Modular centrifugal separator system

Abstract

The present disclosure relates to a modular centrifugal separator system (1) configured to separate a liquid feed mixture into a heavy phase and a light phase. The system comprises a base unit (4) and a set of first and second exchangeable separation inserts (6, 6'). The base unit (4) comprises a stationary frame (8) and a rotatable member (16). The rotatable member (16) delimits an inner space (26) configured to receive at least a portion of the first or second exchangeable separation insert (6, 6') therein. Each of the first and second exchangeable separation inserts (6, 6') comprises a rotor housing (82) forming a separation space (88), and separation discs (92) arranged in the separation space (88). The discs (92) of the first exchangeable separation insert have a first area equivalent, while the discs (92) of the second exchangeable separation insert have a second area equivalent different from the first area equivalent.

Description

TECHNICAL FIELD

[0001] The present invention relates to a set of exchangeable separation inserts for a modular centrifugal separator system, to a modular centrifugal separator system, and to a method for operating a modular centrifugal separator system. BACKGROUND

[0002] In the field of pharmaceuticals, biopharmaceuticals, biotechnology and related fields, separation of substances from liquid mixtures, such as separation of cells from cell culture mixtures, is performed in a sterile environment. Traditionally, equipment is used that is made of, for example, stainless steel, which is sterilized between batches.

[0003] Disposable separation equipment for single use, i.e. for one batch or a limited number of batches, has been proposed. For example, US 2011 / 0319248 discloses a single-use centrifuge, while WO 2015 / 181177 discloses a separator comprising an exchangeable inner drum.

[0004] Such disposable separation equipment is provided to the user in a sterile manner. Thus, a sterile environment can be provided for the product in the separator without the need for sterilization of the separation equipment at the user’s production facility.

[0005] EP 3666394 discloses a base unit and a modular centrifugal separator. The base unit comprises a stationary frame, a rotatable member and a drive unit. The rotatable member bounds an inner space configured to receive at least a portion of an exchangeable separation insert therein. The rotatable member is provided at a first axial end with a first opening configured to extend a first fluid connection of the exchangeable separation insert therethrough. The rotatable member comprises a second opening at a second axial end configured to extend a second fluid connection of the exchangeable separation insert therethrough.

[0006] US 6973925 discloses a ventilation device for a crankcase of an internal combustion engine. The device comprises a centrifugal oil separator comprising a plate / disc, which has an inlet for an oil-air mixture, a ventilation opening for purified air and an oil outlet for oil. In the context of this gas-liquid separator, the use of different numbers of plates suitable for the volumetric flow of gas that needs to be de-oiled is described.

[0007] Different separation processes can require different separation capacities. SUMMARY

[0008] It would be advantageous to achieve different separation capabilities in the context of a modular centrifugal separator system having a base unit and exchangeable separation inserts. In particular, it would be desirable to provide different separation capabilities within the limits set by a particular size of the base unit of the modular centrifugal separator system. To better address one or more of these concerns, at least one of a set of exchangeable separation inserts for a modular centrifugal separator system, a modular centrifugal separator system, and a method for operating a modular centrifugal separator system is provided.

[0009] According to an aspect of the present invention, a set of exchangeable separation inserts for a modular centrifugal separator system comprising a base unit is provided. The set of exchangeable separation inserts comprises at least a first exchangeable separation insert and a second exchangeable separation insert. Each of the first and second exchangeable separation inserts comprises a rotor housing, separation discs, and fluid connections; the rotor housing is configured to rotate about an axis of rotation and forms a separation space; the separation discs are arranged in the separation space; the fluid connections are for a liquid feed mixture, a separated heavy phase, and a separated light phase. The separation discs of the first exchangeable separation insert have a first area equivalent, and the separation discs of the second exchangeable separation insert have a second area equivalent. Each rotor housing of the first and second separation inserts has the same outer shape, such that they fit the rotatable member of the base unit of the modular centrifugal separator system. The first area equivalent is different from the second area equivalent, and each of the first and second area equivalents is calculated for the same rotational speed.

[0010] For example, each rotor housing of the first and second separation inserts can have the same outer shape, such that they fit within an inner space of the rotatable member of the base unit of the modular centrifugal separator system, and abut against at least a portion of an inner surface of the rotatable member that bounds at least a portion of the inner space.

[0011] According to another aspect of the present invention, a modular centrifugal separator system configured for separating a liquid feed mixture into a heavy phase and a light phase is provided. The modular centrifugal separator system comprises a base unit and a first exchangeable separation insert. The base unit comprises a stationary frame, a rotatable member, and a drive unit for rotating the rotatable member about an axis of rotation. The rotatable member is configured to rotate about the axis of rotation arranged in the stationary frame. The rotatable member can bound an inner space at least in a radial direction, which is configured to receive at least a portion of the first exchangeable separation insert therein. The modular separation system comprises a set of exchangeable separation inserts according to any one of the aspects and / or embodiments discussed herein. The first exchangeable separation insert forms a part of the set of exchangeable separation inserts.

[0012] The rotatable member can be a rotatable member into which a separation insert is inserted, so that during operation torque is transmitted to the separation insert by direct contact with the separation insert. However, the rotatable member can also be realized as at least one electromagnetic bearing which does not necessarily have to rotate itself for transmitting torque to the separation insert without direct contact. Thus, the drive unit can be a magnetic drive.

[0013] According to another aspect of the application, there is provided a method of operating a modular centrifugal separator system according to any one of the aspects and / or embodiments discussed herein, configured to separate a liquid feed mixture into a heavy phase and a light phase. The method comprises the steps of:

[0014] - providing a first exchangeable separation insert,

[0015] - mounting the first exchangeable separation insert in an inner space of a rotatable member,

[0016] - separating a first batch of the liquid feed mixture into a first heavy phase and a first light phase in the modular centrifugal separator system with the first exchangeable separation insert,

[0017] - removing the first exchangeable separation insert from the inner space of the rotatable member,

[0018] - providing a second exchangeable separation insert,

[0019] - mounting the second exchangeable separation insert in the inner space of the rotatable member, and

[0020] - separating a second batch of the liquid feed mixture into a second heavy phase and a second light phase in the modular centrifugal separator system with the second exchangeable separation insert.

