Method for dynamic in-line mixing

Abstract

The invention relates to a method for the dynamic in-line mixing of a pressurized medium (1), which contains a liquid and at least one further liquid or solid component, in a bioprocess assembly (3), the liquid and the at least one further liquid or solid component are converged in a predefined volume ratio at the inlet point (4) to form a synthetic liquid flow (5), the bioprocess assembly (3) having a pump assembly (8) with a first pump (9), the first pump (9) being arranged in the line (7) of the line assembly (6), the first pump (9) being arranged in the line (7) of the line assembly (6), and the second pump (9) being arranged in the line (7) of the line assembly (6). The first pump (9) is designed as a rotary pump (10), in particular a centrifugal rotary pump, which is designed for the dynamic inline mixing of the medium (1), the first pump (9) having a liquid inlet (9a) which forms the suction side of the pump in the specified operation and a liquid outlet (9b) which forms the pressure side of the pump in the specified operation, and wherein the first pump (9) is designed as a rotary pump (10), in particular a centrifugal rotary pump, which is designed for the dynamic inline mixing of the medium (1). The medium (1) is guided by a rotary pump (10) for dynamic in-line mixing. According to the invention, the rotary pump (10) is passed through in the opposite flow direction for dynamic in-line mixing in comparison to the specified operation.

Description

Technical Field

[0001] The present invention relates to a method for dynamic inline mixing according to the preamble of claim 1, a bioprocess component for dynamic inline mixing according to claim 13, an electronic process controller for the proposed bioprocess component according to claim 15, the use of a rotary pump for carrying out the proposed method according to claim 17, a computer program for the proposed electronic process controller according to claim 18 and a computer-readable storage medium for storing the computer program according to claim 19. Background Art

[0002] The method discussed for dynamic in-line mixing is used in bioprocesses within the scope of mixing processes, in particular for mixing buffers and / or media (medien, sometimes referred to as culture media), thereby avoiding disadvantageous storage times in intermediate containers.

[0003] The term "bioprocess" herein refers to biotechnology and biopharmaceutical processes involved in the manufacture of therapeutic biological products (such as vaccines, biologics, components for cell or gene therapy) or non-therapeutic biological products (such as pigments, biofuels or nutrients). Such biological products can either be produced by living cells, or the cells themselves can represent the biological product, or the biological product can be a product of cell-free production based on cellular components of either natural or non-natural origin.

[0004] Disposable technology is currently gaining ground in the biopharmaceutical industry. At the same time, the trend is towards intensified processes, whereby continuous or semi-continuous process steps are also being carried out more and more frequently. This also applies to mixing processes, in which two or more liquids are mixed with one another or solids (mostly in powder form) are dissolved or suspended in a liquid. At present, the mixing of buffers or media, especially for fermentation and purification steps, is usually carried out in batches. Here, the container is filled with the base liquid to be mixed, and then the components to be mixed (solid or liquid) are added and mixed for a long time using a dynamic stirrer, that is, until the desired mixing or dissolution degree is reached, so that the finished solution can then be further processed.

[0005] However, the use of such intermediate containers has the decisive disadvantage that essentially sensitive biological products (eg antibodies) from bioprocesses can be destroyed due to excessively long storage times. In this regard, it is applicable to keep the storage time of biological products as short as possible.

[0006] For this reason, the mixing process should preferably not be implemented in an intermediate container, but should be implemented "in-line" (that is, in the pipeline of the pipeline assembly), so that static mixing elements are currently preferably used for in-line mixing (US2017 / 216791AA). This is because there is currently an interesting disposable concept for static mixing elements, which can be directly installed in the pipeline of the equipment on bioprocess technology in a simple way. It is a flow-through system in which mixing is achieved in the following way, that is, the liquid is transported through a pipeline system, which is provided with special geometric mountings (Einbauten, sometimes called accessories), especially worms, paddles and / or pipe wall mountings of various geometric shapes. These mountings are used to interrupt the flow and agitation, and are therefore used to mix the components to be mixed in the throughflow. They can either accommodate two liquid flows to be mixed here, or fully mix each liquid flow.

[0007] However, the problem with all static mixers is that, due to the working principle, the entire system depends on different parameters, which are usually difficult to control. Thus, these systems provide predictable mixing results only when the input parameters (including at least the flow rate, viscosity and temperature of the stream to be mixed) are known and can be kept constant to the greatest extent. Therefore, as soon as the flow rate changes slightly, the dynamic agitation in the static mixer and therefore the mixing performance (Mischleistung, sometimes referred to as mixing power) also change. Therefore, such static mixers are usually used in branches of industry where the precision of the mixing process only plays a secondary role, for example when mixing two-component adhesives.

