WO2019194935A1 - Chromatography media handling and packing equipment - Google Patents

Abstract

Apparatus and method for packing a chromatography column. The apparatus is a rack that may support and/or transport one or more containers of the same or different sizes. The one or more containers and their contents may be agitated in the rack to homogeneously re-suspend the resin. The one or more containers may be fluidly connected to a common manifold for dispensing their contents into a downstream apparatus such as a slurry tank or chromatography column, and for re-introducing contents into the containers such as upon unpacking of a chromatography column.

Description

CHROMATOGRAPHY MEDIA HANDLING AND PACKING EQUIPMENT

This application claims priority of U.S. Provisional Application Serial No. 62/653,042 filed April 5, 2018, the disclosure of which is incorporated herein by reference in its entirety.

BACKGROUND

Chromatography is a general separation technique that uses the distribution of the molecules of interest between a stationary phase and a mobile phase for molecular separation. The stationary phase refers to a porous media and imbibed immobile solvent.

Columns with associated end caps, fittings and tubing are the most common configuration, with the media packed into the tube or column. The mobile phase is pumped through the column. The sample is introduced at one end of the column, and the various components interact with the stationary phase and are adsorbed to or in the media or traverse the column at different velocities. The separated components are collected or detected at the other end of the column. Adsorbed components are released in a separate step by pumping an eluant solvent through the column.

Chromatographic methods include among other methods, gel chromatography, ion exchange chromatography, hydrophobic interaction chromatography, reverse phase chromatography, affinity chromatography, immunoadsorption chromatography, lectin affinity chromatography, ion affinity chromatography and other such well- known chromatographic methods . Current chromatographic or adsorptive separations typically use bead-based, monolith or membrane media to accomplish the desired separation. Chromatographic media such as beads are loaded into a chromatography column forming a bed of media through which a fluid containing the material to be captured is passed. The media is then washed to remove unbound contaminants and then the captured material is eluted and collected.

Several problems exist with such chromatography columns. The packing of the media into a column is a difficult and laborious task. One needs to be sure that the column is properly packed so as to avoid channeling, bypass and blockages within the column. Packing of columns is often considered as much an art as it is a science .

For pilot and industrial chromatography units, varying amounts of media are required in the column. For example, 80L to 600L of media may be required to pack the chromatography column. Typically, chromatographic resin media is shipped in so-called "jerry cans" in amounts of 5L or 10L. This means that from 8 to 60 containers are required, each of which needs to be agitated to re-suspended the resin prior to transferring it into a slurry vessel by manually pouring or pumping. Accordingly, the overall preparation process, depending on the number of jerry cans needed, can take several hours and require substantial effort.

It therefore would be desirable to provide an apparatus and method that facilitated the process of packing such columns. SUMMARY

Problems of the prior art have been addressed by the embodiments disclosed herein, which relate to an apparatus and method for packing a chromatography column. In certain embodiments, the apparatus is a rack that may support and/or transport one or more containers. In some embodiments, where the rack supports a plurality of containers, the containers can be of one or more different sizes. In some embodiments, the containers contain or are configured to contain chromatography media. The chromatography media may be a resin, typically supplied as a slurry, and the resin may require resuspension in the slurry. In certain embodiments, the one or more containers and their contents may be agitated in the rack to homogeneously re-suspend the resin. In certain embodiments, the one or more containers may be fluidly connected to a common manifold for dispensing their contents into a downstream apparatus such as a slurry tank or chromatography column, and/or for re-introducing contents into the containers such as upon unpacking of a chromatography column.

In certain embodiments, a rack for supporting one or more containers is provided, the rack including a base and first and second sides members defining the rack; one or more containers supported or supportable in the rack, each container adapted to contain a volume of fluid such as chromatography media and having an inlet and an outlet; one or more adjustable supports able to adopt to different sizes of containers, each adjustable support configured to support one or more containers in the rack such that the one or more containers is movable, such as by rotation in the rack. Where a plurality of containers are supported in the rack, each of the plurality of containers may be fluidly connected to a common manifold. The common manifold may allow for selectively loading or unloading of respective containers . A container actuating member may be operatively connected to the one or more adjustable supports for rotating or otherwise moving the one or more containers with respect to the rack. The one or more adjustable supports may include first and second spindles rotatably coupled to the first and second rack side members, respectively, and the container actuating member may be operatively connected to the one or more spindles. The one or more adjustable support members may rotation of a plurality of containers between varying amplitudes about a central axis of the containers .

