A radial dynamic compression chromatographic column

Abstract

This invention discloses a radial dynamic compression chromatographic column, comprising an upper flange, a lower flange, and a dynamic compression sleeve fixedly disposed between the upper and lower flanges. The dynamic compression sleeve includes a coaxial inner sleeve and an outer sleeve. The upper flange is provided with a feed port and an upper mobile phase port, and the lower flange is provided with a discharge port and a lower mobile phase port. This invention overcomes the problems of uneven pressure, wall effect, and high pressure and high cost associated with axial compression columns. It solves the problems of ordinary radial flow columns, such as lack of dynamic compression, easy bed loosening, and poor stability. It achieves low-pressure, uniform, and continuous dynamic compaction of the packed bed, eliminating channeling and wall effects.

Description

Technical Field

[0001] This invention relates to the field of compression columns, and more specifically to a radial dynamic compression chromatographic column. Background Technology

[0002] In the fields of biopharmaceuticals, plasma separation, and natural product purification, preparative chromatography and industrial chromatography separation are often involved, which requires compressed column equipment.

[0003] In existing technologies, dynamic axial compression columns (DACs) are generally used, such as the "Dynamic Axial Compression Column" disclosed in Chinese Patent No. CN202422243024.1. Its working principle is as follows: pistons are set at both ends of the column, applying continuous mechanical pressure to the packing bed along the axial direction. The pistons compress to prevent packing settling and column head collapse. However, it has disadvantages such as uneven axial pressure distribution in large-diameter columns, easy occurrence of edge effects, bridging, and voids, high pressure (50–200 bar), complex equipment, high cost, difficult maintenance, inability to eliminate wall effects, and a significant decrease in column efficiency over operating time.

[0004] In existing technologies, there are also conventional radial flow columns, such as Sepragen Superflo, whose main structure consists of annular channels, shallow beds, and radial flow. While they offer advantages such as low back pressure and high throughput, they also suffer from problems such as lack of dynamic compression, easy loosening of the packed bed, channeling, poor separation stability, inability to maintain bed stability at high flow rates, and limited scale-up.

[0005] Both also suffer from drawbacks such as poor filling repeatability, difficulty in verification, unstable column efficiency, fluctuating yield, and high cost during large-scale production. Summary of the Invention

[0006] To address the above technical problems, the purpose of this invention is to provide a radial dynamic compression column that is simple to fill, verifiable online, linearly amplified, and stable over a long period.

[0007] To achieve the above objectives, the technical solution of the present invention is a radial dynamic compression chromatographic column, including an upper flange, a lower flange, and a dynamic compression sleeve fixedly disposed between the upper flange and the lower flange. The dynamic compression sleeve includes a coaxial inner sleeve and an outer sleeve. The upper flange is provided with a feed port and an upper mobile phase port, and the lower flange is provided with a discharge port and a lower mobile phase port.

[0008] The above technical solution also includes a fluid distribution system, a pressurization system, and inlet / outlet components.

[0009] In the above technical solution, a sealing ring is provided between the feed inlet, the upper flow phase inlet and the upper flange; a sealing ring is provided between the discharge outlet, the lower flow phase inlet and the lower flange; and a sealing ring is provided between the dynamic compression sleeve and the upper flange and the lower flange.

[0010] In a preferred embodiment, the inner sleeve is a rigid sleeve, the outer sleeve is a flexible sleeve, and a pressure-bearing outer cylinder is also provided outside the outer sleeve.

[0011] In the above technical solution, the inner sleeve can be made of porous stainless steel or ceramic to support the packing bed and ensure uniform fluid flow. The outer sleeve is made of flexible material and has holes evenly distributed.

[0012] In a further technical solution, an outer filter screen is provided between the outer sleeve and the pressure-bearing outer cylinder, and an outer filter screen space is formed between the outer filter screen and the pressure-bearing outer cylinder; an inner filter screen is also provided between the inner sleeve and the outer sleeve, and an inner filter screen space is formed between the inner filter screen and the inner cylinder.

[0013] In the above technical solution, the outer filter screen prevents the packing material inside the dynamic compression sleeve from entering the outer filter screen space; the inner filter screen prevents the packing material inside the dynamic compression sleeve from entering the inner filter screen space.

[0014] In a preferred embodiment, at least one feed inlet is provided, and the lower end of the feed inlet is connected to the dynamic compression sleeve.

