CN101935614A - Continuous fermentation and separation coupling bioreactor - Google Patents
Continuous fermentation and separation coupling bioreactor Download PDFInfo
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- CN101935614A CN101935614A CN2009101498865A CN200910149886A CN101935614A CN 101935614 A CN101935614 A CN 101935614A CN 2009101498865 A CN2009101498865 A CN 2009101498865A CN 200910149886 A CN200910149886 A CN 200910149886A CN 101935614 A CN101935614 A CN 101935614A
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Abstract
The invention discloses a continuous fermentation and separation coupling bioreactor, which comprises a fermentation culture device, a first feeding pump 15, a first membrane component 16, a finished product storage tank 19, a second feeding pump 20 and a second membrane component 21, wherein the fermentation culture device is connected with the first membrane component 16 by the first feeding pump 15; the first membrane component 16 is connected with the finished product storage tank 19 and a liquid returning opening 12 of the fermentation culture device respectively; the second feeding pump 20 is connected with the finished product storage tank 19 and the second membrane component 21; and the second membrane component 21 is connected with the liquid returning opening 12 of the fermentation culture device and the finished product storage tank 19 respectively. The continuous fermentation and separation coupling bioreactor can online separate and condense a fermentation product in a fermentation process, break a feedback inhibition function in the fermentation process, greatly reduce the separation energy consumption of the fermentation product, improve equipment utilization rate, simplify a process, reduce the production cost, realize continuous and high-density fermentation and improve the production efficiency, along with simple operation, convenient management, easy automation realization and vast development prospect.
Description
Technical field
The invention belongs to fermentation engineering and separation engineering technical field, relate to and a kind ofly continuously ferment and separate coupling bioreactor.
Background technology
Along with quick development of modern science and technology; be based upon on the bases such as molecular biology, molecular genetics, biological chemistry, microbiology, cytology and computer technology modern biotechnology---biochemical engineering becomes one of technical field with fastest developing speed in the world latter half in 20th century, it provides unprecedented power for the development of industries such as human health, husbandry, foodstuffs industry, environment protection and fine chemistry industry.
Bio-reactor is to utilize biological catalyst to provide the equipment of good reaction environment for cell cultures (or fermentation) or enzyme reaction, thereby becomes the core of biochemical industry.Bio-reactor has a variety of, modal bio-reactor is exactly mechanical agitation type fermentor tank (the most traditional microorganism reactor), and other also has such as hollow fiber reactor, the cellular reactor of ceramic rectangular channel, airlift reactor, fluidized-bed reactor, fixed bedreactor etc.Though the bio-reactor kind is a lot, it only finishes the process of biological respinse basically in present stage, still belongs to a link of upstream process, then needs to transfer in addition downstream processes for the extraction separation of the target product of producing and carries out.At present, reaction is separate with separating two processes, need be equipped with corresponding apparatus respectively, and factory need build fermentation plant and extract the workshop, the laboratory will be set up fermenting experiment chamber and separation and Extraction laboratory respectively, be the investment or energy consumption all is very considerable.
Reaction-separation coupling process is meant to be finished reaction simultaneously and separates two processes in a set of equipment, broadly also can be regarded as a series of separators and reactor be integrated in the system to operate.Reaction-separation coupling technology causes that because of it can improve product yield, reduction facility investment and energy consumption people more and more pay attention to, and range of application is progressively promoted expansion.In addition, in biochemical reaction, often there is product to suppress phenomenon, makes productive rate on the low side.For example have product in the fermenting processs such as lactic acid, acetone, microbiotic and suppress, utilize the extractive fermentation production technique, can effectively alleviate product and suppress, improve substrate concn, obviously improve reactor throughput, reduce production costs.
Summary of the invention
The objective of the invention is to utilize the advantage of reaction-separation coupling technology, provide a kind of and continuously ferment and separate coupling bioreactor, can in a covering device, realize continuously fermenting and product ON-LINE SEPARATION, spissated whole process.Use this bio-reactor and can realize the tight connection in the process of upstream and downstream specifically fermentation technology or specific objective product.
