An intelligent continuous column chromatography system

Abstract

This utility model discloses an intelligent continuous column chromatography system, relating to the field of column chromatography technology. Its structure includes a storage unit, a column chromatography unit, a peristaltic pump unit, a valve unit, a recovery unit, an online detection unit, and a core control unit. The column chromatography unit includes n chromatography columns, and the valve unit includes n sets of valve modules. Each chromatography column has a corresponding set of valve modules, and each valve module includes multiple flow valves. The flow valves are used to switch the flow rates to achieve sample loading, washing, elution, and regeneration of the chromatography column, as well as to recover the target solution obtained from the chromatography process and the waste liquid generated during the chromatography process. The online detection unit is used to collect information about the target solution obtained from the chromatography process and to store the chromatography process data. This intelligent continuous column chromatography system enables continuous operation of the chromatography process, exhibiting good process stability, high adaptability, and high fault tolerance.

Description

Technical Field

[0001] This utility model relates to the field of column chromatography technology, specifically to an intelligent continuous column chromatography system. Background Technology

[0002] Traditional Chinese medicine chromatography, a key tool for the separation and purification of Chinese medicinal components, is widely used, but its intermittent operation mode has significant drawbacks. Specifically, the traditional chromatography process relies on manual operation for multiple steps such as sample loading, equilibration, elution, and collection. This is not only cumbersome and time-consuming but also leads to low production efficiency and poor process stability, making it difficult to meet the demands of modern industrial large-scale production. Furthermore, the lack of real-time detection and feedback mechanisms in traditional chromatography equipment further limits the improvement of separation accuracy. Developing an intelligent chromatography system by integrating high-precision sensors, automated control systems, and data algorithms can achieve an intelligent upgrade of the chromatography process. This would help shorten production cycles, reduce costs, standardize procedural control, reduce human intervention, ensure product quality stability and traceability, and provide reliable technical support for the modernization of Chinese medicine production.

[0003] Chinese patent document CN113018906A discloses an intelligent column chromatography system, which includes a chromatography unit, a controller, a detection unit, and a remote terminal. In the system, the controller controls the chromatography unit to perform multiple component separations based on process parameters sent from the remote terminal. The detection unit monitors the eluent components in real time and feeds the data back to the controller. By dynamically analyzing component purity data, the system can automatically determine the chromatography endpoint and synchronize the final process parameters and detection data to the remote terminal, thereby achieving fully automated control of the entire process. This system effectively eliminates human error through a closed-loop feedback mechanism, significantly improving the controllability and separation efficiency of the chromatography process.

[0004] Chinese patent document CN115453982A discloses an intelligent control system for a chromatography process. This system includes a host computer monitoring system, a slave controller, a chromatography column and tubing, and the slave controller is connected to the host computer monitoring system for signal transmission. An actuator and a parameter detection unit are connected between the chromatography column and tubing and the slave controller. This patent enables automatic monitoring and control of the chromatography process, improving product quality and production efficiency.

[0005] While some existing intelligent column chromatography systems have improved operational efficiency to some extent, they often have the following shortcomings:

[0006] (1) Although existing intelligent column chromatography systems support parallel or series operation of multiple columns, they lack the ability to dynamically adjust the operation mode;

[0007] (2) Current online testing systems cannot accurately predict the degradation of resin performance;

[0008] (3) Existing equipment mostly adopts a fixed architecture. Expanding the number of chromatography columns or functional modules requires hardware modification, which increases the enterprise's upgrade costs. Utility Model Content

[0009] To address the shortcomings of the existing technology, this invention provides an intelligent continuous column chromatography system that enables continuous operation of the chromatography process, monitors the state of the chromatography resin in real time and issues an early warning when the performance drops to a set value. It is easy to operate, has good process stability, and high adaptability and fault tolerance.

[0010] The specific technical solution adopted is as follows:

[0011] An intelligent continuous column chromatography system includes a liquid storage unit, a column chromatography unit, a peristaltic pump unit, a valve unit, a recovery unit, an online detection unit, and a core control unit.

