Chromatographic equipment with on-line fluid imaging analysis function

Abstract

The utility model discloses chromatographic equipment with an on-line fluid imaging analysis function, which comprises two pump bodies, a chromatographic column, two FIA analysis modules and a plurality of valves and sensors, the two pump bodies converge to a main pipe flow path through an auxiliary pipe flow path, the chromatographic column is arranged on the main pipe flow path, the FIA analysis modules are arranged at the liquid inlet end and the liquid outlet end of the chromatographic column, and the valves and the sensors are arranged on the FIA analysis modules. The device is used for realizing fluid online sampling detection and imaging analysis in a chromatographic purification process. According to the scheme, two groups of FIA analysis modules are arranged and are used for respectively carrying out online fluid imaging analysis operation before and after chromatographic purification, so that particulate matters which do not meet the standard particle size can be fully screened out, the blockage fault of equipment in the chromatographic purification process is effectively avoided, and the FIA analysis modules can be suitable for being matched with isocratic, gradient or disposable chromatographic structures; therefore, integration on the same equipment is realized, one machine has two purposes, the production and detection efficiency is further improved, and the product quality is ensured.

Description

Technical Field

[0001] This utility model relates to a chromatography device, and more particularly to a chromatography device with online fluid imaging analysis function, belonging to the field of biopharmaceutical purification and separation technology. Background Technology

[0002] Chromatography, as the most commonly used purification technique for biological macromolecules, has wide applications in the purification of antibodies, recombinant proteins, and blood products. The particulate matter content and particle size distribution of the samples collected by chromatography can directly affect product quality and determine whether subsequent processing steps can proceed. Therefore, fluid imaging analysis equipment is often needed for QC detection of particles in the processed samples. The traditional procedure involves using a computer-controlled high-precision syringe pump to inject the sample through a flow cell perpendicular to the optical path. The optical imaging system, similar to a microscope, can take real-time, high-speed images of the particles passing through the flow cell. Powerful image capture and statistical analysis software can analyze and process the captured particle images to provide multi-dimensional parameters about the particles, such as size, length, and width.

[0003] However, during chromatographic purification, the presence of large-diameter particles in the solution or sample can clog the chromatography column sieve, causing system overpressure, process interruption, and unnecessary production disruptions. Therefore, it is necessary to develop a chromatography device with online fluid imaging analysis capabilities to detect large-diameter particles and facilitate timely removal. Summary of the Invention

[0004] The purpose of this invention is to solve the above-mentioned problems and provide a chromatography device with online fluid imaging analysis function.

[0005] The technical solution of this utility model is: a chromatography device with online fluid imaging analysis function, including a first FIA analysis module, a chromatography column, and a second FIA analysis module disposed on the main flow path. The main flow path is characterized by: a first secondary flow path and a second secondary flow path being branched at one end; a first pump body is disposed on the first secondary flow path, and the output end of the first pump body is connected to a valve in the first secondary flow path; a second pump body is disposed on the second secondary flow path, and the second pump body is sequentially connected to a mass flow meter and a valve in the second secondary flow path; a mixing tube, a pressure sensor, and a bubble are sequentially disposed at the other end of the main flow path. The system comprises a bubble trap, a first FIA analysis module, a chromatography column, and a second FIA analysis module. The mixing tube and the pressure sensor are connected in series on the main flow path. The bubble trap is connected between the pressure sensor and the first FIA analysis module and is connected to a first valve on the main flow path. The first FIA analysis module can be switched to the main flow path via a first online three-way sample loading switching valve. The chromatography column is connected to the main flow path via a column position valve group and the precipitate is controlled by a second valve on the main flow path. The second FIA analysis module can be switched to the main flow path via a second online three-way sample loading switching valve.

[0006] Furthermore, in the above-mentioned chromatography device with online fluid imaging analysis function, the bubble trap is provided with an inlet, an outlet and an exhaust port, the inlet and the outlet are cyclically connected to the main flow path; the exhaust port is used to discharge the gas separated by the bubble trap.

