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
  • G01N21/65—Raman scattering
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
  • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
  • G01J3/28—Investigating the spectrum
  • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
  • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
  • G01J3/28—Investigating the spectrum
  • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
  • G01J3/4412—Scattering spectrometry
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
  • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
  • G01N21/65—Raman scattering
  • G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
  • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
  • G01N21/65—Raman scattering
  • G01N2021/653—Coherent methods [CARS]
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
  • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
  • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
  • G01N21/65—Raman scattering
  • G01N2021/653—Coherent methods [CARS]
  • G01N2021/655—Stimulated Raman

Definitions

• the present invention relates to a method for the detection of a non-linear resonant optical signal and to a device for implementing said method. It applies in particular to the detection of broadcast signals CARS.
• Vibrational optical techniques are methods that aim to use the light / matter interaction to obtain information about these molecular vibrations.
• the best known of these techniques is infrared spectroscopy (IR) which observes the specific absorption lines of the chemical bonds present in a sample.
• IR infrared spectroscopy
• the Raman scattering (named after physicist Chandrasekhara Venkata Raman who discovered the effect) makes it possible to use visible light to access the vibrational spectrum of molecules that interact with a light beam.
• a Ramsating pump wave ⁇ ⁇ incident on a molecule is inelastically scattered in a so-called Stokes pulse wave ⁇ $
• FIRE I LLE OF REM PLACEM ENT present in a sample. This process is described, for example, in RW Boyd, Nonlinear Optics (Academy Press, Boston, 1992). It is a question of sending two laser pulses of pulsations ⁇ ⁇ and C ⁇ s (or frequencies and v s ) whose difference of pulsations is made equal to the pulsation ⁇ of the vibrational level which one wants to address.
• a first implementation of CARS is to send on the sample two spectrally fine picosecond pulses whose pulse difference will only address a specific vibrational connection. For optimal identification, all the vibrational links present in the sample are searched for. For this, one operates in "Multiplex CARS" mode (see for example M.Muller and J.Schins, "Imaging the thermodynamic state of lipidic membranes with multiplex CARS spectroscopy", Physical Chemistry B 106, 3715-3723 (2002)). where a spectrally fine pulse and a spectrally broad pulse are sent to the sample ( Figure 2B). We can thus address all the vibrational levels ⁇ .
• the narrow spectrum is for example derived from a picosecond laser and the broad spectrum, for example of a femtosecond laser, or a photonic crystal fiber generating a supercontinuum (SC).
• SC supercontinuum
• FIG. 3A we describe the resonant CARS diffusion process, exploited to have access to the signature of the molecular species that we are trying to identify.
• FIG. 3B shows a non-resonant CARS contribution, shown in Figure 3B, which comes from an electronic sample contribution. This non-resonant contribution can be important when doing CARS spectroscopy on a sample with a wide variety of chemical bonds.
• FIGS. 4A and 4B illustrate the method.
• the method consists of making a CARS differential image between an object and its symmetrical relative to a transverse interface 43 between a resonant medium (reference 41 in FIGS. 4A and 4B) and a non-resonant medium (referenced 42 in FIGS. 4A, 4B ).
• the nonlinear susceptibility of the 3rd order is defined in the resonant medium 41 by a (3) (3)
• FIGS. 4A and 4B show an active volume
• FIG. 6B represents a sample consisting of a layer 61 of DMF (N, N-dimethylformamide) between two glass plates 62, 63.
• the situation corresponds to the case where the pump and Stokes beams are focused on the glass-glass interface.
• DMF interface between 62 and 61
• the situation ⁇ corresponds to the case where the excitation beams are focused on the DMF-glass interface (interface between 61 and 63).
• the CARS intensity of the DMF alone is illustrated as a function of the Raman shift respectively by the curve C l.
• This method has a number of disadvantages. It is notably limited to symmetrical samples, such as the one shown in FIG. 6B, or reversible, in order to have access to the resonant / non-resonant interfaces on the one hand and non-resonant / resonant interfaces on the other hand. This presents a limitation in the case of biological samples that present rarely these properties. On the other hand, if it allows applications in spectroscopy, this method is limited for applications in microscopy.