[0021] Since the set of exchangeable separation inserts of the modular centrifugal separator system comprises the first and the second exchangeable separation inserts having different area equivalents at the same rotational speed, each of the set of exchangeable separation inserts, the modular centrifugal separator system and the method provides a different separation capacity. Thus, within the limits of the same base unit of the modular centrifugal separator system, by using the first or the second exchangeable separation insert, a sufficient separation capacity can be selected.

[0022] The inventors have considered the situation; namely for certain separation operations, centrifugation of certain liquid feed mixtures, their content can not be suitable to be subjected to a centrifugal force above a certain level, say for example liquid feed mixtures including fermentation broth containing CHO cells. The inventors have realized that a modular centrifugal separator including exchangeable separation inserts can realize different separation capabilities at up to a maximum separation speed, i.e. at up to a maximum centrifugal force, the different separation capabilities being defined by the properties of the specific liquid feed mixture but by using different total surface areas provided in the exchangeable separation inserts. Thus, in case of a disposable separation device manufactured for single use, i.e. only for separating one batch or a limited number of batches, the supply of the first and second exchangeable separation inserts discussed herein provides an adaptation to the required or desired separation capability in the modular centrifugal separator system.

[0023] In this way, it is also possible to reduce the costs for lower capacity separations by using separation inserts with less separation discs or separation discs of a smaller diameter.

[0024] In the context of conventional disc stack centrifugal separators configured for continuous or multiple use and designed to be disassembled only for maintenance and / or cleaning purposes, different sizes of separators with different separation capabilities are well known. Further, it is known to use different sizes of disc stacks utilizing separation discs of the same type and size, say for example discussed in the above cited US 6973925.

[0025] However, different sizes of disc stacks providing separation discs of the same type and size are traditionally used for the purpose of providing different versions of centrifugal separators. In selecting a suitable centrifugal separator or version of a centrifugal separator for a specific separation operation, especially the type of the liquid feed mixture, its volumetric flow, viscosity, temperature, feed composition and particle content determine the selection of one specific centrifugal separator. Once selected, the composition of the different parts and in particular the number and size of the separation discs does not change.

[0026] According to the present invention, the exchangeability of the exchangeable separation inserts of the modular centrifugal separator is used to provide different separation performance within the same base unit. Thus, a greater flexibility in using the modular centrifugal separator is exploited, which now forms part of the modular centrifugal separator system including the first and second exchangeable separation inserts. This greater flexibility can for example be exploited in case of separating different cell culture mixtures, specific biomolecules produced or specific cells produced.

[0027] The term separation performance relates to the flow of a liquid feed mixture that can be separated into a heavy phase of a certain concentration and / or a light phase of a certain clarity.

[0028] A modular centrifugal separator can comprise two main parts, namely a base unit and a replaceable separation insert. In such modular centrifugal separator separation of a liquid feed mixture can be performed. A modular centrifugal separator system can comprise such modular centrifugal separator and another replaceable separation insert, namely comprising a set of replaceable separation inserts as described above.

[0029] Herein, a description can refer to a modular centrifugal separator. Such description also relates to a modular centrifugal separator system and its different components. In particular, general aspects of a replaceable separation insert of a modular centrifugal separator relate to both the set of replaceable separation inserts and the first and second replaceable separation inserts of a modular centrifugal separator system.

[0030] The base unit can comprise base components for supporting and rotating the replaceable separation insert. The replaceable separation insert can be configured to perform the actual separation of a liquid feed mixture in its separation space. The liquid feed mixture can flow into the separation space through one fluid connection and the separated heavy and light phases can each exit the separation space via one liquid connection.

[0031] The area equivalent of the separation discs of the first and second replaceable separation inserts is a measure for the separation capacity of the respective replaceable separation insert. That is, the higher the area equivalent, the higher the separation performance of the replaceable separation insert.

[0032] According to embodiments, the separation discs are frustoconical separation discs as known in the art. However, the separation discs can also have any other suitable shape, such as axial separation lamellas, i.e. axial lamellas having an axial extending surface and having a straight or curved extension in radial direction. The extending surface of the separation lamellas can extend parallel to the rotation axis. However, the axial extending surface can also extend at a small angle with respect to the rotation axis or, for example, slightly curved with respect to the rotation axis. Each separation lamella has two axially extending surfaces, a first surface facing forward in the direction of rotation of the rotor housing and a second surface facing backward from the direction of rotation of the rotor housing.

[0033] For frustoconical separation discs, the area equivalent Ae is calculated according to the following formula:

[0034]

[0035] wherein: g = gravity, N = number of frustoconical separation discs of the separation insert, a = half of the top angle of the frustoconical separation discs, i.e. the angle between the rotation axis and the inner surface of one of the frustoconical separation discs, w = rotational speed of the separation insert, r y = outer radius of the frustoconical separation discs, r i = inner radius of the frustoconical separation discs.

[0036] To provide a comparative measure between the first and second exchangeable separation insert when not in use, i.e. when not rotating, a rotation speed neutral value is provided by the respective first and second exchangeable separation insert's area equivalent calculated for the same rotation speed, e.g. ω = 1 for both the first and second exchangeable separation insert.

[0037] The exchangeable separation insert can be configured for single use, i.e. for the separation of only one batch or a limited number of batches of liquid feed mixture. On the other hand, the base unit can be configured for repeated use with different exchangeable separation inserts, such as the first and second exchangeable separation insert, i.e. the base unit can be used for the separation of multiple batches of liquid feed mixture using different exchangeable separation inserts.

