CN116020189A - Tangential flow filtration unidirectional system and control method - Google Patents
Tangential flow filtration unidirectional system and control method Download PDFInfo
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- CN116020189A CN116020189A CN202211579496.3A CN202211579496A CN116020189A CN 116020189 A CN116020189 A CN 116020189A CN 202211579496 A CN202211579496 A CN 202211579496A CN 116020189 A CN116020189 A CN 116020189A
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- 238000000034 method Methods 0.000 title claims abstract description 20
- 239000007788 liquid Substances 0.000 claims abstract description 191
- 239000002699 waste material Substances 0.000 claims abstract description 114
- 238000003306 harvesting Methods 0.000 claims abstract description 78
- 239000012528 membrane Substances 0.000 claims abstract description 69
- 238000011068 loading method Methods 0.000 claims abstract description 13
- 102000004169 proteins and genes Human genes 0.000 claims description 60
- 108090000623 proteins and genes Proteins 0.000 claims description 60
- 238000001914 filtration Methods 0.000 claims description 23
- 230000002572 peristaltic effect Effects 0.000 claims description 9
- 238000005070 sampling Methods 0.000 claims description 5
- 238000004891 communication Methods 0.000 claims description 3
- 230000037452 priming Effects 0.000 claims 1
- 239000010808 liquid waste Substances 0.000 abstract description 5
- 239000012530 fluid Substances 0.000 description 25
- 239000000523 sample Substances 0.000 description 24
- 238000001514 detection method Methods 0.000 description 9
- 239000012488 sample solution Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 238000010586 diagram Methods 0.000 description 3
- 238000005516 engineering process 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
- 239000012460 protein solution Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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Abstract
The invention discloses a tangential flow filtration unidirectional system and a control method, wherein the tangential flow filtration unidirectional system comprises a tangential flow filtration component, a liquid storage tank, a liquid harvesting tank, a liquid waste tank and a control device, and the tangential flow filtration component comprises a tangential flow filtration membrane package; the liquid storage tank is communicated with the inlet end of the tangential flow filtration assembly through a sample loading pipeline; the harvesting liquid tank is communicated with the outlet end of the tangential flow filtration assembly through a liquid discharge pipeline; the waste liquid tank is communicated with the outlet end of the tangential flow filtration assembly through a waste liquid pipeline; the control device can turn on or off tangential flow through the filter cartridge. The invention can be widely applied to the technical field of bioengineering.
Description
Technical Field
The invention relates to the technical field of bioengineering, in particular to a tangential flow filtration unidirectional system and a control method.
Background
The tangential flow filtration technology is mainly applied to biological engineering such as concentration, washing filtration (desalting and buffer replacement) and size separation of biomolecules, and can also be used for removing and clarifying cells and cell fragments in fermentation liquor or cell culture liquor.
The tangential flow filtration technology is different from the conventional direct current filtration technology in that liquid tangentially flows across the surface of a filter membrane, and a part of the solution is pressed against the filter membrane by a transmembrane pressure difference generated by the liquid, so that a harvest liquid and a waste liquid are obtained. In the whole process, liquid continuously flows through the surface of the membrane at a certain speed, and the surface of the filter membrane is flushed during filtration, so that a gel layer is not easy to form on the surface of the membrane, particles in the sample liquid are prevented from blocking the filter membrane, and the stable filtration speed is maintained. The unidirectional tangential flow filtration system comprises a tangential flow filtration assembly, a liquid storage tank, a liquid harvesting tank and a liquid waste tank, wherein a sample liquid in the liquid storage tank enters the liquid harvesting tank after being filtered by the filtration assembly, and the other part of the sample liquid enters the liquid waste tank, so that the device has a complex structure, and especially the operation of the tangential flow filtration assembly has certain requirements on the professional property, so that the existing operation efficiency of technicians is low, and even the operation is not enough in time.
At present, in the filtration of recombinant proteins, a technician is required to select an applicable filter membrane package according to the characteristics of the molecular weight, the sample volume and the like of target proteins, and the technical expertise and experience of the technician are required to be certain. In addition, after the sample is filtered for the first time, whether the protein concentration in the harvest liquid reaches the target concentration or not needs to be measured manually, if the protein concentration does not reach the target concentration, the volume of the protein solution in the harvest tank needs to be measured manually, and an applicable filter membrane package is selected again for secondary filtration, or residual target protein possibly exists in the waste liquid, and the factors can influence the purification efficiency and the 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 unidirectional system and a control method, and the adopted technical scheme is as follows.
