CN2599006Y - Multichannel combined parallel biological reaction system - Google Patents

Multichannel combined parallel biological reaction system Download PDF

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Publication number
CN2599006Y
CN2599006Y CNU032109210U CN03210921U CN2599006Y CN 2599006 Y CN2599006 Y CN 2599006Y CN U032109210 U CNU032109210 U CN U032109210U CN 03210921 U CN03210921 U CN 03210921U CN 2599006 Y CN2599006 Y CN 2599006Y
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bio
reactor
vacuum
reaction system
parallel
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CNU032109210U
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梅晓丹
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Mei Xiaodan
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Baiao Science & Technology Development Co ltd Dalian
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/42Integrated assemblies, e.g. cassettes or cartridges
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/44Multiple separable units; Modules

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  • Life Sciences & Earth Sciences (AREA)
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Abstract

The utility model relates to a biological reaction device, in particular to a multichannel combined parallel biological reaction system, which consists of four parts, namely a control liquor adding mechanism, a parallel miniature electric stirring platform, a bioreactor set and a product solution receiving device. The bioreactor set consists of at least two single bioreactors, wherein each single bioreactor consists of a bioreactor cover with a liquor adding opening and a gas hole, a bioreactor cylinder body, from above to below, is provided with an electric stirrer arranged in the bioreactor cylinder body, a molecular weight interception film washer, a base plate, a charging cushion chamber, a base plate control valve and a charging pipe, and each bioreactor is arranged on the miniature electric stirring platform. The utility model which enables multichannel parallel operation and has a mobile bioreactor set with small size has an application scope of biological reactions such as combined protein expression, parallel renaturation of denaturing protein inclusion body, combined biological catalysis, biosynthesis combinatorial chemistry. The whole system is safe and economical with easy operation and high efficiency.

