WO2023116847A1 - 荧光检测装置和用于荧光物质检测的手持设备 - Google Patents

荧光检测装置和用于荧光物质检测的手持设备 Download PDF

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Publication number
WO2023116847A1
WO2023116847A1 PCT/CN2022/141196 CN2022141196W WO2023116847A1 WO 2023116847 A1 WO2023116847 A1 WO 2023116847A1 CN 2022141196 W CN2022141196 W CN 2022141196W WO 2023116847 A1 WO2023116847 A1 WO 2023116847A1
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Prior art keywords
fluorescence
light
light source
detection device
filter
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PCT/CN2022/141196
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English (en)
French (fr)
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黄立志
谭勇兵
于鸫
刘丽萍
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广东唯实生物技术有限公司
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Publication of WO2023116847A1 publication Critical patent/WO2023116847A1/zh

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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
    • 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
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • 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
    • 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
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • 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
    • G01N2021/6463—Optics
    • 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
    • G01N2021/6463—Optics
    • G01N2021/6471—Special filters, filter wheel
    • 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
    • G01N2021/6463—Optics
    • G01N2021/6478—Special lenses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/02—Mechanical
    • G01N2201/022—Casings
    • G01N2201/0221—Portable; cableless; compact; hand-held

Definitions

  • the present application relates to the technical field of fluorescence detection equipment, in particular, to a fluorescence detection device and a handheld device for fluorescent substance detection.
  • fluorescent substances in the market mainly include fluorescent microspheres, fluorescent beams, quantum dots, etc., and the main excitation-fluorescence wavelengths are concentrated in the visible light range, such as 470-525nm, 635-680nm, 365-610nm and other wavelengths.
  • fluorescence wavelength There is a large difference in fluorescence wavelength, and there are fewer fluorescent substances with near-infrared wavelengths.
  • the near-infrared fluorescent dyes developed in recent years have the advantages of high water solubility and are not prone to conjugate precipitation or fluorescence quenching. The result is inaccurate, which limits the scope of application of this type of fluorescent substance.
  • the interference between the excitation light and the emission light (fluorescence emitted by the detected object) of the near-infrared fluorescent dye can be avoided through the design of the optical path.
  • Multi-layer filter elements are arranged in the light path and the emission light path to filter the excitation light and emission light, thereby suppressing interference noise.
  • POCT immunochromatographic point-of-care testing
  • the main purpose of this application is to provide a fluorescence detection device and a handheld device for fluorescent substance detection, which can solve the problem of interference between excitation light and emission light due to close wavelengths when detecting near-infrared fluorescent substances.
  • a fluorescence detection device including: a frame module; a light source, used to generate excitation light, and the excitation light irradiates the object to be detected after passing through the light source through hole arranged on the frame module, The object to be detected is excited by the excitation light to generate fluorescence; the optical path assembly on the frame module is used to receive the fluorescence and transmit the fluorescence to the optical signal detector; the filter assembly, the fluorescence passes through the filter assembly before being received by the optical signal detector Filtration; where the excitation light irradiated to the object to be detected is not on the same axis as the fluorescence received by the optical path assembly.
  • the optical signal detector is arranged on the frame module.
  • the optical path assembly includes a first lens module and a second lens module arranged coaxially, and the filter assembly includes a first filter located between the first lens module and the second lens module.
  • the first optical filter is a narrow-band optical filter.
  • the first optical filter has at least one of the following characteristics: the central wavelength of the first optical filter is between 800nm and 850nm, and the cut-off depth of the first optical filter is OD6; The cut-off range of the optical filter is from 300nm to 1100nm; the bandwidth of the first optical filter is less than 65nm.
  • the first lens module includes a first lens, the first lens is used to receive fluorescence and collimate the fluorescence, the first lens has a convex surface, and the convex surface of the first lens faces the first filter;
  • the second lens module includes a second lens, the second lens has a convex surface, and the convex surface of the second lens faces the first lens module.
  • the first lens and/or the second lens is a hemispherical lens.
  • the angle between the optical axis of the excitation light and the optical axis of the fluorescent light received by the optical path assembly is between 30 degrees and 70 degrees.
  • the angle between the optical axis of the excitation light and the optical axis of the fluorescent light received by the optical path assembly is between 45 degrees and 60 degrees.
  • the central axis of the light source through hole is inclined relative to the central axis of the optical path assembly.
  • the transmission angle of the optical path assembly is greater than or equal to 40 degrees and less than or equal to 65 degrees.
  • the transmission angle of the optical path assembly is greater than or equal to 50 degrees and less than or equal to 55 degrees.
  • the frame module is further provided with an optical path through hole for accommodating the optical path assembly, the light source through hole is located outside the light path through hole, and the light source through hole and the light path through hole are arranged at an angle.
  • the multiple light sources are arranged in one-to-one correspondence with the multiple light source through holes, and the multiple light source through holes are arranged around the circumference of the light path through hole.
  • the light source includes a first light source and a second light source, and two light source through holes corresponding to the first light source and the second light source are arranged symmetrically along the axis of the light path through hole.
  • the frame module includes a frame and a fixing member
  • the frame has a light path through hole and a light source through hole
  • the fixing member is used to fix the first lens module and the second lens module in the light path through hole.
  • At least a part of the side of the frame is inclined to form a slope
  • the light source is disposed in the groove of the slope
  • the light source through hole is disposed at the bottom of the groove.
  • the surface of the frame away from the object to be detected has a sink for accommodating the optical signal detector.
  • the filter assembly further includes a second filter located between the light source and the object to be detected, and the excitation light is filtered by the second filter before irradiating the object to be detected.
  • the second optical filter is a narrow-band optical filter.
  • the second optical filter has at least one of the following characteristics: the central wavelength of the second optical filter is between 675nm and 725nm; the cut-off depth of the second optical filter is OD6; The cut-off range of the second optical filter is from 300nm to 1100nm; the bandwidth range of the second optical filter is less than 65nm.
  • the fluorescence detection device further includes a slot frame and a plurality of spring pressing wheels, the frame module is arranged on the slot frame; and the plurality of spring pressing wheels are arranged on the upper end surface of the slot frame.
  • a card slot for inserting a reagent card is provided in the card slot frame.
  • a plurality of spring pressure wheels are located on both sides of the card slot, and the inner wall of the card slot is provided with Spring ball: when the reagent card is inserted, the spring pressing wheel abuts against the upper end surface of the reagent card, and the spring ball abuts against the side of the reagent card.
  • a handheld device for detecting fluorescent substances including the above-mentioned fluorescence detection device.
  • the fluorescence detection device includes a light source, an optical path assembly, an optical signal detector and a frame module, which are used to generate excitation light.
  • the object is excited by the excitation light to generate fluorescence;
  • the optical path assembly set on the frame module is used to receive the fluorescence and transmit the fluorescence to the optical signal detector;
  • the fluorescence is filtered by the filter assembly before being received by the optical signal detector; irradiated to the detected
  • the excitation light of the object is not coaxial with the fluorescence received by the optical path assembly.
  • the excitation light irradiated to the detected object and the fluorescence received by the optical path assembly are not in the same axis, so as to reduce the risk of excitation light entering the optical path assembly, and reduce the excitation light and fluorescence. interference between.
  • the fluorescence before the fluorescence enters the optical signal detector, it is filtered by the filter assembly to reduce the interference between the excitation light and the fluorescence and ensure the accuracy of detection.
  • the object to be detected When the object to be detected is irradiated by the light source, it will be stimulated to emit fluorescence, and the fluorescence enters the conductive light signal detector through the optical path assembly. Since the optical path assembly is set in the form of a combination of the first lens module and the second lens module, the collimation and convergence of the fluorescence can be realized to realize the detection of the fluorescence, and the inclined setting of the light source relative to the central axis of the optical path assembly reduces the number of detected objects. The interference between the excited fluorescence and the light reflected by the light source, through the filter component to filter the excitation light, ensures the accuracy of subsequent detection.
  • the optical path system in this application is formed by combining only two lens modules, which is conducive to the miniaturization of the optical path system, and the optical path system in this application can be applied to handheld devices for fluorescent substance detection, greatly The convenience of detecting fluorescent substances is increased, and the frame module can support various components of the device, increasing the stability of the device.
