Multifunctional full-automatic standard chromatography system

Abstract

The invention provides a full-automatic standard chromatography system, which comprises a replaceable multi-column module, a column top pipeline and a column bottom pipeline, 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] The invention relates to separation and purification technology used in the field of biomedicine, and in particular to a multifunctional fully automatic standard chromatography system. Background Art

[0002] The chromatographic system in the prior art uses a single chromatography column to complete the loading and elution. In order to improve the efficiency of chromatography, continuous flow chromatography is often used, that is, two flow paths are used to run simultaneously. The main mode is that one flow path is used for continuous loading, and the other is in the preparation before loading or for elution after loading.

[0003] AKTApcc is a continuous flow chromatography device launched by General Electric, which supports the operation mode of two flow paths and three chromatography columns, or three flow paths and four chromatography columns. However, it cannot switch the flow direction of the chromatography column liquid phase.

[0004] BioSMB is a continuous flow chromatography device launched by Pall, which supports the operation mode of two flow paths and multiple chromatography columns. However, it cannot realize the gradient of buffer.

[0005] When the intermediates produced after the previous step of chromatography are further subjected to chromatography, multiple chromatography columns need to be used in series. However, the chromatography devices are not easy to separate or combine with each other, and have low flexibility, making it difficult to adapt to the needs of laboratory level, pilot and large-scale production at the same time. Summary of the invention

[0006] In order to overcome the shortcomings of the above-mentioned prior art, the present invention provides a multifunctional fully automatic standard chromatography system, which has a gradient function and an independent sample pump. It can be used as a continuous chromatography alternately running as a double-column, and can also be used as a double-column series continuous chromatography. It is highly flexible and can meet various application scenarios.

[0007] In view of the above technical problems, the first aspect of the disclosure of the present invention proposes a fully automatic standard chromatography system. The chromatography system includes: a replaceable multi-column module, the top and bottom of which are respectively connected to a column top pipeline and a column bottom pipeline; a fluid delivery unit, which is connected to the column bottom pipeline and can deliver different fluids to each chromatography column according to different chromatography stages, including products, eluents, cleaning fluids, etc.; a fluid collection unit, which is connected to the column top pipeline of each chromatography column and can collect different fluids after passing through the chromatography column according to different chromatography stages, including waste liquids, intermediate products, etc.

[0008] In some embodiments, the replaceable multi-column module comprises two or more chromatography columns, and the top and bottom of each chromatography column are respectively connected to a column top pipe and a column bottom pipe.

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

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

[0011] In some embodiments, a plurality of corresponding intermediate pipes are arranged between the fluid conveying unit and the fluid collecting unit, and one end of each intermediate pipe is respectively connected to the first liquid inlet main pipe and the outlet end of the bypass module; 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 includes a first liquid inlet main pipeline and a second liquid inlet main pipeline; the first liquid inlet main pipeline is used to transport multiple buffer solutions; the second liquid inlet main pipeline is used to transport a mixed liquid containing a product; the first liquid inlet main pipeline is respectively connected to the inlet of the mixing unit and the bottom pipeline of each chromatography column; the second liquid inlet main pipeline is connected to the inlet of the mixing unit; and the outlet of the mixing unit is respectively connected to the bottom pipeline of each chromatography column.

[0013] In some embodiments, the mixing unit includes at least two static mixing chambers, and the static mixing chambers are connected in series; the static mixing chambers are used to mix the fluid in the second liquid inlet main pipe, and 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 provided on the outlet pipe of the mixing unit.

[0015] In some embodiments, the bypass module includes 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 pipeline of each chromatography column through a valve.

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

[0017] In some embodiments, the inlet end of the first liquid inlet main pipeline is connected to at least three liquid inlet pipelines, valves are respectively provided on the liquid inlet pipelines, and each valve forms a liquid inlet valve group; the liquid inlet pipelines are connected to different liquid storage containers, such as various buffer solutions.

