CN117463184A - Mixed transfer device, antibody coupling reaction device using same and antibody coupling filtration system - Google Patents
Mixed transfer device, antibody coupling reaction device using same and antibody coupling filtration system Download PDFInfo
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- CN117463184A CN117463184A CN202311429237.7A CN202311429237A CN117463184A CN 117463184 A CN117463184 A CN 117463184A CN 202311429237 A CN202311429237 A CN 202311429237A CN 117463184 A CN117463184 A CN 117463184A
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- 238000005859 coupling reaction Methods 0.000 title claims abstract description 66
- 238000012546 transfer Methods 0.000 title claims abstract description 52
- 238000001914 filtration Methods 0.000 title claims abstract description 18
- 230000008878 coupling Effects 0.000 title claims abstract description 17
- 238000010168 coupling process Methods 0.000 title claims abstract description 17
- 239000007788 liquid Substances 0.000 claims abstract description 113
- 238000002156 mixing Methods 0.000 claims abstract description 74
- 239000012528 membrane Substances 0.000 claims description 21
- 230000031018 biological processes and functions Effects 0.000 claims description 16
- 239000003053 toxin Substances 0.000 claims description 8
- 231100000765 toxin Toxicity 0.000 claims description 8
- 239000002699 waste material Substances 0.000 claims description 7
- 238000009826 distribution Methods 0.000 claims description 6
- 230000000149 penetrating effect Effects 0.000 claims description 2
- 238000003756 stirring Methods 0.000 abstract description 9
- 230000008901 benefit Effects 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 4
- 238000004140 cleaning Methods 0.000 abstract description 2
- 238000003760 magnetic stirring Methods 0.000 abstract description 2
- 238000010008 shearing Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 17
- 239000007853 buffer solution Substances 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
- 230000002572 peristaltic effect Effects 0.000 description 7
- 108700012359 toxins Proteins 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 4
- 238000010586 diagram Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000000108 ultra-filtration Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/60—Pump mixers, i.e. mixing within a pump
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F33/00—Other mixers; Mixing plants; Combinations of mixers
- B01F33/80—Mixing plants; Combinations of mixers
- B01F33/836—Mixing plants; Combinations of mixers combining mixing with other treatments
- B01F33/8362—Mixing plants; Combinations of mixers combining mixing with other treatments with chemical reactions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/71—Feed mechanisms
- B01F35/712—Feed mechanisms for feeding fluids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/71—Feed mechanisms
- B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
- B01F35/7174—Feed mechanisms characterised by the means for feeding the components to the mixer using pistons, plungers or syringes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
- B01F35/71—Feed mechanisms
- B01F35/717—Feed mechanisms characterised by the means for feeding the components to the mixer
- B01F35/7176—Feed mechanisms characterised by the means for feeding the components to the mixer using pumps
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/34—Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Water Supply & Treatment (AREA)
- Analytical Chemistry (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
Abstract
The invention discloses a hybrid transfer device, an antibody coupling reaction device using the hybrid transfer device and an antibody coupling filtration system. The mixing transfer device comprises a shell, a driving motor, a plunger rod, a mixing cavity, a liquid inlet pipeline and a liquid outlet pipeline, wherein a pump head is arranged at one end of the shell, an output shaft of the driving motor is connected with a sloping cam plate through a coupling, the driving motor, the coupling and the sloping cam plate are all located in the shell, one end of the plunger rod is arranged in the sloping cam plate, a plunger diaphragm is arranged at the other end of the plunger rod, the mixing cavity is arranged in the pump head, the liquid inlet pipeline is connected with the mixing cavity through a Y-shaped connecting pipeline, and the liquid outlet pipeline is connected with the mixing cavity. The mixing transfer device adopts the mixing cavity, and transfers liquid through positive and negative pressure of the plunger diaphragm, so that compared with the traditional magnetic stirring, the mixing transfer device has the advantages of low shearing force, no limitation of stirring volume, higher stirring efficiency, capability of completely transferring materials and easiness in cleaning.
