阅读说明：本技术 色谱珠粒容器提升系统 (Chromatography bead container lifting system ) 是由 马塞卢斯·约翰尼斯·许贝特斯·瑞德 于 2020-05-04 设计创作，主要内容包括：本发明公开了一种设备,包括：容器,填充有色谱珠粒,用于捕获存在于工艺液体中的产物或准备好所述色谱珠粒以供后续使用；支撑框架,竖立在地面上且为所述容器提供支撑以使得所述容器处于所述地面上方一定间距处；提升系统,位于所述容器外部,紧固到所述支撑框架且由所述支撑框架支撑且紧固到所述容器的部分,使得所述容器的所述部分可由所述提升系统相对于所述支撑框架和所述容器的另一部分升高,其中所述提升系统的至少部分在所述容器旁边从所述容器的底部延伸到所述容器的顶部。(The invention discloses a device, comprising: a container filled with chromatography beads for capturing products present in a process liquid or preparing the chromatography beads for subsequent use; a support frame erected on the ground and providing support for the container such that the container is at a distance above the ground; a lifting system located outside the container, secured to and supported by the support frame and secured to a portion of the container such that the portion of the container can be lifted by the lifting system relative to the support frame and another portion of the container, wherein at least part of the lifting system extends alongside the container from a bottom of the container to a top of the container.)

1. An apparatus, comprising:

-a container (1) filled or designed to be filled with chromatography beads, for example a container designed for capturing products present in a process liquid, designed as a "packed bed" chromatography column, or a container designed for processing or utilizing said chromatography beads in order to prepare them for use, for example, in a preparation vessel in said "packed bed" chromatography column;

-a support frame (31) standing on the ground and providing support for the container so that it is at a distance above the ground;

wherein the container and the support frame are assembled as an integral, rigid, compact apparatus for selective positioning on a floor of a human-accessible process chamber;

-a lifting system (30) located outside the container, fastened to and supported by the support frame and fastened to a portion (3, 24) of the container, the lifting system having a lowered and raised position such that the container portion (3, 24) is raised in the raised position by the lifting system relative to the support frame and possibly relative to the temporarily released container portion (2, 16, 17, 27, 28);

the lifting system is arranged on the equipment;

wherein at least part of the lifting system extends alongside the container from the bottom (28) of the container to the top (3) of the container.

2. Apparatus according to claim 1, wherein said lifting system comprises at least one upwardly extending elongated actuator (30), preferably of the linear type, said elongated actuator (30) being fastened at one longitudinal end to said supporting frame (31) and at the opposite longitudinal end to said container portion (3, 24), so that operation of said actuator causes said raising of said container portion (3, 24).

3. Apparatus according to claim 1 or 2, wherein an axial elongation or extension of a part of the lifting system, such as the actuator (30), causes the raising of the container part (3, 24).

4. The apparatus according to any one of claims 1 to 3, wherein the lifting system is distributed around the container (1) in a top view.

5. The apparatus of claim 4, wherein the lifting system comprises at least three actuators (30), the actuators (30) being arranged at mutual angular intervals of preferably at least 60 degrees in top view, each secured to an associated adjacent position of the container portion (3, 24) to provide a statically balanced support of the container portion (3, 24) by the three actuators (30).

6. The device according to any one of claims 1 to 5, wherein the actuator (30) is of the electric or hydraulic type.

7. The apparatus of any one of claims 1 to 6, wherein the actuator internally comprises a measuring member (42) to measure the axial extension or expansion of the actuator.

8. Apparatus according to claim 7, wherein the measuring means comprises a reference element (42), such as a ruler-like element or a ruler guide, the reference element (42) being concentric inside the piston (37) and/or piston rod (36), and preferably being of the axially linear type and/or extending axially at least the entire actuator stroke length.

9. The device according to any one of claims 1 to 8, wherein the actuator comprises an internal supply channel (47) extending in the axial direction and connected to a space (39), the piston (37) being displaced in the space (39) during extension or expansion of the actuator to supply liquid to the space.

10. The apparatus of claim 9, wherein the internal passage is provided by a gap (47) between two concentrically positioned axially extending walls (46) of the actuator.

