Flow-Through Centrifuge

Abstract

The present invention relates to a flow-through centrifuge (1) with a rotor (6). The flow-through centrifuge (1) comprises a connecting strand (12) with connecting lines (16, 17) through which the medium in containers (8a, 8b) located in the centrifuge chamber of the rotor (6) can be exchanged. According to the invention, in order to counteract heating of the connecting strand (12) as a result of repeated deformations and friction occurring within the connecting strand (12), a temperature-regulating supply line (14) and a temperature-regulating discharge line (15) for a connecting strand temperature-regulating fluid extend through the connecting strand (12). The temperature-regulating supply line (14) and the temperature-regulating discharge line (15) are passed through by the connecting strand temperature-regulating fluid in opposite flow directions. An electronic control unit (28) has control logic that provides open-loop or closed-loop control of the splice strand temperature control output of the splice strand temperature control circuit (36).

Description

[Technical Field]

[0001] The present invention relates to a flow-through centrifuge, in which at least one medium (in particular a fluid, liquid, suspension, etc.) is supplied to and / or discharged from the centrifugation chamber at least temporarily while the centrifugation chamber is rotating. The medium can then be arranged in a container in the centrifugation chamber. The at least one medium is in particular the medium to be centrifuged, a purge liquid, a washing or buffer solution, a medium extracted and transformed from the medium to be centrifuged, and / or a sediment in the centrifugation chamber.

[0002] To give just a few non-limiting examples, a flow-through centrifuge can be a blood centrifuge in which the medium to be centrifuged is blood and the extracted and transformed medium or sediment is blood cells or blood particles, or it can be a flow-through centrifuge in which cells, microcarriers or other particles contained in the medium are to be obtained. It is also possible that the medium to be centrifuged is not a pure liquid, but rather the medium is a solution or suspension containing particles, such as cells, cell debris or cell debris.

[0003] Flow-through centrifuges are used, for example, in biopharmaceutical companies to produce biopharmaceutical products or in bioprocessing applications. They may then be used, for example, for the harvesting and / or clarification of cells or microcarriers, and the cells thus harvested may also be used for cell therapy. A further field of use for flow-through centrifuges is, for example, the production of vaccines. [Background technology]

[0004] The flow-through centrifuges mentioned in the preamble are sold, for example, by the company Sartorius AG (Otto-Brenner-Strasse 20, 37079 Goettingen, Germany) and associated companies under the trademark "Ksep" (registered trademark). On the Internet page about these flow-through centrifuges (Non-Patent Document 1), the functional principle of a flow-through centrifuge, which may also be used in the present invention, is explained as follows, based on the linked video:

[0005] The rotor of the flow-through centrifuge has four centrifuge chambers, which may be formed as blood bags held in the rotor body and are evenly distributed around the circumference. The centrifuge chambers are arranged at the same radial distance from the rotation axis of the rotor. A first communication line opens into the centrifuge chambers at a radially inner position, while a second communication line opens into the centrifuge chambers at a radially outer position. In a first operating phase, while the centrifuge chambers rotate with the rotor, a first medium, for example blood, is supplied to the centrifuge chambers via the second communication line. As a result of centrifugation in the centrifuge chambers, particles contained in the blood (e.g., blood cells) settle outward in the radial direction, while the remaining medium (i.e., the medium supplied at the radially outer position and reduced by the particles displaced radially outward) is discharged from the centrifuge chambers at a radially inner position via the first communication line. In this first operating phase, the first connecting line is thus a discharge line, while the second connecting line is a supply line. As this operation continues, the proportion and concentration of particles in the centrifuge chamber increases until the centrifuge chamber is largely, and eventually completely, filled with particles. In a subsequent, optional, second operating phase, washing of the particles in the centrifuge chamber is carried out. For this purpose, a washing or buffer solution is introduced into the centrifuge chamber via the second connecting line. The washing or buffer solution purges the centrifuge chamber and is discharged radially inward via the first connecting line. In this operating phase, the centrifuge chamber rotates together with the rotor, so that the particles are prevented from escaping from the centrifuge chamber together with the washing or buffer solution via the first connecting line as a result of the centrifugal force acting thereon. During the second operating phase, the first connecting line is also used as an outlet line for the washing or buffer solution, while the second connecting line is used as a supply line for the washing or buffer solution. In the subsequent third operating phase, rotation of the centrifuge chamber together with the rotor continues.In the third operating phase, the flow direction through the centrifuge chamber is reversed, and particles are removed from the centrifuge chamber via the second connecting line, while a wash solution or buffer solution can be replenished into the centrifuge chamber via the first connecting line. The third operating phase ends when all particles have been removed from the centrifuge chamber. Further cycles having the three described operating phases can then be performed sequentially.

[0006] EP 0 999 594 A1 discloses the construction of a media network, which is connected to communicating pipelines and ensures the various operating phases. With regard to this media network, the included pump assemblies, process control units, additional filter assemblies, containers for the different media, and with regard to the process flow, reference is additionally made to EP 0 999 594 A1, EP 0 999 594 B1 and EP 0 999 594 C1.