[0038] The first and second exchangeable separation insert can be configured to form the only part of the modular centrifugal separator system that comes into contact with the liquid feed mixture as well as the separated heavy and light phases. Thus, the first and second exchangeable separation insert can be provided to the user as a sterile entity. The sterile entity can comprise the part configured to separate the liquid feed mixture as well as conduits for the liquid feed mixture and the separated heavy and light phases. The exchangeable separation insert is installed by the user in the base unit. Thus, the user will easily have access to a centrifugal separator with a sterile environment for the separation of liquid feed mixtures.

[0039] The rotatable member of the base unit can be rotatably supported in a stationary frame. The rotatable member can be supported in the stationary frame without the aid of a main shaft or other type of rotor shaft. The stationary frame is stationary in the sense that it is stationary when the modular centrifugal separator is in use.

[0040] According to an embodiment, the first area equivalent, which is different from the second area equivalent, can be provided by a difference in the number of separation discs between the first and second exchangeable separation insert. In this way, by having a different number of separation discs in the first and second exchangeable separation disc, different separation performance can be provided.

[0041] According to embodiments, the truncated conically shaped separation discs of the first exchangeable separation insert and the truncated conically shaped separation discs of the second exchangeable separation insert can have the same total height along the rotational axis. The distance between at least two of the truncated conically shaped separation discs of the first exchangeable separation insert can be different from the distance between at least two of the truncated conically shaped separation discs of the second exchangeable separation insert. In this way, the truncated conically shaped separation discs can occupy the same amount of space in the separation space of the first and second exchangeable separation insert, while the distance between the separation discs in the respective first and second exchangeable separation insert is different to accommodate a different number of separation discs in the first and second exchangeable separation insert.

[0042] According to embodiments, the first area equivalent different from the second area equivalent can be provided by at least one of the following:

[0043] - a difference in the outer diameter of the truncated conically shaped separation discs between the first and second exchangeable separation insert,

[0044] - a difference in the inner diameter of the truncated conically shaped separation discs between the first and second exchangeable separation insert, and / or

[0045] - a difference in the angle between the rotational axis of the first and second exchangeable separation insert and the inner surface of one of the truncated conically shaped separation discs of the first and second exchangeable separation insert. In this way, further or additional alternatives for providing different separation performance in the first and second exchangeable separation insert can be given.

[0046] According to embodiments, the rotor housing of each of the first and second exchangeable separation insert has a first axial end portion and a second axial end portion, and each of the first and second exchangeable separation insert can comprise at least a first fluid connection arranged at the first axial end portion. In this way, the liquid feed mixture can be directed to the exchangeable separation insert, or one of the heavy phase or the light phase can be directed from the exchangeable separation insert at the first axial end of the exchangeable separation insert. Optionally, a second or even a third fluid connection can be provided at the first axial end portion, allowing one or more of the liquid feed mixture, the heavy phase and / or the light phase to enter or exit the exchangeable separation insert also at its first axial end portion.

[0047] According to embodiments of the modular centrifugal separator system, in connection with such embodiments of the set of exchangeable separation inserts, the rotatable member has a first axial end portion and a second axial end portion. The rotatable member is provided with a first opening at the first axial end portion, which first opening is configured to have at least a first fluidic connection of the first or second exchangeable separation insert extend through the first opening. In this way, the liquid feed mixture can be directed to the exchangeable separation insert, or one of the heavy or light phases can be directed from the exchangeable separation insert via the first opening of the rotatable member. Optionally, a second fluidic connection or even a third fluidic connection of the exchangeable separation insert can extend to / from the exchangeable separation insert via the first opening of the rotatable member.

[0048] According to embodiments, each of the first and second exchangeable separation inserts can comprise at least a second fluidic connection arranged at the second axial end portion. In this way, the liquid feed mixture can be directed to the exchangeable separation insert, or one of the heavy or light phases can be directed from the exchangeable separation insert at the second axial end portion of the exchangeable separation insert. A third fluidic connection can be provided at the first or second axial end portion.

[0049] In connection with such embodiments of the set of exchangeable separation inserts, according to embodiments of the modular centrifugal separator system, the rotatable member can comprise a second opening at the second axial end portion, which second opening is configured to have at least a second fluidic connection of the first or second exchangeable separation insert extend through the second opening. In this way, the liquid feed mixture can be directed to the exchangeable separation insert, or one of the heavy or light phases can be directed from the exchangeable separation insert via the second opening of the rotatable member. A third fluidic connection of the exchangeable separation insert can extend through the first or second opening of the rotatable member.

[0050] According to embodiments of the method, each of the first and second batches of liquid feed mixture can comprise solid matter. The first batch of liquid feed mixture can differ from the second batch of liquid feed mixture in at least one of the type of solid matter, the concentration of solid matter, and / or the content of the first separated light phase and the content of the second separated light phase.

[0051] According to embodiments of the method, each of the first and second batches of liquid feed mixture can be a cell culture mixture. The cell culture mixture can be produced as a fermentation broth in a fermenter. The heavy phase separated in the centrifugal separator system can comprise a concentrate of cells in a small fraction of the fermentation broth. The light phase separated in the centrifugal separator system can essentially only contain the fermentation broth.

[0052] Other features and advantages of the present application will become apparent upon reading the following detailed description with reference to the accompanying drawings. BRIEF DESCRIPTION OF DRAWINGS

[0053] The various aspects and / or embodiments of the present application, including its particular features and advantages, will be readily appreciated by those skilled in the art from the following detailed description, with reference to the example embodiments discussed in conjunction therewith and as illustrated in the accompanying drawings.

[0054] Figure 1 schematically illustrates a modular centrifugal separator system according to an embodiment,

[0055] Figure 2 schematically illustrates a cross-section through a base unit and a modular centrifugal separator of a modular centrifugal separator system,

[0056] Figure 3 schematically illustrates a cross-section through a replaceable separation insert according to an embodiment,

[0057] Figure 4 schematically illustrates a cross-section through a part of a modular centrifugal separator, and

[0058] Figure 5 a method for operating a modular centrifugal separator system is shown. DETAILED DESCRIPTION

[0059] Aspects and / or embodiments of the present application will now be described more fully hereinafter. Like numbers refer to like elements throughout. For the sake of clarity, well-known functions or constructions will not be described in detail.

