Intelligent column chromatography device

Abstract

The utility model discloses an intelligent column chromatography device, which belongs to the technical field of separation devices and comprises a liquid storage unit, a column chromatography unit, an on-line monitoring unit and a core control unit, the liquid storage unit comprises a liquid storage tank, a peristaltic pump and a ball valve, and is used for supplying a loading solution, a washing solution, an eluent, a regeneration solution and pure water for chromatography to the column chromatography unit; the column chromatography unit comprises a chromatographic column, the chromatographic column is provided with a liquid level meter, the liquid level meter is used for monitoring the liquid level height of the chromatographic column, a liquid outlet of the column chromatography unit is connected with a peristaltic pump, and the liquid level meter and the peristaltic pump work cooperatively to maintain the stability of the liquid level in the chromatographic column; the on-line monitoring unit is used for collecting and storing information of discharged liquid of the column chromatography unit, and then respectively conveying the discharged liquid of the column chromatography unit to a waste liquid collection part, a target solution collection part and a recovered solution collection part; and the core control unit is used for controlling the chromatography process. According to the device, full-automatic control and intelligent management of a traditional Chinese medicine column chromatography process are realized through integration of multiple unit components.

Description

Technical Field

[0001] The utility model belongs to the technical field of separation devices, and particularly relates to an intelligent column chromatography device. Background Art

[0002] The chemical components of traditional Chinese medicine are complex. Chromatography technology is one of the important methods for separating and purifying the effective components of traditional Chinese medicine. Many large varieties of traditional Chinese medicine (such as Xuesaitong and Ginkgo biloba preparations) are produced using column chromatography technology. Although chromatography technology has now been widely popularized, its intermittent operation mode (including complex steps such as sample loading, elution, and collection) not only lengthens the production cycle and raises costs, but also easily leads to errors in industry due to more manual operations, affecting the consistency of product quality. In addition, the problem of high solvent consumption also highlights the conflict between this traditional technology and the concept of green and efficient development of modern pharmaceutical industry. The intelligent system can effectively break through the limitations of traditional chromatography technology through process optimization, reduction of manual intervention, and realization of continuous production mode.

[0003] The Chinese patent document with the publication number CN210583782U discloses a column chromatography integration system for continuous sample loading. The system includes a liquid storage unit, a pump unit, a rotatable interface, and a column chromatography unit arranged in series. Through the connection of the outlet three-way valve of the liquid storage tank to the pump unit and the design of the rotatable interface between the pump unit and the chromatography column unit, the transmission and control of the liquid material are realized. This patent connects the column chromatography unit in series with two or more levels of chromatography columns, greatly increasing the number of uses of the chromatography column medium. Moreover, through the cooperation of the rotatable column chromatography unit and the channel replacement of the three-way valve, the continuous purification of the sample can be conveniently and quickly realized.

[0004] The Chinese patent document with the publication number CN115738381A discloses a multi-channel column chromatography device capable of automatic sample loading and elution. The device includes an automatic sample loading and elution device and a multi-channel column chromatography device. The multi-channel column chromatography device is provided with a plurality of chromatography column fixing channels, and can fix a plurality of chromatography columns at the same time. The automatic sample loading and elution device is composed of a Mariotte bottle and an automatic lifting device, and is arranged behind the corresponding position of each fixing channel.

[0005] Although the above systems / devices have improved the operation efficiency of chromatography technology to a certain extent, most of the automated column chromatography systems including them still have the following deficiencies: (1) The system structure is relatively complex and the maintenance cost is high; (2) The degree of intelligence needs to be further improved, and it is difficult to achieve real-time feedback and dynamic adjustment; (3) The data acquisition ability is insufficient and cannot provide sufficient data support for process optimization; (4) When performing key steps such as sample loading, washing, elution, and regeneration, it is necessary to frequently adjust the liquid flow rate, switch valves, etc., which not only increases the operation difficulty, but also easily introduces human errors, affecting the separation effect and product quality.