[0007] Patent Document 3 describes problems with fluid connections using rotary feedthroughs to connecting lines that rotate with the rotor in flow-through centrifuges, since rotary feedthroughs are prone to leaks and entail the risk of undesired contamination of the medium. On the other hand, Patent Documents 4, 5, 6, and 7 describe the use of connecting strands in which connecting lines can be integrated. One end region of the connecting strand is fixed to the housing, while the other end region is attached to the rotor and rotates with it. To prevent the connecting strand from becoming twisted as a result of the rotor rotating relative to the end region of the connecting strand, the connecting strand is additionally guided in a guide device formed as a guide pipe. The guide pipe has rounded U-shaped subsections with side legs of different lengths that can easily open up from one another. The opening of the U faces the rotation axis of the rotor. The connecting strands start from the fixed end region of the housing and curve outward to enter one side leg of the U. Within the U-shaped section, the connecting strands are routed around the rotor by a guide pipe. The free end region of the other side leg of the U of the guide pipe is curved back so that it is arranged coaxially with the rotor's rotation axis and directly adjacent to the entry of the connecting strands into the rotor. The guide pipe is driven in this case at half the rotor rotation speed. Patent Document 3 refers to Patent Document 8 to explain how the use of a rotating guide pipe avoids increased twisting of the connecting strands.

[0008] Patent Document 9 discloses a blood pump that can extract blood from a patient, separate it into red blood cells and plasma, and then return the red blood cells to the patient while recovering the plasma. This separation is performed in this case by centrifugation as a result of their different densities. Patent Document 9 describes that supplying blood to a rotating separation chamber via a rotary joint can be problematic because unwanted heat is generated in the area of ​​the rotary joint, which can adversely affect the blood and its components or require additional cooling. A further problem is that blood cells can be destroyed as a result of shear forces in the area of ​​the contact surfaces between the joint parts of the rotary joint. The blood pump proposed in Patent Document 9 has a tubing strand through which multiple tubing lines extend. A blood supply line extends from a first end of the conduit strand through the conduit strand to a separation chamber located in the other end region of the conduit strand, and a blood discharge line extends in the opposite direction from the separation chamber to the first end of the conduit strand. The first end of the conduit strand extends vertically and is immovably held by a machine frame element. Blood arrives from a patient at the first end region, and after fractionation, blood cells return to the patient from the first end region. A rotating device is rotatable about a rotation axis extending vertically and coaxially with respect to the first end region of the conduit strand. Within the rotating device, the conduit strand is fixedly clamped adjacent to the first end region and coaxially with respect to the rotation axis. From this fixed clamping portion, the pipe strand extends radially outward through the rotating device along a quadrant arc so that the second end region of the pipe strand is horizontally oriented with a separation chamber formed therein and is at a maximum distance from the rotation axis. The second end region is clamped within the rotating device so that the orientation of the second end region is predetermined. Between the clamping portions at both end regions, the pipe strand extends freely. As the pipe strand rotates about the rotation axis, a pivoting movement of the pipe strand occurs about the horizontal clamping axis at the second end region to allow for compensatory movement.A cooling liquid may be disposed within one of the pipe strands, and this cooling liquid may absorb heat generated by shear loads on the pipe strand as a result of bending of the pipe strand as it rotates.

[0009] Patent documents 10, 11 and 12 describe flow-through centrifuges with a rotor having a centrifugation chamber and a connecting strand guided in a guide device, the guide device being rotated at half the rotor speed of the rotor to avoid twisting of the connecting strand. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] European Patent Application Publication No. 3936601 [Patent Document 2] European Patent No. 2310486 [Patent Document 3] European Patent No. 2485846 [Patent Document 4] U.S. Patent No. 4,216,770 [Patent Document 5] U.S. Patent No. 4,419,089 [Patent Document 6] U.S. Patent No. 4,389,206 [Patent Document 7] U.S. Patent No. 5,665,048 [Patent Document 8] U.S. Patent No. 3,586,413 [Patent Document 9] International Publication No. 80 / 02653 [Patent Document 10] DE 2612988 A1 [Patent Document 11] DE 3504205 A1 [Patent Document 12] U.S. Patent No. 3,129,174 [Non-patent literature]

[0011] [Non-Patent Document 1] www.sartorius.com / en / products / process-filtration / cell-harvesting / ksep-systems (accessed July 6, 2022) Summary of the Invention [Problem to be solved by the invention]

[0012] The problem underlying the present invention is to improve flow-through centrifuges with regard to the guarantee of predefined operating conditions. [Means for solving the problem]

[0013] The object of the present invention is achieved according to the features of the independent claims. Further preferred configurations according to the invention can be found in the dependent claims.

[0014] The present invention relates to a flow-through centrifuge. The flow-through centrifuge comprises a rotor with (at least) one centrifugation chamber. The medium to be centrifuged can be placed in the centrifugation chamber, either directly or in a suitable container, and the centrifugation chamber can be purged with another medium, for example, a washing solution or a buffer solution. In a flow-through centrifuge, the rotor is rotated around the rotor axis at any rotor speed. The flow-through centrifuge comprises a connecting strand. The connecting strand has a communicating line through which a medium can be supplied to the centrifugation chamber (in particular, a container placed in the centrifugation chamber) during operation of the flow-through centrifuge with the rotor rotating. The connecting strand further has a communicating line through which a medium can be discharged from the centrifugation chamber (in particular, a container placed in the centrifugation chamber). Depending on the current operating phase, the flow direction through the communicating line can be reversed. One end region of the connecting strand is fixed to the housing, while the other end region of the connecting strand rotates together with the rotor. To prevent twisting of the connecting strands, the connecting strands are guided in a guide device, in particular a guide pipe, which is rotated around the rotor axis at half the rotor speed. In this respect, the flow-through centrifuge can be configured similarly to the prior art flow-through centrifuges described at the outset, for example.