The tangential flow filtration unidirectional system provided by the invention comprises a tangential flow filtration assembly, a liquid storage tank, a liquid harvesting tank, a liquid waste tank and a control device, wherein the tangential flow filtration assembly comprises a tangential flow filtration membrane package; the liquid storage tank is communicated with the inlet end of the tangential flow filtration assembly through an upper pipe; the harvesting liquid tank is communicated with the outlet end of the tangential flow filtration assembly through a liquid discharge pipeline; the waste liquid tank is communicated with the outlet end of the tangential flow filtration assembly through a waste liquid pipeline; the control device can turn on or off the tangential flow filtration membrane pack.
In some embodiments of the present invention, the tangential flow filtration assembly includes at least two tangential flow filtration membrane packages of different specifications, the tangential flow filtration membrane packages of different specifications are connected in parallel, and the control device opens the corresponding tangential flow filtration membrane packages according to the volume of the sample solution and the molecular weight of the target protein.
In certain embodiments of the present invention, the tangential flow filtration unidirectional system comprises a first return line, a first meter, and a first flow meter, the first meter being connected to the harvest tank, the first return line being connected to the harvest tank and the loading tube, respectively, the first return line being connected to the loading line via a valve body, the first flow meter being connected to the drain line.
In some embodiments of the present invention, the tangential flow filtration unidirectional system includes a temporary storage tank, a waste fluid branch line, and a second meter, the second meter being connected to the waste fluid line, the waste fluid branch line being connected to the temporary storage tank and the waste fluid line, respectively, the waste fluid branch line being connected to the waste fluid line through a valve body.
In certain embodiments of the present invention, the tangential flow filtration unidirectional system comprises a second return line that connects the temporary storage tank and the loading line, respectively, the second return line being connected to the loading line by a valve body.
In certain embodiments of the present invention, the tangential flow filtration unidirectional system comprises a third meter coupled to the surge tank.
In certain embodiments of the invention, the tangential flow filtration unidirectional system comprises a second flow meter coupled to the waste branch line.
In certain embodiments of the present invention, the tangential flow filtration unidirectional system comprises a peristaltic pump coupled to the loading tube.
The control method provided by the invention is used for controlling the tangential flow filtration unidirectional system to work, and comprises the following steps:
inputting information of sample liquid in the liquid storage tank to a control device, and starting the control device to flow through the filter membrane bag in a tangential direction;
the first detector detects the protein concentration of the harvest liquid in the harvest liquid tank;
if the protein concentration detected by the first detector does not meet the requirement of the harvest liquid, the control device starts the first return pipeline to be communicated with the upper sampling pipeline, and starts the tangential flow filter membrane pack corresponding to the volume of the harvest liquid and the molecular weight specification of the target protein, and the harvest liquid flows back to the tangential flow filter membrane pack of the corresponding specification from the harvest liquid tank.
The control method provided by the invention is used for controlling the tangential flow filtration unidirectional system to work, and comprises the following steps:
inputting information of sample liquid in the liquid storage tank to a control device, and starting the control device to flow through the filter membrane bag in a tangential direction;
a second detector detects the protein concentration in the waste liquid discharged from the tangential flow filtration membrane pack;
if the protein concentration detected by the second detector does not meet the waste liquid requirement, the control device starts the waste liquid branch pipeline to be communicated with the waste liquid pipeline, and the waste liquid is discharged to the temporary storage tank;
the third detector detects the protein concentration of the waste liquid in the temporary storage tank, the second flowmeter detects the volume of the waste liquid flowing into the temporary storage tank, if the protein content in the waste liquid is not in a limited range, the control device starts the second return pipeline to be communicated with the upper pipe, and the control device starts the tangential flow filter membrane package with the corresponding specification, and the waste liquid in the temporary storage tank flows back to the tangential flow filter membrane package with the corresponding specification.
The invention can be widely applied to the technical field of bioengineering, and the embodiment of the invention has at least the following beneficial effects:
the control device is utilized in the tangential flow filtration unidirectional system to realize automatic opening or closing of the tangential flow filtration assembly, thereby realizing automatic operation of equipment and improving the working efficiency;
the tangential flow filtration assembly is designed 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 be automatically matched with the tangential flow filtration membrane packages with corresponding specifications;
the method comprises the steps that a harvest liquid tank is designed to be provided with a first detector and a first return pipeline, the first detector can detect the protein concentration in harvest liquid, if the protein concentration does not reach the standard, the harvest liquid flows back to a tangential flow filtration assembly through the first return pipeline to be subjected to secondary filtration, and a control device is matched with a tangential flow filtration membrane pack of a corresponding specification according to detection data of the first flowmeter and the molecular weight of target protein;
the tangential flow filtration circumferential system is designed to be provided with a temporary storage tank and a second detector, and if the second detector detects that the protein concentration of the filtered waste liquid is not in accordance with the requirement, the waste liquid flows into the temporary storage tank;
the temporary storage tank is designed to be communicated with the tangential flow filtration assembly through a second return pipeline so as to carry out secondary filtration on the waste liquid.
Drawings
The foregoing and/or additional aspects and advantages of the present invention will be 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 unidirectional system, showing a fluid reservoir, a harvest fluid reservoir, and a waste fluid reservoir.
FIG. 2 is a schematic diagram of a tangential flow filtration unidirectional system showing a fluid storage tank, a harvest tank, and a waste fluid tank, and a first return line, a first meter, and a first flowmeter.
FIG. 3 is a schematic diagram of a third embodiment of a tangential flow filtration unidirectional system, showing a fluid reservoir, a harvest tank, a temporary storage tank, and a waste fluid tank, and a first return line, a first meter, a second meter, a third meter, and a first and second flow meter.
Reference numerals:
101. a liquid storage tank; 102. a harvest liquid tank; 103. a waste liquid tank; 104. tangentially flowing through the filter membrane pack; 105. a temporary storage tank; 106. a peristaltic pump;
201. a sample loading pipeline; 202. a liquid discharge pipeline; 203. a waste liquid pipeline; 204. a waste liquid branch pipeline;
301. a first return line; 302. A second return line;
401. a first meter; 402. A second meter; 403. A third meter;
501. a first flowmeter; 502. a second flowmeter.
Detailed Description
Embodiments of the present invention are described in detail below in conjunction with fig. 1-3, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functionality throughout. The embodiments described below by referring to the drawings are illustrative only and are not to be construed as limiting the invention.
In the description of the present invention, it should be understood that, if the terms "center", "middle", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "axial", "radial", "circumferential", etc. are used as directions or positional relationships based on the directions shown in the drawings, the directions are merely for convenience of description and for simplification of description, and do not indicate or imply that the apparatus or element to be referred to must have a specific direction, be constructed and operated in a specific direction, and thus should not be construed as limiting the present invention. Furthermore, features defining "first", "second" may include one or more such features, either explicitly or implicitly. In the description of the present invention, unless otherwise indicated, the meaning of "a plurality" is two or more.
In the description of the present invention, it should be noted that, unless explicitly specified and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be either fixedly connected, detachably connected, or integrally connected, for example; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.
The invention relates to a tangential flow filtration unidirectional system, which comprises a liquid storage tank 101, a tangential flow filtration assembly, a liquid harvesting tank 102 and a waste liquid tank 103, wherein the tangential flow filtration assembly comprises a tangential flow filtration membrane pack 104, the liquid storage tank 101 is communicated with the inlet end of the tangential flow filtration assembly through an upper pipe line 201, the liquid harvesting tank 102 is communicated with the outlet end of the tangential flow filtration assembly through a liquid draining pipeline 202, and the liquid waste tank 103 is communicated with the outlet end of the tangential flow filtration assembly through a waste liquid pipeline 203. It will be appreciated that the sample fluid in the fluid reservoir 101 is processed by the tangential flow filtration assembly to provide a harvest fluid and a reject fluid which are discharged to the harvest fluid reservoir 102 and reject fluid reservoir 103, respectively.
