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WO2004070366A1 - Systeme d'imagerie par fluorescence et systeme de biomanipulation l'utilisant - Google Patents

Systeme d'imagerie par fluorescence et systeme de biomanipulation l'utilisant Download PDF

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Publication number
WO2004070366A1
WO2004070366A1 PCT/JP2003/001136 JP0301136W WO2004070366A1 WO 2004070366 A1 WO2004070366 A1 WO 2004070366A1 JP 0301136 W JP0301136 W JP 0301136W WO 2004070366 A1 WO2004070366 A1 WO 2004070366A1
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WO
WIPO (PCT)
Prior art keywords
light
sample
fluorescence
light source
light emitting
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2003/001136
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English (en)
Japanese (ja)
Inventor
Kunio Isono
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CORRECTMEDIAS Co Ltd
Inabata and Co Ltd
Original Assignee
CORRECTMEDIAS Co Ltd
Inabata and Co Ltd
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
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Priority to PCT/JP2003/001136 priority Critical patent/WO2004070366A1/fr
Publication of WO2004070366A1 publication Critical patent/WO2004070366A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6456—Spatial resolved fluorescence measurements; Imaging
    • G01N21/6458—Fluorescence microscopy
    • 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
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"

Definitions

  • the present invention relates to a fluorescence imaging system for acquiring a fluorescence microscope image using a small light emitting element such as a semiconductor laser or a light emitting diode, and a biomanipulator system using the same.
  • a small light emitting element such as a semiconductor laser or a light emitting diode
  • a fluorescent imaging observation method there is known a technique called a fluorescent antibody method in which a substance that specifically binds to cells of a biological tissue is labeled with a fluorescent sample or the like, and a local portion in the cell is observed.
  • Luminescence includes chemiluminescence due to chemical reactions and bioluminescence involving enzymes in the living body. The latter is an in-vivo chemical reaction between an organic compound that glows by oxidation (for example, luminophore luciferin) and an enzyme that assists its oxidation (luciferase). .
  • GFP Green F 1 ourescent Protein
  • Fluorescent reagents developed to obtain the desired fluorescent image observations are used in typical methods for observing fluorescent images, but typical staining methods include FITC staining, DAPI staining, and plant plantatone. There are three red autofluorescence observation methods.
  • the FITC staining method observes green fluorescence that absorbs light around 470 nm and emits light having a wavelength of 500 to 540 nm, and uses a blue light source as excitation light.
  • the DAPI staining method uses a fluorescent dye that absorbs light around 360 nm and emits 460 nm blue fluorescence, and is used for nuclear staining of cells. Ultraviolet light is used as the excitation light.
  • a plant excitation chlorophyll dye absorbs a wavelength around 480 to 570 nm and observes fluorescence from orange to red of 568 nm or more, using a green excitation light source.
  • a light source for stimulating cells is necessary in order to capture luminescence from cells to be observed using a fluorescence microscope.
  • a xenon lamp, a mercury lamp, or the like is conventionally used.
  • a mercury lamp there is a lamp life (the average life of a 120 W class mercury lamp is 200 It took about 0 hours), required a high voltage of 200 V, required a large space, and was expensive.
  • An object of the present invention is to provide a simpler and simpler fluorescence imaging system that applies the principle of the fluorescent antibody method.
  • dicing that is, cutting out small parts of cells, requires a large-scale system using a laser, and single-molecule observation requires an individual illumination guide.
  • the microscope unit and the manipulator were used as separate units, and what was used in combination is now integrated with the microscope main body, more dedicated, and a separate drive system is provided.
  • the purpose of the present invention is to provide a device that can simplify the mechanism, simplifies the mechanism, saves space, can reduce the cost, and can perform local illumination using this mechanism. Disclosure of the invention
  • the fluorescence imaging system includes an excitation optical system for irradiating the sample with excitation light for illuminating a fluorescent substance contained in the sample, and an optical system for observing fluorescence generated by the sample by excitation. Record images of the microscope system and the fluorescent sample
  • the excitation optical system includes a light source including a small light emitting element such as a semiconductor laser or a light emitting diode.
