CN1038348A - Physics, chemistry, biological process quantity being carried out the arrangement of on-line determination arranges - Google Patents
Physics, chemistry, biological process quantity being carried out the arrangement of on-line determination arranges Download PDFInfo
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- CN1038348A CN1038348A CN 88109275 CN88109275A CN1038348A CN 1038348 A CN1038348 A CN 1038348A CN 88109275 CN88109275 CN 88109275 CN 88109275 A CN88109275 A CN 88109275A CN 1038348 A CN1038348 A CN 1038348A
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- biosystem
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS 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
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/48—Automatic or computerized control
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Analytical Chemistry (AREA)
- Sustainable Development (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Computer Hardware Design (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
The invention discloses a kind of arrangement that physics, chemistry and biological process quantity in the sterilized bio system of sealing are carried out on-line determination arranges: for biomaterial is carried out sterile sampling, adopt to be arranged on outer, and the coupled separation assembly [1] of biosystem; Separation assembly links to each other with the unit [2] of preparation sample; The detection system [3] that also has one or more parallel connections or series connection to be provided with; And with above-mentioned each the group link to each other, carry sample induction system.The process that the comparable past is more fully grasped in the biosystem to be carried out is arranged in such arrangement, for process automation and optimization provide condition precedent.Can be applicable to Biological Technology, medical science, agricultural and field of environment protection.
Description
The present invention relates to the mensuration of process variable in the compound fluid media (medium), can be applicable to Biological Technology, medical science, agricultural and field of environment protection.
Take out biomaterial from closed system (for example from bio-reactor), and in the laboratory its desired characteristic is studied, a kind of like this off-line method is known.The shortcoming of this off-line method is separating on time and the space, thereby the retroaction of process is lagged behind.Like this, can not control this process continuously automatically.
In addition, also set about carrying out on-line determination, connection group German patent application openly illustrates DE-OS 3,516, the arrangement that discloses a kind of on-line determination in 080 arranges that in this arranged, a sample probe that is arranged in the bio-reactor was connected with measurement and control system with online mode.The shortcoming of Bu Zhiing is like this: sample probe that is to say and will often change probe because so-called dirt effect is done for soon.Because sample probe is arranged in bio-reactor, changes probe and will disturb or interrupt this process.Thereby the aseptic that can not keep process.
Another shortcoming of this on-line measurement is: can occur during measurement disturbing, promptly the amount that will measure can be subjected to the influence of undesirable pair of effect, and therefore the measurement structure that obtains more or less is incorrect.
Because above-mentioned shortcoming, in biosystem, for example the process of carrying out at bio-reactor only is not exclusively controlled and with good conditionsi, perhaps can not control automatically.
Target of the present invention is: this more fully grasps the process of carrying out in the biosystem in the past, thereby can realize robotization and optimization according to the biological targets amount of process.
Task of the present invention is: finish a kind of on-line determination and can the sterilized bio system not had a negative impact, as changing the influence of sample probe, and can measure more process variable in series or in parallel, side by side except disturbing.
According to the present invention, under the detection system condition of the mensuration measurement data that the sampler of the aseptic draw samples of living use and one or more parallel connection or series connection are provided with, for what seal, the sterilized bio system, especially the physics in the bio-reactor, chemistry and biological process quantity carry out the arrangement of on-line determination and arrange the biomaterial that is achieved in that to aseptic taking-up liquid state or gaseous state, dispose one and be arranged on outside the biosystem and coupled separation assembly, the unit of preparation sample separation assembly therewith links to each other, means in parallel or series connection measurement sample have also been arranged, existing means of before this preparation sample cell sample being carried out aseptic measurement also have the means of not sterilizing and measuring behind this preparation sample cell; And be that above-mentioned each assembly is equipped with an induction system of carrying sample.Also can arrange to arrange a kind of means of handling sample of setting up to this.