To achieve automatic operation of the tangential flow filtration unidirectional system, the tangential flow filtration unidirectional system is designed to include a control device that can turn on or off the tangential flow filtration membrane package 104, specifically the control device includes an upper computer.
Further, in order to correspond to different molecular weights of target proteins and volumes of sample solutions, the tangential flow filtration assembly is designed to comprise at least two tangential flow filtration membrane packages 104 with different specifications, the tangential flow filtration membrane packages 104 are connected in parallel, and the tangential flow filtration membrane packages 104 are respectively used for processing the liquids with the corresponding specifications, so that the filtration and purification effects are improved. The control device opens the corresponding tangential flow through the filter membrane package 104 according to the molecular weight of the protein of interest and the volume of the sample fluid. After the control device has learned the information about the sample fluid, the control device can initiate a corresponding tangential flow through the filter cartridge 104. The information of the sample solution includes the molecular weight of the target protein and the volume of the sample solution.
In the related art, in the process of filtering the sample liquid of the recombinant protein, an operator selects a proper tangential flow filtration membrane package 104 according to the molecular weight of the target protein and the volume of the protein solution to be purified, which has certain requirements on the experience and the specialty of the operator, so that the design control device automatically compares and matches the tangential flow filtration membrane package 104 with corresponding specifications, and the working difficulty of the operator is reduced.
As an embodiment, the inlet end of the tangential flow filtration module is provided with an inlet split structure, and the upper pipe 201 is connected to the inlet split structure, and the inlets of the tangential flow filtration membrane packages 104 are respectively connected to the inlet split structure through pipes. Further, the control device is electrically connected to the inlet split-flow structure, and the control device can start the inlet split-flow structure to communicate with the tangential flow filtration membrane package 104 of the specification corresponding to the molecular weight of the target protein and the volume of the sample solution.
In some examples, at least two valve bodies corresponding to the tangential flow through the filter membrane package 104 are arranged in the inlet diversion structure, the valve bodies are arranged as electromagnetic valves, and the control device can respectively control the opening and closing of the valve bodies.
As an embodiment, the outlet end of the tangential flow filtration assembly is provided with a first outlet merging structure and a second outlet merging structure. Specifically, the outlets of the harvest liquid flowing through the filter membrane package 104 tangentially are respectively connected with the first outlet confluence structure through pipelines, and the liquid discharge pipeline 202 is connected with the first outlet confluence structure; the outlets of the waste liquid flowing through the filter membrane package 104 tangentially are respectively connected with the second outlet confluence structure through pipelines, and the waste liquid pipeline 203 is connected with the second outlet confluence structure.
In some examples, the tangential flow filtration membrane package 104 is provided in two, the inlet split flow structure is provided as a three-way valve, and the first outlet converging structure and the second outlet converging structure are provided as three-way valves, respectively.
With reference to the figures, the tangential flow filtration unidirectional system comprises a peristaltic pump 106, the peristaltic pump 106 is connected with an upper tube 201, a control device is electrically connected with the peristaltic pump 106, and the control device can operate the starting and stopping of the peristaltic pump 106. It will be appreciated that peristaltic pump 106 provides motive force for the flow of liquid from the upper tube 201 into the tangential flow filtration assembly.
As an embodiment, the tangential flow filtration unidirectional system comprises a first return line 301, the first return line 301 connecting the harvest tank 102 and the upper header line 201, respectively. It will be appreciated that the harvest liquid in the harvest tank 102 may be returned to the tangential flow filtration assembly via the first return line 301 and the upper header line 201 for secondary filtration.
In the related art, after the sample liquid is filtered once by the tangential flow filtration component, the obtained harvest liquid may not reach the set protein concentration, so the invention particularly designs the harvest liquid to be filtered again.
Further, the tangential flow filtration unidirectional system comprises a first meter 401, the first meter 401 is electrically connected with the control device, the first meter 401 is connected with the harvest tank 102, the first meter 401 is used for detecting the protein concentration of the harvest, and the protein concentration can be obtained according to at least one of the conductivity value and the refractive index value of the harvest. It will be appreciated that if the control device determines that the protein concentration detected by the first detector 401 does not meet the requirement of the harvest liquid, the harvest liquid is refluxed for secondary filtration.