[0012] The storage unit includes multiple storage containers, one of which is used to hold a solution required for column chromatography. The solution required for column chromatography includes sample solution, washing solution, elution solution, regeneration solution, or pure water.

[0013] A column chromatography unit consists of n chromatography columns, where n ≥ 2;

[0014] The peristaltic pump unit includes multiple peristaltic pumps. Each storage container and each chromatography column is equipped with one peristaltic pump, which is used to control the flow rate of the solution required for column chromatography and the flow rate of the liquid flowing out of the chromatography column, respectively.

[0015] The valve unit includes n sets of valve modules. Each chromatography column is equipped with a corresponding set of valve modules. Each set of valve modules includes a flow valve installed on the peristaltic pump outlet line of each liquid storage container and a flow valve installed on the peristaltic pump outlet line of the corresponding chromatography column. The flow valve switching enables the sample loading, washing, elution and regeneration steps of the chromatography column, as well as the recovery of the target solution obtained in the chromatography process and the waste liquid generated in the chromatography process.

[0016] The recovery unit includes multiple recovery containers for holding the target solution obtained from the chromatography process and the waste liquid generated from the chromatography process;

[0017] The online detection unit is used to collect information about the target solution obtained during the chromatography process and to save the chromatography process data;

[0018] The core control unit is used to control the operation of the entire system, enabling continuous column chromatography with n chromatography columns in a multi-column parallel mode.

[0019] Preferably, the liquid storage unit includes five liquid storage containers, which are used to hold sample solution, washing solution, elution solution, regeneration solution and pure water, respectively.

[0020] Preferably, the column chromatography unit includes four chromatography columns. When the column chromatography unit includes four chromatography columns, the intelligent continuous column chromatography system can operate in three modes: dual-column parallel, triple-column parallel, or quadruple-column parallel. The intelligent continuous column chromatography system operates in quadruple-column parallel mode by default. If a chromatography column fails, the operation of that column can be paused, and the remaining chromatography columns will automatically switch to the standby mode (dual-column parallel mode or triple-column parallel mode) to ensure continuous and stable operation of the system.

[0021] Preferably, the chromatography column is equipped with a level gauge for monitoring the liquid level in the chromatography column.

[0022] Furthermore, a valve module includes seven flow valves, two of which are installed on the peristaltic pump outlet pipeline of the corresponding chromatography column of the valve module, and are used for the recovery of the target solution obtained in the chromatography process and the waste liquid generated in the chromatography process, respectively. The remaining flow valves are installed on the pump outlet pipelines of the sample solution storage container, the washing solution storage container, the elution solution storage container, the regeneration solution storage container and the pure water storage container, respectively.

[0023] Preferably, the online detection unit uses machine learning to determine the resin state based on the acquired physical quantity signals, including pH, redox potential, or conductivity.

[0024] When the online detection unit detects a 10% decrease in the performance of the chromatography resin in the chromatography column, it sends a warning message to the core control unit.

[0025] Preferably, the intelligent continuous column chromatography system further includes a communication unit for transmitting instructions between the core control unit and other units.

[0026] Compared with the prior art, the beneficial effects of this utility model are as follows:

[0027] (1) The intelligent continuous column chromatography system provided by this utility model can achieve efficient continuous operation for 24 hours, which significantly improves work efficiency compared with traditional intermittent chromatography.

[0028] (2) This utility model realizes continuous operation of the chromatography process through multi-column parallel operation mode and intelligent valve switching technology, solves the technical problem of low efficiency and inability to produce continuously in traditional single-column chromatography, and significantly improves production efficiency.

[0029] (3) The system of this utility model can detect the resin status in real time and issue an early warning when the performance drops by 10%, which solves the problem that resin failure is difficult to detect in the early stage, and ensures the stable operation of the equipment and the consistency of product quality.

[0030] (4) The system of this utility model adopts a modular design and intelligent control system, which can realize flexible switching of different multi-column operation modes and has fault tolerance function. When a certain chromatography column fails, the system can automatically switch to the backup operation mode (such as switching from four-column parallel mode to two-column parallel mode or three-column parallel mode), solve the problem of operation interruption caused by equipment failure or changes in process requirements, improve the adaptability and fault tolerance of the system, and ensure the stability of production. Attached Figure Description

[0031] Figure 1 This is a schematic diagram of the structure of the intelligent continuous column chromatography system.