Also disclosed is a method of homogenizing chromatography media in a container, including supporting a plurality of containers in a rack with adjustable supports able to adopt to varying container sizes; and actuating the adjustable supports to rotate the containers with respect to the rack.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments disclosed herein may take form in various components and arrangements of components, and in various process operations and arrangements of process operations. The drawings are only for purposes of illustrating preferred embodiments and are not to be construed as limiting. This disclosure includes the following drawings .

FIG. 1 is a perspective view of a rack in accordance with certain embodiments;

FIG. 2A is a perspective view of a fastener for a belt to position and hold a container on a rack in accordance with certain embodiments ;

FIG. 2B is a perspective view of a fastener for a belt to position and hold a container on a rack in accordance with an alternative embodiment;

FIG. 2C is a perspective view of a belt and pin system to position and hold a container on a rack in accordance with certain embodiments ;

FIG. 3A is a perspective view of a cap or closure member for a container in accordance with certain embodiments;

FIG. 3B is a cross-sectional view of a cap or closure member for a container in accordance with certain embodiments; and

FIG. 4 is a cross-sectional view of a container shown rotated about a central axis in accordance with certain embodiments.

DETAILED DESCRIPTION

A more complete understanding of the compositions and methods disclosed herein can be obtained by reference to the accompanying drawings. The figures are merely schematic representations based on convenience and the ease of demonstrating the present disclosure, and is, therefore, not intended to indicate relative size and dimensions of the devices or components thereof and/or to define or limit the scope of the exemplary embodiments.

The singular forms "a, " "an, " and "the" include plural referents unless the context clearly dictates otherwise.

As used in the specification, various devices and parts may be described as "comprising" other components. The terms "comprise (s) , " "include ( s ) , " "having," "has," "can," "contain (s) , " and variants thereof, as used herein, are intended to be open- ended transitional phrases, terms, or words that do not preclude the possibility of additional components.

All ranges disclosed herein are inclusive of the recited endpoint and independently combinable (for example, the range of "from 2 inches to 10 inches" is inclusive of the endpoints, 2 inches and 10 inches, and all the intermediate values) .

As used herein, approximating language may be applied to modify any quantitative representation that may vary without resulting in a change in the basic function to which it is related. Accordingly, a value modified by a term or terms, such as "about" and "substantially," may not be limited to the precise value specified, in some cases. The modifier "about" should also be considered as disclosing the range defined by the absolute values of the two endpoints. For example, the expression "from about 2 to about 4" also discloses the range "from 2 to 4."

It should be noted that many of the terms used herein are relative terms. For example, the terms "upper" and "lower" are relative to each other in location, i.e. an upper component is located at a higher elevation than a lower component, and should not be construed as requiring a particular orientation or location of the structure. As a further example, the terms "interior", "exterior", "inward", and "outward" are relative to a center, and should not be construed as requiring a particular orientation or location of the structure.

The terms "top" and "bottom" are relative to an absolute reference, i.e. the surface of the earth. Put another way, a top location is always located at a higher elevation than a bottom location, toward the surface of the earth.

The terms "horizontal" and "vertical" are used to indicate direction relative to an absolute reference, i.e. ground level. However, these terms should not be construed to require structures to be absolutely parallel or absolutely perpendicular to each other .

FIG. 1 shows a rack 10 in accordance with certain embodiments. In some embodiments, the rack 10 include a base 11, sides 12A, 12B extending from the base 11, and a top 13. The base 11 may have support legs 14A, 14B, which may include one or more wheels 9 or the like to facilitate transport of the rack 10 and its contents.

In certain embodiments, one or more straps or belts 20A, 20B may be used to position and support one or more containers 30. Suitable materials for the one or more belts include fabrics, synthetic fibers such as KEVLAR, nylon, plastic, metal, etc. In some embodiments, as best seen in FIG. 2A, two belts 20A, 20B may be used to hold a container 30 or a group of containers. Belt 20A may be positioned generally horizontally about the container 30 or group of containers, while belt 20B is positioned generally vertically about the container 30 or group of containers. Thus, belts 20A and 20B are generally perpendicular to one another when in the assembled position. In certain embodiments, the generally horizontal belt 20A may be attached to the rack 10 via spindles or the like. For example, a first spindle 21A is attached to the belt 20A and may have a free end that attaches to rack side 12A such that the spindle 21A can rotate at least 180°, or even 360°. A second spindle 21B is attached to the belt 20A and may have a free end that attaches to rack side 12B such that the spindle 21B can rotate at least 180°, or even 360°. Each belt 20A, 20B has a fastener 26 such as a buckle or ratchet (FIG. 2A) , or pins 260 that align corresponding holes in the belts (FIGS. 2B and 2C) , to tighten and lock the belt so as to effectively secure the container 30 or group of containers in place on the rack 10. In some embodiments, each belt 20A, 20B is independently positionable , adjustable and fastenable.

