WO2015047172A1

WO2015047172A1 - Method for transferring slurry

Info

Publication number: WO2015047172A1
Application number: PCT/SE2014/051107
Authority: WO
Inventors: Mikael BJÖRLING; Bengt Niklas EDBLAD; Per Karlberg; Jonas Karlsson; Joakim LUNDKVIST
Original assignee: GE Healthcare Bio Sciences Corp
Current assignee: Global Life Sciences Solutions USA LLC
Priority date: 2013-09-30
Filing date: 2014-09-26
Publication date: 2015-04-02
Anticipated expiration: 2016-03-30
Also published as: US10195541B2; JP6461930B2; US20160228790A1; EP4268918C0; EP3052931A4; EP3052931A1; CN105579843B; JP2016533479A; EP3052931B1; DK3052931T3; EP4268918A3; EP4268918A2; EP4268918B1; CN105579843A

Abstract

A method and a slurry tank system for transferring chromatography media slurry from a slurry tank (3) to a chromatography column(9), said method comprising monitoring the content of slurry in the slurry tank (3) during the transferring and controlling the transferring of the slurry to the column (9) in dependence of the content of slurry in the slurry tank(3).

Description

Method for transferring slurry

Field of the Invention

The present invention relates to a method for transferring chromatography media sluny from a sluny tank to a chromatography column, to a sluny tank system and to a control system in said sluny tank system.

Background of the Invention

Columns used in liquid chromatography typically comprise a tubular body enclosing a packed bed of porous chromatography medium through which a carrier liquid flows, with separation taking place by material collection between the carrier liquid and solid phase of the porous medium. Typically, the medium is enclosed in the column as a packed bed fonned by consolidating a suspension of discrete particles, known as sluny that is pumped, poured, or sucked into the column. Consolidation of the sluny into a consolidated packed bed is achieved by compressing the sluny so that it is packed into a volume, which is less than the volume that it would have occupied if it had been allowed to settle under the influence of gravity to fonn a sedimented bed. The efficiency of subsequent chromatographic separation relies strongly on 1 ) the liquid distribution and collection system at the fluid inlet and outlet of the packed bed, 2) on the spatial orientation (also know as the packing geometry) of the media particles in the packed bed, and 3) on the compression of the packed bed. If the compression of the packed bed is too low then chromatographic separations perfonned on that bed suffer from "tailing" and, generally, such insufficiently compressed beds are unstable. If the compression of the packed bed is too high then chromatographic separations perfonned by the bed suffer from "leading" and such over-compressed beds can affect throughput and binding capacity, and, in general, give much higher operating pressures. If the compression is optimum, then the separation peaks formed during use exhibit much less leading or tailing and are substantially symmetrical. The optimum degree of

compression required for a column is determined experimentally for each column size (width or diameter), bed height, and media type.

Prior to any separation process, the bed has to be prepared by starting from the sluny of particles that has to be introduced into the column. The process of bed formation is called 'the packing procedure' and a correctly packed bed is a critical factor influencing the performance of a packed bed. One of the primary goals of the packing procedure is to provide a bed, which is compressed by the optimum amount of compression, i.e. the optimum compression factor. The height of the bed which often is user defined when it is optimally compressed is called the target compressed bed height.

Large-scale columns can be prepared by suctioning or injecting into the column a predetermined volume of sluny having a specified concentration of media particles. Once the predetemiined volume of sluny has been delivered into the column it needs to be consolidated and compressed. This can be accomplished for example by moving a movable adapter down the longitudinal axis of the column towards the bottom of the column, nom ally at a constant speed push both liquid and particles towards the bottom of the column. The excess liquid during this procedure is expelled at the column outlet, while the media particles are retained by means of a filter material, a so-called 'bed support', with pores too small to allow the media particles to pass through. The packing process is complete once the packed bed has been compressed by the optimum degree of compression. There are alternative ways of packing. For example a flow can be applied to force the particles in the sluny to move towards the outlet of the column instead of moving an adapter downwards. A further alternative is to use spray nozzles spraying in sluny until a packed bed is achieved. The packing process is considered successful if the compressed bed allows for a good and robust chromatographic perfonnance. However, packing such an optimally compressed bed of chromatography media in a