[0032] Figure 2 The diagram shows the usage status of the intelligent continuous column chromatography system, where (a) is the valve start-up state and (b) is the valve switching state.

[0033] Figure reference numerals: 1 First reservoir, 2 Second reservoir, 3 Third reservoir, 4 Fourth reservoir, 5 Fifth reservoir, 6 Sample loading pump, 7 Washing pump, 8 Elution pump, 9 Regeneration pump, 10 Pure water delivery pump, 11 Pure water valve for first chromatography column, 12 Pure water valve for second chromatography column, 13 Pure water valve for third chromatography column, 14 Pure water valve for fourth chromatography column, 15 Regeneration valve for first chromatography column, 16 Regeneration valve for second chromatography column, 17 Regeneration valve for third chromatography column, 18 Regeneration valve for fourth chromatography column, 19 Elution valve for first chromatography column, 20 Elution valve for second chromatography column, 21 Elution valve for third chromatography column, 22 Elution valve for fourth chromatography column, 23 Washing valve for first chromatography column, 24 Washing valve for second chromatography column, 25 Washing valve for third chromatography column, 26 Washing valve for fourth chromatography column, 27 Sample loading valve for first chromatography column, 28 Sample loading valve for second chromatography column. 29. Third chromatography column sample loading valve; 30. Fourth chromatography column sample loading valve; 31. Fourth level gauge; 32. Third level gauge; 33. Second level gauge; 34. First level gauge; 35. Fourth chromatography column; 36. Third chromatography column; 37. Second chromatography column; 38. First chromatography column; 39. Fourth peristaltic pump; 40. Third peristaltic pump; 41. Second peristaltic pump; 42. First peristaltic pump; 43. Fourth chromatography column target solution valve; 44. Fourth chromatography column waste liquid valve; 45. Third chromatography column waste liquid valve; 46. Third chromatography column target solution valve; 47. Second chromatography column waste liquid valve; 48. Second chromatography column target solution valve; 49. First chromatography column waste liquid valve; 50. First chromatography column target solution valve; 51. First communication unit; 52. Core control unit; 53. Second communication unit; 54. Online detection unit; 55. First recovery container; 56. Second recovery container. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this utility model, and not all embodiments. The components of the embodiments of this utility model described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0035] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0036] Example 1

[0037] like Figure 1 As shown, the structure of this intelligent continuous column chromatography system includes a liquid storage unit, a column chromatography unit, a peristaltic pump unit, a valve unit, a recovery unit, an online detection unit, and a core control unit.

[0038] The liquid storage unit includes five liquid storage containers: the first liquid storage container 1 is used to hold the sample solution, the second liquid storage container 2 is used to hold the washing solution, the third liquid storage container 3 is used to hold the elution solution, the fourth liquid storage container 4 is used to hold the regeneration solution, and the fifth liquid storage container 5 is used to hold pure water.

[0039] The column chromatography unit includes four chromatography columns: the first chromatography column 38, the second chromatography column 37, the third chromatography column 36, and the fourth chromatography column 35. Each chromatography column is equipped with a level gauge for monitoring the liquid level height of the chromatography column: the first level gauge 34, the second level gauge 33, the third level gauge 32, and the fourth level gauge 31.

[0040] The peristaltic pump unit includes nine peristaltic pumps. Each reservoir and each chromatography column is equipped with one peristaltic pump. The sample loading pump 6 is used to control the flow rate of the sample solution, the washing pump 7 is used to control the flow rate of the washing solution, the elution pump 8 is used to control the flow rate of the elution solution, the regeneration pump 9 is used to control the flow rate of the regeneration solution, the pure water delivery pump 10 is used to control the flow rate of pure water, and the first peristaltic pump 42, the second peristaltic pump 41, the third peristaltic pump 40, and the fourth peristaltic pump 39 are used to control the flow rate of the effluent solution from different chromatography columns, respectively.