11. The apparatus according to any one of claims 1 to 10, wherein the support frame (31) is U-shaped or V-shaped in top view.

12. The apparatus according to any one of claims 1 to 11, wherein the container (1) is located inside the outer circumference of the support frame (31) in top view.

13. The apparatus of any one of claims 1 to 12, wherein the container comprises one or more of: a mixer (24, 25, 26) for mixing the container contents; a filter plate, for example horizontally or radially (27) adjacent to said bottom (28) or vertically or axially (17) adjacent to the outer sidewall (2); an annular cavity (7) housing said beads between concentric axial filtering walls (16, 17).

14. The apparatus according to claim 13, wherein one or more of the mixer, filter plate, axial vessel wall, annular cavity is fastened to the vessel lid (3) by externally accessible fastening means for selective release from the lid (3).

15. The apparatus according to any one of claims 1 to 14, wherein the complete container (1) is suspended from the lifting system (30) in the raised position.

16. The apparatus of any one of claims 1 to 15, the filter comprising at least two layers of stainless steel braided wires directly on top of each other to provide a composite assembly, each layer having a pore size that differs from the immediately adjacent layer by at least 20%; the layer is directly exposed to the gel in the vessel.

17. A method of operating an apparatus according to any one of claims 1 to 16, wherein the fastening of the container part (3) to another container part (2) is temporarily released and the container part is subsequently raised relative to the other container part (2) and the support frame (31) by means of the lifting system.

Technical Field

The present invention relates to the field of containers filled with chromatography beads. In one aspect, a vessel for capturing a product present in a process liquid is designed as a "packed bed" chromatography column (also simply referred to as "column"), e.g. of the axial or radial flow type, for liquid chromatography of a packed bed (also simply referred to as "bed") comprising beads, in particular for downstream processing of engineered biological products from natural sources such as milk, plasma, extracts etc. or such as cell cultures or cell fermentation harvests, e.g. for laboratory analysis operations or industrial scale production operations, in which separation steps, e.g. separation from human blood or capture or removal of impurities from drugs, can be performed on a large scale in a batch process or a continuous process. On the other hand, containers designed as preparation vessels (also simply referred to as "vessels") with "fluidized beds" or "slurries" process/utilize chromatography beads in a pressureless manner in preparation for use in "packed bed" chromatography columns.

Background

US4627918A, US4676898A, US5466377A, W02014/092636, WO03059488, WO2007/136247 and W02019/143251 provide general and specific background on chromatography.

Disclosure of Invention

The material of the packed bed may also be referred to as "adsorbent" or "gel" or "resin" or "matrix". The beads may be smaller or larger in diameter, for example beads having a diameter between 10 and 1100 microns (0.01 to 1.1 mm), for example from 20 to 100 microns or from 100 to 300 microns or from 300 to 500 microns or from 500 to 800 microns or from 800 to 1100 microns (equal to 0.02 to 0.1 mm or 0.1 to 0.3 mm or 0.3 to 0.5 mm or 0.5 to 0.8 mm or 0.8 to 1.1 mm respectively) in diameter.

As seen in the axial view, the column or vessel has a cylindrical, square or any other shape and has an internal processing volume to accommodate the beads. This inner process volume is delimited by a circumferential, axially extending, for example cylindrical wall (a wall extending axially upwards or vertically during normal operation), closed or sealed at both axial ends by a top wall and an opposite bottom wall, also referred to as "baffles" (top or upper and bottom or lower walls extending horizontally during normal operation, respectively). The internal treatment volume is preferably between 10 and 1000 or 5000 litres. The axial direction of the column or vessel is upright or vertical during normal, upright operation.

Both the column and the vessel contain a filtering wall (also called "filter", "sieve" or "frit"), preferably plate-shaped, adapted to the bead size to hold the beads while allowing liquid to pass through, as well as one or more inlets and one or more outlets for the supply and extraction of liquid and beads, respectively. The column is equipped with axially (also referred to as "vertical" or "upright") and/or radially (also referred to as "horizontal") extending filters. Preferably, the column comprises at least one or two vertically extending filters spaced apart from each other, preferably concentrically provided to provide a packed bed in the shape of a toroid or torus. The vessel is preferably equipped with a radially (also referred to as "horizontal") extending filter (also referred to as "bottom filter") adjacent to the bottom wall, e.g. keeping a gap of less than 5 mm or 30 mm or 50 mm or 100 mm from the bottom wall; and/or an axially extending filter.

