CN209485753U - One kind being used for bioprocesses on-line period detection device - Google Patents
One kind being used for bioprocesses on-line period detection device Download PDFInfo
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- CN209485753U CN209485753U CN201822044138.8U CN201822044138U CN209485753U CN 209485753 U CN209485753 U CN 209485753U CN 201822044138 U CN201822044138 U CN 201822044138U CN 209485753 U CN209485753 U CN 209485753U
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Abstract
The utility model relates to one kind to be used for bioprocesses on-line period detection device comprising: hydraulic power supply is connected by pipeline with bioreactor;Pipeline switching valve is multiple, is Multi-channel switching valve;Solenoid electric valve is respectively used to the switch of control liquid or gas piping to be multiple;Syringe pump can accurately control the volume in flow in pipes, the fluid pipeline of wherein at least one syringe pump is connected with fiber spectrometer to be multiple;Waste liquid bottle, for one or more;Reaction detection pond, to be multiple, one end connecting pipe, one end are connected by pipeline with waste liquid bottle;Diluting tank is directly or indirectly connected with syringe pump;Pneumatic pressure power source is used to control in filtrated air flow ipe;Low temperature storage box is provided with automatic safety sampling device;Liquid fusion chip is provided with T-shape channel;Solvent bottle, equipped with for diluted solvent;Pipeline is at least two kinds of different pipelines of internal diameter.
Description
Technical field
It is the utility model relates to on-line period device, in particular to a kind of for bioprocesses on-line period detection dress
It sets.
Background technique
Bioprocesses are the processes that biosystem carries out biochemical reaction in biological reaction apparatus.With chemical reaction phase
Than condition needed for biological respinse is relatively milder, reaction rate process is slow, and process mechanism is complicated.
Bioprocesses include preparation stage, reaction process monitoring and post-reaction treatment three phases before reacting.Wherein,
Culture medium, cell/microorganism state in implementing monitoring biological respinse etc. are conducive to understand biological metabolism state, for biology
The optimization of reaction process provides highly important reference frame.
Currently, there are mainly two types of the monitor modes of bioprocesses: one be using bioreactor carry temperature,
PH, dissolved oxygen etc. can sterilize electrode carry out on-line checking;The other is being detected in the lab by sampling come feedback control.
However, bioreactor can not usually obtain biochemistry although detection control can be carried out to biological respinse conditional parameter in real time
Parameter.In bioprocesses, biological growth metabolism is vigorous, and very big change will occur for biological biochemistry index in a short time
Become, therefore how to realize that bioreactor is continuous or timing on-line checking, and leave and take sample and carry out ex-post analysis, it is particularly significant.
Summary of the invention
The utility model provides one kind for bioprocesses on-line period detection device, overcomes in the prior art
It cannot achieve the defect of sterile on-line continuous or timing sampling and on-line checking, and sample liquid dead volume drops to most in sampling process
It is low, reduce the waste of sample liquid.
Technical solutions of the utility model are as follows:
One kind being used for bioprocesses on-line period detection device comprising hydraulic power supply, the hydraulic power supply
It is connected by pipeline with bioreactor;Multiple pipeline switching valves, the pipeline switching valve is Multi-channel switching valve;Multiple electricity
Magnetic control valve, the solenoid electric valve are respectively used to the switch of control liquid or gas piping;Multiple syringe pumps, the syringe pump
Volume in flow in pipes can accurately be controlled, fluid pipeline and the fiber spectrometer phase of wherein at least one syringe pump
Even;Waste liquid bottle, the waste liquid bottle are one or more;Multiple reaction detection ponds, reaction detection pond one end connecting pipe, one end
It is connected by pipeline with waste liquid bottle;Multiple diluting tanks, the diluting tank are directly or indirectly connected with syringe pump;Pneumatic pressure power
Source, the Pneumatic pressure power source is for controlling in filtrated air flow ipe;Low temperature storage box is provided in the low temperature storage box
Automatic safety sampling device;Liquid fusion chip, the liquid fusion chip are provided with T-type channel;Solvent bottle fills in the solvent bottle
Have for diluted solvent;Pipeline, the pipeline are at least two kinds of different pipelines of internal diameter.