Description
Technical Field
The invention relates to the field of bio-pharmaceuticals, in particular to a mixed transfer device, an antibody coupling reaction device using the same and an antibody coupling filtration system.
Background
In the field of biopharmaceuticals, quaternary plunger diaphragm pumps or peristaltic pumps are all of a relatively common structure, wherein the peristaltic pumps deliver feed liquid by pulsating extrusion of silicone tubing. In peristaltic pumps, liquid is pumped out by connecting a pipeline, a container or a clamp through a silica gel pipe and extruding the silica gel pipe through a pump head, and liquid reflux is often generated at the moment of release due to the fact that a runner of the peristaltic pump needs to be released alternately, so that discharged liquid is suddenly reduced, a peristaltic pump is used for conveying pulses, and the flow speed range is limited by a pump pipe; in particular, when the pump is placed downstream of the container or vessel, cavitation, vacuum and flowability problems are inevitably created, cavitation and unstable flow conditions are created, resulting in low flowability and killing or destroying cells in the vessel.
At present, the above problems are generally solved by using an ADC coupling or ultrafiltration cycle, however, the existing ADC coupling or ultrafiltration cycle uses a disposable stirring bag device, which is configured with a 3D stirring bag and a double-jacketed bracket, different components are added by a peristaltic pump to mix the liquid in the stirring bag and uniformly mixed by a magnetic stirrer at the bottom, and the mixing mode has a disadvantage in that it has a limitation of minimum stirring volume.
Disclosure of Invention
In order to solve the problems, the invention provides a mixed transfer device, an antibody coupling reaction device and an antibody coupling filtration system using the same.
According to an aspect of the present invention, there is provided a hybrid transfer device, and an antibody coupling reaction device and an antibody coupling filtration system using the same, comprising:
a casing, one end of which is provided with a pump head;
the output shaft of the driving motor is connected with a sloping cam plate through a coupler, and the driving motor, the coupler and the sloping cam plate are all positioned in the shell;
the plunger rod, one end of the plunger rod is installed in the sloping cam plate, another end is provided with the plunger diaphragm;
the mixing cavity is arranged in the pump head;
the liquid inlet pipeline is connected with the mixing cavity through a Y-shaped connecting pipeline;
the liquid outlet pipeline is connected with the mixing cavity;
the two branch pipelines of the Y-shaped connecting pipeline are respectively connected with the mixing cavity and the liquid inlet pipeline and are respectively provided with one-way valves, and the main pipeline of the Y-shaped connecting pipeline is connected with the plunger diaphragm.
In some embodiments, a distributor plate is disposed on the outer side of the swash plate, and the other end of the plunger rod and the plunger diaphragm are both located inside the distributor plate. The advantage is that the way of mounting the plunger rod and the plunger membrane is further described.
In some embodiments, the plunger rod, the plunger diaphragm, the liquid inlet conduit, and the Y-connection conduit are all four and evenly distributed around the mixing chamber. The method has the advantage that the number and distribution of the partial related structure pairs are described.
In some embodiments, the liquid outlet pipes have four liquid outlet pipes, and each liquid outlet pipe and each liquid inlet pipe are distributed at intervals around the mixing cavity. The beneficial effect is that the number and distribution mode of the liquid outlet pipelines are described.
According to an aspect of the present invention, there is provided an antibody coupling reaction apparatus to which the above-described hybrid transfer apparatus is applied, comprising:
one said mixing transfer device, one control box and one biological process bag, said mixing transfer device is installed in said control box and said pump head is exposed to the outside;
the top of the pump head is provided with a first liquid inlet pipeline, and the top of the first liquid inlet pipeline is connected with the lower end of the biological process bag through a detachable sanitary valve;
the pump head is provided with a second liquid inlet pipeline and a third liquid inlet pipeline, and the second liquid inlet pipeline and the third liquid inlet pipeline are perpendicular to the outer side face of the pump head;
the bottom of the pump head is provided with a first liquid outlet pipeline, the side surface of the pump head is provided with a second liquid outlet pipeline, and the second liquid outlet pipeline is connected with the upper end of the biological process bag through a hose.
