Automatic sample loading chromatography equipment and chromatography method

Abstract

The invention provides automatic sample loading chromatography equipment and a chromatography method, and relates to the technical field of biological separation.The chromatography equipment comprises a feeding assembly, a processing assembly, a sample loading assembly and a controller, the feeding assembly comprises a plurality of sample containers, a target solution to be subjected to chromatography and an auxiliary solution needed for chromatography of the target solution to be subjected to chromatography; the treatment assembly comprises a chromatographic column; the sample loading assembly is respectively connected with the feeding assembly and the processing assembly, the sample loading assembly comprises a multi-way reversing valve and a fluid driving mechanism, and a fluid interface of the multi-way reversing valve is connected with a plurality of sample containers and chromatographic columns; the fluid driving mechanism is connected with one fluid interface of the multi-way reversing valve and sucks or discharges a sample solution through the multi-way reversing valve; and the controller is in signal connection with the multi-way reversing valve and the fluid driving mechanism so as to control the reversing valve core and the fluid driving mechanism to provide a target solution and / or an auxiliary solution to be subjected to chromatography to the processing assembly. According to the chromatographic equipment, automatic sample loading can be realized, the precision of sample loading quantity is improved, and the chromatographic efficiency is improved.

Description

[0001] Cross-references This application claims priority to Chinese patent application No. 202411675739.2, filed on November 21, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This application relates to the field of bioseparation technology, and in particular to an automated sample loading chromatography device and chromatography method. Background Technology

[0003] Chromatography utilizes the differences in the physicochemical properties of different substances. Chromatography involves a stationary phase and a mobile phase. When the mixture to be separated passes through the stationary phase with the mobile phase, due to the differences in the physicochemical properties of each component, their ability to interact with the two phases varies, resulting in different distributions in the two phases. Furthermore, as the mobile phase moves forward, the components are continuously redistributed between the two phases.

[0004] Currently, existing chromatography equipment typically requires manual addition of samples one by one during sample loading. The accuracy of manual operation in controlling sample loading is limited, and the efficiency of manual operation is low, which cannot meet today's demand for high efficiency and precision. Summary of the Invention

[0005] This application provides an automated sample loading chromatography device and method to achieve automated sample loading, improve the accuracy of sample loading, and enhance chromatography efficiency.

[0006] An embodiment of the first aspect of this application provides an automated sample loading chromatography apparatus, comprising: a feeding assembly including multiple sample containers holding sample solutions, the sample solutions including a target solution to be chromatographically analyzed and an auxiliary solution required for chromatographically analyzing the target solution; a processing assembly including at least one chromatography column; a loading assembly connected to both the feeding assembly and the processing assembly, the loading assembly including a multi-way directional valve and a fluid drive mechanism, the multi-way directional valve having multiple fluid interfaces and a directional valve core, the fluid interfaces being connected to the multiple sample containers and at least one chromatography column; the directional valve core being used to control the opening and closing of the fluid interfaces; the fluid drive mechanism being connected to one fluid interface of the multi-way directional valve and drawing in or discharging sample solution through the multi-way directional valve; and a controller being signal-connected to the multi-way directional valve and the fluid drive mechanism, the controller being used to control the directional valve core and the fluid drive mechanism to provide the target solution to be chromatographically analyzed and / or the auxiliary solution to the processing assembly.

[0007] In some embodiments, the feeding assembly includes a first feeding unit, the first feeding unit including at least one first sample container for holding the target solution to be chromatographically analyzed; the sample loading assembly further includes a sampling member, the sampling member including a first end and a second end connected in communication, the first end of the sampling member being connected to a fluid interface of a multi-way reversing valve, and the second end of the sampling member being able to extend into the first sample container for aspirating the target solution to be chromatographically analyzed.

[0008] In some embodiments, the first end of the sampling element is connected to the multi-way reversing valve through a first pipeline, and a first bubble sensor is provided on the first pipeline; the sample loading assembly also includes a lifting unit, which is used to drive the sampling element to lift.

[0009] In some embodiments, the first feeding unit further includes: a first base for supporting at least one first sample container; and a first driving member connected to the first base and used to drive the first base to move horizontally, such that at least one first sample container moves sequentially below the sampling member.

[0010] In some embodiments, the first base is further provided with a first waste liquid tank, which is used to receive waste liquid discharged from the second end of the sampling member.

[0011] In some embodiments, the first feeding unit further includes a first identification component connected to a controller signal, the first identification component being used to acquire first identification information of the first sample container, the first identification information being used to indicate the type and / or volume of the solution contained in the first sample container.

[0012] In some embodiments, the feeding assembly further includes a second feeding unit, which includes at least one second sample container for holding an auxiliary solution. Each second sample container is connected to the fluid interface of a multi-way reversing valve via a second pipeline, and a second bubble sensor is provided in the second pipeline.

[0013] In some embodiments, at least one chromatography column includes a first chromatography column and a second chromatography column, wherein the first chromatography column is used to perform a first chromatography treatment on the target solution to be chromatographically analyzed, and the second chromatography column is used to perform a second chromatography treatment on the target solution to be chromatographically analyzed; wherein the first chromatography column and the second chromatography column are of the same type; or the first chromatography column and the second chromatography column are of different types.

[0014] In some embodiments, the first chromatography column and the second chromatography column are chromatography columns of different types. The first chromatography column is configured to perform a first chromatography treatment on the target solution to be chromatographyd to obtain an intermediate solution, and the second chromatography column is configured to perform a second chromatography treatment on the intermediate solution to obtain the chromatographically purified target solution.

[0015] In some embodiments, the inlet of the first chromatography column and the inlet of the second chromatography column are connected in parallel to the fluid interface of the multi-way directional valve.

[0016] In some embodiments, the first chromatography column and the second chromatography column are selected from one of the following: affinity chromatography column, ion exchange chromatography column, multimode chromatography column, hydrophobic interaction chromatography column, reverse chromatography column, and size exclusion chromatography column.

[0017] In some embodiments, the processing component further includes a first pressure detection unit and a second pressure detection unit; the first pressure detection unit is located upstream of at least one chromatography column to detect the liquid pressure before entering at least one chromatography column; the second pressure detection unit is located downstream of at least one chromatography column to detect the liquid pressure flowing out of at least one chromatography column.

[0018] In some embodiments, the first pressure detection unit includes a first three-way valve, the inlet of which is connected to the fluid interface of a multi-way directional valve, and the two outlets of which are respectively connected to the inlet of a first chromatography column and the inlet of a second chromatography column; the second pressure detection unit includes a second three-way valve, the two inlets of which are respectively connected to the outlet of the first chromatography column and the outlet of the second chromatography column; the first three-way valve and the second three-way valve are respectively connected to a controller signal.

[0019] In some embodiments, the processing component further includes a detection module, which includes one or more of a UV detection module, a conductivity detection module, and a pH detection module, and the detection module is located downstream of at least one chromatography column.

[0020] In some embodiments, the processing component further includes a bubble trap for reducing bubbles, the bubble trap being disposed between the second pressure detection unit and the detection module.

[0021] In some embodiments, the chromatography apparatus further includes a dispensing component, which includes a multi-way solenoid valve that is signal-connected to a controller; a first inlet of the multi-way solenoid valve is connected to the outlet of at least one chromatography column, and the multi-way solenoid valve includes a first outlet and a second outlet that can communicate with the first inlet; the first outlet is used to discharge the target solution after chromatography, and the second outlet is used to discharge the waste liquid generated by the chromatography process.

[0022] In some embodiments, at least one chromatography column includes a first chromatography column and a second chromatography column; the outlet of the first chromatography column and the outlet of the second chromatography column are respectively connected to the first inlet of a multi-way solenoid valve; the multi-way solenoid valve further includes a third outlet that can be connected to the first inlet, the third outlet being provided with a transfer collection head, the transfer collection head being used to receive and discharge the intermediate solution obtained by the first chromatography column.

[0023] In some embodiments, the multi-way solenoid valve further includes a second inlet and a fourth outlet. The second inlet is connected to a fluid interface of the multi-way directional valve, and the fourth outlet is connected to the second inlet and is used to discharge liquid flowing into the second inlet.

[0024] In some embodiments, a stop solenoid valve is also provided at the fourth outlet, which is used to close the fourth outlet.

[0025] In some embodiments, the dispensing component further includes a collection unit, which includes: a first collection container; a second base for supporting the first collection container; and a second drive member connected to the second base and used to drive the second base to move horizontally, so that the plurality of first collection containers move sequentially below the first outlet to receive the target solution after chromatography.

[0026] In some embodiments, the collection unit further includes: a second collection container placed on a first base for receiving intermediate solution discharged from the transfer collection head; and a second waste liquid tank for receiving liquid discharged from one or more of the first outlet, the second outlet, and the fourth outlet.

[0027] In some embodiments, the processing component further includes a detection module connected to the controller signal, the detection module being located downstream of at least one chromatography column, for detecting information about the solution discharged from the chromatography column, and the controller being configured to issue a control command to a second drive according to the detection information from the detection module, the second drive driving a second base to move according to the control command, so that the first collection container or the second waste liquid tank moves below the multi-way solenoid valve to receive the liquid discharged from the multi-way solenoid valve.

[0028] An embodiment of the second aspect of this application provides a chromatography method applied to the above-described chromatography apparatus. The chromatography method includes: a sample loading stage, comprising: controlling a multi-way reversing valve and a fluid drive mechanism to supply the target solution to be chromatography to at least one chromatography column; and a chromatography stage, comprising: controlling a multi-way reversing valve and a fluid drive mechanism to supply an auxiliary solution required for chromatography to at least one chromatography column for chromatographic treatment of the target solution to obtain a chromatographically purified target solution.

[0029] In some embodiments, the sample loading stage includes: controlling the rotation of the directional valve core of the multi-way reversing valve, such that the first fluid port and the second fluid port of the multi-way reversing valve are respectively connected to a fluid drive mechanism; the first fluid port is a fluid port connected to a sample container holding the target solution to be chromatographically analyzed, and the second fluid port is a fluid port connected to at least one chromatography column; controlling the fluid drive mechanism to supply the target solution to be chromatographically analyzed to at least one chromatography column; and / or the chromatography stage includes: controlling the rotation of the directional valve core of the multi-way reversing valve, such that the third fluid port and the second fluid port of the multi-way reversing valve are respectively connected to a fluid drive mechanism; the third fluid port is a fluid port connected to a sample container holding an auxiliary solution; controlling the fluid drive mechanism to supply the auxiliary solution to at least one chromatography column for chromatographic processing of the target solution to be chromatographically analyzed, to obtain the chromatographically analyzed target solution.

[0030] In some embodiments, at least one chromatography column includes a first chromatography column and a second chromatography column. The first chromatography column is used to perform a first chromatography treatment on the target solution to be chromatographyd to obtain an intermediate solution, and the second chromatography column is used to perform a second chromatography treatment on the intermediate solution to obtain the chromatographically purified target solution. The sample loading stage includes: controlling a multi-way reversing valve and a fluid drive mechanism to supply the target solution to be chromatographyd to the first chromatography column; the chromatography stage includes: controlling a multi-way reversing valve and a fluid drive mechanism to supply an auxiliary solution required for the first chromatography treatment to the first chromatography column for performing the first chromatography treatment on the target solution to obtain an intermediate solution; and wherein the chromatography method further includes: a secondary sample loading stage, including: controlling a multi-way reversing valve and a fluid drive mechanism to supply an intermediate solution to the second chromatography column; and a secondary chromatography stage, including: controlling a multi-way reversing valve and a fluid drive mechanism to supply an auxiliary solution required for the second chromatography treatment to the second chromatography column for performing the second chromatography treatment on the intermediate solution to obtain the chromatographically purified target solution.

[0031] In some embodiments, the sample loading stage further includes: acquiring the detection result of a bubble sensor located upstream of the multi-way reversing valve, and in response to the detection result indicating that the size of the bubble exceeds a preset threshold, controlling the multi-way reversing valve to discharge the bubble from the pipeline before the inlet of at least one chromatography column.

[0032] In some embodiments, the chromatography stage further includes: controlling a multi-way reversing valve and a fluid drive mechanism to cause liquid flowing out of at least one chromatography column to flow through a bubble trap in order to reduce bubbles in the liquid flowing out of at least one chromatography column.

[0033] In some embodiments, the chromatography stage further includes: acquiring the detection result of a detection module disposed downstream of at least one chromatography column; the detection result being used to indicate the type of liquid flowing out of at least one chromatography column; and based on the detection result, controlling a multi-way solenoid valve located downstream of the detection module to discharge the liquid flowing out of at least one chromatography column from the outlet corresponding to the multi-way solenoid valve.

[0034] In some embodiments, prior to the sample loading stage, the chromatography method further includes: acquiring first identification information, the first identification information being used to indicate the solution type and solution volume of the target solution to be chromatographically analyzed; and, based on the first identification information, controlling the feeding assembly, the multi-way reversing valve, and the fluid drive mechanism to perform the actions of the sample loading stage and the chromatography stage.

[0035] In some embodiments, prior to the sample loading stage, the chromatography method further includes a pipeline pre-filling stage, comprising: The directional valve core of the multi-way directional valve is controlled to rotate, so that the first fluid port and the fourth fluid port of the multi-way directional valve are respectively connected to the fluid drive mechanism; the fourth fluid port is connected to the multi-way solenoid valve of the distribution component; the fluid drive mechanism is controlled to draw auxiliary solution from the third fluid port and discharge it from the fourth fluid port; and / or, the directional valve core of the multi-way directional valve is controlled to rotate, so that the first fluid port and the third fluid port of the multi-way directional valve are respectively connected to the fluid drive mechanism; the fluid drive mechanism is controlled to draw auxiliary solution from the third fluid port and discharge it from the first fluid port.

[0036] In some embodiments, before the sample loading stage and after the tubing pre-filling, the chromatography method further includes an equilibration stage, comprising: controlling the rotation of the directional valve core of a multi-way directional valve to connect the second fluid interface and the third fluid interface of the multi-way directional valve to a fluid drive mechanism; and controlling the fluid drive mechanism to provide an auxiliary solution to at least one chromatography column for equilibration of at least one chromatography column.