[0008] However, if this involves a process where precision in the mixing process is important (such as preparing and mixing, for example, buffers or media for use in bioprocessing), dynamic in-line mixers are currently used in the industry. These dynamic in-line mixers meet the requirements for increased mixing performance and predictability of mixing processes in the industry.

[0009] The known device and known method for dynamic in-line mixing (WO 2021 / 133487 A1) based on the present invention are used to dynamically mix two or more substances in order to produce the desired concentration of the substances involved, especially the chromatography buffer, etc. The substances converge into a synthetic liquid flow at the entry point of the pipeline assembly. A first pump is arranged in the pipeline assembly, through which the synthetic liquid flow is guided for dynamic in-line mixing, and the liquid flow is driven by the pump.

[0010] The known devices and known methods for dynamic inline mixing therefore lead to critical pressure increases in the system, which, in particular in the case of hose systems, can cause problems with regard to the metering accuracy of the liquid flows to be mixed and the reproducibility of the mixing result.

[0011] In this case, a “hose system” means that the at least one line is designed as a hose, preferably as a disposable hose, wherein a liquid flow can be generated by means of at least one hose pump associated with the hose, which liquid flow runs through the hose. Summary of the invention

[0012] The invention is based on the problem of designing and improving the known method for dynamic inline mixing in such a way that the mixing performance and the reproducibility of the bioprocess are improved while at the same time increasing the user-friendliness.

[0013] This problem is solved in a method for dynamic inline mixing according to the preamble of claim 1 by the characterizing features of claim 1 .

[0014] The fundamental consideration that is important is that the method provides a rotary pump, in particular a centrifugal rotary pump, which is arranged in a counter-rotating installation direction so that the liquid flow flows counter-rotatingly through the pump for dynamic in-line mixing.

[0015] The special design according to the proposed method has the advantage that the flow through the rotary pump in the opposite direction to the prescribed direction at least reduces, in particular cancels (sometimes referred to as zeroing) the pump delivery capacity, thereby avoiding a critical pressure increase on the downstream side. In addition, the possibility of the rotating impeller acting as a mixer is opened up, which makes it possible to adjust the variable mixing properties (adjust the residence time in the pump chamber / mixing chamber) by adjusting the speed of the impeller (preferably ensured by a synchronous magnetic pump drive) under simultaneously constant flow conditions. If the pump is installed in the usual (that is to say prescribed) installation direction, it is not possible to adjust the desired speed (and therefore the mixing properties) without also increasing the delivery capacity (which would lead to an increase in pressure in the system). This therefore involves a different use (sometimes referred to as non-conventional application) of the rotary pump, because the rotary pump is no longer used for pumping, but instead is used as a resistance unit for generating dynamic agitation of a liquid flow or a suspension.

[0016] In particular, it is proposed that flow be passed through the rotary pump in the opposite direction of flow compared to normal operation in order to achieve dynamic in-line mixing.

[0017] The preferred embodiments according to claims 2 to 4 relate to the elaboration of the reversing installation direction of the rotary pump. These embodiments make it possible to adjust the desired rotational speed of the rotating shaft and thus the mixing performance in a simple manner, but without increasing the delivery capacity, which would lead to an undesirable pressure increase in the system. According to these embodiments, the pump body of the rotary pump can be simply regarded as a channel body with an installed agitator.

[0018] According to a preferred embodiment of claim 5, the method provides at least two containers from which the liquid component and the at least one further liquid or solid component are discharged into a line assembly. This embodiment allows for a particular flexibility in the application possibilities of the method. Thus, for example, it can be used to prepare all types of culture media (Kultivierungsmedien, sometimes referred to as culture media) or buffers and is not limited to only liquid or solid components.

[0019] According to preferred embodiments of claims 6 and 7, the pump arrangement has a second pump and at least one third pump which are designed for metered delivery of liquids or solids. These embodiments also emphasize the particular flexibility with regard to the various possible applications of the method.

[0020] According to another preferred embodiment of claim 8, the first pump is designed as a rotary pump, wherein the mixing performance can be adjusted by adapting at least one parameter of the rotary pump. In addition, it can be provided that the degree of adaptation is derived from the mixing model by the electronic process controller. These embodiments offer the following advantages, namely, on the one hand, the method can be adjusted by adapting the rotation speed of the impeller of the rotary pump, and on the other hand, this adjustment can be carried out automatically.

[0021] According to another preferred embodiment of claim 9, the electronic process controller controls at least the valve assembly and the pump assembly. Furthermore, it can be provided that the pump of the pump assembly can be selectively actuated by the electronic process controller in order to produce predefined target conditions in the resulting liquid flow. With this embodiment, the proposed method can be controlled in a particularly precise manner.

