CN113720818B - Fluorescent immunodetection system - Google Patents
Fluorescent immunodetection system Download PDFInfo
- Publication number
- CN113720818B CN113720818B CN202110998635.5A CN202110998635A CN113720818B CN 113720818 B CN113720818 B CN 113720818B CN 202110998635 A CN202110998635 A CN 202110998635A CN 113720818 B CN113720818 B CN 113720818B
- Authority
- CN
- China
- Prior art keywords
- module
- reaction
- sample
- pool
- tank
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000006243 chemical reaction Methods 0.000 claims abstract description 81
- 238000001514 detection method Methods 0.000 claims abstract description 59
- 239000000758 substrate Substances 0.000 claims abstract description 54
- 238000004458 analytical method Methods 0.000 claims abstract description 36
- 238000004140 cleaning Methods 0.000 claims abstract description 36
- 239000012474 protein marker Substances 0.000 claims abstract description 29
- 238000003018 immunoassay Methods 0.000 claims abstract description 15
- 238000012545 processing Methods 0.000 claims abstract description 12
- 239000003550 marker Substances 0.000 claims abstract description 9
- 239000011248 coating agent Substances 0.000 claims description 34
- 238000000576 coating method Methods 0.000 claims description 34
- 230000005284 excitation Effects 0.000 claims description 19
- 239000000427 antigen Substances 0.000 claims description 9
- 102000036639 antigens Human genes 0.000 claims description 8
- 108091007433 antigens Proteins 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 239000007853 buffer solution Substances 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 5
- 238000001914 filtration Methods 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 238000007689 inspection Methods 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 3
- 238000004891 communication Methods 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 8
- 238000003745 diagnosis Methods 0.000 abstract description 4
- 230000010354 integration Effects 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 description 12
- 238000010586 diagram Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000013461 design Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 208000035473 Communicable disease Diseases 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 239000003163 gonadal steroid hormone Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000001685 thyroid gland Anatomy 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 238000003759 clinical diagnosis Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013500 data storage Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000001215 fluorescent labelling Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002122 magnetic nanoparticle Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N2021/0106—General arrangement of respective parts
- G01N2021/0112—Apparatus in one mechanical, optical or electronic block
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Clinical Laboratory Science (AREA)
- Optics & Photonics (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Dispersion Chemistry (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
Abstract
The invention provides a fluorescence immunoassay system. The system comprises a microfluidic chip and portable analysis equipment; the protein marker substrate is preprocessed to form a multi-index biological array; the chip shell is provided with a sample pool, a driving piston, a piston driving pool, a reaction pool, a cleaning pool and a detection area respectively; the analysis equipment has the function of assisting the substrate to complete biological reaction in the microfluidic chip and collecting signals and analyzing results. The bottom end of the piston driving pool is connected with the top end of the sample pool, the sample liquid enters the reaction pool and reacts with the substrate through the microfluidic structure under the movement of the piston, the instrument controls the substrate to finish cleaning and fluorescent marker capturing in the chip, and the fluorescent signal of the substrate is collected in the detection area. The analysis equipment realizes the automatic realization of the instrument functions and the instrument structure integration through the embedded control module. The invention has the characteristics of low cost, convenient processing, portability and the like, and belongs to the field of instant diagnosis.
Description
Technical Field
The invention belongs to the field of instant diagnosis, and also relates to a micro-fluidic chip technology, in particular to a fluorescence immunoassay system which is suitable for multi-index combined rapid detection.
Background
Microfluidic (Microfluidics) chip technology is a modern technology that integrates basic operation units such as sample preparation, reaction, separation, detection and the like in biological, chemical and medical analysis processes onto a micrometer-scale biochip, and performs analysis by precisely controlling and manipulating microscale fluids and detecting electrical, magnetic or optical signals on the chip. With the progress of research, microfluidic chips have been developed into a new research field crossing various fields such as biology, chemistry, medicine and machinery, and have great potential in various fields such as biochemistry, environmental monitoring and epidemic prevention.
The microfluidic chip has the characteristics of controllable liquid flow, relatively closed environment, small sample consumption, high reaction speed, easy integration and the like, and has unique advantages compared with the detection technology in the current medical diagnosis and analysis fields. At present, the micro-fluidic chip technology has been greatly developed in the aspects of biomarker immunoassay, nucleic acid sequencing, cell sorting, identification and other disease diagnosis, and particularly, compared with the traditional instrument detection at present, the micro-fluidic chip has great potential in the technical fields of portability, convenience and sensitivity detection along with the requirements of early diagnosis products for related diseases such as infectious diseases, tumor markers, sex hormones, thyroid gland and the like in the current medical field.