The present invention is achieved by the following technical solutions:
The present invention includes fermentation culture device, first fresh feed pump 15, first membrane module 16, finished product hold-up vessel 19, second fresh feed pump 20, second membrane module 21.The fermentation culture device links to each other with first membrane module 16 by first fresh feed pump 15, first membrane module 16 is connected with the liquid return hole 12 of finished product hold-up vessel 19 and fermentation culture device respectively again, second fresh feed pump 20 connects finished product hold-up vessel 19 and second membrane module, 21, the second membrane modules 21 are connected with finished product hold-up vessel 19 with the liquid return hole 12 of fermentation culture device respectively again.
The fermentation culture device mainly is made of reactor 8, reduction of feed volume proofing unit, pH detection control apparatus, feed supplement device.Wherein, the reduction of feed volume proofing unit is used for inventories in the detection reaction device 8, and it can be a liquid level detection device, also can be weighing device, the two can be according to actual needs flexible Application in addition.In addition, according to different demands, the fermentation culture device also can be equipped with immobilization and cultivate unit, whipping appts, temperature-control device, foam detection control apparatus, dissolved oxygen detection control apparatus, principal controller and human-computer interaction interface and computer etc., but whether the outfit of these devices does not make restriction to the present invention.
Liquid level detection device comprises liquid level sensor 11 and Level meter 6, and liquid level sensor 11 is connected on the reactor 8.Weighing device comprises LOAD CELLS 22 and weighing instrument 23, and LOAD CELLS 22 is connected on the reactor 8.The feed supplement device is by feed supplement bottle 2, air filter 3-2, and constant flow pump 4-2 and connecting pipeline constitute; The material total amount reduces in reactor 8, adds fresh culture by constant flow pump 4-2 in reactor 8.The pH detection control apparatus comprises pH electrode 9, pH measuring instrument 5, constant flow pump 4-1, acid/alkali lye bottle 1, air filter 3-1 and interconnects pipeline, adds acid solution by constant flow pump 4-1 in reactor 8 or alkali lye is regulated pH automatically when pH departs from set(ting)value in the reactor 8.
When the product in the reactor 8 is accumulated to finite concentration, by first fresh feed pump 15 fermented liquid in the reactor 8 is pumped into the first continuous membrane module 16, the aperture (molecular weight cut-off) of the membrane element that first membrane module 16 is selected can be selected according to the practical situation of fermented liquid, the feed liquid that contains small molecule component (comprising target product) sees through membrane element and enters finished product hold-up vessel 19, the feed liquid that contains macromolecular components (comprising thalline) is held back by membrane element, by connecting pipeline in liquid return hole 12 Returning reactors 8, the feed supplement device is added a certain amount of fresh culture according to the signal of reduction of feed volume proofing unit feedback in trend reactor 8, thalline continues fermentation in reactor 8.
What the feed liquid in the finished product hold-up vessel 19 pumped into that second membrane module, 21, the second membrane modules 21 adopt by second fresh feed pump 20 is the more small membrane element in aperture.Can be according to the aperture of the reading regulated valve 14-5 of tensimeter 13 to control the pressure of second membrane module 21, at this moment the small molecules solute sees through membrane element, in liquid return hole 12 reentered reactor 8, macromole solute (mainly being target product) was trapped and returns in the finished product hold-up vessel 19 through connecting pipeline.Along with the carrying out of this process, the small molecules solute is sent back in the reactor 8 and is utilized again, and the target product in the finished product hold-up vessel 19 is recycled concentrated.
The membrane element that above-mentioned first membrane module 16 adopts is a ultra-filtration membrane, and molecular weight cut-off 5000-50000D is optional.Described membrane element can be an inorganic ceramic film, and material is aluminum oxide, zirconium white or titanium oxide; Described membrane element also can be an organic membrane, and material is polyvinylidene difluoride (PVDF) (PVDF), polycarbonate (PC) or polyvinyl chloride (PVC).
Above-mentioned first fresh feed pump 15 is a constant flow pump, but connecting pipeline is the flexible pipe with certain elasticity and high-temperature sterilization.
The membrane element that above-mentioned second membrane module 21 adopts is a nanofiltration membrane.
