阅读说明：本技术 包括内部支柱的色谱柱 (Chromatography column comprising an internal strut ) 是由 K.葛鲍尔 于 2018-07-05 设计创作，主要内容包括：本发明公开一种生物过程色谱柱，其包括：a)床室，该床室由至少一个侧壁、第一床支承筛和第二床支承筛界定；b)第一端壁，该第一端壁固定到侧壁或与侧壁整体结合，其中第一端口经由第一分配器流体地连接到第一床支承筛；c)第二端壁，该第二端壁固定到侧壁或与侧壁整体结合，其中第二端口经由第二分配器流体地连接到第二床支承筛；d)壁中的填充端口；以及e)内部支柱，该内部支柱固定到端壁中的至少一个或与端壁中的至少一个整体结合，且延伸到床室中。(The invention discloses a bioprocess chromatographic column, which comprises: a) a bed chamber defined by at least one side wall, a first bed support screen, and a second bed support screen; b) a first end wall secured to or integral with the side wall, wherein the first port is fluidly connected to the first bed support screen via a first distributor; c) a second end wall secured to or integral with the side wall, wherein the second port is fluidly connected to the second bed support screen via a second distributor; d) a fill port in the wall; and e) an inner strut secured to or integral with at least one of the end walls and extending into the bed chamber.)

1. A chromatography column (10; 11; 110; 111) for bioprocess separations, the column comprising:

a) a bed chamber (12), the bed chamber (12) being bounded by at least one side wall (14), a first bed support screen (16) and a second bed support screen (18);

b) a first end wall (20), the first end wall (20) being fixed to or integral with the at least one side wall, wherein a first port (22) is fluidly connected to the first bed support screen via a first distributor (24);

c) a second end wall (26), the second end wall (26) being fixed to or integral with the at least one side wall, wherein a second port (28) is fluidly connected to the second bed support screen via a second distributor (30);

d) a fill port (32), the fill port (32) in one of the at least one side wall and the first and second end walls; and

e) an inner strut (34), said inner strut (34) being secured to or integral with at least one of said first and second end walls and extending into said bed chamber.

2. The chromatography column of claim 1, wherein at least a portion of the inner strut spans the entire axial height of the bed chamber, is fixed to or integral with both the first end wall and the second end wall.

3. The chromatography column according to claim 1 or claim 2, wherein the inner strut comprises one or more rods (36), the one or more rods (36) each having: a first stem end (50), said first stem end (50) being secured to or integral with said first end wall; and a second stem end (52), the second stem end (52) being secured to or integrally joined with the second end wall.

4. The chromatography column of any preceding claim, wherein the inner strut comprises at least three rods, such as at least four rods, extending from the first end wall to the second end wall.

5. The chromatography column (110; 111) of any preceding claim, wherein the inner strut (134) comprises at least one rib (136; 136a), the at least one rib (136; 136a) being fixed to or integral with at least one of the first and second end walls and extending into the bed chamber.

6. The chromatography column according to claim 5, wherein the at least one rib comprises at least one side hole (140), such as a plurality of side holes.

7. The chromatography column according to claim 5 or claim 6, wherein said at least one rib (136a) is fixed to or integral with both said first end wall and said second end wall.

8. The chromatography column according to any preceding claim, wherein the chromatography column is a single use column, wherein at least the first end wall and the second end wall are made of plastic.

9. The chromatography column of any preceding claim, wherein the packing port is located in the at least one sidewall.

10. The chromatography column according to any preceding claim, wherein said bed chamber has a cross-sectional diameter or diagonal of at least 10cm, such as at least 20 cm.

11. The chromatography column according to any preceding claim, wherein said bed chamber has a substantially quadrangular shape, such as a quadrangular shape with rounded corners.

12. The chromatography column of claim 11, wherein the first port and the second port are located adjacent to diagonally opposite corners of the bed chamber.

13. The chromatography column of any preceding claim, wherein the side wall, the first and second end walls, and the inner strut are integrally formed.

14. The chromatography column of claim 13, wherein said side wall, said first and second end walls, said inner struts and said first and second bed support screens are integrally formed.

15. The chromatography column according to any preceding claim, further comprising one or more sensors, such as sensors capable of measuring pressure, conductivity, pH and/or temperature.

16. The chromatography column of any preceding claim, wherein the first port and the second port are fitted with sterile connectors or a closed length of weldable flexible tubing.