The detection technology established based on micro-fluidic chips in the current market mostly adopts electric signals or magnetic signals, but the requirements of the biochip on equipment and chips are extremely high, the chip design is complex, the volume of the equipment is large, the detection cost is high, and the popularization and the use are difficult. In recent years, fluorescence as a more direct marker with a mature detection principle is increasingly applied in the field of microfluidic chip development to develop a more convenient detection system. As proposed by BorFuh et al (a magnetic-microfluidic platform for fluorescence immunosensing using quantum dot nanopartics. BorFuh et al nanotechnology,2019,30) functional magnetic nanoparticles labeled with antibodies were pre-deposited on the microfluidics, the antigen reacted with the antibodies through the deposition zone, and the antigen in the immune complex was detected and confirmed using fluorescent nanoparticles labeled with antibodies, and the signal was collected using a fluorescent reader. Meanwhile, fang Xueen et al (Efficient Microfluidic-Based Air Sampling/Monitoring Platform for Detection of Aerosol SARS-CoV-2On-site, X Fang et al analytical Chemistry,2021,93,9) propose the integration of an aerosol SARA-CoV-2 sampling system by constructing a small-volume rotary microfluidic fluorescent chip to realize rapid sample collection in the field and detection in the microfluidic chip. In summary, the above technology guarantees the need and the proceeding of biological reaction by dividing and preprocessing the modules and functions of the microfluidic chip, and then uses the equipment or the sensor to collect and process the signal of the fluorescent marker, so that the design, the material (light transmittance, polarization degree, etc.) of the microfluidic chip, the excitation-emission angle between the equipment and the microfluidic chip, the processing accuracy of the microfluidic chip, and the design of the instrument structure have strict requirements, and it is difficult to realize mass production and large-scale application.
Disclosure of Invention
The invention aims to solve the problems of high processing difficulty, high cost, complex instrument volume and the like of the conventional multi-index fluorescence automatic analysis equipment based on the micro-fluidic technology, combines the micro-fluidic technology with an embedded control system, uses a protein marker substrate as a biological reaction carrier, simplifies and integrates a control and signal acquisition module through interaction between the control substrate and a micro-fluidic chip, and realizes the high-precision and multi-index rapid automatic detection of biomolecules.
The object of the invention is achieved by at least one of the following technical solutions.
The fluorescence immunoassay system comprises a microfluidic chip and analysis equipment, wherein the analysis equipment is used for collecting fluorescence signals and analyzing results of the reacted coating sites in a detection area;
the microfluidic chip comprises a chip shell and a protein marker substrate, wherein the protein marker substrate comprises a coating carrier and a plurality of coating sites arranged on the coating carrier, and is used as a reaction substrate for multi-index joint inspection;
the chip shell is sequentially provided with a sample pool, a driving piston, a piston driving pool, a reaction pool, a cleaning pool and a detection area, wherein the upper end of the sample pool is connected with the piston driving pool, and the lower end of the sample pool is communicated with the reaction pool through a microfluidic structure; the driving piston can move up and down in the piston driving pool; the cleaning pool is used for cleaning the reacted residual reagent; the analysis equipment comprises a signal acquisition module and an embedded control module, wherein the signal acquisition module is connected with the embedded control module and is used for carrying out fluorescent signal acquisition on a reacted coating site in a detection area, the embedded control module is used for controlling the operation of the signal acquisition module, processing signals acquired by the signal acquisition module and calculating the concentration of an antigen to be detected in a sample to be detected.
Through driving the driving piston, air in the piston driving pool enters the sample pool, a sample enters the reaction pool through the microfluidic structure under the driving of pressure, after fluorescent labeling detection antibody is captured, a protein marker substrate is subjected to fluorescent signal acquisition in a detection area by a signal acquisition module of analysis equipment.
Further, the coating sites of the protein marker substrate are uniformly distributed on the coating carrier, and each coating site is respectively pre-coated with an antibody which can be specifically combined with different detection markers.
Further, the sample cell comprises a sample cover and a cavity, wherein the sample cover is positioned above the sample cell and is connected with the lower part of the piston driving cell through a first microfluidic channel, and the bottom end of the cavity is connected with the reaction cell through a microfluidic structure. The sample is driven by pressure to enter the reaction tank through the microfluidic structure.
Further, the microfluidic structure comprises a second microfluidic channel and a filter tank communicated with the second microfluidic channel, one end of the second microfluidic channel is connected with the bottom end of the cavity, the filter tank is connected with the reaction tank, and a blood filtering membrane is arranged in the filter tank. Larger proteins and other impurities are filtered out by arranging a hemofilter.
Further, the reaction tank comprises a first reaction tank and a second reaction tank, the first reaction tank is used for placing buffer solution, the second reaction tank is used for placing fluorescent marked detection antibody solution, and a cleaning tank is arranged among the first reaction tank, the second reaction tank and the detection area. And after the sample is uniformly mixed with the buffer solution of the first reaction tank, the coated antibody which is coated on the coated carrier in advance reacts with the sample which is uniformly mixed with the buffer solution, the residual reagent is cleaned in the cleaning tank and then enters the second reaction tank to improve the detection precision, the cleaned protein marker substrate enters the second reaction tank to finish the capture of the fluorescent marker detection antibody, then continuously enters the cleaning tank to be cleaned, and then enters the detection area to carry out the collection of fluorescent signals.
Further, the signal acquisition module comprises a signal acquisition unit, and comprises a fluorescence excitation module and a signal detection module, wherein the fluorescence excitation module is used for exciting fluorescent molecules, and the signal detection module is used for receiving excitation light.
The signal acquisition module further comprises a signal acquisition motor, the signal acquisition motor controls the signal acquisition unit to approach a certain coating site, excitation light with smaller light spots is provided in the signal acquisition unit to excite fluorescent molecules in the area, the excitation light is received by the signal detection module of the signal acquisition unit, conversion and acquisition of optical-electrical-digital signals of fluorescence of the coating site are completed, and then signal acquisition of each coating site is completed in sequence.