[0006] Therefore, it is necessary to develop an intelligent column chromatography device with a high level of automation that can provide sufficient data support for process optimization. Summary of the Invention

[0007] In order to solve the deficiencies existing in the prior art, the present utility model provides an intelligent column chromatography device, which realizes the full-automatic control and intelligent management of the traditional Chinese medicine column chromatography process through the integration of multi-unit components.

[0008] The specific technical solutions adopted are as follows:

[0009] An intelligent column chromatography device includes: a liquid storage unit, a column chromatography unit, an on-line monitoring unit, and a core control unit;

[0010] The liquid storage unit includes a liquid storage tank, a peristaltic pump, and a ball valve, and realizes the supply of the sample loading liquid, washing liquid, elution liquid, regeneration liquid, and pure water for column chromatography to the column chromatography unit;

[0011] The column chromatography unit includes a chromatography column, and a liquid level gauge is provided on the chromatography column. The liquid level gauge is used to monitor the liquid level height of the chromatography column. The liquid outlet of the column chromatography unit is connected to a peristaltic pump, and the liquid level gauge and the peristaltic pump work together to maintain the liquid level in the chromatography column stable;

[0012] The on-line monitoring unit is used to collect and save the information of the liquid discharged from the column chromatography unit, and then separately transport the liquid discharged from the column chromatography unit to the waste liquid collection place, the target solution collection place, and the recycled solution collection place;

[0013] The core control unit is used to control the progress of the chromatography process.

[0014] Specifically, in the liquid storage unit, the liquid storage tank includes a sample loading liquid storage tank, a washing liquid storage tank, an elution liquid storage tank, a regeneration liquid storage tank, and a pure water storage tank. Each liquid storage tank is provided with a separate peristaltic pump and a ball valve, and the peristaltic pump and the ball valve are used for the control and adjustment of liquid flow.

[0015] Preferably, the chromatography column includes a chromatography column body and an upper cover. The side of the chromatography column body is provided with a liquid inlet, and the bottom is provided with a liquid outlet. The upper cover is equipped with a gasket and has an opening, and a liquid level gauge is installed at the opening.

[0016] Further preferably, the chromatography column body and the upper cover are connected by threads, and the gasket is a silica gel gasket, which can ensure the airtightness of the chromatography column.

[0017] Further preferably, the liquid inlet of the chromatography column body is a pagoda interface with an upward opening, which can be detachably connected to the liquid delivery pipeline of the liquid storage unit.

[0018] The described on-line monitoring unit includes a conductivity sensor, a pH sensor and a redox sensor, which collect the pH value, conductivity and redox potential information of the liquid discharged from the column chromatography unit.

[0019] Specifically, the liquid discharged from the column chromatography unit is shunted after passing through the master control ball valve, and then is respectively transported to the waste liquid collection place, the target solution collection place and the recycled solution collection place through the waste liquid ball valve, the target solution ball valve and the recycled solution ball valve.

[0020] Specifically, the core control unit controls the switch and rotation speed of the peristaltic pump, and controls the switch of the ball valve, so as to realize the switching of steps such as sample loading, washing, elution and regeneration in the traditional Chinese medicine column chromatography process.

[0021] Meanwhile, the core control unit collects the real-time readings of the liquid level gauge, and conducts intelligent feedback control based on this, dynamically adjusting the rotation speed of the peristaltic pump connected to the liquid outlet of the column chromatography unit, so as to maintain the liquid level in the chromatography column stable.

[0022] Compared with the prior art, the beneficial effects of the present utility model are as follows:

[0023] (1) All parts in the equipment of the present utility model can be designed as fixed and durable types, effectively reducing losses, thereby significantly reducing the cost burden of maintenance and repair.

[0024] (2) By precisely controlling the coordinated operation of the peristaltic pump and the valve, the equipment of the present utility model realizes the automatic switching of the whole series of steps from sample loading, washing, elution to regeneration in the traditional Chinese medicine column chromatography process, greatly improving the automation level of the production process.

[0025] (3) The equipment of the present utility model is built-in with an intelligent feedback mechanism, which collects the real-time readings of the liquid level gauge and dynamically adjusts the rotation speed of the peristaltic pump connected to the liquid outlet of the column chromatography unit based on this, ensuring that the liquid level in the chromatography column always remains stable, and enhancing the stability and accuracy of the operation.

