Filling device for efficiently and continuously filling nano-liter chromatographic column

Abstract

The utility model relates to a filling device for efficiently and continuously filling a nano-liter chromatographic column. The filling device comprises a filling cavity, a gas inlet channel and a gas outlet channel, a pipeline connecting port is formed in the side wall of the filling cavity and used for connecting the air inlet channel and the air outlet channel, a pipeline switching valve is arranged at the intersection of the air inlet channel and the air outlet channel, and a pipeline pressure controller is arranged at the position adjacent to the switching valve; an automatic pressure relief controller is arranged on the air outlet channel, an automatic pressure relief program is arranged in the automatic pressure relief controller, and the automatic pressure relief controller is used for automatically controlling discharging of air in the filling cavity according to the pressure relief program arranged in the automatic pressure relief controller. The filling device can slowly release residual gas in the gas inlet pipeline, and can control the pressure of high-pressure gas entering the cavity of the filling device at the same time, so that a large amount of gas is prevented from rushing into the filling cavity when a gas source is started to cause a chromatographic column to be blocked by a filler; besides, automatic pressure relief can be realized according to a preset automatic pressure relief program by adopting an automatic pressure relief controller, so that filler backflow caused by improper manual operation can be avoided, the consistent filling effect of each chromatographic column can be ensured, and the yield of the self-made nano-liter chromatographic column can be improved.

Description

Technical Field

[0001] The utility model relates to the technical field of nanoliter chromatographic column manufacturing, and more specifically to a filling device for efficiently and continuously filling a nanoliter chromatographic column. Background Art

[0002] Liquid chromatography-mass spectrometry (LC-MS) is undoubtedly a powerful tool in proteomics research. Nanoliter LC is a common method, primarily involving the use of nanoliter chromatography columns. Currently, nanoliter chromatography columns are divided into two main categories: commercial nanoliter columns and homemade nanoliter columns. Commercial nanoliter columns are expensive, while homemade nanoliter columns offer significant advantages due to their low cost. In recent years, the use of homemade column packing devices has become increasingly widespread.

[0003] Our team previously applied for patent CN 115598273 A, a nanoliter chromatographic column filling device and filling method with a pressure relief control module. While this filling device solves the technical problem of difficult pressure relief control after nanoliter chromatographic column filling, some shortcomings have been discovered during use. For example, when filling multiple nanoliter chromatographic columns continuously, residual gas in the inlet pipeline is often not removed, resulting in the filler filling into the nanoliter chromatographic column with the remaining gas in the pipeline in an instant when the chromatographic column is filled again, causing blockage inside the nanoliter chromatographic column. The residual gas in the inlet channel must be completely discharged before filling a new chromatographic column, which is time-consuming and labor-intensive. However, if the residual gas in the inlet channel is not discharged and a new chromatographic column is directly filled, it may cause the chromatographic column to fail. In addition, manual pressure relief requires a certain amount of operator experience and a single pressure relief actually takes 0.5 to 1 hour. Therefore, we developed a nanoliter chromatographic column filling device that can achieve continuous filling and automatic pressure relief, which will help improve the efficiency of homemade nanoliter chromatographic columns and ensure the consistent quality of the filled chromatographic columns. Utility Model Content

[0004] In response to the above defects or improvement needs of the prior art, the present invention provides a filling device for efficiently and continuously filling nanoliter chromatographic columns. Its purpose is to set a pipeline pressure controller on the air inlet channel to control the slow discharge of residual gas in the air inlet channel and control the pressure entering the cavity. At the same time, an automatic pressure relief controller (with an automatic pressure relief program built in) is set on the air outlet channel, thereby solving the technical problem that in the existing process of continuously filling nanoliter chromatographic columns, a large amount of pipeline gas instantly enters the filling device cavity, causing the filler to block the chromatographic column.

