Continuous chromatography system based on multifunctional automatic pilot platform

Abstract

The utility model 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 utility model has the advantages that the batch processing time is saved, the filler utilization rate is high, samples can be effectively prevented from penetrating out, the filler volume is saved, the batch processing time is saved, and the production time is shortened.

Description

TECHNICAL FIELD

[0001] The utility model relates to continuous chromatography equipment, especially continuous chromatography system based on 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 and the like. The filtration includes NFF and TFF. Purification is mainly used for separating, purifying and purifying target products, and involves the use of chromatography columns. 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 to match, and the disadvantage is that the types of platforms are many and have limitations. A set of platform can only meet the corresponding process, and the sharing of the platform cannot be realized. Therefore, the utility model can modularize the platform, realize different processes, and reduce the cost.

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

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

[0005] In order to achieve the above-mentioned purpose, the utility model adopts the technical scheme that:

[0006] In order to solve the above-mentioned technical problems, the first aspect of the utility model discloses a continuous chromatography system based on multifunctional automatic pilot platform. The platform system 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 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. 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. 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 the eluent outlet through the valves and connected to two output pipes.

[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 utility model are as follows:

[0017] The utility model discloses a continuous chromatography module is installed in the movable installation module, realizes flexible installation, expands the module group, can realize the modularization. Meanwhile, continuous chromatography can make that sample loading does not stop, saves batch processing time, and the utilization rate of filler is high, can effectively avoid that sample penetrates, saves the volume of filler, saves batch processing time and shortens production time and plays the beneficial role. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 The structure schematic diagram of the utility model.

[0019] Figure 2 The structure schematic diagram of the utility model continuous chromatography module. DETAILED DESCRIPTION

[0020] The utility model will be further described below in combination with the drawings

[0021] The technical content of the utility model is described below through specific embodiments, and other advantages and effects of the utility model can be easily understood by those skilled in the art from the disclosure of the specification. The utility model 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 utility model.

[0022] Before the specific embodiments of the present disclosure are described in detail, first, some terms used in the present disclosure are explained.

[0023] Unless otherwise defined in the following, all technical and scientific terms used herein are intended to have the same meaning as commonly understood by one of ordinary skill in the art. Reference to a technical term used herein is intended to refer to the technical term as commonly understood in the art, including variations or substitutions of the technical term that are obvious to one of ordinary skill in the art or equivalent technical terms. 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 better explain the present disclosure. When a trade name appears herein, it is intended to refer to its corresponding product. All patents, published patent applications, and publications recited herein are incorporated by reference herein.

[0024] Unless otherwise indicated herein, plural instances of items, such as "a", "an", "the", can include one or more of the items. The term "one or more" or "at least one" can mean one, two, three, four, five, six, seven, eight, nine, or more.

[0025] The terms "connected", "coupled", or "coupling", or similar terms as used herein are not limited to direct connections, but also include indirect connections.

[0026] A "sample" as described herein is a biomolecule, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids, and derivatives thereof.

[0027] As used herein, "online monitoring" or "real-time monitoring" refers to the real-time detection of certain parameters or properties of the buffer solution, reaction fluid, or fluid exiting the flow reactor during the use of the chromatography system, such as pH, pressure, flow rate, and conductivity. Unlike offline detection or analysis, online or real-time monitoring provides immediate feedback on the detection results.

[0028] The storage tanks A1, A2, A3, A4, A5, P1, P1-W, P2, and P2-W mentioned in this article refer to tanks used to store different solutions, not necessarily tanks with specific limitations. Any container that can perform the storage function is acceptable.

[0029] The positional terms "up," "down," "left," "right," "front," and "back" used in this article are determined based on the layout direction of the accompanying drawings in the specification. They are only used to indicate relative positional relationships. When the absolute position of the object being described changes, the relative positional relationship may also change accordingly.

[0030] This patent is applicable to laboratory and pilot-scale applications, with a maximum flow rate of 1000 ml / min for a single pump.

[0031] like Figure 1 As shown, the continuous chromatography system based on the multifunctional automatic pilot platform includes a first input main pipeline 1. The inlet end of the first input main pipeline 1 is connected to the outlets of multiple storage tanks, including storage tank A2 and sample storage tank. The outlets of the two storage tanks are respectively equipped with a first valve 106 and a second valve 104. From left to right, the first input main pipeline 1 is equipped 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 to the first input main pipeline 1 through a fourth valve 8, and the outlet end of the air trap 7 is connected to the first input main pipeline 1 through a fifth valve 9. A sixth valve 10 is installed on the pipelines at the inlet and outlet ends of the air trap 7. The second input main pipe 11 has its inlet connected to the outlets of multiple storage tanks, including storage tanks A3, A4, and A5. The outlets of the three storage tanks are respectively equipped with a seventh valve 102, an eighth valve 101, and a ninth valve 103. The outlet of storage tank A3 is connected to the inlet of the first input main pipe 1 via a tenth valve 105. From left to right, the second input main pipe 11 is equipped 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 pipe 1 and the second input main pipe 11 are connected via a thirteenth valve 17, one end of which 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.