In some embodiments, the removable sanitary valve comprises an EC female head and an EC male head, and the EC female head and the EC male head are connected by a TC clip. The detachable sanitary valve has the advantages that the specific structure of the detachable sanitary valve is described.
In some embodiments, the second feed line is 1/4Barb and the third feed line is 3/4Barb. The beneficial point is that the specific conditions of the second liquid inlet pipeline and the third liquid inlet pipeline are further described.
According to an aspect of the present invention, there is provided an antibody-coupled filtration system to which the above-described antibody-coupled reaction apparatus is applied, comprising:
two of the antibody coupling reaction apparatuses, wherein,
the second liquid inlet pipeline of the first antibody coupling reaction device is connected with a toxin container, the third liquid inlet pipeline is connected with a liquid inlet main pipeline, a plurality of feed pumps are connected to the liquid inlet main pipeline, and pipe clamp valves are arranged between the feed pumps and the liquid inlet main pipeline;
the first liquid outlet pipeline of the first antibody coupling reaction device is connected with the top of the biological process bag of the second antibody coupling reaction device through a circulating pipeline;
the second liquid outlet pipeline of the second antibody coupling reaction device is connected with the inlet end of a membrane bag, the top end of the biological process bag is connected with the detention end of the membrane bag through a detention pipeline, and the penetrating end of the membrane bag is connected with a waste discharge pipeline.
In some embodiments, a solution delivery line is also connected to the hold-up line. The beneficial effect is that the solution conveying pipeline can be used for inputting buffer solution into the biological process bag for volume fixing.
In some embodiments, the first outlet conduit of a second one of the antibody-coupled reaction devices is connected to a collection device. It is advantageous to provide a collection device for the filtered solution.
Drawings
FIG. 1 is a schematic cross-sectional view of a hybrid transfer device, an antibody coupling reaction device and an antibody coupling filtration system using the same according to an embodiment of the present invention;
FIG. 2 is a schematic diagram of a pump head of the mixing transfer device of FIG. 1;
FIG. 3 is a schematic structural diagram of an antibody coupling reaction apparatus to which the hybrid transfer apparatus shown in FIG. 1 is applied;
fig. 4 is a schematic diagram of an antibody-coupled filtration system to which the antibody-coupled reaction apparatus shown in fig. 3 is applied.
In the figure: the mixing transfer device 100, a shell 1, a pump head 2, a driving motor 3, a coupler 4, a swash plate 5, a plunger rod 6, a plunger diaphragm 7, a mixing cavity 8, a liquid inlet pipeline 9, a Y-shaped connecting pipeline 10, a liquid outlet pipeline 11, a one-way valve 12, a distribution plate 13, an antibody coupling reaction device 200, a control box 21, a biological process bag 22, a first liquid inlet pipeline 23, a detachable sanitary valve 24, an EC female head 241, an EC male head 242, a TC clamp 243, a second liquid inlet pipeline 25, a third liquid inlet pipeline 26, a first liquid outlet pipeline 27, a second liquid outlet pipeline 28, a hose 29, a toxin container 31, a liquid inlet main pipeline 32, a feed pump 33, a circulating pipeline 34, a membrane bag 35, a retention pipeline 36, a waste discharge pipeline 37 and a solution conveying pipeline 38.
Detailed Description
The invention is described in further detail below with reference to the accompanying drawings.
As shown in fig. 1-2, the mixing transfer device 100 is comprised primarily of a housing 1 in appearance, with a pump head 2 mounted at one end of the housing 1.
A driving motor 3, a coupling 4 and a swash plate 5 are sequentially arranged on the housing 1, wherein an output shaft of the driving motor 3 is connected with the swash plate 5 through the coupling 4, and the swash plate 5 can be driven to rotate through the coupling 4 during operation.
A distributor plate 13 is provided on the side of the swash plate 5 remote from the drive motor 3 (referred to as the outer side), and plunger rods 6 are installed in the swash plate 5 and the distributor plate 13. Wherein one end of the plunger rod 6 is mounted in the swash plate 5 and the other end extends into the distributor plate 13 and is provided with a plunger membrane 7.
