Multimodal Microscope System

Abstract

A multimodal microscope system (1) is disclosed. In a first aspect, the system (1) comprises at least a first base unit (2) including at least one electrical and / or optical base component (14, 15, 16, 17, 18, 19), at least one scanning unit (4) including at least one scanning component (20, 21, 22), and at least one detection unit (5) including at least one detection component (7, 8, 9, 10, 11). The at least one base component (14, 15, 16, 17, 18, 19), the at least one scanning component (20, 21, 22), and the at least one detection component (7, 8, 9, 10, 11) are operatively coupled to one another such that the at least one base component (14, 15, 16, 17, 18, 19) and / or the at least one scanning component (20, 21, 22) and / or the at least one detection component (7, 8, 9, 10) and / or the at least one detection component (11) are jointly usable for multiple modalities. In a further aspect, the system (1) comprises a beam combiner (26) configured to superimpose electromagnetic waves emitted by the electromagnetic wave sources (14, 15, 16, 17, 18, 19) and / or a beam splitter (27) configured to split the electromagnetic wave emitted by the probe (50) into multiple partial electromagnetic waves.

Description

[Technical Field]

[0001] This application relates to multimodal microscopy systems. It is known in the art to provide optical images from multiple optical imaging modalities and combine these images. Systems with this capability are referred to as multimodal microscopy systems. They may be used, for example, in medicine, particularly in tissue imaging. [Background technology]

[0002] One known multimodal system is disclosed, for example, in WO 2010 / 086861 A1. This system includes an optical coherence tomography (OCT) module, a photoacoustic (PA) module, an optical switcher, and an endoscope head, with the PA light source and the OCT light source coupled to the endoscope head via the optical switcher. This system has several drawbacks. In particular, it only allows sequential or pseudo-parallel imaging. Therefore, the processing times of the different modalities are additive, reducing the frame rate at which images can be displayed or further evaluated. Furthermore, processes cannot be visualized simultaneously in different modalities. Furthermore, the switcher is expensive.

[0003] Furthermore, WO 2011 / 150431 A1 discloses a multimodal method and system for imaging tissue, which comprises at least one excitation light source, an optical and alignment system, a detector, a spectral filtering or dispersion device for providing at least two imaging modalities at the detector, and a processor for constructing a dual-mode image.

[0004] EP 2 579 085 A1 further discloses a laser scanning microscope comprising a measurement head connected to a radiation source and an adjustable mirror for deflecting and aligning the excitation beam of pulsed laser radiation from the radiation source. A beam splitter is positioned in front of a focusing lens. A photodetector determines the beam's emission position. A control unit controls the mirror based on the determined deviation of the test beam from the intermediate alignment so that directional stabilization of the test beam is achieved regardless of the degree of positional disturbance of the transmission lens. The beam splitter can be designed as a reflective or transmissive beam splitter.

[0005] Additionally, US2013 / 0088709 A1 discloses a flexible nonlinear laser scanning microscope for non-invasive three-dimensional detection, comprising a measurement head flexibly connected to at least one radiation source by a transmission optical system and freely positionable in space. At least one controllable tilt mirror is arranged to align the excitation beam to keep it coaxial with the aperture-limiting optical element of the measurement head. A test beam is coupled from the excitation beam to a spatial resolution photodetector, which monitors the centering of the test beam as a conjugate position with respect to the target position of the excitation beam, and directional stabilizes the excitation beam by a control unit of the tilt mirror in response to the determined deviation. Summary of the Invention [Problem to be solved by the invention]

[0006] The aim of the present application is to provide an improved multimodal microscopy system in which the drawbacks of the prior art are eliminated or at least reduced. In particular, the system should allow shorter processing times of the different modalities and should reduce the frame rate at which images can be displayed or further evaluated. [Means for solving the problem]

[0007] In a first aspect, the present invention relates to a multimodal microscope system comprising at least one first base unit including at least one electrical and / or optical base component, at least one scanning unit including at least one scanning component, and at least one detection unit including at least one detection component. at least one first base unit includes at least two electrical and / or optical base components; and / or at least one scanning unit includes at least two scanning components; and / or At least one detection unit comprises at least two detection components.

[0008] The scanning unit and / or the detection unit are preferably freely movable, in particular with six degrees of freedom, and are connected to the first base unit via at least one flexible connection line, in particular at least one optical connection line and / or at least one electrical connection line.

[0009] According to a first aspect of the present invention, the at least one base component, the at least one scanning component, and the at least one detection component comprise: at least one base component and / or at least one scanning component and / or at least one detection component are operatively coupled to each other so that they can be used jointly, particularly simultaneously, for multiple modalities.

[0010] In other words, two components of the three units (base unit, scanning unit, detection unit) may be used in conjunction with one identical component or one set of identical components of one remaining unit to provide different modalities.

[0011] Thus, in a first embodiment, the first base unit may include a first base component and a second base component, where the first base component may be used in association with a scanning component or set of scanning components to provide a first modality, and the second base component may be used in association with the same scanning component or set of scanning components to provide a second modality. In a second embodiment, the first base unit may include a first base component and a second base component, where the first base component may be used in association with a detection component or set of detection components to provide a first modality, and the second base component may be used in association with the same detection component or set of detection components to provide a second modality.

[0012] In further embodiments, the first scanning unit may include a first scanning component and a second scanning component, where the first scanning component may be used in association with a detection component or set of detection components to provide a first modality, and the second scanning component may be used in association with the same detection component or set of same detection components to provide a second modality. In yet another embodiment, the first scanning unit may include a first scanning component and a second scanning component, where the first scanning component may be used in association with a base component or set of base components to provide a first modality, and the second scanning component may be used in association with the same base component or set of same base components to provide a second modality.

[0013] In yet another embodiment, the first detection unit may include a first detection component and a second detection component, where the first detection component may be used in association with a base component or set of base components to provide a first modality, and the second detection component may be used in association with the same base component or set of same base components to provide a second modality. In yet another embodiment, the first detection unit may include a first detection component and a second detection component, where the first detection component may be used in association with a scanning component or set of scanning components to provide a first modality, and the second detection component may be used in association with the same scanning component or set of same scanning components to provide a second modality.

[0014] As will be apparent from the discussion below, the interoperability of system components for multiple modalities reduces the number of system components and the size of the system, and furthermore, it enables simultaneous imaging with different modalities in a truly parallel manner.

[0015] Advantageously, the base component is an electromagnetic wave source that can be used for different modalities, providing images using different modalities that may be combined. The different modalities may be selected from the group consisting of two-photon excited fluorescence, two-photon autofluorescence, fluorescence lifetime imaging, autofluorescence lifetime imaging, second harmonic generation, third harmonic generation, incoherent / spontaneous Raman scattering, coherent anti-Stokes Raman scattering (CARS), broadband or multiplexed CARS, stimulated Raman scattering, coherent Raman scattering, stimulated emission depletion (STED), nonlinear absorption, confocal Raman microscopy, optical coherence tomography (OCT), single-photon / linear fluorescence imaging, bright-field imaging, dark-field imaging, three-photon, four-photon, second harmonic generation, third harmonic generation, and fourth harmonic generation.

[0016] In particular, the electromagnetic wave source may be selected from the group consisting of a pulsed laser source, a CW (continuous wave) coherent or incoherent light source, a narrow linewidth laser, a broadband laser source, a broadband incoherent laser source, a swept frequency laser source, an optical amplifier pumped laser, and a white light source. The laser source may comprise a laser amplifier and / or a frequency converter.

[0017] Preferably, the first base unit includes at least one, preferably one single electromagnetic wave source, in particular a light source, used for at least two modalities, which reduces the number of self-contained units of the system and the overall installation space of the system.

[0018] Alternatively, at least one electromagnetic source, particularly the only electromagnetic source, of the system may be included in part or in its entirety in the scanning unit. In the case of a laser source, a laser amplifier and / or a frequency converter of the laser source may be included in the scanning unit. The light source may be connected to the first base unit via at least one electrical cable and / or optical fiber cable. Providing an electromagnetic light source and / or a laser amplifier and / or a frequency converter in the scanning unit has the advantage that the mirror arm disclosed in, for example, US 2013 / 0088709 A1 can be omitted.

[0019] Furthermore, the detection unit may have at least one detection component selected from the group consisting of a photodetector, a single-photon counter, an optical spectrometer, a light intensity meter, and a camera. In particular, the detection unit may comprise at least two different ones of the above detection components.

[0020] The detection unit may be (i) located in the first base unit, or (ii) located in a second base unit different from the first base unit, or (iii) associated with the respective scanning unit. In this respect, the term "associated" means that the detection unit is operatively connected to the respective scanning unit, for example by at least one cable, or is housed within the housing of the scanning unit. At least some of the mentioned alternatives have the advantage that the number of self-contained units of the system and the installation space of the overall system are reduced.

[0021] The configuration of components in the different units may be selected according to the specific requirements of an application, such as the number of different modalities, light sources, scanning components, and detection components, as well as limitations on the overall size of the base unit, scanning unit, and detection unit. For example, the laser source may be located in the base unit and the laser amplifier may be located in the scanning unit. However, if a particular application requires a small scanning unit, the laser amplifier may be located in the base unit as well.

[0022] More preferably, at least one of the scanning units includes a scanning component selected from the group consisting of an optical amplifier, in particular a laser amplifier, a transfer / scanning optics, and an excitation-emission filter. Alternatively, one or more scanning components may be included in one of the base units, in particular the first base unit, or in one of the detection units. In an alternative embodiment, a laser amplifier may also be integrated into the connection line between the base unit and the scanning unit.

[0023] In addition, the scanning unit may include at least one optical scanning component. Hereinafter, "optical scanning component" should be understood as an optical component of the scanning unit that does not necessarily contribute to the scanning process itself. For example, the scanning unit may include at least one of an optical fiber coupling, a galvanometer scanner, a microelectromechanical system (MEMS), and a digital micromirror device (DMD) for directing analytical light to the probe.

[0024] Alternatively, the white light may be emitted directly onto the probe, i.e., without any objective lens or optical fiber optically disposed between the light source and the probe, and thus a modality using this white light does not require any scanning unit (provided, within the scope of the present invention, that the system uses another modality that uses a scanning unit).

[0025] More preferably, the optical scanning components may be arranged in the scanning unit such that the signal emitted from the probe is returned to the detection unit, in particular directly or via the objective lens or a fiber coupling, which further reduces the number of self-contained units of the system.

[0026] Furthermore, the above mentioned filter may be arranged such that the signal emitted from the probe is filtered by said filter.

[0027] In addition, the system may comprise a switching unit that allows selectively routing the signal emitted from the probe to one of the detection units depending on the selected modality.

[0028] A further advantage arises when the first base unit comprises at least one of the electronics, software, power supply and optics, in particular a laser.

[0029] In a second aspect, the present invention also relates to a multimodal microscope system, particularly the system described above. The system according to the second aspect of the present invention comprises at least a first base unit including multiple electromagnetic wave sources and at least one scanning unit, preferably freely movable, particularly having six degrees of freedom. The scanning unit is connected to the first base unit via a flexible connection, particularly an optical connection (especially an optical fiber) and / or an electrical connection. According to the second aspect of the present invention, the system also comprises a beam combiner configured to superimpose the electromagnetic waves emitted by the electromagnetic wave sources to provide a superimposed electromagnetic wave that can be transmitted to the scanning unit. Thus, in contrast to the system disclosed in WO 2010 / 086861 A1, different modalities can be processed simultaneously, and no optical switcher is required, which would reduce the frame rate at which images can be displayed or further evaluated.

[0030] The superposition of electromagnetic waves of the present invention can be achieved by appropriate optical coatings of the optical components of the beam combiner. In particular, the coatings of the optical components of the beam combiner can be selected to provide a predetermined transmission / reflection ratio within a specific wavelength range, for example, within the range of 350 nm to 800 nm, within the range of 900 nm to 1350 nm, or within the range of 1600 nm to 1900 nm. The transmission / reflection ratio within the specific wavelength range can be in the range of 0.1:99.9 to 99.9:0.1, preferably 10:90 to 90:10. This allows the electromagnetic wave of the first modality to be essentially transmitted and the electromagnetic wave of the second modality to be essentially reflected, for example, below a 90° angle, thus combining both electromagnetic waves from both modalities together into one single beam. Both modalities can operate at the same wavelength in this particular scheme.

[0031] The power loss occurring in the coating can be compensated for by increasing the power of the incoming electromagnetic wave, thus compensating for the coating characteristics. In many cases, the remaining power is sufficient for the intended application, and therefore no power increase is required. Alternatively, the coating of the optical component can be precisely matched (in terms of wavelength or polarization) to the electromagnetic wave characteristics of the selected modalities, so that different modalities can be combined simultaneously in one beam without power loss.

[0032] Other beam combiners can be envisaged, such as optical diffraction gratings, which can combine different modalities with different individual wavelengths via different diffraction angles of the grating, thus superimposing the resulting beams into a single beam.

[0033] Addition of modalities via different electromagnetic polarization states of said modalities into a single beam can also be achieved via polarizing optics.

[0034] By adding more optical components with similar properties, more and more modalities can be combined in the same way.

[0035] Alternatively or additionally, the superposition of the electromagnetic waves may be achieved by suitable filters and / or suitable electronics.

[0036] In a third aspect, the present invention also relates to a multimodal microscope system, in particular one of the systems described above, comprising at least two detection units and a beam splitter configured to split an electromagnetic wave emitted by the probe into a plurality of partial electromagnetic waves and to send the partial electromagnetic waves to respective detection units.

[0037] The splitting of electromagnetic waves in the present invention may be achieved by appropriate optical coatings of the optical components of the beam splitter. In particular, the coatings of the optical components of the beam splitter may be selected to provide a predetermined transmission / reflection ratio within a specific wavelength range, for example, within the range of 350 nm to 800 nm, 900 nm to 1350 nm, or 1600 nm to 1900 nm. The transmission / reflection ratio within the specific wavelength range may be in the range of 0.1:99.9 to 99.9:0.1, preferably 10:90 to 90:10. This allows the electromagnetic wave of the first modality to be essentially transmitted and the electromagnetic wave of the second modality to be essentially reflected, for example, below a 90° angle, thus splitting the electromagnetic wave comprising the two modalities into two beams. Both modalities may operate at the same wavelength in this particular scheme.

[0038] Other beam splitters such as optical diffraction gratings can be envisaged that can split different modalities with different individual wavelengths via different diffraction angles of the grating, thus splitting one beam into several beams.

[0039] Splitting a beam containing modalities with different electromagnetic polarization states into several beams can also be achieved via polarization optical elements.

[0040] Alternatively or additionally, the splitting of the electromagnetic waves may be achieved by suitable filters, frequency converters and / or suitable electronic devices.

[0041] When an electromagnetic wave is split by a beam splitter and / or combined by a beam combiner, the partial electromagnetic waves may be spatially separated from one another. Alternatively or additionally, the partial electromagnetic waves may have the same relative spectral power distribution, where the spectral power distribution is understood as the power per unit area per unit wavelength of each partial electromagnetic wave, e.g., the spectral power distribution of a first partial electromagnetic wave may be a multiple of the spectral power distribution of a second partial electromagnetic wave. Also, alternatively or additionally, the partial waves may have the same or different total intensities.

[0042] Preferably, at least two of the detection units are adapted for the detection of different modalities, in particular two-photon excited fluorescence, two-photon autofluorescence, fluorescence lifetime imaging, autofluorescence lifetime imaging, second harmonic generation, third harmonic generation, incoherent / spontaneous Raman scattering, coherent anti-Stokes Raman scattering (CARS), broadband or multiplexed CARS, stimulated Raman scattering, stimulated emission depletion (STED), nonlinear absorption, confocal Raman microscopy, optical coherence tomography (OCT), single-photon / linear fluorescence imaging, bright-field imaging, dark-field imaging, three-photon, four-photon, second harmonic generation, third harmonic generation, and fourth harmonic generation.

[0043] For example, a first partial electromagnetic wave generated by the beam splitter may be sent to a first detection unit adapted for detection of a first modality, and a second partial electromagnetic wave generated by the beam splitter may be sent to a second detection unit adapted for detection of a second, different modality.

[0044] At least one base unit and / or at least one scanning unit and / or at least one detection unit, in particular each of said units, may be accommodated in a separate housing. Furthermore, at least one base unit and at least one scanning unit may be accommodated in a common housing and the detection unit may be accommodated in a separate housing; or at least one base unit and at least one detection unit may be accommodated in a common housing and the scanning unit may be accommodated in a separate housing; or at least one scanning unit and at least one detection unit may be accommodated in a common housing and the base unit may be accommodated in a separate housing. Alternatively, at least one base unit, at least one scanning unit and at least one detection unit may all be accommodated in one and the same housing.

[0045] The invention and its advantages are explained in more detail below with reference to two embodiments shown in the following schematic drawings. [Brief explanation of the drawings]

[0046] [Figure 1] 1 illustrates a first embodiment of a multimodal microscope system according to the present invention. [Figure 2] 1 shows a second embodiment of a multimodal microscope system according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0047] The multimodal microscope system 1 shown in FIG. 1 includes a first base unit 2 (hereinafter referred to as the base unit 2), a scanning unit 4, and a detection unit 5.

[0048] The base unit 2 includes several light sources for different modalities: a laser light source 14, a light source for fluorescence imaging 15, a laser for Raman scattering 16, a light source for optical coherence tomography (OCT) 17, an amplifier pump laser 18, and a white light source 19. The base unit 2 additionally includes electronics 23, software 24, and a power supply 25.

[0049] The scanning unit 4 includes several scanning components: an optical amplifier (particularly a laser amplifier) ​​and / or a frequency converter 20, a transfer / scanning optics 21, and an excitation-emission filter 22. Each light source 14, 15, 16, 17, 18, 19 is connected to the scanning unit 4 via a separate flexible connection 6, e.g., a fiber optic cable. Thus, each of the light sources 14, 15, 16, 17, 18, 19 is operatively connected to this single set of scanning components 20, 21, 22, such that different modalities associated with the light sources 14, 15, 16, 17, 18, 19 can be provided with one and the same set of scanning components 20, 21, 22. Providing the laser amplifier and / or frequency converter within the scanning unit 4 has the advantage that a mirror arm, such as that disclosed in US 2013 / 0088709 A1, can be omitted.

[0050] The scanning unit 4 further includes an objective lens 12 for directing the analytical light towards the probe 50. More specifically, the objective lens 12 is arranged within the scanning unit 4 such that the signal emitted from the probe returns through the objective lens 12. In an alternative embodiment, the objective lens 12 may be replaced by an optical fiber. The filter 22 is arranged such that the signal emitted from the probe 50 is filtered by said filter 22. The scanning unit 4 is also connected to the base unit 2 via an electrical cable 29, which provides power to and controls the scanning unit 4.

[0051] The detection unit 5 is operatively connected to the scanning unit 4 and includes several detection components: a photodetector 7, a single-photon counter 8, an optical spectrometer 9, a light intensity meter 10, and a fluorescence camera 11. Both the scanning unit 4 and the detection unit 5 are freely movable with six degrees of freedom. Each detection component 7, 8, 9, 10, and 11 is connected to the scanning unit 4 via a separate flexible connection 28, e.g., a fiber optic cable. Thus, each detection component 7, 8, 9, 10, and 11 is operatively connected to a single set of scanning components 20, 21, and 22, such that different modalities associated with the detection components 7, 8, 9, 10, and 11 can be provided with the same set of scanning components 20, 21, and 22. Alternatively, light emitted from the light source 17 may be emitted directly onto the probe 50. The detection unit 5 is also connected to the base unit 2 via an electrical cable 30, which provides power and controls the detection unit 5. Alternatively, the detection unit 5 may be powered from a different source and / or controlled wirelessly, for example by an app.

[0052] The system 1 further comprises a switching unit 3 that allows selectively routing signals emitted from the probe 50 to the detection unit 5 depending on the selected modality. Figure 1 shows several positions where the switching unit 3 may be located: inside the excitation-emission filter 22, between the excitation-emission filters 22 within the scanning unit 4, between the excitation-emission filter 22 and the detection unit 5 within the scanning unit 4, between the scanning unit 4 and the detection unit 5, or between the scanning unit 4 and the detection components 7, 8, 9, 10, 11 within the detection unit 5.

[0053] The second multimodal microscope system 1 shown in Figure 2 comprises a beam combiner 26 configured to superimpose the electromagnetic waves emitted by the electromagnetic wave sources 14, 15, 16 to provide a superimposed electromagnetic wave that can be transmitted to the scanning unit 4 via a common optical fiber 6.

[0054] 2 further comprises a beam splitter 27 configured to split the electromagnetic wave emitted by the probe 50 into a plurality of partial electromagnetic waves and send the partial electromagnetic waves to respective detection units 4. In addition to the spatial division, the partial electromagnetic waves may also be split according to their wavelengths. At least two of the detection units 4 are adapted for detection of different modalities.

Claims

1. A multimodal microscope system (1), comprising: at least one first base unit (2) comprising at least one electrical and / or optical base component (14, 15, 16, 17, 18, 19); at least one scanning unit (4) comprising at least one scanning component (20, 21, 22); at least one detection unit (5) comprising at least one detection component (7, 8, 9, 10, 11), - said scanning unit (4) and / or said detection unit (5) are freely movable; - said scanning unit (4) and / or said detection unit (5) are connected to said first base unit (2); The at least one electrical and / or optical base component (14, 15, 16, 17, 18, 19), the at least one scanning component (20, 21, 22), and the at least one detection component (7, 8, 9, 10, 11) are at least one electrical and / or optically based component (14, 15, 16, 17, 18, 19) and / or at least one scanning component (20, 21, 22) and / or - at least one detection component (7, 8, 9, 10, 11) are operatively coupled to each other so as to be jointly usable for multiple modalities, The first base unit (2) is provided with a laser source, and the scanning unit (4) includes a laser amplifier (20) and / or a frequency converter; The multimodal microscope system (1) includes the first base unit (2) and includes at least two electrical and / or optical base components (14, 15, 16, 17, 18, 19), each of which is an electromagnetic wave source (14, 15, 16, 17, 18, 19) usable for different modalities and selected from the group consisting of a pulsed laser source (14), a CW (continuous wave) coherent or incoherent light source, a light source for fluorescence imaging (15), a narrow linewidth laser (16), a broadband laser source, a broadband incoherent laser source, a swept frequency laser source, an optical amplifier pump laser (18), and a white light source (19).

2. 2. The multimodal microscope system (1) according to claim 1, wherein the first base unit (2) comprises at least one electromagnetic wave source (14, 15, 16, 17, 18, 19) used for at least two modalities.

3. 3. A multimodal microscope system (1) according to claim 1 or 2, wherein at least a part of the electromagnetic wave sources (14, 15, 16, 17, 18, 19) is included in the scanning unit (4).

4. 4. The multimodal microscope system (1) according to claim 1, wherein the detection unit (5) comprises at least one detection component (7, 8, 9, 10, 11) selected from the group consisting of a photodetector (7), a single-photon counter (8), an optical spectrometer (9), a light intensity meter (10), and a camera (11).

5. A multimodal microscope system (1) according to any one of claims 1 to 4, wherein the detection unit (5) is (i) arranged in the first base unit (2), or (ii) arranged in a second base unit (2') different from the first base unit (2), or (iii) associated with each scanning unit (4).

6. 6. A multimodal microscope system (1) according to any one of claims 1 to 5, wherein at least one of the scanning units (4) comprises scanning components (20, 21, 22) selected from the group consisting of an optical amplifier (20), a transfer / scanning optical system (21), and an excitation-emission filter (22).

7. 7. A multimodal microscope system (1) according to any one of claims 1 to 6, wherein the scanning unit (4) comprises an optical scanning component (12) for directing analytical light onto a probe (50).

8. 8. A multimodal microscope system (1) as described in claim 7, wherein the optical scanning component (12) is arranged within the scanning unit (4) so ​​that a signal emitted from the probe (50) is returned to the detection unit (5).

9. 7. The multimodal microscope system (1) of claim 6, wherein the excitation-emission filter (22) is positioned such that a signal emitted from a probe (50) is filtered by the excitation-emission filter (22).

10. 10. A multimodal microscope system (1) according to any one of claims 1 to 9, further comprising a switching unit (3) that enables selectively sending a signal emitted from the probe (50) to one of the detection units (5) depending on a selected modality.

11. 11. A multimodal microscope system (1) according to any one of claims 1 to 10, wherein the first base unit (2) includes at least one of electronics (23), software (24) and a power supply (25).

12. The scanning unit (4) is connected to the first base unit (2) via a flexible connecting line (6, 29), The multimodal microscope system (1) of any one of claims 1 to 11, further comprising a beam combiner (26) configured to superimpose electromagnetic waves emitted by the electromagnetic wave sources (14, 15, 16, 17, 18, 19) to provide a superimposed electromagnetic wave that can be transmitted to the scanning unit (4).

13. The at least one detection unit (5) includes at least two detection units (5), The multimodal microscope system (1) of any one of claims 1 to 9, further comprising a beam splitter (27) configured to split the electromagnetic wave emitted by the probe (50) into a plurality of partial electromagnetic waves and send the partial electromagnetic waves to respective detection units (5).

14. 14. The multimodal microscope system of claim 13, wherein the at least two detection units (5) are adapted for the detection of different modalities, the different modalities being selected from the group consisting of two-photon excited fluorescence, two-photon autofluorescence, fluorescence lifetime imaging, autofluorescence lifetime imaging, second harmonic generation, third harmonic generation, incoherent / spontaneous Raman scattering, coherent anti-Stokes Raman scattering (CARS), broadband or multiplexed CARS, stimulated Raman scattering, coherent Raman scattering, stimulated emission depletion (STED), nonlinear absorption, confocal Raman microscopy, optical coherence tomography (OCT), single-photon / linear fluorescence imaging, bright-field imaging, dark-field imaging, three-photon, four-photon, second harmonic generation, third harmonic generation, and fourth harmonic generation.

Images