[0037] This embodiment provides an automated sample loading chromatography device, which includes a feeding component, a processing component, a sample loading component, and a controller. The sample loading component is connected to both the feeding component and the processing component. The fluid interface of a multi-way reversing valve is connected to multiple sample containers and chromatography columns. A fluid drive mechanism is connected to one fluid interface of the multi-way reversing valve. The controller controls the reversing valve core and the fluid drive mechanism to draw in or discharge the target solution and / or auxiliary solution to be chromatographically analyzed through the multi-way reversing valve, and to supply the target solution and / or auxiliary solution to the processing component. By using the controller to control the reversing valve core and the fluid drive mechanism, precise control of sample loading can be achieved, improving the accuracy of sample loading. Furthermore, automated sample loading replaces manual sample loading, which also speeds up the sample loading process, thereby improving the chromatography efficiency of the device.

[0038] It should be understood that the description in this section is not intended to identify key or essential features of the embodiments of this application, nor is it intended to limit the scope of this application. Other features of this application will become readily apparent from the following description. Attached Figure Description

[0039] The accompanying drawings exemplify embodiments and form part of the specification, serving together with the textual description to explain exemplary implementations of the embodiments. The illustrated embodiments are for illustrative purposes only and do not limit the scope of the claims. Throughout the drawings, the same reference numerals refer to similar but not necessarily identical elements.

[0040] Figure 1 A front view of a chromatography apparatus provided in an embodiment of this application; Figure 2 A top view of a chromatography apparatus provided in an embodiment of this application; Figure 3 A side view of a chromatography apparatus provided in an embodiment of this application; Figure 4 A perspective view of a chromatography apparatus provided in an embodiment of this application; Figure 5 This is a schematic diagram of the structure of the chromatography apparatus provided in this application, in which the sampling element extends into the first waste liquid tank; Figure 6 A schematic diagram of the structure of the chromatography apparatus provided in this application, showing the sampling element extending into the first sample container; Figure 7 A schematic diagram of an affinity chromatography apparatus provided in this application embodiment; Figure 8 This is a schematic diagram of a desalination chromatography apparatus provided in an embodiment of this application; Figure 9 This is a schematic diagram of another chromatography device provided in an embodiment of this application; Figure 10 A schematic diagram of a combined affinity chromatography and desalination chromatography apparatus provided in this application embodiment; Figure 11 This is a schematic diagram of the structure of the multi-channel solenoid valve in the chromatography apparatus provided in the embodiments of this application; Figure 12 This is a schematic diagram of the internal flow structure of a multi-way solenoid valve provided in an embodiment of this application; Figure 13 A schematic flowchart of a chromatography method provided in this application embodiment; Figure 14 A schematic flowchart of another tomography method provided in an embodiment of this application; Figure 15 A schematic flowchart of another tomography method provided in an embodiment of this application; Figure 16 A schematic flowchart of an affinity chromatography method provided for an embodiment of this application; Figure 17 A schematic flowchart of a desalination method provided in an embodiment of this application; Figure 18 This is a schematic flowchart illustrating a method for sequentially performing affinity chromatography and desalting, as provided in an embodiment of this application.

[0041] Explanation of reference numerals in the attached figures: 100. Chromatography apparatus; 110. Feeding assembly; 111. First feeding unit; 1111. First sample container; 1112. First waste tank; 1113. First tray; 1114. First handle; 1115. First base; 1116. First liquid guide line; 112. Second feeding unit; 1121. Second sample container; 11211. PBS solution bottle; 11212. Sodium hydroxide solution bottle; 11213. Elution buffer solution bottle; 11214. Neutralization solution bottle; 11215. Ethanol solution bottle; 120. Sample loading assembly; 121. Multi-way reversing valve; 1211. First fluid interface; 1212. Second fluid interface; 1213. Third fluid interface; 12131. Third fluid A interface; 12132. Third fluid B interface; 12133. Third fluid C interface; 12134. Third fluid D interface; 2135. Third fluid E-interface; 1214. Fourth fluid interface; 122. Fluid drive mechanism; 123. Sampling element; 1231. First end of sampling element; 1232. Second end of sampling element; 124. Bubble sensor; 1241. First bubble sensor; 1242. Second bubble sensor; 125. Lifting unit; 130. Processing assembly; 131. Chromatography column; 131A. First chromatography column; 131B. Second chromatography column; 1311. Chromatography column inlet; 1312. Chromatography column outlet; 1313. Column retainer; 132. First pressure detection unit Yuan; 1321, First three-way valve; 1322, First three-way valve inlet; 1323, First three-way valve first outlet; 1324, First three-way valve second outlet; 133, Second pressure detection unit; 1331, Second three-way valve; 1332, Second three-way valve first inlet; 1333, Second three-way valve second inlet; 1334, Second three-way valve outlet; 134, Detection module; 140, Distribution component; 141, Multi-way solenoid valve; 141A, First solenoid valve; 141B, Second solenoid valve; 1411, First inlet; 1412, Second inlet; 1413, First 1414, Second outlet; 1415, Third outlet; 1416, Fourth outlet; 1417, First adapter; 1418, Second adapter; 142, Collection unit; 1421, First collection container; 1422, Second waste liquid tank; 1423, Second tray; 1424, Second handle; 1425, Second base; 1426, Second liquid guide pipe; 1427, Transfer collection head; 1428, Second collection container; 150, Controller; 160, Pipeline; 161, First pipeline; 162, Second pipeline; 170, Housing; 171, Pipeline bayonet. Detailed Implementation

[0042] The following description, in conjunction with the accompanying drawings, illustrates exemplary embodiments of this application, including various details to aid understanding. These embodiments should be considered merely exemplary. Therefore, those skilled in the art will recognize that various changes and modifications can be made to the embodiments described herein without departing from the scope of this application. Similarly, for clarity and brevity, descriptions of well-known functions and structures are omitted in the following description.

[0043] In this application, unless otherwise stated, the use of terms such as "first," "second," etc., to describe various elements is not intended to limit the positional, temporal, or importance relationships of these elements; such terms are merely used to distinguish one element from another. In some examples, the first element and the second element may refer to the same instance of the element, while in other cases, based on the context, they may refer to different instances.

[0044] The terminology used in the description of the various examples in this application is for the purpose of describing particular examples only and is not intended to be limiting. Unless the context clearly indicates otherwise, an element may be one or more unless the number of elements is specifically limited. Furthermore, the term "and / or" as used in this application covers any one of the listed items and all possible combinations thereof.

[0045] The embodiments of this application will now be described in detail with reference to the accompanying drawings.

[0046] In specific embodiments, the automated sample loading chromatography device provided in this application is suitable for the separation, purification, and desalting of any biological macromolecule. For example, the chromatography device can be used for the separation and purification of proteins; for example, the chromatography device can be used for the separation and purification of DNA; for example, the chromatography device can be used for the separation and purification of RNA; for example, the chromatography device can also be used for desalting proteins after separation and purification. For ease of explanation, the following description uses the example of the chromatography device being suitable for the separation, purification, and desalting of proteins as an example.

[0047] Currently, chromatography equipment relies on manual operation during sample loading. Firstly, manual operation can lead to inaccurate sample loading, potentially affecting chromatographic results and subsequent experimental or production processes. Secondly, manual operation is inefficient, reducing sample loading efficiency and consequently lowering the chromatographic efficiency of the equipment. To address these issues, this application provides an automated sample loading chromatography device and method to improve upon these conditions.

[0048] This invention provides an automated sample loading chromatography device, such as... Figures 1 to 4 As shown, Figures 1 to 4The diagram shows the chromatography apparatus 100 from different perspectives. The chromatography apparatus 100 includes a feed assembly 110, a sample loading assembly 120, a processing assembly 130, and a controller 150. The feed assembly 110 includes multiple sample containers for holding sample solutions, which include the target solution to be chromatographically analyzed and auxiliary solutions required for chromatographic analysis of the target solution. The processing assembly 130 includes at least one chromatography column 131. The sample loading assembly 120 is connected to both the feed assembly 110 and the processing assembly 130. The sample loading assembly 120 includes a multi-way directional valve 121 and a fluid drive mechanism 122. The multi-way directional valve 121 has… Multiple fluid interfaces and a reversing valve core are provided. The fluid interfaces are connected to multiple sample containers and at least one chromatography column. The reversing valve core is used to control the opening and closing of the fluid interfaces. The fluid drive mechanism 122 is connected to one fluid interface of the multi-way reversing valve 121 and draws in or discharges sample solution through the multi-way reversing valve 121. The controller 150 is signal-connected to the multi-way reversing valve 121 and the fluid drive mechanism 122. The controller 150 is used to control the reversing valve core and the fluid drive mechanism 122 to provide the target solution and / or auxiliary solution to be chromatographically analyzed to the processing assembly 130.

[0049] Specifically, the chromatography device 100 mainly includes multiple components such as a feeding component 110, a sample loading component 120, and a processing component 130. Each component can be arranged in sequence. Considering the space layout and the convenience of operation, multiple components can be integrated inside and outside the housing 170 of the chromatography device 100.

[0050] The feed assembly 110 is a device for providing raw materials for the chromatography process. It mainly includes sample containers for holding the target solution to be chromatographically analyzed, and sample containers for holding auxiliary solutions required for the target solution. It should be noted that the target solution varies depending on the chromatographic requirements. For example, for protein affinity chromatography, the target solution is a protein sample filtered through a membrane; for protein desalting, the target solution is a crudely purified protein sample. The number of sample containers can be determined based on the requirements and the type of auxiliary solution.

[0051] For example, the sample container holding the target solution to be chromatographically analyzed is a first sample container 1111, and there may be one or more first sample containers 1111; the sample container holding the auxiliary solutions required for chromatographic analysis of the target solution is a second sample container 1121, and there may be one or more second sample containers 1121. In some specific embodiments, the second sample container 1121 includes a PBS solution bottle 11211, a sodium hydroxide solution bottle 11212, an eluent solution bottle 11213, a neutralization solution bottle 11214, and an ethanol solution bottle 11215.

[0052] The processing component 130 includes at least one chromatography column 131, which is a device for performing chromatography processing. The number of columns 131 can be single or multiple. Chromatography includes affinity chromatography (AC), ion exchange chromatography (IEX), multimode chromatography (MMC), hydrophobic interaction chromatography (HIC), reversed-phase chromatography (RPC), and size exclusion chromatography (SEC), etc. Depending on the different chromatography requirements, a single chromatography column 131 or multiple chromatography columns 131 can be used. It should be noted that multiple chromatography columns 131 can be the same column or different columns. For example, as... Figure 7 As shown, affinity chromatography is required. A single chromatography column 131 can be used, which may include an affinity chromatography column. The affinity chromatography column can be a pre-packed column containing 5 ml of protein A resin. For example, as... Figure 8 As shown, desalting is required, and a single chromatography column 131 can be used. The chromatography column 131 may include a desalting column (e.g., a size exclusion chromatography column), which can be a desalting column using 5 ml G-25 chromatography packing material; for example, as... Figure 10 As shown, affinity chromatography and desalting are required, and multiple chromatography columns 131 can be used. Each chromatography column 131 can simultaneously include both affinity chromatography columns and desalting columns. Each chromatography column 131 includes a column inlet 1311 and a column outlet 1312. To facilitate the fixation of the chromatography column 131, it also has a column holder 1313, which secures the chromatography column 131 to the housing 170.

[0053] The sample loading assembly 120 is a device used to transfer the target solution to be chromatography provided by the feed assembly 110 and the auxiliary solution required for chromatography to the target solution to the feed assembly 110 to the processing assembly 130. It is connected to the feed assembly 110 and the processing assembly 130 respectively, and specifically includes a multi-way directional valve 121 and a fluid drive mechanism 122. The fluid drive mechanism 122 can be any device capable of drawing in and discharging solution, such as a syringe pump, gear pump, and peristaltic pump. The multi-way directional valve 121 is a combination valve consisting of two or more directional valves. The directional valve changes the on / off relationship of the flow channel connected to the valve body by means of the relative movement between the directional valve core and the valve body. The multi-way directional valve 121 has multiple fluid ports, which are connected to sample containers and chromatography columns 131, respectively. Inside the multi-way directional valve 121, a directional valve core is driven by a motor. A fluid drive mechanism 122 works in conjunction with the multi-way directional valve 121. The directional valve core allows the fluid passage of the fluid drive mechanism 122 to connect with any one of the fluid ports. A piston inside the fluid drive mechanism 122, driven by the motor, draws liquid from one fluid port into the cavity of the fluid drive mechanism 122. Then, rotating the directional valve core discharges the liquid from the cavity of the fluid drive mechanism 122 through another fluid port, thus completing the liquid transfer process. The specific number of multi-way directional valves 121 is not limited and can be determined according to requirements; the number of fluid ports can be 2, 3, 4, 5, 6, 8, 12, etc.

[0054] For example, such as Figure 7 As shown, the multi-way directional valve 121 has a first fluid port 1211, a second fluid port 1212, a third fluid port 1213 and a fourth fluid port 1214. The third fluid port 1213 includes a third fluid A port 12131, a third fluid B port 12132, a third fluid C port 12133, a third fluid D port 12134 and a third fluid E port 12135. The first fluid interface 1211 is connected to the first sample container 1111 via tubing 160; the second fluid interface 1212 is connected to the chromatography column inlet 1311 via tubing 160; the third fluid A interface 12131 is connected to the PBS solution bottle 11211 via tubing 160; the third fluid B interface 12132 is connected to the sodium hydroxide solution bottle 11212 via tubing 160; the third fluid C interface 12133 is connected to the eluent solution bottle 11213 via tubing 160; the third fluid D interface 12134 is connected to the neutralization solution bottle 11214 via tubing 160; and the third fluid E interface 12135 is connected to the ethanol solution bottle 11215 via tubing 160.

[0055] In some embodiments, in order to reduce the shaking of the pipe 160, a pipe bayonet 171 may be provided on the housing 170, and the pipe 160 is fixed by passing through the pipe bayonet 171.

[0056] The controller 150 is signal-connected to the multi-way directional valve 121 and the fluid drive mechanism 122. This signal connection can be wired (transmitting signals via a data line) or wireless (transmitting signals via a wireless network). The controller 150 controls the rotation of the directional valve core to connect to different fluid interfaces, thereby causing the fluid drive mechanism 122 to draw the target solution and / or auxiliary solution to be chromatographically analyzed into its cavity. The controller 150 also controls the rotation of the directional valve core to switch between different fluid interfaces, thereby providing the target solution and / or auxiliary solution to be chromatographically analyzed to the chromatography column 131 of the processing assembly 130.

