Non-linear optics for label-free microscopy

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Principal investigators : Hervé Rigneault, Sandro Heuke, Sophie Brasselet, Julien Duboisset

keywords : 2-photon fluorescence, second and third harmonic generation, coherent Raman scattering, pump-probe, nonlinear imaging, molecular spectroscopy

We are interested in how nonlinear optical contrast mechanisms can provide novel molecular information in microscopy and micro-spectroscopy. These modalities take advantage of label free capabilities, deep penetration into scattering samples, as well as high order (wave mixing) light matter interaction properties. Our work aims at providing insight into

the fundamental nonlinear light matter interaction and the construction of the generated light fields under tight focusing conditions and
the molecular properties that can be addressed and readout through these nonlinear processes.

On the instrumentation side, we develop multimodal nonlinear microscopy and micro-spectroscopy technologies using ultra-short laser pulses (from 10 fs to ps), possibly synchronized (using electronic synchronization or OPOs). Special attention is given to coherent Raman scattering modalities such as coherent anti-Stokes Raman scattering (CARS ) and stimulated Raman scattering (SRS) for label-free vibrational microscopy and micro-spectroscopy.

Multimodal nonlinear microscopy is used to address a variety of problems such as :

Drug penetration in tissues (cosmetic, pharmaceutical and medical applications)
Architecture of collagen fibers in tissue
Lipid metabolism (cancer tissues)
Myelin organization (neurobiology)
Tissue morphology (developmental biology, cancer tissues)

Image Gallery

Publications

2023

Wide-field coherent anti-Stokes Raman scattering microscopy using random illuminations,
E. M. Fantuzzi, S. Heuke, S. Labouesse, D. Gudavičius, R. Bartels, A. Sentenac, and H. Rigneault, Nat. Photon. 48, 4113-4116 (2023).
10.1038/s41566-023-01294-x

Frequency-encoded two-photon excited fluorescence microscopy,
S. Heuke, C. Silva Martins, R. André, L. LeGoff, and H. Rigneault, Opt. Lett. : Photonics 48, 4113-4116 (2023).
10.1364/OL.496071

Comprendre les processus raman cohérents,
H. Rigneault, S. Heuke, Photoniques 121, 52-56, 2023.
10.1051/photon/202312152

Photon-noise : is a single-pixel camera better than point scanning ? A signal-to-noise ratio analysis for Hadamard and Cosine positive modulation,
C. Scotté, F. Galland, and H. Rigneault, Journal of Physics : Photonics 5, 035003 (2023).
10.1088/2515-7647/acc70b

Coherent Stokes Raman scattering microscopy (CSRS),
S. Heuke, and H. Rigneault, Nature Communications 14, 3337 (2023).
10.1038/s41467-023-38941-4

Selective Detection in Impulsive Low-Frequency Raman Imaging Using Shaped Probe Pulses,
S. Shivkumar, D. Ranann, S. Metais, S. Suresh, N. Forget, R. Bartels, D. Oron, and H. Rigneault, Physical Review Applied 19, 054075 (2023).
10.1103/PhysRevApplied.19.054075

Live Stimulated Raman Histology for the Near-Instant Assessment of Central Nervous System Samples,
R. Appay, B. Sarri, S. Heuke, S. Boissonneau, C. Liu, E. Dougy, L. Daniel, D. Scavarda, H. Dufour, D. Figarella-Branger, and H. Rigneault, J. Phys. Chem. B 127, 3624-3631 (2023).
10.1021/acs.jpcb.3c01156

Double-modulations stimulated Raman scattering : how to image up to 16-fold faster,
S. Heuke, X. Audier, H. Rigneault, Optics Letters 48, 423-426 (2023).
10.1364/OL.467514

2022

Fast Compressive Raman Imaging of Polymorph Molecules and Excipients in Pharmaceutical Tablets,
C. Grand, C. Scotté, and H. Rigneault, Analytical Chemistry 94, 16632-16637 (2022).
10.1021/acs.analchem.2c02680

Nearly degenerate two-color impulsive coherent Raman hyperspectral imaging,
D. R. Smith, S. Shivkumar, J. Field, J. W. Wilson, H. Rigneault, and R. A. Bartels, Optics Letters 47, 5841-5844 (2022).
10.1364/OL.467970