The pipeline switching valve includes the automatic control unit for controlling switching.
The hydraulic power supply, multiple syringe pumps include the control unit for controlling sample introduction, described control unit point
Not Tiao Jie liquid enter flow velocity and flow in pipeline;The Pneumatic pressure power source includes the control unit for controlling sample introduction, institute
Stating control unit, regulating gas enters flow velocity and flow in pipeline respectively.
The on-line period detection device further includes control system, and the control system includes for controlling hydraulic power supply
The feed liquor time, flow velocity, flow controller, for control pressure power source inlet period, flow velocity, flow controller, be used for
The controller for controlling pipeline switching valve, electromagnetic switching valve working condition, for controlling the injection of injection pump startup or back suction liquid
Movement, flow velocity, flow controller, for controlling the controller and general processor, number of low temperature storage box operating status
Signal processor, specific integrated circuit, application-specific integrated circuit ASIC or on-site programmable gate array FPGA.
The on-line period detection device further includes display interface, and the display interface shows liquid sample action state, liquid sample
The real time data of detection, liquid sample release multiple, data analysis curve.
The hydraulic power supply is syringe pump, peristaltic pump, diaphragm pump and/or plunger pump, and the Pneumatic pressure power source is air pump.
Further include the sample introduction container for holding calibration liquid for bioprocesses on-line period detection device, passes through pipeline
Switching valve is connected with reaction tank.
It is set in the reaction detection pond and is equipped with detection solvent in measurement electrode or reaction detection pond.
The measurement electrode is pH electrode, dissolved oxygen electrode, ion detection electrode, glucose enzyme electrode, lactic acid enzyme electrode, paddy
Any one in propylhomoserin enzyme electrode, lysyl oxidase electrode.
The Multi-channel switching valve is triple channel switching valve, four-way switching valve, Five-channel switching valve, the switching of six channels
One or more of valve, seven channel switching valves, eight channel switching valves.
The utility model has the advantage that sampling amount is controllable for bioprocesses on-line period detection device,
Each sampling amount is 0.5-50 ml, is detected based on microbody system, and each sampling amount control at least can be controlled in 0.5 mL;Timeliness
Height, the sample detection time is short, and control is primary in 0.2-30min, and detection speed is fast, while can be avoided dead volume;Automatically, certainly
Dynamic sample detection, periodically keeps sample, automatic to detect, and analysis is automatically stored.
Utility model device, it is convenient for disassembly and assembly, convenient for operation, laboratory room small-sized bioreactor is applicable to industrial
A variety of occasions such as biofermentation;The utility model automatic sampling detection, effective less manual operation, can be effective in industrial application
Reduce cost of labor;Utility model device can be by the high-temperature sterilization of sampling system, it can be achieved that recycling.
Detailed description of the invention
Fig. 1 is a kind of structural schematic diagram of bioprocesses on-line period detection device of the utility model.
Symbol description:
01 bioreactor;11,12,13,14,15,16,17,18 be Multi-way control valve;111,112,113,114 are
Waste liquid bottle;31,32,33 be syringe pump;34 be solvent bottle;221,222 be reaction detection pond;21 be hydraulic power supply;22 be gas
Pressure power source;23 be automatic safety sampling device;24 be low temperature storage box;25 be liquid fusion chip;26 be calibration liquid sample introduction container;
27 be fiber spectrometer;50 be diluting tank a;51 be diluting tank b;61,62,63,64,65,66 be solenoid valve.
Specific embodiment
Specific embodiment of the utility model is more fully described below with reference to accompanying drawings.Although showing this reality in attached drawing
With novel specific embodiment, it being understood, however, that may be realized in various forms the utility model without that should be illustrated here
Embodiment limited.It is to be able to thoroughly understand the utility model on the contrary, providing these embodiments, and can incite somebody to action
The scope of the utility model is fully disclosed to those skilled in the art.
It should be noted that having used some vocabulary in the specification and claims to censure specific components.Ability
Field technique personnel it would be appreciated that, technical staff may call the same component with different nouns.This specification and right
It is required that not in such a way that the difference of noun is as component is distinguished, but with the difference of component functionally as differentiation
Criterion."comprising" or " comprising " as mentioned throughout the specification and claims are an open language, therefore should be solved
It is interpreted into " including but not limited to ".Specification subsequent descriptions are preferred embodiment of the present invention, the right description
It is being not intended to limit the scope of the utility model for the purpose of the rule of specification.The protection scope of the utility model
As defined by the appended claims.