For vessel bottom filters, one or more of the following preferably applies: in the shape of a funnel or inverted dome with its lowest point at the axial center of the vessel (or: at the center of the vessel bottom wall as seen in top view); comprises at least two or three laminated layers and/or is spaced from the bottom wall of the vessel; a region located above the vessel bottom wall and/or covering at least 80% or 90% or completely the vessel bottom wall and/or enclosed by the vessel circumferential wall, for example sealed to the vessel circumferential wall along the entire circumference of the vessel or provided in an alternative manner such that liquid inside the vessel and on the side of the bottom strainer facing the vessel top wall can only enter the space inside the vessel on the opposite side of the bottom strainer by passing through the bottom strainer; its surface facing the interior of the vessel (i.e. the top or upward face during normal operation of the vessel) is such that the gel cannot enter the cavity of the bottom filter, i.e. the filter surface porosity is smaller than the bead size of the gel (this provides that the beads of gel will always remain on top of the filter surface); designed so that the beads remain on top and may not sink into the top surface of the bottom filter.

For vessel axial filters, one or more of the following applies: a short radial distance from the vertical or upright wall of the vessel, and preferably concentrically with the vertical or upright wall of the vessel, preferably sealed to another element of the vessel, such as a bottom filter and/or a vessel bottom wall and an upright wall of the vessel at its lower and upper edges, respectively; the vertical filter is spaced from the vertical wall by between 1 or 5 mm and 10 or 20 or 30 mm; the top edge of this vertical filter is above the maximum filling level of the vessel (for gel); extending at least 50% or 80% of the height of the upstanding container wall and/or extending completely circumferentially.

For the filter, one or more of the following preferably applies: made of stainless steel, preferably sintered, or of plastic or polymer material; pelleting, printing (i.e., by 3D printing), or weaving; electropolishing the surface; a hydrophilic surface; comprising at least or exactly one or two or three or four layers or sheets of stainless steel woven threads directly laminated to each other, at least one of said sheets, such as the sheet providing (during normal operation) the top face or the upward or inward face of the filter, preferably, such as when woven, having a fine and/or well-defined porosity, preferably woven according to a plain or twill weave or a plain dutch weave or a twill dutch weave or a reverse twill dutch weave or a five heddle weave pattern; the sheets provide a union assembly, which is preferably sintered (also known as diffusion bonded) to each other; at least one or two lamellae, e.g. each lamella having a diameter that differs from the immediately adjacent lamella by at least 10% or 20%, e.g. a greater or lesser braiding of threads; the line thickness among the sheets increases from one face of the filter to the other, preferably from the top face or the face upwards or inwards (during normal operation); the linear thickness of the lamellae is at least 25 microns or 50 microns (equal to 0.025 mm and 0.05 mm) and/or not more than 500 microns (equal to 0.5 mm); at least one or two, e.g., each flake has an aperture size that differs from the immediately adjacent flake by at least 10% or 20%, e.g., greater or less; the pore size in the sheets increases from one face of the filter to the other, preferably from the top face or the face up or inward (during normal operation); a sheet with the thickest line and/or largest pore size, e.g. at least 500 micrometers (0.5 mm), e.g. a reinforcing sheet, is the innermost or outermost sheet that is ultimately preferably the filter, preferably the sheet furthest away (during normal operation) from the top surface or upwards or inwards; a thickness of at least 0.3 mm or 0.8 mm or 1.0 mm and/or not more than 1.2 mm or 1.5 mm or 1.8 mm or 3.5 mm; pore size (being "nominal" pore size, defined by the diameter of the largest or smallest rigid sphere that can pass through the pore) of at least 1 micron or 10 microns or 50 microns or 100 microns and/or no more than 100 microns or 200 microns or 500 microns (equal to 0.001 mm, 0.01 mm, 0.05 mm, 0.1 mm, 0.2 mm and 0.5 mm, respectively); comprising a single filter layer; the filter layer is directly exposed to the contents of the column or vessel, e.g., a gel; on the side of the filter layer facing upwards or inwards (during normal operation), a layer, for example a protective layer, is missing; the filter layer provides a surface layer; no layer or only a protective layer at one side of the filter layer and only a protective layer or a dispersion layer at the other side, and possibly just one or two further layers, preferably a reinforcing layer; providing a filter wall or membrane, preferably having and/or covering a surface area (e.g. circumferential, axially extending column walls in the case of a column and bottom walls in the case of a vessel) at east 25% or 50% or 75% or 90% of the surface area of the container adjacent the outer wall and/or at least 500 square centimetres or 1000 square centimetres or 2000; function like a sieve; having a protruding shape, such as for example a container wall; is non-corrugated and/or non-folded; is unfolded.