[0015] In a flow-through centrifuge, it is desirable that the centrifugation of the medium in the centrifuge chamber and the feeding and discharging of the medium are carried out under as defined operating conditions as possible, which includes maintaining the temperature of the medium to be centrifuged within a predefined temperature range. For this reason, a rotor chamber temperature regulation circuit is used in flow-through centrifuges. In this case, the rotor chamber temperature regulation circuit typically has a rotor chamber temperature regulation loop integrated into the wall of the can of the flow-through centrifuge, which is in heat exchange with the rotor chamber in which the rotor rotates. In some cases, a temperature sensor, also integrated into the can of the rotor chamber, detects the temperature in the rotor chamber. Based on the signal of this temperature sensor, a closed-loop control of the temperature regulation output of the rotor chamber temperature regulation circuit can then be carried out so that the temperature in the rotor chamber is maintained as constant as possible, which, according to the prior art, also results in the medium to be centrifuged having a constant temperature.

[0016] The considerations underlying the present invention first address the causes of temperature variations within a flow-through centrifuge. One cause of heating within the rotor chamber is that the air disposed within the rotor chamber is accelerated and swirled as a result of the rotational movement of the rotor, which can lead to heating of the air. Additionally, heat input into the rotor chamber can occur, for example, from the centrifuge drive or as a result of friction, e.g., within the rotor shaft bearings. This heating can be addressed by known rotor chamber temperature regulation circuits.

[0017] Another source of heat input, based on the considerations underlying the present invention, is that the connecting strands are deformed as a result of their boundary conditions, i.e., the fixed connection of one end region with the housing and the rotation of the other end region together with the rotor, and their guidance by a guide device that rotates around the rotor axis at half the rotor speed, which leads in particular to repeated deformation movements in the connecting strands, which can lead to heating of the connecting strands.Furthermore, friction of the connecting strands with the guide device can also lead to heating of the connecting strands.

[0018] Conventional flow-through centrifuges do not take these different heat input possibilities into account, and as a result, the different heat input possibilities are merely averaged and taken into account collectively via the rotor chamber temperature control circuit. While the known open-loop or closed-loop control of the rotor chamber temperature control circuit would ideally achieve a predetermined temperature for the temperature sensor in the can wall, local temperature deviations can still occur. In particular, undesirable high temperatures can occur in the region of the connecting strands as a result of the repeated deformations and friction that occur. When the medium flows through the connecting lines in the connecting strands, undesirable heating of the medium occurs.

[0019] Based on this understanding, the present invention proposes that in the flow-through centrifuge according to the present invention, a temperature-regulating supply line and a temperature-regulating discharge line extend through the connecting strand. The temperature-regulating supply line and the temperature-regulating discharge line are passed through by the connecting strand temperature-regulating fluid in opposite flow directions. The temperature-regulating supply line and the temperature-regulating discharge line are thus part of a connecting strand temperature-regulating circuit, which can specifically cause cooling in the region of the connecting strand, ideally cooling that counteracts the heat generated in the region of the connecting strand as a result of repeated deformation movements and friction. This allows the present invention to address temperature increases directly at the source. This means that operating conditions, i.e., temperatures, can be maintained precisely or within a predetermined temperature range in the flow-through centrifuge, i.e., in the region of the connecting strand.

[0020] According to the invention, the flow-through centrifuge comprises at least one electronic control unit, which in the case of a plurality of electronic control units may be interconnected or networked together, and which has a control logic for implementing open-loop or closed-loop control of the connecting strand temperature regulation output of the connecting strand temperature regulation circuit.

[0021] The temperature-regulating supply lines, the temperature-regulating discharge lines and the communication lines (as well as any other possible components of the connecting strand) can be distributed in any way over the cross section of the connecting strand, for example arranged side by side or overlapping. In one proposal of the invention, the temperature-regulating supply lines, the temperature-regulating discharge lines and the communication lines are distributed in the cross section of the connecting strand in the circumferential direction around the longitudinal axis of the connecting strand, and preferably each directly abuts an adjacent line in the circumferential direction.

[0022] The order in which the listed lines are arranged in the circumferential direction is basically arbitrary. In one proposal of the invention, the temperature-regulating supply lines, the temperature-regulating discharge lines, and the communication lines are distributed in the cross section of the connecting strand around the longitudinal axis of the connecting strand, with at least one communication line being arranged between the temperature-regulating supply lines and the temperature-regulating discharge lines on both sides of the circumference around the longitudinal axis. This means that the at least one communication line is arranged "sandwich-like" between the temperature-regulating supply lines and the temperature-regulating discharge lines, so that the at least one communication line is in a heat exchange relationship with both the temperature-regulating supply line and the temperature-regulating discharge line. This allows for particularly good heat transfer between the temperature-regulating lines and the communication lines.

[0023] Preferably, in the flow-through centrifuge according to the invention, the temperature-regulating supply line and the temperature-regulating discharge line are connected to one another via a turn-back connection. In this case, the turn-back connection can be configured as a U-shaped connecting element. One leg of the U can be connected to the end region of the temperature-regulating supply line, while the other leg of the U can be connected to the end region of the temperature-regulating discharge line. This connection can be implemented, for example, by each leg being introduced into the temperature-regulating line and being held therein (e.g., by a positive and / or frictional connection or clamp; in some cases, also by a seal or sealing means), whereby the temperature-regulating line and the leg of the connecting element can be pressed against each other and plastically deformed. In this case, the turn-back connection is preferably connected in the end region of the connecting strand and the temperature-regulating line that rotates together with the rotor. The turn-back connection ensures a counter-flow through the temperature-regulating line.