In some examples, to make the detection by the first detector 401 more accurate, the harvest tank 102 is provided with a stirrer for stirring the harvest liquid evenly.
The first return line 301 is connected to the loading line 201 through a valve body, specifically, the first return line 301 is communicated with the loading line 201 through a first three-way valve, and the control device is electrically connected to the first three-way valve. It will be appreciated that the control means is capable of operating the first three-way valve to communicate the first return line 301 with the upper sample line 201 or the first three-way valve to communicate the reservoir 101 with the upper sample line 201.
Referring to the figures, the tangential flow filtration unidirectional system comprises a first flow meter 501 coupled to the drain line 202, the first flow meter 501 for sensing the volume of harvest liquid entering the harvest tank 102. Further, the first flow meter 501 is electrically connected to a control device, and the control device obtains the volume of the harvest liquid collected by the harvest liquid tank 102 through the detection of the first flow meter 501.
It will be appreciated that in the case where the harvest liquid needs to be returned to the tangential flow filtration module via the first return line 301, the control device initiates a tangential flow through the filter bag 104 of the corresponding specification to the upper tube 201, based on the harvest liquid volume and the molecular weight of the protein of interest detected by the first flow meter 501.
Of course, in some examples, there is a case where the tangential flow filtration membrane package 104 of the specification corresponding to the harvest liquid volume and the molecular weight of the target protein is identical to the specification of the tangential flow filtration membrane package 104 used in the first filtration, and in this case, the tangential flow filtration membrane package 104 in the tangential flow filtration unidirectional system is set to one as well.
As an embodiment, the tangential flow filtration unidirectional system comprises a temporary storage tank 105, a waste liquid branch pipeline 204 and a second detector 402, wherein the second detector 402 is connected with the waste liquid pipeline 203, the second detector 402 is electrically connected with the control device, and the waste liquid branch pipeline 204 is respectively connected with the temporary storage tank 105 and the waste liquid pipeline 203. Specifically, the second detector 402 detects the protein concentration of the waste liquid discharged from the tangential flow filtration module, where the protein concentration is obtained by detecting at least one of the conductivity value and the refractive index value of the harvest liquid, and if the waste liquid does not meet the requirements of the waste liquid, i.e. the waste liquid contains the target protein, the waste liquid flows into the temporary storage tank 105 through the waste liquid branch pipeline 204.
The waste liquid branch line 204 is connected to the waste liquid line 203 through a valve body, specifically, the waste liquid branch line 204 is communicated with the waste liquid line 203 through a second three-way valve, and the control device is electrically connected to the second three-way valve. It will be appreciated that the control means can operate the second three-way valve to communicate the waste line 203 with the waste branch line 204 or the second three-way valve to communicate the waste line 203 with the waste tank 103.
As an embodiment, the tangential flow filtration unidirectional system comprises a second return line 302, the second return line 302 being connected to the temporary storage tank 105 and the upper sample line 201, respectively. It will be appreciated that the reject from the holding tank 105 may be returned to the tangential flow filtration assembly via the second return line 302 and the upper sample line 201 for secondary filtration.
In the related art, after the sample solution is filtered once by the tangential flow filtration assembly, some target proteins with special structures may be mixed into the waste solution through the tangential flow filtration membrane package 104, so that the target proteins are lost, so that the present invention specifically designs the second detector 402 to check the protein concentration of the waste solution discharged from the tangential flow filtration assembly, determine whether the target proteins are mixed into the waste solution, and further designs the waste solution in the temporary storage tank 105 for secondary filtration.
Further, the tangential flow filtration unidirectional system comprises a third detector 403, the third detector 403 is electrically connected with the control device, the third detector 403 is connected with the temporary storage tank 105, the third detector 403 is used for detecting the protein concentration of the waste liquid in the temporary storage tank 105, and the protein concentration can be obtained according to at least one of the conductivity value and the refractive index value of the detected harvest liquid.