chromatography column by manual means is not easy to accomplish in practice due to the fact that the quality of the final packed bed depends to a great extent on the skill of the operator. During filling and subsequent packing of the column, the operator manually selects and adjusts all packing parameters such as valve positions, pump speed, adapter's speed of movement, etc. The operator has to measure the sluny concentration in order to decide how much sluny that should be filled into the column. If the measure of the sluny concentration is not exact (which is often the case because it is hard to measure the sluny concentration exactly) the volume of the sluny filled into the column is not optimal and the consolidated bed will settle at a bed height that was not expected (as calculated from the measured sluny concentration) and hereby the target packing factor can not be achieved at target bed height. Furthermore, the operator also has to judge the point when the adapter starts compressing the bed. This point is used to calculate how much further the adapter must move in order to obtain the required amount of compression. Mistakes in the selection of any of the packing parameters normally lead to an under performing column. Further, in columns equipped with a transparent tube it may be difficult, and in columns equipped with a non-transparent tube such as stainless steel it is impossible, to judge by eye when compression of the bed actually starts and a significant error at this point makes it impossible to obtain an optimally compressed bed. There is also a risk of damaging the media and the column if the user takes wrong decisions.

The chromatography media sluny is provided to the chromatography column from a sluny tank. The chromatography media is expensive and it would be advantageous if all the sluny present in the tank could be transfen ed to the column. However, the introduction of air into the column needs to be avoided. Air in the column could adversely affect the chromatography perfonnance.

Therefore, there is a need for a system and method for the improved transfemng of sluny from the sluny tank to the chromatography column.

Summary of the Invention

An object of the invention is to provide a sluny transfemng method and system where as much as possible of the sluny in the sluny tank is used when packing a chromatography column and the risk of introducing air into the column is minimized. A further object of the invention is to provide a fully automated method for the transfemng of sluny into the chromatography column that ensures good use of the sluny and no risk of introducing air into the column.

This is achieved in a method according to claim 1, in a sluny tank system according to claim 10 and in a control system according to claim 19.

Hereby the transfemng of sluny is made dependent of the content of sluny in the tank. Therefore it will be possible to use more of the sluny without the risk of introducing air into the column.

In one embodiment of the invention the transfemng of sluny to a column and the monitoring of the content in the sluny tank is perfonned automatically by a control system.

In one embodiment of the invention the controlling of the transfer of the sluny to the column comprises stopping the transfemng of sluny, when the sluny content is below a predefined threshold level. Hereby the risk that air will be introduced into the column is veiy small.

In one embodiment of the invention the controlling of the transfer of the sluny to the column comprises decreasing the transferring speed when the sluny content is below a predefined threshold level. Hereby the risk of introducing air into the column is even more decreased and the possibility to control the transfemng of sluny is improved.

In one embodiment of the invention inside walls of the sluny tank are rinsed by spraying a liquid or a gas into the sluny tank when the sluny content is below a predefined threshold level. Hereby any remaining media on the inside walls of the sluny tank can also be used and no media is wasted.

In one embodiment of the invention the monitoring comprises measuring sluny level in the sluny tank or measuring weight of the sluny tank.

In another embodiment the monitoring comprises measuring air content in a transfemng tube used for the transfemng of the sluny from the sluny tank to the chromatography column.

In one embodiment of the invention transfemng sluny from the sluny tank to the chromatography column is perfonned by raising an adaptor in the chromatography column.

Brief Description of the Drawings

These and other advantages of the present invention will become more apparent as the following description is read in conjunction with the accompanying drawings, wherein:

FIG. 1 is a schematic diagram of a sluny tank system connected to a

chromatography column according to one embodiment of the invention;

FIG. 2 is a flow chart describing a sluny transfemng method according to one embodiment of the invention.

Detailed Description of the Invention The presently preferred embodiments of the invention are described with reference to the drawings. The descriptions of the preferred embodiments are exemplary and are not intended to limit the scope of the invention.

Figure 1 is a schematic view of a sluny tank system 1 connected to a chromatography column 9 according to one embodiment of the invention. The sluny tank system 1 comprises a sluny tank 3 which comprises a chromatography media sluny. The sluny tank system 1 comprises further a monitoring means 5, 5'. In this schematic view two different possible positions for the monitoring means 5, 5' is shown. The monitoring means 5 could be for example a weight measuring means 5. A weight measuring means would typically be positioned in connection with and below the sluny tank 3 in order to be able to measure the weight of the sluny tank. The monitoring means 5 could in another embodiment be an air sensor 5. This air sensor would suitably be positioned at the outlet from the sluny tank for measuring when air is starting to come with the sluny, i.e. when the sluny tank 3 is almost empty. In another embodiment the monitoring means 5' could be a level sensor 5' for example using ultrasonic or spectroscopic measuring for detecting the sluny level in the sluny tank 3.