For columns, the invention is particularly applicable to column types with horizontal or radial flow, but the invention is also applicable to column types with axial flow. As used herein, the terms "horizontal" and "radial flow," which are used interchangeably, are defined as the flow of a liquid or sample (e.g., a biomolecule) or an eluent or wash fluid through a packed bed of a column in a direction perpendicular to the longitudinal axis or axial direction of the column. Preferably, the column is configured so as to have inner and outer annular zones of concentric and aligned equal axial length, each providing a filter, filled with matrix material therebetween. The top and bottom edges of the two concentric filters are sealed to top and bottom sealing plates. Thus, the packed bed has a ring or donut shape, is sealed at the top and bottom sides in the axial direction by the sealing plates, and the flow through the packed bed is radial from one concentric filter to the other. The bed height is thus calculated as the distance between the inner and outer rings. Radial flow is particularly advantageous for high performance low pressure chromatography used in conjunction with the separation of biomolecules, such as proteins or other organic or inorganic compounds that are particularly sensitive to shear forces. Such horizontal or radial flow columns are disclosed, for example, in U.S. patent nos. 4,627,918 and 4,676,898.

The vessel is intended to facilitate and automate the performance of several bead related processing steps, mainly but not exclusively in combination with preparation/cleaning/activation/collection to waste/adsorption or desorption. One of the applications of the vessel is to replace the liquid containing the beads, e.g. buffer exchange. In addition, decantation, delignification and concentration adjustment can be carried out with vessels. Or to prepare the beads for reuse (e.g., washing, treating, cleaning, etc.). Or prepared for concentrated storage after use, or homogenized. In all such cases, the beads are free-flowing inside the vessel in the mixed state.

Typically, the vessel is equipped with a mixer, preferably equipped with blades or designed in an equivalent way to homogenize the contents of the vessel gently but effectively by the mixing action. Preferably, the electric drive motor for the mixer is mounted on top of the top wall of the vessel.

The column is typically operated at a higher internal pressure of 1 bar relative to ambient pressure, typically between 2 and 4 bar above ambient pressure, which means that the process liquid is supplied to the column and flows through the packed bed of beads at said higher internal pressure. These generally higher internal operating pressures require a high level of safety measures and are also used to service the column.

The vessel is typically operated under gravity, meaning that gravity alone acts as the driving force for flow through the filter. Instead, in addition to the action of gravity, a gentle suction at the outlet and/or a gentle overpressure in the head space is exerted, so that in this case the action of gravity is mainly the driving force for the flow through the filter. The top bulkhead carries the mixer and its drive unit, making it a heavy weight sub-assembly requiring a high level of safety measures, and also for maintenance vessels.

Hereinafter, the column and vessel are collectively referred to as "container". An "axial view" also means a "top view" in operation.

It is an object of the present invention to provide a high level of safety during handling of a sub-assembly (e.g. comprising a top bulkhead) of a container, wherein said sub-assembly is lifted from the rest of the container without effort but with a high degree of accuracy, e.g. for maintenance, inspection or replacement of a grid, e.g. of the disposable and/or axial type, preferably without the need for external lifting equipment. For clean room environments, which are typically the case for the present containers, a crane mounted to the ceiling of the room is highly undesirable.