A mixing chamber 8 is provided inside the pump head 2, and the mixing chamber 8 is connected to a liquid inlet pipe 9 through a Y-shaped connecting pipe 10, which can be fed with liquid from the outside. Wherein, Y type connecting tube has a trunk line and two lateral lines, and the trunk line is connected with plunger diaphragm 7 and is provided with the sealing washer with distributing plate 13 between, and two lateral lines are then connected with mixing chamber 8 and feed liquor pipeline 9 respectively to all be provided with check valve 12 on two lateral lines, ensure that liquid can only flow from feed liquor pipeline 9 to mixing chamber 8.
In addition, the mixing chamber 8 is connected with a liquid outlet pipe 11 which can be used for discharging liquid according to the requirement.
Preferably, the plunger rod 6, the plunger membrane 7, the liquid inlet pipe 9, the Y-shaped connecting pipe 10 and the liquid outlet pipe 11 are all four and uniformly distributed around the mixing chamber 8, and each liquid outlet pipe 11 and each liquid inlet pipe 9 can be distributed at intervals around the mixing chamber 8.
When the mixing transfer device 100 is used, the driving motor 3 operates and drives the swash plate 5 to move through the coupler 4, so that radial force is applied to the distribution plate 13 and the plunger rod 6 is driven to move radially, and then the plunger membrane 7 is driven to generate positive and negative pressure, so that the plunger membrane 7 can move to two sides repeatedly. At this time, when the solution is fed from the liquid feed pipe 9, the solution enters the branch pipe of the Y-shaped connecting pipe 10 connected with the mixing chamber 8 when the plunger diaphragm 7 moves to the side where the plunger rod 6 is located; when the plunger diaphragm 7 moves to the side of the Y-shaped connecting pipe 10, the solution is pressed into the mixing chamber 8.
In addition, when the solution is required to be discharged, the liquid outlet pipe 11 is opened, and the plunger diaphragm 7 is moved to the side where the Y-shaped connecting pipe 10 is located, so that the solution in the mixing chamber 8 can be discharged through the liquid outlet pipe 11.
As shown in fig. 3, the antibody coupling reaction apparatus 200 includes a control box 21 and a bio-process bag 22, wherein a mixing transfer apparatus 100 is installed in the control box 21 and a pump head 2 of the mixing transfer apparatus 100 is exposed to the outside, and the bio-process bag 22 is a bottle or a stainless steel can.
The top of the pump head 2 is provided with a first inlet pipe 23, wherein the top of the first inlet pipe 23 is connected to the lower end of the bioprocess bag 22 by a detachable sanitary valve 24.
Preferably, the removable sanitary valve 24 includes an EC female head 241 and an EC male head 242, and the EC female head 241 and the EC male head 242 are connected by a TC clip 243. Wherein, the EC female head 241 is connected to the lower end of the biological process bag 22, and the EC male head 242 is connected to the first liquid inlet pipe 23.
The pump head 2 is further provided with a second liquid inlet pipeline 25 and a third liquid inlet pipeline 26, wherein the second liquid inlet pipeline 25 and the third liquid inlet pipeline 26 are perpendicular to the side surface (called the outer side surface) of the pump head 2, which is far away from the control box 21, the second liquid inlet pipeline 25 adopts 1/4Barb, and the third liquid inlet pipeline 26 adopts 3/4Barb.
The bottom of the pump head 2 is provided with a first liquid outlet pipe 27, and the opening end of the first liquid outlet pipe 27 is downward.
The side of the pump head 2 is also provided with a second liquid outlet pipe 28, the second liquid outlet pipe 28 is connected with the upper end of the biological process bag 22 through a hose 29, and a PH and conductivity monitoring flow cell is arranged between the second liquid outlet pipe 28 and the hose 29, so that PH and conductivity of the solution can be collected and transmitted to an information processor in the control box 21 for processing.