The sluny tank system 1 further comprises a transfemng tube 7a adapted to transfer sluny from the sluny tank 3 to the chromatography column 9. The transfemng tube 7a is connected to an outlet of the sluny tank 3 and to a sluny inlet of the column 9. The transfemng tube 7a is controlled by a transfemng control means 7b. This could be a motor that controls the adaptor in the column. Sluny is in this example sucked into the column tliiough a bottom valve when the adaptor is raised inside the column. A transfemng control means 7b could in another embodiment be a pump provided along the transferring tube 7a or a means for providing a pressure into the slurry tank in order to push out slurry through the transferring tube 7a and into the column 9.

Furthermore the slurry tank system comprises a control system 1 1. This control system 1 1 is comiected to both the monitoring means 5,5' and to the transferring control means 7b. The control system 1 1 is arranged to control the transferring of the slurry to the column in dependence of the content of slurry in the slurry tank 3. The control system 1 1 receives infomiation from the monitoring means 5,5' about the content of slurry in the slurry tank 3. The control system 1 1 is preprogramed with for example different threshold levels for the content of slurry and programs for the transferring between these different threshold levels. For example the transferring speed can in one embodiment be lower after one specific threshold level has been reached. Or the transferring speed can be decreasing according to a predefined fomiula, for example linearly, starting from a predefined threshold level of the slurry content, i.e. when the slurry content is measured to decrease below the threshold level the transferring speed will decrease according to the fomiula. Further threshold levels could also be provided. One threshold level should trigger the transferring to stop completely.

In one embodiment of the invention the slurry tank system 1 further comprises a rinsing control means 13 comiected to the control system 1 1 and adapted to control a rinsing of the slurry tank 3. The rinsing is primarily in purpose to rinse the inside walls of the slurry tank 3 in order to be able to use and transfer all the slurry efficiently to the column. The rinsing control means 13 is in one embodiment comiected to a spray ball 15 provided inside the slurry tank 3. The spray ball can spray liquid or gas to the inside walls of the slurry tank 3 such that the slurry remaining on the walls will come down to the bottom of the slurry tank 3. The liquid could be for example water or packing buffer o

and the gas could be for example air or helium. Another alternative for rinsing the sluny tank would be to shake the whole tank, i.e. the rinsing control means 13 could be connected to some kind of vibrating means adapted to vibrate the sluny tank such that sluny remaining on the inside walls of the sluny tank will come down to the bottom of the tank. Suitably this rinsing of the sluny tank 3 will be provided when the content of sluny in the sluny tank 3 has been detected by the monitoring means 5, 5' to be below a predefined threshold level.

In one embodiment of the invention the added liquid will be measured such that any sluny dilution can be kept in mind. An alternative when liquid is added is to continually measure the sluny concentration. When a threshold concentration is reached the transfening of sluny to the chromatography column is tenninated. The concentration measurement method could be Raman spectrometer or ultrasound.

FIG. 2 is a flow chart describing a sluny transfening method according to one embodiment of the invention. The steps of the method will be described in order below:

S I : Monitoring the content in a sluny tank 3. In one embodiment the monitoring is done by measuring the weight of the tank. Another alternative is to measure the level in the tank by for example ultrasonic or resistance.

S3: Controlling the transfening of the sluny to the column in dependence of the content of sluny in the sluny tank. This can in one embodiment be provided by using predefined threshold levels whereby the transfening speed is decreased or stopped or varied when a specific threshold level has been reached, i.e. when the sluny content in the sluny tank is below a specific threshold level.

S5: Possibly rinsing the inside walls of the sluny tank 3 when the content of sluny in the sluny tank has been measured to be below a specific threshold level. The rinsing can be accomplished by for example spraying a liquid or a gas onto the inside walls or alternatively the sluny tank could be vibrated such that remaining sluny on the walls will come down to the bottom of the tank.

Claims

is claimed is:

A method for transferring chromatography media slurry from a slurry tank (3) to a chromatography column (9), said method comprising monitoring the content of slurry in the slurry tank (3) during the transferring and controlling the transferring of the slurry to the column (9) in dependence of the content of slurry in the slurry tank (3).