The container is preferably a fitting of several separable sub-units and is mounted on a support frame which can provide an array of functions, either exclusively or in combination. Mainly, the frame is intended to support the container and should provide a sturdy base, characterized by height adjustable feet, or optionally, it can be performed by freely rotating castors to freely move the container. Depending on the most efficient match to the application and/or the type of execution, a sensor is preferably installed to evaluate and monitor the filling level of the container, which sensor may act by differential weight, differential static pressure or actual level height monitoring. Thus, the liquid handling process may be fully automated or controlled by an operator.

The frame preferably has a horizontal base, preferably provided by a U-shaped or V-shaped space frame, carrying feet or wheels at its downwardly facing side and/or positioning a container at its upwardly facing side, the bottom of which may be horizontal to or below the base. The U-shape or V-shape facilitates access to the container bottom functionality, e.g., liquid ports. Preferably, the container fits within the footprint of the frame or its base, more preferably between the legs, in an axial view.

The frame is equipped with an integrated synchronized lifting system that separates the upper fitting from the bottom fitting and/or the upper fitting from the vertical filter, and lifts the upper fitting from the bottom fitting and/or the upper fitting from the vertical filter. The lifting system itself is typically made up of at least two and preferably less than six mutually spaced lifting actuators that work together under tightly controlled synchronized action to maintain the center of gravity of the lifting assembly within the tolerance of the center of gravity of the entire unit to allow safe lifting of the upper assembly and ensure absolute vertical (also referred to as "axial") concentric lifting so that, for example, separation of the upper assembly from the rest of the vessel (e.g., the vertical filter assembly) will occur without contact between components of the upper assembly, such as the walls, and components of the rest of the vessel, such as the vertical filter assembly. When less than 3 lift actuators are applied, an additional robust vertical guide ("guard rail") may assist the stability of the vertical lift and ensure that the concentricity tolerance is kept within given limits.

Preferably, in axial view, the lift actuator and guide: distributed around the axially outer wall of the container, in other words the lifting actuators and guides surround or enclose the container, preferably with a close radial spacing for a compact design; and/or extended, fully contracted and/or have a stroke of at least 50% or 75% of the height of the container and/or less than 100% or 150% or 200% of the height of the container, e.g. from bottom level to top level; and/or fastened to a container and/or mixer top (e.g., container top wall, also referred to as a "lid") by, for example, releasable fastening members to lift the container and/or mixer suspended from the associated top.

Preferably, one or more of the outer axial wall, the axially extending inner wall, e.g. the outer frit or screen and other axially extending components, are releasably mounted to the vessel top in such a way that the components mounted to the vessel top can be released without opening the vessel (e.g. via externally accessible mounting members such as screws or bolts) so that one can select which of such components remains mounted to the vessel top to be lifted by the actuator by lifting the vessel top, leaving the released component behind. Obviously, such an assembly to be lifted should have its mounting with the container bottom released before lifting, wherein preferably such an assembly is releasably mounted to the container bottom in such a way that such an assembly mounted to the container bottom can be released without opening the container (e.g. by externally accessible mounting means such as screws or bolts).

The lifting actuators are of, for example, a linear and/or telescopic type and are spaced apart from each other around the circumference of the container outside the container. The lifting actuator extends axially and/or vertically and is external to the container, for example extending upwards from a bottom part of the frame, for example its base, and is mounted on the one hand to the frame and on the other hand to the container in such a way that the container or parts thereof can be lifted relative to the frame.

The mounting of the lifting actuator at a low level, e.g. to the support frame, is preferably vertical and/or similar legs and/or cantilevered.

Preferably there are two different lifting systems and the selection and execution of the lifting systems corresponds for example to the force required by the individual fitting, i.e. the weight to be lifted. For lighter assemblies, an electrical linear drive actuator will suffice, and when the assembly is heavier or is equipped with fewer actuators, hydraulic actuation is preferred, such as a piston moving within a cylinder.