[0022] According to a likewise preferred embodiment of claim 10, a sensor arrangement is provided with at least one sensor for generating sensor data of the resultant liquid flow, wherein the sensor data describe the actual conditions in the resultant liquid flow at the measuring point and are transmitted to the electronic process controller. This offers the advantage of checking the achieved mixing properties and of automatic regulation based on the measured sensor values.

[0023] According to another preferred embodiment of claim 11, a feedback line is provided. This feedback line allows a thorough remixing of the resulting liquid flow by introducing it again and, if necessary, repeatedly upstream of the rotary pump. The feedback line can be selectively switched in when a feedback criterion is met. This allows a particularly precise control of the desired mixing properties, even if these mixing properties could not be successfully achieved after the first thorough mixing.

[0024] According to another preferred embodiment of claim 12, the resulting liquid stream is directed downstream of the rotary pump to at least one downstream unit for intermediate storage or further processing. This opens up a particular flexibility in the further processing of the well-mixed liquid stream. For example, the liquid stream can be directed to a downstream chromatography unit for direct purification of the liquid stream or to an intermediate container for intermediate storage of the liquid stream.

[0025] According to another teaching having independent significance according to claim 13, a bioprocess component for the dynamic inline mixing of a pressurized medium, in particular a buffer and / or a culture medium, containing a liquid and at least one further liquid or solid component, wherein the liquid can be brought together with the at least one further liquid or solid component at a predefined volume ratio at an inlet point to form a resulting liquid flow, wherein the bioprocess component has a line assembly with at least one line through which the medium to be mixed is conducted, wherein the bioprocess component has a pump assembly with a first pump, wherein the first pump is arranged in a line of the line assembly, wherein the first pump is designed as a rotary pump, in particular a centrifugal rotary pump, which is designed for the dynamic inline mixing of the medium, wherein the first pump has a liquid inlet which forms the suction side of the pump in the intended operation and a liquid outlet which forms the pressure side of the pump in the intended operation, and wherein the medium is conducted through the rotary pump for the dynamic inline mixing. In this regard, reference is made to all the explanations of the method according to the proposal for the dynamic inline mixing.

[0026] In particular, it is proposed here that the rotary pump is arranged in such a way that, during operation of the bioprocess module, flow passes through the rotary pump in the opposite direction of flow compared to the intended operation for dynamic in-line mixing.

[0027] According to a particularly preferred embodiment of claim 14, the line assembly and / or the rotary pump in the bioprocess assembly are designed as disposable components. After a single use, correspondingly replacing all or at least some of these components has the advantage that sterility is ensured and a possible cleaning step after the end of the process is omitted. The rotary pump also offers the advantage that it can be fully assembled before use and delivered sterile without the risk of contamination.

[0028] According to a further teaching having independent significance, an electronic process controller for the proposed bioprocess component is claimed. In this regard, reference is made to all the statements concerning the proposed method for dynamic inline mixing and concerning the proposed bioprocess component.

[0029] According to a preferred embodiment of claim 16 , the electronic process control has a data processing system for implementing the proposed method.

[0030] According to a further teaching having independent significance according to claim 17, the use of a rotary pump for carrying out the proposed method is claimed. In this regard, reference is made to all the statements concerning the proposed method for dynamic in-line mixing, the proposed bioprocess component and the proposed electronic process controller.

[0031] According to a further teaching having independent significance, a computer program for an electronic process controller according to the proposal is claimed. In this regard, reference is made to all the statements concerning the method according to the proposal for dynamic inline mixing, the bioprocess component according to the proposal, the electronic process controller according to the proposal and the use according to the proposal.

[0032] According to another teaching having independent significance, a computer-readable storage medium for storing the proposed computer program is claimed. In this regard, reference is made to all the statements concerning the proposed method for dynamic in-line mixing, the proposed bioprocess component, the proposed electronic process controller, the proposed use and the proposed computer program. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The invention is explained in more detail below with reference to the accompanying drawings which show only an exemplary embodiment. In the drawings:

[0034] Figure 1 A schematic diagram showing the proposed method,

[0035] Figure 2 An embodiment of a rotary pump for carrying out the proposed method is shown, and

[0036] Figure 3 Shown according to Figure 2 Schematic diagram of the flow through a rotary pump during operation. DETAILED DESCRIPTION

[0037] exist Figure 1A method for dynamic in-line mixing of a pressure-loaded medium 1 is presented in the specification. The method is used in the production and / or quality control of biopharmaceutical products, for example during the production of proteins by means of bioprocesses. Such proteins can be, for example, growth factors, hormones, enzymes and in particular antibodies, antibody derivatives, etc. The proposed method can be used to ensure dynamic and in-line mixing of a pressure-loaded medium 1 containing a liquid and at least one further liquid or solid component. The method is particularly used for in-line mixing of biotechnological media 2 (such as buffers and / or culture media, etc.) in bioprocess components 3.

