Technical Field

The present invention relates to a rocking apparatus intended for use in a single-use bioreactor for cultivation of micro organisms and a method for producing biologic products by such device. Background of the invention

Since 2005 the commercial product Wave Bioreactor ^® has been used in cell cultivation due to the benefits of the disposable technology and ease of use. Wave bag single-use bioreactors were originally developed by the US company Wave Biotech ^® in 1996. In the Wave Bioreactor system cell culture medium and cells contact only a pre-sterile, disposable chamber, a film bag, that is placed on a special rocking platform. The rocking motion of this platform induces waves in the nutrient liquid promoting agitation in the cell culture. The waves provides simultaneously the agitation and the oxygen, gas transfer, resulting in an environment for cell culturing, which can support over 10x10 ⁶ cells/ml. In a catalogue dated 2006 it is said: "The Wave Bioreactor is a disposable cell culture system. It consists of three major components: 1 ) a rocker platform, 2) a single-use cell culture bag and 3) an aeration/inflation pump. The rocker platform imparts the wave motion to the liquid inside the pre-sterilized CellBag and provides the necessary oxygen transfer and mixing for cell growth and productivity".

GE Healthcare ^' s ^® product WaveBag™ and the Sartorius Stedim ^' s ^® product CultiBag™ are based on similar principles. Both bioreactor products exhibit a rocking motion mechanical machine, which starts and stops, forcing the culture to create turbulent waves for mixing inside the culture bag. Said rocking motion is based on mechanical devices supported centrally on fixed mechanical bearings, pivots around which the single-axis rocking motion is performed.

References are also made to: o US patent 6, 190,913 describes the wave bag concept requiring a wave bag and an external rocking platform device comprising mechanical bearing based pivots

l featuring a fixed rotating centre around a single axis in order to generate waves inside the culture bag. o US patent 2008/0160597 and EP1896564 describe a system for inducing waves in a culture bag on a rocking platform depending on mechanical means such as rotating arms comprising various mechanical bearings all featuring rotating mechanical axis. o WO 2000/0066706 describes a culture bag being fixed in a tray, basin which by

means of an oscillating drive oscillate about an axis in a reactor frame comprising mechanical bearing based pivots featuring a rotating centres around a single axis. o WO 2005/049784 describes a culture bag being fixed to a flat surface and parts of the bag lifted by various means. No mechanical bearing based pivots are described. o Fig 6 of US2008/0274541 describes a toroidal bioreactor with multi directional and rocking motion around a single axis 6.3. Orbiting means orbiting the toroidal shaped bioreactor container in the vertical plane and not in a horizontal plane along the centre axis 6.3. The commercial available products WaveBag™ and CultiBag™ culture bags come in various sizes for use on one rocking platform.

Culture bags are a commodity and supplied pre-sterilized in liquid media volume sizes of 0.5, 1 , 5, 10, 20, 50, 100, 250, 500 litre from various suppliers globally. The media volume corresponds typically half the volume of combined media and process gas.

However, one problem associated with the currently different available bags is that each rocking device is constructed to accommodate only one special bag. In other words it is not possible to use different size bags from different manufacturers on one and same rocking device. As no standards exist around culture bag sizes the user is locked to a specific supplier product and limited in choice to one supplier only.

The present invention comprises flexible elements, which differentiate significantly from the above described fixed and non-flexible mechanical bearing pivots. The present invention further allows multiple platforms to be used on the rocking device benefiting the option of mixing different size bags from any of the manufactures within the same rocking device. Summary of the invention

The present invention concerns a rocking apparatus comprising: a) one or more platform(s) supporting one or more bioreactor(s),

b) one or more flexible element(s) in contact with said platform(s), and

c) one or more drive-unit(s), which is in mechanical connection with the platform(s) and capable of generating a reciprocation and tilting motion to said platform(s) supported on said flexible element(s).