[0060] The disclosure of EP 3666394 is included herein by reference. In particular, details of a modular separator, its base unit and replaceable separation inserts, including a set of replaceable separation inserts, a modular centrifugal separator system and a method for operating a modular centrifugal separator system, are applicable in the context of the present application.

[0061] Figure 1 A modular centrifugal separator system 1 according to an embodiment is schematically illustrated. The modular centrifugal separator system 1 comprises a base unit 4 and a first replaceable separation insert 6 and a second replaceable separation insert 6'. The modular centrifugal separator system 1 can be configured for use in the field of pharmaceuticals, biopharmaceuticals and / or biotechnology. The modular centrifugal separator system 1 can form part of a facility for producing cells in a factory, such as CHO cells (Chinese hamster ovary cells) or other substances produced by processes of the biotechnology industry.

[0062] Here, the base unit 4 with the first replaceable separation insert 6 or the second replaceable separation insert 6' installed can be referred to as a modular centrifugal separator 2.

[0063] The modular centrifugal separator 2 is configured to separate a liquid feed mixture into a heavy phase and a light phase. For example, the liquid feed mixture can be formed by a fermentation broth comprising a cell culture, the heavy phase can comprise cells separated from a major portion of the fermentation broth. The light phase can be formed mainly by the fermentation broth without cells or only with a minimal residual amount of cells.

[0064] The modular centrifugal separator system 1 is modular in the sense that it comprises the base unit 4 and the first replaceable separation insert 6 and the second replaceable separation insert 6'. The first replaceable separation insert 6 and the second replaceable separation insert 6' are replaced for each new batch of liquid feed mixture to be separated. Alternatively, the first replaceable separation insert 6 and the second replaceable separation insert 6' can be replaced for each new type of liquid feed mixture to be separated, i.e. successive batches containing the same type of liquid feed mixture can be separated with the same first replaceable separation insert 6 and the same second replaceable separation insert 6'.

[0065] During use of the modular centrifugal separator system 1, the liquid feed mixture, the heavy phase and the light phase only come into contact with the relevant first replaceable separation insert 6 and the second replaceable separation insert 6' of the modular centrifugal separator system 1. Naturally, the conduits in the form of the tubes 10 also come into contact with the liquid feed mixture as well as the heavy phase and the light phase, the tubes 10 being configured to guide the liquid feed mixture to the first replaceable separation insert 6 and to guide the heavy phase and the light phase from the first replaceable separation insert 6. The tubes 10 can form part of the first replaceable separation insert 6. The base unit 4 does not come into contact with the liquid feed mixture or any of the heavy phase and the light phase.

[0066] The first replaceable separation insert 6 and the second replaceable separation insert 6' form a set of replaceable separation inserts of the modular centrifugal separator system 1.

[0067] Reference is made below to Figure 3 The first replaceable separation insert 6 and the second replaceable separation insert 6' are further discussed.

[0068] The base unit 4 comprises components for supporting and rotating the replaceable separation inserts. Thus, the base unit 4 comprises, inter alia, a stationary frame 8, a rotatable member and a drive unit for rotating the rotatable member. The stationary frame 8 comprises a vertical member 12. A portion of the drive unit can be arranged in the vertical member 12.

[0069] The stationary frame 8 is stationary during use of the modular centrifugal separator. The base unit 4 itself is however movable, for example in order to be placed at different locations in a user's production facility. For this purpose, the stationary frame 8 can be provided with wheels 14.

[0070] Reference is made below to Figure 2 The base unit 4 is further discussed.

[0071] Figure 2 A cross-section through Figure 1 The modular centrifugal separator system 1 and the base unit 4 of the modular centrifugal separator 2 are schematically illustrated. That is, in Figure 2 The replaceable separation insert is omitted.

[0072] As mentioned above, the base unit 4 comprises a stationary frame 8, a rotatable member 16 and a drive unit 18. The rotatable member 16 is arranged in the stationary frame 8 and is configured to rotate about a rotation axis 20. The drive unit 18 is configured to rotate the rotatable member 16 about the rotation axis 20.

[0073] Seen along the rotation axis 20, the rotatable member 16 has a first axial end 22 and a second axial end 24. The rotatable member 16 bounds an inner space 26 at least in a radial direction. The radial direction extends perpendicular to the rotation axis 20. The inner space 26 is configured to receive at least a portion of the first or second replaceable separation insert therein, further see below with reference to Figure 3 and 4 .

[0074] The rotatable member 16 is provided with a first opening 28 at the first axial end 22. The rotatable member 16 is further provided with a second opening 30 at the second axial end 24. Each of the first and second openings 28, 30 forms a through hole in the rotatable member 16. Thus, the inner space 26 is accessible via each of the first and second openings 28, 30. Thus, the first and second openings 28, 30 are configured to have a fluid connection of the first or second replaceable separation insert extend therethrough. Further see below with reference to Figure 3 and Figure 4 According to an alternative embodiment, the rotatable member 16 can only be provided with the first opening 28, in which case all fluid connections of the first or second replaceable separation insert only extend through the first opening 28.

[0075] Access to the interior space 26 is provided via the lid 34. Thus, the first or second exchangeable separation insert can be mounted in or removed from the interior space 26. The rotatable member 16 is arranged inside the stationary housing 52. The housing 52 comprises a lid 54. In the open position of the lid 54, access to the rotatable member 16 inside the housing 52 is provided, e.g. for exchanging the exchangeable separation insert.