Referring to the figures, the tangential flow filtration unidirectional system comprises a second flow meter 502, the second flow meter 502 being connected to the waste branch 204, the second flow meter 502 being adapted to detect the volume of waste entering the holding tank 105. The control device can further obtain the amount of the target protein in the waste liquid by detecting the protein concentration obtained by the third detector 403 and the volume of the waste liquid obtained by detecting the second flowmeter 502, and if the amount of the target protein in the waste liquid exceeds a preset value, the waste liquid is filtered for the second time.
It will be appreciated that in the case where the waste liquid needs to be returned to the tangential flow filtration module via the second return line 302, the control device initiates the tangential flow filtration membrane package 104 of the corresponding specification to communicate with the upper sample line 201, based on the volume of the waste liquid and the molecular weight of the target protein detected by the second flow meter 502. Of course, in some examples, there is a case where the tangential flow filtration membrane package 104 with the corresponding specification of the volume of the waste liquid and the molecular weight of the target protein is identical to the specification of the tangential flow filtration membrane package 104 used in the first filtration, and in this case, the tangential flow filtration membrane package 104 in the tangential flow filtration unidirectional system is set to one as well.
In some examples, to make the detection by the third detector 403 more accurate, the temporary storage tank 105 is provided with a stirrer for stirring the waste liquid uniformly.
The second return line 302 is connected to the loading line 201 through a valve body, specifically, the second return line 302 is communicated with the loading line 201 through a third three-way valve, and the control device is electrically connected to the third three-way valve.
The following detailed description of the invention is of specific embodiments, it being noted that the following description is merely exemplary and is not intended to limit the invention in any way.
Example 1
The tangential flow filtration unidirectional system comprises a tangential flow filtration assembly comprising two tangential flow filtration membrane packages 104, a fluid reservoir 101, a harvest fluid reservoir 102, a waste fluid reservoir 103, a first return line 301, a first meter 401, and a control device, wherein the inlet split flow structure, the first outlet sink flow structure, and the second outlet sink flow structure are each configured as a three-way valve.
The control method for operating the tangential flow filtration unidirectional system comprises the following flow.
Inputting information of sample liquid in the liquid storage tank 101 to a control device, and switching an inlet flow distribution structure by the control device to start tangential flow of corresponding specifications through the filter membrane package 104, wherein the obtained harvest liquid and waste liquid are respectively discharged to the harvest liquid tank 102 and the waste liquid tank 103; the first detector 401 detects the protein concentration of the harvest liquid in the harvest liquid tank 102, and the control device receives the detection data of the first detector 401.
The control device compares the detection data obtained by the first detector 401 with a set value, if the protein concentration detected by the first detector 401 does not meet the requirement of the harvest liquid, the control device switches the first three-way valve, starts the first return pipeline 301 to be communicated with the upper sample pipeline 201, starts the tangential flow filter membrane package 104 corresponding to the volume of the harvest liquid and the molecular weight specification of the target protein, and returns the harvest liquid from the harvest liquid tank 102 to the tangential flow filter membrane package 104 of the corresponding specification for secondary filtration.
It will be appreciated that the process of the control method described above may be cycled until the protein concentration of the harvest is desired.
In other embodiments, the tangential flow filtration unidirectional system may be configured to further include a first flow meter 501, and the control device may determine the volume of harvest fluid in the harvest tank 102 based on the detection of the first flow meter 501.
Example two
The tangential flow filtration unidirectional system comprises a tangential flow filtration assembly comprising two tangential flow filtration membrane packages 104, wherein the inlet split flow structure, the first outlet manifold structure and the second outlet manifold structure are each configured as a three-way valve, a liquid storage tank 101, a harvest liquid tank 102, a waste liquid tank 103, a temporary storage tank 105, a waste liquid branch line 204, a second detector 402, a second return line 302, a third detector 403, and a control device.
The control method for operating the tangential flow filtration unidirectional system comprises the following flow.
Inputting information of sample liquid in the liquid storage tank 101 to a control device, and switching an inlet split flow structure by the control device to start tangential flow of corresponding specifications through the filter membrane package 104, and discharging the obtained harvest liquid to the harvest liquid tank 102; the second detector 402 detects the concentration of protein in the effluent discharged from the tangential flow filtration membrane pack 104, and the control device receives the detection data from the second detector 402.
