Continuous chromatography system based on multi-functional automatic pilot platform

Abstract

A continuous chromatography system based on a multi-functional automatic pilot platform. The continuous chromatography system comprises a first input main tube (1) having a first input pump (2) and a second input main tube (11) having a second input pump (12); the first input main tube (11) is connected to two input tubes, and connection / disconnection is controlled by means of corresponding valves; the second input main tube (11) is also separately connected to said two input tubes, and connection / disconnection is controlled by means of corresponding valves; the two input tubes are connected to a sample loading inlet (60) and an eluent inlet (63) of a continuous chromatography module (32) by means of liquid inlet ports, and a sample loading outlet (60) and an eluent outlet (63) of the continuous chromatography module (32) are connected to two output tubes by means of liquid outlet ports; and a mixer (6) and a bubble trap (7) are separately provided on the first input main tube (1). During use, sample loading in series is carried out in some chromatographic columns, and elution is carried out in the other chromatographic column.

Description

Continuous chromatography system based on multifunctional automatic pilot platform TECHNICAL FIELD

[0001] The present application relates to continuous chromatography equipment, in particular to a continuous chromatography system based on a multifunctional automatic pilot platform. BACKGROUND

[0002] The downstream process of biological medicine includes filtration, mainly used for removing impurities such as cell fragments, bacteria, viruses, etc. The filtration includes NFF and TFF; purification, mainly used for separating, purifying and purifying the target product, involving the use of chromatography column. Therefore, the downstream technology of biological medicine needs to build different platforms for different processes to realize the corresponding process, so different systems are needed, and the disadvantages are: the types of platforms are many, which have limitations, and a set of platform can only meet the corresponding process, and the sharing of the platform cannot be realized. Therefore, the present application can modularize the platform to realize different processes, which can reduce the cost.

[0003] The performance of the continuous chromatography separation and purification instrument is more prominent, however, the existing continuous chromatography separation and purification instrument equipment is complex, the manufacturing cost is high, the separation time of complex compound mixed system is long, the filler volume is large, the utilization efficiency of the filler is not high, and the production efficiency cannot be effectively improved. SUMMARY

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

[0005] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is:

[0006] In order to solve the above-mentioned technical problems, the first aspect of the present application discloses a continuous chromatography system based on a multifunctional automatic pilot platform, which comprises a first input main pipeline with a first input pump, a second input main pipeline with a second input pump; the first input main pipeline is connected with two input pipelines, and the on-off is controlled through the corresponding valve; the second input main pipeline is also connected with the above-mentioned two input pipelines respectively, and the on-off is controlled through the corresponding valve; the outlet ends of the two input pipelines are respectively connected with the liquid inlet ports of the corresponding movable installation modules, and the movable installation modules are also provided with two liquid outlet ports; the liquid outlet ports are respectively connected with two collection pipelines through the output pipelines; the two input pipelines are connected with the sample inlet and the eluent inlet of the continuous chromatography module through the liquid inlet ports, and the sample outlet and the eluent outlet of the continuous chromatography module are connected with the two output pipelines through the liquid outlet ports; the first input main pipeline is respectively provided with a mixer and a bubble trap.

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

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

[0009] In some embodiments, the first input main pipe and the second input main pipe are connected to two input pipes through a first valve array; the first valve array comprises four valves connected end to end to form a rectangular valve array; one pair of opposite sides of the rectangular valve array is connected to the corresponding first input main pipe and second input main pipe, respectively; and the other pair of opposite sides of the rectangular valve array is connected to the corresponding two input pipes, respectively.

[0010] In some embodiments, the two output pipes are connected to two collection pipes through a second valve array; the second valve array comprises four valves connected end to end to form a rectangular valve array; one pair of opposite sides of the rectangular valve array is connected to the corresponding output pipe, respectively; and the other pair of opposite sides of the rectangular valve array is connected to the corresponding two collection pipes, respectively.

[0011] In some embodiments, the outlet end of the second input main pipe is connected to two collection pipes through two valves, respectively.

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

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

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

[0015] In some embodiments, the input pipes are communicated with the output pipes through valves.

[0016] The beneficial effects of the present application are as follows:

[0017] The present application realizes flexible installation, expands the module group, and can 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 uninterrupted, save batch processing time, have high filler utilization rate, effectively avoid sample penetration, save filler volume, save batch processing time, and shorten production time, which plays an advantageous role.

[0018] The accompanying drawings

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

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

[0021] The present application will be further described with reference to the drawings

[0022] The technical content of the present application is described below through specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present application from the disclosure of the present application. The present application can also be implemented or applied through other different embodiments. Those skilled in the art can make various modifications and changes without departing from the spirit of the present application.

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

[0024] Unless otherwise defined in the following, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Reference herein to technical terms used herein is intended to refer to the technical terms as commonly understood by those skilled in the art, including variations or substitutions of the technology that are obvious to those skilled in the art or equivalent replacements of the technology. Although the following terms are believed to be well understood by those skilled in the art, the following definitions are set forth to better explain the present application. When a trade name appears herein, it is intended to refer to its corresponding product. All patents, published patent applications, and publications cited herein are incorporated by reference herein.

[0025] Unless otherwise stated in the text, a plurality of refers to "one or more", "the", includes a plurality of references. The expression "one or more" or "at least one" can mean 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.

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

[0027] The "sample" as described herein is a biomolecule, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and derivatives thereof.

[0028] The term "on-line monitoring" or "real-time monitoring" as used herein refers to detecting 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. in real time 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.

[0029] The A1 reservoir, A2 reservoir, A3 reservoir, A4 reservoir, A5 reservoir, P1 reservoir, P1-W reservoir, P2 reservoir, P2-W reservoir as referred to herein refer to tanks for storing different solutions, and are not specific defined tanks, but any container capable of storing the solution.

[0030] 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, and are only used to represent relative positional relationship, which can change accordingly when the absolute position of the described object changes.

[0031] 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.

[0032] As shown in FIG. 1, the continuous chromatography system based on the multifunctional automatic pilot platform comprises a first input main pipeline 1, the inlet end of the first input main pipeline 1 is connected with the outlets of a plurality of reservoirs including an A2 reservoir and a sample reservoir; the outlets of two reservoirs are respectively provided with a first valve 106 and a second valve 104; the first input main pipeline 1 is provided from left to right 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; the inlet end of the air trap 7 is connected with the first input main pipeline 1 through a fourth valve 8, the outlet end of the air trap 7 is connected with the first input main pipeline 1 through a fifth valve 9, and the pipelines at the inlet end and the outlet end of the air trap 7 are provided with a sixth valve 10. A second input main pipeline 11, the inlet end of the second input main pipeline 11 is connected with the outlets of a plurality of reservoirs including an A3 reservoir, an A4 reservoir, and an A5 reservoir; the outlets of three reservoirs are respectively provided with a seventh valve 102, an eighth valve 101, and a ninth valve 103; the outlet of the A3 reservoir is connected with the inlet end of the first input main pipeline 1 through a tenth valve 105. The second input main pipeline 11 is provided from left to right with a second input pump 12, a second pressure sensor 13, a second flow meter 14, an eleventh valve 15, and a twelfth valve 16; the first input main pipeline 1 and the second input main pipeline 11 are connected through a 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 flow meter 14 and the eleventh valve 15.

[0033] The first valve array group 17 is a rectangular valve array formed by four valves connected in series, which is shown in the figure, the fourteenth valve 18, the fifteenth valve 19, the sixteenth valve 20 and the seventeenth valve 21 in a clockwise direction. The outlet end of the first input main pipe 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 pipe 11 is connected between the fifteenth valve 19 and the sixteenth valve 20. The first input pipe 22 is connected to the fourteenth valve 18 and the fifteenth valve 19, and the other end of the first input pipe 22 is connected to the first liquid inlet port 24 of the movable mounting module 23. The eighteenth valve 25 is arranged on the first input pipe 22. The sixteenth valve 20 and the seventeenth valve 21 are connected to one end of the second input pipe 26, and the other end of the second input pipe 26 is connected to the second liquid inlet port 27 of the movable mounting module 23. The nineteenth valve 29 is arranged on the second input pipe 26.

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

[0035] The continuous chromatography module 32 is placed in the movable 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. 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 end of the first output pipeline 34 is connected to the twenty-first valve 38 and the twenty-second valve 39, and the other end of the second output pipeline 35 is connected to the twentieth valve 37 and the twenty-third valve 40. The twentieth valve 37 and the twenty-first valve 38 are connected to the inlet end of the first collection pipeline 41. The twenty-second valve 39 and the twenty-third valve 40 are connected to the inlet end of the second collection pipeline 42. The first collection pipeline 41 is connected to the P1 storage tank and the P1-W storage tank through the twenty-fourth valve 43 and the twenty-fifth valve 44. The second collection pipeline 42 is connected to the P2 storage tank and the P2-W storage tank through the twenty-sixth valve 45 and the twenty-seventh valve 46. The outlet of the twelfth valve 16 of the second input main pipeline 11 is connected to the first collection pipeline 41 and the second collection pipeline 42 through the first intermediate pipeline 47 and the second intermediate pipeline 48. The two ends of the first intermediate pipeline 47 are respectively provided with the twenty-eighth valve 49 and the twenty-ninth valve 50. The two ends of the second intermediate pipeline 48 are respectively provided with the thirtieth valve 51 and the thirty-first valve 52.

[0036] The twentieth valve 37 and the twenty-first valve 38 are connected to the inlet end of the first collection pipeline 41. The twenty-second valve 39 and the twenty-third valve 40 are connected to the inlet end of the second collection pipeline 42. The first collection pipeline 41 is connected to the P1 storage tank and the P1-W storage tank through the twenty-fourth valve 43 and the twenty-fifth valve 44. The second collection pipeline 42 is connected to the P2 storage tank and the P2-W storage tank through the twenty-sixth valve 45 and the twenty-seventh valve 46. The outlet of the twelfth valve 16 of the second input main pipeline 11 is connected to the first collection pipeline 41 and the second collection pipeline

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

[0038] Referring to the continuous chromatography module shown in FIG. 2, it comprises four chromatography columns, i.e. 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 206 is arranged 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 208 is arranged 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 210 is arranged 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 212 is arranged on the pipeline.

[0039] The continuous chromatography module further comprises a sample loading pipeline 213 and an elution pipeline 214. The fourth inlet and outlet pipeline 211 is connected to the sample loading pipeline 213 through a valve 215 and to the elution pipeline 214 through a valve 216 at a position between the valve 212 and the top inlet and outlet of the first chromatography column 201. The first inlet and outlet pipeline 205 is connected to the sample loading pipeline 213 through a valve 217 and to the elution pipeline 214 through a valve 218 at a position between the valve 206 and the top inlet and outlet of the second chromatography column 202. The second inlet and outlet pipeline 207 is connected to the sample loading pipeline 213 through a valve 219 and to the elution pipeline 214 through a valve 220 at a position between the valve 208 and the top inlet and outlet of the third chromatography column 203. The third inlet and outlet pipeline 209 is connected to the sample loading pipeline 213 through a valve 221 and to the elution pipeline 214 through a valve 222 at a position between the valve 210 and the top inlet and outlet of the fourth chromatography column 204.

[0040] The continuous chromatography module further comprises a sample injection outlet conduit 223 and an elution outlet conduit 224. The fourth inlet and outlet conduit 211 is connected to the sample injection outlet conduit 223 by valve 13 225 and to the elution outlet conduit 224 by valve 14 226. The first inlet and outlet conduit 205 is connected to the sample injection outlet conduit 223 by valve 15 227 and to the elution outlet conduit 224 by valve 16 228. The second inlet and outlet conduit 207 is connected to the sample injection outlet conduit 223 by valve 17 229 and to the elution outlet conduit 224 by valve 18 230. The third inlet and outlet conduit 209 is connected to the sample injection outlet conduit 223 by valve 19 231 and to the elution outlet conduit 224 by valve 20 232.

[0041] In use, three of the columns are in series for sample injection and the fourth column is used for elution. The sample is injected into the first column 201 via the sample injection inlet conduit 213 and valve 5 215, then into the second column 202 via the first inlet and outlet conduit 205 and valve 1 206, then into the third column 203 via the second inlet and outlet conduit 207 and valve 2 208, then into the sample injection outlet conduit 223 via valve 19 231 and the third inlet and outlet conduit 209, and collected and monitored. Simultaneously, the eluent is injected into the fourth column 204 via the eluent inlet conduit 214 and valve 12 222, then into the fourth inlet and outlet conduit 211 via valve 12 222 and the third inlet and outlet conduit 209, and then into the elution outlet conduit 224 via valve 14 226 and the fourth inlet and outlet conduit 211, and collected and monitored.

[0042] By analogy, when the second column 202, the third column 203 and the fourth column 204 are used for sample injection, the first column 201 is used for elution. When the third column 203, the fourth column 204 and the first column 201 are used for sample injection, the second column 202 is used for elution. When the fourth column 204, the first column 201 and the second column 202 are used for sample injection, the third column 203 is used for elution.

Claims

1. A continuous chromatography system based on a multifunctional automated pilot platform, characterized in that, The platform system includes a first input main pipe with a first input pump and a second input main pipe with a second input pump. The first input main pipe connects to the two input pipes and is controlled by corresponding valves. The second input main pipe also connects to the two input pipes and is controlled by corresponding valves. The outlets of the two input pipes are connected to the inlet ports of their respective movable mounting modules. The movable mounting modules also have two outlet ports. The outlet ports are connected to two collection pipes via output pipes. The two input pipes are connected to the sample inlet and eluent inlet of the continuous chromatography module via the inlet ports. The sample outlet and eluent outlet of the continuous chromatography module are connected to two output pipes via the outlet ports. A mixer and a bubble trap are installed on the first input main pipe. The continuous chromatography module includes multiple chromatography columns, which are connected in series through pipes to form a closed loop. Valves are installed on the connecting pipes. The top inlet and outlet of each chromatography column are connected to the sample loading inlet and the eluent inlet through valves, respectively. The bottom inlet of each chromatography column is connected to two output pipes through valves.

2. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 1, characterized in that, The continuous chromatography column module uses four chromatography columns.

3. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 2, characterized in that, The first input main pipe and the second input main pipe are connected to the two input pipes 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 pair of opposite sides of the rectangular valve array is connected to the corresponding first input main pipe and the second input main pipe respectively; the other pair of opposite sides of the rectangular valve array is connected to the corresponding two input pipes respectively.

4. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 2, characterized in that, The two output pipes are connected to two collection pipes through a second valve array; the second valve array includes four valves connected end to end to form a rectangular valve array; one set of opposite sides of the rectangular valve array is connected to the corresponding output pipes; the other set of opposite sides of the rectangular valve array is connected to the corresponding two collection pipes.

5. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 2, characterized in that, The outlet end of the second input main pipeline is connected to two collection pipelines via two valves.

6. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 2, characterized in that, The output end of the second input pump in the second input main pipeline is connected to the first input main pipeline via a valve.

7. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 2, characterized in that, Pressure sensors and / or flow sensors are respectively installed on the first input main pipe and / or the second input main pipe.

8. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 2, characterized in that, The collection pipe is equipped with an ultraviolet sensor and / or a first conductivity sensor and / or a pH sensor.

9. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 2, characterized in that, The input pipe is connected to the output pipe via a valve.

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