Device and method for tangential flow filtration of fluid

Abstract

To provide a device and a method for tangential flow filtration of a fluid that can adjust the transmembrane pressure and / or the tangential flow.SOLUTION: A device for tangential flow filtration includes: a filter unit having first and second fluid openings, a filter element, and a permeate opening; a first flow connection to connect the first fluid opening to a reservoir; a second flow connection to connect the second fluid opening to the reservoir; a first centrifugal pump in the first flow connection for conveying the fluid from the reservoir to the filter unit, the filter unit designed such that the fluid flows substantially parallel to the filter element; and a second centrifugal pump in the second flow connection, with which a counter-pressure is capable of being generated at the second fluid opening.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to an apparatus and a method for tangential flow filtration according to the preambles of the patent independent claims of each category. The present invention further relates to a set of disposable parts for such an apparatus.

Background Art

[0002] Tangential flow filtration, also called cross-flow filtration, is a well-known method for filtering fluids and is used, for example, in the biotechnology and chemical industries, as well as in the food and pharmaceutical industries. In tangential flow filtration, the fluid to be filtered, for example a suspension, is guided parallel to the filter element, for example a filter membrane, at a flow rate different from zero, and the permeate, also referred to as the filtrate, is removed transversely to the direction of flow. Due to the relatively high flow rate, it is necessary to avoid as much as possible the accumulation of a filter cake or a covering layer on the filter element.

[0003] Tangential flow filtration is often carried out as a batch process in which the fluid to be filtered, for example a suspension, is taken out of a reservoir and conveyed by a conveying pump through a filter unit in which a filter element is arranged, and then induced back from the filter unit to the reservoir. The permeate passing through the filter element in the filter unit across the flow direction is discharged or removed through a permeate opening. A flexible tube or a flexible tube connection is often selected for the flow connection between the reservoir and the filter unit.

[0004] In such a process, tangential flow filtration can be used to concentrate the fluid (e.g., the suspension) by circulating the suspension several times and filtering out the liquid components, such as water or nutrient solution, that are removed as permeate, thus increasing the concentration of the suspension in the reservoir. However, it is also possible to remove substances recovered by tangential flow filtration, such as proteins, as permeate.

[0005] In particular, tangential flow filtration is also known to be used in combination with bioreactors in both continuous and batch processes, for example, in processes for culturing cells or other biological materials. For example, a perfusion process using a bioreactor used for continuous cell culture is known, where, for example, cellular metabolites are separated by tangential flow filtration and the cells are guided back into the bioreactor. For example, a nutrient solution for the cells can be continuously supplied to the bioreactor, thereby replacing the mass or volume of the filtered components. Especially for such applications in perfusion bioreactors, there is a growing trend today to design the components of the device as disposable parts in order to avoid or reduce time-consuming sterilization processes.

[0006] One of the parameters that significantly affects the efficiency of tangential flow filtration is the pressure drop across the filter element, which causes the permeate to move through the filter element. A commonly used variable to measure this parameter is the transmembrane pressure (TMP), which is defined as the arithmetic mean of the pressure drop across the filter element. If P1 represents the fluid pressure at the inlet of the filter element, P2 represents the pressure at the outlet of the filter element, and P3 represents the pressure at the permeate opening, then the transmembrane pressure TMP is defined as follows: (Math 1) TMP = (P1 + P2) / 2 - P3

[0007] Transmembrane pressure is also expressed as transmembrane pressure difference. Increasing the fluid flow resistance downstream of the filter unit is a known method to increase the flow of permeate through the filter element, thereby increasing the pressure P2 at the outlet of the filter element. This results in an increase in the transmembrane pressure TMP, which in turn increases the flow of permeate.

[0008] Typically, the flow resistance downstream of a filter unit, and therefore the pressure P2 at the outlet of the filter element, is achieved by narrowing the free flow cross-sectional area of ​​the fluid. This narrowing is known to be achieved by using proportional or (tubular) pinch valves. However, this technique has significant drawbacks.

[0009] Because the relationship between the pinch valve position and the transmembrane pressure is highly nonlinear, even when the conveying pump is delivering at a constant rate, the desired transmembrane pressure can only be adjusted by adjusting the pinch valve over a long period of time. Furthermore, the adjustment range of the pinch valve that allows for at least approximate adjustment of the desired transmembrane pressure is extremely narrow. For example, for known pinch valves, this range may correspond to a pinch device stroke significantly smaller than 1 millimeter.

[0010] Because the cross-sectional area of ​​the flow in a pinch valve is narrowed, very high shear forces can be generated, which can damage the fluid (e.g., particles, cells, or macromolecules such as proteins contained in a suspension). Therefore, undesirable degradation can occur in the fluid or its components. These high shear forces are also caused by high flow velocities, particularly due to the reduction in the cross-sectional area of ​​the flow.

[0011] A further disadvantage is that deformation of the tube within the pinch valve can cause particles to be released from the tube, contaminating the fluid. This poses a significant risk, especially in biotechnology or pharmaceutical applications. [Overview of the project] [Problems that the invention aims to solve]

[0012] Therefore, starting with this cutting-edge technology, the object of the present invention is to propose an apparatus and method for tangential flow filtration of fluids that can reliably control the transmembrane pressure and / or tangential flow with very high precision and in a simple manner over the widest possible operating range. [Means for solving the problem]

[0013] Subject matter that fulfills this purpose is characterized by the structure of the patent-independent claims in each category.

[0014] Accordingly, according to the present invention, an apparatus for tangential flow filtration of a fluid is proposed, comprising a filter unit having a first fluid opening and a second fluid opening for the fluid, as well as a filter element and a permeate opening for discharging a permeate filtered from the fluid, the apparatus further comprising a first flow connection to which the first fluid opening can be connected to a reservoir for the fluid, and a second flow connection to which the second fluid opening can be connected to a reservoir for the fluid, a first centrifugal pump provided at the first flow connection to transport the fluid from the reservoir to the filter unit, a first control unit provided to operate the first centrifugal pump, and the filter unit is designed so that the fluid for tangential flow filtration within the filter unit can flow substantially parallel to the filter element. A second centrifugal pump for the fluid is provided at the second flow connection to generate back pressure at the second fluid opening, and a second control unit provided to operate the second centrifugal pump.

[0015] Accordingly, according to the present invention, in addition to a first centrifugal pump whose main function is to transport or circulate fluid through the filter unit, a second centrifugal pump is provided at a second flow connection, which is connected to a second fluid opening of the filter unit. This second centrifugal pump operates in the opposite direction to the first centrifugal pump and can therefore generate a back pressure at the second fluid opening, resulting in an increase in the pressure at the second fluid opening. In this way, the pressure drop across the filter element is increased, thereby increasing the flow of the permeate. It is particularly advantageous that there is no need to insert a second flow connection to increase the pressure at the second fluid opening, and the cross-section of the free flow at the second flow connection does not need to be altered by other means. In this way, the high nonlinearity of devices known from state-of-the-art technology can be avoided. The fluid pressure at the second fluid opening can be adjusted by the second centrifugal pump with high precision in a simple manner, reproducibly and reliably over a wide operating range.

[0016] Due to the fact that means for reducing the flow cross-section at the second flow connection can be omitted according to the present invention, that is, for example, by omitting pinching at the tube connection, the associated significantly increased flow velocity can also be avoided, resulting in very low shear forces acting on the fluid or its components. This is particularly advantageous with respect to the gentlest possible handling of the fluid or its components. Therefore, a particular advantage of the apparatus according to the present invention is that the apparatus can be designed without pinch valves or other elements for reducing the flow cross-section, especially at the second flow connection.

[0017] Furthermore, strong mechanical deformation at the second flow connection, which is unavoidable, for example when using a pinch valve, can be avoided by the solution according to the present invention. In this way, it is possible to prevent particles from escaping from the second flow connection, such as a tube connection, and contaminating the fluid.

[0018] According to one preferred embodiment, the apparatus includes a flow sensor for determining the flow rate of fluid through a first flow connection, and a first control unit is designed to adjust the flow rate to a desired value via the operating parameters of the first centrifugal pump, particularly the rotational speed. Thus, in this embodiment, the first centrifugal pump is used to adjust or regulate a predetermined desired value for the fluid flow through the first flow connection.