[0038] The liquid and the at least one further liquid or solid component are brought together in a predefined volume ratio at the inlet point 4 to form a resulting liquid flow 5 .

[0039] By "predefined volume ratio" is meant here that the volume ratio of the liquid volume and / or the solid volume of the production medium 1 has been defined before the implementation of the method according to the proposal or has been adapted during the use of the method according to the proposal. Preferably, the definition and / or adaptation of the volume ratio of the liquid volume and / or the solid volume of the production medium 1 is carried out by the user. As also described elsewhere, a possible adaptation is preferably carried out on the basis of measured parameters, whereby a reactive control of the volume ratio can be achieved.

[0040] The bioprocess component 3 has a pipeline assembly 6 with at least one pipeline 7, through which a medium 1 to be mixed or components to be mixed with each other is guided. In addition, the bioprocess component 3 has a pump assembly 8 with a first pump 9, wherein the first pump 9 is arranged in the pipeline 7 of the pipeline assembly 6. The first pump 9 is designed as a rotary pump 10, in particular a centrifugal rotary pump, and is set up for dynamic in-line mixing of the medium 1. The first pump 9 has a liquid inlet 9a which forms the suction side of the pump 9 in a prescribed flow direction and a liquid outlet 9b which forms the pressure side of the pump in a prescribed operation. The medium 1 is guided by the first pump 9 designed as a rotary pump 10 for dynamic in-line mixing.

[0041] The term “as intended” here means compliance with the manufacturer's specifications for the pump 9 . Thus, in the present case, “as intended flow direction” means the manufacturer's specified flow direction of the pump 9 .

[0042] "Medium" here quite generally refers to a liquid, a liquid mixture or a suspension consisting of a liquid and at least one further liquid or solid component. The medium 1 in the sense of the present patent application can be a biotechnological medium 2 in a bioprocess component 3, such as a buffer and / or a culture medium. It is also conceivable that the liquid and / or the at least one further liquid or solid component of the medium 1 or the medium 1 itself can be a concentrate, preferably a product stream, further preferably a protein product stream and / or a solvent, in particular water, ethanol, an acid or a base, etc. Therefore, the proposed method can be widely applied and can be used not only for mixing or diluting buffers and / or culture media, but also, for example, for methods for inactivating viruses in bioprocesses.

[0043] The term “dynamic” here refers to a mixer with dynamic mixing properties, wherein the mixing properties vary as a function of at least one adjustable parameter, in particular as a function of the stirrer rotation speed.

[0044] The term “in-line” here means within the pipeline 7 of the pipeline assembly 6 .

[0045] In the proposed method, it is now essential that flow is passed through the rotary pump 10 in the opposite direction of flow compared to the intended operation in order to achieve dynamic in-line mixing.

[0046] like Figure 2 As shown, here and preferably, the rotary pump 10 has a rotating shaft 11, in particular for driving an impeller 12 with blades, which is driven in particular motorically (sometimes referred to as motor-driven) for dynamic in-line mixing. Preferably, the rotating shaft 11 is driven in such a way that the volume flow of the flow in the flow direction behind the pump 9 is less than or equal to the volume flow in front of the pump 9. This makes it possible for the rotary pump 10 to act as a mixer, wherein, by adjusting the rotation speed of the rotating shaft 11, variable mixing properties can ultimately be achieved.

[0047] The term "speed control" here refers to external speed control of the rotating shaft 11, and not, for example, speed control caused by the flow itself. Therefore, this involves speed control of the rotating shaft 11 achieved by influencing, in particular braking or accelerating, the rotating shaft outside the flow.

[0048] As in Figure 3As presented in , here and preferably, the rotary pump 10 has an impeller 12 with blades, which in turn have a curved blade surface. When flowing through the rotary pump 10, the pressure exerted by the medium 1 to be fully mixed is preferably less on the inner side of the curved portion of the blade surface than on the outer side of the blade surface. Therefore, the flow conditions (such as flow velocity, volume flow, liquid pressure, etc.) can be kept constant, so that there is no need to endure a critical pressure increase. When using such an impeller 12, when the rotary pump 10 flows in reverse according to the proposal, the rotation direction of the impeller 12 preferably also corresponds to the flow direction of the resultant liquid flow 5. Otherwise, the rotation of the impeller 12 will resist the flow of the resultant liquid flow 5 and thus hinder the flow when flowing through the rotary pump 10. However, even if the rotation direction of the impeller 12 extends against the flow direction of the resultant liquid flow 5, the desired reduction of the delivery rate of the rotary pump 10 still occurs, and if necessary, even offsets it, which will lead to a critical pressure increase. A particularly preferred reversal of the direction of rotation of the impeller 12 of the rotary pump 10 can preferably be achieved by corresponding wiring, further preferably by phase reversal.

