit, just like a filtration module 10.

[0046] The cleaning module 30 has a plurality of fluid connections 24, in particular for the supply and discharge of cleaning fluid or for connecting an external pump. The flow path of the cleaning module 30, including a cleaning fluid container 32, is permanently integrated into the cleaning module 30. Furthermore, one or more sensor connections 34 and externally driven valves 20 are provided. The cleaning module 30 can have additional flow paths.

[0047] The cleaning module 30 is used to clean reusable components of the filtration system by flushing them with cleaning fluid. Examples of reusable components include hose lines or pumps. The cleaning fluid required for this purpose can either already be present in the cleaning fluid container 32 or can be supplied from an external source via the fluid connections 24 of the cleaning module 30 and, if necessary, temporarily stored in the cleaning fluid container 32.

[0048] In Figure 4 A cross-flow filtration device 12 with a symbolically indicated pump mechanism 36 is shown schematically. The cross-flow filtration device 12 can be integrated into a filtration module 10 (cf. Figure 1 ) or be used as a separate unit in such a module 10 (cf. Figure 2). Several variants of the pump mechanism 36 partially integrated into the cross-flow filtration device 12 are described below.

[0049] Figure 5a shows a mechanism for a hose pump (peristaltic pump), in which a pump hose 38, which can be deformed by rollers, is designed as a disposable component and permanently integrated into the cross-flow filtration device 12. A rotor with an attached roller unit 40, which are also components of the pump mechanism 36, are designed as reusable separate components or as a reusable separate unit and are not permanently integrated into the cross-flow filtration device 12. The rotor with the roller unit 40 can be inserted into the cross-flow filtration device 12, e.g., by means of a click mechanism, in such a way that the roller unit 40 is in operative connection with the pump hose 38 and the pump mechanism 36 is then immediately ready for operation.

[0050] Figure 5bshows a mechanism for a piston pump with holding valves. The piston-cylinder unit 42 of the piston pump is designed as a disposable component and is permanently integrated into the cross-flow filtration device 12 (with the piston 44, of course, being movable within the cylinder 46). The drive unit, however, with which the piston 44 is driven, is designed as a reusable, separate unit and is not permanently integrated into the cross-flow filtration device 12. The drive unit is coupled to the piston 44 in a suitable manner. To maintain a continuous flow, two such pumps can also be provided for the cross-flow filtration device 12.

[0051] Figure 5cshows a pump mechanism 36 similar to that of a manually operated soap dispenser or a manually operated spray pump. The essential parts of the actual pump mechanism 36, including a pusher 48, are designed as disposable components and are permanently integrated into the cross-flow filtration device 12 (with part of the pusher 48 being movable, of course). As with the previously described variant, the drive unit with which the pusher 48 is driven is designed as a reusable, separate unit and is not permanently integrated into the cross-flow filtration device 12. The drive unit is coupled to the pusher 48 in a suitable manner. To maintain a continuous flow, two such pumps can also be provided for the cross-flow filtration device 12.

[0052] The pump mechanisms 36 described above are suitable not only for a cross-flow filtration device 12 of the filtration module, but also for a cleaning module 30 for conveying the cleaning fluid.

[0053] The pump mechanisms 36 described above can also be provided at locations of a disposable filtration module 10 other than those described, for example on a disposable flow path.

[0054] In the Figures 6a to 6c , a cross-flow filtration device 12 with various connections is shown in various views. The connections are permanently integrated into the cross-flow filtration device 12 or into a disposable flow path that can be inserted into the cross-flow filtration device 12. The cross-flow filtration device 12 can in turn be integrated into a filtration module 10 (see Figure 1 ) or be used as a separate unit in such a module 10 (cf. Figure 2 ).

[0055] As shown in the sectional view of the Figure 6a As can be seen, a filter device 52 with a filter membrane 54, over which the process fluid flows on a first side, is located downstream of a fluid inlet 50 in the flow direction. The retentate remaining on the first side of the filter membrane 54 exits at a first fluid outlet 56. The permeate drawn off through the filter membrane 54 transversely to the flow direction exits at a second fluid outlet 58 on the other side of the filter membrane 54. While the fluid inlet 50 and the first fluid outlet 56 are arranged on opposite side walls of the cross-flow filtration device 12, the second fluid outlet 58 is located in the bottom wall of the device 12.

[0056] A first pressure sensor port 60 is provided between the fluid inlet 50 and the filter device 52. More specifically, the first pressure sensor port 60 leads from the top wall of the cross-flow filtration device 12 into the channel that runs from the fluid inlet 50 to the filter device 52. A second pressure sensor port 62 and a valve port 64 each lead from the top wall into the channel between the filter device 52 and the first fluid outlet 56. A third pressure sensor port 66 leads from the bottom wall into the channel between the filter device 52 and the second fluid outlet 58, i.e., the second fluid outlet 58 and the third pressure sensor port 66 are arranged side by side.