[0057] This embodiment provides an automated sample loading chromatography device 100, which includes a feeding component 110, a processing component 130, a sample loading component 120, and a controller 150. The sample loading component 120 is connected to both the feeding component 110 and the processing component 130. The fluid interface of the multi-way reversing valve 121 is connected to multiple sample containers and a chromatography column 131. The fluid drive mechanism 122 is connected to one fluid interface of the multi-way reversing valve 121. The controller 150 controls the reversing valve core and the fluid drive mechanism 122 to draw in or discharge the target solution and / or auxiliary solution to be chromatographically analyzed through the multi-way reversing valve 121 and to supply the target solution and / or auxiliary solution to be chromatographically analyzed to the processing component 130. By controlling the reversing valve core and the fluid drive mechanism 122 with the controller 150, precise control of sample loading can be achieved, improving the accuracy of the sample loading volume. Furthermore, automated sample loading replaces manual sample loading, which also speeds up the sample loading efficiency, thereby improving the chromatography efficiency of the device.

[0058] In some embodiments, such as Figure 1 and Figure 2 As shown, the feeding assembly 110 includes a first feeding unit 111, which includes at least one first sample container 1111 for holding the target solution to be chromatographically analyzed; the sample loading assembly 120 also includes a sampling member 123, which includes a first end and a second end connected together. The first end 1231 of the sampling member is connected to a fluid interface of a multi-way reversing valve 121, and the second end 1232 of the sampling member can extend into the first sample container 1111 to aspirate the target solution to be chromatographically analyzed.

[0059] Specifically, the first sample container 1111 contains the target solution to be analyzed. There are multiple first sample containers 1111. To facilitate the aspiration of the target solution, the sample loading assembly 120 also includes a sampling element 123. The sampling element 123 can be any device capable of aspirating the solution, transferring the solution through suction at one end and discharge at the other. For example, the sampling element 123 may include a sampling needle, a sampling tube, a sampling pipette tip, etc. The sampling element 123 includes a first end 1231 and a second end 1232. The first end 1231 is connected to the first fluid interface 1211, and the second end 1232 extends into the first sample container 1111. A negative pressure is generated by the fluid drive mechanism 122 and the multi-way reversing valve 121, causing the sampling element 123 to draw in the target solution to be analyzed from the first sample container 1111 and enter the cavity of the fluid drive mechanism 122 through the first fluid interface 1211.

[0060] In some embodiments, such as Figure 1 and Figure 2 As shown, the first end 1231 of the sampling component is connected to the multi-way reversing valve 121 through the first pipeline 161, and the first bubble sensor 1241 is provided on the first pipeline 161; the sample loading assembly 120 also includes a lifting unit 125, which is used to drive the sampling component 123 to lift.

[0061] Specifically, considering that the sampling device 123 may inhale some air during the process of aspirating the target solution to be chromatographically analyzed, in order to minimize the influence of air, the first end 1231 of the sampling device is connected to the first fluid interface 1211 of the multi-way reversing valve 121 through the first pipeline 161. The first pipeline 161 is equipped with a first bubble sensor 1241. The first bubble sensor 1241 detects whether there is air in the first pipeline 161 and performs corresponding processing, including reminding the operator or automatically venting the air.

[0062] The sampling element 123 can aspirate only the target solution to be chromatographically analyzed from a single first sample container 1111. Therefore, the sample loading assembly 120 also includes a lifting unit 125. For example, the lifting unit 125 includes a sliding seat, on which the sampling element 123 is fixed. The sliding seat is fixed to a slide rail on the housing 170 and can be driven by a motor or cylinder to move the sampling element 123 up and down. During chromatography, the controller 150 sends a control command to the lifting unit 125, causing the sliding seat to move up and down along the slide rail, thereby moving the sampling element 123 up and down, thus achieving automatic lifting and lowering of the sampling element 123 and improving the operational flexibility of the chromatography equipment 100.

[0063] Simultaneously, the sampling element 123 is automatically lowered into the first sample container 1111. Then, the fluid drive mechanism 122 is controlled to automatically draw the target solution to be chromatographically analyzed from the first sample container 1111 through the sampling element 123. The first bubble sensor 1241 detects the presence of air in the first pipeline 161, indicating that the target solution to be chromatographically analyzed in the first sample container 1111 has been completely drawn. The controller 150 sends a control command to the lifting unit 125 based on the detection result of the first bubble sensor 1241. The lifting unit 125 drives the sampling element 123 to rise automatically. The entire operation is automated, the operation process is simple, and it saves manpower. Furthermore, the sample loading operation is performed immediately after the sampling element 123 is lowered, which can effectively shorten the switching time between different links and improve the chromatography efficiency of the chromatography equipment 100.

[0064] Meanwhile, it is also considered that after all samples are loaded into a single first sample container 1111, it may be necessary to switch to the next first sample container 1111 for sample loading. In some implementations, the specific operation is as follows: the sampling element 123 is controlled to automatically descend into the first sample container 1111. Then, the fluid drive mechanism 122 is controlled to automatically draw the target solution to be chromatographically analyzed from the first sample container 1111 through the sampling element 123. When the target solution to be chromatographically analyzed in the first sample container 1111 is completely drawn in, the sampling element 123 will draw in air. The first bubble sensor 1241 detects the presence of air in the first pipeline 161. The controller 150 controls the fluid drive mechanism 122 to stop drawing in the target solution to be chromatographically analyzed. The controller 150 sends a control command to the lifting unit 125 based on the detection result of the first bubble sensor 1241. The lifting unit 125 drives the sampling element 123 to rise automatically. At the same time, after moving another first sample container 1111 below the sampling element 123, the controller 150 sends a control command to the lifting unit 125. The sliding seat drives the sampling element 123 to move downward to load the sample.

[0065] In some embodiments, such as Figure 5 As shown, the first feeding unit 111 further includes a first base 1115 and a first driving member. The first base 1115 is used to support at least one first sample container 1111. The first driving member is connected to the first base 1115 and is used to drive the first base 1115 to move in the horizontal direction, so that at least one first sample container 1111 moves sequentially to below the sampling member 123.

[0066] Specifically, in some embodiments, considering that a single first sample container 1111 can be automatically replaced with the next first sample container 1111 after all samples have been loaded, the first feeding unit 111 further includes a first base 1115 and a first driving member. Multiple first sample containers 1111 are arranged sequentially on the first base 1115, and the first driving member is connected to the first base 1115 and used to drive the first base 1115 to move horizontally. For example, the first driving member includes a lead screw, belt, linear motor, etc. The first base 1115 is connected to a guide rail, and the linear motor can be used to rotate the lead screw, thereby moving the first base 1115. This allows the different first sample containers 1111 on the first base 1115 to move sequentially below the second end 1232 of the sampling member. When the target solution to be chromatographically analyzed in the first sample container 1111 is completely aspirated, the sampling element 123 will draw in air. The first bubble sensor 1241 detects the presence of air in the first pipeline 161. The controller 150 controls the fluid drive mechanism 122 to stop drawing in the target solution to be chromatographically analyzed. Based on the detection result of the first bubble sensor 1241, the controller 150 sends a control command to the lifting unit 125, which drives the sampling element 123 to rise automatically. At the same time, based on the detection result of the first bubble sensor 1241, the controller 150 sends a control command to the first drive component, which drives the first base 1115 to move, moving the other first sample container 1111 below the sampling element 123, thus achieving the switching of the first sample container 1111.

[0067] In some implementations, considering the ease of handling the first sample container 1111, the first feeding unit 111 further includes a first tray 1113. The first sample container 1111 can be placed on the corresponding position of the first tray 1113, which can be placed on the first base 1115. The first tray 1113 is also equipped with a first handle 1114, allowing the first tray 1113, along with the first sample container 1111, to be removed from the first base 1115 by gripping the first handle 1114. The first tray 1113 can be configured with different structures depending on the type and quantity of containers placed on it.

[0068] In some embodiments, such as Figure 4 and Figure 5 As shown, the first base 1115 is also provided with a first waste liquid tank 1112, which is used to receive waste liquid discharged from the second end 1232 of the sampling member.

[0069] Specifically, considering that the sampling element 123 needs to be cleaned after aspirating the target solution to be chromatographically analyzed from the first sample container 1111, and that the liquid in the pipeline 160 can also be discharged from the sampling element 123, a first waste liquid tank 1112 is also provided on the first base 1115. The first waste liquid tank 1112 can be arranged close to the first sample container 1111. By moving the first base 1115, the first sample container 1111 or the first waste liquid tank 1112 can be moved to below the second end 1232 of the sampling element as needed. The first waste liquid tank 1112 is provided with a cavity for cleaning the sampling element 123 and collecting the waste liquid discharged by the sampling element 123.

[0070] In some implementations, to facilitate the discharge of waste liquid from the first waste liquid tank 1112, a drain port is provided at the bottom of the first waste liquid tank 1112. The drain port is connected to the first liquid guiding pipe 1116 on the housing 170 through a drain pipe. The waste liquid in the first waste liquid tank 1112 can be discharged directly through the first liquid guiding pipe 1116. The first liquid guiding pipe 1116 can also be extended to guide the waste liquid in the first waste liquid tank 1112 to other waste liquid collection containers through the first liquid guiding pipe 1116.

[0071] In some embodiments, such as Figures 6 to 8 As shown, the first feeding unit 111 also includes a first identification component that is signal-connected to the controller 150. The first identification component is used to acquire the first identification information of the first sample container 1111. The first identification information is used to indicate the type and / or volume of the solution contained in the first sample container 1111.

[0072] Specifically, considering the continuity of the automatic sample loading process, the first feeding unit 111 also includes a first identification component that is signal-connected to the controller 150. The first identification component can be understood as a device that can identify the container size. For example, the first identification component can be a sensor or a scanner.

[0073] For example, the first identification component can identify the first sample container 1111 to obtain the type and volume of the solution contained in the first sample container 1111, and transmit this information to the controller 150. The controller 150 can determine the number of samples taken at one time and the number of samples taken, and can determine the time to switch to the next first sample container 1111, thereby controlling the movement of the first base 1115 to realize automatic adjustment of the sample loading procedure. For example, the first identification component can also identify the specifications of the first tray 1113, and determine the specifications of the first sample container 1111 and the corresponding information based on the specifications of the first tray 1113.

[0074] In some embodiments, such as Figures 1 to 2As shown, the feeding assembly 110 also includes a second feeding unit 112. The second feeding unit 112 includes at least one second sample container 1121 for holding the auxiliary solution. Each second sample container 1121 is connected to the fluid interface of the multi-way reversing valve 121 through a second pipeline 162. A second bubble sensor 1242 is provided in the second pipeline 162.

[0075] Specifically, such as Figure 7 As shown, the second sample container 1121 is used to contain auxiliary solutions. The second sample container 1121 includes a PBS solution bottle 11211, a sodium hydroxide solution bottle 11212, an eluent solution bottle 11213, a neutralization solution bottle 11214, and an ethanol solution bottle 11215. The third fluid A interface 12131 is connected to the PBS solution bottle 11211 via tubing 160; the third fluid B interface 12132 is connected to the sodium hydroxide solution bottle 11212 via tubing 160; the third fluid C interface 12133 is connected to the eluent solution bottle 11213 via tubing 160; the third fluid D interface 12134 is connected to the neutralization solution bottle 11214 via tubing 160; and the third fluid E interface 12135 is connected to the ethanol solution bottle 11215 via tubing 160.

[0076] Considering that the fluid drive mechanism 122 may draw in some air when drawing the auxiliary solution from the second sample container 1121, in order to minimize the influence of air, each of the second sample containers 1121 is connected to the fluid interface of the multi-way reversing valve 121 through a second pipeline 162. A second bubble sensor 1242 is installed on the second pipeline 162 to detect whether there is air in the second pipeline 162 and to take corresponding actions, including reminding the operator or automatically venting the air.

[0077] In some embodiments, such as Figures 9 to 10 As shown, at least one chromatography column 131 includes a first chromatography column 131A and a second chromatography column 131B. The first chromatography column 131A is used to perform a first chromatography treatment on the target solution to be chromatographically analyzed, and the second chromatography column 131B is used to treat the target solution to be chromatographically analyzed. The first chromatography column 131 and the second chromatography column 131B are chromatography columns of the same type; or the first chromatography column 131 and the second chromatography column 131B are chromatography columns of different types.

[0078] Specifically, considering that the chromatography apparatus 100 is suitable for the chromatographic processing of any biomacromolecule, and that the chromatography columns 131 used for different chromatographic needs also differ, the chromatography apparatus 100 can include multiple chromatography columns 131 to increase its application range. Specifically, the chromatography columns 131 can include a first chromatography column 131A and a second chromatography column 131B. The first chromatography column 131A is used to perform a first chromatographic treatment on the target solution to be chromatographically analyzed, such as affinity chromatography; the second chromatography column 131B is used to perform a second chromatographic treatment on the target solution to be chromatographically analyzed, different from the first chromatographic treatment, such as desalting treatment using size exclusion chromatography. It should be noted that, depending on actual needs, the first chromatography column 131A and the second chromatography column 131B can also be of the same type.

[0079] In some embodiments, such as Figures 9 to 10 As shown, the first chromatography column 131 and the second chromatography column 131B are chromatography columns of different types. The first chromatography column 131A is configured to perform a first chromatography treatment on the target solution to be chromatographically analyzed to obtain an intermediate solution. The second chromatography column 131B is configured to perform a second chromatography treatment on the intermediate solution to obtain the chromatographically analyzed target solution.

[0080] Specifically, considering that different chromatography columns 131 can independently process different solutions, different chromatography columns 131 can also process a sample solution sequentially. The first chromatography column 131A performs a first chromatography treatment on the target solution to be chromatographically analyzed, obtaining an intermediate solution. The second chromatography column 131B performs a second chromatography treatment on the intermediate solution, obtaining the chromatographically purified target solution. For example, the first chromatography column 131A performs affinity chromatography on a protein solution, obtaining an affinity-chromatographically purified protein solution. The second chromatography column 131B then desalts the affinity-chromatographically purified protein solution, obtaining an affinity-chromatographically desalted protein solution.

[0081] In some embodiments, such as Figures 9 to 10 As shown, the inlet of the first chromatography column 131A and the inlet of the second chromatography column 131B are connected in parallel to the fluid interface of the multi-way reversing valve 121.

[0082] Specifically, for example, the first chromatography column 131A is an affinity chromatography column, and the second chromatography column 131B is a desalting column. The inlets of the affinity chromatography column and the desalting column are connected in parallel to the fluid interface of the multi-way directional valve 121. This can be understood as the inlets of both the affinity chromatography column and the desalting column being connected to the same fluid interface. For example, the inlets of both the affinity chromatography column and the desalting column are connected to the second fluid interface 1212 of the multi-way directional valve 121 via a three-way valve. The solution in the chamber of the fluid drive mechanism 122 can be discharged into either the affinity chromatography column or the desalting column through the second fluid interface 1212. It should be noted that the solution injected into the affinity chromatography column through the chamber of the fluid drive mechanism 122 is different from the solution injected into the desalting column. The inlets of the affinity chromatography column and the desalting column can also be connected to different fluid interfaces of the multi-way directional valve 121.

