CN116593416A - Membrane adsorption and membrane interception on-line detection device in protein filtration process - Google Patents
Membrane adsorption and membrane interception on-line detection device in protein filtration process Download PDFInfo
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- 239000012528 membrane Substances 0.000 title claims abstract description 138
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 94
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 94
- 238000001914 filtration Methods 0.000 title claims abstract description 59
- 238000001179 sorption measurement Methods 0.000 title claims abstract description 55
- 238000001514 detection method Methods 0.000 title claims abstract description 30
- 239000007788 liquid Substances 0.000 claims abstract description 38
- 238000005374 membrane filtration Methods 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 24
- 239000002699 waste material Substances 0.000 claims abstract description 17
- 230000008569 process Effects 0.000 claims abstract description 11
- 239000012460 protein solution Substances 0.000 claims description 57
- 238000010521 absorption reaction Methods 0.000 claims description 11
- 238000002211 ultraviolet spectrum Methods 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 230000001276 controlling effect Effects 0.000 claims description 5
- 230000002572 peristaltic effect Effects 0.000 claims description 4
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 239000002033 PVDF binder Substances 0.000 claims description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 claims description 2
- 238000002835 absorbance Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 14
- 229940079593 drug Drugs 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 6
- 238000012216 screening Methods 0.000 abstract description 2
- 102000037865 fusion proteins Human genes 0.000 description 16
- 108020001507 fusion proteins Proteins 0.000 description 16
- 238000005070 sampling Methods 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 229940098773 bovine serum albumin Drugs 0.000 description 7
- 239000004696 Poly ether ether ketone Substances 0.000 description 5
- 229920002530 polyetherether ketone Polymers 0.000 description 5
- 230000008859 change Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012527 feed solution Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
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- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Immunology (AREA)
- Pathology (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
The invention provides an online detection device (20) for membrane adsorption and membrane entrapment in a protein filtration process, which comprises: the device comprises a liquid storage tank (1), a pump (2), a four-way valve (3), a membrane filtration module (4), an ultraviolet detector (5), a computer (6) and a waste liquid bottle (7). The invention also provides a method for detecting membrane adsorption and membrane interception in the protein filtering process, and the detection method adopts the detection device to detect. Compared with the prior art, the online detection device for membrane adsorption and membrane entrapment in the protein filtration process can effectively detect the real-time variation trend of the protein concentration after the protein drug filtration, can detect the membrane adsorption and membrane entrapment in the protein filtration process in real time, and can rapidly and efficiently judge the influence of the membrane adsorption and the membrane entrapment on a protein sample, so that the device can be rapidly, efficiently and conveniently used for screening the membrane materials and the operating conditions suitable for different protein drugs, and conveniently regulate and control the protein concentration and the activity of a final protein drug finished product within an acceptable range.
Description
Technical Field
The invention belongs to the field of bio-pharmaceuticals, and particularly relates to a membrane adsorption and membrane interception on-line detection device in a protein filtering process.
Background
Membrane filtration has been widely used in biopharmaceutical and food industries for the last decades. Sterilization and filtration are an indispensable step in the production process of protein drugs, however, the application of the sterilization and filtration is limited by membrane adsorption and interception, such as flux reduction, loss of active ingredients, and increase of operation cost. Membrane adsorption and entrapment are mainly caused by adsorption and rejection of substances on the membrane surface or deposition of substances in the membrane pores, and the degree of membrane adsorption and entrapment is largely dependent on the feed solution properties, membrane materials, operating conditions, and the like. Protein drugs often result in a change in protein concentration and loss of active ingredients after membrane filtration. Therefore, we need to build a membrane adsorption and membrane interception model to accurately and systematically screen out the suitable membrane materials and operation conditions of different protein drugs so as to conveniently regulate and control the protein concentration and activity of the final protein drug finished product within an acceptable range.