[0057] In the Figures 7a to 7c Three variants of a valve mechanism partially integrated into the cross-flow filtration device 12 are shown, which are suitable for the Figures 6a and 6cThe valve connection 64 shown between the filter device 52 and the first fluid outlet 56 or other valve connections of the cross-flow filtration device 12 can be used. Variants are explained below using the example of the valve connection 64.

[0058] At the Figure 7aIn the variant shown, a plunger 68 is guided axially movably in the valve connection 64. The channel running from the filter device 52 to the first fluid outlet 56 is at least partially designed as an elastic hose 70. The valve connection 64 is arranged such that the plunger 68 can be pressed at a first end toward the hose 70, so that the opposite second end of the plunger 68 compresses the hose 70. As a result, the cross-sectional area of ​​the hose interior can be reduced and the flow rate correspondingly reduced. The elastic hose 70 is able to push the plunger 68 back again if no (or only slight) pressure is exerted on its second end.While the elastic tube 70 is a disposable component permanently integrated into the cross-flow filtration device 12, the plunger 68 and any actuating elements coupled thereto, with which the position of the plunger 68 is adjusted, are designed as separate reusable components and are not permanently integrated into the cross-flow filtration device 12.

[0059] In contrast to the previously described variant, the Figure 7bIn the variant shown, no flexible hose is provided. Instead, a flexible seal 72 is provided at the mouth of the valve connection 64 to the channel running from the filter device 52 to the first fluid outlet 56, which seals the channel against the valve connection 64. A plunger 68 or a wedge is guided in the seal 72 such that it can be immersed essentially vertically into the channel. In this way, the flow cross-section is reduced. The plunger 68 or wedge can be moved back by pulling. Here, both the plunger 68 or wedge and the seal 72 are designed as disposable components and are permanently integrated into the cross-flow filtration device 12 (with the plunger 68 naturally being displaceable in the valve connection 64).

[0060] At the Figure 7cIn the variant shown, instead of the seal, an elastic membrane 74 is stretched over the opening of the valve connection 64 into the channel. The membrane 74 can be pressed into the channel by a tappet 68 so that the flow cross-section is reduced. The membrane 74 represents - similar to the hose 70 in the variant according to Figure 7a - a sterile barrier, so that the plunger 68 and any actuating elements coupled thereto, with which the position of the plunger 68 is adjusted, can be designed as separate reusable components and are accordingly not firmly integrated into the cross-flow filtration device 12, while the membrane 74 is a disposable component firmly integrated into the cross-flow filtration device 12.

[0061] In particular, in the last-described variant, compressed gas can also be used to deflect the membrane 74 instead of the plunger 68.

[0062] A valve connection may also be provided at locations other than those described on a disposable filtration module 10, on a disposable flow path or on a cleaning module 30.

[0063] In the Figures 8a and 8b Two variants of a pressure sensor mechanism partially integrated into a cross-flow filtration device 12 are shown, as for example in the Figures 6a to 6c pressure sensor connections 60, 62, 66 shown can be used.

[0064] At the Figure 8aIn the variant shown, a thread 76 is provided at the outer end of the pressure sensor connection 60, e.g., in an opening in the outer wall of the cross-flow filtration device 12, a flange, a connecting piece, or the like, into which a pressure sensor 78 with a matching counter-thread is screwed. A pressure membrane 80 made of an elastomer is clamped at the outer end of the pressure sensor connection 60 such that its pressure-dependent deflection triggers a corresponding signal in the pressure sensor 78. While the pressure membrane 80 is a disposable component permanently integrated into the cross-flow filtration device 12, the pressure sensor 78 is designed as a reusable, separate component and is not permanently integrated into the cross-flow filtration device 12.

[0065] In contrast to the previously described variant, the Figure 8bIn the variant shown, the pressure sensor 78 is not screwed into a thread of the cross-flow filtration device 12, but rather into a thread 76 formed in an opening of a base plate 82 of the filtration system. On this base plate 82, the cross-flow filtration device 12 with the pressure membrane 80 is arranged and secured above the pressure sensor 78 in such a way that the pressure membrane 80 is deflected toward the pressure sensor 78 when pressure is applied, triggering a corresponding signal in the pressure sensor 78.

[0066] The pressure membrane 80 and / or the pressure sensor 78 can also be provided at locations other than those described on a disposable filtration module 10, on a disposable flow path or on a cleaning module 30.

[0067] Other sensor devices may be provided at such ports on a cross-flow filtration device 12 or at another location on a disposable filtration module 10, on a disposable flow path, or on a purification module 30, such as sensor devices for determining electrical conductivity, pH, viscosity, or protein concentration using a suitable UV sensor or other spectroscopy. In these cases, a permeable membrane or other device for diverting a quantity of fluid is provided instead of the pressure membrane 80.