[0083] It should also be noted that for different chromatography columns 131, for example, if column 131 is an affinity chromatography column and a desalting column, the inlets of the affinity chromatography column and the desalting column are structurally connected in parallel to the fluid interface of the multi-way reversing valve 121. However, in actual use, they are operated sequentially in a series configuration. Specifically, the fluid drive mechanism 122 discharges the solution in the chamber into the affinity chromatography column for processing. After obtaining the intermediate solution processed by the affinity chromatography column, the fluid drive mechanism 122 then draws the intermediate solution into the desalting column for further processing. For the same chromatography column 131, for example, if column 131 consists of two affinity chromatography columns, the inlets of the two affinity chromatography columns are structurally connected in parallel to the fluid interface of the multi-way reversing valve 121. Specifically, the fluid drive mechanism 122 discharges the solution in the chamber into both affinity chromatography columns simultaneously for processing, thereby increasing the efficiency of affinity chromatography.

[0084] In some embodiments, the first chromatography column 131A and the second chromatography column 131B are respectively selected from one of the following: affinity chromatography column, ion exchange chromatography column, multimode chromatography column, hydrophobic interaction chromatography column, reverse chromatography column, and size exclusion chromatography column.

[0085] In some embodiments, the processing component 130 further includes a first pressure detection unit 132 and a second pressure detection unit 133; the first pressure detection unit 132 is located upstream of at least one chromatography column 131 to detect the liquid pressure before entering at least one chromatography column 131; the second pressure detection unit 133 is located downstream of at least one chromatography column 131 to detect the liquid pressure flowing out of at least one chromatography column 131.

[0086] Specifically, in order to detect the solution pressure at the inlet 1311 and outlet 1312 of the chromatography column 131 in real time, a first pressure detection unit 132 is set upstream of the chromatography column 131, and a second pressure detection unit 133 is set downstream of the chromatography column 131. It should be noted that the chromatography apparatus 100 may have multiple chromatography columns 131. The first pressure detection unit 132 can be set upstream of each chromatography column 131, or multiple chromatography columns 131 can share a single first pressure detection unit 132. Similarly, the second pressure detection unit 133 can be set downstream of each chromatography column 131, or multiple chromatography columns 131 can share a single second pressure detection unit 133. The first pressure detection unit 132 monitors the pressure changes in the upstream pipeline 160 of the chromatography column 131 in real time. If the detected pressure exceeds a preset pressure threshold, an alarm can be issued. Similarly, the second pressure detection unit 133 monitors the pressure changes in the downstream pipeline 160 of the chromatography column 131 in real time. If the detected pressure exceeds a preset pressure threshold, an alarm can also be issued. The pressure range that the first and second pressure detection units 132 and 133 can detect can be determined according to actual needs, ranging from 0.01 to 6 MPa. The set pressure thresholds can also be determined according to actual needs, for example, 0.1 MPa, 0.3 MPa, 0.6 MPa, 0.8 MPa, 1 MPa, etc.

[0087] In some embodiments, such as Figure 10 As shown, the first pressure detection unit 132 includes a first three-way valve 1321, the inlet of which is connected to the fluid interface of a multi-way directional valve 121, and the two outlets of which are respectively connected to the inlet of the first chromatography column 131A and the inlet of the second chromatography column 131B; the second pressure detection unit 133 includes a second three-way valve 1331, the two inlets of which are respectively connected to the outlet of the first chromatography column 131A and the outlet of the second chromatography column 131B; the first three-way valve 1321 and the second three-way valve 1331 are respectively connected to the controller 150 for signal connection.

[0088] Specifically, to save space, the upstream of the first chromatography column 131A and the upstream of the second chromatography column 131B share a first pressure detection unit 132. The pipeline is divided into two by the first three-way valve 1321 in the first pressure detection unit 132. It can be understood that the first three-way valve 1321 has one inlet, the first three-way valve inlet 1322, and two outlets, the first three-way valve outlet 1323 and the first three-way valve outlet 1324. The downstream of the first chromatography column 131A and the downstream of the second chromatography column 131B share a second pressure detection unit 133. The pipeline is combined into one by the second three-way valve 1331 in the second pressure detection unit 133. It can be understood that the first three-way valve 1321 has two inlets, the second three-way valve inlet 1332 and the second three-way valve inlet 1333, and one outlet, the second three-way valve outlet 1334.

[0089] The specific connection method is as follows: the inlet 1322 of the first three-way valve is connected to the second fluid interface 1212; the first outlet 1323 of the first three-way valve is connected to the inlet of the first chromatography column 131A; the second outlet 1324 of the first three-way valve is connected to the inlet of the second chromatography column 131B; the first inlet 1332 of the second three-way valve is connected to the outlet of the first chromatography column 131A; and the second inlet 1333 of the second three-way valve is connected to the outlet of the second chromatography column 131B. The first three-way valve 1321 and the second three-way valve 1331 are respectively connected to the controller 150 via signal. According to the control signal, the upstream first three-way valve inlet 1322 is connected to the first outlet 1323 or the first outlet 1324, and the downstream second three-way valve inlet 1332 is connected to the second outlet 1334, or the second inlet 1333 is connected to the second outlet 1334.

[0090] In some embodiments, such as Figure 7 , Figure 8 and Figure 10 As shown, the processing component 130 also includes a detection module 134, which includes one or more of a UV detection module, a conductivity detection module, and a pH detection module. The detection module 134 is located downstream of at least one chromatography column 131.

[0091] Specifically, in order to facilitate the detection of relevant parameters of the target solution after passing through the chromatography column 131, the processing component 130 also includes a detection module 134, which can be installed inside the housing 170. For example, the chromatography apparatus 100 has a second pressure detection unit 133, and one end of the detection module 134 is connected to the outlet 1334 of the second three-way valve of the second pressure detection unit 133. The solution discharged through the outlet 1334 of the second three-way valve is detected by the detection module 134. Alternatively, the chromatography apparatus 100 may not have a second pressure detection unit 133, and one end of the detection module 134 may be directly connected to the outlet 1312 of the chromatography column. The solution discharged through the outlet 1312 of the chromatography column is directly detected by the detection module 134. The detection module 134 may include one or more of a UV detection module, a conductivity detection module, and a pH detection module. The UV detection module is a UV detection module designed based on the principle of solute molecules absorbing ultraviolet light. For example, the absorbance value of a UV detection wavelength of 280nm can be used to indicate the protein content. The conductivity detection module is a module for detecting the conductivity of the solution. The pH detection module is a module for detecting the acidity or alkalinity of the solution. The detection module 134 can be connected to the controller 150 via a signal. When the data detected by the detection module 134 exceeds a preset threshold, an alarm can be issued.

[0092] In some embodiments, the processing component 130 also includes a bubble trap (not shown) for reducing bubbles. The bubble trap is disposed between the second pressure detection unit 133 and the detection module 134. The bubble trap can be used to reduce the fine bubbles generated by the sample loading component 120 and the processing component 130, thereby reducing the abnormalities of the detection module 134 caused by fluid factors.

[0093] A bubble trap is a structure that uses the buoyancy and lift between bubbles and liquid to separate gas and liquid. Bubble traps can take many forms. For example, a filter or porous material component can be incorporated inside the bubble trap to reduce the fluid velocity, allowing bubbles sufficient time to rise and separate. Additionally, the filter or porous material component can prevent bubbles from passing through, further improving the separation effect. Of course, in other embodiments, the shape of the flow channel inside the bubble trap can also promote gas-liquid separation.

[0094] It is understandable that when multiple second pressure detection units 133 are provided, a bubble trap can be provided between each second pressure detection unit 133 and the detection module 134.

[0095] In some embodiments, such as Figure 1 , Figure 11 and Figure 12 As shown, Figure 11Parts A and B are schematic diagrams of the multi-way solenoid valve 141 from two different perspectives. The chromatography apparatus 100 also includes a distribution assembly 140, which includes a multi-way solenoid valve 141 that is signal-connected to the controller 150. The first inlet 1411 of the multi-way solenoid valve 141 is connected to the outlet of at least one chromatography column 131. The multi-way solenoid valve 141 includes a first outlet 1413 and a second outlet 1414 that can communicate with the first inlet 1411. The first outlet 1413 is used to discharge the target solution after chromatography, and the second outlet 1414 is used to discharge the waste liquid generated by the chromatography process.

[0096] Specifically, the multi-way solenoid valve 141 can have multiple inlets and multiple outlets. For ease of understanding, the structure of the multi-way solenoid valve 141 is described in detail below. The multi-way solenoid valve 141 internally houses two three-channel solenoid valves, namely the first solenoid valve 141A and the second solenoid valve 141B. These valves control the opening and closing of pipelines via electromagnetic force to achieve different fluid path guidance switching. The first solenoid valve 141A includes three pipeline ports: A1, B1, and C1. When the first solenoid valve 141A is de-energized, pipeline ports A1 and C1 are connected via pipelines; when the first solenoid valve 141A is energized, pipeline ports B1 and C1 are connected via pipelines. The second solenoid valve 141B includes three pipe ports: port A2, port B2, and port C2. When the second solenoid valve 141B is de-energized, port A2 and port C2 are connected through a pipe; when the second solenoid valve 141B is energized, port B2 and port C2 are connected through a pipe. Port B1 and port C2 are connected through an internal passage. Port C1 is connected to the first inlet 1411 through an internal passage. Port A1 can be connected to the second outlet 1414 through an internal passage. Port A1 can also be connected to the second outlet 1414 through an external pipe via a first adapter 1417 and a second adapter 1418. Port A2 is connected to the third outlet 1415 through an internal passage. Port B2 is connected to the first outlet 1413 through an internal passage.

[0097] When the first solenoid valve 141A and the second solenoid valve 141B are both de-energized, the solution can flow in through the first inlet 1411, pass through pipe port C1 and pipe port A1, and finally flow out through the second outlet 1414. The outflowing solution can be collected in a container below the second outlet 1414. When the first solenoid valve 141A and the second solenoid valve 141B are both energized, the solution can flow in through the first inlet 1411, pass through pipe port C1, pipe port B1, pipe port C2, and pipe port B2, and finally flow out through the first outlet 1413. The outflowing solution can be collected in a container below the first outlet 1413. When the first solenoid valve 141A is energized and the second solenoid valve 141B is de-energized, the solution can flow in through the first inlet 1411, pass through pipe port C1, pipe port B1, pipe port C2, and pipe port A2, and finally flow out through the third outlet 1415.

[0098] The first inlet 1411 is connected to the chromatography column outlet 1312 of the chromatography column 131. The solution can be discharged from different outlets according to the actual situation. The solution entering the multi-way solenoid valve 141 can be discharged from the same outlet or from different outlets. For example, the first outlet 1413 is used to discharge the target solution after chromatography, and the second outlet 1414 is used to discharge the waste liquid generated by the chromatography process.

[0099] In some embodiments, such as Figure 10 As shown, at least one chromatography column 131 includes a first chromatography column 131A and a second chromatography column 131B; the outlet of the first chromatography column 131A and the outlet of the second chromatography column 131B are respectively connected to the first inlet 1411 of the multi-way solenoid valve 141; the multi-way solenoid valve 141 also includes a third outlet 1415 that can be connected to the first inlet 1411, and the third outlet 1415 is provided with a transfer collection head 1427, which is used to receive and discharge the intermediate solution obtained by the first chromatography column 131A.

[0100] Specifically, considering that the chromatography apparatus 100 can process sample solutions sequentially, the chromatography apparatus 100 includes a first chromatography column 131A and a second chromatography column 131B. For example, the first chromatography column 131A and the second chromatography column 131B are respectively an affinity chromatography column and a desalting column. The outlet of the affinity chromatography column and the outlet of the desalting column are respectively connected to the first inlet 1411 of the multi-way solenoid valve 141. The first inlet 1411 of the multi-way solenoid valve 141 can be directly connected to the outlet 1312 of the chromatography column, through affinity chromatography... The intermediate solution, after affinity chromatography treatment with the chromatography column, passes through inlet C1 and inlet A1 and is discharged through the third outlet 1415. The third outlet 1415 is equipped with a transfer collection head 1427, which has an inlet and an outlet. The inlet of the transfer collection head 1427 is connected to the third outlet 1415, and the outlet of the transfer collection head 1427 is connected to the intermediate solution collection container. The transfer collection head 1427 can be understood as a transfer structure between the third outlet 1415 and the intermediate solution collection container. Alternatively, the intermediate solution can pass through inlet C1 and inlet A1 and be discharged through the first adapter 1417 connected to inlet A1. The discharged intermediate solution is the affinity chromatography solution.

[0101] In some embodiments, such as Figure 10 As shown, the multi-way solenoid valve 141 also includes a second inlet 1412 and a fourth outlet 1416. The second inlet 1412 is connected to a fluid interface of the multi-way directional valve 121, and the fourth outlet 1416 is connected to the second inlet 1412 and is used to discharge the liquid flowing into the second inlet 1412.

[0102] Specifically, the multi-way solenoid valve 141 also includes a second inlet 1412 and a fourth outlet 1416. The second inlet 1412 and the fourth outlet 1416 are connected through an internal passage. The fourth fluid interface 1214 of the multi-way solenoid valve 141 is connected to the second inlet 1412, allowing the solution in the cavity of the fluid drive mechanism 122 to be discharged through the fourth fluid interface 1214, enter the second inlet 1412 through the pipeline 160, and then be discharged through the fourth outlet 1416. The waste discharged from the fourth outlet 1416 is the cleaning waste from the pipeline, which can be collected and discharged through a waste liquid tank.

[0103] In some embodiments, a stop solenoid valve (not shown in the figure) is also provided at the fourth outlet 1416. The stop solenoid valve is used to close the fourth outlet 1416. It can be understood that the stop solenoid valve can be a common solenoid valve that can realize the opening and closing of the pipeline. It can automatically close the fourth outlet 1416, so that there is no solution leakage at the fourth outlet 1416. In particular, after the entire chromatography purification process is completed, the stop solenoid valve can automatically close the fourth outlet 1416, so that the chromatography column is not prone to drying out.

[0104] In some embodiments, such as Figure 5As shown, the dispensing assembly 140 also includes a collection unit 142, which includes a first collection container 1421, a second base 1425, and a second driving member. The second base 1425 is used to support the first collection container 1421, and the second driving member is connected to the second base 1425 and is used to drive the second base 1425 to move horizontally, so that the multiple first collection containers 1421 move sequentially below the first outlet 1413 to receive the target solution after chromatography.