The general thinking of research of the existing biological medicine aiming at the sterilization and filtration technology is as follows: different filtration volumes are designed, sampling is carried out at multiple points, and the protein concentration after filtration of the different filtration volumes is measured. The detection method can rapidly judge whether the selected filter membrane has an influence on the concentration of the protein sample, but cannot rapidly and accurately judge whether the concentration reduction of the protein sample after filtration is caused by membrane adsorption or membrane interception, if the reason of the concentration reduction of the protein sample is explored, the filtration volume is required to be increased, and a plurality of sampling points are designed until the concentration of the protein after filtration maintains a steady state.
The method in the prior art comprises the following steps: direct bolus injection-direct bolus injection by syringe, the change in protein concentration before and after filtration is detected. The second method is as follows: manual collection method-power is applied by peristaltic pump, samples are collected by time, and protein concentration changes are measured. In the prior art, the sampling points are few, so that the membrane adsorption quantity and the membrane interception quantity cannot be accurately judged, and the manual demand is greatly increased when the sampling points are more. When the concentration of various protein samples is simultaneously examined according to various filter membrane manufacturers, materials and sizes, the sampling point is greatly increased, and the workload of manually sampling and measuring the protein concentration is also greatly increased.
Disclosure of Invention
In order to solve the problems in the prior art, the invention establishes a real-time atlas method, provides a membrane adsorption and membrane interception on-line detection device in the protein filtering process, calculates the protein concentration change condition by detecting the real-time ultraviolet absorption peak atlas of the filtered protein solution at the wavelength of 280nm (the ultraviolet absorption peak of the filtered protein solution at the wavelength of 280nm changes along with the filtering volume), and replaces manual sampling data analysis by an ultraviolet detector and computer real-time sampling measurement and data processing.
The specific technical scheme of the invention is as follows:
the invention provides a membrane adsorption and membrane entrapment on-line detection device (20) for a protein filtration process, which is characterized by comprising the following components: the device comprises a liquid storage tank (1), a pump (2), a four-way valve (3), a membrane filtration module (4), an ultraviolet detector (5), a computer (6) and a waste liquid bottle (7), wherein the liquid storage tank (1) is used for storing protein solution to be filtered, a protein inlet of the pump (2) is connected with the liquid storage tank (1), the pump (2) is used for extracting the protein solution to be filtered from the liquid storage tank (1) and controlling the flow rate of the protein solution to be filtered, a passage (3-1) of the four-way valve (3) is connected with a protein outlet of the pump (2), the four-way valve (3) is used for regulating the flow direction of the protein solution, a protein inlet of the membrane filtration module (4) is connected with a passage (3-2) of the four-way valve (3), the membrane filtration module (4) is used for filtering the protein solution, a protein inlet of the ultraviolet detector (5) is connected with a passage (3-4) of the four-way valve (3), the ultraviolet detector (5) is used for detecting the protein peak, the ultraviolet detector (5) is used for detecting the concentration of the protein solution (5) is calculated, and the concentration of the protein (5) is detected by the ultraviolet detector is used for calculating the concentration, the waste liquid bottle (7) is connected with the protein outlet of the ultraviolet detector (5), and the waste liquid bottle (7) is used for collecting protein waste liquid after the ultraviolet detector (5) is used for measuring.
The online detection device (20) for membrane adsorption and membrane interception in the protein filtering process provided by the invention has the technical characteristics that the liquid storage tank (1), the pump (2), the four-way valve (3), the membrane filtering module (4), the ultraviolet detector (5) and the waste liquid bottle (7) are connected through pipelines.
The online detection device (20) for membrane adsorption and membrane interception in the protein filtration process provided by the invention has the technical characteristics that the pump (2) is a peristaltic pump or a plunger pump.
The membrane adsorption and membrane interception on-line detection device (20) in the protein filtration process provided by the invention has the technical characteristics that the filter membrane used by the membrane filtration module (4) is a PES filter membrane, a PVDF filter membrane or a CA filter membrane.
