Multimodal microscopy system

Abstract

A multi-modal microscopy system (1) is disclosed. In a first aspect, the system (1) comprises: at least a first base unit (2) comprising at least one electrical and / or optical base assembly (14, 15, 16, 17, 18, 19); at least one scanning unit (4) comprising at least one scanning assembly (20, 21, 22); and at least one detection unit (5) comprising at least one detection assembly (7, 8, 9, 10, 11). The at least one base assembly (14, 15, 16, 17, 18, 19), the at least one scanning assembly (20, 21, 22), and the at least one detection assembly (7, 8, 9, 10, 11) are operatively coupled to each other such that the at least one base assembly (14, 15, 16, 17, 18, 19) and / or the at least one scanning assembly (20, 21, 22) and / or the at least one detection assembly (7, 8, 9, 10, 11) are jointly usable for more than one modality. In a further aspect, the system (1) comprises a beam combiner (26) arranged to superimpose electromagnetic waves emitted by an electromagnetic wave source (14, 15, 16, 17, 18, 19); and / or a beam splitter (27) arranged to split electromagnetic waves emitted by a probe (50) into a plurality of partial electromagnetic waves.

Description

TECHNICAL FIELD

[0001] The present application relates to a multi-modal microscopy system. It is known in the art to provide optical images from multiple optical imaging modalities and to combine these images. Systems with this capability are called multi-modal microscopy systems. They can be used, for example, in medicine, in particular for tissue imaging. BACKGROUND

[0002] For example, a known multi-modal system is disclosed in WO 2010 / 086861 Al. The system comprises an optical coherence tomography (OCT) module, a photoacoustic (PA) module, a light switch and an endoscope head, wherein the PA light source and the OCT light source are coupled to the endoscope head through the light switch. The system has several drawbacks. In particular, it only allows sequential or pseudo-parallel imaging. Thus, the processing times of the different modalities add up, reducing the frame rate at which images can be displayed or further evaluated. Furthermore, the different modalities cannot be used simultaneously for visualizing a procedure. Moreover, the mentioned switch is expensive.

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

[0004] Furthermore, EP 2 579 085 Al discloses a laser scanning microscope comprising a measurement head connected with a radiation source, and adjustable mirrors for deflecting and aligning the excitation beam of pulsed laser radiation of the source. A beam splitter is arranged in front of a focusing lens. A photodetector determines the position of the radiation of the beam. A control unit controls the mirrors based on a determined deviation of the test beam from the intermediate alignment, so that a stabilization of the direction of the beam is achieved, independent of the position conditions of the transfer lens which impair the measurement. The beam splitter is designed as a reflective beam splitter or a transmissive beam splitter.

[0005] Furthermore, US 2013 / 0088709 Al discloses a nonlinear laser scanning microscope for flexible, non-invasive three-dimensional detection, comprising a measurement head which is flexibly connected through transfer optics to at least one radiation source and can be freely positioned in space. At least one controllable tilting mirror is arranged for aligning the excitation beam in order to keep the excitation beam concentric with an aperture-limited optical element of the measurement head. A test beam is coupled out of the excitation beam onto a spatially resolving photodetector for monitoring the central alignment of the test beam as a conjugate position of the target position of the excitation beam, and the excitation beam is directed stably by a control unit of the tilting mirror depending on the determined deviation. SUMMARY

[0006] It is an object of the present application to provide an improved multi-modal microscopy system in which the drawbacks of the prior art are eliminated or at least reduced. In particular, the system shall allow to shorten the processing time of different modalities and shall reduce the frame rate at which images can be displayed or further evaluated.

[0007] In a first aspect, the present application relates to a multi-modal microscopy system comprising at least one first base unit comprising at least one electrical and / or optical base component, at least one scanning unit comprising at least one scanning component, and at least one detection unit comprising at least one detection component. Preferably,

[0008] - the at least one first base unit comprises at least two electrical and / or optical base components, and / or

[0009] - the at least one scanning unit comprises at least two scanning components, and / or

[0010] - the at least one detection unit comprises at least two detection components.

[0011] The scanning unit and / or the detection unit are preferably freely movable, in particular with six degrees of freedom. The scanning unit and / or the detection unit 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.

