Liquid constant-pressure dynamic chromatographic column

Abstract

The utility model provides a liquid constant-pressure dynamic chromatographic column, which relates to the field of chromatographic columns, and comprises a rack, and a liftable telescopic frame and a chromatographic column which are arranged on the rack, the telescopic frame comprises hydraulic oil cylinders arranged on the two sides of the machine frame, vertical rods arranged at the output ends of the hydraulic oil cylinders, a transverse rod arranged on the tops of the vertical rods and cover dismounting screws arranged on the transverse rod. According to the utility model, the hydraulic oil cylinder is used for lifting the column head piston, so that the requirement on the installation height of equipment is effectively reduced, the maintenance of the equipment is also facilitated, and the hydraulic oil cylinder lifts the column head piston in a filling column bed replacement process or a daily maintenance process; due to the fact that the self weight of the column head piston is small and the sliding resistance of the column head piston in the column casing is small under non-high pressure, the two hydraulic oil cylinders are arranged and symmetrically distributed on the two sides of the machine frame, the two hydraulic oil cylinders are synchronously controlled, it is guaranteed that the column head piston ascends and descends easily and stably in the column casing, and the situation that the column head piston is stuck in the column casing is avoided.

Description

Liquid constant pressure dynamic chromatography column Technical Field

[0001] This invention belongs to the field of chromatography columns, specifically a liquid constant pressure dynamic chromatography column. Background Technology

[0002] In the field of preparative chromatography today, dynamic axial compression technology is often used to prevent or eliminate the effects of bed collapse in order to ensure the stability of the packed column bed. This is recognized as the only technology that can maintain good separation performance in column chromatography of various sizes, and it is also the best column packing technology. Its principle is to pack, maintain column pressure and unpack the column by moving the piston up and down. The piston is equipped with a specially designed sealing ring that allows the piston to slide freely up and down while maintaining good sealing performance. The piston movement and pressure maintenance come from stable and uniform hydraulic pressure, so that the separation performance of dynamic axial compression preparative column systems of different diameters is comparable to that of analytical columns.

[0003] Advanced dynamic axial compression preparative column (DAC) systems can self-pack, maintain column pressure, and self-unpack, combining the functions of a chromatographic column and a column packer. DAC-packed columns fully meet the requirements for bed continuity, homogeneity, stability, and compactness. Therefore, DAC columns demonstrate enormous application potential in multiple fields:

[0004] In the field of chemistry: it is suitable for the separation and purification of complex samples and the removal of impurities in the process of new drug development, and can provide efficient solutions to accelerate the new drug development process;

[0005] In the biological field: it is used for the separation and purification of biological macromolecules, such as proteins, nucleic acids and polysaccharides, providing efficient and stable separation capabilities;

[0006] Pharmaceutical industry: Ensure the quality of raw material separation and purification, reduce production costs, and improve economic efficiency.

[0007] Existing conventional dynamic axial compression cylinders (DACs) use a pneumatic pump to compress hydraulic oil. The resulting high-pressure hydraulic oil then drives the piston at the cylinder head of the DAC to move up and down, thereby achieving functions such as cylinder loading, unloading, and pressure holding. However, the packing used in conventional DACs often adopts a downward-pressing cylinder loading mode. Structurally, a slender hydraulic cylinder is often installed at the top of the equipment, resulting in relatively high space requirements and requiring sufficient installation height space at the customer's site.

[0008] With the hydraulic cylinders installed, the conventional DAC is very bulky. If the equipment needs to be placed on the second floor or higher, it faces the problem of floor load-bearing capacity, which seriously restricts the smooth implementation of the customer's process flow.

[0009] The excessive height requirements of conventional DACs result in a tall and slender overall device with a high center of gravity, making on-site installation and maintenance very inconvenient and dangerous.

[0010] When a conventional DAC is packed into a packed column bed, a high-pressure gas source with stable pressure is required. The gas buffer capacity is also in high demand during the short packing process. Some customers do not have a stable gas supply on site, and it is necessary to configure a stable high-pressure gas source system for the preparation system separately, which also increases the customer's operating costs.