The invention also provides a method for detecting the membrane adsorption and the membrane interception in the protein filtering process, which is characterized by adopting the device (20) for detecting the membrane adsorption and the membrane interception in the protein filtering process on line, and the method comprises the following steps: step S1, a membrane filtration module (4) is not required to be provided with a filter membrane, a protein solution to be filtered is filled into a liquid storage tank (1), a four-way valve (3) is adjusted to enable the protein solution to be filtered to sequentially flow to a passage (3-1) of the four-way valve (3), a passage (3-2) of the four-way valve (3), the membrane filtration module (4) without the filter membrane, a passage (3-3) of the four-way valve (3) and a passage (3-4) of the four-way valve (3), a pump (2) is opened until a pipeline is filled with the protein solution to be filtered, and a baseline of ultraviolet spectrum of an ultraviolet detector (5) is stable; step S2, adjusting the four-way valve (3) to enable the protein solution to be filtered to sequentially flow to a passage (3-1) of the four-way valve (3) and a passage (3-4) of the four-way valve (3), detecting an ultraviolet absorption peak of the protein solution which is not subjected to membrane filtration at a wavelength of 280nm by an ultraviolet detector (5), and then installing a filter membrane in a membrane filtration module (4); and S3, adjusting the four-way valve (3) to enable the protein solution to be filtered to sequentially flow to a passage (3-1) of the four-way valve (3), a passage (3-2) of the four-way valve (3), a membrane filtration module (4), a passage (3-3) of the four-way valve (3) and a passage (3-4) of the four-way valve (3), filtering the protein solution, and detecting an ultraviolet absorption peak of the protein solution after membrane filtration at a wavelength of 280nm by an ultraviolet detector (5).
The method for detecting membrane adsorption and membrane interception in the protein filtering process also has the technical characteristics that the method further comprises the following steps: step S0, deionized water washes all the pipelines until the ultraviolet spectrum of the ultraviolet detector (5) is stable at the base line.
Effects and effects of the invention
Compared with the prior art, the online detection device for membrane adsorption and membrane entrapment in the protein filtration process can effectively detect the real-time variation trend of the protein concentration after the protein drug filtration, can detect the membrane adsorption and membrane entrapment in the protein filtration process in real time, and can rapidly and efficiently judge the influence of the membrane adsorption and the membrane entrapment on a protein sample, so that the device can be rapidly, efficiently and conveniently used for screening the membrane materials and the operating conditions suitable for different protein drugs, and conveniently regulate and control the protein concentration and the activity of a final protein drug finished product within an acceptable range.
Drawings
FIG. 1 is a schematic diagram of the membrane adsorption and membrane entrapment on-line detection apparatus in the protein filtration process of example 1 of the present invention. In fig. 1: 20 is a membrane adsorption and membrane interception on-line detection device in the protein filtration process; 1 is a liquid storage tank; 2 is a pump; 3 is a four-way valve; 3-1, 3-2, 3-3, 3-4 are all passages of the four-way valve 3; 4 is a membrane filtration module; 5 is an ultraviolet detector; 6 is a computer; 7 is a waste liquid bottle.
FIG. 2 is a schematic representation of membrane adsorption and membrane entrapment of fusion proteins of example 1 of the present invention.
FIG. 3 is a schematic diagram of membrane adsorption and membrane entrapment of bovine serum albumin of example 2 of the present invention.
Detailed Description
The terms used in the present invention generally have meanings commonly understood by those of ordinary skill in the art unless otherwise indicated.
In the following examples, various processes and methods, which are not described in detail, are conventional methods well known in the art.
The reagents used in the examples below are commercially available in general, and the experimental procedures and conditions not noted are referred to in the art as conventional procedures and conditions.
Specific embodiments of the present invention will be described below with reference to examples and drawings.
Example 1 ]
In the embodiment, the membrane adsorption and the membrane interception in the fusion protein filtration process are detected by adopting a membrane adsorption and membrane interception on-line detection device in the protein filtration process.
FIG. 1 is a schematic diagram of the membrane adsorption and membrane entrapment on-line detection apparatus in the protein filtration process of example 1 of the present invention.
As shown in fig. 1, the on-line detection device 20 is composed of a liquid storage tank 1, a pump 2, a four-way valve 3, a membrane filtration module 4, an ultraviolet detector 5, a computer 6 and a waste liquid bottle 7.
