An ultrafiltration dialyzer, an ultrafiltration device and a filtration method

Abstract

The application discloses an ultrafiltration dialyzer, an ultrafiltration device and a filtration method, and belongs to the technical field of biological separation and purification. The ultrafiltration dialyzer comprises a filter cup, a cover plate and a filter tube with a detachable filter membrane, and can realize positive pressure / negative pressure double-mode driving filtration. The ultrafiltration device is provided with two groups of rotatable rotary tray assemblies which can be independently rotated, the tray can accommodate multiple groups of ultrafiltration dialyzers, the rotary column is integrated with a gas path to connect a gas pressure adjusting mechanism, and multi-station batch synchronous filtration is realized. The application matches two sets of filtration processes of positive pressure and negative pressure, adapts to different protein solution processing requirements, is convenient to disassemble and assemble, has strong adaptability, and can significantly improve the efficiency and operation flexibility of protein filtration processing.

Description

Technical Field

[0001] This invention relates to protein ultrafiltration concentration equipment and methods, specifically an ultrafiltration dialyzer, an ultrafiltration device, and a filtration method. Background Technology

[0002] Ultrafiltration is a core technology for protein purification, concentration, desalting, and buffer replacement, and is widely used in biopharmaceutical and life science research. Currently, most laboratory protein ultrafiltration devices are commercially available ultrafiltration tubes with a single-channel structure. This ultrafiltration approach has the following drawbacks: ① The ultrafiltration tube is designed as a standard centrifuge tube with a nested filter membrane. Limited by the centrifuge rotor volume, the maximum sample capacity per tube is 15 mL. For sample volumes in the 15-50 mL range, this is lower than the minimum processing capacity of tangential flow ultrafiltration membrane packs or hollow fiber columns, but significantly exceeds the single-tube capacity of commercial ultrafiltration tubes. Therefore, concentrating samples in this volume range requires frequent starting and stopping of the centrifuge, followed by opening the cap to add liquid and discarding the filtrate. ② The volume of filtrate and the concentration factor cannot be visually judged within the centrifuge tube. This also requires frequent starting and stopping of the centrifuge to remove each tube and observe the liquid volume, making the operation very cumbersome. ③ The filter membrane support component of commercial ultrafiltration tubes is a plastic grid with large grid gaps and low strength, resulting in a very low upper limit of centrifugal driving force and a slow ultrafiltration speed. ④ Both commercial ultrafiltration tubes and membranes are disposable, which is costly and environmentally unfriendly, and cannot balance batch processing efficiency with cost controllability. Summary of the Invention

[0003] The technical problem to be solved by the present invention is how to provide an ultrafiltration dialyzer, ultrafiltration device and filtration method in which only the filter membrane is a disposable and replaceable consumable, multiple ultrafiltration dialyzers can be operated flexibly in parallel, and the amount of filtrate can be easily observed.

[0004] To solve the above problems, the technical solution adopted by the present invention is as follows:

[0005] An ultrafiltration dialyzer, the key technology of which includes:

[0006] The filter cup has a cup body connector on one side;

[0007] A cover plate is detachably mounted on top of the filter cup;

[0008] A filter tube is disposed on the cover plate, with its bottom located inside the filter cup and a filter membrane detachably disposed thereon, and its top protruding from the cover plate and a nut connector assembly detachably disposed thereon. The filter tube is used to hold the solution to be filtered.

[0009] The cup body connector or the nut connector assembly is connected to the air pressure regulating mechanism through a pipeline, so that the air pressure above the solution to be filtered is greater than the air pressure inside the filter cup, thereby driving the solution to be filtered through the filter membrane.

[0010] In one embodiment of the present invention, a pressure nut is threadedly connected to the lower part of the filter tube, and a filter membrane support plate is provided between the pressure nut and the filter tube. The filter membrane support plate is used to support and fix the filter membrane. A filtrate passage is provided in the middle of the filter membrane support plate, and a through hole is provided in the middle of the pressure nut corresponding to the middle of the filter membrane support plate. Tightening the pressure nut will press and fix the filter membrane support plate and the filter membrane to the lower end of the filter tube.

[0011] Another ultrafiltration device based on the above-mentioned ultrafiltration dialyzer is provided, characterized in that it includes:

[0012] A rotating base is provided with a base connector, which is connected to an air pressure regulating mechanism;

[0013] Two sets of rotating tray assemblies are distributed vertically. Each rotating tray assembly includes a rotating column and a tray sleeved on the rotating column. The tray is used to accommodate several ultrafiltration dialyzers. The rotating column has a column cavity, which is connected to the ultrafiltration dialyzers through a tubing assembly. The lower rotating column is rotatably connected to the rotating base, and the two sets of rotating columns are rotatably connected. The column cavity of the lower rotating tray assembly is connected to the base connector, and the column cavities of the two sets of rotating tray assemblies are connected.

[0014] In one embodiment of the present invention, the rotating column is cylindrical, with an annular column base flange at its lower end and several threaded holes annularly opened at its top. Several column joints are evenly arranged around the circumference of the side wall in the middle of the rotating column. The column joints are connected to the column cavity and are connected to the cup joint of the ultrafiltration dialyzer or the nut joint assembly through the tracheal assembly.

[0015] In one embodiment of the present invention, the tray is generally disc-shaped, and a plurality of receiving grooves are evenly provided on its circumference, and the filter cup of the ultrafiltration dialyzer is fitted into the receiving groove.