Typically, the rocking apparatus is intended for being placed on a stationary support which apparatus comprises at least one platform suitable to carry one or more fluid containing culture bag(s) and at least one flexible element attached to the platform in such a way that when the rocking bioreactor apparatus is placed on said stationary support then said flexible element is capable of effecting the reciprocating motions of said platform.

The present invention is suitable for use in cultivation of micro organisms, e.g. for producing of a biologic product or for mixing purposes. In a further aspect the present invention relates to a method for cultivating a micro organism to provide a biologic product comprising the steps:

1 ) placing the bioreactor on a rocking apparatus having:

a) a platform suitable for holding the bioreactor,

b) a flexible element connected to said platform, and

c) a drive-unit, which is in mechanical connection with the platform and capable of generating a reciprocation and tilting motion to said platform supported on the flexible element

2) loading the bioreactor with liquid media,

3) inoculating the bioreactor with micro organisms

4) cultivating the micro organisms for a sufficient time

5) harvesting the biologic product

6) disposal of the bioreactor The apparatus and method of the invention are low cost solutions for providing a rocking apparatus which can be used with any culture bag and thus is not limited to a single culture bag products. Definitions relevant for the present invention: o The term "adherent" as used herein refer to micro organism with affinity to anchor, adhered onto a surface, such as immobilised cells or stem cells or micro organisms in general willing to adhere to growth bodies

o The term "biologic product" as used herein refers to and includes a wide range of medicinal and therapeutic products and drugs such as: antibiotic, antibodies, recombinant antibodies, monoclonal antibodies, vaccines, proteins, recombinant proteins, proteins molecules, blood components, allergenics, somatic (adult) stem cells, tissue cells created by biological processes

o The term "bioreactor" as used herein means a flexible container, a bag or culture bag, a plastic film bag, which provides biologically active, protected environment suitable for cultivation of micro organism

o The term "film" as used herein refers to thermoplastic film or foil made using an

extrusion process typically in one or several layers of different material for different purposes. Films may be permeable or impermeable and translucent or coloured in thickness below 1 mm.

o The term "fluid" as used herein means liquids as well as gases or liquid and gas o The terms "media" or "nutrient" as used herein refer to fluid containing water, carbon source, oxygen, vitamins, etc useful for the cultivation of micro organisms within the bioreactor

o The term "growth bodies" as used herein refer to rashing bodies, micro carriers,

beads, etc ranging in size from 100 μπι to 100 mm or fibrous mini discs made from non-woven polyester fibres.

o The term "micro organism" as used herein are typically divided into: 1. living single- celled organisms, microbes such as; fungus, algae, moss, plankton, yeast, protozoa, eukaryotes, archaea, micro animals, extremophiles and plant cells or the like - 2. adherent or semi adherent or suspended living cells such as animal cells, insect cells, mammalian cells, human cells, stem cells in general, embryonic stem cells, induced pluripotent stem cells, adult (somatic) stem cells in general, regenerative stem cells, tissue-derived stems cells, stromal vascular fraction stem cells or the like - 3.

prokaryotes and a variety of bacteria such as E.coli or the like - most of the above generically modified to solve specific tasks and product needs,

o The term "flexible element" as used herein refers to a non-rigid body, a body with no pivot point or centre, an elastic connected, a non rotating coupling which can be bend in at least one direction, such as a spring, a rubber body, able to accept misalignment, in one embodiment a pedestal which is predominantly a round and combined cylindrical, conical, convex, concave shaped element

o The term "perfusion mode operation" as used herein refer to operation principle for a bioreactor, the media are continuously exchanged, fresh nutrients added and product is harvested throughout the culture period

o The term "platform" as used herein refer to the physical sheet of material, such as a tray, which carry the bioreactor, e.g. the culture bag and to which the culture bag is secured

o The terms "shore A" or "shore hardness" is considered to be equal and refers to

measures of the depth of an indentation in the material created by a given force on a standardized presser foot. Lower number means softer and higher number harder, o The term "single-use" as used herein refers to a product designed for use only once and to be disposed after use typically delivered pre-sterilized and ready to use. The single-use product requires no on-site cleaning or sterilization, providing the ultimate ease of operation and protection against gross contamination at the biologies materials production facility