[0005] To achieve the above-mentioned object, according to one aspect of the present invention, a filling device for efficiently and continuously filling a nanoliter chromatographic column is provided, wherein the filling device comprises a filling cavity 8, an air inlet channel and an air outlet channel;

[0006] The filling cavity 8 is used as a pressure pool to provide power to promote the filling material into the chromatographic column when filling the nanoliter chromatographic column. The side wall of the filling cavity 8 is provided with a pipeline connection port for connecting the inlet and outlet channels;

[0007] The inlet channel and the outlet channel are provided with a pipeline switching valve 4 at the intersection thereof; and a pipeline pressure controller 7 is provided adjacent to the switching valve 4;

[0008] An automatic pressure relief controller 10 is provided on the gas outlet channel. The automatic pressure relief controller 10 has an internal automatic pressure relief program for automatically controlling the gas in the filling cavity to be discharged through the gas outlet channel according to the internal pressure relief program.

[0009] Preferably, in the filling device for efficient and continuous filling of a nanoliter chromatographic column, the pipeline pressure controller 7 includes a pressure control valve 3 and a first pressure gauge 2 .

[0010] Preferably, in the filling device for efficient and continuous filling of nanoliter chromatographic columns, the pressure control valve 3 is a micro pressure reducing valve, the maximum pressure of which is ≤15 MPa and the sensitivity is 0.3%-1%.

[0011] Preferably, the automatic pressure relief controller 10 of the filling device for efficiently and continuously filling a nanoliter chromatographic column comprises a pressure relief valve 5 and a control element 6 connected to the pressure relief valve 5 and comprising a second pressure gauge; the control element 6 is used to control the rotation direction and speed of the pressure relief valve 5 according to a built-in automatic pressure relief program.

[0012] Preferably, in the filling device for efficient and continuous filling of nanoliter chromatographic columns, the pressure relief valve 5 releases the pressure in the filling chamber to 0 within a preset time by receiving a control signal output by the control element 6 .

[0013] Preferably, the preset time of the filling device for efficient and continuous filling of nanoliter chromatographic columns is 15 to 30 minutes.

[0014] Preferably, the filling device for efficiently and continuously filling a nanoliter chromatographic column, wherein the filling cavity 8 comprises a hollow cavity with an upper opening and a matching cavity cover, which can form a sealed filling cavity, and the cavity and the cavity cover are connected mechanically; the mechanical connection includes a threaded connection and a magnetic connector connection.

[0015] Preferably, the filling device for efficient and continuous filling of nanoliter chromatographic columns is provided with one or more sample bottle fixing grooves at the bottom of the cavity.

[0016] Preferably, in the filling device for efficient and continuous filling of nanoliter chromatographic columns, the cavity cover is provided with a capillary chromatographic column channel at a position corresponding to the center of the sample bottle fixing groove.

[0017] Preferably, the capillary chromatographic column channel of the filling device for efficient and continuous filling of nanoliter chromatographic columns is provided with a sealing device.

[0018] In general, the above technical solutions conceived by the present invention have the following beneficial effects compared with the prior art:

[0019] The chromatographic column filling device provided by the present invention, due to the pipeline pressure controller provided on the air inlet channel, can first slowly release the gas remaining in the air inlet pipeline, to avoid a large amount of gas flowing into the filling cavity when the gas source is turned on, causing the filler to block the chromatographic column; at the same time, in conjunction with the automatic pressure relief controller, it can automatically relieve pressure according to a preset automatic pressure relief program, thus avoiding filler backflow caused by improper manual operation, and also saving labor costs, and can also ensure that the filling effect of each chromatographic column is consistent, which is conducive to improving the yield rate of self-made nanoliter chromatographic columns; and when filling multiple nanoliter chromatographic columns continuously, there is no need to relieve the pipeline pressure, thereby simplifying the filling operation. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 Schematic diagram of the structure of the nanoliter chromatography column filling device in Example 1;

[0021] Figure 1 Middle 1: Nitrogen cylinder; 4: Switching valve; 7: Pipeline pressure controller; 8: Filling chamber; 9: Nanoliter chromatography column; 10: Automatic pressure relief controller;