A method according to claim 1, further comprising receiving the slurry content information in a control system ( 1 1 ) and controlling the transferring of the slurry to the column from the control system ( 1 1 ).

A method according to claim 1 or 2, wherein the controlling of the transfer of the slurry to the column comprises stopping the transferring of slurry, when the slurry content is below a predefined threshold level.

A method according to any one of the preceding claims, wherein the controlling of the transfer of the slurry to the column comprises decreasing the transferring speed when the slurry content is below a predefined threshold level.

A method according to any one of the preceding claims, further comprising rinsing the inside walls of the slurry tank.

A method according to claim 5, comprising spraying a liquid or a gas into the slurry tank (3) when the slurry content is below a predefined threshold level.

A method according to any one of the preceding claims, wherein the monitoring comprises measuring slurry level in the slurry tank or measuring weight of the slurry tank.

8. A method according to any one of the preceding claims, wherein the monitoring comprises measuring air content in a transferring tube (7a) used for the transferring of the sluny from the sluny tank (3 ) to the chromatography column

(9).

9. A method according to any one of the preceding claims further comprising

transfening sluny from the sluny tank to the chromatography column by raising an adaptor in the chromatography column.

10. A sluny tank system ( 1 ) comprising a sluny tank (3) comprising a

chromatography media sluny, a monitoring means (5, 5') adapted to monitor the sluny content in the sluny tank (3), a transfening tube (7a) and a transfening control means (7b) adapted to transfer sluny from the sluny tank (3) to a chromatography column (9) and a control system ( 1 1 ) connected to the

monitoring means (5, 5') and the transfening control means (7b), wherein the control system ( 1 1 ) is ananged to control the transferring of the sluny to the column (9) in dependence of the content of sluny in the sluny tank (3).

1 1. A sluny tank system according to claim 10, further comprising a rinsing control means ( 13) connected to the control system ( 1 1 ) and adapted to rinsing the inside walls of the sluny tank (3) such that remaining sluny will come down to the bottom of the tank.

12. A sluny tank system according to claim 1 1, wherein the control means ( 1 1 ) is an anged to control the rinsing of the sluny tank to start when the sluny content is below a predefined threshold level.

13. A sluny tank system according to claim 1 1 or 12, wherein the rinsing control means ( 13) is connected to a spray ball ( 15) adapted to spray liquid or gas to the inside walls of the sluny tank.

14. A sluny tank system according to any one of the claims 10-13, wherein the

control system ( 1 1 ) further is ananged to stop the transfening of sluny when the sluny content is below a predefined threshold level.

15. A sluny tank system according to any one of the claims 10-14, wherein the control system ( 1 1 ) further is ananged to decrease the transfemng speed when the sluny content is below a predefined threshold level.

16. A sluny tank system according to any one of the claims 10-15, wherein the

monitoring means (5, 5') is ananged to measure sluny level in the sluny tank or weight of the sluny tank.

17. A sluny tank system according to any one of the claims 10-16, wherein the

monitoring means (5, 5') is ananged to measure air content in the transfemng tube (7a).

18. A sluny tank system according to any one of the claims 10-17, wherein the

control system ( 1 1 ) further is ananged to control the transfemng of sluny from the sluny tank (3) to the chromatography column (9) by raising an adaptor in the chromatography column.

19. A control system ( 1 1 ) connected to a monitoring means (5, 5') adapted to monitor the sluny content in a sluny tank (3), said control system further being connected to a transfemng control means (7b) adapted to control the transfer in a transfer tube (7a) between the sluny tank (3) and a chromatography column (9), whereby said control system is an anged to control the transfemng of the sluny to the column (9) in dependence of the content of sluny in the sluny tank (3).

20. A control system ( 1 1 ) according to claim 19, wherein the control system is

ananged to stop the transfemng of sluny when the sluny content is below a predefined threshold level.

21. A control system ( 1 1 ) according to claim 19 or 20, wherein the control system ( 1 1 ) further is ananged to decrease the transfemng speed when the sluny content is below a predefined threshold level. A control system ( 1 1 ) according to any one of the claims 19-21, wherein the control system ( 1 1 ) further is connected to a rinsing control means ( 13) adapted to rinsing the inside walls of the sluny tank (3) such that remaining sluny will come down to the bottom of the tank, wherein the control means ( 1 1 ) is arranged to control the rinsing of the sluny tank to start when the sluny content is below a predefined threshold level.