Patent Application
20220267708
The invention relates to the field of mixer-containers, and more particularly relates to a stirring device for a mixer-container, especially a stirring device appropriate for single-use applications.
It also relates to a method of assembling a stirring device, in particular for use in a bioreactor intended for receiving a biopharmaceutical fluid for mixing, as well as a fluid-mixing system that is typically provided with a disposable container and the stirring device.
The term “biopharmaceutical fluid” is understood to mean a product of biotechnology (culture media, cell cultures, buffer solutions, artificial nutrition liquids, blood products and blood product derivatives) or a pharmaceutical product or more generally a product intended for use in the medical field. The invention also applies to other products subject to similar requirements regarding packaging.
Mixer-container systems are known which enable mixing biopharmaceutical fluid. Such systems comprise a rigid outer containment device receiving a sterile disposable container. The container comprises a flexible wall defining an inner space to be filled with the biopharmaceutical fluid. The container also comprises a stirring device, which includes one or more mixing members (typically impellers) attached to a descending shaft. The shaft is attached to the container at a first bearing and a second bearing. The shaft of the container may comprise, at the first bearing, a disc having magnets that can be placed facing a similar disc connected to a motor, the effect of the motor thus magnetically driving the shaft to rotate. The shaft thus forms a drive shaft that turns in order to mix the biopharmaceutical fluid.
A stirring device typically includes a drive shaft with one or more impellers mounted to the drive shaft. Each impeller includes a plurality of blades of that are attached to one or more hubs, which are in turn coupled to the drive shaft. The blades of each impeller extend radially outwardly from the hub. Each hub and blade combination is located inside a vessel or pouch-like container that is filled with a fluid to be mixed. Rotation speed required for mixing operations can be higher than 60 rpm for inner volumes greater than 500 or 1000 L. Rotation speed of the drive shaft is for instance typically higher than 120 rpm for lower volumes. At the radial free ends of the blades, speed is thus especially high and it may create significant stress and vibration. Blades may have a radial extension higher than 25 cm or 30 cm as measured between a hub connection end and the free end, especially when the inner volume of the pouch-like container is higher than 500 or 1000 L.
For mixing biopharmaceutical fluid in large containers, it is desired to have a stirring device that can be easily assembled and attached to a drive shaft, while preventing risk of accidentally disassembling the hub. Besides, for use in a bioreactor, the stirring device is generally made only of plastic material, so that stress during stirring operations causes fatigue and breakage. Such risk should be prevented.
For assembling the blades around the shaft, human operations may be still required, in particular final screwing for having the agitating element positioned around the shaft. Some solutions involve use of a screwing without machine intervention as it could alter the plastic surfaces of the components when handling and maintaining positions for assembling. In any case, screwing a hub of an agitating element is often not satisfactory as particles are generated, especially when the components forming the stirring device are all made of plastic material. Document U.S. Pat. No. 4,456,382 describes an agitator device for use in a reactor tank having a longitudinal shaft coupled to a hub assembly. Several screwing operations are required to obtain the hub assembly.
Besides, screwing may be performed differently (no strict repeatability) when performed by human operators and it would be preferable if torque repeatability can be not dependent from user operations. In system using screwed agitation element, vibration generation may also be an issue.
Connection by clips and gluing connection are also options for having a hub coupled to the drive shaft. However, clips or glue are not recommended for torque transmission. Gluing fails to correspond to a repeatable assembling process (moreover, several problems about material compatibility exist). Toxicity issues also arise due to glue and this can lead to contamination of the assembly if the adhesion process is not carried out correctly, which is particularly troublesome because any chemical and/or particulate contamination of the contents of the bioreactor must absolutely be avoided.
In some solutions, the drive shaft is provided with an outer rod having a non-circular cross section. Document US 2015/0265988 A1 shows use of a polygonal section of a rod to accommodate an impeller assembly. Such solution makes the rod more difficult to be produced, which is not appropriate for single-use applications. Additionally, such arrangement is not simple to obtain due to inherent geometric tolerances and possible variations of temperature (dilation of the plastic parts forming the rod with the non-circular section may occur, thus causing problems for assembling operations).