  • Fixing the frame module directly on the card slot frame can avoid the influence of unnecessary relative movement between the reagent card and the frame module on the fluorescence detection during the detection process.
  • the setting of the spring pressure wheel and the spring ball can make the reagent card enter and exit the card slot more smoothly, so that the reagent card can pass through the frame module at a more uniform speed during the fluorescence detection process to achieve higher precision detection.
  • FIG. 1 shows a schematic diagram of the overall structure of an optical path system in an optional embodiment of the present application
  • Figure 2 shows an exploded view of the optical path system in Figure 1;
  • Fig. 3 shows the spectrogram of fluorescent substance DyLight800
  • Fig. 4 shows the schematic diagram of photoelectric sensor photosensitivity
  • Figure 5 shows a light source spectrum
  • Figure 6 shows the filter spectrogram
  • Fig. 7 shows the structural diagram of the card slot frame
  • Fig. 8 shows the positional relationship between the frame module and the card slot frame in an optional embodiment of the present application
  • Fig. 9 shows a schematic diagram of the overall structure of an optical path system according to another optional embodiment of the present application.
  • orientation words such as “upper, lower, top, bottom” are generally used for the directions shown in the drawings, or for the parts themselves in the vertical, In terms of vertical or gravitational direction; similarly, for the convenience of understanding and description, “inside and outside” refer to inside and outside relative to the outline of each component itself, but the above orientation words are not used to limit the present application.
  • the present application provides a fluorescence detection device and a handheld device for detection of fluorescent substances.
  • the fluorescence detection device includes a light source 10, an optical path assembly 20, an optical signal detector 30, and a frame module 40 for generating excitation light, and the excitation light passes through the light source through hole 42 arranged on the frame module 40 After irradiating the object to be detected, the object to be detected is excited by the excitation light to generate fluorescence; the optical path assembly 20 arranged on the frame module 40 is used to receive the fluorescence and transmit the fluorescence to the optical signal detector 30; the fluorescence is detected by the optical signal detector 30 Before being received, it is filtered by a filter assembly;
  • the excitation light irradiated to the detected object and the fluorescence received by the optical path assembly 20 are out of axis, so as to reduce the risk of the excitation light entering the optical path assembly 20 and reduce the Interference between excitation light and fluorescence.
  • the fluorescence before the fluorescence enters the optical signal detector 30, it is filtered by the filter assembly, so as to reduce the interference between the excitation light and the fluorescence, and ensure the accuracy of detection.
  • the light source 10 is used to irradiate the detected object, and the detected object is excited by the light source 10 to generate fluorescence;
  • the light source 10 is located outside the optical path assembly 20, and the optical path assembly 20 includes a first lens module and a second lens module, and the first lens module is used to receive Fluorescence;
  • the second lens module is located on the side of the first lens module away from the object to be detected, and is used to receive the fluorescence transmitted by the first lens module;
  • the optical signal detector 30 is located on the side of the second lens module away from the first lens module, and the light The signal detector 30 is used for receiving the fluorescent light transmitted by the second lens module. That is to say, the fluorescent light reaches the optical signal detector 30 through the first lens module and the second lens module in sequence.
  • the fluorescence detection device in this application is only formed by combining two lens modules, which is conducive to the miniaturization of the fluorescence detection device, and then the fluorescence detection device in this application can be applied to handheld devices for fluorescent substance detection Among them, the convenience of detecting fluorescent substances is greatly increased.
  • the central wavelength of the excitation light emitted by the light source 10 is between 675nm-725nm, for example, it can be between 675nm, 680nm, 685nm, 690nm, 695nm, 700nm, 705nm, 710nm, 715nm, 720nm, 725nm or 675nm-725nm Any value of , which is not limited here.
  • the filter assembly includes a first filter 22 located between the first lens module and the second lens module, the first filter 22 can filter the excitation light, and then ensure that it enters the second lens Most of the light in the module and the optical signal detector 30 is fluorescence, which effectively reduces the interference between fluorescence and reflected light.
  • the first lens module includes a first lens 21, the first lens 21 is used to receive fluorescence and collimate the fluorescence; the first filter 22 is located at the side of the first lens 21 away from the detected object One side, and the first filter 22 is used to receive the light transmitted by the first lens 21 .
  • the setting of the first lens 21 can collimate the fluorescence excited by the detected object, so that the collimated fluorescent light can pass through the first filter 22 smoothly, and the first filter 22 can also reflect the detected object
  • the light from the light source 10 is filtered out, thereby ensuring that most of the light entering the second lens module and the optical signal detector 30 is the fluorescence excited by the detected object, ensuring the accuracy of the fluorescence, and effectively reducing the difference between the fluorescence and the reflected light. interference between.
  • the first optical filter 22 is a narrow-band optical filter.
  • the narrow-band filter can only transmit a small part of the light, while the rest of the light cannot pass through the first filter 22, so as to effectively distinguish the fluorescence from the reflected light and avoid the occurrence of a gap between the fluorescence and the reflected light. problem of interference.
  • the central wavelength of the first optical filter 22 is between 800nm and 850nm, such as 800nm, 805nm, 810nm, 815nm, 820nm, 825nm, 830nm, 835nm, 840nm, 845nm, 850nm or Any value between 800nm-850nm is not limited here.
  • the first optical filter 22 with a specific central wavelength can be selected according to actual needs, so that light near the central wavelength of the first optical filter 22 can pass through.
  • This setting makes the first optical filter 22 allow the light around the wavelength of 800nm to 850nm to pass through, while the light of the remaining wavelengths cannot, so that the optical path system in this application can allow the light with the wavelength of 800nm to pass through, so that the handheld device can Fluorescence in the range around the wavelength of 800nm is detected.
  • the bandwidth range of the first filter 22 is less than 65nm, for example, may be 15nm, 25nm, 35nm, 45nm, 55nm, 65nm or any value less than 65nm.
  • the bandwidth range is 50 nm, that is to say, the first filter 22 can allow the light within the range of plus or minus 25 nm of the central wavelength to pass through. That is to say, the handheld device in this application can accurately detect near-infrared fluorescent substances whose peak wavelengths of excitation light and emission light are close, especially the fluorescence whose emission peak wavelength is 800nm.
  • the transmittance of the first filter 22 is greater than or equal to 95%.
  • the transmittance of the first filter 22 to the light in the wavelength range of 785nm to 835nm is above 95%, so as to ensure that most of the fluorescence can pass through, which is convenient for subsequent detection and ensures the accuracy of detection.
  • the cut-off depth of the first filter 22 is OD6. Such setting can effectively ensure the cut-off accuracy of the first optical filter and the purity of the transmitted fluorescence.
  • the cut-off range of the first optical filter 22 is 300nm to 1100nm, for example, it can be 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm, 1000nm, 1100nm or any value between 300nm-1100nm, here No limit.
  • the first lens 21 has a convex surface, and the convex surface of the first lens 21 faces the first filter 22 .
  • the convex surface of the first lens 21 faces the first filter 22 so that the first lens 21 can collimate the light and ensure the angle at which the fluorescence is incident on the first filter 22 .
  • the first lens is a biconvex lens, that is to say, both the light incident surface and the light exit surface of the first lens are convex.
  • the first lens is a plano-convex lens, that is to say, one of the light incident surface and the light exit surface of the first lens is a plane, and the other is a convex surface.
  • one of the light incident surface and the light exit surface of the first lens is a convex surface, and the other is a concave surface.
  • the first lens 21 is a hemispherical lens. Setting the first lens 21 as a hemispherical lens can shorten the focal length of the first lens 21, which is beneficial to the miniaturization of the optical path system.
  • the plane of the hemispherical lens faces the detected object, so that the first lens 21 can collimate the light.
  • the second lens module includes a second lens 23 having a convex surface, and the convex surface of the second lens 23 faces the first lens module.
  • the convex surface of the second lens 23 faces the first filter 22 so that the second lens 23 converges the light emitted by the first filter 22 to ensure that most of the light passing through the first filter 22 can
  • the light is transmitted to the optical signal detector 30 by the second lens 23 to reduce the loss of fluorescence.
