CN217901662U

CN217901662U - Continuous flow chromatography system

Info

Publication number: CN217901662U
Application number: CN202221560573.6U
Authority: CN
Inventors: 刘咔; 肖路; 何泽方
Original assignee: Chutianyuanchuang Biotechnology Changsha Co ltd
Current assignee: Chutianyuanchuang Biotechnology Changsha Co ltd
Priority date: 2022-06-21
Filing date: 2022-06-21
Publication date: 2022-11-25
Anticipated expiration: 2032-06-21

Abstract

The utility model discloses a continuous flow chromatography system, including many chromatographic columns and with many chromatographic columns respectively be connected sample loading device, elution device, regenerating unit, the branch road of wasting discharge and collection device, be connected with first circulation branch road and second circulation branch road on the chromatographic column, first circulation branch road and second circulation branch road communicate through a circulation house steward, be equipped with the first ultraviolet detection device who is used for detecting target concentration on the circulation house steward. The utility model has the advantages of continuous production, high production efficiency, high filler utilization rate and the like.

Description

Continuous flow chromatography system

Technical Field

The utility model relates to a food, pharmaceutical packaging machinery technical field especially relate to a continuous flow chromatography system.

Background

In the processing fields of pharmacy, food, health care products, chemical engineering and the like, the purification of certain products needs to use a preparative chromatography, the currently common preparative chromatography is a single-column system, and the system has the advantages of simple operation, suitability for various scenes and the following defects: 1) Loading, elution and regeneration, which cannot be performed simultaneously, for example, the elution flow path is idle during loading, and the loading flow path is idle during elution, which results in discontinuous production and low efficiency; 2) The utilization rate of the filler is low, for example, in order to ensure that the target object needing to be adsorbed does not flow out of the column in an adsorption scene, and the adsorption of the filler cannot reach saturation. In addition, the method has the defects of insufficient intelligent degree and the like.

SUMMERY OF THE UTILITY MODEL

The to-be-solved technical problem of the utility model is to overcome prior art not enough, provide a continuous flow chromatography system that production is continuous, production efficiency is high, the filler utilization ratio is high.

In order to solve the technical problem, the utility model discloses a following technical scheme:

the utility model provides a continuous flow chromatography system, includes many chromatographic columns and with many chromatographic columns respectively connected go up appearance device, elution device, regenerating unit, waste discharge branch road and collection device, be connected with first circulation branch road and second circulation branch road on the chromatographic column, first circulation branch road and second circulation branch road communicate through a circulation house steward, be equipped with the first ultraviolet detection device who is used for detecting target concentration on the circulation house steward.

As a further improvement of the above technical solution:

the continuous flow chromatography system also comprises a sample loading branch, a first elution regeneration branch, a second elution regeneration branch and a switching valve, wherein the elution device and the regeneration device are connected with a first interface of the switching valve, a second interface of the switching valve is connected with each first elution regeneration branch, a third interface of the switching valve is connected with each second elution regeneration branch, a fourth interface of the switching valve is connected with a collection device, each sample loading branch, each first circulation branch and each first elution regeneration branch are connected with an inlet end of the chromatography column, and each waste discharge branch, each second circulation branch and each second elution regeneration branch are connected with an outlet end of the chromatography column.

And a second ultraviolet detection device is arranged at an outlet of the sample loading device, a third ultraviolet detection device is arranged between the switching valve and the collection device, and each waste discharge branch is connected with a fourth ultraviolet detection device.

The sample loading device comprises a raw material pump, a first bubble trap and a first flowmeter which are connected in sequence, and the first flowmeter is connected with the sample loading branch.

And a first pressure detection part is also arranged at the outlet of the first flowmeter.

The elution device comprises an eluent pump, the regeneration device comprises a regeneration liquid pump, outlets of the eluent pump and the regeneration liquid pump are connected with an inlet of a second bubble trap, and an outlet end of the second bubble trap is sequentially connected with a second flow meter and a switching valve.

And the outlet side of the second flowmeter is also provided with a first detection assembly, and the first detection assembly comprises a second pressure detection part, a first PH detection part and a first conductivity sensor.

And a second detection assembly is arranged between the switching valve and the collecting device and comprises a third pressure detection part, a second PH detection part and a second conductivity sensor.

And the two ends of the sample loading branch, the first elution regeneration branch, the second elution regeneration branch, the first circulation branch, the second circulation branch and the waste discharge branch are respectively provided with a first switch valve.