[0024] According to one proposal of the invention, the connecting strands comprise flexible pipes or tubes. In this case, the temperature-regulating supply lines, the temperature-regulating discharge lines, and the connecting lines extend through the flexible pipes or tubes. The pipes or tubes can have a smooth outer surface to keep vortexes in the rotor chamber small. A non-smooth outer geometry of the pipes or tubes is also possible, for example, a flexible corrugated pipe. The flexible pipes or tubes keep the temperature-regulating lines and the connecting lines compact and also ensure their protection. The tubes or pipes can also be used for thermal encapsulation of the connecting strands.

[0025] The temperature-regulating supply and discharge lines can extend from the housing only over a portion of the longitudinal extension of the connecting strand, preferably corresponding to the region of the connecting strand where the aforementioned repeated deformation and / or friction occurs. In this case, the turn-back connection can be arranged at the end of the extension of the temperature-regulating line, which results in the turn-back connection or U-shaped connection element being arranged inside the connecting strand, in particular inside the flexible pipe or flexible tube. As an alternative, the turn-back connection is arranged in the exit region of the temperature-regulating supply and discharge lines from the flexible pipe or tube, so that the temperature-regulating lines extend over the entire length of the connecting strand. Arranging the turn-back connection in the exit region in this case utilizes the relatively large structural space outside the pipe or tube.

[0026] In another embodiment of the present invention, the turn-back connection is U-shaped. In this case, the U-shaped turn-back connection can at least partially surround the at least one communicating line. The communicating line can be bent outward with an extension from the pipe or tube. In this case, the extension and the bent portion can be at least partially located inside the U of the U-shaped turn-back connection, thereby providing additional guidance and / or protection and positioning for the at least one communicating line. On the other hand, the partial surrounding of the communicating line by the turn-back connection leads to a particularly compact design.

[0027] In the flow-through centrifuge according to the invention, it is also possible for at least one electrical line to extend through the connecting strand. In this case, possible heating of the connecting strand and thus of the medium in the connecting lines as a result of heating of the electrical line can be avoided by closed-loop control of the connecting strand temperature regulation circuit. By way of a few non-limiting examples, the electrical line can be any measurement line, an electrical supply line for a sensor located in or attached to the rotor, an electrical control line for a valve of the rotor, etc.

[0028] In the flow-through centrifuge according to the invention, open-loop or closed-loop control of the connecting strand temperature regulation circuit can be carried out in any manner and taking into account any signals of temperature sensors, flow sensors and / or any operating parameters of the flow-through centrifuge (speed of rotation, external temperature, internal temperature, rotor configuration and / or equipment, centrifugation program and centrifugation parameters, etc.). In one proposal of the invention, open-loop or closed-loop control of the temperature of the connecting strand temperature regulation fluid and / or its flow (in particular mass flow and / or volume flow) is carried out taking into account the temperature of the medium present in and / or pumped through at least one communicating line. Preferably, the open-loop or closed-loop control is carried out taking into account the temperature difference in the communicating lines. For example, if the temperature is measured in the outlet region of a communicating line discharging a medium from the centrifuge chamber and in the inlet region of another communicating line supplying a medium to the centrifuge chamber, the temperature difference provides information about the heat supplied to the medium between the two measuring points. The greater the heat, the greater the cooling power required, which can be provided by open-loop or closed-loop control of the temperature and / or flow of the connecting strand temperature-regulating fluid. For example, open-loop or closed-loop control can be carried out with the goal of a zero temperature difference or below a threshold value. At least one sensor for detecting the temperature or both sensors for detecting the temperature difference can then be arranged in the housing, in assigned end regions of one or more communicating lines, and thus in a fixed position.

[0029] Preferably, in the flow-through centrifuge, a rotor chamber thermoregulation circuit is also present in addition to the connecting strand thermoregulation circuit. Preferably, the rotor chamber thermoregulation circuit is arranged stationarily, in particular with a cooling loop integrated into the can wall. The connecting strand thermoregulation circuit and the rotor chamber thermoregulation circuit can be fluidically independent of each other, in which case coordination of the circuits can be achieved via at least one control unit. However, it is also possible that a fluid connection exists in the connecting strand thermoregulation circuit and the rotor chamber thermoregulation circuit, or common elements can be used. Thus, for example, the same thermoregulation fluid can be used. Alternatively or additionally, the same pressure source, in particular a pump or pressure vessel, can be used to provide the flow of thermoregulation fluid through both thermoregulation circuits.

[0030] The invention also proposes the presence of an electronic control unit, which has a control logic and which controls the rotor chamber temperature regulation output of the rotor chamber temperature regulation circuit in an open-loop or closed-loop manner, where the electronic control unit may be formed separately from the control unit of the connecting strand temperature regulation circuit, or the control units may be integrated into one overall control unit.

[0031] Various possibilities exist within the scope of the present invention for the configuration of the rotor chamber thermoregulation circuit. In one configuration of the present invention, a temperature sensor is present, which detects the temperature of the rotor chamber (directly or indirectly). For example, the temperature sensor may be integrated into the wall, lid, etc. of the flow-through centrifuge can, protrude into the rotor chamber from there, or be adjacent to the rotor chamber. The temperature sensor may be located on the rotor and rotate with the rotor. Preferably, the temperature sensor is located in a region of the rotor chamber where the flow is quenched. The control logic performs closed-loop control of the rotor chamber thermoregulation circuit, taking into account the temperature signal of the temperature sensor. Preferably, the closed-loop control is performed toward a temperature target value. Any closed-loop control strategy may be used in this case.

[0032] According to one aspect of the present invention, the control logics for the open-loop or closed-loop control of the rotor chamber temperature control output of the rotor chamber temperature control circuit, on the one hand, and the open-loop or closed-loop control of the connecting strand temperature control output of the connecting strand temperature control circuit, on the other hand, are not independent of each other but are coordinated with each other. This can mean, for example, that an increase in the rotor chamber temperature control output is automatically coupled by the control logic with an increase in the connecting strand temperature control output. However, the control logic can also ensure that the sum of the rotor chamber temperature control output, on the one hand, and the connecting strand temperature control output, on the other hand, remains constant, does not fall below and / or exceed a threshold value, or corresponds to a characteristic map or curve profile depending on the operating parameters.

[0033] In one particular configuration of the control logic, the control logic for open-loop or closed-loop control of the connecting strand temperature control output takes into account the heat capacity of the medium flowing through the connecting line. For example, when the supply and / or discharge of the medium to be centrifuged and / or medium residue through the connecting line is switched to the supply of purge solution or buffer solution, the medium on the one hand and the purge solution or buffer solution on the other hand may have different heat capacities. Under the simplified assumption, used only for illustrative purposes, that the same heat is absorbed by the medium per unit time, in this case the heat absorption of a medium with a high heat capacity leads to a smaller temperature change than a medium with a low heat capacity. As a result, for closed-loop control based on the temperature difference, a different amplification factor of the temperature difference must be taken into account to determine the signal for open-loop or closed-loop control of the connecting strand temperature control output. The same applies to the flow of the medium through the connecting lines: if a closed-loop control based on the temperature difference in the connecting lines is carried out, it can be seen that, assuming the same heat input, a higher flow results in a smaller heat change than a lower flow. In some cases, the rotor speed can also be taken into account in the open-loop or closed-loop control of the connecting strand temperature control output, since the repetitive deformation movements in the connecting strand depend on the rotor speed.

[0034] Another aspect of the invention relates to the fact that different heat inputs are implemented at different points in the connecting strand, so that heat is preferably generated in the areas where repeated deformation movements occur, while partial sections of the connecting strand that are not deformed or not repeatedly loaded are not heated, or are heated only to a lesser extent. The invention takes this observation into account by configuring the connecting strand temperature regulation circuit in such a way that different cooling outputs are emitted in different partial sections of the connecting strand. The following are just some non-limiting examples:

[0035] This can be caused, in a first variant, by the cross-sectional area of ​​the temperature-regulated supply line and / or the temperature-regulated discharge line varying over their longitudinal extent, which results in different flow conditions and therefore different cooling outputs depending on the cross-sectional area.

[0036] Alternatively or cumulatively, the cross-sectional geometry of the attemperated supply and / or discharge lines can be varied, for example, in one subsection the cross-sectional geometry can be selected such that a large circumferential surface is created, thereby ensuring good heat transfer, while in another subsection the cross-sectional geometry can be selected such that a smaller circumferential surface is created, with the resulting worsening of heat transfer.

[0037] In this area, it is also possible to implement branching of the thermoregulated supply line and / or the thermoregulated discharge line in areas where an increased release of cooling power is desired.

[0038] As an alternative or cumulative further proposal, the thermal conductivity of the walls or jackets of the temperature-regulated supply and / or discharge lines in various sections may be increased or decreased depending on the desired cooling output, which may be achieved by using different wall and / or jacket materials and / or different wall thicknesses of the walls and / or jackets in the partial sections.

[0039] It is also possible that in the partial sections, restrictions or other fluid components are used that affect the flow relationships.

[0040] Advantageous developments of the invention can be seen from the claims, the description and the drawings.

[0041] The advantages listed in the specification of features and combinations of features are merely examples, and these advantages are not necessarily achieved by an embodiment according to the invention, but may act alternatively or cumulatively.

[0042] With respect to the disclosure of the original application documents and patents, the following applies, except to the scope of protection: further features, in particular the geometric shapes shown and the relative dimensions of the various components to one another, as well as their relative arrangement and interaction, can be seen in the drawings. Combinations of features of different embodiments of the invention or of features of different claims are likewise possible and are envisaged hereby apart from selected references in the claims. This also relates to features shown in different drawings or mentioned in the description thereof. These features may also be combined with features of different claims. Likewise, features recited in the claims may be omitted for the sake of another embodiment of the invention, but this does not apply to the independent claims of the granted patent.

[0043] Features recited in the claims and the description should be understood as being present in exactly that number or in a greater number than the recited number, without the need to explicitly use the adverb "at least" in relation to the number. That is, for example, when referring to one element, this should be understood as meaning that there is exactly one element, two elements, or more elements. Features recited in the claims may be supplemented by further features or may be a single feature possessed by the subject matter of each claim.

[0044] The reference numerals included in the claims do not limit the scope of the subject matter protected by the claims, but are used solely to facilitate the understanding of the claims.