More generally, problems with geometric tolerances and problems with risks of fatigue and breakage still exist so that there is a need for a better compromise between ease at assembling a stirring device for single-use applications and robustness for efficient torque transmission, even for high speed rotations.
The invention aims to solve at least one or some of the disadvantages described above, and in particular aims to optimize the way the agitation element is mounted onto an outer tubular surface, typically a cylindrical surface, of a shaft.
For this purpose, in a first aspect, the invention relates to a stirring device, in particular for a mixer-container, the device comprising:
With such arrangement, the hub and the blades may be indirectly rotationally coupled to the rod of the drive shaft via the sleeve that is engaged in the inner space through an axial insertion opening. Assembly is improved and less time is required to assemble and lock the hub, as compared to solutions using screwing operations.
The mounting area is preferably axially distant from the rod ends, the insertion opening being included in one of a first axial open face and a second axial open face of the annular side wall.
Typically, the fastening arrangement comprises one or more abutment members that prevent axial movement between the hub and the sleeve, in the locked configuration in which the one or more abutment members are engaged with complementary abutment means formed on the hub. In preferred options, the complementary abutment means are provided on the annular side wall with a radial shift (in order to be more radially distant from the central axis of the hub, as compared to the inner surface of the annular side wall which forms the guiding surface).
Thanks to progressive reduction of cross section in one or more areas forming the guiding surface, assembling the hub around the sleeve can be performed without causing high stress between the contact surfaces at the sleeve-hub interface. Moreover, the other surface for contact against the guiding surface may be provided with gaps as in labyrinth seals, so that a concentric configuration can be obtained without high insertion force when mounting the agitating element. As a result, it has been observed that stresses in contact areas are better dissipated and fatigue is highly reduced.
Ribs may be provided to have contact surfaces axially spaced in the other surface, the ribs being for instance provided with rounded/curved longitudinal profile at their ends (without sharp edges). With use of such ribs to have spaced contact areas, tolerance may be erased/compensated due to cooperation with the guiding surface that is typically tapering at the contact areas. In other words, tightness is distributed with a slightly increased ability for adaptation (via the tapering guiding surface), which is of interest to suppress any looseness (due to dimension tolerance for the respective pieces) at contacts between the hub and the rod.
According to a particular, at least two agitating elements are provided around the same rod, using same tapering guiding surface formed in the annular side wall of the hub. Preferably, each agitating element is adapted to be axially moved over the coupling sleeve that surrounds a corresponding mounting area of the rod.
Plastic material (biocompatibility, suitable to be sterilized by gamma irradiation) is used to produce each part of the agitating element, all the sleeve portions and each part of the shaft.
In assembled state of the stirring device, the blades of each impeller assembly are pieces having each a radial extension greater than an outer diameter of the inner surface of the annular side wall measured at the insertion opening. Additionally, there are blades in a first impeller assembly, which are different in shape as compared to blades of a second impeller assembly.
In various embodiments of the stirring device, one or more of the following arrangements may possibly be employed, separately or in combination:
According to a second aspect, embodiments of the invention provide a use of the stirring device in a bioreactor, preferably without any metal particle introduced in an inner volume of the bioreactor, at least one biopharmaceutical fluid being mixed inside a flexible container delimiting the inner volume by the stirring device.
Preferably, the stirring device is used to mix a biopharmaceutical fluid inside a flexible container, wherein the sleeve of the stirring device is a sleeve having a constant inner diameter that is chosen/selected amongst different sleeves that vary in their inner diameter and/or in their maximal outer diameter, so that the chosen sleeve is an adapting part to couple the agitating element to the rod of the drive shaft.
According to another aspect, embodiments of the invention provide a fluid mixing system comprising:
With such arrangement, one or more tapering guiding surfaces may be provided, possibly at each interface connection between a specific coupling sleeve and the hub of a corresponding agitating element. Same tapering orientation is typically used for each of the annular side walls when there are several agitating elements rotatably coupled vie the same kind of sleeve (typically an identical sleeve for each interface with a hub). Alternatively, opposite tapering may be provided for two respective hubs.