Convenient for the understanding to the utility model embodiment, to be done by taking specific embodiment as an example below in conjunction with attached drawing further
Explanation, and each attached drawing does not constitute the restriction to the utility model embodiment.
Fig. 1 is a kind of structural schematic diagram of one embodiment of bioprocesses on-line measuring device of the utility model.
It is described in the utility model to be divided into sampling for bioprocesses on-line period detection device and keep sample module and reaction
The big functional module of detection module two.Sample the fermentation cycle circuit system and sampling that the module that keeps sample includes and biological respinse 01 forms
Keep sample pipe-line system, and the fermentation cycle circuit system formed with biological respinse 01 includes forming circulation loop with biological respinse 01
Hydraulic power supply 21, Multi-channel switching valve 11, the wherein optional four-way control valve 11 of Multi-channel switching valve 11, in addition both ends point
It Lian Jie not Pneumatic pressure power source 22;Sampling keep sample pipe-line system include Multi-channel switching valve 12,13,14, it is automatic safety sampling device 23, low
Warm storage box 24, hydraulic power supply 31 are wherein provided with the liquid storage chamber of transparent material on hydraulic power supply 31.It is real one
It applies in example, the functional module that keeps sample further includes waste liquid bottle 111.
During the fermentation, it does not enter sampling, keep sample, under detecting state, it is hydraulic dynamic that biological respinse 01 forms circulation loop
Power source 21, Multi-channel switching valve 11 form liquid sample circulation loop, and Multi-channel switching valve 11 and Pneumatic pressure power source 22, multichannel switch
Valve 12 is in an off state.
During keeping sample, circulation loop is disconnected by Multi-channel switching valve 11, the liquid sample in bioreactor is in liquid
Under the driving in pressure power source 21, cut by Multi-channel switching valve 11, Multi-channel switching valve 12, Multi-channel switching valve 13, multichannel
Change 14 access of valve, flow into sample-holding container 23, optionally carry out following steps: Pneumatic pressure power source 22 drive aseptic gas into
Enter pipeline and liquid is all driven in raising liquid sample allowance precision in sample-holding container 23.Sample-holding container multiple can form, and further lead to
It crosses automatic control switching and forms automatic sample-holding container.Sample-holding container 23 is arranged in low temperature storage box 24.
In sampling process, circulation loop is disconnected by Multi-channel switching valve 11, the liquid sample in bioreactor is in liquid
Under the driving in pressure power source 21, syringe pump is flowed by Multi-channel switching valve 11, Multi-channel switching valve 12, Multi-channel switching valve 13
In 31, optionally carry out following steps: Pneumatic pressure power source 22 drives aseptic gas to enter pipeline and liquid is all driven in note
It penetrates pump 31 and is driven in waste liquid bottle 111 alternatively, the liquid in pipeline is bent.Keep sample, after the completion of sampling process, keeps aneroid in pipeline
Body.
Hydraulic power supply 21 includes the control unit for controlling sample introduction, and described control unit adjusts liquid and enters diluting tank
In time, flow velocity and flow to control the sample volume of liquid.
The Pneumatic pressure power source 22 includes the control unit for controlling gas inlet, Pneumatic pressure power source control unit
For controlling inlet period, flow velocity and air inflow.
Syringe pump, peristaltic pump, diaphragm pump and/or plunger pump, the Pneumatic pressure power source can be selected in the hydraulic power supply 21
22 optional air pumps.
Multi-channel switching valve described in the utility model includes the control unit for controlling the switching of pipe path interface.
The bioprocesses on-line measuring device further includes control system and display interface, and the control system includes
General processor, digital signal processor, application-specific integrated circuit ASIC or on-site programmable gate array FPGA, it is hydraulic for controlling
The control unit of power source, the control unit in Pneumatic pressure power source, the control unit of Multi-channel switching valve;The display interface is shown
The flow velocity of liquid and/or gas, sample volume.
Reaction detection module and the sampling module that keeps sample closely are connect.Reaction detection module by different detection functions structure group
At.Electrode is set in the reaction detection pond and directly detects or add detection solvent progress reaction detection, and setting electrode is directly examined
Survey includes pH electrode, dissolved oxygen electrode, ion detection electrode detection;It is first with detection solvent that addition detection solvent, which carries out reaction detection,
Calibration, then detected using glucose enzyme electrode, lactic acid enzyme electrode, glutamic acid enzyme electrode, lysyl oxidase electrode.It may be implemented
OD, pH, dissolved oxygen DO, concentration of substrate and production concentration detection, the concentration of substrate and production concentration include carbon source content in liquid sample,
Nitrogen source content.
Before carrying out reaction detection, it is often necessary to handle sample, the utility model bioprocesses are examined online
Surveying in device and sampling the module that keeps sample further includes liquid sample dilution module.Liquid sample dilution module include solvent bottle 34, syringe pump 32,
Multi-channel switching valve 15, liquid hybrid chip 25, the liquid hybrid chip 25 are kept sample by Multi-channel switching valve 13 with sampling
Module is connected.Liquid sample after dilution is respectively enterd in diluting tank 1 and diluting tank 2 by Multi-channel switching valve 16, for further
Index checking.
Sampling the module that keeps sample to further include includes several different detection modules.
In one embodiment, pH detection module is set.It is above-mentioned keep sample functional module on the basis of, setting cut with multichannel
The connected reaction detection pond 221 of valve 14 is changed, pH detecting electrode is put into the reaction tank, pH on-line checking can be carried out.
In one embodiment, it is incorporated in the sampling structure that keeps sample to further describe, under the control of Multi-way control valve 14, disconnect
Keep sample access, opens sampling access, and liquid sample is entered in reaction detection pond 221 by Multi-way control valve 13,14.As for first keeping sample
Still first sample in reaction detection pond 21 to determine as needed.
After the completion of pH on-line checking, under the action of solenoid electric valve 63, the liquid in reaction detection pond 221 is discharged into useless
In liquid bottle 112, and can by air pump by liquid of the Multi-channel switching valve 11,12,13,14 into 221 pipeline of reaction detection pond into
One step empties.The control that syringe pump 33 can further be passed through, injects retarder thinner to " Multi-channel switching valve 15, liquid mixed core
The access that piece 25, Multi-channel switching valve 13, syringe pump 31 form ", " Multi-channel switching valve 15, liquid hybrid chip 25, multichannel
The access that switching valve 13, Multi-channel switching valve 14, reaction detection pond 221, waste liquid bottle 112 form ", " Multi-channel switching valve 15, liquid
The access that body hybrid chip 25, Multi-channel switching valve 13, Multi-channel switching valve 12, waste liquid bottle 111 form " is cleaned.
In another embodiment, fiber spectrometer detection module is added.It is provided on the hydraulic power supply syringe pump 31
Light spectral instrument is set at the liquid storage chamber of transparent material.The fibre-optical probe of the fiber spectrometer is located at hydraulic power supply
Outside 31 chamber of syringe pump, it is close to chamber wall.When liquid sample enters syringe pump 31, starting fiber spectrometer 27 carries out the light of stoste sample
Optical fiber spectrograph detection module.
For the accuracy for further increasing fiber spectrometer detection, need to be diluted sample processing.It is dilute that liquid sample is set
Release system 1(liquid hybrid chip 25, Multi-channel switching valve 15 and 16, syringe pump 32, solvent bottle 34, diluting tank a 50), pass through
Control system, the diluted multiple of analytical solution, is arranged according to Automatic parameter, controls in the sample liquid and solvent bottle 34 in syringe pump 31
Enter the amount in diluting tank a for diluted solvent, sample liquid be used for diluted solvent basis at liquid hybrid chip 25
Flow control mixes well, and syringe pump 32 is used to control the inlet for diluted solvent in solvent bottle 34, syringe pump 31
The inlet of liquid sample is controlled by injecting.Before carrying out second detecting, syringe pump 31 and Multi-channel switching valve 12,13 connect
It is logical, enter solution in waste liquid bottle 111, and extract the dilution in diluting tank a 50 by syringe pump 31 and carry out syringe pump
31 rinse, rinse liquid are discharged into waste liquid bottle 111.General rinse 3 times, after the completion of rinse, dilution is extracted again to injection
Pump 31 can measure original sample liquid under control system logical operation by the detection parameters that fiber spectrometer 27 measures dilution
Detection data.