17. The chromatography column according to any preceding claim, wherein the bed chamber is filled with a packed bed of separation matrix particles.

18. The chromatography column according to any preceding claim, wherein the first port and the second port are fitted with sterile connectors or a closed length of weldable flexible tubing, and wherein the chromatography column is pre-sterilized, such as by radiation sterilization.

19. The chromatography column according to any preceding claim, wherein the chromatography column is stackable with a similar chromatography column.

20. A stack comprising a plurality of chromatography columns according to claim 19.

21. The stack of claim 20, wherein the chromatography columns are connected in series.

22. The stack of claim 20, wherein the chromatography columns are connected in parallel.

23. The stack of claim 22, wherein the chromatography columns are packed with the same separation matrix, and wherein the difference in dry weight of the amount of separation matrix of any two chromatography columns in the stack is less than 5 wt.%.

24. A method of packing a chromatography column comprising the steps of:

a) providing a chromatography column according to any one of claims 1 to 16;

b) transferring a weighed quantity of dry expandable separation matrix microparticles to the bed chamber; and

c) delivering a liquid to the column to swell the dry swellable separation matrix particles.

25. The method of claim 24, comprising the step of determining the liquid uptake of the dry expandable separation matrix particles prior to step b), and wherein in step b) the amount of dry expandable separation matrix particles is calculated to give an unconstrained expanded volume which is greater than 100% of the internal volume of the bed chamber.

26. The method as claimed in claim 25, wherein the amount of dry expandable separation matrix particles is calculated to give an unconstrained expanded volume of 101-130%, such as 105-120% of the internal volume of the bed chamber.

27. The method according to any one of claims 24 to 26, wherein the liquid is water or an aqueous solution, such as a buffer or a salt solution.

28. The method according to any one of claims 24 to 27, comprising a step of radiation sterilizing the chromatography column with the dry swellable separation matrix microparticles before step c).

29. The method according to any one of claims 24 to 27, wherein prior to step a) the chromatography column and the dry swellable separation matrix microparticles are radiation sterilized, and wherein the method is performed under sterile conditions.

30. A method of preparing a stack of chromatography columns comprising the steps of:

1) packing a plurality of chromatography columns according to the method of any one of claims 24 to 28; and

2) stacking the chromatography columns and connecting them to each other in series or in parallel.

31. The method of claim 30, wherein the dry expandable separation matrix microparticles of any two chromatography columns in the stack are weighed with less than 5 wt.%.

Technical Field

The present invention relates to a chromatography column for bioprocess separations. The invention also relates to a stack of chromatography columns, a method of packing one or more chromatography columns, and a method of assembling a stack of chromatography columns.

Background

Columns used in liquid chromatography typically comprise a tubular body enclosing a packed bed of porous chromatography media through which a carrier liquid flows, wherein separation occurs by separation between the solid phase of the porous media and the carrier liquid.

Prior to any separation process, the bed must be prepared by starting with the particulate medium to be introduced into the column. The process of bed formation is referred to as the "packing process" and a properly packed bed is a critical factor affecting the performance of a column containing the packed bed. Typically, a packed bed is prepared by slurry packing (i.e., consolidating a suspension of discrete particles in a liquid state, referred to as a slurry, which is pumped, poured, or drawn into a column). Once a predetermined volume of slurry is delivered into the column, it needs to be further consolidated and compressed by moving a movable adapter (adapter) down the longitudinal axis of the column towards the bottom of the column (typically at a constant speed). During this process, excess liquid is discharged at the column outlet, while the media particles are retained by means of a filter material (so-called 'bed support'), in which the pores are too small to allow the media particles to pass through (pass through). Once the packed bed is compressed by the optimum degree of compression, the packing process is complete. Another method for column slurry packing is the flow packing method, where the compression of the porous structure is mainly achieved by applying a high flow rate over the column, thereby forming a porous structure starting at the outlet bed support. The resulting resistance on the particulates in the porous structure ultimately causes a pressure drop and compression of the bed. Finally the compressed bed is restrained by placing the adapter in position.