Description

A kind of multi-channel assembled parallel bio-reaction system
Technical field
The utility model relates to biological reaction apparatus, specifically a kind of multi-channel assembled parallel bio-reaction system.
Background technology
Last century end, tentatively finishing to life science of the Human Genome Project brought unlimited life, and science has entered the genome times afterwards comprehensively.It is reported that the gene of domination hereditary property is less than 40,000 in the human body, thereby started the upsurge of research functional genome; Life comes from protein, has only the proteinic abundant understanding of the key product of gene, and we just might understand life, optimizes life, conquers a stubborn disease; But obtaining functional protein in a large number is not a nothing the matter; Therefore, the technology of high-throughput preparation or protein purification has become the bottleneck of back genome project.Traditional protein preparation or purifying all are one operations one by one, and efficient is lower, is difficult to adapt to the rate request of biological development in Hi-Tech.
The utility model content
The purpose of this utility model provides the high multi-channel assembled parallel bio-reaction system of a kind of efficient.
To achieve these goals, the technical solution adopted in the utility model is: the principle of parallel preprocessor in the utility model utilization combinatorics, multi-channel assembled parallel bio-reaction system is stirred platform, bio-reactor group and product solution receiving trap four parts and is constituted by control liquid feeding mechanism, parallel miniature electric;
Control liquid feeding mechanism is that the multiple container for storing liquid of controllable type links to each other with the bio-reactor liquid adding hole by the pipeline that is provided with valve;
The bio-reactor group is made up of at least 2 independent bio-reactors, and each bio-reactor is from top to bottom successively by being furnished with liquid adding hole and ventage reactor cap, reactor cylinder body, placing the intravital electric mixer of reactor cylinder, molecular weight mwco membrane packing ring and base, blowing cushion chamber and base control valve and vomit pipe to form; Bio-reactor is installed on miniature electric and stirs on the platform;
Parallel miniature electric stirring platform is fixed on the support by motor unit and constitutes, and itself and electric mixer are in transmission connection;
Product solution receiving trap by vacuum tank and on vacuum panels with holes and place the product susceptor in it to constitute, product susceptor bottom pass-out vacuum tank cell wall links to each other with a control valve, the product susceptor communicates with vomit pipe by vacuum panels.
Described bio-reactor group is preferably by 12~96 bio-reactors to be formed; Base is a film packing ring damascene structures; Vomit pipe is and the screwed arm of base disjunctor, can be fixed on the top panel of vacuum receiver by nut; The product susceptor is a horn shape under cylindric, inclination horn shape or the waist spheroid, and product receptor and vacuum tank are the body-lined type structure; Vacuum tank is a rectangle, and the top is the semiclosed device of open type, and cell body one side has hole, two gardens, and the upper end is connected with vacuum valve, is used as ventilating pit, and the below is connected with vacuum pump by glass evacuated valve; A circular hole is with in the opposite side top of vacuum tank, connects the vacuum gauge outfit by soft rubber ball with holes; The housing of vacuum tank is positioned over the vacuum panels bottom that has lute naturally; Valve in the described control liquid feeding mechanism is connected with computer circuits, and reservoir is the liquid-adding device that protein expression damping fluid, denatured protein solubilization of inclusion bodies damping fluid (urea or guanidine), protein renaturation damping fluid can be automatically controlled; The feeding quantity of liquid, order of addition(of ingredients) and reinforced time can be controlled by computer.
The vacuum tank cell body is made by thick matter vacuum-resistant glass, and each product receptor lower end is connected to outside the vacuum tank by arm, and control valve (vacuum valve) control is arranged, but the liquid intermittent type of reception parallel blowing under normal pressure.
The utlity model has following advantage:
1. compact construction, volume are little, and the parallel running process is simple, can be manually or semi-automatic operation.
2. but used various biological and chemical reagent closure is handled, operate continuously, and speed is fast, pollution is little; For the small-sized bio-reaction system of environmental type, safe and reliable.
3. functional strong.Collection biological or chemical reaction, product filter, concentrate, separation, fluid transport are the system integrated apparatus of one; Function with high-throughput synthesis of biologically active molecule has overcome a plurality of proteinic isolating one by one difficulties, improves preparation protein, the proteinic efficient of separation and purification; It can not only be used to operate single proteinic renaturation and purifying, and the high-throughput ground parallel running of energy polyprotein matter, not only can be used for same protein expression, renaturation condition optimizing but also can be used for amplifying preparation, renaturation purifying when also can be used for different proteins; In addition, used bio-reactor is movable combined device, according to the principle of microbial fermentation, according to the model of shaking table, carries out supporting design, is used as the parallel synthesizer of amounts of protein; It can combine with membrane technique, as micro-Combinatorial biocatalysis, trace combination biosynthesizing bio-reactor; Also can be used as the condition optimizing system of same biological respinse; Especially apply to high throughput protein expression, inclusion body denatured protein high-throughput refolding renaturation, Combinatorial biocatalysis, combinatorial chemistry and solid phase synthesis; The general high-throughput preparation that is used for macromole such as protein, nucleic acid and polysaccharide.
4. at unsettled product of air or reactant, this system can operate under protection of inert gas, is suitable for the reaction and the aftertreatment of anaerobism material.
5. save the man power and material, the equipment material therefor mostly is plastic and glass greatly simultaneously, device fabrication is with low cost, has the bright prospects of production in enormous quantities.
6. bio-reactor and each parts of product receiving device are all detachable, and cleaning, sterilization are conveniently.
The utility model can apply to the high-throughput renaturation of denatured protein, also can be used for the biological respinse that reaction of high-throughput Combinatorial biocatalysis and macromole participate in; Can be used for basic micro-biological respinse, also can be used for milligram level and even the production of bio-active products on a large scale of gram level, also can hold back the concentrating unit of the film of the different aperture in the packing ring by regulating the molecular weight film as biological product.
Description of drawings
Fig. 1 is a sectional view of the present utility model.
Fig. 2 is a side sectional view of the present utility model.
Fig. 3 is the sectional view of three kinds of reaction solution receptor 14A-C.
Embodiment
Below in conjunction with accompanying drawing structure of the present utility model and fundamental diagram are described in further detail.
As shown in Figure 1, the parallel bio-reactor of built-up type is made up of damping fluid container for storing liquid 1, the reinforced by-pass valve control 5 of damping fluid, computer 29, bioreactor cover 7, venting or rare gas element interface, loam cake liquid device control main valve, cylindrical reactor cylinder 9, molecular weight mwco membrane packing ring 11, base control valve 24, bio-reactor base 10; Liquid in the damping fluid storage tank 1 can be by computer 29 control liquid flowing valves 5, and intermittent type or continous way are reinforced, the internal gas environment of venting or the reaction of ventilating pit may command; Entire reaction cylinder 9 is detachable glass or plastic device, is installed on the base 10 that has molecular weight mwco membrane packing ring 11; Parallel miniature electric stirs platform 2 and is made of double 12 electric motor and is fixed on the support 22, and each electric motor is by speed setting button 28 control speed;
Described bio-reactor group 3 is an integral body, and the filtration unit that not only can be used as reaction vessel but also can be used as the finished product (is promptly having column two row's multi-channel miniature molecule evaporating columns in configuration garden above the vacuum tank of receptor; ); When being used for biocatalysis, macromole or cell can being stayed in the reactor and reused; The material of macromolecule can be stayed in the reactor when being used for the refolding renaturation of denatured protein, required product and reagent, solution are put into product receptor 14 by the vomit pipe 25 of base 10 lower ends;
As depicted in figs. 1 and 2, product solution receiving trap 4 is by 12 product receptors 14 of the rectangular vacuum panel 12 that has 12 circular holes, rubber washer, vacuum meter 13, the glass evacuated groove 15 of rectangle column, double parallel, each product receptor by the disjunctor arm be connected on the cell body inwall, a control valve 16 in receptor lower end is outer with glass guide channel body-lined type pass-out groove, the exit is connected with control valve and arm, purging valve and corrosion-resistant plastic nut are formed outside; Vacuum tank 15 tops are the semiclosed device of open type, and cell body one side has hole, two gardens, and the upper end is connected with the ceramic vacuum valve, be used as ventilating pit, the below is connected with vacuum pump 18 by glass evacuated valve 17, and hole, a garden is with in the opposite side top of vacuum tank, connects vacuum gauge outfit 13 by soft rubber ball with holes;
As shown in Figure 2, the top is the parallel bio-reactors of two rows, and every row is equipped with 6 parallel one combined bioreactor groups as shown in fig. 1, the below be in the vacuum tank of the solution receiving tube of two row's body-lined types, each liquid receiving tube links to each other with vacuum control valve by outside the cell wall pass-out groove;
As shown in Figure 3, the vacuum tank that has three kinds of difform product susceptor 14A-C; The characteristics of each receiving tube are that the vacuum tank of upper shed straight-tube shape 14A has convenient for washing, and liquid outlet quantity is medium, conserve space; For the separation of micro substance, the curved cone angle type 14B of upper shed does not have the characteristics at dead angle when having tapping, in the upper shed under the ball vacuum tank of cone angle shape 14C have the big advantage of 14A liquid storage amount, the solution big for viscosity has the 14B blowing to be easy to characteristics again simultaneously; Be that thick matter glass is made, the last side of each susceptor is fired by glass on the inwall of vacuum tank 15, and susceptor 14 lower end body-lined types are by the glass cell body, and groove has a vacuum outward and props up valve 16.
The concrete operations mode is an example with the denatured protein renaturation:
Install system as Fig. 1, in parallel bio-reactor, add the protein inclusion body behind the purifying, build loam cake 7 after, with the parallel drop rifle that adds, add the guanidine damping fluid unfolding of 8M urea element damping fluid or 6~8M, be transferred to the appointment protein concn; Add the overlapping renaturation buffer of protein at 4 ℃ in as required respectively with gradient dilution normal direction reactor, or molecular chaperones is (as β-Cyclodextrin/stain remover, GroEL, GroES, DnaJ, DnaK, GrpE assists the patent of renaturation to apply for about practical molecular chaperones) the method refolding renaturation, by selecting to be suitable for best folded condition, on shaking table, hatch appropriate time, be contained on the vacuum tank on the vacuum panels 12, close a product receptor lower end control valve 16, open the reactor tap valve respectively, check whether each connecting interface connects, then whole vacuum tank is connected on the vacuum pump 18 enrichment crude product in solution under vacuum by vacuum valve 17; Not enough as product receptor load, but intermittent type props up valve 16 with solution in the product receptor 14 by control, be discharged in the appointment liquid vessel by peristaltic pump, filtration finishes, with damping fluid washing reaction device twice, vacuum diaphragm is filtered, and merges reaction solution, be used for next step purification step, or be directly used in biological activity determination.
Principle of work of the present utility model is:
Denatured protein can dissolve rapidly in the unfolding damping fluid of high density, and become the one-level protein structure, and required solution amount is little, and refolding renaturation is the intramolecular reaction process, and unfolding protein combines the knowledge intermolecular reaction with stain remover, and high density is more favourable; After denatured protein and stain remover load thing is diluted to proper concn, slowly drip refolding renaturation liquid again, the protein of slow release primary structure, because this moment, protein concn was lower, very favourable refolding forms natural active protein, owing to can keep the proteinic relative concentration of primary structure not increase so always, can avoid the aggregation between partially folded protein molecule; Because formed natural protein does not change molecular weight, select the molecular size of the aperture of molecular weight mwco membrane according to the protein molecular weight after the renaturation greater than desired protein, but the protein of required like this purifying is with outflow reactor, and the polymer that molecular weight increases will rest in the reactor; The process of sex change repeatedly, refolding becomes desired protein with the inclusion body highly efficient renaturation; By carrying out parallel running, realize the biology laboratory purpose on the desk, raise the efficiency, conserve space and the energy.In addition, when being used for micromolecular bioconversion reaction, the principle of holding back by the molecular weight of film, reacted small molecules product, reagent and solvent are discharged bio-reactor fully, and macromole is stayed in the reactor, and recycling particularly represents its superiority in enzyme catalysis field.

Claims (8)

1. a multi-channel assembled parallel bio-reaction system is stirred platform (2), bio-reactor group (3) and product solution receiving trap (4) four parts and is constituted by control liquid feeding mechanism, parallel miniature electric, it is characterized in that:
Control liquid feeding mechanism is that the multiple container for storing liquid of controllable type (1) links to each other with the bio-reactor liquid adding hole by the pipeline that is provided with valve (5);
Bio-reactor group (3) is made up of at least 2 single bio-reactors, and each bio-reactor is from top to bottom successively by being furnished with liquid adding hole and ventage reactor cap (7), reactor shell (9), placing electric mixer (8), molecular weight mwco membrane packing ring (11), base (10), blowing cushion chamber, base control valve (24) and vomit pipe (25) in the reactor shell (9) to form; Bio-reactor is installed on miniature electric and stirs on the platform (2);
Parallel miniature electric stirs platform (2) and is fixed on upward formation of support (22) by motor unit (27), and itself and electric mixer (8) are in transmission connection;
Product solution receiving trap (4) by vacuum tank (15) and on vacuum panels with holes (12) and place the product susceptor (14) in it to constitute, product susceptor (14) bottom pass-out vacuum tank (15) cell wall links to each other with a control valve (16), and product susceptor (14) communicates with vomit pipe (25) by vacuum panels (12).
2. according to the described multi-channel assembled parallel bio-reaction system of claim 1, it is characterized in that: described bio-reactor group (3) is made up of 12~96 bio-reactors.
3. according to the described multi-channel assembled parallel bio-reaction system of claim 1, it is characterized in that: base (10) is a film packing ring damascene structures.
4. according to the described multi-channel assembled parallel bio-reaction system of claim 1, it is characterized in that: described vomit pipe (25) is and the screwed arm of base disjunctor, can be fixed on the top panel (12) of vacuum receiver by nut (26).
5. according to the described multi-channel assembled parallel bio-reaction system of claim 1, it is characterized in that: described product susceptor (14) is horn shape under cylindric, inclination horn shape or the waist spheroid, and product receptor (14) is the body-lined type structure with vacuum tank (15).
6. according to the described multi-channel assembled parallel bio-reaction system of claim 1, it is characterized in that: described vacuum tank is a rectangle, the top is the semiclosed device of open type, cell body one side has hole, two gardens, the upper end is connected with vacuum valve (20), be used as ventilating pit, the below is connected with vacuum pump (18) by glass evacuated valve (17); A circular hole is with in the opposite side top of vacuum tank, connects vacuum gauge outfit (13) by soft rubber ball with holes.
7. according to the described multi-channel assembled parallel bio-reaction system of claim 1, it is characterized in that: described valve (5) is connected with computer (29) circuit.
8. according to the described multi-channel assembled parallel bio-reaction system of claim 1, it is characterized in that: the housing of described vacuum tank (15) is positioned over vacuum panels (12) bottom that has lute naturally.
CNU032109210U 2003-01-13 2003-01-13 Multichannel combined parallel biological reaction system Expired - Fee Related CN2599006Y (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2270129A3 (en) * 2009-07-01 2011-07-06 The Automation Partnership (Cambridge) Limited Bioreactor systems and associated methods of processing bioreactor vessels
CN105136865A (en) * 2015-09-14 2015-12-09 冯越 Four-path solid-phase chemical-reaction conductivity instrument

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2270129A3 (en) * 2009-07-01 2011-07-06 The Automation Partnership (Cambridge) Limited Bioreactor systems and associated methods of processing bioreactor vessels
US8563301B2 (en) 2009-07-01 2013-10-22 The Automation Partnership Ltd. Bioreactor systems and associated methods of processing bioreactor vessels
CN105136865A (en) * 2015-09-14 2015-12-09 冯越 Four-path solid-phase chemical-reaction conductivity instrument
CN105136865B (en) * 2015-09-14 2018-08-24 盐城师范学院 Four road solid state reaction conductivity meters

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Legal Events

Date Code Title Description
C14 Grant of patent or utility model
GR01 Patent grant
ASS Succession or assignment of patent right

Owner name: MEI XIAODAN

Free format text: FORMER OWNER: DALIAN BAIAO SCIENCE + TECHNOLOGY DEVELOPMENT CO., LTD.

Effective date: 20050114

C41 Transfer of patent application or patent right or utility model
TR01 Transfer of patent right

Effective date of registration: 20050114

Address after: 116025 No. 26, high energy street, hi tech Zone, Liaoning, Dalian

Patentee after: Mei Xiaodan

Address before: 516, room 1, block A, Pioneer Park, No. 116025 Torch Road, Dalian hi tech park, Liaoning, China

Patentee before: Dalian Baiao Science & Technology Development Co., Ltd.

C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20040114

Termination date: 20120113