[0076] The interior space 26 of the rotatable member 16 is at least partially delimited by an inner surface 67. The first and second separation inserts have the same outer shape such that they fit inside the interior space 26. Each of the first and second separation inserts abuts at least a portion of the inner surface 67 when fitted in the interior space 26. Thus, the first and second exchangeable separation inserts are supported in the interior space 26.

[0077] In the illustrated embodiment, the rotatable member 16 comprises a frustoconical wall member 68 having an imaginary apex in the region of the second axial end 24. The frustoconical wall member 68 delimits a portion of the interior space 26 and comprises the inner surface 67. When positioned in the interior space 26, the exchangeable separation inserts having a conical or frustoconical shape can be supported by the frustoconical wall member 68.

[0078] Figure 3 A cross-section through a first exchangeable separation insert 6 and a second exchangeable separation insert 6' according to an embodiment is schematically illustrated. The first exchangeable separation insert 6 can form part of a modular centrifugal separator system, such as the modular centrifugal separator system 1 discussed above in connection with Figure 1 The illustrated first exchangeable separation insert 6 and second exchangeable separation insert 6' exemplify both the first exchangeable separation insert 6 and the second exchangeable separation insert 6' discussed above in connection with Figure 1 The following discussion relates both to the first exchangeable separation insert 6 and the second exchangeable separation insert 6' as well as to a group of exchangeable separation inserts. Aspects in which the first exchangeable separation insert 6 and the second exchangeable separation insert 6' differ from each other are specifically discussed.

[0079] The first exchangeable separation insert 6 and the second exchangeable separation insert 6' are configured such that a portion thereof is arranged inside an interior space 26 of a rotatable member 16 of a base unit, e.g. the base unit 4 discussed above in connection with Figure 2 The first exchangeable separation insert 6 and the second exchangeable separation insert 6' are configured such that a portion thereof is arranged inside an interior space 26 of a rotatable member 16 of a base unit, e.g. the base unit 4 discussed above in connection with

[0080] The first and second replaceable separation insert 6, 6' comprises a rotor housing 82, a first fixed portion 84 arranged at a first end portion 85 of the rotor housing 82 and a second fixed portion 86 arranged at a second end portion 87 of the rotor housing 82. The first replaceable separation insert 6 is configured to rotate about the rotation axis 20. The rotor housing 82 is arranged between the first fixed portion 84 and the second fixed portion 86. During operation of the modular centrifugal separator, the first fixed portion 84 is arranged at an axially upper end of the first replaceable separation insert 6, while the second fixed portion 86 is arranged at an axially lower end of the replaceable separation insert.

[0081] Each rotor housing 82 of the first and second replaceable separation insert 6, 6' has the same outer shape, such that they fit within the inner space 26 of the rotatable member 16 of the base unit 4 of the modular centrifugal separator system 1 and abut against at least a portion of the inner surface 67 of the rotatable member, e.g. as described above with reference to Figure 2 .

[0082] The rotor housing 82 delimits a separation space 88 therein. The first replaceable separation insert 6 comprises a stack 90 of truncated conical separation discs 92 arranged in the separation space 88. The separation discs 92 in the stack 90 are arranged to have an imaginary apex at and / or pointing towards the second fixed portion 86. The stack 90 can comprise at least 50 separation discs 92, such as at least 100 separation discs 92, such as at least 150 separation discs 92. By way of example, the separation discs 92 can have an outer radius r y in the range of 80-200 millimetres, an inner radius r i in the range of 30-50 millimetres, and an angle a between the rotation axis 20 and the inner surface of the separation disc 92 (half of the top angle of the truncated conical separation disc 92) in the range of 35-45 degrees. For the sake of clarity, Figure 3 only a few separation discs 92 are shown in the figure.

[0083] In the illustrated embodiment, each of the first and second replaceable separation insert 6, 6' comprises at least a first fluid connection 94 arranged at the first axial end portion 85. Each of the first and second replaceable separation insert 6, 6' comprises at least a second fluid connection 96 arranged at the second axial end portion 87.

[0084] More specifically, the first replaceable separation insert 6 and the second replaceable separation insert 6' comprise a first fluid connection 94 arranged at the first stationary portion 84. A first conduit portion 95 forms part of the first fluid connection 94. The first conduit portion 95 of the first fluid connection 94 extends through the first stationary portion 84. The first replaceable separation insert 6 comprises a second fluid connection 96 arranged at the second stationary portion 86. A second conduit portion 97 forms part of the second fluid connection 96. The second conduit portion 97 of the second fluid connection 96 extends through the second stationary portion 86. In these embodiments, the first replaceable separation insert 6 comprises a third fluid connection 98 arranged at the second stationary portion 86. A third conduit portion 99 forms part of the third fluid connection 98. The third conduit portion 99 of the third fluid connection 98 extends through the second stationary portion 86. One or more outlet conduits 102 are arranged inside the rotor housing 82 for a heavy phase separated from the separation space 88. The first, second and third fluid connections 94, 96, 98 can comprise tubing, such as plastic tubing.

[0085] The first stationary portion 84 abuts against the rotor housing 82. The second stationary portion 86 abuts against the rotor housing 82. A seal 104 is provided between the respective first and second stationary portions 84, 86 and the rotor housing 82. The seal 104 forms a mechanical seal between the first and second stationary portions 84, 86 and the rotor housing 82. Thus, the first replaceable separation insert 6 is provided with a mechanically sealed inlet and outlet. The mechanical seal comprises an abutment between a part of the rotatable rotor housing and the stationary portion.

[0086] During operation, the first replaceable separation insert 6 and the second replaceable separation insert 6' arranged in the rotatable member 16 are brought into rotation about the rotation axis 20. A liquid feed mixture to be separated is supplied into the separation space 88 via the second fluid connection 96 and the guiding channel 106 arranged in the second stationary portion 86. The liquid feed mixture to be separated is guided into the separation space 88 along an axially upward path. Due to a density difference, the liquid feed mixture is separated into a liquid light phase and a liquid heavy phase. This separation is facilitated by the spacing between the separation discs 92 of the stack 90 mounted in the separation space 88. The heavy phase can comprise particles, such as for example cells. The heavy phase can comprise a concentrated mixture of the light phase and the particles.