As shown in fig. 4, the antibody-coupled filtration system includes two antibody-coupled reaction devices 200, and both antibody-coupled reaction devices 200 have a mixed transfer device 100 and a bioprocess bag 22.
The second liquid inlet pipe 25 connected to the mixing transfer device 100 of the first antibody coupling reaction device 200 is connected to a toxin container 31 containing small molecule toxins, the third liquid inlet pipe 26 is connected to a main liquid inlet pipe 32, a plurality of feed pumps 33 are connected to the main liquid inlet pipe 32, and pinch valves are provided between each feed pump 33 and the main liquid inlet pipe 32. Wherein each feed pump typically employs peristaltic pumps and is used to feed different solvents, respectively, four feed pumps are provided in fig. 4 for feeding buffer solution, mAb, linker (Linker) and inhibitor, respectively.
In addition, the first liquid outlet pipe 27 connected to the mixing transfer device 100 of the first antibody-coupling reaction device 200 is connected to the top of the bioprocess bag 22 of the second antibody-coupling reaction device 200 through a circulation pipe 34.
The second liquid outlet pipe 27 connected to the mixing transfer device 100 of the second antibody coupling reaction device 200 is connected to a membrane pack 35, wherein the membrane pack 35 has an inlet end, a retention end and a permeation end, and the second liquid outlet pipe 27 is connected to the inlet end of the membrane pack 35 and is provided with a pinch valve and a pressure sensor, respectively, on the connection pipe; the top end of the biological process bag 22 is also connected with the retention end of the membrane bag 35 through a retention pipeline 36, a valve, a pressure sensor and a flow sensor are arranged on the retention pipeline 36, and a solution conveying pipeline 38 is also connected with the retention pipeline 36, and a buffer solution can be input through the solution conveying pipeline 37 by using a pump.
In addition, a waste discharge pipe 37 is connected to the permeate end of the membrane pack 35, and a pressure sensor, a flow sensor, a UV sensor, and a valve are provided on the waste discharge pipe 37.
Preferably, the first outlet pipe 26 connected to the mixing transfer device 100 of the second antibody coupling reaction device 200 is connected to a collecting device (not shown).
The use of the antibody-coupled filtration system involves a major step, each as described below.
Step one: and (3) filling the Buffer solution. The Buffer solution is conveyed into the mixing cavity 8 of the mixing transfer device 100 of the first antibody coupling reaction device 200 through the corresponding feeding pump 33, and after a specified amount is reached, the corresponding pinch valve is closed, and then the Buffer solution is conveyed into the biological process bag 22 through the second liquid outlet pipeline 28 connected to the mixing transfer device 100;
step two: injection of antibodies. The mAb is delivered by the corresponding feed pump 33 into the mixing chamber 8 of the mixing transfer device 100 of the first antibody-coupled reaction device 200 and after a defined amount is reached, the corresponding pinch valve is closed and then delivered to the bioprocess bag 22 via the second outlet conduit 28 connected to the mixing transfer device 100.
Step three: and (5) injecting a connector. The connector is fed by means of a corresponding feed pump 33 into the mixing chamber 8 of the mixing transfer device 100 of the first antibody-coupling reaction device 200, and after a defined amount has been reached, the corresponding pinch valve is closed and then fed via a second outlet line 28 connected to the mixing transfer device 100 into the bioprocess bag 22.
Step four: small molecule toxin injection. The small molecular toxins in the toxin container 31 are injected into the mixing chamber 8 of the mixing transfer device 100 of the first antibody-coupled reaction device 200 through the second liquid inlet pipe 25, and after a prescribed amount is reached, the corresponding pinch valve is closed, and then transferred into the bioprocess bag 22 through the second liquid outlet pipe 28 connected to the mixing transfer device 100.
Step five: and (3) reacting. The bioprocess bag 22 of the first antibody-coupling reaction apparatus 200 and the mixing chamber 8 of the mixing transfer apparatus 100 are respectively communicated with each other through the first liquid inlet pipe 23 and the second liquid outlet pipe 28 and the hose 29 to form a circulation, so that the mixed solution therein circulates between the bioprocess bag 22 and the mixing chamber 8 to achieve a sufficient reaction.
