CN115845612A - Tangential flow filtration circumferential system and control method - Google Patents
Tangential flow filtration circumferential system and control method Download PDFInfo
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- CN115845612A CN115845612A CN202211570839.XA CN202211570839A CN115845612A CN 115845612 A CN115845612 A CN 115845612A CN 202211570839 A CN202211570839 A CN 202211570839A CN 115845612 A CN115845612 A CN 115845612A
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- 238000009295 crossflow filtration Methods 0.000 title claims abstract description 235
- 238000000034 method Methods 0.000 title claims abstract description 40
- 239000007788 liquid Substances 0.000 claims abstract description 191
- 239000012528 membrane Substances 0.000 claims abstract description 90
- 102000004169 proteins and genes Human genes 0.000 claims description 100
- 108090000623 proteins and genes Proteins 0.000 claims description 100
- 239000002699 waste material Substances 0.000 claims description 86
- 238000003306 harvesting Methods 0.000 claims description 57
- 238000001514 detection method Methods 0.000 claims description 36
- 239000012530 fluid Substances 0.000 claims description 15
- 238000004891 communication Methods 0.000 claims description 4
- 238000001914 filtration Methods 0.000 abstract description 22
- 239000000523 sample Substances 0.000 description 53
- 238000000746 purification Methods 0.000 description 18
- 230000002572 peristaltic effect Effects 0.000 description 9
- 238000005516 engineering process Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000010612 desalination reaction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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Abstract
The invention discloses a tangential flow filtration circumferential system and a control method, wherein the tangential flow filtration circumferential system comprises a tangential flow filtration assembly, a first tank body, a second tank body and a control device; the first tank body is used for storing sample liquid to be processed, the first tank body is communicated with the inlet end of the tangential flow filtration assembly through a first pipeline, and the outlet end of the tangential flow filtration assembly is communicated with the first tank body through a second pipeline; the second tank body is communicated with the outlet end of the tangential flow filtering component through a third pipeline; wherein the tangential flow filtration module comprises a tangential flow filtration membrane package and the control means is capable of opening or closing the tangential flow filtration membrane package. The invention can be widely applied to the technical field of biological engineering.
Description
Technical Field
The invention relates to the technical field of bioengineering, in particular to a tangential flow filtration circumferential system and a control method.
Background
The tangential flow filtration technology is mainly applied to concentration, washing filtration (desalination and buffer solution replacement), biological engineering for separating biomolecules by using sizes, and the like, and can also be used for removing and clarifying cells and cell debris in fermentation liquor or cell culture solution.
The tangential flow filtration technology is different from the conventional direct flow filtration technology, in the tangential flow filtration technology, liquid tangentially flows through the surface of a filter membrane, transmembrane pressure difference generated by the liquid presses part of solution against the filter membrane, and harvest liquid and waste liquid are obtained. Liquid continuously flows through the surface of the membrane at a certain speed in the whole process, and the surface of the filter membrane is washed while filtering, so that a gel layer is not easily formed on the surface of the membrane, thereby preventing particles in the sample liquid from blocking the filter membrane and keeping stable filtering speed.
The tangential flow filtration circumferential system comprises a tangential flow filtration component, a first tank body and a second tank body, wherein the part of the sample liquid in the first tank, which contains the target protein after being filtered by the filtration component, returns to the first tank body, the other part of the sample liquid enters the second tank body, or the part of the sample liquid, which contains the target protein after being filtered, enters the second tank body, and the other part of the sample liquid returns to the first tank body. The tangential flow filtration loop system can be set to re-filter the liquid returning to the first tank, generally referred to as a filtration cycle ending with a filtration cycle.
Currently, in the filtration of recombinant proteins, the purification of the sample liquid may be affected because the tangential flow filtration membrane package is not matched with the sample volume and the molecular weight of the target protein. In addition, the concentration of the target protein in the harvest obtained by the conventional filtration system may not meet the standard, or the waste liquid may have residual target protein, which may affect the purification effect of the sample liquid.
Disclosure of Invention
In order to solve at least one of the above technical problems, the present invention provides a tangential flow filtration loop system and a control method thereof, and adopts the following technical solutions.
The tangential flow filtration ring system provided by the invention comprises a tangential flow filtration component, a first tank body, a second tank body and a control device; the first tank body is used for storing sample liquid to be processed, the first tank body is communicated with the inlet end of the tangential flow filtering component through a first pipeline, and the outlet end of the tangential flow filtering component is communicated with the first tank body through a second pipeline; the second tank body is communicated with the outlet end of the tangential flow filtration assembly through a third pipeline; wherein the tangential flow filtration module comprises a tangential flow filtration membrane package, and the control means is capable of opening or closing the tangential flow filtration membrane package.
In some embodiments of the present invention, the tangential flow filtration module comprises at least two tangential flow filtration membranes of different specifications, each tangential flow filtration membrane is connected in parallel, and the control device opens the corresponding tangential flow filtration membrane according to the sample liquid volume and the target protein molecular weight.
In some embodiments of the invention, the tangential flow filtration loop system comprises a first meter connected to the first tank and a first flow meter connected to the second pipe.
In some embodiments of the invention, the tangential flow filtration circulating system comprises a third tank, a fourth pipeline and a second detector, the second detector is connected with the third pipeline, the fourth pipeline is respectively connected with the third pipeline and the third tank, and the fourth pipeline is connected with the third pipeline through a valve body.