  • the second lens is a biconvex lens, that is to say, both the light incident surface and the light exit surface of the second lens are convex.
  • the second lens is a plano-convex lens, that is to say, one of the light incident surface and the light exit surface of the second lens is a plane, and the other is a convex surface.
  • one of the light incident surface and the light exit surface of the second lens is convex, and the other is concave.
  • the second lens 23 is a hemispherical lens. Setting the second lens 23 into a hemispherical shape can shorten the focal length of the second lens 23, which is beneficial to the miniaturization of the optical path system.
  • the light source 10 and the light path assembly 20 are arranged at an angle.
  • the light source 10 and the optical path assembly 20 are arranged at an angle to avoid the light source 10 from affecting the optical path assembly 20 .
  • the angle between the light source 10 and the optical path assembly 20 is greater than 0 degrees and less than 90 degrees, for example, it can be 1 degree, 10 degrees, 20 degrees, 30 degrees, 40 degrees, 50 degrees, 60 degrees, 70 degrees, 80 degrees degree or any value between greater than 0 degree and less than 90 degree, which is not limited here.
  • the angle between the optical axis of the excitation light and the optical axis of the fluorescence received by the optical path assembly 20 is between 30 degrees and 70 degrees, for example, it can be 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees. degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, or any value between greater than 30 degrees and less than 70 degrees, which is not limited here.
  • the transmission angle of the optical path assembly 20 is greater than or equal to 40 degrees and less than or equal to 65 degrees, for example, it can be 40 degrees, 45 degrees, 50 degrees, 51 degrees, 52 degrees, 53 degrees, 54 degrees, 55 degrees, 60 degrees, 65 degrees degrees or any value between greater than 40 degrees and less than 65 degrees, which is not limited here. Limiting the transmission angle of the optical path assembly 20 within the range of 40 to 65 degrees can effectively reduce the interference between fluorescence and reflected light, and ensure the accuracy of fluorescence, so as to facilitate the accuracy of subsequent detection of fluorescence.
  • the transmission angle of the optical path assembly 20 refers to the maximum angle between the light rays received by the optical path assembly 20 .
  • the light source 10 is a high-power LED packaged with a metal bullet.
  • the focus of the light source can be increased through the bullet package, and the metal dissipates the heat generated by the high-power LED shaping circuit to ensure the stability and safety of the light source 10 .
  • high-power LEDs refer to LEDs with power greater than 50mw.
  • the optical path system also includes a frame module 40.
  • the frame module 40 has an optical path through hole 41 for accommodating the optical path assembly 20 and a light source through hole 42 for accommodating the light source 10.
  • the light source through hole 42 is located at the The outer side of the hole 41, and the light source through hole 42 and the light path through hole 41 are set at an angle.
  • the frame module 40 is used to integrate the light source 10, the optical path assembly 20 and the optical signal detector 30, so as to facilitate the movement of the optical path system, and enable the optical path system to be directly applied to other devices, greatly increasing the application scenarios of the optical path system.
  • the frame module 40 can also reduce the interference between other structures on the light source 10, the optical path assembly 20, and the optical signal detector 30, and protect the light source 10, the optical path assembly 20, and the optical signal detector 30, so that the optical path system can work stably.
  • the fact that the light source through hole 42 is located outside the light path through hole 41 means that the light source through hole 42 is spaced apart from the light path through hole 41 .
  • multiple light sources 10 and multiple light source through holes 42 there are multiple light sources 10 and multiple light source through holes 42 , and the multiple light sources 10 are arranged in one-to-one correspondence with the multiple light source through holes 42 , and the multiple light sources 10 are arranged at intervals around the light path through hole 41 in the circumferential direction.
  • the light source 10 includes a first light source and a second light source, and two light source through holes 42 corresponding to the first light source and the second light source are arranged symmetrically along the axis of the light path through hole 41 .
  • the first light source and the second light source are arranged symmetrically so as to irradiate the detected object from different directions, which is beneficial to excite more fluorescence.
  • the frame module 40 includes a frame 43 and a fixing member 44, the frame 43 has an optical path through hole 41 and a light source through hole 42; the fixing member 44 is used to fix the first lens module and the second lens module on Inside the light path through hole 41.
  • the setting of the fixing member 44 can fix the first lens module and the second lens module in the optical path through hole, so as to ensure the stability of the connection between the first lens module and the second lens module and the frame 43, and ensure the connection between the first lens module and the second lens module.
  • the stability of the relative position of the second lens module further ensures the stability of the operation of the optical path assembly 20 .
  • At least a part of the side of the frame 43 is inclined to form a slope 431, and a plurality of light source through holes 42 are located on the slope 431.
  • the light source 10 is far away from the object to be detected.
  • the surface of is flush with the slope 431.
  • the angle between the light source through hole 42 and the light path through hole 41 is set, and the inclined surface 431 on the frame 43 will not affect the work of the light source 10. In the case of work, it is beneficial to the miniaturization of the frame 43 .
  • the surface of the light source 10 away from the detected object is flush with the slope 431 , ensuring that the volume of the frame 43 will not be increased after the light source 10 is assembled on the frame 43 , effectively ensuring the miniaturization of the frame 43 .
  • the slope 431 has a groove 432 , and the light source through hole 42 is disposed at the bottom of the groove 432 .
  • a groove 432 is provided at the position of the slope 431 so that the bottom of the groove 432 can support the light source 10 to ensure that the light emitting part of the light source 10 can be stably accommodated in the light source through hole 42 .
  • the light source through hole 42 includes a large-diameter section 421, a transition section 422 and a small-diameter section 423 that are connected in sequence.
  • the setting of is conducive to focusing the light emitted by the light source 10, which greatly guarantees the energy emitted by the light source 10.
  • the optical signal detector 30 is connected to the frame module 40 , and the optical signal detector 30 is covered on the side of the optical path through hole 41 away from the detected object. Such setting can ensure that the optical signal detector 30 can receive the outgoing light of the optical path assembly 20, so as to perform subsequent detection.
  • the surface of the frame 43 away from the object to be detected has a sunken groove 433 for accommodating the optical signal detector 30, the optical path through hole 41 is arranged at the bottom of the sunken groove 433, and the optical signal detector 30 is arranged at the bottom of the sunken groove 433.
  • the setting of the sinking groove 433 can limit the optical signal detector 30, facilitate the connection between the optical signal detector 30 and the frame 43, and at the same time ensure that the optical signal detector 30 can block the light exit side of the optical path through hole 41, so as to ensure The optical signal detector 30 works stably.
  • the plane where the notch of the sinker 433 is located is set at an angle to the slope 431 . That is to say, the sinker groove 433 is arranged directly opposite to the object to be detected, which can reduce the optical path of the optical path assembly, so that the fluorescence generated by the excitation of the object to be detected directly enters the optical path assembly, and then enters the optical signal detector 30. This facilitates the miniaturization of the frame 43 to ensure the miniaturization of the entire optical path system.
  • the extension of the plane where the notch of the sinker 433 is located intersects the extension of the inclined plane 431 , or in other words, there is an included angle between the plane where the notch of the sinker 433 is located and the inclined plane 431 .
  • the frame 43 has a protruding edge 434 on a side close to the detected object.
  • the protruding edge 434 facilitates the cooperation of the optical path system with other structures.
  • the convex edge 434 is spaced apart from the slope 431 .
  • the filter assembly further includes a second filter 24 located between the light source 10 and the object to be detected, and the excitation light is filtered by the second filter 24 before irradiating the object to be detected.
  • the setting of the second optical filter 24 can filter the excitation light to reduce the influence of other stray light, and ensure that the wavelength of the excitation light irradiated to the detected object is within a preset range, which is beneficial to reduce the impact of light of other wavelengths on the detected object. Irradiation of the test object will affect the test results.
  • the second filter 24 is a narrow band filter.
  • the narrow-band filter can only transmit a small part of the light, while the rest of the light cannot pass through the second filter 24, thereby ensuring that the excitation light irradiated to the detected object is within a preset range.
