WO2023077306A1 - 检测设备、基因测序系统及检测方法 - Google Patents

检测设备、基因测序系统及检测方法 Download PDF

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Publication number
WO2023077306A1
WO2023077306A1 PCT/CN2021/128444 CN2021128444W WO2023077306A1 WO 2023077306 A1 WO2023077306 A1 WO 2023077306A1 CN 2021128444 W CN2021128444 W CN 2021128444W WO 2023077306 A1 WO2023077306 A1 WO 2023077306A1
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Prior art keywords
incident
dichroic mirror
light
lights
fluorescence
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PCT/CN2021/128444
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English (en)
French (fr)
Chinese (zh)
Inventor
韦毅
黄怡
姜鹤鸣
杨斌
温欣
黄恒
曹明友
邓茜
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MGI Tech Co Ltd
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MGI Tech Co Ltd
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Priority to EP21962825.2A priority Critical patent/EP4394027A4/en
Priority to CN202180100932.1A priority patent/CN117716017A/zh
Priority to US18/705,710 priority patent/US20250059599A1/en
Priority to CA3236241A priority patent/CA3236241A1/en
Priority to PCT/CN2021/128444 priority patent/WO2023077306A1/zh
Priority to AU2021472582A priority patent/AU2021472582A1/en
Priority to JP2024525413A priority patent/JP7850253B2/ja
Publication of WO2023077306A1 publication Critical patent/WO2023077306A1/zh
Anticipated expiration legal-status Critical
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6869—Methods for sequencing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0663—Whole sensors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/168—Specific optical properties, e.g. reflective coatings
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N2021/6417—Spectrofluorimetric devices
    • G01N2021/6419—Excitation at two or more wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N2021/6417—Spectrofluorimetric devices
    • G01N2021/6421—Measuring at two or more wavelengths
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6484—Optical fibres
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458—Fluorescence microscopy

Definitions

  • the invention relates to the technical field of detection, in particular to a detection device, a gene sequencing system and a detection method.
  • Gene detection is accomplished by exciting the sample with a laser to generate fluorescence, and then using an imaging system to detect and analyze the generated fluorescence to obtain the target base sequence.
  • Various bases present in the sample to be detected are marked with different primers for tracking, wherein the primers are excited by lasers of different wavelengths to obtain corresponding fluorescence (fluorescence corresponds to the base one by one).
  • the photobleaching phenomenon greatly reduces the fluorescence yield or even denatures, resulting in poor detection results
  • the fluorescence crosstalk phenomenon refers to the fact that some primers are stimulated to obtain The excited fluorescence will be affected by the excitation process of other primers, which will affect the quantum yield and the phenomenon that multiple fluorescences are generated simultaneously in the region and mixed with each other.
  • the existing genetic detection equipment outputs lasers of different wavelengths coaxially through an optical fiber.
  • the principal rays of all wavelengths are transmitted coaxially, and finally irradiated on the sample. on the same area.
  • Figure 6 shows a known arrangement 60 for implementing the first prior art technique (ie simultaneous excitation).
  • the multimode fiber 610 when adopting the first prior art (that is, simultaneous excitation), the multimode fiber 610 simultaneously outputs n kinds of lasers of different wavelengths (n is the number of lasers of different wavelengths, the same below), and these lasers pass through
  • the beam shaping device 670 is shaped, the laser filter 620 filters light, the first dichroic mirror 630 reflects, the objective lens 640 focuses, etc., and then focuses on the sample 600, and n kinds of lasers with different wavelengths are focused on the same position of the sample (Fig. 6 The location of the multi-wavelength laser spot in the sample) and excite the fluorescence at this location on the sample.
  • the fluorescence detection speed of each field of view is equal to the time for a single photo taken by the camera, but the laser power in the illuminated area is the sum of all laser powers, that is, the density becomes n times when a single laser is irradiated ( Assuming the same laser power density for each wavelength).
  • the first existing technology focuses on "high speed". The method is: n kinds of lasers with different wavelengths excite fluorescence at the same time, and the fluorescence detection of all channels can be completed by taking a single photo of a single field of view area, but the power density It is n times that when irradiated with laser light of a single wavelength.
  • Figure 7 shows a known arrangement 70 for implementing the second prior art technique, ie time-shared excitation.
  • the multimode optical fiber 710 sequentially outputs n kinds of lasers with different wavelengths, and the output lasers are shaped by a beam shaping device 770, and laser filters After filtering at 720 , reflecting with dichroic mirror 730 , and focusing with objective lens 740 , etc., focus on a position of the sample 700 (the position of the laser spot at different times in FIG. 7 ) and excite fluorescence at this position on the sample.
  • the fluorescence is detected by the objective lens 740, and then passes through the dichroic mirror 730, the fluorescence filter 750 (only passes through the fluorescence, and filters out stray light other than the fluorescence) and the imaging lens 760, and is photographed by the camera 780 to output fluorescence information. It takes n times to take pictures to complete the fluorescence detection of the FOV. All lasers need to be output from the multimode fiber in sequence and fluorescence detection is performed in sequence accordingly, that is, the laser power density irradiated on the sample is the same as that of a single laser (assuming that the power density of each laser is the same). Thus, photobleaching is weaker and crosstalk between fluorophores is reduced.