[0105] Specifically, considering that a single first collection container 1421, after being filled, can be automatically replaced into the corresponding waste liquid tank or the next first collection container 1421 according to actual needs, the collection unit 142 also includes a second base 1425 and a second driving member. Multiple first collection containers 1421 are sequentially arranged on the second base 1425, and the second driving member is connected to the second base 1425 and used to drive the second base 1425 to move horizontally. For example, the second base 1425 includes a screw, belt, and linear motor assembly. The second base 1425 is connected to a guide rail, and the linear motor can be used to rotate the screw, thereby moving the second base 1425. This allows the different first collection containers 1421 on the second base 1425 to sequentially move below the first outlet 1413, thereby receiving the target solution after chromatography at the first outlet 1413.

[0106] In some embodiments, considering the ease of handling the first collection container 1421, the collection unit 142 further includes a second tray 1423. The first collection container 1421 can be placed on a corresponding position on the second tray 1423, which can be placed on a second base 1425. A second handle 1424 is also provided on the second tray 1423, allowing the second tray 1423, along with the first collection container 1421, to be removed from the second base 1425 by gripping the second handle 1424. The second tray 1423 can be configured with different structures depending on the type and number of containers placed on it. In some embodiments, such as Figure 5 As shown, the collection unit 142 also includes a second collection container 1428 and a second waste liquid tank 1422. The second collection container 1428 is placed on the first base 1115 and is used to receive the intermediate solution discharged from the transfer collection head 1427. The second waste liquid tank 1422 is used to receive the liquid discharged from the first outlet 1413, the second outlet 1414 and the fourth outlet 1416.

[0107] Specifically, the chromatography apparatus 100 has multiple chromatography columns 131. After chromatography is completed on a single chromatography column 131, the chromatographic solution is collected and used as the raw material for the second chromatography column 131. To facilitate the absorption by the second chromatography column 131, a transfer collection head 1427 is provided on the housing 170, and a second collection container 1428 is provided directly below the transfer collection head 1427. The intermediate solution formed after chromatography on the first chromatography column 131 flows through the third outlet 1415 through the transfer collection head 1427 and is discharged into the second collection container 1428 directly below the transfer collection head 1427. The second collection container 1428 is placed on a first base 1115, which can move the second collection container 1428 to achieve switching. By aspirating the intermediate solution in the second collection container 1428, chromatography on the second chromatography column 131 is performed.

[0108] It should be noted that the second collection container 1428 is both a collection container for the intermediate solution and a sample container for the second chromatography. Considering that the intermediate solution may come into contact with the target solution to be chromatographically analyzed in the first sample container 1111 and may interfere with each other, the second collection container 1428 can be understood as the first sample container 1111 of the empty bottle.

[0109] Specifically, considering that cleaning of pipeline 160 and chromatography column 131 will generate waste liquid, a second waste liquid tank 1422 can be provided on the second base 1425. The second waste liquid tank 1422 can be arranged close to the first collection container 1421. The second waste liquid tank 1422 can receive liquid discharged from the first outlet 1413, the second outlet 1414 and the fourth outlet 1416. By moving the second base 1425, the second waste liquid tank 1422 can be moved below the outlet of the multi-way solenoid valve 141 as needed. The second waste liquid tank 1422 is provided with a cavity for containing the discharged waste liquid.

[0110] In some embodiments, to facilitate the discharge of waste liquid in the second waste liquid tank 1422, a drain port is provided at the bottom of the second waste liquid tank 1422. The drain port is connected to the second liquid guiding pipe 1426 on the housing 170 through a drain pipe. The waste liquid in the second waste liquid tank 1422 can be discharged directly through the second liquid guiding pipe 1426. The second liquid guiding pipe 1426 can also be extended to guide the waste liquid in the second waste liquid tank 1422 to other waste liquid collection containers through the second liquid guiding pipe 1426.

[0111] In some embodiments, the processing component 130 further includes a detection module 134 signal-connected to the controller 150. The detection module 134 is located downstream of at least one chromatography column 131 and is used to detect information about the solution discharged from the chromatography column 131. The controller 150 is configured to issue a control command to a second drive according to the detection information of the detection module 134. The second drive drives the second base 1425 to move according to the control command, so that the first collection container 1421 or the second waste liquid tank 1422 moves to below the multi-way solenoid valve 141 to receive the liquid discharged from the multi-way solenoid valve 141.

[0112] Specifically, the detection module 134 includes one or more of a UV detection module, a conductivity detection module, and a pH detection module. The detection module 134 detects relevant parameters of the target solution passing through the chromatography column 131. Each of the UV, conductivity, and pH detection modules has a set threshold value. The UV, conductivity, and pH detection modules send the detection information to the controller 150. The controller 150 sends a control command to the second drive unit based on the detection information from the detection module 134. The second drive unit then drives the second base 1425 to move, moving the corresponding first collection container 1421 or second waste liquid tank 1422 below the multi-way solenoid valve 141 to receive the liquid discharged from the multi-way solenoid valve 141. There can be multiple first collection containers 1421.

[0113] For example, when the UV detection module detects that the absorbance value has reached the set threshold, the controller 150 sends a control command to the second drive unit according to the detection information of the UV detection module. The second drive unit drives the second base 1425 to move according to the control command. The second base 1425 moves the first collection container 1421 to below the multi-way solenoid valve 141 for collection. When the volume of solution collected in the first collection container 1421 reaches the set collection volume, and the UV detection module detects that the absorbance value has not dropped to the stop-collection threshold, the controller 150 sends a control command to the second drive unit. The second drive unit drives the second base 1425 to move according to the control command. The second base 1425 moves the other first collection container 1421 to below the multi-way solenoid valve 141 for collection.

[0114] It should be noted that the collection volume of the first collection container 1421 can be pre-entered into the system of the chromatography equipment 100. The controller 150 can determine whether the first collection container 1421 has reached the set collection volume by combining the flow rate of the multi-way solenoid valve 141, so as to switch to another first collection container 1421.

[0115] In some embodiments, such as Figure 10As shown, the collection unit 142 also includes a second identification component that is signal-connected to the controller 150. The second identification component is used to acquire second identification information, which is used to indicate the container volume of the first collection container 1421 and the type of solution being collected.

[0116] Specifically, considering the continuity of the automatic collection process, the collection unit 142 also includes a second identification component that is signal-connected to the controller 150. The second identification component can be understood as a device capable of identifying container specifications. For example, the second identification component can be a sensor or a scanner.

[0117] For example, the second identification component can identify the first collection container 1421 to obtain the type and volume of the solution contained in it, and transmit this information to the controller 150. The controller 150 can determine the quantity collected in a single collection and the number of collections, and thus determine the time to switch to the next first collection container 1421, thereby controlling the movement of the second base 1425 to automatically adjust the collection program. Alternatively, the second identification component can also identify the specifications of the second tray 1423 to determine the specifications of the first collection container 1421 and related information.

[0118] This invention provides a chromatography method, such as... Figure 13 As shown, the chromatography method includes the following steps: Step S110, the sample loading stage, includes: controlling the multi-way reversing valve and the fluid drive mechanism 122 to supply the target solution to be chromatographically analyzed to at least one chromatography column.

[0119] Specifically, the directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface with the first sample container 1111, the fluid drive mechanism 122 is controlled to draw the target solution to be chromatographically analyzed from the first sample container 1111 into the cavity of the fluid drive mechanism 122, the directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface with the chromatography column 131, and the fluid drive mechanism 122 is controlled to discharge the target solution to be chromatographically analyzed into the chromatography column 131.

[0120] Step S120, the chromatography stage, includes: controlling a multi-way reversing valve and a fluid drive mechanism to provide the auxiliary solution required for chromatography to at least one chromatography column for chromatographic treatment of the target solution to obtain the chromatographic target solution.

[0121] Specifically, the auxiliary solutions used in the chromatography stage differ depending on the chromatography column 131. The rotation of the reversing valve core of the multi-way reversing valve 121 connects the fluid interface to the second sample container 1121. The fluid drive mechanism 122 draws the auxiliary solution from the second sample container 1121 into its cavity. The rotation of the reversing valve core of the multi-way reversing valve 121 connects the fluid interface to the chromatography column 131. The fluid drive mechanism 122 then delivers the auxiliary solution to the chromatography column 131, performing chromatography treatments on the column 131, such as affinity chromatography and desalting treatment.

[0122] In some embodiments, such as Figure 14 As shown, step S110, the sample loading stage, includes: Step S111: Control the rotation of the directional valve core of the multi-way directional valve 121 so that the first fluid interface 1211 and the second fluid interface 1212 of the multi-way directional valve 121 are respectively connected to the fluid drive mechanism 122; the first fluid interface 1211 is a fluid interface connected to the sample container holding the target solution to be chromatographically analyzed, and the second fluid interface 1212 is a fluid interface connected to at least one chromatography column.

[0123] Specifically, the reversing valve core of the multi-way reversing valve 121 is controlled to rotate, so that the first fluid interface 1211 is connected to the fluid drive mechanism 122. The fluid drive mechanism 122 is controlled to draw the protein sample in the first sample container 1111 into the cavity of the fluid drive mechanism 122. Then, the reversing valve core of the multi-way reversing valve 121 is controlled to rotate, so that the second fluid interface 1212 is connected to the chromatography column 131.

[0124] Step S112, controlling the fluid drive mechanism 122 to supply the target solution to be chromatographically analyzed to at least one chromatography column 131 includes: Specifically, the fluid drive mechanism 122 controls the flow of protein samples from the chamber into at least one chromatography column 131.

[0125] In some embodiments, such as Figure 14 As shown, step S120, the chromatography stage, includes: Step S121: Control the rotation of the reversing valve core of the multi-way reversing valve 121 so that the third fluid interface 1213 and the second fluid interface 1212 of the multi-way reversing valve 121 are respectively connected to the fluid drive mechanism 122; the third fluid interface 1213 is a fluid interface connected to the sample container holding the auxiliary solution.

[0126] Specifically, the auxiliary solutions used in the chromatography stages differ depending on the chromatography column 131, and there are various types of auxiliary solutions. The chromatography column can be affinity chromatography (AC), ion exchange chromatography (IEX), multimode chromatography (MMC), hydrophobic interaction chromatography (HIC), reversed-phase chromatography (RPC), or size exclusion chromatography (SEC). The number of third fluid ports 1213 of the multi-way reversing valve 121 can be multiple. For ease of description, the fluid ports connected to the sample container holding the auxiliary solution are defined sequentially as: Third Fluid A Port 12131, Third Fluid B Port 12132, Third Fluid C Port 12133, Third Fluid D Port 12134, and Third Fluid E Port 12135.

[0127] For example, for crude purity, controlling the rotation of the directional valve core of the multi-way directional valve 121 switches the fluid interface to the third fluid C interface 12133, and controlling the fluid drive mechanism 122 to draw the eluent from the eluent solution bottle 11213 into the cavity of the fluid drive mechanism 122.

[0128] For example, in the case of desalination, controlling the rotation of the directional valve core of the multi-way directional valve 121 switches the fluid interface to the third fluid A interface 12131, and controlling the fluid drive mechanism 122 to draw the PBS solution in the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122.

[0129] Step S122: Control the fluid drive mechanism 122 to provide an auxiliary solution to at least one chromatography column for chromatography treatment of the target solution to be chromatographically processed, so as to obtain the chromatographically processed target solution.

[0130] For example, in affinity chromatography, controlling the rotation of the directional valve core of the multi-way reversing valve 121 switches the fluid interface to the second fluid interface 1212, and controlling the fluid drive mechanism 122 to discharge the eluent into the chromatography column 131. The eluent can quickly change the pH environment inside the resin, and the target protein immediately detaches from the resin. The target protein is discharged along with the eluent through the first outlet 1413 of the multi-way solenoid valve 141 to obtain the chromatographic target solution.

[0131] For example, in the case of desalting, the directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212, and the fluid drive mechanism 122 is controlled to discharge the PBS solution into the chromatography column 131. The PBS solution continues to flow through the molecular sieve effect of the desalting column to separate the target protein and salt ions. The separated solution is discharged through the first outlet 1413 of the multi-way solenoid valve 141 to obtain the target solution after chromatography.

[0132] In some embodiments, such as Figure 15As shown, the at least one chromatography column 131 includes a first chromatography column 131A and a second chromatography column 131B. The first chromatography column 131A is used to perform a first chromatography treatment on the target solution to be chromatographically analyzed to obtain an intermediate solution. The second chromatography column 131B is used to perform a second chromatography treatment on the intermediate solution to obtain the chromatographically analyzed target solution. Step S210, the sample loading stage, includes controlling the multi-way reversing valve 121 and the fluid drive mechanism 122 to supply the target solution to be chromatographically analyzed to the first chromatography column 131A.

[0133] Specifically, the directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface to the first sample container 1111. The fluid drive mechanism 122 is controlled to draw the target solution to be chromatographically analyzed from the first sample container 1111 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface to the first chromatography column 131A. The fluid drive mechanism 122 is controlled to discharge the target solution to be chromatographically analyzed from the cavity into the first chromatography column 131A.

[0134] Step S220, the chromatography stage, includes controlling the multi-way reversing valve 121 and the fluid drive mechanism 122 to provide the auxiliary solution required for the first chromatography process to the first chromatography column 131A for the first chromatography process of the target solution to obtain an intermediate solution.

[0135] Specifically, the directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface to the second sample container 1121. The fluid drive mechanism 122 is controlled to draw the auxiliary solution in the second sample container 1121 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface to the first chromatography column 131A. The fluid drive mechanism 122 is controlled to discharge the auxiliary solution in the cavity into the first chromatography column 131A to perform chromatography treatment on the first chromatography column 131A, such as affinity chromatography treatment.

[0136] Chromatography methods also include: Step S230, the second sample loading stage, includes: controlling the multi-way reversing valve 121 and the fluid drive mechanism 122 to supply the intermediate solution to the second chromatography column 131B.

[0137] Specifically, the intermediate solution is introduced into the first sample container 1111, the directional valve core of the multi-way directional valve 121 is controlled to rotate to connect the fluid interface with the first sample container 1111, and the fluid drive mechanism 122 is controlled to draw the intermediate solution in the first sample container 1111 into the cavity of the fluid drive mechanism 122.

[0138] Step S240, the secondary chromatography stage, includes: controlling the multi-way reversing valve 121 and the fluid drive mechanism 122 to provide the auxiliary solution required for the second chromatography process to the second chromatography column 131B, so as to perform the second chromatography process on the intermediate solution to obtain the chromatographic target solution.