  • the central wavelength of the second filter 24 is between 675nm and 725nm, such as 675nm, 680nm, 685nm, 690nm, 695nm, 700nm, 705nm, 710nm, 715nm, 720nm, 725nm or Any value between 675nm-725nm is not limited here; the second optical filter 24 can be selected according to actual needs, so that the light near the central wavelength can pass through the second optical filter 24, while the rest of the wavelengths cannot pass through, It is beneficial to ensure that the wavelength of the excitation light irradiated to the object to be detected is within a preset range, and the accuracy of the excitation light is ensured.
  • the bandwidth of the second filter 24 is less than 65nm, for example, 15nm, 25nm, 35nm, 45nm, 55nm, 65nm or any value less than 65nm.
  • the bandwidth range is 50 nm, that is to say, the second filter 24 can allow light within the range of plus or minus 25 nm of the central wavelength to pass through.
  • the wavelength of the fluorescent light produced by exciting the detected object with light of different wavelengths will be different, and the setting of the second filter 24 is to ensure the accuracy of the excitation light irradiated on the detected object, thereby ensuring The fluorescence generated by the detected object is within the preset range, reducing the interference between other light and fluorescence.
  • the cut-off depth of the second optical filter is OD6, such setting can effectively ensure the cut-off accuracy of the second optical filter 24 and the purity of the transmitted excitation light.
  • the cut-off range of the second filter 24 is 300nm to 1100nm.
  • the frame module 40 is arranged on the draw-in frame 50 ; the draw-in frame 50 is provided with a draw-in slot 56 ;
  • a plurality of spring pressing wheels 51 are located on both sides of the card slot 56; when the reagent card 60 is inserted, the spring pressing wheels 51 abut against the upper end surface of the reagent card; the spring ball 52 is arranged in the card slot 56; when the reagent card 60 is inserted, the spring ball 52 abuts against the side of the reagent card.
  • the driving device pushes the reagent card 60 to move through the through hole 53 opened on the card slot frame 50 , and the card slot frame 50 is fixed on the instrument housing through the connecting screw 54 , and the connecting screw 54 is covered with an insulating particle pad 55 .
  • the arrangement of the card slot frame 50 is beneficial to ensure the distance between the reagent card and the frame module 40, so that multiple light sources 10 can simultaneously irradiate the reagent card 60 for excitation.
  • the reagent card contains the above-mentioned detected substances.
  • the frame module 40 and the card slot frame 50 may be fixedly connected or may be detachably connected, as long as the frame module 40 is placed on the card slot frame 50 .
  • a handheld device for detecting fluorescent substances includes the above-mentioned fluorescence detection device.
  • the handheld device with the above-mentioned fluorescence detection device can detect 800nm fluorescence, and at the same time, the volume is smaller and lighter.
  • the near-infrared fluorescent substance is Thermo Fisher Dylight 800, and its absorption light and fluorescence spectrum are shown in Figure 3.
  • the peak excitation wavelength of the fluorescent substance appears at 770nm Nearby, the wavelength of the fluorescent signal with strong emission light signal is concentrated between 740nm-840nm, and the peak appears around 790nm. sex.
  • the spectrum diagram of the light source 10 in this embodiment is shown in FIG. 5 .
  • the light source 10 emits excitation light with a peak wavelength of 700nm, and the wavelength range of the light emitted by the light source 10 is concentrated in the range of 640nm-760nm.
  • the spectrum diagram of the first filter 22 is shown in Figure 6, the bandwidth of the first filter 22 is about 50nm, the wavelength range of the filtered light is concentrated in 785nm-835nm, and the light with a wavelength lower than 760nm is almost completely filtered.