o The term "stationary support" as used herein refers to a horizontal surface such as a table or a desk-top or a laboratory desk-top or an incubator or the floor,

o The term "suspension dependent" as used herein refers to micro organism, stem cells, cell lines in general being suspended in a fluid with no or weak affinity to adhere to surfaces, such as mobilised micro organism of semi-adherent or non-adherent character, though willing to agglomerate, willing to semi-adherent to similar micro organism, willing to semi-adherent to other micro organism by agglomeration o The terms "tumbling" and "rocking" as used herein are used interchangeable and refers to the reciprocating motion, movements of the platform typically within plus and minus typically 1 - 15 degrees from the horizontal plane

o The terms "wave-bag" and "culture bag" as used herein are interchangeable and meaning refers to a film based container operating as a bioreactor Brief description to the drawings

Other features and advantages will emerge on reading the following description, with reference to the appended figures in which: o figure 1 illustrates the tumbling device with drive-unit and platform sharing an

common assembling-frame o figure 2 illustrates the tumbling device with drive-unit-frame separated from the platform by flexible elements and said flexible elements placed directly on the stationary support

o figure 3 illustrates the second platform connected mechanically to the first platform o figure 4 illustrates the second platform connected to and of difference size to the first platform

o figure 5 illustrates the flexible element attached to and between the assembling-frame and the platform

o figure 6 illustrates the suction cup element placed on the stationary support and the platform surrounding one body part of the suction cup

o figure 7 illustrates the flexible element without fixtures

o figure 8 illustrates the extraordinary simple stacking opportunities

Detailed presentation

The present invention concerns a rocking apparatus comprising: a) one or more platform(s) suitable for holding a bioreactor, such as a culture bag, b) one or more flexible element(s) in contact with said platform, and

c) one or more drive-unit, which is in mechanical connection with the platform and capable of generating a reciprocation and tilting motion to said platform supported on flexible element(s).

The rocking apparatus carrying the bioreactor, such as a culture bag, is intended for being placed on a stationary support. Typically, the platform is suitable to carry one or more fluid containing culture bag(s) and has at least one flexible element attached to the platform in such a way that when the rocking apparatus is placed on said stationary support then said flexible element is capable of effecting the reciprocating motions of said platform.

In a first embodiment the flexible element(s) (14a, 14b) is not in contact with the stationary support (55), but separating the platform 1 1 from the assembling-frame (13) said frame combines by assembling; 1. the flexible elements (14a, 14b), 2. the drive-unit (12), 3. the rubber feet (54) and the complete device is placed on a stationary support. The assembling-frame may consist of a flat or rectangular or square shaped solid piece of material, such as metal, wood or plastic like 1 -20 thick and 20 to 200 mm wide, such as 6x100 mm in cross section and a length (270+100 mm according to table 1 ) suitable for support of at least one platform. Extending the central part of the assembling-frame facilitates the expansion preferable with two or more platforms. Reference is made to figure 1 and 5. In a second embodiment the flexible element (24a, 24e) is separating the platform(s) (21 ) from the stationary support (65) with a specific drive-unit-frame (23) supporting the drive- unit (22) only. The flexible element rests, such as suction cups adhered directly onto the stationary support. This is considered to be an important part of the invention facilitating the low cost manufacturing, simple deployment and easy laboratory implementation. Reference is made to figure 2 and 6.

The platform comprises a rigid and flat surface manufactured from a piece of sheet material with thickness ranging from 0.5 to 10 mm and size (width and length) according to the culture bag or bags the platform is supposed to carry. To carry single-use culture bags the platform sizes preferably range from 100 x 200 mm until 1000 x 2000 mm. Reference for the current culture bag sizes is made to table 1.

The rocking device of the invention may comprise one platform or more than one platform such as 1 , 2, 3, 4, 5, 6 or more platforms. The platforms may be arranged in the vertical plane such as above each other or in the horizontal plane such as in series next each other in a line.