[0016] A tray groove is centrally located on the lower end face of the tray, and a through hole is provided in the tray groove corresponding to the rotating column. The rotating column passes through the through hole, so that the column base flange is embedded in the tray groove, and then a bolt assembly is used to connect the tray to the column base flange.

[0017] As one embodiment of the present invention, it also includes two sets of slewing bearings, wherein the outer diameter contour of the slewing bearings corresponds to the contour of the edge of the tray groove;

[0018] A rotary support platform is provided on the rotary base, and the inner ring of the rotary bearing is fixedly connected to the rotary support platform by a through bolt assembly; the outer ring of the rotary bearing is connected to the tray of the rotary tray assembly below by a through bolt assembly.

[0019] The top of the rotating column of the rotary pallet assembly described below is provided with an end cap, which is fixedly connected to the inner ring of another rotary bearing by a through bolt assembly. The outer ring of the rotary bearing is connected to the pallet of the rotary pallet assembly described above by a through bolt assembly.

[0020] In one embodiment of the present invention, a core plate is provided at the bottom of the column cavity, and a column bottom connector communicating with the column cavity is provided on the core plate.

[0021] The base connector is connected to the column bottom connector of the rotary tray assembly below;

[0022] The end cap is provided with an end cap connector that communicates with the column cavity of the rotary tray assembly below, and the end cap connector is connected to the column bottom connector of the rotary tray assembly above.

[0023] Another filtration method based on the above-mentioned ultrafiltration device is proposed, the key technology of which is as follows:

[0024] S1. When the pore size of the filter membrane is ≥0.1μm, select the negative pressure driven filtration mode;

[0025] S2. Connect the cover plate and the filter tube, place a transparent container for receiving the solution into the filter cup, and then install the cover plate on the filter cup; connect and fix one end of the air tube assembly to the column connector on the rotary column, and close the air tube valves on each air tube assembly.

[0026] S3. Turn on the negative pressure vacuum pump connected to the base connector and adjust the air pressure in the two column chambers to between -0.1005 and -0.08 MPa.

[0027] S4. Open the nut connector assembly, use a pipette to add the solution to be filtered into the filter tube, so that the liquid level of the solution to be filtered is lower than the preset height, and then close the nut connector assembly.

[0028] S5. Connect the other end of the air tube assembly to the cup body connector, connect the air tube of the meter to the nut connector assembly, and open the air tube valve on each air tube assembly for filtration.

[0029] S6. Rotate the tray periodically to observe and record the filtration status inside the filter cup;

[0030] S7. After filtration is complete, close the tracheal valve on the tracheal assembly, disconnect the connection between the tracheal assembly and the cup body connector, disconnect the connection between the meter's tracheal tube and the nut connector assembly, remove the cover plate and filter tube, take out the transparent container, and suck out the concentrated liquid in the filter tube for storage.

[0031] In one embodiment of the present invention, the metering device includes a metering shaft and a metering tube wound around the metering shaft. The metering tube is provided with a metering scale and an indicating liquid section is provided inside the metering tube. When the liquid level in the filter tube decreases, the indicating liquid section moves to indicate the filtration process.

[0032] One end of the metering tube is unused, while the other end is equipped with an air inlet valve for connection to the nut connector assembly.

[0033] Another filtration method based on the above-mentioned ultrafiltration device is proposed. The key technology is as follows: S1. For samples with filter membrane pore size < 0.1 μm, select the positive pressure drive filtration mode, select a suitable filter membrane support sheet, and place the ultrafiltration device in a sterile environment.

[0034] S2. Connect the cover plate and the filter tube, place a transparent container for receiving the solution into the filter cup, and then install the cover plate on the filter cup; connect and fix one end of the air tube assembly to the column connector on the rotary column, and close the air tube valves on each air tube assembly.

[0035] S3. Turn on the air compressor connected to the base connector and adjust the air pressure in the two column chambers to between 0.2 and 0.6 MPa.

[0036] S4. Open the nut connector assembly, use a pipette to add the solution to be filtered into the filter tube, so that the liquid level of the solution to be filtered is lower than the preset height, and then close the nut connector assembly.

[0037] S5. Connect the other end of the air tube assembly to the nut connector assembly, leaving the cup body connector empty, and open the air tube valves on each air tube assembly for filtration.

[0038] S6. Rotate the tray periodically to observe and record the filtration status inside the filter cup;

[0039] S7. After filtration is complete, close the airway valve on the airway assembly, disconnect the airway assembly from the nut connector assembly, remove the cover plate and filter tube, and take out the transparent container.

[0040] The beneficial effects of adopting the above technical solution are as follows:

[0041] The ultrafiltration dialyzer of this invention supports ultrafiltration with a membrane pore size <0.1μm and also has filtration capabilities with a membrane pore size ≥0.1μm. It is highly adaptable, and the membrane support plate is detachable and replaceable, offering convenient assembly and disassembly and stable sealing. Except for the membrane, all other components of the ultrafiltration device are reusable, resulting in a significantly lower cost compared to disposable centrifugal ultrafiltration tubes. The membrane support structure of this invention—the membrane support plate—is a 300-mesh 304 stainless steel sand core filter plate. Its fine pore size and high strength allow it to support the membrane under high transmembrane pressure. In contrast, the membrane support in existing disposable centrifugal ultrafiltration tubes is a plastic grid, which has large pores, low strength, and limited transmembrane pressure.

