Multifunctional full-automatic standard chromatography system

Abstract

The utility model provides a full-automatic standard chromatography system, which comprises a replaceable multi-column module, a column top pipeline and a column bottom pipeline, wherein the top and the bottom of the replaceable multi-column module are respectively connected with the column top pipeline and the column bottom pipeline; the fluid conveying unit is connected with the column bottom pipeline and can convey different fluids to each chromatographic column according to different chromatographic stages, and the fluids comprise products, eluent cleaning fluid and the like; the fluid collection unit is connected with a column top pipeline of each chromatographic column and can collect different fluids, including waste liquid, intermediate products and the like, passing through the chromatographic columns according to different chromatographic stages; when in use, the two chromatographic columns can be alternately used to realize alternate operation of continuous chromatography; the device has the advantages that the device can operate independently, and the working efficiency is improved.

Description

Technical Field

[0001] This invention relates to separation and purification techniques for use in the biopharmaceutical field, and particularly to a multifunctional fully automated standard chromatography system. Background Technology

[0002] Current chromatographic systems use a single column for sample loading and elution. To improve chromatography efficiency, continuous flow chromatography is often used, which involves two flow paths operating simultaneously. The main mode is that one flow path is used for continuous sample loading, while the other is used for pre-loading preparation or post-loading elution.

[0003] The AKTApcc is a continuous flow chromatography system from General Electric that supports two flow paths with three or three flow paths with four flow paths. However, it cannot switch the direction of the liquid phase flow in the chromatography columns.

[0004] The BioSMB is a continuous flow chromatography device from Pall, which supports operation with two flow paths and multiple chromatography columns. However, it cannot implement buffer gradients.

[0005] When the intermediates produced after the previous chromatography step are loaded for further chromatography, multiple chromatography columns need to be used in series. However, chromatography devices are not easy to set up separately or combine with each other, resulting in low flexibility and difficulty in meeting the needs of laboratory-level, pilot-scale and large-scale production at the same time. Utility Model Content

[0006] To overcome the shortcomings of the existing technology, this invention provides a multifunctional fully automated standard chromatography system with gradient function and independent sample pump. It can be used as a continuous chromatography system with alternating column operation or as a dual-column tandem continuous chromatography system, offering high flexibility to meet various application scenarios.

[0007] To address the aforementioned technical problems, the first aspect of this utility model disclosure proposes a fully automated standard chromatography system. This chromatography system includes: a replaceable multi-column module, the top and bottom of which are respectively connected to a column top pipe and a column bottom pipe; a fluid delivery unit connected to the column bottom pipe, capable of delivering different fluids, including products, eluents, and washing solutions, to each chromatography column according to different chromatography stages; and a fluid collection unit connected to the column top pipe of each chromatography column, capable of collecting different fluids after passing through the chromatography column, including waste liquid and intermediate products, according to different chromatography stages.

[0008] In some embodiments, the alternative multi-column module includes two or more chromatography columns, each chromatography column having a column top conduit and a column bottom conduit connected to its top and bottom, respectively.

[0009] In some embodiments, the fluid collection unit comprises at least two collection pipes, each of which is connected to the column top pipe of each chromatography column, respectively; and the outlet end of each collection pipe is connected to a plurality of discharge pipes, respectively.

[0010] In some embodiments, the column bottom pipe of each chromatography column is connected to one of the discharge pipes in the corresponding collection pipe.

[0011] In some embodiments, a plurality of intermediate pipes are arranged between the fluid delivery unit and the fluid collection unit, one end of each intermediate pipe is connected to the outlet end of the first liquid inlet main pipe and the bypass module, respectively; the other end of each intermediate pipe is connected to the corresponding discharge pipe connected to the bottom pipe.