[0007] Furthermore, in the aforementioned chromatography device with online fluid imaging analysis function, the bubble trap is also equipped with a liquid level sensor and a sound-activated alarm.

[0008] Furthermore, in the aforementioned chromatography device with online fluid imaging analysis function, the end of the first secondary pipe flow path is provided with a first liquid inlet port, and an air flow meter and several pneumatic diaphragm valves are installed on the first liquid inlet port.

[0009] Furthermore, in the aforementioned chromatography device with online fluid imaging analysis function, the end of the second secondary pipe flow path is provided with a second liquid inlet port, and several pneumatic diaphragm valves are installed on the second liquid inlet port.

[0010] Furthermore, in the aforementioned chromatography device with online fluid imaging analysis function, the other end of the main flow path is provided with a liquid outlet port, and several pneumatic diaphragm valves are installed on the liquid outlet port.

[0011] Furthermore, in the aforementioned tomography device with online fluid imaging analysis function, the column position valve group is a regulating valve structure composed of four single column position valve bodies.

[0012] Furthermore, in the above-mentioned chromatography device with online fluid imaging analysis function, a comprehensive sensor group is also provided between the chromatography column and the second FIA analysis module. The comprehensive sensor group includes, but is not limited to, a pressure sensor, a pH sensor, a conductivity sensor, and an ultraviolet sensor.

[0013] Compared with existing technologies, the present invention incorporates two sets of FIA analysis modules, which perform two online fluid imaging analyses on the chromatographic purification process. This effectively filters out particulate matter that does not meet the standard particle size, thus preventing equipment blockage during the chromatographic purification process. Furthermore, the FIA ​​analysis modules are compatible with isocratic, gradient, or single-pass chromatographic structures, allowing for integration onto the same equipment and achieving dual functionality. This further improves production and testing efficiency and ensures product quality. Attached Figure Description

[0014] Figure 1 This is a schematic diagram of the overall structure of this utility model.

[0015] The meanings of the labels in the attached figures are as follows: 1-Main flow path, 2-First auxiliary flow path, 3-Second auxiliary flow path, 4-First pump body, 5-Second pump body, 6-First FIA analysis module, 7-Chromatography column, 8-Second FIA analysis module, 9-Bubble trap, 91-Inlet, 92-Outlet, 93-Exhaust port, 94-Level sensor, 95-Audible alarm, 10-First inlet port, 11-Second inlet port, 12-Outlet port, 13-Valve of first auxiliary flow path, 14-Valve of second auxiliary flow path, 15-First valve of main flow path, 16-First online three-way sample loading switching valve, 17-Column position valve group, 18-Second valve of main flow path, 19-Second online three-way sample loading switching valve, 20-Air flow meter, 21-Mass flow meter, 22-Mixing tube, 23-Pressure sensor, 24-Comprehensive sensor group. Detailed Implementation

[0016] The technical solution of this utility model will be further described below with reference to the accompanying drawings to make it easier to understand and master. The pump body, valves, and sensors involved are all commonly used components that are generally recognized by those skilled in the art, and there are no special requirements for them in this application.

[0017] like Figure 1 As shown, the present invention provides a chromatography device with online fluid imaging analysis function, including a first FIA analysis module 6, a chromatography column 7, and a second FIA analysis module 8 disposed on the main flow path 1.

[0018] According to the technical solution of this utility model, one end of the main flow path 1 is branched into a first secondary flow path 2 and a second secondary flow path 3. A first pump body 4 is provided on the first secondary flow path 2, and the output end of the first pump body 4 is connected to a valve 13 of the first secondary flow path. A second pump body 5 is provided on the second secondary flow path 3, and the second pump body 5 is sequentially connected to a mass flow meter 21 and a valve 14 of the second secondary flow path. The other end of the main flow path 1 is sequentially provided with a mixing tube 22, a pressure sensor 23, a bubble trap 9, a first FIA analysis module 6, a chromatography column 7, and a second FIA analysis module 8. The tube 22 and the pressure sensor 23 are connected in series on the main flow path 1. The bubble trap 9 is connected between the pressure sensor 23 and the first FIA analysis module 6 and is connected to the first valve 15 of the main flow path. The first FIA analysis module 6 can be switched to the main flow path 1 through the first online three-way sample loading switching valve 16. The chromatography column 7 is connected to the main flow path 1 through the column position valve group 17 and the precipitate is controlled by the second valve 18 of the main flow path. The second FIA analysis module 8 can be switched to the main flow path 1 through the second online three-way sample loading switching valve 19.