• the present invention proposes an original device for detecting a non-linear resonant optical signal, based on the principle of detection at the transverse interfaces as described in the prior art, but which can be applied to any sample having an interface between a resonant medium and a non-resonant medium, both for spectroscopy and microscopy applications.
• the invention relates to a device for the detection of a resonant nonlinear optical signal induced in a sample of the type comprising a resonant medium and a non-resonant medium forming an interface
• the device comprising: a source of emission of at least a first excitation light beam, said pump beam, at a first given pulsation cop adapted to the excitation of the resonant medium of a sample of the given type, a first optical module adapted to the detection of the nonlinear optical signal resulting from the interaction of said incident pump beam with an axial interface between the resonant and non-resonant media of the sample, reflection means of said pump beam, arranged in such a way that said beam pumps and reflected intercepts said transverse interface substantially at the same position as said incident pump beam, a second optical module adapted to detecting the non-linear optical signal resulting from the interaction of said pump beam reflected with the sample, a module for processing the optical signals
• the device according to the invention comprises a focus objective of the incident excitation beams in a common focusing volume, allowing said interface between the resonant medium and the non-resonant medium to be intercepted and a non-linear signal collection objective resulting from the interaction of the incident excitation beams with the sample, said collection objective being identical to the objective of focussing the incident beams and the collecting lens forming a focusing objective of the reflected excitation beams and focusing objective of the incident beams forming a nonlinear signal collection objective resulting from the interaction of the excitation beams reflect with the sample.
• each of the optical detection modules comprises an image recording device, the nonlinear optical signal being collected in each of the optical detection modules respectively in directions symmetrical with respect to the optical axis, the difference being performed for each pair of signals thus detected.
• an angular scanning device of the excitation beams allows the excitation beams to intercept the sample at different positions of the interface between the resonant and non-resonant medium.
• the emission source emits at least one variable wavelength excitation beam, making it possible to obtain a spectrum of the vibrational or electronic resonances of the resonant medium.
• the invention relates to a method for the detection of a non-linear resonant optical signal induced in a sample, the sample comprising a resonant medium and a non-resonant medium forming an interface, the method comprising: at least a first light beam for exciting the resonant medium, said pump beam, at a given first pulsation, said pump beam being incident on the sample along an optical axis, and intercepting the sample at a given position d a transverse interface between the resonant and non-resonant medium, the detection of a first nonlinear optical signal resulting from the interaction of said beam (s) with the sample, the reflection of said excitation beam (s), the beam (s) of the excitation thus reflected intercepting said transverse interface substantially at the same position as the incident excitation beam or beams, the detection of a cond nonlinear optical signal resulting from the interaction of said one or more excitation beams reflected with the sample, the processing of the first and second optical signals detected
• the first and second nonlinear optical signals are respectively detected in directions symmetrical with respect to the optical axis of the incident excitation beams, the difference being made for each pair of signals thus detected.
• the excitation beams undergo an angular sweep to intercept the sample at different positions of the interface between the resonant and non-resonant medium.
• At least one of the excitation beams has a variable emission wavelength, making it possible to obtain a spectrum of the vibrational or electronic resonances of the resonant medium.
• FIGS. 1A and 1B (already described), principle of Stokes and anti-Stokes emission in a Raman scattering process
• FIGS. 3A and 3B illustrations of CARS resonant and non-resonant processes
• FIGS. 4A and 4B illustrations of situations a and ⁇ for the implementation of the method according to the prior art
• Figure 5 (already described), numerical simulations of results obtained with the method according to the prior art
• Figures 6A and 6B (already described), experimental results obtained with a symmetrical sample, with the method according to the prior art
• FIGS. 7A, 7B illustrations of the situations a and ⁇ for the implementation of the method according to the invention
• Figures 8A and 8B experimental setup example for the implementation of the method according to the invention
• Figure 13 diagram of the geometric conditions for the implementation of CARS diffusion at an axial interface between resonant and non-resonant media
• FIGS. 14A to 14E illustration of the deviation of the broadcast signal CARS as a function of the relative position of the focussing point of the excitation beams with an axial interface between resonant and non-resonant media;
• FIGS. 16A to 16C diagrams illustrating 3 possible modes for the implementation of CARS detection according to the invention.
• FIGS. 7A and 7B illustrate in two diagrams the principle of the detection method according to the invention in the case of the CARS diffusion.
• a pulsation pump beam and a linear coaxial stokes beam intercept a transverse interface 70, that is to say having a non-zero component along a plane perpendicular to the axis of the incident beams. (optical axis), between a non-resonant medium and a resonant medium.
• the two beams are focussed and the common focusing volume of the beams which intercept the transverse interface 70 is noted.
• the excitation beams pass through the interface in a first direction, referred to as a situation.
• the excitation beams first pass through the interface in the non-resonant medium / resonant medium direction (FIG. 7A, situation a) and then in the resonant / non-resonant medium direction (FIG. 7B, situation ⁇ ).
• the intensities of the scattered CARS signals I a (Fwd) and I (Fwd) are respectively measured in the two situations a and ⁇ , and their difference AI Fw d is calculated, after calibration, to give a signal which the applicant has
• a single pulse of the pump beam and the stokes beam is used to excite the sample in the situations a and ⁇ , making it possible to increase the signal-to-noise ratio compared with the method according to the prior art such that described in Figures 4 to 6.
• Dz-CARS Making the difference of the CARS signals generated by an object and its symmetrical with respect to a plane perpendicular to the optical axis, the method according to the invention is named Dz-CARS in the following description (for Differential imaging in Z symmetry) .
• FIG. 8A illustrates an exemplary device for implementing the detection method according to the invention.
• the detection device 800 generally comprises a laser system 801 for emitting a first co p pulse excitation beam (pump beam) and a second pulse excitation beam co s (Stokes beam) collinear , the two excitation beams being symbolized by the arrow 802.
• the device generally comprises a laser system 801 for emitting a first co p pulse excitation beam (pump beam) and a second pulse excitation beam co s (Stokes beam) collinear , the two excitation beams being symbolized by the arrow 802.
• the device generally comprises a laser system 801 for emitting a first co p pulse excitation beam (pump beam) and a second pulse excitation beam co s (Stokes beam) collinear , the two excitation beams being symbolized by the arrow 802.
• the device generally comprises a laser system 801 for emitting a first co p pulse excitation beam (pump beam)
• 800 further comprises an optical element, for example a reflective plate 804, for sending the two excitation beams into a first optical detection module of the device generally referenced 803, in a main direction Z.
• an optical element for example a reflective plate 804, for sending the two excitation beams into a first optical detection module of the device generally referenced 803, in a main direction Z.
• the laser system 801 comprises, for example, in a so-called two-color application, two spectrally thin tunable laser sources 808, for example of the Titanium-Sapphire type, emitting between 690 and 1000 nm, pumped by a pump laser 809, type
• Nd YV04 emitting at 532 nm.
• Tunable lasers emit e.g., picosecond pulses, typically of the order of 3 ps, to form the pulse pump excitation beams C0p (typical wavelength of 730 nm) and Stokes pulse co s.
• An 810 pulse selector (or "pick-up") can be used to reduce the rate of the pump and probe excitation lasers without reducing the peak power of the pulses.
• the use of a Stokes beam or a tunable pump beam notably makes it possible to scan the anti-Stokes emission spectrum for spectroscopic applications intended to determine the Raman spectrum of the resonant medium.
• tunable laser sources may be used, for example of the optical parametric oscillator (OPO) type, optical parametric amplifier (OPA), Nd-type picosecond oscillators: glass, Ytterbium or Erbium-doped fibered lasers, etc.
• OPO optical parametric oscillator
• OPA optical parametric amplifier
• Nd-type picosecond oscillators glass, Ytterbium or Erbium-doped fibered lasers, etc.
• the sources can also be nanosecond or femtosecond laser sources, depending on the spectral width of the Raman lines that one wants to observe.
• the nanosecond pulses if very good from a spectral point of view, have a lower peak power than the ps pulses.
• thermal effects associated with ns pulses are more likely to damage biological samples.
• the first optical detection module 803 comprises a focusing objective 807 aimed at focusing the pump and Stokes beams in a common focusing volume for the analysis of the sample 805, represented in FIG. 8B.
• the use of a focus lens is particularly suitable in microscopy type applications. However, it is not essential for the transmission of the CARS signal to work in focussed beams, and in particular in the case of the study of thin samples.