Besides, the stirring device can be rotated by a motor close to the top of the flexible bag, using a single rod of rigid plastic to support each agitating element. For instance, the shaft of the stirring device can be magnetically driven, typically by use of a rotary driving disc located outside the flexible bag, the rotary driving disc being operatively engaged with a rotary driven disc attached to a top end of the shaft.
According to another aspect, embodiments of the invention provide a method for assembling a stirring device, the method comprising:
According to a particular, for obtaining a locked configuration of the hub, a radially flexible locking member of the sleeve is firstly compressed by an annular front end (typically top end) of the annular side wall and then expanded when all or part of the locking member engages in a recess or slot provided in the annular side wall.
The radially flexible locking member may be included in the one or more abutment members, the radially flexible locking member preventing a front annular side of the sleeve from axially abutting against an inner flange of the hub formed at the open axial face opposite to the insertion opening of the hub.
According to a particular, the hub and impeller assembly form a pre-assembled unit or a monolithic unit.
Optionally, the rod is provided with a first mounting area and a second mounting area to permit assembling two distinct agitating elements, the sleeve being a first sleeve encircling a cylindrical face defined at the first mounting area, the stirring device comprising a second sleeve identical to the first sleeve and configured to encircle the second mounting area. Each sleeve may be fastened to a same inner space delimited by a hub of a corresponding agitating element.
In preferred embodiments, the agitating element is firstly formed as a pre-assembled unit, by inserting and accommodating each attachment end the blades of an impeller assembly in a respective hollow part included in one of the hubs.
With such arrangement, there is no requirement for using a screw.
We will now describe several embodiments of the invention with the aid of the drawings, in which:
Referring to
The biopharmaceutical fluid C comprises one or at least one liquid phase. Where appropriate, the biopharmaceutical fluid C is formed from multiple components of which at least one is in a liquid phase and of which one or more may be in a solid phase, such as powder.
The stirring device 1 has here a rotatable drive shaft 2 extending along a longitudinal axis X between a first end, which may forms the top end 25, and a second end, here forming a lower end 26. These ends may be provided with a cavity or hollow and/or may be inserted in an hollow cylinder part of a bearing.
As shown in
As illustrated in
Besides, the stirring device 1 may also be in plastic material, preferably completely or partially transparent or translucent material. Use of plastic material maybe preferred as the fluid-mixing system 50 is a disposable part of the bioreactor, which means only the motorized driving part M and the outer containment device 18 can be re-used. In
The bag B may have a capacity of up to 5000 liters, depending on requirements and applications. However, the container B preferably has a capacity of between 10 and 500 liters, more preferably between 50 and 200 or 2000 liters.
The word “axial” on the one hand, and the words “radial” and “transverse” on the other hand, typically refer to what extends in or parallel or substantially parallel to the longitudinal axis X for the former, and perpendicularly or orthogonally or substantially perpendicularly or orthogonally to the longitudinal X for the latter.
According to some options not represented in the figures, the shaft 2 may be partially located outside of the container or bag B. For instance, the shaft 8 passes through the bag B, in particular at the bearing 11 in a fluid-tight manner. The rotary driven disc of the shaft 2 or similar top driven part is then located outside the bag B of the fluid-mixing bioreactor and is designed to engage functionally, in particular magnetically, with a rotary driving disc or similar rotary driving part of the motorized part M.
Referring to
The blades 6a, 6b can be fixed on the hub 10 without interfering with fastening of the drive shaft 2 though an inner space 9 of the hub 10. Typically, three blades 6a, 6b are used and may have each a weight greater than 500 or 600 g (for high bag capacities for instance). The blades 6a, 6b are made of plastic material and may have a radial extension higher than 25 cm or 30 cm. The blades 6a, 6b, as assembled or connected with the hub 10, form an impeller assembly 6. As used in the specification and appended claims, the term “impeller” is broadly intended to include all conventional types of impellers and impeller blades along with other structures that can be mounted around mounting portions 20a, 20b of the drive shaft 2 so that when drive shaft 2 is rotated within the container or bag B, the structures can uniformly mix the fluid within the bag B. In the current embodiment, as depicted in
Referring to
Referring to
The fins F6 may extend each radially outwards, either from the corresponding attachment end 6, or from an intermediary part forming a first blade portion 66 to which the fin F6 is directly connected. The outer fin F6 shown in
More generally, it is understood that fins F6 or the like can comprise any type of impeller blade or blade portion that will function for mixing in the intended application. The hub 10 has an interior surface that corresponds to an inner surface S8 of an annular side wall 8 delimiting the inner space 9 of the hub 10. The inner space 9 may be accessed via an insertion opening O centrally intersected by a central axis A of the hub 10.