  • the fluorescence imaging system includes an epi-illumination optical system for guiding light from a light source to a sample, an optical microscope system, and a digital recording system for imaging and recording fluorescence passing through the optical microscope system.
  • the light source of the above-mentioned epi-illumination optical system is composed of a small light emitting element such as a semiconductor laser or a light emitting diode for emitting excitation light for illuminating a fluorescent substance contained in the sample to the sample.
  • the microscope system includes an exciter filter that selectively transmits the light from the light source, a dichroic mirror that reflects the excitation light toward the sample and transmits the fluorescence generated from the sample, and an objective lens.
  • the light source of the epi-illumination optical system is composed of a plurality of small light-emitting elements such as semiconductor lasers and light-emitting diodes, and these are annular and concentric with the optical axis of the optical microscope system. It is good to place it in.
  • the fluorescence imaging system includes a reflection illumination optical system for guiding light from a light source to the sample, an optical microscope system, and a digital recording system, wherein the reflection illumination optical system is configured to emit a fluorescent substance contained in the sample.
  • a light source composed of a small light emitting element such as a semiconductor laser or a light emitting diode for emitting excitation light for emitting light to the sample; guiding light from the light source to the sample;
  • the digital recording system comprises an objective lens for directing light from a light source to the sample and an emission filter for transmitting only the fluorescence transmitted through the objective lens.
  • the digital recording system records and records the fluorescence transmitted through the optical microscope system. Configuration to be performed It can be.
  • the reflection illumination optical system includes an incident optical system including an optical fiber for allowing light emitted from a small light emitting element such as a semiconductor laser or a light emitting diode to enter from a side surface of the sample. Good to do. Further, the reflection illumination optical system may include an incident optical system including an optical fiber for allowing light emitted from a small light emitting element such as a semiconductor laser or a light emitting diode to be incident from obliquely above the sample.
  • the light source may be configured to include a plurality of small light emitting elements that emit light of different wavelengths in various combinations.
  • the fluorescence imaging system is a system that can easily perform microscope fluorescence observation.
  • the epi-illumination (oblique light) method can directly irradiate the sample corresponding to each excitation wavelength, which is particularly effective for observation under a stereoscopic microscope at low magnification.
  • the epi-illumination (coaxial illumination) method can illuminate under a biological microscope at a higher magnification than a stereo microscope, and can irradiate at various wavelengths or simultaneously excite multiple wavelengths.
  • the total reflection method (horizontal optical fiber injection method) and the reflection method (optical fiber oblique light incidence method) correspond to single-molecule fluorescence imaging, which is particularly effective for localization of proteins in cells.
  • the biomanipulator system emits a fluorescent material contained in a sample.
  • the system consists of an excitation optical system that irradiates the sample with the excitation light, an optical microscope system that observes the generated fluorescence, and a digital recording system that records an image of the sample that emits fluorescence.
  • a fluorescence imaging system in which the excitation optical system includes a small light-emitting element such as a semiconductor laser diode as a light source; and an operation such as cutting a microscopic portion of cell tissue by attaching to a lens barrel of the optical microscope system. And a manipulator mechanism to be used.
  • the biomanipulator system includes a fluorescence imaging system and a manipulator mechanism used for operations such as cutting a minute portion of cell tissue.
  • the fluorescence imaging system includes an excitation light for illuminating a fluorescent substance contained in a sample.
  • a small light emitting element such as a semiconductor laser or a light emitting diode as a light source for emitting light to the sample, and an epi-illumination optical system for guiding light from the light source to the sample; and selectively transmitting light from the light source.
  • An optical microscope system consisting of an emission filter that transmits light through the It consists of a digital recording system for doing the imaging and recording, also manipulator mechanism may be configured to be attached to the lens barrel of the optical microscope system.
  • the epi-illumination optical system may have a configuration in which a plurality of small light-emitting elements such as a plurality of semiconductor lasers and light-emitting diodes are arranged annularly and concentrically with the optical axis of the optical microscope system. it can.