[0011] According to Chinese patent application number CN215741931 U, a dynamic axial compression chromatography column device is disclosed, proposing a solution to replace the hydraulic cylinder of the conventional DAC system. Instead, pressure solvent acts on the upper hydraulic chamber of the DAC piston and the lower packed column bed, respectively, to achieve the functions of piston compression and lifting. This solves to some extent the problems of secondary contamination risk of hydraulic oil and excessive space requirements of the equipment. Because the packing material in the low-pressure chromatography column system has a very large particle size (mostly above 70 μm), the packing column bed has low pressure resistance, often below 30 bar, and the gaps between packing particles are large. When the pressure solvent passes through the lower packed column bed, it can reduce the pressure... Force is directly transmitted to the piston, thus achieving the piston lifting function. However, in the field of high-pressure preparation, the particle size of the packing material is relatively small (most of the particle sizes used are 10μm or 7μm, and there are even cases where 5μm packing material is used). At this time, the entire packed column bed is very tightly compressed and the pressure is very high, reaching 100-200 bar. The gaps between the packing particles are small, and when the pressurized solvent passes through the lower packed column bed, it is difficult to transmit the pressure directly to the piston. The piston lifting function cannot be realized normally. Therefore, the practical application scenarios are limited. It can be realized in low-pressure chromatography column systems, but it cannot be realized in high-pressure chromatography columns.

[0012] In addition, the patent has the following shortcomings: because the proposed solution integrates a homogenization system, the overall design of the solution is too complicated and the cost to customers is too high.

[0013] In summary, this invention provides a liquid constant pressure dynamic chromatography column to solve the above problems. Summary of the Invention

[0014] To solve the above-mentioned technical problems, this utility model provides the following technical solution:

[0015] Liquid constant-pressure dynamic chromatography column, including,

[0016] A frame, and a telescopic frame and chromatographic column mounted on the frame that can be raised and lowered;

[0017] The telescopic frame includes hydraulic cylinders disposed on both sides of the frame, a vertical rod disposed at the output end of the hydraulic cylinder, a horizontal rod disposed at the top of the vertical rod, and a cap removal screw disposed on the horizontal rod;

[0018] The chromatographic column includes a column barrel, a column head piston disposed in the inner cavity of the column barrel, a column top cap and a column bottom cap disposed at the top and bottom of the column barrel, and a pipe connected to one end of the column head piston. One end of the column head piston is connected to a mobile phase inlet through the pipe, and the mobile phase can be pumped into the column barrel through the pipe.

[0019] Furthermore, in this utility model, one end of the vertical rod is fixedly connected to the horizontal rod, the vertical rod is driven by the hydraulic cylinder to realize the lifting and lowering of the telescopic frame, and the horizontal rod and the vertical rod are connected by a screw.

[0020] Furthermore, in this utility model, a sleeve is provided on the outside of the pipe, one end of the sleeve is fixedly connected to the upper surface of the piston head, and the other end is fixed to the crossbar. The cylinder is detachably connected to the top cap of the cylinder, and the bottom cap of the cylinder is detachably connected to the lower end of the cylinder.

[0021] Furthermore, in this utility model, the top of the column top cover is provided with a positioning screw hole, and the cover removal screw is screwed into the positioning screw hole.

[0022] Furthermore, in this invention, the top cover of the column has several pressure solvent inlets and outlets, which can be connected to the outlet of the pressure solvent pump, the inlet of the pressure solvent storage tank, or a pressure gauge can be installed to monitor the pressure of the pressure solvent after it is pumped into the column.

[0023] Furthermore, in this invention, a slurry inlet is provided at the lower end of the column, and a limiter is also provided on the piston at the column head.

[0024] Furthermore, in this utility model, a control box is provided on the frame, the control box includes a hydraulic unit, a tilting motor and a control panel, wherein the output shaft of the tilting motor is fixedly connected to the column.

[0025] Beneficial effects: This utility model has the following beneficial effects:

[0026] This invention, when high-pressure conditions are required, i.e., when filling or maintaining the stability of the packing column bed, uses a pressure solvent pump to deliver pressure solvent to the upper cavity of the piston head, generating stable high pressure. In non-high-pressure conditions, such as when unloading packing or during routine maintenance, two small hydraulic cylinders operate the piston head for raising and lowering. This effectively reduces the installation height requirements of the equipment and facilitates maintenance. During packing column bed replacement or routine maintenance, the hydraulic cylinders raise and lower the piston head. Because the piston head itself is relatively light and the resistance to sliding within the cylinder is low under non-high-pressure conditions, this design is particularly useful. Two hydraulic cylinders are symmetrically distributed on both sides of the frame. The two hydraulic cylinders are synchronously controlled to ensure that the piston head moves up and down easily and smoothly in the cylinder without getting stuck. The cylinder is designed to be able to flip up and down at any angle within 108°. In extreme cases, if the packing material used by the customer becomes caked and the piston head cannot be pressed down to unload the packing material, the flipping function can be used to facilitate manual removal of the packing material. If the piston head needs to be cleaned quickly, the flipping function can keep the piston head in the cylinder and allow the cleaning solvent to quickly rinse the piston head. Attached Figure Description

[0027] Figure 1 is a schematic diagram of the main structure of this utility model;

[0028] Figure 2 is a schematic diagram of the side cross-sectional structure of the cylindrical column of this utility model;

[0029] Figure 3 is a side view of the structure of this utility model.