The efficiency of the subsequent chromatographic separation (strongly) depends strongly on: 1) a liquid distribution and collection system at the fluid inlet and outlet of the packed bed; 2) specific orientation of media particles in the packed bed (also referred to as packing geometry); and 3) compression of the packed bed. If the compression of a packed bed is too low, the chromatographic separation performed on that bed suffers from "tailing" and, in general, such an under-compressed bed is unstable. If the compression of the packed bed is too high, the chromatographic separation performed by the bed suffers "look ahead" and such over-compressed beds can affect throughput (throughput) and binding capacity and generally give higher operating pressures. If compression is optimal, the separation peaks formed during use show less leading or trailing and are substantially symmetrical. An optimum degree of compression is also crucial for achieving good long-term stability of the porous structure, thereby ensuring optimum performance during multiple process cycles. The optimum degree of compression required for the column is determined experimentally for each column size (width or diameter), bed height and media type.

A particular problem is that it is often desirable to scale up (scale) the chromatographic process by parallel coupling of several columns in order to improve capacity. However, the variability of the current packing process is a serious obstacle, as the permeability and corresponding flow rates will vary from column to column, causing excessive band broadening on parallel modules. Methods of drying the filled swellable media are suggested as remedies for this problem (see US20140224738 and US20120267299, both of which are hereby incorporated by reference in their entirety).

Columns used for preparation in bioprocess separations need to have a relatively large diameter to accommodate sufficient bed volume for the required absorption capacity. This means that the column needs to withstand significant forces from hydrodynamic back pressure without cracking or deforming. For repeated use, the column is typically constructed with a heavy end piece of stainless steel, and the hydraulic pressure acting on the end piece is used to counteract the back pressure. Single use posts need to be constructed from low cost materials, such as plastic, which require different constructions. Typically, plastic end pieces are very thick to prevent expansion, and they are held together by a plurality of external tie rods (see, e.g., US8702983 and US20080017579, which are hereby incorporated by reference in their entirety). Even when these remedies are used, the diameter of the single-use column is still limited. Alternatively, a stack of single-use posts may be clamped together for compression by a heavy stainless steel plate using hydraulic or threaded rods (see, e.g., US201330068671, which is hereby incorporated by reference in its entirety).

Accordingly, there is a need for a single use bioprocess column that allows for a lighter construction to reduce cost and improve convenience during use of the column.

Disclosure of Invention

One aspect of the present invention is to provide a compact bioprocess chromatography column suitable for single use applications. This is achieved by a column comprising:

a) a bed chamber defined by at least one side wall, a first bed support screen (screen), and a second bed support screen;

b) a first end wall secured to or integral with the side wall, wherein the first port is fluidly connected to the first bed support screen via a first distributor;

c) a second end wall secured to or integral with the side wall, wherein the second port is fluidly connected to the second bed support screen via a second distributor;

d) a fill port in the wall; and

e) an inner strut secured to or integral with at least one of the end walls and extending into the bed chamber.

One advantage is that it allows a lighter construction. An additional advantage is that no cumbersome external tie rods or compression plates are required.

A second aspect of the invention is a stack of chromatography columns assembled from a plurality of chromatography columns as disclosed above.

A third aspect of the present invention is a method of filling the above column by: transferring a weighed (weighedamount) quantity of dry expandable separation matrix microparticles to the bed chamber; and delivering the liquid to the column to swell the dry swellable separation matrix particles.

A fourth aspect of the invention is a method of preparing a stack of chromatography columns by packing the individual columns with the above method, stacking them and connecting them to each other in series or in parallel.

Further suitable embodiments of the invention are described in the dependent claims.

Drawings

Figure 1 shows a post of the invention a) in side view and b) in end view.

Figure 2 shows an exploded view of the column of the present invention.

Fig. 3 shows a post of the invention, a) in side view, b) in end view.

Fig. 4 shows a post of the invention, a) in side view, b) in end view.

Fig. 5 shows a stack of the columns of fig. 1, wherein the columns are coupled in parallel.

Fig. 6 shows a stack of the columns of fig. 1, wherein the columns are coupled in series.

Detailed Description

Define a limit

To more clearly and concisely describe and point out the subject matter of the claimed invention, the following definitions provide specific terms used in the following description and the claims appended hereto.

The singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise. Approximating language, as used herein throughout the specification and claims, may be applied to modify any quantitative representation that could permissibly 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," is not to be limited to the precise value specified. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties (such as molecular weight), reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about. Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the embodiments of the present invention. At the very least, each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

As used herein to describe the present invention, directional terms (such as "upper," "lower," "upward," "downward," "top," "bottom," "vertical," "horizontal," "above," "below," and any other directional terms) refer to those directions in the drawings.