[0015] In a preferred embodiment, at least one discharge port is provided, and the upper end of the discharge port is connected to the dynamic compression sleeve.

[0016] In a further technical solution, the inner sleeve is provided with multiple holes evenly distributed on it.

[0017] In a further technical solution, the upper flow phase port is fixedly installed at the center of the upper flange, and multiple outlets are provided at the bottom of the upper flow phase port. An upper flow phase channel is provided inside the upper flange, with one end of the upper flow phase channel connected to the outlet and the other end connected to the external filter space.

[0018] In a preferred embodiment, the lower flow phase inlet is fixedly located at the center of the lower flange, the top of the lower flow phase inlet is provided with multiple inlets, and a lower flow phase channel is provided inside the lower flange, with one end of the lower flow phase channel connected to the inlet and the other end connected to the inner filter space.

[0019] A preferred technical solution includes a movable bracket, which is fixed to the lower surface of the lower flange.

[0020] A preferred technical solution includes at least one set of hydraulic devices, which are fixed to the upper flange. The hydraulic devices include a compression cylinder, a piston, a hydraulic inlet, a hydraulic outlet, a piston guide rod, a piston fixing block, a piston fixing rod, and a compression cylinder flange. The compression cylinder is fixed to the upper flange, the piston is movably disposed within the compression cylinder, the compression cylinder flange is fixed to the compression cylinder, the hydraulic inlet and hydraulic outlet are fixed to the compression cylinder flange, a piston guide rod is fixedly disposed on the upper part of the piston, the piston guide rod is slidably disposed outside the piston fixing rod, and a piston fixing block is fixedly disposed on the top of the piston guide rod.

[0021] A preferred technical solution includes a movable bracket, which is fixed to the lower surface of the lower flange.

[0022] Working principle of the invention:

[0023] Packing material is introduced into the dynamic compression sleeve to form annular packing. Product material is introduced through the feed inlet, allowing it to permeate the packing. The feed inlet is then closed, and the upper flowing phase inlet is opened. Hydraulic pressure is applied to achieve dynamic radial compression, causing the flowing phase to flow uniformly from the outer filter space through the annular packing into the inner filter space, and finally exit from the lower flowing phase inlet. This achieves axial entry, radial passage, and axial exit without altering the separation mechanism.

[0024] The advantages of this invention are:

[0025] 1. Zero-wall effect: This invention can achieve radial uniform compression and completely eliminate near-wall channeling.

[0026] 2. Lower pressure: The working pressure (radial compression pressure of the hydraulic device) of this invention is 5–30 bar, which is much lower than that of the axial compression column.

[0027] 3. More stable bed: This invention achieves dynamic pressure real-time compensation, and the column efficiency does not decrease during continuous operation.

[0028] 4. Higher flux: The radial flow + shallow bed of the present invention increases the flow rate by 3-9 times and reduces the time to 1 / 3.

[0029] 5. Lower cost: This invention uses a hollow annular packing column, which reduces the column volume and the amount of packing used, thus reducing equipment and maintenance costs.

[0030] 6. Easier to scale up: The bed depth of this invention is constant, allowing for linear scaling up without changing the pressure drop and separation behavior.

[0031] 7. Compliance-friendly: This invention has no blind spots, can be CIP / SIP, and meets GMP verification requirements. Attached Figure Description

[0032] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. The accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0033] The present invention will be further described below with reference to the accompanying drawings and embodiments:

[0034] Figure 1 This is a schematic diagram of the structure of the present invention;

[0035] Figure 2 This is a schematic diagram of the appearance of the present invention;

[0036] Figure 3 This is a top sectional view of the present invention;

[0037] Figure 4 This is a lower sectional view of the present invention.

[0038] The components are as follows: 1. Feed inlet; 2. Upper flowing phase inlet; 3. Upper flange; 4. Pressure-bearing outer cylinder; 5. Outer filter screen; 6. Inner filter screen; 7. Inner sleeve; 8. Lower flange; 9. Discharge port; 10. Lower flowing phase inlet; 11. Moving support; 12. Piston; 13. Compression cylinder; 14. Hydraulic inlet; 15. Piston guide rod; 16. Piston fixing block; 17. Piston fixing rod; 18. Hydraulic outlet; 19. Compression cylinder flange; 20. Outer filter screen space; 21. Inner filter screen space; 22. Upper flowing phase channel; 23. Lower flowing phase channel; 24. Hydraulic device. Detailed Implementation

[0039] Example 1: As shown in Figures 1-4, a radial dynamic compression chromatographic column includes an upper flange 3, a lower flange 8, and a dynamic compression sleeve fixedly disposed between the upper flange 3 and the lower flange 8. The dynamic compression sleeve includes a coaxial inner sleeve 7 and an outer sleeve. The upper flange 3 is provided with a feed port 1 and an upper mobile phase port 2, and the lower flange 8 is provided with a discharge port 9 and a lower mobile phase port 10.