  • the fluorescence detection time of each FOV is n times longer than that of a single photoshoot.
  • the second existing technology focuses on "high detection quality and long read length".
  • the method is: n kinds of lasers with different wavelengths sequentially excite fluorescence (at the same time, the corresponding camera takes pictures for fluorescence detection), and the power density and It is the same as when a single laser excites fluorescence, but n times of excitation and n times of fluorescence detection are required.
  • the total time of fluorescence detection is n times that of the first prior art, and the total detection time required for the detection of the same sample is the first. N times of the existing technology.
  • the first existing technology improves the detection speed, the power density of laser irradiation is increased by n times, different fluorescent lights are excited at the same position, the photobleaching phenomenon is obvious, and there is fluorescent crosstalk, resulting in a decrease in fluorescent yield.
  • the second prior art is significantly better than the first prior art in terms of detection error rate, but it takes n times more time to take pictures than the first prior art.
  • an improved solution for biochemical detection is needed to solve or alleviate the photobleaching and fluorescence crosstalk problems caused by high optical power density while taking into account the detection speed.
  • the purpose of the present invention is to propose an improved solution for biochemical detection, so as to solve or alleviate the problems of photobleaching and fluorescent crosstalk caused by high optical power density while taking into account the detection speed.
  • a detection device which includes: a spectroscopic device, a first dichroic mirror, an objective lens, a fluorescence guiding device, and an imaging system including a plurality of imaging devices, wherein,
  • the spectroscopic device is used to receive and separate a plurality of incident lights of different wavelengths from the optical fiber, so that each of the plurality of incident lights of different wavelengths is emitted from the spectroscopic device along different outgoing directions as corresponding excitation light , where the wavelength of each excitation light is the same as that of the corresponding incident light;
  • the first dichroic mirror is positioned to: receive a plurality of excitation lights emitted from the spectroscopic device and respectively corresponding to the plurality of incident lights of different wavelengths, and transmit the plurality of excitation lights to the
  • the objective lens enables the plurality of excitation lights to be respectively focused on a plurality of different regions of the sample to be detected through the objective lens to respectively excite fluorescence in corresponding regions of the sample to which they are focused, and receive photoexciting a plurality of fluorophores and transporting the plurality of fluorophores to the fluorescence guiding device;
  • the objective lens is positioned to: receive the plurality of excitation lights transmitted through the first dichroic mirror, respectively focus the plurality of excitation lights on the plurality of different regions of the sample, and The plurality of fluorescent lights respectively excited by the plurality of excitation lights are transmitted to the first dichroic mirror;
  • the fluorescence guiding device is positioned to: receive the plurality of fluorescences transmitted through the first dichroic mirror, and direct the plurality of fluorescences to the plurality of imaging devices respectively such that the plurality of fluorescences each of which is imaged by a respective one of the plurality of imaging devices;
  • Each of the plurality of imaging devices is positioned to receive a respective one of the plurality of fluorophores guided by the fluorescence guiding device and to image the fluorophores to obtain corresponding fluorochromes information for detection.
  • a gene sequencing system which includes an imaging system for collecting fluorescent signals on a sequencing chip and an optical system located between the imaging system and the sequencing chip, characterized in that, The optical system includes:
  • a light source for emitting incident light of a plurality of different wavelengths
  • a spectroscopic device for receiving and separating a plurality of incident lights of different wavelengths from the light source, so that each of the plurality of incident lights of different wavelengths is emitted from the spectroscopic device in a different outgoing direction as a corresponding excitation light, wherein each excitation light has the same wavelength as the corresponding incident light;
  • a first dichroic mirror configured to receive a plurality of excitation lights emitted from the spectroscopic device and respectively corresponding to the plurality of incident lights of different wavelengths
  • a fluorescence guiding device configured to receive the plurality of fluorescence transmitted through the first dichroic mirror, and guide the plurality of fluorescence to the imaging system respectively;
  • the imaging system includes a plurality of imaging devices, the plurality of imaging devices are in one-to-one correspondence with the plurality of fluorophores, respectively corresponding to receive one of the plurality of fluorophores guided by the fluorescence guiding device, and respond to the corresponding fluorescence of the plurality of fluorophores.
  • the fluorescence imaging described above was used to obtain the corresponding fluorescence information.
  • a detection method comprising:
  • Emitting a plurality of incident lights of different wavelengths via the light source Emitting a plurality of incident lights of different wavelengths via the light source
  • each of the plurality of incident lights of different wavelengths is emitted from the spectroscopic device in a different outgoing direction as a corresponding excitation light, wherein each excitation light has the same wavelength as the corresponding incident light;
  • the inventive structure through the inventive structure, light of different wavelengths can be simultaneously and separately irradiated on different positions of the sample to be detected to simultaneously excite fluorescence at these different positions.
  • the laser as the excitation light as an example
  • the power density of the laser on the sample is reduced to 1/n of the laser density during simultaneous excitation, and only a single excitation in a single field of view can complete the fluorescence detection of all channels, and the total detection
  • the time is equal to the time required for a single fluorescence excitation and detection when the fluorescence is excited multiple times in the same area (that is, in the case of time-sharing excitation) for detection.
  • the power density of the laser on the sample can be reduced without increasing the detection time, which solves the problem that the existing technology is not compatible in terms of "high speed” and "high detection quality, long read length".
  • the problem is that the detection speed can be taken into account while solving or alleviating the photobleaching and fluorescence crosstalk problems caused by high optical power density.
  • Figure 1b is a schematic diagram of the composition and structure of an example fluorescent guiding device that can be used in the detection device of the present invention
  • Fig. 1c is a schematic diagram of the composition and structure of another example fluorescence guiding device that can be used in the detection device of the present invention.
  • FIG. 2 is a schematic diagram of the composition and structure of a detection device according to another preferred embodiment of the present invention.
  • Fig. 3 is a schematic diagram showing a detection device according to yet another preferred embodiment of the present invention.
  • Fig. 6 schematically shows a known device for realizing the existing detection technology using simultaneous excitation
  • Fig. 7 schematically shows a known device for realizing the existing detection technology using time-sharing excitation
  • a detection device 10 according to a preferred embodiment of the present invention, as shown in FIG.
  • the imaging system 160 of wherein, i represents the number of incident laser light of different wavelengths from the optical fiber, which is an integer greater than 1.
  • the spectroscopic device 120 is used to receive and split a plurality of incident laser light with different wavelengths from the optical fiber, so that each of the multiple incident laser light with different wavelengths is emitted from the spectroscopic device along different outgoing directions as corresponding excitation laser light, Laser 1, Laser 2, Laser i as shown in Figure 1.
  • Each excitation laser has the same wavelength as the corresponding incident laser.
  • the light splitting device can be realized by various optical devices with dispersion capability or a combination of such optical devices.
  • the spectroscopic device may be, for example, a single dispersion prism, multiple dispersion prisms, one or more gratings, etc., which will be further described later.
  • the optical fiber may be a single optical fiber, such as but not limited to coupled optical fibers. It is advantageous, although not necessary, for a plurality of incident laser lights of different wavelengths to be incident on the spectroscopic device in the same incident direction. Although the multiple incident lasers are transmitted to the spectroscopic device by optical fibers in FIG. 1 , it is possible to provide multiple incident lasers to the spectroscopic device by replacing the optical fibers with another optical transmission device.
  • the optical fiber or further optical transmission means may be included in the detection device or external to the detection device.
  • the dichroic mirror After being reflected by a dichroic mirror, they are all focused on a plurality of different regions of the sample by the objective lens, and the plurality of fluorescent lights respectively excited by the plurality of excitation lasers received from the sample through the objective lens are all transmitted to the set by the first dichroic mirror.
  • the fluorescence guiding device described above.
  • the orientation of the first dichroic mirror can be determined, for example, based on the exit angle of the respective excitation laser light relative to the beam splitting device and the objective lens. According to circumstances, the first dichroic mirror can have different placement angles.
  • the objective lens 140 is positioned to: receive the multiple excitation lasers transmitted through the first dichroic mirror, respectively focus the multiple excitation lasers on multiple different regions of the sample, and respectively The plurality of fluorescent lights excited by the plurality of excitation lasers are transmitted to the first dichroic mirror.
  • the objective lens is composed of a single lens or a lens group composed of multiple lenses.
  • the lenses may include, for example but not limited to, convex lenses, concave lenses, cemented lenses, and the like.
  • the fluorescence guiding device 150 is positioned to: receive the plurality of fluorescences transmitted through the first dichroic mirror, and respectively guide the plurality of fluorescences to the plurality of imaging devices such that the plurality of fluorescences Each of is imaged by a corresponding one of the plurality of imaging devices.
  • the fluorescence guide can be realized in various possible ways.
  • the fluorescence guiding device may be a plurality of second dichroic mirrors arranged as required, and the number of the plurality of second dichroic mirrors may be equal to the number of excitation lasers, ie i.
  • each second dichroic mirror can be set to achieve one of the following: transmit a certain kind of fluorescence and reflect the rest of the fluorescence; reflect a certain kind of fluorescence and transmit the rest of the fluorescence, so that the plurality of second dichroic mirrors
  • the combination of mirrors achieves the desired guidance of the fluorescence as described above.
  • Each of the plurality of fluorophores guided by the fluorescence guiding device corresponds to each of the plurality of imaging devices in one-to-one correspondence.
  • the fluorescence guiding device includes a plurality of second dichroic mirrors arranged sequentially, and the plurality of second dichroic mirrors include the last second dichroic mirror farthest from the first dichroic mirror. dichroic mirror and at least one preceding second dichroic mirror located between the last second dichroic mirror and the first dichroic mirror, the first dichroic mirror receives all The plurality of fluorophores propagate sequentially through the plurality of second dichroic mirrors, each of the preceding second dichroic mirrors being positioned to direct at least one fluorophore of the plurality of fluorophores incident thereon One fluorescent light in the at least one fluorescent light is guided to a corresponding imaging device, and the remaining fluorescent light in the at least one fluorescent light is guided to the next second dichroic mirror next to it, and the last second dichroic mirror are positioned to direct fluorescent light incident thereon to a corresponding imaging device.
  • Said at least one of said plurality of second dichroic mirrors is said second dichroic mirror closest to said first dichroic mirror among the preceding second dichroic mirrors, i.e.
  • dichroic mirror 1 Can be selected to transmit fluorescence from the plurality of fluorescence from the first dichroic mirror directed by it to the corresponding imaging device and reflect the remainder of the plurality of fluorescence incident thereon to its adjacent
  • the next second dichroic mirror is dichroic mirror 2
  • the last second dichroic mirror in the plurality of second dichroic mirrors is dichroic mirror i is selected to convert incident Fluorescent light thereon is directed to a corresponding imaging device, and for the plurality of second dichroic mirrors except for the second dichroic mirror closest to the first dichroic mirror and
  • Each second dichroic mirror other than the last second dichroic mirror, such as dichroic mirror 2 is selected to reflect the fluorescent light guided by it to the corresponding imaging device and The rest of the at least one fluorescent light incident thereon is transmitted to its next adjacent second dichroic mirror.
  • the example fluorescence guiding device 150'' shown in Fig. 1c it includes a plurality of second dichroic mirrors arranged in sequence: dichroic mirror 1, dichroic mirror 2, ... dichroic mirror i .
  • Said at least one of said plurality of second dichroic mirrors is said second dichroic mirror closest to said first dichroic mirror among the preceding second dichroic mirrors, i.e.
  • the dichroic mirror can be positioned such that light to be received by it is incident on it at a range of angles of incidence, which facilitates reflection and/or transmission of the received light by the dichroic mirror, in the case of mixed light This is especially true below.
  • the positioning of the dichroic mirror can be determined considering the upstream components that transmit light to the dichroic mirror.
  • the range may be, for example, an angular range including 45°. Different dichroic mirrors can have different design requirements for the range of incident angles.
  • Each of the plurality of imaging devices is positioned to receive and image a respective one of the plurality of fluorophores directed by the fluorescence guiding device to obtain corresponding fluorescence information for detection.
  • the imaging device can be realized in various possible ways. According to a possible implementation manner, each imaging device in the plurality of imaging devices includes sequentially arranged optical filters, imaging lenses, and cameras, and for each imaging device, its optical filter is positioned so that it will be controlled by the fluorescence guiding device The fluorescence guided to the imaging device is filtered and transmitted to its imaging lens, and its imaging lens is positioned to focus the fluorescence transmitted through its optical filter on its camera to be imaged by its camera to obtain corresponding fluorescence information. for detection.
  • each imaging device including its lens and camera
  • its center can be aligned with the transmission/reflection center of its corresponding element in the fluorescence guiding device, such as the second dichroic mirror that guides the corresponding fluorescence to the imaging device.
  • the camera may be a TDI camera, adapted for TDI imaging.
  • a plurality of different wavelengths of laser light may be generated by at least one laser source, and the optical fiber may be positioned to receive the plurality of different wavelengths of laser light from the at least one laser source and transmit the plurality of different wavelengths of laser light to the spectroscopic device as the incident laser light of the plurality of different wavelengths.
  • the at least one laser source may be included in the detection device or external to the detection device.
  • the at least one laser source includes a plurality of laser sources, and the plurality of laser sources can be respectively used to generate the plurality of laser lights of different wavelengths.
  • the spectroscopic device 120 can be selected so that, among the plurality of excitation lasers emitted from the spectroscopic device, the emission directions of the excitation lasers of adjacent wavelengths are sandwiched between The angle is not smaller than a threshold angle, so that the difference between the incident angles of excitation laser light of adjacent wavelengths incident on the first dichroic mirror is not smaller than a desired angle difference.
  • the desired angular difference may be determined based on a ratio of a minimum spot distance to the focal length of the objective lens, for example equal to or greater than the ratio of the minimum light spot distance to the focal length of the objective lens.
  • the minimum spot distance indicates the minimum distance that the focused spots of the multiple excitation lasers on the sample need to be separated from each other, which can be properly determined in various possible ways according to the situation.
  • the minimum spot distance may be related to the requirements of specific applications, and may be predetermined based on the specific applications targeted by the detection device.
  • the required minimum spacing between light spots may be different.
  • the minimum spot distance can be determined to meet the following conditions: greater than the size of the spots in the corresponding directions formed by the multiple lasers coupled from the optical fiber without dispersion of the multiple lasers on the sample surface (spot The size of the narrow side, ie the width of the light spot; in the case of FIG.
  • the minimum spot distance is determined to be equal to the height of the field of view of the imaging system on the sample in a specific application.
  • the threshold angle may be determined based on the ratio of the minimum spot distance to the focal length of the objective lens.
  • the threshold angle can be determined to be equal to the ratio of the minimum spot distance to the focal length of the objective lens multiplied by a coefficient, and the coefficient can be predetermined to take into account, for example but not limited to: Whether the excitation laser light needs to undergo shaping/zooming before being received by the first dichroic mirror, the angular magnification that the excitation laser light emitted from the spectroscopic device may need to undergo before being received by the first dichroic mirror, etc.
  • said coefficient may be equal to 1, for example if there is no shaping means between said beam splitting means and said first dichroic mirror.
  • the detection device may include at least one of the following shaping devices: a first beam shaping device positioned between the optical fiber and the splitting device, positioned to convert the The incident laser beam is shaped and then transmitted to the beam splitting device; the second beam shaping device located between the beam splitting device and the first dichroic mirror is positioned so that the beams emitted from the beam splitting device are respectively connected to the beam splitting device.
  • the multiple excitation lasers corresponding to the multiple incident lasers with different wavelengths are shaped and transmitted to the first dichroic mirror.
  • Each of the first beam shaping means and the second beam shaping means can be realized in various possible ways.
  • the first beam shaping device may include a first lens group for performing desired shaping and zooming on the incident laser light to be incident on the spectroscopic device, such as but not limited to the way of making the incident laser light form a spot of desired shape and/or size Incident to the beam splitting device;
  • the second beam shaping device may include a second lens group for performing desired shaping and zooming of the excitation laser light emitted from the beam splitting device, such as but not limited to making the excitation laser light form a desired shape and/or size
  • the light spot is incident on the first dichroic mirror.
  • its angular magnification can be appropriately determined according to the situation, and its specific composition and structure can be designed based on the desired angular magnification.
  • the spectroscopic device includes a single dispersive prism, and the single dispersive prism is positioned so that each of the multiple incident laser light with different wavelengths from the optical fiber is incident on the first dispersive prism of the single dispersive prism.
  • a refractive surface then emerges from a second refractive surface of the single dispersive prism different from the first refractive surface.
  • the incident angles of the multiple incident lasers with different wavelengths incident on the first refracting surface of the single dispersive prism may be different, and not necessarily fixed angles, and may be related to the orientation and arrangement angle of the single dispersive prism.
  • the single dispersive prism may be positioned such that each of the plurality of incident laser light of different wavelengths is incident on the first refractive surface of the single dispersive prism at a predetermined angle of incidence, the predetermined angle of incidence being selected In order to minimize the deflection angle between the incident direction of the incident laser light incident on the first refraction surface and the corresponding emission direction of the excitation laser light emitted from the second refraction surface.
  • the single dispersion prism may have an apex angle formed between the first refraction surface and the second refraction surface, the first refraction surface and the second refraction surface being adjacent to the single dispersion prism , the single dispersion prism is selected such that the combination of its apex angle and the material forming it is such that the included angle is not less than the threshold angle.
  • the single dispersion prism may be, for example but not limited to, a triangular prism such as a right-angle prism with an apex angle of 45° and a material of N-SF11, a quadrangle prism, and the like.
  • a certain corner of the quadrangular prism can be used as an apex angle, and two adjacent refraction surfaces defining the corner of the quadrangular prism can be respectively used as an incident surface for receiving laser light and an outgoing surface for outputting laser light.
  • the laser light is refracted, which can be achieved by properly positioning the quadrangular prism.
  • its material, apex angle, etc. are known, and the predetermined incident angle can be determined by means of prior art such as table lookup and calculation.
  • the first dispersion prism among the plurality of dispersion prisms that first receives the incident laser light of the plurality of different wavelengths from the optical fiber may be positioned so that the incident laser light of the plurality of different wavelengths from the optical fiber
  • Each of the dispersing prisms is incident on its first refracting surface and then emerges from its second refracting surface
  • each of the plurality of dispersing prisms except the first dispersing prism may be positioned such that from its adjacent previous
  • Each of the laser beams emitted by the dispersion prism is incident on its first refraction surface and then exits from its second refraction surface.
  • the light splitting device can also be realized by a grating.
  • the orientation, position and possible An appropriate combination of the quantity and the like enables the spectroscopic device to meet the above-mentioned relevant requirements.
  • the terms "front”/"rear”, “front”/”rear”, “before”/”after”, “previous”/”next” are based on the light propagation direction.
  • the component that the light passes through first may be referred to as the preceding component, the preceding component or Previous component.
  • the detection device of the present invention it is not limited to using laser light from an optical fiber as described in the above embodiments, but can use excitation light from various other light sources, such as light emitted by an LED light source, by Light from a halogen light source, etc.
  • a detection device 20 includes the following components: a multimode optical fiber 210, a first beam shaping device 270, a laser filter 290, a dispersion prism 220, and a second beam shaping device 280 , dichroic mirror 1 230, objective lens 240, dichroic mirror 2-dichroic mirror i+1 and filter 1-filter i forming the fluorescence guiding device 250, imaging lens 1- forming imaging system 260 Imaging lens i and camera 1-camera i, wherein, i represents the type/quantity of lasers of different wavelengths coupled through multimode fiber, which is an integer greater than 1. It should be understood that, for the purpose of clarity and simplification, only 3 kinds of wavelengths of laser light are shown in FIG. Applicable in the case of lasers with more or less wavelengths.
  • the detection device uses a multimode fiber 210 to coaxially couple lasers of i different wavelengths (i ⁇ 2) through the multimode fiber, and these lasers pass through the first beam shaping device 270 for optical path After shaping and filtering by the laser filter 290 , the light enters the first refraction surface of the dispersion prism 220 .
  • i ⁇ 2 different wavelengths of laser light
  • the detection device uses a multimode fiber 210 to coaxially couple lasers of i different wavelengths (i ⁇ 2) through the multimode fiber, and these lasers pass through the first beam shaping device 270 for optical path After shaping and filtering by the laser filter 290 , the light enters the first refraction surface of the dispersion prism 220 .
  • different wavelengths of laser light have different refractive indices, that is, different refraction angles.
  • the transmission angles of lasers with different wavelengths will be different after being refracted by the first refraction surface of the dispersion prism, and then refracted by the second refraction surface of the dispersion prism, the difference in transmission angles of lasers with different wavelengths will be enlarged. In this way, an included angle greater than zero will be generated between the transmission directions of laser light with different wavelengths.
  • the shorter the wavelength of the laser the larger the corresponding refractive index and the larger the refraction angle.
  • each laser will form its own spot (shown schematically by spot 1, spot 2, and spot i in Figure 2) and irradiate different positions of the sample.
  • the laser spots at all positions are all derived from a single wavelength of laser light.
  • the device uses multimode fiber coupling A, B, C three kinds of lasers (not shown) as an example for this equipment for further illustration.
  • the lasers A, B, and C are reflected by the dichroic mirror 1 230 and focused by the objective lens 240, and then irradiate different positions on the surface of the sample.
  • the illumination areas of the three lasers A, B, and C on the sample are respectively a, b, c (not shown), correspondingly excite fluorescence AX, BX, CX (not shown) in regions a, b, and c, respectively.
  • the scanning direction of the sample is the same as the forward direction of the illumination area of laser A (currently area a).
  • the three lasers A, B, and C excite fluorescence at the same time, and only one kind of fluorescence is excited and emitted at each irradiated position on the sample at each moment.
  • the A laser excites the fluorescence AX' in the new area
  • the B laser excites the fluorescence BX' in the a area
  • the C laser excites the fluorescence CX' in the b area.
  • the dichroic mirror 2 is chosen to transmit one of the fluorophores AX, BX, CX transmitted thereto such as AX to direct it to the corresponding filter 1 and to reflect the remaining fluorophores such as BX, CX to the dichroic Chromatic mirror 3; dichroic mirror 3 is selected to reflect one of the fluorescent light BX, CX transmitted thereto such as BX to direct it to the corresponding filter 2 and to transmit the remaining fluorescent light such as CX to the dichroic mirror 4; The dichroic mirror 4 is chosen to reflect the fluorescent light transmitted thereto such as CX to direct it to the corresponding filter 3 .
  • the single-channel fluorescence detection time of each FOV is T
  • the power of each laser is Wi
  • the laser spot size on the sample is Si.
  • the dispersing prisms can be suitably placed in many possible angles and orientations.
  • the placement of the dispersing prism can be determined based at least in part on the dichroic mirror 1, for example, so that the exit angle of the excitation laser beam refracted by the dispersing prism conforms to the range of incident light angles required by the design of the dichroic mirror 1.
  • the selection of the dispersion prism (for example, prism material, vertex angle, etc.) will be further illustrated below. Assuming that the focal length of the objective lens in the detection equipment is denoted by f, and the minimum required distance (i.e.
  • the minimum spot spacing) that the spots formed by different lasers on the sample need to be separated is denoted by d, when the approximate condition "the objective lens is a thin lens and the field angle of the objective lens ⁇ In the case of 5°", the minimum required angle ⁇ T ⁇ d/f that is incident on the laser beams of adjacent wavelengths incident on the dichroic mirror 1 to be separated can be determined, and the angle ⁇ T can be called the first threshold angle.
  • the dispersion ability of a prism is determined by the material of the prism, the size of the apex angle (the included angle formed by the incident surface and the outgoing surface of the prism), etc.
  • ⁇ T it is possible to determine the condition that the angle between the excitation lasers of adjacent wavelengths emitted from the dispersive prism needs to be satisfied—that is, the angle must not be less than the second threshold angle ⁇ T ', which can be
  • ⁇ T ' the angular magnification of the second beam shaping device arranged between the beam splitting device and the dichroic mirror 1 and determining based on the angle ⁇ T and the angular magnification, for example ⁇ T ' can be equal to the first threshold angle divided by the The absolute value of the angular magnification.
  • an appropriate prism can be selected from the available prisms based on the prism dispersion equation, so that the material and apex angle of the selected prism make the angle between the excitation lasers of adjacent wavelengths emitted from the prism meet the relevant requirements.
  • the degree of curvature of the laser image generated is the smallest (that is, the aberration is the smallest).
  • the prism Angular dispersion power D ⁇ is shown in formula (1):
  • ⁇ is the vertex angle of the prism
  • n is the refractive index of the prism (determined by the material of the prism)
  • ⁇ is the wavelength of the laser
  • dn/d ⁇ is the dispersion rate of the prism
  • b is the base length of the prism
  • a is the beam Width (related to the specific application, the beam width required by different applications is inconsistent).
  • a detection device 30 according to yet another embodiment of the present invention is shown in FIG. 3 .
  • the beam shaping device includes a first illuminating lens group 370 and a second illuminating lens group 380, and the dispersion prism is a triangular prism 320 as an example.
  • the detection device of the invention is further exemplified.
  • the combination of the first lighting lens group and the second lighting lens group forms a shaping zoom system.
  • Dichroic mirror group 330 may correspond in function and structure to the combination of the first dichroic mirror and the fluorescence guide in FIG. 1 or dichroic mirror 1 - dichroic mirror i+1 in FIG. 2 .
  • the prism is a 45° dispersion prism.
  • the beam path lies in the YZ plane, and the sample plane 300 of the sample to be irradiated by the laser is perpendicular to the YZ plane.
  • Lasers of two wavelengths, green laser and red laser are output through the coaxial coupling fiber 310 .
  • an angle is formed between the principal rays of the two lasers.
  • the light is then shaped by the second illuminating lens group 380 , and the final included angle between the central rays of the two lasers emitted from the second illuminating lens group must not be smaller than the aforementioned threshold angle ⁇ T .
  • the chief rays of the two lasers with different emission angles are transmitted to the objective lens 340 through the dichroic mirror in the dichroic mirror group 330, and are focused and imaged on the sample by the objective lens.
  • the spots of the two lasers are formed on different positions of the sample. split on the sample.
  • the fluorescence excited by the laser on the sample is collected by the objective lens 340 , split by the dichroic mirrors in the dichroic mirror group 330 , and guided to the imaging system 360 for imaging.
  • the central wavelength difference between the green laser and the red laser is 128nm, and the field of view height of the imaging system on the sample is 80 ⁇ m.
  • central wavelength can be understood as the peak wavelength of laser light.
  • the distance between the laser spots of adjacent wavelengths on the sample can be preset to be greater than 80 ⁇ m.
  • the beam diameter of the laser light is about 13.5 mm.
  • the distance between the intermediate position and the first illumination lens group is related to the size of the optical fiber and the focal length of the first illumination lens group. Assuming that in this embodiment the intermediate position is about 50 mm behind the first lighting lens group, the diameter of the light beam is about 50 mm behind the first lighting lens group for the laser beam emitted from the first lighting lens group beam diameter.
  • of lasers with different wavelengths needs to satisfy the inequality (2)
  • a prism with an apex angle of 45° and a material of N-SF11 is selected. Since the variation of the dispersion rate of most optical materials within the selected laser wavelength does not exceed an order of magnitude, the dispersion rate
  • ⁇ represents the wavelength difference between the red laser and the green laser.
  • the incident angle of the laser to the prism can be adjusted to meet the minimum deflection angle condition.
  • the minimum deviation angle condition is satisfied when the incident angle is 43.1°.
  • optical simulation it is obtained that the angle between the chief rays of the two wavelengths of lasers after dispersion by the prism is 1.2°, and when they finally reach the imaging objective lens, the angle between the chief rays of the red and green lasers is 0.82°>0.57°, which meets the requirements.
  • the spot distance between the spot formed by the red laser and the spot formed by the green laser on the final sample is about 0.16 mm. The simulation results are shown in Figure 4.
  • the upper part of the striped light spot is the light spot 4001 formed by the red laser
  • the lower part of the striped light spot is the light spot 4002 formed by the green laser.
  • the distance between the centers of the red and green light spots is about 0.16 mm.
  • TDI imaging technology is used.
  • the corresponding camera is triggered to take pictures.
  • the camera integration process when the sample is scanned by the system is shown in FIG. 5 .
  • the red and green lasers respectively excite different areas of the sample, and the excitation area of the laser spot on the sample corresponds to the corresponding camera object image one-to-one.
  • the red laser corresponds to camera A
  • the green laser corresponds to camera B.
  • the camera integration direction is along the direction of the narrow side of the light spot, and the fluorescence excitation has a sequence.
  • the camera integration is triggered synchronously, that is, the trigger interval of the camera trigger source corresponding to the red and green lasers is equal to the distance required for the spot to move 0.16mm relative to the sample (the spot is fixed and the sample is driven by a sliding table located in the XY plane). time interval.
  • the present invention can also be implemented as a detection system, such as but not limited to a gene sequencing system, which includes the detection device as described above.
  • a detection system such as but not limited to a gene sequencing system, which includes the detection device as described above.
  • the imaging system of the detection device of the present invention is used to collect the fluorescent signal on the sequencing chip as the sample to be detected.
  • Figure 8a shows the genes obtained by using the first prior art technique (i.e., simultaneous excitation), using the second prior art technique (i.e., time-sharing excitation) and using the present invention for the paired-end test of the test object DNA sequence The relationship between the data quality Q30 of the assay results and the read length.
  • Figure 8b shows the genes obtained by using the first prior art technique (i.e., simultaneous excitation), using the second prior art technique (i.e., time-sharing excitation) and using the present invention to perform double-end testing on the DNA sequence of the test subject The relationship between detection error rate and read length of detection results. Under the same conditions, the first prior art, the second prior art and the present invention are used for gene detection respectively.
  • the dotted line represents the test result obtained by using the first prior art
  • the hollow line (“time-sharing excitation 1") represents the test result obtained by using the second prior art
  • the solid line (“this "Invention") represents the test results obtained using the present invention.
  • evaluation index adopts Q30 and detection error rate (base recognition error rate) in the gene detection result, the higher Q30, the detection error rate The lower the value, the better and more accurate the detection result. From Fig. 8a and Fig.
  • the scheme of the present invention can be used in various applications that require excitation of fluorescence and detection of fluorescence, and is especially suitable for biochemical detection, such as gene detection or other occasions that require laser samples to generate fluorescence and detect the excited fluorescence.

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EP21962825.2A EP4394027A4 (en) 2021-11-03 2021-11-03 DETECTION DEVICE, GENETIC SEQUENCING SYSTEM AND DETECTION METHOD
CN202180100932.1A CN117716017A (zh) 2021-11-03 2021-11-03 检测设备、基因测序系统及检测方法
US18/705,710 US20250059599A1 (en) 2021-11-03 2021-11-03 Detecting apparatus, gene sequencing system, and detecting method
CA3236241A CA3236241A1 (en) 2021-11-03 2021-11-03 Detection apparatus, gene sequencing system, and detecting method
PCT/CN2021/128444 WO2023077306A1 (zh) 2021-11-03 2021-11-03 检测设备、基因测序系统及检测方法
AU2021472582A AU2021472582A1 (en) 2021-11-03 2021-11-03 Detection device, gene sequencing system, and detection method
JP2024525413A JP7850253B2 (ja) 2021-11-03 2021-11-03 検出装置、遺伝子配列決定システム、および検出方法

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117169185A (zh) * 2023-11-02 2023-12-05 深圳赛陆医疗科技有限公司 成像设备及基因测序仪
CN119044140A (zh) * 2024-10-15 2024-11-29 重庆生强医疗科技有限公司 用于荧光原位杂交的单通道三色扫描方法、系统及其应用
EP4563982A1 (en) * 2023-12-01 2025-06-04 GeneMind Biosciences Company Limited Optomechanical system and sequencing system

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107576639A (zh) * 2017-08-28 2018-01-12 博奥生物集团有限公司 便携式全集成dna现场检验微型全分析系统检测光路
CN109596587A (zh) * 2018-12-12 2019-04-09 中国科学院苏州生物医学工程技术研究所 双层同时成像的光学系统及其图像处理方法、设备、介质
CN111566528A (zh) * 2017-11-03 2020-08-21 加利福尼亚太平洋生物科学股份有限公司 用于改进光学波导传输和对准的系统、装置和方法
CN112646703A (zh) * 2020-12-29 2021-04-13 中国科学院长春光学精密机械与物理研究所 一种单分子荧光基因测序光学系统
CN113155826A (zh) * 2020-01-07 2021-07-23 深圳华大智造科技有限公司 检测装置

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108700460B (zh) * 2015-12-21 2020-11-03 威里利生命科学有限责任公司 成像系统和成像方法
JP6810167B2 (ja) * 2016-05-27 2021-01-06 ヴェリリー ライフ サイエンシズ エルエルシー ４ｄハイパースペクトル撮像のためのシステムおよび方法
US10394008B2 (en) * 2016-10-19 2019-08-27 Cornell University Hyperspectral multiphoton microscope for biomedical applications
US11029506B2 (en) * 2018-04-20 2021-06-08 Coluxa Inc. Scanning microscope with multiplexed light sources

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107576639A (zh) * 2017-08-28 2018-01-12 博奥生物集团有限公司 便携式全集成dna现场检验微型全分析系统检测光路
CN111566528A (zh) * 2017-11-03 2020-08-21 加利福尼亚太平洋生物科学股份有限公司 用于改进光学波导传输和对准的系统、装置和方法
CN109596587A (zh) * 2018-12-12 2019-04-09 中国科学院苏州生物医学工程技术研究所 双层同时成像的光学系统及其图像处理方法、设备、介质
CN113155826A (zh) * 2020-01-07 2021-07-23 深圳华大智造科技有限公司 检测装置
CN112646703A (zh) * 2020-12-29 2021-04-13 中国科学院长春光学精密机械与物理研究所 一种单分子荧光基因测序光学系统

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP4394027A4 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117169185A (zh) * 2023-11-02 2023-12-05 深圳赛陆医疗科技有限公司 成像设备及基因测序仪
CN117169185B (zh) * 2023-11-02 2024-02-13 深圳赛陆医疗科技有限公司 成像设备及基因测序仪
EP4563982A1 (en) * 2023-12-01 2025-06-04 GeneMind Biosciences Company Limited Optomechanical system and sequencing system
CN119044140A (zh) * 2024-10-15 2024-11-29 重庆生强医疗科技有限公司 用于荧光原位杂交的单通道三色扫描方法、系统及其应用

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