[0042] The matching ultrafiltration unit adopts a dual-group rotating tray structure that can be independently rotated, enabling multi-station batch synchronous filtration. The integrated gas path design simplifies pipeline connection, and the tray can be rotated at any time to observe the filtration status of each station, greatly improving the ease of operation.

[0043] The accompanying dual-mode filtering method has the following effects:

[0044] 1. For solution samples containing volatile solutes or solvents, selecting the positive pressure mode can prevent the solute or solvent from evaporating and being lost due to accelerated evaporation or the solvent from boiling over under negative pressure.

[0045] 2. For samples requiring sterilization filtration, select positive pressure mode. In this mode, the non-clean gas inside the air compressor is introduced into the filter tube through the gas tubing assembly and the nut connector assembly at the top of the filter tube, only contacting the liquid on the membrane to be sterilized inside the filter tube. This avoids contact between the vacuum pump pipeline gas and the sterile liquid in the sterile filter cup in negative pressure mode.

[0046] 3. For filtration operations with a membrane pore size <0.1μm, select positive pressure mode. The upper limit of the driving pressure is determined by the pressure resistance of the pipeline and the air supply pressure of the air compressor. The driving pressure is significantly higher than that of negative pressure mode, and the ultrafiltration speed is faster.

[0047] For filtration operations with a membrane pore size ≥ 0.1 μm, select negative pressure mode. Due to the large membrane pore size and fast filtration speed, only a lower driving pressure is needed. The pressure adjustment range of negative pressure mode is more suitable. On the contrary, excessive driving pressure in positive pressure mode can easily cause the solution to be filtered to dry out quickly, resulting in dry membrane phenomenon.

[0048] 4. For trace amounts of liquid requiring precise measurement of the filtration concentration or dialysis ratio, the negative pressure mode can be selected. In this mode, the volume of the filtered liquid can be visually observed through the transparent filter cup at the scale inside the receiving cup, or a measuring shaft can be connected at the nut connector. Depending on the sample volume and required accuracy, coils of different lengths and inner diameters can be selected to achieve high-resolution indication of the filtered liquid volume.

[0049] 5. The multi-channel ultrafiltration device allows for flexible selection of the number of samples to be filtered and the sample volume per tube, eliminating the need to consider balancing issues during centrifugal filtration. The multi-channel ultrafiltration device, with its acrylic filter cup and rotating mechanism, allows for observation of the filtrate volume in each tube and calculation of the concentration factor without shutting down the centrifuge, avoiding the need for frequent start-stop cycles during centrifugal filtration. Each channel of the ultrafiltration device has an independent throttling valve, allowing for individual control of pressure release for any sample tube when replenishment or filtration is completed, without affecting the continuous filtration of other samples. This avoids the need to start and stop the centrifuge for all samples during centrifugal filtration when observing the filtrate volume, replenishing filtrate, or completing filtration in any single tube. Attached Figure Description

[0050] Figure 1 This is a schematic diagram of the internal structure of the ultrafiltration dialyzer in an embodiment.

[0051] Figure 2 This is a cross-sectional structural diagram of the ultrafiltration dialyzer in the embodiment.

[0052] Figure 3 This is a structural schematic diagram of the components of the ultrafiltration dialyzer in the embodiment from a bottom view.

[0053] Figure 4 This is a structural schematic diagram of the components of the ultrafiltration dialyzer in the embodiment from a top view.

[0054] Figure 5 This is a front view structural schematic diagram of the ultrafiltration device in the embodiment.

[0055] Figure 6 This is a structural schematic diagram of the ultrafiltration device in the embodiment from a lower view.

[0056] Figure 7 This is a structural schematic diagram from above, showing the two sets of rotary tray assemblies after separation in an embodiment.

[0057] Figure 8 This is a structural schematic diagram from below after the two sets of rotary tray assemblies in the embodiment have been separated.

[0058] Figure 9 The diagram below shows a cross-sectional view of the rotating tray assembly and rotating base after separation, as described in the embodiment.

[0059] Figure 10 This is a schematic diagram of the meter in the embodiment.

[0060] Among them: 100 ultrafiltration dialyzers;

[0061] 1. Filter cup; 1-1. Connector mounting hole; 1-2. Filter cup flange;

[0062] 2. Filter tube; 2-1 Lower threaded section; 2-2 Filter tube flange; 2-3 Upper threaded section; 2-4 Bottom of the tube; 2-5 Filtrate hole;

[0063] 3. Filter membrane support plate; 4. Tableting nut; 5. Mounting nut; 6. Nut connector assembly; 6-1 Nut connector;

[0064] 7. Cover plate; 8. Cup body connector; 9. Filter membrane;

[0065] 200 Tray; 201 Receiving slot; 202 Tray recess;

[0066] 300 Rotary base; 301 Base connector; 302 Piping channel; 303 Rotary support platform;

[0067] 400 Rotary column; 401 Column connector; 402 Column base flange; 403 Core plate; 404 Column base connector;

[0068] 500 tracheal assembly;

[0069] 600 Measuring instrument; 601 Measuring shaft; 602 Measuring tube; 603 Measuring scale; 604 Inlet valve;

[0070] 700 Pressure gauge; 800 End cap; 801 End cap connector; 900 Slewing bearing; 1000 Transition flange; 1001 Transition groove. Detailed Implementation

[0071] To make the objectives, technical solutions, and advantages of the present invention clearer, the invention will be described clearly and completely below in conjunction with specific embodiments.

[0072] like Figures 1 to 4 The ultrafiltration dialyzer 100 shown includes a filter cup 1 made of transparent material, a cover plate 7, and a filter tube 2.

[0073] The filter cup 1 can be made of glass or acrylic. A ring-shaped filter cup flange 1-2 is located at the top of the filter cup 1, and a through hole is provided on the filter cup flange 1-2. The cover plate 7 is generally circular, and its edge has a cover plate through hole corresponding to the through hole of the filter cup flange 1-2. Bolts can be used to connect and fix the two together. A connector mounting hole 1-1 is provided in the middle of one side of the filter cup, and a cup body connector 8 is installed on the connector mounting hole 1-1.

[0074] The filter tube 2 is mounted on the cover plate 7, with its bottom located inside the filter cup 1 and detachably mounted with a filter membrane support plate 3. The top of the filter tube 2 protrudes from the cover plate 7 and is detachably mounted with a nut connector assembly 6. The filter tube 2 is used to hold the solution to be filtered.

[0075] The cover plate 7 has a filter tube through hole in the middle for the filter tube 2 to pass through. A polygonal filter tube flange 2-2 is provided in the middle of the filter tube 2 corresponding to the filter tube through hole. The outer dimensions of the filter tube flange 2-2 are larger than the outline dimensions of the filter tube through hole.

[0076] The filter tube 2 has an upper threaded section 2-3 located above the filter tube flange 2-2. The upper threaded section 2-3 can be used to rotate and fit the mounting nut 5. After the mounting nut 5 is rotated into place, it can be clamped and fixed to the cover plate 7 in conjunction with the filter tube flange 2-2. The lower end of the filter tube 2 has a lower threaded section 2-1, and the pressure nut 4 is rotatably connected to the lower threaded section 2-1.

[0077] A sealing gasket is installed between the filter tube flange 2-2 and the filter tube through hole, and a sealing gasket is installed between the cover plate 7 and the filter cup flange 1-2 to ensure airtightness.

[0078] The nut connector assembly 6 includes a nut and a nut connector 6-1 disposed on the nut. The top of the upper threaded section 2-3 is threadedly connected to the nut, thereby enabling the installation and fixation of the nut connector assembly 6 and the filter tube 2. A sealing ring is provided between the top of the upper threaded section 2-3 and the inside of the nut to increase airtightness.

[0079] The cup body connector 8 or the nut connector assembly 6 is connected to the air pressure regulating mechanism via a pipeline, so that the air pressure above the solution to be filtered is greater than the air pressure inside the filter cup 1, thereby driving the solution to be filtered through the filter membrane 9 and the filter membrane support sheet 3. In this embodiment, both the cup body connector 8 and the nut connector 6-1 are quick-connect couplings, which can be used to quickly insert the air guiding hose. In this embodiment, in positive pressure mode, the air pressure regulating mechanism can be an air compressor to provide gas at a pressure higher than standard atmospheric pressure; in negative pressure mode, the air pressure regulating mechanism can be a vacuum pump to provide gas at a pressure lower than standard atmospheric pressure.

[0080] See Figure 2 The lower end of the filter tube 2 is provided with a tube bottom 2-4. The tube bottom 2-4 is provided with a tube bottom hole corresponding to the filter part of the filter membrane support plate 3. The inner side of the tube bottom hole is truncated cone-shaped, and its diameter gradually decreases along the direction close to the filter membrane support plate 3 so as to guide the solution to be filtered to the filter part for filtration. At the same time, the reduced diameter structure ensures that the liquid film will not be too thin and dry when there is only a small amount of liquid at the bottom of the tube.

[0081] See Figure 2 and Figure 3 The filter membrane support plate 3 is in the shape of a circular plate, which includes a solid ring in the shape of an annulus on the edge and a sieve-shaped sand core in the center of the solid ring. The position of the sand core is the filtrate passage part. In this embodiment, the pore size of the sand core can be selected as 300 mesh 316 stainless steel sand core, which is used to support filter membranes of various pore sizes.

[0082] like Figures 5 to 10 The ultrafiltration device shown includes a rotary base 300 and two sets of rotary tray assemblies distributed vertically.

[0083] A base connector 301 is provided on the rotating base 300, and the base connector 301 is connected to the air pressure regulating mechanism.

[0084] The rotary tray assembly includes a rotary column 400 and a tray 200 sleeved on the rotary column 400. The tray 200 is used to accommodate eight sets of ultrafiltration dialyzers. The rotary column 400 has a column cavity, which is connected to the ultrafiltration dialyzers via a tubing assembly 500. The lower rotary column 400 is rotatably connected to the rotary base 300, and the upper and lower sets of rotary columns 400 are rotatably connected. The column cavity of the lower rotary tray assembly communicates with the base connector 301, and the column cavities of the two sets of rotary tray assemblies are also connected. In this embodiment, the base connector 301 penetrates the rotary base 300, and its lower end is located between the rotary base 300 and the worktable, and is connected to a flexible tubing. The rotary base 300 has a through-channel 302 for the flexible tubing to pass through and connect to a pressure regulating mechanism.

[0085] The rotating column 400 is cylindrical, with an annular column base flange 402 at its lower end and several threaded holes annularly opened at its top. Several column joints 401 are evenly arranged around the circumference of the side wall in the middle of the rotating column 400. The column joints 401 are connected to the column cavity. The column joints 401 are connected to the cup joint 8 of the ultrafiltration dialyzer or the nut joint assembly 6 through the tracheal assembly 500.

[0086] The tray 200 is generally disc-shaped, with several accommodating grooves 201 evenly distributed around its circumference. The filter cup 1 of the ultrafiltration dialyzer is fitted into the accommodating groove 201.