More specifically, each belt 20A, 20B may be adjustable in size, and is configured to secure one or more containers 30 in the rack 10. The adjustability of each belt 20A, 20B allows it to secure containers of different sizes and shapes, and allows it to secure a varying number of containers 30. In some embodiments, each belt 20A, 20B is adjustable with a fastener or ratchet mechanism or the like, which can be the same fastener or ratchet used to lock the belt.

In certain embodiments, the containers 30 are positioned in the rack 10 in a row, side-by-side, and can be spaced from one another or can be touching. In some embodiments, the row of contains is linearly arranged or substantially linearly arranged, e.g., in the x-direction shown in FIG. 1. The number of containers 30 in a given row is not particularly limited, and depends in part on the container sizes and the size of the rack, e.g., the distance between side members 12A and 12B. In some embodiments, there can be more than one row of containers 30, with a second row positioned behind a first row, e.g., in the y-direction shown in FIG. 1. Each container 30 in a second row of containers can be positioned directly behind a respective container 30 in a first row of containers, or can be offset therefrom. Additional rows of containers can be present, depending in part on the size of the containers and the depth of the rack 10. Typical container sizes are 5L and 10L. In certain embodiments, multiple levels of container rows are provided, one above another. In some embodiments, a catch basin 35 or the like may be positioned below each level of containers, to catch any drippage of contents of the containers that might occur, such as during storage or during emptying or filling of a container 30.

In certain embodiments, the belts 20A, 20B are capable of supporting one or more containers 30 even when a container 30 is not present in a row of containers, i.e., even when the spacing between containers 30, or the spacing between a container 30 and a side wall 12A or 12B, exceeds the dimensions of a single container. Stated differently, if belts 20A, 20B are capable of supporting a maximum of X number of containers, they also can support fewer than X; it does not need X containers to properly function, as the space in the rack intended for a container 30 can be left unoccupied by a container 30.

In some embodiments, a single container may be used. In some embodiments where a single container is used, it may be directly attached to the spindles 21A, 21B and the belts may be omitted.

In some embodiments, mechanical agitation of the containers 30 in the rack 10 may be carried out by tilting or otherwise changing the position of the containers 30 with respect to the rack 10. In certain embodiments, the containers 30 may be rotated between varying amplitudes about a central axis Z (FIG. 4) to allow for varying loading or unloading positions of the containers 30. In some embodiments, a container actuating member such as a rack handle 40 may be used to change the position of the containers 30, the handle 40 being operatively connected to one or more of the belts 20A, 20B, such as with suitable connectors that may include wires, rods, gears, etc. Reducing gears may be used. Actuation of the handle 40, such as by applying a twisting force to the handle 40, causes the spindles 21A, 21B of each belt 20 to twist or rotate about an axis of rotation defined by spindles 21A, 21B, relative to the side walls 12A, 12B of the rack 10. The containers 30 held by the belt 20 rotate or tilt with the belt, causing agitation and ultimately homogenization of the contents of the containers 30. The handle 40 can be continually or continuously moved in a back-and-forth motion to further agitate the containers 30. Actuation of the handle 40 can be carried out manually or automatically. For automatic control, a controller may be used. The controller may include a processing unit which executes computer readable instructions, adapted to perform the actuation of the handle 40 described. The processing unit may be a general purpose computing device, such as a microprocessor. Alternatively, it may be a specialized processing device, such as a programmable logic controller (PLC) . The controller may also contain a storage element, which is used to store the instructions, as well as provide temporary storage for the processor's use. The storage element may utilize any memory technology, such as RAM, ROM, EEPROM, Flash ROM, NVRAM, or any other suitable technology. The controller may also include an input device, such as a touchscreen, keyboard, or other suitable device. The input device is used to allow the operator to input a set of parameters which should be used by the controller. This input device may also be referred to as a human machine interface or HMI . The controller may also has outputs adapted to control the handle described above. These outputs may be analog or digital in nature, and may provide a binary output (i.e. either on or off), or may provide a range of possible outputs, such as an analog signal or a multi-bit digital output. Using these outputs, the controller is able to control the actuation of the handle, which may include the speed and extend to which the handle is moved. A single actuating member can be operatively connected to more than one belt, or each belt can be operatively connected to a respective dedicated actuating member. A plurality of containers may be linked such that a single actuating member rotates all of the containers to the same amplitude at the same time.