[0012] According to the first aspect of the present application, the at least one base component, the at least one scanning component, and the at least one detection component are operatively coupled to each other such that

[0013] - the at least one base component, and / or

[0014] - the at least one scanning component, and / or

[0015] - the at least one detection component

[0016] are jointly and in particular simultaneously usable for more than one modality.

[0017] In other words, two components of the three units (base unit, scanning unit, detection unit) can be used in combination with one identical component or a group of identical components of one remaining unit in order to provide different modalities.

[0018] Thus, in a first embodiment, the first base unit can comprise a first base assembly and a second base assembly, where the first base assembly can be used in conjunction with one scanning assembly or a set of scanning assemblies to provide a first modality, and where the second base assembly can be used in conjunction with the same scanning assembly or the same set of scanning assemblies to provide a second modality. In a second embodiment, the first base unit can comprise a first base assembly and a second base assembly, where the first base assembly can be used in conjunction with one detection assembly or a set of detection assemblies to provide a first modality, and where the second base assembly can be used in conjunction with the same detection assembly or the same set of detection assemblies to provide a second modality.

[0019] In a further embodiment, the first scanning unit can comprise a first scanning assembly and a second scanning assembly, where the first scanning assembly can be used in conjunction with one detection assembly or a set of detection assemblies to provide a first modality, and where the second scanning assembly can be used in conjunction with the same detection assembly or the same set of detection assemblies to provide a second modality. In a further embodiment, the first scanning unit can comprise a first scanning assembly and a second scanning assembly, where the first scanning assembly can be used in conjunction with one base assembly or a set of base assemblies to provide a first modality, and where the second scanning assembly can be used in conjunction with the same base assembly or the same set of base assemblies to provide a second modality.

[0020] In a further embodiment, the first detection unit can comprise a first detection assembly and a second detection assembly, where the first detection assembly can be used in conjunction with one base assembly or a set of base assemblies to provide a first modality, and where the second detection assembly can be used in conjunction with the same base assembly or the same set of base assemblies to provide a second modality. In a further embodiment, the first detection unit can comprise a first detection assembly and a second detection assembly, where the first detection assembly can be used in conjunction with one scanning assembly or a set of scanning assemblies to provide a first modality, and where the second detection assembly can be used in conjunction with the same scanning assembly or the same set of scanning assemblies to provide a second modality.

[0021] As will be apparent from the discussion below, the combined availability of one component of the system for more than one modality reduces the number of components and the size of the system. Furthermore, it allows for simultaneous imaging using different modalities in a truly parallel fashion.

[0022] Advantageously, the base assembly is usable for electromagnetic wave sources of different modalities. This provides images of different modalities which can be combined. The different modalities can be selected from the group consisting of two-photon excitation fluorescence, two-photon autofluorescence, fluorescence lifetime imaging, autofluorescence lifetime imaging, second harmonic generation, third harmonic generation, incoherent / autofluorescence 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, brightfield imaging, darkfield imaging, three-photon, four-photon, second harmonic generation, third harmonic generation, and fourth harmonic generation.

[0023] In particular, the electromagnetic wave source can 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 can comprise a laser amplifier and / or a frequency converter.

[0024] Preferably, the first base unit comprises at least one, preferably a single, electromagnetic wave source, in particular a light source, for at least two modalities. This reduces the number of independent units of the system and the installation space of the entire system.

[0025] Alternatively, at least a part of the at least one electromagnetic wave source or the entire at least one electromagnetic wave source, in particular the only electromagnetic wave source of the system, can be contained in the scanning unit. In case of a laser source, the laser amplifier and / or the frequency converter of the laser source can be contained in the scanning unit. The light source can be connected to the first base unit via at least one electrical cable and / or optical fiber cable. Providing the electromagnetic light source and / or the laser amplifier and / or the frequency converter in the scanning unit has the advantage that a mirror arm as disclosed in US 2013 / 0088709 Al can be omitted.

[0026] Further, the detection unit can have at least one detection component selected from the group consisting of a photodetector, a single photon counter, a spectrometer, an optical power meter, and a camera. In particular, the detection unit can comprise at least two different components of the above-mentioned detection components.

[0027] The detection unit can be (i) arranged in said first base unit or (ii) arranged 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 with" means that the detection unit is operatively connected with the respective scanning unit, e.g. by at least one electrical cable, or contained in the housing of the scanning unit. At least some of the mentioned alternatives have the advantage of reducing the number of independent units of the system and the installation space of the entire system.