And a second switch valve is arranged at the inlet and the outlet of each chromatographic column.

Compared with the prior art, the beneficial effects of the utility model reside in that: the utility model discloses a continuous flow chromatography system, which comprises a plurality of chromatography columns, and a sample loading device, an elution device, a regeneration device, a waste discharge branch and a collection device which are respectively connected with the plurality of chromatography columns, so that sample loading, elution and regeneration can be carried out on each chromatography column, waste liquid is discharged through a liquid discharge branch, and liquid to be collected is collected through the collection device; the first circulation branch and the second circulation branch are connected to each chromatographic column, and the first circulation branch and the second circulation branch are connected through a circulation main pipe to form an internal circulation flow path, the chromatographic columns can be mutually connected or disconnected through the internal circulation flow path, namely, continuous process can be carried out on each chromatographic column.

Drawings

FIG. 1 is a schematic diagram of a continuous flow chromatography system according to the present invention.

FIG. 2 is a schematic view of the flow structure of the present invention (a is to perform sample loading on column 1 and column 2, and b is to perform elution and regeneration on column 3).

FIG. 3 is a schematic view of the flow structure of the present invention (a is to sample the column 2, and b is to elute and regenerate the column 3 and the column 1).

The reference numerals in the figures denote: 1. a chromatography column; 2. a sample loading device; 21. a sample loading branch circuit; 22. a second ultraviolet detection device; 23. a feedstock pump; 24. a first bubble trap; 25. a first flow meter; 26. a first pressure detecting member; 3. an elution device; 31. an eluent pump; 4. a regeneration device; 42. a regeneration liquid pump; 5. a waste discharge branch; 6. a collection device; 7. a circulation main pipe; 71. a first circulation branch; 72. a second circulation branch; 73. a first ultraviolet detection device; 8. a switching valve; 81. a first elution regeneration branch; 82. a second elution regeneration branch; 9. a third ultraviolet detection device; 10. a fourth ultraviolet detection device; 11. a second bubble trap; 12. a second flow meter; 13. a second pressure detecting member; 14. a first pH detection section; 15. a first conductivity sensor; 16. a third pressure detecting member; 17. a second pH detecting section; 18. a second conductivity sensor; 19. a first on-off valve; 20. and a second on-off valve.

Detailed Description

The technical solution of the present invention will be further described in detail with reference to the drawings and specific embodiments.

As used in this disclosure and in the claims, the terms "a," "an," "the," and/or "the" are not intended to be inclusive in the singular, but rather are inclusive in the plural unless the context clearly dictates otherwise. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another. Likewise, the word "comprising" or "comprises", and the like, means that the element or item listed before the word covers the element or item listed after the word and its equivalents, but does not exclude other elements or items. The terms "connected" or "coupled" and the like are not restricted to physical or mechanical connections, but may include electrical connections, whether direct or indirect.

Fig. 1 to fig. 3 show an embodiment of the continuous flow chromatography system of the present invention, the continuous flow chromatography system of this embodiment, including many chromatography columns 1 and with many chromatography columns 1 respectively be connected go up appearance device 2, elution device 3, regenerating unit 4, exhaust branch 5 and collection device 6, be connected with first circulation branch 71 and second circulation branch 72 on the chromatography column 1, first circulation branch 71 and second circulation branch 72 communicate through a circulation house steward 7, be equipped with the first ultraviolet detection device 73 that is used for detecting target concentration on the circulation house steward 7.

The continuous flow chromatography system comprises a plurality of chromatographic columns 1, and a sample loading device 2, an elution device 3, a regeneration device 4, a waste discharge branch 5 and a collection device 6 which are respectively connected with the plurality of chromatographic columns 1, wherein each chromatographic column 1 can be subjected to sample loading, elution and regeneration, waste liquid is discharged through the waste discharge branch 5, and liquid to be collected is collected through the collection device 6; connect first circulation branch road 71 and second circulation branch road 72 on each chromatographic column 1, and first circulation branch road 71 and second circulation branch road 72 connect through a circulation house steward 7, constitute the inner loop flow path, make and to communicate or break off each other between each chromatographic column 1 through the inner loop flow path, can carry out continuous process to each chromatographic column 1, compare in single-column chromatography system, the utility model discloses the appearance of going up of continuous flow chromatography system, elution, regeneration three can go on simultaneously on different chromatographic columns 1, and the production continuity is good, and efficiency is higher, and be equipped with the first ultraviolet detection device 73 that is used for detecting target compound concentration on the circulation house steward 7, when first ultraviolet detection device 73 detects target compound, show that the interior filler of chromatographic column 1 adsorbs and reaches the saturation promptly, and the appearance stoste that contains the target object can pass through the inner loop flow path and get into next chromatographic column 1 in, can neither waste the target object in the appearance stoste, and the filler adsorption in the chromatographic column 1 also can reach the saturation, and the filler utilization ratio is high.

