US-12623169-B2 - Device and a method for tangential flow filtration of a fluid

US12623169B2US 12623169 B2US12623169 B2US 12623169B2US-12623169-B2

Abstract

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 to convey the fluid from the reservoir to the filter unit, a first controller to actuate the first centrifugal pump, the filter unit designed such that the fluid for tangential flow filtration is capable of flowing substantially parallel to the filter element, a second centrifugal pump in the second flow connection, with which a counter-pressure is capable of being generated at the second fluid opening, and a second controller to actuate the second centrifugal pump.

Inventors

Antony SIBILIA
Simon STÖCKLI

Assignees

LEVITRONIX GMBH

Dates

Publication Date: 20260512
Application Date: 20220513
Priority Date: 20210610

Claims (13)

1 . A device for tangential flow filtration of a fluid, comprising: a filter unit having a first fluid opening and a second fluid opening for the fluid, as a filter element and a permeate opening configured to discharge a permeate filtered out of the fluid; a first flow connection by which the first fluid opening is capable of being connected to a reservoir for the fluid; a second flow connection by which the second fluid opening is capable of being connected to the reservoir for the fluid; a first centrifugal pump disposed in the first flow connection, with which the fluid is capable of being conveyed from the reservoir to the filter unit; a first controller configured to actuate the first centrifugal pump, the filter unit configured such that the fluid for tangential flow filtration in the filter unit is capable of flow substantially parallel to the filter element; a second centrifugal pump for the fluid disposed in the second flow connection, which a counter-pressure is configured to be generated at the second fluid opening; and a second controller configured to actuate the second centrifugal pump.
2 . The device according to claim 1 , further comprising a flow sensor configured to determine a flow rate of the fluid through the first flow connection, the first controller configured to adjust a desired value for the flow rate via an operating parameter of the first centrifugal pump.
3 . The device according to claim 1 , further including a plurality of pressure sensors arranged and configured to determine a transmembrane pressure via the filter element, and the second controller is configured to adjust a desired value for the transmembrane pressure via an operating parameter of the second centrifugal pump.
4 . The device according to claim 3 , wherein the plurality of the pressure sensors comprises a first pressure sensor configured to determine a first pressure of the fluid at the first fluid opening, and a second pressure sensor configured to determine a second pressure of the fluid at the second fluid opening, and a third pressure sensor configured to determine a third pressure of the fluid at the permeate opening.
5 . The device according to claim 1 , further comprising a central controller signal-connected to the first controller and to the second controller, and the central controller configured to actuate the first controller and the second controller.
6 . The device according to claim 1 , wherein the second centrifugal pump comprises a rotor configured to convey the fluid, and a stator which forms with the rotor an electromagnetic rotary drive configured to rotate the rotor about an axial direction, the rotor comprises a magnetically effective core, and a plurality of vanes configured to convey the fluid, and the stator is a bearing and drive stator with which the rotor is capable of being magnetically driven without contact and magnetically levitated without contact with respect to the stator.
7 . The device according to claim 1 , wherein the first centrifugal pump comprises a rotor configured to convey the fluid, and a stator which forms with the rotor an electromagnetic rotary drive configured to rotate the rotor about an axial direction, the rotor comprises a magnetically effective core, and a plurality of vanes configured to convey the fluid, and the stator is a bearing and drive stator with which the rotor is capable of being magnetically driven without contact and magnetically levitated without contact with respect to the stator.
8 . The device according to claim 6 , wherein the second centrifugal pump comprises in a pump unit having a pump housing, the pump housing comprises an inlet and an outlet for the fluid to be conveyed, the rotor is arranged in the pump housing, and the pump unit is configured to be inserted into the stator.
9 . A set of single-use parts for the device according to claim 8 , comprising: the filter unit; the pump unit; and a plurality of tubes configured to enable the first flow connection and the second flow connection.
10 . The device according to claim 1 , further comprising a flow sensor configured to determine a flow rate of the fluid through the first flow connection, the first controller configured to adjust a desired value for the flow rate via a rotational speed of the first centrifugal pump.
11 . The device according to claim 1 , further including a plurality of pressure sensors arranged and configured to determine a transmembrane pressure via the filter element, and the second controller is configured to adjust a desired value for the transmembrane pressure via a rotational speed of the second centrifugal pump.
