Continuous chromatography system based on multifunctional automatic pilot platform

Abstract

The invention provides a continuous chromatography system based on a multifunctional automatic pilot platform. The continuous chromatography system comprises a first input main pipeline with a first input pump and a second input main pipeline with a second input pump, the first input main pipeline is connected with the two input pipelines, and on-off of the first input main pipeline is controlled through corresponding valves; the second input main pipeline is also respectively connected with the two input pipelines, and the on-off of the second input main pipeline is controlled through corresponding valves; the outlet ends of the two input pipelines are connected with liquid inlet ports of the corresponding movable installation modules respectively, and each movable installation module is further provided with two liquid outlet ports. The liquid outlet port is respectively connected with two collecting pipelines through output pipelines; the two input pipelines are connected with a sample adding inlet and an eluent inlet of the continuous chromatography module through liquid inlet ports, and a sample adding outlet and an eluent outlet of the continuous chromatography module are connected with the two output pipelines through liquid outlet ports; a mixer and a bubble trap are respectively arranged on the first input main pipeline; during use, part of the chromatographic columns are connected in series for sampling, and the other part of the chromatographic columns are used for elution; the method has the advantages that batch treatment time is saved, the filler utilization rate is high, samples can be effectively prevented from penetrating out, the filler volume is saved, the batch treatment time is saved, and the production time is shortened.

Description

Technical Field

[0001] The invention relates to a continuous chromatography device, in particular to a continuous chromatography system based on a multifunctional automatic pilot platform. Background Art

[0002] The downstream processes of biomedicine include filtration, which is mainly used to remove impurities such as cell debris, bacteria, viruses, etc. Filtration includes NFF and TFF; purification is mainly used to separate, purify and purify the target product, involving the use of chromatography columns. Therefore, the downstream technology of biomedicine requires different platforms to be built for different processes to achieve the corresponding processes, so different system combinations are required. The disadvantages are: there are many types of platforms and they have limitations. One set of platforms can only meet the corresponding processes and cannot achieve platform sharing. Therefore, the present invention can modularize the platform, realize different processes, and reduce costs.

[0003] The performance of continuous chromatography separation and purification instruments is more outstanding. However, the existing continuous chromatography separation and purification instruments have complex structures and high production costs. The separation time for complex compound mixtures is long, the filler volume is large, and the filler utilization efficiency is low, and the production efficiency cannot be effectively improved. Summary of the invention

[0004] In order to overcome the above-mentioned deficiencies of the prior art, the present invention provides a continuous chromatography system based on a multifunctional automatic pilot platform, which can realize continuous chromatography and improve the working efficiency of chromatography.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] In view of the above technical problems, the first aspect of the disclosure of the present invention proposes a continuous chromatography system based on a multifunctional automatic pilot platform, wherein the platform system comprises a first input main pipeline with a first input pump and a second input main pipeline with a second input pump; the first input main pipeline connects the two input pipelines and is controlled on and off by corresponding valves; the second input main pipeline is also respectively connected to the above two input pipelines and is controlled on and off by corresponding valves; the outlet ends of the two input pipelines are respectively connected to the liquid inlet ports of the corresponding movable installation modules, and the movable installation module is also provided with two liquid outlet ports; the liquid outlet ports are respectively connected to two collecting pipelines through output pipelines; the two input pipelines are connected to the sample inlet and the eluent inlet of the continuous chromatography module through the liquid inlet port, and the sample outlet and the eluent outlet of the continuous chromatography module are connected to the two output pipelines through the liquid outlet port; a mixer and a bubble trap are respectively provided on the first input main pipeline.

[0007] In some embodiments, the continuous chromatography module includes multiple chromatography columns, and the chromatography columns are connected in series through pipes to form a closed loop, and valves are respectively provided on the connecting pipes; the top inlet and outlet of each chromatography column are respectively connected to the sample inlet and the eluent inlet through valves; the bottom inlet of each chromatography column is respectively connected to the liquid outlet port through valves to connect the two output pipes.

[0008] In some embodiments, the continuous chromatography column module includes four chromatography columns.