The lifting system, e.g. either of the two lifting systems described above, the electric linear drive or the hydraulic pressure preferably fulfils the requirement of a synchronized movement that needs to be tightly controlled for safety, proper operation and a tight fit. The electric linear drive unit is preferably equipped with a rotary spindle about its axis, associated with a precision rotary encoder that allows the adjustment and tuning of the individual actuators so as to guarantee synchronous movements within a horizontal tolerance of < 0.1 mm.

Synchronous hydraulic actuation of more than 1 actuator is preferably controlled with sufficient accuracy by valve trim and/or accurately distributed pressure, and this is assumed to be possible only if there is accurate and real-time feedback from each hydraulic actuator as to its absolute position in the synchronously moving actuator group. When synchronous movement will depend on the equilibrium pressure in the cylinder and by controlling the absolute position, any uneven load or resistance is not relevant to synchronous lifting, the difference in resistance to movement of the individual actuators can confound synchronicity in hydraulic operation. The synchronized lifting is preferably based only on the actual and absolute axial position or extension of each actuator in the group. The high pressure hydraulic valve system is preferably controlled to accurately distribute the hydraulic fluid provided by the single hydraulic pump so that it will accurately deliver an amount of force/pressure to each of the actuators resulting in synchronous movement over the entire actuator stroke length within a horizontal tolerance of < 0.1 mm. The hydraulic fluid distribution for achieving accurate synchronous operation of multiple units preferably requires an arrangement comprising highly accurate and tightly controlled high pressure proportional valves fed by a single hydraulic pump.

The special requirements of any application of mechanical devices in a pharmaceutical production environment are the "hygienic design" of such solutions. Accepted sanitary design solutions minimize the chance of microbial growth "by design" and provide effective cleaning capability for all areas that may pose a risk of microbial growth. The materials applied need to be protected or resistant to corrosive, aggressive liquids, and the application of any kind of external addenda, which may and will conflict in terms of risk of microbial growth, should be designed to be minimized as desired.

The hydraulic fluid used in the hydraulic system preferably complies with usage regulations within a pharmaceutical environment and is intrinsically safe when accidentally released in the area.

Preferably, the actual and accurate measurement of the absolute position (e.g. extension) of the or each actuator is measured by a measuring system, preferably internal to the actuator, over the entire stroke length of the actuator, preferably with an absolute position accuracy of at least +/-0.01 mm, for example provided with, especially for hydraulic linear actuators, a preferably high resolution reference element, such as a straightedge guide, extending axially and in a straight line within the actuator. The information for each absolute position within the set of sync-action actuators is fed to a controller that converts the individual position information into a fluid/pressure profile for each of the individual actuators.

One or more of the following preferably applies to the reference element: of the axially linear type; extends axially at least the full stroke length; by a piston (the "piston" also refers to another extension providing a component of the actuator) and/or a piston rod, enclosing or surrounding and/or protruding through said piston and/or piston rod, e.g. into an axial groove of the piston rod and extending at least 50% of the length of the piston rod; concentric with the piston and/or piston rod; has a prism shape; fixed relative to the piston; from a fully retracted position of the piston to a fully extended position of the piston; scales are axially arranged; associated with a sensor designed to detect the relative axial position of the piston and the reference element; the sensor and piston are combined so that they move as a unit; the sensor is communicatively connected to the controller.

The transmission of electrical signals to and from, for example, actuator sensors and/or to and from a controller associated with the position measurement system, is preferably carried out by cables enclosed in ducts of the frame, which are protected from external influences and are themselves protected by a casing designed for hygiene.

The hydraulic fluid for retracting the extended piston or the retracting piston of the extension actuator is preferably not fed through a commonly applied external conduit or channel, but is preferably supplied internally via an axially extending annular channel, which is preferably provided by a gap between the radially outer wall of the linear actuator and a circumferentially enclosed sleeve-like housing of the linear actuator provided with a spacing, e.g. a concentric cylinder, which e.g. also represents the outer body of the linear actuator. With this arrangement, there is no tip which is difficult to clean and a hygienic design is achieved. Accurate and safe lifting of any vessel assembly is possible only by supporting this complex combination of accurately moving attributes without adding any devices or ends that conflict with pharmaceutical manufacturing (GMP) and hygiene design.