[0087] A tray groove 202 is centrally located on the lower end surface of the tray 200. A through-hole is provided in the tray groove 202 corresponding to the rotating column 400. The rotating column 400 passes through the through-hole, so that the column base flange 402 is embedded in the tray groove 202. Then, a bolt assembly is used to connect the tray 200 and the column base flange 402.

[0088] See Figure 7 and Figure 8In this embodiment, the rotary connection is achieved by two sets of slewing bearings 900. Specifically, the outer diameter contour of the slewing bearing 900 corresponds to the edge contour of the tray groove 202, so that the slewing bearing 900 is embedded in the tray groove 202, but protrudes from the lower end face of the tray 200, so as to be aligned with the transition flange 1000.

[0089] A rotary support platform 303 is provided on the rotary base 300. The inner ring of a set of rotary bearings 900 is fixedly connected to the rotary support platform 303 by a bolt assembly. A transition flange 1000 is provided above the outer ring of the rotary bearing 900. A transition groove 1001 is formed in the middle of the transition flange 1000 corresponding to the inner ring of the rotary bearing 900. The inner ring of the rotary bearing 900 is fixedly connected to the rotary support platform 303 by bolts. The bolt nuts are accommodated in the transition groove 1001. Bolt through holes are formed on the transition flange 1000 corresponding to the through holes on the outer ring of the rotary bearing 900. See [reference needed]. Figure 9 The bolt holes on the transition flange 1000, the through holes on the outer ring of the slewing bearing 900, the through holes on the column base flange 402, and the through holes on the tray groove 202 are fixed by bolt assemblies.

[0090] The diameter of the slewing support platform 303 corresponds to the inner ring diameter of the slewing bearing 900, so that the outer ring of the slewing bearing 900 is suspended, which facilitates the installation of nuts and bolts under the outer ring of the slewing bearing 900.

[0091] The rotary pallet assembly described below has an end cap 800 on top of its rotary column 400. In this embodiment, the column cavity of the lower rotary column 400 is sealed into a closed cavity by the end cap 800, and a sealing ring is provided between the end cap 800 and the rotary column 400. The top of the upper rotary column 400 is also connected to an end cap 800, and a pressure gauge 700 is installed on this end cap 800. While sealing the column cavity of the upper rotary column 400, the pressure inside the column cavity can also be measured.

[0092] The end cap 800 at the top of the lower slewing column 400 is fixedly connected to the inner ring of the other slewing bearing 900 by a bolt assembly. A transition flange 1000 is also provided above the outer ring of the slewing bearing 900. The transition flange 1000 is used to connect the slewing bearing 900, the column flange and the tray, while making way for the nuts on the middle end cap 800.

[0093] See Figure 9In this embodiment, the top of the rotary column 400 is provided with several threaded holes in a ring shape. After the through hole on the inner ring of the rotary bearing 900 is aligned with the through hole on the end cover 800, bolts are passed through and tightened to connect it to the threaded hole on the top of the rotary column 400, thereby installing and fixing the rotary bearing 900 on the top of the rotary column 400. Then, the upper column base flange 402, tray 200, transition flange 1000 and the outer ring of the rotary bearing 900 are fixedly connected together by a bolt assembly, realizing the rotational connection of the upper and lower sets of rotary tray assemblies, so that the upper tray 200 and the lower tray 200 can rotate independently, which is convenient for observing and adjusting the filtration process.

[0094] See Figure 9 The bottom of the column cavity is provided with a core plate 403, and the core plate 403 is provided with a column bottom connector 404 that communicates with the column cavity. The base connector 301 is connected to the column bottom connector 404 of the lower rotary tray assembly. The end cap 800 is provided with an end cap connector 801 that communicates with the column cavity of the lower rotary tray assembly, and the end cap connector 801 is connected to the column bottom connector 404 of the upper rotary tray assembly.

[0095] Existing centrifugal ultrafiltration methods are limited by the standard volume of centrifuge rotors. Ultrafiltration tubes are designed as standard centrifuge tubes (commercially available in 1.5ml, 15ml, and 50ml sizes) with an embedded filter membrane. The maximum single-tube capacity for ultrafiltration is 15ml, and the maximum single-tube filtrate capacity is approximately 20ml (for common angle rotor centrifuges). This filtration process requires frequent replenishment and filtrate disposal. In this embodiment, the ultrafiltration device uses a 50ml filter tube, which can be entirely used to hold the liquid to be filtered. A transparent container (such as a measuring cup) with a volume greater than 100ml can be used to hold the filtrate, avoiding frequent replenishment and filtrate disposal. This invention's 50ml filter tube fills the equipment selection gap for liquid filtration in the 15-50ml range.

[0096] The filtration methods of ultrafiltration devices under two modes are described below:

[0097] For filtration operations requiring precise metering and / or a membrane pore size ≥ 0.1 μm, select the negative pressure driven filtration mode, and follow these steps:

[0098] S1. Based on the actual filtration speed of the test sample, preset the air pressure parameters of the negative pressure vacuum pump equipment and select a suitable filter membrane 9;

[0099] S2. Connect the cover plate 7 and the filter tube 2, place a transparent container for receiving the solution into the filter cup 1, and then install the cover plate 7 on the filter cup 1; connect and fix one end of the air tube assembly 500 to the column connector 401 on the rotary column 400, and close the air tube valves on each air tube assembly 500.