[0012] In some embodiments, the fluid delivery unit comprises a first liquid inlet main pipe and a second liquid inlet main pipe; the first liquid inlet main pipe is used to deliver a plurality of buffers; the second liquid inlet main pipe is used to deliver a mixed solution containing products; the first liquid inlet main pipe is connected to the inlet of the mixing unit and the column bottom pipe of each chromatography column, respectively; the second liquid inlet main pipe is connected to the inlet of the mixing unit; the outlet of the mixing unit is connected to the column bottom pipe of each chromatography column, respectively.

[0013] In some embodiments, the mixing unit comprises at least two static mixing chambers, which are connected in series; the static mixing chambers are used for mixing the fluid in the second liquid inlet main pipe and mixing the fluid in the first liquid inlet main pipe and the second liquid inlet main pipe, respectively.

[0014] In some embodiments, a bypass module is arranged on the outlet pipe of the mixing unit.

[0015] In some embodiments, the bypass module comprises a bubble trap, the inlet of the bubble trap is connected to the outlet of the mixing unit through a valve, and the outlet of the bubble trap is connected to the column bottom pipe of each chromatography column through a valve.

[0016] In some embodiments, a bypass branch pipe is arranged in the bypass module, the bypass branch pipe is provided with a valve, and the two ends of the bypass branch pipe are connected to the mixing unit and the column bottom pipe, respectively.

[0017] In some embodiments, the inlet end of the first liquid inlet main pipe is connected to at least three liquid inlet pipes, each of which is provided with a valve, and each valve forms a liquid inlet valve group; the liquid inlet pipes are connected to different liquid storage containers, such as various buffer solutions, etc.

[0018] In some embodiments, the inlet end of the second liquid inlet main pipeline is connected to at least three liquid inlet pipelines, and valves are arranged on the liquid inlet pipelines respectively, and each valve forms a liquid inlet valve group; the liquid inlet pipelines are connected to different liquid outlet containers, such as various buffer solutions, products, etc.

[0019] In some embodiments, at least one of the liquid inlet pipelines connected to the first liquid inlet main pipeline is in communication with the liquid inlet pipelines connected to the second liquid inlet main pipeline.

[0020] In some embodiments, the first liquid inlet main pipeline and / or the second liquid inlet main pipeline are respectively provided with pressure sensors or / and flow sensors.

[0021] In some embodiments, the collection pipelines of the fluid collection unit are respectively provided with pH sensors and / or conductivity sensors and / or ultraviolet sensors.

[0022] The use of the novel has the following beneficial effects:

[0023] 1. The use of the novel adopts multiple chromatography columns, which can be independently operated to improve work efficiency.

[0024] 2. The column bottom pipelines of each chromatography column are connected to the fluid delivery unit respectively, and the column top pipelines are connected to the fluid collection unit, and the fluid collection unit includes at least two collection pipelines, the inlet end of each collection pipeline is connected to the column top pipeline of each chromatography column respectively, and the outlet end of each collection pipeline is in communication with multiple discharge pipelines, so that two chromatography columns can be alternately used to realize alternating operation and continuous chromatography.

[0025] 3. The two column bodies can be connected in series.

[0026] Description of the Drawings

[0027] Figure 1 The use of the novel is a structural schematic diagram. DETAILED DESCRIPTION

[0028] The use of the novel will be further described below with reference to the accompanying drawings.

[0029] The technical content of the use of the novel will be described below through specific specific embodiments, and those skilled in the art can easily understand other advantages and effects of the use of the novel from the disclosure of the specification. The use of the novel can also be implemented or applied through other different specific embodiments. Those skilled in the art can make various modifications and changes without departing from the spirit of the use of the novel.

[0030] Before the specific embodiments of the disclosure are described in detail, first, some terms used in the disclosure are explained.

[0031] General terms and definitions

[0032] Unless otherwise defined herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. References to techniques employed herein are intended to refer to the techniques as commonly understood in the art, including variations and equivalents of the techniques that are apparent to one of ordinary skill in the art. Although the following terms are believed to be well understood by one of ordinary skill in the art, the following definitions are set forth to facilitate a better understanding of the present inventive subject matter. When referring to trade names herein, it is intended to refer to the corresponding product. All patents, published patent applications, and publications recited herein are incorporated herein by reference.