The inner surface S8 of the hub 10 has a configuration complementary to exterior surface of a sleeve 3 surrounding a mounting area 20a, 20b of the shaft 2, such sleeve 3 being described in greater detail below. It is understood that the impeller assembly 6 and the hub 10 form together an agitating element 5a, 5b, which is configured to be keyed with or otherwise secured to the drive shaft 2, here via a specific coupling sleeve 3, so that rotation of the drive shaft 2 along a longitudinal axis thereof causes each agitating element 5a, 5b to concurrently rotate therewith.
During assembly, each agitating element 5a, 5b has a central passage (corresponding to the inner space 9) so that it can be slide along the drive shaft 2 until the hub 10 is centrally located around the mounting area 20a, 20b, the sleeve 3 being either fastened to the mounting area 20a, 20b, or to the hub 10 by being engaged in the inner space 9. Axial retaining of the agitating element 5a, 5b will be described later.
Referring to
As shown in
0<(A2−A1)/2≤θ.
As the housing parts are slightly tapering toward the radial portion PR, optional removal of the attachment end 6f may be facilitated if the flange 7 has been removed, for example by unclipping the tabs 75 of the flange 7. Of course, other configurations may be used for the contacts around the side wall 8, possibly without such tapering.
Here, as illustrated in
A recess or through hole 180 may be formed in the annular side wall 8, in the recessed flat part of the tubular projection 10a, in order to have the abutment surface B2 included in circumference of such recess or hole 180.
In the non-limiting embodiments of
The junction portion, which extends between the attachment end 6f and the corresponding fin F6, crosses the peripheral exterior surface 106 through the opening of the corresponding radial slot forming the housing part HP. Each attachment end 6f is typically hollow, while the hub 10 is provided with hollow blocks 10i alternated with the housing parts HP on the outer circumference of the hub 10, as clearly apparent in
Referring to
Referring to
Respective pairs of the partitioning radial walls PW of the hub 10 are circumferentially delimiting the housing parts HP. Between two adjacent pairs, the hub 10 delimits a chamber CH forming a passage for the tabs 75 of the flange 7. The chambers CH are alternated with the housing parts HP. Similarly on the flange 7, the pairs of slightly spaced tapering protrusions TR1, TR2 (for instance three pairs) are alternated with the tabs 75 (for instance three tabs 75). Besides, the tapering protrusions TR1, TR2 can be spaced by a small distance d suitable for adjusted insertion of a partition wall PW 6 separating two adjacent cavities 6c of a blade attachment end 6f, between the two adjacent tapering protrusions TR1, TR2.
Referring to
The radial portion PR may be provided with slots used to form radial windows O10, respectively through the outermost wall portion P10 of each hollow block 10i. An engaging end part 75b of the clip-like tabs 75 can be biased radially inward by the inner tapering face FC during insertion of the tabs 75 in the chambers CH (which occurs simultaneously with insertion of the tapering protrusions TR1, TR2 in the cavities 6c), until reaching the window O10. As a result, the tab 75 is released in a locked configuration, in which the engaging end part 75 engage radially outward inside the window O10 and remains in axial abutment relationship against a retaining rim 10r delimiting the window O10 or similar recess in the hollow block 10i. The local protrusion R facing the window O10 and formed as an axial protrusion from the radial portion PR may serve to progressively push radially outward the engaging end part 75b when it reaches the level of the window O10, to obtain a more efficient locking of the flange 7 as the plastic material of the flange 7 is relatively rigid and radial movement of the tabs 75 due to elastic deformation is limited to be less than maximal thickness of the outermost wall portion P10, and/or less than 3 mm.