[0019] Furthermore, it is preferable that multiple pressure sensors are provided, arranged such that the transmembrane pressure can be determined by the multiple pressure sensors via a filter element, and that a second control unit is designed so that the second control unit can adjust the transmembrane pressure to a desired value via the operating parameters of the second centrifugal pump, particularly the rotational speed. Thus, in this embodiment, the transmembrane pressure is adjusted or regulated to a desired value by the second centrifugal pump.

[0020] Preferably, the multiple pressure sensors include a first pressure sensor capable of determining a first fluid pressure at a first fluid opening, a second pressure sensor capable of determining a second fluid pressure at a second fluid opening, and a third pressure sensor capable of determining a third pressure at a permeate opening. In this way, the actual value of the transmembrane pressure can be determined in a very simple and accurate manner.

[0021] In another preferred embodiment, a central control unit is provided that is signal-connected to a first control unit and a second control unit, and the central control unit is designed to operate the first control unit and the second control unit. Thus, in addition to operating the first and second centrifugal pumps independently of each other, it is also possible to provide a central control unit that operates the first and second control units for the first and second centrifugal pumps in a coordinated manner. One advantage of embodiments with a central control unit is that, in the case of a single centrifugal pump, quadratic terms arising from the fact that the pressure, or more precisely the discharge head, is proportional to the square of the rotational speed of the centrifugal pump can be eliminated in operation or regulation.

[0022] Particularly preferably, the second centrifugal pump includes a rotor for conveying fluid and a stator that, together with the rotor, forms an electromagnetic rotation drive for rotating the rotor axially, wherein the rotor includes a magnetically active core and a plurality of vanes for conveying fluid, and the stator is designed as a bearing-drive stator that can magnetically drive the rotor non-contact and can magnetically levitate the rotor non-contact. Thus, non-contact magnetic levitation of the rotor eliminates the need for mechanical bearings, which could lead to fluid contamination due to wear, for example. Non-contact magnetic levitation of the rotor also allows for very precise and easy adjustment of the pressure generated by the second centrifugal pump, for example, via the rotational speed of the rotor.

[0023] Alternatively, but preferably complementary, the first centrifugal pump includes a rotor for conveying fluid and a stator that, together with the rotor, forms an electromagnetic rotary drive for rotating the rotor axially, wherein the rotor includes a magnetically active core and a plurality of vanes for conveying fluid, and the stator is designed as a bearing-drive stator that can magnetically drive the rotor non-contact and magnetically levitate the stator non-contact.

[0024] Therefore, it is possible to design only the first centrifugal pump having a rotor that can be magnetically driven and magnetically levitated in a non-contact manner with respect to the stator, or only the second centrifugal pump having a rotor that can be magnetically driven and magnetically levitated in a non-contact manner with respect to the stator. Preferably, both the first and second centrifugal pumps are each designed with a rotor that can be magnetically driven in a non-contact manner and magnetically levitated in a non-contact manner with respect to the stator.

[0025] Regarding the magnetic levitation of the rotor, it is particularly preferable that each rotor is actively magnetically levitated in a radial plane perpendicular to the axial direction and is passively magnetically stabilized with respect to the inclination in the axial direction.

[0026] A particularly preferred embodiment is an embodiment as a template motor. Each stator includes a plurality of coil cores each including a longitudinal limb portion extending in the axial direction and a lateral limb portion disposed in a radial plane and extending radially from the longitudinal limb portion, and at least one concentrated winding is disposed on each longitudinal limb portion surrounding each longitudinal limb portion. The embodiment as a template motor is a particularly compact and efficient embodiment.

[0027] According to a particularly preferred embodiment, each centrifugal pump includes a pump unit each having a pump housing. The pump housing includes an inlet and an outlet for conveying fluid. The rotor is disposed within the pump housing and includes a plurality of vanes for conveying fluid. The pump unit is designed such that the pump unit can be inserted into the stator.

[0028] Preferably, some components of the device, particularly those in contact with the fluid, are designed as disposable parts that can be used only once according to the purpose of use and need to be replaced with new, i.e., unused, disposable parts after this use. The device according to the present invention is designed in this way.

[0029] Therefore, a set of disposable parts for the apparatus according to the present invention is further proposed by the present invention, which comprises at least the following components: Filter unit and Each centrifugal pump has one pump unit, Multiple tubes designed to realize a first flow connection and a second flow connection, Optionally, it includes a reservoir for the fluid or an insert for the reservoir, with each component designed as a disposable part.

[0030] It should be understood that this list of components designed as disposable parts is not exhaustive. The set of disposable parts may include other disposable parts, such as components of a pressure sensor.

[0031] Furthermore, the present invention further proposes a method for tangential flow filtration of a fluid, in which a fluid is supplied to a filter unit having a first fluid opening and a second fluid opening for the fluid, as well as a filter element and a permeate opening for discharging the permeate filtered from the fluid, the filter unit being designed so that the fluid for tangential flow filtration within the filter unit is guided substantially parallel to the filter element, in which the fluid is further transported from a reservoir through a first flow connection to the filter unit by a first centrifugal pump, the fluid can be guided back to the reservoir through a second fluid opening and a second flow connection, the first centrifugal pump being operated by a first control unit. A back pressure is generated at the second fluid opening using a second centrifugal pump provided at the second flow connection, the second centrifugal pump being operated by a second control unit.

[0032] The advantages of the method according to the present invention are the same as those already described in relation to the apparatus according to the present invention.

[0033] Preferably, the flow rate of the fluid through the first flow connection is determined by a flow sensor, and a desired value of the flow rate is determined by a first control unit via the operating parameters of the first centrifugal pump, particularly the rotational speed.

[0034] Furthermore, it is preferable that the first pressure at the first fluid opening is determined by a first pressure sensor, or the second pressure at the second fluid opening is determined by a second pressure sensor, or the third pressure at the permeate opening is determined by a third pressure sensor, and the desired value of the first, second, or third pressure is adjusted by a second control unit via the operating parameters of the second centrifugal pump, particularly the rotational speed.

[0035] Furthermore, the transmembrane pressure is determined by multiple pressure sensors via a filter element, and a desired value of the transmembrane pressure is adjusted by a first or second control unit via the operating parameters of a first centrifugal pump or a second centrifugal pump, wherein the operating parameters are preferably the rotational speed of the first or second centrifugal pump.

[0036] In one preferred variation, tangential flow filtration is performed in alternating modes, which include a first operating mode in which the fluid flows from a first fluid inlet to a second fluid inlet, and a second operating mode in which the fluid flows from the second fluid inlet to the first fluid inlet. This means that the two centrifugal pumps are operated such that the fluid to be filtered flows from a first centrifugal pump through the filter unit to the second centrifugal pump in the first operating mode, and in the second operating mode in the opposite direction from the second centrifugal pump through the filter unit to the first centrifugal pump. This can be achieved, in particular, by operating the two centrifugal pumps in the second operating mode such that the back pressure generated by the second centrifugal pump at the second fluid inlet is greater than the pressure generated by the first pump at the first fluid inlet of the filter unit.

[0037] The direction of flow in the two operating modes is determined by the pressure difference generated by the two centrifugal pumps in each mode.

[0038] The advantage of this operation in alternating mode is that the filter elements alternately overflow in opposite directions, which in many applications more efficiently avoids accumulation on the filter elements or buildup of unwanted filter cake on the filter elements.

[0039] In alternating mode, the change between the first operating mode and the second operating mode is preferably performed according to a predetermined time scheme.

[0040] It is possible to run the first and second operating modes in a 50%:50 ratio, but of course, other ratios such as 75%:25% are also possible. The appropriate ratio can be selected according to the application, or optimized for each application.

[0041] The frequency of change between the first and second operating modes can also be adjusted as needed. Furthermore, for each operating mode, the respective flow rate or one of the three pressures, namely the pressure at the first fluid opening, the pressure at the second fluid opening, or the pressure at the permeate opening, and therefore the transmembrane pressure, can also be adjusted as needed.