[0040] This includes fluid distribution systems, pressurization systems, and inlet / outlet components.

[0041] The inner sleeve 7 is a rigid sleeve, the outer sleeve is a flexible sleeve (fluororubber composite membrane, pressure resistant 30 bar), and the outer sleeve is also covered with a pressure-bearing outer cylinder 4.

[0042] The inner sleeve 7 can be made of porous stainless steel to support the packing bed and ensure uniform fluid flow. The outer sleeve is made of flexible material and has holes evenly distributed.

[0043] An outer filter screen 5 is also provided between the outer sleeve and the pressure-bearing outer cylinder 4, forming an outer filter space 20 between the outer filter screen 5 and the pressure-bearing outer cylinder 4; an inner filter screen 6 is also provided between the inner sleeve 7 and the outer sleeve, forming an inner filter space 21 between the inner filter screen 6 and the inner cylinder.

[0044] The outer filter screen 5 prevents the packing material inside the dynamic compression sleeve from entering the outer filter screen space 20; the inner filter screen 6 prevents the packing material inside the dynamic compression sleeve from entering the inner filter screen space 21.

[0045] The feed inlet 1 is provided with at least one, and the lower end of the feed inlet 1 is connected to the dynamic compression sleeve.

[0046] At least one discharge port 9 is provided, and the upper end of the discharge port 9 is connected to the dynamic compression sleeve.

[0047] The sleeve has multiple holes evenly distributed on it.

[0048] The upper flow phase port 2 is fixedly installed at the center of the upper flange 3. Multiple outlets are provided at the bottom of the upper flow phase port 2. An upper flow phase channel 22 is provided inside the upper flange 3. One end of the upper flow phase channel 22 is connected to the outlet and the other end is connected to the external filter space 20.

[0049] The lower flow phase inlet 10 is fixedly installed at the center of the lower flange 8. Multiple inlets are provided at the top of the lower flow phase inlet 10. A lower flow phase channel 23 is provided inside the lower flange 8. One end of the lower flow phase channel 23 is connected to the inlet and the other end is connected to the inner filter space 21.

[0050] Includes a movable bracket 11, which is fixed to the lower surface of the lower flange 8.

[0051] It includes at least one set of hydraulic devices 24, which are fixed on the upper flange 3. The hydraulic device 24 includes a compression cylinder 13, a piston 12, a hydraulic inlet 14, a hydraulic outlet 18, a piston guide rod 15, a piston fixing block 16, a piston fixing rod 17, and a compression cylinder flange 19. The compression cylinder 13 is fixed on the upper flange 3, the piston 12 is movably disposed inside the compression cylinder 13, the compression cylinder flange 19 is fixed on the compression cylinder 13, the hydraulic inlet 14 and the hydraulic outlet 18 are fixedly disposed on the compression cylinder flange 19, the piston guide rod 15 is fixedly disposed on the upper part of the piston 12, the piston guide rod 15 is slidably disposed outside the piston fixing rod 17, and the piston fixing block 16 is fixedly disposed on the top of the piston guide rod 15.

[0052] The preferred technical solution includes a movable bracket 11, which is fixed to the lower surface of the lower flange 8.

[0053] How to use this embodiment:

[0054] Taking plasma protein separation as an example, packing material is added to the dynamic compression sleeve using Q Sepharose Fast Flow anion exchange medium, dry packing is employed. This forms a ring-shaped packed bed with an inner diameter of 100 mm, an outer diameter of 250 mm, and a bed height of 500 mm. Inlet 1 is opened to allow the product material to permeate the packing. Inlet 1 is closed, and the upper mobile phase inlet 2 is opened. The hydraulic device 24 is pressurized (using clean water, with a constant radial compression pressure of 10 bar), causing the mobile phase to flow uniformly from the dynamic compression sleeve to the inner sleeve 7 (flow rate 75–95 L / hr, fluid back pressure < 2 bar), achieving axial entry, radial penetration, and axial exit without altering the separation mechanism. The lower mobile phase inlet 10 is opened to receive the separated liquid.

