WO1999003008A1 - Dispositif d'analyse optique d'echantillons - Google Patents

Dispositif d'analyse optique d'echantillons Download PDF

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Publication number
WO1999003008A1
WO1999003008A1 PCT/EP1998/004227 EP9804227W WO9903008A1 WO 1999003008 A1 WO1999003008 A1 WO 1999003008A1 EP 9804227 W EP9804227 W EP 9804227W WO 9903008 A1 WO9903008 A1 WO 9903008A1
Authority
WO
WIPO (PCT)
Prior art keywords
mirror
optical
light
optical axis
sample
Prior art date
Application number
PCT/EP1998/004227
Other languages
German (de)
English (en)
Inventor
Stefan Hummel
Rolf Günther
Norbert Garbow
Original Assignee
Evotec Biosystems Ag
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 Evotec Biosystems Ag filed Critical Evotec Biosystems Ag
Publication of WO1999003008A1 publication Critical patent/WO1999003008A1/fr

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Classifications

    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B17/00—Systems with reflecting surfaces, with or without refracting elements
    • G02B17/08—Catadioptric systems
    • G02B17/0804—Catadioptric systems using two curved mirrors
    • G02B17/0808—Catadioptric systems using two curved mirrors on-axis systems with at least one of the mirrors having a central aperture
    • 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
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B17/00—Systems with reflecting surfaces, with or without refracting elements
    • G02B17/08—Catadioptric systems
    • G02B17/0856—Catadioptric systems comprising a refractive element with a reflective surface, the reflection taking place inside the element, e.g. Mangin mirrors
    • G02B17/086—Catadioptric systems comprising a refractive element with a reflective surface, the reflection taking place inside the element, e.g. Mangin mirrors wherein the system is made of a single block of optical material, e.g. solid catadioptric systems
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B19/00—Condensers, e.g. light collectors or similar non-imaging optics
    • G02B19/0004—Condensers, e.g. light collectors or similar non-imaging optics characterised by the optical means employed
    • G02B19/0028—Condensers, e.g. light collectors or similar non-imaging optics characterised by the optical means employed refractive and reflective surfaces, e.g. non-imaging catadioptric systems
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B19/00—Condensers, e.g. light collectors or similar non-imaging optics
    • G02B19/0033—Condensers, e.g. light collectors or similar non-imaging optics characterised by the use
    • G02B19/0047—Condensers, e.g. light collectors or similar non-imaging optics characterised by the use for use with a light source
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G02B21/0024—Confocal scanning microscopes (CSOMs) or confocal "macroscopes"; Accessories which are not restricted to use with CSOMs, e.g. sample holders
    • G02B21/0052—Optical details of the image generation
    • G02B21/0072—Optical details of the image generation details concerning resolution or correction, including general design of CSOM objectives
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N2021/4704—Angular selective
    • G01N2021/4728—Optical definition of scattering volume
    • 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
    • G01N21/65—Raman scattering
    • 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
    • G01N2201/08—Optical fibres; light guides

Definitions

  • the present invention relates to a device for the optical detection of samples, which has a mirror lens, and to the use of this device for different application areas.
  • WO 94/16313 describes a method and a device for identifying one or a few molecules by using laser-excited fluorescence correlation spectroscopy (FCS).
  • FCS laser-excited fluorescence correlation spectroscopy
  • Molecules with a corresponding excitation spectrum that are in this volume are excited emitted fluorescence from this measurement volume can then be imaged on a detector of high sensitivity, the change in the fluorescence intensity resulting from the changing number of molecules in the measurement volume due to the diffusion movement is analyzed, the device described in WO 94/16313, equipped with confocal optics, is drawn is characterized in particular by a pinhole arranged in the emission beam path in the image plane of the objective or by a detector replacing the pinhole, in particular the optics used have a high numerical aperture.
  • WO 96/13744 describes a method and a device for determining substance-specific parameters of one or fewer molecules by means of correlation spectroscopy, the principles of near-field optics being used.