[0042] Further advantageous means and embodiments of the present invention arise from the dependent claims.

[0043] The present invention will be described in more detail below, based on embodiments and drawings, from the viewpoint of both apparatus and process technology. The drawings (partially in cross-sectional views) are shown below. [Brief explanation of the drawing]

[0044] [Figure 1] A schematic diagram of a first embodiment of the apparatus according to the present invention for tangential flow filtration. [Figure 2] A schematic diagram of the first embodiment in the second operating mode. [Figure 3] Modified form of the first embodiment, [Figure 4] A schematic diagram of a second embodiment of the apparatus according to the present invention for tangential flow filtration. [Figure 5] A schematic diagram of the second embodiment in the second operating mode. [Figure 6] A perspective view of an electromagnetic rotary drive designed as a temple motor. [Figure 7] An embodiment of a centrifugal pump having a rotor that can be magnetically levitated without contact in the axial cross-section. [Figure 8] A schematic diagram showing one embodiment of a reservoir. [Modes for carrying out the invention]

[0045] Figure 1 is a schematic diagram of a first embodiment of the apparatus according to the present invention for tangential flow filtration of a fluid, which is collectively denoted by reference numeral 1. The fluid is, for example, a suspension from which at least one component is filtered. Here, the filtered component discharged as permeate may be a target product (e.g., a protein) recovered during filtration, or the fluid remaining as a retaining solution after filtering the permeate may be a target product to be concentrated by filtration, for example, one or more components of the fluid.

[0046] The tangential flow filtration apparatus 1 includes a filter unit 2 on which filter elements 25 are arranged, a first flow connection 31 that can connect the filter unit 2 to a fluid reservoir 8, and a second flow connection 32 that can connect the filter unit 2 to the reservoir 8.

[0047] For example, reservoir 8 can also be a bioreactor for a perfusion process for continuous cell culture, thereby using filter unit 2 to filter and remove cell metabolites or to obtain cell-free medium, and the cells or cell-containing suspension is then returned to the bioreactor.

[0048] A first centrifugal pump 41 for the fluid is located in a first flow connection 31 having a fluid inlet 411 and an outlet 412. Furthermore, a first control unit 51 is provided to operate the first centrifugal pump 41. Preferably, the first control unit 51 includes a control device that can adjust the operation of the first centrifugal pump 41.

[0049] A second centrifugal pump 42 for the fluid is located in a second flow connection 32 having a fluid inlet 421 and an outlet 422. Furthermore, a second control unit 52 is provided to operate the second centrifugal pump 42. Preferably, the second control unit 52 includes a control device that can adjust the operation of the second centrifugal pump 42.

[0050] The second centrifugal pump 42 is positioned in this manner and operated to move in the opposite direction to the first centrifugal pump 41. This means that the outlet 412 of the first centrifugal pump 41 is connected to the outlet 422 of the second centrifugal pump 42 via the filter unit 2. Both the outlet 412 of the first centrifugal pump 41 and the outlet 422 of the second centrifugal pump 42 are connected to the filter unit 2, respectively.

[0051] The fluid flow, particularly the direction of the flow, is represented in Figure 1 by arrows denoted by the symbol F.

[0052] The filter unit 2 includes a first fluid opening 21 and a second fluid opening 22 for the fluid, as well as a permeate opening 23 for discharging the permeate filtered from the fluid, indicated by the arrow labeled P in Figure 1.

[0053] In the direction of flow F shown in Figure 1, the first fluid opening 21 functions as an inlet to the filter unit 2 through which the fluid flows in, and the second fluid opening 22 functions as an outlet through which the retaining liquid flows out of the filter unit 2.

[0054] Filter unit 2 is designed for tangential flow filtration, also known as cross-flow filtration. This means that the fluid within filter unit 2 is guided parallel to the filter element 25, resulting in the fluid flowing across the entire filter element 25 and filtration from the permeate occurring perpendicular to the direction of fluid flow.

[0055] Such filter units 2 designed for tangential flow filtration are well known to those skilled in the art from the latest technology and therefore require no further explanation.

[0056] The substantial variable in tangential flow filtration is the pressure difference across the filter element 25 that drives the filtration from the permeate. As is common practice, this pressure difference across the filter element 25 is also characterized by the so-called transmembrane pressure (TMP) within the framework of this application. The transmembrane pressure (TMP) is a mathematical variable that represents the arithmetic mean of the pressure drops across the filter element 25.

[0057] The fluid pressure at the first fluid opening 21 is shown as the first pressure P1. The fluid pressure at the second fluid opening 22 is shown as the second pressure P2. The fluid pressure at the permeate opening 23 is shown as the third pressure P3. The transmembrane pressure TMP is defined as follows: (Math 2) TMP = (P1 + P2) / 2 - P3

[0058] Transmembrane pressure is also called transmembrane pressure difference.

[0059] The first flow connector 31 and the second flow connector 32 are preferably realized by pipes designed as flexible pipes, i.e., pipes whose walls can be deformed. Each pipe is designed as a tube (particularly as a plastic tube) (e.g., made of silicone rubber, PVC (polyvinyl chloride), PU (polyurethane), PE (polyethylene), HDPE (high-density polyethylene), PP (polyethylene), EVA (ethyl vinyl acetate), or nylon). Preferably, each tube belonging to the first flow connector 31 or the second flow connector 32 is designed for single use. When designed for single use, their components that come into contact with the material being processed (i.e., the tubes in this case) are used exactly once and then replaced with new (i.e., unused) disposable parts between uses.

[0060] The first flow connection section 31 includes a supply tube 311 that connects the first opening 81 of the reservoir 8 to the inlet 411 of the first centrifugal pump 41, and a supply tube 312 that connects the outlet 412 of the first centrifugal pump 41 to the fluid opening 21 of the filter unit 2.

[0061] Furthermore, a flow sensor 6 is provided to determine the flow rate of the fluid passing through the first flow connection 31. For example, the flow sensor 6 is provided in or on the supply tube 311 of the first flow connection 31, i.e., between the reservoir 8 and the first centrifugal pump 41. In particular, the flow sensor 6 can be designed as a so-called clamp-on sensor, i.e., the flow sensor 6 is clamped on the supply tube 311 so that the supply tube 311 is clamped within the measuring range of the flow sensor 6.

[0062] The second flow connection section 32 includes a discharge tube 322 that connects the second fluid opening 22 of the filter unit 2 to the outlet 422 of the second centrifugal pump 42, and a return tube 321 that connects the inlet 421 of the second centrifugal pump 42 to the second opening 82 of the reservoir 8.

[0063] In this way, both the outlet 412 of the first centrifugal pump 41 and the outlet 422 of the second centrifugal pump 42 are connected to the filter unit 2, that is, the outlet 412 of the first centrifugal pump 41 is connected to the first fluid opening of the filter unit 2, and the outlet 422 of the second centrifugal pump 42 is connected to the second fluid opening 22 of the filter unit 2. Therefore, the second centrifugal pump 42 can generate back pressure at the second fluid opening 22, and thus the second pressure P2 can be adjusted at the second fluid opening 22.

[0064] In operation, the first centrifugal pump 41 functions to move the fluid through the filter unit 2 and filter element 25. The first centrifugal pump 41 circulates the fluid from the reservoir 8 through the first flow connection 31, through the filter unit 2, through the second flow connection 32, and back to the reservoir 8.

[0065] In operation, the second centrifugal pump 42 functions to generate a back pressure at the second fluid opening 22 of the filter unit 2, that is, the second centrifugal pump 42 is operated to increase the dominant second pressure P2 at the second fluid opening 22 of the filter unit 2.

[0066] Preferably, the apparatus 1 further includes a plurality of pressure sensors 71, 72, 73, which are arranged and designed to be used to determine the TMP via a filter element 25.

[0067] In the embodiment shown in Figure 1, a total of three pressure sensors 71 are provided: a first pressure sensor 71 capable of determining a first fluid pressure P1 at a first fluid opening 21, a second pressure sensor 72 capable of determining a second fluid pressure P2 at a second fluid opening 22, and a third pressure sensor 73 capable of determining a third pressure P3 at a permeate opening 23.