2021

Shot-noise limited tunable dual-vibrational frequency stimulated Raman scattering microscopy,
S. Heuke, I. Rimke, B. Sarri, P. Gasecka, R. Appay, L. Legoff, P. Volz, E. Büttner, and H. Rigneault, Biomed. Opt. Express 12, 7780-7789 (2021).
doi.org/10.1364/BOE.446348

Observation of the compatibility of stimulated Raman histology with pathology workflow and genome sequencing,
B. Sarri, R. Appay, S. Heuke, F. Poizat, F. Franchi, S. Boissonneau, F. Caillol, H. Dufour, D. Figarella-Branger, M. Giovaninni, and H. Rigneault,Translational Biophotonics n/a e202000020 (2021).
doi.org/10.1002/tbio.202000020

3D-coherent anti-Stokes Raman scattering Fourier ptychography tomography (CARS-FPT)
S. Heuke, H. Rigneault, and A. Sentenac, Optics Express 29, 4230-4239 (2021).
doi.org/10.1364/OE.416290

Laser scanning dark-field coherent anti-Stokes Raman scattering (DF-CARS) : a numerical study,
S. Heuke, and H. Rigneault, Optics Express 29, 3985-3995 (2021).
doi.org/10.1364/OE.414972

2020

Noise in stimulated Raman scattering measurement : From basics to practice,
X. Audier, S. Heuke, P. Volz, I. Rimke, and H. Rigneault, APL Photonics 5, 011101 (2020).
doi.org/10.1063/1.5129212

Simultaneous stimulated Raman gain and loss detection (SRGAL),
S. Heuke, A. Lombardini, E. Büttner, and H. Rigneault, Optics Express 28, 29619-29630 (2020).
doi.org/10.1364/OE.400298

Background-suppressed SRS fingerprint imaging with a fully integrated system using a single optical parametric oscillator,
A. Lombardini, P. Berto, J. Duboisset, E. R. Andresen, S. Heuke, E. Büttner, I. Rimke, S. Vergnole, V. Shinkar, P. de Bettignies, and H. Rigneault, Optics Express 28, 14502 (2020).
doi.org/10.1364/OE.390381

Line-scan compressive Raman imaging with spatiospectral encoding,
C. Scotté, S. Sivankutty, R. A. Bartels, and H. Rigneault, Optics Letters 45, 5567-5570 (2020)
doi.org/10.1364/OL.400151

High-speed chemical imaging of dynamic and histological samples with stimulated Raman micro-spectroscopy,
X. Audier, N. Forget, and H. Rigneault, Optics Express 28, 15505-15514 (2020).
doi.org/10.1364/OE.390850

Spatial frequency modulated imaging in coherent anti-Stokes Raman microscopy,
S. Heuke, S. Sivankutty, C. Scotte, P. Stockton, R. A. Bartels, A. Sentenac, and H. Rigneault, Optica 7, 417-424 (2020).

Background-suppressed SRS fingerprint imaging with a fully integrated system using a single optical parametric oscillator
A. Lombardini, P. Berto, J. Duboisset, E. R. Andresen, S. Heuke, E. Büttner, I. Rimke, S. Vergnole, V. Shinkar, P. de Bettignies, and H. Rigneault, Optics Express 28, 14490-14502 (2020)

2019

Discriminating polymorphdistributions in pharmaceutical tablets usingstimulated Raman scattering microscopy
B. Sarri, R. Canonge, X. Audier, V. Lavastre, G. Pénardier, J. Alie, H. Rigneault, J Raman Spectrosc. (2019)

Sub-second hyper-spectral low-frequency vibrational imaging via impulsive Raman excitation
D. Raanan, X. Audier, S. Shivkumar, M. Asher, M. Menahem, O. Yaffe, N. Forget, H. Rigneault, and D. Oron, Optics Letters 44, 5153-5156 (2019)

Stimulated Raman histology : one to one comparison with standard hematoxylin and eosin staining
B. Sarri, F. Poizat, S. Heuke, J. Wojak, F. Franchi, F. Caillol, M. Giovannini, and H. Rigneault, Biomed. Opt. Express 10, 5378-5384 (2019)

In vivo quantitative molecular absorption of glycerol in human skin using coherent anti-Stokes Raman scattering (CARS) and two-photon auto-fluorescence
B. Sarri, X. Chen, R. Canonge, S. Grégoire, F. Formanek, J.-B. Galey, A. Potter, T. Bornschlögl, and H. Rigneault, Journal of Controlled Release 308, 190-196 (2019)

2018

Dual-focus stimulated Raman scattering microscopy : a concept for multi-focus scaling
S. Heuke, B. Sarri, A. Lombardini, X. Audier, and H. Rigneault, Optics Letters 43, 4763-4766 (2018)

Simultaneous dual-channel stimulated Raman scattering microscopy demultiplexed at distinct modulation frequencies
S. Heuke, B. Sarri, X. Audier, and H. Rigneault, Optics Letters 43, 3582-3585 (2018)

2017

Programmable single-pixel-based broadband stimulated Raman scattering
P. Berto, C. Scotté, F. Galland, H. Rigneault, and H. B. de Aguiar, Optics Letters 42, 1696-1699 (2017)

Pump-probe micro-spectroscopy by means of an ultra-fast acousto-optics delay line
X.Audier, N. Balla, and H. Rigneault, Optics Letters 42, 294-297 (2017)

2016

Implementation of a Coherent Anti-Stokes Raman Scattering (CARS) System on a Ti:Sapphire and OPO Laser Based Standard Laser Scanning Microscope
Mytskaniuk, V., Bardin, F., Boukhaddaoui, H., Rigneault, H., Tricaud, N.
J. Vis. Exp. 113, e54262, doi:10.3791/54262 (2016)

Direct imaging of molecular symmetry by coherent anti-stokes Raman scattering
C. Cleff, A. Gasecka, P. Ferrand, H. Rigneault, S. Brasselet, and J. Duboisset
Nat Commun 7, 11562 (2016), doi:10.1038/ncomms1156

Nonlinear femtosecond pump-probe spectroscopy using a power encoded soliton delay line
S. Saint-Jalm, E. R. Andresen, A. Bendahmane, A. Kudlinski, and H Rigneault
Opt. Lett. 41, 115-118 (2016)

In vivo single human sweat gland activity monitoring using coherent anti-Stokes Raman scattering and two-photon excited auto-fluorescence microscopy
X. Chen, P. Gasecka, F. Formanek, J. B. Galey, and H. Rigneault
British Journal of Dermatology (2016) - DOI : 10.1111/bjd.14292

2015

Quantitative 3D molecular cutaneous absorption in human skin using label free nonlinear microscopy
X. Chen, S. Grégoire, F. Formanek, J.-B. Galey, H. Rigneault
Journal of Controlled Release 200, 78-86 (2015)

2014

Fiber-based ultrashort pulse delivery for nonlinear imaging using high energy solitons
S. Saint-Jalm, E. R. Andresen, P. Ferrand, A. Bendahmane, A. Mussot, O. Vavincq, G. Bouwnmans, A. Kudlinski, H. Rigneault
Journal of Biomedical Optics 19, 086021 (2014)

Rapidly tunable and compact coherent Raman scattering light source for molecular spectroscopy
S. Saint-Jalm, P. Berto, L. Jullien, E. R. Andresen, and H. Rigneault
Journal of Raman Spectroscopy 45, 515-520 (2014)

Background free stimulated Raman spectroscopy and microscopy
P. Berto, E. R. Andresen, H. Rigneault
Phys. Rev. Lett 112, 053905 (2014)

2013

Wide-field vibrational phase imaging in an extremely folded box-coherent anti-Stokes Raman scattering geometry
P. Berto, A. Jesacher, C. Roider, S. Monneret, H. Rigneault, and M. Ritsch-Marte
Optics Letters 38, 709-711 (2013)

2012

Fast and label free’, News and Views
H. Rigneault, E. Andresen
Nat. Phot 6, 802-803 (2012)

Wide-Field Vibrational Phase Imaging
P. Berto, D. Gachet, P. Bon, S. Monneret and H. Rigneault
Phys. Rev. Lett. 109, 093902 (2012)

Polarization resolved stimulated Raman scattering : probing depolarization ratios of liquids
F. Munhoz, S. Brustlein, R. Hostein, P. Berto, S. Brasselet and H. Rigneault
Journal of Raman Spectroscopy 43, 419–424 (2012)

2011

Detection of chemical interfaces in coherent anti-Stokes Raman scattering microscopy : D-CARS. II. Arbitrary interfaces
D. Gachet, H. Rigneault
J. Opt. Soc Am. A 28, pp. 2531-2539 (2011)

Detection of chemical interfaces in coherent anti-Stokes Raman scattering microscopy : Dk-CARS. I. Axial interfaces
D. Gachet, H. Rigneault
J. Opt. Soc Am. A 28, pp.2519-2530 (2011)

Transverse chemical interface detection with coherent anti-Stokes Raman scattering microscopy
S. Brustlein ; D. Gachet ; F. Billard ; H. Rigneault
Journal of Biomedical Optics 16, 086006 (2011)

Stimulated-Raman scattering microscopy by spectral focussing and fiber-generated soliton as Stokes pulse
E.R. Andresen, P. Berto, H. Rigneault
Opt Lett 36, 2387-2389 (2011)

Optical Parametric Oscillators based light source for Coherent Raman Scattering microscopy : a practical overview
S. Brustlein, P. Ferrand, N. Walther, S. Brasselet, C. Billaudeau, D. Marguet and H Rigneault
J. Biomed. Opt. 16, 021106 (2011)

Polarized multiplex CARS using a picosecond laser and a fiber supercontinuum
S. Michel, A. Courjaud, E. Mottay, J. Dudley, C. Finot, H. Rigneault
J. Biomed. Opt. 16, 021108 (2011)

2010

High Order Symmetry Structural Properties of Vibrational Resonances Using Multiple-Field Polarization Coherent Anti-Stokes Raman Spectroscopy Microscopy
F. Munhoz, H. Rigneault, S. Brasselet
Phys. Rev. Lett. 105, 123903 (2010)

Revisiting the Young’s Double Slit Experiment for Background-Free Nonlinear Raman Spectroscopy and Microscopy
D. Gachet, S. Brustlein, H. Rigneault
Phys. Rev. Lett. 104, pp.213905 (2010)

2009

Coherent anti-Stokes Raman scattering in a microcavity
David Gachet, Franck Billard, and Hervé Rigneault
Opt. Lett. 34, 1789-1791 (2009)

Coherent anti-Stokes Raman scattering in a Fabry-Perot cavity : A theoretical study
F. Billard, D. Gachet, and H. Rigneault
J. Opt. Soc. Am. B 26, 1295-1309 (2009)

Raman depolarization ratio of liquids probed by linear polarization Coherent Anti-Stokes Raman spectroscopy
F. Munhoz, S. Brustlein, D. Gachet, F. Billard, S. Brasselet and H. Rigneault
Journal of Raman Spectroscopy 40, 775-780 (2009)

2008

Background-free coherent anti-stokes Raman spectroscopy near transverse interfaces : a vectorial study
D. Gachet, F. Billard, H. Rigneault
J. Opt. Soc. Am. B 25, 1655-1666 (2008)

Focused field symmetries for background-free coherent anti-Stokes Raman spectroscopy
D. Gachet, F. Billard, and H. Rigneault
Phys. Rev. A 77, 061802(R) (2008)

2007

Coherent anti-Stokes Raman scattering (CARS) microscopy imaging at interfaces : evidence of interference effects
D. Gachet, F. Billard, N. Sandeau and H. Rigneault
Optics Express 15 (16), 10408-10420 (2007)

Coherent anti-Stokes Raman scattering microscopy (CARS) : Instrumentation and applications
N. Djaker, P.-F. Lenne, D. Marguet, A. Colonna, C. Hadjur, H. Rigneault
Nuclear Instruments and Methods in Physics Research A 571, 177–181 (2007)

2006

Microscopie Raman stimulée (CARS) : principes et applications
N. Djaker, D. Marguet, H. Rigneault
Médecine-Sciences 22 (10), pp853-858 (2006)

Influence of the Raman depolarisation ratio on far-field radiation patterns in coherent anti-Stokes Raman scattering (CARS) microscopy
D. Gachet, N. Sandeau, H. Rigneault
J. Europ. Opt. Soc. Rap. Com 1, 6013 (2006)

Refractive effects in coherent anti-Stokes Raman scattering microscopy
N. Djaker, D. Gachet, N. Sandeau, P.-F. Lenne, and H. Rigneault
Applied Optics 45 (27), 7005-7011 (2006)