[0018] In some embodiments, the inlet end of the second liquid inlet main pipeline is connected to at least three liquid inlet pipelines, valves are respectively provided on the liquid inlet pipelines, 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 pipes connected to the first liquid inlet main pipe is interconnected with the liquid inlet pipe connected to the second liquid inlet main pipe.

[0020] In some embodiments, a pressure sensor and / or a flow sensor is respectively disposed on the first liquid inlet main pipe and / or the second liquid inlet main pipe.

[0021] In some embodiments, a pH sensor and / or a conductivity sensor and / or a UV sensor are respectively disposed on the collection pipe of the fluid collection unit.

[0022] Beneficial effects of the present invention:

[0023] 1. The present invention adopts multiple chromatography columns, which can operate independently and improve work efficiency.

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

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

[0026] Instruction Manual

[0027] Figure 1 It is a structural schematic diagram of the present invention. DETAILED DESCRIPTION

[0028] The present invention will be further described below in conjunction with the accompanying drawings.

[0029] The technical content of the present invention is described below by specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention 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 present invention. Before introducing the specific embodiments of the present disclosure in detail, some terms used in the present disclosure are first explained.

[0030] General Terms and Definitions

[0031] Unless otherwise defined below, the meaning of all technical terms and scientific terms used herein is intended to be the same as those commonly understood by those skilled in the art. Mentioning the technology used in this article is intended to refer to the technology commonly understood in the art, including those changes in technology that are obvious to those skilled in the art or the replacement of equivalent technology. Although it is believed that the following terms are well understood by those skilled in the art, the following definitions are still set forth to better explain the present invention. When a trade name appears in this article, it is intended to refer to the corresponding commodity. All patents, published patent applications and publications cited herein are incorporated herein by reference.

[0032] Unless otherwise indicated herein, singular references such as "a", "the" include plural references. The expression "one or more" or "at least one" may mean 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.

[0033] As used herein, the terms “connected”, “connected”, “coupled” or “coupled” and the like are not limited to direct connections but also include indirect connections.

[0034] As used herein, "products" are biomolecules, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and their derivatives.

[0035] As used herein, the term "online monitoring" or "real-time monitoring" refers to real-time detection of certain parameters or properties of buffers, reaction fluids, and fluids flowing out of flow reactors during use of the chromatography system, such as pH, pressure, flow rate, conductivity, etc. Unlike offline detection or analysis, online monitoring or real-time monitoring can provide real-time feedback of the detection results.

[0036] The position relationship words "up", "down", "left", "right", "front", "back", etc. involved in this article are determined according to the layout direction of the drawings in the specification. They are only used to indicate relative position relationships. When the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0037] The application scenarios of this patent are laboratory scale and pilot scale, and the maximum flow range of a single pump is 1000ml / min.

[0038] Reference Figure 1As shown, the fully automatic standard chromatograph comprises a first liquid inlet main pipeline 1, the inlet end of the first liquid inlet pipeline 1 is respectively connected to three liquid inlet pipelines, namely, the liquid inlet pipeline of buffer A, the liquid inlet pipeline of buffer B and the liquid inlet pipeline of buffer C, each of which is respectively provided with a first valve 2, a second valve 3 and a third valve 4, and the three valves constitute an import 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. The second liquid inlet main pipeline 8, the inlet end of the second liquid inlet main pipeline 8 is respectively connected to two liquid inlet pipelines, namely, the liquid inlet pipeline of buffer A, the liquid inlet pipeline of the product liquid and the liquid inlet pipeline of buffer C, each of which is respectively provided with a fourth valve 9 and a fifth valve 10, and the two valves constitute an import 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 to the inlet of the mixing unit and is connected to the first intermediate pipeline 16 and the second intermediate pipeline 17 through the fifth valve 14 and the sixth valve 15 respectively; the second liquid inlet main pipeline 8 is connected to another inlet of the mixing unit. The mixing unit includes a plurality of static mixing chambers 18 connected in series. As shown in the figure, a static mixing chamber 18 can be set up. The first intermediate pipe 16 and the second intermediate pipe 17 are respectively connected to the inlet of the static mixing chamber 18, and the inlet of the static mixing chamber 18 is respectively provided with a seventh valve 19 and an eighth valve 20; the outlet of the static mixing chamber 18 is connected to the inlet of an air trap 21, and the outlet of the air trap 21 is respectively connected to the first intermediate pipe 16 and the second intermediate pipe 17 through a twelfth valve 22 and a thirteenth valve 23; the inlet end and the outlet end of the air trap 21 are respectively provided with a ninth valve 24 and a tenth valve 25; a bypass branch pipe 26 is provided between the inlet end and the outlet end of the air trap 21, and the bypass branch pipe 26 is provided with an eleventh valve 27.