Drawings

The accompanying drawings, which are incorporated in and form a part of this specification, illustrate presently preferred embodiments of the invention and together with the description, serve to explain the principles of the invention. Shown is that:

fig. 1 to 3 are examples of chromatography columns of the radial type in a cross-sectional side view.

Fig. 4 is the column of fig. 3 in a top view.

Fig. 5 is another column partially cut away in a perspective view from below.

FIG. 6 is a perspective view of an annular shaped filter bed.

Fig. 7-8 are perspective views of two examples of containers mounted in a wheeled frame.

Fig. 9A to 9C are different arrangements of the linear actuator and the guard rail in the top view.

Fig. 10 is an example of a hydraulic circuit.

Fig. 11 to 12 are sectional side views of the hydraulic actuator.

Figures 13 to 18 are possible lifting positions of the container.

Fig. 19 to 21 are alternative views of the perspective views of fig. 7 to 8.

Detailed Description

A detailed description of the preferred function of the strictly controlled synchronous hydraulic embodiment of the lift system is provided below.

In order to ensure compatibility for all components acting together on an accurate synchronous movement, the internal and external dimensions of the hydraulic actuators are preferably calculated, so that the maximum load of any form of assembly is handled with a hydraulic limitation of 20 bar or between 50 bar and 100 bar by synchronous operation of at least 2 and a maximum of 6 actuators.

In order to provide the best possible hygienic design, the hydraulic actuator is preferably implemented in advanced mirror-finished stainless steel and has been designed without ends like hydraulic lines and/or fittings. The telescopic pressure line is preferably connected to the bottom plug of the main cylinder casing or cylinder barrel. The extension fluid/pressure is preferably delivered directly into the extension chamber below the piston. The contracting fluid/pressure is preferably fed to the top of the actuator assembly through a preferably double-walled barrel, creating a narrow channel or gap through concentric alignment. The hydraulic line between the hydraulic pump and the linear actuator preferably extends inside the frame.

The actuator preferably has a stroke length of between 30 and 300 cm. For a single hydraulic pump common to all actuators, hydraulic fluid is preferably delivered at a preferentially constant pressure to a valve system having alternating proportional valves that are preferably controlled by a computer, preferably a high speed PLC, having data input of a preferentially high accuracy piston positioning sensor in each of the actuators/pistons.

In the case where there are exactly three elements from the group: actuators and vertical guides (i.e. three actuators or respectively one or two actuators and two or one vertical guide), preferably as seen in a top view of the container, the elements are located at the corners of an imaginary triangle in which preferably not all sides of the triangle are of equal length, preferably two sides are of equal length and longer than the third side (i.e. e.g. fig. 9B). The difference in length is preferably at least 10 cm or 5% or 10%.

The outer wall of the linear actuator is preferably made of stainless steel, for example one of the following: 1.4403, 1.4404, 1.4435, 1.4539, 1.4462, 304(L)316(L), 904(L), biphasic.

Non-limiting examples

The following reference numerals are used: container 1 (either column or vessel); a cylindrical housing wall 2; an axial housing end plate (also referred to as top wall or cap) 3; a seal 4; a liquid inlet 5; a liquid outlet 6; a packed bed 7; an inner flow channel 8; a packed bed packing opening 9; a connector 10; a packed tube 11 for packed bed; a seal member 12; a seal 13; an outer flow channel 14; a core 15; an inner frit 16; an outer frit 17; an axial bed end plate 18; a distribution space 19; a collector space 20; an outflow channel 21; a liquid outlet 22; an axial housing end plate (also referred to as a bottom wall) 28; bed height H; the outer frit radius Rl; inner frit radius R2; axial direction arrow a (fig. 3). The radial direction is perpendicular to the axial direction.

Each of the containers 1 (e.g. liquid chromatography columns) shown in fig. 1-5 comprises: a housing, cylindrical in shape, defining a chamber therein and including a removable axial end plate 3 of circular shape; a first (outer) porous frit 16 and a second (inner) porous frit 17 or a cylindrically shaped membrane; bed 7 or packing of particulate chromatographic separation material in the middle of the porous frit; optionally extending the core 15 axially. The axially extending cylindrical outer housing wall 2, the first frit 17 and the second frit 16 are coaxial with the core 15.