[0028] The arrangement of components within the different units can be chosen according to the specific requirements of a particular application, e.g. the number of different modalities, the number of light sources, the number of scanning components and the number of detection components and restrictions on the overall size of the base unit, the scanning unit and the detection unit. For example, the laser source can be arranged in the base unit and the laser amplifier can be arranged in the scanning unit. However, when a particular application requires a smaller scanning unit, the laser amplifier can also be arranged in the base unit.

[0029] It is further preferred that the at least one scanning unit comprises scanning components selected from the group consisting of: a light amplifier, in particular a laser amplifier, a transmission / scanning optics and an excitation emission filter. Alternatively, one or more scanning components can be contained in one of the base units, in particular the first base unit, or in one of the detection units. In alternative embodiments, the laser amplifier can also be integrated in the connection line between the base unit and the scanning unit.

[0030] Further, the scanning unit can comprise at least one optical scanning component. Here and in the following, an "optical scanning component" is to be understood as an optical component of the scanning unit which does not necessarily contribute to the scanning process itself. For example, the scanning unit can comprise at least one of a fiber coupler for guiding the analysis light to the probe, a galvanometer scanner, a microelectromechanical system (MEM) and a digital micromirror device (DMD).

[0031] Alternatively, the white light can be emitted directly onto the probe, i.e. without any objective or fiber optics between the light source and the probe. Thus, the modality using this white light does not require any scanning unit (provided that, in the present invention, the system employs another modality using a scanning unit).

[0032] It is further preferred that the optical scanning component can be arranged in the scanning unit such that the signal emitted from the probe is transmitted back to the detection unit, in particular directly or through the objective or the fiber coupler. This further reduces the number of independent units of the system.

[0033] Further, the above-mentioned filter can be arranged such that the signal emitted from the probe is filtered by means of the filter.

[0034] Further, the system can comprise a switching unit which allows to selectively transmit the signal emitted from the probe to one of the detection units depending on the selected modality.

[0035] Further advantages arise when the first base unit comprises at least one of electronics, software, a power supply and optics, in particular a laser.

[0036] In a second aspect, the present application also relates to a multi-modal microscopy system, in particular a system as described above. The system according to the second aspect of the present application comprises at least one first base unit comprising a plurality of electromagnetic wave sources and at least one scanning unit, which is preferably freely movable, in particular with six degrees of freedom. The scanning unit is connected to the first base unit via a flexible connection line, in particular an optical connection line, in particular an optical fiber, and / or an electrical connection line. According to the second aspect of the present application, the system comprises a beam combiner which is arranged to superimpose electromagnetic waves emitted by the electromagnetic wave sources to provide superimposed electromagnetic waves which can be transmitted to the scanning unit. Thus, in contrast to the system disclosed in WO 2010 / 086861 Al, no optical switch is necessary, so that different modalities can be processed simultaneously and the frame rate for displaying or further evaluating the images can be reduced.

[0037] The superimposition of electromagnetic waves of the present application can be achieved by a suitable optical coating of the optical components of the beam combiner. In particular, the coating of the optical components of the beam combiner can be chosen to provide a predetermined transmission / reflection ratio in a certain wavelength range, e.g. in the range from 350 nm to 800 nm, in the range from 900 nm to 1350 nm, or in the range from 1600 nm to 1900 nm. The transmission / reflection ratio in a certain wavelength range can be in the range from 0.1 : 99.9 to 99.9 : 0.1, preferably in the range from 10 : 90 to 90 : 10. This allows electromagnetic waves of the first modality to be substantially transmitted and electromagnetic waves of the second modality to be substantially reflected, e.g. at 90° angle, thus combining both electromagnetic waves from both modalities in one single beam. In this particular approach, both modalities can operate with the same wavelength.

[0038] The power loss occurring in the coating can be compensated by increasing the power of the incoming electromagnetic waves, thus compensating the coating properties. Usually, the remaining power is sufficient for the intended application, so that no increase of the power is necessary. Alternatively, the coating of the optical components can be exactly matched to the electromagnetic wave properties of the selected modality (in terms of wavelength or polarization), so that different modalities can be combined in one beam simultaneously without power loss.