[0033] The singular forms "a," "an," and "the" refer to both the singular as well as the plural, unless the context clearly indicates otherwise. The expressions "one or more" or "at least one" can mean 1, 2, 3, 4, 5, 6, 7, 8, 9, or more.

[0034] The terms "connected," "coupled," or "coupling," and like terms as used herein, are not limited to direct connections, but can also include indirect connections.

[0035] The "products" as described herein are biomolecules, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids, and derivatives thereof.

[0036] The terms "on-line monitoring" or "real-time monitoring" as used herein refer to the real-time detection of certain parameters or properties of the buffer, reaction fluid, fluid flowing out of the flow reactor, such as pH value, pressure, flow rate, conductivity, etc. during the use of the chromatography system. Unlike off-line detection or analysis, on-line monitoring or real-time monitoring can provide real-time feedback of the detection results.

[0037] The positional relationship words "upper", "lower", "left", "right", "front", "back", etc. as referred to herein are determined according to the layout direction of the drawings of the specification, and are only used to express relative positional relationship. When the absolute position of the described object changes, the relative positional relationship may

[0038] The application scenario of the present patent is laboratory scale and pilot scale, and the maximum flow range of a single pump is 1000 ml / min.

[0039] Reference Figure 1As shown, the full-automatic standard chromatograph comprises a first liquid inlet main pipeline 1, an inlet end of the first liquid inlet main pipeline 1 is connected with three liquid inlet pipelines respectively, which are a buffer solution A liquid inlet pipeline, a buffer solution B liquid inlet pipeline and a buffer solution C liquid inlet pipeline, a first valve 2, a second valve 3 and a third valve 4 are arranged on each liquid inlet pipeline respectively, and the three valves form an inlet module. The first liquid inlet main pipeline 1 is provided with a first liquid inlet pump 5, a first pressure sensor 6 and a first flow sensor 7. A second liquid inlet main pipeline 8, an inlet end of the second liquid inlet main pipeline 8 is connected with two liquid inlet pipelines respectively, which are a buffer solution A liquid inlet pipeline, a product liquid inlet pipeline and a buffer solution C liquid inlet pipeline, a fourth valve 9 and a fifth valve 10 are arranged on each liquid inlet pipeline respectively, and the two valves form an inlet module. The second liquid inlet main pipeline 8 is provided with a second liquid inlet pump 11, a second pressure sensor 12 and a second flow sensor 13; the first liquid inlet main pipeline 1 is connected with an inlet of a mixing unit respectively and is connected with a first intermediate pipeline 16 and a second intermediate pipeline 17 through a fifth valve 14 and a sixth valve 15 respectively; the second liquid inlet main pipeline 8 is connected with another inlet of the mixing unit. The mixing unit comprises a plurality of static mixing chambers 18 connected in series, one static mixing chamber 18 can be arranged according to the figure, the first intermediate pipeline 16 and the second intermediate pipeline 17 are connected with inlets of the static mixing chamber 18 respectively, and the inlets of the static mixing chamber 18 are provided with a seventh valve 19 and an eighth valve 20 respectively; an outlet of the static mixing chamber 18 is connected with an inlet of an air trap 21, an outlet of the air trap 21 is connected with the first intermediate pipeline 16 and the second intermediate pipeline 17 through a twelfth valve 22 and a thirteenth valve 23 respectively; a ninth valve 24 and a tenth valve 25 are arranged at the inlet end and the outlet end of the air trap 21 respectively; a bypass branch pipe 26 is arranged between the inlet end and the outlet end of the air trap 21, and an eleventh valve 27 is arranged on the bypass branch pipe 26.

[0040] The chromatography system is provided with a first chromatographic column 28 and a second chromatographic column 29, the bottom of the first chromatographic column 28 and the second chromatographic column 29 is respectively provided with a first column bottom pipe 30 and a second column bottom pipe 31, the top of the first chromatographic column 28 and the second chromatographic column 29 is respectively provided with a first column top pipe 32 and a second column top pipe 33; the first column top pipe 32 is connected with a first collection pipe 36 and a second collection pipe 37 through a twelfth valve 34 and a thirteenth valve 35 respectively; the second column top pipe 33 is connected with the first collection pipe 36 and the second collection pipe 37 through a fourteenth valve 38 and a fifteenth valve 39 respectively; the outlet end of the first collection pipe 36 is connected with three discharge pipes respectively, which are a first discharge pipe 40, a second discharge pipe 41 and a third discharge pipe 42; the first discharge pipe 40, the second discharge pipe 41 and the third discharge pipe 42 are respectively provided with a sixteenth valve 43, a seventeenth valve 44 and an eighteenth valve 45; the outlet end of the second collection pipe 37 is connected with three discharge pipes respectively, which are a fourth discharge pipe 46, a fifth discharge pipe 47 and a sixth discharge pipe 48; the fourth discharge pipe 46, the fifth discharge pipe 47 and the sixth discharge pipe 48 are respectively provided with a nineteenth valve 49, a twentieth valve 50 and a twenty-first valve 51. The first column bottom pipe 30 is connected with the second discharge pipe 41; the second column bottom pipe 31 is connected with the fifth discharge pipe 47.

[0041] The outlet end of the first intermediate pipe 16 and the second intermediate pipe 17 is respectively provided with a twenty-second valve 52 and a twenty-third valve 53; the outlet end of the first intermediate pipe 16 is connected with the second discharge pipe 41; the outlet end of the second intermediate pipe 17 is connected with the fifth discharge pipe 47.

[0042] The inlet end of the first column bottom pipe 30 is provided with a twenty-fourth valve 54; the inlet end of the second column bottom pipe 31 is provided with a twenty-fifth valve 55. Two valves are connected in series on the first column top pipe 32, which are a twenty-sixth valve 56 and a twenty-seventh valve 57; two valves are connected in series on the second column top pipe 33, which are a twenty-eighth valve 58 and a twenty-ninth valve 59.

[0043] The first chromatographic column 28 and the second chromatographic column 29 are respectively provided with a first bypass branch pipe 60 and a second bypass branch pipe 61; one end of the first bypass branch pipe 60 is connected between the twenty-sixth valve 56 and the twenty-seventh valve 57, and the other end is connected to the inlet end of the twenty-fourth valve 54; the first bypass branch pipe 60 is provided with a thirtieth valve 62. One end of the second bypass branch pipe 61 is connected between the twenty-eighth valve 58 and the twenty-ninth valve 59, and the other end is connected to the inlet end of the twenty-fifth valve 55; the second bypass branch pipe is provided with a thirty-first valve 63.

[0044] A third pressure sensor 64 and a fourth pressure sensor 65 are respectively provided on the first intermediate pipe 16 and the second intermediate pipe 17.

[0045] A first pH value measuring sensor 66, a first conductivity sensor 67, and an ultraviolet sensor 68 are provided on the first collecting pipe 36. A second pH value measuring sensor 69, a second conductivity sensor 70 are provided on the second collecting pipe 37.

