EP4656292A1

EP4656292A1 - Centrifuge for continuous flow centrifugation

Info

Publication number: EP4656292A1
Application number: EP24179380.1A
Authority: EP
Inventors: Thomas EBERHAGEN
Original assignee: Sartorius Stedim Biotech GmbH
Current assignee: Sartorius Stedim Biotech GmbH
Priority date: 2024-05-31
Filing date: 2024-05-31
Publication date: 2025-12-03
Also published as: WO2025247980A1

Abstract

The invention relates to a centrifuge for continuous flow centrifugation with a drum (3), a rotor (4) and a motor (5) for driving the drum (3) and the rotor (4), wherein the drum (3), driven by the motor (5), rotates around a common rotation axis (A) with a rotational frequency during use of the centrifuge (1), wherein the rotor (4) is coupled to the drum (3), wherein the rotor (4) rotates around the common rotation axis (A) with the double of the rotational frequency, wherein the centrifuge (1) comprises at least one main bearing (7) between the rotor (4) and the drum (3) via which the rotor (4) is mounted onto the drum (3). It is proposed that the rotor (4) comprises at least one cooling fin (10) which moves air in a direction radially outwards from the common rotation axis (A) when the rotor (4) rotates.

Description

The present invention relates to a centrifuge for continuous flow centrifugation according to the general part of claim 1 and to a method of using a centrifuge according to the general part of claim 11.
Centrifuges for continuous flow centrifugation and in particular centrifuges for fluidized bed centrifugation, which are of particular interest here, are used for a range of applications in biotechnology, including cell therapy, vaccine production and cell cultivation for recombinant protein production like antibody production. Generally, the type of continuous centrifuge in focus here comprises a rotor with chambers which are usually single-use chambers that can be fed with media while rotating. A force equilibrium between the centrifugal force and a fluid flow in the opposite direction suspends particles of different sizes at different locations in the chambers. Accordingly, applications of fluidized bed centrifuges comprise for example cell separation.
As the chambers can be filled and emptied while rotating, an anti-twisting mechanism is implemented for the tubes leading to the chambers. This anti-twisting mechanism is based on the known principle that the chambers may rotate with double the velocity of the tubes without the tubes twisting. Implementing this principle puts a number of constructional restraints on the centrifuge, leading to complex mechanics.
The known prior art ( EP 4 321 255 A1 ) that builds the basis of the invention is related to a centrifuge according to the general part of claim 1. This document also summarizes the general working principle of fluidized bed centrifuges. This document shows a centrifuge for continuous flow centrifugation, wherein the centrifuge comprises a drum, a rotor and a motor for driving the drum and the rotor, wherein the drum, driven by the motor, rotates around a common rotation axis with a rotational frequency during use of the centrifuge, wherein the rotor is coupled to the drum, wherein due to being coupled to the drum, the rotor, driven by the motor, rotates around the common rotation axis with the double of the rotational frequency, wherein the centrifuge comprises at least one main bearing between the rotor and the drum via which the rotor is mounted onto the drum.
It is a challenge that the main bearing between drum and rotor generates heat which is hard to transfer and dissipate via the drum. At the same time, the centrifuge may be used for thermally sensitive process fluids, for example proteins or cells, which should not be heated during centrifugation. There is therefore a need for an efficient cooling of the main bearing which protects the process fluid.
The invention is based on the problem of improving the heat dissipation of the main bearing of the known centrifuge.
The above-noted problem is solved by the features of the characterizing part of claim 1.
The main realization of the present invention is that the rotor and/or the drum may be equipped with at least one cooling fin which creates an airflow away from the rotor and has an increased surface area for dissipating heat.
In detail, it is proposed that the rotor and/or the drum comprises at least one cooling fin which moves air in a direction radially outwards from the common rotation axis when the rotor and the drum rotate.
According to claim 2 the cooling fin may be curved around the common rotation axis, improving the airflow towards a center of the rotor and from the center of the rotor to the outer part of the rotor similar to a centrifugal fan. Also, several cooling fins may be used.
A preferred embodiment according to claim 3 relates to a heat conductor thermally connected to the main bearing which is cooled by a main airflow created by the cooling fin. The heat conductor may be a separate piece from a chamber carrier carrying the chambers, such that the chambers are protected from the heat of the main bearing.
The airflow can be focused onto the heat conductor by a throttle section of the drum which restricts the airflow towards the heat conductor (claim 4).
The centrifuge may comprise a cooling arrangement for cooling the air inside the centrifuge and specifically the air flow, thereby indirectly regulating the temperature of the process fluid (claim 5). The air may be cooled through a wall of a centrifuge housing outside of which the cooling arrangement may be located (claim 6).
In an embodiment according to claim 7, the drum comprises at least one hole and the airflow is directed through the hole and preferably completely through the drum along the direction of the common rotation axis. Thereby, a narrow airflow path can be designed, which passes along the cooling arrangement and is focused on the main bearing.
Claim 8 relates to further preferred constructional details which provide a compact centrifuge and flow path.
A preferred embodiment according to claim 9 relates to a feeding pipe for the rotor in which tubes may be placed. The feeding pipe of this embodiment helps provide an anti-twisting mechanism.
It is proposed in an embodiment according to claim 10 to mount a main shaft for the drum and the rotor of the centrifuge to a side located opposite a front side. In that case, the main shaft and the feeding pipe do not interfere with each other.
Another teaching according to claim 11, which is of equal importance, relates to a method of using a proposed centrifuge, wherein a process fluid, in particular a process fluid containing cells, in particular viable cells, is centrifuged, in particular with the cells forming a fluidized bed, by the centrifuge.
Here, it is essential that the process fluid comprises organic components that are destroyed by temperature exceeding a limit, and, that the limit is below 60° C, preferably 45° C, more preferably 40° C. For such process fluids containing for example viable cells or proteins like antibodies that may be denatured, temperature control is very important. Preferably, a maximum temperature for the process fluid is 37° C. It is preferably the case that the main bearing does not apply temperatures above 30° C to the chamber carrier.
All explanations given with regard to the proposed centrifuge are fully applicable.
In the following, embodiments of the invention are explained with respect to the drawing. The drawing shows in