[0087] The separated liquid heavy phase is collected from the periphery of the separation space 88 via the outlet conduit 102 and is extruded out of the rotor housing 82 to a first fluid connection 94 arranged in the first stationary part 84. The separated liquid light phase is forced radially inwards through the stack 90 of separation discs 92 and out of the rotor housing 82 to a third fluid connection 98 arranged in the second stationary part 86. Thus, in this embodiment, the liquid feed mixture is supplied at the axially lower end of the first exchangeable separation insert 6, the separated light phase is discharged at the axially lower end, and the separated heavy phase is discharged at the axially upper end of the first exchangeable separation insert 6.

[0088] The first exchangeable separation insert 6 and the second exchangeable separation insert 6' differ from each other in a number of aspects of the frustoconical separation discs 92. More specifically, the separation discs 92 of the first exchangeable separation insert 6 have a first area equivalent, while the separation discs 92 of the second exchangeable separation insert 6' have a second area equivalent. The first area equivalent is different from the second area equivalent, and each of the first and second area equivalents is calculated for the same rotational speed. Thus, different separation performance is provided in the first exchangeable separation insert 6 and the second exchangeable separation insert 6'.

[0089] According to an embodiment, the first area equivalent different from the second area equivalent is provided by a difference in the number of frustoconical separation discs 92 between the first exchangeable separation insert 6 and the second exchangeable separation insert 6'. Thus, the stack 90 of separation discs 92 of the first exchangeable separation insert 6 and the second exchangeable separation insert 6' can have different heights along the rotational axis 20.

[0090] According to an alternative embodiment, the stack 90 of separation discs 92 of the first exchangeable separation insert 6 and the second exchangeable separation insert 6' can have the same height, but the number of frustoconical separation discs 92 is still different. Thus, the frustoconical separation discs 92 of the first exchangeable separation insert 6 and the frustoconical separation discs 92 of the second exchangeable separation insert 6' can have the same total height along the rotational axis 20. The same height of the two separation disc stacks 90 can be achieved in case the distance between at least two of the frustoconical separation discs 92 of the first exchangeable separation insert 6 is different from the distance of at least two of the frustoconical separation discs 92 of the second exchangeable separation insert 6'. The difference in the distance between the separation discs 92 of the first exchangeable separation insert 6 and the second exchangeable separation insert 6' can be achieved by a difference in the height of caulking or other distance members, such as pointed protrusions, provided on the surface of the separation discs 92.

[0091] According to an embodiment, the first area equivalent different from the second area equivalent is alternatively or further provided by at least one of the following:

[0092] - a difference in the outer diameter of the frustoconical separation disc 92 between the first exchangeable separation insert 6 and the second exchangeable separation insert 6’,

[0093] - a difference in the inner diameter of the frustoconical separation disc 92 between the first exchangeable separation insert 6 and the second exchangeable separation insert 6’ and / or

[0094] - a difference in the angle a between the rotational axis 20 and the inner surface of one of the frustoconical separation discs 92 of the first exchangeable separation insert 6 and the second exchangeable separation insert 6’, i.e. a difference in the taper of the separation disc 92.

[0095] According to an alternative embodiment, the stack 90 of frustoconical separation discs 92 can be arranged with an imaginary apex at and / or pointing towards the first stationary portion 84.

[0096] According to an alternative embodiment, the first, second and third fluid connections and the respective fluid paths within the rotor housing 82 and the separation space 88 can be arranged differently from the illustrated embodiment, e.g. two fluid connections can be provided at the first stationary portion 84 and one fluid connection at the second stationary portion 86.

[0097] According to an alternative embodiment, the first exchangeable separation insert 6 and the second exchangeable separation insert 6’ can comprise only the first stationary portion 84 or the second stationary portion 86. In such an embodiment, the first, second and third fluid connections are provided at the first stationary portion 84 and the second stationary portion 86, respectively.

[0098] Figure 4 A cross-section through a portion of the modular centrifugal separator 2 is schematically illustrated. More specifically, Figure 4 A cross-section through the housing 52, the rotatable member 16 and the first exchangeable separation insert 6 and the second exchangeable separation insert 6’ of the modular centrifugal separator 2 is illustrated. The modular centrifugal separator 2 forms part of the modular centrifugal separator system 1 described above in connection with Figure 1 and Figure 2 The modular centrifugal separator system 1 described above in connection with Figures 1-3 is described above. Accordingly, in the following, reference is also made to Figures 1-3 .

[0099] In Figure 4 , the first exchangeable separation insert 6 is illustrated as being installed in the base unit 4. A portion of the first exchangeable separation insert 6 is received in the inner space 26 of the rotatable member 16.

[0100] The inner space 26 of the rotatable member 16 is at least partly delimited by an inner surface 67. The inner space 26 is configured to receive at least a portion of the first and second exchangeable separation inserts 6, 6’ therein, respectively.

[0101] The first and second exchangeable separation inserts 6, 6’ have the same outer shape, such that they fit within the inner space 26. Each of the first and second separation inserts abuts at least a portion of the inner surface 67 when fitted in the inner space 26. Thus, the first and second exchangeable separation inserts 6, 6’ are supported in the inner space 26.

[0102] For example, and also as referred to above Figure 2 The rotatable member 16 comprises a frustoconical wall member 68 forming a portion of the inner surface 67. A portion of the first and second exchangeable separation inserts 6, 6’ has a conical or frustoconical shape. The conical or frustoconical portion of the first and second exchangeable separation inserts 6, 6’ is supported by the frustoconical wall member 68.