  • the optical sensitivity of the optical signal detector 30 in this embodiment is shown in FIG. 4 .
  • the optical signal detector 30 adopts Hamamatsu Optoelectronics S1133-01 photoelectric sensor, which still has a very high sensitivity to light with a wavelength greater than 800 nm.
  • the emitted light signal generated by the stimulated radiation of the object to be detected has a stronger optical signal with a wavelength concentrated in the range of 740nm-840nm. Since there is very little overlap between the excitation light wavelength and the emission light wavelength, light interference rarely occurs between the two, and the detection accuracy will not be affected by the interference between the excitation light and the emission light during the detection process. In addition, through the comprehensive filtering of the excitation light with a wavelength below 760 nm by the first filter 22 , the interference of the excitation light on the detection signal can be further reduced and the detection accuracy can be improved. At the same time, the strong detection capability of the optical signal detector 30 for long wavelengths, especially long wavelengths with a wavelength greater than 800 nm, enables the device to perform comprehensive detection of near-infrared emitted light.
  • Optical signal detector 30 adopts low dark current ceramic package photodiode, cooperates with 50 to 55 degree transmission fluorescent circuit components, to minimize the interference between excitation and emission light, because optical glass has obvious transmittance to light Advantages, using optical glass lenses to focus and collect received light signals.
  • the optical glass is K9 glass.
  • the optical path assembly with 50 to 55 degree transmission can effectively solve the problem of excitation energy efficiency, and can also solve the problem of equipment miniaturization; the overall volume of the optical detection part of the finally designed fluorescence detection device can be kept below 10cm3, and reflection and transmission The optical path can be controlled within 13mm, and the overall volume of the final fluorescence detection device is controlled within 616.25cm3, realizing the handheld application of the fluorescence detector.

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Abstract

一种荧光检测装置和用于荧光物质检测的手持设备。荧光检测装置，包括：框架模块（40）；光源（10），用于产生激发光，激发光经设于框架模块（40）上的光源通孔（42）后照射被检测物，被检测物受激发光的激发产生荧光；设于框架模块（40）上的光路组件（20），用于接收荧光并将荧光传输至光信号检测器（30）；荧光被光信号检测器（30）接收之前经滤光组件过滤；照射到被检测物的激发光与被光路组件（20）接收的荧光不同轴。在检测近红外荧光物质时，解决了激发光和发射光由于波长接近而出现的干涉问题。

Description

荧光检测装置和用于荧光物质检测的手持设备
本申请要求于2021年12月24日提交至中国国家知识产权局、申请号为202111605306.6，发明名称为“用于侧向免疫层析仪器的光路系统和手持设备”的专利申请的优先权。
技术领域
本申请涉及荧光检测设备技术领域，具体而言，涉及一种荧光检测装置和用于荧光物质检测的手持设备。
背景技术
目前市场上常用荧光物质主要有荧光微球、荧光束、量子点等，主要激发-荧光波长集中在可见光范围内，例如470-525nm、635-680nm、365-610nm等波长，激发光和产生的荧光波长差距较大，近红外光波长荧光物质则较少。近年来开发出的近红外光荧光染料具有高水溶性、不容易出现偶联物沉淀或荧光猝灭等优点，但由于近红外荧光染料激发波长和发射波长过于接近而易于产生干涉现象，导致检测结果不准确，限制了这类荧光物质的应用范围。
对于该问题，目前大型的荧光检测设备由于具有足够的空间结构，能够通过光路设计来避免近红外荧光染料的激发光和发射光(被检测物发射的荧光)之间的干涉问题，例如在激发光路和发射光路中设置多层滤光元件对激发光和发射光进行过滤，从而抑制干扰噪声。
然而在免疫层析即时检测(point-of-care testing，POCT)检测领域，由于对于仪器的可移动性要求高，POCT检测设备体积通常较小，而在有限的较小空间中难以避免波长相近的激发光和发射光之间的干涉。
发明内容
本申请的主要目的在于提供一种荧光检测装置和用于荧光物质检测的手持设备，在检测近红外荧光物质时，解决激发光和发射光由于波长接近而出现干涉的问题。
为了实现上述目的，根据本申请的一个方面，提供了一种荧光检测装置包括：框架模块；光源，用于产生激发光，激发光经设于框架模块上的光源通孔后照射被检测物，被检测物受激发光的激发产生荧光；设于框架模块上的光路组件，用于接收荧光并将荧光传输至光信号检测器；滤光组件，荧光被光信号检测器接收之前经滤光组件过滤；其中，照射到被检测物的激发光与被光路组件接收的荧光不同轴。
在本申请的一个实施例中，光信号检测器设于框架模块上。
在本申请的一个实施例中，光路组件包括同轴设置的第一透镜模块和第二透镜模块，滤光组件包括位于第一透镜模块和第二透镜模块之间的第一滤光片。
在本申请的一个实施例中，第一滤光片为窄带滤光片。
在本申请的一个实施例中，第一滤光片至少具有以下特性中的一个：第一滤光片的中心波长在800nm至850nm之间，第一滤光片的截止深度为OD6；第一滤光片的截止范围在300nm至1100nm；第一滤光片的带宽小于65nm。
在本申请的一个实施例中，第一透镜模块包括第一透镜，第一透镜用于接收荧光并对荧光进行准直，第一透镜具有凸面，第一透镜的凸面朝向第一滤光片；第二透镜模块包括第二透镜，第二透镜具有凸面，第二透镜的凸面朝向第一透镜模块。
在本申请的一个实施例中，第一透镜和/或第二透镜为半球形透镜。
在本申请的一个实施例中，激发光的光轴和光路组件接收的荧光的光轴之间夹角在30度至70度之间。
在本申请的一个实施例中，激发光的光轴和光路组件接收的荧光的光轴之间夹角在45度至60度之间。
在本申请的一个实施例中，光源通孔的中心轴相对于光路组件的中心轴倾斜设置。
在本申请的一个实施例中，光路组件的透射角度大于等于40度且小于等于65度。
在本申请的一个实施例中，光路组件的透射角度大于等于50度且小于等于55度。
在本申请的一个实施例中，框架模块上还设有用于容置光路组件的光路通孔，光源通孔位于光路通孔的外侧，且光源通孔与光路通孔成夹角设置。
在本申请的一个实施例中，光源为多个，光源通孔为多个，多个光源与多个光源通孔一一对应设置，多个光源通孔绕光路通孔的周向设置。
在本申请的一个实施例中，光源包括第一光源和第二光源，第一光源和第二光源对应的两个光源通孔沿光路通孔的轴线对称设置。
在本申请的一个实施例中，框架模块包括框架和固定件，框架具有光路通孔和光源通孔，固定件用于将第一透镜模块和第二透镜模块固定在光路通孔内。
在本申请的一个实施例中，框架的侧面的至少一部分倾斜设置形成斜面，光源设置在斜面的凹槽中，光源通孔设置在凹槽的槽底。
在本申请的一个实施例中，框架远离被检测物的表面具有用于容置光信号检测器的沉槽。
在本申请的一个实施例中，滤光组件还包括位于光源与被检测物之间的第二滤光片，激发光照射到被检测物之前被第二滤光片过滤。
在本申请的一个实施例中，第二滤光片为窄带滤光片。
在本申请的一个实施例中，第二滤光片至少具有以下特性中的至少一个：第二滤光片的中心波长在675nm至725nm之间；第二滤光片的截止深度为OD6；第二滤光片的截止范围在300nm至1100nm；第二滤光片的带宽范围小于65nm。
在本申请的一个实施例中，荧光检测装置还包括卡槽框和多个弹簧压轮，框架模块设置于卡槽框上；多个弹簧压轮设置在卡槽框的上端面。
在本申请的一个实施例中，卡槽框内设有用于插入试剂卡的卡槽，沿试剂卡的插入方向，多个弹簧压轮位于卡槽的两侧，卡槽的内侧壁中设有弹簧滚珠；在试剂卡插入时，弹簧压轮与试剂卡的上端面抵接，弹簧滚珠与试剂卡的侧面抵接。
根据本申请的另一方面，提供了一种用于荧光物质检测的手持设备，包括上述的荧光检测装置。
应用本申请的技术方案，荧光检测装置包括光源、光路组件、光信号检测器和框架模块，用于产生激发光，激发光经设于框架模块上的光源通孔后照射被检测物，被检测物受激发光的激发产生荧光；设于框架模块上的光路组件，用于接收荧光并将荧光传输至光信号检测器；荧光被光信号检测器接收之前经滤光组件过滤；照射到被检测物的激发光与被光路组件接收的荧光不同轴。
通过对光路组件与光源之间的设计，以使照射到被检测物的激发光与被光路组件接收的荧光不同轴，以减少激发光射入到光路组件中的风险，减少激发光与荧光之间的干涉。同时在荧光进入到光信号检测器之前被滤光组件过滤，以减少激发光与荧光之间的干涉，保证检测的准确性。
被检测物在被光源照射的情况下，会受激发射荧光，而荧光通过光路组件进入导电光信号检测器内。由于将光路组件设置第一透镜模块与第二透镜模块组合的形式，能够实现对荧光的准直和汇聚，以实现对荧光的检测，光源相对于光路组件的中心轴倾斜设置减少了被检测物的被激发出的荧光和对光源反射的光之间的干涉，通过滤光组件对激发光的过滤，保证了后续检测的精度。此外，本申请中的光路系统仅采用了两个透镜模块组合在一起形成，有利于光路系统的小型化，进而可以将本申请中的光路系统应用到用于荧光物质检测的手持设备中，大大增加了对荧光物质检测的便捷性，框架模块能够为装置的各部件起到支撑作用，增加装置的稳定性。
将框架模块直接固定于卡槽框上，能够避免检测过程中试剂卡与框架模块之间不必要的相对运动对荧光检测的影响。弹簧压轮和弹簧滚珠的设置能够使试剂卡进出卡槽更加顺畅，使得荧光检测过程中试剂卡能够以更加均匀的速度经过框架模块，实现更高精度的检测。
附图说明
构成本申请的一部分的说明书附图用来提供对本申请的进一步理解，本申请的示意性实施例及其说明用于解释本申请，并不构成对本申请的不当限定。在附图中：
图1示出了本申请的一个可选实施例的光路系统的整体结构示意图；
图2示出了图1中光路系统的爆炸图；
图3示出了荧光物质DyLight800的光谱图；
图4示出了光电传感器光灵敏度示意图；
图5示出了光源光谱图；
图6示出了滤光片光谱图；
图7示出了卡槽框的结构图；
图8示出了本申请的一个可选实施例的框架模块与卡槽框之间的位置关系；
图9示出了本申请的另一个可选实施例的光路系统的整体结构示意图。
其中，上述附图包括以下附图标记：
10、光源；20、光路组件；21、第一透镜；22、第一滤光片；23、第二透镜；24、第二滤光片；30、光信号检测器；40、框架模块；41、光路通孔；42、光源通孔；421、大径段；422、过渡段；423、小径段；43、框架；431、斜面；432、凹槽；433、沉槽；434、凸沿；44、固定件；50、卡槽框；51、弹簧压轮；52、弹簧滚珠；53、通孔；54、连接螺丝；55、绝缘粒子垫；56、卡槽；60、试剂卡。
具体实施方式
需要说明的是，在不冲突的情况下，本申请中的实施例及实施例中的特征可以相互组合。下面将参考附图并结合实施例来详细说明本申请。
需要指出的是，除非另有指明，本申请使用的所有技术和科学术语具有与本申请所属技术领域的普通技术人员通常理解的相同含义。
在本申请中，在未作相反说明的情况下，使用的方位词如“上、下、顶、底”通常是针对附图所示的方向而言的，或者是针对部件本身在竖直、垂直或重力方向上而言的；同样地，为便于理解和描述，“内、外”是指相对于各部件本身的轮廓的内、外，但上述方位词并不用于限制本申请。
为了解决现有技术中对激发光和发射光峰值波长接近的近红外荧光物质，特别是发射光峰值波长为800nm的荧光物质进行检测时，激发光和发射光由于波长接近而出现干涉的问题，本申请提供了一种荧光检测装置和用于荧光物质检测的手持设备。
如图1至图8所示，荧光检测装置包括光源10、光路组件20、光信号检测器30和框架模块40，用于产生激发光，激发光经设于框架模块40上的光源通孔42后照射被检测物，被检测物受激发光的激发产生荧光；设于框架模块40上的光路组件20，用于接收荧光并将荧光传输至光信号检测器30；荧光被光信号检测器30接收之前经滤光组件过滤；照射到被检测物的激发光与被光路组件20接收的荧光不同轴。
通过对光路组件20与光源10之间的设计，以使照射到被检测物的激发光与被光路组件20接收的荧光不同轴，以减少激发光射入到光路组件20中的风险，减少激发光与荧光之间的干涉。同时在荧光进入到光信号检测器30之前被滤光组件过滤，以减少激发光与荧光之间的干涉，保证检测的准确性。
光源10用于照射被检测物，被检测物受光源10的激发产生荧光；光源10位于光路组件20的外侧，光路组件20包括第一透镜模块和第二透镜模块，第一透镜模块用于接收荧光；第二透镜模块位于第一透镜模块远离被检测物的一侧，用于接收第一透镜模块透射的荧光；光信号检测器30位于第二透镜模块远离第一透镜模块的一侧，光信号检测器30用于接收第二透镜模块透射的荧光。也就是说，荧光依次经第一透镜模块和第二透镜模块到达光信号检测器30。
被检测物在被光源10照射的情况下，会受激发射荧光，而荧光通过光路组件20进入光信号检测器30内。由于将光路组件20是第一透镜模块与第二透镜模块组合的形式，能够实现对荧光的准直和汇聚，以实现对荧光的检测，减少了被检测物的被激发出的荧光和对光源10发射的激发光之间的干涉，保证了后续检测的精度。此外，本申请中的荧光检测装置仅采用了两个透镜模块组合在一起形成，有利于荧光检测装置的小型化，进而可以将本申请中的荧光检测装置应用到用于荧光物质检测的手持设备中，大大增加了对荧光物质检测的便捷性。
可选地，光源10发射的激发光的中心波长在675nm-725nm之间，例如可以是675nm、680nm、685nm、690nm、695nm、700nm、705nm、710nm、715nm、720nm、725nm或者675nm-725nm之间的任意值，在此不做限定。
如图1所示，滤光组件包括位于第一透镜模块与第二透镜模块之间的第一滤光片22，第一滤光片22能够将激发光过滤掉，进而保证进入到第二透镜模块和光信号检测器30中的光大部分都是荧光，有效减少了荧光与反射光之间的干涉。
如图1和图2所示，第一透镜模块包括第一透镜21，第一透镜21用于接收荧光并对荧光进行准直；第一滤光片22位于第一透镜21远离被检测物的一侧，且第一滤光片22用于接收第一透镜21透过的光。第一透镜21的设置能够对被检测物激发产生的荧光进行准直，以便于准直后的荧光能够顺利通过第一滤光片22，而第一滤光片22还能够将被检测物反射光源10的光进行过滤掉，进而保证了进入到第二透镜模块和光信号检测器30中绝大部分都是被检测物激发产生的荧光，保证了荧光的精度，有效减少了荧光与反射光之间的干涉。
在一个可选实施例中，第一滤光片22为窄带滤光片。窄带滤光片仅能让很小一部分的光进行透过，而其余部分的光则不能透过第一滤光片22，进而将荧光与反射光进行有效区分，避免荧光与反射光之间产生干涉的问题。
在另一个可选实施例中，第一滤光片22的中心波长在800nm至850nm之间，例如可以是800nm、805nm、810nm、815nm、820nm、825nm、830nm、835nm、840nm、845nm、850nm或者800nm-850nm之间的任意值，在此不做限定。可以根据实际需要来选用具体的中心波长的第一滤光片22，让第一滤光片22的中心波长附近的光能够通过。这样设置使得第一滤光片22能够让波长800nm至850nm周围的光进行通过，而其余波长的光则不能，以使得本申请中的光路系统能够让波长800nm的光通过，进而使得手持设备能够对波长800nm前后范围内的荧光进行检测。
具体的，第一滤光片22的带宽范围小于65nm，例如可以是15nm、25nm、35nm、45nm、55nm、65nm或者小于65nm的任意值。例如当带宽范围为50nm，也是就说，第一滤光片22能够让中心波长加减25nm范围内的光通过。也就是说，本申请中的手持设备能够对激发光和发射光峰值波长接近的近红外荧光物质，特别是发射光峰值波长为800nm的荧光进行准确检测。
具体的，第一滤光片22的透射率大于等于95％。第一滤光片22能够对波长785nm至835nm范围内的光的透过率在95％以上，以保证大部分荧光均能够通过，便于后续的检测，保证检测的准确性。