Wherein the liquid storage tank 1 is used for storing a protein solution to be filtered.
The protein inlet of the pump 2 is connected with the liquid storage tank 1, the pump 2 is used for pumping the protein solution to be filtered from the liquid storage tank 1 and controlling the flow rate of the protein solution to be filtered, and the pump 2 in the embodiment is a peristaltic pump.
The passage 3-1 of the four-way valve 3 is connected with the protein outlet of the pump 2, and the four-way valve 3 is used for regulating and controlling the flow direction of the protein solution.
The protein inlet of the membrane filtration module 4 is connected with the passage 3-2 of the four-way valve 3, the protein outlet of the membrane filtration module 4 is connected with the passage 3-3 of the four-way valve 3, the membrane filtration module 4 is used for filtering protein solution, and the filter membrane used by the membrane filtration module 4 in the embodiment is a PES filter membrane.
The protein inlet of the ultraviolet detector 5 is connected to the passage 3-4 of the four-way valve 3, and the ultraviolet detector 5 is used for detecting an ultraviolet absorption peak of the protein solution to obtain the concentration of the protein solution.
A computer 6 is connected to the ultraviolet detector 5, and the computer 6 is configured to process the ultraviolet absorption peak signal of the protein solution detected by the ultraviolet detector 5 to calculate the concentration of the protein solution.
A waste liquid bottle 7 is connected with the protein outlet of the ultraviolet detector 5, and the waste liquid bottle 7 is used for collecting protein waste liquid after the ultraviolet detector 5 is used for measuring.
The liquid storage tank 1, the pump 2, the four-way valve 3, the membrane filtration module 4, the ultraviolet detector 5 and the waste liquid bottle 7 are connected through pipelines.
The membrane adsorption and membrane interception detection method in the fusion protein filtration process of the embodiment comprises the following steps:
step S0, washing all pipelines with deionized water until the base line of the ultraviolet spectrum of the ultraviolet detector 5 is stable, wherein the specific process is as follows:
and a filter membrane is not required to be installed in the membrane filter module 4, deionized water is filled into the liquid storage tank 1, the four-way valve 3 is adjusted to enable the deionized water to flush all pipelines, the pump 2 is turned on until the baseline of the ultraviolet spectrum of the ultraviolet detector 5 is stable, and the flow rate of the deionized water is controlled to be 1mL/min by the pump 2.
Step S1, a filter membrane is not required to be installed in the membrane filtration module 4, the fusion protein solution to be filtered is filled into the liquid storage tank 1, the four-way valve 3 is adjusted so that the fusion protein solution to be filtered flows to a passage 3-1 of the four-way valve 3, a passage 3-2 of the four-way valve 3, the membrane filtration module 4 without the filter membrane, a passage 3-3 of the four-way valve 3 and a passage 3-4 of the four-way valve 3 in sequence, the pump 2 is opened until a pipeline is filled with the fusion protein solution to be filtered, the ultraviolet spectrum baseline of the ultraviolet detector 5 is stable, the concentration of the fusion protein solution to be filtered is 1mg/mL, and the flow rate of the fusion protein solution is controlled to be 1mL/min by the pump 2.
Step S2, adjusting the four-way valve 3 to enable the fusion protein solution to be filtered to sequentially flow to a passage 3-1 of the four-way valve 3 and a passage 3-4 of the four-way valve 3, detecting an ultraviolet absorption peak of the fusion protein solution which is not subjected to membrane filtration at a wavelength of 280nm by the ultraviolet detector 5, and then installing a PES (polyether-ether-ketone) filter membrane in the membrane filtration module 4;
and S3, adjusting the four-way valve 3 to enable the fusion protein solution to be filtered to sequentially flow to a passage 3-1 of the four-way valve 3, a passage 3-2 of the four-way valve 3, a membrane filtration module 4, a passage 3-3 of the four-way valve 3 and a passage 3-4 of the four-way valve 3, filtering the protein solution, and detecting an ultraviolet absorption peak of the fusion protein solution after PES membrane filtration at a wavelength of 280nm by an ultraviolet detector 5.