Above-mentioned second fresh feed pump 20 is the high-pressure rotary vane pump.
The invention has the beneficial effects as follows: the present invention has adopted original position isolation technique (ISPR), and tunning during the fermentation can ON-LINE SEPARATION, concentrate, and reduces the concentration of cumulative tunning in the reactor, can break the feedback inhibition in the fermenting process.The present invention reduces the separating energy consumption of tunning greatly, has improved plant factor, has simplified technology, reduces production costs.Use that this device can be realized continuously, high density fermentation, improved production efficiency.This device is simple to operate, and convenient management easily is automated, and has good development prospect.
Description of drawings
Accompanying drawing is a structural representation of the present invention.
Among the figure:
1. acid/alkali lye bottle, 2. feed supplement bottle, 3-1,3-2,3-3. air filter, 4-1,4-2. constant flow pump, 5.pH measuring instrument, 6. Level meter, 7. inlet mouth, 8. reactor, 9.pH electrode, 10. venting port, 11. liquid level sensors, 12. liquid return holes, 13. tensimeter, 14-1～14-7. valve, 15. first fresh feed pumps, 16. first membrane modules, 17. air feed port, 18. Butterworth Hatchs, 19. finished product hold-up vessels, 20. second fresh feed pumps, 21. second membrane module, 22. LOAD CELLS, 23. weighing instruments
Embodiment
The present invention will be further described below by embodiment, but the present invention is not made restriction.
This device comprises fermentation culture device, first fresh feed pump 15, first membrane module 16, finished product hold-up vessel 19, second fresh feed pump 20, second membrane module 21.The fermentation culture device links to each other with first membrane module 16 with supporting connecting pipeline by first fresh feed pump 15, first membrane module 16 is connected by pipeline with the liquid return hole 12 of finished product hold-up vessel 19 and fermentation culture device respectively again, second fresh feed pump 20 and relevant connection pipeline connect finished product hold-up vessel 19 and second membrane module, 21, the second membrane modules 21 and are connected by pipeline with the liquid return hole 12 of fermentation culture device and finished product hold-up vessel 19 respectively again.
The fermentation culture device mainly is made of reactor 8, reduction of feed volume proofing unit, pH detection control apparatus, feed supplement device.Wherein, the reduction of feed volume proofing unit is used for inventories in the detection reaction device 8, and it can be a liquid level detection device, also can be weighing device, the two can be according to actual needs flexible Application in addition.Also be provided with venting port 10 and air feed port 7 by pipeline on the reactor 8, air feed port 7 also is provided with gas filter 3-3.In addition, according to different demands, the fermentation culture device also can be equipped with immobilization and cultivate unit, whipping appts, temperature-control device, foam detection control apparatus, dissolved oxygen detection control apparatus, principal controller and human-computer interaction interface and computer etc., but whether the outfit of these devices does not make restriction to the present invention.
Liquid level detection device comprises liquid level sensor 11 and Level meter 6, and liquid level sensor 11 is connected on the reactor 8.Weighing device comprises LOAD CELLS 22 and weighing instrument 23, and LOAD CELLS 22 is connected on the reactor 8.The feed supplement device is by feed supplement bottle 2, air filter 3-2, and constant flow pump 4-2 and connecting pipeline constitute, and the total amount of material reduces in reactor 8, adds fresh culture by constant flow pump 4-2 in reactor 8 and reaches original quantity.The pH detection control apparatus comprises pH electrode 9, pH measuring instrument 5, constant flow pump 4-1, acid/alkali lye bottle 1, air filter 3-1 and interconnects pipeline, adds acid solution by constant flow pump 4-1 in reactor 8 or alkali lye is regulated pH automatically when pH departs from set(ting)value in the reactor 8.Mend acid and still mend alkali and decide, can also dispose acid simultaneously if necessary, alkali carries out two-ways regulation to pH according to technology.But the feed supplement bottle 2 that feed supplement device of the present invention and pH detection control apparatus are adopted, acid/alkali lye bottle 1, air filter 3-1, air filter 3-2 and the sterilization of connecting pipeline high temperature high voltage resistant, described connecting pipeline is for having certain elastic flexible pipe.