[0009] In some embodiments, the first input main pipeline and the second input main pipeline are connected to the two input pipelines through a first valve array group; the first valve array group includes four valves connected end to end to form a rectangular valve array; one group of opposite sides of the rectangular valve array are respectively connected to the corresponding first input main pipeline and the second input main pipeline; another group of opposite sides of the rectangular valve array are respectively connected to the corresponding two input pipelines.

[0010] In some embodiments, the two output pipes are connected to the two collecting pipes through a second valve array group; the second valve array group includes four valves connected end to end to form a rectangular valve array; one group of opposite sides of the rectangular valve array are respectively connected to the corresponding output pipes; and another group of opposite sides of the rectangular valve array are respectively connected to the corresponding two collecting pipes.

[0011] In some embodiments, the outlet end of the second input main pipeline is connected to two collecting pipelines through two valves respectively.

[0012] In some embodiments, one side of the output end of the second input pump of the second input main pipeline is connected to the first input main pipeline through a valve.

[0013] In some embodiments, the first input main pipeline and / or the second input main pipeline are respectively provided with a pressure sensor and / or a flow sensor.

[0014] In some embodiments, the collection pipe is respectively provided with an ultraviolet sensor and / or a first conductivity sensor and / or a pH sensor.

[0015] In some embodiments, the input pipeline is connected to the output pipeline through a valve.

[0016] Beneficial effects of the present invention:

[0017] The present invention can realize flexible installation, expand the module group, and realize modularization by installing the continuous chromatography module in the movable installation module. At the same time, the continuous chromatography can make the sample loading non-stop, save the batch processing time, have a high filler utilization rate, effectively avoid the sample from passing out, save the filler volume, save the batch processing time and shorten the production time.

[0018] Instruction Manual

[0019] Figure 1 It is a schematic diagram of the structure of the present invention.

[0020] Figure 2 It is a schematic diagram of the structure of the continuous chromatography module of the present invention. DETAILED DESCRIPTION

[0021] The present invention will be further described below in conjunction with the accompanying drawings.

[0022] 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.

[0023] Before describing the specific embodiments of the present disclosure in detail, some terms used in the present disclosure are first explained.

[0024] 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.

[0025] Unless otherwise indicated herein, multiple 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.

[0026] As used herein, the terms “connected”, “connected”, “coupled” or “coupled” and the like are not limited to direct connections but also include indirect connections.

[0027] As used herein, a "sample" is a biomolecule, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and their derivatives.

[0028] 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.

[0029] As mentioned in this article, the A1 liquid storage tank, A2 liquid storage tank, A3 liquid storage tank, A4 liquid storage tank, A5 liquid storage tank, P1 liquid storage tank, P1-W liquid storage tank, P2 liquid storage tank, and P2-W liquid storage tank refer to tanks used to store different solutions, not tanks with specific limitations. Any container that can realize the storage function is sufficient.

[0030] 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.

[0031] The application scenarios of this patent are laboratory scale and pilot scale, and the maximum flow range of a single pump is 1000ml / min.

[0032] like Figure 1 As shown, a continuous chromatography system based on a multifunctional automatic pilot platform comprises a first input main pipeline 1, the inlet end of the first input main pipeline 1 is respectively connected to the outlets of multiple liquid storage tanks including an A2 liquid storage tank and a sample liquid storage tank; a first valve 106 and a second valve 104 are respectively arranged at the outlets of the two liquid storage tanks; the first input main pipeline 1 is respectively provided with a first input pump 2, a first pressure sensor 3, a first flow meter 4, a third valve 5, a mixer 6, and an air trap 7 from left to right; the inlet end of the air trap 7 is connected to the first input main pipeline 1 through a fourth valve 8, the outlet end of the air trap 7 is connected to the first input main pipeline 1 through a fifth valve 9, and a sixth valve 10 is arranged on the pipelines at the inlet and outlet ends of the air trap 7. The second input main pipeline 11, the inlet end of the second input main pipeline 11 is respectively connected to the outlets of multiple liquid storage tanks, including the A3 liquid storage tank, the A4 liquid storage tank, and the A5 liquid storage tank; the outlets of the three liquid storage tanks are respectively provided with the seventh valve 102, the eighth valve 101, and the ninth valve 103; the outlet of the A3 liquid storage tank is connected to the inlet end of the first input main pipeline 1 through the tenth valve 105. The second input main pipeline 11 is respectively provided with the second input pump 12, the second pressure sensor 13, the second flowmeter 14, the eleventh valve 15, and the twelfth valve 16 from left to right; the first input main pipeline 1 and the second input main pipeline 11 are connected through the thirteenth valve 17, one end of the thirteenth valve 17 is connected between the third valve 5 and the mixer 6, and the other end is connected between the second flowmeter 14 and the eleventh valve 15.