The control device compares the detection data obtained by the second detector 402 with a set value: if the protein concentration detected by the second detector 402 does not meet the requirement of the waste liquid, the control device switches the second three-way valve, starts the waste liquid branch pipeline 204 to be communicated with the waste liquid pipeline 203, and discharges the waste liquid to the temporary storage tank 105; if the protein concentration detected by the second detector 402 meets the waste liquid requirement, the waste liquid pipeline 203 is communicated to the waste liquid tank 103, and the waste liquid is discharged to the waste liquid tank 103.
The control device starts the second return line 302 to communicate with the upper sample line 201, and the waste liquid in the temporary storage tank 105 is returned for secondary filtration. It is understood that the third detector 403 detects the protein concentration of the waste liquid in the temporary storage tank 105.
In other embodiments, the tangential flow filtration unidirectional system may be configured to further include a second flow meter 502. The second flow meter 502 is used to detect the volume of waste liquid entering the holding tank 105.
The control device can further obtain the amount of the target protein in the waste liquid by detecting the protein concentration obtained by the third detector 403 and the volume of the waste liquid obtained by detecting the second flowmeter 502, if the amount of the target protein in the waste liquid exceeds a preset value, the waste liquid is subjected to secondary filtration, and if the amount of the target protein in the waste liquid is small and does not exceed the preset value, secondary filtration is not needed.
In the case that the waste liquid needs to flow back to the tangential flow filtration assembly through the second return line 302, the control device starts the tangential flow filtration membrane package 104 with the corresponding specification according to the volume of the waste liquid and the molecular weight of the target protein detected by the second flowmeter 502, and the waste liquid in the temporary storage tank 105 flows back to the tangential flow filtration membrane package 104 with the corresponding specification.
Example III
The tangential flow filtration unidirectional system comprises a tangential flow filtration assembly comprising two tangential flow filtration membrane packages 104, wherein an inlet split flow structure, a first outlet manifold structure and a second outlet manifold structure are each configured as a three-way valve, a liquid storage tank 101, a harvest liquid tank 102, a waste liquid tank 103, a first return line 301, a first meter 401, a temporary storage tank 105, a waste liquid branch line 204, a second meter 402, a second return line 302, a third meter 403, and a control device.
It will be appreciated that in this case, the tangential flow filtration module may obtain harvest and reject, if not satisfactory, for secondary filtration of the harvest and reject, respectively.
In other embodiments, the tangential flow filtration unidirectional system may be configured to further comprise a first flow meter 501.
In the description of the present specification, if a description appears that makes reference to the term "one embodiment," "some examples," "some embodiments," "an exemplary embodiment," "an example," "a particular example," or "some examples," etc., it is intended that the particular feature, structure, material, or characteristic described in connection with the embodiment or example be included in at least one embodiment or example of the invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The embodiments of the present invention have been described in detail with reference to the drawings, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of one of ordinary skill in the art without departing from the spirit of the present invention.
In the description of the present invention, the terms "and" if used in the singular are intended to mean "and" as opposed to "or". For example, the patent name "a A, B" describes that what is claimed in the present invention is: a technical scheme with a subject name A and a technical scheme with a subject name B.
Claims (10)
1. A tangential flow filtration unidirectional system, characterized by: comprising
A tangential flow filtration assembly comprising a tangential flow filtration membrane package (104);
a liquid storage tank (101), wherein the liquid storage tank (101) is communicated with an inlet end of the tangential flow filtration assembly through an upper sampling pipe (201);
a harvest tank (102), the harvest tank (102) being in communication with an outlet end of the tangential flow filtration assembly via a drain line (202);
a waste liquid tank (103), the waste liquid tank (103) being in communication with an outlet end of the tangential flow filtration assembly via a waste liquid line (203);
-control means capable of switching on or off said tangential flow filtration membrane pack (104).
2. The tangential flow filtration unidirectional system of claim 1, wherein: the tangential flow filtration assembly comprises at least two tangential flow filtration membrane packages (104) with different specifications, the tangential flow filtration membrane packages (104) with different specifications are connected in parallel, and the control device opens the corresponding tangential flow filtration membrane packages (104) according to the volume of the sample liquid and the molecular weight of the target protein.
