WO2017005075A1 - 感光芯片采集信号的方法和装置及追踪细胞的方法和装置 - Google Patents

感光芯片采集信号的方法和装置及追踪细胞的方法和装置 Download PDF

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WO2017005075A1
WO2017005075A1 PCT/CN2016/084913 CN2016084913W WO2017005075A1 WO 2017005075 A1 WO2017005075 A1 WO 2017005075A1 CN 2016084913 W CN2016084913 W CN 2016084913W WO 2017005075 A1 WO2017005075 A1 WO 2017005075A1
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Prior art keywords
photosensitive chip
signal
optical signal
dark room
film
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English (en)
French (fr)
Inventor
张英豪
张志豪
詹克团
宛佳
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Shanghai Qingliu Bio-Pharm Technology Co Ltd
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Shanghai Qingliu Bio-Pharm Technology Co Ltd
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Priority to JP2018520007A priority Critical patent/JP2018524613A/ja
Priority to KR1020187003230A priority patent/KR102084233B1/ko
Priority to EP16820726.4A priority patent/EP3315971A4/en
Priority to RU2018104813A priority patent/RU2715228C2/ru
Priority to AU2016289902A priority patent/AU2016289902B2/en
Priority to CA2993873A priority patent/CA2993873C/en
Publication of WO2017005075A1 publication Critical patent/WO2017005075A1/zh
Priority to US15/864,170 priority patent/US20180136219A1/en
Anticipated expiration legal-status Critical
Priority to US17/674,836 priority patent/US20220260499A1/en
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    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6842—Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent materials, e.g. electroluminescent or chemiluminescent
    • C09K11/08—Luminescent materials, e.g. electroluminescent or chemiluminescent containing inorganic luminescent materials
    • C09K11/61—Luminescent materials, e.g. electroluminescent or chemiluminescent containing inorganic luminescent materials containing fluorine, chlorine, bromine, iodine or unspecified halogen elements
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • G01N21/763—Bioluminescence
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/66—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving luciferase
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • 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
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • 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
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/535—Production of labelled immunochemicals with enzyme label or co-enzymes, co-factors, enzyme inhibitors or enzyme substrates
    • 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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • 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
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • 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
    • G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
    • G01N33/561—Immunoelectrophoresis
    • 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
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N2001/4038—Concentrating samples electric methods, e.g. electromigration, electrophoresis, ionisation
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N2021/1765—Method using an image detector and processing of image signal

Definitions

  • the invention relates to the field of information collection technology, in particular to a method and a device for collecting signals by a photosensitive chip and a method and a device for tracking cells.
  • Western blotting is a hybrid technique that combines high-resolution gel electrophoresis with immunochemical analysis techniques. Western blotting has the advantages of large analytical capacity, high sensitivity, and high specificity. It is the most commonly used method for detecting protein properties, expression and distribution, such as qualitative and quantitative detection of tissue antigen, mass determination of polypeptide molecules and virus. Antibody or antigen detection, etc.
  • Method 1 The photographic film and the NC film are closely attached together, and after exposure for a certain period of time, development and fixing are performed. The image is displayed on the film. Advantages: high sensitivity and high resolution. The following disadvantages exist:
  • Image quality is unstable: in the darkroom, researchers can't monitor the exposure in real time, often after several attempts to get a better image. Most of the time it is not underexposed or overexposed. Time-consuming.
  • Method 2 Directly photograph the sample using a photographic device such as a CCD.
  • Advantages Overcome all the shortcomings of Method 1.
  • Only individual brands claim to be able to use the low-light photography of WB.
  • its exposure time is greatly extended.
  • Some brands use pixel merging methods to sacrifice resolution to increase sensitivity and achieve sensitivity comparable to film. However, the image is slightly enlarged, and the mosaic is presented, which is difficult to meet various needs.
  • Method 3 Scanning and collecting the low light signal by using a linearly arranged CCD photosensitive unit. Advantages: Increased the acquisition rate of optical signals, thus improving sensitivity. Disadvantages: Since the linear signal is used to collect the optical signal, the entire image cannot be acquired at the same time, so there is a time difference between the scanning of different regions. Also, since the light source is attenuated over time, there is no comparability in the intensity of the signals collected at different points in time. Many control experiments could not be compared.
  • the technical problem to be solved by the embodiments of the present invention is to provide a method for collecting signals by a photosensitive chip and a method for tracking cells, and converting the signal to be tested from an optical signal into a digital signal to quickly realize quantitative analysis.
  • the embodiment of the invention further provides a device for collecting signals by a photosensitive chip and a device for tracking cells, which are used to ensure the implementation and application of the above method.
  • the present invention discloses a method for collecting signals by a photosensitive chip, including:
  • the light emitting surface carrying the optical signal film to be collected is closely attached to the photosensitive chip;
  • the collected optical signal is signal processed and output.
  • performing optical signal acquisition on the dark room photosensitive chip comprises the following steps:
  • the acquiring of the optical signal film to be collected includes the following steps:
  • reaction polyvinylidene fluoride film or nitrocellulose membrane is subjected to a chemiluminescence treatment.
  • the film comprises a nitrocellulose membrane and/or a polyvinylidene fluoride membrane.
  • the photosensitive chip comprises a CMOS sensor chip and a CCD sensor chip.
  • the invention also discloses a device for collecting signals by a photosensitive chip, comprising:
  • a bonding module for closely bonding the light emitting surface carrying the optical signal film to be collected on the photosensitive chip
  • a holding module for placing a photosensitive chip attached with a film for holding a light signal to be collected in a dark room; the dark room
  • a signal acquisition module configured to perform optical signal collection in the dark room photosensitive chip
  • the signal processing module is configured to perform signal processing and output on the collected optical signal.