The annular shaped packed bed 7 (illustrated schematically in fig. 6, where the wedge shaped pieces have been removed for clarity) allows radial flow of process liquid (according to the arrows in fig. 6) from the outer frit 17 through the column 1 to the inner frit 16.

Fig. 7 illustrates the container 1 as a preparation vessel supported by a wheeled frame 31 (U-shaped in plan view). Above the top wall 3 there is a drive motor 24 from which a drive shaft 25 extends vertically downwards towards a mixing blade 26 at the bottom of the vessel for mixing the vessel contents. Below the mixing blades, a bottom filter plate 27 is present just above the vessel bottom wall 28. A control box 29 at the back side contains a control unit and hydraulic valves to control three linear actuators 30 (only two are visible) extending upwards from a frame 31, from which linear actuators 30 the container 1 is suspended. A hydraulic motor (not shown) is located remotely from the vessel. The mounting of the linear lift actuator 30 at a low level, i.e. to the support frame, is upright (i.e. like a leg or cantilever).

In fig. 8, the container is, for example, a chromatography column.

To ensure stable and accurate vertical movement of the vessel 1 or parts thereof by the lifting system, fig. 9A applies two linear actuators 30 and two guard rails 32, fig. 9B applies three linear actuators 30, and fig. 9C applies six linear actuators. Fig. 9B and 9C do not apply the guard rail 32. The vessel of fig. 9C is at right angles in top view, and may be square with, for example, four actuators 30 (see dashed lines). Fig. 9A may apply four actuators and no guard rail 32. Different combinations of actuators 30 and tracks 32 are possible.

In fig. 10, three actuators 30 are controlled in synchronism by control valves 33, individually controlled by control box 29, receiving individual actuator position feedback returned through sensor lines 35. The valve 33 controls the supply of pressurized liquid from the reservoir 34 to the individual actuators 30.

In fig. 11 (fully retracted/partially extended), the linear actuator 30 has an extension rod 36 integral with a piston 37 separating an extension chamber 38 from a retraction chamber 39. During extension of the rod 36, liquid enters the chamber 38 at 40 and exits the chamber 39 at 41. The displacement of the piston 37 along the inner straight edge 42 of the actuator penetrating the piston 42 is detected by a sensor 43. Chamber 38, which encloses ruler 42, rod 36 and extends at the opposite side of piston 37, has vent 44 at the distal rod end, penetrating chamber 39.

Fig. 12A-12B show the legs 48 of the U-shaped frame 31 in the form of sections. Hydraulic actuator 30 is mounted on the top, and hydraulic supply and exhaust lines extend inside legs 48 and connect to the lower ends of hydraulic cylinders 46. The direction of flow of the hydraulic fluid inside the annular gap 47 of the double-walled hydraulic cylinder is indicated by arrows. Fig. 12A illustrates piston rod 36 extending from a fully retracted state. Figure 12B illustrates the piston rod beginning to retract from the intermediate extended state. Fig. 12B also illustrates that the upper part 3 of the container has been lifted from the lower part by the hydraulic actuator via the bracket 49.

In fig. 13 and 15, the container 1 of fig. 7 is in the lower operating position, with the actuator 30 fully retracted (fig. 13) or extended (fig. 15), and in fig. 14, the container 1 is in the upper operating position, with the actuator 30 partially extended. By extension, the actuator 30 lifts the entire container 1 (fig. 14) or only the mixing blade 26 and associated motor 24 and shaft 25 (fig. 15). In fig. 16, the top wall 3 (after release from the container 1) is lifted by the fully extended actuator 30. In fig. 17, wall 2 is raised (after release from bottom wall 28) and outer frit 17 is not raised. In fig. 18, the bottom wall 28 and the bottom filter plate 27 remain un-lifted.

The measures disclosed herein can be individually combined together in any other conceivable combination and permutation to provide an alternative to the present invention. Also technical equivalents and kinds or generalizations of the disclosed measures are included. The measures of the examples are also generally applicable within the scope of the invention. The measures disclosed herein, such as examples, can be easily generalized for inclusion in the general definition of the invention, such as found in the patent claims.