[0032] 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 at one end, 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, and the nineteenth valve 29 is arranged on the second input pipe 26.

[0033] The movable mounting module 23 further comprises a first liquid outlet port 30 and a second liquid outlet port 31.

[0034] The swing installation module 23 is provided with a continuous chromatography module 32, and 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 end of the first output pipeline 34 and the second output pipeline 35 is respectively connected to the second valve array 36, and the second valve array 36 is formed by four valves connected in a rectangular shape in a clockwise direction, as shown in the figure, the twentieth valve 37, the twenty-first valve 38, the twenty-second valve 39 and the twenty-third valve 40; the other end of the first output pipeline 34 is connected between the twenty-first valve 38 and the twenty-second valve 39, and the other end of the second output pipeline 35 is connected between the twentieth valve 37 and the twenty-third valve 40. The first collection pipeline 41 is connected to the inlet end between the twentieth valve 37 and the twenty-first valve 38; the second collection pipeline 42 is connected to the inlet end between the twenty-second valve 39 and the twenty-third valve 40; the first collection pipeline 41 is respectively 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 respectively 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 respectively 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.

[0035] The first output pipeline 34 is provided with the thirty-second valve 53 and the thirty-third valve 54. The second output pipeline 35 is provided with the thirty-fourth valve 55 and the thirty-fifth valve 56. The first input pipeline 22 is connected to the first output pipeline 34 through the first connecting pipeline 57, and the first connecting pipeline 57 is provided with the fifty-sixth valve 58. One end of the first connecting pipeline 57 is located between the first valve array 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 the second connecting pipeline 59, and the second connecting pipeline 59 is provided with the fifty-seventh valve 64. One end of the second connecting pipeline 59 is located between the first valve array 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.

[0036] 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.

[0037] Referring to Figure 2 The continuous chromatography module shown in the figure comprises 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 is connected to the top inlet and outlet of the second chromatography column 202 through a first inlet and outlet pipeline 205, and a valve one 206 is arranged on the pipeline. The bottom inlet and outlet of the second chromatography column 202 is connected to the top inlet and outlet of the third chromatography column 203 through a second inlet and outlet pipeline 207, and a valve two 208 is arranged on the pipeline. The bottom inlet and outlet of the third chromatography column 203 is connected to the top inlet and outlet of the fourth chromatography column 204 through a third inlet and outlet pipeline 209, and a valve three 210 is arranged on the pipeline. The bottom inlet and outlet of the fourth chromatography column 204 is connected to the top inlet and outlet of the first chromatography column 201 through a fourth inlet and outlet pipeline 211, and a valve four 212 is arranged on the pipeline.

[0038] The continuous chromatography module further comprises a sample loading pipeline 213 and an elution liquid pipeline 214. The fourth inlet and outlet pipeline 211 is connected to the sample loading pipeline 213 through a valve five 215 and to the elution liquid pipeline 214 through a valve six 216 at a position between the valve four 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 seven 217 and to the elution liquid pipeline 214 through a valve eight 218 at a position between the valve one 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 nine 219 and to the elution liquid pipeline 214 through a valve ten 220 at a position between the valve two 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 eleven 221 and to the elution liquid pipeline 214 through a valve twelve 222 at a position between the valve three 210 and the top inlet and outlet of the fourth chromatography column 204.

[0039] 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.

[0040] In use, three of the columns are in series for sample injection and the fourth column is used for elution. The sample is injected through the sample injection inlet conduit 213, valve 5 215 is opened and the sample is injected into the first column 201. Valve 1 206 is opened and the sample is injected through the first inlet and outlet conduit 205 into the second column 202. Valve 2 208 is opened and the sample is injected through the second inlet and outlet conduit 207 into the third column 203. Valve 19 231 is opened and the sample is collected and monitored through the sample injection outlet conduit 223. Simultaneously, the elution liquid is injected through the elution inlet conduit 214 and valve 12 222 is opened. The elution liquid is injected through valve 12 222, the third inlet and outlet conduit 209 and into the fourth column 204. The elution liquid is collected and monitored through the elution outlet conduit 224.

[0041] 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.

2. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 1, characterized in that, The continuous chromatography module includes multiple chromatography columns, which are connected in series 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, respectively, through valves. The bottom inlet of each chromatography column is connected to the liquid outlet port, which is connected to two output pipes, through valves.

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

4. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 3, 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.

5. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 3, 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 pair of opposite sides of the rectangular valve array is connected to the corresponding output pipes; the other pair of opposite sides of the rectangular valve array is connected to the corresponding two collection pipes.

6. The continuous chromatography system based on a multifunctional automated pilot platform according to claim 3, characterized in that, The outlet end of the second input main pipe is connected to two collection pipes via two valves.

7. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 3, 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.

8. The continuous chromatography system based on a multifunctional automatic pilot platform according to claim 3, 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.

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

10. The continuous chromatography system based on a multifunctional automated pilot platform according to claim 3, characterized in that, The input pipe is connected to the output pipe via a valve.

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