The platform(s) are attached to the flexible! element(s) by known methods, such as with fasteners in general such as threaded bolts or screws, with holes in the platform material for partial penetration of a part the flexible element, with flanges attached to the platform material locked to the flexible element or with glue or vulcanising methods. The means and methods to be used depending on desired design and choice of material and will be easily chosen by the person skilled in the art. In further an embodiment the platform is equipped with means for controlling the temperature within the media in said culture bag. Such means can be a heating and / or cooling device for selectable temperature within the culture bag liquids, such as ranging between 15° and 40° Celsius depending on the micro organism to cultivated. For cultivation of algae or other light demanding micro organisms a light source may be integrated into the platform and said light source further act as an additional heat source and the media in the bioreactor hereby participate in the cooling of the light source.

Said flexible element supports: the bare weight of the platform - towards earth centre of gravity the culture bag weight - towards earth centre of gravity

the weight of the static liquid content in balance - towards earth centre of gravity the dynamics of the liquid forced to be out of the balance of gravity - opposing ea centre of gravity

radial movements

In variations of the embodiment said flexible element (reference is made to figure 5) shaped as a pedestal with a first rigid flanged mounting part and a second rigid flanged mounting part, forming a cavity in between said flanges and interposed between them a cylindrical or conical or concave elastic body such as a elastic or resilient elastomeric rubber body element based on one or more deformable polymeric and/or elastomeric materials such as; latex, silicone, polyurethane, nitril, vinyl or rubber in general with shore hardness ranging between 20 and 90 Shore A.

In yet a variation of the embodiment the flexible element is metal based and shaped such as a pedestal spring body with variable stiffness according to the level of compaction which comprises a body in which the spring is a wire of variable wire cross section: Or one or more flat flexible elements formed from sheets of metal connecting the

assembling-frame and the rocking platform where in between the flat flexible elements rests directly on the stationary support further supporting the rocking platform in its tilting movements.

In a preferred variation of the embodiment said flexible element is shaped as a suction cup with a first semi-rigid body part and a second soft cone or skirt part, forming a cavity between said first semi-rigid part and second soft part said second soft part interposed towards and in contact with the stationary support. The suction cup type of pedestal comprises elastic body parts such as elastomeric rubber body element based on one or more deformable resiliently polymeric and/or elastomeric materials such as; latex, silicone, polyurethane, nitril, vinyl or rubber in general with shore hardness ranging between 20 and 90 Shore A. The flexible elements may be round, circular, race track shaped serving different purposes simultaneously, such as isolating the tilting movements from the assembling-frame, allowing the tilting platform(s) to tumble the container fluid, insuring permanent location on said stationary support. Said flexible element may comprise two suction cups within the same body. Such as the first suction cup in contact with the stationary support and a second suction cup oriented in opposite direction of the first suction cup and thus in contact with the platform. The rocking device of the invention comprises a drive unit. The drive-unit comprises a rotating motor rotor on an axle connected through a stationary gearbox comprising a rotating axle equipped with the crank device comprising further a shaft around which a barrel is rotating as the piston in a selectable distance from the crack centre axis defining the stroke. Said stroke is ranging from 5 to 100 mm in a reciprocation manner around the crank centre. In a variation of the embodiment at least one barrel rotates and slides reciprocation in contact with the platform creating the tilting motion. Said barrel may rotate and slide within a body with a U-profile design. The platform motion is further determined by the crank centre axis to flexible element axis with a distance ranging between 0 and 500 mm such as 0 to 200 mm. Said drive-unit may be driven by electrical or pneumatics means or other means supplied by external sources.

In yet a variation of the embodiment the crank is via one or more connection rods transferring via bearings the reciprocating motion to the platform. Stroke width is further determined by the crank centre to flexible element axis with a distance ranging betweenl and 500 mm. Said rotating motor may be driven by electrical or pneumatic means supplied by external sources.