The agitation element 5a, 5b is advantageously deprived from any clip or similar elastically/resiliently deformable plastic part. The impeller assembly 6 is either fastened to the hub 10 or integrally made with the hub 10. In any case, the agitating element 5a, 5b is robust, especially in areas where rotation torque is high.
Referring to
Each mounting area 20a, 20b of the rod 20 is provided with two diametrically opposed fastening areas so that each of the sleeve portion 3a, 3b (each piece) may be engaged, typically clipped, in a recess 201, 202 of the rod 20. A clipping is typically used, as a slight elastic deformation is sufficient to maintain the sleeve portions 3a, 3b relative to the rod 20. Here a recess 201 of small size, possibly of circular section is provided, while another recess 202 is provided with oblong shape. As illustrated in
An assembled state of the sleeve 3, as shown in
As illustrated in
Embodiments with a combination of two halves, preferably two identical halves, may be preferred as it makes initial mounting of the sleeve 3 onto a mounting area 20a, 20b easy. More generally, each of the sleeve portions 3a, 3b can have a C-shaped cross-section.
In the initial mounting state, the sleeve 3 has its inner face CF1 of cylindrical shape matching with the outer cylindrical surface 200 of the mounting area 20a or 20b. This inner face CF1 is obtained by assembling the two sleeve portions 3a, 3b. Tight contact of this cylindrical inner face CF1 against the rod 20, at the mounting area 20a or 20b shown in
Typically, the longitudinal separation 300 corresponds to a gap of about 1 mm (more or less) edge to edge. Mounting the hub 10, in order to obtain a plurality of radial contact areas C1, C2, C3, C4 against the outer ribs R1, R2, R3, R4 cannot deform the inner face CF1 (no crush of the shells forming the sleeve portions 3a, 3b and the edges L3, L3′ cannot touch). Referring to
Referring to
Each of the sleeve portion 3a, 3b is rigid and has a half cylindrical wall stiffened by peripheral outer ribs having each a C-Shape. In assembled state of the sleeve 3, each C-shaped profile of the sleeve portions 3a, 3b is viewed in a plane perpendicular to the longitudinal axis X of the drive shaft 2. The peripheral outer ribs R1, R2, R3, R4 of two adjacent sleeve portions are typically contiguous, so that generally circular ribs (with only interruptions at the separation(s) 300) are formed on an outer cylindrical face of the sleeve 3 in assembled state.
The sleeve 3 and the impeller assembly 6 may be made of same plastic material, possibly without any metal compound or any mineral compound (no mineral fibers or the like) for use with a biopharmaceutical fluid C, typically a biopharmaceutical fluid including living cells, organic compounds).
Before obtaining the locked configuration of the hub 10, the sleeve 3 can be held in a predefined reception or mounting area of the rod 20 where anchoring recesses 201, 202 are provided for each sleeve portion 3a, 3b. Each sleeve portion 3a, 3b has inner protrusions 31, 32 acting for clipping the sleeve portion directly onto the rod 20. The inner protrusions 31, 32 have a circumference shape and size matching the circumference shape and size of the anchoring recesses 201, 202, respectively.
After obtaining the locked configuration of the hub 10, the agitation element 5a, 5b extends axially around the entire predefined mounting area 20a or 20b. An anchoring recess 202 of larger size (as compared to another anchoring recess of same mounting area) may extend to be located in an axial position coinciding with axial position of all the attachment ends 6f of the blades 6a, 6b, while the other anchoring recess 201, of smaller size, is provided in another axial position, which preferably coincides with axial position of the retaining recess 100 provided to retain the radially flexible locking member included in the one or more abutment members.
Here, each of the sleeve portion 3a, 3b is provided with an inner face forming part (half part) of a generally cylindrical face. Typically, the sleeve 3 acts as an adapter that can efficiently transmit rotation movement from the rod 20 to the side wall 8 of the hub 10.