  • the invention also discloses a method for tracking cells by a photosensitive chip, comprising:
  • Cells or animals carrying luciferase are planted on a photosensitive chip;
  • a photosensitive chip implanted with cells or animals carrying luciferase is placed in a dark room; the dark room is not affected by external light;
  • the collected optical signal is signal processed and output.
  • the method further comprises: adding a glass layer on the photosensitive chip before planting the luciferase-carrying cell or animal on the photosensitive chip, and then planting the cell or animal carrying the luciferase on the photosensitive chip.
  • the glass layer on the top.
  • the obtaining of the luciferase-bearing cell or animal comprises the following steps:
  • Fluorescein is added to the cell culture medium.
  • the invention also discloses a device for tracking cells by a photosensitive chip, comprising:
  • a planting module for planting cells or animals carrying luciferase on a photosensitive chip
  • a holding module for placing a photosensitive chip implanted with cells or animals carrying luciferase in a dark room
  • the dark room is not affected by external light
  • a signal acquisition module configured to perform optical signal collection in the dark room photosensitive chip
  • the signal processing module is configured to perform signal processing and output on the collected optical signal.
  • the embodiments of the invention include the following advantages:
  • the solution provided by the invention closely adheres the light-emitting surface carrying the optical signal film to be collected to the photosensitive chip,
  • the photosensitive chip carrying the film of the optical signal to be collected is placed in a dark room, and the photosensitive chip performs optical signals in the dark room.
  • the acquisition is performed, and the collected optical signal is processed and output. Direct contact with the sensor to complete signal acquisition, which can be used for the entire frame.
  • the images are acquired simultaneously, minimizing the loss of optical signals, thereby improving sensitivity without reducing resolution.
  • FIG. 1 is a schematic flow chart of a method for collecting signals by a photosensitive chip of the present invention
  • FIG. 2 is a schematic structural diagram of an apparatus for collecting signals by a photosensitive chip of the present invention
  • FIG. 3 is a schematic flow chart of a method for tracking cells by a photosensitive chip of the present invention.
  • FIG. 4 is a schematic view showing the structure of a device for tracking cells by a photosensitive chip of the present invention.
  • FIG. 1 a flow chart of a method for acquiring a signal by a photosensitive chip of the present invention is shown.
  • the body can include the following steps:
  • Step 101 The light emitting surface carrying the optical signal film to be collected is closely attached to the photosensitive chip;
  • the acquisition of the optical signal film to be collected includes the following steps:
  • the polyvinylidene fluoride film or the nitrocellulose membrane after the reaction is subjected to a chemiluminescence treatment.
  • the film used mainly includes a nitrocellulose membrane (NC membrane) and/or a polyvinylidene fluoride membrane (PVDF membrane).
  • the photosensitive chip used includes a CMOS sensor chip, a CCD sensor chip, and the like. Considering that the larger size of the photosensitive chip is expensive to manufacture, in practice, if the chip splicing technique is used, the cost can be greatly reduced, and thus the CMOS sensor chip or the CCD sensor chip array can also be used.
  • Step 102 placing a photosensitive chip with a film carrying the optical signal to be collected in a dark room; the dark room is not affected by external light;
  • the photosensitive chip carrying the optical signal film to be collected is placed in a dark environment, and the implementation manner can be selected according to the specific environment, which is relatively easy to implement, and a light blocking cover can be attached thereto.
  • Step 103 performing optical signal collection on the dark room photosensitive chip
  • the optical signal acquisition in the darkroom photosensitive chip includes the following steps:
  • step 104 the collected optical signal is processed and output.
  • the application can use a processor of a single chip microcomputer, an FPGA, a CPU, etc. to perform signal processing on the collected optical signal and output it.
  • the current signal processing method is relatively mature, and the signal processing described in the present scheme can be completed, and therefore will not be described herein.
  • the cell or tissue extract is longitudinally separated on the polypropylene gel by an electric field (as shown in the left figure, the following figure is the flow of this step);
  • the electric field is used to transfer the protein strip laterally to the nitrocellulose membrane (NC membrane), and the relative position of the strip does not change, which is called Blot;
  • the blotted membrane was soaked in a bovine serum albumin (BSA) solution.
  • BSA bovine serum albumin
  • the BSA is occupied by an area that the protein band does not occupy. Avoid subsequent adsorption of antibodies by these regions, allowing antibodies to bind exclusively to their antigens.
  • HRP horseradish peroxidase
  • the NC membrane was immersed in a liquid containing an HRP substrate. HRP Fluorescence is emitted when the substrate is catalyzed. The fluorescent signal is collected using a photosensitive film or an electronic photosensitive system.
  • Protein sample obtained After bacterial-induced expression, cells can be directly lysed by electrophoresis loading buffer, eukaryotic cells plus homogenization buffer, mechanical or ultrasonic room temperature homogenate for 0.5-1 min. It was then centrifuged at 13,000 g for 15 min at 4 °C. Take the supernatant as a sample.
  • Electrophoresis An electrophoresis gel was prepared and subjected to SDS-PAGE.
  • Transfer 1 After the electrophoresis is finished, the strip is cut to a suitable size and equilibrated with a transfer buffer, 5 min ⁇ 3 times.
  • 2 Membrane treatment The filter paper and NC membrane of the same size as the strip were pre-cut and immersed in the transfer buffer for 10 min.
  • 3 Transfer film The film transfer device is placed in the order of anode carbon plate, 24 layer filter paper, NC film, gel, 24 layer filter paper and cathode carbon plate from bottom to top, and the filter paper, gel and NC film are precisely aligned. The bubbles were removed, and a weight of 500 g was applied to absorb excess liquid on the carbon plate. Turn on the power, constant current 1mA/cm2, transfer 1.5hr.
  • the power is removed and the membrane is taken out, and the strip to be tested is cut for immunoblotting.
  • the protein standard strips were stained, placed in the membrane staining solution for 50 s, and then decolorized in 50% methanol several times to a clear background, then washed with double distilled water, air-dried in two layers of filter paper, and left to color The results are compared.
  • the primary antibody and 1% BSA were discarded and the membrane was washed with 0.01 M PBS for 5 min x 4 times.
  • Horseradish peroxidase-conjugated secondary antibody (diluted with 0.01 M PBST at the appropriate dilution ratio) was added and shaken smoothly for 2 hr at room temperature.
  • the secondary antibody was discarded and the membrane was washed with 0.01 M PBST for 5 min x 4 times.
  • the chemiluminescent solution treats the membrane, and HRP reacts with the chemical substrate in the liquid, catalyzing the substrate and emitting fluorescence.
  • the fluorescent signal is collected by directly bonding the digital sensor to the film:
  • the film soaked in the chemiluminescence liquid is taken out, excess liquid is drained on the absorbent paper, and then the light emitting surface of the film is attached to the digital photosensitive chip;
  • the sensor is controlled by a computer and the chemiluminescence signal is collected. Observe the exposure level in real time through the computer screen, and stop the exposure when the signal accumulates to the appropriate intensity;
  • the signal acquisition is completed by the contact type photosensitive chip, and the quantitative analysis can be completed well by converting the optical signal into a digital signal.
  • a device for collecting signals by a photosensitive chip according to an embodiment of the present invention is described in detail.
  • FIG. 2 a schematic structural diagram of an apparatus for collecting signals by a photosensitive chip according to the present invention is shown, which specifically includes:
  • the bonding module 201 is configured to closely attach the light emitting surface carrying the optical signal film to be collected to the photosensitive chip;
  • a holding module 202 configured to place a photosensitive chip attached with a film for holding a light signal to be collected in a dark room; the dark room is not affected by external light;
  • the signal acquisition module 203 is configured to perform optical signal collection on the dark room photosensitive chip
  • the signal processing module 204 is configured to perform signal processing on the collected optical signal and output the signal.
  • the description is relatively simple, and the relevant parts can be referred to the description of the method embodiment.
  • a method for tracking cells by a photosensitive chip of the present invention is shown, which may specifically include:
  • Step 301 the cells or animals carrying luciferase are planted on the photosensitive chip;
  • the photosensitive chip is usually covered with a transparent protective layer, or a glass layer or a resin layer or other materials, etc., and the thickness of the protective layer is usually less than 0.5 mm.
  • a cell layer can be added to the sensor chip before the cell or animal carrying the luciferase is implanted on the sensor chip, and then the cell carrying the luciferase can be carried. Or the animal is planted in the glass layer of the sensor chip, which will be more convenient in the later cleaning.
  • Luciferase (English name: Luciferase) is a protein produced by the firefly tail that catalyzes the reaction of luciferin with oxygen in the presence of ATP. Using bioengineering methods, luciferase genes and regulatory transcription The DNA sequences are transferred together into cells or plants and plants and integrated into the chromosome of the host. The expression of the luciferase gene is enhanced by the use of certain protein molecules expressed by the host that have a special structure and function to regulate gene expression, and specifically bind to the DNA sequence that regulates transcription.
  • Fluorescein is added to the cell culture medium, and luciferase uses the intracellular ATP to provide energy to catalyze the reaction of fluorescein with oxygen to produce fluorescence. In this way, the instrument can track the migration trajectory of cells or animals. This method can be used in animal behavioral experiments.
  • Step 302 placing a photosensitive chip implanted with cells or animals carrying luciferase in a dark room; the dark room is not affected by external light;
  • Step 303 performing optical signal collection on the dark room photosensitive chip
  • Step 304 Perform signal processing on the collected optical signal and output.
  • a device for tracking cells by a photosensitive chip according to an embodiment of the present invention is described in detail.
  • FIG. 4 a schematic structural diagram of a device for tracking cells by a photosensitive chip of the present invention is shown, which specifically includes:
  • a planting module 401 for planting cells or animals carrying luciferase on a photosensitive chip
  • Shelving module 402 for placing a photosensitive chip implanted with cells or animals carrying luciferase in a dark room; the dark room is not affected by external light;
  • the signal acquisition module 403 is configured to perform optical signal collection on the dark room photosensitive chip
  • the signal processing module 404 is configured to perform signal processing on the collected optical signal and output.
  • the solution of the invention can be widely applied to collecting immunoblotting signals, monitoring the intensity of the low light in the comparative droplet array, implanting cells on the photosensitive chip to observe cell migration, division, or dynamic process of expression of certain molecules, and the like.
  • the description is relatively simple, and the relevant parts can be referred to the description of the method embodiment.

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Abstract

一种感光芯片采集信号的方法和装置及追踪细胞的方法和装置，涉及信号采集技术领域，其中所述感光芯片采集信号的方法包括：携带待采集光信号膜的发光面紧密贴合在感光芯片上(101)，将贴合有携带待采集光信号膜的感光芯片置于暗室中(102)，在所述暗室感光芯片进行光信号采集(103)，对所采集光信号进行信号处理并输出(104)。感光芯片采集信号的方法和装置借助接触感光芯片完成信号的采集，将光信号转化为数字信号，很好的完成定量分析。

Description

感光芯片采集信号的方法和装置及追踪细胞的方法和装置 感光芯片采集信号的方法和装置及追踪细胞的方法和装置
技术领域
本发明涉及信息采集技术领域，特别是涉及一种感光芯片采集信号的方法和装置及追踪细胞的方法和装置。
背景技术
免疫印迹法(Western blotting)是一种将高分辨率凝胶电泳和免疫化学分析技术相结合的杂交技术。免疫印迹法具有分析容量大、敏感度高、特异性强等优点，是检测蛋白质特性、表达与分布的一种最常用的方法，如组织抗原的定性定量检测、多肽分子的质量测定及病毒的抗体或抗原检测等。
现有的采集免疫印迹法(Western blotting)信号的装置和方法：
方法一：将感光胶片与NC膜紧贴在一起，曝光一定时间后，进行显影、定影。图像显示在胶片上。优点：灵敏度高，分辨率高。存在以下缺点：
1 ，占用空间大：需要专用的暗室(房间)，水槽，及下水管道等。
2 ，花费高：不但需要购买洗片机，暗匣，还需要大量感光胶片、显影液、定影液等耗材。因洗涤胶片，还会造成水资源浪费。
3 ，污染环境：冲洗胶片需要大量的显影液、定影液。同时产生因质量不合格而废弃的胶片。这些能造成重金属和芳香化合物等污染。
4 ，图像质量不稳定：暗室中，研究人员无法实时监测曝光程度，往往经过数次尝试才能得到较好的图像。大部分的时候不是曝光不足就是曝光过度。费时费力。
5 ，费时：如今数据保存、传输和发表普遍采用数字化，因而，胶片图像还要经扫描转换成数字图像。
6 ，定量不准确：大多时候，研究人员肉眼判断认为较好的图像，实际上已经在灰度上过饱和。因而后续的灰度扫描很难准确定量。
方法二：利用CCD等感光设备对样品直接照相。优点：克服了方法一的所有缺点。缺点：丢失了胶片采集的优点，即灵敏度严重降低。原因是：当前市场上所有此类设备都是将一台CCD数码相机架在NC膜上方一定距离处拍摄图像。光源辐射的光能量只有在某一小角度内的光线才能被相机采集。90％以上的能量流失。因而这类设备被经常用于强光照相。只有个别品牌的声称能用于WB的微光照相。但与胶片相比，其曝光时间大大延长。有些品牌采用像素合并的方法，牺牲分辨率以提高灵敏度，可达到与胶片匹敌的灵敏度。但图像稍微放大，便呈现马赛克，很难满足多方面的需求。
方法三：利用线性排列的CCD感光单元，扫描收集微光信号。优点：提高了对光信号的采集率，从而提高了灵敏度。缺点：由于是线性扫描收集光信号，不能同时采集整幅的图像，因而不同区域扫描存在时间差。又由于光源是随时间不断衰减的，因而会造成不同时间点上收集的信号强度没有可比性。使很多对照试验无法比较。
因此，目前需要本领域技术人员迫切解决的一个技术问题就是：如何能够创新地提出一种有效措施，以解决现有技术中存在的问题，满足实际应用中的更多需求。
发明内容
本发明实施例所要解决的技术问题是提供一种感光芯片采集信号的方法及追踪细胞的方法，将待测信号由光信号转化为数字信号，快速实现定量分析。
相应的，本发明实施例还提供了一种感光芯片采集信号的装置及追踪细胞的装置，用以保证上述方法的实现及应用。
为了解决上述问题，本发明公开了一种感光芯片采集信号的方法，包括：
携带待采集光信号膜的发光面紧密贴合在感光芯片上；
将贴合有携带待采集光信号膜的感光芯片置于暗室中 ；所述暗室不受外界光影响；
在所述暗室感光芯片进行光信号采集；
对所采集光信号进行信号处理并输出。
优选的，在所述暗室感光芯片进行光信号采集包括以下步骤：
收集光信号；
通过电脑屏幕实时观察曝光程度；
待信号累积到预设强度时停止曝光；
获取并保存曝光产生的影像。
优选的，所述感光芯片采集信号为免疫印迹信号时，所述携带待采集光信号膜的获取包括以下步骤：
先将待测蛋白跑电泳；
跑完电泳的凝胶进行蛋白转移；
将凝胶中的待测蛋白转移至聚偏二氟乙烯膜或硝酸纤维素膜；
对转移完的聚偏二氟乙烯膜或硝酸纤维素膜进行封闭，加抗待测蛋白的一抗反应，加二抗HRP反应；
对反应后的聚偏二氟乙烯膜或硝酸纤维素膜进行化学发光液处理。
优选的，所述膜包括硝酸纤维素膜和\或聚偏二氟乙烯膜。
优选的，所述感光芯片包括CMOS感光芯片和CCD感光芯片。
本发明还公开了一种感光芯片采集信号的装置，包括：
贴合模块，用于将携带待采集光信号膜的发光面紧密贴合在感光芯片上；
搁置模块，用于将贴合有携带待采集光信号膜的感光芯片置于暗室中；所述暗室
不受外界光影响；
信号采集模块，用于完成在所述暗室感光芯片进行光信号采集；
信号处理模块，用于对所采集光信号进行信号处理并输出。
本发明还公开了一种感光芯片追踪细胞的方法，包括：
携带有荧光素酶的细胞或动物种植在感光芯片上；
将种植有携带有荧光素酶的细胞或动物的感光芯片置于暗室中 ；所述暗室不受外界光影响；
在所述暗室感光芯片进行光信号采集；
对所采集光信号进行信号处理并输出。
优选的，所述方法在将携带有荧光素酶的细胞或动物种植在感光芯片上之前还包括：在感光芯片上加装玻璃层，进而将携带有荧光素酶的细胞或动物种植在感光芯片上的玻璃层。
优选的，所述携带有荧光素酶的细胞或动物的获取包括以下步骤：
构建一个将靶启动子的特定片段插入到荧光素酶表达序列前方的报告基因质粒；
将调控序列和荧光素酶基因质粒共转染细胞或动物的受精卵内；