  • the biomanipulator system comprises a fluorescence imaging system and a manipulator mechanism used for operations such as cutting a minute portion of cell tissue, and the fluorescence imaging system comprises an excitation light for illuminating a fluorescent substance contained in a sample.
  • the above sample A reflective illumination optical system that includes a small light emitting element such as a semiconductor laser or a light emitting diode as a light source for emitting light to the sample, and an object that directs light from the light source to the sample;
  • An optical microscope system including a lens and an emission filter that transmits only the fluorescence transmitted through the objective lens; and a digital recording system for performing image recording of the fluorescence transmitted through the optical microscope system, and
  • the manipulator mechanism may be configured to be used by being attached to a lens barrel of the optical microscope system.
  • the reflection illumination optical system includes an incident optical system including an optical fiber for allowing light emitted from a small light emitting element such as a semiconductor laser or a light emitting diode to enter from a side surface of the sample.
  • the reflection illumination optical system may be configured to include an incident optical system including an optical fiber for allowing light emitted from a small light emitting element such as a semiconductor laser or a light emitting diode to be incident obliquely from above the sample. .
  • the light source may be configured to include a plurality of small light emitting elements that emit light of different wavelengths in various combinations.
  • the biomanipulator system according to the present invention is not a combination of a microscope unit and a manipulator unit of a separate unit as in the related art, but is integrated with a microscope main body. Therefore, by using the system together with the fluorescence imaging system of the present invention, it is possible to make a more dedicated and common drive system, etc., thereby simplifying the mechanism, saving space, and reducing costs.
  • FIG. 1 is a conceptual diagram showing a configuration of one embodiment of a fluorescence imaging system according to the present invention.
  • FIG. 2 is a diagram illustrating a fluorescence spectrum and a filter transmission characteristic.
  • Figure 3 is a diagram showing the configuration of the epi-illumination (coaxial illumination) system.
  • FIG. 4 is a diagram showing an arrangement of an epi-illumination (oblique light) system.
  • FIG. 5 is a diagram showing an arrangement of an epi-illumination (oblique light) system.
  • Fig. 6 is a diagram showing the configuration of the total reflection method (optical fiber horizontal incidence method).
  • Fig. 7 is a diagram showing the configuration of the reflection method (optical fiber oblique light incidence method).
  • FIG. 8 is a conceptual diagram showing the configuration of one embodiment of the bio-muputer system according to the present invention.
  • FIG. 1 is a conceptual diagram showing a configuration of one embodiment of a fluorescence imaging system according to the present invention.
  • 1 is a microscope optical system
  • 2 is a digital recording system
  • 3 is a sample.
  • the microscope optics 1 consists of one or more lenses (two lenses in the figure: objective lens 10a, eyepiece 10b) and, if necessary, other optical elements 10c, and some more.
  • the mirror 11a, lib, and 11c are provided so that the fluorescence emitted from the sample 3 can be observed through the eyepiece 1Ob.
  • a transmission illumination system 12 for illuminating the sample 3 from below, and an excitation light for illuminating the pre-stained fluorescent dye on the sample 3 are applied to the sample 3.
  • An epi-illumination system 13 for illuminating the sample 3 from above is provided as an illumination system for emitting light to the sample 3.
  • 14 is a condenser lens
  • 15 is a slit
  • 16 is an exciter filter.
  • the epi-illumination system 13 includes a small light-emitting element such as a semiconductor laser or a light-emitting diode (hereinafter sometimes abbreviated as LED) as the excitation light source 17.
  • the transmitted illumination system 12 enables the combined use with various microscope observation methods, and is provided to be used together with ordinary bright field observation, phase difference observation, fluorescence observation, and the like.
  • the transmission illumination system 12 illuminates from just below the objective lens 10 a and the epi-illumination illumination system 13 illuminates from just above the objective lens 10 a.
  • Both 12 and 13 may be illuminated from obliquely below or obliquely above, rather than directly below or directly above, and the illumination direction is not limited to the illustrated example.