Fig. 1,: a fluidized bed centrifuge from the outside without an outer housing,
Fig. 2,: a cut through Fig. 1,
Fig. 3,: a close up of the section marked with III in Fig. 2 (without tubes) and
Fig. 4,: the rotor from two sides with the chambers of the single-use tube set indicated.

Fig. 1 shows as a preferred embodiment a centrifuge 1 for continuous flow centrifugation. The centrifuge 1 is here and preferably usable for fluidized bed centrifugation. The outer view of Fig. 1 shows a front side of the centrifuge 1 with a closed door 2. The centrifuge 1 may comprise an outer housing not shown in Fig. 1.
Fig. 2 shows a longitudinal cut through the centrifuge 1 in Fig. 1 along the line marked with II. As can be seen, the centrifuge 1 comprises a drum 3, a rotor 4 and a motor 5 for driving the drum 3 and the rotor 4. The drum 3, driven by the motor 5, rotates around a common rotation axis A with a rotational frequency during use of the centrifuge 1. The rotational frequency here and preferably can be set arbitrarily by the user in a range leading up to for example a g-force of 2000g applied to a medium in the rotor 4.
The rotor 4 is coupled to the drum 3. Due to being coupled to the drum 3, the rotor 4, driven by the motor 5, rotates around the common rotation axis A with the double of the rotational frequency. It is a known principle that providing a ratio of 1:2 leads to an anti-twisting mechanism for tubes 6 feeding the rotor 4. The rotor 4 is preferably coupled mechanically to the drum 3, though a software coupling is conceivable. The mechanical coupling ensures that the rotational frequencies of the drum 3 and the rotor 4 keep the ratio of 1:2 without high precision sensors and software, such that the anti-twisting mechanism works.
The centrifuge 1 comprises at least one main bearing 7 between the rotor 4 and the drum 3 via which the rotor 4 is mounted onto the drum 3. Further bearings (without references numbers) between the drum 3 and a main shaft 8 and as part of a rotor drive train 9 leading from the motor 5 to the rotor 4 through the drum 3 are shown but not in focus here. Fig. 3 shows a close up of a section in Fig. 2 marked with III (without tubes 6). Fig. 4 shows the rotor 4 from two sides.
As can be seen in Figs. 2 and 3 but best in Fig. 4, it is proposed that the rotor 4 comprises at least one cooling fin 10 which moves air in a direction radially outwards from the common rotation axis A when the rotor 4 rotates. Additionally or alternatively the drum 3 comprises at least one cooling fin 10 which moves air in a direction radially outwards from the common rotation axis A when the drum 3 rotates (not shown). As explained, when the rotor 4 rotates, the drum 3 also rotates (and vice versa). Here and preferably, the cooling fin 10 extends from a surface of the rotor 4 away from the surface along the common rotation axis A. The cooling fin 10 may extend radially from a starting point away from a center of the rotor 4 towards an outer radial end of the rotor 4. When the rotor 4 rotates, here and preferably, the cooling fin 10 draws in air to the center of the rotor 4 and expels it radially outwards. Here and preferably, the cooling fin 10 by moving the air cools the main bearing 7 which may be near the center of the rotor 4. The rotor 4 may contain a fluid which is temperature-controlled and should not be heated by the heat generated by the main bearing 7. Dispelling the heat through the drum 3 is difficult. The cooling fin 10 therefore helps transfer less heat towards the chambers 11 of the rotor 4 by carrying away the heat via air.