[0103] It is noted that the first and second exchangeable separation inserts 6, 6’ are not necessarily supported in the inner space 26 exactly in the same way. Each of the first and second exchangeable separation inserts 6, 6’ can be supported by the inner surface 67 in a different way. For example, one of the exchangeable separation inserts can be supported at a larger diameter portion of the frustoconical wall member 68, while the other exchangeable separation insert can be supported at a smaller diameter portion of the frustoconical wall member 68.

[0104] During use of the modular centrifugal separator 2, the first fixation portion 84 is fixed relative to the stationary frame 8 and the second fixation portion 86 is fixed relative to the stationary frame 8.

[0105] In the illustrated embodiment, the rotatable member 16 has a first axial end portion 22 and a second axial end portion, and the rotatable member 16 is provided with a first opening 28 at the first axial end portion 22 configured to extend at least a first fluid connection 94 of the first and second exchangeable separation inserts 6, 6’ through the first opening 28. In this way, the first fluid connection 94 can be arranged to extend into or out of the rotatable member 16.

[0106] In the illustrated embodiment, the rotatable member 16 comprises a second opening 30 at the second axial end 24, which is configured to have the second fluid connections 96 of at least the first and second exchangeable separation insert 6, 6' extend through the second opening 30. In this way, the second fluid connections 96 can be arranged to extend into or out of the rotatable member 16.

[0107] In the illustrated embodiment, the third fluid connections 98 of the first and second exchangeable separation insert 6, 6' can extend through the second opening 30.

[0108] According to an alternative embodiment, the third fluid connections 98 of the first and second exchangeable separation insert 6, 6' can extend through the first opening 28.

[0109] According to a further alternative embodiment, only the first or second opening 28, 30 is provided in the rotatable member, and all fluid connections of the first and second exchangeable separation insert 6, 6' extend through the first or second opening 28, 30, respectively.

[0110] Figure 5 A method 100 for operating a modular centrifugal separator system configured to separate a liquid feed mixture into a heavy phase and a light phase is illustrated. The modular centrifugal separator system can be the modular centrifugal separator system 1 as described above in connection with Figures 1-4 The modular centrifugal separator system 1. Thus, in the following reference is also made to Figures 1-4 .

[0111] The method 100 comprises the steps of:

[0112] - providing 1102 a first exchangeable separation insert 6,

[0113] - installing 1104 the first exchangeable separation insert 6 in the inner space 26 of the rotatable member 16,

[0114] - separating 1106 a first batch of the liquid feed mixture into a first heavy phase and a first light phase in the modular centrifugal separator system 1 with the first exchangeable separation insert,

[0115] - removing 1108 the first exchangeable separation insert 6 from the inner space 26 of the rotatable member 16,

[0116] - providing a second exchangeable separation insert 6',

[0117] - installing 112 the second exchangeable separation insert 6' in the inner space 26 of the rotatable member 16,

[0118] - separating 1114 the second batch of liquid feed mixture into a second heavy phase and a second light phase in the modular centrifugal separator system 1 using the second exchangeable separation insert 6'.

[0119] According to embodiments, the liquid feed mixture can be a cell culture mixture, i.e. each of the first and second batches of liquid feed mixture can be a cell culture mixture. The first batch of liquid feed mixture in the form of a cell culture mixture can be produced in a fermentation broth in a fermenter. Thus, after a fermentation period in the fermenter can follow the separation of the first batch of liquid feed mixture in the modular centrifugal separator system 1 using the first exchangeable separation insert 6. That is, steps 102-108 of the method 100 can be performed after the fermentation period. The second batch of liquid feed mixture can subsequently be subjected to a subsequent or parallel fermentation period in the fermenter, followed by the separation in the modular centrifugal separator system 1 using the second exchangeable separation insert 6'. That is, steps 110-114 of the method 100 can be performed after the subsequent or parallel fermentation period.

[0120] According to embodiments, each of the first and second batches of liquid feed mixture can comprise solid matter. The first batch of liquid feed mixture can differ from the second batch of liquid feed mixture in at least one of the type of solid matter, the concentration of solid matter, and / or the content of the separated first light phase and the content of the separated second light phase.

[0121] In embodiments where the liquid feed mixture is a cell culture mixture, the solid matter corresponds to cells in the cell culture mixture. The light phase is the liquid of the cell culture mixture with the cells removed. The heavy phase comprises the separated cells and a small amount of liquid.

[0122] The fermentation in the fermenter can for example be used to express extracellular biomolecules, such as antibodies, from a mammalian cell culture mixture. The extracellular biomolecules can be extracted from the separated light phase in a subsequent process step. In other processes, the cells of the cell culture mixture can be, or can comprise, a desired substance from the fermentation in the fermenter. The cells or substance can be extracted from the separated heavy phase in a subsequent process step.

[0123] Thus, the difference in the type of solid matter of the first batch of liquid feed mixture and the second batch of liquid feed mixture can be different types of cells of the first and second cell culture mixtures. The difference in the concentration of solid matter of the first batch of liquid feed mixture and the second batch of liquid feed mixture can be different concentrations of the same or different kinds of cells. The difference in the content of the separated first light phase and the content of the separated second light phase of the first batch of liquid feed mixture and the second batch of liquid feed mixture can be a difference in extracellular biomolecules.

[0124] According to embodiments, after the separation step 114, the second replaceable separation insert 6' can be removed from the inner space 26 of the rotatable member 16 and another first replaceable separation insert 6 or another second replaceable separation insert 6' can be provided and installed in the inner space 26. Alternatively, another kind of replaceable separation insert with a further different separation capacity can be provided and installed in the inner space 26.

[0125] It will be appreciated that the foregoing is a description of various example embodiments and that the invention is defined solely by the claims that follow. Those skilled in the art will realize that the example embodiments can be modified and that different features of the example embodiments can be combined to produce embodiments other than those described herein, as defined by the appended claims.

