WO2018000664A1 - Capillary electrophoresis detection system and detection method - Google Patents

Capillary electrophoresis detection system and detection method Download PDF

Info

Publication number
WO2018000664A1
WO2018000664A1 PCT/CN2016/102707 CN2016102707W WO2018000664A1 WO 2018000664 A1 WO2018000664 A1 WO 2018000664A1 CN 2016102707 W CN2016102707 W CN 2016102707W WO 2018000664 A1 WO2018000664 A1 WO 2018000664A1
Authority
WO
WIPO (PCT)
Prior art keywords
capillary
fluorescence
laser
photodetector
fluorescent dye
Prior art date
Application number
PCT/CN2016/102707
Other languages
French (fr)
Chinese (zh)
Inventor
金见睿
万戈江
冯栋
Original Assignee
山东科立森生物股份有限公司
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 山东科立森生物股份有限公司 filed Critical 山东科立森生物股份有限公司
Publication of WO2018000664A1 publication Critical patent/WO2018000664A1/en

Links

Images

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N21/6402Atomic fluorescence; Laser induced fluorescence
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/416Systems
    • G01N27/447Systems using electrophoresis
    • G01N27/44704Details; Accessories
    • G01N27/44717Arrangements for investigating the separated zones, e.g. localising zones
    • G01N27/44721Arrangements for investigating the separated zones, e.g. localising zones by optical means
    • G01N27/44726Arrangements for investigating the separated zones, e.g. localising zones by optical means using specific dyes, markers or binding molecules
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/01Arrangements or apparatus for facilitating the optical investigation
    • G01N2021/0106General arrangement of respective parts
    • G01N2021/0112Apparatus in one mechanical, optical or electronic block
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N2021/6417Spectrofluorimetric devices
    • G01N2021/6419Excitation at two or more wavelengths
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64Fluorescence; Phosphorescence
    • G01N2021/6417Spectrofluorimetric devices
    • G01N2021/6421Measuring at two or more wavelengths