[0039] Other beam combiners like optical diffraction gratings can be envisaged, in which different modalities with different individual wavelengths can be combined by different diffraction angles of the grating, thus superimposing the resulting beams into a single beam.

[0040] It is also possible to add modalities via different electromagnetic wave polarization states of the modalities into a single beam via polarizing optical elements.

[0041] By adding more optical components with similar properties, an increasing number of modalities can be combined in the same way.

[0042] Alternatively or additionally, the superposition of electromagnetic waves can be achieved by appropriate filters and / or appropriate electronics.

[0043] In a third aspect, the present application also relates to a multi-modal microscopy system, in particular one of the systems as described above. The system according to the third aspect of the present application comprises at least two detection units and a beam splitter arranged to split the electromagnetic waves emitted by the probe into a plurality of partial electromagnetic waves and to transmit the partial electromagnetic waves to the respective detection units.

[0044] The separation of electromagnetic waves of the present application can 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 can be chosen to provide a predetermined transmission / reflection ratio in a certain wavelength range, e.g. in the range from 350 nm to 800 nm, in the range from 900 nm to 1350 nm, or in the range from 1600 nm to 1900 nm. The transmission / reflection ratio in a certain wavelength range can be in the range of 0.1 : 99.9 to 99.9 : 0.1, preferably in the range of 10 : 90 to 90 : 10. This allows the electromagnetic waves of the first modality to be substantially transmitted and the electromagnetic waves of the second modality to be substantially reflected, e.g. at a 90° angle, thus splitting the electromagnetic waves containing both modalities into two beams. In this particular scenario, both modalities can operate with the same wavelength.

[0045] Other beam splitters are conceivable, like optical diffraction gratings, where different modalities with different individual wavelengths can be separated by different diffraction angles of the grating, thus splitting the beam into several beams.

[0046] It is also possible to split a beam comprising modalities with different electromagnetic wave polarization states into several beams via polarizing optical elements.

[0047] Alternatively or additionally, the separation of electromagnetic waves can be achieved by appropriate filters, frequency converters and / or appropriate electronics.

[0048] The partial electromagnetic waves into which and / or of which the beam splitter separates the electromagnetic waves can be spatially separated from each other. Alternatively or additionally, the partial electromagnetic waves can have the same relative spectral power distribution, where the spectral power distribution is understood as the power per unit wavelength per unit area of the respective partial electromagnetic wave; for example, the spectral power distribution of the first partial electromagnetic wave can be a multiple of the spectral power distribution of the second partial electromagnetic wave. Also alternatively or additionally, the partial waves can have the same or different total intensities.

[0049] Preferably, at least two of the detection units are adapted to detect different modalities, in particular two-photon excitation fluorescence, two-photon autofluorescence, fluorescence lifetime imaging, autofluorescence lifetime imaging, second harmonic generation, third harmonic generation, incoherent / autofluorescence Raman scattering, coherent anti-Stokes Raman scattering (CARS), broadband or multiplex CARS, stimulated Raman scattering, stimulated emission depletion (STED), nonlinear absorption, confocal Raman microscopy and optical coherence tomography (OCT), single-photon / linear fluorescence imaging, brightfield imaging, darkfield imaging, three-photon, four-photon, second harmonic generation, third harmonic generation, and fourth harmonic generation.

[0050] For example, the first portion of electromagnetic waves generated by the beam splitter can be transmitted to a first detection unit adapted to detect a first modality, while the second portion of electromagnetic waves generated by the beam splitter can be transmitted to a second detection unit adapted to detect a second, different modality.

[0051] The at least one base unit and / or the at least one scanning unit and / or the at least one detection unit, in particular each of said units, can be housed in a separate housing. Further, the at least one base unit and the at least one scanning unit can be housed in a common housing, and the detection units can be housed in separate housings; or, the at least one base unit and the at least one detection unit can be housed in a common housing, and the scanning unit can be housed in a separate housing; or, the at least one scanning unit and the at least one detection unit can be housed in a common housing, and the base unit can be housed in a separate housing. Alternatively, the at least one base unit and the at least one scanning unit and the at least one detection unit can all be housed in the same housing. BRIEF DESCRIPTION OF DRAWINGS

[0052] The application and its advantages will be explained in more detail below with reference to two embodiments, which are shown in the following schematic drawings. In the drawings:

[0053] Figure 1 A first embodiment of a multi-modal microscopy system according to the application is shown;

[0054] Figure 2 A second embodiment of a multi-modal microscopy system according to the application is shown. DETAILED DESCRIPTION

[0055] Figure 1 The multi-modal microscopy system 1 shown in Fig. 1 comprises a first base unit 2 (hereinafter referred to as base unit 2), a scanning unit 4 and a detection unit 5.

[0056] The base unit 2 comprises several light sources for different modalities: a laser 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 comprises electronics 23, software 24 and a power supply 25.

[0057] The scanning unit 4 comprises several scanning components: a light amplifier (in particular a laser amplifier) and / or a frequency converter 20, a transmission / 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 line 6 (e.g. an optical fiber cable). Thus, each of the light sources 14, 15, 16, 17, 18, 19 is operatively connected to the same set of scanning components 20, 21, 22, so that the different modalities associated with the light sources 14, 15, 16, 17, 18, 19 can be provided with this single set of scanning components 20, 21, 22. Providing a laser amplifier and / or a frequency converter in the scanning unit 4 has the advantage of dispensing with a mirror arm as disclosed, for example, in US 2013 / 0088709 Al.

[0058] The scanning unit 4 further comprises an objective lens 12 for guiding the analysis light to the probe 50. In more detail, the objective lens 12 is arranged in the scanning unit 4 so that the signals emitted from the probe pass back through the objective lens 12. In an alternative embodiment, the objective lens 12 can be replaced by an optical fiber. The filter 22 is arranged so that the signals emitted from the probe 50 are filtered by means of said filter 22. The scanning unit 4 is also connected to the base unit 2 via a cable 29, which powers and controls the scanning unit 4.

[0059] The detection unit 5 is operatively connected with the scanning unit 4 and comprises several detection components: a photodetector 7, a single photon counter 8, a spectrometer 9, a light power meter 10 and a fluorescence camera 11. Both the scanning unit 4 and the detection unit 5 are freely movable in six degrees of freedom. Each detection component 7, 8, 9, 10, 11 is connected to the scanning unit 4 via a separate flexible connection line 28 (e.g. an optical fiber cable). Thus, each detection component 7, 8, 9, 10, 11 is operatively connected to the same set of scanning components 20, 21, 22, so that the different modalities associated with the detection components 7, 8, 9, 10, 11 can be provided with this single set of scanning components 20, 21, 22. Alternatively, the light emitted from the light source 17 can be emitted directly onto the probe 50. The detection unit 5 is also connected to the base unit 2 via a cable 30, which powers and controls the detection unit 5. Alternatively, the detection unit 5 can be powered by a power supply from a different source and / or controlled in a wireless manner (e.g. by an application software).

[0060] The system 1 further comprises a switching unit 3 which allows selectively transmitting the signals emitted from the probe 50 to the detection units 5 depending on the selected modality. Figure 1 Several positions are shown in which the switching unit 3 can be arranged: inside the excitation emission filter 22, inside the scanning unit 4 between the excitation emission filters 22, inside the scanning unit 4 between the excitation emission filters 22 and the detection units 5, between the scanning unit 4 and the detection units 5, or inside the detection units 5 between the scanning unit 4 and the detection assembly 7, 8, 9, 10, 11.

[0061] Figure 2 The second multi-modality microscopy system 1 shown in Fig. 2 comprises a beam combiner 26 arranged to superimpose the electromagnetic waves emitted by the electromagnetic wave sources 14, 15, 16 to provide superimposed electromagnetic waves which can be transmitted via the common optical fiber 6 to the scanning unit 4.

[0062] Figure 2 The system 1 shown in Fig. 2 further comprises a beam splitter 27 arranged to split the electromagnetic waves emitted by the probe 50 into a plurality of partial electromagnetic waves and to transmit the partial electromagnetic waves to respective detection units 4. In addition to a spatial separation, the partial electromagnetic waves can also be separated according to their wavelengths. At least two of the detection units 4 are adapted for detection of different modalities.

Claims

1. A multi-modal microscopy 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), and - at least one detection unit (5) comprising at least one detection component (7, 8, 9, 10, 11), wherein - the scanning unit (4) and / or the detection unit (5) is freely moveable, and - the scanning unit (4) and / or the detection unit (5) is connected to the first base unit (2), wherein 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 each other such that - at least one base 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) can be jointly used for more than one modality, characterized in that a laser source is arranged in the base unit (2) and a laser amplifier and / or a frequency converter are contained in the scanning unit (4), wherein the first base unit (2) comprises at least two base components (14, 15, 16, 17, 18, 19) which are electromagnetic wave sources and can be used for different modalities.

2. The system (1) according to claim 1, wherein, The electromagnetic wave sources are selected from the group consisting of pulsed laser sources, CW (continuous wave) coherent or incoherent light sources, light sources for fluorescence imaging, narrow linewidth lasers, broadband laser sources, broadband incoherent laser sources, swept frequency laser sources, optical amplifier pump lasers and white light sources.

3. The system (1) according to claim 1 or 2, wherein, The first base unit (2) comprises at least one electromagnetic wave source for at least two modalities.

4. The system (1) according to claim 1 or 2, wherein, At least a part of the at least one electromagnetic wave source is contained in the scanning unit (4).

5. The system (1) according to claim 1 or 2, wherein, The detection unit (5) has at least one detection component (7, 8, 9, 10, 11) selected from the group consisting of photodetectors, single photon counters, spectrometers, optical power meters and cameras.

6. The system (1) according to claim 1 or 2, 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 a respective scanning unit (4).

7. The system (1) according to claim 1 or 2, wherein, At least one of the scanning units (4) comprises a scanning component (20, 21, 22) selected from the group consisting of optical amplifiers, transmission / scanning optics and excitation emission filters.

8. The system (1) according to claim 1 or 2, wherein, The scanning unit (4) comprises an optical scanning component (12), such as an objective lens or a fiber coupler for directing analysis light to a probe (50).

9. The system (1) according to claim 8, wherein, The optical scanning assembly (12) is arranged in the scanning unit (4) such that signals emitted from the probe head (50) are transmitted back to the detection unit (5).

10. The system (1) according to claim 7, wherein, The filter is arranged such that signals emitted from the probe head (50) are filtered by means of the filter.

11. The system (1) according to claim 1 or 2, further comprising a switching unit (3) which allows selectively transmitting signals emitted from the probe head (50) to one of the detection units (5) depending on the selected modality.

12. The system (1) according to claim 1 or 2, wherein, The first base unit (2) comprises at least one of electronics (23), software (24) and a power supply (25).

13. The system (1) according to claim 1, wherein, The system (1) comprises - at least a first base unit (2) comprising a plurality of electromagnetic wave sources, and - at least one scanning unit (4) which is freely movable, wherein the scanning unit (4) is connected to the first base unit (2) via a flexible connection line (6, 29), characterized in that the system (1) further comprises a beam combiner (26) which is arranged to superimpose electromagnetic waves emitted by the electromagnetic wave sources to provide superimposed electromagnetic waves which can be transmitted to the scanning unit (4).

14. The system (1) according to claim 1, wherein, The system (1) comprises - at least a first base unit (2) comprising a plurality of electromagnetic wave sources, - at least two detection units (5), - a beam splitter (27) which is arranged to split electromagnetic waves emitted by the probe head (50) into a plurality of partial electromagnetic waves and to transmit the partial electromagnetic waves to the respective detection units (5).

15. The system (1) according to claim 14, wherein, At least two of the detection units (5) are adapted to detect different modalities selected from the group consisting of two-photon excited fluorescence, two-photon auto fluorescence, fluorescence lifetime imaging, auto fluorescence lifetime imaging, second harmonic generation, third harmonic generation, incoherent / auto Raman scattering, coherent anti-Stokes Raman scattering (CARS), broadband or multiple 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, brightfield imaging, darkfield imaging, three-photon, four-photon, second harmonic generation, third harmonic generation and fourth harmonic generation. At least two of the detection units (5) are adapted to detect different modalities selected from the group consisting of two-photon excited fluorescence, two-photon auto fluorescence, fluorescence lifetime imaging, auto fluorescence lifetime imaging, second harmonic generation, third harmonic generation, incoherent / auto Raman scattering, coherent anti-Stokes Raman scattering (CARS), broadband or multiple 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, brightfield imaging, darkfield imaging, three-photon, four-photon, second harmonic generation, third harmonic generation and fourth harmonic generation.

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