  • GB 21 19 112 A relates to an optical system for reflective focusing of the electromagnetic radiation entering the optical system through an aperture onto a detector shielded from undesired background radiation by means of reflective surfaces.
  • the object of the present invention is to enable the use of a single objective for both the illumination and the detection beam path, it being intended to ensure that the “fields of view” of the excitation radiation source and the detector overlap in the sample to be examined or are essentially identical.
  • the invention provides a device for optical
  • Detection of samples provided with at least one light source for generating electromagnetic radiation, a mirror objective arranged on a first optical axis, which receives electromagnetic radiation generated by the light source and generates a focus in a sample to be examined and receives the electromagnetic radiation generated therein, wherein the mirror objective is provided with at least one optical element made of an optically transparent material, the optical element has a first outer side and a second outer side facing away from it and facing the focus, the first outer surface has a concave first mirror surface with a light transmission opening, and the second outer surface has a convex second mirror surface which is arranged on the optical axis of the light transmission opening opposite the first outer surface and has a light transmission surface arranged around the second mirror surface, and on the optical axis At least one aperture and / or at least one detector element and / or at least one optical fiber is arranged in the area of the common beam path of the electromagnetic radiation generated by the light source and the radiation generated in the sample between the light source and the mirror lens or in the area of the light passage opening
  • the device according to the invention shows its advantage particularly when "small” measurement volumes, in particular less than 10 "12 1, are to be generated.
  • the measurement volume is determined by the intersection of the" field of view "of the transmitter and detector
  • the dye of the sample is excited to glow in the area of the entire transmitted beam, ie the field of view of the excitation radiation source.
  • the excitation density at every point of the sample is proportional to the brightness of the beam, ie in the area of the focus, much larger than in the environment
  • the proportion of the focus area in the total fluorescence light generated is small, since the focus has only a small extent.
  • the "field of view" of the detector can be viewed in a completely analogous manner.
  • the detector fluorescence light mainly comes from the focus of the transmitted beam receives, one receives well-defined "small" measuring volume.
  • the bright, high-weight areas of the focus enhance their contribution to the measurement volume; the areas with less weight outside the focal point are mutually reduced.
  • the measurement volume is defined as an integral over the product of the so-called point spread functions (PSF) of the transmitter and detector:
  • PSF point spread functions
  • V e ß ⁇ A - j JljJijJ PSF transmitter (x, y, z) PSF detector (x, y, z) dx dy dz V
  • the point spread functions have their maximum in focus and have only small values outside of it, so that their product is very small and negligible in the integral.
  • the construction according to the invention using an aperture, a detector or an optical fiber in the region of the light transmission opening or in the above-mentioned common beam path ensures that the two functions are essentially identical.
  • the arrangement according to the invention advantageously enables measurements without the need for complex readjustments of individual optical elements.
  • a diaphragm is arranged in the area of the light transmission opening.
  • this can itself take on the function of an aperture.
  • It can also be preferred to replace the diaphragm by a detector, in particular by miniaturized detector elements. This fills only a part of the light transmission opening, so that it is ensured that electromagnetic radiation generated by the light source can enter the mirror objective 10.
  • the mirror objective has only very low chromatic and transverse aberration, so that it is particularly advantageous to use an optical fiber in the area of the light transmission opening, in particular especially a single-mode fiber to connect.
  • the emission radiation emanating from the sample can be collected with this fiber and, for example, fed to a suitable detection device via a dichroic mirror. It has proven to be advantageous to couple the glass fiber to the mirror lens, which has a suitable coupling material, by fusing it with the fiber or using a so-called plug-in microconnector (Kufner et al., Micro-optics and lithography, VUBPress, Brussels, 1997 , Pp. 103 and 104; Sazaki et al., Put-in microconnectors for alignment-free coupling of optical fiber arrays, IEEE Photon. Technol. Lett. Vol. 4, p. 908-911, 1992).