[0019] Preferably, in the above structure: the bubble trap 9 is provided with an inlet 91, an outlet 92, and an exhaust port 93, the inlet 91 and the outlet 92 are cyclically connected to the main flow path 1; the exhaust port 93 is used to discharge the gas separated by the bubble trap 9 in order to remove the bubbles generated during the chromatography purification process; the bubble trap 9 is also equipped with a liquid level sensor 94 and a sound alarm 95 so that when the liquid level exceeds the standard, the sound alarm 95 will provide an audible alert.

[0020] Preferably, in the above structure: the end of the first secondary pipe flow path 2 is provided with a first liquid inlet port 10, and an air flow meter 20 and several pneumatic diaphragm valves are installed on the first liquid inlet port 10; the end of the second secondary pipe flow path 3 is provided with a second liquid inlet port 11, and several pneumatic diaphragm valves are installed on the second liquid inlet port 11 to control the flow of fluid in each secondary pipe flow path.

[0021] Preferably, in the above structure: the other end of the main flow path 1 is provided with a liquid outlet port 12, and several pneumatic diaphragm valves are installed on the liquid outlet port 12 to control the fluid flow out of the main flow path 1.

[0022] Specifically, in the structure of the above-mentioned chromatography equipment with online fluid imaging analysis function, the column position valve group 17 is a regulating valve structure composed of four single column position valve bodies. According to the requirements, the single column position valve bodies are selected in pairs to control the forward, reverse or bypass fluid to enter the chromatography column 7.

[0023] Specifically, in the structure of the above-mentioned chromatography device with online fluid imaging analysis function, a comprehensive sensor group 24 is also provided between the chromatography column 7 and the second FIA analysis module 8. The comprehensive sensor group 24 includes, but is not limited to, pressure sensors, pH sensors, conductivity sensors and ultraviolet sensors, so as to realize the comprehensive detection and collection of fluid parameters.

[0024] The combination of the two sets of FIA analysis modules and the tomographic structure in this invention is the key technical aspect. Figure 1 The focus is on showcasing the two sets of FIA analysis modules and the related components and specific flow path connections involved in the chromatography structure. These two sets of FIA analysis modules enhance particle detection during the chromatography purification process, enabling the removal of particles that are too large or do not meet processing standards. For components such as the pump body, valves, and sensors, those skilled in the art can perform conventional setups based on existing technology; this application does not have special requirements regarding model selection or combination.

[0025] Thus, using the technical solution of this utility model, the original solution to be chromatographically processed merges with the flow paths of the first pump body 4 and the second pump body 5 into the main flow path 1, and then enters the bubble trap 9 for defoaming. The first online three-way sample loading switching valve 16 is then switched, and the first FIA analysis module 6 performs a primary imaging detection and analysis. Then, depending on the requirements, two-way combination single-column valves are selected to control the forward, reverse, or bypass flow into the chromatography column 7. After chromatography purification by the chromatography column 7, and after a series of detection sensors confirm that the sample meets the standards, the second online three-way sample loading switching valve 19 is switched, transferring the chromatographically purified sample to the second FIA analysis module 8 for a secondary imaging detection and analysis. Therefore, by adding a fluid imaging analysis system and combining it with the chromatography structure, online sampling and detection analysis during the chromatography process can be achieved. The flow paths of the chromatography system, the number of valves, the types and number of detection units, and the number and installation positions of the fluid imaging analysis modules can all be appropriately adjusted according to the actual operating conditions to maximize the working range and application scenarios of the equipment.