[0068] It is understood that embodiments of the apparatus 1 according to the present invention are also possible in which only one of the pressure sensors 71, 72, and 73 is provided (for example, only the first pressure sensor 71, or only the second pressure sensor 72, or only the third pressure sensor 73). Furthermore, embodiments are also possible in which exactly two pressure sensors are provided (i.e., only the first pressure sensor 71 and the second pressure sensor 72, or only the first pressure sensor 71 and the third pressure sensor 73, or only the second pressure sensor 72 and the third pressure sensor 73).

[0069] The number of pressure sensors 71, 72, and 73, and which pressure sensors 71, 72, and 73 are provided, depend in particular on the specific design of the regulating device or control system in which the method according to the present invention is implemented.

[0070] In the first embodiment shown in Figure 1, the first pressure sensor 71 is provided between the first centrifugal pump 41 and the filter unit 2, i.e., in or on the supply tube 312. The second pressure sensor 72 is provided between the filter unit 2 and the second centrifugal pump 42, i.e., in or on the discharge tube 322. The third pressure sensor 73 is located in or downstream of the permeate opening 23.

[0071] The method according to the present invention preferably uses the apparatus 1 according to the present invention, in which one of the two centrifugal pumps 41 or 42 is used to adjust or regulate the flow rate to a desired value, and the other of the two centrifugal pumps 42 or 41 is used to adjust or regulate the transmembrane pressure (TMP) to a desired value.

[0072] Therefore, it is preferable that, in order to adjust the flow rate and TMP to desired values, each adjustment is performed by the first control unit 51 or the second control unit 52, respectively, via the operating parameters of the first centrifugal pump 41 or the second centrifugal pump 42. Particularly preferable is that each operating parameter is the rotational speed of the first centrifugal pump 41 or the second centrifugal pump 42.

[0073] The following describes some variations of the operation of apparatus 1. A common feature of these variations is that the first control unit 51 is used for flow control, that is, to adjust the flow of fluid through the first flow connection 31 to a desired value of flow rate. The second control unit 52 is used for pressure adjustment, that is, to adjust the transmembrane pressure (TMP) to a desired value of TMP, or to adjust the first pressure P1, the second pressure P2, or the third pressure P3 to their respective desired values. Thus, the second control unit 52 is used for pressure adjustment.

[0074] The two control units 51 and 52 can each be designed as independent control units 51 and 52. It is not necessary for control units 51 and 52 to exchange signals or information with each other, but it is possible.

[0075] The first control unit 51 receives a first input variable E1 which may include one or more measurement signals or actual and / or desired values, and determines a first output variable A1 by the first input variable E1, thereby operating the first centrifugal pump 41 to adjust or maintain a desired flow rate. The first output variable A1 may include, in particular, information that can adjust the rotational speed of the first centrifugal pump 41, or a value of the rotational speed of the first centrifugal pump 41.

[0076] The second control unit 52 receives a second input variable E2 which may contain one or more measurement signals or actual and / or desired values, and determines a second output variable A2 by the second input variable E2, thereby operating the second centrifugal pump 42 to adjust or maintain a desired value of TMP or first pressure P1 or second pressure P2 or third pressure P3. The second output variable A2 may include, in particular, information that can adjust the rotational speed of the second centrifugal pump 52, or a value of the rotational speed of the second centrifugal pump 42.

[0077] According to the first modification, the first input variable E1 includes a desired value for the flow rate and the actual value of the flow rate determined with the help of the flow sensor 6. The rotational speed of the first centrifugal pump 41 is changed by the first output variable A1 so that the actual value of the flow rate is adjusted to the desired value of the flow rate. The second input variable E2 includes the actual values ​​of the first pressure P1, the second pressure P2, and the third pressure P3, as well as a desired value for TMP. The rotational speed of the second centrifugal pump 42 is changed by the second output variable A2 so that the actual value of TMP is adjusted to the desired value of TMP. The actual value of TMP can be determined, for example, from three pressures P1, P2, and P3.

[0078] In a further modification, the first input variable E1 includes a desired value of the flow rate and the actual value of the flow rate determined with the help of the flow sensor 6. The rotational speed of the first centrifugal pump 41 is changed by the first output variable A1 so that the actual value of the flow rate is adjusted to the desired value of the flow rate. The second input variable E2 includes only one actual value of pressure P1, P2, or P3, i.e., the actual value of the first pressure P1, or the actual value of the second pressure P2, or the actual value of the third pressure P3. The second input variable E2 further includes a desired value of this pressure, i.e., the desired value of the first pressure P1, or the desired value of the second pressure P2, or the desired value of the third pressure P3. The rotational speed of the second centrifugal pump 42 is changed by the second output variable A2 so that the actual value of pressure P1, P2, or P3 is adjusted to the desired value of this pressure P1, P2, or P3. In this modified example, both the flow rate control of the first control unit 51 and the pressure control of the second control unit 52 are preferably designed as proportional-integral (PI) control, respectively.

[0079] Depending on the application, the tangential flow filtration method may be performed as a batch process in which the fluid to be filtered (e.g., a suspension) is drawn from the reservoir 8 by a first centrifugal pump 41, passes through a first flow connection 31, through a filter unit 2 in which a filter element 25 is located, and returns to the reservoir 8 through a second flow connection 32. Permeate passing through the filter element 25 in the filter unit 2 in a direction perpendicular to the flow direction is discharged or removed through a permeate opening 23. This generates a back pressure by the second centrifugal pump 42, which adjusts the second pressure P2 at the second fluid opening 22. The first control unit 51 adjusts the fluid flow rate to a desired value via the first centrifugal pump 41, preferably via the rotational speed of the first centrifugal pump 41. The second control unit 52 adjusts the pressure, preferably TMP, or the first pressure P1, the second pressure P2, or the third pressure P3, to a desired value of this pressure via the second centrifugal pump 42, preferably via the rotational speed of the second centrifugal pump 42.

[0080] However, for example, in applications using perfusion bioreactors for the continuous removal of metabolites, it is also possible to implement a method for tangential flow filtration as a continuous method.

[0081] According to the first modification for carrying out this method, the fluid is always circulated through the apparatus 1 in the same direction throughout the entire filtration process, i.e., for example, throughout the entire batch process or throughout the entire continuous process.

[0082] According to another modification for carrying out the method according to the present invention, tangential flow filtration is carried out in alternating mode. The alternating mode includes a first operating mode in which the fluid flows through the filter unit 2 from the first fluid opening 21 to the second fluid opening 22, as described above, and a second operating mode in which the direction of fluid flow is reversed, so that in the second operating mode the fluid flows from the second fluid opening 22 to the first fluid opening 21 of the filter unit 2.

[0083] In Figure 2, the second operating mode is shown in a schematic diagram of the first embodiment of device 1, and Figure 2 otherwise corresponds to Figure 1.

[0084] The change from the first operating mode to the second operating mode can be achieved in a simple manner by operating the two centrifugal pumps 41 and 42. For example, in the second operating mode, the two centrifugal pumps 41 and 42 are operated such that the back pressure generated by the second centrifugal pump 42 is so large that the second pressure P2 at the second fluid opening 22 of the filter unit 2 is greater than the first pressure P1 generated by the first centrifugal pump 41 at the first fluid inlet 21 of the filter unit 2.

[0085] In the second operating mode, it is preferable that the functions of the first control unit 51 and the second control unit 52 are swapped compared to the first operating mode. Therefore, in the second operating mode, the second control unit 52 is preferably used for flow rate adjustment, i.e., to adjust the fluid flow rate to a desired value. The first control unit 51 is used for pressure adjustment, i.e., to adjust the transmembrane pressure (TMP) to a desired value, or to adjust the first pressure P1, the second pressure P2, or the third pressure P3 to their respective desired values. Here, the first control unit 51 is thus used for pressure adjustment.

[0086] Therefore, in the second operating mode, the second control unit 52 receives a first input variable E1 which can include one or more measurement signals or actual and / or desired values ​​as described above, and the second centrifugal pump 42 determines a first output variable A1 with the help of the first input variable E1 which is actuated to adjust or maintain a desired value of flow rate.

