WO2018000663A1 - 一种毛细管电泳检测***及检测方法 - Google Patents

一种毛细管电泳检测***及检测方法 Download PDF

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Publication number
WO2018000663A1
WO2018000663A1 PCT/CN2016/102704 CN2016102704W WO2018000663A1 WO 2018000663 A1 WO2018000663 A1 WO 2018000663A1 CN 2016102704 W CN2016102704 W CN 2016102704W WO 2018000663 A1 WO2018000663 A1 WO 2018000663A1
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capillary
laser
group
fluorescence
detector
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PCT/CN2016/102704
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English (en)
French (fr)
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万戈江
金见睿
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山东科立森生物股份有限公司
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Publication of WO2018000663A1 publication Critical patent/WO2018000663A1/zh

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    • 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
    • G01N21/01Arrangements 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
    • 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 biological substance contained in a sample. Marking a fluorescent dye on a biological substance.
  • the fluorescent dye is excited by the laser to generate fluorescence, the detector receives the generated fluorescence, analyzes the received fluorescence, and detects the target substance to be tested in the sample in the capillary. Type 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, resulting in a slow detection speed and a large consumption of the detection sample.
  • 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 plurality of detection samples by using a plurality of capillary tubes at one time, and can detect a large amount of biological substances in the same detection sample at one time, thereby improving the detection speed. Reduce the consumption of test samples.
  • a capillary electrophoresis detection system comprising:
  • a laser group comprising at least two lasers each having a different wavelength of output
  • a capillary group comprising at least two capillaries, each of the test samples in the capillaries including a target substance to be tested,
  • the target substance to be tested includes a biological substance labeled with a fluorescent dye or a biological substance bound with an antibody labeled with a fluorescent dye
  • the detector group has the same number of detectors in the detector group as the number of lasers in the laser group Each laser is equipped with a detector;
  • Each laser in the laser group sequentially illuminates each capillary in the capillary group, and the fluorescent dye in the detection sample in each capillary is excited by a laser to generate fluorescence in a plurality of wavelength ranges, and each laser sequentially illuminates each Fluorescence of a plurality of wavelength ranges excited by the capillary is sequentially received by a detector provided to the laser, and the type or content of the target substance to be tested included in the test sample in each capillary is sequentially detected.
  • system further includes:
  • a controller and a scan head connected to the controller, a plurality of beamsplitters;
  • Each laser corresponds to a beam splitter, each laser is equipped with a detector, the number of beamsplitters, the number of lasers, and the number of detectors are the same;
  • the scan head receives a control signal of the controller, scans the capillary group according to the control signal, and laser light output by each laser in the laser group is transmitted through a first optical fiber in the scan head a spectroscope corresponding to the laser is sequentially irradiated on each of the capillaries in the capillary group, and each of the capillaries detects fluorescence generated by the excitation of the fluorescent dye in the sample, and is reflected by the corresponding spectroscope of the laser to the a second optical fiber in the scanning head is transmitted to a detector provided to the laser;
  • Each of the capillaries in the capillary set is excited by a laser to excite fluorescence of a plurality of wavelength ranges, the laser of which is received by a detector that is provided to a laser that illuminates the capillary.
  • each 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 to reflect 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 5.
  • a capillary electrophoresis detection method comprising:
  • the laser output from at least two lasers in the laser group is sequentially irradiated on at least two capillaries in the capillary group, each laser output has a different wavelength, and the detection samples in each capillary are different, and the detection samples in each capillary include a target to be treated.
  • the fluorescent dye in the detection sample in each capillary in the capillary group is excited by the laser to generate fluorescence in a plurality of wavelength ranges;
  • Fluorescence of a plurality of wavelength ranges excited in each capillary is received by a detector that is provided to a laser that illuminates the capillary;
  • the detector group detects the type or content of the target substance to be tested included in the detection sample in each capillary in the capillary group according to the fluorescence of the plurality of wavelength ranges received.
  • the detector group detects fluorescence of the plurality of wavelength ranges received, and further detects target substance to be detected included in the detection sample in each capillary in the capillary group, including:
  • the detector group detects the protein molecules, polypeptide molecules, amino acid molecules, amino acid derivative molecules in the body fluids included in the detection sample in each capillary of the capillary group according to the fluorescence of the plurality of wavelength ranges received.