  • the digital recording system 2 digitally stores the image obtained by the above-described microscope optical system 1 and enables the image to be displayed.
  • the digital recording system 2 includes an emission filter 18, imaging means 19, and a monitor 20.
  • the imaging means 19 is not shown in detail, it is composed of a CCD camera or the like and a recording medium (hard disk, CF card, smart media, etc.), and known means may be appropriately adopted as components such as the CCD. .
  • a CCD camera no special camera is required, and a camera with an accuracy level equivalent to that of a commercial product may be used.
  • the observation magnification can be increased by a combination of a CCD camera or the like and a monitor 20 such as a CRT.
  • the emission filter 18 is observed with a specific wavelength light source, as described later, it becomes possible to observe more accurately by using a wavelength cut filter.
  • the fluorescence imaging system of the first embodiment originated from the epi-illumination system 13. After passing through the light, the wavelength is selected by the exciter filter 16 and the sample 3 is irradiated as excitation light.
  • the excitation light illuminates sample 3 through a mirror (diclock mirror) 11b and objective lens 10a. If necessary, the sample 3 can be illuminated from below with the transmitted illumination system 12.
  • Sample 3 is stained with a fluorescent dye in advance, and emits fluorescence when irradiated with excitation light.
  • the fluorescent light passes through the objective lens 10a, passes through the dichroic mirror 11b and the emission filter 18, and is used for observation by the eyepiece 10b and imaging and recording by the digital recording system 2.
  • a known method may be used for staining the sample 3 with a fluorescent dye, but a finely-granulated fluorescent substance developed in recent years may be included in the sample 3. In this case, if the sample 3 is collected from an animal, a plant, or the like, it can be used as a sample after ingesting fine-grained fluorescent substances.
  • the first embodiment uses a small light emitting element such as a semiconductor laser or a light emitting diode as a light source, thereby reducing the size of the light source unit, the size of the microscope unit, the power consumption, and the amount of heat generation. Has been realized. Also, the thermal deformation of the components as a microscope is reduced. Next, selection of the excitation light source will be described.
  • the above-described various fluorescence observations are configured by combining light-emitting diodes as follows. The case of using other small light emitting elements such as a semiconductor laser may be examined in substantially the same manner.
  • Excitation light is from a blue light source (around 470 nm), and a cut filter is used as a fluorescent filter to observe green fluorescence with a wavelength of 500 to 540 nm.
  • ⁇ DAPI staining method The excitation light used was ultraviolet light (light near 360 nm), and a cut filter was used as the fluorescence filter to observe the blue fluorescence at 460 nm.
  • an excitation filter can be omitted from the characteristics of a light emitting diode or a semiconductor laser capable of emitting excitation light at a predetermined emission wavelength in advance, but may be added to each.
  • a multiband filter corresponding to each fluorescence wavelength band may be used for the emission filter and the dichroic mirror.
  • a combination of a filter and a dichroic mirror as shown below is used to obtain the transmission characteristics of a specific wavelength by avoiding the interference of excitation light to extract only a weak fluorescence wavelength.
  • Fig. 2 The relationship between ordinary fluorescent statal and filters is as shown in Fig. 2 (A).
  • An excitation filter (EX) is provided for certain types of excitation light.
  • the UV excitation light (around 400 nm) is oscillated and the fluorescent light is transmitted, so that fluorescence observation can be performed with a configuration of a fluorescent filter (EM) and a dichroic mirror (DM).
  • EM fluorescent filter
  • DM dichroic mirror
  • EM fluorescent filter
  • DM dichroic mirror
  • a fluorescent filter (EM) that transmits excitation light based on UV light and transmits the emission fluorescent region. Assuming that blue (near 470 nm) and green (near 520 nm) are used as excitation light in addition to UV, a tang pass filter should be used for EM.
  • the triple band configuration is intended to simultaneously excite various types of excitation light, and uses a combination of a fluorescent filter and a dichroic mirror that efficiently transmits only each fluorescent wavelength region, as described later. Used for coaxial epi-illumination.
  • Figure 2 (C) shows a filter and a mirror that transmit the fluorescence wavelengths corresponding to each of the three excitation lights.
  • the excitation light source 17 uses a plurality of small light-emitting elements having different emission wavelengths so as to be able to perform both excitation for various wavelengths and excitation combining arbitrary wavelengths.
  • FIG. 1 When using the epi-illumination method and the coaxial illumination method as shown in FIG. 1, as shown in FIG. 1 is arranged cyclically or semi-circularly, or randomly.
  • the lamp 21 is preferably arranged such that a plurality of small-sized light emitting elements of each color of ultraviolet light (UV), blue (B 1 u e), and green (G r e en) can be used by switching.
  • reference numeral 22 denotes a light control tube
  • reference numeral 23 denotes a concave mirror.
  • the ramp 21 is made annular (Fig. 4A) or horseshoe-shaped (Fig. 4B). It is arranged alternately for each wavelength to be excited, and is switched by a switch or the like (not shown) to emit a predetermined wavelength.
  • the lamp 21 may be formed by alternately arranging a plurality of small light emitting elements of each color of ultraviolet light (UV), blue (B 1 ue), and green (Green).
  • UV ultraviolet light
  • B 1 ue blue
  • Green green
  • an annular or horseshoe-shaped light source 17 is arranged immediately below the objective lens 10a as shown in FIG.
  • the lamp 21 may be irradiated from the side surface of the sample 3 by using the optical fiber 24 as a guide.
  • the optical fiber 24 used should be one corresponding to the ultraviolet wavelength. This is because, for a light source having an ultraviolet wavelength, the material is deteriorated and the life is shortened.
  • the optical fiber 24 is preferably fixed in such a manner that it can be moved in the X and Y axes and a small guide light can be irradiated using a fixed guide mechanism 25 having a centering mechanism.
  • a gap material 28 is provided between the preparation 26 for holding the sample 3 and the cover glass 27 to form a gap, and the tip of the optical fiber 24 is directed toward the gap to collect light. I try to make it.
  • the optical fiber 24 may be configured to irradiate the optical fiber 24 obliquely or horizontally.
  • a fixed holder 31 for fixing and moving the optical fiber 24 is provided on the optical lens barrel (revolver) 30 of the microscope optical system 1 so that the installation angle of the optical fiber 24 can be changed. It is preferable that the installation angle of the optical fiber 24 can be adjusted from horizontal to oblique.
  • FIG. 8 is a conceptual diagram showing the configuration of one embodiment of the biomanipulator system according to the present invention. Similar to the fluorescence imaging system shown in FIG. 1, the microscope optical system 1 and the digital recording system 2 are composed of a microscope optical system 1, and the microscope optical system 1 has a manipulator mechanism 5 serving also as the fixing holder of the previous embodiment. 0 is provided, through which the angles of the pit 51 and the optical fiber 24 are variable.
  • manipulator mechanism 50 can be controlled and driven together with the XY drive system stage 53 on which the sample 3 is mounted by a common control unit 52.
  • a device such as a joystick 54 may be used.
  • the computer 55 for controlling the imaging means 19 and the monitor 20 of the digital recording system 2 is also used for controlling the manipulator mechanism 50.
  • the manipulator mechanism 50 is provided in the optical lens barrel 30, the objective lens 10a can be easily replaced, and the use of a drive system as an optical microscope makes it simple, compact, and low-cost.
  • a single control system is required, and by using a dedicated control unit, the efficiency of the original fluorescence observation work can be improved. Also in this device, it is possible to easily construct an optical trap and dicing using laser.