  • means for variable coupling of the optical fiber can be provided in the region of the light transmission opening 28 and / or along the optical axis.
  • the structure according to the invention is particularly suitable for parallelization or for the design of an array.
  • a large number of light sources for generating electromagnetic radiation can be provided; Alternatively, however, the electromagnetic radiation generated by one or a few light sources can be split into light paths that are essentially parallel to one another by means of suitable optical elements. This results in a large number of optical axes on which the mirror lenses already described can be arranged.
  • the samples to be examined can be located, for example, in known micro- or nanotiter plates. Radiation emanating from the samples to be examined - for example fluorescence radiation - is received by the respective mirror objective and fed to an associated detector.
  • each of the plurality of optical axes is also located in the area of the common one Beam path of the electromagnetic radiation generated by the respective light source and the radiation generated in the respective focus between the respective light source and the respective mirror lens or in each case in the region of the light passage opening of the relevant mirror lens at least one diaphragm and / or at least one detector element and / or at least one optical fiber.
  • the distance between it and the focus is less than 1000 ⁇ m and in particular between 50 ⁇ m and 300 ⁇ m.
  • adsorption effects of the substances to be examined on the optically transparent film and interference effects such as Minimize scattering effects when the excitation and / or emission radiation passes through the sample.
  • the shape of the light transmission surface 34 and the choice of materials can be adapted to the desired optical set-up in such a way that chromatic errors are almost impossible become.
  • the person skilled in the art can, for example, use optical software available on the market (e.g.
  • the light transmission surface is curved, in particular hyperbolic or spherical. However, it can also be advantageous to emboss the light transmission surface in a planar manner. It can also be provided with diffractive optical elements.
  • the light transmission surface can in particular have a coating of dielectric and / or polarization-selective and / or colored materials.
  • the optically transparent material of the optical element can have a homogeneous refractive index.
  • the optical element consists of optically transparent materials with different refractive indices.
  • the refractive index of the optical element preferably varies in a radially symmetrical manner with respect to the optical axis and / or along the optical axis.
  • first mirror surface is elliptical or spherical, while the second mirror surface is in particular spherical.
  • the imaging properties of the mirror objective are preferably to be adapted to the thickness of the film and / or the refractive indices of the immersion liquid, the film, which can in particular be a cover glass, and / or the sample.
  • the radii of curvature of the first mirror surface and / or the second mirror surface and / or the light transmission surface can be designed in a suitable manner.
  • the imaging properties of the mirror objective with regard in particular to the radii of curvature of the first and second mirror surfaces and / or the light transmission surface and / or the refractive index of the optical element to the thickness of the film and / or the refractive index of the immersion liquid, the film and / or are adapted to the sample.
  • the mirror objective can also be used without a film and / or immersion liquid, the sample in this case in particular as so-called hanging drop is in contact with the outside.
  • an optically transparent material with a suitable refractive index can be selected for the optical element. These can be glass materials known in the prior art or also suitable plastic materials, such as polycarbonates, of optical quality.
  • optical elements in particular lenses and / or mirrors and / or optical filters along the optical axis of the mirror objective.
  • piezo actuators and / or electrostrictive actuators in particular on the first outside.
  • a change in the radius of curvature of the mirror surfaces and / or the light transmission surface can also be achieved by a suitable arrangement of an expandable material, for example a metal frame that can be tempered, in the region of the optical element.
  • the second outside is completely or at least partially coated with an optically transparent material.
  • This has in particular the same refractive index as the immersion liquid used.
  • a planar surface of the mirror lens on the side facing the immersion liquid can be achieved by suitable coating.
  • the position of the mirror objective according to the invention in relation to a vessel containing the sample to be examined can be controlled three-dimensionally, for example by means of piezo technology.
  • means for positioning the mirror objective relative to the sample can be provided. be seen. It is also possible to rasterize the sample.