Biosystem can be a bio-reactor, bio-reactor is continuous therewith for a strainer filter, and therewith constitute an assembly, a separating component that biocommunity and filtrate are separated is set after this strainer filter, this separating component links to each other with a biocenological measuring unit with a degas module, a biocenological intermediate storage device, above-mentioned parts are sterilizable, and can aseptic operation.
Be the preparation sample, a pump is connected with the not sterilising zone of separating component, this pump links to each other with water storage container, buffer solution hold-up vessel, marker hold-up vessel and reagent hold-up vessel by valve, this pump also by other valves and the measuring technique of not sterilizing measure sample means, be connected with the intermediate storage device and a floss hole of filtrate.
Such arrangement is arranged and might be realized a kind of on-line measurement of will sample probe not stretching into biosystem for the first time.Like this, even when requiring to change parts in sampling unit, this bio-reactor can also continuous aseptic operation.
Such arrangement is arranged equally and might be carried out freely washing to separating component by the cleaning device that backwashes for the first time, thereby avoided the dirt effect.Arrange the aseptic that also can remain there by arrangement of the present invention.
In addition, the present invention might obtain the sample of a plurality of serial or parallel connections for the first time, finishes various measurements, that is to say to carry out preprocessing like this, makes the best service condition that obtains detection system in described scheduled measurement method.
Owing to after sampling, obtain a plurality of measured values in the short time, just might carry out automated procedure for the first time and regulate.This might reach the optimization of process for the process manual adjustment.
Using arrangement of the present invention to arrange for the first time might be for providing the condition precedent that carries out the transition to continuous process control from the process control that is interrupted with biological parameter as the process of major parameter.
Another tangible advantage is: might adopt the pick-up unit of not sterilizing in on-line measurement and do not influence gnotobiosis in the biosystem.
The invention will be further described below in conjunction with drawings and Examples.
Fig. 1 has provided the present invention with the block diagram illustrations form and has arranged the basic structure of arranging.
Fig. 2 has provided the present invention and has arranged the detailed structure of arranging.
From closed system 7, the representational sample that the biological example reactor takes out separates in separation assembly 1 under aseptic condition, and carries out preprocessing, makes its in loop (for example between parts 7-1 and 1-7) reach the boundary condition of detection.For the detection system in the loop of can not packing into, in the 2nd assembly 2, finish the preparation sample, reach there and detect necessary boundary condition, i.e. the physics of sample, chemical parameters are such as the addition of temperature, pressure, pH value, concentration, reagent and marker.The parts 2 of preparation sample link to each other with the detection components 3 of test samples composition.Be provided with there that one or more is in parallel or series connection, measure chemistry, physics and in the detection system of thing parameter.This detection system also is connected with an assembly 4 of handling sample, finishes the sterilization and the storage that make danger inefficacy, sample in this assembly 4.
The conveying between described assembly of sample and medium realizes by means of induction system 5.All these assemblies are carried out center control by control system 6.Might modulate the process in the closed system 7 with detection components 3 and/or with control system 6 by Process Adjustment Device 8.
Assembly described in Fig. 1 can be by realizing as the given instrument of Fig. 2.Under this routine situation, this closed system 7 is made of a sterilized bio reactor 9 and a strainer filter 10.This closed system also can be the biological cycle of a nature.
The sterilized bio reactor comprises reactor vessel, with and all assembly parts, pipeline, lead to the valve of sterilizing filter and sample delivery to the separation assembly and the pipeline of discharging from separation assembly.
Under this routine situation, this separation assembly 1 is made of together with all necessary pipelines and valve separating component 11, degas module 12.Finish biocommunity and the aseptic of filtrate separates in separating component, wherein the entrance side of the separating component that links to each other with closed system is an aseptic area, and its outlet side is not sterilized.For separating sample, the tangential overflow filtrator of the different materials of can packing into (have or not with the commingled system that is used for avoiding concentration polarization), dialysis parts, have or not with the static filtering unit and the hollow fiber of the different materials of commingled system.
Aseptic side at separating component 11 is provided with a biocenological intermediate storage device 13, and what link to each other with intermediate storage device 13 is biocenological measuring unit 14.