• the sample is formed, as in the example of FIG. 6B, of a layer 61 of DMF ( ⁇ , ⁇ -dimethylformamide) between two glass plates 62, 63.
• the first optical detection module 803 also includes a collection objective 811 for collecting the nonlinear optical signal transmitted, in this example the distributed signal CARS, and a detector 816, for example a point detector of the avalanche photodiode (APD), fast photodiode (PIN), or photomultiplier (PMT) type, preceded by a collection lens 818 and a filter 812 for cut off the residual excitation beams.
• a collection objective 811 for collecting the nonlinear optical signal transmitted, in this example the distributed signal CARS
• a detector 816 for example a point detector of the avalanche photodiode (APD), fast photodiode (PIN), or photomultiplier (PMT) type, preceded by a collection lens 818 and a filter 812 for cut off the residual excitation beams.
• APD avalanche photodiode
• PIN fast photodiode
• PMT photomultiplier
• the second optical detection module 806 comprises in common with the first optical detection module, the objectives 811 and 807, but the objective 81 1 serves as a focusing objective for the excitation beams reflected by the mirror 813 and the objective 807 serves as the objective of collection for the nonlinear optical signal resulting from the interaction of the excitation beams reflected with the sample 805.
• the second optical module 806 also comprises a detector 817, for example a point detector of the same type as the detector 816, preceded a collection lens 819 and a filter 820 for cutting the residual excitation beams. The signal collected backwards by the detector 817 is then I (Fwd).
• the difference of the signals I a (Fwd) -I (Fwd), whose applicant has shown to be proportional to the Raman spectrum of the resonant medium, is operated in real time by means of a processing unit denoted 830 in FIG. 8A.
• the reflecting plate 804 is a dichroic plate, making it possible to reflect the excitation beams emitted by the laser source 801 towards the sample 805 (situation a) while transmitting the broadcast signal CARS in the situation ⁇ .
• the focusing objectives 807 and collection 811 are identical to obtain a symmetrical mounting in situations a and ⁇ . In practice, a calibration of the detectors 816, 817 is performed prior to the measurement.
• this calibration is performed on a sample comprising only the solvent.
• the device according to the invention allows the same pump and Stokes pulses to intercept the sample at the same position of the transverse interface, respectively in the situations a and ⁇ .
• the method can thus be used with any type of sample having an interface between a resonant medium and a non-resonant medium, and no longer only a symmetrical or reversible sample.
• device 800 also includes a scanning beam device for excitation in the XY plane of the sample (not shown).
• This scanning device may be useful both in an application in spectroscopy, to adjust the focus of the excitation beams on a transverse interface of the resonant and non-resonant media forming the sample, or in an imaging application. It may be a device for moving the sample, or preferably a scanning device excitation beams.
• it will be possible to use a reflection mirror of the spherical excitation beams 813, so as to return the excitation beams in an opposite parallel direction, which will allow the reflected excitation beams (situation ⁇ ) to intercept the excitation beams. sample at the same position as that of the incident beams (situation a).
• FIG. 9 illustrates experimental results obtained with the device of FIG. 8A and a sample of the type of that of FIG. 8B, in which a thin layer of DMF (N, N-dimethylformamide) acts as a resonant medium between two lamellae of glass (which serve here as a non-resonant medium).
• the wavelength of the pump beam is 730 nm, that of the Stokes excitation beam around 814 nm.
• FIG. 9 illustrates, as a function of the Raman shift respectively by the curve D1, the diffused signal CARS measured in the DMF, by the curve D2, the intensity I a (Fwd) measured in the situation a (FIG.
• Curve D1 clearly shows the distortion effect due to the non-resonant contribution of the resonant medium, while the difference AI Fw d is exactly superimposed on the Raman spectrum of DMF (in dotted lines). It is thus possible to appreciate the ability of Dz-CARS to extract the Raman spectrum from the resonant medium without any distortion due to the non-resonant part of the resonant medium.
• FIGS. 10A to 10D show numerical simulations obtained with the method according to the invention, on another type of sample.
• the images are calculated by taking as a sample a ball of 3 ⁇ in diameter in an aqueous-type solvent (pump wavelength 730 nm, Stokes wavelength 814 nm, numerical aperture of the excitation objective 1.2 in FIG. water, numerical opening of 1.2 collection lens in water).
• the image is calculated in each case in a plane XZ of the ball corresponding to a longitudinal plane containing the direction of incidence of the excitation beams.
• FIGS. 10A and 10B show an image of the ball in conventional detection, that is to say that only the broadcast signal CARS in situation a is represented. At resonance (Figure 10A), the signal is more intense than out of resonance ( Figure 10B), but the contrast difference is small because of the non-resonant contributions of the ball and its environment.
• FIG. 10C and 10D represent images of the ball at resonance and off resonance, but calculated with the Dz-CARS method according to the invention, that is to say by subtracting the scattered CARS signals in situations a and ⁇ with an assembly of the type of that of FIG. 8 A.
• Out of resonance (FIG. 10D)
• the contrast is zero because the difference of the signals which contain only a non-resonant contribution is canceled out.
• Figure 10C calculated at resonance, the contrast at transverse interfaces is maximal.
• FIG. 11 illustrates an exemplary experimental setup for implementing the detection according to the invention according to a variant.
• the assembly is substantially identical to that of FIG. 8A, but the point detectors 816, 817 are replaced by matrix detectors 901, 902, for example of the CCD or CMOS type.
• matrix detectors 901, 902 for example of the CCD or CMOS type.
• FIG. 11 illustrates an exemplary experimental setup for implementing the detection according to the invention according to a variant.
• the assembly is substantially identical to that of FIG. 8A, but the point detectors 816, 8
• the CARS broadcast signal in situation a, is measured in a direction represented by the wave vector k, with coordinates k x , k y in the XY projection plane perpendicular to the main axis z, and in the situation ⁇ , the CARS broadcast signal is measured in a direction represented by the wave vector k "of coordinates -k x , -k y in the XY projection plane.
• FIG. 13 represents a sample comprising the resonant medium 131, for example a medium containing the medium to be analyzed, that is to say the medium of biological interest, and the non-resonant medium 132, typically a medium containing the solvent.
• the resonant medium 131 for example a medium containing the medium to be analyzed, that is to say the medium of biological interest
• the non-resonant medium 132 typically a medium containing the solvent.
• 3 rd order is defined in the resonant medium 131 by a resonant term ⁇ and a term not
• non-resonant medium 132 it is defined by the term non-resonant
• the pump pulsation C0p excitation beams and probe pulse co s, collinear are incident on the sample in a volume of focus 135, intercepting an axial interface 133 of the sample.
• the light intensity of the nonlinear optical beam is analyzed in the space of the wave vectors k, that is, say in the space of the directions of emission of the signal emitted by CARS processes, on both sides of the interface, this intensity being noted in FIG.
• FIGS. 14A to 14E show, by a series of diagrams, the deviation of the broadcast signal CARS as a function of the relative position of the pump and Stokes beams incident with the interface.
• FIGS. 14A to 14E show the active volume CARS 135 (focussing spot of the pump and Stokes beams) which is displaced through a CARS object 140 (each sticker corresponds to a different position of the active volume in the object).
• the object CARS is considered as resonant while the medium surrounding the object is considered as non-resonant (it will be called in the following description "the solvent").
• the CARS volume is focused on the interface between the CARS object and the solvent, the broadcast signal CARS is then emitted with a positive angle ⁇ (relative to the axis of incidence of the pump and Stokes beams), thereby deflecting the beam in a direction defined by (k x > 0) in the space of the wave vectors k.
• the CARS volume is centered in the CARS object, the CARS signal is then intense and is directed in the normal direction (parallel to the axis of incidence of the pump and Stokes beams).
• FIG. 15A presents the results of a rigorous numerical calculation taking into account the vector nature of the pump and Stokes beams focused on an axial interface between a resonant medium 1 and a non-resonant medium 2 (FIG. 13).
• FIGS. 15B and 15C represent numerical simulations in which the broadcast signal CARS is integrated respectively in the half-spaces (k x > 0) and (k x ⁇ 0), and then the difference of the signals thus integrated is carried out.
• FIG. 16A to 16C thus present 3 possible detection modes for the D-CARS microscopy associating the Dz-CARS approach and the Dk-CARS approach.
• a numerical simulation represents the image obtained for a 3 ⁇ diameter ball in an aqueous-type solvent (pump wavelength 730 nm, Stokes wavelength 814 nm, numerical aperture of the objective excitement 1.2 in the water, numerical aperture of the 1.2 collection lens in the water).
• FIG. 16A represents the detection mode XZ allowing detection at the interfaces perpendicular to the X axis and at the interfaces perpendicular to the Z axis.
• the difference of the CARS diffused signals is calculated respectively in the situations a and ⁇ by integrating the CARS signal in space (k x > 0) (problem a, Figure 7A) and in space (k x ⁇ 0) (problem ⁇ , Figure 7B), the chosen reference being that of the direction of the beams of 'excitation.
• the image of FIG. 16A is obtained in an equatorial plane of the ball.
• Fig. 16B shows the YZ detection mode allowing detection at the interfaces perpendicular to the Y axis and the interfaces perpendicular to the Z axis.
• the difference of the integrated luminous intensities in the space (k y > 0) is calculated for different positions (problem a, Figure 7 A) and in space (k y ⁇ 0) (problem ⁇ , Figure 7B).
• Fig. 16C shows the XYZ detection mode.
• the image is calculated by making the two-by-two difference of the light intensities I a (k x , k y ) and I (-k x , -k y ) measured in two directions k (k x , k y , k z ) and k "(-k x , -k y , k z ) opposite, respectively in situations a and ⁇ , the directions being contained in the angular cone whose opening angle is defined by the numerical aperture of the distributed signal CARS (for example 1.2 in water)
• the coordinates of the wave vectors k and k "are expressed in the reference frames of the excitation beams specific to situations a and ⁇ , respectively.
• the excitation beams in particular for applications in microscopy.
• a calibration of the cameras in solution is also possible in order to identify, in each of the situations a and ⁇ , and for each scanning angle, the direction of the excitation beams with respect to which the deflection of the broadcast signal CARS will be measured.
• the Dz-CARS or D-CARS detection has been described by means of the exemplary embodiments of FIGS. 8A and 11 in a two-color application, using two spectrally fine laser sources.
• a source of emission of the spectrally broad Stokes beam generated for example by a femtosecond pulse or by a supercontinuum generated by an optical fiber or another dispersive medium.
• the pump signal remains thin spectrally.
• three associated pulse wavelengths ⁇ , ⁇ 2 and ⁇ 3 are used to generate a CARS signal at the pulsation ⁇ - ⁇ + ⁇ .
• the signal CARS can be rendered without non-resonant noise by detecting the signals at the pulsation ⁇ ⁇ - ⁇ 2 + ⁇ 3 in situations (a or ⁇ ) and making their difference.
• the detection method has been described in the case of the CARS diffusion, it is equally applicable to other non-linear process, the 2 nd or 3 rd order for both spectroscopy applications or for detection microscopy applications at axial interfaces, thus revealing interfaces between resonant and non-resonant media.
• an analysis of the non-linear optical signal resulting from the interaction of one or more excitation beams with a sample having an interface between a resonant medium and a non-resonant medium is carried out.
• This spatial analysis makes it possible either to reveal the interface between the resonant medium and the non-resonant medium, or to characterize a spectrum of the resonant medium.
• a resonant third harmonic generation process in which the resonance is an electronic resonance, by exciting with a single pump excitation beam, a C0p pulse, a sample comprising an interface between a resonant medium and a non-resonant medium.
• a picosecond or femtosecond laser source of Ti: Saphir, Nd: glass, Ytterbium doped or Erbium doped lasers type is used.
• a resonant four-wave mixing process in which the resonance is an electron resonance can be used, by exciting with a single pump excitation beam, a pulse C0p, a sample comprising an interface between a resonant medium and a non-resonant medium.
• a picosecond or femtosecond laser source of Ti: Saphir, Nd: glass, Ytterbium doped or Erbium doped lasers type is used.
• the second harmonic can be excite resonant beam with a single pump, or it may make the sum frequency with a pump beam and a probe beam (non-linear effect of the 2 nd order).
• the detection device and the method according to the invention comprise various variants, modifications and improvements which will be apparent to those skilled in the art, being understood that these various variants, modifications and improvements are within the scope of the invention, as defined by the claims that follow.

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