In some embodiments of the invention, the tangential flow filtration ring system comprises a fifth pipeline, the fifth pipeline is respectively connected with the third tank body and the first pipeline, and the fifth pipeline is connected with the first pipeline through a valve body.
In certain embodiments of the present invention, the tangential flow filtration loop system comprises a third detector connected to the third tank.
In certain embodiments of the invention, the tangential flow filtration loop system comprises a second flow meter connected to the fourth line.
In some embodiments of the present invention, the tangential flow filtration loop system includes a first detection meter, a first flow meter and a sixth pipeline, the first detection meter is connected to the second tank, the first flow meter is connected to the third pipeline, the sixth pipeline is respectively connected to the second tank and the first pipeline, and the sixth pipeline is connected to the first pipeline through a valve body.
In some embodiments of the present invention, the tangential flow filtration loop system comprises a second meter and a second flow meter, the second meter is connected to the first tank, and the second flow meter is connected to the second pipeline.
In certain embodiments of the present invention, the tangential flow filtration loop system comprises a peristaltic pump connected to the first tubing.
The control method provided by the invention is used for controlling the tangential flow filtration ring to work towards a system, and comprises the following working procedures:
inputting information of the sample liquid in the first tank body into a control device, and starting a tangential flow filtration membrane package with a corresponding specification by the control device;
the first detector detects the protein concentration of the harvest liquid entering the first tank body through the second pipeline;
if the protein concentration detected by the first detector does not meet the requirement of the harvest liquid, the control device starts a tangential flow filtration membrane package corresponding to the harvest liquid volume and the target protein molecular weight specification, and the sample liquid flows into the tangential flow filtration component again through the first pipeline.
The control method provided by the invention is used for controlling the tangential flow filtration ring to work towards a system, and comprises the following working procedures:
inputting information of the sample liquid in the first tank body into a control device, and starting a tangential flow filtration membrane package with a corresponding specification by the control device;
the first detector detects the protein concentration of the harvest liquid entering the first tank body through the second pipeline;
if the protein concentration detected by the first detector does not meet the requirement of the harvest liquid, the control device starts a tangential flow filtration membrane package corresponding to the harvest liquid volume and the target protein molecular weight specification, and the sample liquid flows into the tangential flow filtration component again through the first pipeline.
The control method provided by the invention is used for controlling the tangential flow filtration ring to work towards a system, and comprises the following working procedures:
a second detector detects the protein concentration in the waste liquid discharged by the tangential flow filtration membrane package;
if the protein concentration detected by the second detector does not meet the requirement of the waste liquid, the control device starts the fourth pipeline to be communicated with the third pipeline, and the waste liquid is discharged to the third tank body;
a third detector detects the protein concentration of the waste liquid in the third tank, and a second flowmeter detects the volume of the waste liquid entering the third tank;
if the protein content in the waste liquid is not in the limited range, the control device starts the fifth pipeline to be communicated with the first pipeline, the control device starts a tangential flow filtration membrane package with the specification corresponding to the volume of the waste liquid and the molecular weight of the target protein in the third tank body, and the waste liquid in the third tank body flows back to the tangential flow filtration component.
The control method provided by the invention controls the tangential flow filtration ring to work towards the system, and comprises the following working procedures:
inputting information of the sample liquid in the first tank body into a control device, and starting a tangential flow filtration membrane package with a corresponding specification by the control device;
the first detector detects the protein concentration of the harvest liquid entering the second tank body through the third pipeline;
if the protein concentration detected by the first detector does not meet the requirement of the harvest liquid, the control device starts a tangential flow filtration membrane package corresponding to the harvest liquid volume and the target protein molecular weight specification, and the sample liquid flows back to the tangential flow filtration component through the sixth pipeline.
The control method provided by the invention is used for controlling the tangential flow filtration ring to work towards a system, and comprises the following working procedures:
inputting information of the sample liquid in the first tank body into a control device, and starting a tangential flow filtration membrane package with a corresponding specification by the control device;
the first detector detects the protein concentration of the harvest liquid entering the second tank body through the third pipeline, if the protein concentration detected by the first detector does not meet the requirements of the harvest liquid, the control device starts a tangential flow filtration membrane package corresponding to the harvest liquid volume and the target protein molecular weight specification, and the sample liquid flows back to the tangential flow filtration component through the sixth pipeline;
the second detector detects the protein concentration of the waste liquid in the first tank, the second flowmeter detects the volume of the waste liquid entering the first tank, if the protein content in the waste liquid is not in a limited range, the control device starts a tangential flow filtration membrane package corresponding to the volume of the waste liquid and the target protein molecular weight specification, and the waste liquid flows into the tangential flow filtration component again through the first pipeline.
The invention can be widely applied to the technical field of biological engineering, and the embodiment of the invention at least has the following beneficial effects:
the tangential flow filtration annular system can realize the automatic opening or closing of the tangential flow filtration component by using the control device, realize the automatic operation of the equipment and improve the working efficiency;
the tangential flow filtration component is provided with a plurality of tangential flow filtration membrane packages with different specifications, the information of the sample liquid is input into the control device, and the control device can automatically match the tangential flow filtration membrane packages with the corresponding specifications;
designing a detector, wherein the detector can detect the concentration of protein in the harvest liquid obtained by filtration, and if the concentration of protein in the harvest liquid does not reach the standard, performing secondary purification on the obtained harvest liquid through a tangential flow filtration component;
designing a tangential flow filtration circulating system which is provided with a third tank body and a detection meter, wherein if the detection meter detects that the concentration of protein contained in the filtered waste liquid does not meet the requirement, the waste liquid flows into the third tank body;
and the third tank body is communicated with the tangential flow filtration assembly through a fifth pipeline so as to carry out secondary purification on the waste liquid.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings.
FIG. 1 is a schematic diagram of a tangential flow filtration ring system showing a first tank and a second tank.
FIG. 2 is a schematic diagram of a tangential flow filtration ring system showing a first tank and a second tank and a first detector and a first flow meter.
FIG. 3 is a schematic diagram of a tangential flow filtration ring system showing a first tank, a second tank, and a third tank and first, second, third, first, and second flow meters.
Reference numerals:
101. a first tank; 102. a second tank; 103. a tangential flow filtration membrane package; 104. a third tank body; 105. a peristaltic pump;
201. a first pipeline; 202. a second pipeline; 203. a third pipeline; 204. a fourth pipeline; 205. a fifth pipeline;
301. a first detector; 302. a second detector; 303. a third detector;
401. a first flow meter; 402. a second flow meter.
Detailed Description
Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the accompanying drawings are illustrative only for the purpose of explaining the present invention, and are not to be construed as limiting the present invention.
In the description of the present invention, it is to be understood that if the terms "center", "middle", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc., are used in an orientation or positional relationship indicated based on the drawings, it is merely for convenience of description and simplicity of description, and it is not intended to indicate or imply that the referenced device or element must have a particular orientation, be constructed and operated in a particular orientation, and therefore, is not to be considered as limiting the present invention. The features defined as "first" and "second" are used for distinguishing feature names rather than having special meanings, and further, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, "a plurality" means two or more unless otherwise specified.
In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.
The invention relates to a tangential flow filtration circulation system which comprises a first tank 101, a tangential flow filtration assembly and a second tank 102, wherein the tangential flow filtration assembly comprises a tangential flow filtration membrane pack 103, the first tank 101 is used for storing sample liquid to be treated, the first tank 101 is communicated with the inlet end of the tangential flow filtration assembly through a first pipeline 201, the outlet end of the tangential flow filtration assembly is communicated with the first tank 101 through a second pipeline 202, and the second tank 102 is communicated with the outlet end of the tangential flow filtration assembly through a third pipeline 203.
To achieve the automated operation of the tangential flow filtration loop system, the tangential flow filtration loop system is designed to include a control device that can open or close the tangential flow filtration membrane module 103. Specifically, the control device comprises an upper computer.
Furthermore, in order to correspond to different molecular weights of target proteins and sample volumes, the tangential flow filtration module is designed to comprise at least two tangential flow filtration membrane packages 103 with different specifications, the tangential flow filtration membrane packages 103 are connected in parallel, and the tangential flow filtration membrane packages 103 are respectively used for processing liquid with corresponding specifications, so that the filtration and purification effects are improved.
The control means turns on the corresponding tangential flow filtration membrane module 103 in dependence on the sample volume and the molecular weight of the protein of interest, it being understood that the control means is capable of activating the corresponding tangential flow filtration membrane module 103 after the control means has learned information about the sample liquid. It should be noted that the information on the sample solution includes the volume of the sample solution and the molecular weight of the target protein.
In the related art, in the sample liquid filtering process of the recombinant protein, an operator selects a proper tangential flow filtration membrane module 103 according to the molecular weight of the target protein and the sample volume, which has higher requirements on the experience and the specialty of the operator, so that the control device is designed to automatically compare and match the tangential flow filtration membrane module 103 with the corresponding specification, and the working difficulty of the operator is reduced.
In one embodiment, the inlet end of the tangential flow filtration module is provided with an inlet flow dividing structure, the first pipeline 201 is connected with the inlet flow dividing structure, and the inlet of each tangential flow filtration membrane module 103 is connected with the inlet flow dividing structure through a pipeline. Further, the control device is electrically connected with the inlet shunting structure, and the control device can start the inlet shunting structure to be communicated with the tangential flow filtration membrane package 103 with the specification corresponding to the protein concentration.
In some examples, at least two valve bodies corresponding to each tangential flow filtration membrane module 103 are disposed in the inlet flow dividing structure, the valve bodies are configured as solenoid valves, and the control device can control the opening and closing of each valve body respectively.
As an embodiment, the outlet end of the tangential flow filtration assembly is provided with a first outlet confluence structure and a second outlet confluence structure. Specifically, the outlet of the harvest liquid of each tangential flow filtration membrane module 103 is respectively connected with a first outlet confluence structure through a pipeline, and a second pipeline 202 is connected with the first outlet confluence structure; the outlet of the waste liquid of each tangential flow filtration membrane package 103 is respectively connected with the second outlet confluence structure through a pipeline, and the third pipeline 203 is connected with the second outlet confluence structure.
In some examples, the tangential flow filtration membrane package 103 is provided in two, the inlet flow splitting structure is provided as a three-way valve, and the first outlet flow converging structure and the second outlet flow converging structure are each provided as a three-way valve.
It will be appreciated that the tangential flow filtration loop system includes peristaltic pump 105, peristaltic pump 105 connected to first conduit 201, and a control device electrically connected to peristaltic pump 105, the control device being capable of actuating peristaltic pump 105 on and off. It will be appreciated that peristaltic pump 105 provides the motive force for the flow of liquid from first conduit 201 into the tangential flow filtration assembly.