[0022] Figure 2 7 is a schematic structural diagram of the pipeline pressure controller;

[0023] Figure 2 2 is the first pressure gauge, 3 is the pressure control valve;

[0024] Figure 3 1 is a schematic structural diagram of the automatic pressure relief controller 10;

[0025] Figure 3 5 is a pressure relief valve, and 6 is a control element including a second pressure gauge. DETAILED DESCRIPTION

[0026] In order to further illustrate the technical means and effects adopted by the present invention to achieve the predetermined purpose of the utility model, the following is a detailed description of the specific implementation method, structure, characteristics and effects of the present invention in combination with the accompanying drawings and preferred embodiments.

[0027] Patent CN 115598273 A discloses a nanoliter chromatographic column filling device with a pressure relief control module. However, when refilling a column, residual gas in the inlet channel is difficult to completely remove. This can cause the filler to instantly enter the nanoliter column along with the remaining gas in the pipeline during refilling, leading to internal clogging of the nanoliter column. To address this shortcoming, the present invention improves upon this device by providing a pipeline pressure controller to prevent clogging of the column caused by the instantaneous entry of large amounts of gas from the pipeline into the filling device cavity. The details are as follows:

[0028] First, allow the residual gas in the pipeline to enter the chromatographic column filling device to start filling the chromatographic column, then open the gas source and control the gas pressure entering the filling device through the pipeline pressure controller to ensure that the filler reaches the specified position of the chromatographic column smoothly to complete the filling of the chromatographic column.

[0029] It is preferred that an automatic pressure relief control program is set in the pressure relief module to realize automatic pressure relief control to avoid backflow of filler in the chromatographic column caused by excessive pressure relief.

[0030] The utility model provides a filling device for efficiently and continuously filling a nanoliter chromatographic column, which comprises a filling cavity 8, an air inlet channel and an air outlet channel;

[0031] The filling cavity 8 can be sealed and used as a pressure pool to provide power to promote the filling material into the chromatographic column when filling the nanoliter chromatographic column. Its side wall is provided with a pipeline connection port for connecting the inlet and outlet pipes to form an inlet and outlet channel;

[0032] The inlet and outlet channels are connected at their intersection with a pipeline switching valve 4 for switching between the inlet and outlet channels. Specifically, one connector of the switching valve 4 is connected to the inlet channel, and the other connector is connected to the outlet channel, thereby controlling the opening and closing of the inlet and outlet channels. The other end of the inlet channel is connected to the gas source, and the other end of the outlet channel is preferably connected to an automatic pressure relief controller, which controls the outlet channel to automatically release pressure according to a preset automatic pressure relief control program, thereby preventing backflow of the filler in the chromatographic column due to manual pressure relief too quickly.

[0033] A pipeline pressure controller 7 is connected adjacent to the switching valve 4. The pipeline pressure controller 7 is used, on the one hand, to slowly discharge the residual gas in the air inlet channel into the filling cavity. At this time, the air pressure in the cavity is higher than the atmospheric pressure, and the filler will slowly and uniformly enter the chromatographic column along with the discharged gas, which can avoid a large amount of gas entering the filling cavity instantaneously after the gas source is turned on, causing the filler to block the chromatographic column; on the other hand, after the residual gas in the air inlet pipe is discharged (at this time the pressure of the air inlet channel is consistent with that of the filling cavity), the air source is turned on, which can also be used to control the pressure entering the filling cavity, so as to avoid excessive pressure entering the cavity causing the filler to block the inside of the chromatographic column, resulting in failure in the production of the chromatographic column.

