Plug-and-play type disposable chromatography device

Abstract

The utility model discloses a plug-and-play type disposable chromatography device, a chromatography pipeline structure comprises a pump body, a bubble hydrazine and a disposable chromatography column, the pump body and the bubble hydrazine are sequentially arranged on a disposable main pipeline, and the disposable chromatography column is communicated and connected with the bubble hydrazine through a disposable auxiliary pipeline; a first flow meter and a first pressure sensor are respectively arranged at two ends of the pump body, a second flow meter and a second pressure sensor are arranged at a liquid inlet end of the disposable chromatographic column, a conductivity sensor, an ultraviolet sensor and a pH value sensor are sequentially arranged at a liquid outlet end of the disposable chromatographic column, and the sensors are integrally connected with a PLC (Programmable Logic Controller) control system and a data management system. According to the scheme, a plug-and-play one-time assembly mode is adopted, the capacity of rapidly replacing consumables is provided, and different process requirements can be met; data management is carried out through an integrated PLC control system, it is ensured that each step of operation is recorded in detail, data integrity and traceability are enhanced, and the development and verification process is accelerated.

Description

TECHNICAL FIELD

[0001] The utility model relates to a chromatography device, especially a plug and play disposable chromatography device, and belongs to the technical field of chromatography. BACKGROUND

[0002] Chromatography technology is a technology established by utilizing the differences in the physical and chemical properties of different substances. chromatography The system is composed of two phases: one is the stationary phase, and the other is the mobile phase. When the mixture to be separated passes through the stationary phase with the mobile phase, due to the differences in the physical and chemical properties of each component, the ability to interact with the two phases (adsorption, dissolution, combination, etc.) is different, the distribution (content ratio) in the two phases is different, and each component continuously redistributes in the two phases as the mobile phase moves forward. Collecting the effluent can obtain each single component contained in the sample, thereby achieving the purpose of separating each component.

[0003] However, the traditional chromatography technology has the following disadvantages: 1) In the traditional chromatography device, the fixed column needs to be used repeatedly, which can easily cause cross contamination between different batches, affecting product quality and causing inconsistency between batches, increasing the difficulty of quality control; 2) The cleaning verification process of the traditional chromatography device is complex and time-consuming, requiring strict cleaning procedures and verification tests, increasing production cycle and cost, and reducing production efficiency; 3) The traditional chromatography device needs a long time to adjust and prepare when switching between different products or processes. It is not suitable for multi-product production facilities or research laboratories, limiting the flexibility and response speed of production; 4) The installation, maintenance and cleaning of the traditional chromatography device require a large amount of capital investment and continuous operating cost, increasing equipment investment and operating cost, especially for small and medium-sized enterprises; 5) The traditional chromatography device may introduce the risk of microbial contamination, especially during long-term operation, which increases the biological safety risk and affects product quality and safety; 6) The operation process of the traditional system is complex and involves multiple manual steps, which is prone to errors. It increases the difficulty of operation, reduces the efficiency of operation, and increases the possibility of human error; 7) The traditional system may have deficiencies in data recording and tracking, affecting quality control and compliance, and is difficult to meet the strict regulatory requirements in modern pharmaceutical production; 8) The development and verification period of the related system of the traditional chromatography device is long, especially in the new product development stage. It prolongs the time for new products to enter the market and increases the development cost; 9) The traditional chromatography device needs to use chemical cleaning agents frequently, which increases the generation of harmful waste. It causes great burden to the environment and does not meet the environmental protection requirements.

[0004] Therefore, it is necessary to provide a plug and play disposable chromatography device to overcome the above problems. SUMMARY

[0005] The utility model discloses a purpose is to solve above -mentioned problem, provide a plug and play disposable chromatography device to solve the problem of high cross -contamination risk, cleaning verification complex and time -consuming, poor flexibility, capital expenditure and operating cost are high, biological safety is insufficient, operation process is complex, data integrity and traceability are poor, development cycle is long and the problem of big environmental burden, improve the device operating performance.

[0006] The technical solution of the utility model is: a plug and play disposable chromatography device, including chromatography pipeline structure, automation control system and data management system, its characteristics are: the chromatography pipeline structure includes pump body, bubble hydrazine and disposable chromatography column, the pump body with bubble hydrazine is sequentially arranged on disposable main pipeline, the disposable chromatography column is communicated with bubble hydrazine through disposable sub - pipeline and connects, and the disposable main pipeline and disposable sub - pipeline are connected through column position valve group;The both ends of pump body are equipped with first flowmeter and first pressure sensor respectively;The liquid inlet end of disposable chromatography column is equipped with second flowmeter and second pressure sensor, and the liquid outlet end of disposable chromatography column is sequentially equipped with electric conductivity sensor, ultraviolet sensor and pH sensor;Each sensor is integrally connected with PLC control system, data management system.