Step six: inhibitor injection. Is fed into the mixing chamber 8 of the mixing transfer device 100 of the first antibody-coupled reaction device 200 by means of the corresponding feed pump 33, and after a defined amount has been reached, closes the corresponding pinch valve and is then fed into the bioprocess bag 22 via the second outlet conduit 28 connected to the mixing transfer device 100.
Step seven: quenching. The bioprocess bag 22 of the first antibody-coupled reaction apparatus 200 and the mixing chamber 8 of the mixing transfer apparatus 100 are again communicated and circulated, and the inhibitor is mixed with the mixed solution and circulated.
Step eight: and (5) sterilizing and filtering. The first outlet pipe 27 of the first antibody-coupled reaction apparatus 200 is opened, and the reacted solution is entirely fed into the bioprocess bag 22 of the second antibody-coupled reaction apparatus 200 through the circulation pipe 34, and then the solution is transferred into the membrane bag 35 through the mixing transfer apparatus 100 thereof, and then transferred back into the bioprocess bag 22 through the retention pipe 36 by the membrane bag 35, thereby forming circulation filtration to achieve concentration effect, and the filtered waste liquid is discharged through the waste discharge pipe 37.
Step nine: and (5) constant volume. At the same time as the recirculation filtration, buffer solution is delivered to bioprocess bag 22 through solution delivery line 38 until the solution therein reaches the desired concentration.
Step ten: and (5) collecting. The solution in the bioprocess bag 22 is fed into the mixing transfer device 100 and transferred through the first outlet conduit 26 to the collection device for collection.
The mixed transfer device and the antibody coupling reaction device and the antibody coupling filtration system using the same have the following beneficial effects:
1. a special feeding pump and a main circulating pump are designed at the inlet of the pump to perform proportioning feeding, and materials immediately enter a pump cavity to be mixed to be similar to an online liquid preparation mechanism after being added, so that the stability of the concentration of the materials can be maintained compared with the traditional titration mode;
2. the mixing cavity is adopted, liquid is transferred through positive and negative pressure of the plunger diaphragm, and compared with the traditional magnetic stirring, the stirring device has the advantages of low shearing force, no limitation of stirring volume, higher stirring efficiency, capability of completely transferring materials and easiness in cleaning.
What has been described above is merely some embodiments of the present invention. It will be apparent to those skilled in the art that various modifications and improvements can be made without departing from the spirit of the invention.
Claims (10)
1. A hybrid transfer device, characterized by: the mixing transfer device (100) comprises
A shell (1), wherein one end of the shell (1) is provided with a pump head (2);
the driving motor (3), the output shaft of the driving motor (3) is connected with a sloping cam plate (5) through a coupling (4), and the driving motor (3), the coupling (4) and the sloping cam plate (5) are all positioned in the shell (1);
a plunger rod (6), wherein one end of the plunger rod (6) is arranged in the swash plate (5), and the other end of the plunger rod is provided with a plunger diaphragm (7);
a mixing chamber (8), the mixing chamber (8) being arranged inside the pump head (2);
the liquid inlet pipeline (9), the liquid inlet pipeline (9) is connected with the mixing cavity (8) through a Y-shaped connecting pipeline (10);
the liquid outlet pipeline (11), the liquid outlet pipeline (11) is connected with the mixing cavity (8);
the two branch pipelines of the Y-shaped connecting pipeline (10) are respectively connected with the mixing cavity (8) and the liquid inlet pipeline (9) and are respectively provided with one-way valves (12), and the main pipeline of the Y-shaped connecting pipeline (10) is connected with the plunger diaphragm (7).
2. A mixing transfer device according to claim 1, wherein: the outer side surface of the swash plate (5) is provided with a distribution plate (13), and the other end of the plunger rod (6) and the plunger membrane (7) are both positioned in the distribution plate (13).
