CN207727013U - A kind of antibody purification efflux automatic collecting device - Google Patents

A kind of antibody purification efflux automatic collecting device Download PDF

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Publication number
CN207727013U
CN207727013U CN201721799483.1U CN201721799483U CN207727013U CN 207727013 U CN207727013 U CN 207727013U CN 201721799483 U CN201721799483 U CN 201721799483U CN 207727013 U CN207727013 U CN 207727013U
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antibody
efflux
pipeline
plasma resonance
surface plasma
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钱卫珠
郭怀祖
徐进
杨立敏
陶静
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Taizhou Mai Bartec Pharmaceutical Co Ltd
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Taizhou Mai Bartec Pharmaceutical Co Ltd
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Abstract

A kind of antibody purification efflux automatic collecting device, belong to bio-pharmaceuticals equipment, limitation of the UV absorption monitoring method in specificity during liquid chromatogram efflux can be overcome to collect, mainly it is made of surface plasma resonance sensor, electronic controller, electric T-shaped valve and liquid conducting pipes etc., the censorchip surface conjugate of sensor is the albumen that can be combined with purified antibody specificity, the precision that the collection of antibody purification efflux can be improved by the equipment reduces the waste of efflux, improves the purification efficiency of antibody.

Description

A kind of antibody purification efflux automatic collecting device
Technical field
The utility model belongs to bio-pharmaceuticals equipment, more particularly to a kind of for collecting antibody drug purifying outflow The automatic device of liquid.
Background technology
Antibody drug generally refers to the monoclonal antibody for treating or preventing disease, and the antibody drug of broad sense also includes single Chain antibody(ScFv), single domain antibody(sdAb), Fc fusion proteins(Merged with antibody Fc section by the binding domain of receptor or ligand and At)Deng.Antibody drug by specifically combine the relevant target of disease, as tumor cell surface antigen, the inflammatory reaction factor, Immunologic test point albumen etc. plays label cancer cell, disabling signal access, activates the effects that immune response, to reach treatment Or prevent the effect of disease.
Antibody drug becomes important medicine in the major diseases such as malignant tumour, autoimmune disease field, Global annual sales amount breaks through 100,000,000,000 dollars, accounts for the market share of biological products market half or so, and it is mono- to produce A Damu Multiple widely used heavy pound drugs such as anti-, Rituximab, Herceptin, Avastin.
Antibody drug is grouped as by groups such as monoclonal antibody and auxiliary materials, and monoclonal antibody used is usually that IgG types are immune Globulin, 2 light chains connected by disulfide bond(L chains)With 2 heavy chains(H chains)It constitutes, light chain and heavy chain are again by variable region(VL、 VH)And constant region(CL、CH1、CH2、CH3)It constitutes, variable region can be combined with antigentic specificity, and the sequence of constant region is opposite to protect It keeps, is mainly responsible for and maintains antibody structure, combined with complement, combined with Fc receptors.IgG antibody is hydrolyzed according to papain As a result, antibody can be divided into Fab section and Fc sections, wherein Fc sections is mainly made of CH2, CH3, and having on Fc sections can be with staphylococcus Albumin A(Abbreviation albumin A, english abbreviation SPA), Fc γ receptors(Fc γ R, including Fc γ RI, Fc γ RII and Fc γ RIII etc. are sub- Type), the protein bound site such as anti-Fc antibody.
The production technology of antibody drug includes fermentation, purifying, preparation.Liquid chromatogram is antibody drug purifying process Core procedure, the common liquid chromatography technology of antibody drug has affinity chromatography(Staphylococcal protein A affinity chromatography), ion hand over Change chromatography, sieve chromatography, reversed phase chromatography etc..Liquid chromatogram process generally comprises balance(balance), loading(load), punching It washes(wash), elution(elute), regeneration(regeneration)And etc., it is related to the elution efflux containing target protein Collection and other steps in efflux discharge.
The collection for eluting efflux in liquid chromatogram at present uses ultraviolet monitoring, when the ultraviolet absorption value of efflux reaches one Determine to start collection process when degree.However ultraviolet absorption method can only be general roughly monitoring efflux in Tot Prot, cannot Target protein in the identification efflux of specificity, can not determine whether the target protein in efflux has in conjunction with activity.
Invention content
Limitation of the UV absorption monitoring method in specificity during being collected for liquid chromatogram efflux, this practicality are new Type provides the better antibody purification efflux automatic collecting device of a species specificity, and technical solution is as follows:
A kind of antibody purification efflux automatic collecting device(Fig. 1), by surface plasma resonance sensor(1), electronics control Device processed(2), electric T-shaped valve(3)And liquid conducting pipes composition, wherein liquid conducting pipes include main pipeline(4)And its bifurcated Made of waste collection pipeline(5), antibody collection conduit(6);The sensing chip of surface plasma resonance sensor(7)It is installed on In liquid conducting pipes, it can be in contact with antibody purification efflux and combine antibody therein, surface plasma resonance sensor (1)Convert the signal that antibody flows through to electronic signal;Electronic controller(2)Input terminal and surface plasma resonance sensor (1)Connection, output end and electric T-shaped valve(3)It is connected, surface plasma resonance sensor can be received(1)The e-mail sent out Number and control electric T-shaped valve(3)On off state;Electric T-shaped valve(3)It is installed on the crotch of liquid conducting pipes, can be controlled Antibody processed purifying flows out liquid stream to waste collection pipeline(5)Or antibody collection conduit(6).
Preferably, the main pipeline(4)Inside branch out a collateral pipeline(8), the surface plasma resonance passes The sensing chip of sensor(7)Positioned at collateral pipeline(8)Interior, respectively there are one electric T-shaped valves at the both ends of collateral pipeline(9), can control Collateral pipeline(8)Both ends and main pipeline(4)It is connected to or is in communication with the outside, as shown in Figure 2.
The surface plasma resonance sensor(1)Including optical system, sensing chip(7), photo-translating system (11), optical system includes light source(12)And prism(13), as shown in Figure 3.
Preferably, the sensing chip(7)Surface conjugate is can be with purified antibody(14)Specific binding Albumen(10), such as:Antigen, Fc receptors, antiantibody, staphylococcal protein A etc..