[0039] The chromatographic system is provided with a first chromatography column 28 and a second chromatography column 29, wherein the bottoms of the first chromatography column 28 and the second chromatography column 29 are respectively provided with a first column bottom pipeline 30 and a second column bottom pipeline 31, and the tops of the first chromatography column 28 and the second chromatography column 29 are respectively provided with a first column top pipeline 32 and a second column top pipeline 33; the first column top pipeline 32 is connected to a first collecting pipeline 36 and a second collecting pipeline 37 through a twelfth valve 34 and a thirteenth valve 35, respectively; the second column top pipeline 33 is connected to the first collecting pipeline 36 and the second collecting pipeline 37 through a fourteenth valve 38 and a fifteenth valve 39, respectively; the first collecting pipeline The outlet end of the channel 36 is connected to three discharge pipes, namely the first discharge pipe 40, the second discharge pipe 41, and the 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 collecting pipe 37 is connected to three discharge pipes, namely the fourth discharge pipe 46, the fifth discharge pipe 47, and the 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 to the second discharge pipe 41; the second column bottom pipe 31 is connected to the fifth discharge pipe 47.

[0040] The outlet ends of the first intermediate pipeline 16 and the second intermediate pipeline 17 are respectively provided with a twenty-second valve 52 and a twenty-third valve 53 ; the outlet end of the first intermediate pipeline 16 is connected to the second discharge pipeline 41 ; the outlet end of the second intermediate pipeline 17 is connected to the fifth discharge pipeline 47 .

[0041] The inlet end of the first column bottom pipeline 30 is provided with a twenty-fourth valve 54; the inlet end of the second column bottom pipeline 31 is provided with a twenty-fifth valve 55. The first column top pipeline 32 is connected in series with two valves, namely, a twenty-sixth valve 56 and a twenty-seventh valve 57; the second column top pipeline 33 is connected in series with two valves, namely, a twenty-eighth valve 58 and a twenty-ninth valve 59.

[0042] The first chromatography column 28 and the second chromatography column 29 are respectively provided with a first bypass branch 60 and a second bypass branch 61; one end of the first bypass branch 60 is connected between the 26th valve 56 and the 27th valve 57, and the other end is connected to the inlet end of the 24th valve 54; the first bypass branch 60 is provided with a 30th valve 62. One end of the second bypass branch 61 is connected between the 28th valve 58 and the 29th valve 59, and the other end is connected to the inlet end of the 25th valve 55; the second bypass branch is provided with a 31st valve 63.

[0043] 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 .

[0044] The first collecting pipe 36 is provided with a first pH value measuring sensor 66, a first conductivity sensor 67, and an ultraviolet sensor 68. The second collecting pipe 37 is provided with a second pH value measuring sensor 69 and a second conductivity sensor 70.

Claims

1. A multifunctional fully automatic standard chromatography system, characterized in that The chromatography system comprises: a replaceable multi-column module, wherein the top and bottom of the replaceable multi-column module are respectively connected to a column top pipeline and a column bottom pipeline; a fluid delivery unit, which is connected to the column bottom pipeline and can deliver different fluids to each chromatography column according to different chromatography stages, including products, eluents and cleaning fluids; and a fluid collection unit, which is connected to the column top pipeline of each chromatography column and can collect different fluids after passing through the chromatography column according to different chromatography stages, including waste liquids and intermediate products.