Furthermore, the continuous flow chromatography system is communicated with the first circulation branch 71 and the second circulation branch 72 through a circulation main pipe 7, the connection mode is diversified, any chromatographic column 1 can be selected in the sampling process, and the connection mode can be changed according to the conditions that a single chromatographic column 1 fails and the like; meanwhile, the pipeline structure is simplified; and, the utility model discloses install first ultraviolet detection device 73 on circulation house steward 7, only need a detection device can detect the process of going up the appearance, judge the first chromatography column 1 behavior of going up the appearance, simple structure, low cost.

In this embodiment, the continuous flow chromatography system further includes a sample loading branch 21, a first elution regeneration branch 81, a second elution regeneration branch 82, and a switching valve 8, wherein the elution device 3 and the regeneration device 4 are both connected to a first interface of the switching valve 8, a second interface of the switching valve 8 is connected to each first elution regeneration branch 81, a third interface of the switching valve 8 is connected to each second elution regeneration branch 82, a fourth interface of the switching valve 8 is connected to the collection device 6, each sample loading branch 21, the first circulation branch 71, and the first elution regeneration branch 81 are all connected to an inlet end of the chromatography column 1, and each waste discharge branch 5, the second circulation branch 72, and the second elution regeneration branch 82 are all connected to an outlet end of the chromatography column 1. The sample loading device 2 controls the on-off of each sample loading branch 21 to load samples on each chromatographic column 1 to form a sample loading flow path; the switching valve 8 can select elution or regeneration of each chromatographic column 1, and the on-off of each first elution regeneration branch 81 and each second elution regeneration branch 82 is controlled, so that eluent or regeneration liquid passes through one or more chromatographic columns 1 to form two flow paths of elution and regeneration; the liquid after elution or regeneration enters a collecting device 6 to be collected, and the waste liquid is discharged through each waste discharge branch 5 to form a waste discharge flow path.

In this embodiment, a second ultraviolet detection device 22 is disposed at an outlet of the sample loading device 2, a third ultraviolet detection device 9 is disposed between the switching valve 8 and the collection device 6, and each waste discharge branch 5 is connected to a fourth ultraviolet detection device 10. Through the analysis of the detection data of the first ultraviolet detection device 73, the second ultraviolet detection device 22, the third ultraviolet detection device 9 and the fourth ultraviolet detection device 10, the intelligent judgment of the saturation degree when each column is combined with the target compound can be realized, the flow paths can be intelligently switched, and the intelligent degree is high.

In this embodiment, the sample loading device 2 includes a raw material pump 23, a first bubble trap 24, and a first flow meter 25, which are connected in this order, and the first flow meter 25 is connected to the sample loading branch 21. The sample loading solution enters a first bubble trap 24 from a raw material pump 23 for bubble elimination, flow detection is carried out through a first flow meter 25, and then the sample loading solution enters the chromatographic column 1 through a sample loading branch 21.

Further preferably, in the present embodiment, a first pressure detecting part 26 is further provided at the outlet of the first flow meter 25. And detecting the flow and the pressure of the sample feeding stock solution, and then feeding the sample feeding stock solution into the chromatographic column 1.

In this embodiment, the elution device 3 includes an eluent pump 31, the regeneration device 4 includes a regeneration pump 42, outlets of the eluent pump 31 and the regeneration pump 42 are both connected to an inlet of the second bubble trap 11, and an outlet of the second bubble trap 11 is sequentially connected to the second flow meter 12 and the switching valve 8. The eluent enters the second bubble trap 11 from the eluent pump 31 or the regeneration liquid enters the second bubble trap 42 from the regeneration liquid pump 42 for bubble elimination, the flow rate is detected through the second flow meter 12, and then the eluent enters each chromatographic column 1 through the switching valve 8.