  • the detector group detects fluorescence of the plurality of wavelength ranges received, and further detects target substance to be detected included in the detection sample in each capillary in the capillary group, including:
  • the detector group simultaneously detects the DNA according to the fluorescence of the plurality of wavelength ranges received, and at least one of the biological substances of claim 5.
  • the present invention has the following beneficial effects:
  • Embodiments of the present invention provide a capillary electrophoresis detection system and a detection system and method, a laser group, the laser group including at least two lasers, each of which outputs a different wavelength; a capillary group including at least two capillaries,
  • the detection sample in each capillary includes a target substance to be tested, the target substance to be detected includes a biological substance labeled with a fluorescent dye or a biological substance combined with an antibody labeled with a fluorescent dye; a detector group, the detector group
  • the number of detectors in the laser is the same as the number of lasers in the laser group, each laser is equipped with a detector; each laser in the laser group sequentially illuminates each capillary in the capillary group, in each capillary
  • the fluorescent dye in the detection sample is excited by the laser to generate fluorescence in a plurality of wavelength ranges, and each laser sequentially irradiates fluorescence of a plurality of wavelength ranges excited by each capillary, and is sequentially received
  • the type or source of the detection samples in each capillary tube may be different, and detection samples of different sources or types may be simultaneously detected; the types and sources of the detection samples of each capillary tube may also be In the same way, it is possible to detect a plurality of different target substances to be tested in the test sample of the same kind and source at one time, thereby improving the detection speed and reducing the consumption of 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 a schematic structural diagram of a detector according to an embodiment of the present invention.
  • FIG. 4 is a schematic structural diagram of another detector according to an embodiment of the present invention.
  • FIG. 5 is a flowchart of a capillary electrophoresis detection method according to an embodiment of the present invention.
  • the embodiment of the present invention provides a capillary electrophoresis detection system and a detection method.
  • FIG. 1 is a schematic structural diagram of a capillary electrophoresis detection system according to an embodiment of the present invention, where the system includes:
  • a laser group 101 the laser group 101 includes at least two lasers, each of which outputs a different wavelength; a capillary group 102, the capillary group 102 includes at least two capillary tubes, and the detection sample in each capillary includes a target to be inspected a substance, the target substance to be tested includes a biological substance labeled with a fluorescent dye or a biological substance bound with an antibody labeled with a fluorescent dye; a detector group 103, a number of detectors in the detector group 103 and a laser group The number of lasers is the same, and each laser is equipped with a detector.
  • Each of the lasers in the laser group 101 sequentially illuminates each capillary in the capillary group 102, and the fluorescent dye in the detection sample in each capillary is excited by a laser to generate fluorescence in a plurality of wavelength ranges, and each laser sequentially irradiates The fluorescence of a plurality of wavelength ranges excited by each capillary is sequentially received by a detector provided to the laser, and the substances contained in the test sample in each capillary are sequentially detected.
  • the fluorescent dye may be a fluorescent dye directly labeled on the target substance to be tested, or a fluorescent dye labeled on the antibody bound to the target substance to be tested.
  • the laser group 101 includes at least two lasers each having a different wavelength. It can be understood that a wavelength laser can excite a limited number of wavelengths of fluorescence, and a laser of different wavelengths can increase the number of wavelengths of fluorescence that can be excited. The more lasers, the laser that can be output The more the type of wavelength, the more the range of wavelengths of fluorescence that can be excited. The fluorescence of one wavelength range represents a target substance to be tested, and the more kinds of target substances to be detected can be detected. The number of lasers in the laser group 101 can be specifically set according to actual needs.
  • the capillary set 102 contains at least two capillaries, each of which has a different test sample, and how many capillaries can simultaneously detect the type of sample or source of the test sample.
  • Capillary set 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 number of capillaries in the capillary set 102 can be specifically set according to actual needs. For example, in Fig. 1, the number of capillaries in the capillary group 102 is 32, and in practical applications, it is not limited to the number of capillaries shown in Fig. 1.
  • the capillary group may include 2 capillaries, may include 10 capillaries, and may also include 384 capillaries and the like.
  • Each laser in the laser set 101 sequentially illuminates each capillary in the capillary set 102.
  • one laser a1 in the laser group sequentially irradiates each capillary in the capillary group 102, and when the laser a1 illuminates one capillary in the capillary group 102, the fluorescent dye in the detection sample in the capillary is excited to emit fluorescence.
  • the fluorescent dye in the detection sample in the capillary is also excited to emit fluorescence. That is, the laser a1 illuminates which capillary in the capillary group 102, and the fluorescent dye in the detection sample in the capillary is excited to emit fluorescence.
  • each of the lasers in the laser group 101 sequentially illuminates each of the capillary tubes 102 as the laser a1 in the above example.
  • the detector group 103 includes a plurality of detectors, and the number of detectors is the same as the number of lasers. Each laser is equipped with a detector. The fluorescence excited by each of the lasers 101 is received by a detector provided to the laser. For example, if the detector b1 is a detector for the laser a1, the fluorescence generated by the laser a1 illuminating each capillary in the capillary group 102 is received by the detector b1.
  • the system further includes:
  • the controller 201 and a scan head 202 connected to the controller 201, 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 scan head 202 receives a control signal of the controller 201, scans the capillary group 102 according to the control signal, and laser light output by each laser in the laser group 101 passes through the first optical fiber in the scan head 202. Transmitted through the corresponding beam splitter of the laser, sequentially irradiated on each capillary in the capillary group 102, and each of the capillary tubes detects fluorescence excited by the fluorescent dye in the sample, and is reflected by the corresponding spectroscope of the laser to The second fiber in the scan head 202 is transmitted to a detector provided to the laser.
  • Each capillary in the capillary set 102 is illuminated by a laser that excites fluorescence of a plurality of wavelength ranges that are received by a detector that is provided to a laser that illuminates the capillary.
  • the scanning head 202 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 each capillary of the capillary group 102 through a corresponding beam splitter of the laser.
  • the fluorescent dye in the sample is detected in each capillary of the capillary group 102.
  • the excited fluorescence is reflected by a corresponding spectroscope of the laser to a second optical fiber corresponding to the laser, and the second optical 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 splitting mirror y1 to each capillary in the capillary group 102, and each capillary of the capillary group 102 is detected.
  • the fluorescence excited by the fluorescent dye in the sample is reflected by the beam splitter y1 to the second optical fiber z1 in the scanning 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 scanned by the scanning head
  • the first optical fiber x2 is transmitted, and transmitted through the beam splitter y2 to each capillary in the capillary group 102.
  • the fluorescence excited by the fluorescent dye in the detection sample in each capillary of the capillary group 102 is reflected by the beam splitter y2 to The second fiber z2 in the scan head,
  • the second optical fiber z2 transmits fluorescence to the detector b2 provided to the laser a2;
  • the laser output from the laser a3 is transmitted by the first optical fiber x3 in the scanning head, and transmitted through the beam splitter y3 to impinge on each capillary in the capillary group 102, the capillary
  • the fluorescence excited by the fluorescent dye in the test sample in each capillary in the group 102 is reflected by the beam splitter y3 to the second optical fiber z3 in the scan head, and the second optical fiber z3 transmits the fluorescence to the detector provided to the laser a3.
  • the laser output from the laser a4 is transmitted by the first optical fiber x4 in the scanning head, and transmitted through the beam splitter y4 to each capillary in the capillary 102 group, and the fluorescence in the detection sample in each of the capillary tubes 102
  • the fluorescence excited by the dye is reflected by the beam splitter y4 to the second optical fiber z4 in the scan head, and the second optical fiber z4 transmits the fluorescence to the detector b4 provided to the laser a4.
  • Each laser in the laser set 101 sequentially sweeps each capillary in the capillary set 102. For example, at a certain moment, when the laser output from the laser a1 illuminates the c-th capillary of the capillary group, the fluorescence excited by the target fluorescent dye in the c-th capillary is received by the detector b1; the laser irradiated by the laser a2 is irradiated to the capillary group The d-th capillary, the fluorescence excited by the fluorescent dye in the d-th capillary is received by the detector b2; when the laser outputted by the laser a3 illuminates the e-th capillary of the capillary group, the fluorescent dye in the e-th capillary is excited The fluorescence is received by the detector b3; the laser output from the laser a4 illuminates the f-th capillary of the capillary group, and the fluorescence excited by the fluorescent dye in the f-th capillary is received by the detector
  • the capillary irradiated by each laser is different. Also, the laser light output from the laser that is arranged farther from the capillary group 102 may not be irradiated to any one of the capillary tubes.
  • 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. 2, and the number of lasers and detectors can be the same.
  • the laser output from the laser group 101 can also be directly irradiated on the capillary in the capillary group 102.
  • the laser output from the laser group 101 can also be transmitted through the optical fiber and then irradiated on the capillary in the capillary group 102. Need specific settings.
  • the controller 201 controls the scanning head 202 to scan the capillary group 102 such that the laser light output by each laser sequentially illuminates each capillary in the capillary group 102 via the first optical fiber in the scanning head, and the detector receives the capillary group 102.
  • the direction in which the scanning head 202 scans is as shown in FIG. What needs to be explained here is that the scanning head The direction of the 202 scanning can also be opposite to the scanning direction shown in FIG. 2, and the technician can set it according to actual needs.
  • each 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 301, 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 301 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 301.
  • the received fluorescence is reflected by the mirror 301 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 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. Any one or more of a nucleotide molecule, a nucleotide 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.
  • 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:
  • Multiple lasers are used to sequentially illuminate multiple capillary tubes, and the type of test sample in each capillary Or the source can be different, and the detection samples with different sources or different types can be detected at the same time; the types and sources of the detection samples of each capillary can be the same, and the detection samples of the same type and source can be detected at one time.
  • the target substance to be inspected increases the detection speed and reduces the consumption of the test sample.
  • FIG. 5 is a flowchart of a capillary electrophoresis detection method according to an embodiment of the present invention, where the method includes:
  • the laser output from at least two lasers in the laser group is sequentially irradiated on at least two capillaries in the capillary group, each laser output has a different wavelength, and the detection samples in each capillary are different, and the detection samples in each capillary include A variety of target substances to be tested.
  • the fluorescent dye in the detection sample in each capillary in the capillary group is excited by a laser to generate fluorescence in a plurality of wavelength ranges, and the detection sample in each capillary includes a target substance to be inspected, and the target is to be inspected.
  • the substance includes a biological substance labeled with a fluorescent dye or a biological substance to which an antibody labeled with a fluorescent dye is bound.
  • Fluorescence of a plurality of wavelength ranges excited in each capillary is received by a detector that is provided to a laser that illuminates the capillary.
  • the detector group detects fluorescence of a plurality of wavelength ranges received, thereby detecting a type or content of a target substance to be detected included in the detection sample in each capillary in the capillary group.
  • 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. 5 is a method corresponding to the capillary electrophoresis detection system shown in FIG. 1 to FIG. 4 .
  • the specific implementation manner is described in the system shown in FIG. 1 to FIG. 4 , and details are not described herein again.

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Abstract

一种毛细管电泳检测***及检测方法,该装置包括激光器组(101)、毛细管组(102)和探测器组(103)。激光器组(101)中每个激光器依次照射毛细管组(102)中的每根毛细管,每根毛细管中的检测样品中包括目标待检物质,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,每个激光器依次照射每根毛细管,每根毛细管中的荧光染料受激发所产生的多个波长范围的荧光被为该激光器配备的探测器依次接收,进而依次检测每根毛细管中的检测样品所含的物质的种类或含量。采用多个激光器依次照射多根毛细管,能够一次性检测不同种类或不同来源的检测样品,也能够一次性检测种类和来源相同的检测样品中的多种不同的目标待检物质,提高检测速度,减少检测样品的消耗。

Description

一种毛细管电泳检测***及检测方法
本申请要求于2016年06月29日提交中国专利局、申请号为201610496479.1、发明名称为“一种毛细管电泳检测***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。
技术领域
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***及检测方法。
背景技术
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。
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生物物质进行检测。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,荧光染料受到激光激发产生荧光,探测器接收所产生的荧光,分析所接收的荧光,进而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,导致检测速度慢,检测样品耗费大。
发明内容
本发明解决的技术问题在于提供一种毛细管电泳检测***及检测方法,从而能够一次性采用多个毛细管检测多种检测样品,并且能够一次性检测同一检测样品中大量种类的生物物质,提高检测速度,减少检测样品的消耗。
为此,本发明解决技术问题的技术方案是:
一种毛细管电泳检测***,所述***包括:
激光器组,所述激光器组包括至少两个激光器,每个激光器输出的波长不同;毛细管组,所述毛细管组包括至少两根毛细管,每根毛细管中的检测样品中包括目标待检物质,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;探测器组,所述探测器组中的探测器的个数与激光器组中激光器的个数相同,每个激光器配备有一个探测器;
所述激光器组中每个激光器依次照射所述毛细管组中的每根毛细管,每根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,每个激光器依次照射每根毛细管所激发的多个波长范围的荧光,被给该激光器配备的探测器依次接收,进而依次检测每根毛细管中的检测样品所包括的目标待检物质种类或含量。
可选的,所述***还包括:
控制器,以及与所述控制器相连的扫描头,多个分光镜;
每个激光器对应于一个分光镜,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,以及探测器的个数都相同;
所述扫描头接收所述控制器的控制信号,根据所述控制信号扫描过所述毛细管组,所述激光器组中的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组中的每根毛细管上,每根毛细管中检测样品中的的荧光染料被激发所产生的荧光,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;
所述毛细管组中的每根毛细管被激光照射激发多种波长范围的荧光,该多个波长范围的激光被探测器所接收,该探测器是给照射该毛细管的激光器所配备的探测器。
可选的,每个探测器包括:
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;
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;
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至所述反射镜;
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。
可选的,所述探测器还包括:
多个聚焦镜,聚焦镜的个数与光电探测器的个数相同;
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。
可选的,
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。
可选的,
所述目标待检物质包括DNA,以及至少一种权利要求5所述的生物物质。
一种毛细管电泳检测方法,所述方法包括:
激光器组中至少两个激光器输出的激光依次照射在毛细管组中的至少两根毛细管上,每个激光输出的波长不同,每根毛细管中的检测样品不同,每根毛细管中的检测样品包括目标待检物质;
所述毛细管组中的每根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;
每根毛细管中所激发的多个波长范围的荧光被探测器所接收,该探测器是给照射该毛细管的激光器所配备的探测器;
探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的目标待检物质的种类或含量。
可选的,所述探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的目标待检物质包括:
探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的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。
可选的,所述探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的目标待检物质包括:
探测器组根据所接收的多个波长范围的荧光,进而同时检测DNA,以及至少一种权利要求5所述的生物物质。
通过上述技术方案可知,本发明有如下有益效果:
本发明实施例提供了毛细管电泳检测***及检测***及方法,激光器组,所述激光器组包括至少两个激光器,每个激光器输出的波长不同;毛细管组,所述毛细管组包括至少两根毛细管,每根毛细管中的检测样品中包括目标待检物质,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;探测器组,所述探测器组中的探测器的个数与激光器组中激光器的个数相同,每个激光器配备有一个探测器;所述激光器组中每个激光器依次照射所述毛细管组中的每根毛细管,每根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,每个激光器依次照射每根毛细管所激发的多个波长范围的荧光,被给该激光器配备的探测器依次接收,进而依次检测每根毛细管中的目标待检物质的种类或含量。采用多个激光器依次照射多根毛细管,每根毛细管中的检测样品的种类或来源也可以不同,可以同时检测来源不同或者种类不同的检测样品;每根毛细管的检测样品中的种类和来源也可以相同,能够一次性检测种类和来源相同的检测样品中的多种不同的目标待检物质,提高检测速度,减少检测样品的消耗。
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。
图1为为本发明实施例提供的毛细管电泳检测***结构示意图;
图2为本发明实施例提供的毛细管电泳检测***一种可能的结构示意图;
图3为本发明实施例提供的一种探测器结构示意图;
图4为本发明实施例提供的另一种探测器结构示意图;
图5为本发明实施例提供的毛细管电泳检测方法流程图。
具体实施方式
为了给出提高检测速度,减少检测样品的消耗的实现方案,本发明实施例提供了一种毛细管电泳检测***及检测方法,以下结合说明书附图对本发明的优选实施例进行说明。
图1为本发明实施例提供的毛细管电泳检测***结构示意图,所述***包括:
激光器组101,所述激光器组101包括至少两个激光器,每个激光器输出的波长不同;毛细管组102,所述毛细管组102包括至少两根毛细管,每根毛细管中的检测样品中包括目标待检物质,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;探测器组103,所述探测器组103中的探测器的个数与激光器组中激光器的个数相同,每个激光器配备有一个探测器。
所述激光器组101中每个激光器依次照射所述毛细管组102中的每根毛细管,每根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,每个激光器依次照射每根毛细管所激发的多个波长范围的荧光,被给该激光器配备的探测器依次接收,依次检测每根毛细管中的检测样品所含的物质。荧光染料可以是直接标记在目标待检物质上的荧光染料,也可是标记在与目标待检物质结合的抗体上的荧光染料。
激光器组101中包括至少两个激光器,每个激光器的波长都不同。可以理解的是,一种波长的激光器可以激发有限的几个波长范围的荧光,不同波长的激光器可以激发的荧光的波长范围的个数增多。激光器越多,能够输出的激光 的波长的种类越多,能够激发的荧光的波长范围的个数也就越多。一个波长范围的荧光代表一种目标待检物质,则能够检测的目标待检物质的种类也越多。激光器组101中激光器的个数可以根据实际需要具体设置。
毛细管组102中包含至少两根毛细管,每根毛细管中的检测样品不同,有多少根毛细管就能同时检测多少种类或来源的检测样品。毛细管组102中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。毛细管组102中的毛细管的个数可以根据实际需要具体设置。例如,图1中,毛细管组102中毛细管的数量为32,在实际应用中,并不仅限于图1所示的毛细管的数量。例如,毛细管组可以包括2根毛细管,可以包括10根毛细管,还可以包括384根毛细管等。
激光器组101中的每个激光器依次照射毛细管组102中的每根毛细管。举例说明:激光器组中的一个激光器a1,依次照射毛细管组102中的每根毛细管,激光器a1照射毛细管组102中的一根毛细管时,该毛细管中的检测样品中的荧光染料会被激发出荧光;激光器a1照射毛细管组102中的另一根毛细管时,该毛细管中的检测样品中的荧光染料也会被激发出荧光。即激光器a1照射毛细管组102中哪根毛细管,该毛细管中检测样品中的荧光染料都会被激发出荧光。假设毛细管组102中包含384根毛细管,则384根毛细管在激光器a1的照射下都会被激发出荧光。前提是,毛细管组102中每根毛细管中的检测样品上标记了能够被激光器a1激发出荧光的荧光染料。以此类推,激光器组101中每个激光器都如上述实例中的激光器a1,依次照射毛细管组102中的每根毛细管。
探测器组103中包括多个探测器,探测器的个数与激光器的个数相同。每个激光器都配备有一个探测器。激光器组101中的每个激光器激发的荧光,由给该激光器配备的探测器接收。举例说明:若探测器b1为给激光器a1配备的探测器,则激光器a1照射所述毛细管组102中每根毛细管所产生的荧光,都由探测器b1所接收。
在一个例子中,如图2所示,所述***还包括:
控制器201,以及与所述控制器201相连的扫描头202,多个分光镜。
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。
所述扫描头202接收所述控制器201的控制信号,根据所述控制信号扫描过所述毛细管组102,激光器组101中的每个激光器输出的激光通过所述扫描头202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组102中的每根毛细管上,每根毛细管中检测样品中的的荧光染料被激发出的荧光,经由该激光器对应的分光镜反射至所述扫描头202中的第二光纤,传输至给该激光器配备的探测器。
所述毛细管组102中的每根毛细管被激光照射激发多个波长范围的荧光,该多个波长范围的激光被探测器所接收,该探测器是给照射该毛细管的激光器所配备的探测器。
扫描头202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组102的每根毛细管上,毛细管组102的每根毛细管中检测样品中的荧光染料被激发出的荧光,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。
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。
举例说明,如图2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照射在毛细管组102中的每根毛细管上,毛细管组102的每根毛细管中检测样品中的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照射在毛细管组102中的每根毛细管上,毛细管组102的每根毛细管中的检测样品中的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照射在毛细管组102中的每根毛细管上,毛细管组102中的每根毛细管中的检测样品中的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组中的每根毛细管上,毛细管组102中的每根毛线管中的检测样品中的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。
激光器组101中每个激光器依次扫照射毛细管组102中每根毛细管。举例说明:在某一时刻,激光器a1输出的激光照射毛细管组第c根毛细管时,第c根毛细管中目的荧光染料被激发出的荧光被探测器b1所接收;激光器a2输出的激光照射毛细管组第d根毛细管,第d根毛细管中的荧光染料被激发出的荧光被探测器b2所接收;激光器a3输出的激光照射毛细管组第e根毛细管时,第e根毛细管中的荧光染料被激发出的荧光被探测器b3所接收;激光器a4输出的激光照射毛细管组第f根毛细管,第f根毛细管中的荧光染料被激发出的荧光被探测器b4所接收。由此可知,同一时刻,每个激光器所照射的毛细管不同。并且,排列在距离毛细管组102较远的激光器输出的激光有可能没有照射到任意一个毛细管。
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2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。
在实际应用中,激光器组101输出的激光还可以直接照射在毛细管组102中的毛细管上,激光器组101输出的激光也可以通过光纤传输后照射在毛细管组102中的毛细管上,技术人员根据实际需要具体设置即可。
控制器201控制扫描头202扫描过所述毛细管组102,以使得每个激光器输出的激光经由扫描头中的第一光纤依次照射在毛细管组102中的每根毛细管上,探测器接收毛细管组102中每根毛细管中的检测样品中的荧光染料所产生的荧光。扫描头202扫描的方向如图2所示。这里需要说明的是,扫描头 202扫描的方向也可以与图2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。
在一个例子中,如图3所示,每个探测器包括:
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;
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;
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;
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。
在毛细管电泳检测***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。
以图3为例,所述探测器包括一个反射镜301,四个滤光片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。
反射镜301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301紧贴放置。所接收的荧光被反射镜301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。
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。
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。
在一个例子中,如图4所示,所述探测器还包括:
多个聚焦镜,聚焦镜的个数与光电探测器的个数相同;
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。
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4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。
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。
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。
本发明提供的毛细管电泳检测***,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。
由上述内容可知,本发明有如下有益效果:
采用多个激光器依次照射多根毛细管,每根毛细管中的检测样品的种类 或来源也可以不同,可以同时检测来源不同或者种类不同的检测样品;每根毛细管的检测样品中的种类和来源也可以相同,能够一次性检测种类和来源相同的检测样品中的多种不同的目标待检物质,提高检测速度,减少检测样品的消耗。
图5为本发明实施例提供的毛细管电泳检测方法流程图,所述方法包括:
501:激光器组中至少两个激光器输出的激光依次照射在毛细管组中的至少两根毛细管上,每个激光输出的波长不同,每根毛细管中的检测样品不同,每根毛细管中的检测样品包括多种目标待检物质。
502:所述毛细管组中的每根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,每根毛细管中的检测样品中包括目标待检物质,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。
503:每根毛细管中所激发的多个波长范围的荧光被探测器所接收,该探测器是给照射该毛细管的激光器所配备的探测器。
504:探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的目标待检物质的种类或含量。
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。
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。
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。
图5所示的毛细管电泳检测方法是与图1至图4所示的毛细管电泳检测***所对应的方法,具体实现方式参考图1至图4所示的***中的描述,这里不再赘述。
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。

Claims (9)

  1. 一种毛细管电泳检测***,其特征在于,所述***包括:
    激光器组,所述激光器组包括至少两个激光器,每个激光器输出的波长不同;毛细管组,所述毛细管组包括至少两根毛细管,每根毛细管中的检测样品中包括目标待检物质,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;探测器组,所述探测器组中的探测器的个数与激光器组中激光器的个数相同,每个激光器配备有一个探测器;
    所述激光器组中每个激光器依次照射所述毛细管组中的每根毛细管,每根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,每个激光器依次照射每根毛细管所激发的多个波长范围的荧光,被给该激光器配备的探测器依次接收,进而依次检测每根毛细管中的检测样品所包括的目标待检物质种类或含量。
  2. 根据权利要求1所述的***,其特征在于,所述***还包括:
    控制器,以及与所述控制器相连的扫描头,多个分光镜;
    每个激光器对应于一个分光镜,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,以及探测器的个数都相同;
    所述扫描头接收所述控制器的控制信号,根据所述控制信号扫描过所述毛细管组,所述激光器组中的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组中的每根毛细管上,每根毛细管中检测样品中的荧光染料被激发所产生的荧光,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;
    所述毛细管组中的每根毛细管被激光照射激发多种波长范围的荧光,该多个波长范围的激光被探测器所接收,该探测器是给照射该毛细管的激光器所配备的探测器。
  3. 根据权利要求2所述的***,其特征在于,每个探测器包括:
    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;
    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;
    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至所述反射镜;
    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。
  4. 根据权利要求3所述的***,其特征在于,所述探测器还包括:
    多个聚焦镜,聚焦镜的个数与光电探测器的个数相同;
    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。
  5. 根据权利要求1-4任意一项所述的***,其特征在于,
    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。
  6. 根据权利要求5所述的***,其特征在于,
    所述目标待检物质包括DNA,以及至少一种权利要求5所述的生物物质。
  7. 一种毛细管电泳检测方法,其特征在于,所述方法包括:
    激光器组中至少两个激光器输出的激光依次照射在毛细管组中的至少两根毛细管上,每个激光输出的波长不同,每根毛细管中的检测样品不同,每根毛细管中的检测样品包括目标待检物质;
    所述毛细管组中的每根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;
    每根毛细管中所激发的多个波长范围的荧光被探测器所接收,该探测器是给照射该毛细管的激光器所配备的探测器;
    探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的目标待检物质的种类或含量。
  8. 根据权利要求7所述的方法,其特征在于,所述探测器组根据所接收 的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的目标待检物质包括:
    探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的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。
  9. 根据权利要求8所述的方法,其特征在于,所述探测器组根据所接收的多个波长范围的荧光,进而检测所述毛细管组中的每根毛细管中的检测样品中包括的目标待检物质包括:
    探测器组根据所接收的多个波长范围的荧光,进而同时检测DNA,以及至少一种权利要求5所述的生物物质。
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112262308A (zh) * 2018-06-22 2021-01-22 株式会社日立高新技术 电泳装置
CN112782141A (zh) * 2020-12-29 2021-05-11 中国科学院合肥物质科学研究院 一种基于荧光方法的塑料快速分类设备

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105973860B (zh) * 2016-06-29 2019-07-30 山东科立森生物股份有限公司 一种毛细管电泳检测***及检测方法
CN105973859B (zh) * 2016-06-29 2019-01-29 山东科立森生物股份有限公司 一种毛细管电泳检测***及检测方法
CN106908421A (zh) * 2017-01-18 2017-06-30 北京蓝色星语科技有限公司 一种多通道危险物质检测方法及检测装置
CN114450586A (zh) * 2019-08-07 2022-05-06 生命技术公司 用于毛细管电泳的多毛细管光学检测***

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110147217A1 (en) * 2009-12-17 2011-06-23 The Curators Of The University Of Missouri Method and apparatus for cancer screening
CN202196015U (zh) * 2011-06-15 2012-04-18 公安部第一研究所 一种基于光谱校正的毛细管阵列电泳检测装置
CN203310753U (zh) * 2013-05-24 2013-11-27 南开大学 多波长毛细管电泳荧光激发器
WO2015134925A1 (en) * 2014-03-07 2015-09-11 Life Technologies Corporation Optical system for capillary electrophoresis
CN105973859A (zh) * 2016-06-29 2016-09-28 山东科立森生物股份有限公司 一种毛细管电泳检测***及检测方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3400650B2 (ja) * 1996-06-28 2003-04-28 株式会社日立製作所 電気泳動分離検出方法及び装置
AU2002242004A1 (en) * 2001-01-26 2002-08-06 Biocal Technology, Inc. Optical detection in a multi-channel bio-separation system
CN101748207A (zh) * 2008-12-09 2010-06-23 湖北师范学院 单一波长的dna测序装置
CN101718696A (zh) * 2009-12-10 2010-06-02 上海交通大学 激光荧光扫描成像-荧光相关光谱单分子探测仪
CN104181133A (zh) * 2013-05-24 2014-12-03 南开大学 多波长毛细管电泳荧光激发装置
CN205879793U (zh) * 2016-06-29 2017-01-11 山东科立森生物股份有限公司 一种毛细管电泳检测***

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110147217A1 (en) * 2009-12-17 2011-06-23 The Curators Of The University Of Missouri Method and apparatus for cancer screening
CN202196015U (zh) * 2011-06-15 2012-04-18 公安部第一研究所 一种基于光谱校正的毛细管阵列电泳检测装置
CN203310753U (zh) * 2013-05-24 2013-11-27 南开大学 多波长毛细管电泳荧光激发器
WO2015134925A1 (en) * 2014-03-07 2015-09-11 Life Technologies Corporation Optical system for capillary electrophoresis
CN105973859A (zh) * 2016-06-29 2016-09-28 山东科立森生物股份有限公司 一种毛细管电泳检测***及检测方法

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112262308A (zh) * 2018-06-22 2021-01-22 株式会社日立高新技术 电泳装置
EP3812741A4 (en) * 2018-06-22 2022-06-22 Hitachi High-Tech Corporation ELECTROPHORESIS DEVICE
US11733205B2 (en) 2018-06-22 2023-08-22 Hitachi High-Tech Corporation Electrophoresis apparatus
CN112782141A (zh) * 2020-12-29 2021-05-11 中国科学院合肥物质科学研究院 一种基于荧光方法的塑料快速分类设备
CN112782141B (zh) * 2020-12-29 2023-12-19 中国科学院合肥物质科学研究院 一种基于荧光方法的塑料快速分类设备

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