Those skilled in the art know that when using a tangential flow filtration loop system, there are two cases: after the sample liquid in the first tank is filtered, the liquid containing the target protein returns to the first tank, and the rest of the liquid enters the second tank; and the filtered liquid containing the target protein enters the second tank body, and the rest liquid returns to the first tank body.
In the following embodiment, after the sample liquid in the first tank is filtered, the liquid containing the target protein is returned to the first tank, and the rest of the liquid enters the second tank.
In one embodiment, the tangential flow filtration loop system comprises a first detector 301, the first detector 301 is electrically connected to the control device, and the first detector 301 is connected to the first tank 101. It will be appreciated that the harvest fluid obtained from the tangential flow filtration module process is returned to the first tank 101 and the first detector 301 is used to detect the protein concentration of the harvest fluid in the first tank 101, which can be derived from at least one of the conductivity and refractive index values of the harvest fluid.
If the control device judges that the protein concentration detected by the first detector 301 does not meet the requirement of the harvest liquid, the control device starts the peristaltic pump 105, and the harvest liquid in the first tank 101 flows into the tangential flow filtration component again for secondary purification. In the related art, the harvest obtained by flowing the sample liquid into the first tank may not reach the predetermined protein concentration after the sample liquid is filtered by the tangential flow filtration module for one time, so the invention specifically designs the harvest in the first tank 101 for the second purification. Those skilled in the art will appreciate that "one filtration" does not mean that the sample liquid passes through only one tangential flow filtration assembly.
Further, the tangential flow filtration loop system comprises a first flow meter 401, the first flow meter 401 is connected with the second pipeline 202, and the first flow meter 401 is used for detecting the volume of the harvest liquid entering the first tank 101. Further, the first flow meter 401 is electrically connected to a control device, and the control device determines the volume of the harvest liquid in the first tank 101 through the detection of the first flow meter 401.
It will be appreciated that in the case where the harvest liquid is required to flow into the tangential flow filtration module for secondary purification, the control device activates the tangential flow filtration membrane module 103 of the corresponding specification in communication with the first conduit 201 according to the harvest liquid volume and the molecular weight of the protein of interest detected by the first flow meter 401.
Of course, in some examples, the tangential flow filtration membrane module 103 with the specification corresponding to the volume of the sample liquid and the molecular weight of the target protein is the same as the specification of the tangential flow filtration membrane module 103 used in the first filtration, and in this case, the tangential flow filtration membrane module 103 in the tangential flow filtration loop system is configured to be one and also meets the requirement.
In some examples, in order to make the detection of the first detection meter 301 more accurate, the first tank 101 is provided with a stirrer, and the stirrer is used for uniformly stirring the sample liquid.
In one embodiment, the tangential flow filtration loop system comprises a third tank 104, a fourth pipeline 204 and a second detector 302, wherein the second detector 302 is connected with the third pipeline 203, the second detector 302 is electrically connected with the control device, and the fourth pipeline 204 is respectively connected with the third pipeline 203 and the third tank 104. Specifically, the second detector 302 detects the protein concentration of the waste fluid discharged from the tangential flow filtration module, the protein concentration can be obtained by detecting at least one of the conductivity value and the refractive index value of the harvest fluid, and if the waste fluid does not meet the requirement of the waste fluid, i.e. the waste fluid contains the target protein, the waste fluid flows into the third tank 104 through the fourth pipeline 204.
The fourth pipeline 204 is connected with the third pipeline 203 through a valve body, specifically, the fourth pipeline 204 is communicated with the third pipeline 203 through a second three-way valve, and the control device is electrically connected with the second three-way valve. It will be appreciated that the control means can operate a second three-way valve to communicate the third 203 and fourth 204 lines or a second three-way valve to communicate the third 203 and second 102 tanks.
In one embodiment, the tangential flow filtration ring system comprises a fifth pipeline 205, and the fifth pipeline 205 connects the third tank 104 and the first pipeline 201, respectively. It will be appreciated that the waste liquid in the third tank 104 may be returned to the tangential flow filtration module via the fifth line 205 and the first line 201 for secondary purification.
Further, the tangential flow filtration ring system comprises a third detector 303, the third detector 303 is electrically connected to the control device, the third detector 303 is connected to the third tank 104, the third detector 303 is configured to detect a protein concentration of the waste fluid in the third tank 104, and the protein concentration is obtained by detecting at least one of a conductivity value and a refractive index value of the harvest fluid.
In the related art, after the sample liquid is filtered by the tangential flow filtration module for one time, some target proteins with special structures may be mixed into the waste liquid through the tangential flow filtration membrane 103 to cause target protein loss, so the second detector 302 is specially designed to check the protein concentration of the waste liquid discharged by the tangential flow filtration module, judge whether the target proteins are mixed into the waste liquid, and further design the waste liquid in the third tank 104 for secondary purification.
Referring to the figures, the tangential flow filtration loop system includes a second flow meter 402, the second flow meter 402 being connected to the fourth line 204, the second flow meter 402 being configured to detect the volume of waste liquid entering the third tank 104. Further, the second flow meter 402 is electrically connected to the control device.