[0100] S3. Turn on the negative pressure vacuum pump to bring the air pressure inside the column cavity between -0.1005 and -0.08 MPa.

[0101] S4. Open the nut connector assembly 6, and use a pipette to add the solution to be filtered into the filter tube 2, so that the liquid level of the solution to be filtered is more than 1 cm below the opening of the filter tube 2, and then close the nut connector assembly 6.

[0102] S5. Connect the other end of the air tube assembly 500 to the cup body connector 8, connect the air tube of the meter 600 to the nut connector assembly 6, and open the air tube valve on each air tube assembly 500 for filtration.

[0103] S6. Rotate tray 200 periodically and observe and record the amount of filtrate in filter cup 1 and the indication scale of meter 600;

[0104] S7. After filtration is complete, close the air valve on the air tube assembly 500, disconnect the connection between the air tube assembly 500 and the cup body connector 8, disconnect the air tube of the meter 600 from the nut connector assembly 6, remove the cover plate 7 and the filter tube 2, take out the transparent container, and suck out the concentrated liquid in the filter tube for storage.

[0105] The negative pressure vacuum pump equipment can be the CDP408C model from Beijing Weike Saide Instrument Co., Ltd.

[0106] The transparent container can be a graduated test tube, the shape of which matches the shape of the bottom of the cavity inside the filter cup 1; it can also be a graduated disposable plastic cup; or a measuring cup. The height of the top of the transparent container is lower than the position of the cup body connector 8.

[0107] The endotracheal valve is a solenoid valve. The tray 200 is equipped with a control module and a power supply module for the solenoid valve. According to the settings, the endotracheal valve of the lower endotracheal assembly 500 is closed periodically to reduce the pressure fluctuation range within the upper ultrafiltration dialyzer. A pressure gauge is also installed on the endotracheal assembly 500 to monitor the pressure in each filter cup. A filter element structure is connected to the rear of the endotracheal valve on the endotracheal assembly 500 to filter large particulate impurities such as dust in the gas delivered by the air compressor in positive pressure mode. Preferably, the endotracheal valve is a three-way solenoid valve, which includes a first port connected to the column connector 401, a second port connected to the nut connector 6-1 or the cup body connector 8, and a third port left empty. When a sample finishes filtration or needs to be opened for replenishment, the three-way solenoid valve closes the first port, connecting the second and third ports, isolating the ultrafiltration dialyzer 100 from the pressure regulating mechanism and depressurizing the filter tube 2. When filtration is restored, the first and second ports of the three-way solenoid valve are connected, the third port is closed, the air pressure regulating mechanism is connected to the filter tube 2, and the external atmospheric environment is isolated.

[0108] See Figure 10 The metering device 600 includes a metering shaft 601 and a metering tube 602 wound around the metering shaft 601. The metering tube 602 has metering graduations 603 and an indicating liquid section inside. When the liquid level in the filter tube 2 decreases, the indicating liquid section moves, thus indicating the filtration process. (See also...) Figure 10 In this embodiment, the metering shaft 601 has two flange structures at both ends. The flange structures have arc-shaped inclined through holes to guide the metering tube 602 outwards, preventing bending of the metering tube 602, which would increase the resistance to movement of the indicating liquid section inside the metering tube 602 and thus affect metering accuracy. In this embodiment, one end of the metering tube 602 is equipped with an air inlet valve 604 for connection to the nut connector 6-1, while the other end is unused. This air inlet valve 604 needs to be closed before disassembling and installing the metering device 600 to prevent the indicating liquid section from leaking out of the pipe under gravity.

[0109] In negative pressure mode, the criteria for judging whether filtration is complete can be referenced in the following case:

[0110] Take 50 mL of the sample solution to be filtered. Select a filter membrane with a pore size of 0.22 μm. Add 50 mL of the sample solution to be filtered into filter tube 2. Make the pressure in filter cup 1 1500 Pa for filtration. As the filtration process proceeds, the indicator liquid segment moves. When the indicator liquid segment moves to a position 45 mL away from the initial position, there is 5 mL of solution remaining in filter tube 2. At this time, it is equivalent to completing a 10-fold concentration.

[0111] For filtration operations where the solution to be filtered is volatile and / or the pore size of the filter membrane is <0.1μm, select the positive pressure driven filtration mode, and the steps are as follows:

[0112] S1. Based on the actual filtration speed of the test sample, preset the air pressure parameters of the air compressor equipment, select the appropriate filter membrane 9, and sterilize the filter cup 1, pressing nut 4, filter membrane support plate 3, and filter membrane 9 with high pressure steam in advance. Then place the ultrafiltration device in the clean bench.

[0113] S2. Connect the cover plate 7 and the filter tube 2, place a sterile transparent container for receiving the solution into the filter cup 1, and then install the cover plate 7 on the filter cup 1; connect and fix one end of the tracheal assembly 500 to the column connector 401 on the rotary column 400, and close the tracheal valves on each tracheal assembly 500.

[0114] S3. Turn on the air compressor. The air pressure in the two column chambers should be between 0.2 and 0.6 MPa (gauge pressure).

[0115] S4. Open the nut connector assembly 6, and use a pipette to add the solution to be filtered into the filter tube 2, so that the liquid level of the solution to be filtered is more than 1 cm below the opening of the filter tube 2, and then close the nut connector assembly 6.

[0116] S5. Connect the other end of the air tube assembly 500 to the nut connector assembly 6, leave the cup body connector 8 empty, and open the air tube valves on each air tube assembly 500 for filtration.