[0055] Results: After 500 hours of continuous operation, the column efficiency retention rate was >95%, and the yield was >98%.

[0056] A single batch processing of 350 L of feed liquid requires only one shift (axial compression columns require three shifts), with a product recovery rate of >98% and purity meeting standards. Compared to a traditional 16 L axial compression column, the flow rate is increased by 3 times, and the separation time is reduced to 1 / 3.

[0057] Comparative example:

[0058] Comparison of Cod Dnase purification results

[0059] project 20L radial column (this invention) 16L Axial Compression Column Flow rate (CV / h) 70 10 Purification time (h) 0.25 1.3 Production capacity (mg / h / ml) 0.7 0.13 Target product recovery rate (%) 107% 100% Enlarged (5L → 160L) Completely linear amplification The height of the column bed remains constant, but the diameter increases. However, due to the change in the length-to-diameter ratio, the gradient length needs to be changed.

Claims

1. A radially dynamic compression chromatographic column, characterized in that: It includes an upper flange, a lower flange, and a dynamic compression sleeve fixedly disposed between the upper flange and the lower flange. The dynamic compression sleeve includes a coaxial inner sleeve and an outer sleeve. The upper flange is provided with a feed port and an upper flow phase port, and the lower flange is provided with a discharge port and a lower flow phase port.

2. The radial dynamic compression chromatographic column according to claim 1, characterized in that: The inner sleeve is a rigid sleeve, the outer sleeve is a flexible sleeve, and a pressure-bearing outer cylinder is also provided outside the outer sleeve.

3. The radial dynamic compression chromatographic column according to claim 2, characterized in that: An outer filter screen is also provided between the outer sleeve and the pressure-bearing outer cylinder, and an outer filter screen space is formed between the outer filter screen and the pressure-bearing outer cylinder; an inner filter screen is also provided between the inner sleeve and the outer sleeve, and an inner filter screen space is formed between the inner filter screen and the inner cylinder.

4. A radial dynamic compression chromatographic column according to claim 1, characterized in that: The feed inlet is provided with at least one, and the lower end of the feed inlet is connected to the dynamic compression sleeve.

5. A radial dynamic compression chromatographic column according to claim 1, characterized in that: The discharge port is provided with at least one, and the upper end of the discharge port is connected to the dynamic compression sleeve.

6. A radial dynamic compression chromatographic column according to claim 2, characterized in that: The inner sleeve has multiple holes evenly distributed on it.

7. A radial dynamic compression chromatographic column according to claim 2, characterized in that: The upper flow phase port is fixedly installed at the center of the upper flange. Multiple outlets are provided at the bottom of the upper flow phase port. An upper flow phase channel is provided inside the upper flange. One end of the upper flow phase channel is connected to the outlet and the other end is connected to the external filter space.

8. A radial dynamic compression chromatographic column according to claim 2, characterized in that: The lower flow phase inlet is fixedly installed at the center of the lower flange. Multiple inlets are provided at the top of the lower flow phase inlet. A lower flow phase channel is provided inside the lower flange. One end of the lower flow phase channel is connected to the inlet and the other end is connected to the inner filter space.

9. A radial dynamic compression chromatographic column according to claim 1, characterized in that: It includes a movable bracket, which is fixed to the lower surface of the lower flange.

10. A radially dynamic compression chromatographic column according to claim 1, characterized in that: The device includes at least one hydraulic unit fixed to the upper flange. The hydraulic unit comprises a compression cylinder, a piston, a hydraulic inlet, a hydraulic outlet, a piston guide rod, a piston fixing block, a piston fixing rod, and a compression cylinder flange. The compression cylinder is fixed to the upper flange, the piston is movably disposed within the compression cylinder, the compression cylinder flange is fixed to the compression cylinder, the hydraulic inlet and hydraulic outlet are fixed to the compression cylinder flange, a piston guide rod is fixedly disposed on the upper part of the piston, the piston guide rod is slidably disposed outside the piston fixing rod, and a piston fixing block is fixedly disposed on the top of the piston guide rod.

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