[0041] The valve unit includes four valve modules, with one corresponding valve module for each chromatography column. Each valve module includes a flow valve on the peristaltic pump outlet line of each storage container and a flow valve on the peristaltic pump outlet line of the corresponding chromatography column. Switching the flow valves enables the loading, washing, elution, and regeneration steps of the chromatography column, as well as the recovery of the target solution obtained from the chromatography process and the waste liquid generated during the chromatography process. The valve module corresponding to the first chromatography column 38 includes a first chromatography column pure water valve 11, a first chromatography column regeneration valve 15, a first chromatography column elution valve 19, a first chromatography column washing valve 23, a first chromatography column sample loading valve 27, a first chromatography column waste liquid valve 49, and a first chromatography column target solution valve 50. The valve module corresponding to the second chromatography column 37 includes a second chromatography column pure water valve 12. The valve module corresponding to the second chromatography column 36 includes: a second chromatography column regeneration valve 16, a second chromatography column elution valve 20, a second chromatography column washing valve 24, a second chromatography column sample loading valve 28, a second chromatography column waste liquid valve 47, and a second chromatography column target solution valve 48; the valve module corresponding to the fourth chromatography column 36 includes: a third chromatography column pure water valve 13, a third chromatography column regeneration valve 17, a third chromatography column elution valve 21, a third chromatography column washing valve 25, a third chromatography column sample loading valve 29, a third chromatography column waste liquid valve 45, and a third chromatography column target solution valve 46; the valve module corresponding to the fourth chromatography column 35 includes: a fourth chromatography column pure water valve 14, a fourth chromatography column regeneration valve 18, a fourth chromatography column elution valve 22, a fourth chromatography column washing valve 26, a fourth chromatography column sample loading valve 30, a fourth chromatography column waste liquid valve 44, and a fourth chromatography column target solution valve 43. The peristaltic pump outlet line of each storage container is connected to an auxiliary line, through which the pumped liquid enters the chromatography column inlet.

[0042] The recovery unit includes a first recovery container 55 and a second recovery container 56. The first recovery container 55 is used to hold the target solution obtained in the chromatography process, and the second recovery container 56 is used to hold the waste liquid generated in the chromatography process.

[0043] The online detection unit 54 is used to collect information about the target solution obtained in the chromatography process and to save the chromatography process data. It can determine the resin state based on the collected physical quantity signals, including pH, redox potential or conductivity.

[0044] The core control unit 52 is used to control the operation of the entire system, enabling continuous column chromatography in a multi-column parallel mode; the first communication unit 51 and the second communication unit 53 are used for instruction transmission between the core control unit and other units.

[0045] Operational Flow: The intelligent continuous column chromatography system is started by the core control unit 52 receiving an operation command, which then activates the online detection unit 54, enabling real-time data recording and status monitoring. The system adopts a multi-column parallel operation mode, achieving continuous chromatography purification through intelligent valve switching. The valves are functionally divided into four zones: adsorption, impurity removal, elution, and regeneration (the regeneration zone includes valves for regenerated solution and pure water). Each zone's valves are color-coded to correspond to the four chromatography columns. When the valve color matches the column marking, a fluid flow connection is established. Initially, each zone's chromatography columns are active, with only one valve active in each zone, while the others are closed: the adsorption zone is operated by the fourth column's sample loading valve 30, the impurity removal zone by the first column's washing valve 23, the elution zone by the second column's elution valve 20, and the regeneration zone by the third column's regeneration valve 17. Figure 2 (a) in the middle.

[0046] After the operating cycle is completed, the valves perform a switching operation: the adsorption zone switches from the fourth chromatography column sample loading valve 30 to the third chromatography column sample loading valve 29; the impurity removal zone switches from the first chromatography column washing valve 23 to the fourth chromatography column washing valve 26; the elution zone switches from the second chromatography column elution valve 20 to the first chromatography column elution valve 19; and the regeneration zone switches from the third chromatography column regeneration valve 17 to the second chromatography column regeneration valve 16. Figure 2 (b)). By periodically switching valves, the dynamic rotation of the chromatography column function and the continuity of the process are achieved.

[0047] This intelligent continuous column chromatography system supports three operating modes: dual-column parallel, triple-column parallel, and quadruple-column parallel, with the default startup mode being quadruple-column parallel. Different modes are divided into process stages through valve timing control: dual-column parallel mode is divided into two stages, triple-column parallel mode is simplified to three stages, and quadruple-column mode executes four stages simultaneously. The system automatically completes cyclic operation based on preset switching parameters and flow rate settings. If a column malfunctions, its operation can be paused independently, and the remaining columns automatically switch to standby mode (configured as dual-column or triple-column parallel mode), ensuring continuous and stable system operation. Furthermore, the online monitoring unit monitors the resin status in real time and issues early warnings for malfunctions. An early warning is issued when resin performance decreases by 10%, and fault information is fed back through the software interface, providing strong support for the stable operation of the equipment.

[0048] The embodiments described above provide a detailed explanation of the technical solution of this utility model. It should be understood that the above descriptions are only specific embodiments of this utility model and are not intended to limit this utility model. Any modifications, additions, or similar substitutions made within the scope of the principles of this utility model should be included within the protection scope of this utility model.

Claims

1. An intelligent continuous column chromatography system, characterized in that, The structure includes a liquid storage unit, a column chromatography unit, a peristaltic pump unit, a valve unit, a recovery unit, an online detection unit, and a core control unit; The storage unit includes multiple storage containers, one of which is used to hold a solution required for column chromatography. The solution required for column chromatography includes sample solution, washing solution, elution solution, regeneration solution, or pure water. A column chromatography unit consists of n chromatography columns, where n ≥ 2; The peristaltic pump unit includes multiple peristaltic pumps, with one peristaltic pump for each reservoir and each chromatography column; The valve unit includes n sets of valve modules. Each chromatography column is equipped with a corresponding set of valve modules. Each set of valve modules includes a flow valve installed on the peristaltic pump outlet line of each liquid storage container and a flow valve installed on the peristaltic pump outlet line of the corresponding chromatography column. The flow valve switching enables the sample loading, washing, elution and regeneration steps of the chromatography column, as well as the recovery of the target solution obtained in the chromatography process and the waste liquid generated in the chromatography process. The recovery unit includes multiple recovery containers for holding the target solution obtained from the chromatography process and the waste liquid generated from the chromatography process; The online detection unit is used to collect information about the target solution obtained during the chromatography process and to save the chromatography process data; The core control unit is used to control the operation of the entire system, enabling continuous column chromatography with n chromatography columns in a multi-column parallel mode. 2.The intelligent continuous column chromatography system according to claim 1, characterized in that, The liquid storage unit includes five liquid storage containers, which are used to hold sample solution, washing solution, elution solution, regeneration solution and pure water, respectively.

3. The intelligent continuous column chromatography system according to claim 1, characterized in that, The column chromatography unit includes four chromatography columns. This intelligent continuous column chromatography system realizes continuous column chromatography in the form of two parallel columns, three parallel columns, or four parallel columns.

4. The intelligent continuous column chromatography system according to claim 1, characterized in that, The chromatography column is equipped with a level gauge for monitoring the liquid level in the chromatography column.

5. The intelligent continuous column chromatography system according to claim 2, characterized in that, A valve module includes seven flow valves. Two of these flow valves are installed on the peristaltic pump outlet line of the corresponding chromatography column of the valve module, and are used for the recovery of the target solution obtained in the chromatography process and the waste liquid generated in the chromatography process, respectively. The remaining flow valves are installed on the pump outlet lines of the sample solution storage container, the washing solution storage container, the elution solution storage container, the regeneration solution storage container and the pure water storage container, respectively.

6. The intelligent continuous column chromatography system according to claim 1, characterized in that, The online detection unit determines the resin state based on the acquired physical quantity signals, including pH, redox potential, or conductivity.

7. The intelligent continuous column chromatography system according to claim 1, characterized in that, The intelligent continuous column chromatography system also includes a communication unit for transmitting instructions between the core control unit and other units.

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