  • the mirror lens according to the invention is particularly useful in optical scanning microscopy, e.g. laser-excited fluorescence scanning microscopy. It can also preferably be used in spectroscopy. Luminescence spectroscopy such as fluorescence correlation spectroscopy (FCS) or molecular-independent fluorescence techniques, Raman spectroscopy, light scattering and absorption spectroscopy should be mentioned here in particular.
  • FCS fluorescence correlation spectroscopy
  • Raman spectroscopy Raman spectroscopy
  • the molecules in sample 16 can be excited by single or multi-photon excitation.
  • FCS fluorescence correlation spectroscopy
  • Raman spectroscopy Raman spectroscopy
  • the molecules in sample 16 can be excited by single or multi-photon excitation.
  • a method based on a molecular brightness analysis that is independent of the molecular weight is disclosed in detail in WO 98/16814, the disclosure content of which is hereby expressly incorporated by reference.
  • Applications of the FCS
  • Another field of use of the device according to the invention can be seen in medical technology and here in particular in endoscopy.
  • 1 is a side view of a miniaturized mirror lens
  • 2 shows a schematic representation of a large number of mirror lenses arranged in arrays for quasi-parallel examination of a large number of samples
  • 3 shows an optical construction with an aperture arranged in the region of the light passage opening of the mirror objective
  • FIG. 5 is a side view of a further embodiment of a mirror lens with fiber coupling
  • Fig. 6 is a side view of another embodiment of a mirror lens with fiber coupling
  • Fig. 7 is a side view of another embodiment of a mirror lens.
  • a mirror lens is shown schematically in side view.
  • the mirror objective 10 is used to focus incident excitation light or radiation 12 in a focus 14 which is arranged within the sample 16 to be examined, with the result of the excitation light 12 in the sample 16 being emission light or Emission radiation is generated, which leaves the mirror lens 10 in the opposite direction to the direction of incidence of the excitation light.
  • the mirror objective 10 has at least one optical element 18 made of an optically transparent material and has a first outer side 20 facing the incident excitation light 12 and a second outer side 22 facing the sample 16 and thus the focus 14 and facing away from the first outer side 20.
  • the first outer side has a concave first outer surface 24, which carries an essentially light-reflecting coating 26.
  • the first outer surface 24 has a region 28 enclosed on all sides by the coating 26, in which it is free of the coating 26.
  • the area 28 represents thus a through opening for the excitation and emission light.
  • the material of the coating 26 is selected such that the first outer surface 24 acts in its area provided with the coating material 26 for radiation incident from the inside like a mirror surface (first mirror surface).
  • the second outer side 22 has a second outer surface 30, which comprises differently curved sections.
  • the second outer surface 30 is provided with a relatively strongly convexly curved section 32, to which a less strongly curved surface section 34 adjoins on the outside in a ring shape.
  • the section 32 of the second outer surface 30 is coated from the outside with a coating material which is essentially light-reflecting.
  • the second outer surface 30 is translucent, so that light can enter or leave the element 18 via this section 34, in particular with refraction of light.
  • section 34 of second outer surface 30 is a light transmission surface, in particular a refraction surface, while section 32 acts like a mirror surface (second mirror surface) for light that strikes from the inside.
  • the mirror lens 10 is in the immediate vicinity of a glass or plastic plate or film 38, the area between the film 38 and the second outside 22 of the element 18 being filled with an immersion liquid 40, which is in particular water or always - Sion oil is trading.
  • the sample 16 to be examined is located on the side of the film 38 facing away from the mirror objective 10.
  • the thickness of the film is preferably between 100 and 200 ⁇ m.
  • the operation of the mirror lens 10 and in particular the propagation of light within the mirror lens are as follows. Excitation light 12 enters the optical element 18 via the opening 28. This excitation light 12 is reflected divergently on the second mirror surface 32 until it strikes the first mirror surface 24. From there, the excitation light 12 is reflected in the direction of the light transmission surface 34.
  • the excitation light 12 emerges through this light transmission surface 34, in particular with refraction of light, and through the immersion liquid 40. Furthermore, the excitation light 12 penetrates the film 38 and is focused in the focus 14.
  • the focus 14 located in the sample 16 to be examined has in particular a volume in the range of 10 10 "12 1, preferably ⁇ 10 ⁇ 14 1. In the sample 16, emission radiation excited by the excitation light 12 reaches the direction of propagation of the excitation light 12 opposite direction back into the optical element 18 and out of the opening 28.
  • the advantage of the mirror objective 10 described here and shown in FIG. 1 is that the reflection surfaces and the light transmission surface 34, which is designed in particular as a refraction surface, are formed on a common element. This allows the mirror - objectively in one piece, i.e. realize monolithic. This in turn has advantages in terms of miniaturization of the mirror lens. In this way, for example, mirror lenses 10 can be produced, the extensions of which lie transversely to the direction of light incidence and in the direction of light incidence in the millimeter or sub-millimeter range.
  • FIG. 2 schematically shows a large number of mirror lenses arranged in arrays for quasi-parallel examination of a large number of samples.
  • the mirror lenses are arranged here in the form of a multi-array, in order to be able to examine a large number of samples 16, which are present in suitable so-called multi-well plates - which may have a 96 format, for example - at the same time. This results in particular uses in the area of high-throughput screening for pharmacologically active substances or for diagnostic examinations.
  • the optical elements 18 arranged in columns and rows are integrally formed on a common carrier body 44 and have light guides 46, which lead to an optical lens array 48 with a plurality of lenses 50, are coupled into the light guides 46 via the excitation radiation and emit emission radiation of the samples the optical fibers 46 is coupled out.
  • FIG. 3 shows a further embodiment of the device according to the invention.
  • Electromagnetic radiation generated in a light source 80 (for example a He-Ne laser with a wavelength of 543 nm, Uniphase Ine,, USA) strikes a dichroic mirror or beam splitter 70 and, after passing through a lens arrangement 62 and diaphragm 66, reaches the light transmission opening 28 of the mirror lens 10, which is an optical element 18 from, for example Has quartz glass.
  • the mirror lens has in particular a numerical aperture ⁇ 0.9.
  • the laser light that enters the sample through a cover glass BK7 excites the molecules in the observation volume, for example, to fluoresce.
  • the resulting fluorescent light passes through the mirror lens 10, the aperture 66 and the lens arrangement 62 onto the dichroic mirror or beam splitter 70. From there it is fed to a further lens arrangement 64 and by means of a detector 90 (eg avalanche photo diode SPCM-AQ-131 , EG & G Inc., Canada).
  • a detector 90 eg avalanche photo diode SPCM-AQ-131 , EG & G Inc., Canada.
  • the mirror objective 10 is embedded in a body made of quartz, for example consists of a first part 104 and a second part 102 serving as a "front panel".
  • a body made of quartz for example consists of a first part 104 and a second part 102 serving as a "front panel".
  • This configuration offers advantages in terms of production technology in particular if the optical element 18 is filled with an immersion liquid.
  • the fiber tip 47 of the coupled single-mode fiber 46 serves as a common field of view diaphragm for excitation and detection light.
  • the refractive surfaces of the front plate 102 are chosen to be flat. With a suitable choice of the immersion liquid, the remaining axial focus shift, which is caused by the dispersion of the front plate and sample holder, can be reduced to below 0.1 ⁇ m for the entire visual range.
  • the micro-optics map two diffraction-limited points, the core mode on the fiber front surface and the focal point in the sample.
  • the focus diameter is inversely proportional to the wavelength and proportional to the numerical aperture of the focused beam.
  • the divergence angle of the light emerging from the fiber is proportional to the wavelength.
  • the numerical aperture (on the focal point side) therefore increases with the wavelength, so that the focus diameter is almost independent of the wavelength.