[0030] In the picture:

[0031] 1. Frame; 2. Telescopic frame; 201. Hydraulic cylinder; 202. Vertical rod; 203. Horizontal rod; 204. Capping screw; 3. Chromatographic column; 301. Column barrel; 301a. Homogenizer inlet; 302. Column head piston; 302a. Limiter; 303. Column top cap; 303a. Pressure solvent inlet / outlet; 304. Column bottom cap; 305. Piping; 305a. Sleeve; 306. Mobile phase inlet; 307. Positioning screw hole; 4. Control box. Detailed Implementation

[0032] To better understand the technical content of this utility model, specific embodiments are described below in conjunction with the accompanying drawings. Various aspects of this utility model are described in this disclosure with reference to the accompanying drawings, which illustrate numerous illustrative embodiments. The embodiments of this disclosure are not necessarily defined to include all aspects of this utility model. It should be understood that the various concepts and embodiments described above, as well as those described in more detail below, can be implemented in any of many ways, because the concepts and embodiments disclosed in this utility model are not limited to any particular implementation. Furthermore, some aspects of this utility model can be used alone or in any suitable combination with other aspects disclosed in this utility model.

[0033] Example 1

[0034] As shown in Figures 1-3, this is the first embodiment of the present invention. This embodiment provides a liquid constant-pressure dynamic chromatography column, comprising...

[0035] The frame 1, and the telescopic frame 2 and the chromatographic column 3 mounted on the frame 1 that can be raised and lowered;

[0036] The telescopic frame 2 includes hydraulic cylinders 201 disposed on both sides of the frame 1, a vertical rod 202 disposed at the output end of the hydraulic cylinder 201, a horizontal rod 203 disposed at the top of the vertical rod 202, and a cover removal screw 204 disposed on the horizontal rod 203.

[0037] The chromatographic column 3 includes a column barrel 301, a column head piston 302 disposed in the inner cavity of the column barrel 301, a column top cap 303 and a column bottom cap 304 disposed at the top and bottom of the column barrel 301, and a pipe 305 connected to one end of the column head piston 302. One end of the column head piston 302 is connected to a mobile phase inlet 306 through the pipe 305, and the mobile phase can be pumped into the column barrel 301 through the pipe 305.

[0038] As shown in Figure 1-3, under non-high pressure conditions, two small hydraulic cylinders 201 perform the lifting and lowering operation of the piston head 302, thereby effectively reducing the installation height requirements of the equipment and facilitating equipment maintenance. During the packing bed replacement process or routine maintenance process, the hydraulic cylinders 201 lift and lower the piston head 302. Since the piston head 302 itself is relatively light and the resistance of the piston head 302 sliding in the cylinder 301 is relatively small under non-high pressure conditions, two hydraulic cylinders 201 are set up and symmetrically distributed on both sides of the frame 1. The two hydraulic cylinders 201 are synchronously controlled to ensure that the piston head 302 lifts and lowers easily and smoothly in the cylinder 301, and will not get stuck in the cylinder 301.

[0039] Example 2

[0040] Referring to Figures 1-2, this is the second embodiment of the present invention, which is based on the previous embodiment.

[0041] In this embodiment, one end of the vertical rod 202 is fixedly connected to the horizontal rod 203. The vertical rod 202 is driven by the hydraulic cylinder 201 to realize the lifting and lowering of the telescopic frame 2. The horizontal rod 203 and the vertical rod 202 are connected by a screw.

[0042] The pipe 305 is fitted with a sleeve 305a. One end of the sleeve 305a is fixedly connected to the upper surface of the piston 302, and the other end is fixed to the crossbar 203. The cylinder 301 is detachably connected to the top cap 303, and the bottom cap 304 is detachably connected to the lower end of the cylinder 301.

[0043] The top of the column top cover 303 is provided with a positioning screw hole 307, and the cover removal screw 204 is screwed into the positioning screw hole 307.