The control device can further obtain the amount of the target protein in the waste liquid by the protein concentration detected by the third detector 303 and the volume of the waste liquid detected by the second flowmeter 402, and if the amount of the target protein in the waste liquid exceeds a preset value, the waste liquid is secondarily filtered.
It can be understood that, in the case that the waste liquid needs to flow back to the tangential flow filtration module through the fifth pipe 205, the control device activates the tangential flow filtration membrane module 103 with the corresponding specification to communicate with the first pipe 201 according to the volume of the waste liquid detected by the second flowmeter 402 and the molecular weight of the target protein. Under certain conditions, the tangential flow filtration membrane module 103 with the corresponding specification of the waste liquid volume and the molecular weight of the target protein is the same as the tangential flow filtration membrane module 103 used in the first filtration, and in this case, the tangential flow filtration membrane module 103 in the tangential flow filtration loop system is set to be one which also meets the requirement.
In some examples, to make the detection of the third detector 303 more accurate, the third tank 104 is provided with a stirrer for stirring the waste liquid uniformly.
The fifth pipeline 205 is connected with the first pipeline 201 through a valve body, specifically, the fifth pipeline 205 is communicated with the first pipeline 201 through a third three-way valve, and the control device is electrically connected with the third three-way valve.
In the following embodiment, after the sample liquid in the first tank is filtered, the liquid containing the target protein enters the second tank, and the rest of the liquid returns to the first tank.
In one embodiment, the tangential flow filtration loop system comprises a first detector 301, the first detector 301 is electrically connected to the control device, and the first detector 301 is connected to the second tank 102. It will be appreciated that the harvest obtained from the tangential flow filtration module processing enters the second tank 102 and the first detector 301 is used to detect the protein concentration of the harvest in the second tank 102, which can be derived from at least one of the conductivity and refractive index values of the harvest.
Further, the tangential flow filtration ring system comprises a sixth pipeline, and the sixth pipeline is respectively connected with the second tank 102 and the first pipeline 201. It is understood that the sample liquid in the second tank 102 can be returned to the tangential flow filtration module via the sixth line and the first line 201 for secondary purification.
The sixth pipeline is connected with the first pipeline 201 through a valve body, specifically, the sixth pipeline is communicated with the first pipeline 201 through a fourth three-way valve, and the control device is electrically connected with the fourth three-way valve.
If the control device judges that the protein concentration detected by the first detector 301 does not meet the requirement of the harvest liquid, the control device starts the peristaltic pump 105, and the harvest liquid in the second tank 102 flows into the tangential flow filtration component again for secondary purification. In the related art, the harvest liquid obtained by flowing the sample liquid into the second tank may not reach the set protein concentration after the sample liquid is filtered by the tangential flow filtration assembly for the first time, so the harvest liquid in the second tank is specially designed for the second purification.
Further, the tangential flow filtration loop system comprises a first flow meter 401, the first flow meter 401 is connected to the third pipeline 203, and the first flow meter 401 is used for detecting the volume of the sample liquid entering the second tank 102. Further, the first flowmeter 401 is electrically connected to a control device, and the control device determines the volume of the sample liquid in the second tank 102 by the detection of the first flowmeter 401.
It can be understood that, in the case that the sample liquid needs to flow into the tangential flow filtration module for secondary purification, the control device activates the tangential flow filtration membrane module 103 of corresponding specification to communicate with the first pipeline 201 according to the volume of the sample liquid and the molecular weight of the target protein detected by the first flowmeter 401.
Of course, in some examples, the tangential flow filtration membrane module 103 with the specification corresponding to the volume of the sample liquid and the molecular weight of the target protein is the same as the specification of the tangential flow filtration membrane module 103 used in the first filtration, and in this case, the tangential flow filtration membrane module 103 in the tangential flow filtration loop system is configured to be one and also meets the requirement.
In some examples, to make the detection of the first detection meter 301 more accurate, the second tank 102 is provided with a stirrer for stirring the sample liquid uniformly.
In one embodiment, the tangential flow filtration loop system includes a second detector 302, and the second detector 302 is coupled to the first tank 101. It will be appreciated that the waste stream obtained from the tangential flow filtration module treatment enters the first tank 101, and the first detector 301 is configured to detect a protein concentration of the waste stream in the first tank 101, wherein the protein concentration is determined based on at least one of a conductivity value and a refractive index value of the harvest stream.
Further, the tangential flow filtration ring system includes a second flow meter 402, the second flow meter 402 being connected to the second pipe 202. The second flow meter 402 is used to detect the volume of waste liquid entering the first tank 101. Further, the second flow meter 402 is electrically connected to the control device.
The control device can further obtain the amount of the target protein in the waste liquid by the protein concentration detected by the second detector 302 and the volume of the waste liquid detected by the second flowmeter 402, and if the amount of the target protein in the waste liquid exceeds a preset value, the waste liquid is subjected to secondary filtration. It can be understood that, according to the volume of the waste liquid and the molecular weight of the target protein detected by the second flowmeter 402, the control device activates the tangential flow filtration membrane module 103 with the corresponding specification to communicate with the first pipeline 201. Under certain conditions, the tangential flow filtration membrane module 103 with the specification corresponding to the molecular weight of the protein of interest and the waste liquid volume is the same as the specification of the tangential flow filtration membrane module 103 used in the first filtration, and in this case, the tangential flow filtration membrane module 103 in the tangential flow filtration loop system is set to be one which also satisfies the requirement.