12 . The set of single-use parts for the device according to claim 9 , further comprising the reservoir for the fluid or an insert for the reservoir.
13 . The device according to claim 1 , further comprising a central control unit configured to actuate the first and second control units in a coordinated manner.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to European Patent Application 21178687.6, filed Jun. 10, 2021, the contents of which is hereby incorporated in their entirety. BACKGROUND Field of the Invention The disclosure relates to a device and a method for tangential flow filtration of a fluid. The disclosure further relates to a set of single-use parts for such a device. Background Information Conventional tangential flow filtration, which is also designated as cross-flow filtration, is a method of filtering fluids that is used, for example, in the biotechnology and chemical industries, as well as in the food and pharmaceutical industries. In conventional tangential flow filtration, the fluid to be filtered, for example a suspension, is guided parallel to a filter element, e.g., a filter membrane, at a flow velocity different from zero, and the permeate, also designated as filtrate, is removed transverse to the flow direction. Due to a relatively high flow velocity, having a filter cake or a cover layer building up on the filter element should be avoided. Tangential flow filtration is often performed as a batch process in which the fluid to be filtered, for example a suspension, is taken from a reservoir, conveyed by a conveying pump through the filter unit with the filter element arranged therein, and then guided hack from the filter unit to the reservoir. The permeate, which passes through the filter element in the filter unit transverse to the flow direction, is discharged or removed through a permeate opening. Flexible tubes or flexible tube connections are often selected for the flow connections between the reservoir and the filter unit. SUMMARY In such processes, tangential flow filtration can be used to concentrate a fluid, e.g., a suspension, by circulating the suspension several times and in each case filtering out a liquid component, e.g., water or a nutrient solution, which is removed in each case as permeate, so that the suspension in the reservoir becomes increasingly concentrated. However, it is also possible to remove the substance to be recovered by tangential flow filtration, for example a protein, as permeate. In particular, tangential flow filtration can be used in combination with bioreactors, both in continuous processes and in batch processes, for example in processes for culturing cells or other biological material. For example, perfusion processes with bioreactors are known that are used for the continuous cultivation of cells, whereby, for example, metabolic products of the cells are separated out by tangential flow filtration and the cells are guided back to the bioreactor. For example, a nutrient solution for the cells can be continuously fed to the bioreactor, thereby replacing the mass or volume of the filtered-out components. In particular also for such applications in perfusion bioreactors, there is an increasing tendency to design components of the device as single-use parts in order to avoid or reduce to a minimum time-consuming sterilization processes. It has been determined that one parameter that significantly influences the efficiency of tangential flow filtration is the pressure drop across the filter element, by which the permeate is moved through the filter element. A variable often used as a measure of this parameter is the transmembrane pressure (TMP), which is defined as the arithmetic mean of the pressure drop across the filter element. If the pressure of the fluid at the inlet of the filter element is designated by P1, the pressure at the outlet of the filter element by P2, and the pressure at the permeate opening by P3, the transmembrane pressure TMP is defined as: TMP=(P1+P2)/2−P3 The transmembrane pressure is also designated as transmembrane pressure difference. In order to increase the flow of permeate through the filter element, the flow resistance for the fluid downstream of the filter unit can be increased, whereby the pressure P2 at the outlet of the filter element is increased. Due to this, an increase of the transmembrane pressure TMP results, whereby the permeate flow is enlarged. Usually, the flow resistance downstream of the filter unit and thus the pressure P2 at the outlet of the filter element is realized by a narrowing of the free flow cross-section for the fluid. This narrowing can be realized by using proportional or (tube) pinch valves. However, it has been determined that this technology has considerable disadvantages. Since the relationship between the position of the pinch valve and the transmembrane pressure is highly non-linear, even at a constant delivery of the conveying pump, a desired transmembrane pressure can only be adjusted by lengthy adjustment of the pinch valve. In addition, there is only a very narrow range for the adjustment of the pinch valve in which an at least approximate adjustment of the desired transmembrane pressure is at all reliably possible. In the case of conventional pinch valves,