In a further variation of the embodiment the platform motion is initiated by the drive-unit aligned with the platform motion axis. The drive-unit expresses the desired reciprocation motion without a crank and barrel associated with previous mentioned variation. The drive-unit internally converts the continuing motor rotor rotating through a converting gearbox to the rocking and reciprocating motion expressed though a clutch in contact with the first platform. Said drive-unit may be driven by electrical or pneumatics means supplied by external sources.

In one embodiment said drive-unit is a reciprocating device such as the pneumatic actuator with reciprocating rotation of less than 270 degree aligned with the platform motion axis. Said actuator based on a moving piston in contact with or fixed to the driving axle. The drive axle penetrates through the housing containing the piston. Gas pressure variation on at least one side of the piston creates the reciprocating motion.

In one embodiment said drive-unit is one or more reciprocating device such as the pneumatic or hydraulic piston actuator(s) being in contact with said platform and expressing the desired reciprocating motion of said platform. In one embodiment said drive-unit is a linear motor device which linear reciprocating movements defines the stroke length within 5 to 100 mm. Said linear motor may be oriented vertical or horizontal and driven by electrical or pneumatic means supplied by external sources. Transfer of movements from said linear motor to the platform by mechanics.

In one variation the linear motor is an elongated piston moving inside a stator tube substantially longer than said piston with electromagnets around the outside of said tube and permanent magnets inside the piston sliding inside the tube. The tube appears as a guide, circumference track to the moving piston. If said tube is closed in each the drive- unit tube hereby are able to transfer the piston movement and kinetic energy on each side of said piston to a fluid. The fluid motion may be transferred via hoses to flexible motion bellows arranged one bellow under each side of the platform further being expanded or deflated according to the piston movements. The reciprocating height of said flexible motion bellows generates the tilting motion of said platform.

Traditionally the culture bag is attached to the platform in one single layer insuring the bag is kept in a static position and stretch in order to insure maximum bag life time. The present invention is not considered to be limited to one single layer of traditional culture bags. Suitable culture bags with one or more compartments may be stacked on top of each other. Preferably with a flexible heating element placed in between the bags. The present invention is further not considered to be limited to one single horizontal oriented platform carrying one bag. The platforms may be stacked vertically on top of each other each with one bag the platform separated by flexible elements on stilts and motion interconnected via rods.

At least the assembling-frame or the drive-unit-frame supports the drive-unit and converts the forces to the stationary support initiated by the drive-unit as according to Newton's law predict that a first motion will initiate a second counter directed motion.

The limits for tilting the platform back and Forth may be 0.1 -50 strokes per minute and as much as plus and minus 1 to 15 degree angled around the vertical axis or the stationary support. The acceleration profile, deceleration profile, stroke/angle profile of tilting, rotation is adjustable by the drive-unit device.

The present invention relies on flexible elements with variable flexibility in a non-static structure controlled in dynamic balance by the drive-unit. In structural engineering, the flexibility method is the classical consistent deformation method for computing member forces and displacements in structural systems. Flexibility is the inverse of stiffness.

In one variation the flexible element(s) has a first static part and a second dynamic part capable of misalignment of 30 degree between first static part axis and a second dynamic part axis. Said static part either in contact with the stationary support or secured onto the assembling-frame. The dynamic part of said flexible element is in contact with the platform. Reference is made to figure 5. Platform tilting axis preferably symmetrical arranged along the platform tilting axis. In order to obtain a non symmetrical tilting axis the flexible elements may arranged asymmetrical to the platform axis.

In another variation a part of the flexible element(s) is predominantly of static character such as the suction cup (62) secured to the stationary support. The upper parts of the flexible element show semi static properties with the platform rocking around the cylindrical part (64) freely. Said suction cup preferably manufactured from elastic materials with design reference made to figure 6.

In yet another variation the flexible element(s) is of combined static and flexible character- such as attachment of the suction cup to the platform facilitated by fasteners. Such as a suction cup with a first semi-rigid body part and a second soft and more elastic cone or skirt part, forming a cavity between said first semi-rigid part and second soft part. Said second soft part interposed towards and in close contact with the stationary support. Reference is made to figure 5.