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

Abstract

L'invention concerne l'imagerie par fluorescence efficace dans l'observation locale d'une protéine dans une cellule et permettant l'observation par fluorescence et excitation multiples. Le système d'imagerie de l'invention comprend : un système d'illumination vertical (13) conçu pour émettre une lumière d'excitation et illuminer un échantillon (3) pour induire l'émission de lumière par un colorant fluorescent ou un luminophore contenu dans l'échantillon (3) ; un système optique de microscope (1) pour l'observation par fluorescence, doté de lentilles (10a, 10b) ; un filtre excitateur (16) conçu pour transmettre sélectivement de la lumière provenant d'une source de lumière d'excitation (17) ; et un miroir dichroïque (11b) conçu pour réfléchir la lumière d'excitation, la renvoyer vers l'échantillon et transmettre la fluorescence provenant de l'échantillon (3) ; et un système d'enregistrement numérique (2) conçu pour enregistrer la fluorescence mise en image, possédant un filtre d'émission (18) destiné à ne transmettre que la fluorescence traversant le système optique de microscope (1). La source de lumière d'excitation d'illumination (17) se compose de petits dispositifs électroluminescents, tels que des laser à semiconducteur ou des diodes électroluminescentes à différentes longueurs d'onde, capables d'exciter pour chaque longueur d'onde et pour une combinaison de longueurs d'onde sélectionnées.
PCT/JP2003/001136 2003-02-04 2003-02-04 Systeme d'imagerie par fluorescence et systeme de biomanipulation l'utilisant Ceased WO2004070366A1 (fr)

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CN102519881A (zh) * 2011-12-29 2012-06-27 北京国科华仪科技有限公司 适用于吸收光检测和荧光检测的光学检测系统
CN103080807A (zh) * 2010-08-23 2013-05-01 欧蒙医学诊断技术有限公司 用来在荧光显微术中对培养基进行自动聚焦的方法和设备
CN103245611A (zh) * 2012-02-07 2013-08-14 鸿林堂科技股份有限公司 多重激发光源系统
WO2014111674A1 (fr) * 2013-01-15 2014-07-24 Coolled Limited Eclairage à del
CN104964953A (zh) * 2015-04-09 2015-10-07 苏州飞时曼精密仪器有限公司 一种全自动大范围生物荧光分析仪
US9180593B2 (en) 2008-12-30 2015-11-10 Cella Vision AB Analyser for optical analysis of a biological specimen
CN110057724A (zh) * 2019-05-10 2019-07-26 中国科学院苏州生物医学工程技术研究所 小型荧光倒置显微成像系统
WO2021129588A1 (fr) * 2019-12-25 2021-07-01 上海睿钰生物科技有限公司 Dispositif d'éclairage fluorescent et système d'imagerie microscopique
CN114894113A (zh) * 2022-04-27 2022-08-12 山东大学 基于荧光追踪样点的材料表层去除原位测量装置及方法

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US9180593B2 (en) 2008-12-30 2015-11-10 Cella Vision AB Analyser for optical analysis of a biological specimen
US9776322B2 (en) 2008-12-30 2017-10-03 Cellavision Ab Analyser for optical analysis of a biological specimen
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CN103080807A (zh) * 2010-08-23 2013-05-01 欧蒙医学诊断技术有限公司 用来在荧光显微术中对培养基进行自动聚焦的方法和设备
CN102519881A (zh) * 2011-12-29 2012-06-27 北京国科华仪科技有限公司 适用于吸收光检测和荧光检测的光学检测系统
CN103245611A (zh) * 2012-02-07 2013-08-14 鸿林堂科技股份有限公司 多重激发光源系统
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CN104964953A (zh) * 2015-04-09 2015-10-07 苏州飞时曼精密仪器有限公司 一种全自动大范围生物荧光分析仪
CN110057724A (zh) * 2019-05-10 2019-07-26 中国科学院苏州生物医学工程技术研究所 小型荧光倒置显微成像系统
WO2021129588A1 (fr) * 2019-12-25 2021-07-01 上海睿钰生物科技有限公司 Dispositif d'éclairage fluorescent et système d'imagerie microscopique
CN114894113A (zh) * 2022-04-27 2022-08-12 山东大学 基于荧光追踪样点的材料表层去除原位测量装置及方法
CN114894113B (zh) * 2022-04-27 2024-01-12 山东大学 基于荧光追踪样点的材料表层去除原位测量装置及方法

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