After the detection of fiber spectrometer relevant parameter, the dilution in diluting tank a 50 is put into waste liquid bottle 113, and is passed through
Syringe pump 32, solvent bottle 34, Multi-channel switching valve 15, liquid hybrid chip 25, Multi-channel switching valve 16, diluting tank a 50 are formed
Access it is cleaned, waste liquid is discharged into waste liquid bottle 113.
It is further OD detection by the index that fiber spectrometer detects, is also applied for other and is detected by fiber spectrometer
Index, only need the arithmetic logic of adjustment control system.
In one embodiment, calibration detection module is added.The diluting tank b being connected with Multi-channel switching valve 16 is further set
51, Multi-channel switching valve 17, calibration liquid sample introduction container 26, Multi-channel switching valve 18, syringe pump 33, reaction detection pond 222, waste liquid
Bottle 114.Stoste in syringe pump 31 is used for together with diluted solvent by Multi-channel switching valve 13 with what is driven by syringe pump 32
Enter in diluting tank b 51 by liquid hybrid chip 25, Multi-channel switching valve 16.Diluted multiple can be controlled by system and be set
It sets, the calibration liquid in dilution, sample introduction container 26 in diluting tank b 51 passes through syringe pump 33 and quantitatively enters reaction detection pond
Reaction detection in 222 is discharged into after the completion in waste liquid bottle 114.Cleaning drives the solvent pair contained in solvent bottle 34 by syringe pump 32
Liquid hybrid chip 25, Multi-channel switching valve 16, in diluting tank b 51, Multi-channel switching valve 17 and 18, syringe pump 32, react inspection
It surveys pond 222 to be cleaned repeatedly, final waste liquid is discharged into waste liquid bottle 114.
Above-mentioned calibration detection module is other than for glucose concentration determination, it may also be used for other of substrate and product carbon source
The detection of the indexs such as content, nitrogen source content, i.e. other parameters that can demarcate detection are also suitable.
It is furthermore provided with solenoid electric valve 61,62,63,64,65,66, further controls the access of liquid.
Pipe diameter described in the utility model in bioprocesses on-line measuring device is 0.1-15mm, into one
Preferably 0.2-15 millimeters, further preferably 1-2 millimeters of step;The transparent material without self-luminous, acid and alkali-resistance of the selection for pipeline
Material.Each sampling amount is 0.5-50 mL, further preferably 1-20 milliliters, further preferably 5-15 milliliters;When every sub-sampling
Between be -1 minute 30 seconds, can continuous several times sampling, twice sampling interval time be -0.5 day 5 minutes, further preferably 1-2 is small
When;The liquid dead volume formed every time can control in 0.02-2 mL;When completing total overall reaction detection in the reaction detection pond
Between be 0.2-30 min.
In one embodiment, hydraulic power supply 21 uses peristaltic pump, and flow velocity is set as 20 mL/min;Its silica gel connected
Bore is 2 mm;It is 1.0 mm that the connecting line of four-way valve and keep sample bottle and waste liquid bottle, which is organic plastics hard tube internal diameter,.
Method according to the present utility model, can be automatic, reduces manual operation, cost of labor is effectively reduced;Pass through circulation
Circuit, dead volume is small, reduces the waste of liquid sample;Timeliness is high, and detection speed is fast;Automatically, automatic detection, periodically keeps sample,
Automatic detection, is automatically stored analysis.In addition, the utility model is carrying out high-temperature sterilization processing to pipeline and switching valve using preceding,
It is not necessarily to disinfecting action in the process, realizes sterile.
The application receives various modifications and interchangeable form, and specific embodiment is in the accompanying drawings by means of implementing
Example is to show and in the application detailed description.But the application is not intended to be limited to disclosed particular form.On the contrary,
The application is intended to include all modifications form, equivalent and the refill within the scope of the application, and scope of the present application is by appended
Claim and its legal equivalents limit.