The cooling fin 10 may be curved around the common rotation axis A, which, in Fig. 4, goes through the hole in the center of the rotor 4 and stands orthogonally on the sides of the rotor 4 that are shown in Fig. 4. The rotor 4 may comprise several cooling fins 10 which move air in a direction radially outwards from the common rotation axis A when the rotor 4 rotates. Preferably, the cooling fins 10 are curved around the common rotation axis A. The rotor 4 then works similar to a centrifugal fan.
As can best be seen in Fig. 3, it may be the case that the rotor 4 comprises a heat conductor 12 thermally connected to the main bearing 7. The heat conductor 12 may for example comprise a metal with a good thermal conductivity. Here and preferably, the cooling fins 10 create a, in particular circular, main airflow AF along an airflow path 13 when the rotor 4 rotates. Fig. 3 shows an arrow indicating the airflow path 13 and the main airflow AF. As can be seen, the air is sucked in at the center of the rotor 4 and expelled outwards. As the space from which the air is sucked towards the rotor 4 is rather small, a circular airflow is created. Naturally, some air is also directed away from the airflow path 13, therefore, the shown airflow is just the main airflow AF. Also naturally, the airflow path 13 varies with a rotational position of the rotor 4 and drum 3 to some extent. The cooling fin 10 or cooling fins 10 can also be attached to the heat conductor 12.
The airflow path 13 passes along the heat conductor 12, thereby cooling the heat conductor 12. This indirectly cools the main bearing 7. Here and preferably, the rotor 4 comprises a chamber carrier 14 in which at least one chamber 11 is located (Fig. 4). The heat conductor 12 is a separate piece from the chamber carrier 14 and not shown in Fig. 4. A connection between the heat conductor 12 and the chamber carrier 14 may form a thermal barrier between the heat conductor 12 and the chamber carrier 14.
According to one embodiment it is proposed that the drum 3 comprises a throttle section 15 constricting the airflow path 13 to a vicinity of the heat conductor 12 by blocking air at a section extending radially away from heat conductor 12 and leaving an opening between the drum 3 and the heat conductor 12. Radially is meant regarding the common rotation axis A. Here and preferably and as best visible in Fig. 3, the drum 3 comprises a blocking element 16 which creates the throttle section 15 and which may extend from a side of the drum 3 radially outwards towards the main bearing 7. A further blocking element 17 may be present at a side of the drum 3 opposite the rotor 4 to narrow the overall space for the main airflow AF.
It is preferably the case that the centrifuge 1 comprises a cooling arrangement 18 for cooling air inside the centrifuge 1 (Figs. 2 and 3). Preferably, the airflow path 13 passes along the cooling arrangement 18. The cooling arrangement 18 therefore cools the air of the main airflow AF before it returns to the rotor 4. It may be possible for a user to arbitrarily set a temperature of the inside of the centrifuge 1. The cooling arrangement 18 may be located radially outside the drum 3, around which the airflow path 13 may lead.
The centrifuge 1 may comprise a centrifuge housing 19, which may define the space inside the centrifuge 1. The cooling arrangement 18 is preferably located outside the centrifuge housing 19 and cools a section of a wall 20 of the centrifuge housing 19. Here, the section of the wall 20 is located on a top side of the centrifuge housing 19. Additionally or alternatively, the section of the wall 20 can extend along a backside of the centrifuge housing 19. The airflow path 13 may pass along the cooled section of the wall 20. Preferably, the airflow path 13 is completely located inside the centrifuge housing 19. The centrifuge housing 19 may be an inner housing with a further inner housing 21 (shown in Fig. 1) being located outside the cooling arrangement 18. The mentioned outer housing is still not shown.