[0049] At this point it should be pointed out in particular that the effect according to the invention proposed (i.e. variable mixing properties can be set by adjusting the speed of the impeller 12 under simultaneously constant flow conditions, without having to tolerate a critical pressure increase) cannot be achieved by simply reversing the direction of rotation of the impeller 12 of the rotary pump 10. In fact, a pump arranged in the intended installation direction and whose impeller 12 rotates in the reversed direction will continue to pump in the same intended direction as before, even if the efficiency of the pump is significantly limited, the flow rate is reduced and the noise is increased. The delivery effect remains at least partially unchanged, so that an undesirable pressure increase still occurs.

[0050] like Figure 3 As explained, the rotary pump 10 preferably has a pump housing 13. The impeller 14 ( Figure 2 ) takes place parallel to the rotation axis of the impeller 14. Preferably, the inflow into the pump housing 13 takes place at an angle to the rotation axis of the impeller 14, more preferably orthogonally.

[0051] Preferably, if Figure 1 As explained, the liquid is discharged from the first container 15 and the at least one further liquid or solid component is discharged from the at least one second container 16 into the pipeline assembly 6. The pipeline assembly 6 can have a plurality of pipelines 7, which are each fluidically connected to an associated container 15, 16. In this case and preferably, the pipeline assembly 6 is associated with a valve assembly 17 with at least one valve 18, which is designed to selectively connect the pipelines 7 in a fluidic manner.

[0052] Here and preferably, the pump assembly 8 has a second pump 19, which is designed to discharge a liquid in a metered manner, preferably from the first container 15 into the pipeline 7 of the pipeline assembly 6. In addition, the pump assembly 8 has at least one third pump 20, which is designed to discharge a corresponding further liquid or solid component in a metered manner, preferably from the second container 16 into the second pipeline 7 of the pipeline assembly 6 ( Figure 1 ).

[0053] Furthermore, at least the second pump 19 and / or the third pump 20 and preferably all pumps set up for metered discharge of liquid flows can be designed as metering pumps, in particular as hose pumps, rotary piston pumps or diaphragm pumps. Additionally or alternatively, at least the third pump 20 and preferably all pumps set up for metered discharge of solids can be designed as solids pumps (Feststoffpumpe, sometimes called solid handling pumps), preferably as wastewater pumps or slurry pumps.

[0054] Here and preferably, all pumps set up for dynamic in-line mixing of liquids are designed as rotary pumps 10, preferably as centrifugal rotary pumps, further preferably as disposable centrifugal rotary pumps. Additionally or alternatively, the first pump 9 and preferably all pumps set up for dynamic in-line mixing of liquids are set up for adjusting the desired mixing properties in the resulting liquid flow 5. The mixing properties can preferably be adjusted, in particular steplessly adjusted, by adapting at least one parameter of the at least one rotary pump 10, preferably by adapting the rotational speed of the impeller 12 of the rotary pump 10. Preferably, the bioprocess component 3 has an electronic process controller 21, which adjusts the at least one parameter of the at least one rotary pump 10, in particular the rotational speed of the impeller 12 of the rotary pump 10. Also additionally or alternatively, the degree of adaptation of the at least one parameter of the rotary pump 10, preferably the rotational speed of the impeller 12 of the rotary pump 10, is derived by a mixing model 22, preferably by the electronic process controller 21 (see Figure 1 ). Preferably, the mixing model 22 represents the dependency between the mixing behavior on the one hand and the at least one parameter of the rotary pump 10 , preferably the rotational speed of the impeller 12 of the rotary pump 10 , on the other hand.

[0055] The electronic process controller 21 controls at least the valve assembly 17 and the pump assembly 8. The pumps of the pump assembly 8 can preferably be selectively controlled by the electronic process controller 21 in order to produce predefined theoretical conditions in the resultant liquid flow 5. The theoretical conditions are preferably buffer conditions or medium conditions, such as a specific pH, a concentration of at least one substance, conductivity, etc.

[0056] As in Figure 1As presented in , here and preferably in the method according to the proposal, a sensor arrangement 23 is provided with at least one sensor 24 for generating sensor data of the synthetic liquid flow 5, in particular a pH sensor, a conductivity sensor, a flux sensor or a concentration sensor or the like. The sensor 24 is here and preferably arranged downstream of the rotary pump 10 in the pipeline 7 of the pipeline arrangement 6. Preferably, the sensor data describing the actual conditions in the synthetic liquid flow 5 at the measuring point 25 are transmitted to the electronic process controller 21. Alternatively or additionally, the sensor data can be incorporated into the mixing model 22 and / or preferably used by the electronic process controller 21 in order to evaluate the mixing properties in the synthetic liquid flow 5.