2. A multifunctional fully automatic standard chromatography system according to claim 1, characterized in that The replaceable multi-column module comprises two or more chromatography columns, and the top and bottom of each chromatography column are respectively connected to a column top pipeline and a column bottom pipeline.

3. A multifunctional fully automatic standard chromatography system according to claim 2, characterized in that A bypass branch pipe is arranged between the top and the bottom of each chromatography column, and the column top pipeline and the column bottom pipeline are connected through the bypass branch pipe.

4. A multifunctional fully automatic standard chromatography system according to claim 1 or 2, characterized in that The fluid collection unit comprises at least two collection pipes, wherein the inlet end of each collection pipe is respectively connected to the column top pipe of each chromatography column; and the outlet end of each collection pipe is respectively connected to a plurality of discharge pipes.

5. A multifunctional fully automatic standard chromatography system according to claim 4, characterized in that The column bottom pipe is connected to a discharge pipe in the corresponding collection pipe.

6. A multifunctional fully automatic standard chromatography system according to any one of claims 1, 2 or 5, characterized in that A plurality of corresponding intermediate pipes are arranged between the fluid conveying unit and the fluid collecting unit, one end of each intermediate pipe is respectively connected to the first liquid inlet main pipe and the outlet end of the bypass module; the other end of each intermediate pipe is connected to the corresponding discharge pipe connected to the bottom pipe.

7. A multifunctional fully automatic standard chromatography system according to any one of claims 1, 2 or 5, characterized in that The fluid delivery unit comprises a first liquid inlet main pipeline and a second liquid inlet main pipeline; the first liquid inlet main pipeline is used to transport a variety of buffer solutions; the second liquid inlet main pipeline is used to transport a mixed solution containing a product; the first liquid inlet main pipeline is respectively connected to the inlet of the mixing unit and the bottom pipeline of each chromatography column; the second liquid inlet main pipeline is connected to the inlet of the mixing unit; and the outlet of the mixing unit is respectively connected to the bottom pipeline of each chromatography column.

8. A multifunctional fully automatic standard chromatography system according to claim 7, characterized in that 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 pipeline and the fluid in the first liquid inlet main pipeline and the second liquid inlet main pipeline.

9. A multifunctional fully automatic standard chromatography system according to claim 8, characterized in that A bypass module is arranged on the outlet pipeline of the mixing unit; 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 pipeline of each chromatography column through a valve.

10. A multifunctional fully automatic standard chromatography system according to claim 9, characterized in that A bypass branch pipe is provided in the bypass module, and a valve is provided on the bypass branch pipe, with two ends respectively connected to the mixing unit and the column bottom pipeline.

11. A multifunctional fully automatic standard chromatography system according to claim 7, characterized in that The inlet end of the first liquid inlet main pipeline is connected to at least three liquid inlet pipelines, valves are respectively arranged on the liquid inlet pipelines, and each valve forms a liquid inlet valve group; the liquid inlet pipelines are connected to different liquid storage containers.

12. A multifunctional fully automatic standard chromatography system according to claim 7 or 11, characterized in that The inlet end of the second liquid inlet main pipeline is connected to at least three liquid inlet pipelines, valves are respectively arranged on the liquid inlet pipelines, and each valve forms a liquid inlet valve group; the liquid inlet pipelines are connected to different liquid outlet containers.

13. A multifunctional fully automatic standard chromatography system according to claim 12, characterized in that At least one of the liquid inlet pipes connected to the first liquid inlet main pipe is communicated with the liquid inlet pipe connected to the second liquid inlet main pipe.

14. A multifunctional fully automatic standard chromatography system according to claim 13, characterized in that A pressure sensor and / or a flow sensor are respectively arranged on the first liquid inlet main pipeline and / or the second liquid inlet main pipeline.

15. A multifunctional fully automatic standard chromatography system according to claim 1, characterized in that The collecting pipe of the fluid collecting unit is provided with a pH sensor and / or a conductivity sensor and / or an ultraviolet sensor respectively.

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