In an alternative embodiment, vibration may be used to agitate the contents of the containers 30, and the handle (s) 40 is not needed. For example, one or more vibration or sonicating devices can be operatively connected to each container 30 to effectively agitate the container contents for homogenization, e.g., for a time and extent to mix the contents so that they are effective for use in a chromatography column. In certain embodiments, as seen in FIGS. 3A and 3B, each container 30 has an inlet 31 and an outlet 32, each in fluid communication with the internal volume of the container 30. Preferably the inlet 31 and the outlet 32 may be on the same side of the container 30, such as in a cap or closure member 33 for the container 30. The cap or closure member 33 may also include a vent 34. Fluid contents can be loaded into the container 30 via the inlet 31, optionally with the assistance of a driving force such as pressure, and fluid contents can be discharged from the container via the outlet 32, again optionally with the assistance of a driving force such as pressure. In certain embodiments, the outlet 32 is used to discharge the container contents from the container 30 and introduce the contents to downstream apparatus such as a slurry tank or a chromatography column (not shown) . The outlet 32 later can be used as an inlet to re-introduce the contents back from the chromatography column or slurry tank into the container 30. In other words, the outlet may be placed in fluid communication with downstream apparatus, such as a slurry tank and/or a chromatography column, and be used to discharge container contents to the downstream apparatus, followed by re-introduction back into the container from the downstream apparatus, such as upon completion of a downstream operation such as chromatography packing. A pump may be used to facilitate loading or unloading of the contents of a container 30. In some embodiments, each container 30 may include an internal mixing or agitating device to help fluidize the contents, or an external mixing or agitating device such as with a sonicator or the like.

In certain embodiments, the container 30 may include an angled edge where the cap is positioned, as best seen in FIG. 4. So angling the container and locating the cap 33 there facilities draining of the contents of each container 30; the cap 33 is at the low point of the container 30 when the container 30 is properly oriented, which helps ensure that all of the contents of the container 30 can be eliminated from the container while minimizing or eliminating dead spots . Suitable angles include an angle ranging from about 30° to about 60°, preferably about 45°, relative to horizontal. In certain embodiments, the cap 33 seals to the container 30 and the contents can be pumped out of the container 30 through the outlet 32 while simultaneously injecting flushing buffer or the like through the inlet 31 to recover any residual contents remaining in the container 30.

In some embodiments, there are a plurality of containers 30 held by one or more belts 20A, 20B, and each of the plurality of containers 30 is fluidly connected such as with a common yoke or manifold. The yoke or manifold enables the selective loading and/or unloading of contents from each container 30, either independently or together with the contents of other containers. Suitable valving can be associated with the manifold to effectuate the loading and/or unloading of the container contents.

While various aspects and embodiments have been disclosed herein, other aspects, embodiments, modifications and alterations will be apparent to those skilled in the art upon reading and understanding the preceding detailed description. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting. It is intended that the present disclosure be construed as including all such aspects, embodiments, modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.

Claims

What is claimed is :

1. A rack for supporting one or more containers, comprising: a. a base and first and second sides members defining said rack;

b. one or more containers supported in said rack, each container adapted to contain chromatography media and having an inlet and an outlet;

c. one or more adjustable supports able to adopt to different sizes of said one or more containers, each said adjustable support configured to support said one or more containers in said rack such that said at one or more containers is rotatable in said rack.

2. The rack of clam 1, wherein there are a plurality of containers supported in said rack, and wherein each of said plurality of containers are fluidly connected to a common manifold .

3. The rack of claim 2, wherein said common manifold allows for selectively loading or unloading of respective containers.

4. The rack of claim 1, further comprising a container actuating member operatively connected to said one or more adjustable supports for rotating said one or more containers with respect to said rack.

5. The rack of claim 1, wherein said one or more adjustable supports comprises first and second spindles rotatably coupled to said first and second side members, respectively.

6. The rack of claim 4, wherein said one or more adjustable supports comprises first and second spindles rotatably coupled to said first and second side members, respectively, and wherein said container actuating member is operatively connected to one of said first and second spindles .

7. The rack of claim 1, wherein there are a plurality of containers having a common central axis, and wherein said one or more adjustable support members enables rotation of the plurality of containers between varying amplitudes about said central axis.

8. A method of homogenizing chromatography media in a container, comprising: supporting a plurality of containers in a rack with adjustable supports able to adopt to varying container sizes; and actuating said adjustable supports to rotate said plurality of containers with respect to said rack.

9. The method of claim 8, wherein said adjustable supports comprise first and second spindles rotatably coupled to said first and second side members, respectively, and further comprising actuating said adjustable supports with a container actuating member operatively connected to one of said first and second spindles.