[0044] As shown in Figure 1-2, the piston 302 moves up and down with the telescopic frame 2. Its effective stroke is between the bottom end cap 304 and the top end cap 303. Under non-high pressure conditions, the piston 302 is lifted and lowered by two specially configured hydraulic cylinders 201, which effectively reduces the installation height requirement of the equipment and facilitates the maintenance of the equipment. In addition, the equipment no longer has the bulky hydraulic cylinder required by conventional DACs. Instead, two small hydraulic cylinders 201 are configured, which greatly reduces the overall weight. For DACs with an inner diameter of more than 450mm, the overall weight is reduced by 1 / 3 to 1 / 2.

[0045] Example 3

[0046] Referring to Figures 1-3, this is the third embodiment of the present invention, which is based on the first two embodiments.

[0047] In this embodiment, the top cover 303 of the column has several pressure solvent inlets and outlets 303a, which can be connected to the outlet of the pressure solvent pump, the inlet of the pressure solvent storage tank, or a pressure gauge can be installed to monitor the pressure after the pressure solvent is pumped into the column cylinder 301.

[0048] A slurry inlet 301a is provided at the lower end of the column cylinder 301, and a limiter 302a is also provided on the piston 302 at the column head.

[0049] A control box 4 is installed on the frame 1. The control box 4 includes a hydraulic unit, a tilting motor and a control panel. The output shaft of the tilting motor is fixedly connected to the column 301.

[0050] As shown in Figure 1-3, when filling new filler, the slurry can be quickly pumped in through the slurry inlet 301a. According to the customer's process requirements, it is also possible to rotate the slurry inlet 301a to the upper position of the column cylinder 301 after the column cylinder 301 is flipped to pump in the slurry. The limiter 302a plays a positioning role when the column head piston 302 moves upward to prevent the column head piston 302 from colliding with the column top cap 303.

[0051] The control panel is equipped with a safety button, an air pressure gauge, an oil pressure gauge, an air pressure regulating valve, a directional valve, and a start / stop button for the tilting motor. The hydraulic unit enables the telescopic frame to rise or fall, and the tilting motor enables the column 301 to tilt.

[0052] The column cylinder 301 is designed to be able to flip up and down at any angle within 108°. Through the flipping function, the flipping motor drives the column cylinder 301 to flip. If extreme working conditions occur and the packing material used by the customer becomes caked and cannot be unloaded by pressing down the piston 302, the flipping function can be used to facilitate manual removal of the packing material. If it is necessary to quickly clean the piston 302, the piston 302 can be kept inside the column cylinder and the cleaning solvent can quickly rinse the piston 302. The flipping structure design also ensures that the height requirements of the equipment at the installation site are effectively controlled, and the overall height of the equipment can be reduced by 1-2m.

[0053] When using it, the following column loading procedure should be followed:

[0054] First, add the weighed packing material to the metered homogenizing solution and stir thoroughly to disperse the packing material evenly. Then, use a pump to pump the homogenized packing material from the homogenizing solution inlet 301a into the column cylinder 301 cavity. Start the pressure solvent pump and pump the pressure solvent inlet 303a. The piston 302 of the column head is squeezed downward by the pressure solvent to compress the homogenizing solution in the column cylinder 301. After the solution is stably discharged from the mobile phase inlet 306 without obvious bubbles, open the valve at the bottom end cap 304 of the column to allow the solution to be discharged from the bottom of the column. At the same time, close the valve at the mobile phase inlet 306. When the pumped pressure solvent reaches the set pressure value, the pressure solvent pump stops working and maintains the pressure holding state.

[0055] Standard procedure:

[0056] After the hydraulic column with packed packing has been pressurized and stabilized for a period of time, normal operations can be carried out in sequence, such as balancing the packed column bed, loading samples, and eluting.

[0057] Column unloading operation:

[0058] When the pressure solvent pump is shut down, the valve on the pressure solvent inlet / outlet 303a is depressurized. A drain pipe is inserted through one of the pressure solvent inlets / outlets 303a. The valve on the pipe is switched to connect the drain pipe to the pressure solvent pump inlet. The valve is then switched again to connect the pressure solvent pump outlet to the pressure solvent storage tank. The pressure solvent pump is then started to drain the pressure solvent from the cavity between the upper surface of the piston 302 and the top cap 303.