[0057] As in Figure 1 As can be seen in FIG. 1 , a feedback line 26 is provided, which branches off downstream of the rotary pump 10. The feedback line 26 is set up to introduce the resultant liquid stream 5 upstream of the rotary pump 10 to fully mix the liquid stream again, and when the feedback criteria are met, the feedback line can preferably be selectively connected by the electronic process controller 21. The feedback line 26 here and preferably has a fourth pump 27, so as to introduce the resultant liquid stream 5 upstream of the rotary pump 10 to fully mix the liquid stream again ( Figure 1 ). Preferably, the feedback criterion is met if the actual conditions in the resultant liquid flow 5 measured by the sensor 24 fluctuate by more than a preset value, preferably by more than 5%, further preferably by more than 10% and / or deviate from the theoretical conditions.

[0058] For example, if the concentration desired by the user has not yet been reached, so that the parameter measured by the at least one sensor 24 deviates by more than a preset value, the resultant liquid flow 5 can be introduced upstream of the rotary pump 10 to fully mix the liquid flow again, preferably for such a long time, that is, until the resultant liquid flow 5 has the desired theoretical conditions. It can also be provided that the feedback line 26 is set up for feedback control.

[0059] The term “feedback control” here refers to the self-regulation of the behavior of the system, in particular with regard to the rotational speed of the impeller 12 of the rotary pump 10 , based on sensor data measured by means of at least one data-connected sensor 24 .

[0060] In the specified installed state, the resulting liquid flow 5 is directed here, preferably downstream of the rotary pump 10, to at least one downstream unit 28 for intermediate storage or further processing ( Figure 1 ). The downstream unit 28 is preferably an intermediate container for intermediate storage of the resultant liquid stream 5. For example, in the case of intermediate storage, the aim may be that a certain minimum theoretical volume has accumulated in the intermediate container before its further processing.

[0061] Alternatively, the downstream unit 28 is preferably a treatment unit consisting of a group including a filtration unit, a chromatography unit, a virus filtration unit, etc. It can also be provided that the resulting liquid stream 5 is firstly conducted to an intermediate container for intermediate storage and after a predefined, preferably user-defined, time is conducted to at least one treatment unit for further processing.

[0062] According to another teaching of independent significance, a bioprocess component 3 is provided for the dynamic in-line mixing of a pressure-loaded medium 1, in particular a buffer and / or a culture medium, containing a liquid and at least one other liquid or solid component. The liquid and the at least one other liquid or solid component are combined at a predefined volume ratio at an inlet 4 to form a combined liquid flow 5. The bioprocess component 3 has a pipeline component 6 with at least one pipeline 7, through which the medium 1 to be mixed is guided. In addition, the bioprocess component 3 has a pump component 8 with a first pump 9, wherein the first pump 9 is arranged in the pipeline 7 of the pipeline component 6. The first pump 9 is designed as a rotary pump 10, in particular a centrifugal rotary pump, and is set up for the dynamic in-line mixing of the medium 1. The first pump 9 has a liquid inlet 9a, which forms the suction side of the pump in the specified operation, and a liquid outlet 9b, which forms the pressure side of the pump in the specified operation, wherein the medium 1 is guided through the rotary pump 10 for dynamic in-line mixing. In this regard, reference is made to all statements regarding the method according to the proposal.

[0063] In the proposed bioprocess module 3 , it is now important that the rotary pump 10 is arranged in such a way that, during operation of the bioprocess module 3 , flow passes through the rotary pump in the opposite direction compared to intended operation for dynamic in-line mixing.

[0064] Here and preferably, the line assembly 6 and / or the rotary pump 10 are designed as disposable components. Additionally or alternatively, the rotary pump 10 has at least one disposable pump head and / or a disposable pump housing. Thus, according to the proposed method, it is provided to use a rotary pump 10, preferably a centrifugal rotary pump, further preferably a disposable centrifugal rotary pump for in-line mixing in an inverted (wrong) installation orientation, which rotary pump is preferably fully assembled before use and delivered sterile without risk of contamination.

[0065] According to a further teaching having independent significance, an electronic process controller for the proposed bioprocess component is claimed. In this regard, reference is made to all the statements concerning the proposed method for dynamic inline mixing and concerning the proposed bioprocess component.

[0066] According to a preferred embodiment of claim 16 , the electronic process control has a data processing system for implementing the proposed method.

[0067] According to a further teaching having independent significance according to claim 17, the use of a rotary pump for carrying out the proposed method is claimed. In this regard, reference is made to all the statements concerning the proposed method for dynamic in-line mixing, the proposed bioprocess component and the proposed electronic process controller.