The hub 10 and/or the blades 6a, 6b may be made of rigid plastic material such as a polyester plastic, preferably PETG. Same plastic as the sleeve 3 and the rod 20 can be used, for sake of homogeneity in plastic material in the stirring device 1 and for having homogenous rigidity around the main contacts (for instance around the generally circular contact areas C1, C2, C3) between the hub 10 and the sleeve 3 and directly around the rod 20.
Referring to
On the cylindrical sleeve tube T3 for contact with the rod 20, on the outer face thereof, abutment members 33, 34, 35 are provided for axially retaining the hub 10 in a locked configuration. The abutment members may comprise two handles 34 and at least one longitudinal rib 33, or similar fastening arrangement able to penetrate inside the respective retaining recesses 100 of the annular side wall, using at least one indexed angle. The longitudinal rib 33 may extend form the front end FR of the sleeve portion to an outer shoulder forming junction between the rib 33 and the handle 34; of course, other configurations for angle indexation reliefs may be used. It is understood that the abutment members 33, 34, 35 comprise:
Here, rotation of the hub 10 around the sleeve 3 is prevented by the interlocked configuration between the abutment members 33, 34, 35 and the inner recessed areas of the side wall 8. More generally, the sleeve 3 may be provided with any suitable outer protrusions (forming abutment members) for axially retain the hub 10, while also preventing rotation between the hub 10 and the sleeve 3, in a locking configuration in which the outer protrusions are engaged in hub recesses. In variants, recesses may be provided in the sleeve 3 and inner protrusions of the hub 10 are engaged in such recesses, in order to prevent relative rotation.
Referring to
The process to assemble the sleeve 3 and the different parts of the agitating element 5a, 5b may begin with assembling two shells forming the sleeve portions 3a, 3b, for instance by inserting the inner protrusions 31, 32 in corresponding rod recesses 201, 202. A clipping may be performed and each tab 37 extends within a corresponding the slot 38, between the two parallel surfaces 38a, 38b of this slot 38. The sleeve portions 3a and 3b may be identical so that there is no assembly order for having the sleeve 3 correctly mounted. The sleeve 3 can define a cylindrical inner face, having a constant diameter D30 (see
Besides, the blades 6a, 6b may be assembled to be fastened to the hub 10 when the hub is a single separate piece. A cap or flange 7 serve to maintain the hub-blades arrangement by axially covering the axial open face 8b, as illustrated in
When having the sleeve 3 mounted onto the rod 20 and the agitating element 5a, 5b already pre-assembled (with the flange 7 locking the blades 6a, 6b in the housing parts HP of the hub 10), the hub 10 can simply slide (possibly with a rotation component) along the drive shaft 2 to surround the sleeve 3.
The shell-like portions 3a, 3b forming the sleeve 3 are translated in the hub 10 so that the annular side wall 8 tightens the halves on the rod 20 under the cone effect (frustoconical guiding surface S8). When fully inserted, the sleeve 3 is thus sandwiched between a mounting area 20a or 20b of the rod 20 and the agitating element 5a or 5b, as illustrated in
Referring to
Here the guiding surface is included in the annular side wall 8, as illustrated in
Referring to
Besides, at least one and preferably several second sleeve-hub annular contact areas C2, C3, C4 are provided, at positions less distant from the axial insertion opening O than the first contact area C1. Accordingly, there exists one or more contact areas defining a second diameter greater than the first diameter D1 Here in the non-limiting embodiment of
Axial locking by the shoulder or similar abutment region 301 included in the sleeve 3 is obtained to block translation movement, simultaneously with a clipping action to stop possible reverse translation inside the inner space 9. The locking member 302 may be engaged through the hole 180 for having this clipping action. Referring to
While the fixing by the sleeve 3 is here described using a translation to clip the one or more locking members 302, some variants may be used: for instance, rotation with translation of one of the hub or the sleeve may be performed and then clipping or just stop in abutment (like a screw) can be sufficient to have the hub 10 fastened and axially blocked around the sleeve 3.
In some variants, axial blocking is obtained with several positions (axial position) of clips, in order to vary/adapt the radial clamping force. Some clips may optionally be not used for locking the axial final position of the hub. Typically, the hub 10 cannot be disassembled as the locking members 302 are not available from outside. The hole 180 may be replaced by a recess without any outer access to the tab 75.