Claims (10)
1. one kind is used for bioprocesses on-line period detection device, including hydraulic power supply, pipeline switching valve, Electromagnetic Control
Valve, syringe pump, waste liquid bottle, reaction detection pond, diluting tank, Pneumatic pressure power source, low temperature storage box, liquid fusion chip, solvent bottle,
And pipeline, which is characterized in that the hydraulic power supply is connected by pipeline with bioreactor;The pipeline switching valve is more
It is a, it is Multi-channel switching valve;The solenoid electric valve be it is multiple, be respectively used to control liquid or gas piping switch;Institute
State syringe pump be it is multiple, the volume in flow in pipes can accurately be controlled, the liquid line of wherein at least one syringe pump
Road is connected with fiber spectrometer;The waste liquid bottle is one or more;The reaction detection pond is multiple, one end connecting tube
Road, one end are connected by pipeline with waste liquid bottle;The diluting tank is directly or indirectly connected with syringe pump;The Pneumatic pressure power source
For controlling in filtrated air flow ipe;Automatic safety sampling device is provided in the low temperature storage box;The liquid merges core
Piece is provided with T-shape channel;Equipped with for diluted solvent in the solvent bottle;The pipeline is at least different two kinds of internal diameter
Pipeline.
2. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that the pipeline
Switching valve includes the automatic control unit for controlling switching.
3. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that described hydraulic
Power source, syringe pump include the control unit that it is used to control sample introduction, the control unit of the hydraulic power supply control sample introduction
The flow velocity and flow that liquid enters in pipeline are adjusted respectively with the control unit of syringe pump control sample introduction;The Pneumatic pressure power source packet
Its control unit for being used to control sample introduction is included, the control unit of the control sample introduction in the Pneumatic pressure power source enters for regulating gas
Flow velocity and flow in pipeline.
4. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that described online
Sampling detecting device further includes control system, and the control system includes for controlling hydraulic power supply feed liquor time, flow velocity, stream
The controller of amount, for control pressure power source inlet period, flow velocity, flow controller, for controlling pipeline switching valve, electricity
The controller of magnetic switching valve working condition, for controlling the injection of injection pump startup or the movement of back suction liquid, the control of flow velocity, flow
Device processed, for controlling the controller and general processor, digital signal processor, dedicated collection of low temperature storage box operating status
At circuit, application-specific integrated circuit ASIC or on-site programmable gate array FPGA.
5. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that described online
Sampling detecting device further includes display interface, and the display interface shows liquid sample action state, the real time data of liquid sample detection, liquid
Sample releases multiple, data analysis curve.
6. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that described hydraulic
Power source is syringe pump, peristaltic pump, diaphragm pump and/or plunger pump, and the Pneumatic pressure power source is air pump.
7. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that described online
Sampling detecting device further includes the sample introduction container for holding calibration liquid, is connected by pipeline switching valve with reaction tank.
8. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that the reaction
It is set in detection cell and is equipped with detection solvent in measurement electrode or reaction detection pond.
9. according to claim 8 be used for bioprocesses on-line period detection device, which is characterized in that the measurement
Electrode is pH electrode, dissolved oxygen electrode, ion detection electrode, glucose enzyme electrode, lactic acid enzyme electrode, glutamic acid enzyme electrode, relies ammonia
Any one in sour enzyme electrode.
10. according to claim 1 be used for bioprocesses on-line period detection device, which is characterized in that described more
Channel switching valve be triple channel switching valve, four-way switching valve, Five-channel switching valve, six channel switching valves, seven channel switching valves,
One or more of eight channel switching valves.
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CN111624357A (en) * | 2020-05-13 | 2020-09-04 | 中国科学院电工研究所 | Online automatic sampling proportioning system |
CN113311163A (en) * | 2020-02-26 | 2021-08-27 | 深圳迈瑞生物医疗电子股份有限公司 | Cleaning method of detection pool |
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CN113311163A (en) * | 2020-02-26 | 2021-08-27 | 深圳迈瑞生物医疗电子股份有限公司 | Cleaning method of detection pool |
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CN111624357A (en) * | 2020-05-13 | 2020-09-04 | 中国科学院电工研究所 | Online automatic sampling proportioning system |
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