All said modules form aseptic area.
At sterilising zone not, degas module 12 is provided with gas measurement unit 15, for example a gas chromatograph.
The not sterilization outlet of separating component is connected with pump 16, and this pump becomes the member of induction system 5 with valve.Pump 16 links to each other with the intermediate storage device 17 of filtrate by corresponding valve, also links to each other with filtrate measuring unit 18.But but this pump can adopt common dosing pump or have pre-selected frequency and the dedicated pump of preliminary election pistons work volume.
Pump 16 links to each other with the parts 2 of preparation sample.These parts have the hold-up vessel 20 of water storage container 19, buffer solution, the hold-up vessel 21 of marker and the hold-up vessel 22 of reagent.The possibility that this provides the preparation sample is each measuring method that links to each other sample is carried out best preprocessing.
Measuring unit 14,15 and 18 has constituted detection components 3.Adopt cellular construction because this arrangement is arranged, so these measuring units are removable.Both can adopt at the aseptic area that this arrangement is arranged as measuring unit and directly to have determined biological in the closed system, chemistry and pick-up unit physical quantity, that satisfy high dynamic requirements, also can adopt the pick-up unit of measuring biological, chemistry and physical quantity at sterilising zone not.Behind the preparation sample, these are connected in the process.As such pick-up unit, except above-mentioned gas chromatograph, also can adopt optics, high frequency spectrophotometer, sample is offered them with pre-processed form.
In this arrangement was arranged, the biomaterial that produces in bio-reactor 9 was at first given strainer filter.This material is delivered to separating component 11 by valve from strainer filter, carries out separating of biocommunity and filtrate there.Then this biocommunity is extracted into intermediate storage device 13 then by drain gas in the biocommunity of degas module 12.This process is after separating component 11 has been removed filtrate and filtrate drained into filtrate intermediate storage device 17, is undertaken by pump 16 at corresponding valve location.When the biocommunity of said sample and filtrate are delivered to detection system or carried out preprocessing, after separating component 11 emptyings, can carry out next step sampling at corresponding valve location.
So just might carry out turbidimetry to biocommunity.Just can reach high measuring accuracy by the foregoing coarse filtration and the degassing.Up to the present, such measurement must be directly against or in reactor, carry out, wherein bubble and impurity can only be got rid of by halves.Eliminate this defective although take measures, do not obtain high measuring accuracy yet.
Because biocenological measuring unit 14 is at aseptic area, so after finishing measurement, also biocommunity can be sent back to 9 li of bio-reactors.
Deliver to measuring unit 15 from degas module 12 isolated gases, for example in the gas chromatograph, thereby can provide an additional information about process in the bio-reactor, this does not accomplish in known arrangement is up to now arranged.
Pump 16 is extracted filtrate out in the middle of it reservoir, and by means of parts 19 to 22 it is carried out preprocessing, thereby is adapted to the measuring method that is connected best.
The cellular construction mode has realized taking out sample in the short time, and it is carried out different preparations, just makes it be adapted to different measuring methods best.Thereby people have fundamentally obtained than more manying in the past and better measurement result.
Because sampling is carried out in the reactor outside, then bio-reactor no longer needs sampled part, therefore might make bio-reactor carry out effectively continuous operation now.And up to the present, when the dirt effect can not be used sample probe, this operation must be interrupted.