Claims

1. Multifunctional fully automatic standard chromatography system, characterized in that The chromatography system comprises: a replaceable multi-column module, the top and bottom of which are connected with column top pipes and column bottom pipes respectively; a fluid delivery unit connected with the column bottom pipes, which can deliver different fluids to each chromatography column according to different chromatography stages, including products, eluent and cleaning liquid; a fluid collection unit connected with the column top pipes of each chromatography column, which can collect different fluids after passing through the chromatography column according to different chromatography stages, including waste liquid and intermediate products; the replaceable multi-column module comprises two or more chromatography columns, the top and bottom of each chromatography column are connected with column top pipes and column bottom pipes respectively; the fluid collection unit comprises at least two collection pipes, the inlet end of each collection pipe is connected with the column top pipe of each chromatography column respectively; the outlet end of each collection pipe is connected with a plurality of discharge pipes respectively; the fluid delivery unit comprises a first liquid inlet main pipe and a second liquid inlet main pipe; the first liquid inlet main pipe is used for delivering a plurality of buffers; the second liquid inlet main pipe is used for delivering mixed liquid containing products; the first liquid inlet main pipe is connected with the inlet of a mixing unit and the column bottom pipe of each chromatography column respectively; the second liquid inlet main pipe is connected with the inlet of the mixing unit; the outlet of the mixing unit is connected with the column bottom pipe of each chromatography column respectively.

2. The multi-functional fully automated standard chromatography system according to claim 1, characterized in that A bypass branch pipe is arranged between the top and the bottom of each chromatography column, and the column top pipe and the column bottom pipe are connected through the bypass branch pipe.

3. The multi-functional fully automated standard chromatography system according to claim 1, characterized in that The column bottom pipe is connected with one discharge pipe in the corresponding collection pipe.

4. The multi-functional fully automated standard chromatography system according to claim 1, characterized in that A plurality of corresponding intermediate pipes are arranged between the fluid delivery unit and the fluid collection unit, one end of each intermediate pipe is connected with the first liquid inlet main pipe and the outlet end of a bypass module respectively; the other end of each intermediate pipe is connected with the corresponding discharge pipe connected with the bottom pipe.

5. The multi-functional fully automated standard chromatography system according to claim 1, characterized in that The mixing unit comprises at least two static mixing chambers, and the static mixing chambers are connected in series; the static mixing chambers are used for mixing the fluid in the second liquid inlet main pipe and mixing the fluids in the first liquid inlet main pipe and the second liquid inlet main pipe respectively.

6. The multi-functional fully automated standard chromatography system according to claim 5, characterized in that A bypass module is arranged on the outlet pipe of the mixing unit; the bypass module comprises a bubble trap, the inlet of the bubble trap is connected with the outlet of the mixing unit through a valve, and the outlet of the bubble trap is connected with the column bottom pipe of each chromatography column through a valve.

7. The multi-functional fully automated standard chromatography system according to claim 6, characterized in that A bypass branch pipe is arranged in the bypass module, the bypass branch pipe is provided with a valve, and the two ends are connected with the mixing unit and the column bottom pipe respectively.

8. The multi-functional fully automated standard chromatography system according to claim 1, characterized in that The inlet end of the first liquid inlet main pipe is connected with at least three liquid inlet pipes, valves are arranged on the liquid inlet pipes respectively, and each valve forms a liquid inlet valve group; the liquid inlet pipes are connected with different liquid storage containers.

9. The multi-functional fully automated standard chromatography system according to claim 8, characterized in that The inlet end of the second liquid inlet main pipe is connected with at least three liquid inlet pipes, valves are arranged on the liquid inlet pipes respectively, and each valve forms a liquid inlet valve group; the liquid inlet pipes are connected with different liquid outlet containers.

10. The multi-functional fully automated standard chromatography system according to claim 9, characterized in that At least one of the liquid inlet pipes connected with the first liquid inlet main pipe is connected with the liquid inlet pipes connected with the second liquid inlet main pipe.

11. The multi-functional fully automated standard chromatography system according to claim 10, characterized in that The first liquid inlet main pipeline and / or the second liquid inlet main pipeline are respectively provided with a pressure sensor or / and a flow sensor.

12. The multi-functional fully automatic standard chromatography system according to claim 1, wherein The collecting pipeline of the fluid collecting unit is respectively provided with a pH sensor and / or an electric conductivity sensor and / or an ultraviolet sensor.

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