[0087] The first control unit 51 receives a second input variable E2 which may include one or more measurement signals or actual and / or desired values ​​as described above, and determines a second output variable A2 with the help of the second input variable E2 which is actuated to adjust or maintain a desired value of TMP or first pressure P1 or second pressure P2 or third pressure P3.

[0088] Implementing the tangential flow filtration method in alternating mode has the advantage that the filter elements 25 alternately overflow in opposite directions, thereby more efficiently avoiding deposits on or accumulation of undesirable filter cake on the filter elements 25 in many applications. By reversing the direction of flow, it is also possible to remove (at least partially) any deposits already formed on or inside the filter elements 25.

[0089] By reversing the flow direction, clogging or partial clogging of the filter element 25 is prevented or at least reduced, thus maintaining the permeability of the filter element and thus increasing the yield of the permeate compared to, for example, operation with only one flow direction. Furthermore, compared to operation with only one flow direction, the filter unit 2 or filter element 25 can be used for a longer period of time.

[0090] In alternating mode, the change between the first operating mode and the second operating mode is preferably performed according to a predetermined time scheme.

[0091] The differential pressure between the two pressures generated by the first centrifugal pump 41 and the second centrifugal pump 42, which ultimately determines the direction of fluid flow through the filter unit, and thus the difference between the first pressure P1 and the second pressure P2, can be adjusted independently for each operating mode. In particular, with respect to the amount of operation in the first operating mode, a different value can be adjusted for the difference between the first pressure P1 and the second pressure P2 compared to the second operating mode. Furthermore, for example, it is possible to adjust or regulate a different transmembrane pressure (TMP) in the first operating mode than in the second operating mode. It is also possible to adjust or regulate a different fluid flow rate in the first operating mode than in the second operating mode.

[0092] The number of changes or the frequency of changes between the first and second operating modes can also be freely adjusted and optimized for each application.

[0093] The percentage of the first or second operating mode in the entire tangential flow filtration process can also be freely selected. For example, it is possible to run the first and second operating modes in a 50%:50 ratio, i.e., an equal ratio, but of course other ratios are also possible, such as 75%:25% or even 99%:1%. The appropriate ratio can be selected according to the application, or optimized for each application.

[0094] In a figure similar to Figure 1, Figure 3 shows a modified example of the first embodiment of the apparatus according to the present invention.

[0095] In this modification of Apparatus 1, a viscosity sensor 9 is further provided, for example, located in the second flow connection 32, which can be used to determine the viscosity of the fluid. Preferably, the viscosity sensor 9 is designed for in-line measurement of the fluid viscosity. The viscosity sensor is preferably located in or on the return tube 321 of the second flow connection 32. For example, the viscosity sensor 9 can determine the progression of the fluid concentration, particularly in applications where filtration of permeate from the fluid results in a change in the fluid's viscosity.

[0096] Furthermore, in the modified configuration shown in Figure 3, a second flow sensor 62 is also provided, positioned downstream of the permeate opening 23 (for example, downstream of the third pressure sensor 73). The flow of the permeate filtered from the fluid by the filter element 25 can be determined using the second flow sensor 62, and therefore, for example, by the amount of permeate (amount or volume or mass of substance). From this, information regarding the efficiency of tangential flow filtration can be obtained.

[0097] In some embodiments, both the viscosity sensor 9 and the second flow sensor 62 are provided. In other embodiments, only one of the two elements is provided, either only the viscosity sensor 9 or only the second flow sensor 62.

[0098] Furthermore, instead of using a viscosity sensor, it is possible to determine protein concentration using, for example, an in-line refractometer or an in-line optical spectrometer. However, since such instruments are very expensive, it is important that these devices can be reused without the need to clean and sterilize them before each use. For example, this can be achieved by inserting a component made of transparent plastic, such as polycarbonate, into each tube through which the light from the refractometer or optical spectrometer can be guided. Here, it is advantageous that the inserted component is not circular, but rather designed with flat walls such as a rectangle, hexagon, or octagon.

[0099] In Figures 4 and 5, a second embodiment of the apparatus 1 according to the present invention for tangential flow filtration is shown in schematic diagrams, with Figure 4 showing the second embodiment in the first operating mode and Figure 5 showing the second embodiment in the second operating mode.

[0100] The following description of the second embodiment will focus only on the differences from the first embodiment. The same parts, or functionally equivalent parts, in the second embodiment are indicated by the same reference numerals as in the first embodiment or its variations. In particular, the reference numerals have the same meaning as those already described in relation to the first embodiment. It will be understood that all the preceding descriptions of the first embodiment and its variations also apply to the second embodiment in the same or similar manner.

[0101] In the second embodiment, the apparatus 1 further includes a central control unit 5 which is signal-connected to the first control unit 51 and the second control unit 52, and the central control unit 5 is designed to operate the first control unit 51 and the second control unit 52.

[0102] The second embodiment of Apparatus 1 is particularly advantageous for embodiments in which tangential flow filtration is performed in alternating mode. Of course, the second embodiment of Apparatus 1 is not limited to use in tangential flow filtration in alternating mode, but can also be used in such embodiments of the method according to the present invention in which no reversal of the flow direction occurs during tangential flow filtration.

[0103] In the embodiments shown in Figures 4 and 5, the second embodiment of the device 1 is specifically designed to operate in alternating mode.

[0104] The central control unit 5 receives an input variable E which includes several desired values. The input variable E of the central control unit 5 includes, for example, one or more of the following desired values: a desired value for the first pressure P1, a desired value for the second pressure P2, a desired value for the third pressure P3, a desired value for the transmembrane pressure TMP, a desired value for the fluid flow rate, a desired value for the frequency of change between the first and second operating modes, and a desired value for the relative duty cycle of the first or second operating mode (i.e., the percentage share of the first or second operating mode in tangential flow filtration). Some of the desired values ​​(e.g., desired values ​​for pressures P1, P2, P2 or TMP, or desired values ​​for flow rate) may have different values ​​for the first operating mode than for the second operating mode (but do not necessarily have to).

[0105] The central control unit 5 generates a first control signal S1 from the input variable E to activate the first control unit 51, and generates a second control signal S2 to activate the second control unit 52. The first control signal S1 is transmitted to the first control unit 51, and the second control signal S2 is transmitted to the second control unit 52.

[0106] In the first operating mode, the first control unit 51 receives, in addition to the first control signal S1, an input variable E1 which includes one or more of the following actual values: the actual value of the fluid flow rate, the actual value of the first pressure P1, the actual value of the second pressure P2, and the actual value of the third pressure P3. The first control unit 51 determines a first output variable A1 which operates the first centrifugal pump 41 based on the first control signal S1 and the first input variable E1.

[0107] In the first operating mode, the second control unit 52 receives an input variable E2 in addition to the second control signal S2, which includes, in particular, one or more of the following actual values: the actual value of the fluid flow rate, the actual value of the first pressure P1, the actual value of the second pressure P2, and the actual value of the third pressure P3. The second control unit 52 determines a second output variable A2 in which the second centrifugal pump 42 is operated, based on the second control signal S2 and the second input variable E2.

[0108] In a manner similar to the first embodiment, it is understood that the first control unit 51 can receive the input variable E2 in the second operating mode (Figure 5), and the second control unit 52 can receive the input variable E1.

[0109] In the embodiments shown in Figures 4 and 5, the information received by the first control unit 51 as input variable E1 is identical to the information received by the second control unit as input variable E2. Therefore, in alternating operation mode, the first control unit 51 and the second control unit 52 have all the information available to function as flow control or pressure control depending on the desired direction of fluid flow. Based on the control signals S1 or S2, the first control unit 51 or the second control unit 52 can recognize whether they are currently operating as flow control or pressure control, and when the change from the first operating mode to the second operating mode and vice versa will occur. By controlling both centrifugal pumps 41 and 42, it is possible to achieve both pressure control and flow control simultaneously.

[0110] In principle, all types of centrifugal pumps through which the fluid can move are suitable as the first centrifugal pump 41 and the second centrifugal pump 42.

[0111] Below, with reference to Figures 6 and 7, a type of centrifugal pump particularly preferred for a first centrifugal pump 41 or a second centrifugal pump 42, preferably both the first and second centrifugal pumps 41 and 42, will be described.

[0112] Preferably, both the first centrifugal pump 41 and the second centrifugal pump 42 are designed according to the embodiments shown in Figures 6 and 7. Therefore, in the following description, no further linguistic distinction is made between the first centrifugal pump 41 and the second centrifugal pump 42, but when centrifugal pumps 41 and 42 are referred to, the description applies equally to both the first centrifugal pump 41 and the second centrifugal pump 42.

[0113] Particularly preferred, but not necessarily, the first centrifugal pump 41 and the second centrifugal pump 42 are designed to be at least substantially identical.

[0114] The centrifugal pumps 41 and 42 described below include a rotor 30 for conveying fluid and a stator 20 that, together with the rotor 30, forms an electromagnetic rotary drive 10 for rotating the rotor 30 around an axial direction A. The rotor 30 includes a magnetically active core 301 and a plurality of vanes 305 (Figure 7) for conveying fluid. The stator 20 is designed as a bearing-drive stator that can magnetically drive the rotor 30 in a non-contact manner and can magnetically levitate the stator 20 in a non-contact manner.

[0115] A particular advantage of this embodiment of centrifugal pumps 41 and 42 is that the rotor 30 is designed as an integrated rotor, since the fluid is conveyed by both the rotor 30 of the electromagnetic rotary drive 10 and the rotor 30 of the centrifugal pumps 41 and 42. Thus, the rotor 30 performs three functions in total: it is the rotor 30 of the electromagnetic drive 10, it is the rotor 30 of the magnetic levitation, and it is the impeller on which the fluid acts. This embodiment as an integrated rotor offers the advantage of a very compact and space-saving design.

[0116] A further advantage is the non-contact magnetic levitation of the rotor 30 relative to the stator 20, which ensures that no contaminants that may occur in mechanical bearings enter the fluid, as there are no mechanical bearings for the rotor 30. Also, because there are no mechanical bearings and the frictional forces generated by them, the relationship between electrical operating variables such as drive current and drive voltage and the rotational speed of the rotor 30 can be defined much more precisely, which improves or simplifies the adjustment of the centrifugal pumps 41, 42.

[0117] Figure 6 shows a perspective view of one embodiment of an electromagnetic rotary drive 10 designed according to the principle of a bearingless motor, as a so-called temple motor. Figure 7 shows one embodiment of centrifugal pumps 41, 42 equipped with rotors 30 that can be magnetically levitated without contact in an axial cross-section.

[0118] The electromagnetic rotary drive 10 is designed and operates according to the principle of a bearingless motor. The term bearingless motor refers to the electromagnetic rotary drive 10 in which the rotor 30 is fully magnetically levitated relative to the stator 20 and no separate magnetic bearings are provided. For this purpose, the stator 20 is designed as a bearing-drive stator, which is both an electric drive stator and a magnetically levitated stator. The stator 20 includes an electric winding 206 that can generate a rotating magnetic field, which on the one hand exerts a torque on the rotor 30 that affects rotation around a desired axis of rotation defining the axial direction A, and on the other hand exerts a shear force on the rotor 30 that can be adjusted as needed so that its radial position can be actively controlled or adjusted. Thus, the three degrees of freedom of the rotor 30, namely its rotation and its radial position (two degrees of freedom), can be actively adjusted. Furthermore, with respect to three degrees of freedom, namely its position in the axial direction A and its inclination with respect to a radial plane perpendicular to the desired axis of rotation (two degrees of freedom), the rotor 30 is preferably passively magnetically levitated or stabilized by magnetoresistive force, i.e., it is uncontrollable. The complete magnetic levitation of the rotor 30, without the need for a separate magnetic bearing, is the characteristic that gives the bearingless motor its name. In a bearing-driven stator, the bearing function cannot be separated from the drive function.

[0119] The desired axis of rotation refers to the axis around which the rotor 30 rotates in operation when the rotor 30 is centered and not tilted relative to the stator 20, as shown in Figures 6 and 7. This desired axis of rotation defines axial direction A. Typically, the desired axis of rotation defining axial direction A corresponds to the central axis of the stator 20.

[0120] In the following, the radial direction refers to the direction perpendicular to the axial direction A.

[0121] The rotor 30 includes a magnetically active core 310 designed in the shape of a ring or disk. As shown in Figure 6, the magnetically active core 310 is designed as a permanent magnetic disk and defines a magnetic center plane C (Figure 7). The magnetic center plane C of the magnetically active core 310 of the rotor 30 refers to the plane perpendicular to the axial direction A from which the magnetically active core 310 of the rotor 30 levitates in operation, assuming the rotor 30 is not tilted or deflected in the axial direction A. In principle, for a disk-shaped or ring-shaped magnetically active core 301, the magnetic center plane C is the geometric center plane of the magnetically active core 301 of the rotor 30, perpendicular to the axial direction A. The plane from which the magnetically active core 310 of the rotor 30 levitates within the stator 20 in operation is also called the radial plane E. The radial plane defines the xy plane of the Cartesian coordinate system, where the z axis extends in the axial direction A. If the magnetically active core 310 of the rotor 30 is not tilted or deflected with respect to the axial direction (A), the radial plane E coincides with the magnetic center plane C.

[0122] The radial position of the magnetically active core 310 or rotor 30 refers to the position of the rotor 30 in the radial plane E.

[0123] The "magnetically active core 310" of the rotor 30 refers to the region of the rotor 30 that magnetically interacts with the stator 20 for torque generation and magnetic levitation force generation.

[0124] The electromagnetic rotary drive 10 is designed as a temple motor and includes a stator 20 having a plurality of coil cores 205 (in this case, six coil cores 205), each of which includes a longitudinal limb 251 extending in the axial direction A and a transverse limb 252 positioned perpendicular to the longitudinal limb 251, extending radially, and bounded by an end face. The coil cores 205 are arranged equidistantly on a circular line such that the end faces of the transverse limbs 252 surround the magnetically effective core of the rotor 30. The concentrated winding 206 is positioned on each longitudinal limb 251 surrounding each of the longitudinal limbs 252.

[0125] The longitudinal limbs 251 of the coil core 205 are aligned parallel to each other, all of which extend parallel to the axial direction A, surrounding the rotor 30 (or, in the case of an external rotor design, surrounded by the rotor 30), and these parallel longitudinal limbs 251 are reminiscent of temple pillars, hence the name Temple Motor.

[0126] In Figure 6, only the magnetically active core 310 of the rotor 30 is shown. Of course, it is understood that the rotor 30 may also include other components such as a jacket or encapsulation, preferably made of plastic, metal, metal alloy, or ceramic or ceramic material. Furthermore, the rotor 30 may also include vanes 305 for pumping fluid (see Figure 7). The rotor 30 may also include other components.

[0127] These ends of the longitudinal limbs 251 facing away from the transverse limbs 252 (in Figures 6 and 7, these are the lower ends according to the figures) are connected to one another by a return section 207. The return section 207 is preferably designed in a ring shape or includes several segments that connect the longitudinal limbs 251 to one another. Both the return section 207 and the coil core 205 of the stator 20 are made of soft magnetic material, as they function as flux-conducting elements that guide the magnetic flux. Suitable soft magnetic materials for the coil core 205 and the return section 207 are, for example, ferromagnetic or ferrimagnetic materials, i.e., iron, nickel iron, cobalt iron, silicon iron, or mu-metal in particular. In this case, for the stator 20, it is preferable that the coil core 205 and the return section 207 are designed from sheet metal, i.e., as a stator sheet stack consisting of several thin sheet metal elements stacked on top of each other.

[0128] To generate the rotating electromagnetic field necessary for the magnetic drive and magnetic levitation of the rotor 30, the longitudinal limbs 251 of the coil core 205 support windings designed as concentrated windings 206, with exactly one concentrated winding 206 positioned around each longitudinal limb 251 in the embodiment described herein. In operation, these rotating electromagnetic fields are generated in these concentrated windings 206, thereby applying torque to the rotor 30 and adjustable lateral forces to the rotor 30 radially, so that the radial position of the rotor 30, i.e., its position in the radial plane E perpendicular to the axial direction A, can be actively controlled or adjusted. Of course, embodiments in which each longitudinal limb 251 has two or more concentrated windings 206, for example, exactly two concentrated windings, are also possible.