Besides, some embodiments provide a lever part or similar unlatching member, which may be included in the fastening arrangement (30, 30′), so that the hub 10 is removable. The lever part or similar unlatching member is possibly included in each of the sleeve portions 3a, 3b and a pushing action or similar appropriate actuation, using the unlatching member, can cause the locking member 302 to reach a retracted position outside the recess or hole 180.
Due to frustoconical distribution of tightness contacts of the concentric hub-sleeve-rod assembly, without using longitudinal edges or threads at least in a cylindrical tube T3 of the sleeve 3, the agitating element 5a, 5b may be mounted in simple manner without tendency for vibration and fatigue. The gaps 58 between the surface S3 and the tapering inner surface S8 can be compared to gaps of a labyrinth seal. They do not lower tightness contact for torque transmission as several contact areas C1, C2, C3, C4 of generally circular shape are provided along length of the annular side wall 8. Preferably, at least three annular contact areas are provided with three different diameters defined at the contact interfaces.
Referring to
Besides, it is permitted to erase dimension tolerance in the assembled state, due to tightness contacts that are distributed and not extending in a cylindrical manner. Indeed, the sleeve 3 is provided with outer ribs R1, R2, R3, R4 that are typically rounded/curved at their ends. More generally it is understood that use of the outer ribs R1, R2, R3, R4 to have spaced contact areas C1, C2, C3, C4 provides some additional tolerance when cooperating with the tapering surface of the inner surface S8 of the side wall 8. In other words, tightness is distributed with a slightly increased tolerance via the tapering guiding surface, typically formed on the annular side wall 8, which is of interest to suppress any empty gap between the hub 10 and the rod 20. It may advantageously decrease vibration and fatigue.
Referring to
The fluid-mixing container 50 may also comprise at least one through-port 56 for draining biopharmaceutical fluid C from the bag B, engaging with at least one drain hole formed in the bag B. The drain port 56 is able to be closed when necessary and opened for draining.
The term “port” is understood to refer to a physical connection means. Such a port is a through-port when it places in communication the inner volume V and the exterior of the container 2, for example for the introduction or discharge of what is to be placed or has been placed in the container 2. Such a port may also not be a non-through-port when it serves to hold a member of the mixer-container.
Ducts, pouches, reservoirs, if necessary flexible, may be associated with the introduction port 55, in fluid communication and with a sealed connection and removable where appropriate. Similarly, ducts, pouches, reservoirs, if necessary flexible, may be associated with the drain port 56, in fluid communication and with a sealed connection and removable where appropriate.
In the embodiment represented in
Optionally, the system 50 may also comprise an aeration device 13 adapted to deliver to the biopharmaceutical fluid C a certain quantity of aeration gas. This device 13 thus allows aeration of what is in the inner volume V, whether it is biopharmaceutical fluid or part of its components.
With such configuration, the stirring device 1 may advantageously comprise agitation elements 5a, 5b that include a lower agitation element 5a or 5b at a small distance from the lower part or bottom 50a of the bag B and an upper agitation element 5a or 5b at a comparatively higher distance from the upper part or top 50c of the bag B, in an expanded state of the bag B. Typically, in a vertical position of the rod 20:
Still referring to
In some embodiments, the fluid-mixing system 50 may also comprise other ports which are known per se, for example for mounting an operative means, suitable for retaining a member typically for the collection or measurement of data for example, or sample collection for analysis.
The stirring device 1 allows mixing what is in the inner volume V, whether this is biopharmaceutical fluid C or some of its components. A telescopic arrangement is here provided. Typically, the rod 20 forms an outermost surface of the rotatable drive shaft 2, in sliding relationship with a tube T that is provided in an upper region of the inner volume V. In variants as shown in
When beginning assembling of the fluid-mixing system 50, the container or bag B may be initially separate and arranged outside of the rigid outer containment device 18, as well as empty of biopharmaceutical fluid C and more or less flattened on itself. The bag B is placed in the housing within the rigid outer containment device 18, resting on its bottom wall 19.