The antibody purification efflux automatic collecting device can be used for collecting the elution stream of infliximab, Cetuximab Go out liquid, at this time the sensing chip(7)Surface conjugate is respectively the human tumour necrosis factor a recombinantly expressed(TNFa)Egg In vain, human epidermal growth factor acceptor(EGFR)Extracellular fragment.
The electronic controller(ECU)It is the microcomputer system based on microcontroller, it is with signal(Data) Acquisition, calculation processing, analytical judgment, decision game as input, then using send out control instruction, commander actuator work as Output;Sometimes, it will also provide stabilized power source or reference voltage to sensor.
The electric T-shaped valve is made of driver and valve body, can pass through the on off state of current controlled valves.
It is flowed out the utility model has the beneficial effects that can start and close according to the specific recognition to purified antibody The collection step of liquid reduces the waste of efflux, improves the purifying of antibody to improve the precision of antibody purification efflux collection Efficiency.
Description of the drawings
Fig. 1:The structure chart of one embodiment of the utility model;
Fig. 2:The structure chart of one embodiment of the utility model;
Fig. 3:The structure chart of surface plasma resonance sensor.
Specific implementation mode
Embodiment 1, a kind of antibody purification efflux automatic collecting device
A kind of antibody purification efflux automatic collecting device(Fig. 1), by surface plasma resonance sensor(1), electronics control Device processed(2), electric T-shaped valve(3)And liquid conducting pipes composition, wherein liquid conducting pipes include main pipeline(4)And its bifurcated Made of waste collection pipeline(5), antibody collection conduit(6).Surface plasma resonance sensor(1)Including optical system, pass Sense chip(7), photo-translating system(11), optical system includes light source(12)And prism(13), sensing chip(7)Surface is coupled Object be and purified antibody(14)The antigen of specific binding(10).Sensing chip(7)It is installed in liquid conducting pipes, energy It is in contact with antibody purification efflux and combines antibody therein, surface plasma resonance sensor(1)The letter that antibody is flowed through Number it is converted into electronic signal;Electronic controller(2)Input terminal and surface plasma resonance sensor(1)Connection, output end with Electric T-shaped valve(3)It is connected, surface plasma resonance sensor can be received(1)The electronic signal that sends out simultaneously controls electric three passes Valve(3)On off state;Electric T-shaped valve(3)It is installed on the crotch of liquid conducting pipes, antibody purification efflux can be controlled Flow to waste collection pipeline(5)Or antibody collection conduit(6).
The mode of action of the device is, when the purifying efflux containing target antibody passes through the main pipeline of liquid conducting pipes (4)When, purify the antibody contained in efflux(14)With sensing chip(7)The antigen of surface coupling(10)In conjunction with according to table The principle of face plasma resonance can cause the variation of optical system reflected light, photo-translating system(11)The variation of reflected light is turned Become photosignal and sends electronic controller to(2), control electric T-shaped valve(3)Purifying is set to flow out liquid stream to antibody collecting pipe Road(6).When purifying in efflux without containing target antibody, it is incorporated into sensing chip(7)The antibody on surface(14)With antigen (10)Dissociation, can also cause the variation of optical system reflected light, and be changed into photosignal to make electronic controller(2)Change electronic Triple valve(3)State makes purifying flow out liquid stream to waste collection pipeline(5).
Embodiment 2, a kind of antibody purification efflux automatic collecting device
A kind of antibody purification efflux automatic collecting device(Fig. 2), by surface plasma resonance sensor(1), electronics control Device processed(2), electric T-shaped valve(3)And liquid conducting pipes composition, wherein liquid conducting pipes include main pipeline(4)And its bifurcated Made of waste collection pipeline(5), antibody collection conduit(6), the main pipeline(4)Inside branch out a collateral pipeline(8). Surface plasma resonance sensor(1)Including optical system, sensing chip(7), photo-translating system(11), optical system includes Light source(12)And prism(13), sensing chip(7)Surface conjugate behaviour tumor necrosis factor a(TNFa)Albumen.Sensing chip (7)Positioned at collateral pipeline(8)Interior, respectively there are one electric T-shaped valves at the both ends of collateral pipeline(9), with electronic controller(2)It is connected, Collateral pipeline can be controlled(8)Both ends and main pipeline(4)It is connected to or is in communication with the outside.The sensing core of surface plasma resonance sensor Piece(7)It can be in contact with antibody purification efflux and combine antibody therein, surface plasma resonance sensor(1)By antibody stream The signal crossed is converted into electronic signal, and sends electronic controller to(2)Input terminal;Electronic controller(2)Output end with Electric T-shaped valve(3)It is connected, surface plasma resonance sensor can be received(1)The electronic signal that sends out simultaneously controls electric three passes Valve(3)On off state;Electric T-shaped valve(3)It is installed on the crotch of liquid conducting pipes, antibody purification efflux can be controlled Flow to waste collection pipeline(5)Or antibody collection conduit(6);Electronic controller(2)Also with computer(15)It is connected, meter can be passed through Calculation machine software carries out more convenient, complicated control and feedback.
The mode of action of the device is, when the purifying efflux containing target antibody passes through the main pipeline of liquid conducting pipes (4)When, partial purification efflux can flow to collateral pipeline(8), the antibody contained in efflux(14)With sensing chip(7)Table The antigen of face coupling(10)In conjunction with the variation of optical system reflected light, photoelectricity can be caused according to the principle of surface plasma resonance Converting system(11)It is photosignal by the change transitions of reflected light and sends electronic controller to(2), control electric T-shaped valve (3)Purifying is set to flow out liquid stream to antibody collection conduit(6).When purifying in efflux without containing target antibody, it is incorporated into sensing Chip(7)The antibody on surface(14)With antigen(10)Dissociation, can also cause the variation of optical system reflected light, and be changed into photoelectricity Signal makes electronic controller(2)Change electric T-shaped valve(3)State makes purifying flow out liquid stream to waste collection pipeline(5).
Further, it is also possible to pass through electric T-shaped valve(9)Collateral pipe ends are made to lead to the external world, convenient for sensing chip(7) The operations such as cleaned, regenerated.

Claims (5)

1. a kind of antibody purification efflux automatic collecting device, characterized in that by surface plasma resonance sensor, electronic control Device, electric T-shaped valve and liquid conducting pipes composition, wherein liquid conducting pipes include waste liquid made of main pipeline and its bifurcated Collection conduit, antibody collection conduit;The sensing chip of surface plasma resonance sensor is installed in liquid conducting pipes, can be with Antibody purification efflux is in contact and antibody therein, the signal that surface plasma resonance sensor flows through antibody is combined to convert For electronic signal;The input terminal of electronic controller is connect with surface plasma resonance sensor, output end and electric T-shaped valve phase Connection, can receive the electronic signal that surface plasma resonance sensor is sent out and the on off state for controlling electric T-shaped valve;It is electronic Triple valve is installed on the crotch of liquid conducting pipes, can control antibody purification efflux and flow to waste collection pipeline or antibody receipts Collect pipeline.
2. antibody purification efflux automatic collecting device according to claim 1, characterized in that divide in the main pipeline A collateral pipeline is paid, the sensing chip of the surface plasma resonance sensor is located in collateral pipeline, collateral pipeline Both ends respectively there are one electric T-shaped valve, collateral pipe ends can be controlled and be connected to or be in communication with the outside with main pipeline.
3. antibody purification efflux automatic collecting device according to claim 1 or 2, characterized in that the sensing core Piece surface conjugate is the albumen that can be combined with purified antibody specificity.
4. antibody purification efflux automatic collecting device according to claim 3, characterized in that the sensing chip table Face conjugate is the antigen combined with purified antibody specificity.
5. antibody purification efflux automatic collecting device according to claim 3, characterized in that the sensing chip table Face conjugate is the human tumour necrosis factor a of recombinant expression(TNFa)Or human epidermal growth factor acceptor(EGFR)Extracellular fragment.
CN201721799483.1U 2017-12-21 2017-12-21 A kind of antibody purification efflux automatic collecting device Active CN207727013U (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109364525A (en) * 2018-12-25 2019-02-22 山东博森医学工程技术有限公司 A kind of mesenchyma excretion body separating extraction device and its method
CN111965277A (en) * 2020-08-06 2020-11-20 天津科德通生物科技有限公司 Automatic collection device for antibody purification effluent liquid

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109364525A (en) * 2018-12-25 2019-02-22 山东博森医学工程技术有限公司 A kind of mesenchyma excretion body separating extraction device and its method
CN109364525B (en) * 2018-12-25 2021-06-15 山东博森医学工程技术有限公司 Mesenchymal exosome separation and extraction device and method
CN111965277A (en) * 2020-08-06 2020-11-20 天津科德通生物科技有限公司 Automatic collection device for antibody purification effluent liquid

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