Further, the analysis equipment also comprises an instrument shell, a mechanical framework, an electronic touch pad, an embedded control module, a power module and an operation module,
the mechanical framework is arranged in the instrument shell;
the electronic touch control board, the embedded control module and the operation module are all arranged on the mechanical framework, and the electronic touch control board, the operation module and the signal acquisition module are all connected with the power supply module through the embedded control module;
the operation module comprises a substrate moving submodule, a piston driving submodule and a clamping submodule, wherein the substrate moving submodule is used for controlling movement of the protein marker substrate, the piston driving submodule is used for controlling up-and-down movement of a driving piston so as to send a sample in the sample pool into the reaction pool through pressure change, and the clamping submodule is used for fixing the microfluidic chip.
Further, the substrate moving submodule comprises a moving motor, a guide rail, a gripper motor and a mechanical gripper controlled by the motor, wherein the three groups of moving motors are respectively used for controlling the movement of the gripper and the grabbing action of the protein marker substrate.
Further, in the substrate moving sub-module, an output shaft of the gripper motor is connected with the gripper and fixed with an output shaft of the moving motor through a nut.
Further, the clamping submodule is located below the base moving submodule and the piston driving submodule and comprises a fixed clamping seat and a temperature control device, and the fixed clamping seat is connected with an external bayonet of the instrument shell through a sliding rail. The microfluidic chip slides along with the card seat on the slide rail from the card inlet to the lower part of the substrate moving sub-module.
Further, the piston driving sub-module is positioned above the inner part of the bayonet outside the instrument shell, comprises a pushing pull rod of the piston, a group of motors and guide rails, and is connected with an output shaft of the motor through a nut, so that the pull rod can be driven to move up and down.
The invention combines a microfluidic chip and an embedded control system, and constructs a biological microarray by taking a protein marker substrate as a carrier of a fluorescent immunoassay biological reaction, so as to develop a portable multi-index fluorescent immunoassay system and a method based on a microfluidic technology, and compared with the prior art, the invention has the following beneficial effects:
1) The chip processing technology has low difficulty and controllable cost. The microfluidic technology is combined with the embedded control module, biological reaction automation is realized through interaction between the system control substrate and the microfluidic chip, and the signal acquisition module is used for sequentially exciting and acquiring the coating sites on the substrate, so that compared with the chip frequently used in the market at present, the complex requirement of chip processing is avoided, the processing difficulty is reduced, and the cost is lower;
2) The instrument is small in size and high in integration degree. According to the invention, the piston driving sub-module is used as the driving force of the microfluid, and a series of automatic control devices such as the piston driving sub-module and the embedded control module are integrated in the mechanical framework, so that automation from sample processing and biological reaction to signal detection and analysis in an instrument with smaller volume is realized, and the device has the characteristics of convenience in carrying, simplicity in operation and rapidness in detection.
3) The invention is suitable for clinical diagnosis and disease screening field, especially for early preliminary screening and self-detection of a series of diseases such as infectious diseases, tumor markers, sex hormones, thyroid gland, etc.
Drawings
Fig. 1 is a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention.
FIG. 2 is a schematic diagram of the structure of a protein marker substrate according to an embodiment of the present invention.
Fig. 3 is a schematic diagram of a bottom structure of a microfluidic chip according to an embodiment of the present invention.
Fig. 4 is a schematic diagram of an internal structure of a microfluidic chip according to an embodiment of the present invention.
Fig. 5 is a schematic diagram of a portable analysis device.
Fig. 6 is a schematic structural diagram of a fluorescent signal acquisition module.
Fig. 7 is a schematic view of a substrate movement sub-module structure.
FIG. 8 is a schematic diagram of a clip submodule structure.
Fig. 9 is a schematic diagram of a piston drive sub-module.
Detailed Description
For the purpose of making the objects, technical solutions and features of the embodiments of the present invention more apparent, the present invention will be described in further detail below with reference to the accompanying drawings and the embodiments, and it is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments; based on the embodiments of the present invention, all other embodiments that can be obtained by a person of ordinary skill in the art without making any inventive effort are within the scope of the present invention.
Referring to fig. 1-6, the fluorescent immunodetection system provided by the invention comprises a microfluidic chip and portable analysis equipment. The portable analysis device has the functions of assisting the microfluidic chip to complete biological reaction and complete signal acquisition and result analysis.
Referring to fig. 1-4, the microfluidic chip includes a chip housing 1 and a protein marker substrate 2, wherein the protein marker substrate 2 includes a coating carrier 2-1 and a plurality of coating sites 2-2 disposed on the coating carrier 2-1 as a reaction substrate for multi-index joint inspection.
In the invention, a sample pool 3, a driving piston 4-1, a piston driving pool 4-2, a reaction pool 5, a cleaning pool 6 and a detection area 7 are sequentially arranged in a chip shell 1, the upper end of the sample pool 3 is connected with the piston driving pool 4-2, and the lower end is communicated with the reaction pool 5 through a microfluidic structure; the cleaning tank 6 is used for cleaning residual reagent after the reaction; the analysis equipment comprises a signal acquisition module and an embedded control module, wherein the signal acquisition module is connected with the embedded control module and is used for acquiring fluorescent signals at the coating sites 2-2 after reaction in the detection zone 7. The embedded control module is used for controlling the signal acquisition module 13 to work, processing the signals acquired by the signal acquisition module 13 and calculating the concentration of the antigen to be detected in the sample to be detected.