向细胞培养基内加入荧光素。
本发明还公开了一种感光芯片追踪细胞的装置，包括：
种植模块，用于将携带有荧光素酶的细胞或动物种植在感光芯片上；
搁置模块，用于将种植有携带有荧光素酶的细胞或动物的感光芯片置于暗室中 ；
所述暗室不受外界光影响；
信号采集模块，用于完成在所述暗室感光芯片进行光信号采集；
信号处理模块，用于对所采集光信号进行信号处理并输出。
与现有技术相比，本发明实施例包括以下优点：
本发明提供的方案通过将携带待采集光信号膜的发光面紧密贴合在感光芯片上，
将贴合有携带待采集光信号膜的感光芯片置于暗室中，在所述暗室中感光芯片进行光信号
采集，并对所采集光信号进行信号处理并输出。直接接触感光芯片完成信号采集，可对整幅
的图像同时采集，最大程度地避免光信号损失，从而在提高灵敏度的同时，不降低分辨率。
这样不但保留了背景技术中三种方法的全部优点，同时也避免了它们各自的缺点。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现
有技术描述中所需要使用的附图作一简单地介绍，显而易见地，下面描述中的附图是本发
明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根
据这些附图获得其他的附图。
图1是本发明的一种感光芯片采集信号的方法流程示意图；
图2是本发明的一种感光芯片采集信号的装置结构示意图；
图3是本发明的一种感光芯片跟踪细胞的方法流程示意图；
图4是本发明的一种感光芯片跟踪细胞的装置结构示意图。
具体实施方式
为使本发明实施例的目的、技术方案和优点更加清楚，下面将结合本发明实施例
中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例是
本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员
在没有作出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例一
详细介绍本发明实施例提供的一种感光芯片采集信号的方法。
参照图1，示出了本发明的一种感光芯片采集信号的方法实施例的流程示意图，具
体可以包括如下步骤：
步骤101，携带待采集光信号膜的发光面紧密贴合在感光芯片上；
在实际应用中，使用感光芯片采集免疫印迹信号时，携带待采集光信号膜的获取包括以下步骤：
先将待测蛋白跑电泳；
跑完电泳的凝胶进行蛋白转移；
将凝胶中的待测蛋白转移至聚偏二氟乙烯膜或硝酸纤维素膜；
对转移完的聚偏二氟乙烯膜或硝酸纤维素膜进行封闭，加抗待测蛋白的一抗反应，加二抗HRP反应；
将反应后的聚偏二氟乙烯膜或硝酸纤维素膜进行化学发光液处理。
应用中，所使用的膜主要包括硝酸纤维素膜(NC膜)和\或聚偏二氟乙烯膜(PVDF膜)。所使用的感光芯片包括CMOS感光芯片和CCD感光芯片等。考虑到较大尺寸的感光芯片制造成本高，在实践中如果利用芯片拼接技术能到较好的效果，成本将会大大降低，因此也可以是CMOS感光芯片或CCD感光芯片的阵列。
步骤102，将贴合有携带待采集光信号膜的感光芯片置于暗室中；所述暗室不受外界光影响；
为了不受外界光的影响，需将贴合有携带待采集光信号膜的感光芯片置于黑暗环境中，实现方式可根据具体环境进行选择，比较容易实现，可以给其扣个挡光盖子。
步骤103，在所述暗室感光芯片进行光信号采集；
实际的应用中，在所述暗室感光芯片进行光信号采集包括以下步骤：
收集光信号；
通过电脑屏幕实时观察曝光程度；
待信号累积到预设强度时停止曝光；
获取并保存曝光产生的影像。
步骤104，对所采集光信号进行信号处理并输出。
应用中可采用单片机、FPGA、CPU等等的处理器对所采集的光信号进行信号处理并将其输出。基于目前信号处理的方式比较成熟，且都可以完成本方案中所述的信号处理，因此这里不再赘述。
以下结合实际应用对感光芯片采集免疫印迹(WB信号)进行详细介绍：
免疫印迹工作原理：
1 、利用电场将细胞或组织提取物在聚丙烯凝胶上纵向分离(如左图，下图为此步骤地流程)；
2 、利用电场将蛋白条带横向转移到硝酸纤维素膜(NC膜)上，条带相对位置不发生改变，称为印迹(Blot)；
3 、封闭。将印迹后的膜在牛血清白蛋白(BSA)溶液中浸泡。使BSA占据蛋白条带没有占据的区域。避免后续的抗体被这些区域吸附，使抗体只能与其抗原专一结合。
4 、抗体孵育。抗体事先和辣根过氧化物酶(HRP)铰链。将抗体和NC膜一起浸泡孵育。抗体与其抗原特异结合。
5 ，信号采集。将NC膜浸在含有 HRP底物的液体中。HRP 催化其底物时释放出荧光。利用光敏胶片或电子感光系统采集荧光信号。
WB 光信号采集前的步骤：
(1) 蛋白质样品获得：细菌诱导表达后，可通过电泳上样缓冲液直接裂解细胞，真核细胞加匀浆缓冲液，机械或超声波室温匀浆0.5-1min。然后4℃，13,000g离心15min。取上清液作为样品。
(2) 电泳：制备电泳凝胶，进行SDS-PAGE。
(3) 转移：①电泳结束后将胶条割至合适大小，用转膜缓冲液平衡，5min×3次。②膜处理：预先裁好与胶条同样大小的滤纸和NC膜，浸入转膜缓冲液中10min。③转膜：转膜装置从下至上依次按阳极碳板、24层滤纸、NC膜、凝胶、24层滤纸、阴极碳板的顺序放好，滤纸、凝胶、NC膜精确对齐，每一步去除气泡，上压500g重物，将碳板上多余的液体吸干。接通电源,恒流1mA/cm2，转移1.5hr。转移结束后，断开电源将膜取出,割取待测膜条做免疫印迹。将有蛋白标准的条带染色，放入膜染色液中50s后，在50％甲醇中多次脱色，至背景清晰，然后用双蒸水洗，风干夹于两层滤纸中保存，留与显色结果作对比。
(4) 免疫反应：用0.01M PBST洗膜，5min×3次。
加入封闭液，平稳摇动，室温1hr。
弃包被液，用0.01M PBST洗膜，5min×3次。
加入一抗(按合适稀释比例用0.01M PBS稀释，液体必须覆盖膜的全部)，4℃放置12hr以上。阴性对照，以1％BSA取代一抗，其余步骤与实验组相同。
弃一抗和1％BSA，用0.01M PBS分别洗膜，5min×4次。
加入辣根过氧化物酶偶联的二抗(按合适稀释比例用0.01M PBST稀释)，平稳摇动，室温2hr。
弃二抗，用0.01M PBST洗膜，5min×4次。
化学发光液处理膜，HRP遇液体中的化学底物，催化底物并发出荧光。
利用数码感光芯片直接与膜贴合的方法采集荧光信号：
将浸泡在化学发光液中的膜取出，在吸水纸上沥去多余液体，然后将膜的发光面贴在数码感光芯片上；
用平整的物体压膜，使其与数码感光芯片直接紧密贴合；
扣上盖子，使数码感光芯片和膜处于黑暗环境，避免外界光污染；
通过计算机控制感光芯片，开始收集化学发光的信号。通过电脑屏幕实时观察曝光程度，待信号累积到合适的强度时停止曝光；
获得并保存曝光产生的影像，影像可用于定量和定性分析。
本实施例中，借助接触式感光芯片完成信号的采集，通过将光信号转化为数字信号，能够很好的完成定量分析。
实施例二
详细介绍本发明实施例提供的一种感光芯片采集信号的装置。
参见图2，示出了本发明的一种感光芯片采集信号的装置结构示意图，具体包括：
贴合模块201，用于将携带待采集光信号膜的发光面紧密贴合在感光芯片上；
搁置模块 202，用于将贴合有携带待采集光信号膜的感光芯片置于暗室中；所述暗室不受外界光影响；
信号采集模块203，用于完成在所述暗室感光芯片进行光信号采集；
信号处理模块204，用于对所采集光信号进行信号处理并输出。
对于装置实施例而言，由于其与方法实施例基本相似，所以描述的比较简单，相关之处参见方法实施例的部分说明即可。
实施例三
详细介绍本发明实施例提供的一种感光芯片追踪细胞的方法。
参照图3，示出了本发明一种感光芯片追踪细胞的方法，具体可以包括：
步骤301，携带有荧光素酶的细胞或动物种植在感光芯片上；
感光芯片上通常会覆盖一层透明的保护层，或玻璃层或树脂层又或其他材质等等，保护层的厚度通常小于0.5mm。
实践中考虑到追踪效果及感光芯片的二次使用，在将携带有荧光素酶的细胞或动物种植在感光芯片上之前可以在感光芯片上加装玻璃层，进而将携带有荧光素酶的细胞或动物种植在感光芯片的玻璃层，这样在后期的清理中会更加方便。
对于使用了感光芯片而不具有发光模块的仪器，通常设法让细胞或小型动物(如线虫和果蝇等)等具备自发光能力，具体的转入荧光素酶基因使细胞或动植物产生自发光能力是比较常用的办法。
萤光素酶(英文名称：Luciferase)是萤火虫尾部产生的一种蛋白，能在ATP存在的情况下能催化荧光素(luciferin)与氧气反应，发出荧光。利用生物工程的办法，将荧光素酶的基因和用于调控转录的 DNA序列一起转入细胞或动植物体内，并整合在宿主的染色体上。利用宿主表达的某些具有特殊结构、行使调控基因表达功能的蛋白质分子，特异地结合调控转录的DNA序列，从而对萤光素酶基因的表达起增强的作用。
所述携带有荧光素酶的细胞或动物的获取包括以下步骤：
构建一个将靶启动子的特定片段插入到荧光素酶表达序列前方的报告基因质粒；具体如pGL3-basic等；
将调控序列和荧光素酶基因质粒共转染细胞或动物的受精卵内(转基因动物)；
向细胞培养基内加入荧光素，荧光素酶利用细胞内的ATP提供能量催化荧光素与氧气反应，产生荧光。这样，仪器可以追踪细胞或动物的迁移轨迹。此方法可用于动物行为学实验。
步骤302，将种植有携带有荧光素酶的细胞或动物的感光芯片置于暗室中；所述暗室不受外界光影响；
步骤303，在所述暗室感光芯片进行光信号采集；
步骤304，对所采集光信号进行信号处理并输出。
实施例四
详细介绍本发明实施例提供的一种感光芯片追踪细胞的装置。
参见图4，示出了本发明的一种感光芯片追踪细胞的装置结构示意图，具体包括：
种植模块401，用于将携带有荧光素酶的细胞或动物种植在感光芯片上；
搁置模块 402，用于将种植有携带有荧光素酶的细胞或动物的感光芯片置于暗室中；所述暗室不受外界光影响；
信号采集模块403，用于完成在所述暗室感光芯片进行光信号采集；
信号处理模块404，用于对所采集光信号进行信号处理并输出。
本发明所述的方案可以广泛应用于采集免疫印迹信号、监测比较液滴阵列中的微光强度，感光芯片上种植细胞观察细胞迁移，分裂，或某些分子表达的动态过程等等。
需要说明的是，对于方法实施例，为了简单描述，故将其都表述为一系列的动作组合，但是本领域技术人员应该知悉，本发明实施例并不受所描述的动作顺序的限制，因为依据本发明实施例，某些步骤可以采用其他顺序或者同时进行。其次，本领域技术人员也应该知悉，说明书中所描述的实施例均属于优选实施例，所涉及的动作并不一定是本发明实施例所必须的。
对于装置实施例而言，由于其与方法实施例基本相似，所以描述的比较简单，相关之处参见方法实施例的部分说明即可。
本说明书中的各个实施例均采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似的部分互相参见即可。
以上对本发明所提供的一种感光芯片采集信号的方法和装置及追踪细胞的方法和装置，进行了详细介绍，本文中应用了具体个例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想；同时，对于本领域的一般技术人员，依据本发明的思想，在具体实施方式及应用范围上均会有改变之处，综上所述，本说明书内容不应理解为对本发明的限制。

Claims (10)

  1. 一种感光芯片采集信号的方法，其特征在于，包括：
    携带待采集光信号膜的发光面紧密贴合在感光芯片上；
    将贴合有携带待采集光信号膜的感光芯片置于暗室中；所述暗室不受外界光影响；
    在所述暗室感光芯片进行光信号采集；
    对所采集光信号进行信号处理并输出。
  2. 如权利要求 1所述的方法，其特征在于，在所述暗室感光芯片进行光信号采集包括以下步骤：
    收集光信号；
    通过电脑屏幕实时观察曝光程度；
    待信号累积到预设强度时停止曝光；
    获取并保存曝光产生的影像。
  3. 如权利要求1所述的方法，其特征在于，所述感光芯片采集信号为免疫印迹信号时，所述携带待采集光信号膜的获取包括以下步骤：
    先将待测蛋白跑电泳；
    跑完电泳的凝胶进行蛋白转移；
    将凝胶中的待测蛋白转移至聚偏二氟乙烯膜或硝酸纤维素膜；
    对转移完的聚偏二氟乙烯膜或硝酸纤维素膜进行封闭，加抗待测蛋白的一抗反应，加二抗HRP反应；
    对反应后的聚偏二氟乙烯膜或硝酸纤维素膜进行化学发光液处理。
  4. 如权利要求1所述的方法，其特征在于，所述膜包括硝酸纤维素膜和\或聚偏二氟乙烯膜。
  5. 如权利要求1所述的方法，其特征在于，所述感光芯片包括CMOS感光芯片和CCD感光芯片。
  6. 一种感光芯片采集信号的装置，其特征在于，包括：
    贴合模块，用于将携带待采集光信号膜的发光面紧密贴合在感光芯片上；
    搁置模块，用于将贴合有携带待采集光信号膜的感光芯片置于暗室中；所述暗室不受外界光影响；
    信号采集模块，用于完成在所述暗室感光芯片进行光信号采集；
    信号处理模块，用于对所采集光信号进行信号处理并输出。
  7. 一种感光芯片追踪细胞的方法，其特征在于，包括：
    携带有荧光素酶的细胞或动物种植在感光芯片上；
    将种植有携带有荧光素酶的细胞或动物的感光芯片置于暗室中；所述暗室不受外界光影响；
    在所述暗室感光芯片进行光信号采集；
    对所采集光信号进行信号处理并输出。
  8. 如权利要求 7所述的方法，其特征在于，所述方法在将携带有荧光素酶的细胞或动物种植在感光芯片上之前还包括：在感光芯片上加装玻璃层，进而将携带有荧光素酶的细胞或动物种植在感光芯片上的玻璃层。
  9. 如权利要求7或8所述的方法，其特征在于，所述携带有荧光素酶的细胞或动物的获取包括以下步骤：
    构建一个将靶启动子的特定片段插入到荧光素酶表达序列前方的报告基因质粒；
    将调控序列和荧光素酶基因质粒共转染细胞或动物的受精卵内；
    向细胞培养基内加入荧光素。
  10. 一种感光芯片追踪细胞的装置，其特征在于，包括：
    种植模块，用于将携带有荧光素酶的细胞或动物种植在感光芯片上；
    搁置模块，用于将种植有携带有荧光素酶的细胞或动物的感光芯片置于暗室中；所述暗室不受外界光影响；
    信号采集模块，用于完成在所述暗室感光芯片进行光信号采集；
    信号处理模块，用于对所采集光信号进行信号处理并输出。
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Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105067817B (zh) * 2015-07-08 2017-05-10 上海清流生物医药科技有限公司 感光芯片采集信号的方法和装置及追踪细胞的方法和装置
CN107446569B (zh) * 2017-07-14 2019-09-27 广西师范大学 一种藻蓝蛋白吸附聚偏二氟乙烯荧光膜的制备方法及其应用
CN109387639A (zh) * 2017-08-07 2019-02-26 上海易孛特光电技术有限公司 一种非晶硅平板探测器
CN114076762A (zh) * 2020-08-13 2022-02-22 南京金斯瑞生物科技有限公司 成像装置、图像处理方法及装置和成像系统
CN113973772A (zh) * 2021-10-22 2022-01-28 中国水产科学研究院珠江水产研究所 无源集成收发芯片在鼋个体跟踪监测中的应用
KR20230090811A (ko) * 2021-12-15 2023-06-22 주식회사 피디젠 생체모방 오간온어칩을 이용한 실시간세포추적시스템 및 이를 구현하는 방법

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010071903A (ja) * 2008-09-22 2010-04-02 Panasonic Corp 発光測定方法及び発光測定装置
CN101868727A (zh) * 2007-11-23 2010-10-20 （株）赛丽康 荧光生物芯片诊断设备
CN102156345A (zh) * 2004-11-26 2011-08-17 奥林巴斯株式会社 发光试料摄像方法、发光细胞摄像方法及物镜
US20120144507A1 (en) * 2009-07-24 2012-06-07 National Health Research Institutes F1b-tmir plasmid vector and transgenic mouse
CN102703301A (zh) * 2012-05-24 2012-10-03 中国科学院北京基因组研究所 用于测序芯片的安装座与ccd相机间的暗室
CN203960183U (zh) * 2014-05-14 2014-11-26 杨栎 一种用于ccd相机的暗室连接头
CN105067817A (zh) * 2015-07-08 2015-11-18 上海清流生物医药科技有限公司 感光芯片采集信号的方法和装置及追踪细胞的方法和装置

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1327174A (zh) * 2000-06-04 2001-12-19 刘玉坤 粘贴式感光胶片及其制作方法
US20040014043A1 (en) * 2002-07-16 2004-01-22 Emp Biotech Gmbh Sensitizer-labeled analyte detection
US20050079598A1 (en) * 2003-10-08 2005-04-14 Davis Randall W. Apparatus and method for identification of biomolecules, in particular nucleic acid sequences, proteins, and antigens and antibodies
US20090253217A1 (en) * 2005-09-12 2009-10-08 Japan Science And Technology Agency Method of Quickly Detecting Antigen Using Fluorescence Correlation Spectroscopy or Fluorescence Cross-Correlation Spectroscopy
US8512678B2 (en) * 2005-10-19 2013-08-20 Agency For Science, Technology And Research Non-invasive, in vivo fluorescent imaging of the nervous system in whole living animal
JP2007285749A (ja) 2006-04-13 2007-11-01 Kitasato Gakuen インフルエンザ感染検査薬及び検査方法
JP4889437B2 (ja) * 2006-10-16 2012-03-07 オリンパス株式会社 微弱光撮像装置
JP2008241447A (ja) * 2007-03-27 2008-10-09 Fujifilm Corp 画像読取装置及び画像読取方法
JP5265140B2 (ja) 2007-06-14 2013-08-14 学校法人日本医科大学 卵巣癌の検出方法及び検出用キット
US8828658B2 (en) * 2008-05-23 2014-09-09 The Regents Of The University Of California Spatio-temporal control of protein interactions using phytochromes
JP2010271078A (ja) 2009-05-19 2010-12-02 Mcbi:Kk 認知機能障害疾患を含む精神疾患のバイオマーカーおよび該バイオマーカーを用いた認知機能障害疾患を含む精神疾患の検出方法
CN102095867B (zh) 2009-12-09 2013-11-27 中国农业科学院上海兽医研究所 自发光材料用于化学发光Western blot的用途及其组合物
CN102062776A (zh) * 2010-12-16 2011-05-18 中华人民共和国天津出入境检验检疫局 一种驽巴贝斯虫病免疫印迹检测方法及试剂盒制备
CN102181556B (zh) * 2011-04-15 2013-03-13 中国农业科学院兰州兽医研究所 用于检测马梨形虫的试剂盒及制备与使用方法
CA2859475C (en) * 2011-12-16 2015-07-07 Li-Cor, Inc. Luminescence imaging scanner
US9383336B2 (en) * 2014-04-04 2016-07-05 General Electric Company System and method for flat panel detector gel and blot imaging
WO2016007353A1 (en) * 2014-07-07 2016-01-14 Bio-Rad Laboratories, Inc. Contact imager
CN104730038B (zh) * 2014-12-25 2018-02-02 中北大学 一种手持式高通量生物传感器

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102156345A (zh) * 2004-11-26 2011-08-17 奥林巴斯株式会社 发光试料摄像方法、发光细胞摄像方法及物镜
CN101868727A (zh) * 2007-11-23 2010-10-20 （株）赛丽康 荧光生物芯片诊断设备
JP2010071903A (ja) * 2008-09-22 2010-04-02 Panasonic Corp 発光測定方法及び発光測定装置
US20120144507A1 (en) * 2009-07-24 2012-06-07 National Health Research Institutes F1b-tmir plasmid vector and transgenic mouse
CN102703301A (zh) * 2012-05-24 2012-10-03 中国科学院北京基因组研究所 用于测序芯片的安装座与ccd相机间的暗室
CN203960183U (zh) * 2014-05-14 2014-11-26 杨栎 一种用于ccd相机的暗室连接头
CN105067817A (zh) * 2015-07-08 2015-11-18 上海清流生物医药科技有限公司 感光芯片采集信号的方法和装置及追踪细胞的方法和装置

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