[0026] (4) An on-line monitoring unit is introduced into the equipment of the present utility model, which can continuously collect and display in real time the physical quantity data of the liquid discharged from the column chromatography unit, and automatically save these key information at the same time, providing strong data support for data analysis and process optimization.

[0027] (5) By presetting the chromatography conditions, the equipment of the present utility model can automatically realize the continuous operation of the chromatography column without manual intervention, improving the production efficiency and consistency.

[0028] (6) The chromatography column with optimized structure in the equipment of the present utility model can enhance the durability and maintenance convenience of the equipment, providing a solid guarantee for long-term stable operation. Description of the Drawings

[0029] Figure 1This is a schematic structural diagram of the intelligent column chromatography device in the present utility model.

[0030] Reference numerals: 1 - first liquid storage tank, 2 - second liquid storage tank, 3 - third liquid storage tank, 4 - fourth liquid storage tank, 5 - fifth liquid storage tank, 6 - first peristaltic pump, 7 - second peristaltic pump, 8 - third peristaltic pump, 9 - fourth peristaltic pump, 10 - fifth peristaltic pump, 11 - first electric ball valve, 12 - second electric ball valve, 13 - third electric ball valve, 14 - fourth electric ball valve, 15 - fifth electric ball valve, 16 - liquid level gauge, 17 - first three-way joint, 18 - second three-way joint, 19 - third three-way joint, 20 - fourth three-way joint, 21 - sixth peristaltic pump, 22 - online monitoring unit, 23 - sixth electric ball valve, 24 - seventh electric ball valve, 25 - eighth electric ball valve, 26 - ninth electric ball valve, 27 - sixth liquid storage tank, 28 - seventh liquid storage tank, 29 - eighth liquid storage tank, 30 - column body of chromatography column, 35 - core control unit. Detailed implementation manners

[0031] Next, the technical solutions in the embodiments of the present utility model will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present utility model. Obviously, the described embodiments are only partial embodiments of the present utility model, rather than all embodiments. Based on these embodiments, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present utility model.

[0032] Embodiment 1

[0033] The schematic structural diagram of the intelligent column chromatography device in the present utility model is as Figure 1 shown. The intelligent column chromatography device includes: a liquid storage unit, a column chromatography unit, an online monitoring unit, and a core control unit;

[0034] In the liquid storage unit, liquid storage tanks 1-5 store one of the sample loading solution, washing solution, eluent, regeneration solution, and pure water respectively. The first peristaltic pump 6, the second peristaltic pump 7, the third peristaltic pump 8, the fourth peristaltic pump 9, and the fifth peristaltic pump 10 correspond to the first liquid storage tank 1, the second liquid storage tank 2, the third liquid storage tank 3, the fourth liquid storage tank 4, and the fifth liquid storage tank 5 respectively. As the power core, they can ensure that the liquid is injected into the column chromatography unit at a set flow rate. To precisely control the flow direction and distribution of the liquid, the liquid storage unit is also equipped with 5 electric ball valves (the first electric ball valve 11, the second electric ball valve 12, the third electric ball valve 13, the fourth electric ball valve 14, the fifth electric ball valve 15). Each valve corresponds to a liquid treatment step, including sample loading, washing, elution, regeneration, and pure water supply, and can achieve flexible switching of the flow path. 4 three-ways (the first three-way 17, the second three-way 18, the third three-way 19, the fourth three-way 20) ensure the smooth flow of the liquid in the system. The liquid storage unit can supply the sample loading solution, washing solution, eluent, regeneration solution, and pure water for chromatography to the column chromatography unit.