[0034] Furthermore, the pipeline pressure controller 7 includes a pressure control valve 3 and a first pressure gauge 2. By rotating the valve switch of the pressure control valve 3, the high-pressure gas in the air inlet channel is controlled to slowly enter the filling cavity. For example, when filling a chromatographic column, the valve of the pressure control valve 3 is first rotated to discharge the residual gas in the air inlet pipeline into the filling cavity first, and the filler in the sample bottle enters the chromatographic column under the action of the internal and external pressure difference; when the pointer of the first pressure gauge does not change (the first pressure gauge works normally, the internal and external pressures are consistent at this time, and the pointer does not change), the gas source is turned on, and the valve of the pressure control valve 3 can be rotated to control the pressure entering the filling cavity, so that the filler can be smoothly filled to the preset position of the chromatographic column.

[0035] Preferably, an automatic pressure relief controller 10 is provided on the gas outlet channel, and the automatic pressure relief controller 10 includes a pressure relief valve 5 and a control element 6 connected to the pressure relief valve and containing a second pressure gauge. The control element 6 is used to control the rotation direction and speed of the pressure relief valve 5 according to the built-in electronic automatic pressure relief program, so as to automatically control the pressure and speed of the gas in the filling cavity discharged through the gas outlet channel, so as to achieve the goal of slowly and uniformly unloading the pressure in the filling device, and avoid the backflow of the filler in the chromatographic column caused by excessive pressure relief due to lack of experience during manual operation, which makes the chromatographic column useless.

[0036] Preferably, the pressure control valve 3 is a micro-pressure reducing valve with a maximum pressure of ≤15Mpa and a sensitivity of 0.3%-1%, which can slowly discharge the residual gas in the air inlet channel into the filling cavity within 2 minutes; specifically, after the first nanoliter chromatographic column is filled, the second chromatographic column to be filled is placed in the filling cavity and sealed (the air outlet channel remains closed), the pressure valve on the nitrogen bottle is kept closed, the valve of the switching valve 4 is rotated first to connect the filling cavity with the air inlet channel, and then the pressure control valve 3 on the air inlet channel is opened to slowly discharge the residual gas in the air inlet channel into the filling cavity, so that the filler in the sample bottle is slowly and uniformly entered with the discharged gas. Chromatographic column, wait until the data displayed on the first pressure gauge 2 on the pressure control valve 3 no longer changes with the rotation of the pressure control valve 3 (because there is actually gas in the cavity and the air inlet pipeline at this time, the pressure gauge display will not be 0, but is fixed at a certain value and no longer changes with the rotation of the pressure control valve 3. At this time, the pressure in the cavity and the air inlet channel are consistent and can be regarded as a whole, until the pressure valve on the nitrogen bottle is opened and new gas enters this whole), then open the pressure valve on the nitrogen bottle, and rotate the pressure control valve 3 at the same time to control the pressure of the gas entering the filling cavity, so as to ensure that the filler enters the chromatographic column continuously and smoothly to the preset position, and close the gas source valve.

[0037] The automatic pressure relief controller 10 includes a pressure relief valve 5 and a control element 6 connected to the pressure relief valve and containing a second pressure gauge. The pressure relief valve 5 can receive a control signal output by a control unit in the control element 6 containing the second pressure gauge, thereby changing the flow rate of the high-pressure gas in the pressure relief pipeline with the help of power operation. After the nanoliter chromatographic column is filled, the gas source 1 is closed, and the rotating switching valve 4 connects the filling cavity to the gas outlet channel. The second pressure gauge in the automatic pressure relief controller detects that the pressure starts to rise from 0, and automatically starts the pressure relief. The pressure is relieved according to the built-in pressure relief program to ensure that the gas in the filling cavity is slowly discharged through the gas outlet channel, thereby avoiding the change of the position of the filler filled in the nanoliter chromatographic column due to improper manual operation during the pressure relief process, such as backflow.

[0038] The filling chamber 8 comprises a hollow, open-top chamber and a matching chamber cover. When in use, the chamber and chamber cover form a sealed filling chamber, serving as a pressure reservoir. In some embodiments, the chamber and chamber cover are mechanically connected to form a sealed filling chamber, such as by a threaded connection or a magnetic connector.

[0039] One or more sample bottle fixing grooves are provided at the bottom of the cavity; a capillary chromatographic column channel is provided on the cavity cover at a position corresponding to the center of the sample bottle fixing groove, which is used to insert the capillary chromatographic column to be filled into the sample bottle for filling; a sealing device is also provided at the capillary chromatographic column channel, which is used to seal the capillary chromatographic column channel, thereby ensuring that the filling cavity is in a sealed state.

[0040] The following are examples

[0041] Example 1 Nanoliter Chromatographic Column Filling Device

[0042] The nanoliter chromatography column filling device, such as Figure 1 As shown, it includes a filling cavity 8, an air inlet channel and an air outlet channel, wherein the filling cavity 8 is composed of a hollow cavity with an upper opening and a matching cavity cover, which can form a sealed filling cavity when in use, serving as a pressure pool; one or more sample bottle fixing grooves are provided at the bottom of the cavity for fixing sample bottles filled with filler suspension, and inlet and outlet channel connecting ports are provided on the side walls of the cavity for connecting the inlet and outlet channels, and a pipeline switching valve 4 is provided at the intersection of the inlet channel and the outlet channel, wherein one connector of the switching valve 4 is connected to the inlet channel, and the other connector is connected to the outlet channel, and a pipeline pressure controller 7 is connected adjacent to the switching valve; wherein the other end of the inlet channel is connected to the gas source 1.

[0043] like Figure 2 As shown, the pipeline pressure controller 7 includes a pressure control valve 3 and a first pressure gauge 2; the pressure control valve 3 is a micro pressure reducing valve with a maximum pressure of 15 MPa and a sensitivity of 1%.

[0044] An automatic pressure relief controller 10 is provided at one end of the gas outlet channel. Figure 3 As shown, the automatic pressure relief controller 10 includes a pressure relief valve 5 and a control element 6 connected to the pressure relief valve and including a second pressure gauge, for controlling the rotation direction and speed of the pressure relief valve 5 according to a built-in electronic automatic pressure relief program.

[0045] In the present invention, a non-automatic pressure relief controller may also be provided at one end of the air outlet channel, preferably an automatic pressure relief controller.

[0046] Example 2 Nanoliter Chromatography Column Filling Method

[0047] The chromatographic column was filled using the filling device in Example 1, as follows:

[0048] Install the first nanoliter chromatographic column 9 on the filling device, close the pressure control valve 3, rotate the switching valve 4 to connect the filling device cavity with the air inlet channel, open the gas source 1 (open the nitrogen bottle valve), and the high-pressure gas begins to flow. Then slowly rotate the pressure control valve 3, and the first pressure gauge 2 on the air inlet channel displays the pressure in the air inlet channel. The pressure control valve 3 is rotated until the filler in the sample bottle is slowly and evenly filled into the chromatographic column, and maintained until the chromatographic column is filled.

[0049] After the first chromatographic column is filled, the gas source 1 is turned off (the gas valve of the nitrogen bottle is closed) and the pressure control valve 3 of the air inlet channel are turned off, and the switching valve 4 is rotated to connect the filling cavity 8 to the air outlet channel. The pressure gauge detects that the pressure in the air outlet channel starts to rise from 0, and the automatic pressure relief controller 10 is automatically opened. The controller of the pressure relief valve 5 receives the control signal from the control element 6. Under the control of the pressure relief control program, the pressure relief valve 5 is slowly released, so that the pressure in the filling cavity slowly and uniformly drops to 0 within a preset time, and the pressure relief after the nanoliter chromatographic column is filled is automatically completed; preferably, the pressure in the filling cavity is released to 0 within 15 to 30 minutes.

