CN2483723Y - Real-time quantitative analyser for piezoelectric gene dianostic - Google Patents

Real-time quantitative analyser for piezoelectric gene dianostic Download PDF

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Publication number
CN2483723Y
CN2483723Y CN 01206779 CN01206779U CN2483723Y CN 2483723 Y CN2483723 Y CN 2483723Y CN 01206779 CN01206779 CN 01206779 CN 01206779 U CN01206779 U CN 01206779U CN 2483723 Y CN2483723 Y CN 2483723Y
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piezoelectric
module
gene diagnosis
gene
piezoelectric gene
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CN 01206779
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莫志宏
吴中福
靳萍
田学隆
郭刚
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Chongqing University
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Chongqing University
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Abstract

The utility model is a real-time quantitative analyzer of piezoelectric gene diagnosis, belonging to the instrument of gene diagnosis. The aim of the utility model is to solve the problems of low veracity, low sensitivity, low efficiency and being difficult to realize the automation. The utility model comprises a shell, a control panel, a display, a power supply and the connecting circuit thereof, a mainboard module<60> of the microcomputer, analysis software, a sample preparation module<30> distilling at lest one clinic DNA sample at once, a location flow module changing and transporting the samples, a detection cell<52> amplifying and checking the target gene, a biochip of piezoelectric gene<51>, a device for heating and refrigerating and a piezoelectric gene diagnosis chip checking module<50> of the temperature controller thereof<53>. The utility model is suitable for clinical diseases diagnosis, molecular mechanism research, inspecting the epidemic and infectious disease diffusion, and inspecting the harmful microbe occurrence and diffusion, and so on.

Description

Piezoelectric gene diagnosis real-time quantitative analysis instrument
Technical field
The utility model belongs to the detecting instrument of outer-gene diagnosis.
Background technology
The generation development of most diseases is all relevant with patient's genetic background or its change, and gene diagnosis is meant the method for using genetic analysis disease to be made diagnosis.The object of gene diagnosis at first is the intrusion of causal organism, directly the inhereditary material that detects causal organism can improve the susceptibility and the specificity of diagnosis greatly, and in the time can't obtaining commercialization antibody, gene diagnosis just becomes the detection cause pathogeny imcrobe infection, especially the only resource of virus infections; Next is the congenital heredity illness, the disease that the heredity illness that some pathogenic factors are determined and other cause of disease it be unclear that all may with the holding or change relevant of certain or some genes; Moreover be the disease that gene mutation will cause the day after tomorrow, for example the cell infinite multiplication of undergoing mutation and causing owing to individual cells gene such as tumor suppressor gene or oncogene can be tentatively thought in the generation of tumour; Other is as dna fingerprint, individual identification, parent identification, forensic etc.Gene diagnosis is not only to clinical diagnosis, and to the cause of disease of disease and pathogenetic research, for patient detects curative effect, analyze more after, the objective health status of correctly estimating human body all has great importance.The gene diagnosis The Application of Technology makes the diagnosis of many difficult disease become easy, accurate, avoided some illness clinically to instruct the blindness of treatment by experience, reached the earliest, the most effective, the most most economical therapeutic purposes.
The real-time fluorescence quantitative PCR technology proposed in 1996, it have specificity stronger, effectively solve characteristics such as PCR pollution problem, automaticity height, be used widely at present.Disclosed " the DNA/RNA Real-Time Quantitative PCR-Rev.A﹠amp in 1999 of U.S. AppliedBiosystems company; B " report, introduced the principle and the characteristics of real-time fluorescence quantitative PCR technology.So-called real-time fluorescence quantitative PCR technology is meant in the PCR reaction system to add fluorescence probe, utilizes the fluorescence signal accumulation whole PCR process of monitoring in real time, the method for by typical curve unknown template being carried out quantitative test at last.
In addition, the gene piezoelectric gene diagnosis chip technology that occurs in recent years also is expected to be applied to gene diagnosis.Gene piezoelectric gene diagnosis chip technology is hybridized with the sample molecule of mark after being meant and being fixed in a large amount of gene probe molecules (gene probe array) on the holder, by hybridization signal intensity that detects each probe molecule and then quantity and the sequence information that obtains sample molecule, realize to gene accurately, fast, the detection of large information capacity.Deficiencies such as gene piezoelectric gene diagnosis chip technology has solved traditional nucleic acid blot hybridization technique trivial operations, automaticity is low, sequence of operation quantity is few, detection efficiency is low.And, by designing different probe arrays, using specific analytical approach can make this technology have multiple different gene diagnosises application." bioengineering progress " 1999, " gene piezoelectric gene diagnosis chip technology and applied research progress " article that Vol.19 (No.4): 45-51 delivers has been summarized both at home and abroad gene piezoelectric gene diagnosis chip technology in the main achievement in research aspect processing and preparing, the function and application.The existing gene piezoelectric gene diagnosis chip technology preparation of gene piezoelectric gene diagnosis chip on the one hand mainly is to adopt solid phase original position synthetic technology synthetic, stationary probe molecular array on carriers such as glass sheet in conjunction with photolithography; The detection of gene piezoelectric gene diagnosis chip mainly is to utilize labels targets gene such as fluorescein on the other hand, detects and analyzes by laser co-focusing microscan technology or the Charge Coupled Device (CCD) camera technique fluorescence signal to hybridization target gene on the piezoelectric gene diagnosis chip.
Above-mentioned real-time fluorescence quantitative PCR and gene piezoelectric gene diagnosis chip technology, on the one hand, all be to adopt fluoroscopic examination, need large complicated, accurate expensive detection equipment, need the long period simultaneously (3-4 hour), promptly need after (more than 15 times) amplification cycles repeatedly, or detect after finishing hybridization reaction, and impact analysis the factor of accuracy is more as a result, being difficult to control holds, easily produce false positive results, and need target gene or probe are carried out fluorescence labeling, increased the consumption reagent cost; On the other hand, analytic process comprises the multistep operation, comprises that especially sample pretreatment, target gene obtain with mark etc., complex operation, and that whole analytic system is difficult to is integrated, robotization and miniaturization.These defectives are the obstacles that are difficult to go beyond that popularize the gene diagnosis technology at present.
The utility model content
Given this, the purpose of this utility model is the mail topic that exists at existing gene diagnosis technology, provide a kind of accurate sensitivity, rapidly and efficiently, piezoelectric gene diagnosis real-time quantitative analysis instrument easy, with low cost automatically.
For reaching above-mentioned purpose, the utility model is based on the multiple PCR technique multiple target gene technology that increases simultaneously, the piezoelectric gene diagnosis chip technology that combines with the piezoelectric sensor array technology with the gene piezoelectric gene diagnosis chip, each module that gene diagnosises such as sample preparation, sample detection, interpretation of result are analyzed is integrated in a system, adopt microcomputer and automatic program control to carry out gene diagnosis quantitative test and dynamic each link information that shows, be built into piezoelectric gene diagnosis real-time quantitative analysis instrument.
Piezoelectric gene diagnosis real-time quantitative analysis instrument of the present utility model is (referring to accompanying drawing 1,2), comprise housing (10), control panel on the housing, display, power supply in the housing (20) and joining circuit thereof, the mainboard module of microcomputer (60), analysis software, it is characterized in that having in the housing and circuit and the joining specimen preparation module (30) that can once extract at least one clinical DNA sample of mainboard module, the selection of joining with the specimen preparation module is also carried the location flow module of sample, with the location flow module amplification of joining and detect the piezoelectric gene diagnosis chip detection module (50) of target gene, this piezoelectric gene diagnosis chip detection module has the long-pending circulation type detection cell (52) of microbody and is encapsulated in the piezoelectric gene diagnosis chip (51) that is made of piezoelectric gene sensor array wherein and semiconductor heating and refrigeration device and joining temperature controller (53) thereof on detection cell are arranged.
It is 0.2-2cm that above-mentioned specimen preparation module (30) has 2-100, volume 3The microwell plate (31) of micropore of splendid attire solution, the temperature controller (32) that is made of heating and refrigeration device and joining temperature sensor thereof is arranged.
Above-mentioned location flow module has the mechanical arm (41) that is driven by driving machine and suction spindle (42), peristaltic pump (43), piezoelectric gene diagnosis chip detection module (50), the waste liquid storage bottle (47) of linking to each other to be communicated with successively, and the import of piezoelectric gene diagnosis chip detection module and outlet have liquid level sensor (44,45) respectively.
Use piezoelectric gene diagnosis real-time quantitative analysis instrument of the present utility model (referring to accompanying drawing), at first, according to the clinical diagnosis object, select corresponding piezoelectric gene diagnosis detection module and gene diagnosis reagent, the piezoelectric gene diagnosis chip detection module is inserted in the piezoelectric gene diagnosis real-time quantitative analysis instrument, the test tube that is equipped with good sample solution and standard solution adding gene diagnosis reagent is inserted the specimen preparation module.Then, by the set up standard parameter of solution concentration, sample sequence and target gene group to be checked thereof and specimen preparation, location liquid stream and piezoelectric gene diagnosis chip detection module of analysis software.At last, automatically implement the state of also dynamically show sample preparation, location liquid stream and piezoelectric gene diagnosis chip detection module by programmed control, and the detection signal of piezoelectric gene diagnosis chip (frequency change), when frequency change reaches the frequency variable domain value of setting, stop circulation, the piezoelectric gene diagnosis chip detection module remains on the sex change stage, begin to draw cleaning solution simultaneously, after the every dot frequency of piezoelectric gene diagnosis chip indicates each site to recover to detect preceding frequency, emptying detection cell solution is measured next sample.After finishing all samples and measuring, enter the data analysis interface, provide the typical curve and the linear dimensions (slope, intercept and related coefficient) thereof of each target gene, and the concentration of each target gene to be measured in each sample.
The utility model and existing gene diagnosis instrument relatively have following advantage and effect.
At first, the piezoelectric gene diagnosis chip that the utility model adopts piezoelectric sensor to combine with gene piezoelectric gene diagnosis chip technology, the one, have the unique advantage of highly sensitive, the real-time monitoring probe of piezoelectric sensor-target gene hybridization reaction, be implemented in and carry out hybridization reaction and two steps of input on the piezoelectric gene diagnosis chip simultaneously, set up novel gene diagnosis real-time quantitative analysis technology on this basis, the hybridization reaction situation is followed the tracks of in dynamic reflection, eliminated the impact analysis factor of accuracy as a result, more simple and efficient, sensitive reliable; Simultaneously have gene piezoelectric gene diagnosis chip large information capacity, high efficiency advantage again, can once detect a plurality of target genes simultaneously.
Secondly, the utility model adopts piezoelectric gene diagnosis chip also to have following characteristics: 1. determine target gene by probe hybridization, because of the sequence of probe has specificity, so avoided false positive, the result is more reliable; 2. by the hybridization analysis experimental result, only need be expanded to the pg order of magnitude, need be expanded to the 50-100ng order of magnitude with common PCR with the fluoroscopic examination gene compares, significantly reduced cycle index, shortened detection time, also significantly reduce the consumption of reagent such as Taq enzyme simultaneously, saved the consumption costs that detects; 3. used probe and target gene do not need mark, and the thing of also not labelling had in addition both reduced the reagent expense, and was pollution-free again; 4. the detection of piezoelectric gene diagnosis chip is a frequency measurement accuracy height and interlock circuit is simple, and is inexpensive and be easy to miniaturization.
Moreover, the piezoelectric gene diagnosis real-time quantitative analysis instrument that the utility model makes up, the The whole analytical process that will comprise specimen preparation, gene magnification and detection, data analysis is integrated, easy and simple to handle, automatic high speed can be finished in the short time from primary sample to the complete set operation of obtaining required analysis result a system; The integrated analysis system that makes simultaneously of total analysis process is tightly isolated with extraneous, has effectively avoided pollution, and environment need not strict clean requirement to external world.
The utility model is suitable for research, monitoring epidemic disease and infectious disease diffusion, the generation of monitoring harmful microbe and the diffusion etc. of clinical disease diagnosis and molecule mechanism, is with a wide range of applications.
Below, the utility model is further described to use embodiment and accompanying drawing thereof again.
Description of drawings
Fig. 1 is the structural representation of a kind of piezoelectric gene diagnosis real-time quantitative analysis instrument of the present utility model.
Fig. 2 is the structure principle chart of Fig. 1.
The temperature cycles figure of piezoelectric gene diagnosis detection module when Fig. 3 is to use Fig. 1 to carry out the gene diagnosis analysis.
Site frequency change-time chart corresponding of piezoelectric gene diagnosis chip when Fig. 4 is to use Fig. 1 to carry out the gene diagnosis analysis with Fig. 3.
Frequency change-cycle index graph of a relation of when Fig. 5 is to use Fig. 1 to carry out the gene diagnosis analysis same target gene concentration repeatedly being measured.
Fig. 6 is the canonical plotting of a kind of target gene of the utility model piezoelectric gene diagnosis real-time quantitative analysis method.
Embodiment
A kind of piezoelectric gene diagnosis real-time quantitative analysis instrument of the present utility model is shown in accompanying drawing 1,2.Constitute by housing 10, power supply 20, specimen preparation module 30, location flow module, piezoelectric gene diagnosis chip detection module 50, circuit and mainboard module 60 and piezoelectric gene diagnosis real-time quantitative analysis instrument software etc.
Power supply 20 in above-mentioned housing 10 and the housing adopts the housing and the power supply architecture of common analytical instrument.Housing provides interior structure and appearance and modeling, makes each intermodule of instrument internal compact and noiseless, aesthetic in appearance.The control panel 11 and the display 12 that link to each other with microcomputer are arranged on the housing face, common numerical key, key and affirmation and cancel key are up and down arranged on the control panel, display is the display of common analytical instrument.Power supply provides working power to each module.
Above-mentioned specimen preparation module 30, the DNA extraction of a plurality of clinical samples is promptly once finished in preparation when realizing a plurality of sample, is made of microwell plate 31 and temperature controller 32.Above-mentioned microwell plate 31 usefulness heat conductance good metal materials as gold, silver, copper, aluminium etc., are made rectangle or circular slab, open on the plate and are shaped on a plurality of micropores, and micro pore volume is 0.2-2cm 3, number cells is 2-100, the quantity of micropore and volume, and the size of fixed therefrom plate are decided on the needs of practical application.Above-mentioned temperature controller 32 is made of the heating made from semiconductor and refrigeration device and temperature sensor, link to each other with related circuit in mainboard and the circuit module 60, controlled by subprograms corresponding, the precision of said temperature control is below ± 0.1 ℃, the heating and refrigerating speed 1.5 ℃/more than the sec, the fluctuation of per minute is less than ± 0.1 ℃ during constant temperature.
Above-mentioned location flow module, realization are selected sample introduction automatically, and selected absorption solution to be measured is also sent into detection cell, are made of mechanical arm 41, suction spindle 42, peristaltic pump 43, liquid level sensor 44,45, connection sebific duct 46.Above-mentioned mechanical arm 41 comprises X, Y two coordinates are numerical control linked and Z coordinate driving device structure, link to each other with related circuit in mainboard and the circuit module 60, controlled by subprograms corresponding.Above-mentioned suction spindle 42 with material heat-resisting, resistance to chemical attack, is made as stainless steel, teflon etc., is fixed on the mechanical arm 41.Above-mentioned peristaltic pump 43 adopts the housing and the structure of common peristaltic pump, links to each other with related circuit in mainboard and the circuit module 60, controlled by subprograms corresponding.Above-mentioned liquid level sensor 44,45 adopts photo-electric liquid position sensor, is placed in the front and back of piezoelectric gene diagnosis chip detection cell 52 respectively, links to each other with related circuit in circuit and the mainboard module 60.Above-mentioned connection sebific duct 46 adopts resilient material heat-resisting, heat-resisting, resistance to chemical attack, makes as teflon etc., links to each other with detection cell 52 with suction spindle 42, leads to waste liquid storage bottle 47.
Above-mentioned piezoelectric gene diagnosis chip detection module 50 is realized the amplification and the detection of target gene, is made of piezoelectric gene diagnosis chip 51, the long-pending circulation type detection cell 52 of microbody, temperature controller 53.Above-mentioned piezoelectric gene diagnosis chip 51 is made of piezoelectric gene sensor array, and above-mentioned piezoelectric gene diagnosis chip is packaged in the long-pending circulation type detection cell 52 of microbody, links to each other with piezoelectric gene diagnosis chip testing circuit in circuit and the mainboard module 60.Above-mentioned microbody amasss circulation type detection cell 52, by detection cell 52 be installed in semiconductor heating on the detection cell and refrigeration device and temperature sensor 53 constitute, links to each other with control circuit with the middle temperature detection of circuit and mainboard module 60.The precision of above-mentioned piezoelectric gene diagnosis chip testing circuit frequency measurement is that 1Hz is following, the fluctuation of per minute is less than ± 1Hz, the precision that said temperature is measured is below ± 0.1 ℃, the heating and refrigerating speed 1.5 ℃/more than the sec, the fluctuation of per minute is less than ± 0.1 ℃ during constant temperature.
Foregoing circuit and mainboard module 60, for each module provides operating circuit and interface circuit, and micro-computer function, circuit and computer motherboard by above-mentioned each module constitute, computer motherboard adopts more than the Pentium II, good stable and extensibility is arranged, as the standard motherboard P3V133 in 2000 of Asus.Each modular circuit links to each other with computer motherboard by interface.
Above-mentioned piezoelectric gene diagnosis real-time quantitative analysis software is realized system's master control and data analysis.Analysis software is made of master control interface and data analysis interface.Above-mentioned master control interface by with above-mentioned each module subprogram communication, carry out system's master control, system initialization and detecting pattern setting, each functions of modules shows, detects subroutines such as data call and performance graph demonstration and constitutes.Above-mentioned data analysis interface provides typical curve and linear dimensions (slope, intercept and related coefficient) and target gene concentration.
The course of work that use the utility model carries out the gene diagnosis real-time quantitative analysis is as follows:
At first, in cleaning, common test tube such as Ependoff pipe, add 10-100 ready standard solution series of μ L and sample solution.Standard solution series comprises the solution of blank (target gene concentration is 0) and concentration known target gene group to be checked for two or more, is 0,0.1 * 10 as target gene concentration -5Two standard solution of mol/L, or 0,0.1 * 10 -5, 1 * 10 -5Three standard solution of mol/L, or 0,0.1 * 10 -5, 0.5 * 10 -5, 1 * 10 -5Four standard solution of mol/L etc.In above-mentioned each solution test tube, add the gene diagnosis reagent that contains primer, Taq-DNA polymerase, deoxy-ribonucleoside triphosphate, target gene to be checked is contacted with piezoelectric gene diagnosis chip with the sample of corresponding primer, Taq-DNA polymerase, deoxy-ribonucleoside triphosphate, subsequently, put into each micropore of the microwell plate of specimen preparation module respectively.Then, by the input of master control interface and control panel set up standard solution concentration, sample sequence and target gene group to be checked thereof, the temperature and time of specimen preparation and the parameters such as temperature and time of temperature cycles.
Then, implement down and the dynamic the following step that shows by the programmed control of computer motherboard:
1. by temperature controller control, heated sample prepares module and prefabricated sample, and promptly heating-up temperature 85-99 ℃, and retention time 10-100 second.
2. mechanical arm moves to suction spindle in the sample tube in the predetermined microwell plate, opens peristaltic pump and draws sample and also inject detection cell, after liquid level sensor indication detection cell is full of sample, stops to draw, stops to inject.
3. by hybridizing-extend-temperature cycles of sex change, the temperature and time of temperature cycles is: 85-99 ℃ of middle sex change stage, 10-60 second, crossing phase 30-70 ℃, 10-60 second, extend stage 65-80 ℃, 10-60 second, as shown in Figure 3.In temperature cycles, on display, show in real time piezoelectric gene diagnosis chip each with the predetermined corresponding site frequency change-time curve of target gene group to be checked, as shown in Figure 4, and determine the frequency variable domain value in this site in the frequency change of first crossing phase according to each site, as 10-100Hz, when every dot frequency variation meets or exceeds the frequency variable domain value of setting, stop temperature cycles, and the cycle index when determining that each site reaches variable domain value frequently.
4. with detection cell heating and remain on denaturation temperature, begin to draw cleaning solution by suction spindle simultaneously and clean detection cell, treat the every dot frequency of piezoelectric gene diagnosis chip indicate each site to recover to detect before after the frequency, emptying detection cell solution is also delivered to the waste liquid storage bottle.
Repeat 2.~4. step operation, measure all the other samples.
5. after finishing the detection of all solution, by the data analysis interface, program processing data, result by standard solution series draws the typical curve that each target gene detects cycle index-target gene concentration logarithm, as shown in Figure 6, more per sample the cycle index that detects of target gene draw the concentration of sample target gene.
As previously mentioned, the utility model only needs less circulation number of times, usually is less than 10 times, just can reach target Gene detects required frequency change, as shown in Figure 5, to the solution of same concentration target gene, repeatedly measures The relation of frequency change and temperature cycles number of times, result show that reaching frequently, the circulation number of times of variable domain value has fabulous Reappearance, but after this with the increase of temperature cycles number of times, the frequency change under different the mensuration differs more big. Therefore, Usually comparing the utility model gene quantification more than 15 times with real-time fluorescence quantitative PCR technology circulation number of times Analysis has higher accuracy and reappearance, and shorter advantage of time.

Claims (3)

1, piezoelectric gene diagnosis real-time quantitative analysis instrument, comprise housing (10), control panel on the housing, display, power supply in the housing (20) and joining circuit thereof, the mainboard module of microcomputer (60), analysis software, it is characterized in that having in the housing and circuit and the joining specimen preparation module (30) that can once extract at least one clinical DNA sample of mainboard module, the selection of joining with the specimen preparation module is also carried the location flow module of sample, with the location flow module amplification of joining and detect the piezoelectric gene diagnosis chip detection module (50) of target gene, this piezoelectric gene diagnosis chip detection module has the long-pending circulation type detection cell (52) of microbody and is encapsulated in the piezoelectric gene diagnosis chip (51) that is made of piezoelectric gene sensor array wherein and semiconductor heating and refrigeration device and joining temperature controller (53) thereof on detection cell are arranged.
2, piezoelectric gene diagnosis real-time quantitative analysis instrument according to claim 1 is characterized in that it is 0.2-2cm that said specimen preparation module (30) has 2-100, volume 3The microwell plate (31) of micropore of splendid attire solution, the temperature controller (32) that is made of heating and refrigeration device and joining temperature sensor thereof is arranged.
3, piezoelectric gene diagnosis real-time quantitative analysis instrument according to claim 1 and 2, it is characterized in that said location flow module has the mechanical arm (41) that is driven by driving machine and suction spindle (42), peristaltic pump (43), piezoelectric gene diagnosis chip detection module (50), the waste liquid storage bottle (47) of linking to each other to be communicated with successively, the import of piezoelectric gene diagnosis chip detection module and outlet have liquid level sensor (44,45) respectively.
CN 01206779 2001-07-10 2001-07-10 Real-time quantitative analyser for piezoelectric gene dianostic Expired - Fee Related CN2483723Y (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101892150A (en) * 2009-05-21 2010-11-24 蔡志明 Mobile genetic information analysis device and method
CN102021615A (en) * 2010-06-01 2011-04-20 无锡市金义博仪器科技有限公司 Galvanizing ammonium salt flux bath solution analyzer
CN102435726A (en) * 2010-09-23 2012-05-02 财团法人工业技术研究院 Chemical or biochemical analysis device and chemical or biochemical analysis method
CN109100502A (en) * 2018-07-28 2018-12-28 湖南中瑞互信医疗科技有限公司 A kind of full-automatic immunoblotting instrument
CN110791422A (en) * 2019-11-08 2020-02-14 宁波胤瑞生物医学仪器有限责任公司 Regulating and controlling method of nucleic acid amplification instrument

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101892150A (en) * 2009-05-21 2010-11-24 蔡志明 Mobile genetic information analysis device and method
CN102021615A (en) * 2010-06-01 2011-04-20 无锡市金义博仪器科技有限公司 Galvanizing ammonium salt flux bath solution analyzer
CN102021615B (en) * 2010-06-01 2012-04-18 无锡市金义博仪器科技有限公司 Galvanizing ammonium salt flux bath solution analyzer
CN102435726A (en) * 2010-09-23 2012-05-02 财团法人工业技术研究院 Chemical or biochemical analysis device and chemical or biochemical analysis method
CN109100502A (en) * 2018-07-28 2018-12-28 湖南中瑞互信医疗科技有限公司 A kind of full-automatic immunoblotting instrument
CN109100502B (en) * 2018-07-28 2024-01-09 湖南中瑞互信医疗科技有限公司 Full-automatic immunoblotting appearance
CN110791422A (en) * 2019-11-08 2020-02-14 宁波胤瑞生物医学仪器有限责任公司 Regulating and controlling method of nucleic acid amplification instrument

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