The present invention will be described in detail below with reference to specific examples, and it should be noted that the following descriptions are only illustrative and not specific limitations of the present invention.
Example one
The tangential flow filtration loop-directional system comprises a first tank 101, a tangential flow filtration assembly, a second tank 102, a first pipeline 201, a second pipeline 202, a third pipeline 203, a first detector 301 and a control device, wherein the tangential flow filtration assembly comprises two tangential flow filtration membranes 103, and an inlet flow splitting structure, a first outlet flow converging structure and a second outlet flow converging structure are respectively set to be three-way valves.
The control method for controlling the tangential flow filtration ring to work towards the system comprises the following procedures.
Inputting information of the sample liquid in the first tank 101 into the control device, switching the inlet shunting structure by the control device to start the tangential flow filtration membrane package 103 with corresponding specification, enabling the obtained harvest liquid to flow into the first tank 101 through the second pipeline 202, and enabling the waste liquid to flow into the second tank 102 through the third pipeline 203; the first detection meter 301 detects the protein concentration of the sample liquid in the first tank 101, and the control device receives the detection data of the first detection meter 301.
The tangential flow filtration loop system may be further configured to include a first flow meter 401, and the control device determines the volume of the harvest liquid entering the first tank 101 based on the detection of the first flow meter 401.
The control device compares the detection data obtained by the first detector 301 with a set value, if the protein concentration detected by the first detector 301 does not meet the requirement of the harvest liquid, the harvest liquid in the first tank 101 flows into the tangential flow filtration module again through the first pipeline 201, and the control device starts the tangential flow filtration membrane package 103 corresponding to the volume of the sample liquid and the molecular weight specification of the target protein for secondary purification.
It is understood that the above control method may be performed in a loop until the protein concentration of the sample liquid in the first tank 101 reaches a desired level.
Example two
The tangential flow filtration loop-directional system comprises a first tank 101, a tangential flow filtration assembly, a second tank 102, a first pipeline 201, a second pipeline 202, a third pipeline 203, a third tank 104, a fourth pipeline 204, a second detector 302, a fifth pipeline 205, a third detector 303 and a control device, wherein the tangential flow filtration assembly comprises two tangential flow filtration membranes 103, and an inlet flow dividing structure, a first outlet confluence structure and a second outlet confluence structure are respectively set as three-way valves.
The control method for controlling the operation of the tangential flow filtration ring to the system comprises the following procedures.
Inputting information of the sample liquid in the first tank 101 into the control device, switching the inlet shunting structure by the control device to start the tangential flow filtration membrane package 103 with corresponding specification, and enabling the obtained harvest liquid to flow into the first tank 101 through the second pipeline 202; the second detector 302 detects the protein concentration in the waste liquid discharged from the tangential flow filtration membrane module 103, and the control means receives the detection data from the second detector 302.
The control device compares the detection data obtained by the second detector 302 with the set values: if the protein concentration detected by the second detector 302 does not meet the waste liquid requirement, the control device switches the second three-way valve, starts the fourth pipeline 204 to be communicated with the third pipeline 203, and discharges the waste liquid to the third tank 104; if the protein concentration detected by the second detector 302 meets the requirement of the waste liquid, the third pipeline 203 is connected to the second tank 102, and the waste liquid is discharged to the second tank 102.
The tangential flow filtration ring system further comprises a third detector 303 and a second flow meter 402, and the control device obtains the protein concentration of the waste liquid in the third tank 104 according to the detection of the third detector 303 and obtains the volume of the waste liquid in the third tank 104 according to the detection of the second flow meter 402.
The control device can further obtain the amount of the target protein in the waste liquid entering the third tank 104 by detecting the protein concentration obtained by the third detector 303 and the volume of the waste liquid obtained by the second flowmeter 402, and if the amount of the target protein in the waste liquid entering the third tank 104 exceeds a preset value, the waste liquid is filtered for the second time.
The control device starts the fifth pipeline 205 to be communicated with the first pipeline 201, and the waste liquid in the third tank 104 flows back for secondary purification. It is understood that, in the third tank 104, the control device starts the tangential flow filtration membrane module 103 with the corresponding specification according to the volume of the waste liquid obtained by the detection of the second flowmeter 402 and the molecular weight of the target protein, and the waste liquid in the third tank 104 flows back to the tangential flow filtration membrane module 103 with the corresponding specification.
EXAMPLE III
The tangential flow filtration ring system comprises a tangential flow filtration assembly, a first tank 101, a second tank 102, a first pipeline 201, a second pipeline 202, a third pipeline 203, a first detector 301, a third tank 104, a fourth pipeline 204, a second detector 302, a fifth pipeline 205, a third detector 303 and a control device, wherein the tangential flow filtration assembly comprises two tangential flow filtration membranes 103, and an inlet flow splitting structure, a first outlet converging structure and a second outlet converging structure are respectively set as three-way valves.
It will be appreciated that in this case, the harvest liquid obtained after filtration in the tangential flow filtration module in the first tank 101 and the waste liquid in the third tank 104 may be purified separately if neither is satisfactory.
In some other embodiments, the tangential flow filtration ring system can be designed to further comprise a first flow meter 401 and a second flow meter 402.