[0050] After the above-mentioned automatic pressure relief is completed, the second nanoliter chromatographic column 9 is installed on the filling device, and the switching valve 4 is rotated to connect the filling cavity 8 with the air inlet channel. First, slowly rotate the pressure control valve 3. The first pressure gauge 2 on the air inlet channel displays the pressure in the air inlet channel. The pressure control valve 3 is rotated to enable the filler in the sample bottle to be slowly and uniformly filled into the chromatographic column. After the residual gas in the air inlet pipe is discharged (at this time, the pressure of the air inlet channel is consistent with that of the filling cavity, and the pointer of the first pressure gauge does not change); open the gas source 1, and at the same time rotate the pressure control valve 3 to control the pressure entering the filling cavity to avoid excessive pressure entering the cavity causing the filler to clog the inside of the chromatographic column. After the filler is successfully filled to the preset position of the chromatographic column, the filling of the second nanoliter chromatographic column is completed.

[0051] After the filling of the second chromatographic column is completed, the gas source 1 is turned off (the gas valve of the nitrogen bottle is closed) and the pressure control valve 3 of the air inlet channel are turned off, and the switching valve 4 is rotated to connect the filling cavity 8 with the air outlet channel. The pressure gauge detects that the pressure in the air outlet channel starts to rise from 0, and the automatic pressure relief controller 10 is automatically opened. The controller of the pressure relief valve 5 receives the control signal from the control element 6. Under the control of the pressure relief control program, the pressure relief valve 5 is slowly released, so that the pressure in the filling cavity slowly and uniformly drops to 0 within the same time, and the pressure relief after the nanoliter chromatographic column is automatically completed.

[0052] Repeating the above steps allows for efficient and continuous preparation of nanoliter chromatography columns, with consistent quality across the various nanoliter chromatography columns. The approximate times for filling and depressurizing are not fixed but are determined by the characteristics of the nanoliter chromatography column itself. Automatic filling devices for nanoliter chromatography columns that meet other characteristics are also encompassed within the scope of this invention, provided they do not depart from the technical scope of this invention.

[0053] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment as above, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to equivalent embodiments using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any brief modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A filling device for efficiently and continuously filling a nanoliter chromatographic column, characterized in that: The filling device comprises a filling cavity (8), an air inlet channel and an air outlet channel; The filling cavity (8) has a side wall provided with a pipeline connection port for connecting the inlet and outlet channels. The inlet channel and the outlet channel are provided with a pipeline switching valve (4) at the intersection thereof, and a pipeline pressure controller (7) is provided adjacent to the switching valve (4). An automatic pressure relief controller (10) is provided on the gas outlet channel. The automatic pressure relief controller (10) has an internal automatic pressure relief program for automatically controlling the discharge of gas in the filling cavity according to the internal pressure relief program.

2. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 1, characterized in that: The pipeline pressure controller (7) comprises a pressure control valve (3) and a first pressure gauge (2).

3. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 2, characterized in that: The pressure control valve (3) is a micro pressure reducing valve with a maximum pressure of ≤15 MPa and a sensitivity of 0.3%-1%.

4. The filling device for efficient continuous filling of nanoliter chromatographic columns according to any one of claims 1 to 3, characterized in that: The automatic pressure relief controller (10) comprises a pressure relief valve (5) and a control element (6) connected to the pressure relief valve (5) and comprising a second pressure gauge; The control element 6 is used to control the rotation direction and speed of the pressure relief valve 5 according to the built-in automatic pressure relief program.

5. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 4, characterized in that: The pressure relief valve (5) releases the pressure in the filling cavity to 0 within a preset time by receiving a control signal output by the control element (6).

6. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 5, characterized in that: The preset time is 15 to 30 minutes.

7. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 6, characterized in that: The filling cavity (8) comprises a hollow cavity with an upper opening and a matching cavity cover, which are connected mechanically. The mechanical connection includes a threaded connection and a magnetic connector connection.

8. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 7, characterized in that: One or more sample bottle fixing grooves are provided at the bottom of the cavity.

9. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 8, characterized in that: The cavity cover is provided with a capillary chromatographic column channel at a position corresponding to the center of the sample bottle fixing groove.

10. The filling device for efficient and continuous filling of nanoliter chromatographic columns according to claim 9, characterized in that: The capillary chromatographic column channel is provided with a sealing device.

Images