When the product in the reactor 8 is accumulated to finite concentration, by first fresh feed pump 15 fermented liquid in the reactor 8 is pumped into the first continuous membrane module 16, the aperture (molecular weight cut-off) of the membrane element that first membrane module 16 is selected can be selected according to the practical situation of fermented liquid, the feed liquid that contains small molecule component (comprising target product) sees through membrane element and enters finished product hold-up vessel 19, the feed liquid that contains macromolecular components (comprising thalline) is held back by membrane element, by connecting pipeline in liquid return hole 12 Returning reactors 8, the feed supplement device is added a certain amount of fresh culture according to the signal of liquid level detection device or weighing device feedback in trend reactor 8, thalline continues fermentation in reactor 8.
What the feed liquids in the finished product hold-up vessel 19 are pumped into that second membrane module, 21, the second membrane modules 21 adopt by second fresh feed pump 20 is the more small membrane element in aperture.Can be according to the aperture of the reading regulated valve 14-5 of tensimeter 13 to control the pressure of second membrane module 21, at this moment the small molecules solute sees through membrane element, in liquid return hole 12 reentered reactor 8, macromole solute (mainly being target product) was trapped and returns in the finished product hold-up vessel 19 through connecting pipeline.Along with the carrying out of this process, the small molecules solute is sent back to be continued in the reactor 8 to utilize, and the target product in the finished product hold-up vessel 19 is recycled concentrated.
The membrane element that above-mentioned first membrane module 16 adopts is a ultra-filtration membrane, and molecular weight cut-off 5000-50000D is optional.Described membrane element can be an inorganic ceramic film, and material is aluminum oxide, zirconium white or titanium oxide; Described membrane element also can be an organic membrane, and material is polyvinylidene difluoride (PVDF) (PVDF), polycarbonate (PC) or polyvinyl chloride (PVC).
Above-mentioned first membrane module 16 also is provided with Butterworth Hatch 18 and inlet mouth 17, can adopt the external-compression type back flushing that first membrane module 16 is cleaned, thereby improves the ultrafiltration rate of film, the work-ing life of prolongation film.
Above-mentioned first fresh feed pump 15 is a constant flow pump, but connecting pipeline is the flexible pipe with certain elasticity and high-temperature sterilization, as silicone tube, rubber hose etc.
The membrane element that above-mentioned second membrane module 21 adopts is a nanofiltration membrane.
Above-mentioned second membrane module 21 can cleaning nanofiltration membrane on the throne, and suitable clean-out system is poured in the finished product hold-up vessel 19, by two fresh feed pumps 20 clean-out system is pumped into second membrane module 21 and carries out clean-out operation.Nanofiltration membrane that can also above-mentioned second membrane module 21 unloads cleans.
Above-mentioned second fresh feed pump 20 is the high-pressure rotary vane pump, is characterized in pressure height, constant flow.
Claims (10)
1. one kind continuously ferments and separates coupling bioreactor, comprise the fermentation culture device, first fresh feed pump (15), first membrane module (16), finished product hold-up vessel (19), second fresh feed pump (20), second membrane module (21), it is characterized in that: described fermentation culture device links to each other with first membrane module (16) by first fresh feed pump (15), first membrane module (16) is connected with the liquid return hole (12) of finished product hold-up vessel (19) and fermentation culture device respectively again, second fresh feed pump (20) connects finished product hold-up vessel (19) and second membrane module (21), and second membrane module (21) is connected with finished product hold-up vessel (19) with the liquid return hole (12) of fermentation culture device respectively again; Described fermentation culture device mainly is made of reactor (8), inventory proofing unit, pH detection control apparatus, feed supplement device; When the tunning in the reactor (8) is accumulated to finite concentration, by first fresh feed pump (15) fermented liquid in the reactor (8) is pumped into first membrane module (16) via connecting pipeline, the aperture of the membrane element that first membrane module (16) is selected can be selected according to the practical situation of fermented liquid, the feed liquid that contains small molecule component sees through membrane element and enters finished product hold-up vessel (19), the feed liquid that contains macromolecular components is held back by membrane element, by connecting pipeline in liquid return hole (12) Returning reactor (8), the feed supplement device is added a certain amount of fresh culture according to the signal of inventory proofing unit feedback in trend reactor (8), thalline continues fermentation in reactor 8; Feed liquid in the finished product hold-up vessel (19) pumps into second membrane module (21) by second fresh feed pump (20) via connecting pipeline, and what second membrane module (21) adopted is the more small membrane element in aperture; Can be according to the aperture of the reading regulated valve (14-5) of tensimeter (13) to control the pressure of second membrane module (21), at this moment the small molecules solute sees through membrane element, in liquid return hole (12) reentered reactor (8), the macromole solute was trapped and returns in the finished product hold-up vessel (19) through connecting pipeline; Along with the carrying out of this process, the small molecules solute is sent back in the reactor (8) and is utilized again, and the target product in the finished product hold-up vessel (19) is recycled concentrated.
2. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that described inventory proofing unit is a liquid level detection device, described liquid level detection device comprises liquid level sensor (11) and Level meter (6), and liquid level sensor (11) is connected on the reactor (8).
3. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that described inventory proofing unit is a weighing device, described weighing device comprises LOAD CELLS (22) and weighing instrument (23), and LOAD CELLS (22) is connected on the reactor (8).
4. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that described pH detection control apparatus comprises pH electrode (9), pH measuring instrument (5), constant flow pump (4-1), acid/alkali lye bottle (1), air filter (3-1) and interconnects pipeline, when pH departs from set(ting)value in the reactor (8), in reactor (8), add acid solution or alkali lye is regulated pH automatically by constant flow pump (4-1).
5. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that described feed supplement device is by feed supplement bottle (2), air filter (3-2), constant flow pump (4-2) and connecting pipeline constitute, the material total amount reduces in reactor (8), adds fresh culture by constant flow pump (4-2) in reactor (8).
6. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that the membrane element that described first membrane module 16 adopts is a ultra-filtration membrane, molecular weight cut-off 5000-50000D is optional.
7. according to claim 6ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that described membrane element is inorganic ceramic film and organic membrane.
8. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that described first fresh feed pump (15) is a constant flow pump, but described connecting pipeline is the flexible pipe with certain elasticity and high-temperature sterilization.
9. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that the membrane element that described second membrane module (21) adopts is a nanofiltration membrane.
10. according to claim 1ly a kind ofly continuously ferment and separate coupling bioreactor, it is characterized in that described second fresh feed pump (20) is the high-pressure rotary vane pump.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104805008A (en) * | 2015-04-30 | 2015-07-29 | 浙江农林大学 | Process and device for recovering reverse osmosis-nanofiltration combination membrane separation material of fermentation liquor |
| CN105821100A (en) * | 2016-01-25 | 2016-08-03 | 南京工业大学 | Process for realizing high yield of polyoxin by continuous fermentation and separation coupling |
| CN108004140A (en) * | 2018-01-30 | 2018-05-08 | 济南大学 | A kind of bioreactor population parameter detecting system and its measurement control method |
| CN109609378A (en) * | 2018-12-20 | 2019-04-12 | 杭州洪扬生物工程有限公司 | A kind of bioreactor |
| JPWO2019009044A1 (en) * | 2017-07-03 | 2020-03-26 | 株式会社村田製作所 | Concentrator |
| CN111111592A (en) * | 2020-01-03 | 2020-05-08 | 山东润德生物科技有限公司 | Circulating separation system based on ceramic membrane process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104805008A (en) * | 2015-04-30 | 2015-07-29 | 浙江农林大学 | Process and device for recovering reverse osmosis-nanofiltration combination membrane separation material of fermentation liquor |
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| JPWO2019009044A1 (en) * | 2017-07-03 | 2020-03-26 | 株式会社村田製作所 | Concentrator |
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| CN111111592A (en) * | 2020-01-03 | 2020-05-08 | 山东润德生物科技有限公司 | Circulating separation system based on ceramic membrane process |
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Application publication date: 20110105 |