[0129] As already mentioned, the magnetically active core 310 is designed to be permanently magnetic. For this purpose, the magnetically active core 301 may contain at least one permanent magnet, but may also contain several permanent magnets, or, in the embodiments described herein, may be made entirely of permanent magnet material so that the magnetically active core 301 becomes a permanent magnet. The magnetization of the magnetically active core 308 of the rotor 30 is represented in Figure 6 by an unsigned arrow in the magnetically active core 301. Thus, the magnetically active core 301 is magnetized radially.

[0130] Figure 7 shows one embodiment of centrifugal pumps 41 and 42 in a cross-section in the axial direction A.

[0131] The centrifugal pumps 41 and 42 include a pump unit 40 having a pump housing 60 including inlets 411 and 421 and outlets 412 and 422 for conveying fluid, and a rotor 30 located within the pump housing 60 and including a plurality of vanes 305 for conveying fluid. The pump unit 40 is designed to be inserted into the stator 20 such that the magnetically effective core 310 of the rotor 30 is surrounded by the end faces of the lateral limbs 252.

[0132] The pump housing 60 of the pump unit 40 includes a base portion 601 and a cover 602, which are sealed and connected to each other, and the outlets 412, 422 are preferably, but not necessarily, entirely located within the base portion 601 of the pump housing. The cover 602 includes inlets 411, 412 that extend in the axial direction A so that fluid flows from the axial direction A to the rotor 30.

[0133] The rotor 30 includes a plurality of vanes 305 for conveying fluid, for example, a total of four vanes 305, thereby this number having exemplary characteristics. The rotor 30 further includes a jacket 308 that encloses, preferably sealed, the magnetically effective core 308 of the rotor 30 so that the magnetically effective core 310 of the rotor 30 does not come into contact with the fluid being conveyed. All vanes 305 are positioned on the jacket 308 and are equidistant with respect to the circumferential direction of the rotor 30. Each vane 305 extends radially outward and is connected to the jacket 308 to withstand torque. The vanes 305 can then be separate components fixed to the jacket 308. Of course, it is also possible for all of the vanes 305 to be an integral part of the jacket 308, i.e., the jacket 308 can be designed so that all of the vanes 305 are a single part. The rotor 30, equipped with vanes 305, forms the vanes or impellers of the centrifugal pumps 41 and 42, respectively, through which one or more fluids act.

[0134] The design of centrifugal pumps 41, 42 equipped with an electromagnetic rotary drive 10 relating to the principle of a bearingless motor also allows the rotor 30 to be separated from the stator 20 very easily. This is a significant advantage because, for example, the rotor 30 or the pump unit 40 including the rotor can be designed as a disposable part for single use. Today, such disposable applications often replace processes where, due to very high purity requirements, all components that come into contact with the substance being processed previously had to be cleaned and sterilized in an elaborate manner (e.g., by steam sterilization). When designed for single use, the components that come into contact with the substance being processed are used exactly once and replaced with new (i.e., unused) disposable parts for the next use.

[0135] Accordingly, the apparatus according to the present invention may also be designed to include, in particular, reusable apparatus designed for multiple uses and disposable apparatus designed for single use. The reusable apparatus includes, in particular, components that do not come into contact with fluid, i.e., the stators 20 of the centrifugal pumps 41, 42 and, for example, at least a portion of the pressure sensors 71, 72, 73. The pressure sensors 71, 72, 73 may be designed to include disposable and reusable parts, respectively.

[0136] The apparatus 1 according to the present invention may further include a reservoir 8. Embodiments are possible in which the entire reservoir 8 is designed as a disposable part, for example, as a dimensionally stable plastic container, and embodiments are possible in which only one component of the reservoir 8 is designed as a disposable part.

[0137] Such an embodiment of the reservoir 8 is shown in the schematic diagram of Figure 8. The reservoir 8 includes a flexible plastic insert 80 for receiving fluid. The insert 80 is preferably a flexible bag (e.g., a plastic bag or a synthetic bag) that can be folded to take up as little space as possible during storage. The insert 80 may include additional inlets or outlets (not shown) for supplying additional substances (e.g., nutrient solution or gases such as oxygen). It is also possible to use further inlets for receiving probes or measuring sensors to monitor parameters such as temperature, pressure, and concentration. The inlets(s) may also be used for mass transfer. In particular, any necessary gases can be supplied or discharged here, for example, in an embodiment as a bioreactor. In particular in the culture of microorganisms or biological cells, it is often necessary to be able to supply oxygen or air to the container 80 and discharge other gases (in particular carbon dioxide) from the container.

[0138] In particular, so-called sampling ports (not shown) can be bonded or welded to the reservoir 8 or insert 80. These are short, tubular plastic structures through which, for example, a sample can be taken out of the insert 80. Each sampling port is typically secured by a clamp at its end, which protrudes from the insert 80 in a manner known to itself, so that undesirable substances cannot enter the interior of the insert 80 through these sampling ports.

[0139] The reservoir 8 further includes a dimensionally stable support container 85, which is a reusable component and designed to receive the insert 80. At least one window 86 can be provided in the wall of the support container 85, through which visual access to the insert 80 is possible.

[0140] Even in the highly schematic embodiment shown in Figure 8, each of the two tubes through which the fluid exits or returns to the reservoir 8 with the insert 80, namely the return tube 321 and the supply tube 311, can be used for both the removal and return of the fluid, respectively. This is because, when the device 1 operates in alternating mode, the supply tube 311 is used in one operating mode, such as the first operating mode, to remove the fluid from the insert 80, and in the other operating mode, such as the second operating mode, to return the fluid to the insert 80. The same is true for the return tube 321. This means that both tubes 321 and 311 are specifically designed so that fluid can be drawn through them, or other means are provided, for example in the design of the insert 80, through each of the two tubes (i.e., the supply tube 311 and the return tube 321) so that the fluid can be drawn in (i.e., removed and returned).

[0141] In particular, with respect to such embodiments of the apparatus 1 that include reusable components for multiple uses and components for single use, a set of disposable components for the apparatus 1 according to the present invention is further proposed, each of which is designed as a disposable component: a filter unit 2, a pump unit 40 for each centrifugal pump 41, 42, a plurality of tubes 311, 312, 321, 322 designed to realize a first flow connection 31 and a second flow connection, and optionally a reservoir 8 for fluid or an insert 80 for the reservoir 8.

[0142] A further substantial aspect is that all parts of the apparatus 1 for tangential flow filtration that come into contact with the fluid, in particular the filter unit 2 or filter element 25, the reservoir 8 or insert 80 designed as a plastic bag, the flow connectors 31, 32, and optionally the pressure sensors 71, 72, 73, and the pump units 40 of the centrifugal pumps 41 and 42, or their components, also need to be sterilizable for a specific application area. It is particularly advantageous if all of the above components are gamma-ray sterilizable. In this type of sterilization, the components to be sterilized are exposed to gamma rays. An advantage of gamma-ray sterilization compared to, for example, steam sterilization is that sterilization can also be performed through the packaging. Especially in the case of disposable parts, it is common practice for parts to be placed in shipping packages after manufacturing and stored for a certain period before being shipped to the customer. In such cases, sterilization is performed through the packaging immediately before delivery to the customer, which cannot be done by steam sterilization or other processes.

[0143] On the other hand, since the pump unit 40 can only be used once, there is a significant advantage in that, if used as intended, there is no need to clean the pump unit 40, and therefore good cleanability of the pump unit 40 does not need to be a priority in the design. Furthermore, generally speaking, the pump unit 40 or its components do not need to be sterilizable multiple times. This is a significant advantage, especially in the case of gamma ray sterilization, as exposure to gamma rays degrades plastics, and multiple gamma ray sterilizations can render the plastics unusable.