Table 1. Culture bag manufactures, the maximum liquid volume in litre /physical size in mm and availability (na). Larger bags are available as well.

The table 1 illustrates relevant various culture bag sizes based on their liquid content in litres. In real life the fluid volume of the culture bag is approximately twice the liquid volume. Half is media liquid and half is a gas composition of air and typically 5-10% CO ² to the air controlling the media gas composition.

Table 1 further illustrates dominating manufactures bag sizes. Even though the volume is identical the physical dimension are different. This culture bag dimensional difference from different suppliers prohibits alteration of the bags on prior-art rocking devices and is considered to obstruct the industry demands of more flexibility. Reference is made to figure 4. Based on table 1 it is possible to calculate the assembling-frame length as the drive-unit attachment prolongs the length with app 100 mm according to figure 1.

Wave agitation is efficiently achieved by using gravity to accelerate the fluid contained inside the culture bag at the rocking maximum. The wave sweeps up solids, avoids sediments and disperses them into the liquid. Frequent direction reversals are used to cause a reciprocating chaotic fluid motion inside the bag. This greatly increases the effectiveness of the mixing and homogeneity can typically be achieved within minutes. The greater the tilt angle, the higher the velocity of the resulting wave. However, the momentum of the wave also increases, which requires that the angle be reduced as liquid volume increases. Inclusion of growth bodies in the culture bag further extend the variety of micro organism possible to cultivate efficiently.

The invented tumbling device may benefit from the integration of a balancer. Calibrating the load sensors with a known load on the culture bag will allow the associated controller to seek information about the actual load periodically during operation. This information is transmitted to a controller which in perfusion mode simultaneously adjusts the feed pump and the permeate pump, retentate pump.

Detailed description of the figures

Figure 1 illustrates a rocking apparatus of the present invention, such as one first platform 1 1 and one second drive-unit 12 connected to one third assembling-frame 13. The platform 1 1 is supported on two flexible elements 14a, 14b (14b hidden below the platform) on each side of the platform 1 1 along the platform rocking axis 14c. On the perpendicular side 15 to the platform axis 14c next to the drive-unit 12 an attached u- shaped profile 16 allow a barrel 17 mounted on the piston axle on the crack wheel 19 to lift and dip the profile 16 hereby creating the reciprocating strokes and platform 1 1 motion. Distance between flexible element axis and drive-unit crank is 155 mm and the stroke is 40 mm. The drive-unit 12 and the platform 1 1 share the same assembling-frame 13.

Figure 2 illustrates the option with the drive-unit 22 on a separate drive-unit-frame 23 for the drive-unit 22 only with integrated flexible elements 24a, 24b, 24c (24d not visible being the drive-unit) facing downwards and towards the stationary support which is not illustrated. The culture bag platform 21 share the use of one flexible element 24a with the drive-unit 22 on the drive-unit-frame 23. Said flexible elements further illustrated in figure 6. Opposite the drive side of said platform 21 said platform facilitates a free standing flexible element 24e. The frame 23 with four legs takes advantage of 4 pieces flexible elements 24a, 24b, 24c (24d not visible) arranged on the frame 23 legs. Two such and opposite arranged flexible element 24a, 24c are aligned with the axis of the rocking platform 21. The two other flexible elements 24b, (24d not visible) arranged on the frame 23 perpendicular to the platform 21 axis 21 a coping with Newton's forces. When the flexible elements are suction cups the adhesion to the stationary support (not illustrated) insures the drive-unit 22 frame 23 stays in place (no movements) for extended duration on said stationary support (not illustrated). One through going hole 21 b in the sheet material of said platform 21 fits onto and around flexible element 24a cylindrical body part otherwise shared with the drive-unit frame 23 insuring constant alignment among the platform 21 and drive-unit 22. Suction cup 24e is not in contact with the frame 23 but with platform 21 and stationary support (not illustrated) only.