Definitions

  • the invention relates to the field of detection technology, in particular to a capillary electrophoresis detection system and a detection method.
  • Capillary electrophoresis (CE) technology is a new liquid phase separation technology with a capillary as a separation channel and a high-voltage DC electric field as the driving force.
  • Capillary electrophoresis generally uses a quartz capillary column. Under the action of a high voltage electric field outside the capillary, the buffer on one side moves toward the negative electrode due to positive charge. At the same time, in the buffer solution, the charged biomolecules move in the direction of the electrode opposite to the charge polarity of the charged biomolecule at different speeds under the action of a high voltage electric field outside the capillary to form an electrophoresis.
  • a capillary electrophoresis technique is combined with a fluorescent labeling analysis technique to detect a substance contained in a sample.
  • a fluorescent dye is labeled on a biological substance.
  • the fluorescent dye is excited by the light source to generate fluorescence, the detector receives the generated fluorescence, and the received fluorescence is analyzed to detect the type of the target substance to be tested in the sample in the capillary. Or content.
  • the commonly used detection method is to use a laser to excite the fluorescence generated by a fluorescent dye on a sample in a capillary tube for detection, and only one target substance to be tested can be detected at a time. If there are a large number of target substances to be tested in the test sample that need to be detected, the test can only be divided into multiple times, the detection speed is slow, and the test sample is expensive.
  • the technical problem to be solved by the present invention is to provide a capillary electrophoresis detection system and a detection method, which can detect a large amount of biological substances in the same detection sample at one time, and the detection speed is fast, and the detection sample consumption is small.
  • a capillary electrophoresis detection system comprising:
  • At least two lasers each having a different wavelength of the output; a capillary tube, the detection sample in the capillary tube comprising a plurality of target substances to be tested, the target substance to be tested comprising a biological substance labeled with a fluorescent dye or a labeled substance a biological substance of an antibody to a fluorescent dye; a plurality of detectors;
  • the laser light output by the at least two lasers is irradiated on the capillary, and the fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence of a plurality of wavelength ranges, and the plurality of detectors receive a plurality of wavelength ranges Fluorescence, which in turn detects the type or content of a plurality of target substances to be tested included in the test sample in the capillary.
  • each detector includes:
  • Each filter transmits fluorescence in a range of wavelengths, and each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
  • system further includes:
  • a controller and a scan head connected to the controller, a plurality of beamsplitters;
  • Each beam splitter corresponds to one laser, each laser is equipped with one detector, the number of beamsplitters, the number of lasers and the number of detectors are the same;
  • the laser light output by each laser is sequentially irradiated on the capillary through a first optical fiber in the scanning head and a corresponding spectroscope of the laser, and the fluorescent dye in the capillary
  • the excited fluorescence is transmitted to a second optical fiber reflected in the scanning head via a corresponding beam splitter of the laser to a detector provided to the laser;
  • the laser illumination from each laser output excites fluorescence at least one wavelength range on the capillary, and the fluorescence excited by each laser is received by a detector equipped with the laser.
  • the at least two lasers are mounted within the scan head.
  • the detector comprises:
  • a mirror a plurality of filters, and a plurality of photodetectors, the number of the filters being the same as the number of photodetectors, each photodetector being mounted behind a filter;
  • the mirror reflects fluorescence received by the detector onto the plurality of filters
  • Each filter transmits fluorescence of one wavelength range, and reflects fluorescence of other wavelength ranges to the mirror;
  • Each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
  • the detector further includes:
  • focusing mirrors a plurality of focusing mirrors, the number of focusing mirrors being the same as the number of photodetectors;
  • Each focusing mirror is placed in front of a photodetector to focus the fluorescence transmitted by a filter to a photodetector.
  • the target substance to be tested includes protein molecules, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterol molecules, nucleotide molecules, and nucleus in body fluids.
  • the target substance to be tested includes DNA, and at least one of the biomass according to claim 7.
  • a capillary electrophoresis detection method comprising:
  • Laser light output from at least two lasers is irradiated on the capillary, and each laser output has a different wavelength
  • the fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence in a plurality of wavelength ranges, and the detection sample in the capillary includes a plurality of target substances to be tested, the target substance including the biological substance labeled with the fluorescent dye Or a biological substance that binds to an antibody labeled with a fluorescent dye;
  • the plurality of detectors receive fluorescence of a plurality of wavelength ranges, thereby detecting the kind or content of the plurality of target substances to be tested included in the detection sample in the capillary.
  • the plurality of detectors receive fluorescence of a plurality of wavelength ranges, and further detecting the type or content of the plurality of target substances to be tested included in the detection sample in the capillary comprises:
  • Multiple detectors receive fluorescence in multiple wavelength ranges to simultaneously detect detection in the capillary
  • the present invention has the following beneficial effects:
  • the invention provides a capillary electrophoresis detection system and a detection method, at least two lasers, a capillary tube, the detection sample in the capillary tube comprises a plurality of target substances to be tested, and the target substance to be tested comprises a fluorescent dye-labeled substance.
  • a biological substance or a biological substance to which an antibody labeled with a fluorescent dye is bound a plurality of detectors; laser light output from the at least two lasers is irradiated on the capillary, and a fluorescent dye in the detection sample in the capillary is subjected to laser light
  • the excitation generates fluorescence of a plurality of wavelength ranges
  • the plurality of detectors receive fluorescence of a plurality of wavelength ranges, thereby detecting the kind or content of the substance contained in the detection sample in the capillary.
  • At least two lasers are used to illuminate the capillary. Each laser outputs a different wavelength of laser light.
  • the number of wavelengths of fluorescence that can be excited is greater than the wavelength range of fluorescence that a laser can excite.
  • One wavelength range of fluorescence represents a kind of fluorescence.
  • the target substance to be tested uses at least two lasers to detect more kinds of target substances to be detected than one laser, thereby improving the detection speed and saving the test sample.
  • FIG. 1 is a schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention
  • FIG. 2 is a schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention
  • FIG. 3 is another schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention.
  • FIG. 4 is a schematic structural diagram of a detector according to an embodiment of the present invention.
  • FIG. 5 is a schematic structural diagram of another detector according to an embodiment of the present invention.
  • FIG. 6 is a flowchart of a capillary electrophoresis detection method according to an embodiment of the present invention.
  • an embodiment of the present invention provides a capillary electrophoresis detection system and method, and a preferred embodiment of the present invention will be described below with reference to the accompanying drawings.
  • a laser is used to excite the fluorescence generated by a sample in a capillary tube for detection.
  • a laser can excite a limited range of wavelengths of fluorescence, and a wavelength range of fluorescence represents a target substance to be tested, that is, a laser.
  • the type of target substance to be tested in the test sample that can be detected is limited, and only four or five kinds of biological substances can be detected at a time.
  • each test requires the detection of a large variety of biological substances, which requires multiple tests to complete. Not only does the time required for the test be very long, but a test sample is required for each test. The amount of test sample required is large, especially if the test sample is mostly blood, which will cause certain damage to the patient.
  • the present invention provides a system and method for simultaneously detecting a large variety of substances from a single test sample.
  • FIG. 1 is a schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention, including:
  • At least two lasers 101 each having a different wavelength of laser output; a capillary 102, the detection sample in the capillary 102 comprising a plurality of target substances to be tested, the target substance to be detected comprising a biological substance labeled with a fluorescent dye or a biological substance combined with an antibody labeled with a fluorescent dye; a plurality of detectors 103;
  • the laser light output from the at least two lasers 101 is irradiated on the capillary 102, and the fluorescent dye in the detection sample in the capillary 102 is excited by the laser to generate fluorescence in a plurality of wavelength ranges, and the plurality of detectors 103 receive fluorescence detection in various wavelength ranges.
  • the fluorescent dye may be a fluorescent dye directly labeled on the target substance to be tested, or may be a fluorescent dye labeled on the antibody bound to the target substance to be tested.
  • each laser is irradiated onto the capillary 102 via mirror reflection or transmission of the optical fiber, transmitted through the capillary 102, and the fluorescent dye in the detection sample in the excitation capillary 102 fluoresces.
  • Each laser outputs a different wavelength of laser light, and the range of wavelengths of fluorescence that can be excited is also different. Fluorescence in different wavelength ranges represents different types of target analytes in the sample detected in the capillary. The more the number of fluorescent wavelength ranges obtained by excitation, the more species that can be detected.
  • a wavelength laser can excite a limited range of wavelengths of fluorescence, using different wavelengths At least two lasers are capable of exciting a range of wavelengths of fluorescence that is greater than the range of wavelengths of fluorescence that a laser can excite. Fluorescence of different wavelength ranges represents different types of biological species, and thus the types of biological species that can be detected There are also many.
  • Capillary 102 employs a capillary having an inner diameter of from 5 micrometers to 100 micrometers, an outer diameter of from 50 micrometers to 300 micrometers, and a length of from 3 centimeters to 80 centimeters.
  • the capillary electrophoresis detection system detects at least two possible structures.
  • the first possible structure as shown in Figure 2, includes:
  • Each filter transmits fluorescence in a range of wavelengths, and each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
  • each of the plurality of detectors includes a filter and a photodetector.
  • a filter can only reflect fluorescence in a range of wavelengths, reflecting fluorescence in other wavelength ranges, and a photodetector disposed behind each filter is used to receive the fluorescence transmitted by the filter.
  • the filter m1 and the photodetector n1 are one detector, the filter m1 is disposed in front of the photodetector n1, and the photodetector n1 receives the fluorescence transmitted by the filter m1; the filter m2 And the photodetector n2 is a detector, the filter m2 is disposed in front of the photodetector n2, the photodetector n2 receives the fluorescence transmitted by the filter m2; the filter m3 and the photodetector n3 are a detector, The filter m3 is disposed before the photodetector n3, the photodetector n3 receives the fluorescence transmitted by the filter m3, and so on, the filter mi and the photodetector ni are one detector, and the filter mi is disposed at Before the photodetector ni, the photodetector ni receives the fluorescence transmitted by the filter mi
  • a second possible structure as shown in FIG. 3, the system further includes:
  • the controller 301 has a scan head 302 connected to the controller, and a plurality of beamsplitters.
  • Each beam splitter corresponds to one laser, each laser is equipped with a detector, the number of beamsplitters, the number of lasers and the number of detectors are the same.
  • the laser output from each laser passes through
  • the first optical fiber in the scanning head 302 is sequentially irradiated on the capillary 102 through a spectroscope corresponding to the laser, and the fluorescent light excited by the fluorescent dye in the detecting sample 102 is reflected by the corresponding spectroscope of the laser to
  • the second optical fiber in the scan head 302 is transmitted to a detector provided to the laser;
  • the laser illumination from each laser output excites fluorescence at least one wavelength range on the capillary, and the fluorescence excited by each laser is received by a detector equipped with the laser.
  • the scanning head 302 includes a plurality of beam splitters, a plurality of first fibers, and a plurality of second fibers.
  • Each laser corresponds to a beam splitter, a first fiber, and a second fiber.
  • the laser output from each laser is transmitted by the corresponding first optical fiber of the laser, and is irradiated onto the capillary 102 through a spectroscope corresponding to the laser.
  • the capillary 102 detects the fluorescence excited by the fluorescent dye in the sample, and the corresponding spectroscopic light is passed through the laser.
  • the mirror is reflected to a second fiber corresponding to the laser, and the second fiber transmits the received fluorescence to a detector provided to the laser.
  • the “first” in the first optical fiber and the “second” in the second optical fiber represent not the order but a type, and the first optical fiber is not an optical fiber but a type of optical fiber.
  • the second fiber is not a fiber, but a type of fiber.
  • the scanning head 302 has a plurality of first fibers, a plurality of second fibers, and the number of the first fibers.
  • the number of the second fibers is the same as the number of the lasers.
  • Each laser corresponds to a first fiber and a second fiber.
  • the laser light output by the laser a1 is transmitted by the first optical fiber x1 in the scanning head, and transmitted through the beam splitter y1 to be irradiated in the capillary 102.
  • the fluorescence of the fluorescent dye excited by the detection sample of the capillary 102 is split.
  • the mirror y1 is reflected to the second optical fiber z1 in the scan head, and the second optical fiber z1 transmits the fluorescence to the detector b1 provided to the laser a1;
  • the laser output from the laser a2 is transmitted by the first optical fiber x2 in the scanning head, and transmitted through the beam splitter y2 Irradiated in the capillary 102, the fluorescence of the fluorescent dye excited in the detection sample of the capillary 102 is reflected by the beam splitter y2 to the second optical fiber z2 in the scanning head, and the second optical fiber z2 transmits the fluorescence to the detector b2 provided to the laser a2.
  • the laser outputted by the laser a3 is transmitted by the first optical fiber x3 in the scanning head, and transmitted through the beam splitter y3 to be irradiated in the capillary 102.
  • the fluorescent light excited by the fluorescent dye in the detection sample of the capillary 102 is reflected by the spectroscope y3 to the scanning head.
  • the second fiber z3 transmits the fluorescence from the second fiber z3 to the detector b3 provided to the laser a3; the laser output from the laser a4 is transmitted by the first fiber x4 in the scanning head, transmitted through Y4 irradiating light microscope in the capillary 102, the capillary test sample a fluorescent dye 102 is excited by a fluorescence spectroscope y4 Reflected to the second fiber z4 in the scan head, the second fiber z4 transmits the fluorescence to the detector b4 provided to the laser a4.
  • the number of lasers and detectors can be specifically set according to actual needs, and is not limited to the four lasers and four detectors shown in FIG. 3, and the number of lasers and detectors can be the same.
  • At least two lasers are mounted in scan head 302.
  • at least two lasers can also be mounted outside of the scanning head 302.
  • a plurality of detectors can be mounted outside of the scanning head 302 and can also be mounted within the scanning head 302. The technician can set it according to the actual needs.
  • the controller 301 controls the scanning head 302 to scan the capillary 102 such that the laser light output by each laser is irradiated onto the capillary 102 one by one, and the fluorescence generated by the excitation of the fluorescent dye in the detection sample in the capillary 102 is received.
  • the direction in which the scanning head 302 scans is as shown in FIG. It should be noted that the scanning direction of the scanning head 302 can also be opposite to the scanning direction shown in FIG. 3, and the technician can set it according to actual needs.
  • the detector includes:
  • a mirror a plurality of filters, and a plurality of photodetectors, the number of the filters being the same as the number of photodetectors, each photodetector being mounted behind a filter;
  • the mirror reflects fluorescence received by the detector onto the plurality of filters
  • Each filter transmits fluorescence of one wavelength range, and reflects fluorescence of other wavelength ranges to the mirror;
  • Each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
  • a capillary electrophoresis detection system there are multiple detectors, each of which includes a mirror, a plurality of filters, and a plurality of photodetectors.
  • a laser can excite fluorescence in several wavelength ranges, and the detector equipped with the laser receives fluorescence in several wavelength ranges that are excited.
  • the detector includes a mirror that reflects the fluorescence received by the detector to the filter.
  • Each filter transmits fluorescence in one wavelength range and reflects fluorescence in other wavelength ranges back to the mirror.
  • a photodetector is disposed behind each filter, and the photodetector receives only fluorescence of a wavelength range transmitted by the filter. In turn, the detector receives fluorescence in all wavelength ranges excited by a laser.
  • each filter is placed in close contact with the mirror.
  • the detector includes a mirror 401, four filters p1 to p4, and four photodetectors q1 to q4.
  • the number of filters is the same as the number of photodetectors.
  • the mirror 401 is large and covers all of the filters p1 to p4, and each of the filters p1 to p4 is placed in close contact with the mirror 501.
  • the received fluorescence is reflected by the mirror 401 to each of the filters p1 to p4.
  • the fluorescence transmitted by the filter p1 is received by the photodetector q1
  • the fluorescence transmitted by the filter p2 is received by the photodetector q2
  • the fluorescence transmitted by the filter p3 is received by the photodetector q3, and the filter is filtered.
  • the fluorescence transmitted by the sheet p4 is received by the photodetector q4.
  • the number of filters and photodetectors provided in each detector is not less than the number of wavelengths of fluorescence that a laser can excite.
  • a laser can excite fluorescence in four or five wavelength ranges, and four or five filters and four or five photodetectors can be placed in one detector.
  • the photodetector includes a charge-coupled device (CCD) image sensor, an Avalanche Photo Diode (APD), a Complementary Metal Oxide Semiconductor (CMOS) image sensor, and a photomultiplier tube (Photo Multiplier Tube, PMT).
  • CCD charge-coupled device
  • APD Avalanche Photo Diode
  • CMOS Complementary Metal Oxide Semiconductor
  • PMT Photo Multiplier Tube
  • the detector further includes:
  • focusing mirrors a plurality of focusing mirrors, the number of focusing mirrors being the same as the number of photodetectors;
  • Each focusing mirror is placed in front of a photodetector to focus the fluorescence transmitted by a filter to a photodetector.
  • a focusing mirror is added in front of each photodetector that focuses the fluorescence transmitted by one filter to the photodetector.
  • the focusing mirror L1 focuses the fluorescence transmitted by the filter p1 to the photodetector q1;
  • the focusing mirror L2 focuses the fluorescence transmitted by the filter p2 to the photodetector q2;
  • the focusing mirror L3 filters the light.
  • the fluorescence transmitted by the sheet p3 is focused to the photodetector q3;
  • the focusing mirror L4 focuses the fluorescence transmitted by the filter p4 to the photodetector q4.
  • the target substance to be tested includes protein molecules, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterol molecules, and nucleus in body fluids.
  • Glycosylate molecule, nucleotide derivative molecule, lipid, fatty acid derivative Any one or more of substances, sugars, vitamins, lipoproteins, apolipoproteins, glycoproteins, mucins, metalloproteins, glycolipids.
  • the target substance to be tested includes DNA, protein molecules in a body fluid, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterols Any of a class of molecules, nucleotide molecules, nucleotide derivative molecules, lipids, fatty acid derivatives, sugars, vitamins, lipoproteins, apolipoproteins, glycoproteins, mucins, metalloproteins, glycolipids Or a variety.
  • the capillary electrophoresis detection system realizes the simultaneous detection of DNA and non-DNA biological substances in the same test sample, and unifies genetic detection, clinical biochemical detection and immunological detection, and has a major breakthrough in clinical diagnosis. .
  • the present invention has the following beneficial effects:
  • At least two lasers are used to illuminate the capillary. Each laser outputs a different wavelength of laser light.
  • the number of wavelengths of fluorescence that can be excited is greater than the wavelength range of fluorescence that a laser can excite.
  • One wavelength range of fluorescence represents a kind of fluorescence.
  • the target substance to be tested uses at least two kinds of lasers to detect more kinds of biological substances than one laser, which improves the detection speed and saves the test sample.
  • FIG. 6 is a flowchart of a capillary electrophoresis detection method according to an embodiment of the present invention, including:
  • Laser light output from at least two lasers is irradiated on the capillary, and each laser output has a different wavelength.
  • the fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence of a plurality of wavelength ranges, the detection sample in the capillary includes a plurality of target substances to be tested, and the target substance to be tested includes a fluorescent dye-labeled substance.
  • the plurality of detectors receive fluorescence of a plurality of wavelength ranges, thereby detecting the kind or content of the plurality of target substances to be tested included in the detection sample in the capillary.
  • a plurality of detectors receive fluorescence in a plurality of wavelength ranges, thereby detecting protein molecules, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing molecules in the test sample in the capillary.
  • a plurality of detectors receive fluorescence in a plurality of wavelength ranges, and simultaneously detect DNA labeled with a fluorescent dye in the detection sample in the capillary, and molecules of a protein molecule, a polypeptide molecule, an amino acid molecule, and an amino acid derivative, Alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterol molecules, nucleotide molecules, nucleotide derivative molecules, lipids, fatty acid derivatives, sugars, vitamins, lipoproteins, apolipoproteins, Any one or more of glycoprotein, mucin, metalloprotein, and glycolipid.
  • the detector receives fluorescence in multiple wavelength ranges and is capable of detecting the wavelength range of the received fluorescence. By comparing with the preset test standards, it is possible to know which type of biological substance is contained in the test sample and the content of the substance.
  • the capillary electrophoresis detection method shown in FIG. 6 is a method corresponding to the capillary electrophoresis detection system shown in FIG. 1 to FIG. 5. The specific implementation manner is described in the system shown in FIG. 1 to FIG. 5, and details are not described herein again.

Landscapes

  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Optics & Photonics (AREA)

Abstract

A capillary electrophoresis detection system and detection method, the system comprising at least two lasers (101); one capillary (102), a detection sample in the capillary (102) comprising a plurality of target substances to be detected, each of which comprising a biological substance labeled with a fluorescent dye or a biological substance binding an antibody labeled with a fluorescent dye; and a plurality of detectors (103). A laser ray outputted from the at least two lasers (101) irradiates on the capillary (102), and the fluorescent dye in the test sample in the capillary (102) is excited by the laser ray to generate fluorescence in a plurality of wavelength ranges, and the plurality of detectors (103) receive the fluorescence in a plurality of wavelength ranges so as to detect the type and content of the plurality of target substances to be detected as contained in the detection sample in the capillary. At least two lasers are used in the method to irradiate the capillary. As the wavelength of the laser ray outputted by each laser is different, the number of wavelength ranges that can excite fluorescence herein is greater than the number of wavelength ranges that can excite fluorescence in the case of just one laser, thereby increasing the detection speed, and saving detection samples.

Description

一种毛细管电泳检测系统及检测方法Capillary electrophoresis detection system and detection method
本申请要求于2016年06月29日提交中国专利局、申请号为201610496480.4、发明名称为“一种毛细管电泳检测系统及检测方法”的中国专利申请的优先权,其全部内容通过引用结合在本申请中。The present application claims priority to Chinese Patent Application No. 201610496480.4, entitled "Capillary Electrophoresis Detection System and Detection Method", filed on June 29, 2016, the entire contents of which are incorporated herein by reference. In the application.
技术领域Technical field
本发明涉及检测技术领域,特别是涉及一种毛细管电泳检测系统及检测方法。The invention relates to the field of detection technology, in particular to a capillary electrophoresis detection system and a detection method.
背景技术Background technique
毛细管电泳(capillary electrophoresis,CE)技术是以毛细管为分离通道,以高压直流电场为驱动力的新型液相分离技术。毛细管电泳一般采用石英毛细管柱,在毛细管外部高压电场作用下,一侧的缓冲液由于带正电而向负极方向移动。于此同时,在缓冲溶液中,带电生物分子在毛细管外部高压电场作用下,以各自不同速度,向与该带电生物分子所带电荷极性相反的电极方向移动,形成电泳。Capillary electrophoresis (CE) technology is a new liquid phase separation technology with a capillary as a separation channel and a high-voltage DC electric field as the driving force. Capillary electrophoresis generally uses a quartz capillary column. Under the action of a high voltage electric field outside the capillary, the buffer on one side moves toward the negative electrode due to positive charge. At the same time, in the buffer solution, the charged biomolecules move in the direction of the electrode opposite to the charge polarity of the charged biomolecule at different speeds under the action of a high voltage electric field outside the capillary to form an electrophoresis.
现有技术中,把毛细管电泳技术与荧光标记分析技术相结合,对检测样品中所含的物质进行检测。在生物物质上标记荧光染料,生物物质在毛细管中移动的过程中,荧光染料受到光源激发产生荧光,探测器接收所产生的荧光,分析所接收的荧光来检测毛细管中样品中目标待检物质的种类或含量。目前常用的检测手段,是采用一个激光器激发一根毛细管中检测样品上的荧光染料所产生的荧光进行检测,每次只能检测一种目标待检物质。若检测样品中有大量种类的目标待检物质需要检测时,只能分为多次进行检测,检测速度慢,检测样品耗费大。In the prior art, a capillary electrophoresis technique is combined with a fluorescent labeling analysis technique to detect a substance contained in a sample. A fluorescent dye is labeled on a biological substance. During the movement of the biological substance in the capillary, the fluorescent dye is excited by the light source to generate fluorescence, the detector receives the generated fluorescence, and the received fluorescence is analyzed to detect the type of the target substance to be tested in the sample in the capillary. Or content. At present, the commonly used detection method is to use a laser to excite the fluorescence generated by a fluorescent dye on a sample in a capillary tube for detection, and only one target substance to be tested can be detected at a time. If there are a large number of target substances to be tested in the test sample that need to be detected, the test can only be divided into multiple times, the detection speed is slow, and the test sample is expensive.
发明内容Summary of the invention
本发明解决的技术问题在于提供一种毛细管电泳检测系统及检测方法,从而能够一次性检测同一检测样品中大量种类的生物物质,检测速度快,检测样品消耗少。The technical problem to be solved by the present invention is to provide a capillary electrophoresis detection system and a detection method, which can detect a large amount of biological substances in the same detection sample at one time, and the detection speed is fast, and the detection sample consumption is small.
为此,本发明解决技术问题的技术方案是: To this end, the technical solution of the present invention to solve the technical problem is:
一种毛细管电泳检测系统,所述系统包括:A capillary electrophoresis detection system, the system comprising:
至少两个激光器,每个激光输出的波长不同;一根毛细管,所述毛细管中的检测样品包括多种目标待检物质,所述目标待检物质包括标记了荧光染料的生物物质或者结合有标记了荧光染料的抗体的生物物质;多个探测器;At least two lasers each having a different wavelength of the output; a capillary tube, the detection sample in the capillary tube comprising a plurality of target substances to be tested, the target substance to be tested comprising a biological substance labeled with a fluorescent dye or a labeled substance a biological substance of an antibody to a fluorescent dye; a plurality of detectors;
所述至少两个激光器输出的激光照射在所述毛细管上,所述毛细管中的检测样品中荧光染料受到激光的激发产生多个波长范围的荧光,所述多个探测器接收多个波长范围的荧光,进而检测所述毛细管中的检测样品中包括的多种目标待检物质的种类或含量。The laser light output by the at least two lasers is irradiated on the capillary, and the fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence of a plurality of wavelength ranges, and the plurality of detectors receive a plurality of wavelength ranges Fluorescence, which in turn detects the type or content of a plurality of target substances to be tested included in the test sample in the capillary.
可选的,每个探测器包括:Optionally, each detector includes:
一个滤光片,以及一个光电探测器;a filter, and a photodetector;
每个滤光片透过一个波长范围的荧光,每个光电探测器接收该光电探测器前方设置的滤光片透过的荧光。Each filter transmits fluorescence in a range of wavelengths, and each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
可选的,所述系统还包括:Optionally, the system further includes:
控制器,以及与所述控制器相连的扫描头,多个分光镜;a controller, and a scan head connected to the controller, a plurality of beamsplitters;
每个分光镜对应于一个激光器,每个激光器配备有一个探测器,分光镜的个数,激光器的个数与探测器的个数都相同;Each beam splitter corresponds to one laser, each laser is equipped with one detector, the number of beamsplitters, the number of lasers and the number of detectors are the same;
所述扫描头扫描过所述毛细管时,每个激光器输出的激光通过所述扫描头中的第一光纤透射过该激光器对应的分光镜依次照射在所述毛细管上,所述毛细管中的荧光染料被激发的荧光经由该激光器对应的分光镜反射至所述扫描头中的第二光纤传输至给该激光器配备的探测器;When the scanning head scans the capillary, the laser light output by each laser is sequentially irradiated on the capillary through a first optical fiber in the scanning head and a corresponding spectroscope of the laser, and the fluorescent dye in the capillary The excited fluorescence is transmitted to a second optical fiber reflected in the scanning head via a corresponding beam splitter of the laser to a detector provided to the laser;
每个激光器输出的激光照射在所述毛细管上激发出至少一个波长范围的荧光,每个激光器激发的荧光被该激光器配备的探测器所接收。The laser illumination from each laser output excites fluorescence at least one wavelength range on the capillary, and the fluorescence excited by each laser is received by a detector equipped with the laser.
可选的,Optional,
所述至少两个激光器安装在所述扫描头内。The at least two lasers are mounted within the scan head.
可选的,所述探测器包括:Optionally, the detector comprises:
反射镜,多个滤光片,以及多个光电探测器,所述滤光片的个数与光电探测器的个数相同,每个光电探测器安装在一个滤光片后面; a mirror, a plurality of filters, and a plurality of photodetectors, the number of the filters being the same as the number of photodetectors, each photodetector being mounted behind a filter;
所述反射镜将入射至所述探测器所接收的荧光反射至所述多个滤光片上;The mirror reflects fluorescence received by the detector onto the plurality of filters;
每个滤光片透过一个波长范围的荧光,将其他波长范围的荧光反射至所述反射镜;Each filter transmits fluorescence of one wavelength range, and reflects fluorescence of other wavelength ranges to the mirror;
每个光电探测器接收该光电探测器前方设置的滤光片透过的荧光。Each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
可选的,所述探测器还包括:Optionally, the detector further includes:
多个聚焦镜,聚焦镜的个数与光电探测器的个数相同;a plurality of focusing mirrors, the number of focusing mirrors being the same as the number of photodetectors;
每个聚焦镜设置在一个光电探测器前,将一个滤光片透过的荧光聚焦至一个光电探测器。Each focusing mirror is placed in front of a photodetector to focus the fluorescence transmitted by a filter to a photodetector.
可选的,其特征在于,Optionally, characterized in that
所述目标待检物质包括体液中的蛋白质分子,多肽分子,氨基酸分子,氨基酸衍生物的分子,生物碱分子,含氮类非蛋白生物分子,类固醇分子,甾醇类分子,核苷酸分子,核苷酸衍生物分子,脂类,脂肪酸衍生物,糖类,维生素,脂蛋白,载脂蛋白,糖蛋白,粘蛋白,金属蛋白,糖脂中的任意一种或多种。The target substance to be tested includes protein molecules, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterol molecules, nucleotide molecules, and nucleus in body fluids. A glycoside derivative molecule, a lipid, a fatty acid derivative, a saccharide, a vitamin, a lipoprotein, an apolipoprotein, a glycoprotein, a mucin, a metalloprotein, or a glycolipid.
可选的,Optional,
所述目标待检物质包括DNA,以及至少一种权利要求7所述的生物物质。The target substance to be tested includes DNA, and at least one of the biomass according to claim 7.
一种毛细管电泳检测方法,所述方法包括:A capillary electrophoresis detection method, the method comprising:
至少两个激光器输出的激光照射在所述毛细管上,每个激光输出的波长不同;Laser light output from at least two lasers is irradiated on the capillary, and each laser output has a different wavelength;
毛细管中的检测样品中的荧光染料受到激光的激发产生多个波长范围的荧光,所述毛细管中的检测样品包括多种目标待检物质,所述目标待检物质包括标记了荧光染料的生物物质或者结合有标记了荧光染料的抗体的生物物质;The fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence in a plurality of wavelength ranges, and the detection sample in the capillary includes a plurality of target substances to be tested, the target substance including the biological substance labeled with the fluorescent dye Or a biological substance that binds to an antibody labeled with a fluorescent dye;
多个探测器接收多个波长范围的荧光,进而检测所述毛细管中的检测样品中包括的所述多种目标待检物质的种类或含量。The plurality of detectors receive fluorescence of a plurality of wavelength ranges, thereby detecting the kind or content of the plurality of target substances to be tested included in the detection sample in the capillary.
可选的,所述多个探测器接收多个波长范围的荧光,进而检测所述毛细管中的检测样品中包括的所述多种目标待检物质的种类或含量包括:Optionally, the plurality of detectors receive fluorescence of a plurality of wavelength ranges, and further detecting the type or content of the plurality of target substances to be tested included in the detection sample in the capillary comprises:
多个探测器接收多个波长范围的荧光,进而同时检测所述毛细管中的检测 样品中所包括的DNA,以及至少一种权利要求7所述的生物物质的种类或含量。Multiple detectors receive fluorescence in multiple wavelength ranges to simultaneously detect detection in the capillary The DNA included in the sample, and at least one species or content of the biomass according to claim 7.
通过上述技术方案可知,本发明有如下有益效果:According to the above technical solution, the present invention has the following beneficial effects:
本发明提供了一种毛细管电泳检测系统及检测方法,至少两个激光器,一根毛细管,所述毛细管中的检测样品包括多种目标待检物质,所述目标待检物质包括标记了荧光染料的生物物质或者结合有标记了荧光染料的抗体的生物物质;多个探测器;所述至少两个激光器输出的激光照射在所述毛细管上,所述毛细管中的检测样品中的荧光染料受到激光的激发产生多个波长范围的荧光,所述多个探测器接收多个波长范围的荧光,进而检测所述毛细管中的检测样品所含的物质的种类或含量。采用至少两个激光器照射毛细管,每个激光器输出的激光波长不同,能够激发的荧光的波长范围的个数比一个激光器能够激发的荧光的波长范围的个数多,一个波长范围的荧光代表一种目标待检物质,采用至少两个激光器比一个激光能够检测的目标待检物质的种类多,提高检测速度,节省检测样品。The invention provides a capillary electrophoresis detection system and a detection method, at least two lasers, a capillary tube, the detection sample in the capillary tube comprises a plurality of target substances to be tested, and the target substance to be tested comprises a fluorescent dye-labeled substance. a biological substance or a biological substance to which an antibody labeled with a fluorescent dye is bound; a plurality of detectors; laser light output from the at least two lasers is irradiated on the capillary, and a fluorescent dye in the detection sample in the capillary is subjected to laser light The excitation generates fluorescence of a plurality of wavelength ranges, and the plurality of detectors receive fluorescence of a plurality of wavelength ranges, thereby detecting the kind or content of the substance contained in the detection sample in the capillary. At least two lasers are used to illuminate the capillary. Each laser outputs a different wavelength of laser light. The number of wavelengths of fluorescence that can be excited is greater than the wavelength range of fluorescence that a laser can excite. One wavelength range of fluorescence represents a kind of fluorescence. The target substance to be tested uses at least two lasers to detect more kinds of target substances to be detected than one laser, thereby improving the detection speed and saving the test sample.
附图说明DRAWINGS
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简单地介绍,显而易见地,下面描述中的附图仅仅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。In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments or the description of the prior art will be briefly described below. Obviously, the drawings in the following description are only It is a certain embodiment of the present invention, and other drawings can be obtained from those skilled in the art without any creative work.
图1为本发明实施例提供的一种毛细管电泳检测系统结构示意图;1 is a schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention;
图2为本发明实施例提供的毛细管电泳检测系统一种可能的结构示意图;2 is a schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention;
图3为本发明实施例提供的毛细管电泳检测系统另一种可能的结构示意图;3 is another schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention;
图4为本发明实施例提供的一种探测器结构示意图;4 is a schematic structural diagram of a detector according to an embodiment of the present invention;
图5为本发明实施例提供的另一种探测器结构示意图;FIG. 5 is a schematic structural diagram of another detector according to an embodiment of the present invention; FIG.
图6为本发明实施例提供的毛细管电泳检测方法流程图。FIG. 6 is a flowchart of a capillary electrophoresis detection method according to an embodiment of the present invention.
具体实施方式 detailed description
为了给出同时检测多种标记了荧光染料的生物物质的实现方案,本发明实施例提供了一种毛细管电泳检测系统及方法,以下结合说明书附图对本发明的优选实施例进行说明。In order to provide an implementation scheme for simultaneously detecting a plurality of biological substances labeled with a fluorescent dye, an embodiment of the present invention provides a capillary electrophoresis detection system and method, and a preferred embodiment of the present invention will be described below with reference to the accompanying drawings.
现有技术中采用一个激光器激发一个毛细管中检测样品所产生的荧光进行检测,一个激光器能够激发的荧光的波长范围的个数有限,一个波长范围的荧光代表一种目标待检物质,即一个激光器能够检测的检测样品中目标待检物质的种类有限,一次只能检测四、五种生物物质。一般情况下,每次检测都需要检测大量种类的生物物质,需要采用多次检测才能完成。不仅检测所需的时间很长,每次检测都需要一份检测样品,所需的检测样品量大,尤其是检测样品大都是血液,会给患者带来一定的伤害。In the prior art, a laser is used to excite the fluorescence generated by a sample in a capillary tube for detection. A laser can excite a limited range of wavelengths of fluorescence, and a wavelength range of fluorescence represents a target substance to be tested, that is, a laser. The type of target substance to be tested in the test sample that can be detected is limited, and only four or five kinds of biological substances can be detected at a time. In general, each test requires the detection of a large variety of biological substances, which requires multiple tests to complete. Not only does the time required for the test be very long, but a test sample is required for each test. The amount of test sample required is large, especially if the test sample is mostly blood, which will cause certain damage to the patient.
本发明提供了一种可以从一份检测样品中同时检测大量种类的物质的系统和方法。The present invention provides a system and method for simultaneously detecting a large variety of substances from a single test sample.
图1为本发明实施例提供的一种毛细管电泳检测系统结构示意图,包括:FIG. 1 is a schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention, including:
至少两个激光器101,每个激光输出的波长不同;一根毛细管102,所述毛细管102中的检测样品包括多种目标待检物质,所述目标待检物质包括标记了荧光染料的生物物质或者结合有标记了荧光染料的抗体的生物物质;多个探测器103;At least two lasers 101, each having a different wavelength of laser output; a capillary 102, the detection sample in the capillary 102 comprising a plurality of target substances to be tested, the target substance to be detected comprising a biological substance labeled with a fluorescent dye or a biological substance combined with an antibody labeled with a fluorescent dye; a plurality of detectors 103;
至少两个激光器101输出的激光照射在毛细管102上,毛细管102中的检测样品中的荧光染料受到激光的激发产生多种波长范围的荧光,多个探测器103接收多种波长范围的荧光检测所述毛细管中的检测样品所含物质的种类或含量。荧光染料可以是直接标记在目标待检物质上的荧光染料,还可以是标记在与目标待检物质结合的抗体上的荧光染料。The laser light output from the at least two lasers 101 is irradiated on the capillary 102, and the fluorescent dye in the detection sample in the capillary 102 is excited by the laser to generate fluorescence in a plurality of wavelength ranges, and the plurality of detectors 103 receive fluorescence detection in various wavelength ranges. The type or content of the substance contained in the test sample in the capillary. The fluorescent dye may be a fluorescent dye directly labeled on the target substance to be tested, or may be a fluorescent dye labeled on the antibody bound to the target substance to be tested.
每个激光器输出的激光经由反射镜反射或者光纤的传输照射到毛细管102上,透射过毛细管102,激发毛细管102中检测样品中的荧光染料发出荧光。每个激光器输出的激光波长不同,能够激发出的荧光的波长范围也不同。不同波长范围的荧光代表毛细管中检测样品中不同种类的目标待检物质。激发所得的荧光波长范围的个数越多,所能检测的物质种类也越多。The laser light output by each laser is irradiated onto the capillary 102 via mirror reflection or transmission of the optical fiber, transmitted through the capillary 102, and the fluorescent dye in the detection sample in the excitation capillary 102 fluoresces. Each laser outputs a different wavelength of laser light, and the range of wavelengths of fluorescence that can be excited is also different. Fluorescence in different wavelength ranges represents different types of target analytes in the sample detected in the capillary. The more the number of fluorescent wavelength ranges obtained by excitation, the more species that can be detected.
一种波长的激光器能够激发的荧光的波长范围的个数有限,采用不同波长 的至少两个激光器能够激发的荧光的波长范围的个数比一个激光器能够激发的荧光的波长范围的个数多,不同的波长范围的荧光代表不同的生物物质种类,进而能够检测的生物物质种类也多。A wavelength laser can excite a limited range of wavelengths of fluorescence, using different wavelengths At least two lasers are capable of exciting a range of wavelengths of fluorescence that is greater than the range of wavelengths of fluorescence that a laser can excite. Fluorescence of different wavelength ranges represents different types of biological species, and thus the types of biological species that can be detected There are also many.
毛细管102所采用的毛细管内径为5微米至100微米,外径为50微米至300微米,长度为3厘米至80厘米。 Capillary 102 employs a capillary having an inner diameter of from 5 micrometers to 100 micrometers, an outer diameter of from 50 micrometers to 300 micrometers, and a length of from 3 centimeters to 80 centimeters.
毛细管电泳检测系统检测物质至少包括两种可能的结构,第一种可能的结构,如图2所示,每个探测器包括:The capillary electrophoresis detection system detects at least two possible structures. The first possible structure, as shown in Figure 2, includes:
一个滤光片,以及一个光电探测器;a filter, and a photodetector;
每个滤光片透过一个波长范围的荧光,每个光电探测器接收该光电探测器前方设置的滤光片透过的荧光。Each filter transmits fluorescence in a range of wavelengths, and each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
在第一种可能的结构中,多个探测器中,每个探测器包括一个滤光片,以及一个光电探测器。一个滤光片只能透过一个波长范围的荧光,将其他波长范围的荧光反射出去,而每个滤光片后面所设置的光电探测器,用于接收该滤光片所透过的荧光。In a first possible configuration, each of the plurality of detectors includes a filter and a photodetector. A filter can only reflect fluorescence in a range of wavelengths, reflecting fluorescence in other wavelength ranges, and a photodetector disposed behind each filter is used to receive the fluorescence transmitted by the filter.
以图2为例,滤光片m1和光电探测器n1为一个探测器,滤光片m1设置在光电探测器n1前,光电探测器n1接收滤光片m1透过的荧光;滤光片m2和光电探测器n2为一个探测器,滤光片m2设置在光电探测器n2前,光电探测器n2接收滤光片m2透过的荧光;滤光片m3和光电探测器n3为一个探测器,滤光片m3设置在光电探测器n3前,光电探测器n3接收滤光片m3透过的荧光,以此类推,滤光片mi和光电探测器ni为一个探测器,滤光片mi设置在光电探测器ni前,光电探测器ni接收滤光片mi透过的荧光。其中,i为至少两个激光器激发毛细管中的检测样品中的荧光染料所产生的荧光的波长范围的个数。Taking FIG. 2 as an example, the filter m1 and the photodetector n1 are one detector, the filter m1 is disposed in front of the photodetector n1, and the photodetector n1 receives the fluorescence transmitted by the filter m1; the filter m2 And the photodetector n2 is a detector, the filter m2 is disposed in front of the photodetector n2, the photodetector n2 receives the fluorescence transmitted by the filter m2; the filter m3 and the photodetector n3 are a detector, The filter m3 is disposed before the photodetector n3, the photodetector n3 receives the fluorescence transmitted by the filter m3, and so on, the filter mi and the photodetector ni are one detector, and the filter mi is disposed at Before the photodetector ni, the photodetector ni receives the fluorescence transmitted by the filter mi. Where i is the number of wavelength ranges of fluorescence produced by the fluorescent dye in the test sample in at least two laser excitation capillaries.
第二种可能的结构,如图3所示,所述系统还包括:A second possible structure, as shown in FIG. 3, the system further includes:
控制器301,以及与所述控制器相连的扫描头302,多个分光镜。The controller 301 has a scan head 302 connected to the controller, and a plurality of beamsplitters.
每个分光镜对应于一个激光器,每个激光器配备有一个探测器,分光镜的个数,激光器的个数与探测器的个数都相同。Each beam splitter corresponds to one laser, each laser is equipped with a detector, the number of beamsplitters, the number of lasers and the number of detectors are the same.
所述扫描头302扫描过所述毛细管102时,每个激光器输出的激光通过所 述扫描头302中的第一光纤透射过该激光器对应的分光镜依次照射在所述毛细管102上,所述毛细管102中检测样品中的荧光染料被激发的荧光经由该激光器对应的分光镜反射至所述扫描头302中的第二光纤传输至给该激光器配备的探测器;When the scanning head 302 scans the capillary 102, the laser output from each laser passes through The first optical fiber in the scanning head 302 is sequentially irradiated on the capillary 102 through a spectroscope corresponding to the laser, and the fluorescent light excited by the fluorescent dye in the detecting sample 102 is reflected by the corresponding spectroscope of the laser to The second optical fiber in the scan head 302 is transmitted to a detector provided to the laser;
每个激光器输出的激光照射在所述毛细管上激发出至少一个波长范围的荧光,每个激光器激发的荧光被该激光器配备的探测器所接收。The laser illumination from each laser output excites fluorescence at least one wavelength range on the capillary, and the fluorescence excited by each laser is received by a detector equipped with the laser.
扫描头302中包括多个分光镜,多个第一光纤,以及多个第二光纤。每个激光器对应于一个分光镜,一个第一光纤,一个第二光纤。每个激光器输出的激光由该激光器对应的第一光纤传输,透过该激光器对应的分光镜照射在毛细管102上,毛细管102中检测样品中的荧光染料被激发的荧光,经由该激光器对应的分光镜反射至该激光器对应的第二光纤,第二光纤将接受到的荧光传输至给该激光器配备的探测器。The scanning head 302 includes a plurality of beam splitters, a plurality of first fibers, and a plurality of second fibers. Each laser corresponds to a beam splitter, a first fiber, and a second fiber. The laser output from each laser is transmitted by the corresponding first optical fiber of the laser, and is irradiated onto the capillary 102 through a spectroscope corresponding to the laser. The capillary 102 detects the fluorescence excited by the fluorescent dye in the sample, and the corresponding spectroscopic light is passed through the laser. The mirror is reflected to a second fiber corresponding to the laser, and the second fiber transmits the received fluorescence to a detector provided to the laser.
这里需要说明的是,第一光纤中的“第一”,第二光纤中的“第二”,表示的不是顺序,而是一类,第一光纤不是一个光纤,而是一类光纤,第二光纤也不是一个光纤,而是一类光纤,扫描头302中有多个第一光纤,多个第二光纤,第一光纤的个数,第二光纤的个数与激光器的个数相同,每个激光器都对应一个第一光纤和第二光纤。It should be noted that the “first” in the first optical fiber and the “second” in the second optical fiber represent not the order but a type, and the first optical fiber is not an optical fiber but a type of optical fiber. The second fiber is not a fiber, but a type of fiber. The scanning head 302 has a plurality of first fibers, a plurality of second fibers, and the number of the first fibers. The number of the second fibers is the same as the number of the lasers. Each laser corresponds to a first fiber and a second fiber.
举例说明,如图3所示,激光器a1输出的激光由扫描头中第一光纤x1传输,透射过分光镜y1照射在毛细管102中,毛细管102的检测样品中荧光染料被激发出的荧光由分光镜y1反射至扫描头中第二光纤z1,由第二光纤z1将荧光传输至给激光器a1配备的探测器b1;激光器a2输出的激光由扫描头中第一光纤x2传输,透射过分光镜y2照射在毛细管102中,毛细管102的检测样品中荧光染料被激发出的荧光由分光镜y2反射至扫描头中第二光纤z2,由第二光纤z2将荧光传输至给激光器a2配备的探测器b2;激光器a3输出的激光由扫描头中第一光纤x3传输,透射过分光镜y3照射在毛细管102中,毛细管102的检测样品中荧光染料被激发出的荧光由分光镜y3反射至扫描头中第二光纤z3,由第二光纤z3将荧光传输至给激光器a3配备的探测器b3;激光器a4输出的激光由扫描头中第一光纤x4传输,透射过分光镜y4照射在毛细管102中,毛细管102的检测样品中荧光染料被激发出的荧光由分光镜y4 反射至扫描头中第二光纤z4,由第二光纤z4将荧光传输至给激光器a4配备的探测器b4。For example, as shown in FIG. 3, the laser light output by the laser a1 is transmitted by the first optical fiber x1 in the scanning head, and transmitted through the beam splitter y1 to be irradiated in the capillary 102. The fluorescence of the fluorescent dye excited by the detection sample of the capillary 102 is split. The mirror y1 is reflected to the second optical fiber z1 in the scan head, and the second optical fiber z1 transmits the fluorescence to the detector b1 provided to the laser a1; the laser output from the laser a2 is transmitted by the first optical fiber x2 in the scanning head, and transmitted through the beam splitter y2 Irradiated in the capillary 102, the fluorescence of the fluorescent dye excited in the detection sample of the capillary 102 is reflected by the beam splitter y2 to the second optical fiber z2 in the scanning head, and the second optical fiber z2 transmits the fluorescence to the detector b2 provided to the laser a2. The laser outputted by the laser a3 is transmitted by the first optical fiber x3 in the scanning head, and transmitted through the beam splitter y3 to be irradiated in the capillary 102. The fluorescent light excited by the fluorescent dye in the detection sample of the capillary 102 is reflected by the spectroscope y3 to the scanning head. The second fiber z3 transmits the fluorescence from the second fiber z3 to the detector b3 provided to the laser a3; the laser output from the laser a4 is transmitted by the first fiber x4 in the scanning head, transmitted through Y4 irradiating light microscope in the capillary 102, the capillary test sample a fluorescent dye 102 is excited by a fluorescence spectroscope y4 Reflected to the second fiber z4 in the scan head, the second fiber z4 transmits the fluorescence to the detector b4 provided to the laser a4.
在实际应用中,激光器和探测器的个数可以根据实际需要具体设置,并不仅限于图3所示的四个激光器和四个探测器,激光器和探测器的个数相同即可。In practical applications, the number of lasers and detectors can be specifically set according to actual needs, and is not limited to the four lasers and four detectors shown in FIG. 3, and the number of lasers and detectors can be the same.
在一个例子中,至少两个激光器安装在扫描头302中。当然,至少两个激光器还可以安装在扫描头302外。多个探测器可以安装在扫描头302外,还可以安装在扫描头302内。技术人员可以按照实际需要具体设置。In one example, at least two lasers are mounted in scan head 302. Of course, at least two lasers can also be mounted outside of the scanning head 302. A plurality of detectors can be mounted outside of the scanning head 302 and can also be mounted within the scanning head 302. The technician can set it according to the actual needs.
控制器301控制扫描头302扫描过所述毛细管102,以使得每个激光器输出的激光逐一照射在毛细管102上,接收毛细管102中的检测样品中荧光染料被激发所产生的荧光。扫描头302扫描的方向如图3所示。这里需要说明的是,扫描头302扫描的方向也可以与图3所示的扫描方向相反,技术人员根据实际需要自行设定即可。The controller 301 controls the scanning head 302 to scan the capillary 102 such that the laser light output by each laser is irradiated onto the capillary 102 one by one, and the fluorescence generated by the excitation of the fluorescent dye in the detection sample in the capillary 102 is received. The direction in which the scanning head 302 scans is as shown in FIG. It should be noted that the scanning direction of the scanning head 302 can also be opposite to the scanning direction shown in FIG. 3, and the technician can set it according to actual needs.
第二种可能的实现方式中,在一个例子中,如图4所示,所述探测器包括:In a second possible implementation, in one example, as shown in FIG. 4, the detector includes:
反射镜,多个滤光片,以及多个光电探测器,所述滤光片的个数与光电探测器的个数相同,每个光电探测器安装在一个滤光片后面;a mirror, a plurality of filters, and a plurality of photodetectors, the number of the filters being the same as the number of photodetectors, each photodetector being mounted behind a filter;
所述反射镜将入射至所述探测器所接收的荧光反射至所述多个滤光片上;The mirror reflects fluorescence received by the detector onto the plurality of filters;
每个滤光片透过一个波长范围的荧光,将其他波长范围的荧光反射至所述反射镜;Each filter transmits fluorescence of one wavelength range, and reflects fluorescence of other wavelength ranges to the mirror;
每个光电探测器接收该光电探测器前方设置的滤光片透过的荧光。Each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
在毛细管电泳检测系统中,有多个探测器,每个探测器都包括反射镜,多个滤光片,以及多个光电探测器。一个激光器能激发几个波长范围的荧光,给该激光器配备的探测器接收所激发的几个波长范围的荧光。探测器中包括反射镜,反射镜将探测器所接收的荧光反射至滤光片。每个滤光片透过一种波长范围的荧光,将其他波长范围的荧光反射回反射镜。在每个滤光片后面设置有一个光电探测器,该光电探测器只接收滤光片所透过的一种波长范围的荧光。进而实现探测器接收一个激光器所激发的所有波长范围的荧光。并且,为了减少光能的损失,每个滤光片与反射镜紧贴放置。 In a capillary electrophoresis detection system, there are multiple detectors, each of which includes a mirror, a plurality of filters, and a plurality of photodetectors. A laser can excite fluorescence in several wavelength ranges, and the detector equipped with the laser receives fluorescence in several wavelength ranges that are excited. The detector includes a mirror that reflects the fluorescence received by the detector to the filter. Each filter transmits fluorescence in one wavelength range and reflects fluorescence in other wavelength ranges back to the mirror. A photodetector is disposed behind each filter, and the photodetector receives only fluorescence of a wavelength range transmitted by the filter. In turn, the detector receives fluorescence in all wavelength ranges excited by a laser. Also, in order to reduce the loss of light energy, each filter is placed in close contact with the mirror.
以图4为例,所述探测器包括一个反射镜401,四个滤光片p1~p4,四个光电探测器q1~q4。滤光片的个数与光电探测器的个数相同。Taking FIG. 4 as an example, the detector includes a mirror 401, four filters p1 to p4, and four photodetectors q1 to q4. The number of filters is the same as the number of photodetectors.
反射镜401较大,可以覆盖所有的滤光片p1~p4,每个滤光片p1~p4与该反射镜501紧贴放置。所接收的荧光被反射镜401反射至每个滤光片p1~p4。滤光片p1透过的荧光被光电探测器q1所接收,滤光片p2透过的荧光被光电探测器q2所接收,滤光片p3透过的荧光被光电探测器q3所接收,滤光片p4透过的荧光被光电探测器q4所接收。The mirror 401 is large and covers all of the filters p1 to p4, and each of the filters p1 to p4 is placed in close contact with the mirror 501. The received fluorescence is reflected by the mirror 401 to each of the filters p1 to p4. The fluorescence transmitted by the filter p1 is received by the photodetector q1, the fluorescence transmitted by the filter p2 is received by the photodetector q2, and the fluorescence transmitted by the filter p3 is received by the photodetector q3, and the filter is filtered. The fluorescence transmitted by the sheet p4 is received by the photodetector q4.
在实际应用中,每个探测器中设置的滤光片和光电探测器的个数,不会少于一个激光器能够激发的荧光的波长范围的个数。一般情况下,一个激光器能够激发四五个波长范围的荧光,一个探测器中设置四五个滤光片和四五个光电探测器即可。In practical applications, the number of filters and photodetectors provided in each detector is not less than the number of wavelengths of fluorescence that a laser can excite. In general, a laser can excite fluorescence in four or five wavelength ranges, and four or five filters and four or five photodetectors can be placed in one detector.
光电探测器包括电荷耦合元件(Charge-coupled Device,CCD)图像传感器,雪崩光电二极管(Avalanche Photo Diode,APD),互补金属氧化物半导体(Complementary Metal Oxide Semiconductor,CMOS)图像传感器,以及光电倍增管(Photo Multiplier Tube,PMT)中任意一种。The photodetector includes a charge-coupled device (CCD) image sensor, an Avalanche Photo Diode (APD), a Complementary Metal Oxide Semiconductor (CMOS) image sensor, and a photomultiplier tube ( Photo Multiplier Tube, PMT).
第二种可能的实现方式中,在一个例子中,如图5所示,所述探测器还包括:In a second possible implementation manner, in an example, as shown in FIG. 5, the detector further includes:
多个聚焦镜,聚焦镜的个数与光电探测器的个数相同;a plurality of focusing mirrors, the number of focusing mirrors being the same as the number of photodetectors;
每个聚焦镜设置在一个光电探测器前,将一个滤光片透过的荧光聚焦至一个光电探测器。Each focusing mirror is placed in front of a photodetector to focus the fluorescence transmitted by a filter to a photodetector.
在每个光电探测器前面添加一个聚焦镜,该聚焦镜将一个滤光片透过的荧光聚焦至光电探测器。如图5所示,聚焦镜L1将滤光片p1透过的荧光聚焦至光电探测器q1;聚焦镜L2将滤光片p2透过的荧光聚焦至光电探测器q2;聚焦镜L3将滤光片p3透过的荧光聚焦至光电探测器q3;聚焦镜L4将滤光片p4透过的荧光聚焦至光电探测器q4。A focusing mirror is added in front of each photodetector that focuses the fluorescence transmitted by one filter to the photodetector. As shown in FIG. 5, the focusing mirror L1 focuses the fluorescence transmitted by the filter p1 to the photodetector q1; the focusing mirror L2 focuses the fluorescence transmitted by the filter p2 to the photodetector q2; the focusing mirror L3 filters the light. The fluorescence transmitted by the sheet p3 is focused to the photodetector q3; the focusing mirror L4 focuses the fluorescence transmitted by the filter p4 to the photodetector q4.
在一个例子中,所述目标待检物质包括体液中的蛋白质分子,多肽分子,氨基酸分子,氨基酸衍生物的分子,生物碱分子,含氮类非蛋白生物分子,类固醇分子,甾醇类分子,核苷酸分子,核苷酸衍生物分子,脂类,脂肪酸衍生 物,糖类,维生素,脂蛋白,载脂蛋白,糖蛋白,粘蛋白,金属蛋白,糖脂中的任意一种或多种。In one example, the target substance to be tested includes protein molecules, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterol molecules, and nucleus in body fluids. Glycosylate molecule, nucleotide derivative molecule, lipid, fatty acid derivative Any one or more of substances, sugars, vitamins, lipoproteins, apolipoproteins, glycoproteins, mucins, metalloproteins, glycolipids.
在另一个例子中,所述目标待检物质包括DNA,以及体液中的蛋白质分子,多肽分子,氨基酸分子,氨基酸衍生物的分子,生物碱分子,含氮类非蛋白生物分子,类固醇分子,甾醇类分子,核苷酸分子,核苷酸衍生物分子,脂类,脂肪酸衍生物,糖类,维生素,脂蛋白,载脂蛋白,糖蛋白,粘蛋白,金属蛋白,糖脂中的任意一种或多种。In another example, the target substance to be tested includes DNA, protein molecules in a body fluid, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterols Any of a class of molecules, nucleotide molecules, nucleotide derivative molecules, lipids, fatty acid derivatives, sugars, vitamins, lipoproteins, apolipoproteins, glycoproteins, mucins, metalloproteins, glycolipids Or a variety.
本发明提供的毛细管电泳检测系统,第一次实现了在同一检测样品中,同时检测DNA以及非DNA生物物质,将基因检测和临床生化检测,免疫学检测相统一,在临床诊断上有重大突破。The capillary electrophoresis detection system provided by the invention realizes the simultaneous detection of DNA and non-DNA biological substances in the same test sample, and unifies genetic detection, clinical biochemical detection and immunological detection, and has a major breakthrough in clinical diagnosis. .
由上述内容可知,本发明有如下有益效果:As can be seen from the above, the present invention has the following beneficial effects:
采用至少两个激光器照射毛细管,每个激光器输出的激光波长不同,能够激发的荧光的波长范围的个数比一个激光器能够激发的荧光的波长范围的个数多,一个波长范围的荧光代表一种目标待检物质,采用至少两个激光器比一个激光能够检测的生物物质的种类多,提高检测速度,节省检测样品。At least two lasers are used to illuminate the capillary. Each laser outputs a different wavelength of laser light. The number of wavelengths of fluorescence that can be excited is greater than the wavelength range of fluorescence that a laser can excite. One wavelength range of fluorescence represents a kind of fluorescence. The target substance to be tested uses at least two kinds of lasers to detect more kinds of biological substances than one laser, which improves the detection speed and saves the test sample.
图6为本发明实施例提供的毛细管电泳检测方法流程图,包括:FIG. 6 is a flowchart of a capillary electrophoresis detection method according to an embodiment of the present invention, including:
601:至少两个激光器输出的激光照射在所述毛细管上,每个激光输出的波长不同。601: Laser light output from at least two lasers is irradiated on the capillary, and each laser output has a different wavelength.
602:毛细管中的检测样品中的荧光染料受到激光的激发产生多个波长范围的荧光,所述毛细管中的检测样品包括多种目标待检物质,所述目标待检物质包括标记了荧光染料的生物物质或者结合有标记了荧光染料的抗体的生物物质。602: The fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence of a plurality of wavelength ranges, the detection sample in the capillary includes a plurality of target substances to be tested, and the target substance to be tested includes a fluorescent dye-labeled substance. Biological material or biological substance that binds to an antibody labeled with a fluorescent dye.
603:多个探测器接收多种波长范围的荧光,进而检测所述毛细管中的检测样品中包括的所述多种目标待检物质的种类或含量。603: The plurality of detectors receive fluorescence of a plurality of wavelength ranges, thereby detecting the kind or content of the plurality of target substances to be tested included in the detection sample in the capillary.
在一个例子中,多个探测器接收多个波长范围的荧光,进而检测所述毛细管中的检测样品中的蛋白质分子,多肽分子,氨基酸分子,氨基酸衍生物的分子,生物碱分子,含氮类非蛋白生物分子,类固醇分子,甾醇类分子,核苷酸分子,核苷酸衍生物分子,脂类,脂肪酸衍生物,糖类,维生素,脂蛋白,载 脂蛋白,糖蛋白,粘蛋白,金属蛋白,糖脂中的任意一种或多种。In one example, a plurality of detectors receive fluorescence in a plurality of wavelength ranges, thereby detecting protein molecules, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing molecules in the test sample in the capillary. Non-protein biomolecules, steroid molecules, sterol molecules, nucleotide molecules, nucleotide derivative molecules, lipids, fatty acid derivatives, sugars, vitamins, lipoproteins, Any one or more of lipoprotein, glycoprotein, mucin, metalloprotein, glycolipid.
在一个例子中,多个探测器接收多种波长范围的荧光,同时检测所述毛细管中的检测样品中标记了荧光染料的DNA,以及蛋白质分子,多肽分子,氨基酸分子,氨基酸衍生物的分子,生物碱分子,含氮类非蛋白生物分子,类固醇分子,甾醇类分子,核苷酸分子,核苷酸衍生物分子,脂类,脂肪酸衍生物,糖类,维生素,脂蛋白,载脂蛋白,糖蛋白,粘蛋白,金属蛋白,糖脂中的任意一种或多种。In one example, a plurality of detectors receive fluorescence in a plurality of wavelength ranges, and simultaneously detect DNA labeled with a fluorescent dye in the detection sample in the capillary, and molecules of a protein molecule, a polypeptide molecule, an amino acid molecule, and an amino acid derivative, Alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterol molecules, nucleotide molecules, nucleotide derivative molecules, lipids, fatty acid derivatives, sugars, vitamins, lipoproteins, apolipoproteins, Any one or more of glycoprotein, mucin, metalloprotein, and glycolipid.
探测器接收多个波长范围的荧光,能够检测到所接收的荧光的波长范围。再跟预先设定的检测标准比对,即可获知检测样品中包含哪种类型的生物物质以及该物质的含量。The detector receives fluorescence in multiple wavelength ranges and is capable of detecting the wavelength range of the received fluorescence. By comparing with the preset test standards, it is possible to know which type of biological substance is contained in the test sample and the content of the substance.
图6所示的毛细管电泳检测方法是与图1至图5所示的毛细管电泳检测系统所对应的方法,具体实现方式参考图1至图5所示的系统中的描述,这里不再赘述。The capillary electrophoresis detection method shown in FIG. 6 is a method corresponding to the capillary electrophoresis detection system shown in FIG. 1 to FIG. 5. The specific implementation manner is described in the system shown in FIG. 1 to FIG. 5, and details are not described herein again.
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。 The above description is only a preferred embodiment of the present invention, and it should be noted that those skilled in the art can also make several improvements and retouchings without departing from the principles of the present invention. It should be considered as the scope of protection of the present invention.

Claims (9)

  1. 一种毛细管电泳检测系统,其特征在于,所述系统包括:A capillary electrophoresis detection system, characterized in that the system comprises:
    至少两个激光器,每个激光输出的波长不同;一根毛细管,所述毛细管中的检测样品包括多种目标待检物质,所述目标待检物质包括标记了荧光染料的生物物质或者结合有标记了荧光染料的抗体的生物物质;多个探测器;At least two lasers each having a different wavelength of the output; a capillary tube, the detection sample in the capillary tube comprising a plurality of target substances to be tested, the target substance to be tested comprising a biological substance labeled with a fluorescent dye or a labeled substance a biological substance of an antibody to a fluorescent dye; a plurality of detectors;
    所述至少两个激光器输出的激光照射在所述毛细管上,所述毛细管中的检测样品中荧光染料受到激光的激发产生多个波长范围的荧光,所述多个探测器接收多个波长范围的荧光,进而检测所述毛细管中的检测样品中包括的多种目标待检物质的种类或含量。The laser light output by the at least two lasers is irradiated on the capillary, and the fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence of a plurality of wavelength ranges, and the plurality of detectors receive a plurality of wavelength ranges Fluorescence, which in turn detects the type or content of a plurality of target substances to be tested included in the test sample in the capillary.
  2. 根据权利要求1所述的系统,其特征在于,每个探测器包括:The system of claim 1 wherein each detector comprises:
    一个滤光片,以及一个光电探测器;a filter, and a photodetector;
    每个滤光片透过一个波长范围的荧光,每个光电探测器接收该光电探测器前方设置的滤光片透过的荧光。Each filter transmits fluorescence in a range of wavelengths, and each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
  3. 根据权利要求1所述的系统,其特征在于,所述系统还包括:The system of claim 1 wherein the system further comprises:
    控制器,以及与所述控制器相连的扫描头,多个分光镜;a controller, and a scan head connected to the controller, a plurality of beamsplitters;
    每个分光镜对应于一个激光器,每个激光器配备有一个探测器,分光镜的个数,激光器的个数与探测器的个数都相同;Each beam splitter corresponds to one laser, each laser is equipped with one detector, the number of beamsplitters, the number of lasers and the number of detectors are the same;
    所述扫描头扫描过所述毛细管时,每个激光器输出的激光通过所述扫描头中的第一光纤透射过该激光器对应的分光镜依次照射在所述毛细管上,所述毛细管中的荧光染料被激发的荧光经由该激光器对应的分光镜反射至所述扫描头中的第二光纤传输至给该激光器配备的探测器;When the scanning head scans the capillary, the laser light output by each laser is sequentially irradiated on the capillary through a first optical fiber in the scanning head and a corresponding spectroscope of the laser, and the fluorescent dye in the capillary The excited fluorescence is transmitted to a second optical fiber reflected in the scanning head via a corresponding beam splitter of the laser to a detector provided to the laser;
    每个激光器输出的激光照射在所述毛细管上激发出至少一个波长范围的荧光,每个激光器激发的荧光被该激光器配备的探测器所接收。The laser illumination from each laser output excites fluorescence at least one wavelength range on the capillary, and the fluorescence excited by each laser is received by a detector equipped with the laser.
  4. 根据权利要求3所述的系统,其特征在于,The system of claim 3 wherein:
    所述至少两个激光器安装在所述扫描头内。The at least two lasers are mounted within the scan head.
  5. 根据权利要求3所述的系统,其特征在于,所述探测器包括:The system of claim 3 wherein said detector comprises:
    反射镜,多个滤光片,以及多个光电探测器,所述滤光片的个数与光电探 测器的个数相同,每个光电探测器安装在一个滤光片后面;a mirror, a plurality of filters, and a plurality of photodetectors, the number of the filters and photodetection The number of detectors is the same, and each photodetector is mounted behind a filter;
    所述反射镜将入射至所述探测器所接收的荧光反射至所述多个滤光片上;The mirror reflects fluorescence received by the detector onto the plurality of filters;
    每个滤光片透过一个波长范围的荧光,将其他波长范围的荧光反射至所述反射镜;Each filter transmits fluorescence of one wavelength range, and reflects fluorescence of other wavelength ranges to the mirror;
    每个光电探测器接收该光电探测器前方设置的滤光片透过的荧光。Each photodetector receives fluorescence transmitted by a filter disposed in front of the photodetector.
  6. 根据权利要求5所述的系统,其特征在于,所述探测器还包括:The system of claim 5 wherein said detector further comprises:
    多个聚焦镜,聚焦镜的个数与光电探测器的个数相同;a plurality of focusing mirrors, the number of focusing mirrors being the same as the number of photodetectors;
    每个聚焦镜设置在一个光电探测器前,将一个滤光片透过的荧光聚焦至一个光电探测器。Each focusing mirror is placed in front of a photodetector to focus the fluorescence transmitted by a filter to a photodetector.
  7. 根据权利要求1-6任意一项所述的系统,其特征在于,A system according to any one of claims 1-6, wherein
    所述目标待检物质包括体液中的蛋白质分子,多肽分子,氨基酸分子,氨基酸衍生物的分子,生物碱分子,含氮类非蛋白生物分子,类固醇分子,甾醇类分子,核苷酸分子,核苷酸衍生物分子,脂类,脂肪酸衍生物,糖类,维生素,脂蛋白,载脂蛋白,糖蛋白,粘蛋白,金属蛋白,糖脂中的任意一种或多种。The target substance to be tested includes protein molecules, polypeptide molecules, amino acid molecules, molecules of amino acid derivatives, alkaloid molecules, nitrogen-containing non-protein biomolecules, steroid molecules, sterol molecules, nucleotide molecules, and nucleus in body fluids. A glycoside derivative molecule, a lipid, a fatty acid derivative, a saccharide, a vitamin, a lipoprotein, an apolipoprotein, a glycoprotein, a mucin, a metalloprotein, or a glycolipid.
  8. 根据权利要求7所述的系统,其特征在于,The system of claim 7 wherein:
    所述目标待检物质包括DNA,以及至少一种权利要求7所述的生物物质。The target substance to be tested includes DNA, and at least one of the biomass according to claim 7.
  9. 一种毛细管电泳检测方法,其特征在于,所述方法包括:A capillary electrophoresis detection method, characterized in that the method comprises:
    至少两个激光器输出的激光照射在所述毛细管上,每个激光输出的波长不同;Laser light output from at least two lasers is irradiated on the capillary, and each laser output has a different wavelength;
    毛细管中的检测样品中的荧光染料受到激光的激发产生多个波长范围的荧光,所述毛细管中的检测样品包括多种目标待检物质,所述目标待检物质包括标记了荧光染料的生物物质或者结合有标记了荧光染料的抗体的生物物质;The fluorescent dye in the detection sample in the capillary is excited by the laser to generate fluorescence in a plurality of wavelength ranges, and the detection sample in the capillary includes a plurality of target substances to be tested, the target substance including the biological substance labeled with the fluorescent dye Or a biological substance that binds to an antibody labeled with a fluorescent dye;
    多个探测器接收多个波长范围的荧光,进而检测所述毛细管中的检测样品中包括的所述多种目标待检物质的种类或含量。 The plurality of detectors receive fluorescence of a plurality of wavelength ranges, thereby detecting the kind or content of the plurality of target substances to be tested included in the detection sample in the capillary.
PCT/CN2016/102707 2016-06-29 2016-10-20 Capillary electrophoresis detection system and detection method WO2018000664A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201610496480.4 2016-06-29
CN201610496480.4A CN105973860B (en) 2016-06-29 2016-06-29 Capillary electrophoresis detection system and detection method

Publications (1)

Publication Number Publication Date
WO2018000664A1 true WO2018000664A1 (en) 2018-01-04

Family

ID=57020489

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2016/102707 WO2018000664A1 (en) 2016-06-29 2016-10-20 Capillary electrophoresis detection system and detection method

Country Status (2)

Country Link
CN (1) CN105973860B (en)
WO (1) WO2018000664A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109632741A (en) * 2018-12-27 2019-04-16 苏州和迈精密仪器有限公司 A kind of detection method of composite fluorescence microballoon reagent card

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105973860B (en) * 2016-06-29 2019-07-30 山东科立森生物股份有限公司 Capillary electrophoresis detection system and detection method
CN114354729B (en) * 2022-03-18 2022-06-21 南昌大学 Capillary electrophoresis detection device

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101165472A (en) * 2006-10-20 2008-04-23 中国科学院大连化学物理研究所 Multiple-pass mode capillary tube electrophoresis device
US20110147217A1 (en) * 2009-12-17 2011-06-23 The Curators Of The University Of Missouri Method and apparatus for cancer screening
CN202196015U (en) * 2011-06-15 2012-04-18 公安部第一研究所 Capillary array electrophoresis detecting device based on spectrum correction
CN104181133A (en) * 2013-05-24 2014-12-03 南开大学 Multi-wavelength capillary electrophoresis fluorescence excitation device
WO2015134925A1 (en) * 2014-03-07 2015-09-11 Life Technologies Corporation Optical system for capillary electrophoresis
CN105973860A (en) * 2016-06-29 2016-09-28 山东科立森生物股份有限公司 Capillary electrophoresis detection system and detection method
CN105973859A (en) * 2016-06-29 2016-09-28 山东科立森生物股份有限公司 Capillary electrophoresis detection system and detection method

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3400650B2 (en) * 1996-06-28 2003-04-28 株式会社日立製作所 Electrophoretic separation detection method and apparatus
DE60220497T2 (en) * 2001-01-26 2008-01-31 Biocal Technology, Inc., Irvine OPTICAL DETECTION IN A MULTI-CHANNEL BIOSEPARATION SYSTEM
CN101748207A (en) * 2008-12-09 2010-06-23 湖北师范学院 DNA sequencing device with single wavelength
CN101718696A (en) * 2009-12-10 2010-06-02 上海交通大学 Lasing fluorescence scanning imaging-fluorescence correlation spectrum unimolecule detecting instrument
CN206002443U (en) * 2016-06-29 2017-03-08 山东科立森生物股份有限公司 Capillary electrophoresis detection system

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101165472A (en) * 2006-10-20 2008-04-23 中国科学院大连化学物理研究所 Multiple-pass mode capillary tube electrophoresis device
US20110147217A1 (en) * 2009-12-17 2011-06-23 The Curators Of The University Of Missouri Method and apparatus for cancer screening
CN202196015U (en) * 2011-06-15 2012-04-18 公安部第一研究所 Capillary array electrophoresis detecting device based on spectrum correction
CN104181133A (en) * 2013-05-24 2014-12-03 南开大学 Multi-wavelength capillary electrophoresis fluorescence excitation device
WO2015134925A1 (en) * 2014-03-07 2015-09-11 Life Technologies Corporation Optical system for capillary electrophoresis
CN105973860A (en) * 2016-06-29 2016-09-28 山东科立森生物股份有限公司 Capillary electrophoresis detection system and detection method
CN105973859A (en) * 2016-06-29 2016-09-28 山东科立森生物股份有限公司 Capillary electrophoresis detection system and detection method

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109632741A (en) * 2018-12-27 2019-04-16 苏州和迈精密仪器有限公司 A kind of detection method of composite fluorescence microballoon reagent card

Also Published As

Publication number Publication date
CN105973860A (en) 2016-09-28
CN105973860B (en) 2019-07-30

Similar Documents

Publication Publication Date Title
WO2018000663A1 (en) Capillary electrophoresis detection system and detection method
Lee et al. High-sensitivity laser-induced fluorescence detection of native proteins in capillary electrophoresis
Fang et al. A handheld laser-induced fluorescence detector for multiple applications
JP6283104B2 (en) Optical analyzer
JP3566207B2 (en) Rotary confocal scanner for capillary array detection
US20070131870A1 (en) Multiplexed CE fluorescence system
Xiao et al. CE detector based on light‐emitting diodes
WO2018000664A1 (en) Capillary electrophoresis detection system and detection method
JPH09113448A (en) Device for performing laser-induced two-photon flurescence-correlation spectrochemical analysis
US20080203319A1 (en) Multicapillary Multilaser Detection System
US8314407B2 (en) Optical illumination apparatus for illuminating a sample with a line beam
WO2005093392A1 (en) Fluorescence spectrometer
JP2004354348A (en) Spectroscopic analyzer
CN101464411A (en) Capillary array analyzer
US7277169B2 (en) Whole spectrum fluorescence detection with ultrafast white light excitation
CN115078326A (en) Stimulated Raman microscopic imaging device combined with optical tweezers
Ma et al. Simultaneous, hybrid single-molecule method by optical tweezers and fluorescence
WO2019131947A1 (en) Spectroscopic analysis device, spectroscopic analysis method, program, recording medium, and microscope
JP5685492B2 (en) Biomolecule detection apparatus and biomolecule detection method
Zhang et al. LIFGO: A modular laser-induced fluorescence detection system based on plug-in blocks
CN206002443U (en) Capillary electrophoresis detection system
JP2001311690A (en) Biochip reader and electrophoretic apparatus
US20230221178A1 (en) Apparatus and a method for fluorescence imaging
WO2009098624A1 (en) Analysis system and method
CN205879793U (en) Capillary electrophoresis detection system

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16907060

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16907060

Country of ref document: EP

Kind code of ref document: A1