[0117] S6. Rotate the tray 200° periodically and observe and record the filtration status inside the filter cup 1;

[0118] S7. After filtration is complete, close the air valve on the air tube assembly 500, disconnect the air tube assembly 500 from the nut connector assembly 6, remove the cover plate 7 and the filter tube 2, take out the transparent container, and suck out the concentrated liquid in the filter tube for storage.

[0119] The air compressor equipment can be the Q1E-FF-1200W-30L model from Jiangsu Dongcheng Electric Tools Co., Ltd.

[0120] For ordinary filtration processes with filter membrane pore sizes ≥0.01μm and <0.1μm, a positive pressure mode is adopted, with an operating pressure of 0.2 to 0.4MPa.

[0121] For ordinary filtration processes with filter membrane pore sizes ≥0.001μm and <0.01μm, a positive pressure mode is adopted with an operating pressure of 0.4 to 0.6MPa, preferably 0.6MPa.

[0122] In addition, it is not recommended to use the equipment in this embodiment for filtration processes with filter membrane pore sizes <0.001μm.

[0123] In positive pressure mode, the criteria for judging whether filtration is complete can be referenced from the following ultrafiltration experiment case:

[0124] If 50 mL of sample is to be ultrafiltered, and the filter membrane has a pore size of 0.004 μm, then 50 mL of the sample is added to filter tube 2. A positive pressure of 0.6 MPa is applied to filter tube 2 for filtration. When 5 mL of the liquid to be filtered remains in filter tube 2, the 10-fold concentration is complete. At this point, the transparent container below the filter tube, used to collect the filtrate, receives a total of 45 mL of solution. Since the amount of liquid remaining in filter tube 2 is difficult to observe during positive pressure filtration, and the transparent container for collecting the filtrate is graduated and the amount of filtrate can be observed through the acrylic filter cup 1 and the transparent container, in practical work, the concentration factor can be calculated using the difference method by measuring the amount of liquid received in the transparent container.

[0125] During sterile filtration, a positive pressure driven filtration mode is adopted. The filter membrane pore size is selected as the general standard pore size of sterile filtration, 0.22μm. The working pressure is gauge pressure of 0.3MPa. The concentrated liquid after filtration is collected by a transparent container through filter membrane 9. After filtration is completed, the transparent container is removed and the sterile filtrate in the container is aspirated and stored.

Claims

1. An ultrafiltration dialyzer, characterized in that, It includes: The filter cup (1) has a cup body connector (8) on one side. The cover plate (7) is in the shape of a circular plate, and its edge is provided with a cover plate through hole; the top of the filter cup (1) is provided with an annular filter cup flange (1-2), and the filter cup flange (1-2) is provided with a through hole. The through hole of the filter cup flange (1-2) corresponds to the through hole of the cover plate, and a bolt assembly can be inserted to detachably install the cover plate (7) on the top of the filter cup (1); A filter tube (2) is set on the cover plate (7). Its bottom is located inside the filter cup (1) and a filter membrane (9) is detachably provided. Its top protrudes from the cover plate (7) and a nut connector assembly (6) is detachably provided. The filter tube (2) is used to hold the solution to be filtered. A filter tube through hole is opened in the middle of the cover plate (7). A polygonal filter tube flange (2-2) is set in the middle of the filter tube (2) corresponding to the filter tube through hole. An upper threaded section (2-3) is set on the upper part of the filter tube flange (2-2). The upper threaded section (2-3) can be used to rotate and fit the mounting nut (5). After the mounting nut (5) is rotated into place, it can be clamped and fixed on the cover plate (7) in conjunction with the filter tube flange (2-2). A pressure nut (4) is threadedly connected to the lower part of the filter tube (2). A filter membrane support plate (3) is set between the pressure nut (4) and the filter tube (2). The filter membrane support plate (3) is used to support and fix the filter membrane (9). The cup body connector (8) or the nut connector assembly (6) is connected to the air pressure regulating mechanism through a pipeline, so that the air pressure above the solution to be filtered is greater than the air pressure inside the filter cup (1), thereby driving the solution to be filtered through the filter membrane (9).

2. The ultrafiltration dialyzer according to claim 1, characterized in that, The filter membrane support plate (3) has a filtrate passage in the middle. The middle of the pressing nut (4) has a through hole corresponding to the middle of the filter membrane support plate (3). Tighten the pressing nut (4) to press and fix the filter membrane support plate (3) and the filter membrane (9) to the lower end of the filter tube (2).

3. An ultrafiltration device comprising the ultrafiltration dialyzer of claim 1, characterized in that, It includes: A rotating base (300) is provided with a base connector (301), which is connected to an air pressure regulating mechanism; Two sets of rotating tray assemblies are distributed vertically. Each rotating tray assembly includes a rotating column (400) and a tray (200) sleeved on the rotating column (400). The tray (200) is used to accommodate several ultrafiltration dialyzers. A column cavity is provided inside the rotating column (400). The column cavity is connected to the ultrafiltration dialyzer through a tubing assembly (500). The lower rotating column (400) is rotatably connected to the rotating base (300). The two sets of rotating columns (400) are rotatably connected. The column cavity of the lower rotating tray assembly is connected to the base connector (301). The column cavities of the two sets of rotating tray assemblies are connected.