Figure 3 illustrates the option of adding the second platform 31 b next to the first platform 31 connected to the drive-unit 32 along the same axis 31 c. Said first platform 31 a and second 31 b platform are separated by a distance 31 d though mechanical connected by two devices, clips 31 e, 31 e transferring the tilting forces. Said second platform 31 b facilitates two free standing and independent suction cups 34a and 34b (partially visible).

Figure 4 illustrates the option of adding the second platform 41 b next to the first platform 41 a being connected to the drive-unit 42 along the same axis 41 a. Said second platform 41 b differentiates from said first platform 41 a in physical dimension in order to facilitate the support of a culture bag from a manufacturer different to the culture bag manufacturer on the fist platform. Said second platform 41 b facilitates two free standing and

independent flexible elements 44a and 44b (partially visible). One motion transfer device 41 e connects the two platforms and further act as alignment toll 41 e between suction cup 44b and suction cup 44c respectively the two platforms mounted invisible under the platforms though shown. Figure 5 illustrates the flexible element, the pedestal 52 attached between the platform 5t and the assembling-frame 53 which is further in contact via rubber feet 54 with the stationary support 55 being a table. The platform 51 is attached to the pedestal 52 with one fastener 56b into the upper flange of pedestal 52. The flexible element 52 elastic body 52a is glued or vulcanised to both the flanges 52b, 52c. The lower flange 52c is secured with a fastener 56a from underneath of the frame 53 passing through the frame 53 into the flange 52c. Figure 6 illustrates the flexible element as used in figure 2, a suction cup 62 being a one piece suction cup with a first cylindrical soft body part being in close contact with the platform 61 and the second flexible side in contact with the stationary support 65 being a table or desk-top. The soft part of the suction cup 62 are partially emptied from air in the . cavity 63 and the suction cup 61 first cylindrical body part 64 attached with a screw through a hole in the culture bag platform 61 being load supported on said flexible element 61 second and large diameter body part 66.

Figure 7a illustrates the flexible element, a suction cup 72 being a one double suction cup assembly in close contact with the platform 71 and with the stationary support 75 being a table or desk-top. Both suction cups 73a, 73b are partially emptied from air in the cavities 73c, 73d and the two suction cups are assembled around a body part 74. The smaller suction cup 73b is in contact with the culture bag platform 71 being load supported through flexible element 74 to second and large diameter suction cup 73a.

The body part could further be a rigid frame part 75 or the like as illustrates on 7b connecting the two suction cups 73e, 73f facing the cavities 73g, 73h away from each other.

Figure 8 illustrates the principle of stacking multiple rocking apparatuses 81 , 82, 83 vertical in a frame 84 for reduced occupation of floor space. Known prior art or in practise rocking apparatus is mounted, located on a desk-top next to each other in a horizontal position only. The benefit is obvious by stacking any rocking apparatuses vertically such as cost savings and vastly increased number of bioreactors on a given floor space. The illustration exposes the option of individual and different rocking frequency of the multiple stacked platforms. The illustration also exposes the option of individual sized or dimension rocking devices from a variety of suppliers for a variety of film based bags within the very same frame. Said frame may be fabricated from practical sized structural beams or tubing 85 and supported by wheels 86 in each corner for ease of transportation. The mechanical connection between the rocking apparatuses 81 , 82, 83 and the frame 84 are not shown neither are dimensions shown for simplicity of the illustration.

This invention includes all modifications and equivalents of the subject matter re-cited in the aspects or claims presented herein to the maximum extent permitted by applicable law.

The present invention is further illustrated by the figures which, however, are not to be construed as limiting the scope of protection. The features disclosed in the foregoing description and in the figures may, both separately and in any combination thereof, be material for realising the invention in diverse forms thereof.

All methods described herein can be performed in any suitable order unless other-wise indicated herein or otherwise clearly contradicted by context.

The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise indicated. No language in the specification should be construed as indicating any element is essential to the practice of the invention unless as much is explicitly stated.

The citation and incorporation of patent documents herein is done for convenience only and does not reflect any view of the validity, patentability and/or enforceability of such patent documents.