It is here and preferably the case that the cooling fin 10 or cooling fins 10 are located on a side of the rotor 4 oriented towards the drum 3 and/or the main bearing 7. Preferably, the drum 3 comprises at least one drum hole 22 through which the airflow path 13 runs. More preferably, the airflow path 13 runs completely through the drum 3 along the direction of the common rotation axis A through one or more drum holes 22 of the drum 3.
According to one embodiment it is proposed that a fin plane P1 orthogonal to the common rotation axis A exists which runs through the cooling fin 10, in particular all cooling fins 10, and the main bearing 7 and/or heat conductor 12, in particular balls of the main bearing 7. The fin plane P1 is shown in Fig. 3 as running through the balls of the main bearing 7, the heat conductor 12 and the cooling fins 10.
Additionally or alternatively it is proposed that a flow plane P2 orthogonal to the common rotation axis A exists which runs through the main bearing 7 and/or heat conductor 12 but not through the cooling fins 10. The combination of both planes shows that the cooling fin 10 or fins may be offset along the common rotation axis A with regard to the main bearing 7, such that the air is sucked over the heat conductor 12, in particular at the throttle section 15. This creates a strong main airflow AF where it is needed due to a small cross-section area of the main airflow AF, increasing the cooling efficiency.
Here and preferably the centrifuge 1 comprises a feeding pipe 23 for continuously feeding the rotor 4 with a medium for centrifugation, which can be seen in Fig. 2. The feeding pipe 23 may be connected to the drum 3. The feeding pipe 23 preferably rotates around the common rotation axis A with the rotational frequency. The feeding pipe 23 leads from a front side of the centrifuge 1 around the rotor 4 and is connected to the drum 3 from a back side 24 of the centrifuge 1, such that the feeding pipe 23 rotates around the rotor 4 around the common rotation axis A. As can be seen, the rotation of the feeding pipe 23 completely envelopes the rotor 4.
Preferably, the feeding pipe 23 takes in tubes 6 of a single-use tube set 25 connected to chambers 11 of the single-use tube set 25 and the rotor 4 takes in the chambers 11. The anti-twister mechanism aims at not intertwining these tubes 6. The chambers 11 may comprise a volume of at least 25 ml, preferably at least 50 ml, and/or, at most 200 ml, preferably at most 100 ml, more preferably exactly 50 ml, per chamber 11. The tube 6 set may comprise two or four or six chambers 11. The chambers 11 may also have a greater volume for example of 100 ml or 1000 ml.
As can be seen on the right side of Fig. 2, the centrifuge 1 may comprise a main shaft 8 defining the common rotation axis A. The main shaft 8 is mounted to the further inner housing 21, in particular at a back side 24 of the centrifuge 1, though it could also be mounted to a top side at the back of the centrifuge 1 or the like. The drum 3 and the rotor 4 are mounted onto the main shaft 8. The motor 5 may be mounted onto the centrifuge housing 19, too, here from the outside.
Another teaching which is of equal importance relates to a method of using a centrifuge 1 wherein a process fluid, in particular a process fluid containing cells, in particular viable cells, is centrifuged, in particular with the cells forming a fluidized bed, by the centrifuge 1.
Essential according to this further teaching is that the process fluid comprises organic components that are destroyed by temperature exceeding a limit, and, that the limit is below 60° C, preferably 50° C, more preferably 45° C. This limit may for example be a denaturing limit of proteins.
All explanations given with regard to the proposed centrifuge 1 are fully applicable.