Example four
The tangential flow filtration loop-directional system comprises a first tank 101, a tangential flow filtration assembly, a second tank 102, a first pipeline 201, a second pipeline 202, a third pipeline 203, a first detector 301 and a control device, wherein the tangential flow filtration assembly comprises two tangential flow filtration membranes 103, and an inlet flow splitting structure, a first outlet flow converging structure and a second outlet flow converging structure are respectively set to be three-way valves.
The control method for controlling the operation of the tangential flow filtration ring to the system comprises the following procedures.
Inputting information of the sample liquid in the first tank 101 into the control device, switching the inlet shunting structure by the control device to start the tangential flow filtration membrane package 103 with corresponding specification, enabling the obtained harvest liquid to flow into the second tank 102 through the third pipeline 203, and enabling the waste liquid to flow into the first tank 101 through the second pipeline 202; the first detector 301 detects the protein concentration of the harvest fluid in the second tank 102, and the control device receives the detection data of the first detector 301.
The tangential flow filtration loop system further comprises a first flow meter 401, and the control device determines the volume of the harvest liquid entering the second tank 102 according to the detection of the first flow meter 401.
The control device compares the detection data obtained by the first detector 301 with a set value, if the protein concentration detected by the first detector 301 does not meet the requirement of the harvest liquid, the harvest liquid in the second tank 102 flows into the tangential flow filtration module again through the sixth pipeline, and the control device starts the tangential flow filtration membrane package 103 corresponding to the volume of the sample liquid and the molecular weight specification of the target protein for secondary purification.
It is understood that the above control method can be performed in a loop until the protein concentration of the sample liquid in the second tank 102 reaches the desired concentration.
EXAMPLE five
The tangential flow filtration circulating system comprises a first tank 101, a tangential flow filtration assembly, a second tank 102, a first pipeline 201, a second pipeline 202, a third pipeline 203, a second detector 302 and a control device, wherein the tangential flow filtration assembly comprises two tangential flow filtration membranes 103, and an inlet flow splitting structure, a first outlet converging structure and a second outlet converging structure are respectively set to be three-way valves.
The control method for controlling the operation of the tangential flow filtration ring to the system comprises the following procedures.
The information of the sample liquid in the first tank 101 is input to the control device, the control device switches the inlet shunting structure to start the tangential flow filtration membrane package 103 with the corresponding specification, the obtained harvest liquid flows into the second tank 102 through a third pipeline 203, and the waste liquid flows back to the first tank 101 through a second pipeline 202; the second detector 302 detects the protein concentration of the waste liquid in the first tank 101, and the control device receives the detection data of the second detector 302.
The tangential flow filtration loop system further comprises a second flow meter 402, and the control device determines the volume of waste liquid entering the first tank 101 based on the detection of the second flow meter 402.
The control device can obtain the content of the target protein in the waste liquid entering the first tank 101 according to the detection data obtained by the second detector 302 and the detection data of the second flowmeter 402, if the content of the target protein in the waste liquid exceeds a set value, the waste liquid in the first tank 101 flows into the tangential flow filtration assembly again through the first pipeline 201, and the control device starts the tangential flow filtration membrane module 103 corresponding to the volume of the waste liquid and the molecular weight specification of the target protein for secondary purification.
Example six
The tangential flow filtration loop system comprises a tangential flow filtration assembly, a first tank body 101, a second tank body 102, a first pipeline 201, a second pipeline 202, a third pipeline 203, a first detector 301, a second detector 302, a sixth pipeline and a control device, wherein the tangential flow filtration assembly comprises two tangential flow filtration membrane packages 103, and an inlet diversion structure, a first outlet confluence structure and a second outlet confluence structure are respectively set to be three-way valves.
It is understood that in this case, after the tangential flow filtration module filters, the sample liquid flowing into the second tank 102 and the waste liquid flowing into the first tank 101 may be purified for a second time if neither is satisfactory.
In some other embodiments, the tangential flow filtration loop system may be designed to further include a first flow meter 401 and a second flow meter 402.
In the description herein, references to the terms "one embodiment," "some examples," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples" or the like, if any, mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
While the embodiments of the present invention have been described in detail with reference to the drawings, the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the spirit of the present invention.
In the description of the present invention, the appearances of the patent names and phrases in the specification are not necessarily the same but are different. For example, the patent name "a A, B" illustrates what is claimed in the present invention: the technical scheme with the subject name of A and the technical scheme with the subject name of B.
Claims (10)
1. A tangential flow filtration annular system characterized by: comprises that
A tangential flow filtration assembly comprising a tangential flow filtration membrane package (103);
a first tank (101), the first tank (101) being for storing a sample liquid to be treated, the first tank (101) being in communication with an inlet end of the tangential flow filtration assembly via a first conduit (201), an outlet end of the tangential flow filtration assembly being in communication with the first tank (101) via a second conduit (202);
a second tank (102), said second tank (102) being in communication with the outlet end of said tangential flow filtration assembly via a third conduit (203);
a control device capable of opening or closing the tangential flow filtration membrane package (103).
2. The tangential flow filtration hoop system of claim 1, wherein: the tangential flow filtration assembly comprises at least two tangential flow filtration membranes (103) with different specifications, the tangential flow filtration membranes (103) are connected in parallel, and the control device opens the corresponding tangential flow filtration membranes (103) according to the volume of the sample liquid and the molecular weight of the target protein.
3. The tangential flow filtration circulation system of claim 1 or 2, wherein: the tangential flow filtration circulating system comprises a first detection meter (301) and a first flow meter (401), wherein the first detection meter (301) is connected with the first tank body (101), and the first flow meter (401) is connected with the second pipeline (202).