3. The tangential flow filtration unidirectional system of claim 1 or 2, wherein: the tangential flow filtration unidirectional system comprises a first backflow pipeline (301), a first detector (401) and a first flowmeter (501), wherein the first detector (401) is connected with the harvest liquid tank (102), the first backflow pipeline (301) is respectively connected with the harvest liquid tank (102) and the sampling pipeline (201), the first backflow pipeline (301) is connected with the sampling pipeline (201) through a valve body, and the first flowmeter (501) is connected with the liquid discharge pipeline (202).
4. The tangential flow filtration unidirectional system of claim 1 or 2, wherein: the tangential flow filtering unidirectional system comprises a temporary storage tank (105), a waste liquid branch pipeline (204) and a second detector (402), wherein the second detector (402) is connected with the waste liquid pipeline (203), the waste liquid branch pipeline (204) is respectively connected with the temporary storage tank (105) and the waste liquid pipeline (203), and the waste liquid branch pipeline (204) is connected with the waste liquid pipeline (203) through a valve body.
5. The tangential flow filtration unidirectional system of claim 4, wherein: the tangential flow filtration unidirectional system comprises a second return pipeline (302), the second return pipeline (302) is respectively connected with the temporary storage tank (105) and the sample loading pipeline (201), and the second return pipeline (302) is connected with the sample loading pipeline (201) through a valve body.
6. The tangential flow filtration unidirectional system of claim 5, wherein: the tangential flow filtration unidirectional system comprises a third meter (403), the third meter (403) being connected to the temporary storage tank (105).
7. The tangential flow filtration unidirectional system of claim 6, wherein: the tangential flow filtration unidirectional system includes a second flow meter (502), the second flow meter (502) being coupled to the waste branch line (204).
8. The tangential flow filtration unidirectional system of claim 1, wherein: the tangential flow filtration unidirectional system comprises a peristaltic pump (106), the peristaltic pump (106) being connected with the priming line (201).
9. A control method, characterized in that: the control method operating the tangential flow filtration unidirectional system of claim 3, the control method comprising
Inputting information of sample liquid in the liquid storage tank (101) to a control device, and starting the control device to flow through the filter membrane pack (104) tangentially;
a first detector (401) detects the protein concentration of the harvest liquid in the harvest liquid tank (102);
if the protein concentration detected by the first detector (401) does not meet the requirement of the harvest liquid, the control device starts the first return pipeline (301) to be communicated with the upper sampling pipeline (201), and starts the tangential flow filtration membrane package (104) corresponding to the volume of the harvest liquid and the molecular weight specification of the target protein, and the harvest liquid flows back to the tangential flow filtration membrane package (104) corresponding to the specification from the harvest liquid tank (102).
10. A control method, characterized in that: the control method operating the tangential flow filtration unidirectional system of claim 7, the control method comprising
Inputting information of sample liquid in the liquid storage tank (101) to a control device, and starting the control device to flow through the filter membrane pack (104) tangentially;
a second detector (402) for detecting the concentration of protein in the waste liquid discharged from the tangential flow filtration membrane pack (104);
if the protein concentration detected by the second detector (402) does not meet the waste liquid requirement, the control device starts the waste liquid branch pipeline (204) to be communicated with the waste liquid pipeline (203), and the waste liquid is discharged to the temporary storage tank (105);
the third detector (403) detects the protein concentration of the waste liquid in the temporary storage tank (105), the second flowmeter (502) detects the volume of the waste liquid flowing into the temporary storage tank, if the protein content in the waste liquid is not in a limited range, the control device starts the second backflow pipeline (302) to be communicated with the upper pipe line (201), and starts the tangential flow filter membrane package (104) with the corresponding specification, and the waste liquid in the temporary storage tank (105) flows back to the tangential flow filter membrane package (104) with the corresponding specification.
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| CN202211579496.3A CN116020189A (en) | 2022-12-08 | 2022-12-08 | Tangential flow filtration unidirectional system and control method |
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| CN202211579496.3A CN116020189A (en) | 2022-12-08 | 2022-12-08 | Tangential flow filtration unidirectional system and control method |
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| CN202211579496.3A Pending CN116020189A (en) | 2022-12-08 | 2022-12-08 | Tangential flow filtration unidirectional system and control method |
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