[0045] In the following, the invention will be further explained and illustrated on the basis of preferred embodiments shown in the drawings. [Brief explanation of the drawings]

[0046] [Figure 1] 1 is a highly schematic, three-dimensional half-section longitudinal section of a flow-through centrifuge; FIG. [Figure 2] FIG. 2 is a diagram showing a main part II of the flow-through centrifuge shown in FIG. [Figure 3]FIG. 3 shows one configuration of a cross section of a connecting strand of the flow-through centrifuge shown in FIGS. 1 and 2. [Figure 4] FIG. 3 shows another configuration of the cross section of the connecting strand of the flow-through centrifuge shown in FIGS. 1 and 2. [Figure 5] FIG. 1 is a block diagram for open-loop or closed-loop control of a flow-through centrifuge. DETAILED DESCRIPTION OF THE INVENTION

[0047] In the figures, corresponding or similar components or features are in part designated by the same reference numerals, and these components or features may then be distinguished from one another by the addition of the letters a, b, .... In this case, the components or features may be associated with or without the addition of the letters, and thus reference may be made to one, several or all of the components or features.

[0048] FIG. 1 shows a highly schematic, three-dimensional half-section longitudinal section of a flow-through centrifuge 1. The flow-through centrifuge 1 comprises a housing 2 and, in particular, a can 3 having a wall 4. The wall 4 of the can 3 defines a rotor chamber 5 in which a rotor 6 is rotated about a rotor axis 7 at a given rotor speed. Of the rotor 6, the schematic view shown in FIG. 1 shows only containers 8a, 8b (here, two containers 8a, 8b; however, any other number of containers 8 may also be present) arranged in the centrifugation chamber of the rotor 6. The containers 8 may be, for example, blood bags 9 or any other container. The containers 8 are then evenly distributed around the rotor axis 7 and have the same distance from the rotor axis 7.

[0049] The flow-through centrifuge 1 includes a rotor chamber thermoregulation circuit 10, of which only rotor chamber thermoregulation loop 11 is shown in Figure 1. Rotor chamber thermoregulation loop 11 is embedded in the wall 4 of can 3 and wraps around the rotor axis 7 and rotor chamber 5 with multiple turns.

[0050] Also visible in FIG. 1 is a connecting strand 12. The connecting strand 12 comprises a flexible tube or flexible pipe 13. Through the tube or pipe 13 extend a temperature-regulated supply line 14, a temperature-regulated discharge line 15 (although these lines 14, 15 may also be referred to collectively as "temperature-regulated lines") and two communicating lines 16, 17, through which fluid flows in different directions during different operating phases of the centrifugation process. At one end region 18, the connecting strand 12 is attached to the wall 4 of the housing 2 or can 3, while at the other end region 19, the connecting strand 12 is attached to the rotor 6 and rotates together with it. Guide devices, in particular guide pipes, which rotate at half the rotor speed, are not shown in the schematic diagram of FIG. 1 (see the prior art cited at the beginning for this information).

[0051] 2 shows part II shown in FIG. 1. In this part, the end regions 19 of the connecting strands 12, the extension of the temperature-regulating lines 14, 15 from the tubes or pipes 13, and their connections to the containers 8a, 8b can be seen. As an optional feature, it can be seen here that the containers 8a, 8b are each connected to individual communicating lines 17a, 17b, which are flowed through by the medium in the same direction, while the containers 8a, 8b are connected to a common communicating line 16 for medium flow in another direction. Individual or variable open-loop or closed-loop control of the flow through the communicating lines 17a, 17b via valves or switching devices allows for specific and variable control of the supply of medium to the containers 8a, 8b. In this way, it is possible, for example, to carry out the filling of only a single vessel 8a, 8b, or to start and / or finish the removal of the centrifuged sediment from the vessels 8a, 8b at different times.

[0052] At its exit from the pipe or tube 13, the communicating line 16 is connected via a branch 20 to two connecting lines 21a, 21b, which in turn are connected to the assigned vessels 8a, 8b, respectively. The communicating lines 17a, 17b are connected directly to the assigned vessels 8a, 8b via assigned connecting lines 22a, 22b. In the transition region from the communicating lines 16, 17 to the connecting lines 21, 22, there is a 90° bend in each case, so that the connecting lines 21, 22 extend in a plane extending transversely to the rotor axis 7.

[0053] The temperature-regulating lines 14, 15 are connected to one another directly adjacent to the ends of the pipes or tubes 13 via a turn-back connection 23, here formed as a U-shaped connecting element 24. The bends and transition areas between the communicating lines 16, 17 and the connecting lines 21, 22 extend through the inside of the U-shaped connecting element 24. This results in the turn-back connection 23 at least partially surrounding at least one communicating line 16, 17. The U-shaped connecting element 24 can also ensure the positional fixation of the bends and the connecting lines 21, 22.

[0054] 3 shows a cross section of the connecting strand 12. It can be seen that the temperature-controlling lines 14, 15 and the communicating lines 16, 17a, 17b are distributed around the circumference on a circular arc, directly abutting each other around the circumference and abutting the inner surface of the pipe or tube 13 at their radially outer sides. Preferably, the order around the circumference is selected so that at least one communicating line 16, 17 is arranged between the temperature-controlling lines 14, 15 on each side of the circumference. Thus, the communicating line 16 is arranged between the temperature-controlling lines 14, 15 on one side of the circumference, while both communicating lines 17a, 17b are arranged between the temperature-controlling lines 14, 15 on the other side of the circumference.

[0055] 4, it is also possible for only four lines to be arranged in the cross section, namely the temperature-regulating lines 14, 15 and the communication lines 16, 17. In this case, the communication lines 16, 17 can each have one branch to a different container 8a, 8b. It is clear that by using a different branching arrangement and / or a different number of lines, more than two containers 8 can be present in the rotor 6, each supplied with a different medium.

[0056] FIG. 5 shows a schematic diagram of the control system of the flow-through centrifuge 1 .