[0035] The column chromatography unit includes a chromatography column. A liquid level gauge 16 is provided on the chromatography column. The liquid level gauge 16 is used to monitor the liquid level height of the chromatography column. The liquid outlet of the column chromatography unit is connected to the sixth peristaltic pump 21. The liquid level gauge 16 and the sixth peristaltic pump 21 work together to maintain the liquid level in the chromatography column stable. Specifically, the chromatography column includes a chromatography column body 30 and an upper cover. The chromatography column body 30 and the upper cover are connected by threads. The side of the chromatography column body 30 is provided with a pagoda interface with an upward opening as the liquid inlet, and the bottom is provided with a liquid outlet. The upper cover is equipped with a silica gel gasket and has an opening, and the liquid level gauge 16 is installed at the opening. The liquid level gauge 16 monitors the liquid level height of the chromatography column in real time, providing key data support for automatic control. The sixth peristaltic pump 21 and the liquid level gauge 16 work together to form a closed-loop feedback mechanism, effectively maintaining the stability of the liquid level during the chromatography process and preventing the influence of liquid level fluctuations on the chromatography effect.

[0036] The on-line monitoring unit 22 includes a conductivity sensor, a pH sensor, and a redox sensor, which collect the pH value, conductivity, and redox potential information of the liquid outlet of the column chromatography unit and save them. Then, the liquid outlet of the column chromatography unit is respectively transported to the target solution collection place, the recycled solution collection place, and the waste liquid collection place through the liquid outlet ball valve. Among them, the sixth electric ball valve 23 is the main control ball valve for the liquid outlet, the seventh electric ball valve 24 is the target solution ball valve, the eighth electric ball valve 25 is the recycled liquid ball valve, and the ninth electric ball valve 26 is the waste liquid ball valve. The sixth liquid storage tank 27, the seventh liquid storage tank 28, and the eighth liquid storage tank 29 are respectively provided at the target solution collection place, the recycled solution collection place, and the waste liquid collection place for collecting solutions.

[0037] The core control unit 35 is used to control the progress of the chromatography process. It can control the on / off and rotation speed of the peristaltic pump, and control the on / off of the ball valve (the peristaltic pump and ball valve in different processes can be controlled separately), realize the switching of steps including sample loading, washing, elution and regeneration in the chromatography process, and can also collect the real-time readings of the liquid level gauge, and perform intelligent feedback control based on this, dynamically adjust the rotation speed of the peristaltic pump connected to the liquid outlet of the column chromatography unit to maintain the liquid level in the chromatography column stable. It can also collect the sensor and time data in the on-line monitoring unit 22 and save them to a specified file, and can export the waveforms of pH value, redox potential and conductivity collected by the sensor over time in real time.

[0038] Specifically, the operation process of the intelligent column chromatography device includes: when starting the intelligent column chromatography device, the core control unit 35 first receives the operation instruction, and then the on-line monitoring unit 22 is immediately activated to start the data recording and monitoring function. Then, the first peristaltic pump 6 (sample loading peristaltic pump) is automatically started, while the other peristaltic pumps remain closed to ensure the specificity and accuracy of the sample loading operation. During the sample loading stage, the first electric ball valve 11 (sample loading ball valve) is accurately opened to form a fluid path, while the other inlet ball valves are tightly closed to prevent liquid cross-flow. At the same time, the liquid level gauge 16 starts the real-time reading function to provide key liquid level data for the core control unit 35, and then realizes the dynamic balance and stability of the liquid level by adjusting the rotation speed of the sixth peristaltic pump 21 at the outlet; at the liquid outlet end, the sixth electric ball valve 23 and the ninth electric ball valve 26 at the liquid outlet are opened, and the other liquid outlet ball valves are closed to ensure that the sample loading liquid is directly guided to the eighth storage tank 29 (waste liquid storage tank) for collection after chromatography.

[0039] When the sample loading stage is over, the system automatically switches to the washing program. At this time, the first peristaltic pump 6 (sample loading peristaltic pump) stops working, the second peristaltic pump 7 (washing peristaltic pump) is activated, and the second electric ball valve 12 (washing ball valve) is correspondingly opened, while the other inlet valves remain closed. The liquid level gauge 16 and the sixth peristaltic pump 21 continue to work together to keep the liquid level of the system stable, and the liquid outlet path remains unchanged to ensure that the washing liquid is also discharged into the eighth storage tank 29 (waste liquid storage tank) after being detected by the on-line monitoring unit 22. When entering the elution stage, the switching of the inlet part follows the established logic, while the outlet part is adjusted to open the sixth electric ball valve 23 and the seventh electric ball valve 24 (target solution ball valve), and the other outlet ball valves are closed to collect the target product. Finally, in the regeneration stage, the switching of the inlet part still follows the above principle, while the outlet part flexibly adjusts the on / off states of the sixth electric ball valve 23 and the eighth electric ball valve 25 (recycled solution ball valve) according to the recyclability of the regeneration liquid.