[0068] According to a further teaching having independent significance, a computer program for an electronic process controller according to the proposal is claimed. In this regard, reference is made to all the statements concerning the method according to the proposal for dynamic inline mixing, the bioprocess component according to the proposal, the electronic process controller according to the proposal and the use according to the proposal.

[0069] According to another teaching having independent significance, a computer-readable storage medium for storing the proposed computer program is claimed. In this regard, reference is made to all the statements concerning the proposed method for dynamic in-line mixing, the proposed bioprocess component, the proposed electronic process controller, the proposed use and the proposed computer program.

Claims

1. A method for the dynamic inline mixing of a pressure-loaded medium (1) containing a liquid and at least one further liquid or solid component, in particular for the inline mixing of a buffer and / or a culture medium, in a bioprocess component (3), wherein: The liquid and the at least one further liquid or solid component are brought together at an inlet point (4) in a predefined volume ratio to form a resulting liquid flow (5), wherein the bioprocess component (3) has a pipeline component (6) with at least one pipeline (7) through which the medium (1) to be mixed is guided, wherein the bioprocess component (3) has a pump component (8) with a first pump (9), wherein the first pump (9) is arranged in the pipeline (7) of the pipeline component (6), wherein the first pump (9) is designed as a rotary pump (10), in particular a centrifugal rotary pump, which is designed for dynamic in-line mixing of the medium (1), wherein the first pump (9) has a liquid inlet (9a) which forms the suction side of the pump in accordance with the intended operation and a liquid outlet (9b) which forms the pressure side of the pump in accordance with the intended operation, and wherein the medium (1) is guided through the rotary pump (10) for dynamic in-line mixing, It is characterized in that Compared to normal operation, flow passes through the rotary pump (10) in the opposite direction of flow for dynamic in-line mixing.

2. The method according to claim 1, characterized in that The rotary pump (10) has a rotating shaft (11) which is driven, in particular motor-driven, for dynamic in-line mixing, preferably in such a way that the volume flow of the flow in the flow direction downstream of the pump (9) is less than or equal to the volume flow upstream of the pump (9).

3. The method according to claim 1 or 2, characterized in that: The rotary pump (10) has an impeller (12) with blades which in turn have curved blade surfaces and when the medium (1) to be mixed flows through the pump (9), the pressure exerted on the inner side of the curvature is lower than on the outer side.

4. The method according to any one of the preceding claims, characterized in that The rotary pump (10) has a pump housing (13), and the outflow from the pump housing (13) occurs parallel to the rotation axis of the impeller (14), and preferably the inflow into the pump housing (13) occurs at an angle, in particular orthogonal, to the rotation axis of the impeller (14).

5. The method according to any one of the preceding claims, characterized in that The liquid is discharged from a first container (15) and the at least one further liquid or solid component is discharged from at least one second container (16) into the pipeline assembly (6). Preferably, the pipeline assembly (6) has a plurality of pipelines (7), which are respectively in fluidic connection with the associated containers (15, 16). Further preferably, the pipeline assembly (6) is associated with a valve assembly (17) having at least one valve (18) for selectively connecting the pipelines (7) in a fluidic manner.

6. The method according to any one of the preceding claims, characterized in that The pump assembly (8) comprises: a second pump (19) which is designed to discharge liquid in a metered manner, preferably from the first container (15) into the pipeline (7) of the pipeline assembly (6); and at least one third pump (20) which is designed to discharge a corresponding other liquid or solid component in a metered manner, preferably from the second container (16) into the second pipeline (7) of the pipeline assembly (6).

7. The method according to claim 6, characterized in that At least the second pump (19) and / or the third pump (20), preferably all pumps set up for metered discharge of liquid flows are designed as metering pumps, preferably, the corresponding pumps are designed as hose pumps, rotary piston pumps or diaphragm pumps, and / or at least the third pump (20), preferably all pumps set up for metered discharge of solids are designed as solid pumps, preferably, the corresponding pumps are designed as wastewater pumps or slurry pumps.

8. The method according to any one of the preceding claims, characterized in that All pumps configured for dynamic inline mixing of liquids are designed as rotary pumps (10), preferably as centrifugal rotary pumps, further preferably as disposable centrifugal rotary pumps, and / or the first pump (9), preferably all pumps configured for dynamic inline mixing of liquids, are configured for adjusting the desired mixing properties in the resulting liquid flow (5), and the mixing properties can be adjusted, in particular steplessly adjusted, by adapting at least one parameter of the at least one rotary pump (10), preferably by adapting the rotational speed of the impeller (12) of the rotary pump (10), preferably, the bioprocess component (3) has an electronic process controller (21 ), further preferably, the electronic process controller (21) regulates the at least one parameter of the at least one rotary pump (10), in particular the rotational speed of the impeller (12) of the rotary pump (10), and / or the degree of adaptation of the at least one parameter of the rotary pump (10), preferably the rotational speed of the impeller (12) of the rotary pump (10) is derived from a mixing model (22), preferably by the electronic process controller (21), preferably, the mixing model (22) represents the correlation between the mixing performance on the one hand and at least one parameter of the rotary pump (10), preferably the rotational speed of the impeller (12) of the rotary pump (10) on the other hand.