[0057] The rotor chamber thermoregulation circuit 10 comprises a preparation unit 25 in which rotor chamber thermoregulation fluid is prepared under open-loop or closed-loop control at the required flow and temperature. The rotor chamber thermoregulation fluid is then supplied in a closed circuit to the rotor chamber thermoregulation loop 11, which may be integrated into the wall 4 of the rotor chamber 5. A temperature sensor 26 detects the temperature in the rotor chamber 5, preferably integrated into or attached to the wall 4 of the rotor chamber 5. The measurement signal of the temperature sensor 26 is supplied via a sensor signal connection 27 to an electronic control unit 28. The control unit 28 comprises a control logic which generates an open-loop or closed-loop control signal in a control line 29 for driving and controlling the preparation unit 25 to ensure a closed-loop controlled flow of the rotor chamber thermoregulation fluid at a closed-loop controlled temperature.

[0058] The centrifugation medium circuit 30 includes a preparation unit 31, which ensures the various operating phases mentioned at the outset and prepares the media, in particular the media to be centrifuged and the purge or buffer solution, with the required flow and flow direction in the various operating phases. A temperature sensor 32, 33 is arranged in each end region 18 of the communicating lines 16, 17 of the centrifugation medium circuit 30, and detects the temperature of the media being fed to and discharged from the centrifugation chamber or vessel 8. The temperature signals of the temperature sensors 32, 33 are transmitted via sensor signal connections 34, 35 to the control unit 28. The control unit 28 includes a control logic, which determines a temperature difference from the temperature signals of the temperature sensors 32, 33. This temperature difference is used for open-loop or closed-loop control of the connecting strand temperature regulation circuit 36, as will be explained further below. Via control line 37, control unit 28 controls preparation unit 31 in an open or closed loop manner to ensure the required flows and the various operating phases.

[0059] In the connecting strand temperature control circuit 36, a connecting strand temperature control fluid is prepared by a preparation unit 38. The control unit 28 controls the preparation unit 38 via a control line 39 so that the connecting strand temperature control fluid circulating in the temperature control lines 14, 15 provides a desired cooling output. Preferably, the control unit 28 performs closed-loop control of the preparation unit 38 based on the temperature difference between the temperature signals of the temperature sensors 32, 33.

[0060] It should be emphasized that Figure 5 is only a highly schematic diagram, and that the individual components shown separately in Figure 5 may actually be integrated into a single component. This can already be seen from the fact that the connecting strand temperature control circuit 36 ​​is shown separately from the rotor chamber 5 with the temperature control lines 14, 15, even though these lines extend into the rotor chamber 5. It is also possible that the two temperature control circuits 10, 36 are not formed separately, as in Figure 5, but rather that there is a fluid coupling between the two circuits 10, 36. In this way, a single common preparation unit can prepare the same temperature control fluid for the rotor chamber temperature control circuit 10 and the connecting strand temperature control circuit 36, with the flow and temperature in both circuits 10, 36 being guaranteed via suitable throttle devices, valves, or other fluid components.

[0061] Contrary to what has been described and illustrated above, the closed loop control within the connecting strand temperature regulation circuit 36 ​​may be implemented based on a temperature sensor incorporated within the connecting strand 12 .

[0062] The described sensor signal connections 27, 34, 35 may be wired or wireless connections. The provision of the sensor signals may also be carried out via a bus system. The same applies correspondingly to the control lines 29, 37, 39.

[0063] 5 shows only one control unit 28, which ensures open-loop or closed-loop control of the rotor chamber temperature regulation circuit 10, the centrifugation medium circuit 30 and the connecting strand temperature regulation circuit 36. These tasks can also be shared by several control units, which in this case can also be connected or networked to one another.

[0064] The heat generated as a result of the repeated deformation operations, and therefore the cooling power to be provided by the connecting strand temperature regulation circuit, may be, for example, a maximum of 50 Watts to 200 Watts, in particular 0 Watts to 150 Watts. When the medium to be centrifuged is blood, the temperature threshold that should not be exceeded may be, for example, 37°C.

[0065] When in one operating phase the medium to be centrifuged is pumped through the communicating lines and in another operating phase the purge fluid is pumped through the communicating lines, different open-loop or closed-loop controls can be implemented for the different operating phases, in particular the processing of the temperature difference measured in the communicating lines can be implemented differently or with different amplification factors. [Explanation of symbols]

[0066] 1 Flow-through centrifuge 2. Housing 3 cans 4. Wall 5 Rotor chamber 6 rotors 7 Rotor axis 8 containers 9 Blood Bags 10 Rotor chamber temperature control circuit 11. Rotor chamber temperature control loop 12 connecting strands 13 Tubes and pipes 14 Temperature control supply line 15 Temperature control discharge pipe 16 Communication pipeline 17 Communication pipeline 18 End area 19 End area 20 Branches 21 Connecting Pipe 22 Connecting Pipe 23 Fold-over connection 24 Connecting member 25 Preparation Unit 26 Temperature Sensor 27 Sensor signal connection 28 Control Unit 29 Control Line 30 Centrifugal medium circuit 31 Preparation Unit 32 Temperature Sensor 33 Temperature Sensor 34 Sensor signal connection 35 Sensor signal connection 36 Connecting strand temperature control circuit 37 Control Line 38 Preparation Unit 39 Control Line

Claims

1. A flow-through centrifuge (1), comprising: a) a rotor (6) having a centrifugal chamber, said rotor (6) being rotatable about a rotor axis (7) at any rotor speed; b) a connecting strand (12) having a communication line (16; 17) through which a medium can be supplied to the centrifuge chamber and a communication line (17; 16) through which a medium can be discharged from the centrifuge chamber during operation of the flow-through centrifuge (1) with the rotor (6) rotating, c) one end region (18) of the connecting strand (12) is arranged fixedly in the housing, and the other end region (19) of the connecting strand (12) is rotated together with the rotor (6); d) in order to avoid twisting of the connecting strands (12), the connecting strands (12) are guided in a guide device which is rotated around the rotor axis (7) at half the rotor speed; In a flow-through centrifuge (1), e) a temperature-regulating supply line (14) and a temperature-regulating discharge line (15) extend through the connecting strand (12), the temperature-regulating supply line (14) and the temperature-regulating discharge line (16) being passed through the connecting strand by a temperature-regulating fluid in opposite flow directions; f) at least one electronic control unit (28) having a control logic for open-loop or closed-loop control of the spliced ​​strand temperature control output of the spliced ​​strand temperature control circuit (36); A flow-through centrifuge (1) characterized in that:

2. 2. The flow-through centrifuge (1) according to claim 1, characterized in that the temperature-regulated supply pipes (14), the temperature-regulated discharge pipes (15) and the communication pipes (16, 17) are distributed in the circumferential direction around the longitudinal axis of the connecting strand (12) within the cross section of the connecting strand (12).

3. 3. The flow-through centrifuge (1) according to claim 2, characterized in that the temperature-regulated supply pipes (14), the temperature-regulated discharge pipes (15) and the communication pipes (16, 17) are distributed in the cross section of the connecting strand (12) in the circumferential direction around the longitudinal axis of the connecting strand (12), and at least one communication pipe (16, 17) is arranged between the temperature-regulated supply pipes (14) and the temperature-regulated discharge pipes (15) in both circumferential directions around the longitudinal axis.

4. 4. The flow-through centrifuge (1) according to claim 1, wherein the temperature-regulated supply line (14) and the temperature-regulated discharge line (15) are connected to each other via a turn-back connection (23).

5. 5. The flow-through centrifuge (1) according to claim 1, wherein the connecting strand (12) comprises a flexible pipe or flexible tube (13) through which the temperature-regulated supply line (14), the temperature-regulated discharge line (15) and the communication lines (16, 17) extend at least partially.

6. 6. A flow-through centrifuge (1) according to claim 5, which is dependent on claim 4, characterized in that the turn-back connections (23) are arranged in the extension areas of the temperature-regulated supply lines (14) and the temperature-regulated discharge lines (15) from the flexible pipes or tubes (13).

7. 7. The flow-through centrifuge (1) according to claim 6, characterized in that the turn-back connection (23) is U-shaped and at least partially surrounds at least one communication line (16, 17).

8. 8. A flow-through centrifuge (1) according to any one of claims 1 to 7, characterized in that at least one electrical line extends through said connecting strand (12).

9. a) the temperature of the connecting strand temperature regulating fluid and / or b) the flow of temperature regulating fluid through the connecting strands 9. The flow-through centrifuge (1) according to claim 1, wherein the open-loop or closed-loop control of the flow-through centrifuge (1) is carried out taking into account the temperature of the medium in the communicating lines (16; 17), in particular taking into account the temperature difference in the communicating lines (16, 17).

10. A flow-through centrifuge (1) according to any one of claims 1 to 9, characterized in that it comprises a rotor chamber temperature regulation circuit (10).

11. 11. The flow-through centrifuge (1) according to claim 10, characterized in that it comprises at least one electronic control unit (28), said control unit (28) having a control logic, said control logic controlling the rotor chamber temperature regulation output of said rotor chamber temperature regulation circuit (10) in an open-loop or closed-loop manner.

12. 12. The flow-through centrifuge (1) according to claim 11, further comprising a temperature sensor (26) for detecting the temperature of the rotor chamber (5), and the control logic controls the rotor chamber temperature regulation circuit (10) in an open loop or closed loop taking into account the temperature signal of the temperature sensor (26).

13. a) open-loop or closed-loop control of the rotor chamber temperature control output of said rotor chamber temperature control circuit (10); and b) open-loop or closed-loop control of the spliced ​​strand temperature control output of said spliced ​​strand temperature control circuit (36); 13. Flow-through centrifuge (1) according to claim 11 or 12, when relying on any one of claims 1 to 9, characterized in that the control logics for are coordinated with one another.

14. The control logic for open-loop or closed-loop control of the spliced ​​strand temperature regulation output comprises: a) the heat capacity of the medium flowing through the communicating pipes (16, 17) and / or b) the heat capacity of the connecting strand temperature regulating fluid and / or c) the flow of the medium through the communicating conduits (16, 17) and / or d) the rotor rotation speed A flow-through centrifuge (1) according to any one of claims 1 to 9 or any one of claims 10 to 13 relying on any one of claims 1 to 9, characterized in that it takes into account

15. a) the cross-sectional area of ​​the temperature-regulated supply line (14) and / or the temperature-regulated discharge line (15), b) the cross-sectional geometry of the temperature-regulated supply line (14) and / or the temperature-regulated discharge line (15); c) the heat transfer coefficient of the walls or jackets of the temperature-regulated supply line (14) and / or the temperature-regulated discharge line (15) 15. The flow-through centrifuge (1) according to claim 1, wherein at least one of the following is different for the temperature-regulated supply line (14) and the temperature-regulated discharge line (15), respectively, or is not constant over the longitudinal extension of the temperature-regulated supply line (14) and / or the temperature-regulated discharge line (15).

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