FIG. 2 is a schematic representation of membrane adsorption and membrane entrapment of fusion proteins of example 1 of the present invention.
The membrane rejection (M) is calculated as follows:
M＝(1-C t /C 0 )×100％
wherein: c (C) 0 Is the concentration of the protein solution to be filtered; c (C) t To stabilize the protein concentration of the protein solution after filtration.
The calculation formula of the membrane adsorption amount q (t (n)) is as follows:
wherein q (t (n)) is the adsorption amount per square centimeter of the film when t (n); c (C) q Protein concentration when the concentration of the protein solution reaches stability after filtration; c (C) t(n) The concentration of the protein solution at time t (n); v is the flow rate; s is the membrane area.
The membrane rejection rate of fusion protein filtration obtained by calculation according to the formula is as follows: m= (1-254.621/256.654) ×100% =0.792), the membrane adsorption amount is: q= (0.892 mg/ml×0.4min×1mL/min×1000)/4.9 cm 2 ＝72.9μg/cm 2 。
Example 2 ]
In the embodiment, the membrane adsorption and the membrane interception in the protein filtration process are detected by adopting the on-line detection device for membrane interception and membrane adsorption in the bovine serum albumin filtration process.
The on-line detection device for membrane adsorption and membrane entrapment in the protein filtration process used in this example was the same as that in example 1.
The membrane adsorption and membrane entrapment detection method in the bovine serum albumin filtration process of this example was the same as that in example 1 except that the fusion protein solution in example 1 was replaced with bovine serum albumin solution.
FIG. 3 is a schematic diagram of membrane adsorption and membrane entrapment of bovine serum albumin of example 2 of the present invention.
The membrane rejection of the bovine serum albumin filter was calculated as in the formula of example 1: m= (1-95.029/111.355) ×100% =14.66), the film adsorption amount is: q= (0.315 mg/mL. Times.1.3 min. Times.1 mL/min. Times.1000)/4.9 cm 2 ＝83.6μg/cm 2 。
In conclusion, different proteins have membrane adsorption effect, and when the membrane loading is achieved, the saturated state is achieved, the proteins are not adsorbed any more, and when the total amount of the proteins is large, the membrane adsorption is not obviously influenced. The different protein has larger membrane retention rate difference, the membrane retention rate of the fusion protein is smaller (approaching 0.5%), the membrane retention rate of the bovine serum albumin is larger (approaching 15%), and the whole protein concentration change can be greatly influenced when the membrane retention rate is larger.
Therefore, the online detection device for membrane adsorption and membrane interception in the protein filtration process can effectively detect the real-time variation trend of the protein concentration of the protein drug after filtration, can rapidly and efficiently judge the influence of the membrane adsorption and the membrane interception on a protein sample, can rapidly, efficiently and conveniently screen the membrane materials and the operation conditions suitable for different protein drugs, and is convenient to regulate and control the protein concentration and the activity of a final protein drug finished product within an acceptable range.
The foregoing is a detailed description of the embodiments, convenient those skilled in the art are able to make and use the present invention. Those skilled in the art, based on the present invention, should not be subjected to innovative work, but rather should be able to obtain improvements or modifications by means of analysis, analogies or limited enumeration, etc. within the scope of protection defined by the following claims.