[0033] The first valve array group 17, the first valve array group 17 is a rectangular valve array formed by connecting four valves at the end, as shown in the figure, the fourteenth valve 18, the fifteenth valve 19, the sixteenth valve 20, and the seventeenth valve 21 in the clockwise direction. The outlet end of the first input main pipeline 1 is connected between the fourteenth valve 18 and the seventeenth valve 21, and the outlet end of the twelfth valve 16 of the second input main pipeline 11 is connected between the fifteenth valve 19 and the sixteenth valve 20. One end of the first input pipeline 22 is connected between the fourteenth valve 18 and the fifteenth valve 19, and the other end of the first input pipeline 22 is connected to the first liquid inlet port 24 of the movable installation module 23; the first input pipeline 22 is provided with an eighteenth valve 25; the sixteenth valve 20 and the seventeenth valve 21 are connected to one end of the second input pipeline 26, and the other end of the second input pipeline 26 is connected to the second liquid inlet port 27 of the movable installation module 23, and the second input pipeline 26 is provided with a nineteenth valve 29.

[0034] The movable installation module 23 further includes a first liquid outlet port 30 and a second liquid outlet port 31 .

[0035] The continuous chromatography module 32 is placed in the swinging installation module 23. The sample inlet 60 of the continuous chromatography module 32 is connected to the first input pipeline 22 through the first liquid inlet port 24; the eluent inlet 61 of the continuous chromatography module 32 is connected to the second input pipeline 26 through the second liquid inlet port 27. The sample outlet 62 of the continuous chromatography module 32 is connected to the first output pipeline 34 through the first liquid outlet port 30, and the eluent inlet 63 of the continuous chromatography module 32 is connected to the second output pipeline 35 through the second liquid outlet port 31. The other ends of the first output pipeline 34 and the second output pipeline 35 are respectively connected to the second valve array 36. The second valve array group 36 is a rectangular valve array formed by four valves connected at the end. As shown in the figure, the 20th valve 37, the 21st valve 38, the 22nd valve 39 and the 23rd valve 40 are clockwise; the other end of the first output pipeline 34 is connected between the 21st valve 38 and the 22nd valve 39, and the other end of the second output pipeline 35 is connected between the 20th valve 37 and the 23rd valve 40. The inlet end of the first collecting pipe 41 is connected between the 20th valve 37 and the 21st valve 38; the inlet end of the second collecting pipe 42 is connected between the 22nd valve 39 and the 23rd valve 40; the first collecting pipe 41 is connected to the P1 liquid storage tank and the P1-W liquid storage tank through the 24th valve 43 and the 25th valve 44 respectively. The second collecting pipe 42 is connected to the P2 liquid storage tank and the P2-W liquid storage tank through the 26th valve 45 and the 27th valve 46 respectively. The outlet of the twelfth valve 16 of the second input main pipe 11 is connected to the first collecting pipe 41 and the second collecting pipe 42 through the first intermediate pipe connection 47 and the second intermediate pipe 48 respectively. The two ends of the first intermediate pipe 47 are respectively provided with the 28th valve 49 and the 29th valve 50; the two ends of the second intermediate pipe 48 are respectively provided with the 30th valve 51 and the 31st valve 52.

[0036] The first output pipeline 34 is provided with a thirty-second valve 53 and a thirty-third valve 54. The second output pipeline 35 is provided with a thirty-fourth valve 55 and a thirty-fifth valve 56. The first input pipeline 22 is connected to the first output pipeline 34 through a first connecting pipeline 57, and a fifty-sixth valve 58 is provided on the first connecting pipeline 57. One end of the first connecting pipeline 57 is located between the first valve array group 17 and the eighteenth valve 25, and the other end of the first connecting pipeline 57 is located between the thirty-second valve 53 and the thirty-third valve 54. The second input pipeline 26 is connected to the second output pipeline 35 through a second connecting pipeline 59, and a fifty-seventh valve 64 is provided on the second connecting pipeline 59. One end of the second connecting pipeline 59 is located between the first valve array group 17 and the nineteenth valve 29, and the other end of the second connecting pipeline 59 is located between the thirty-fourth valve 55 and the thirty-fifth valve 56.

[0037] The first collecting pipe 41 is provided with a UV sensor 93, a first conductivity sensor 94, and a first pH sensor 95. The second collecting pipe 42 is provided with a second conductivity sensor 96 and a second pH sensor 97.

[0038] Reference Figure 2 The continuous chromatography module shown includes four chromatography columns, namely, a first chromatography column 201, a second chromatography column 202, a third chromatography column 203, and a fourth chromatography column 204. The bottom inlet and outlet of the first chromatography column 201 are connected to the top inlet and outlet of the second chromatography column 202 through a first inlet and outlet pipeline 205, and a valve 1 206 is provided on the pipeline; the bottom inlet and outlet of the second chromatography column 202 are connected to the top inlet and outlet of the third chromatography column 203 through a second inlet and outlet pipeline 207, and a valve 2 208 is provided on the pipeline; the bottom inlet and outlet of the third chromatography column 203 are connected to the top inlet and outlet of the fourth chromatography column 204 through a third inlet and outlet pipeline 209, and a valve 3 210 is provided on the pipeline; the bottom inlet and outlet of the fourth chromatography column 204 are connected to the top inlet and outlet of the first chromatography column 201 through a fourth inlet and outlet pipeline 211, and a valve 4 212 is provided on the pipeline.

[0039] The continuous chromatography module also includes a sample inlet pipeline 213 and an elution inlet pipeline 214; the fourth inlet and outlet pipeline 211 is located between the valve 4 212 and the inlet and outlet at the top of the first chromatography column 201, connected to the sample inlet pipeline 213 through the valve 5 215, and connected to the elution inlet pipeline 214 through the valve 6 216. The first inlet and outlet pipeline 205 is located between the valve 1 206 and the inlet and outlet at the top of the second chromatography column 202, connected to the sample inlet pipeline 213 through the valve 7 217, and connected to the elution inlet pipeline 214 through the valve 8 218. The second inlet and outlet pipeline 207 is located between the valve 208 and the inlet and outlet at the top of the third chromatography column 203, connected to the sample inlet pipeline 213 through the valve 9 219, and connected to the elution inlet pipeline 214 through the valve 10 220. The third inlet and outlet pipe 209 is located at the inlet and outlet of the valve three 210 and the top of the fourth chromatography column 204 , and is connected to the sample inlet pipe 213 through the valve eleven 221 , and is connected to the elution inlet pipe 214 through the valve twelve 222 .

[0040] The continuous chromatography module also includes a sample-adding liquid outlet pipeline 223 and an elution liquid outlet pipeline 224. The fourth inlet and outlet pipeline 211 is located between the valve 4 212 and the inlet and outlet at the bottom of the fourth chromatography column 204, connected to the sample-adding liquid outlet pipeline 222 through the valve 13 225, and connected to the elution liquid outlet pipeline 223 through the valve 14 226. The first inlet and outlet pipeline 205 is located between the valve 1 206 and the inlet and outlet at the bottom of the first chromatography column 201, connected to the sample-adding liquid outlet pipeline 223 through the valve 15 227, and connected to the elution liquid outlet pipeline 224 through the valve 16 228. The second inlet and outlet pipeline 207 is located between the valve 208 and the inlet and outlet at the bottom of the second chromatography column 202, connected to the sample-adding liquid outlet pipeline 223 through the valve 17 229, and connected to the elution liquid outlet pipeline 224 through the valve 18 230. The third inlet and outlet pipe 209 is located at the inlet and outlet of the valve three 210 and the bottom of the third chromatography column 203, and is connected to the sample outlet pipe 223 through the valve nineteen 231, and is connected to the elution outlet pipe 224 through the valve twenty 232.

[0041] When in use, three of the chromatography columns are in series continuous loading, and the other chromatography column is in elution. The sample enters the first chromatography column 201 through the sample inlet pipeline 213 after the valve five 215 is opened, the valve one 206 is opened, and then enters the second chromatography column 202 through the first inlet and outlet pipeline 205, the valve two 208 is opened, and enters the third chromatography column 203 through the second inlet and outlet pipeline 207, and then the valve nineteen 231 is opened, and the liquid enters the sample outlet pipeline 223 through the valve nineteen 231, so as to be collected and monitored; at the same time, the eluent enters through the elution inlet pipeline 214, the valve twelve 222 is opened, and the eluent enters the fourth chromatography column 204 through the valve twelve 222 and the third inlet and outlet pipeline 209, and the eluent enters the fourth inlet and outlet pipeline 211 from the bottom outlet of the fourth chromatography column 204, and at this time, the valve fourteen 226 is opened, and the eluent enters the elution outlet pipeline 224 through the valve fourteen 226, so as to be collected and monitored.

[0042] By analogy, when the second chromatography column 202, the third chromatography column 203, and the fourth chromatography column 204 are loaded with samples, the first chromatography column 201 is eluted. When the third chromatography column 203, the fourth chromatography column 204, and the first chromatography column 201 are loaded with samples, the second chromatography column 202 is eluted. When the fourth chromatography column 204, the first chromatography column 201, and the second chromatography column 202 are loaded with samples, the third chromatography column 203 is eluted.

Claims

1. A continuous chromatography system based on a multifunctional automatic pilot platform, characterized in that: The platform system includes a first input main pipeline with a first input pump and a second input main pipeline with a second input pump; the first input main pipeline connects the two input pipelines and is controlled on and off by corresponding valves; the second input main pipeline is also respectively connected to the above-mentioned two input pipelines and is controlled on and off by corresponding valves; the outlet ends of the two input pipelines are respectively connected to the liquid inlet ports of the corresponding movable installation modules, and the movable installation module is also provided with two liquid outlet ports; the liquid outlet ports are respectively connected to two collecting pipelines through output pipelines; the two input pipelines are connected to the sample inlet and eluent inlet of the continuous chromatography module through the liquid inlet port, and the sample outlet and eluent outlet of the continuous chromatography module are connected to the two output pipelines through the liquid outlet port; a mixer and a bubble trap are respectively provided on the first input main pipeline.

2. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 1, characterized in that: The continuous chromatography module comprises a plurality of chromatography columns, each of which is connected in series through pipelines to form a closed loop, and valves are respectively arranged on the connecting pipelines; the top inlet and outlet of each chromatography column are respectively connected to the sample inlet and the eluent inlet through valves; the bottom inlet of each chromatography column is respectively connected to the liquid outlet port and two output pipelines through valves.

3. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 2, characterized in that: The continuous chromatography column module comprises four chromatography columns.

4. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 3, characterized in that: The first input main pipeline and the second input main pipeline are connected to the two input pipelines through a first valve array group; the first valve array group includes four valves connected end to end to form a rectangular valve array; one group of opposite sides of the rectangular valve array are respectively connected to the corresponding first input main pipeline and the second input main pipeline; the other group of opposite sides of the rectangular valve array are respectively connected to the corresponding two input pipelines.

5. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 3, characterized in that: The two output pipes are connected to the two collecting pipes through a second valve array group; the second valve array group includes four valves connected end to end to form a rectangular valve array; one group of opposite sides of the rectangular valve array are respectively connected to the corresponding output pipes; the other group of opposite sides of the rectangular valve array are respectively connected to the corresponding two collecting pipes.

6. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 3, characterized in that: The outlet end of the second input main pipeline is connected to two collecting pipelines through two valves respectively.

7. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 3, characterized in that: One side of the output end of the second input pump of the second input main pipeline is connected to the first input main pipeline through a valve.

8. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 3, characterized in that: The first input main pipeline and / or the second input main pipeline are respectively provided with a pressure sensor and / or a flow sensor.

9. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 3, characterized in that: The collecting pipe is respectively provided with an ultraviolet sensor and / or a first conductivity sensor and / or a pH sensor.

10. The continuous chromatography system based on the multifunctional automatic pilot platform according to claim 3, characterized in that: The input pipeline is communicated with the output pipeline through a valve.

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