Claims

Centrifuge for continuous flow centrifugation, wherein the centrifuge (1) comprises a drum (3), a rotor (4) and a motor (5) for driving the drum (3) and the rotor (4), wherein the drum (3), driven by the motor (5), rotates around a common rotation axis (A) with a rotational frequency during use of the centrifuge (1), wherein the rotor (4) is coupled to the drum (3), wherein due to being coupled to the drum (3), the rotor (4), driven by the motor (5), rotates around the common rotation axis (A) with the double of the rotational frequency,
wherein the centrifuge (1) comprises at least one main bearing (7) between the rotor (4) and the drum (3) via which the rotor (4) is mounted onto the drum (3),

characterized in

that the rotor (4) and/or the drum (3) comprises at least one cooling fin (10) which moves air in a direction radially outwards from the common rotation axis (A) when the rotor (4) rotates.
Centrifuge according to claim 1, characterized in that the cooling fin (10) is curved around the common rotation axis (A), and/or, that the rotor (4) comprises several cooling fins (10) which move air in a direction radially outwards from the common rotation axis (A) when the rotor (4) rotates, preferably, that the cooling fins (10) are curved around the common rotation axis (A).
Centrifuge according to claim 1 or 2, characterized in that the rotor (4) comprises a heat conductor (12) thermally connected to the main bearing (7), that the cooling fins (10) create a, in particular circular, main airflow (AF) along an airflow path (13) when the rotor (4) rotates, and, that the airflow path (13) passes along the heat conductor (12), thereby cooling the heat conductor (12), preferably, that the rotor (4) comprises a chamber carrier (14) in which at least one chamber (11) is located and that the heat conductor (12) is a separate piece from the chamber carrier (14).
Centrifuge according to claim 3, characterized in that the drum (3) comprises a throttle section (15) constricting the airflow path (13) to a vicinity of the heat conductor (12) by blocking air at a section extending radially away from heat conductor (12) and leaving an opening between the drum (3) and the heat conductor (12).
Centrifuge according to one of the preceding claims, characterized in that the centrifuge (1) comprises a cooling arrangement (18) for cooling air inside the centrifuge (1), preferably, that the airflow path (13) passes along the cooling arrangement (18).
Centrifuge according to claim 5, characterized in that the centrifuge (1) comprises a centrifuge housing (19), that the cooling arrangement (18) is located outside the centrifuge housing (19) and cools a section of a wall (20) of the centrifuge housing (19), and, that the airflow path (13) passes along the cooled section of the wall (20), preferably, that the airflow path (13) is completely located inside the centrifuge housing (19).
Centrifuge according to one of the preceding claims, characterized in that the cooling fin (10) or cooling fins (10) are located on a side of the rotor (4) oriented towards the drum (3) and/or the main bearing (7), preferably, that the drum (3) comprises at least one drum hole (22) through which the airflow path (13) runs, more preferably, that the airflow path (13) runs completely through the drum (3) along the direction of the common axis through one or more drum holes (22) of the drum (3).
Centrifuge according to one of the preceding claims, characterized in that a fin plane (P1) orthogonal to the common rotation axis (A) exists which runs through the cooling fin (10), in particular all cooling fins (10), and the main bearing (7) and/or heat conductor (12), in particular balls of the main bearing (7), and/or, that a flow plane (P2) orthogonal to the common rotation axis (A) exists which runs through the main bearing (7) and/or heat conductor (12) but not through the cooling fins (10).
Centrifuge according to one of the preceding claims, characterized in that the centrifuge (1) comprises a feeding pipe (23) for continuously feeding the rotor (4) with a medium for centrifugation, that the feeding pipe (23) rotates around the common rotation axis (A) with the rotational frequency, that the feeding pipe (23) leads from a front side of the centrifuge (1) around the rotor (4) and is connected to the drum (3) from a back side (24) of the centrifuge (1), such that the feeding pipe (23) rotates around the rotor (4) around the common rotation axis (A), preferably, that the feeding pipe (23) takes in tubes (6) of a single-use tube set (25) connected to chambers (11) of the single-use tube set (25) and that the rotor (4), in particular the chamber carrier (14), takes in the chambers (11).
Centrifuge according to one of claims 6 to 9, characterized in that the centrifuge (1) comprises a main shaft (8) defining the common rotation axis (A), that the main shaft (8) is mounted to the centrifuge housing (19), in particular at a back side (24) of the centrifuge (1), and, that the drum (3) and the rotor (4) are mounted onto the main shaft (8).
Method of using a centrifuge (1) according to one of the preceding claims, wherein a process fluid, in particular a process fluid containing cells, in particular viable cells, is centrifuged, in particular with the cells forming a fluidized bed, by the centrifuge (1),
characterized in
that the process fluid comprises organic components that are destroyed by temperature exceeding a limit, and, that the limit is below 60° C, preferably 45° C, more preferably 40° C.