Further preferably, in this embodiment, a first detection assembly is further disposed on an outlet side of the second flowmeter 12, and the first detection assembly includes a second pressure detection component 13, a first PH detection component 14, and a first conductivity sensor 15. After the flow rate of the eluent from the eluent pump 31 or the flow rate of the regeneration liquid from the regeneration liquid pump 42 is detected by the second flowmeter 12, the eluent is detected by the second pressure detection part 13, the first PH detection part 14 and the first conductivity sensor 15, and then the eluent enters each chromatographic column 1.

In this embodiment, a second detection assembly is disposed between the switching valve 8 and the collecting device 6, and the second detection assembly includes a third pressure detection component 16, a second PH detection component 17, and a second conductivity sensor 18. The liquid to be collected after the chromatographic column 1 is subjected to sampling or elution regeneration enters the collecting device 6 after being detected by the third pressure detecting part 16, the second pH detecting part 17 and the second conductivity sensor 18.

In this embodiment, the two ends of the sample loading branch 21, the first elution regeneration branch 81, the second elution regeneration branch 82, the first circulation branch 71, the second circulation branch 72, and the waste discharge branch 5 are respectively provided with a first switch valve 19. The first switch valve 19 is arranged, so that the on-off of each branch can be controlled conveniently, and the problem that the process of the chromatographic column 1 is influenced due to the fact that the on-off control of each branch is not timely caused by the fact that the system is large and the length of each branch is long is avoided.

In this embodiment, a second switch valve 20 is provided at the inlet and the outlet of each chromatography column 1. The total on-off of the inlet and the outlet of the chromatographic column 1 can be controlled by the second switch valve 20.

Three chromatographic columns 1 are taken as an example (from left to right, sequentially marked as column 1, column 2 and column 3), and two of the working procedures of the continuous flow chromatography system of the present invention are described.

First, as shown in fig. 2, fig. 2a and fig. 2b are processes performed simultaneously, and for the sake of clarity, they are respectively shown in 2 schematic diagrams:

1) Passing a feed solution comprising at least one target compound through column 1 and directing the effluent from column 1 into column 2;

2) Passing a washing liquid through the column 1, which is completed by binding with the target compound, and introducing an effluent of the washing liquid into the column 2;

3) Reintroducing the raw material solution into column 2 and introducing the effluent from column 2 into column 3, eluting, and regenerating column 1;

4) Passing a cleaning liquid through the column 2 completed by binding with the target compound, and introducing an effluent of the cleaning liquid into the column 3;

5) Reintroducing the feed solution into column 3 and the effluent from column 3 into column 1, eluting, regenerating column 2;

6) Passing a washing liquid through the column 3 completed by binding with the target compound, and introducing an effluent of the washing liquid into the column 1;

7) Reintroducing the raw material solution into column 1 and the effluent from column 1 into column 2, eluting, regenerating column 3;

8) And repeating the steps.

Second, as shown in fig. 3, fig. 3a and fig. 3b are the processes performed simultaneously, and for the sake of clarity, they are represented by 2 schematic diagrams:

1) Passing a feed solution comprising at least one target compound through column 1 and directing the effluent from column 1 into column 2, exiting column 2 to waste branch 5 (when column 3 is not in operation);

2) After column 1 is saturated, the feed solution is directed to column 2, and the wash liquid is passed through column 1 where binding with the target compound is completed and the wash liquid effluent is directed to column 3. (the washing process is called washing when the washing solution passes through the saturated column 1. The column 1 is saturated, because the column 1 is full of proteins that are 'adsorbed' and there is a part of proteins that are not 'adsorbed' in the column 1. Therefore, the washing process washes the non-adsorbed proteins and the remaining raw materials in the column 1 to the column 3, thereby preventing the waste of proteins);

3) After the column 1 is washed, only the protein 'adsorbed' in the column 1 is left, then the effluent liquid from the column 2 is introduced into a column 3, and the column 1 is eluted and regenerated (the elution is to elute the protein adsorbed in the column and discharge the protein from the top outlet in the figure, the regeneration is introduced into the solution to restore the function of the column 1, and the regeneration liquid is also discharged from the other top outlet in the figure);

4) Reintroducing said starting solution into column 3, passing a washing liquid through column 2, the binding of which with the target compound is completed, the effluent of the washing liquid being introduced into column 1;

5) Then the effluent from column 3 is introduced into column 1, and column 2 is eluted and regenerated;

6) Reintroducing said starting solution into column 1, passing a washing liquid through column 3, the binding of which with the target compound is completed, the effluent of the washing liquid being introduced into column 2;

7) Then, the effluent from the column 1 is introduced into a column 2, and the column 3 is eluted and regenerated;

8) And repeating the steps.