Claims

1. A set of replaceable separation inserts (6, 6') for a modular centrifuge system (1) including a base unit (4), said set comprising at least a first replaceable separation insert (6) and a second replaceable separation insert (6'), wherein Each of the first and second replaceable separation inserts (6, 6') includes a rotor housing (82), a separation disc (92), and fluid connections (10, 94, 96, 98); the rotor housing (82) is configured to rotate about a rotation axis (20) and form a separation space (88); the separation disc (92) is arranged in the separation space (88); the fluid connections (10, 94, 96, 98) are used for the liquid feed mixture, the separation of the heavy phase, and the separation of the light phase, wherein... The separation disc (92) of the first replaceable separation insert (6) has a first area equivalent, while the separation disc (92) of the second replaceable separation insert (6') has a second area equivalent, wherein Each of the rotor housings (82) of the first and second replaceable separation inserts (6, 6') has the same external shape, making them suitable for the rotatable component (16) of the base unit (4) of the modular centrifuge system (1). Its features are, The first area equivalent is different from the second area equivalent, and each of the first and second area equivalents is calculated for the same rotational speed.

2. The set of replaceable detachable inserts according to claim 1, wherein, Each rotor housing (82) of the first and second separation inserts (6, 6') has the same external shape, such that they are fitted into the interior space (26) of the rotatable member (16) of the base unit (4) of the modular centrifugal separator system (1) and abut against at least a portion of the inner surface (67) of the rotatable member (16), which defines at least a portion of the interior space (26).

3. The set of replaceable detachable inserts according to claim 1 or 2, wherein, The first area equivalent, which differs from the second area equivalent, is provided by the difference in the number of separation discs (92) between the first and second replaceable separation inserts (6, 6').

4. The set of replaceable detachable inserts according to claim 1 or 2, wherein, The separation disk is a truncated conical separation disk.

5. The set of replaceable detachable inserts according to claim 4, wherein, The truncated conical separation discs (92) of the first replaceable separation insert (6) and the truncated conical separation discs (92) of the second replaceable separation insert (6') have the same total height along the axis of rotation (20), and the distance between at least two of the truncated conical separation discs (92) of the first replaceable separation insert (6) is different from the distance between at least two of the truncated conical separation discs (92) of the second replaceable separation insert (6').

6. The set of replaceable detachable inserts according to claim 4, wherein, The first area equivalent, which is different from the second area equivalent, is provided by at least one of the following: - The difference in the outer diameter of the truncated conical separation disc (92) between the first and second replaceable separation inserts (6, 6') - The difference in the inner diameter of the truncated conical separation disc (92) between the first and second replaceable separation inserts (6, 6'), and / or - The difference in angle α between the rotation axis (20) of the first and second replaceable separation inserts (6, 6') and the inner surface of one of the truncated conical separation discs (92).

7. The set of replaceable detachable inserts according to claim 1 or 2, wherein, The rotor housing (82) of each of the first and second replaceable separable inserts (6, 6') has a first axial end portion (85) and a second axial end portion (87), and each of the first and second replaceable separable inserts (6, 6') includes at least a first fluid connection (94) disposed at the first axial end portion (85).

8. The set of replaceable detachable inserts according to claim 7, wherein, Each of the first and second replaceable separable inserts (6, 6') includes at least a second fluid connection (96) disposed at the second axial end portion (87).

9. A modular centrifuge system (1) configured to separate a liquid feed mixture into a heavy phase and a light phase, the modular centrifuge system comprising a base unit (4) and a first replaceable separation insert (6), wherein The base unit (4) includes a fixed frame (8), a rotatable member (16), and a drive unit (18) for rotating the rotatable member (16) about a rotation axis (20), wherein The rotatable member (16) is at least limited in the radial direction to an interior space (26), the interior space (26) being configured to receive at least a portion therein of the first replaceable detachable insert (6). Its features are, The modular centrifuge system (1) includes a set of replaceable separation inserts (6, 6') according to any of the preceding claims, wherein The first replaceable detachable insert (6) forms part of the set of replaceable detachable inserts (6, 6').

10. The modular centrifuge system (1) according to claim 9, wherein, The rotatable member (16) is configured to rotate about a rotation axis (20) arranged in the fixed frame (8) and has a first axial end (22) and a second axial end (24), and the rotatable member (16) has a first opening (28) at the first axial end (22), the first opening (28) being configured to allow at least a first fluid connection (94) of the first or second replaceable separable insert (6, 6') to extend through the first opening (28).

11. The modular centrifuge system (1) according to claim 10, wherein, The rotatable member (16) includes a second opening (30) at the second axial end (24), the second opening (30) being configured to allow at least a second fluid connection (96) of the first or second replaceable disengagement insert (6, 6') to extend through the second opening (30).

12. A method for operating a modular centrifugal separator system (1) according to any one of claims 9-11, said modular centrifugal separator system (1) being configured to separate a liquid feed mixture into a heavy phase and a light phase, said method comprising the steps of: - Provide the first replaceable detachable insert (6), - The first replaceable detachable insert (6) is installed in the internal space (26) of the rotatable member (16). - The first replaceable separator insert is used to separate the first batch of liquid feed mixture into a first heavy phase and a first light phase in the modular centrifugal separator system (1). - Remove the first replaceable detachable insert (6) from the internal space (26) of the rotatable member (16). - Provides the second replaceable detachable insert (6'), - The second replaceable detachable insert (6') is installed in the internal space (26) of the rotatable member (16). - The second batch of liquid feed mixture in the modular centrifugal separator system (1) is separated into a second heavy phase and a second light phase using the second replaceable separation insert (6').

13. The method according to claim 12, wherein, Each of the first and second batches of the liquid feed mixture comprises a solid substance, and the first batch of the liquid feed mixture differs from the second batch of the liquid feed mixture by comprising at least one of the following: -Types of solid substances - The concentration of the solid substance, and / or -The contents of the separated first light phase and the contents of the separated second light phase.

14. The method according to claim 12 or 13, wherein, Each of the first and second batches of liquid feed mixtures is a cell culture mixture.

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