4. The tangential flow filtration circulation system of claim 1 or 2, wherein: the tangential flow filtration circulating system comprises a third tank body (104), a fourth pipeline (204) and a second detection meter (302), wherein the second detection meter (302) is connected with the third pipeline (203), the fourth pipeline (204) is respectively connected with the third pipeline (203) and the third tank body (104), and the fourth pipeline (204) is connected with the third pipeline (203) through a valve body; the tangential flow filtration ring system comprises a fifth pipeline (205), the fifth pipeline (205) is respectively connected with the third tank body (104) and the first pipeline (201), and the fifth pipeline (205) is connected with the first pipeline (201) through a valve body;
preferably, the tangential flow filtration loop-wise system comprises a third detector (303), the third detector (303) being connected to the third tank (104);
more preferably, the tangential flow filtration loop-wise system comprises a second flow meter (402), the second flow meter (402) being connected to the fourth line (204).
5. The tangential flow filtration circulation system of claim 1 or 2, wherein: the tangential flow filtration circulating system comprises a first detection meter (301), a first flow meter (401) and a sixth pipeline, wherein the first detection meter (301) is connected with the second tank body (102), the first flow meter (401) is connected with the third pipeline (203), the sixth pipeline is respectively connected with the second tank body (102) and the first pipeline (201), and the sixth pipeline is connected with the first pipeline (201) through a valve body.
6. The tangential flow filtration circulation system of claim 1 or 2, wherein: the tangential flow filtration loop system comprises a second detection meter (302) and a second flow meter (402), wherein the second detection meter (302) is connected with the first tank body (101), and the second flow meter (402) is connected with the second pipeline (202).
7. A control method characterized by: the control method for operating the tangential flow filtration ring system of claim 3, the control method comprising
Inputting information of sample liquid in a first tank body (101) into a control device, and starting a tangential flow filtration membrane package (103) with a corresponding specification by the control device;
the first detector (301) detects the protein concentration of the harvest liquid flowing into the first tank (101) through the second pipeline (202);
if the protein concentration detected by the first detector (301) does not meet the requirements of the harvest fluid, the control device starts a tangential flow filtration membrane module (103) corresponding to the volume of the harvest fluid and the molecular weight specification of the target protein, and the sample fluid flows into the tangential flow filtration module again through the first pipeline (201).
8. A control method characterized by: the control method for operating the tangential flow filtration ring system of claim 4, the control method comprising
Inputting information of sample liquid in a first tank body (101) into a control device, and starting a tangential flow filtration membrane package (103) with a corresponding specification by the control device;
a second detector (302) detects the protein concentration in the waste liquid discharged from the tangential flow filtration membrane (103);
if the protein concentration detected by the second detector (302) does not meet the requirement of the waste liquid, the control device starts a fourth pipeline (204) to be communicated with a third pipeline (203), and the waste liquid is discharged to a third tank body (104);
a third detector (303) detects the protein concentration of the waste liquid in the third tank (104), and a second flowmeter (402) detects the volume of the waste liquid entering the third tank (104);
if the protein content in the waste liquid is not in the limited range, the control device starts the fifth pipeline (205) to be communicated with the first pipeline (201), the control device starts a tangential flow filtration membrane module (103) with the specification corresponding to the volume of the waste liquid and the molecular weight of the target protein in the third tank body (104), and the waste liquid in the third tank body (104) flows back to the tangential flow filtration module.
9. A control method characterized by: the control method for operating the tangential flow filtration ring system of claim 5, the control method comprising
Inputting information of sample liquid in a first tank body (101) into a control device, and starting a tangential flow filtration membrane package (103) with a corresponding specification by the control device;
the first detector (301) detects the protein concentration of the harvest liquid entering the second tank (102) through the third pipeline (203);
if the protein concentration detected by the first detector (301) does not meet the requirements of the harvest liquid, the control device starts a tangential flow filtration membrane package (103) corresponding to the harvest liquid volume and the molecular weight specification of the target protein, and the sample liquid flows back to the tangential flow filtration module through the sixth pipeline.
10. A control method characterized by: the control method for operating the tangential flow filtration ring system of claim 6, the control method comprising
Inputting information of sample liquid in a first tank body (101) into a control device, and starting a tangential flow filtration membrane package (103) with a corresponding specification by the control device;
the second detector (302) detects the protein concentration of the waste liquid in the first tank body (101), the second flowmeter (402) detects the volume of the waste liquid entering the first tank body (101), if the protein content in the waste liquid is not in a limited range, the control device starts a tangential flow filter membrane pack (103) corresponding to the volume of the waste liquid and the target protein molecular weight specification, and the waste liquid flows into the tangential flow filter assembly again through the first pipeline (201).
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| Application Number | Priority Date | Filing Date | Title |
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| CN202211570839.XA CN115845612A (en) | 2022-12-08 | 2022-12-08 | Tangential flow filtration circumferential system and control method |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202211570839.XA CN115845612A (en) | 2022-12-08 | 2022-12-08 | Tangential flow filtration circumferential system and control method |
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| CN115845612A true CN115845612A (en) | 2023-03-28 |
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| CN202211570839.XA Pending CN115845612A (en) | 2022-12-08 | 2022-12-08 | Tangential flow filtration circumferential system and control method |
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