[0144] For disposable parts, sterilization under high temperature and / or high (steam) pressure is usually not required, so cheaper plastics that cannot withstand high temperatures or be exposed to multiple high-temperature and high-pressure levels can be used.

[0145] Therefore, considering all these aspects, it is preferable to use plastics that can be gamma-ray sterilized at least once for the manufacture of disposable devices or disposable parts. To enable a single gamma-ray sterilization, the material must be gamma-ray stable at a dose of at least 40 kGy. It is also necessary that no toxic substances are generated during gamma-ray sterilization. Furthermore, it is preferable that all materials being mixed or in contact with the mixed materials meet USP Class VI standards.

[0146] For example, to manufacture the components of a plastic pump unit 40, the following plastics are preferred: polypropylene (PP), low-density polyethylene (LDPE), ultra-low-density polyethylene (ULDPE), ethylene vinyl acetate (EVA), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyvinylidene fluoride (PVDF), acrylonitrile butadiene styrene (ABS), polyacrylic, and polycarbonate (PC).

[0147] Materials that are not very suitable, or even unsuitable, for manufacturing plastic parts for disposable devices 70 include, for example, materials known by the trade names Teflon, polytetrafluoroethylene (PTFE), and perfluoroalkoxy polymer (PFA). In the case of these materials, there is actually a risk that hazardous gases such as fluorine may escape during gamma ray sterilization, which may then form toxic or harmful compounds such as hydrofluoric acid (HF).

Claims

1. 1. An apparatus for tangential flow filtration of a fluid, comprising: a filter unit (2) having a first fluid opening (21) and a second fluid opening (22) for said fluid, as well as a filter element (25), and a permeate opening (23) for discharging permeate filtered from said fluid, The device further comprises a first flow connection (31) capable of connecting the first fluid opening (21) to a reservoir (8) for the fluid, and a second flow connection (32) capable of connecting the second fluid opening (22) to a reservoir (8) for the fluid, a first centrifugal pump (41) is provided at the first flow connection (31), by means of which the fluid can be conveyed from the reservoir (8) to the filter unit (2); A first control unit (51) is provided for operating the first centrifugal pump (41); The filter unit (2) is designed so that the fluid for tangential flow filtration within the filter unit (2) can flow substantially parallel to the filter element (26), a second centrifugal pump (42) for said fluid is provided in said second flow connection (32), said second centrifugal pump (42) being capable of generating a counter pressure at said second fluid opening (22); CHARACTERIZED IN THAT said second control unit (52) is provided for operating said second centrifugal pump (42).

2. a flow sensor (6) for determining a flow rate of said fluid through said first flow connection (31), 2. The device according to claim 1, wherein the first control unit (51) is designed to be able to adjust the desired value of the flow rate via an operating parameter, in particular the rotational speed, of the first centrifugal pump (41).

3. 3. The device according to claim 1 or 2, wherein a plurality of pressure sensors (71, 72, 73) are provided, the plurality of pressure sensors (71, 72, 73) being arranged such that a transmembrane pressure can be determined by the plurality of pressure sensors via the filter element (25), and the second control unit (52) is designed such that the second control unit (52) is able to adjust the desired value of the transmembrane pressure via an operating parameter, in particular a rotational speed, of the second centrifugal pump (42).

4. The plurality of pressure sensors (71, 72, 73) a first pressure sensor (71) adapted to determine a first pressure (P1) of said fluid at said first fluid opening (21); a second pressure sensor (72) adapted to determine a second pressure (P2) of said fluid at said second fluid opening (22); a third pressure sensor (73) adapted to determine a third pressure (P3) at said permeate opening (23); The apparatus of claim 3 , comprising:

5. 3. The device according to claim 1 or 2, wherein a central control unit (5) is provided which is signal-connected to the first control unit (51) and to the second control unit (52), the central control unit (5) being designed to operate the first control unit (51) and the second control unit (52).

6. The second centrifugal pump (42) comprises: a rotor (30) for conveying said fluid; and a stator (20) which together with said rotor (30) forms an electromagnetic rotary drive (10) for rotating said rotor about an axis (A), The rotor (30) is A magnetically active core (301); a plurality of vanes (305) for conveying said fluid; 3. The device according to claim 1 or 2, wherein the stator (20) is designed as a bearing drive stator such that the rotor (30) can be magnetically driven without contact and magnetically levitated without contact with respect to the stator (20).

7. The first centrifugal pump (41) comprises: a rotor (30) for conveying said fluid; a stator (20) forming, together with said rotor, an electromagnetic rotary drive (10) for rotating said rotor (30) about an axis (A), The rotor (30) is A magnetically active core (301); a plurality of vanes (305) for conveying said fluid; 3. The device according to claim 1 or 2, wherein the stator (20) is designed as a bearing drive stator such that the rotor (30) can be magnetically driven without contact and magnetically levitated without contact with respect to the stator (20).

8. Each centrifugal pump (41, 42) includes a pump unit (40) having a pump housing (60); The pump housing (60) has an inlet (411, 421) and an outlet (412, 422) for conveying the fluid; The rotor (30) is disposed within the pump housing (60) and includes a plurality of vanes (305) for conveying the fluid; 7. The device according to claim 6, wherein the pump unit (40) is designed so that the pump unit (40) can be inserted into the stator (20).

9. At least the following components: The filter unit (2), one pump unit (40) for each centrifugal pump (41, 42); a number of tubes (311, 312, 321, 322) designed to realize said first flow connection (31) and said second flow connection; 9. A set of disposable parts for a device according to claim 8, optionally comprising a reservoir (8) for said fluid or an insert (80) for said reservoir (8), each of said components being designed as a disposable part.

10. 1. A method for tangential flow filtration of a fluid, comprising: said fluid is fed to a filter unit (2) having a first fluid opening (21) and a second fluid opening (22) for said fluid, as well as a filter element (25) and a permeate opening (23) for discharging permeate filtered from said fluid, The filter unit (2) is designed such that the fluid for tangential flow filtration in the filter unit (2) is guided substantially parallel to the filter element (25), In said method, said fluid is further conveyed from a reservoir (8) through a first flow connection (31) to said filter unit (2) by a first centrifugal pump (41); The fluid can be guided from the second fluid opening (22) through a second flow connection (32) back to the reservoir (8), The method, wherein the first centrifugal pump (41) is operated by a first control unit (51), a counter pressure is generated in the second fluid opening (22) by means of a second centrifugal pump (42) provided in the second flow connection (32); The method of claim 1, wherein the second centrifugal pump (42) is operated by a second control unit (52).

11. 11. The method according to claim 10, wherein the flow rate of the fluid through the first flow connection (31) is determined by a flow sensor (6) and the desired value of the flow rate is determined by the first control unit (51) via operating parameters of the first centrifugal pump (41), in particular the rotational speed.

12. the first pressure (P1) at the first fluid opening (21) is determined by a first pressure sensor (71), or a second pressure (P2) at the second fluid opening (22) is determined by a second pressure sensor (72); or a third pressure (P3) at the permeate opening (23) is determined by a third pressure sensor (73); 12. The method according to claim 10 or 11, wherein the desired value of the first pressure (P1), or the second pressure (P2), or the third pressure (P3) is regulated by the second control unit (52) via an operating parameter, in particular a rotational speed, of the second centrifugal pump (42).

13. a transmembrane pressure is determined by a plurality of pressure sensors (71, 72, 73) through said filter element (26); the desired value of the transmembrane pressure is adjusted by the first control unit (51) or by the second control unit (52) via operating parameters of the first centrifugal pump (41) or via operating parameters of the second centrifugal pump (42), The method according to claim 10 or 11, wherein the operating parameter is preferably the rotational speed of the first centrifugal pump (41) or the second centrifugal pump (42).

14. 12. The method according to claim 10 or 11, wherein the tangential flow filtration is performed in alternating modes including a first operation mode in which the fluid flows from the first fluid opening (21) to the second fluid opening (22) and a second operation mode in which the fluid flows from the second fluid opening (22) to the first fluid opening (21).

15. The method of claim 14 , wherein changing between the first and second operating modes is performed according to the predetermined time scheme.

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