[0007] Further, the above-mentioned plug and play disposable chromatography device, wherein: the liquid inlet end of the disposable main pipeline is provided with a liquid inlet valve group, and the liquid inlet valve group includes at least two control valves.

[0008] Further, the above-mentioned plug and play disposable chromatography device, wherein: the liquid inlet end of the disposable main pipeline is movably connected with a disposable liquid storage container.

[0009] Further, the above-mentioned plug and play disposable chromatography device, wherein: the liquid outlet end of the disposable main pipeline is connected with a liquid outlet valve group, and the liquid outlet valve group includes at least two control valves.

[0010] Further, the above-mentioned plug and play disposable chromatography device, wherein: the liquid outlet end of the disposable main pipeline is movably connected with a receiving container.

[0011] Still further, the above-mentioned plug and play disposable chromatography device, wherein: the column position valve group is provided with a first normally open valve and a second normally open valve at both ends, and the first normally open valve and the second normally open valve are arranged on the disposable sub-pipeline.

[0012] Still further, the above-mentioned plug and play disposable chromatography device, wherein: the column position valve group is a rhombus regulating valve structure composed of four single column position valves.

[0013] Specifically, the above-mentioned plug and play disposable chromatography device, wherein: the pump body is a feed pump.

[0014] Compared with the prior art, the utility model discloses a plug and play disposable assembly mode, reduces the operation step, reduces the possibility of human error, improves the operation efficiency simultaneously, through using the disposable chromatographic column of prefilling, ensures complete isolation between each batch, avoids cross contamination, improves product quality and consistency, through integrated PLC control system data management, ensures that each operation has detailed record, enhances the data integrity and traceability, utilizes aseptic connection technology and presterilization disposable assembly, greatly reduces the risk of microbial contamination, improves the biological safety, and each disposable assembly is discarded after use, reduces the use of harmful substances such as chemical cleaning agent, also reduces the complex cleaning verification cost and time, accelerates the development and verification process, improves the production efficiency, and moreover, can provide the ability of quick replacement, adapts to different process requirements, is suitable for the production facility or research and development laboratory of multiple products, improves the production flexibility and response speed. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figure 1 It is the structural schematic diagram of the utility model;

[0016] Figure 2 It is the system framework drawing of the utility model;

[0017] Figure 3 It is the operation flow chart of the utility model fault monitoring and processing.

[0018] The meaning of each reference sign in the drawing is: 1 - disposable main pipeline, 2 - pump body, 3 - bubble hydrazine, 4 - disposable chromatographic column, 5 - disposable sub-pipeline, 6 - column valve group, 7 - first normally open valve, 8 - second normally open valve, 9 - liquid inlet valve group, 10 - liquid outlet valve group, 11 - first flowmeter, 12 - first pressure sensor, 13 - second flowmeter, 14 - second pressure sensor, 15 - electric conductivity sensor, 16 - ultraviolet sensor, 17 - pH sensor. DETAILED DESCRIPTION

[0019] The technical scheme of the utility model will be further explained in combination with the drawings, so that it is more easy to understand and master. The pump body 2, bubble hydrazine 3, flowmeter and each sensor and other components involved are the commonly used ones of the ordinary skill in the art, and the case has no special requirements.

[0020] For example, Figure 1The utility model provides a plug and play disposable chromatography device, the whole structure includes: chromatography pipeline structure, automation control system and data management system. Chromatography pipeline structure includes pump body 2, bubble hydrazine 3 and disposable chromatography column 4, pump body 2 is feed pump, pump body 2 and bubble hydrazine 3 are sequentially arranged on disposable main pipeline 1, disposable chromatography column 4 is communicated with bubble hydrazine 3 through disposable sub - pipeline 5 and connects. Wherein, disposable main pipeline 1 and disposable sub - pipeline 5 are connected through column valve group 6, the both ends of pump body 2 are equipped with first flowmeter 11 and first pressure sensor 12 respectively, the liquid inlet end of disposable chromatography column 4 is equipped with second flowmeter 13 and second pressure sensor 14, and the liquid outlet end of disposable chromatography column 4 is sequentially equipped with electric conductivity sensor 15, ultraviolet sensor 16 and pH sensor 17.