9. The method according to claim 5 or 8, characterized in that: The electronic process controller (21) controls at least the valve assembly (17) and the pump assembly (8), preferably, the pump of the pump assembly (8) can be selectively controlled by the electronic process controller (21) so as to produce predefined theoretical conditions, preferably buffer conditions or medium conditions in the synthetic liquid flow (5).

10. The method according to any one of the preceding claims, characterized in that A sensor assembly (23) is provided, which has at least one sensor (24) for generating sensor data of the synthetic liquid flow (5), the sensor (24) being arranged downstream of the rotary pump (10) in the pipeline (7) of the pipeline assembly (6), the sensor data being transmitted to the electronic process controller (21) and describing the actual conditions in the synthetic liquid flow (5) at a measuring point (25).

11. The method according to any one of the preceding claims, characterized in that A feedback line (26) is provided, which branches off downstream of the rotary pump (10), and the feedback line (26) is set up to introduce the synthetic liquid flow (5) upstream of the rotary pump (10) to fully mix the liquid flow again, and when a feedback criterion is met, the feedback line (26) can preferably be selectively connected by the electronic process controller (21), preferably, if the actual conditions in the synthetic liquid flow (5) measured by the sensor (24) fluctuate by more than a preset value, preferably by more than 5%, further preferably by more than 10% and / or deviate from the theoretical conditions, then the feedback criterion is met.

12. The method according to any one of the preceding claims, characterized in that The resulting liquid stream (5) is conducted downstream of the rotary pump (10) to at least one downstream unit (28) for intermediate storage or further processing.

13. A bioprocess component for the dynamic inline mixing of a pressurized medium (1), in particular a buffer and / or a culture medium, comprising a liquid and at least one further liquid or solid component, wherein: The liquid can be combined with the at least one further liquid or solid component in a predefined volume ratio at an inlet point (4) to form a resultant liquid flow (5), wherein the bioprocess component (3) has a pipeline component (6) with at least one pipeline (7) through which the medium (1) to be mixed is guided, wherein the bioprocess component (3) has a pump component (8) with a first pump (9), wherein the first pump (9) is arranged in the pipeline (7) of the pipeline component (6), wherein the first pump (9) is designed as a rotary pump (10), in particular a centrifugal rotary pump, which is designed for dynamic in-line mixing of the medium (1), wherein the first pump (9) has a liquid inlet (9a) which forms the suction side of the pump in proper operation and a liquid outlet (9b) which forms the pressure side of the pump in proper operation, and wherein the medium (1) is guided through the rotary pump (10) for dynamic in-line mixing, It is characterized in that The rotary pump (10) is arranged in such a way that, during operation of the bioprocess module (3), flow passes through it in the opposite direction of flow compared to normal operation for dynamic in-line mixing.

14. The bioprocessing component according to claim 13, characterized in that The line assembly (6) and / or the rotary pump (10) are designed as disposable components and / or the rotary pump (10) has at least one disposable pump head and / or a disposable pump housing.

15. An electronic process controller for a bioprocess component (3) according to claim 13 or 14, characterized in that The pipeline assembly (6) is associated with a valve assembly (17) having at least one valve (18) for selectively connecting the pipeline (7) in a fluidic manner, and the electronic process controller (21) is set up to carry out the method according to any one of claims 1 to 12 by controlling at least the rotary pump (10), the pump assembly (8) and / or the valve assembly (17).

16. The electronic process controller according to claim 15, characterized in that The electronic process control (21) has a data processing system for implementing the method according to any one of claims 1 to 12.

17. A rotary pump (10), in particular a centrifugal rotary pump, for use in performing a method according to any one of claims 1 to 12, preferably, the rotary pump (10), in particular including at least a pump head and a pump housing (13), at least the components necessary for the prescribed functions form a structural assembly, further preferably, the structural assembly is designed as a pre-assembled or one-piece unit, the unit is preferably designed as a disposable component and / or has a sterile packaging for sterile use.

18. A computer program for an electronic process controller (21) according to any one of claims 15 or 16.

19. A computer-readable storage medium on which a computer program according to claim 18 is stored, preferably in a non-volatile manner.

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