[0059] Disconnect the bottom end cap 304 from the column tube 301, start the hydraulic cylinder 201, and drive the piston 302 to press the packing column bed downwards. Use a sufficiently large container below the column tube to receive the packing. After the packing is completely ejected from the column tube 301, change the direction of movement of the hydraulic cylinder 201 and lift the piston 302 upwards.

[0060] After lifting the piston head 302, a spray nozzle can be inserted into the cylinder 301 to quickly clean the inner wall of the cylinder 301 and the lower surface of the piston head 302. The disassembled end cap 304 should be cleaned separately.

[0061] When necessary, during maintenance and installation, the cap screw 204 can be screwed into the positioning screw hole 307 of the top cap 303, and the hydraulic cylinder 201 can be activated to lift the top cap 303, so that maintenance work can be carried out on the relevant connecting parts on the upper surface of the piston 302.

[0062] Column 301 flipping operation:

[0063] Remove the connecting screws of the horizontal bar 203 and the vertical bar 202 on the telescopic frame 2, carefully check that there are no obstructions in the space required for the flipping, and start the flipping button on the operation panel of the control box 4 to realize the cleaning and maintenance work or the unloading of the packing.

[0064] All standard parts used in this application can be purchased from the market, and can be customized according to the description and drawings. The specific connection methods of each part adopt conventional methods such as bolts, rivets, and welding that are mature in the prior art. The machinery, parts and equipment adopt conventional models in the prior art. The control method is automatic control through a controller. The control circuit of the controller can be implemented by simple programming by those skilled in the art and is common knowledge in the field. Since this application is mainly used to protect mechanical devices, the control method and circuit connection will not be explained in detail in this application.

[0065] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Those skilled in the art to which this invention pertains can make various modifications and refinements without departing from the spirit and scope of the present invention. Therefore, the scope of protection of this invention shall be determined by the claims.

Claims

1. A liquid constant-pressure dynamic chromatographic column, characterized in that: include, The instrument includes a frame (1), a telescopic frame (2) and a chromatographic column (3) mounted on the frame (1); the telescopic frame (2) includes hydraulic cylinders (201) mounted on both sides of the frame (1), a vertical rod (202) mounted on the output end of the hydraulic cylinders (201), a horizontal rod (203) mounted on the top of the vertical rod (202), and capping screws (204) mounted on the horizontal rod (203); the chromatographic column (3) includes a column cylinder ( 301) A piston head (302) disposed in the inner cavity of the column (301), a top cap (303) and a bottom cap (304) disposed at the top and bottom of the column (301), and a pipe (305) connected to one end of the piston head (302). One end of the piston head (302) is connected to a mobile phase inlet (306) through the pipe (305). The mobile phase can be pumped into the column (301) through the pipe (305).

2. The liquid constant pressure dynamic chromatographic column as described in claim 1, characterized in that: One end of the vertical rod (202) is fixedly connected to the horizontal rod (203). The vertical rod (202) is driven by the hydraulic cylinder (201) to realize the lifting and lowering of the telescopic frame (2). The horizontal rod (203) and the vertical rod (202) are connected by a screw.

3. The liquid constant pressure dynamic chromatographic column as described in claim 1, characterized in that: The pipe (305) is fitted with a sleeve (305a), one end of which is fixedly connected to the upper surface of the piston head (302), and the other end is fixed to the crossbar (203). The cylinder (301) is detachably connected to the top cap (303), and the bottom cap (304) is detachably connected to the lower end of the cylinder (301).

4. The liquid constant pressure dynamic chromatographic column as described in claim 1, characterized in that: The top of the column top cap (303) is provided with a positioning screw hole (307), and the cap removal screw (204) is screwed into the positioning screw hole (307).

5. The liquid constant-pressure dynamic chromatographic column as described in claim 1, characterized in that: The top cover (303) of the column has several pressure solvent inlets and outlets (303a), which can be connected to the outlet of the pressure solvent pump, the inlet of the pressure solvent storage tank, or a pressure gauge can be installed to monitor the pressure after the pressure solvent is pumped into the column (301).

6. The liquid constant pressure dynamic chromatographic column as described in claim 1, characterized in that: The lower end of the column (301) is provided with a slurry inlet (301a), and the piston (302) is also provided with a limiter (302a).

7. The liquid constant pressure dynamic chromatographic column as described in claim 1, characterized in that: A control box (4) is provided on the frame (1). The control box (4) includes a hydraulic unit, a tilting motor and a control panel, wherein the output shaft of the tilting motor is fixedly connected to the column (301).

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