4. The ultrafiltration device according to claim 3, characterized in that, The rotating column (400) is cylindrical, with an annular column bottom flange (402) at its lower end and several threaded holes in an annular shape at its top. Several column joints (401) are evenly arranged on the circumference of the side wall in the middle of the rotating column (400). The column joints (401) are connected to the column cavity. The column joints (401) are connected to the cup joint (8) of the ultrafiltration dialyzer or the nut joint assembly (6) through the tracheal assembly (500).

5. The ultrafiltration device according to claim 4, characterized in that, The tray (200) is generally disc-shaped, with several accommodating grooves (201) evenly distributed around its circumference. The filter cup (1) of the ultrafiltration dialyzer is fitted into the accommodating groove (201). The tray (200) has a tray groove (202) centered on its lower end surface. The tray groove (202) has a through-hole corresponding to the rotating column (400). The rotating column (400) passes through the through-hole, so that the column base flange (402) is embedded in the tray groove (202). Then, a bolt assembly is used to connect the tray (200) and the column base flange (402).

6. The ultrafiltration device according to claim 5, characterized in that, It also includes two sets of slewing bearings (900), the outer diameter of which corresponds to the outline of the edge of the tray groove (202); A rotary support platform (303) is provided on the rotary base (300), and the inner ring of the rotary bearing (900) is fixedly connected to the rotary support platform (303) by a through bolt assembly; the outer ring of the rotary bearing (900) is connected to the tray (200) of the rotary tray assembly below by a through bolt assembly. The top of the rotating column (400) of the lower rotating pallet assembly is provided with an end cap (800), which is fixedly connected to the inner ring of another rotating bearing (900) by a through bolt assembly. The outer ring of the rotating bearing (900) is connected to the pallet (200) of the upper rotating pallet assembly by a through bolt assembly.

7. An ultrafiltration device according to claim 6, characterized in that, The bottom of the column cavity is provided with a core plate (403), and the core plate (403) is provided with a column bottom connector (404) that communicates with the column cavity. The base connector (301) is connected to the column base connector (404) of the rotary tray assembly below; The end cap (800) is provided with an end cap connector (801) that communicates with the column cavity of the rotary tray assembly below, and the end cap connector (801) is connected to the column bottom connector (404) of the rotary tray assembly above.

8. A filtration method based on the ultrafiltration device according to any one of claims 3-7, characterized in that, The steps are as follows: S1. When the pore size of the filter membrane (9) is ≥0.1μm, select the negative pressure driven filtration mode; S2. Connect the cover plate (7) and the filter tube (2), place a transparent container for receiving the filtrate in the filter cup (1), and then install the cover plate (7) on the filter cup (1); connect and fix one end of the air tube assembly (500) to the column connector (401) on the rotary column (400), and close the air tube valves on each air tube assembly (500); S3. Turn on the negative pressure vacuum pump connected to the base connector (301) and adjust the air pressure in the two column chambers to between -0.1005 and -0.08 MPa. S4. Open the nut connector assembly (6), use a pipette to add the solution to be filtered into the filter tube (2) so that the liquid level of the solution to be filtered is lower than the preset height, and then close the nut connector assembly (6). S5. Connect the other end of the air tube assembly (500) to the cup body connector (8), connect the air tube of the meter (600) to the nut connector assembly (6), and open the air tube valve on each air tube assembly (500) for filtration. S6. Rotate the tray (200) periodically and observe and record the filtration status inside the filter cup (1); S7. After filtration is completed, close the tracheal valve on the tracheal assembly (500), disconnect the connection between the tracheal assembly (500) and the cup connector (8), disconnect the tracheal tube of the meter (600) from the nut connector assembly (6), remove the cover plate (7) and the filter tube (2), take out the transparent container, and suck out the concentrated liquid in the filter tube for storage.

9. The filtration method according to claim 8, characterized in that, The meter (600) includes a metering shaft (601) and a metering tube (602) wound around the metering shaft (601). The metering tube (602) is provided with a metering scale (603). An indicator liquid section is provided inside the metering tube (602). When the liquid level in the filter tube (2) drops, the indicator liquid section moves to indicate the filtration process. One end of the metering tube (602) is unused, and the other end is provided with an air inlet valve (604) for connection with the nut connector assembly (6).

10. A filtration method based on the ultrafiltration device according to any one of claims 3-7, characterized in that, The steps are as follows: S1. For the sample filtration requirements of filter membrane (9) with pore size < 0.1 μm, select the positive pressure driven filtration mode, select the appropriate filter membrane support sheet (3), and place the ultrafiltration device in a sterile environment. S2. Connect the cover plate (7) and the filter tube (2), place a transparent container for receiving the solution into the filter cup (1), and then install the cover plate (7) on the filter cup (1); connect and fix one end of the air tube assembly (500) to the column connector (401) on the rotary column (400), and close the air tube valves on each air tube assembly (500); S3. Turn on the air compressor connected to the base connector (301) and adjust the air pressure in the two column cavities to between 0.2 and 0.6 MPa. S4. Open the nut connector assembly (6), use a pipette to add the solution to be filtered into the filter tube (2) so that the liquid level of the solution to be filtered is lower than the preset height, and then close the nut connector assembly (6). S5. Connect the other end of the air tube assembly (500) to the nut connector assembly (6), leave the cup body connector (8) empty, and open the air tube valve on each air tube assembly (500) for filtration. S6. Rotate the tray (200) periodically and observe and record the filtration status inside the filter cup (1); S7. After filtration is complete, close the air valve on the air tube assembly (500), disconnect the air tube assembly (500) from the nut connector assembly (6), remove the cover plate (7) and filter tube (2), and take out the transparent container.

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