WO2024092682A1 - Système optique et procédé de détection - Google Patents

Système optique et procédé de détection Download PDF

Info

Publication number
WO2024092682A1
WO2024092682A1 PCT/CN2022/129701 CN2022129701W WO2024092682A1 WO 2024092682 A1 WO2024092682 A1 WO 2024092682A1 CN 2022129701 W CN2022129701 W CN 2022129701W WO 2024092682 A1 WO2024092682 A1 WO 2024092682A1
Authority
WO
WIPO (PCT)
Prior art keywords
lens
sample
mobile terminal
biochemical
reaction
Prior art date
Application number
PCT/CN2022/129701
Other languages
English (en)
Chinese (zh)
Inventor
杨斌
严育宜
姜鹤鸣
Original Assignee
深圳华大智造科技股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 深圳华大智造科技股份有限公司 filed Critical 深圳华大智造科技股份有限公司
Priority to PCT/CN2022/129701 priority Critical patent/WO2024092682A1/fr
Publication of WO2024092682A1 publication Critical patent/WO2024092682A1/fr

Links

Images

Classifications

    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements

Definitions

  • the present invention relates to the field of optics, and in particular to an optical system and a detection method.
  • an object of the present invention is to provide an optical system and a detection method to popularize and facilitate gene sequencing.
  • the present invention has the following technical solutions:
  • optical system including:
  • a first lens and a second lens are sequentially arranged along the optical axis from the object side toward the image side, the first lens and the second lens are correspondingly arranged, the second lens is configured in a mobile terminal, the first lens and the second lens have the same aperture number and the same focal length, and the exit pupil of the first lens is located at the entrance pupil of the second lens; the mobile terminal is used to collect image data of an external sample to be detected through the second lens and the first lens in sequence and obtain a corresponding optical image.
  • the first lens has a first optical element combination
  • the second lens has a second optical element combination
  • the first optical element combination and the second optical element combination are arranged in mirror symmetry with each other.
  • the first lens includes a first lens, a second lens, a third lens, a fourth lens and a fifth lens from the object side to the image side, the first lens is a plane mirror, the object side surface of the second lens is concave, and the image side surface is convex, the third lens and the fifth lens are both biconvex lenses, and the object side surface of the fourth lens is a plane, and the image side surface is concave.
  • first lenses and multiple second lenses there are multiple first lenses and multiple second lenses, and the multiple first lenses and multiple second lenses are arranged corresponding to each other in pairs, different first lenses have different focal planes, and the different focal planes are parallel to each other.
  • the number of the first lens and the second lens is 2, two second lenses are arranged in the same mobile terminal and have different focal lengths; and a line connecting the center points of the two second lenses is parallel to any of the focal planes.
  • a filter is arranged between the corresponding first lens and the second lens, and the filter is used to pass light of a preset band and block light of bands outside the preset band.
  • the plane where the filter is located is the symmetric center plane of the corresponding first lens and the second lens.
  • the present application provides a detection method, which includes:
  • a first image is obtained by photographing a first field of view area of a sample chip with an additional lens connected to an external mobile terminal, wherein the mobile terminal has a built-in lens, the additional lens and the built-in lens have the same aperture number and the same focal length, and the exit pupil of the additional lens is located at the entrance pupil of the built-in lens; the mobile terminal and the additional lens are located on one side of the sample chip, and the sample chip can generate a detectable fluorescence signal.
  • the method further includes:
  • the excitation light source When the excitation light source is used to illuminate the second field of view area of the sample chip from the side of the sample chip away from the mobile terminal, the second field of view area is photographed by the mobile terminal to obtain a second image.
  • the fluorescent signal is generated by a catalytic reaction in the sample chip, and the method further comprises:
  • the sample chip After photographing the first field of view area, the sample chip is moved so that the built-in lens and the additional lens face the second field of view area of the sample chip and the second field of view area is photographed by the mobile terminal to obtain a second image.
  • a filter is provided between the built-in lens and the additional lens, the filter is used to pass light of a preset band and block light emitted by the excitation light source, and the central wavelength of the fluorescence excited by the sample chip after being irradiated by the excitation light source belongs to the preset band.
  • the multiple built-in lenses and the multiple additional lenses are arranged in one-to-one correspondence, different additional lenses have different focal planes, and the different focal planes are parallel to each other; the first field of view area includes multiple detection areas respectively located at multiple focal planes, and the multiple detection areas are opposite to the multiple additional lenses.
  • the number of the additional lens and the built-in lens is 2, the two built-in lenses are arranged in the same mobile terminal and have different focal lengths; a line connecting the center points of the two built-in lenses is parallel to any of the focal planes;
  • the sample chip includes a stacked substrate and a cover plate, and two layers of samples to be tested located between the substrate and the cover plate, the two layers of samples to be tested are respectively located at a first focal plane and a second focal plane, the first focal plane is a surface of the substrate facing the cover plate, and the second focal plane is a surface of the cover plate facing the substrate.
  • the additional lens has a first optical element combination
  • the additional lens has a second optical element combination
  • the first optical element combination and the second optical element combination are arranged in mirror symmetry with each other.
  • An embodiment of the present application also provides a portable biochemical testing optical system, including a mobile terminal and an auxiliary mechanism cooperating with the mobile terminal, the mobile terminal having a second lens, the auxiliary mechanism being detachably mounted on the mobile terminal, and the auxiliary mechanism comprising a first lens, the first lens corresponding to the second lens and being mounted on the object side of the second lens, the first lens and the second lens having the same aperture number and the same focal length, the exit pupil of the first lens being located at the entrance pupil of the second lens; the mobile terminal being used to collect detectable signals of an external biochemical sample to be detected through the second lens and the first lens in sequence and obtain corresponding optical images.
  • the first lens has a first optical element combination
  • the second lens has a second optical element combination
  • the first optical element combination and the second optical element combination are arranged in mirror symmetry with each other.
  • the auxiliary mechanism includes a filter located on a side of the second lens close to the first lens, and the second optical element combination and the second optical element combination are arranged in a mirror-symmetrical manner with respect to the filter.
  • the biochemical sample to be detected is a nucleic acid sequencing library.
  • the biochemical sample to be tested is a tissue sample.
  • the biochemical sample to be detected undergoes a biochemical reaction with reagents of multiple different reaction components to generate the detectable signal;
  • the reaction components include at least one of a sample generation component or a sample analysis component;
  • the biochemical reaction includes controlling reaction conditions so that different sample generating components generate the sample.
  • the biochemical reaction includes analyzing the sample, including reacting a sample analysis component with the sample to provide the associated detectable signal.
  • the embodiment of the present application provides a biochemical testing method, comprising: loading a sample to be tested into a channel of a chip circulation pool; and loading a reagent having a plurality of different reaction components into the channel of the chip circulation pool to perform a biochemical reaction between the sample to be tested and the reagent;
  • the reaction components include at least one of a sample generation component or a sample analysis component;
  • the biochemical reaction comprises generating a sample in a channel of the chip flow cell, comprising allowing different sample generating components to flow into the channel and controlling reaction conditions of the channel to generate the sample;
  • the biochemical reaction includes analyzing the sample in the channel, including flowing a sample analysis component into the channel, the sample analysis component reacting with the sample to provide an associated detectable signal;
  • the biochemical testing method also includes: using a portable optical system to identify the detectable signal, the portable optical system includes a mobile terminal and an auxiliary mechanism cooperating with the mobile terminal, the mobile terminal has a second lens, the auxiliary mechanism is detachably installed on the mobile terminal, and the auxiliary mechanism includes a first lens, the first lens corresponds to the second lens and is installed on the object side of the second lens, the first lens and the second lens have the same aperture number and the same focal length, and the exit pupil of the first lens is located at the entrance pupil of the second lens; the mobile terminal collects the detectable signal through the second lens and the first lens in turn and obtains the corresponding optical image.
  • the biochemical reaction is a nucleic acid sequencing reaction
  • the sample to be detected is a nucleic acid sequencing library.
  • the detectable signal is an optical signal.
  • the sample to be detected is a tissue sample
  • the biochemical reaction is a specific binding reaction
  • An embodiment of the present invention provides an optical system and a detection method.
  • the optical system includes a first lens and a second lens which are arranged in sequence from the object side to the image side along the optical axis.
  • the first lens and the second lens are arranged correspondingly.
  • the second lens is configured in a mobile terminal.
  • the first lens and the second lens have the same aperture number and the same focal length.
  • the exit pupil of the first lens is located at the entrance pupil of the second lens.
  • the mobile terminal can be used to collect image data of an external sample to be detected through the second lens and the first lens in sequence and obtain a corresponding optical image, so as to analyze and obtain a target base sequence, thereby making a gene sequencer more miniaturized and making gene sequencing more miniaturized, convenient and popular.
  • FIG1 is a schematic diagram of a current gene sequencing method
  • FIG2 is a schematic diagram of the structure of an optical system provided in an embodiment of the present application.
  • FIG3 is an optical principle diagram of an optical system provided in an embodiment of the present application.
  • FIG4 is a schematic diagram of a detection process provided in an embodiment of the present application.
  • FIG5 is a schematic diagram of the structure of a sample chip provided in an embodiment of the present application.
  • FIG6 is a wavelength schematic diagram provided in an embodiment of the present application.
  • FIG7 is a schematic diagram of field of view distribution in a sample chip provided in an embodiment of the present application.
  • FIG8 is a parameter diagram provided in an embodiment of the present application.
  • FIG. 9 is a schematic diagram of the structure of another sample chip provided in an embodiment of the present application.
  • FIG. 1 a schematic diagram of a current gene sequencing method is shown.
  • the dotted line portion is the imaging system of the gene sequencer, which is composed of a microscope objective, a dichroic mirror, a filter, a tube lens, and a camera.
  • the biological sample is combined with a fluorescent dye, and the sample is excited to generate a fluorescent signal through an illumination system including an excitation light source and a beam shaping module.
  • the fluorescent signal generated by the sample is photographed by a camera after passing through a microscope system composed of a microscope objective, a series of dichroic mirrors, a filter, and a tube lens.
  • the target base sequence can be analyzed by analyzing the captured image.
  • the imaging system of such a gene sequencer is large in size and complex in structure.
  • the installation and use of the microscope objective requires professionals, which is not universal to the general public.
  • the field of view of the microscope objective is small, and the requirements for the preparation of biological samples are relatively high.
  • an embodiment of the present application provides an optical system and a detection method, wherein the optical system includes a first lens and a second lens which are sequentially arranged along an optical axis from an object side toward an image side, the first lens and the second lens are arranged correspondingly, the second lens is configured in a mobile terminal, the first lens and the second lens have the same aperture number and the same focal length, and the exit pupil of the first lens is located at the entrance pupil of the second lens.
  • the mobile terminal can be used to collect image data of an external sample to be detected through the second lens and the first lens in sequence and obtain a corresponding optical image, thereby analyzing and obtaining a target base sequence, making the gene sequencer more miniaturized, and making gene sequencing more miniaturized, convenient and popular.
  • FIG. 2 is a structural schematic diagram of an optical system provided in an embodiment of the present application.
  • the optical system includes a first lens 10 and a second lens 20 arranged in sequence from the object side to the image side along the optical axis direction.
  • the first lens 10 and the second lens 20 are arranged correspondingly.
  • the second lens 20 is configured in a mobile terminal 200 as a built-in lens of the mobile terminal 200.
  • the first lens 10 serves as an additional lens of the mobile terminal.
  • the first lens 10 and the second lens 20 have the same aperture number and the same focal length.
  • the mobile terminal 200 can be a device with a camera such as a mobile phone or a tablet computer.
  • the first lens 10 and the second lens 20 may have the same structure or different structures. Of course, different structures need to achieve the same aperture number and the same focal length.
  • the first lens 10 and the second lens 20 have the same structure, the first lens 10 and the second lens 20 are symmetrical about the center plane between the first lens 10 and the second lens 20.
  • the first lens 10 may be an inverted lens in another mobile terminal, or an independent lens.
  • the first lens 10 and the second lens 20 may each include a plurality of lenses, that is, the first lens 10 includes a first optical element combination, the second lens 20 includes a second optical element combination, and the first optical element combination and the second optical element combination are arranged in mirror symmetry with each other.
  • the optical element combination defined in the present application includes the surface structure of each optical element, the arrangement method, and the distance between the optical elements.
  • the exit pupil of the first lens 10 is located at the entrance pupil of the second lens 20, so that the light diffused by the first lens 10 can be completely received by the second lens 20 without causing signal loss, thereby achieving measurement of a large numerical aperture (NA) and a large field of view (FOV), so that the mobile terminal can be used to collect image data of an external sample to be detected through the second lens 20 and the first lens 10 in sequence and obtain a corresponding optical image.
  • NA numerical aperture
  • FOV large field of view
  • the aperture number of the first lens 10 and the second lens 20 is recorded as F, then the NA of the optical system is about 1/2F, the magnification ⁇ is 1, the image plane size is equal to the field of view size, the pixel size is recorded as ⁇ , the pixel size is recorded as X*Y, and the size of the FOV is ⁇ *(X+Y).
  • the pixel size ⁇ 1.7um
  • the pixel size is 3024*4032.
  • the structure in the left box is the structure of the first lens 10
  • the structure in the right box is the structure of the second lens 20.
  • the first lens 10 includes a first lens, a second lens, a third lens, a fourth lens and a fifth lens in sequence.
  • the first lens is a plane mirror
  • the object side surface of the second lens is a concave surface
  • the image side surface is a convex surface.
  • the third lens and the fifth lens are both biconvex lenses
  • the object side surface of the fourth lens is a plane surface
  • the image side surface is a concave surface.
  • the second lens 20 is symmetrical to the first lens 10, and the second lens 20 includes a fifth lens, a fourth lens, a third lens, a second lens and a first lens in sequence.
  • the two first lenses have the same structure and are symmetrical about the central plane
  • the two second lenses have the same structure and are symmetrical about the central plane
  • the two third lenses have the same structure and are symmetrical about the central plane
  • the two fourth lenses have the same structure and are symmetrical about the central plane
  • the two fifth lenses have the same structure and are symmetrical about the central plane.
  • the number of the first lens 10 and the second lens 20 can be multiple, and the multiple first lenses 10 and the multiple second lenses 20 are arranged in pairs, that is, a corresponding first lens 10 and the first second lens 20 are regarded as a lens group.
  • the optical system may include multiple lens groups.
  • the first lens 10 and the second lens 20 belonging to the same lens group have the same focal length and the same aperture number, and the exit pupil of the first lens 10 is located at the entrance pupil of the second lens 20.
  • Different first lenses 10 can have different focal planes, and these focal planes are parallel to each other.
  • multiple second lenses 20 can be set in different mobile terminals, so that the planes where the center points of the multiple second lenses 20 are located are perpendicular to the optical axis of the lens group.
  • the second lenses 20 can have different focal lengths, so that the first lens 10 has different focal planes; or multiple second lenses 20 can also be set in different mobile terminals.
  • the first lens 10 can have different focal planes.
  • the planes where the center points of the multiple second lenses 20 are located can be perpendicular to the optical axis of the lens group.
  • the second lenses 20 can have different focal lengths, so that the first lens 10 has different focal planes.
  • the multiple second lenses 20 can be at different distances from the same focal plane, and the multiple second lenses 20 have the same focal length, so that the first lens 10 has different focal planes.
  • the number of the first lens 10 and the second lens 20 is 2, the two second lenses 20 are arranged in the same mobile terminal and have different focal lengths, and the center point line of the two second lenses 20 is parallel to any focal plane, then the two second lenses 20 can have two focal planes respectively, which are recorded as the first focal plane and the second focal plane.
  • objects in the first focal plane and the second focal plane can be photographed, for example, focusing on the first focal plane to photograph a first object in the first focal plane, and then focusing on the second focal plane to photograph a second object in the second focal plane.
  • a filter 30 may be arranged between the corresponding first lens 10 and the second lens 20.
  • the filter 30 may pass light of a preset band and block light of bands outside the preset band.
  • the plane where the filter is located is the symmetrical center plane of the corresponding first lens 10 and the second lens 20.
  • an embodiment of the present application also provides a detection method, in which a sample chip can generate a detectable fluorescence signal, and a first image can be obtained by photographing a first field of view area of the sample chip 40 by connecting an additional lens to the mobile terminal 200.
  • the mobile terminal 200 has a built-in lens, and the additional lens and the built-in lens have the same aperture number and the same focal length, and the exit pupil of the additional lens is located at the entrance pupil of the built-in lens.
  • the excitation light source 50 can be used to illuminate the first field of view area of the sample chip 40 from the side of the sample chip 40 away from the mobile terminal to excite a detectable fluorescent signal.
  • the sample chip 40 has a sample to be detected, and the sample to be detected can be a biochemical sample to be detected, such as a DNA nanoball (DNB) combined with a fluorescent dye.
  • DNB DNA nanoball
  • the DNA nanoball combined with the fluorescent dye generates fluorescence when irradiated with the excitation light emitted by the excitation light source.
  • an additional lens and a built-in lens are used to directly capture images of the fluorescence signal of the sample chip.
  • an excitation light source and a filter there is no need to apply an excitation light source and a filter.
  • the catalytic reaction in the sample chip produces a detectable fluorescence signal.
  • the detectable fluorescence signal in the sample chip is produced by enzyme-catalyzed substrates.
  • the arrangement of the additional lens and the built-in lens may refer to the arrangement of the aforementioned first lens 10 and the second lens 20.
  • Both the additional lens and the built-in lens may include a plurality of lenses, that is, the additional lens has a first optical element combination, the built-in lens has a second optical element combination, and the first optical element combination and the second optical element combination are arranged in mirror symmetry with each other.
  • the excitation light source 50 and the mobile terminal may be located on opposite sides of the sample chip 40, the side where the excitation light source 50 is located is recorded as the first side, and the side where the mobile terminal is located is recorded as the second side, and the additional lens is also located on the second side of the sample chip 40.
  • the excitation light source 50 is used to illuminate the first field of view area of the sample chip 40 from the first side of the sample chip 40
  • the mobile terminal 200 may be used to photograph the first field of view area to obtain a first image.
  • the size of the first field of view area is determined according to the field of view sizes of the additional lens and the built-in lens.
  • the first image is formed on a sensor of the mobile terminal 200.
  • the illumination of the first field of view area of the sample chip 40 by the mobile terminal 200 may be achieved by the shooting system of the mobile terminal 200 itself.
  • the sample chip 40 may include a substrate 401 and a cover plate 402, and the sample 403 to be tested is disposed between the substrate 401 and the cover plate 402.
  • the sample 403 to be tested may be a nucleic acid library, wherein the cover plate 402 may be located on the side of the sample chip 40 facing the optical system, and the substrate 401 may be located on the side of the sample chip 40 facing the excitation light source 50.
  • the nucleic acid library may be placed on the substrate 401 and then fixed by the top cover plate 402.
  • the excitation light source 50 irradiates the nucleic acid library from the bottom, and the mobile terminal 200 is located above the sample chip 40 so that the mobile terminal 200 can shoot from above the sample chip 40.
  • the filter 30 can be used to pass light of a preset wavelength band and suppress light of other wavelength bands outside the preset wavelength band.
  • the preset wavelength band can be selected, so that the central wavelength of the fluorescence excited by the sample chip 40 after being irradiated by the excitation light source 50 belongs to the preset wavelength band, while the excitation light emitted by the excitation light source 50 does not belong to the preset wavelength band.
  • the filter 30 can be used to select the fluorescence and filter the excitation light.
  • the sample to be detected is a DNA nanosphere, which is combined with the fluorescent dye Alexa Fluor 532, the central wavelength of the excitation light is 532nm, and the central wavelength of the emission light is 553nm
  • an excitation light source with a central wavelength of 532nm and a filter with a preset wavelength of 540nm to 580nm can be selected, as shown in Figure 6, which is a wavelength schematic diagram provided in an embodiment of the present application, wherein the horizontal axis is the wavelength and the vertical axis is dimensionless. It can be seen that the filter 30 can be used to select the fluorescence and filter the excitation light.
  • the sample chip 40 may have a larger size so that more samples to be detected can be set. If the first field of view area is smaller than the entire area of the sample chip 40, after photographing the first field of view area, the second field of view area of the sample chip 40 may also be photographed. Specifically, if the detectable fluorescent signal is excited by the irradiation of the excitation light source, the excitation light source 50 may be turned off, and the sample chip 40 may be moved so that the built-in lens and the additional lens face the second field of view area of the sample chip 40.
  • the second field of view area of the sample chip 40 is irradiated from the side of the sample chip 40 away from the mobile terminal by the excitation light source 50, the second field of view area is photographed by the mobile terminal 200 to obtain a second image; if the fluorescent signal is generated by a catalytic reaction in the sample chip, after photographing the first field of view area, the sample chip may be moved so that the built-in lens and the additional lens face the second field of view area of the sample chip, and the second field of view area may be photographed by the mobile terminal to obtain a second image.
  • the first field of view area and the second field of view area may have the same size.
  • the third field of view area and other areas of the sample chip 40 may also be photographed until all areas of the sample chip 40 are photographed.
  • the target base sequence may be obtained by analyzing the photographed images.
  • the size of the sample chip 40 is 20mm*100mm, according to the size of the FOV, a chip has approximately 16 FOVs, as shown in Figure 7, which is a schematic diagram of the field of view distribution in a sample chip provided in an embodiment of the present application, and multiple FOVs are arranged vertically in the sample chip.
  • each DNB can occupy one pixel, and the distance between different DNBs can be one pixel. Then each DNB occupies at least 2 pixels in the horizontal direction and at least 2 pixels in the vertical direction, for a total of four pixels. Referring to FIG7 , the black circle represents the pixel.
  • the sample chip 40 can be photographed to obtain an image corresponding to the base.
  • the biochemical reaction time required for the fluorescent dye to combine with the base is 20 seconds
  • the time required to photograph a FOV in the sample chip 40 is 10 seconds
  • FIG8A a parameter diagram is provided in an embodiment of the present application, wherein the fluorescence wavelength (Longest dye wavelength) is 553 nm, the NA is 0.3125, the interval of each DNB obtained by the Rayleigh criterion (Resolution By Rayleigh) is 1079 nm, the size (Pitch) occupied by each DNB in the sample chip is 3400 nm, the pixel size (Pixel Size) is 1.7 um, the ratio of pixel (pixel) to DNB is 2, the amplification (Amplification) is 1.00, the pixel size is: the X-direction size (Resolution-X) is 4032, the Y-direction size (Resolution-Y) is 3024, the diagonal size (Diagonal) in the mobile terminal sensor size (CMOS Sensor Size) is 8.57 mm, and the target FOV size (Objective FOV) is 1.7 um.
  • the fluorescence wavelength Longest dye wavelength
  • the NA is 0.3125
  • the diagonal size of the objective FOV is 8.568 mm
  • the number of DNBs in each FOV is 3048192
  • the X-direction size of the target FOV is 6.8544 mm
  • the Y-direction size of the target FOV is 5.1408 mm
  • the number of FOVs contained in each sample chip is 16
  • the shooting time required for each sample chip is 12 min
  • the number of samples contained in each sample chip is 48.771M.
  • the specifications of the sample chip include: FOV area (FOV Area) is 35.23709952 mm 2 , each round of imaging time (Imaging Time/chip) is 3 min, the width (chip width) of the sample chip (chip width) is 20 mm, the length (chip length) is 100 mm, and the area (chip area) is 2000 mm 2 .
  • the number of additional lenses and built-in lenses can be multiple, and the multiple additional lenses and the multiple built-in lenses are arranged corresponding to each other in pairs. Different additional lenses can have different focal planes, and the different focal planes are parallel to each other.
  • the first field of view area may include multiple detection areas respectively located at the multiple focal planes, and the multiple detection areas are facing the multiple additional lenses, so that the multiple additional lenses and the built-in lenses corresponding to the multiple additional lenses are used to shoot the multiple detection areas, thereby further improving the shooting efficiency and reducing the number of times the sample chip is moved.
  • multiple built-in lenses can be arranged in different mobile terminals, so that the planes where the center points of the multiple built-in lenses are located are perpendicular to the optical axis of the lens group.
  • the built-in lenses can have different focal lengths, so that the additional lenses have different focal planes; or multiple built-in lenses can also be arranged in different mobile terminals, and by setting the positions of multiple mobile terminals and the focal lengths of the multiple built-in lenses, the additional lenses can have different focal planes.
  • the planes where the center points of the multiple built-in lenses are located can be perpendicular to the optical axis of the lens group.
  • the built-in lenses can have different focal lengths, so that the additional lenses have different focal planes.
  • the multiple built-in lenses can be at different distances from the same focal plane, and the multiple built-in lenses have the same focal length, so that the additional lenses have different focal planes.
  • the number of additional lenses and built-in lenses is 2, and the two built-in lenses are set in the same mobile terminal and have different focal lengths.
  • the line connecting the center points of the two built-in lenses is parallel to any focal plane, and the two built-in lenses can have two focal planes respectively, which are recorded as the first focal plane and the second focal plane.
  • FIG. 9 it is a structural schematic diagram of another sample chip provided in an embodiment of the present application.
  • the sample chip includes a stacked substrate 401 and a cover plate 402, and two layers of samples to be tested 403 located between the substrate 401 and the cover plate 402. The two layers of samples to be tested 403 are located in the first focal plane and the second focal plane respectively.
  • the first focal plane is the surface of the substrate 401 facing the cover plate 402
  • the second focal plane is the surface of the cover plate 402 facing the substrate 401.
  • the mobile terminal can be used to focus on the first focal plane to shoot the sample to be tested at the first focal plane, and then focus on the second focal plane to shoot the sample to be tested at the second focal plane.
  • the DNBs in the two layers of samples to be tested can be staggered to avoid mutual influence during shooting.
  • the spacing between adjacent focal planes in the plurality of focal planes can enable one of the focal planes to be located within the focal depth range of other additional lenses other than the corresponding additional lens.
  • the spacing between adjacent focal planes is 1 um to 10 um.
  • the embodiment of the present invention provides a detection method, by shooting a first field of view area of a sample chip with an additional lens connected to an external mobile terminal to obtain a first image, the mobile terminal has a built-in lens, the additional lens and the built-in lens have the same aperture number and the same focal length, the exit pupil of the additional lens is located at the entrance pupil of the built-in lens, the mobile terminal and the additional lens are located on one side of the sample chip, and a detectable fluorescent signal can be generated in the sample chip.
  • the sample chip when the sample chip is irradiated with a laser light source, the sample chip can be photographed with a mobile terminal, so as to analyze and obtain the target base sequence, making the gene sequencer more miniaturized, and making gene sequencing more miniaturized, convenient and popular.
  • the embodiment of the present application also provides a portable biochemical inspection optical system, including a mobile terminal and an auxiliary mechanism that cooperates with the mobile terminal. The relationship between the mobile terminal and the auxiliary mechanism is equivalent to that between the above-mentioned mobile terminal 200 and the additional lens.
  • the mobile terminal has a second lens
  • the auxiliary mechanism is detachably mounted on the mobile terminal
  • the auxiliary mechanism includes a first lens
  • the first lens corresponds to the second lens and is mounted on the object side of the second lens
  • the first lens and the second lens have the same aperture number and the same focal length
  • the exit pupil of the first lens is located at the entrance pupil of the second lens
  • the mobile terminal is used to collect detectable signals of an external biochemical sample to be detected through the second lens and the first lens in sequence and obtain a corresponding optical image.
  • the first lens has a first optical element combination
  • the second lens has a second optical element combination
  • the first optical element combination and the second optical element combination are arranged in mirror symmetry with each other.
  • the auxiliary mechanism includes a filter located on a side of the second lens close to the first lens, and the second optical element combination and the second optical element combination are arranged in a mirror-symmetrical manner with respect to the filter.
  • the biochemical sample to be detected is a nucleic acid sequencing library.
  • the biochemical sample to be tested is a tissue sample.
  • the biochemical sample to be detected undergoes a biochemical reaction with reagents of multiple different reaction components to generate the detectable signal;
  • the reaction components include at least one of a sample generation component or a sample analysis component.
  • the biochemical reaction includes controlling reaction conditions so that different sample generating components generate the sample; and the biochemical reaction includes analyzing the sample, including allowing the sample analyzing components to react with the sample to provide the associated detectable signal.
  • An embodiment of the present application also provides a biochemical testing method, comprising: loading a sample to be tested into a channel of a chip circulation pool; and loading a reagent having a plurality of different reaction components into the channel of the chip circulation pool to perform a biochemical reaction of the sample to be tested and the reagent; the reaction component comprises at least one of a sample generation component or a sample analysis component.
  • the biochemical reaction includes generating a sample in a channel of the chip circulation pool, including allowing different sample generation components to flow into the channel and controlling the reaction conditions of the channel to generate the sample; and the biochemical reaction includes analyzing the sample in the channel, including allowing sample analysis components to flow into the channel, and the sample analysis components react with the sample to provide a related detectable signal.
  • the biochemical testing method also includes: using the above-mentioned portable optical system to identify the detectable signal, the portable optical system includes a mobile terminal and an auxiliary mechanism cooperating with the mobile terminal, the mobile terminal has a second lens, the auxiliary mechanism is detachably installed on the mobile terminal, and the auxiliary mechanism includes a first lens, the first lens corresponds to the second lens and is installed on the object side of the second lens, the first lens and the second lens have the same aperture number and the same focal length, and the exit pupil of the first lens is located at the entrance pupil of the second lens; the mobile terminal collects the detectable signal through the second lens and the first lens in turn and obtains the corresponding optical image.
  • the biochemical reaction is a nucleic acid sequencing reaction
  • the sample to be detected is a nucleic acid sequencing library.
  • the detectable signal is an optical signal.
  • the sample to be detected is a tissue sample
  • the biochemical reaction is a specific binding reaction

Landscapes

  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Engineering & Computer Science (AREA)
  • Multimedia (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

L'invention concerne un système optique et un procédé de détection. Le système optique comprend une première lentille (10) et une seconde lentille (20) qui sont agencées séquentiellement d'un côté objet à un côté image dans une direction d'axe optique. La première lentille (10) est disposée en correspondance avec la seconde lentille (20) ; la seconde lentille (20) est configurée dans un terminal mobile (200) ; la première lentille (10) et la seconde lentille (20) ont le même nombre F et la même longueur focale ; et la pupille de sortie de la première lentille (10) est située au niveau de la pupille d'entrée de la seconde lentille (20). De cette manière, le terminal mobile (200) peut être utilisé pour collecter séquentiellement, par l'intermédiaire de la première lentille (10) et de la seconde lentille (20), des données d'image d'un échantillon externe à détecter et obtenir une image optique correspondante, de façon à obtenir une séquence de base cible au moyen d'une analyse, rendant ainsi un séquenceur de gènes plus miniaturisé, et rendant le séquençage de gènes plus miniaturisé, pratique et populaire.
PCT/CN2022/129701 2022-11-04 2022-11-04 Système optique et procédé de détection WO2024092682A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/129701 WO2024092682A1 (fr) 2022-11-04 2022-11-04 Système optique et procédé de détection

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CN2022/129701 WO2024092682A1 (fr) 2022-11-04 2022-11-04 Système optique et procédé de détection

Publications (1)

Publication Number Publication Date
WO2024092682A1 true WO2024092682A1 (fr) 2024-05-10

Family

ID=90929211

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/129701 WO2024092682A1 (fr) 2022-11-04 2022-11-04 Système optique et procédé de détection

Country Status (1)

Country Link
WO (1) WO2024092682A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6838650B1 (en) * 1999-11-16 2005-01-04 Agilent Technologies, Inc. Confocal imaging
CN101952762A (zh) * 2008-01-02 2011-01-19 加利福尼亚大学董事会 高数值孔径远程显微镜设备
CN107260123A (zh) * 2017-06-09 2017-10-20 苏州大学 一种手机外接眼底成像镜头及眼底图像获取方法
CN110365915A (zh) * 2019-08-13 2019-10-22 苏州瑞霏光电科技有限公司 阵列透射式显微图像采集系统
CN111465882A (zh) * 2017-02-08 2020-07-28 Essenlix公司 用于测定的光学器件、装置和系统
WO2021189453A1 (fr) * 2020-03-27 2021-09-30 肯维捷斯（武汉）科技有限公司 Module d'imagerie microscopique à fluorescence miniature

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6838650B1 (en) * 1999-11-16 2005-01-04 Agilent Technologies, Inc. Confocal imaging
CN101952762A (zh) * 2008-01-02 2011-01-19 加利福尼亚大学董事会 高数值孔径远程显微镜设备
CN111465882A (zh) * 2017-02-08 2020-07-28 Essenlix公司 用于测定的光学器件、装置和系统
CN107260123A (zh) * 2017-06-09 2017-10-20 苏州大学 一种手机外接眼底成像镜头及眼底图像获取方法
CN110365915A (zh) * 2019-08-13 2019-10-22 苏州瑞霏光电科技有限公司 阵列透射式显微图像采集系统
WO2021189453A1 (fr) * 2020-03-27 2021-09-30 肯维捷斯（武汉）科技有限公司 Module d'imagerie microscopique à fluorescence miniature

Similar Documents

Publication Publication Date Title
US7463353B2 (en) Modular, micro-scale, optical array and biodetection system
CN1609593B (zh) 用于分析井板、凝胶和斑点的数字成像系统
TWI263072B (en) Method and system for reading microarrays
JP2009537021A (ja) 蛍光顕微鏡法におけるレーザー照射システム
US9338408B2 (en) Image obtaining apparatus, image obtaining method, and image obtaining program
US7978885B2 (en) Analysing biological entities
GB2351556A (en) Improved assay analysis
JP3824135B2 (ja) バイオチップ読取り装置
CN110824165B (zh) 基于微流控芯片和手机的肺癌肿瘤标志物检测装置及方法
US7499166B2 (en) Wide field imager for quantitative analysis of microarrays
WO2021159285A1 (fr) Système de formation d'image optique et système de détection de substance biochimique l'utilisant
Bilhorn et al. Elemental analysis with a plasma emission echelle spectrometer employing a charge injection device (CID) detector
US10921252B2 (en) Image processing apparatus and method of operating image processing apparatus
CN111896517A (zh) 微液滴三荧光信号检测装置
JP2008508537A (ja) 生物学的反応支持体微小付着物を支えるプレートを読み取るための装置
CN115524839A (zh) 一种用于数字elisa的大视野、高分辨成像系统和检测方法
CN110702657A (zh) 微液滴双荧光信号检测装置
WO2024092682A1 (fr) Système optique et procédé de détection
CN111349553A (zh) 一种基因测序仪光学系统
JP4043925B2 (ja) 生体関連物質マイクロアレイの読取装置及び方法
JP2001194303A (ja) 蛍光分子拡散運動解析装置
US20230221178A1 (en) Apparatus and a method for fluorescence imaging
WO2022120595A1 (fr) Système de mesure de super-résolution et procédé de mesure de super-résolution
JP2008051772A (ja) 蛍光画像取得装置、及び蛍光画像取得方法
JP2011209573A (ja) 合焦装置、合焦方法、合焦プログラム及び顕微鏡

Legal Events

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

Ref document number: 22963992

Country of ref document: EP

Kind code of ref document: A1