+

WO2018197230A1 - Imagerie par contraste de phase dotée d'une fonction de transfert - Google Patents

Imagerie par contraste de phase dotée d'une fonction de transfert Download PDF

Info

Publication number
WO2018197230A1
WO2018197230A1 PCT/EP2018/059452 EP2018059452W WO2018197230A1 WO 2018197230 A1 WO2018197230 A1 WO 2018197230A1 EP 2018059452 W EP2018059452 W EP 2018059452W WO 2018197230 A1 WO2018197230 A1 WO 2018197230A1
Authority
WO
WIPO (PCT)
Prior art keywords
transfer function
image
aperture
sample object
imaging optics
Prior art date
Application number
PCT/EP2018/059452
Other languages
German (de)
English (en)
Inventor
Lars STOPPE
Thomas Milde
Original Assignee
Carl Zeiss Microscopy Gmbh
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 Carl Zeiss Microscopy Gmbh filed Critical Carl Zeiss Microscopy Gmbh
Priority to CN201880025065.8A priority Critical patent/CN110520780B/zh
Publication of WO2018197230A1 publication Critical patent/WO2018197230A1/fr

Links

Classifications

    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/06Means for illuminating specimens
    • G02B21/08Condensers
    • G02B21/14Condensers affording illumination for phase-contrast observation
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/06Means for illuminating specimens
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/36Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/365Control or image processing arrangements for digital or video microscopes
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/36Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/365Control or image processing arrangements for digital or video microscopes
    • G02B21/367Control or image processing arrangements for digital or video microscopes providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison

Definitions

  • TECHNICAL FIELD Various examples of the invention generally relate to an optical system having a lighting module configured to illuminate a sample object having a structured illumination geometry. Various examples of the invention relate in particular to techniques based on a
  • phase contrast image In one embodiment, it may often be desirable to create a so-called phase contrast image of the sample object.
  • Phase contrast image is at least a part of the image contrast by a
  • phase shift of the light caused by the imaged sample object can be imaged with comparatively high contrast, which cause no or only a slight weakening of the amplitude, but a significant phase shift;
  • sample objects are often referred to as phase objects.
  • biological samples as a sample object in a microscope can cause a comparatively larger phase change than an amplitude change of the electromagnetic field.
  • phase-contrast imaging such as
  • phase-contrast imaging This can be constructive Restrictions result. Furthermore, application restrictions may exist: For example, fluorescence imaging may be hampered by providing the additional optical elements.
  • phase contrast can be achieved by means of structured illumination.
  • a first example of techniques which can achieve an image with phase contrast by means of structured illumination is disclosed in DE 10 2014 1 12 242 A1. However, such techniques have certain
  • Phase contrast technique (English, quantitative differential phase contrast, QDPC). See, for example, L. Tian and L. Waller: “Quantitative differential phase contrast imaging in an LED array microscope", Optics Express 23 (2015), 1 1394 (hereinafter Tian, Waller), however, such techniques have the disadvantage that, depending on For example, certain requirements with respect to the size of an aperture of the lighting module relative to a size of an aperture may be optic-to-detection
  • an optical system in one example, includes a sample holder.
  • the sample holder is arranged to fix a sample object.
  • the optical system also includes a lighting module.
  • the illumination module is set up to illuminate the sample object with at least one structured illumination geometry.
  • the optical system also includes imaging optics configured to generate an image of the sample object illuminated with the at least one structured illumination geometry on a detector.
  • the optical system also includes the detector.
  • the detector is configured to generate at least one image of the image based on the image
  • the optical system also includes a controller.
  • the controller is configured to determine a result image based on a transfer function and the at least one image.
  • the result image has a phase contrast.
  • the transfer function corresponds to a reference transfer function scaled based on a size of an aperture of the imaging optics.
  • an optical system in one example, includes a sample holder.
  • the sample holder is arranged to fix a sample object.
  • the optical system also includes a lighting module.
  • the illumination module is set up to illuminate the sample object with at least one structured illumination geometry.
  • the optical system also includes imaging optics configured to generate an image of the sample object illuminated with the at least one structured illumination geometry on a detector.
  • the optical system also includes the detector. Of the Detector is arranged to generate at least one image of the image based on the image
  • the optical system also includes a controller.
  • the controller is configured to determine a result image based on a transfer function and the at least one image.
  • the result image has a phase contrast.
  • a size of the aperture of the illumination module is smaller than a size of the aperture of the imaging optics.
  • a method in one example, includes illuminating a sample object having at least one structured illumination geometry. The method also includes generating an image of the one having the at least one structured one
  • Illumination geometry illuminated specimen object Based on the image, the method further comprises capturing at least one image of the sample object. Based on a transfer function and the at least one image, a result image is determined which has a phase contrast.
  • Transfer function corresponds to a reference transfer function that is scaled based on a size of an aperture of the imaging optics.
  • a computer program product includes program code that can be executed by at least one processor. Running the program code causes the at least one processor to perform a method. The method includes illuminating a sample object with at least one structured one
  • the method also includes generating an image of the illuminated one with the at least one structured illumination geometry
  • the method further comprises capturing at least one image of the sample object. Based on a transfer function and the at least one image, a result image is determined which contains a
  • the transfer function corresponds to a reference transfer function that is scaled based on a size of an aperture of the imaging optics.
  • a computer program includes program code that can be executed by at least one processor. Executing the program code causes the at least one processor performs a method. The method includes the
  • the method also includes generating an image of the illuminated one with the at least one structured illumination geometry
  • the method further comprises capturing at least one image of the sample object. Based on a transfer function and the at least one image, a result image is determined which contains a
  • the transfer function corresponds to a reference transfer function that is scaled based on a size of an aperture of the imaging optics.
  • Phase contrast to determine particularly flexible are based on the knowledge that, by suitably selecting the transfer function, it may be possible to determine the result image with the phase contrast, even if, for example, a particularly large aperture of the imaging optics is used.
  • the result image does not necessarily encode a quantitative description of the phase of the sample object by means of the phase contrast, but with a suitable choice of the transfer function, a qualitative description of the phase of the
  • Sample object e.g. as height profile provides.
  • FIG. 1 schematically illustrates an optical system according to various examples, the optical system having a lighting module configured to illuminate a sample object having a structured illumination geometry.
  • FIG. 2 schematically illustrates the lighting module having a plurality of
  • FIG. 3 schematically illustrates an exemplary illumination geometry that can be used to illuminate the sample object by means of the illumination module.
  • FIG. 4 schematically illustrates an exemplary illumination geometry that can be used to illuminate the sample object by means of the illumination module.
  • FIG. 5 schematically illustrates an exemplary illumination geometry that can be used to illuminate the sample object by means of the illumination module.
  • FIG. 6 schematically illustrates a transfer function that may be used in determining a result image according to various examples.
  • FIG. 7 schematically illustrates a transfer function that may be used in determining a result image, according to various examples, wherein the transfer function of FIG. 7 with respect to the transfer function according to FIG. 8 is scaled.
  • FIG. 8 schematically illustrates a transfer function that may be used in determining a result image according to various examples.
  • FIG. 9 schematically illustrates transfer functions that may be used to determine a result image according to various examples.
  • FIG. 10 is a flowchart of an example method.
  • connections and couplings between functional units and elements illustrated in the figures may also be implemented as an indirect connection or coupling.
  • a connection or coupling may be implemented by wire or wireless.
  • Functional units can be implemented as hardware, software or a combination of hardware and software.
  • the result image can map a phase object with a phase contrast.
  • the result image can be in
  • Sample object are intensity images which themselves have no phase contrast.
  • the one or more images of the sample object may be associated with different illumination geometries. This means that the one or more images can each be detected by a detector with simultaneous illumination of the sample object by means of a corresponding illumination geometry.
  • the different lighting geometries can, for example, with
  • Illumination geometries or associated different images can be separated from one another by time multiplexing or frequency multiplexing. It would also be possible to separate by means of different polarizations.
  • Illumination geometries may have a directionality, for example, the illumination geometries may have a gradient of illuminance along one or more spatial directions.
  • the illuminance could vary in steps along a spatial direction, such as between zero and a finite value, or between two different finite values.
  • the sample object may comprise a phase object, such as a cell or cell culture, etc.
  • the sample object may be a-priori unknown, i. Different sample objects can be fixed by the sample holder.
  • the sample object could also be non-translucent for the light used.
  • the transfer function can be a
  • the transfer function may be suitable for predicting the at least one image for a specific illumination and a specific sample object.
  • the transfer function may have a real-valued component and / or an imaginary component.
  • the real-valued component of the transfer function can contribute to a decrease in the intensity of the light Pass through the sample object correspond.
  • An amplitude object typically has significant attenuation of the light.
  • the imaginary portion of the transfer function may be a shift in the phase of the sample object
  • phase object typically has a significant shift in the phase of the light.
  • techniques are described in particular to determine the imaginary part of the transfer function. For the sake of simplicity, reference will not be made below to the fact that the techniques relate to the imaginary part of the transfer function. In some examples, a purely imaginary transfer function without real valued part may be used.
  • the transfer function could be determined based on a technique according to Abbe.
  • a technique according to Abbe a reference transfer function could be determined.
  • the sample object can be separated into different spatial frequency components.
  • an overlay of infinitely many harmonic gratings can model the sample object.
  • the light source can also be decomposed into the sum of different point light sources.
  • Another example relates to the determination of the optics transfer function which describes the image of the sample object for a particular illumination geometry based on a Hopkins technique, see H.H.
  • TCC transmission cross-coefficient matrix
  • the frequencies that transmit the optics are limited to the area in which the TCC assumes values other than 0.
  • a system with a high coherence factor or coherence parameter consequently has a larger area with TCC ⁇ 0 and is capable of higher
  • the TCC typically contains all the information of the optical system and the TCC often takes into account even complex valued pupils such. B. in Zernike phase contrast or triggered by aberrations.
  • the TCC may allow separation of the optics transfer function from the object transfer function. In some examples, it is also possible that the
  • Transfer function is specified and no determination must be made as TCC or Abbe.
  • Sample object can be determined with different illumination geometries:
  • I DPC describes the spectral decomposition of a combination of two images / approximately IB, which were recorded at different illumination geometries that illuminate mutually complementary semicircles:
  • the illumination geometry need not be strictly semi-circular.
  • four LEDs could be used, which are arranged on a semicircle.
  • a semicircle For example, could be defined
  • Phase shift can be caused by a change in the thickness of the sample object or the topography of the sample object and / or by a change in the optical properties.
  • two images I DPC and I DPC, 2 can be determined, once with a pair of semi-circular illumination geometries that are arranged top-bottom in a lateral plane perpendicular to the beam path (I D pc, i) an d once with a pair of semicircular illumination geometries arranged left-right in the lateral plane (l DPC , 2) - Then both I DPC and I DPC> 2 can be taken into account in determining the result image, see Summation Index in Eq. 1 .
  • FIG. 1 illustrates an example optical system 100.
  • the optical system 100 according to the example of FIG. 1 implement a light microscope, for example in transmitted-light geometry.
  • a microscope could for example
  • Phase contrast imaging can be used.
  • the optical system 100 according to the example of FIG. 1 also implement a light microscope, in Auflichtgeometrie.
  • a corresponding Light microscope used in Auflichtgeometrie for material testing.
  • a height profile of the sample object can be created.
  • the optical system 100 it may be possible to enlarge small structures of a sample object fixed by a sample holder 13.
  • the optical system 100 could implement a wide field microscope in which a sample is fully illuminated.
  • the imaging optics 12 may generate an image of the sample object on a detector 14.
  • the detector 14 may then be configured to capture one or more images of the sample object. A viewing through an eyepiece is conceivable.
  • imaging optics 112 could have a numerical aperture of not less than 0.2, optionally not less than 0.3, more optionally not less than 0.5.
  • the imaging optics 1 12 could have an immersion objective.
  • the optical system 100 also includes a lighting module 1 1 1. Das
  • Illumination module 1 1 1 is set up to the sample object, which on the
  • Sample holder 1 13 is fixed to light.
  • this lighting could be implemented by means of Köhler illumination.
  • Köhler illumination There will be a
  • Condenser lens and a condenser aperture used This leads to a particularly homogeneous intensity distribution of the light used for the illumination in the plane of the sample object.
  • a partially incoherent lens and a condenser aperture used This leads to a particularly homogeneous intensity distribution of the light used for the illumination in the plane of the sample object.
  • Lighting be implemented.
  • the lighting module 1 1 1 could also be set up to illuminate the sample object in dark field geometry.
  • the lighting module 1 1 1 is set up to allow structured lighting. This means that by means of
  • Illumination module 1 1 1 different illumination geometries of the
  • Illumination of the sample object used light can be implemented.
  • the different illumination geometries can correspond to illumination of the sample object from different illumination directions.
  • the lighting module 1 1 1 could include a plurality of adjustable lighting elements configured to locally modify or emit light.
  • a controller 1 15 can the
  • Lighting module 1 1 1 or the lighting elements to implement a specific lighting geometry to control.
  • the controller 1 15 could be implemented as a microprocessor or microcontroller. Alternatively or additionally, the controller 1 15 could include, for example, an FPGA or ASIC. The controller 1 15 may alternatively or additionally also the sample holder 1 13, the imaging optics 1 12, and / or the detector 1 14 control.
  • FIG. 2 illustrates aspects relating to the lighting module 1 1 1.
  • the lighting module 1 1 1 a variety of adjustable
  • Illumination elements 121 in a matrix structure.
  • the matrix structure is oriented in a plane perpendicular to the beam path of the light (lateral plane;
  • the adjustable illumination elements 121 could be implemented as light sources, such as light emitting diodes. For example, it would then be possible for different light-emitting diodes with different light intensity to emit light for illuminating the sample object. As a result, a lighting geometry can be implemented.
  • the Illumination module 1 1 1 as a spatial light modulator (English, spatial light modulator, SLM) to be implemented. The SLM can be spatially resolved into an intervention
  • Condenser pills which may have a direct impact on imaging - for example, formalized by the TCC.
  • FIG. FIG. 3 illustrates aspects related to an exemplary illumination geometry 300.
  • FIG. 3 is the provided luminous intensity 301 for the various adjustable ones
  • the illumination geometry 300 has a dependence on the position along the axis XX 'and is therefore structured.
  • FIG. 4 illustrates aspects related to an example illumination geometry 300.
  • FIG. 4 illustrates the illumination geometry 300 abstractly from the illumination module 1 1 1 used.
  • an illumination geometry 300 is used in which one side is illuminated (black color in FIG. 4) and the other side is not illuminated (white color in FIG. 4).
  • FIG. 5 another exemplary illumination geometry is shown (with corresponding color coding as already described with respect to FIG. 4).
  • FIG. 6 illustrates aspects relating to an example transfer function 400
  • the transfer function 400 may be used to generate, based on an image, for example, the
  • Illumination geometry 300 according to the example of FIG. 4 was recorded
  • the result image may have a phase contrast.
  • the result image may include a height profile of the sample object.
  • the transmission function 400 has an axis of symmetry 405 which corresponds to an axis of symmetry 305 of the illumination geometry 300.
  • the transfer function 400 it may be possible for the transfer function 400 to match the Illumination geometry 300 is selected.
  • the result image can have a particularly strong contrast.
  • the diameter of the detector aperture of the imaging optics 1 12 is also shown. Because a partially incoherent illumination is used, the
  • Imaging optics 1 12 not equal to zero.
  • FIG. 7 also illustrates aspects relating to a transfer function 400.
  • the example of FIG. 7 basically corresponds to the example of FIG. 6. However, in the example of FIG. 6, the size of the detector aperture is greater than in the example of FIG. 6 (see horizontal dashed lines, NA indicates the size of the detector aperture).
  • the transfer function 400 is scaled correspondingly to the in FIG. 7 compared to FIG. 6 enlarged detector aperture.
  • the transfer function 400 is scaled correspondingly to the in FIG. 7 compared to FIG. 6 enlarged detector aperture.
  • Transfer function 400 according to the example of FIG. 6 serve as a reference transfer function.
  • the controller 1 15 could be configured to perform the transfer function 400 according to the example of FIG. 7 based on a scaling of this reference transfer function on the enlarged aperture of the imaging optics 1 12 to determine.
  • a particularly large aperture for the imaging optics 1 12 used becomes what happens at certain
  • Illumination module 1 1 1 is less than 50% of the size of the aperture of the imaging optics 1 12, optionally less than 20%, further optionally less than 5%. This makes it possible to measure particularly sensitive. From the examples of FIGS. 6 and 7 it can be seen that it may be possible to transfer function 400 irrespective of the size of the aperture of the
  • Illumination module 1 1 1 to determine.
  • this may mean that, for example, an extension or certain features - such as e.g. Extreme values, zeros, inflection points, etc. - the transfer function 400 does not depend on the size of the aperture of the lighting module 1 1 1.
  • the transfer function 400 does not depend on the size of the aperture of the lighting module 1 1 1.
  • Transfer functions 400 in the examples of FIGS. 6 and 7 have no features, such as local extreme values or zeros, which depend on the size of the aperture of the illumination module 1 1 1 in the spatial frequency space - i. in the space conjugated to the space - would be positioned. Between the place space and the
  • Spatial frequency space can be transformed by Fourier analysis and inverse Fourier analysis. Spatial frequencies thereby denote the sweep of a spatial
  • the contrast in the result image may not include a quantitative description of the phase of the sample object, but a qualitative description of the phase of the sample object.
  • the qualitative description of the phase of the sample object can be consistently provided in the area of the entire image.
  • reference techniques such as e.g. described in DE 10 2014 1 12 242 A1 in which different gradients of the phase of the sample object - for example, on opposite edges of the sample object - are mapped with different signs of contrast in the result image, this may have an advantage.
  • FIG. Figure 8 illustrates aspects relating to a transfer function 400 (in Figure 8, black encodes an amount of +1 and knows an amount of -1; the coordinates u x and ty are defined in the spatial frequency space and correspond there the
  • the transfer function 400 may be used to generate, based on an image, for example, the
  • Illumination geometry 300 according to the example of FIG. 5 was recorded
  • the transfer function 400 can be determined as a function of the structured illumination geometry 300.
  • the geometry of the transfer function 400 in the spatial frequency space can simulate the illumination geometry 300 in the spatial domain.
  • a particularly strong contrast can be achieved in the resulting image, i. a high signal-to-noise ratio, for example for the phase contrast or the height profile.
  • FIG. 9 illustrates aspects related to various transfer functions 400
  • FIG. 9 (Different transfer functions are shown in Fig. 9 by the solid line, the dashed line, the dotted line, and the dashed-dotted line).
  • the in FIG. 9 can be used for different illumination geometries, for example (in FIG. 9
  • FIG. 9 is the transfer function 400 along an axis u x of
  • a transfer function 400 is formed as a monotonically increasing linear function (solid line).
  • another transfer function 400 is formed as a monotone increasing Sigmoid function formed (dashed line).
  • another transfer function 400 is formed as a folded, monotonically decreasing, linear function (dotted line).
  • FIG. 9 is another
  • Transfer function 400 formed as a step function (dotted line).
  • transfer functions 400 are purely exemplary, and in other examples, differently configured transfer functions may be used or overlays of the type shown in the example of FIG. 9 shown
  • transfer functions 400 have certain characteristics or characteristics that allow a particularly good determination of the result image. Such features of transfer functions used will be described below. From the examples of the transfer functions 400 in FIG. 9, it is apparent that it is possible to form the spatial frequency transfer functions 400 within the aperture of the imaging optics 112 without local extremes, i. without local maxima or minima which would be smaller than the absolute extremes (i.e., the amplitudes of +1 and -1, respectively, in the example of FIG. This can be achieved by a monotone increasing or decreasing transfer function, or by a step function.
  • Detector aperture is used, such an erroneous amplification of frequencies contained in the images due to a shifted positioned local extreme value of the transfer function can be avoided. It results in one
  • Transfer function for spatial frequencies within the aperture of the imaging optics 1 12 or within the double aperture of the imaging optics 1 12 comparatively small values - for example, based on a maximum of all magnitude values of the
  • Such behavior may be e.g. be provided by a step function.
  • Transfer function 400 may correspond to a suppression of the corresponding frequencies contained in the images. Often, however, it may be desirable that within the aperture of the imaging optics 1 12 or within the double aperture of the imaging optics 1 12 no suppression of corresponding in the
  • the transfer function may be possible by the appropriate choice of the transfer function without values equal to zero or very small values within the simple aperture of the imaging optics 1 12 or the double aperture of the imaging optics 1 12, even for comparatively large apertures of the imaging optics 1 12 or comparatively small apertures of the illumination module 1 1 1 to determine the result image with the phase contrast.
  • Transmission functions for spatial frequencies outside the double aperture of the imaging optics 1 12 assume values equal to zero. In general, it may be possible to use transfer functions outside of that
  • Imaging optics 1 12 transmitted spatial frequencies assume values substantially equal to zero, ie typically outside the single aperture or the double aperture with partially phase-incoherent illumination.
  • the transfer functions used for spatial frequencies outside the single or double aperture of the imaging optics it would be possible for the transfer functions used for spatial frequencies outside the single or double aperture of the imaging optics to have no magnitude values of> 5% of a maximum of all absolute values of the transfer functions for spatial frequencies within the single or double aperture of the imaging optics, optionally no values greater than 2%, further optional no values greater than 0.5%. In this way it can be avoided that artifacts or noise in the result image is amplified.
  • FIG. 10 is a flowchart of an example method.
  • a sample object is fixed in 1001, for example using a sample holder.
  • the sample object may be a phase object.
  • the sample object could Cells or cell cultures.
  • the sample object could comprise a phase object.
  • 1001 is optional.
  • the sample object is structured with one or more
  • Illuminated lighting geometries This can be a corresponding
  • Lighting module to be controlled accordingly.
  • the sample object it would be possible for the sample object to be illuminated with two complementary illumination geometries, for example semicircular and different
  • one or more images of the sample object are scanned using a
  • Imaging optics and by means of a detector, such as a CMOS or CCD sensor, detected. 1003 may include the appropriate driving of the detector.
  • the image or images each include an image of the sample object. Different images are associated with different illumination geometries from 1002.
  • two pairs of images may be detected, each associated with complementary semicircular illumination directions. In other examples, however, only two images or three images could be captured.
  • l (left) and l (right) denote the images respectively associated with a left or right oriented semicircular illumination geometry and where l (top) and I (below) denote the images respectively associated with a top or bottom oriented semicircular illumination geometry.
  • the determination of the result image is made in 1004 based on a transfer function which describes the imaging of the sample object by means of the corresponding optical system for the corresponding illumination geometries.
  • the result image is also determined based on the at least one image captured in 1003. For this purpose, for example, a difference formation and, if necessary, standardization could be carried out beforehand from a plurality of images recorded in 1003, which with
  • the method of FIG. 10 further comprises scaling a reference transfer function to a size of the aperture of the imaging optics. This means that an adaptation of the reference transfer function to the size of the aperture of the imaging optics can take place.
  • a predetermined reference transfer function can be scaled according to the size of the aperture of the imaging optics.
  • the reference transfer function can therefore also be referred to as an artificial transfer function because it can have deviations from the theoretically expected transfer function due to the illumination geometry.
  • Such techniques may have certain advantages.
  • the size of the aperture of the imaging optics can be flexibly dimensioned. In particular, for example, immersion objectives could be used.
  • phase contrast By means of the techniques described herein, by suitable choice of the transfer function, a particularly large phase contrast can be achieved in the resulting image. In particular, a gain of the phase contrast, for example, compared to the reference implementations according to Tian and Waller done. In addition, for example, it would be possible to digitally replicate certain forms of hardware-implemented phase-contrast images, such as Zernike contrast.
  • Transfer functions is purely exemplary. For example, transfer functions having amplitudes of +1 and -1, respectively, have often been illustrated in the various examples described herein, however, in other examples, it may also be possible to use transfer functions of other amplitudes.
  • the bandwidth of the transmitted spatial frequencies is equal to twice the aperture of
  • Imaging optics In other examples, however, other techniques could be used for illumination, so the bandwidth of the transmitted

Landscapes

  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Engineering & Computer Science (AREA)
  • Multimedia (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Microscoopes, Condenser (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne un système optique (100) qui comprend : un support d'échantillon (113) qui est conçu pour fixer un objet d'échantillon ; et un module d'éclairage (111) qui est conçu pour éclairer l'objet d'échantillon par au moins une géométrie d'éclairage (300) structurée ; et une optique de représentation (112) qui est conçue pour générer une image de l'objet d'échantillon éclairé par ladite au moins une géométrie d'éclairage (300) structurée sur un détecteur (114) ; et le détecteur (114) qui est conçu pour détecter au moins une représentation de l'objet d'échantillon sur la base de l'image ; et un dispositif de commande (115) qui est conçu pour déterminer une représentation résultante, qui présente un contraste de phase, sur la base d'une fonction de transfert (400) et de ladite au moins une représentation. La fonction de transfert (400) correspond à une fonction de transfert de référence dimensionnée sur la base d'une grandeur d'une ouverture de l'optique de représentation (112)
PCT/EP2018/059452 2017-04-26 2018-04-12 Imagerie par contraste de phase dotée d'une fonction de transfert WO2018197230A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201880025065.8A CN110520780B (zh) 2017-04-26 2018-04-12 具有传输函数的相衬成像

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102017108873.3 2017-04-26
DE102017108873.3A DE102017108873A1 (de) 2017-04-26 2017-04-26 Phasenkontrast-Bildgebung mit Übertragungsfunktion

Publications (1)

Publication Number Publication Date
WO2018197230A1 true WO2018197230A1 (fr) 2018-11-01

Family

ID=62063493

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2018/059452 WO2018197230A1 (fr) 2017-04-26 2018-04-12 Imagerie par contraste de phase dotée d'une fonction de transfert

Country Status (3)

Country Link
CN (1) CN110520780B (fr)
DE (1) DE102017108873A1 (fr)
WO (1) WO2018197230A1 (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102017115658A1 (de) 2017-07-12 2019-01-17 Carl Zeiss Microscopy Gmbh Flackern bei Winkel-variabler Beleuchtung
DE102018114005A1 (de) 2018-06-12 2019-12-12 Carl Zeiss Jena Gmbh Materialprüfung von optischen Prüflingen
DE102019100419A1 (de) 2019-01-09 2020-07-09 Carl Zeiss Microscopy Gmbh Winkelvariable Beleuchtung zur Phasenkontrast-Bildgebung mit Absorptionsfilter

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102011050674A1 (de) * 2011-05-27 2012-11-29 Hseb Dresden Gmbh Anordnung zur Erzeugung eines Differentialinterferenzkontrastbildes
WO2014169197A1 (fr) * 2013-04-12 2014-10-16 Duky University Systèmes et procédés pour microscopie avec contraste de phase à super-résolution et éclairage structuré
WO2015179452A1 (fr) * 2014-05-19 2015-11-26 The Regents Of The University Of California Microscopie ptychographique de fourier ayant un éclairage multiplexé
DE102014112242A1 (de) 2014-08-26 2016-03-03 Carl Zeiss Ag Phasenkontrast-Bildgebung

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1945778B2 (de) * 1969-09-10 1972-02-10 Osoboje konstruktorskoje bjuro mini sterstwa geologii SSSR, Leningrad (So wjetumon) Analysator zur phasenanalyse von objekten unter dem mikroskop
JP2001194592A (ja) * 2000-01-07 2001-07-19 Nikon Corp 位相物体観察装置
WO2008008084A2 (fr) * 2005-09-19 2008-01-17 Cdm Optics, Inc. Systèmes d'imagerie basés sur des tâches
US8081378B2 (en) * 2005-10-13 2011-12-20 Nikon Corporation Microscope
DE102007014640B4 (de) * 2007-03-23 2015-04-02 Carl Zeiss Microscopy Gmbh Mikroskopobjektiv
DE102007027084B4 (de) * 2007-06-12 2021-01-14 Carl Zeiss Microscopy Gmbh Mikroskop für die Beobachtung einer Probe im Hellfeld-Durchlicht- oder im Fluoreszenz-Auflicht-Kontrastverfahren
JP2009086392A (ja) * 2007-10-01 2009-04-23 Nikon Corp 位相差顕微鏡
DE102007061214A1 (de) * 2007-12-19 2009-06-25 Carl Zeiss Microimaging Gmbh Mikroskop zum Beobachten einer Probe mittels verschiedener Kontrastverfahren
JP2011002514A (ja) * 2009-06-16 2011-01-06 National Institute Of Advanced Industrial Science & Technology 位相差顕微鏡
DE102009038027A1 (de) * 2009-08-18 2011-02-24 Carl Zeiss Microimaging Gmbh Beleuchtungseinrichtung für Mikroskope und Makroskope
JP2011220932A (ja) * 2010-04-13 2011-11-04 Olympus Corp 撮像装置
CN102004276B (zh) * 2010-08-25 2012-06-06 中国科学院深圳先进技术研究院 光子筛相衬物镜、制造方法及成像方法
JP5804441B2 (ja) * 2011-05-18 2015-11-04 株式会社ニコン 顕微鏡システム
US20150087902A1 (en) * 2012-03-30 2015-03-26 Trustees Of Boston University Phase Contrast Microscopy With Oblique Back-Illumination
US8896827B2 (en) * 2012-06-26 2014-11-25 Kla-Tencor Corporation Diode laser based broad band light sources for wafer inspection tools
CN102998789B (zh) * 2012-12-31 2015-04-01 华中科技大学 一种超分辨微分干涉相衬显微成像方法
CN104568859B (zh) * 2013-10-22 2017-10-13 承奕科技股份有限公司 具多组异角度光源的荧光观测装置、基架及荧光显微镜

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102011050674A1 (de) * 2011-05-27 2012-11-29 Hseb Dresden Gmbh Anordnung zur Erzeugung eines Differentialinterferenzkontrastbildes
WO2014169197A1 (fr) * 2013-04-12 2014-10-16 Duky University Systèmes et procédés pour microscopie avec contraste de phase à super-résolution et éclairage structuré
WO2015179452A1 (fr) * 2014-05-19 2015-11-26 The Regents Of The University Of California Microscopie ptychographique de fourier ayant un éclairage multiplexé
DE102014112242A1 (de) 2014-08-26 2016-03-03 Carl Zeiss Ag Phasenkontrast-Bildgebung

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
H.H. HOPKINS: "On the Diffraction Theory of Optical Images", PROCEEDINGS OF THE ROYAL SOCIETY A: MATHEMATICAL, PHYSICAL ENGINEERING SCIENCES, vol. 217, 1953, pages 408 - 432
L. TIAN; L. WALLER: "Quantitative differential phase contrast imaging in an LED array microscope", OPTICS EXPRESS, vol. 23, 2015, pages 11394
LEI TIAN ET AL: "3D differential phase-contrast microscopy with computational illumination using an LED array", OPTICS LETTERS, vol. 39, no. 5, 28 February 2014 (2014-02-28), US, pages 1326, XP055431827, ISSN: 0146-9592, DOI: 10.1364/OL.39.001326 *
SHALIN MEHTA B ET AL: "Quantitative phase-gradient imaging at high resolution with asymmetric illumination-based differential phase contrast", OPTICS LETTERS, OPTICAL SOCIETY OF AMERICA, US, vol. 34, no. 13, 1 July 2009 (2009-07-01), pages 1924 - 1926, XP001524101, ISSN: 0146-9592 *

Also Published As

Publication number Publication date
DE102017108873A1 (de) 2018-10-31
CN110520780B (zh) 2022-04-15
CN110520780A (zh) 2019-11-29

Similar Documents

Publication Publication Date Title
WO2018197389A1 (fr) Contrôle de matériau avec un éclairage à angle variable
DE102006011707B4 (de) Verfahren und Vorrichtung zum Erzeugen einer strukturfreien fiberskopischen Aufnahme
WO2016030390A2 (fr) Formation d'images de contraste de phase
DE102012106584B4 (de) Verfahren und Vorrichtung zur Bildrekonstruktion
EP3602163B1 (fr) Éclairage structuré présentant une géométrie d'éclairage optimisée
DE102018114005A1 (de) Materialprüfung von optischen Prüflingen
EP3608831A1 (fr) Procédé de fourniture d'un moyen d'évaluation pour au moins un système d'application optique d'une technologie d'application microscopique
DE112016001559T5 (de) Abbildungssystem, das strukturiertes Licht zur Tiefenrückgewinnung nutzt
EP3304165A1 (fr) Agencement et procédé de formation de faisceau et de microscopie à feuille de lumière
WO2018197230A1 (fr) Imagerie par contraste de phase dotée d'une fonction de transfert
WO2016012391A1 (fr) Procédé et dispositif de formation d'un objet
WO2016041944A1 (fr) Procédé de production d'une image résultante et dispositif optique
EP2497412A1 (fr) Microscope à balayage laser et son procédé de fonctionnement
EP3447559A1 (fr) Microscopie 2d haute résolution à épaisseur de coupe améliorée
DE102020113313A1 (de) Verfahren, computerprogramm und mikroskopsystem zum verarbeiten von mikroskopbildern
DE102019208114A1 (de) Vorrichtung zur 3D Vermessung von Objektkoordinaten
WO2019068519A1 (fr) Microscope confocal à grande résolution
WO2017093227A1 (fr) Procédé et dispositif de correction d'image
EP3988989B1 (fr) Procédé et microscope doté d'un dispositif de détection des déplacements d'un échantillon par rapport à une lentille
EP2033447A1 (fr) Procede de compression sans perte pour interferogrammes
DE102017115021A1 (de) Digitale Bestimmung der Fokusposition
EP4133322A1 (fr) Microscope à plan incliné ayant une efficacité de collecte améliorée
DE102007015599A1 (de) Vermeidung von Halos um intensive Lichtquellen bei optischen Systemen, insbesondere bei Nachtsichtsystemen
DE102023100439A1 (de) Mikroskopiesystem und Verfahren zum Berechnen eines Ergebnisbildes durch ein ordinales Klassifikationsmodell
DE102023115087A1 (de) Verfahren zum Trainieren eines Maschinenlernsystems, Verfahren zum Erzeugen eines Ergebnis-Mikroskopbilds mit einem Maschinenlernsystem, Computerprogramm-Produkt, sowie Bildverarbeitungssystem

Legal Events

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

Ref document number: 18720535

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18720535

Country of ref document: EP

Kind code of ref document: A1

点击 这是indexloc提供的php浏览器服务,不要输入任何密码和下载