The above two schemes are selected according to the column idle condition.

The utility model discloses a continuous flow chromatography system possesses following advantage:

first, a guard column is connected in series after each column to introduce the raw material solution into each column for binding with the target compound. This allows the column to bind to full saturation with the target compound without loss of the target compound.

Secondly, a raw material pump is used for introducing the raw material solution into each column to be combined with the target compound, and simultaneously, the combined and cleaned column is eluted and regenerated, so that the production is continuous and efficient.

And thirdly, the intelligent judgment of the saturation degree when each column is combined with the target compound can be realized through the analysis of the data of the four UV detectors, and the flow path is intelligently switched, so that the intelligent degree is high.

It should be noted that although the present invention has been described with reference to the preferred embodiments, the present invention is not limited thereto. The technical solution of the present invention can be used by anyone skilled in the art to make many possible variations and modifications, or to modify equivalent embodiments, without departing from the scope of the present invention, using the technical content disclosed above. Therefore, any simple modification, equivalent change and modification made to the above embodiments by the technical entity of the present invention should fall within the protection scope of the technical solution of the present invention, all without departing from the contents of the technical solution of the present invention.

Claims

1. A continuous flow chromatography system, comprising: including many chromatographic columns (1) and with many chromatographic columns (1) sample loading device (2), elution device (3), regenerating unit (4), useless branch road (5) and collection device (6) of being connected respectively, be connected with first circulation branch road (71) and second circulation branch road (72) on chromatographic column (1), first circulation branch road (71) and second circulation branch road (72) are through a circulation house steward (7) intercommunication, be equipped with first ultraviolet detection device (73) that are used for detecting target object concentration on circulation house steward (7).

2. The continuous flow chromatography system of claim 1, wherein: the elution device (3) and the regeneration device (4) are connected with a first interface of the switching valve (8), a second interface of the switching valve (8) is connected with each first elution regeneration branch (81), a third interface of the switching valve (8) is connected with each second elution regeneration branch (82), a fourth interface of the switching valve (8) is connected with the collecting device (6), each loading branch (21), each first circulation branch (71) and each first elution regeneration branch (81) are connected with an inlet end of the chromatographic column (1), and each waste discharge branch (5), each second circulation branch (72) and each second elution regeneration branch (82) are connected with an outlet end of the chromatographic column (1).

3. The continuous flow chromatography system of claim 2, wherein: a second ultraviolet detection device (22) is arranged at an outlet of the sample loading device (2), a third ultraviolet detection device (9) is arranged between the switching valve (8) and the collecting device (6), and each waste discharge branch (5) is connected with a fourth ultraviolet detection device (10).

4. The continuous flow chromatography system of claim 2, wherein: the sample loading device (2) comprises a raw material pump (23), a first bubble trap (24) and a first flowmeter (25) which are connected in sequence, and the first flowmeter (25) is connected with the sample loading branch (21).

5. The continuous flow chromatography system of claim 4, wherein: and a first pressure detection part (26) is also arranged at the outlet of the first flowmeter (25).

6. The continuous flow chromatography system according to any of claims 1 to 3, wherein: the elution device (3) comprises an eluent pump (31), the regeneration device (4) comprises a regeneration liquid pump (42), outlets of the eluent pump (31) and the regeneration liquid pump (42) are connected with an inlet of a second bubble trap (11), and an outlet end of the second bubble trap (11) is sequentially connected with a second flow meter (12) and a switching valve (8).

7. The continuous flow chromatography system of claim 6, wherein: and a first detection assembly is further arranged on the outlet side of the second flowmeter (12), and comprises a second pressure detection part (13), a first PH detection part (14) and a first conductivity sensor (15).

8. The continuous flow chromatography system of claim 2 or 3, wherein: and a second detection assembly is arranged between the switching valve (8) and the collecting device (6), and comprises a third pressure detection part (16), a second PH detection part (17) and a second conductivity sensor (18).

9. The continuous flow chromatography system of claim 2, wherein: and two ends of the sample loading branch (21), the first elution regeneration branch (81), the second elution regeneration branch (82), the first circulation branch (71), the second circulation branch (72) and the waste discharge branch (5) are respectively provided with a first switch valve (19).

10. The continuous flow chromatography system according to any of claims 1 to 3, wherein: and a second switch valve (20) is arranged at the inlet and the outlet of each chromatographic column (1).