[0068] The automated filtration system with the described modules 10, 30, and components is primarily intended for concentration and diafiltration (especially for stabilization, final formulation, and / or impurity removal) of protein solutions using crossflow technology. Modules 10, 30, and components can be adapted to various types of crossflow filtration, particularly single-pass, batch, or feed-and-bleed configurations. In principle, the automated filtration system can also be designed for other filtration technologies, such as classic dead-end filtration. Reference symbol list

[0069] 10Filtration module 12Cross-flow filtration device 14Connector (module) 16Recirculation tank 18Sensor device 20Valve 22Pump 24Fluid connection 26Outer wall 28Connector (cross-flow filtration device) 30Cleaning module 32Cleaning fluid tank 34Sensor connection 36Pump mechanism 38Pump hose 40Roller unit 42Piston-cylinder unit 44Piston 46Cylinder 48Pressure device 50Fluid inlet 52Filter device 54Filter membrane 56First fluid outlet 58Second fluid outlet 60First pressure sensor connection 62Second pressure sensor connection 64Valve connection 66Third pressure sensor connection 68Plunger 70Hose 72Seal 74Diaphragm 76Thread 78Pressure sensor 80Pressure diaphragm 82Base plate

Claims

1. Modular cross-flow filtration system, for low-volume screening applications, comprising a prefabricated filtration module (10), wherein the filtration module (10) includes fluid ports (24) and a plurality of components adjusted to low-volume screening applications, which are firmly integrated into the filtration module (10), wherein the entire filtration module (10) is designed as a single-use filtration module, and a cleaning module (30) for cleaning reusable components of the filtration system, wherein the entire cleaning module (30) is designed as a single-use cleaning module and includes a firmly integrated cleaning fluid container (32) filled with a cleaning fluid, wherein the fluid ports (24) and the mechanical ports of the filtration module (10) and the cleaning module (30) are constructed such that they can alternatively be arranged and connected at the same point in the filtration system.

2. Modular cross-flow filtration system according to claim 1, characterized by a separate single-use cross-flow filtration device (12) comprising a filter, which is plugged into or onto the filtration module (10) as a unit.

3. Modular cross-flow filtration system according to claim 1, characterized by a firmly integrated cross-flow filtration device (12) comprising a filter.

4. Modular cross-flow filtration system according to any one of the preceding claims, characterized by a single-use flow path in the filtration module (10), into which at least one of the following components is at least partly firmly integrated: a recirculation container (16) for process fluid; a sensor (18); a flow valve (20); a pump (22); a storage container for a diafiltration medium; a port for supplying a medium from an external source.

5. Modular cross-flow filtration system according to claim 3 and claim 4, characterized in that the filtration device (12) is firmly integrated into the single-use flow path.

6. Modular cross-flow filtration system according to any one of the preceding claims, characterized by a temperature control for the filtration module (10), wherein preferably an outer wall (26) of the filtration module (10) is coupled to a temperature-controlled surface, in particular of a Peltier element.

7. Modular cross-flow filtration system according to any one of claims 2 to 6, characterized by at least one pump mechanism (36) which is at least partly formed of single-use components which are firmly integrated into the filtration module (10), in particular into the filtration device (12), wherein preferably the pump mechanism (36) includes a single-use pump hose (38) and a reusable drive, in particular with a rotor and a roller unit (40) mounted thereon for deforming the single-use pump hose (38), or the pump mechanism (36) includes a single-use piston-cylinder unit (42) or a single-use pressing device (48) and a reusable drive for actuating the piston (44) or the pressing device (48).

8. Modular cross-flow filtration system according to any one of the preceding claims, characterized in that the filtration module, in particular the filtration device (12), includes at least one valve port (64) on which a valve mechanism partly formed of single-use components is arranged, wherein the single-use components are firmly integrated into the filtration module (10), in particular into the filtration device (12).

9. Modular cross-flow filtration system according to claim 8, characterized in that the valve mechanism includes a flexible single-use hose (70) and a reusable guided tappet (68), by means of which the flow cross-section of the single-use hose (70) can be changed.

10. Modular cross-flow filtration system according to claim 8, characterized in that the valve mechanism includes a single-use tappet (68) guided in a single-use seal (72), which tappet can penetrate into a flow channel of the filtration module (10), in particular into a flow channel of the filtration device (12).

11. Modular cross-flow filtration system according to claim 8, characterized in that the valve mechanism includes an elastic single-use membrane (74) which by means of a reusable tappet (68) can be pressed into a flow channel of the filtration module (10), in particular into a flow channel of the filtration device (12).

12. Modular cross-flow filtration system according to claim 9 or 11, characterized in that, instead of the reusable tappet (68), a compressed gas source is provided for pressurizing the single-use hose (70) or the single-use membrane (74).

13. Modular cross-flow filtration system according to any one of the preceding claims, characterized in that the filtration module (10), in particular its filtration device (12), includes at least one sensor port (34) on which a sensor device (18), in particular a pressure sensor device, partly formed of single-use components is arranged, wherein the single-use components are firmly integrated into the filtration module (10), in particular into the filtration device (12), wherein preferably a single-use membrane (74), in particular a pressure membrane, is stretched over an orifice of the sensor port (34), which membrane cooperates with a reusable sensor device (18), in particular a pressure sensor (78), arranged on the orifice.