3. A mixing transfer device according to claim 1, wherein: the plunger rod (6), the plunger membrane (7), the liquid inlet pipeline (9) and the Y-shaped connecting pipeline (10) are four and uniformly distributed around the mixing cavity (8).
4. A mixing transfer device according to claim 3, wherein: the liquid outlet pipelines (11) are four, and the liquid outlet pipelines (11) and the liquid inlet pipelines (9) are distributed at intervals around the mixing cavity (8).
5. An antibody coupling reaction apparatus to which the mixed transfer apparatus according to any one of claims 1 to 4 is applied, characterized in that: the antibody coupling reaction device (200) comprises one mixing transfer device (100), one control box (21) and one biological process bag (22), wherein the mixing transfer device (100) is arranged in the control box (21) and the pump head (2) is exposed to the outside;
the top of the pump head (2) is provided with a first liquid inlet pipeline (23), and the top of the first liquid inlet pipeline (23) is connected with the lower end of the biological process bag (22) through a detachable sanitary valve (24);
the pump head (2) is provided with a second liquid inlet pipeline (25) and a third liquid inlet pipeline (26), and the second liquid inlet pipeline (25) and the third liquid inlet pipeline (26) are perpendicular to the outer side surface of the pump head (2);
the bottom of the pump head (2) is provided with a first liquid outlet pipeline (27), the side surface of the pump head is provided with a second liquid outlet pipeline (28), and the second liquid outlet pipeline (28) is connected with the upper end of the biological process bag (22) through a hose (29).
6. An antibody coupling reaction apparatus using a hybrid transfer device according to claim 5, wherein: the detachable sanitary valve (24) comprises an EC female head (241) and an EC male head (242), and the EC female head (241) and the EC male head (242) are connected by a TC clamp (243).
7. An antibody coupling reaction apparatus using a hybrid transfer device according to claim 5, wherein: the second liquid inlet pipeline (25) adopts 1/4Barb, and the third liquid inlet pipeline (26) adopts 3/4Barb.
8. An antibody-coupled filtration system to which the antibody-coupled reaction apparatus according to claim 5 is applied, characterized in that: comprising two of said antibody coupling reaction devices (200), wherein,
the second liquid inlet pipeline (25) of the first antibody coupling reaction device (200) is connected with a toxin container (31), the third liquid inlet pipeline (26) is connected with a liquid inlet main pipeline (32), a plurality of feeding pumps (33) are connected to the liquid inlet main pipeline (32), and a pipe clamping valve is arranged between each feeding pump (33) and the liquid inlet main pipeline (32);
the first liquid outlet pipeline (27) of the first antibody coupling reaction device (200) is connected with the top of the biological process bag (22) of the second antibody coupling reaction device (200) through a circulating pipeline (34);
the second liquid outlet pipe (27) of the second antibody coupling reaction device (200) is connected with the inlet end of a membrane pack (35), the top end of the biological process bag (22) is connected with the detention end of the membrane pack (35) through a detention pipe (36), and the penetrating end of the membrane pack (35) is connected with a waste discharge pipe (37).
9. An antibody-coupled filtration system using an antibody-coupled reaction apparatus according to claim 8, wherein: a solution delivery line (38) is also connected to the hold-up line (36).
10. An antibody-coupled filtration system using an antibody-coupled reaction apparatus according to claim 8, wherein: the first liquid outlet pipeline (26) of the second antibody coupling reaction device (200) is connected with a collecting device.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311429237.7A CN117463184A (en) | 2023-10-31 | 2023-10-31 | Mixed transfer device, antibody coupling reaction device using same and antibody coupling filtration system |
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| Application Number | Priority Date | Filing Date | Title |
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| CN202311429237.7A CN117463184A (en) | 2023-10-31 | 2023-10-31 | Mixed transfer device, antibody coupling reaction device using same and antibody coupling filtration system |
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| CN117463184A true CN117463184A (en) | 2024-01-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN202311429237.7A Pending CN117463184A (en) | 2023-10-31 | 2023-10-31 | Mixed transfer device, antibody coupling reaction device using same and antibody coupling filtration system |
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| Country | Link |
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