A bearing 12 of the bag B, here a lower bearing 12, is connected to the rigid outer containment device 18, for example with an opening 29 located at the center of the bottom wall 19. Then the other bearing 11 of the bag 2 is positioned with respect to the motorized driving part M. The wall 3 of the container 2 is therefore brought to the level of the motorized driving part M.
When provided with a telescopic arrangement, the drive shaft 2 is in an at least partially retracted position and each agitating element 5a, 5b is already mounted and locked onto the rod 20 of the shaft 2. As the shaft 2 is here adjustable in length, it is possible to first place the bearing 11 at a distance away from the motorized driving part M. The coupling parts of the magnetic driving arrangement or similar coupling parts may be facing each other. A rotatory disc or similar coupling element integral with the bearing 11 can be located facing motorized driving part M. Next, the length of the shaft 2 is increased so that the bearing 11 (here the upper bearing) is positioned next to the motor of the part M, in particular connected without friction and with a runout clearance between a rotary driving disc of the motor and the bearing 11, so that the motorized driving part M can rotate easily. Such kind of tube T is not necessary to vary the position of the motor when connecting the bearing 11 with the motor. In some options the slot TS is provided on the rod 20. Besides, the sliding in the slot TS to increase the length may be obtained without any locking element in the shaft 2.
Referring to
Alternatively, it is possible to connect the bearing 11 of the container 2 with the motorized driving part M before connecting the other bearing 12 (lower bearing) with the rigid outer containment device 18.
The biopharmaceutical fluid C is introduced into the inner volume V, by means of the introduction port 55.
Finally, the stirring device 1 is used to stir the biopharmaceutical fluid C located in the inner volume V. If required, the length of the shaft 2 adjusts to guarantee the optimal relative positioning of the motorized driving part M and the bearing 11.
In the context of a bioreaction process, an aeration device 13 may be used to deliver a certain amount of aeration gas into the contents of the container or bag B. Stirring and aeration are carried out at least partially simultaneously, where appropriate entirely simultaneously. After mixing the biopharmaceutical fluid C and then draining it, in particular through the drain port 56, the bag B can be disassembled from the rigid outer containment device 18. The bag is then discarded, as it is disposable.
The method described above may be carried out only partially, as the steps described above can be carried out independently of one another. In particular, the bag B can be arranged in the rigid outer containment device 18 when it is already filled with biopharmaceutical fluid C.
Obviously, the invention is not limited to the embodiments described above and provided only as examples. It encompasses various modifications, alternative forms, and other variants conceivable to a person skilled in the art in the context of the invention, in particular any combination of the different modes of operation described above, which may be taken separately or in combination. For instance, the vessel receiving the stirring device 1 may be different. The vessel is possibly configured so that the rod 20 extends not vertically, for instance horizontally.
Of course, the depicted embodiments are in no way limiting the construction options for the stirring device 1. While the hub 10 has been described has forming an annular side wall 8 made of a single piece, an assembly of two or more pieces may also be used to form such side wall.
In some variants, the sleeve 3 as assembled may be provided with notching elements or threads cooperating with a corresponding interface present in a mounting area of the rod 2. Also, it is understood that the sleeve 3 can also be assembled by firstly be fastened to the hub 10, before being mounted onto the corresponding mounting area 20a, 20b.
Besides, the tapering or similar progressive reduction of cross section for contacting the hub 10 may be provided with a regularly curved profile surface (in cross section perpendicular to the rod) or with partly irregular profiles. While the contact tube of the sleeve 3 has a generally cylindrical shape in the illustrated examples, it is understood that the contact tube may have a different shape, depending on particulars of the rod area for receiving the sleeve 3. For instance, flat spots or other non-circular parts may be provided in the contact tube, which may be of partial cylindrical shape or provided with angles (typically polygonal shape). In some variants, a star shape or other shape with angles can also be provided for the contact tube of the sleeve 3, in order to match with complementary receiving portions of the rod 20.
| Number | Date | Country | Kind |
|---|---|---|---|
| 19185585.7 | Jul 2019 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2020/068871 | 7/3/2020 | WO |