The reference numerals list that is adopted is as follows:
1. separation assembly 12. degas modules
2. prepare sample assembly 13. biocenological intermediate storage devices
3. detection components 14. biocenological measuring units
4. handle sample assembly 15. gas measurement units
5. induction system 16. pumps
6. the intermediate storage device of control system 17. filtrates
7. the measuring unit of closed system 18. filtrates
8. the hold-up vessel of Process Adjustment Device 19. water
9. the hold-up vessel of bio-reactor 20. buffer solution
10. the hold-up vessel of strainer filter 21 markers
11. the hold-up vessel of separating component 22. reagent
Claims (4)
1, a kind of sampler and one or more parallel connection of sterile sampling or detection system setting, that determine measurement data of connecting utilized is to sealing, sterilized bio system, especially the physics in the bio-reactor, chemistry and biological process quantity carry out the arrangement layout of on-line determination, it is characterized in that: carry out sterile sampling for liquid towards or gaseous biological material, adopt a separation assembly [1] that is arranged on outside the biosystem and links to each other with this biosystem; Separation assembly [1] links to each other with the unit [2] of a preparation sample; Also be provided with the means of parallel connection or series connection test samples, the existing preceding means that are used for aseptic measurement sample of this preparation sample cell [2] that are positioned at have also that being positioned at is used for not sterilizing behind the preparation sample cell [2] measures the means of sample; And the induction system that links to each other, carries sample and essential preparation medium with above-mentioned each assembly.
2, arrangement according to claim 1 is arranged, it is characterized in that: this arrangement is arranged with the means of handling sample.
3, arrangement according to claim 1 and 2 arranges that it is characterized in that: this biosystem is a bio-reactor (9), and a strainer filter (10) bio-reactor therewith links to each other, and therewith constitutes an assembly; Be provided with the separating component (11) of a separating bio group and filtrate behind the strainer filter (10), these parts link to each other with degas module (12), biocenological intermediate storage device (13) and biocenological measuring unit (14); Above-mentioned each assembly is sterilizable, and can aseptic operation.
4, described arrangement is arranged according to any one claim in the claim 1 to 3, it is characterized in that: be the preparation sample, a pump (16) imperial decree is thrown argon examines 1) not sterilising zone be connected, this pump links to each other with the hold-up vessel (19) of water, the hold-up vessel (20) of buffer solution, the hold-up vessel (21) of marker and the hold-up vessel (22) of reagent by valve; And this pump is connected by other valves and the means (15,18) of measuring sample of not sterilizing, a filtrate intermediate storage device (17) and with a floss hole.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DDWPC12M/310 | 1987-12-18 | ||
| DD31067387A DD269162B1 (en) | 1987-12-18 | 1987-12-18 | ARRANGEMENT FOR ON-LINE DETECTION OF PHYSICAL, CHEMICAL AND BIOLOGICAL PROCESSES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1038348A true CN1038348A (en) | 1989-12-27 |
Family
ID=5595257
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 88109275 Pending CN1038348A (en) | 1987-12-18 | 1988-12-18 | Physics, chemistry, biological process quantity being carried out the arrangement of on-line determination arranges |
Country Status (6)
| Country | Link |
|---|---|
| CN (1) | CN1038348A (en) |
| CH (1) | CH677539A5 (en) |
| DD (1) | DD269162B1 (en) |
| DE (1) | DE3842902A1 (en) |
| HU (1) | HUT52884A (en) |
| SE (1) | SE8804562L (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4339584A1 (en) * | 1993-11-20 | 1995-05-24 | Thomas Dr Hertel | Process and assembly for controlled reversible charging of measuring cell with microorganisms |
-
1987
- 1987-12-18 DD DD31067387A patent/DD269162B1/en not_active IP Right Cessation
-
1988
- 1988-12-16 CH CH465088A patent/CH677539A5/de not_active IP Right Cessation
- 1988-12-16 HU HU647588A patent/HUT52884A/en unknown
- 1988-12-16 DE DE19883842902 patent/DE3842902A1/en not_active Withdrawn
- 1988-12-16 SE SE8804562A patent/SE8804562L/en not_active Application Discontinuation
- 1988-12-18 CN CN 88109275 patent/CN1038348A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| SE8804562L (en) | 1989-06-19 |
| SE8804562D0 (en) | 1988-12-16 |
| HUT52884A (en) | 1990-08-28 |
| DE3842902A1 (en) | 1989-06-29 |
| DD269162A1 (en) | 1989-06-21 |
| DD269162B1 (en) | 1991-05-29 |
| CH677539A5 (en) | 1991-05-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |