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WO2018100083A1 - Dispositif détecteur de luminescence, microscope de fluorescence et procédé pour la détection d'un signal de luminescence - Google Patents

Dispositif détecteur de luminescence, microscope de fluorescence et procédé pour la détection d'un signal de luminescence Download PDF

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Publication number
WO2018100083A1
WO2018100083A1 PCT/EP2017/081023 EP2017081023W WO2018100083A1 WO 2018100083 A1 WO2018100083 A1 WO 2018100083A1 EP 2017081023 W EP2017081023 W EP 2017081023W WO 2018100083 A1 WO2018100083 A1 WO 2018100083A1
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WO
WIPO (PCT)
Prior art keywords
time interval
luminescence
light source
emission light
memory cell
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/EP2017/081023
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German (de)
English (en)
Inventor
Christian Schumann
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.)
Leica Microsystems CMS GmbH
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Leica Microsystems CMS 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 Leica Microsystems CMS GmbH filed Critical Leica Microsystems CMS GmbH
Publication of WO2018100083A1 publication Critical patent/WO2018100083A1/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
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/16—Microscopes adapted for ultraviolet illumination ; Fluorescence microscopes
    • 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
    • G01N2021/6417—Spectrofluorimetric devices
    • G01N2021/6419—Excitation at two or more wavelengths
    • 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
    • G01N2201/06—Illumination; Optics
    • G01N2201/069—Supply of sources
    • G01N2201/0696—Pulsed

Definitions

  • Luminescence detector arrangement fluorescence microscope and method for detecting a luminescence signal
  • the present invention relates to a luminescence detector arrangement
  • Fluorescence microscope and a method for detecting a luminescence signal are particularly in the field of fluorescence microscopy, in particular in the field of wide-field microscopy.
  • monochrome cameras ie color-sensitive cameras
  • monochrome cameras are often used in this type of microscopy, since they are typically available with a higher sensitivity and / or a faster readability than other camera systems which also offer a color resolution.
  • various methods can be used. For example, for this purpose changing devices for assemblies with excitation spectral filters, a dichroic beam splitter and a
  • Emission spectral filters used which can be combined in so-called fluorescence filter cubes. These fluorescence filter cubes can then be used for
  • dichroic multiband beam splitters with matching emission and excitation filter sets have been used. These often have relatively small filters, which can be moved, for example, by means of fast filter wheels, so that a filter change can possibly be carried out faster than when changing from fluorescence filter cubes. However, even such a mechanical change process still takes considerable time.
  • a disadvantage may also result from the fact that the images of different fluorophores at
  • multi-camera methods can be used. However, these are often cost-intensive and expensive, since several cameras must be purchased and the different cameras also synchronized and their images must be overlapped, which can often be associated with tolerance-related different lateral layers and geometric distortions with a great deal of effort.
  • camera splitters are known in which a microscopic field of view is spectrally divided and imaged on different areas of the same sensor. Such systems are often non-telecentric and also suffer from overlap problems, such as the multiple camera methods mentioned above.
  • multi-pixel taps or area sensors is known, i.
  • Cameras with so-called multitap or two-tap pixels such camera systems being used, for example, as FLIM cameras (pco.flim, PCO AG, MEMFLIM, TELEDYNE DALSA PROFESSIONAL IMAGING) or as time-of-flight cameras (epc660, ESPROS PHOTONICS CORPORATION ) are known.
  • FLIM cameras pco.flim, PCO AG, MEMFLIM, TELEDYNE DALSA PROFESSIONAL IMAGING
  • time-of-flight cameras epc660, ESPROS PHOTONICS CORPORATION
  • an electrical charge resulting from the detection process in a detector pixel is collected in two or more memory cells, wherein the
  • Integration time per memory cell in a fixed phase range of a high-frequency modulation frequency (pixel switching frequency) is located.
  • pixel switching frequency a high-frequency modulation frequency
  • Fluorescence lifetime microscopy used. It is therefore the object of the invention to provide a luminescence detector arrangement, a fluorescence microscope and a method for detecting a luminescence signal, which enable a simplified detection of luminescence signals at different excitation wavelengths at short time intervals.
  • a luminescence detector arrangement a luminescence detector arrangement
  • the invention in a first aspect, relates to a luminescence detector arrangement for detecting a luminescence signal, which has a sensor element with at least one multitap pixel having at least a first memory cell and a second memory cell, wherein the sensor element is adapted to the multitap pixel in a first time interval by means of read the first memory cell and read in a second time interval different from the first time interval by means of the second memory cell.
  • the luminescence detector arrangement has a light source which is set up to emit a first emission light in at least one first spectral range and independently emit a second emission light in a second spectral range, wherein the first spectral range and the second spectral range are at least partially different from one another ( Overlaps not excluded).
  • the light source is synchronized with the sensor element to the first in the first time interval
  • the luminescence detecting device is further configured to be one through the first emission light and through the second emission light
  • the invention relates to a fluorescence microscope with a luminescence detector arrangement according to the invention, wherein the
  • Fluorescence microscope is adapted to at least partially optically excite an object to be examined by means of the light source and at least partially detect a fluorescence signal generated by the optically excited object to be examined as a luminescence signal.
  • the invention relates to a method for detecting a luminescence signal with the steps of a) providing a sensor element having at least one multitap pixel with at least one first memory cell and a second memory cell; b) providing a light source; c) emitting a first emission light in at least a first spectral range by means of the light source in a first time interval and reading out the at least one multitap pixel by means of the first memory cell in the first time interval; and d) emitting a second emission light in at least a second spectral range by means of the light source in a second time interval and reading out the at least one multitap pixel by means of the second memory cell in the second time interval.
  • a first emission light in at least a first spectral range by means of the light source in a first time interval and reading out the at least one multitap pixel by means of the first memory cell in the first time interval
  • a second emission light in at least a second spectral range by means of the light source in a second time interval
  • Time interval and the second time interval different from each other and the first spectral range and the second spectral range are at least partially different from each other.
  • An emission light is preferably in particular
  • the first Sepktral Scheme and the second spectral range are at least partially different from each other, ie, the first and the second Sepktral Scheme do not overlap each other completely, with a partial spectral overlap is possible but not mandatory.
  • a luminescence signal can have, for example, a fluorescence signal and / or a phosphorescence signal, which can be detected, for example, by an optical signal Excitation of a to be examined, fluorescent and / or phosphorescent object occurs or is emitted from the object.
  • multitap pixels can be pixels which are connected to a plurality of memory cells in order to be read out at different times from in each case one of the several memory cells. This can serve, for example, to accelerate the read-out process of the multitap pixel compared to the read-out process of conventional pixels with only one memory cell.
  • a multi-tap pixel may be in the form of a two-tap pixel having two memory cells.
  • other embodiments of multitap pixels may also have any other number greater than 1 of memory cells, for example 3, 4, 8 or 16 memory cells.
  • a light source As a light source is to be understood a source of electromagnetic radiation. Accordingly, as light or emission light
  • electromagnetic radiation This may, but not necessarily, be in the visible optical spectral range, but may
  • the spectral range is a wavelength range or
  • Frequency range of the frequencies of the electromagnetic radiation understood which may be single wavelengths or frequencies in the case of monochromatic light or in the case of more or less broadband
  • the invention offers the advantage that for the detection of the luminescence not necessarily spectral filters, such as excitation spectral filters for selecting the excitation wavelength (s) and / or emission spectral filters for selecting the wavelength (s) to be detected must be used. This can
  • a time-consuming change of spectral filters omitted whereby the measurement time can be shortened and in particular several in very short Time intervals successive measurements in different spectral ranges can be made. For example, this can make it possible to carry out detections of luminescence in different spectral ranges within a few microseconds or milliseconds.
  • the invention makes it possible to emit only emission light of the desired spectral range at certain time intervals and to detect the luminescence produced thereby and, at other specific time intervals, emission light of another desired one
  • Emission radiation and the detection means of the sensor element are synchronized such that a preferably complete assignability of the detected signal to a specific emission radiation or excitation radiation is possible, although the sensor element is optionally color insensitive, in particular none
  • Excitation spectral or emission spectral filters are used.
  • a luminescence detector arrangement can be provided which can be operated without a cost-intensive spectral filter and which can be operated in particular without mechanically changing spectral filters and / or without manipulating filter wheels.
  • the invention offers the advantage that no color-sensitive cameras must be used, but a use of a monochrome sensor element is sufficient. This allows, especially sensitive and / or very quickly readable
  • the first time interval and the second time interval each pass at least twice. That is to say, during a measurement, at least twice the first emission light and the second emission light are emitted and the at least one multitap pixel is read out at least twice by means of the first and by the second memory cell.
  • the measurement takes place over a measurement period or a measurement duration which is such that a lifetime or decay time of the luminescence of the object to be measured, which depends, for example, on a decay time of the fluorescence of the fluorophores in the object to be examined, Detection of luminescence or the measurement signal is not substantially affected.
  • a measurement duration can be selected which is longer, in particular significantly longer, than an average decay time of the
  • Luminescence of the object to be detected is.
  • the radiative lifetime is on the time scale of a few nanoseconds, so that a measurement period in the microsecond range is unaffected by the radiofrequency life of the fluorophore, on the time scale of cellular processes in the
  • the sensor element has a plurality of multitap pixels, which are preferably arranged in a matrix.
  • This offers the advantage that a spatial resolution of the detected luminescence signal can be achieved.
  • the provision of optical elements may be advantageous in order, for example, to image the luminescence signal onto the sensor element.
  • the sensor element may have a CMOS matrix in which a plurality of multitap pixels is arranged, for example, in a rectangular matrix.
  • the sensor element may comprise a matrix comprising 1008 ⁇ 1008 multitap pixels, wherein also other matrix sizes and / or
  • the luminescence detector arrangement is preferably set up to synchronize the sensor element and the light source by means of an externally provided synchronization signal.
  • the synchronization signal can be provided, for example, by an electrical signal transmitter and / or an electric pulse generator. This has the advantage that the readout of the memory cells and the Emitting the emission light can be synchronized by the light source in a particularly simple manner.
  • the luminescence detector arrangement can have a synchronization signal generator, which is preferably set up to provide a synchronization signal.
  • the synchronization signal may in particular be adapted to the
  • the sensor element may comprise the synchronization signal generator.
  • the synchronization signal generator is optionally integrated in the sensor element. This has the advantage that, for example, the sensor element an internal
  • Synchronization signal provides to control the reading of the memory cells, which can also be used externally for the synchronization of other components, such as the light source.
  • the light source is modulated.
  • the light source is preferably configured to emit the first emission light and / or the second emission light in response to the synchronization signal.
  • the light source can have one or more emission elements.
  • the light source can be designed such that it has a single emission element for the first and the second emission light, or that it has a separate emission element for each emission light. This offers the advantage that with a single light source, the first emission light and the second emission light can be provided or emitted and not necessarily multiple light sources must be provided. This can on the one hand a compact structure of
  • Luminescence detector arrangement can be achieved. On the other hand, this can be advantageous with regard to the synchronization of the light source with the sensor element, since this way, only a single light source needs to be synchronized with the sensor element.
  • the synchronization signal comprises a periodic signal, which preferably has a repetition frequency which is in a range of 100 Hz to 100 MHz, preferably in a range of 1 kHz to 10 MHz, most preferably in a range of 10 kHz to 1 MHz ,
  • a periodic signal which preferably has a repetition frequency which is in a range of 100 Hz to 100 MHz, preferably in a range of 1 kHz to 10 MHz, most preferably in a range of 10 kHz to 1 MHz ,
  • Synchronization signal be designed as an electrical voltage signal or include such.
  • the synchronization signal may have a sinusoidal and / or rectangular and / or sawtooth-shaped voltage signal.
  • the amplitudes of the voltage signal can be between 0.1 V and 20 V, for example.
  • the sensor element and / or the light source can be set up such that they are triggered by the synchronization signal at times when the synchronization signal has a rising edge and / or a falling edge. This has the advantage that the synchronization signal can be provided in a simple and reliable manner, without requiring high demands on the hardware of a synchronization signal generator.
  • the light source preferably has at least one semiconductor light source.
  • At least one emission element of the light source can have a semiconductor light source.
  • the semiconductor light source may have at least one light emitting diode (LED) or light emitting diode and / or a laser diode and / or a diode laser.
  • LED light emitting diode
  • a plurality of semiconductor light sources may be provided, which in mutually different colors or
  • Emit emission spectra a plurality of different types of semiconductor light sources are integrated in the light source.
  • the use of semiconductor light sources offers the advantage that they can be modulated particularly quickly in comparison to other light sources, ie, they can be switched on and off particularly quickly. This can be advantageous, in particular in the case of particularly short and / or rapidly successive measurement intervals, in order to achieve a fast Transition of emission light of the first spectral range to reach emission light of the second spectral range.
  • the individual semiconductor light sources may further include bandpass filters for adjusting the emitted spectral range.
  • a fluorescence microscope according to the invention is set up such that the optical excitation of the object to be examined takes place without the use of an excitation spectral filter. More preferably, the fluorescence microscope is set up such that the fluorescence signal generated by the optically excited object to be examined is carried out without the use of a luminescence spectral filter.
  • Luminescence spectral filters need not be replaced during a measurement, so that no disadvantages caused thereby arise.
  • the readout of the at least one multitap pixel by means of the first memory cell is synchronized with the emission of the first emission light and the reading of the at least one multitap pixel by means of the second memory cell is synchronized with the emission of the second emission light.
  • the at least one multitap pixel may also be more as two memory cells and the light source more than two different types of emission light, ie emission light in more than two different
  • the readout of the multitap pixel by a specific memory cell particularly preferably takes place synchronously with the emission of determined emission light by the light source.
  • steps c) and d) are repeated alternately, preferably at a repetition frequency ranging from 100 Hz to 100 MHz, preferably in a range from 1 kHz to 10 MHz, most preferably in a range from 10 kHz to 1 MHz is.
  • the steps c) and d) are particularly preferably run through at least twice. This has the advantage that it can be measured over a longer period, i. that optional also faint
  • Luminescences can be detected and, in particular, short-lived
  • Luminescences can be detected time-dependent. Furthermore, by an alternating or alternating excitation and detection at different
  • FIG. 1 shows a schematic illustration of a fluorescence microscope according to a preferred embodiment.
  • FIG. 2 shows an exemplary chronological sequence of events of a
  • FIG. 1 shows a schematic representation of a fluorescence microscope 100 according to a preferred embodiment.
  • the fluorescence microscope 100 is set up to detect the luminescence or fluorescence of an object 102 to be examined, in particular in a time-dependent or time-resolved manner.
  • the fluorescence microscope 100 has a light source 104, by means of which emission light, which can serve in particular as excitation light and / or as illumination light for optically exciting or illuminating the object to be examined, can be emitted in at least a first and a second spectral range.
  • the emission light is emitted in such a way that the emission light propagates at least partially along an illumination beam path 106.
  • an excitation spectral filter 108 may be arranged in the illumination beam path 106 in order to optionally perform a spectral filtering of the emission light in the first and / or the second spectral range.
  • the emission light is at a beam splitter 1 10 at least partially reflected in the direction of an objective 1 12.
  • the beam splitter 1 10 is formed as a multi-band beam splitter, so that preferably the emission light in both the first spectral range and in the second
  • the beam splitter 110 can be set up to also reflect the further spectral ranges with the highest possible reflectivity.
  • the beam splitter 110 may be configured not to reflect light in spectral regions other than the emission light but to transmit it with the greatest possible transmissivity.
  • the beam splitter 110 may be configured as a dichroic multiband beam splitter.
  • the emission light reflected by the beam splitter 110 is at least partially focused by the objective 1 12 onto a region of the object 102 to be examined, so that possibly present fluorescence and / or phosphorescence can be excited in the region to be examined.
  • the lens 1 12 is preferably designed as a microscope objective and is also used for the collection of light or luminescence of the object 102 for microscopic evaluation. The collected by the lens 1 12 luminescent light or
  • Fluorescent light which is optionally emitted after excitation of the object 102 with the emission light from the object 102, is collected by the lens 1 10 and propagates in the direction of the beam splitter 1 10, wherein the beam splitter 1 10 is adapted to that of the lens be collected
  • an emission filter 14 may optionally be arranged in order to spectrally filter the luminescent light collected by the lens 12, if necessary.
  • the emission spectral filter 1 14 may be formed as a multi-band spectral filter.
  • the luminescent light is focused by means of an optical element 1 16 on a sensor element 1 18 or optically imaged along the beam path 1 16a.
  • the optical element 1 16 can do this For example, be designed as a convex optical lens or a converging lens, in particular as a tube lens or more generally a tube optic.
  • the sensor element 118 may be formed as a camera, which preferably has a plurality of multitap pixels arranged in a matrix. According to the embodiment shown, the sensor element 118 and the light source 104 are controlled by means of a control unit 120. It can the
  • Receive control unit in particular the received or detected by the sensor element 1 18 18 or read from the memory cells encompassed signals and optionally further processed and / or store.
  • a synchronization signal can be provided by the control unit 120 in order to temporally synchronize the light source with the sensor element.
  • the control unit 120 may provide one provided by the sensor element 118
  • FIG. 2 shows an exemplary, schematic time sequence of operations of a method according to the invention according to a preferred embodiment, which are plotted against the time t.
  • the uppermost graph shows a progression of the pixel switching frequency 201 with a period length 202, an emission of the first emission light in the first spectral range 203, an emission of the second
  • Image pickup 207 Preferably, the pixel switching frequency in frequency and phase corresponds to the synchronization signal.
  • the applied amplitudes claim no quantitative comparability, but the graphs are intended to illustrate only a relative, temporal sequence. For example, in the graphs 203, 204, 205 and 206, a large amplitude value means that the corresponding emission light is emitted or the corresponding memory cell is read out, while the small amplitude value means that the corresponding emission light is not emitted or the corresponding memory cell is not read out.
  • Image acquisition takes place and no image acquisition takes place at a small amplitude value.
  • the dashed lines indicate the first time interval 208 and the second time interval 209 in a period 202.
  • the pixel switching frequency 201 is set such that complete exposure and detection of the overall image, i. the entire period of an image acquisition 207 or the acquisition of an image, a plurality of complete cycles or periods 202 of the pixel switching frequency 201, or longer, preferably, more than two cycles.
  • complete exposure and detection of the overall image i. the entire period of an image acquisition 207 or the acquisition of an image, a plurality of complete cycles or periods 202 of the pixel switching frequency 201, or longer, preferably, more than two cycles.
  • the pixel switching frequency 201 so low or the period 202 chosen so large that an influence of changes due to a decay of the
  • the pixel switching frequency 201 is chosen such that a suitable compromise results from a total measurement duration which is long enough to neglect temporal changes in the fluorescence or luminescence, but nevertheless to perform a plurality of measurement cycles in order to obtain a sufficient time To ensure integration to obtain signal intensity with quasi-simultaneity ("real time").
  • the pixel switching frequency may be in the range between 10 kHz and 1 MHz.
  • the emission of the first and second emission light 203, 204 of the modulatable light source 104 may be in the range between 10 kHz and 1 MHz.
  • Readout of the second memory cell 206 is set.
  • semiconductor light sources such as diode lasers or light-emitting diodes (LEDs) are suitable as correspondingly rapidly modulated light sources 104, so that the method is preferred for inter alia
  • Epifluorescence microscopy in TIRF microscopy, in structured illumination microscopy, in light-sheet microscopy, in multifocal microscopy
  • the modulation of the light source 203, 204 may, for example, also take place separately from the pixel switching frequency 201.
  • a modulation of a light source which emits light continuously over time can be effected by electro-optical and / or acousto-optical and / or electromechanical (eg chopper) or other methods.
  • the readout of the memory cells 205, 206 is preferably carried out such that the signal is integrated over more than two complete cycles or periods 202 of the pixel switching frequency 201, so that the shortest possible time interval between the
  • Excitation wavelengths can be done. This can be done by means of a conventional, simple mutual synchronization of the illumination to the exposure time of the camera, i. in a complete image pickup 207 with the first emission light and only then a complete image pickup 207 with the second
  • Pixel switching frequency 201 is selected within a total exposure time of the image pickup 207, the lower the effects of the time-dependent changes of the object to be examined and the better the comparability of measurements with emission light or excitation light in different spectral ranges.

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

Abstract

L'invention concerne un dispositif détecteur de luminescence pour détecter un signal de luminescence, pourvu d'un élément capteur (118) présentant au moins un pixel à sorties multiples présentant au moins une première cellule de mémoire et une deuxième cellule de mémoire, l'élément capteur (118) étant conçu pour lire le pixel à sorties multiples dans un premier intervalle de temps (208) à l'aide de la première cellule de mémoire et pour le lire dans un deuxième intervalle de temps (209) différent du premier intervalle de temps (208) à l'aide de la deuxième cellule de mémoire. En outre, le dispositif détecteur de luminescence présente une source lumineuse (104), qui est conçue pour émettre une première lumière d'émission dans au moins une première plage spectrale et, indépendamment, pour émettre une deuxième lumière d'émission dans une deuxième plage spectrale, la première plage spectrale et la deuxième plage spectrale étant au moins partiellement différentes l'une de l'autre, la source lumineuse (104) étant synchronisée avec l'élément capteur (118) pour émettre la première lumière d'émission dans le premier intervalle de temps (208) et pour émettre la deuxième lumière d'émission dans le deuxième intervalle de temps (209). Le dispositif détecteur de luminescence est en outre conçu pour détecter, à l'aide de l'élément détecteur (118), un signal de luminescence provoqué par la première lumière d'émission et par la deuxième lumière d'émission. Dans un autre aspect, l'invention concerne un microscope de fluorescence et un procédé de détection d'un signal de luminescence.
PCT/EP2017/081023 2016-12-01 2017-11-30 Dispositif détecteur de luminescence, microscope de fluorescence et procédé pour la détection d'un signal de luminescence Ceased WO2018100083A1 (fr)

Applications Claiming Priority (2)

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DE102016123258.0A DE102016123258B4 (de) 2016-12-01 2016-12-01 Lumineszenzdetektoranordnung, Fluoreszenzmikroskop und Verfahren zum Detektieren eines Lumineszenzsignals
DE102016123258.0 2016-12-01

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