In some embodiments of the present invention, referring to fig. 1, a substrate carrying cavity 12 is further disposed in the chip housing 1, and the protein marker substrate 2 is disposed on the substrate carrying cavity 12, so as to ensure the preservation and transportation of the protein marker substrate 2 and the microfluidic chip, and also facilitate the automation operation of the detection process by the instrument.
In some embodiments of the present invention, as shown in fig. 2, the coating sites 2-2 of the protein marker substrate 2 are distributed on the coating carrier 2-1, and antibodies capable of specifically binding to different kinds of markers are pre-coated on the coating sites 2-2 to prepare a multi-index joint inspection bioarray.
In some embodiments of the present invention, the coating sites 2-2 are square or round, each coating site is uniformly distributed and orderly arranged, and the signal acquisition module excites the middle area of each coating site 2-2 site by site and acquires signals so as to ensure that each site has sufficient reaction and balanced signal intensity.
In some embodiments of the present invention, referring to fig. 1, 3 and 4, the sample cell 3 is a relatively sealed structure formed by the sample cover 3-1 and the cavity, and the sample can be conveniently injected into the cavity by opening the sample cover 3-1. The sample cover 3-1 is positioned at the upper end of the sample pool 3, a mounting hole is formed in the sample cover 3-1, a first micro-flow channel 11 which can be communicated with a cavity is arranged in the mounting hole, the free end of the first micro-flow channel 11 is communicated with the lower part of the piston driving pool 4-2, and the bottom end of the cavity is communicated with the reaction pool 5 through a micro-flow control structure.
In some embodiments of the present invention, as shown in fig. 1 and 3, the lower end of the piston driving pool 4-2 is externally connected to the small hole at the inner bottom end of the chip housing 1 through the micro-channel 10, and is communicated with the mounting hole on the sample cover 3-1 through the soft first micro-flow channel 11, so as to provide power for the sample in the sample pool 3 through the micro-flow structure between the sample pool 3 and the reaction pool 5, and also facilitate the processing of the chip housing.
In some embodiments of the present invention, as shown in fig. 3, the microfluidic structure includes a second microfluidic channel 8 and a filter tank 9 in communication with the second microfluidic channel 8, one end of the second microfluidic channel 8 is connected to the bottom end of the cavity of the sample tank 3, the filter tank 9 is connected to the reaction tank 5, and a blood filtering membrane is provided in the filter tank 9. By arranging the blood filtering membrane to block larger protein and other impurities, the influence on the detection result can be avoided, and the detection accuracy is improved.
In some embodiments of the present invention, the reaction cell 5 includes a first reaction cell 5-1 for placing a buffer solution and a second reaction cell 5-2 for placing a fluorescent-labeled detection antibody solution, and a washing cell 6 is provided between the first reaction cell 5-1 and the second reaction cell 5-2, between the second reaction cell 5-2 and the detection zone 7, wherein the filtration cell 9 communicates with the first reaction cell 5-1. Preferably, two mutually independent cleaning tanks are arranged behind the first reaction tank 5-1, namely a first cleaning tank 6-1 and a second cleaning tank 6-2, and two mutually independent cleaning tanks are also arranged behind the second reaction tank 5-2, namely a third cleaning tank 6-3 and a fourth cleaning tank 6-4, and the adjacent two cleaning tanks act in a consistent manner, so as to ensure that excessive residual reagents reacted in the previous reaction tanks are completely cleaned.
When the device works, the driving piston 4-1 on the microfluidic chip is driven, air in the piston driving pool 4-2 enters the sample pool 3, a sample enters the first reaction pool 5-1 through the microfluidic structure under the driving of pressure and is uniformly mixed with buffer solution in the sample, then the protein marker substrate 2 is washed in the first washing pool 6-1 and the second washing pool 6-2 in sequence, fluorescent marker detection antibody capturing is completed in the second reaction pool 5-2, residual reagents are washed in the third washing pool 6-3 and the fourth washing pool 6-4, and then the sample enters the detection area 7, and the analysis equipment completes fluorescent signal acquisition on the protein marker substrate 2.
In the embodiment of the invention, the initial state of the microfluidic chip is as follows:
the detection marker antibody is pre-coated on the coating site 2-2 on the protein marker substrate 2;
the first reaction tank 5-1 is preloaded with buffer formulation liquid, and the first cleaning tank 6-1 and the second cleaning tank 6-2 are preloaded with cleaning liquid 1;
the second reaction tank 5-2 is preloaded with a fluorescent-labeled detection antibody solution;
the third cleaning tank 6-3 and the fourth cleaning tank 6-4 are preloaded with cleaning liquid 2.
The cleaning liquid 1 and the cleaning liquid 2 are selected according to the experimental reaction conditions of the project.
In some embodiments of the present invention, referring to fig. 6, the signal acquisition module 13 controls the smaller signal acquisition unit to approach the coating site through the signal acquisition motor 13-1, and excitation light with smaller light spots is provided in the signal acquisition unit to excite fluorescent molecules in the area, and the excitation light is received by the signal detection module of the signal acquisition unit, so as to complete conversion and acquisition of the photo-electro-digital signal. Specifically, the signal acquisition module comprises a signal acquisition motor 13-1, a signal acquisition guide rail 13-2 and a signal acquisition unit, wherein the signal acquisition motor 13-1 drives the signal acquisition unit to move up and down along the signal acquisition guide rail 13-2, so that the position of the signal acquisition unit can be adjusted, and signals of coating sites with different heights can be acquired.