[0139] Specifically, the directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface to the second sample container 1121. The fluid drive mechanism 122 is controlled to draw the auxiliary solution in the second sample container 1121 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to connect the fluid interface to the second chromatography column 131B. The fluid drive mechanism 122 is controlled to discharge the auxiliary solution in the cavity into the second chromatography column 131B to perform chromatography treatment on the second chromatography column 131B, such as desalting treatment.

[0140] In some embodiments, step S110, the sample loading stage further includes: Step S113: Obtain the detection result of the bubble sensor 124 located upstream of the multi-way reversing valve 121.

[0141] In step S114, in response to the detection result indicating that the size of the bubble exceeds a preset threshold, the multi-way reversing valve 121 is controlled to discharge the bubble from the pipeline 160 before the inlet of at least one chromatography column 131.

[0142] Specifically, the bubble sensor acquires bubble information in the pipeline 160 and sends the detection information to the controller 150. In response to the detection result, the controller 150 controls the multi-way reversing valve 121 to discharge the bubbles from the pipeline 160 before the chromatography column inlet 1311, or issues an alarm to remind the operator to perform venting.

[0143] In some embodiments, the chromatography stage further includes controlling a multi-way reversing valve 121 and a fluid drive mechanism 122 to cause liquid flowing from at least one chromatography column 131 to pass through a bubble trap in order to reduce bubbles in the liquid flowing from at least one chromatography column.

[0144] A bubble trap can be placed downstream of the chromatography column 131, for example, between the second pressure detection unit 133 and the detection module 134, to eliminate bubbles in the outflowing fluid.

[0145] It is understood that when multiple chromatography columns 131 are provided, the multiple chromatography columns can share a single bubble trap, or a bubble trap can be provided downstream of each chromatography column 131. The structure and function of the bubble trap are the same as in the above embodiment, and specific details can be found in the above embodiment.

[0146] In this embodiment, by controlling the multi-way reversing valve 121 and the fluid drive mechanism 122, for example, by maintaining the current state of the multi-way reversing valve 121 and the fluid drive mechanism 122, the liquid flowing out after passing through the chromatography column 131 can be eliminated by the bubble trap, which is beneficial to improving the quality of chromatography and the accuracy of the detection results of the subsequent detection module.

[0147] In some embodiments, step S120, the tomography stage further includes: Step S123: Obtain the detection result of the detection module 134 located downstream of at least one chromatography column 131; the detection result is used to indicate the type of liquid flowing out from at least one chromatography column 131.

[0148] Step S124: Based on the detection results, control the multi-way solenoid valve 141 located downstream of the detection module to discharge the liquid flowing from at least one chromatography column 131 from the outlet corresponding to the multi-way solenoid valve 141.

[0149] Specifically, the solution discharged from the chromatography column outlet 1312 is directly detected by the detection module 134. The detection module 134 acquires relevant parameter information of the solution in the pipeline 160. The detection module 134 includes one or more of the UV detection module, conductivity detection module, and pH detection module. Based on the detection results, the multi-way solenoid valve 141 located downstream of the detection module 134 is controlled to discharge the liquid flowing out of the chromatography column 131 from the outlet corresponding to the multi-way solenoid valve 141, for example, from the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141.

[0150] In some embodiments, prior to the sample loading stage, the chromatography method further includes: Step S310: Obtain first identification information, which is used to indicate the solution type and solution volume of the target solution to be chromatographically analyzed.

[0151] Specifically, the first feeding unit 111 also includes a first identification component that is signal-connected to the controller 150. The first identification component can be understood as a device capable of identifying container specifications; for example, the first identification component can be a sensor or a scanner. The information identified and acquired by the first identification component is first identification information.

[0152] In step S320, based on the first identification information, the feeding assembly 110, the multi-way reversing valve 121, and the fluid drive mechanism 122 are controlled to perform the actions of the sample loading stage and the chromatography stage.

[0153] Specifically, step S320 includes the sample loading stage in step S110 and the chromatography stage in step S120. Based on the first identification information, the fluid drive mechanism 122 is controlled to draw the amount of the target solution to be chromatographically analyzed from the first sample container 1111 and the amount of the auxiliary solution from the second sample container 1121 during the sample loading stage.

[0154] In some embodiments, prior to the sample loading stage, the chromatography method further includes: Step S410, pipeline pre-charging stage, includes: Step S411: Control the rotation of the directional valve core of the multi-way directional valve 121 so that the third fluid port 1213 and the fourth fluid port 1214 of the multi-way directional valve 121 are respectively connected to the fluid drive mechanism 122; the fourth fluid port 1214 is connected to the multi-way solenoid valve 141 of the distribution component 140. In step S412, the fluid drive mechanism 122 is controlled to draw the auxiliary solution from the third fluid interface 1213 and discharge it from the fourth fluid interface 1214.

[0155] Specifically, the directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid D interface 12134. The fluid drive mechanism 122 is controlled to draw the neutralizing liquid from the neutralizing solution bottle 11214 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the fourth fluid interface 1214. The fluid drive mechanism 122 is controlled to allow the neutralizing liquid in the cavity to enter through the second inlet 1412 of the multi-way solenoid valve 141 and be discharged into the second waste liquid tank 1422 through the fourth outlet 1416.

[0156] In some embodiments, prior to the sample loading stage, the chromatography method further includes: Step S410, pipeline pre-charging stage, includes: Step S413: Control the rotation of the directional valve core of the multi-way directional valve 121 so that the first fluid port 1211 and the third fluid port 1213 of the multi-way directional valve 121 are connected to the fluid drive mechanism 122 respectively.

[0157] In step S414, the fluid drive mechanism 122 is controlled to draw in the auxiliary solution from the third fluid interface 1213 and discharge it from the first fluid interface 1211.

[0158] Specifically, the directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid C interface 12133. The fluid drive mechanism 122 is controlled to draw the eluent from the eluent solution bottle 11213 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 is controlled to discharge the eluent in the cavity into the first waste liquid tank 1112 via the sampling element 123.

[0159] In some embodiments, the processing component 130 further includes a detection module 134, and the chromatography method further includes: before the sample loading stage and after the tubing pre-filling. Step S420, the balancing phase, includes: Step S421: Control the rotation of the directional valve core of the multi-way directional valve 121 so that the second fluid port 1212 and the third fluid port 1213 of the multi-way directional valve 121 are connected to the fluid drive mechanism 122. In step S422, the control fluid drive mechanism 122 provides an auxiliary solution to at least one chromatography column 131 for equilibration of at least one chromatography column 131.

[0160] Specifically, the directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is then rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 then discharges the PBS solution in the cavity through the chromatography column 131 and the UV detection module, conductivity detection module, and pH detection module in the detection module 134, via the first outlet 1413 of the multi-way solenoid valve 141. The PBS solution can equilibrate the chromatography column 131. Combined with the real-time online monitoring results of the UV detection module, conductivity detection module, and pH detection module, the equilibrium is automatically confirmed. For ease of understanding, the chromatography methods are now divided into affinity chromatography, desalting methods, and affinity chromatography-desalting methods, and will be explained in detail with three examples.

[0161] In some embodiments, the chromatography method may include an affinity chromatography method, such as... Figure 16As shown, the third fluid A interface 12131 is connected to the PBS solution bottle 11211 via tubing 160; the third fluid B interface 12132 is connected to the sodium hydroxide solution bottle 11212 via tubing 160; the third fluid C interface 12133 is connected to the eluent solution bottle 11213 via tubing 160; the third fluid D interface 12134 is connected to the neutralization solution bottle 11214 via tubing 160; the third fluid E interface 12135 is connected to the ethanol solution bottle 11215 via tubing 160; the first fluid interface 1211 is connected to the sampling device 123 via tubing 160; the second fluid interface 1212 is connected to the chromatography column inlet 1311 via tubing 160; and the fourth fluid interface 1214 is connected to the second inlet 1412 via tubing 160. The sample solution and auxiliary solutions are determined according to actual needs. The embodiments in this application are for reference only. The PBS solution is phosphate-buffered saline, formulated with 20 mM phosphate and 0.15 M sodium chloride, with the pH adjusted to 7.0. The sodium hydroxide concentration is 0.5 M. The eluent is formulated with 0.1 M glycine at pH 3.0. The neutralization solution is formulated with 1 M Tris-HCl at pH 8.5. The ethanol solution has an ethanol content of 20%. The target solution to be chromatographically analyzed is a protein sample that needs purification and has been filtered through a 0.45 μm filter membrane. There can be two first sample containers 1111 and four first collection containers 1421. Two first collection containers 1421 are used to collect the solution processed by one first sample container 1111. Column 131 is an affinity chromatography column, pre-packed with 5 ml of protein A resin. It utilizes the high affinity between Protein A and the Fc region of IgG antibody to achieve the separation and purification of the target antibody through affinity chromatography. Upstream of column 131 is a first pressure detection unit 132, downstream of column 131 is a second pressure detection unit 133, downstream of the second pressure detection unit 133 is a detection module 134, and downstream of detection module 134 is a multiplex solenoid valve 141. The specific steps include the following: Step S510, affinity chromatography tubing pre-filling stage, specifically includes the following processes: The directional valve core of the multi-way directional valve 121 is rotated to switch the fluid interface to the third fluid D interface 12134. The fluid drive mechanism 122 is controlled to draw the neutralized liquid from the neutralized liquid solution bottle 11214 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way directional valve 121 is rotated to switch the fluid interface to the fourth fluid interface 1214. The fluid drive mechanism 122 is controlled to allow the neutralized liquid in the cavity to enter through the second inlet 1412 of the multi-way solenoid valve 141 and be discharged into the second waste liquid tank 1422 through the fourth outlet 1416.

[0162] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid C interface 12133. The fluid drive mechanism 122 is controlled to draw the eluent from the eluent solution bottle 11213 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 is controlled to discharge the eluent in the cavity into the first waste liquid tank 1112 via the sampling element 123.

[0163] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution in the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The sampling element 123 is controlled to extend into the first waste liquid tank 1112. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 is controlled to discharge the PBS solution into the first waste liquid tank 1112 through the sampling element 123. The PBS solution is repeatedly drawn in and discharged. The discharged PBS solution can rinse the inside and outside of the sampling element 123 cleanly. The sampling element 123 is controlled to rise and reset.

[0164] If air is present in the upstream pipeline of the chromatography column 131, manually unscrew the pipeline 160 from the chromatography column inlet 1311 of the chromatography column 131. Control the rotation of the reversing valve core of the multi-way reversing valve 121 to switch the fluid interface to the third fluid A interface 12131. Control the fluid drive mechanism 122 to draw the PBS solution in the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. Control the rotation of the reversing valve core of the multi-way reversing valve 121 to switch the fluid interface to the second fluid interface 1212. Control the fluid drive mechanism 122 to discharge the PBS solution in the cavity through the first pressure detection unit 132. Stop when there are no air bubbles in the pipeline 160 and screw the pipeline 160 back into the chromatography column inlet 1311.

[0165] Step S520, affinity chromatography equilibration stage, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 then discharges the PBS solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, and the UV detection module, conductivity detection module, and pH detection module in the detection module 134, into the second waste liquid tank 1422 below it via the first outlet 1413 of the multi-way solenoid valve 141. The waste liquid is then discharged into other waste liquid containers via the second liquid guide pipe 1426. The PBS solution can equilibrate the chromatography column 131. Combined with the real-time online monitoring results of the UV detection module, conductivity detection module, and pH detection module, the equilibration is automatically confirmed. After equilibration, the sample loading step is performed.

[0166] Step S530, affinity chromatography sample loading stage, specifically includes the following process: Control the first base 1115 to move so that the first sample container 1111 is located below the sampling member 123, and control the sampling member 123 to move downward to the bottom of the first sample container 1111.

[0167] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid driving mechanism 122 is controlled to draw the protein sample in the first sample container 1111 into the cavity of the fluid driving mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid driving mechanism 122 discharges the protein sample in the cavity into the chromatography column 131 through the first pressure detection unit 132. The resin in the chromatography column 131 specifically captures the target protein. Other impurities and extraneous proteins that cannot be specifically bound are discharged into the second waste liquid tank 1422 directly below the multi-way solenoid valve 141 from the first outlet 1413 or the second outlet 1414 through the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module.

[0168] Repeat the sample loading until the sample is completely aspirated. Air bubbles appear in the first tubing 161 connected to the first fluid interface 1211 and are detected by the first bubble sensor 1241. The controller 150 activates the dead volume discharge program of the tubing 160 to discharge the sample in the first tubing 161 into the chromatography column 131 as completely as possible.

[0169] The chromatographic phase of affinity chromatography includes two parts: washing and elution.

[0170] Step S540, affinity chromatography washing stage, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is then rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 then discharges the PBS solution into the chromatography column 131 via the first pressure detection unit 132. The PBS solution can discharge impurities in the liquid phase through the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module in the detection module 134, and through the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 into the second waste liquid tank 1422 below it. The real-time online monitoring results of the UV detection module, the conductivity detection module, and the pH detection module can automatically confirm whether the washing of impurities has been completed. The system automatically confirms whether washing is complete. After washing is complete, the fluid drive mechanism 122 is controlled to drain the PBS solution from the chamber and perform the elution step.

[0171] Step S550, the affinity chromatography elution stage, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid C interface 12133. The fluid drive mechanism 122 draws the eluent from the eluent solution bottle 11213 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 discharges the eluent into the chromatography column 131 through the first pressure detection unit 132. The eluent can quickly change the pH environment inside the resin, and the target protein immediately detaches from the resin. The target protein passes through the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module in the detection module 134 with the eluent, and is discharged through the first outlet 1413 of the multi-way solenoid valve 141.

[0172] When the UV detection module detects that the absorbance value has reached the set threshold, it controls the second base 1425 to move, moving the first collection container 1421 below the first outlet 1413. After one first collection container 1421 is full, if the absorbance value of the eluent has not dropped to the stop-collection threshold, the second base 1425 is moved again to switch to different first collection containers 1421 for sequential collection. When the absorbance value of the eluent drops to the stop-collection threshold, the following neutralization step is performed.

[0173] Step S560, affinity chromatography neutralization stage, specifically includes the following processes: The directional valve core of the multi-way directional valve 121 is rotated to switch the fluid interface to the fourth fluid interface 1214. The fluid drive mechanism 122 is controlled to allow excess eluent in the cavity to enter through the second inlet 1412 of the multi-way solenoid valve 141 and be discharged into the second waste liquid tank 1422 below it through the first outlet 1413 or the second outlet 1414.

[0174] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid D interface 12134. The fluid drive mechanism 122 is controlled to draw the neutralizing liquid from the neutralizing solution bottle 11214 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the fourth fluid interface 1214. The fluid drive mechanism 122 is controlled to allow the neutralizing liquid in the cavity to enter through the second inlet 1412 of the multi-way solenoid valve 141 via the pipeline 160, and to be discharged into the second waste liquid tank 1422 below it through the first outlet 1413 or the second outlet 1414, thereby flushing the pipeline 160.

[0175] The second base 1425 is moved to sequentially move multiple first collection containers 1421 below the fourth outlet 1416. The fluid drive mechanism 122 is then controlled to discharge the neutralizing liquid in the cavity into the corresponding first collection container 1421 through the fourth outlet 1416. The controller 150 will automatically determine the amount of neutralizing liquid to be added according to the set logic, for example, adding neutralizing liquid to account for 1 / 10 of the solution volume in the first collection container 1421.

[0176] Step S570, affinity chromatography cleaning stage, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 discharges the PBS solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module in the detection module 134, and through the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 to the second waste liquid tank 1422. In some embodiments, the amount of PBS solution used to clean the chromatography column 131 during the cleaning stage is 2-20 times the internal space capacity of the chromatography column 131.

[0177] Step S580, affinity chromatography regeneration stage, specifically includes the following processes: The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid B interface 12132. The fluid drive mechanism 122 is controlled to draw the sodium hydroxide solution in the sodium hydroxide solution bottle 11212 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 is controlled to discharge the sodium hydroxide solution in the cavity into the first waste liquid tank 1112 via the sampling element 123. The sampling element 123 is controlled to extend into the first waste liquid tank 1112 and the inside and outside of the sampling element 123 are cleaned with sodium hydroxide solution.

[0178] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid B interface 12132. The fluid drive mechanism 122 is controlled to draw the sodium hydroxide solution in the sodium hydroxide solution bottle 11212 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 is controlled to discharge the sodium hydroxide solution in the cavity to the second waste liquid tank 1422 through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, and the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141.

[0179] Sodium hydroxide is a strong oxidizing agent that can denature proteins, bacteria, endotoxins, and other biomolecules, preventing cross-contamination between different sample batches. The cleaning effect can be improved by increasing the soaking time and the concentration of the sodium hydroxide solution. For example, a sodium hydroxide solution volume of 2-100 times the pipeline volume can be used for cleaning; for narrowing the scope, a volume of 5-10 times can be used. For example, a 0.1-2M sodium hydroxide solution can be used for cleaning; for narrowing the scope, a 0.3-1M sodium hydroxide solution can also be used. For example, the sodium hydroxide solution soaking time can be extended to 72 hours; the narrowing time range can also be 5-120 minutes. After the pipeline is soaked at 160°C, the following steps are performed.

[0180] The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is then rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 then discharges the PBS solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, the detection module 134, and the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 to the second waste liquid tank 1422. This process is repeated multiple times until the pH value meets the standard, which can be determined according to actual needs.

[0181] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is then rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 then discharges the PBS solution in the cavity into the first waste liquid tank 1112 via the sampling element 123. The sampling element 123 is then controlled to extend into the first waste liquid tank 1112. The PBS solution is repeatedly drawn in and discharged. The discharged PBS solution can rinse the inside and outside of the sampling element 123 cleanly. The sampling element 123 is then controlled to rise and reset. In some embodiments, 5-100 times the volume of PBS solution is used for cleaning. In other cases, 10-30 times the volume of PBS solution can be used for cleaning.

[0182] After the protein sample affinity chromatography is completed in the first sample container 1111, the first base 1115 is controlled to move the second sample container 1111 below the sampling member 123, and the above sample loading stage is repeated.

[0183] In some embodiments, after the regeneration stage ends in step S580, the directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid E interface 12135. The fluid drive mechanism 122 is then controlled to draw the ethanol solution from the ethanol solution bottle 11215 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is then rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 then discharges the ethanol solution in the cavity to the second waste tank 1422 via the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, the detection module 134, and the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141. In some embodiments, an ethanol solution with a volume of 2-20 times that of the chromatography column 131 is used for cleaning and preservation.

[0184] In some embodiments, such as Figure 17As shown, the chromatography method may include a desalting method. The third fluid A interface 12131 is connected to the PBS solution bottle 11211 via tubing 160; the third fluid B interface 12132 is connected to the sodium hydroxide solution bottle 11212 via tubing 160; the third fluid E interface 12135 is connected to the ethanol solution bottle 11215 via tubing 160; the first fluid interface 1211 is connected to the sampling device 123 via tubing 160; the second fluid interface 1212 is connected to the chromatography column inlet 1311 via tubing 160; and the fourth fluid interface 1214 is connected to the second inlet 1412 via tubing 160. The chromatography column 131 is connected upstream to a first pressure detection unit 132, downstream to a second pressure detection unit 133, downstream of the second pressure detection unit 133 to a detection module 134, and downstream of the detection module 134 to a multi-way solenoid valve 141. The target solution to be chromatographically analyzed is a protein sample requiring desalting. Two first sample containers (1111) and four first collection containers (1421) can be used. Two first collection containers (1421) are used to collect the solution processed by one first sample container (1111). The chromatography column (131) is a desalting column, using 5ml G-25 chromatography packing material. It utilizes the molecular sieving effect of a dextran gel with a porous network structure to separate substances based on their molecular size. Specifically, during chromatography, large molecules larger than the gel pore size, i.e., the target protein, are blocked outside the gel phase and rapidly descend along the gaps between gel particles, eluting first. Medium-sized molecules partially enter the gel interior, eluting at a slower rate. Small molecules enter the gel entirely, encountering the greatest resistance and eluting last, thus achieving separation. The specific steps include the following: Step S610, the pre-charging stage of the desalination pipeline, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid E interface 12135. The fluid drive mechanism 122 is controlled to draw the ethanol solution in the ethanol solution bottle 11215 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the fourth fluid interface 1214. The fluid drive mechanism 122 is controlled to allow the ethanol solution in the cavity to enter through the second inlet 1412 of the multi-way solenoid valve 141 and be discharged into the second waste liquid tank 1422 through the fourth outlet 1416.

[0185] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution in the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The sampling element 123 is controlled to extend into the first waste liquid tank 1112. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 is controlled to discharge the PBS solution in the cavity into the first waste liquid tank 1112 through the sampling element 123. The PBS solution is repeatedly drawn in and discharged. The discharged PBS solution can rinse the inside and outside of the sampling element 123 cleanly. The sampling element 123 rises and resets.

[0186] If air is present in the upstream pipeline of the chromatography column 131, manually unscrew the pipeline 160 from the chromatography column inlet 1311 of the chromatography column 131. Control the rotation of the reversing valve core of the multi-way reversing valve 121 to switch the fluid interface to the third fluid A interface 12131. Control the fluid drive mechanism 122 to draw the PBS solution in the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. Control the rotation of the reversing valve core of the multi-way reversing valve 121 to switch the fluid interface to the second fluid interface 1212. Control the fluid drive mechanism 122 to discharge the PBS solution in the cavity through the first pressure detection unit 132. Stop when there are no air bubbles in the pipeline 160 and screw the pipeline 160 back into the chromatography column inlet 1311.

[0187] Step S620, the desalination equilibrium stage, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 then discharges the PBS solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, and the UV detection module, conductivity detection module, and pH detection module in the detection module 134, through the first outlet 1413 of the multi-way solenoid valve 141 into the second waste liquid tank 1422 below it. The waste liquid is then discharged into other waste liquid containers through the second liquid guide pipe 1426. The PBS solution can equilibrate the chromatography column 131. Combined with the real-time online monitoring results of the UV detection module, conductivity detection module, and pH detection module, the equilibration is automatically confirmed. After equilibration, the sample loading step is performed.

[0188] Step S630, the desalting and sample loading stage, specifically includes the following process: Control the first base 1115 to move so that the first sample container 1111 is located below the sampling member 123, and control the sampling member 123 to move downward to the bottom of the first sample container 1111.

[0189] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid driving mechanism 122 is controlled to draw the protein sample in the first sample container 1111 into the cavity of the fluid driving mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid driving mechanism 122 is controlled to discharge the protein sample in the cavity into the chromatography column 131 through the first pressure detection unit 132. The original solution in the chromatography column 131 is discharged from the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 into the second waste liquid tank 1422 directly below it through the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module.

[0190] Repeat the sample loading until the sample is completely aspirated. Air bubbles appear in the first tubing 161 connected to the first fluid interface 1211 and are detected by the first bubble sensor 1241. The controller 150 activates the dead volume discharge program of the tubing 160 to discharge the sample in the first tubing 161 into the chromatography column 131 as completely as possible.

[0191] The chromatographic phase of a desalting method includes elution.

[0192] Step S640, the desalting and elution stage, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution in the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 is controlled to discharge the PBS solution in the cavity into the chromatography column 131 through the first pressure detection unit 132. The PBS solution continues to flow and passes through the molecular sieve effect of the desalting column to separate the target protein and salt ions. The separated solution passes through the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module in the detection module 134, and is discharged through the first outlet 1413 of the multi-way solenoid valve 141.

[0193] When the UV detection module detects that the absorbance value has reached the set threshold, it controls the second base 1425 to move, moving the first collection container 1421 below the first outlet 1413. After the first collection container 1421 is full, if the absorbance value of the elution effluent has not dropped to the stop-collection threshold, the second base 1425 is controlled to move again, switching to different first collection containers 1421 for sequential collection, and an alarm reminder can also be issued at the same time.

[0194] During the collection process, if the conductivity detection module detects an increase in conductivity concentration, it indicates that the target protein and salt ions are mixed together and flowing out, and the controller 150 will issue an alarm. When the absorbance value of the elution effluent drops to the stop-collection threshold, the following washing steps are performed.

[0195] Step S650, the desalination and washing stage, specifically includes the following processes: The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution in the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 is controlled to discharge the PBS solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module in the detection module 134, and through the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 to the second waste liquid tank 1422.

[0196] Step S660, the desalination and regeneration stage, specifically includes the following processes: The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid B interface 12132. The fluid drive mechanism 122 is controlled to draw the sodium hydroxide solution in the sodium hydroxide solution bottle 11212 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 is controlled to discharge the sodium hydroxide solution in the cavity into the first waste liquid tank 1112 via the sampling element 123. The sampling element 123 is controlled to extend into the first waste liquid tank 1112 and the inside and outside of the sampling element 123 are cleaned with sodium hydroxide solution.

[0197] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid B interface 12132. The fluid drive mechanism 122 is controlled to draw the sodium hydroxide solution from the sodium hydroxide solution bottle 11212 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 is controlled to discharge the sodium hydroxide solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, and the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 to the second waste liquid tank 1422. After the pipeline 160 is soaked, the following steps are performed.

[0198] The directional valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The directional valve core of the multi-way reversing valve 121 is then rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 then discharges the PBS solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, the detection module 134, and the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 to the second waste liquid tank 1422. This process is repeated multiple times until the pH value meets the standard.

[0199] The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the first fluid interface 1211. The fluid drive mechanism 122 is controlled to discharge the PBS solution in the cavity into the first waste liquid tank 1112 via the sampling element 123. The sampling element 123 is controlled to extend into the first waste liquid tank 1112. The PBS solution is repeatedly drawn in and discharged. The discharged PBS solution can rinse the inside and outside of the sampling element 123 cleanly. The sampling element 123 is controlled to rise and reset.

[0200] After the protein sample in the first sample container 1111 is desalted, the first base 1115 is controlled to move the second sample container 1111 below the sampling member 123, and the above sample loading stage is repeated.

[0201] In some embodiments, after the regeneration stage ends in step S660, the reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid E interface 12135. The fluid drive mechanism 122 is controlled to draw the ethanol solution from the ethanol solution bottle 11215 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is then rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 discharges the ethanol solution in the cavity through the first pressure detection unit 132, the chromatography column 131, the second pressure detection unit 133, the detection module 134, and the first outlet 1413 or the second outlet 1414 of the multi-way solenoid valve 141 to the second waste liquid tank 1422. In some embodiments, 2-20 times the volume of ethanol solution inside the chromatography column 131 is used for cleaning and preservation.

[0202] In some embodiments, such as Figure 18 As shown, the chromatography method may include affinity chromatography desalting, which connects affinity chromatography and desalting steps in series to achieve higher automation. A transfer collection head 1427 is fixed on the housing 170, with the second collection container 1428 directly below it. The transfer collection head 1427 is connected to the third outlet 1415 of the multi-way solenoid valve 141. A chromatography column 131, including a first chromatography column 131A and a second chromatography column 131B, is fixed on the housing 170. The first chromatography column 131A is an affinity chromatography column, and the second chromatography column 131B is a desalting column. The inlet of the affinity chromatography column is connected to the first outlet 1323 of the first three-way valve, the inlet of the desalting column is connected to the second outlet 1324 of the first three-way valve, the outlet of the affinity chromatography column is connected to the first inlet 1332 of the second three-way valve, and the outlet of the desalting column is connected to the second inlet 1333 of the second three-way valve. The outlet 1334 of the second three-way valve is connected to the detection module 134 via pipeline 160. The specific steps include the following: Step S710, the affinity chromatography tubing pre-filling stage, is the same as step S510 in the affinity chromatography method.

[0203] Step S720, the affinity chromatography equilibration stage, is the same as step S520 in the affinity chromatography method.

[0204] Step S730, the affinity chromatography loading stage, is the same as step S530 in the affinity chromatography method.

[0205] Step S740, the affinity chromatography washing stage, is the same as step S540 in the affinity chromatography method: Step S750, the washout stage, specifically includes: The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the third fluid A interface 12131. The fluid drive mechanism 122 is controlled to draw the PBS solution from the PBS solution bottle 11211 into the cavity of the fluid drive mechanism 122. The reversing valve core of the multi-way reversing valve 121 is rotated to switch the fluid interface to the second fluid interface 1212. The fluid drive mechanism 122 discharges the PBS solution in the cavity into the chromatography column 131 via the first pressure detection unit 132. The PBS solution continues to flow through the molecular sieve effect of the desalting column, separating the target protein and salt ions. The separated solution passes through the second pressure detection unit 133, the UV detection module, the conductivity detection module, and the pH detection module in the detection module 134, and is discharged through the third outlet 1415 of the multi-way solenoid valve 141. After passing through the transfer collection head 1427, the affinity chromatography protein solution discharged from the third outlet 1415 is collected through the second collection container 1428, so that the intermediate solution in the second collection container 1428 serves as the sample solution in the desalting process.

[0206] The first three-way valve 1321 is controlled to connect the inlet 1322 of the first three-way valve to the second outlet 1324 of the first three-way valve, and the second three-way valve 1331 is controlled to connect the second inlet 1333 of the second three-way valve to the outlet 13234 of the second three-way valve.

[0207] Step S760, the desalting and sample loading stage, is the same as step S630 in the desalting method.

[0208] Step S770, the desalting and elution stage, is the same as step S640 in the desalting method.

[0209] Step S780, the desalination and washing stage, is the same as step S650 in the desalination method.

[0210] Step S790, the desalination and regeneration stage, is the same as step S660 in the desalination method.

[0211] It should be understood that the various forms of processes shown above can be used to rearrange, add, or delete steps. For example, the steps described in this application can be executed in parallel, sequentially, or in a different order, as long as the desired result of the technical solution disclosed in this application can be achieved, and this is not limited herein.

[0212] While embodiments or examples of this application have been described with reference to the accompanying drawings, it should be understood that the methods, systems, and devices described above are merely exemplary embodiments or examples, and the scope of this application is not limited by these embodiments or examples, but only by the granted claims and their equivalents. Various elements in the embodiments or examples may be omitted or replaced by their equivalents. Furthermore, the steps may be performed in a different order than that described in this application. Further, various elements in the embodiments or examples may be combined in various ways. Importantly, as technology evolves, many elements described herein can be replaced by equivalents that appear later in this application.

Claims

1. An automated sample loading chromatography device, characterized in that, include: The feeding assembly includes multiple sample containers for containing sample solutions, the sample solutions including a target solution to be chromatographically analyzed and an auxiliary solution required for chromatographically analyzing the target solution; The processing components include at least one chromatography column; The sample loading assembly is connected to both the feeding assembly and the processing assembly. The sample loading assembly includes a multi-way reversing valve and a fluid drive mechanism. The multi-way reversing valve has multiple fluid interfaces and a reversing valve core. The fluid interfaces are connected to the multiple sample containers and the at least one chromatography column. The reversing valve core controls the opening and closing of the fluid interfaces. The fluid drive mechanism is connected to one fluid interface of the multi-way reversing valve and draws in or discharges the sample solution through the multi-way reversing valve. as well as A controller, signal-connected to the multi-way reversing valve and the fluid drive mechanism, is used to control the reversing valve core and the fluid drive mechanism to provide the target solution to be chromatography and / or the auxiliary solution to the processing assembly.

2. The chromatography apparatus according to claim 1, characterized in that, The feeding assembly includes a first feeding unit, which includes at least one first sample container for holding the target solution to be chromatographically analyzed. The sample loading assembly also includes a sampling component, which has a first end and a second end connected together. The first end of the sampling component is connected to a fluid interface of the multi-way reversing valve, and the second end of the sampling component can extend into the first sample container to aspirate the target solution to be chromatographically analyzed.

3. The chromatography apparatus according to claim 2, characterized in that, The first end of the sampling element is connected to the multi-way reversing valve through a first pipeline, and a first bubble sensor is installed on the first pipeline. The sample loading assembly also includes a lifting unit, which is used to drive the sampler to move up and down.

4. The chromatography apparatus according to claim 2 or 3, characterized in that, The first feeding unit further includes: A first base is used to support the at least one first sample container; A first driving member is connected to the first base and is used to drive the first base to move horizontally, so that the at least one first sample container moves sequentially to below the sampling member.

5. The chromatography apparatus according to claim 4, characterized in that, The first base is also provided with a first waste liquid tank, which is used to receive waste liquid discharged from the second end of the sampling member.

6. The chromatography apparatus according to claim 4 or 5, characterized in that, The first feeding unit further includes a first identification component connected to the controller signal. The first identification component is used to acquire first identification information of the first sample container. The first identification information is used to indicate the type and / or volume of the solution contained in the first sample container.

7. The chromatography apparatus according to any one of claims 1-6, characterized in that, The feeding assembly further includes a second feeding unit, which includes at least one second sample container for holding the auxiliary solution. Each of the second sample containers is connected to the fluid interface of the multi-way reversing valve through a second pipeline, and a second bubble sensor is provided in the second pipeline.

8. The chromatography apparatus according to any one of claims 1-7, characterized in that, The at least one chromatography column includes a first chromatography column and a second chromatography column, wherein the first chromatography column is used to perform a first chromatography treatment on the target solution to be chromatography, and the second chromatography column is used to perform a second chromatography treatment on the target solution to be chromatography. Wherein, the first chromatography column and the second chromatography column are the same type of chromatography column; or The first chromatography column and the second chromatography column are different types of chromatography columns.

9. The chromatography apparatus according to claim 8, characterized in that, The first chromatography column and the second chromatography column are different types of chromatography columns. The first chromatography column is configured to perform a first chromatography treatment on the target solution to be chromatographically analyzed to obtain an intermediate solution. The second chromatography column is configured to perform a second chromatography treatment on the intermediate solution to obtain the chromatographically analyzed target solution.

10. The chromatography apparatus according to claim 9, characterized in that, The inlet of the first chromatography column and the inlet of the second chromatography column are connected in parallel to the fluid interface of the multi-way reversing valve.

11. The chromatography apparatus according to any one of claims 8-10, characterized in that, The first chromatography column and the second chromatography column are respectively selected from one of the following: affinity chromatography column, ion exchange chromatography column, multimode chromatography column, hydrophobic interaction chromatography column, reverse chromatography column, and size exclusion chromatography column.

12. The chromatography apparatus according to any one of claims 8-11, characterized in that, The processing component further includes a first pressure detection unit and a second pressure detection unit. The first pressure detection unit is located upstream of the at least one chromatography column to detect the liquid pressure before entering the at least one chromatography column; The second pressure detection unit is located downstream of the at least one chromatography column to detect the pressure of the liquid flowing out of the at least one chromatography column.

13. The chromatography apparatus according to claim 12, characterized in that, The first pressure detection unit includes a first three-way valve, the inlet of which is connected to a fluid interface of one of the multi-way directional valves, and the two outlets of the first three-way valve are respectively connected to the inlet of the first chromatography column and the inlet of the second chromatography column. The second pressure detection unit includes a second three-way valve, the two inlets of which are respectively connected to the outlet of the first chromatography column and the outlet of the second chromatography column; The first three-way valve and the second three-way valve are respectively connected to the controller signal.

14. The chromatography apparatus according to claim 12 or 13, characterized in that, The processing component further includes a detection module, which includes one or more of a UV detection module, a conductivity detection module, and a pH detection module, and the detection module is located downstream of the at least one chromatography column.

15. The chromatography apparatus according to claim 14, characterized in that, The processing component also includes a bubble trap for reducing bubbles, the bubble trap being disposed between the second pressure detection unit and the detection module.

16. The chromatography apparatus according to any one of claims 1-15, characterized in that, The chromatography apparatus further includes a distribution component, which includes a multi-way solenoid valve that is signal-connected to the controller. The first inlet of the multi-way solenoid valve is connected to the outlet of the at least one chromatography column, and the multi-way solenoid valve includes a first outlet and a second outlet that can communicate with the first inlet; The first outlet is used to discharge the target solution after chromatography, and the second outlet is used to discharge the waste liquid generated by the chromatography process.

17. The chromatography apparatus according to claim 16, characterized in that, The at least one chromatography column includes a first chromatography column and a second chromatography column; the outlet of the first chromatography column and the outlet of the second chromatography column are respectively connected to the first inlet of the multi-way solenoid valve; The multi-way solenoid valve also includes a third outlet that can communicate with the first inlet. The third outlet is provided with a transfer collection head, which is used to receive and discharge the intermediate solution obtained after processing by the first chromatography column.

18. The chromatography apparatus according to claim 17, characterized in that, The multi-way solenoid valve further includes a second inlet and a fourth outlet. The second inlet is connected to a fluid interface of the multi-way directional valve, and the fourth outlet is connected to the second inlet and is used to discharge liquid flowing into the second inlet.

19. The chromatography apparatus according to claim 18, characterized in that, A stop solenoid valve is also provided at the fourth outlet, which is used to close the fourth outlet.

20. The chromatography apparatus according to claim 18 or 19, characterized in that, The allocation component further includes a collection unit, the collection unit comprising: First collection container; A second base is used to support the first collection container; and The second driving component is connected to the second base and is used to drive the second base to move horizontally, so that a plurality of first collection containers move sequentially below the first outlet to receive the target solution after chromatography.

21. The chromatography apparatus according to claim 20, characterized in that, The collection unit also includes: The second collection container, placed on the first base, is used to receive the intermediate solution discharged from the transfer collection head; The second waste liquid tank is used to receive liquid discharged from one or more of the first outlet, the second outlet and the fourth outlet.

22. The chromatography apparatus according to claim 21, characterized in that, The processing component further includes a detection module connected to the controller signal, the detection module being located downstream of the at least one chromatography column, for detecting information about the solution discharged from the chromatography column, the controller being configured to issue a control command to the second drive unit based on the detection information from the detection module, the second drive unit driving the second base to move according to the control command, so that the first collection container or the second waste liquid tank moves below the multi-way solenoid valve to receive the liquid discharged from the multi-way solenoid valve.

23. A chromatography method, applied to the chromatography apparatus as described in any one of claims 1-22, characterized in that, The chromatography method includes: The sample loading stage includes: controlling the multi-way reversing valve and the fluid drive mechanism to supply the target solution to be chromatographically analyzed to the at least one chromatography column; The chromatography stage includes: controlling the multi-way reversing valve and the fluid drive mechanism to provide the auxiliary solution required for chromatography to the at least one chromatography column for chromatographic treatment of the target solution to obtain the chromatographic target solution.

24. The chromatography method according to claim 23, characterized in that, The sample loading stage includes: The directional valve core of the multi-way directional valve is controlled to rotate, so that the first fluid interface and the second fluid interface of the multi-way directional valve are respectively connected to the fluid drive mechanism; the first fluid interface is a fluid interface connected to the sample container holding the target solution to be chromatographically analyzed, and the second fluid interface is a fluid interface connected to the at least one chromatography column. The fluid drive mechanism is controlled to supply the target solution to be chromatographically analyzed to the at least one chromatography column; and / or The chromatography stage includes: The directional valve core of the multi-way directional valve is controlled to rotate, so that the third fluid interface and the second fluid interface of the multi-way directional valve are respectively connected to the fluid drive mechanism; the third fluid interface is a fluid interface connected to the sample container holding the auxiliary solution. The fluid drive mechanism is controlled to supply the auxiliary solution to the at least one chromatography column for chromatography treatment of the target solution to be chromatographically processed, so as to obtain the chromatographically processed target solution.

25. The chromatography method according to claim 23 or 24, characterized in that, The at least one chromatography column includes a first chromatography column and a second chromatography column. The first chromatography column is used to perform a first chromatography treatment on the target solution to be chromatographyd to obtain an intermediate solution. The second chromatography column is used to perform a second chromatography treatment on the intermediate solution to obtain the chromatographically purified target solution. The sample loading stage includes: controlling the multi-way reversing valve and the fluid drive mechanism to supply the target solution to be chromatographically analyzed to the first chromatography column; The chromatography stage includes: controlling the multi-way reversing valve and the fluid drive mechanism to provide the auxiliary solution required for the first chromatography treatment to the first chromatography column, so as to perform the first chromatography treatment on the target solution to obtain an intermediate solution; and wherein, The chromatography method further includes: The secondary loading stage includes: controlling the multi-way reversing valve and the fluid drive mechanism to supply the intermediate solution to the second chromatography column; The secondary chromatography stage includes: controlling the multi-way reversing valve and the fluid drive mechanism to provide the auxiliary solution required for the second chromatography process to the second chromatography column for the second chromatography process of the intermediate solution to obtain the target solution after chromatography.

26. The chromatography method according to any one of claims 23-25, characterized in that, The sample loading stage also includes: Obtain the detection result from the bubble sensor located upstream of the multi-way directional valve. In response to the detection result indicating that the size of the bubble exceeds a preset threshold, the multi-way reversing valve is controlled to discharge the bubble from the pipeline before the inlet of the at least one chromatography column.

27. The method according to any one of claims 23-26, characterized in that, The chromatography stage further includes controlling the multi-way reversing valve and the fluid drive mechanism to cause the liquid flowing out of the at least one chromatography column to flow through the bubble trap in order to reduce the bubbles in the liquid flowing out of the at least one chromatography column.

28. The chromatography method according to any one of claims 23-27, characterized in that, The chromatography stage also includes: Obtain the detection result of a detection module located downstream of the at least one chromatography column; the detection result is used to indicate the type of liquid flowing out from the at least one chromatography column; Based on the detection results, the multi-way solenoid valve located downstream of the detection module is controlled to discharge the liquid flowing from the at least one chromatography column from the outlet corresponding to the multi-way solenoid valve.

29. The chromatography method according to any one of claims 23-28, characterized in that, Prior to the sample loading stage, the chromatography method further includes: Obtain first identification information, which is used to indicate the solution type and solution volume of the target solution to be chromatographically analyzed; Based on the first identification information, the feeding assembly, the multi-way reversing valve, and the fluid drive mechanism are controlled to perform the actions of the sample loading stage and the chromatography stage.

30. The chromatography method according to claim 24, characterized in that, Prior to the sample loading stage, the chromatography method further includes: The pipeline pre-charging stage includes: The directional valve core of the multi-way directional valve is controlled to rotate, so that the first fluid port and the fourth fluid port of the multi-way directional valve are respectively connected to the fluid drive mechanism; the fourth fluid port is connected to the multi-way solenoid valve of the distribution component. The fluid drive mechanism is controlled to draw the auxiliary solution into the third fluid port and discharge it from the fourth fluid port; and / or, Control the rotation of the directional valve core of the multi-way directional valve so that the first fluid interface and the third fluid interface of the multi-way directional valve are respectively connected to the fluid drive mechanism; The fluid drive mechanism is controlled to draw the auxiliary solution into the third fluid interface and discharge it from the first fluid interface.

31. The chromatography method according to claim 30, characterized in that, Before the sample loading stage and after the tubing pre-filling, the chromatography method further includes: The equilibrium phase includes: Control the rotation of the directional valve core of the multi-way directional valve so that the second fluid port and the third fluid port of the multi-way directional valve are connected to the fluid drive mechanism; The fluid drive mechanism is controlled to supply the auxiliary solution to the at least one chromatography column for equilibration of the at least one chromatography column.

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