[0026] As can be seen from the above description, compared with the prior art, the present invention provides two sets of FIA analysis modules, which perform two online fluid imaging analyses on the chromatography purification process. This effectively screens out particulate matter that does not meet the standard particle size, thus avoiding equipment blockage during the chromatography purification process. Moreover, the FIA ​​analysis modules are compatible with isocratic, gradient, or single-pass chromatography structures, allowing for integration onto the same equipment and achieving dual-purpose functionality. This further improves production and testing efficiency and ensures product quality.

[0027] The technical solution, working process and implementation effect of this utility model have been described in detail above. It should be noted that the described example is only a typical example of this utility model. In addition, this utility model may have many other specific implementation methods. All technical solutions formed by equivalent substitution or equivalent transformation fall within the scope of protection claimed by this utility model.

Claims

1. A chromatography device with online fluid imaging analysis function, comprising a first FIA analysis module (6), a chromatography column (7), and a second FIA analysis module (8) disposed on the main flow path (1), characterized in that: One end of the main flow path (1) is branched into a first secondary flow path (2) and a second secondary flow path (3). The first secondary flow path (2) is equipped with a first pump body (4), and the output end of the first pump body (4) is connected to the valve (13) of the first secondary flow path. The second secondary flow path (3) is equipped with a second pump body (5), and the second pump body (5) is connected in sequence to a mass flow meter (21) and a valve (14) of the second secondary flow path. The other end of the main flow path (1) is equipped with a mixing tube (22), a pressure sensor (23), a bubble trap (9), a first FIA analysis module (6), a chromatography column (7), and a second FIA analysis module (8). The mixing tube (22) is connected in sequence to the second secondary flow path (3). The pressure sensor (23) and the bubble trap (9) are connected in series on the main flow path (1). The bubble trap (9) is connected between the pressure sensor (23) and the first FIA analysis module (6) and is connected to the first valve (15) of the main flow path. The first FIA analysis module (6) can be switched to the main flow path (1) through the first online three-way sample switching valve (16). The chromatography column (7) is connected to the main flow path (1) through the column position valve group (17) and the chromatography liquid is controlled by the second valve (18) of the main flow path. The second FIA analysis module (8) can be switched to the main flow path (1) through the second online three-way sample switching valve (19).

2. The tomographic apparatus with online fluid imaging analysis function according to claim 1, characterized in that: The bubble trap (9) is provided with an inlet (91), an outlet (92) and an exhaust port (93). The inlet (91) and the outlet (92) are cyclically connected to the main flow path (1). The exhaust port (93) is used to discharge the gas separated by the bubble trap (9).

3. The tomographic apparatus with online fluid imaging analysis function according to claim 2, characterized in that: The bubble trap (9) is also equipped with a liquid level sensor (94) and a sound alarm (95).

4. The tomographic apparatus with online fluid imaging analysis function according to claim 1, characterized in that: The first secondary pipe flow path (2) is provided with a first liquid inlet port (10) at its end. An air flow meter (20) and several pneumatic diaphragm valves are installed on the first liquid inlet port (10).

5. The tomographic apparatus with online fluid imaging analysis function according to claim 1, characterized in that: The second secondary pipe flow path (3) is provided with a second liquid inlet port (11) at the end, and several pneumatic diaphragm valves are installed on the second liquid inlet port (11).

6. The tomographic apparatus with online fluid imaging analysis function according to claim 1, characterized in that: The other end of the main flow path (1) is provided with a liquid outlet port (12), and several pneumatic diaphragm valves are installed on the liquid outlet port (12).

7. The tomographic apparatus with online fluid imaging analysis function according to claim 1, characterized in that: The column position valve group (17) is a regulating valve structure composed of four single column position valve bodies.

8. The tomographic apparatus with online fluid imaging analysis function according to claim 1, characterized in that: A comprehensive sensor group (24) is also provided between the chromatography column (7) and the second FIA analysis module (8). The comprehensive sensor group (24) includes, but is not limited to, a pressure sensor, a pH sensor, a conductivity sensor and an ultraviolet sensor.

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