[0040] The above-described embodiments have elaborated on the technical solutions of the present utility model. It should be understood that the above are only specific embodiments of the present utility model and are not intended to limit the present utility model. Any modifications, supplements, or substitutions in a similar manner made within the scope of the principles of the present utility model should be included within the protection scope of the present utility model.

Claims

1. An intelligent column chromatography device, characterized in that, It includes: a liquid storage unit, a column chromatography unit, an on-line monitoring unit, and a core control unit; The liquid storage unit includes a liquid storage tank, a peristaltic pump, and a ball valve, and realizes the supply of the sample loading liquid, washing liquid, elution liquid, regeneration liquid, and pure water for chromatography to the column chromatography unit; The column chromatography unit includes a chromatography column, and a liquid level gauge is provided on the chromatography column. The liquid level gauge is used to monitor the liquid level height of the chromatography column. The liquid outlet of the column chromatography unit is connected to a peristaltic pump, and the liquid level gauge and the peristaltic pump work together to maintain the liquid level in the chromatography column stable; The on-line monitoring unit is used to collect and save the information of the liquid discharged from the column chromatography unit, and then respectively transport the liquid discharged from the column chromatography unit to the waste liquid collection place, the target solution collection place, and the recycled solution collection place; The core control unit is used to control the progress of the chromatography process.

2. The intelligent column chromatography device according to claim 1, wherein In the described liquid storage unit, the liquid storage tank includes a sample loading liquid storage tank, a washing liquid storage tank, an elution liquid storage tank, a regeneration liquid storage tank, and a pure water storage tank. Each liquid storage tank is provided with a separate peristaltic pump and a ball valve, and the peristaltic pump and the ball valve are used for the control and adjustment of liquid flow.

3. The intelligent column chromatography device according to claim 1, characterized in that, The described chromatography column includes a chromatography column body and an upper cover. The side of the chromatography column body is provided with a liquid inlet, and the bottom is provided with a liquid outlet. The upper cover is equipped with a gasket and has an opening, and a liquid level gauge is installed at the opening.

4. The intelligent column chromatography device according to claim 3, wherein The chromatography column body and the upper cover are connected by threads, and the gasket is a silica gel gasket.

5. The intelligent column chromatography device according to claim 3, wherein The liquid inlet of the chromatography column body is a pagoda interface with an upward opening, and is detachably connected to the liquid delivery pipeline of the liquid storage unit.

6. The intelligent column chromatography device according to claim 1, characterized in that The described on-line monitoring unit includes a conductivity sensor, a pH sensor, and a redox sensor, and collects the pH value, conductivity, and redox potential information of the liquid discharged from the column chromatography unit.

7. The intelligent column chromatography device according to claim 1, wherein The liquid discharged from the column chromatography unit is shunted after passing through the master control ball valve, and then is respectively transported to the waste liquid collection place, the target solution collection place, and the recycled solution collection place through the waste liquid ball valve, the target solution ball valve, and the recycled solution ball valve.

8. The intelligent column chromatography device according to claim 1, characterized in that, The core control unit controls the switch and rotation speed of the peristaltic pump, and controls the switch of the ball valve, and realizes the switching of steps including sample loading, washing, elution, and regeneration in the chromatography process.

9. The intelligent column chromatography device according to claim 1, wherein, The core control unit collects the real-time readings of the liquid level gauge, and performs intelligent feedback control based on this, dynamically adjusts the rotation speed of the peristaltic pump connected to the liquid outlet of the column chromatography unit, and maintains the liquid level in the chromatography column stable.

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