  • FIG. 5 shows a further preferred embodiment of the mirror objective 10.
  • the optical element 18 consists of two different “optically transparent materials. This can be, for example, immersion liquid in the part of the optical element 18 facing the body 104, while quartz glass can be used as a further material.
  • This embodiment also has mounting plates 120 that connect the monolithically shaped body 104 to the mirror lens 10.
  • the mirror objective 10 is in turn embedded in a body which consists of a first part 104 and a second part 102 serving as a “front plate”.
  • a curved light transmission surface 34 is arranged around the mirror surface 32.
  • FIG. 7 shows, compared to FIG. 6, an optical setup without a sample carrier.
  • the sample 16 to be examined - such as an assay solution - is in direct contact with the front plate 102.

Abstract

L'invention concerne un dispositif d'analyse optique d'échantillon, qui comprend au moins une source de lumière (80) servant à produire un rayonnement électromagnétique (12) et un objectif à miroir (10) disposé sur un premier axe optique (11), qui reçoit le rayonnement électromagnétique (12) produit par la source de lumière, définit un foyer (14) dans un échantillon (16) à analyser et reçoit également le rayonnement électromagnétique produit dans le foyer (14). L'objectif à miroir (10) est pourvu d'au moins un élément optique (18) constitué d'un matériau optique transparent, qui présente un premier côté extérieur (20) et un second côté extérieur (22) opposé au premier côté et tourné vers le foyer (14). Le premier côté extérieur (20) est pourvu d'une première surface réfléchissante (24) qui est concave et comporte une ouverture de passage de lumière (28), tandis que le second côté extérieur (22) présente une seconde surface réfléchissante (32) qui est convexe et qui est disposée sur l'axe optique (11), en vis-à-vis de l'ouverture de passage de lumière (28) du premier côté extérieur (20) et présente une surface de passage de lumière (34) disposée autour de la seconde surface réfléchissante (32).
PCT/EP1998/004227 1997-07-09 1998-07-08 Dispositif d'analyse optique d'echantillons WO1999003008A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19729245.3 1997-07-09
DE1997129245 DE19729245C1 (de) 1997-07-09 1997-07-09 Spiegelobjektiv und dessen Verwendung

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EP1469349A1 (fr) * 2003-04-17 2004-10-20 ASML Netherlands B.V. Appareil de projection lithographique avec un collecteur comprenant un miroir concave et un miroir convexe
DE102004016361A1 (de) * 2004-04-01 2005-11-03 Cybio Ag Optisches Analysenmessgerät für Fluoreszenzmessungen an Multiprobenträgern
US7489385B2 (en) 2003-04-17 2009-02-10 Asml Netherlands B.V. Lithographic projection apparatus with collector including concave and convex mirrors
DE102015001033A1 (de) * 2015-01-27 2016-07-28 Leibniz-Institut für Photonische Technologien e. V. Hochdurchsatz-Screening-System zur Durchführung von optischen Messungen
JP2016143057A (ja) * 2015-01-30 2016-08-08 アスフェリコン ゲゼルシャフト ミット ベシュレンクテル ハフツング ほぼコリメートされた光線を焦束するための光学素子
US9563044B2 (en) 2012-07-17 2017-02-07 Ecole Polytechnique Federale De Lausanne Reflective optical objective
US10088427B2 (en) 2015-03-31 2018-10-02 Samantree Medical Sa Systems and methods for in-operating-theatre imaging of fresh tissue resected during surgery for pathology assessment
US10539776B2 (en) 2017-10-31 2020-01-21 Samantree Medical Sa Imaging systems with micro optical element arrays and methods of specimen imaging
US10928621B2 (en) 2017-10-31 2021-02-23 Samantree Medical Sa Sample dishes for use in microscopy and methods of their use
US11747603B2 (en) 2017-10-31 2023-09-05 Samantree Medical Sa Imaging systems with micro optical element arrays and methods of specimen imaging

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