具体的，第一滤光片22的截止深度为OD6。这样设置可以有效保证第一滤光片的截止精度，保证透过的荧光的纯洁度。
可选地，第一滤光片22的截止范围在300nm至1100nm，例如可以是300nm、400nm、500nm、600nm、700nm、800nm、900nm、1000nm、1100nm或者300nm-1100nm之间的任意值，在此不做限定。
如图1至图2所示，第一透镜21具有凸面，第一透镜21的凸面朝向第一滤光片22。将第一透镜21的凸面朝向第一滤光片22，使得第一透镜21能够对光线起到准直的作用，保证荧光入射到第一滤光片22的角度。
可选地，第一透镜为双凸透镜，也就是说第一透镜的入光面和出光面均为凸面。
可选地，第一透镜为平凸透镜，也就是说第一透镜的入光面和出光面中一个为平面，另一个为凸面。
可选地，第一透镜的入光面和出光面中一个为凸面，另一个为凹面。
如图1至图2所示，第一透镜21为半球形透镜。将第一透镜21设置成半球形透镜，可以缩短第一透镜21的焦距，有利于光路系统的小型化。而半球形透镜的平面朝向被检测物，以使得第一透镜21对光线起到准直的作用。
如图1至图2所示，第二透镜模块包括第二透镜23，第二透镜23具有凸面，第二透镜23的凸面朝向第一透镜模块。第二透镜23的凸面朝向第一滤光片22，以便于第二透镜23对经过第一滤光片22射出后的光进行汇聚，以保证透过第一滤光片22的光大部分都能够被第二透镜23传输到光信号检测器30内，减少荧光的损失。
可选地，第二透镜为双凸透镜，也就是说第二透镜的入光面和出光面均为凸面。
可选地，第二透镜为平凸透镜，也就是说第二透镜的入光面和出光面中一个为平面，另一个为凸面。
可选地，第二透镜的入光面和出光面中一个为凸面，另一个为凹面。
具体的，第二透镜23为半球形透镜。将第二透镜23设置成半球形可以缩短第二透镜23的焦距，有利于光路系统的小型化。
如图1所示，光源10与光路组件20呈角度设置。将光源10与光路组件20之间呈夹角设置，以避免光源10对光路组件20产生影响。需要同时保证光源10能够照射到被检测物上，且被激发的荧光能够射入到光路组件20中。也就是说，光源10与光路组件20之间具有夹角，或者说光源10相对于光路组件20倾斜设置。还可以说光源10的中心光路与光路组件20的中心光路之间具有夹角。
具体的，光源10与光路组件20之间的夹角大于0度且小于90度，例如可以是1度、10度、20度、30度、40度、50度、60度、70度、80度或者大于0度且小于90度之间的任意值，在此不做限定。
如图1所示，激发光的光轴和光路组件20接收的荧光的光轴之间夹角在30度至70度之间，例如可以是30度、35度、40度、45度、50度、55度、60度、65度、70度或者大于30度且小于70度之间的任意值，在此不做限定。
具体的，光路组件20的透射角度大于等于40度且小于等于65度，例如可以是40度、45度、50度、51度、52度、53度、54度、55度、60度、65度或者大于40度且小于65度之间的任意值，在此不做限定。将光路组件20的透射角度限制在40至65度的范围内，能够有效减少荧光与反射光之间的干涉，保证荧光的精度，以便于后续对荧光检测的准确性。
需要说明的是，光路组件20的透射角度是指光路组件20接收的光线之间的最大角度。
具体的，光源10为金属子弹头封装的大功率LED。通过子弹头封装能够增加光源的聚焦，而金属对大功率LED整型电路产生的热量进行散热，保证光源10工作的稳定性和安全性。需要说明的是大功率LED是指功率大于50mw的LED。
如图2所示，光路系统还包括框架模块40，框架模块40具有用于容置光路组件20的光路通孔41和用于容置光源10的光源通孔42，光源通孔42位于光路通孔41的外侧，且光源通孔42与光路通孔41成角度设置。框架模块40用于将光源10、光路组件20和光信号检测器30集成在一起，以便于光路系统的移动，且使光路系统可以直接应用到其他设备上，大大 增加了光路系统的应用场景。此外，框架模块40还可以减少其他结构对光源10、光路组件20和光信号检测器30之间的干涉，对光源10、光路组件20和光信号检测器30形成保护，以使得光路系统能够稳定工作。
需要说明的是，光源通孔42位于光路通孔41的外侧是指光源通孔42与光路通孔41间隔设置。
可选地，光源10为多个，光源通孔42为多个，多个光源10与多个光源通孔42一一对应设置，多个光源10通过绕光路通孔41的周向间隔设置。光源10为多个，可以在不同的角度对被检测物进行照射，保证被检测物受激产生荧光的效率，以增加后续检测的准确性。
在图1所示的具体实施例中，光源10包括第一光源和第二光源，第一光源和第二光源对应的两个光源通孔42沿光路通孔41的轴线对称设置。第一光源与第二光源对称设置，以从不同的方向对被检测物进行照射，有利于激发出更多的荧光。
如图1至图2所示，框架模块40包括框架43和固定件44，框架43具有光路通孔41和光源通孔42；固定件44用于将第一透镜模块和第二透镜模块固定在光路通孔41内。固定件44的设置可以将第一透镜模块和第二透镜模块固定在光路通孔内，以保证第一透镜模块和第二透镜模块与框架43之间连接的稳定性，保证第一透镜模块与第二透镜模块相对位置的稳定性，进而保证光路组件20工作的稳定性。
如图1至图2所示，框架43的侧面的至少一部分倾斜设置形成斜面431，多个光源通孔42位于斜面431处，光源10安装到光源通孔42内后，光源10远离被检测物的表面与斜面431平齐。光源通孔42与光路通孔41之间呈夹角设置，在框架43上设置斜面431不会影响光源10的工作，同时斜面431的设置使得框架43的体积更加的小巧，在不影响光源10工作的情况下，有利于框架43的小型化。而光源10远离被检测物的表面与斜面431之间平齐，保证在将光源10装配到框架43上后不会增加框架43的体积，有效保证了框架43的小型化。
如图1至图2所示，斜面431具有凹槽432，光源通孔42设置在凹槽432的槽底。在斜面431位置处设置凹槽432以便于凹槽432的槽底对光源10进行支撑，以保证光源10的发光部分能够稳定容置在光源通孔42内。
如图1所示，光源通孔42包括顺次连接的大径段421、过渡段422和小径段423，大径段421的设置有利于光源10装配到光源通孔42内，而小径段423的设置有利于光源10发出的光进行聚焦，大大保证光源10发射的能量。
如图1所示，光信号检测器30与框架模块40连接，且光信号检测器30盖设在光路通孔41远离被检测物的一侧。这样设置可以保证光信号检测器30能够接收到光路组件20的出射光，以便于进行后续的检测。
如图1所示，框架43远离被检测物的表面具有用于容置光信号检测器30的沉槽433，光路通孔41设置在沉槽433的槽底，光信号检测器30设置在沉槽433内，且与沉槽433的槽口平齐。沉槽433的设置能够对光信号检测器30进行限位，便于光信号检测器30与框架43 之间的连接，同时保证光信号检测器30能够封堵光路通孔41的出光侧，以保证光信号检测器30稳定工作。
如图1所示，沉槽433的槽口所在的平面与斜面431呈角度设置。也就是说，沉槽433与被检测物正对设置，这样可以减少光路组件的光程，以使得被检测物激发产生的荧光直接进入到光路组件，然后进入到光信号检测器30中，有利于框架43的小型化，以保证整个光路系统的小型化。也就是说，沉槽433的槽口所在的平面的延长面与斜面431的延长面相交，或者说，沉槽433的槽口所在的平面与斜面431之间具有夹角。
如图1所示，框架43靠近被检测物的一侧具有凸沿434，凸沿434的设置便于光路系统与其他结构配合。凸沿434与斜面431间隔设置。
在图9所示的具体实施例中，滤光组件还包括位于光源10与被检测物之间的第二滤光片24，激发光照射到被检测物之前被第二滤光片24过滤。第二滤光片24的设置能够对激发光进行过滤，以减少其他杂光的影响，保证照射到被检测物的激发光的波长在预设范围内，这样有利于减少其他波长的光对被检测物照射，影响检测结果。
在一个可选实施例中，第二滤光片24为窄带滤光片。窄带滤光片仅能让很小一部分的光进行透过，而其余部分的光则不能透过第二滤光片24，进而保证照射到被检测物的激发光在预设范围内。
在另一个可选实施例中，第二滤光片24的中心波长在675nm至725nm之间，例如可以是675nm、680nm、685nm、690nm、695nm、700nm、705nm、710nm、715nm、720nm、725nm或者675nm-725nm之间的任意值，在此不做限定；可以根据实际需要选用第二滤光片24，让中心波长附近的光能够透过第二滤光片24，而其余波长则不能通过，有利于保证照射到被检测物的激发光的波长在预设范围内，保证激发光的精度。
在另一个可选实施例中，第二滤光片24的带宽范围小于65nm，例如可以是15nm、25nm、35nm、45nm、55nm、65nm或者小于65nm的任意值。例如当带宽范围为50nm，也是就说，第二滤光片24能够让中心波长加减25nm范围内的光通过。
需要说明的是，不同波长的光对被检测物进行激发产生的荧光的波长会不同，而第二滤光片24的设置是为了保证照射到被检测物上的激发光的精度，进而保证了被检测物产生的荧光在预设范围内，减少其他光与荧光之间的干涉。
第二滤光片的截止深度为OD6，这样设置可以有效保证第二滤光片24的截止精度，保证透过的激发光的纯洁度。
可选地，第二滤光片24的截止范围在300nm至1100nm。
如图7所示，框架模块40设置于卡槽框50上；卡槽框50的内部设置有卡槽56；多个弹簧压轮51设置在卡槽框50的上端面。沿试剂卡60的插入方向，多个弹簧压轮51位于卡槽56的两侧；在试剂卡60插入时，弹簧压轮51与试剂卡的上端面抵接；弹簧滚珠52，设置在 卡槽56的内侧壁中；在试剂卡60插入时，弹簧滚珠52与试剂卡的侧面抵接。驱动装置通过卡槽框50上开设的通孔53推动试剂卡60运动，卡槽框50通过连接螺丝54固定于仪器壳体上，连接螺丝54上套有绝缘粒子垫55。卡槽框50的设置有利于保证试剂卡与框架模块40之间的距离，以便于多个光源10同时照射到试剂卡60上进行激发。
试剂卡上具有上述的被检测物。
框架模块40与卡槽框50之间可以固定连接，也可以为可拆卸式连接，只需要将框架模块40放置在卡槽框50上即可。
用于荧光物质检测的手持设备包括上述的荧光检测装置。具有上述荧光检测装置的手持设备能够检测800nm的荧光，同时体积更加的小巧轻便。
以下采用具体实施例进行说明，在本实施例中，近红外荧光物质为赛默飞世尔Dylight 800，其吸收光和荧光光谱图如图3所示，该荧光物质的激发波长峰值出现在770nm附近，发射光信号较强的荧光信号的波长集中在740nm-840nm之间，峰值出现在790nm附近，激发波长和发射波长的峰值相差仅约20nm，二者非常容易发生干涉现象，影响检测的准确性。
本实施例光源10的光谱图如图5所示，光源10发射峰值波长为700nm的激发光，光源10发射的光的波长范围集中在640nm-760nm区间。第一滤光片22的光谱图如6所示，第一滤光片22的带宽在50nm左右，过滤后的光线的波长范围集中在785nm-835nm，波长低于760nm的光几乎完全被过滤。本实施例光信号检测器30的光灵敏度如图4所示，光信号检测器30采用滨松光电S1133-01光电传感器，其对于波长大于800nm的光依然有非常高的灵敏度。
在本实施例中，当光源10发射出波长集中于640nm-760nm范围的激发光照射被检测物，被检测物受激辐射产生的发射光信号较强光信号的波长集中在740nm-840nm。由于激发光波长和发射光波长之间重叠的部分非常少，二者极少发生光干涉现象，检测过程中不会因为激发光和发射光之间发生干涉而影响检测精确度。此外，通过第一滤光片22对于波长760nm以下激发光的全面过滤，能够将激发光对于检测信号的干扰进一步的降低，提升检测的精确度。同时，光信号检测器30对于长波长特别是波长大于800nm以上的长波的强检测能力，使得本设备能够对于近红外发射光进行全面的检测。
光信号检测器30采用低暗电流陶瓷封装光电二极管，配合50至55度透射的荧光路组件，以尽可能减小激发和发射光之间的干涉，由于光学玻璃对于光的透射率具有明显的优势，使用光学玻璃的透镜聚焦并采集接收光信号。优选地，光学玻璃选用K9玻璃。
50至55度透射的光路组件能够有效地解决激发能效问题，也能解决设备小型化问题；使最终设计出的荧光检测装置的光学检测部分的整体的体积能够保持在10cm3以下，并且反射和透射光路能够控制在13mm以内，最终的荧光检测装置的整体体积控制在616.25cm3以内，实现荧光检测仪的手持应用。
以上所述仅为本申请的优选实施例而已，并不用于限制本申请，对于本领域的技术人员来说，本申请可以有各种更改和变化。凡在本申请的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本申请的保护范围之内。

Claims (24)

  1. 一种荧光检测装置，其特征在于，包括：
    框架模块(40)；
    光源(10)，用于产生激发光，所述激发光经设于所述框架模块(40)上的光源通孔(42)后照射被检测物，所述被检测物受所述激发光的激发产生荧光；
    设于所述框架模块(40)上的光路组件(20)，用于接收所述荧光并将所述荧光传输至光信号检测器(30)；
    滤光组件，所述荧光被所述光信号检测器(30)接收之前经所述滤光组件过滤；
    其中，照射到所述被检测物的激发光与被所述光路组件(20)接收的荧光不同轴。
  2. 根据权利要求1所述的荧光检测装置，其特征在于，所述光信号检测器(30)设置于所述框架模块(40)上。
  3. 根据权利要求1所述的荧光检测装置，其特征在于，所述光路组件包括同轴设置的第一透镜模块和第二透镜模块，所述滤光组件包括位于所述第一透镜模块和所述第二透镜模块之间的第一滤光片(22)。
  4. 根据权利要求3所述的荧光检测装置，其特征在于，所述第一滤光片(22)为窄带滤光片。
  5. 根据权利要求3所述的荧光检测装置，其特征在于，所述第一滤光片具有以下特性中的至少一个：
    所述第一滤光片(22)的中心波长在800nm至850nm之间；
    所述第一滤光片(22)的截止深度为OD6；
    所述第一滤光片(22)的截止范围在300nm至1100nm；
    所述第一滤光片(22)的带宽范围小于65nm。
  6. 根据权利要求3所述的荧光检测装置，其特征在于，所述第一透镜模块包括第一透镜(21)，所述第一透镜(21)用于接收所述荧光并对所述荧光进行准直，所述第一透镜(21)具有凸面，所述第一透镜(21)的凸面朝向所述第一滤光片(22)；所述第二透镜模块包括第二透镜(23)，所述第二透镜(23)具有凸面，所述第二透镜(23)的凸面朝向所述第一透镜模块。
  7. 根据权利要求6所述的荧光检测装置，其特征在于，所述第一透镜(21)和/或所述第二透镜(23)为半球形透镜。
  8. 根据权利要求1所述的荧光检测装置，其特征在于，所述激发光的光轴和所述光路组件(20)接收的荧光的光轴之间夹角在30度至70度之间。
  9. 根据权利要求8所述的荧光检测装置，其特征在于，所述激发光的光轴和所述光路组件(20)接收的荧光的光轴之间夹角在45度至60度之间。
  10. 根据权利要求1至9中任一项所述的荧光检测装置，其特征在于，所述光源通孔(42)的中心轴相对于所述光路组件(20)的中心轴倾斜设置。
  11. 根据权利要求1至9中任一项所述的荧光检测装置，其特征在于，所述光路组件(20)的透射角度大于等于40度且小于等于65度。
  12. 根据权利要求1至9中任一项所述的荧光检测装置，其特征在于，所述光路组件(20)的透射角度大于等于50度且小于等于55度。
  13. 根据权利要求1至9中任一项所述的荧光检测装置，其特征在于，所述框架模块(40)上还设有用于容置所述光路组件(20)的光路通孔(41)，所述光源通孔(42)位于所述光路通孔(41)的外侧，且所述光源通孔(42)与所述光路通孔(41)成夹角设置。
  14. 根据权利要求13所述的荧光检测装置，其特征在于，所述光源(10)为多个，所述光源通孔(42)为多个，多个所述光源(10)与多个所述光源通孔(42)一一对应设置，多个所述光源通孔(42)绕所述光路通孔(41)的周向设置。
  15. 根据权利要求13所述的荧光检测装置，其特征在于，所述光源(10)包括第一光源和第二光源，所述第一光源和第二光源对应的两个光源通孔(42)沿所述光路通孔(41)的轴线对称设置。
  16. 根据权利要求3至7任一项所述的荧光检测装置，其特征在于，所述框架模块(40)包括框架(43)和固定件(44)，所述框架(43)具有光路通孔(41)和所述光源通孔(42)，所述固定件(44)用于将所述第一透镜模块和所述第二透镜模块固定在所述光路通孔(41)内。
  17. 根据权利要求16所述的荧光检测装置，其特征在于，所述框架(43)的侧面的至少一部分倾斜设置形成斜面(431)，所述光源(10)设置在所述斜面(431)的凹槽(432)中，所述光源通孔(42)设置在所述凹槽(432)的槽底。
  18. 根据权利要求16所述的荧光检测装置，其特征在于，所述框架(43)远离所述被检测物的表面具有用于容置所述光信号检测器(30)的沉槽(433)。
  19. 根据权利要求3至7中任一项所述的荧光检测装置，其特征在于，所述滤光组件还包括位于所述光源(10)与所述被检测物之间的第二滤光片(24)，所述激发光照射到所述被检测物之前被所述第二滤光片(24)过滤。
  20. 根据权利要求19所述的荧光检测装置，其特征在于，所述第二滤光片(24)为窄带滤光片。
  21. 根据权利要求19所述的荧光检测装置，其特征在于，所述第二滤光片具有以下特性中的至少一个：
    所述第二滤光片(24)的中心波长在675nm至725nm之间；
    所述第二滤光片(24)的截止深度为OD6；
    所述第二滤光片(24)的截止范围在300nm至1100nm；
    所述第二滤光片(24)的带宽范围小于65nm。
  22. 根据权利要求1所述的荧光检测装置，其特征在于，所述荧光检测装置还包括卡槽框(50)和多个弹簧压轮(51)，所述框架模块(40)设置于所述卡槽框(50)上；多个所述弹簧压轮(51)设置在所述卡槽框(50)的上端面。
  23. 根据权利要求22所述的荧光检测装置，其特征在于，所述卡槽框(50)内设有用于插入试剂卡(60)的卡槽(56)，沿所述试剂卡(60)的插入方向，所述多个弹簧压轮(51)位于所述卡槽(56)的两侧，所述卡槽(56)的内侧壁中设有弹簧滚珠(52)；在所述试剂卡(60)插入时，所述弹簧压轮(51)与所述试剂卡(60)的上端面抵接，所述弹簧滚珠(52)与所述试剂卡(60)的侧面抵接。
  24. 一种用于荧光物质检测的手持设备，其特征在于，包括权利要求1至23中任一项所述荧光检测装置。
PCT/CN2022/141196 2021-12-24 2022-12-22 荧光检测装置和用于荧光物质检测的手持设备 WO2023116847A1 (zh)

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