Claims (6)
1. An on-line detection device (20) for membrane adsorption and membrane entrapment in a protein filtration process, comprising: a liquid storage tank (1), a pump (2), a four-way valve (3), a membrane filtration module (4), an ultraviolet detector (5), a computer (6) and a waste liquid bottle (7),
wherein the liquid storage tank (1) is used for storing protein solution to be filtered,
the protein inlet of the pump (2) is connected with the liquid storage tank (1), the pump (2) is used for extracting the protein solution to be filtered from the liquid storage tank (1) and controlling the flow rate of the protein solution to be filtered,
the passage (3-1) of the four-way valve (3) is connected with the protein outlet of the pump (2), the four-way valve (3) is used for regulating and controlling the flow direction of protein solution,
the protein inlet of the membrane filtration module (4) is connected with the passage (3-2) of the four-way valve (3), the protein outlet of the membrane filtration module (4) is connected with the passage (3-3) of the four-way valve (3), the membrane filtration module (4) is used for filtering protein solution,
the protein inlet of the ultraviolet detector (5) is connected with the passage (3-4) of the four-way valve (3), the ultraviolet detector (5) is used for detecting the ultraviolet absorption peak of the protein solution so as to obtain the concentration of the protein solution,
said computer (6) is connected to said ultraviolet detector (5), the computer (6) is adapted to process the ultraviolet absorbance peak signal of the protein solution detected by said ultraviolet detector (5) to calculate the concentration of the protein solution,
the waste liquid bottle (7) is connected with the protein outlet of the ultraviolet detector (5), and the waste liquid bottle (7) is used for collecting protein waste liquid after the detection of the ultraviolet detector (5) is completed.
2. The membrane adsorption and membrane entrapment on-line detection apparatus (20) for a protein filtration process according to claim 1, wherein,
the liquid storage tank (1), the pump (2), the four-way valve (3), the membrane filtration module (4), the ultraviolet detector (5) and the waste liquid bottle (7) are connected through a pipeline.
3. The membrane adsorption and membrane entrapment on-line detection apparatus (20) for a protein filtration process according to claim 1, wherein,
wherein the pump (2) is a peristaltic pump or a plunger pump.
4. The membrane adsorption and membrane entrapment on-line detection apparatus (20) for a protein filtration process according to claim 1, wherein,
wherein the filter membrane used by the membrane filter module (4) is a PES filter membrane, a PVDF filter membrane or a CA filter membrane.
5. A method for detecting membrane adsorption and membrane entrapment in a protein filtration process, characterized in that the method for detecting membrane adsorption and membrane entrapment in a protein filtration process in an on-line detection apparatus (20) according to any one of claims 1 to 4 comprises the steps of:
step S1, a filter membrane is not required to be installed in the membrane filtration module (4), the protein solution to be filtered is filled into the liquid storage tank (1), the four-way valve (3) is adjusted to enable the protein solution to be filtered to sequentially flow to a passage (3-1) of the four-way valve (3), a passage (3-2) of the four-way valve (3), the membrane filtration module (4) without the filter membrane, the passage (3-3) of the four-way valve (3) and the passage (3-4) of the four-way valve (3), the pump (2) is opened until a pipeline is filled with the protein solution to be filtered, and the ultraviolet spectrum baseline of the ultraviolet detector (5) is stable;
step S2, adjusting the four-way valve (3) to enable the protein solution to be filtered to sequentially flow to a passage (3-1) of the four-way valve (3) and a passage (3-4) of the four-way valve (3), detecting an ultraviolet absorption peak of the protein solution which is not subjected to membrane filtration at a wavelength of 280nm by the ultraviolet detector (5), and then installing a filter membrane in the membrane filtration module (4);
and S3, adjusting the four-way valve (3) to enable the protein solution to be filtered to sequentially flow to a passage (3-1) of the four-way valve (3), a passage (3-2) of the four-way valve (3), the membrane filtration module (4), the passage (3-3) of the four-way valve (3) and the passage (3-4) of the four-way valve (3), filtering the protein solution, and detecting an ultraviolet absorption peak of the protein solution after membrane filtration at a wavelength of 280nm by the ultraviolet detector (5).
6. The method for detecting membrane adsorption and membrane entrapment in a protein filtration process according to claim 5, wherein the step S1 is preceded by:
step S0, deionized water washes all pipelines until the ultraviolet spectrum of the ultraviolet detector (5) is stable at the base line.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310362622.8A CN116593416A (en) | 2023-04-07 | 2023-04-07 | Membrane adsorption and membrane interception on-line detection device in protein filtration process |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202310362622.8A CN116593416A (en) | 2023-04-07 | 2023-04-07 | Membrane adsorption and membrane interception on-line detection device in protein filtration process |
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