[0021] All the above sensors are integrated with PLC control system and data management system, real-time monitoring system operation state, and data transmission to PLC control system. PLC control system can be used with host computer system, realizes the automation operation of system, successfully integrates multiple sensors, realizes overall monitoring and automation control, data management system records system operation data (such as flow, pressure, temperature etc.), and shows real-time data and historical data through display screen or computer interface, according to production batch produces corresponding sensor data: flow rate, pressure, ph, cd etc., shows the trend with time / volume / column volume, shows the state of continuous change, can evaluate the separation effect of target molecule and other components by observing UV spectrum or other detection means, also can calculate the liquid amount passing through per unit time, evaluates the processing capacity of system.

[0022] Preferably, among the above structure: the liquid inlet end of disposable main pipeline 1 is equipped with liquid inlet valve group 9, and the liquid inlet valve group 9 includes at least two control valves; the liquid inlet end of disposable main pipeline 1 is movably connected with a liquid storage container.

[0023] Preferably, among the above structure: the liquid outlet end of disposable main pipeline 1 is connected with liquid outlet valve group 10, and the liquid outlet valve group 10 includes at least two control valves; the liquid outlet end of disposable main pipeline 1 is movably connected with a receiving container.

[0024] Preferably, among the above structure: the both ends of column valve group 6 are respectively equipped with first normally open valve 7 and second normally open valve 8, and the first normally open valve 7 and the second normally open valve 8 are arranged on the disposable sub - pipeline 5; the column valve group 6 is a diamond-shaped regulating valve structure composed of four single-column valves. The compact structure of column valve group 6 is internally provided with a flow pipeline, which can assist the disposable chromatography column 4 to carry out high-efficiency filtration operation.

[0025] As Figure 2As shown: chromatography system can be run according to the method of setting, so as to start the corresponding production operation, open the discharge pump and liquid inlet valve group 9, send the raw material liquid from the disposable liquid storage bag to the bubble hydrazine 3 and the disposable chromatography column 4, adjust the flow rate and pressure of the discharge pump, maintain a stable feeding rate, the raw material liquid separates the bubbles in the solution through the bubble hydrazine 3, the macromolecular material is intercepted by the membrane pore of the bubble hydrazine 3, and the other materials (for example: water and small molecular material) are allowed to pass through the disposable chromatography column 4 for affinity chromatography treatment, and can be directly penetrated into the receiving container after passing through the filler. The system can also be continuously operated by the operation of the pump body 2. The material liquid entering the disposable chromatography column 4 enters the corresponding receiving container (which can also be a collection vessel) through the liquid outlet valve group 10. During the period, each sensor monitors the running state of the system in real time. The PLC control system automatically adjusts the pump speed, pressure and valve state according to the sensor data. Data recording and analysis processing are carried out through the data management system. The system automatically uses SQL Server for data verification. It covers data integrity, consistency, accuracy and other aspects of inspection. Finally, the data results are directly displayed on the display screen or computer interface.

[0026] As shown in Figure 3 Fault monitoring and alarm processing is the key operation to ensure stable operation of the system, timely discovery and solution of problems, including monitoring points, alarm mechanisms, processing procedures and preventive measures. When automatic processing is adopted, the on-site buzzer alarm will issue an alarm when serious faults of sensors, valves or other equipment (such as: pump body 2 running state, current, vibration, etc.; the opening and closing state of each valve; the state of the disposable chromatography column is indirectly judged by parameters such as pressure and flow rate) are detected, or the alarm log information is displayed on the software interface (HMI), and the corresponding icon flashes red. For example, if the pressure is too high, the system will automatically shut down and stop the pump to prevent further damage. In some cases, the system will automatically close the related valves to prevent leakage or overflow. When manual processing is adopted, the operator will first confirm the alarm information on the HMI after receiving the alarm. The system automatically records the alarm time, type and location. According to the alarm information, the operator makes a preliminary diagnosis to determine the cause of the fault, checks the related equipment and sensors on site, confirms the fault condition, including checking whether the pump, pipeline, valve, bubble hydrazine, column is blocked or leaked, adjusting the pump speed or valve switch, and also including checking the pump, valve and other equipment, and necessary maintenance or replacement (for example: if the actual value of a sensor exceeds the highest value set in the alarm parameter, the sensor is faulty), and after the fault is eliminated, the system is restarted and the running condition is observed to ensure normal recovery.