The signal acquisition unit comprises a fluorescence excitation module 13-3-1 and a signal detection module 13-3-2, wherein the fluorescence excitation module 13-3-1 is used for exciting fluorescent molecules, and the signal detection module 13-3-2 is used for receiving excitation light. In some embodiments of the present invention, the fluorescent excitation module 13-3-1 includes 3 groups of ultraviolet LED light sources and ultraviolet filters, which can provide excitation light with a specific wavelength with concentrated energy, the excitation light is converged through the ultraviolet filters and irradiates the middle area of the coating sites, fluorescent molecules in the area are excited, the excited light is received by the signal detection module 13-3-2 to complete conversion and collection of optical-electrical-digital signals of site fluorescence, and then signal collection of each coating site is sequentially completed. Preferably, the signal detection module 13-3-2 comprises a half-mirror, a narrow-band filter and a signal detector, wherein the half-mirror is used for shielding stray light and excitation light, and the signal detector is used for receiving fluorescence and converting signals.
In some embodiments of the present invention, the fluorescence excitation module 13-3-1 uses 2-4 sets of excitation wavelengths to excite different labeled fluorescence on the protein marker substrate.
In some embodiments of the invention, the signal detector selected is a CCD detector, and in other embodiments of the invention, other photodetectors may be selected as desired.
In some embodiments of the present invention, the signal acquisition module 13 performs the acquisition mode of scanning the biological array grid by grid to ensure the accuracy of the fluorescence intensity values in the single reaction region.
In the present invention, referring to fig. 5, the analysis device further includes an instrument housing, a mechanical skeleton 14, an electronic touch pad, an embedded control module, a power module, and an operation module, where the mechanical skeleton 14 is disposed in the analysis housing; the electronic touch pad, the embedded control module and the operation module are all arranged on the mechanical framework 14, and the electronic touch pad, the operation module and the signal acquisition module are all connected with the power supply module through the embedded control module; the embedded control module comprises a main control board and a control circuit, and is used for controlling the electronic touch control board and the operation module to move in a coordinated manner, and is also used for carrying operation software and carrying out data transmission and processing. The operation module comprises a substrate moving sub-module 15-1, a piston driving sub-module 15-2 and a clamping sub-module 15-3, wherein the substrate moving sub-module 15-1 is used for controlling the movement of the protein marker substrate 2, the piston driving sub-module 15-2 is used for controlling the up-and-down movement of the driving piston 4-1 so as to send the sample liquid in the sample cell 3 into the reaction cell 5 through pressure change, and the clamping sub-module 15-3 is used for fixing the microfluidic chip.
In the invention, the substrate moving sub-module 15-1 comprises an up-and-down moving motor 15-1-1, a left-and-right moving motor 15-1-2, a gripper motor 15-1-3, a mechanical gripper 15-1-4 and a guide rail, wherein the mechanical gripper 15-1-4 is driven by the gripper motor 15-1-3 to grasp the protein marker substrate 2, and the up-and-down moving motor 15-1-1 and the left-and-right moving motor 15-1-2 are respectively used for controlling the movement of the mechanical gripper 15-1-4 in the up-and-down direction and the left-and-right direction.
In some embodiments of the present invention, referring to FIG. 7, the output shaft of the gripper motor 15-1-3 is fixed to the output shaft of the mechanical gripper 15-1-4 and to the up-down movement motor 15-1-1 and the left-right movement motor 15-1-2 by nuts.
The output shafts of the up-and-down moving motor 15-1-1 and the left-and-right moving motor 15-1-2 are respectively connected with a module formed by the gripper motor 15-1-3 and the mechanical gripper 15-1-4 for controlling the movement of the module, so that the movement of the gripper on the chip and the cleaning and reaction actions are realized. The gripper motor is used for controlling the gripping piece of the mechanical gripper to complete the gripping action of the protein marker substrate 2, the output shafts of the gripper motor are respectively connected with gears on the mechanical gripper 15-1-4, and the mechanical gripper 15-1-4 is controlled by the gears to move on the guide rail to perform the gripping and fixing actions.
In some embodiments of the present invention, referring to fig. 8, the clip module 15-3 is used for fixing the position of the microfluidic chip, and includes a clip motor 15-3-3, a clip guide rail 15-3-2 driven by the clip motor 15-3-3, a fixing clip seat 15-3-1, and a temperature control device, where the fixing clip seat 15-3-1 is located at the bottom end of the mechanical frame 14, and the temperature control device is used for controlling the temperature of the environment during the reaction, and the fixing clip seat 15-3-1 is connected with an external inlet of the analysis housing through the clip guide rail 15-3-2. The fixing clip seat 15-3-1 with the micro-fluidic chip is moved to a preset position by driving the clip motor 15-3-3, and then the subsequent steps are performed.
The piston driving sub-module 15-2 is positioned above the inner part of the inlet opening at the outer part of the analysis shell and comprises a pushing pull rod 15-2-1, a pushing motor 15-2-2 and a pushing guide rail 15-2-3, wherein an output shaft of the pushing motor 15-2-2 is connected with the pushing pull rod 15-2-1 through a nut, the pushing pull rod 15-2-1 can be driven to move up and down, the driving piston 4-1 is connected with the pushing pull rod 15-2-1, and the up-and-down movement of the pushing pull rod 15-2-1 can drive the piston 4-1 to move up and down in the piston driving pool 4-2.
In some embodiments of the present invention, referring to fig. 5, the substrate moving sub-module 15-1 is located above the clip module 15-3, the piston driving sub-module 15-2 is located above the inside of the inlet, and when the microfluidic chip moves to a fixed position through the clip module 15-3, the piston driving sub-module 15-2 operates to push the driving piston 4-1 to the bottom first, so that the substrate moving sub-module 15-1 operates on the protein marker substrate 2. The three sub-modules are respectively connected with an independent motor to provide driving force for the operation of the modules and realize the control of accurate movement, and are connected with the electronic touch control panel through the main control panel and the power supply module for controlling the coordinated operation among the modules.
In some embodiments of the present invention, an operator may perform functions such as man-machine interaction, instruction transmission, data analysis, result presentation, and data storage through a main control board, and input and output of data through ports such as GRPS, bluetooth, LAN, and USB.
The fluorescence immunoassay system provided by the previous embodiment is used for detection, and comprises the following steps:
s1, adding 200uL of sample into a cavity of a sample pool 3, covering a sample cover 3-1, placing a microfluidic chip into a fixed clamping seat 15-3-1, starting equipment, and enabling the microfluidic chip to enter a fixed position;
s2, sample injection and dilution: the analysis equipment presses a driving piston 4-1 on the microfluidic chip, and a sample in the sample tank 3 passes through a filter tank 9, enters a first reaction tank 5-1 and is uniformly mixed with buffer solution in the first reaction tank;
s3, capturing a marker: the analysis equipment transfers the coated carrier into a first reaction tank 5-1, the coated antibody pre-coated on the coated carrier reacts with the sample in the reaction tank, and the reaction is stopped after incubation for 5 minutes;
s4, cleaning: the analysis equipment sequentially transfers the coated carrier into a first cleaning tank 6-1 and a second cleaning tank 6-2 to wash off residual reagents on the surface;
s5, capturing fluorescent markers: transferring the coated carrier into a second reaction tank 5-2 by the analysis equipment, wherein the coated carrier is coated with an antibody-antigen complex to be detected or reacts with a fluorescent-labeled detection antibody or antigen in the reaction tank 5-2;
s6, cleaning: the analysis equipment sequentially transfers the coated carrier into a third cleaning tank 6-3 and a fourth cleaning tank 6-4 to wash away residual reagent;
s7, signal acquisition: the analysis equipment moves the coated carrier into a detection area 7, and a detection instrument excites the coated carrier, coated antibodies on the coated sites, antigens to be detected and fluorescent labeled antibodies, and captures excited fluorescent signals;
s8, analyzing results: and the analysis equipment calculates the concentration of the antigen to be detected in the sample to be detected, takes out the microfluidic detection chip and closes the analysis equipment.
It should be noted that, in the above embodiment, the sandwich method in the immunoassay method is selected, and in other embodiments of the present invention, the sandwich method, the competition method or other fluorescent immunoassay-based analysis methods may be selected according to the molecular characteristics of the marker to be detected.
In some embodiments of the present invention, the control software of the instrument includes embedded software and upper computer software, the embedded software is used for independently completing the control of each part of the instrument, and the upper computer software is used for completing the control of the embedded system of the instrument and the writing of the instrument data through a computer, and the embedded software and the upper computer software are connected by wireless or wired connection.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the invention.
Claims (9)
1. The fluorescence immunoassay system is characterized by comprising a microfluidic chip and analysis equipment;
the microfluidic chip comprises a chip shell (1) and a protein marker substrate (2), wherein the protein marker substrate (2) comprises a coating carrier (2-1) and a plurality of coating sites (2-2) arranged on the coating carrier (2-1) as a reaction substrate for multi-index joint inspection;
the chip shell (1) is sequentially provided with a sample tank (3), a driving piston (4-1), a piston driving tank (4-2), a reaction tank (5), a cleaning tank (6) and a detection area (7), wherein the upper end of the sample tank (3) is connected with the piston driving tank (4-2), and the lower end of the sample tank is communicated with the reaction tank (5) through a microfluidic structure; the driving piston (4-1) can move up and down in the piston driving pool (4-2); the cleaning tank (6) is used for cleaning residual reagent after the reaction; the analysis equipment comprises a signal acquisition module (13) and an embedded control module, wherein the signal acquisition module (13) is connected with the embedded control module, the signal acquisition module is used for carrying out fluorescent signal acquisition on a reacted coating site (2-2) in a detection area (7), and the embedded control module is used for controlling the operation of the signal acquisition module (13), processing the signal acquired by the signal acquisition module (13) and calculating the concentration of an antigen to be detected in a sample to be detected;
the analysis equipment also comprises an instrument shell, a mechanical framework (14), an electronic touch control board, a power supply module and an operation module,
the mechanical framework (14) is arranged in the instrument shell;
the electronic touch control board, the embedded control module and the operation module are all arranged on the mechanical framework (14), and the electronic touch control board, the operation module and the signal acquisition module (13) are all connected with the power supply module through the embedded control module;
the running module comprises a substrate moving submodule (15-1), a piston driving submodule (15-2) and a clamping submodule (15-3), wherein the substrate moving submodule (15-1) is used for controlling movement of the protein marker substrate (2), the piston driving submodule (15-2) is used for controlling up-and-down movement of the driving piston (4-1) so as to send a sample in the sample tank (3) into the reaction tank (5) through pressure change, and the clamping submodule (15-3) is used for fixing the microfluidic chip.
2. A fluorescent immunoassay system according to claim 1, wherein the coating sites (2-2) of the protein marker matrix (2) are evenly distributed on the coating carrier (2-1), each coating site (2-2) being pre-coated with an antibody capable of specifically binding to a different detection marker, respectively.
3. A fluorescent immunoassay system according to claim 1, wherein the sample cell (3) comprises a sample cap (3-1) and a cavity,
the sample cover (3-1) is positioned above the sample pool and connected with the lower part of the piston driving pool (4-2) through the first microfluidic channel (11), and the bottom end of the cavity is connected with the reaction pool (5) through the microfluidic structure.
4. The fluorescence immunoassay system according to claim 1, wherein the microfluidic structure comprises a second microfluidic channel (8) and a filter tank (9) in communication with the second microfluidic channel (8), one end of the second microfluidic channel (8) is connected with the bottom end of the cavity, the filter tank (9) is connected with the reaction tank (5), and a blood filtering membrane is disposed in the filter tank (9).
5. A fluorescent immunoassay system according to claim 1, wherein the reaction cell (5) comprises a first reaction cell (5-1) and a second reaction cell (5-2), the first reaction cell (5-1) being for holding a buffer solution, the second reaction cell (5-2) being for holding a fluorescent-labeled detection antibody solution, and a washing cell (6) being provided between the first reaction cell (5-1) and the second reaction cell (5-2), the second reaction cell (5-2) and the detection zone (7).
6. A fluorescent immunodetection system according to claim 1, characterized in that the signal acquisition module (13) comprises a signal acquisition unit comprising a fluorescent excitation module (13-3-1) and a signal detection module (13-3-2), the fluorescent excitation module (13-3-1) being adapted to excite fluorescent molecules and the signal detection module (13-3-2) being adapted to receive excitation light.
7. The fluoroimmunoassay system of claim 1, wherein the substrate movement submodule comprises a movement motor and guide rail, a gripper motor and a mechanical gripper controlled by the gripper motor for controlling the up-and-down movement of the mechanical gripper and the gripping action of the protein marker substrate.
8. A fluorescent immunoassay system according to claim 1, wherein the piston driving sub-module comprises a push motor (15-2-2) and a push rod (15-2-1) driven by the push motor (15-2-2) to move up and down, and the driving piston (4-1) is connected to the push rod (15-2-1).
9. The fluoroimmunoassay system of claim 1, wherein the clamp submodule is positioned below the base movement submodule and comprises a fixed clamping seat, a clamp motor and a clamp guide rail, and the fixed clamping seat is connected with an external bayonet of the analysis housing through the clamp guide rail.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110998635.5A CN113720818B (en) | 2021-08-27 | 2021-08-27 | Fluorescent immunodetection system |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110998635.5A CN113720818B (en) | 2021-08-27 | 2021-08-27 | Fluorescent immunodetection system |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113720818A CN113720818A (en) | 2021-11-30 |
| CN113720818B true CN113720818B (en) | 2023-11-14 |
Family
ID=78678686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110998635.5A Active CN113720818B (en) | 2021-08-27 | 2021-08-27 | Fluorescent immunodetection system |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113720818B (en) |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1869695A (en) * | 2006-06-27 | 2006-11-29 | 中国科学院力学研究所 | Micro fluid control chip for investigating cell surfact marker |
| CN203164120U (en) * | 2012-03-30 | 2013-08-28 | 北京博晖创新光电技术股份有限公司 | Microfluidic time-resolved fluoroimmune assay device |
| CN104293649A (en) * | 2014-10-09 | 2015-01-21 | 中国科学院合肥物质科学研究院 | Micro-fluidic chip and detecting device suitable for PCR (polymerase chain reaction) or HRM (high resolution melting) detection analysis |
| CN204462172U (en) * | 2015-03-27 | 2015-07-08 | 基蛋生物科技股份有限公司 | A kind of full-automatic high flux multicolor fluorescence immunochromatography chip analysis system |
| CN104919035A (en) * | 2012-12-21 | 2015-09-16 | 精密公司 | Portable fluorescence detection system and microassay cartridge |
| WO2017128806A1 (en) * | 2016-01-27 | 2017-08-03 | 广州万孚生物技术股份有限公司 | Automatic fluorescence quantitative immunoassay analyzer and detection method |
| CN108181458A (en) * | 2018-02-26 | 2018-06-19 | 北京华科泰生物技术有限公司 | A kind of micro-fluidic chip based on fluorescence immunoassay joint-detection and its preparation method and application |
| CN108896751A (en) * | 2018-05-24 | 2018-11-27 | 深圳市帝迈生物技术有限公司 | A kind of micro-fluidic chip and immunofluorescence analysis instrument |
| CN109870582A (en) * | 2019-02-27 | 2019-06-11 | 华中科技大学 | A kind of more target magnetic immunochemiluminescence micro-fluidic chip detection platforms and method |
| CN110567929A (en) * | 2019-05-08 | 2019-12-13 | 南京农业大学 | Double-signal side-stream immunochromatography detection method for imidaclothiz |
| CN111282605A (en) * | 2020-02-17 | 2020-06-16 | 苏州大学 | Microfluidic chip and application method thereof |
| CN111686826A (en) * | 2019-03-15 | 2020-09-22 | 国家纳米科学中心 | Micro-fluidic chip with layered structure and application thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050130226A1 (en) * | 2003-09-26 | 2005-06-16 | The University Of Cincinnati | Fully integrated protein lab-on-a-chip with smart microfluidics for spot array generation |
| US20070281288A1 (en) * | 2004-01-27 | 2007-12-06 | Shimshon Belkin | Method and System for Detecting Analytes |
| US20070154895A1 (en) * | 2005-12-30 | 2007-07-05 | Caliper Life Sciences, Inc. | Multi-assay microfluidic chips |
| DE102007052281A1 (en) * | 2007-11-02 | 2009-05-07 | Zenteris Gmbh | Single-step multiplex immunoassay |
-
2021
- 2021-08-27 CN CN202110998635.5A patent/CN113720818B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1869695A (en) * | 2006-06-27 | 2006-11-29 | 中国科学院力学研究所 | Micro fluid control chip for investigating cell surfact marker |
| CN203164120U (en) * | 2012-03-30 | 2013-08-28 | 北京博晖创新光电技术股份有限公司 | Microfluidic time-resolved fluoroimmune assay device |
| CN104919035A (en) * | 2012-12-21 | 2015-09-16 | 精密公司 | Portable fluorescence detection system and microassay cartridge |
| CN104293649A (en) * | 2014-10-09 | 2015-01-21 | 中国科学院合肥物质科学研究院 | Micro-fluidic chip and detecting device suitable for PCR (polymerase chain reaction) or HRM (high resolution melting) detection analysis |
| CN204462172U (en) * | 2015-03-27 | 2015-07-08 | 基蛋生物科技股份有限公司 | A kind of full-automatic high flux multicolor fluorescence immunochromatography chip analysis system |
| WO2017128806A1 (en) * | 2016-01-27 | 2017-08-03 | 广州万孚生物技术股份有限公司 | Automatic fluorescence quantitative immunoassay analyzer and detection method |
| CN108181458A (en) * | 2018-02-26 | 2018-06-19 | 北京华科泰生物技术有限公司 | A kind of micro-fluidic chip based on fluorescence immunoassay joint-detection and its preparation method and application |
| CN108896751A (en) * | 2018-05-24 | 2018-11-27 | 深圳市帝迈生物技术有限公司 | A kind of micro-fluidic chip and immunofluorescence analysis instrument |
| CN109870582A (en) * | 2019-02-27 | 2019-06-11 | 华中科技大学 | A kind of more target magnetic immunochemiluminescence micro-fluidic chip detection platforms and method |
| CN111686826A (en) * | 2019-03-15 | 2020-09-22 | 国家纳米科学中心 | Micro-fluidic chip with layered structure and application thereof |
| CN110567929A (en) * | 2019-05-08 | 2019-12-13 | 南京农业大学 | Double-signal side-stream immunochromatography detection method for imidaclothiz |
| CN111282605A (en) * | 2020-02-17 | 2020-06-16 | 苏州大学 | Microfluidic chip and application method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113720818A (en) | 2021-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6824310B2 (en) | Assay equipment, methods and reagents | |
| CN108660074B (en) | Integrated solution for nucleic acid extraction PCR amplification detection | |
| CN110564607B (en) | Full-automatic nucleic acid extraction amplification micro-fluidic chip dynamic quantitative detection integrated device | |
| CN105628947B (en) | Whole blood automatic luminous immunoassay instant detector | |
| CN103901189B (en) | Immune detection micro-fluidic chip fluorescent quantitation automatic detection device | |
| CN102016540A (en) | Assay apparatuses, methods and reagents | |
| CN102719357B (en) | Hybridization system for real-time monitoring parsing process of micro array chip | |
| RU2010117267A (en) | CARTRIDGE FOR AUTOMATIC DETECTION OF ANALYTES IN THE Sample of BODY LIQUID AND CONTAINING ITS SYSTEM | |
| CN101614655B (en) | Detection method of microfluidic chip based on photoacoustic technique and device thereof | |
| CN101696971B (en) | Biochip analyzer and control system thereof | |
| CN103207169B (en) | Microfluidic time-resolved fluorescence immunoassay device and application thereof | |
| CN102980996A (en) | Chemiluminescence immunoassay system, as well as method and application thereof | |
| CN102243165B (en) | Photonic crystal coded microsphere biochip detection device | |
| CN219245553U (en) | Full-automatic dry-type fluorescence immunoassay appearance | |
| CN207439936U (en) | A kind of fluorescence analyser and its liquid phase biological chips detection system | |
| CN106226540A (en) | Full-automatic protein chip analyzer | |
| CN114836309A (en) | Full-automatic nucleic acid detection and analysis equipment and system | |
| CN201517993U (en) | Micro-fluidic chip detecting device based on photoacoustic technique | |
| CN113720818B (en) | Fluorescent immunodetection system | |
| CN113189255A (en) | Full-automatic sample pretreatment device and treatment method | |
| CN201527430U (en) | Biochip analyzer | |
| CN101696976A (en) | Biochip analysis process and control method thereof | |
| CN205720248U (en) | A kind of fluorescence detection device | |
| CN105115949A (en) | Assay apparatuses, methods and reagents | |
| CN204086274U (en) | A kind of time-resolved fluorescence immunoassay instrument |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |