Continuous chromatography system based on a multifunctional automated pilot platform

Abstract

The application provides a continuous chromatography system based on a multifunctional automatic pilot platform, which 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 two input pipelines and the connection and disconnection are controlled through corresponding valves; the second input main pipeline is also connected with the two input pipelines respectively and the connection and disconnection are controlled through corresponding valves; the outlet ends of the two input pipelines are connected with the liquid inlet ports of the corresponding movable installation modules respectively, the movable installation modules are further provided with two liquid outlet ports; the liquid outlet ports are connected with two collection pipelines through output pipelines respectively; the two input pipelines are connected with the sample inlet and the eluent inlet of a continuous chromatography module through liquid inlet ports; the sample outlet and the eluent outlet of the continuous chromatography module are connected with two output pipelines through liquid outlet ports; a mixer and a bubble trap are respectively arranged on the first input main pipeline; when in use, part of the chromatographic columns are connected in series for sample loading and the other part of the chromatographic columns are used for elution; the application has the advantages of saving batch processing time, high filler utilization rate, effectively avoiding sample breakthrough, saving filler volume, saving batch processing time and shortening production time.

Description

Technical Field

[0001] This invention relates to continuous chromatography equipment, and more particularly to a continuous chromatography system based on a multifunctional automated pilot platform. Background Technology

[0002] Downstream biopharmaceutical processes include filtration, primarily used to remove impurities such as cell debris, bacteria, and viruses. Filtration includes NFF and TFF. Purification, mainly used for the separation, purification, and refining of target products, involves the use of chromatography columns. Therefore, downstream biopharmaceutical technologies require different platforms to implement different processes, necessitating different system combinations. The drawbacks are: the variety of platforms is limited, and a single platform can only meet the specific process requirements, preventing platform sharing. This invention modularizes the platform to implement different processes, thereby reducing costs.

[0003] Continuous chromatography separation and purification instruments have superior performance; however, existing continuous chromatography separation and purification instruments are complex in structure and high in manufacturing cost. They also have long separation times for complex compound mixtures, large packing volume, and low packing utilization efficiency, which fails to effectively improve production efficiency. Summary of the Invention

[0004] To overcome the shortcomings 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] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0006] To address the aforementioned technical problems, the first aspect of this invention discloses a continuous chromatography system based on a multifunctional automatic pilot platform. This 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 to the two input pipelines, and their on / off states are controlled by corresponding valves. The second input main pipeline also connects to the two input pipelines, and their on / off states are controlled by corresponding valves. The outlet ends of the two input pipelines are respectively connected to the inlet ports of their respective movable mounting modules. The movable mounting modules also have two outlet ports. The outlet ports are respectively connected to two collection pipelines via output pipelines. The two input pipelines are connected to the sample loading inlet and eluent inlet of a continuous chromatography module via their inlet ports. The sample loading outlet and eluent outlet of the continuous chromatography module are connected to two output pipelines via their outlet ports. A mixer and a bubble trap are respectively installed on the first input main pipeline.

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

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

[0009] In some embodiments, 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.

[0010] In some embodiments, the two output pipes are connected to two collection pipes via 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.

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

[0012] In some embodiments, one side of 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.

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

[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 pipe is connected to the output pipe via a valve.

[0016] The beneficial effects of this invention are:

[0017] This invention achieves flexible installation and modularization by installing a continuous chromatography module within an active mounting module. Simultaneously, continuous chromatography allows for uninterrupted sample loading, saving batch processing time, increasing packing material utilization, effectively preventing sample leakage, saving packing material volume, and thus reducing batch processing time and production time.

[0018] Instruction manual illustrations

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

[0020] Figure 2 This is a schematic diagram of the continuous chromatography module structure of the present invention. Detailed Implementation

[0021] The invention will now be further described with reference to the accompanying drawings.

[0022] The technical content of the present invention is illustrated below through specific embodiments. Those skilled in the art can easily understand other advantages and effects of the present invention from the content 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 detailing the specific embodiments of this disclosure, some terms used in this disclosure will be explained first.

[0024] Unless otherwise defined below, 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. References to technical terms herein refer to techniques commonly understood in the art, including variations or equivalent substitutions of techniques that are obvious to one of ordinary skill in the art. While it is believed that the following terms will be well understood by one of ordinary skill in the art, the following definitions are set forth to better explain the invention. When trade names appear herein, they are intended to refer to the corresponding goods or services. All patents, published patent applications, and publications cited herein are incorporated herein by reference.

[0025] Unless otherwise stated in the text, multiple references such as "a kind of" or "the" include plural references. The expressions "a kind of or more kinds of" or "at least one kind of" can mean 1, 2, 3, 4, 5, 6, 7, 8, 9 kinds of or more kinds of.

[0026] The terms “connection,” “link,” “coupled,” or “coupled” used in this article are not limited to direct connections; they also include indirect connections.

[0027] As used in this article, “sample” refers to biomolecules, including proteins, nucleic acids, lipids, carbohydrates, small nucleotides, amino acids and their derivatives.

[0028] 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.

[0029] 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.

[0030] 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.

[0031] This patent is applicable to laboratory and pilot-scale applications, with a maximum flow rate of 1000 ml / min for a single pump.

[0032] 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.

[0033] The first valve array 17 is a rectangular valve array formed by four valves connected end to end, as shown in the figure, in a clockwise direction: fourteenth valve 18, fifteenth valve 19, sixteenth valve 20, and seventeenth valve 21. The outlet end of the first main input pipe 1 is connected between fourteenth valve 18 and seventeenth valve 21. The outlet end of the twelfth valve 16 of the second main input pipe 11 is connected between fifteenth valve 19 and sixteenth valve 20. One end of the first input pipe 22 is connected between fourteenth valve 18 and fifteenth valve 19, and the other end of the first input pipe 22 is connected to the first inlet port 24 of the movable mounting module 23. An eighteenth valve 25 is provided on the first input pipe 22. One end of the second input pipe 26 is connected between sixteenth valve 20 and seventeenth valve 21, and the other end of the second input pipe 26 is connected to the second inlet port 27 of the movable mounting module 23. A nineteenth valve 29 is provided on the second input pipe 26.

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

[0035] The active installation module 23 houses a continuous chromatography module 32. The sample inlet 60 of the continuous chromatography module 32 is connected to the first input pipe 22 via the first inlet port 24; the eluent inlet 61 of the continuous chromatography module 32 is connected to the second input pipe 26 via the second inlet port 27. The sample outlet 62 of the continuous chromatography module 32 is connected to the first output pipe 34 via the first outlet port 30; the eluent inlet 63 of the continuous chromatography module 32 is connected to the second output pipe 35 via the second outlet port 31. The other ends of the first output pipe 34 and the second output pipe 35 are respectively connected to a second valve array 36. The second valve array 36 is a rectangular valve array formed by four valves connected end-to-end, as shown in the figure, clockwise as 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 pipe 34 connects between the twenty-first valve 38 and the twenty-second valve 39, and the other end of the second output pipe 35 connects between the twentieth valve 37 and the twenty-third valve 40. The 20th valve 37 and the 21st valve 38 are connected to the inlet end of the first collection pipe 41; the 22nd valve 39 and the 23rd valve 40 are connected to the inlet end of the second collection pipe 42; the first collection pipe 41 is connected to the P1 storage tank and the P1-W storage tank via the 24th valve 43 and the 25th valve 44 respectively. The second collection pipe 42 is connected to the P2 storage tank and the P2-W storage tank via the 26th valve 45 and the 27th valve 46 respectively. The outlet of the 12th valve 16 of the second input main pipe 11 is connected to the first collection pipe 41 and the second collection pipe 42 via the first intermediate pipe 47 and the second intermediate pipe 48 respectively. The two ends of the first intermediate pipe 47 are respectively equipped with the 28th valve 49 and the 29th valve 50; the two ends of the second intermediate pipe 48 are respectively equipped with the 30th valve 51 and the 31st valve 52.

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

[0037] A UV sensor 93, a first conductivity sensor 94, and a first pH sensor 95 are respectively installed on the first collection pipe 41. A second conductivity sensor 96 and a second pH sensor 97 are respectively installed on the second collection pipe 42.

[0038] Reference Figure 2 The continuous chromatography module shown includes four chromatography columns: 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 via a first inlet / outlet pipe 205, and a valve 206 is installed on the pipe. 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 via a second inlet / outlet pipe 207, and a valve 208 is installed on the pipe. 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 via a third inlet / outlet pipe 209, and a valve 210 is installed on the pipe. 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 via a fourth inlet / outlet pipe 211, and a valve 212 is installed on the pipe.

[0039] The continuous chromatography module also includes a sample loading inlet pipe 213 and an elution inlet pipe 214. The fourth inlet / outlet pipe 211, located between valve four 212 and the top inlet / outlet of the first chromatography column 201, is connected to the sample loading inlet pipe 213 via valve five 215 and to the elution inlet pipe 214 via valve six 216. The first inlet / outlet pipe 205, located between valve one 206 and the top inlet / outlet of the second chromatography column 202, is connected to the sample loading inlet pipe 213 via valve seven 217 and to the elution inlet pipe 214 via valve eight 218. The second inlet / outlet pipe 207, located between valve two 208 and the top inlet / outlet of the third chromatography column 203, is connected to the sample loading inlet pipe 213 via valve nine 219 and to the elution inlet pipe 214 via valve ten 220. The third inlet and outlet pipe 209 is located at the inlet and outlet of the valve 3 210 and the top of the fourth chromatography column 204. It is connected to the sample feeding pipe 213 through valve 11 221 and to the elution feeding pipe 214 through valve 12 222.

[0040] The continuous chromatography module also includes a sample dispensing line 223 and an elution line 224. The fourth inlet / outlet line 211, located between valve 4 212 and the bottom inlet / outlet of the fourth chromatography column 204, is connected to the sample dispensing line 223 via valve 13 225 and to the elution line 224 via valve 14 226. The first inlet / outlet line 205, located between valve 1 206 and the bottom inlet / outlet of the first chromatography column 201, is connected to the sample dispensing line 223 via valve 15 227 and to the elution line 224 via valve 16 228. The second inlet / outlet line 207, located between valve 2 208 and the bottom inlet / outlet of the second chromatography column 202, is connected to the sample dispensing line 223 via valve 17 229 and to the elution line 224 via valve 18 230. The third inlet and outlet pipe 209 is located at the inlet and outlet of the valve 3 210 and the bottom of the third chromatography column 203. It is connected to the sample addition and discharge pipe 223 through valve 19 231 and to the elution discharge pipe 224 through valve 20 232.

[0041] In operation, three chromatography columns are continuously loaded in series, while the other column is used for elution. The sample enters the first chromatography column 201 through the sample inlet pipe 213, after valve 5 215 is opened. Valve 1 206 is opened, and the sample then enters the second chromatography column 202 through the first inlet / outlet pipe 205. Valve 2 208 is opened, and the sample enters the third chromatography column 203 through the second inlet / outlet pipe 207. Valve 19 231 is then opened, and the liquid enters the sample outlet pipe 223 for collection and monitoring. Simultaneously, the eluent enters through the eluent inlet pipe 214, valve 12 222 is opened, and the eluent enters the fourth chromatography column 204 through valve 12 222 and the third inlet / outlet pipe 209. The eluent then enters the fourth inlet / outlet pipe 211 from the bottom outlet of the fourth chromatography column 204. At this point, valve 14 226 is opened, and the eluent enters the eluent outlet pipe 224 for collection and monitoring.

[0042] Similarly, when samples are loaded onto the second chromatography column 202, the third chromatography column 203, and the fourth chromatography column 204, the first chromatography column 201 elutes. When samples are loaded onto the third chromatography column 203, the fourth chromatography column 204, and the first chromatography column 201, the second chromatography column 202 elutes. When samples are loaded onto the fourth chromatography column 204, the first chromatography column 201, and the second chromatography column 202, the third chromatography column 203 elutes.

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 respectively 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 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.

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 pipe is connected to two collection pipes 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.

Images