[0027] In the technical scheme of the utility model, under the automatic control of the PLC control system and the data management system, the disposable chromatography device with plug and play and replaceable consumables is the technical key of the case.Figure 1 The key point of the present application is to provide a disposable chromatography device, which is designed as plug-and-play to reduce installation time and complexity, Figure 2 The present application is a disposable chromatography system framework structure, which is monitored in real time by an automatic control system to ensure process stability and intuitive chromatography data. Figure 3 The present application is a disposable chromatography device failure monitoring and processing operation process. For pump body 2, bubble hydrazine 3, flow meter and various sensors, etc. The ordinary skilled in the art can make routine settings according to the prior art, and there is no special requirement for the selection and combination of the type.

[0028] Thus, the technical scheme of the present application can monitor and adjust the flow rate of the pump in real time, and according to the sensor value, the automatic and manual methods can be used for troubleshooting. Set a reasonable alarm threshold to discover and handle abnormal situations in time; at the same time, through the data management system, the data can be input into the graphical user interface (GUI) for direct display, which is convenient for operators to monitor and adjust parameters, can accurately record experimental data, and store the data in the database for subsequent analysis and research.

[0029] Through the above description, it can be found that compared with the prior art, the technical scheme of the present application uses a plug-and-play assembly mode, reduces the operation steps, reduces the possibility of human error, improves the operation efficiency, uses a pre-filled disposable column to ensure complete isolation between each batch, avoids cross contamination, improves product quality and consistency; through the integrated PLC control system for data management, it ensures that each operation is recorded in detail, enhances the data integrity and traceability; using aseptic connection technology and pre-sterilized disposable components greatly reduces the risk of microbial contamination, improves biological safety, and each disposable component is discarded after use, reduces the use of harmful substances such as chemical cleaning agents, also reduces the cost and time of complex cleaning verification, speeds up the development and verification process, and improves the production efficiency; moreover, it can provide the ability to replace quickly, adapt to different process requirements, suitable for multi-product production facilities or research laboratories, improve the flexibility and response speed of production.

[0030] The technical scheme, working process and implementation effect of the present application are described in detail above. It should be noted that the described is only a typical example of the present application, in addition to this, the present application can have other various specific implementation manners, and any technical scheme formed by equivalent substitution or equivalent transformation falls within the scope of the present application.

Claims

1. A plug and play disposable chromatography device comprising a chromatography tubing structure, an automated control system and a data management system, characterized in that: The chromatography pipeline structure comprises a pump body (2), a bubble hydrazine (3) and a disposable chromatography column (4), the pump body (2) and the bubble hydrazine (3) are sequentially arranged on a disposable main pipeline (1), the disposable chromatography column (4) is connected with the bubble hydrazine (3) through a disposable auxiliary pipeline (5), the disposable main pipeline (1) and the disposable auxiliary pipeline (5) are connected through a column position valve group (6); both ends of the pump body (2) are respectively provided with a first flow meter (11) and a first pressure sensor (12); the liquid inlet end of the disposable chromatography column (4) is provided with a second flow meter (13) and a second pressure sensor (14), the liquid outlet end of the disposable chromatography column (4) is sequentially provided with an electric conductivity sensor (15), an ultraviolet sensor (16) and a pH sensor (17); each sensor is integrally connected with an automatic control system and a data management system.

2. A plug and play disposable chromatography device according to claim 1, characterized in that: The liquid inlet end of the disposable main pipeline (1) is provided with a liquid inlet valve group (9), the liquid inlet valve group (9) comprises at least two control valves.

3. A plug and play disposable chromatography device according to claim 2, characterized in that: The liquid inlet end of the disposable main pipeline (1) is movably connected with a liquid storage container.

4. A plug and play disposable chromatography device according to claim 1, characterized in that: The liquid outlet end of the disposable main pipeline (1) is connected with a liquid outlet valve group (10), the liquid outlet valve group (10) comprises at least two control valves.

5. A plug and play disposable chromatography device according to claim 4, characterized in that: The liquid outlet end of the disposable main pipeline (1) is movably connected with a receiving container.

6. A plug and play disposable chromatography device according to claim 1, characterized in that: Both ends of the column position valve group (6) are respectively provided with a first normally open valve (7) and a second normally open valve (8), the first normally open valve (7) and the second normally open valve (8) are arranged on the disposable auxiliary pipeline (5).

7. A plug and play disposable chromatography device according to claim 1, characterized in that: The column position valve group (6) is a rhombic regulating valve structure composed of four single column position valves.

8. A plug and play disposable chromatography device according to claim 1, characterized in that: The pump body (2) is a feeding pump.

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