©2013 Old City Publishing, Inc. Published by license under the OCP Science imprint, a member of the Old City Publishing Group Nonlinear Optics and Quantum Optics, Vol. 0, pp. 1–10 Reprints available directly from the publisher Photocopying permitted by license only 1 New Multimodal Probes for Correlative Light-Electron Microscopy HUSSEIN FTOUNI 1 , FRÉDÉRIC BOLZE 1, *, JEAN-FFRANÇOIS NICOUD 1 , YANNICK SCHWAB 2 , JEAN-LUC REHSPRINGER 3 , RODRIGUES R. MAFOUANA 4 AND YOURI ARNTZ 5 1 Laboratoire de Conception et Application des molécules Bioactives, UMR 7911 Université de Strasbourg-CNRS, Faculté de Pharmacie, 74 route du Rhin, F-67401 Illkirch-Graffenstaden cedex, France; E-mail: Frederic.bolze@unistra.fr 2 Cell Biology and Biophysics Unit – European Molecular Biology Laboratory, Heidelberg, Germany 3 Institut de Physique et Chimie des Matériaux de Strasbourg, Université de Strasbourg-CNRS, 23 Rue du Loess, 67034 Strasbourg Cedex 2, France 4 RBnano sarl, c/oIPCMS 23 rue du loess 67034 Strasbourg Cedex 2, France 5 Laboratoire de Biophotonique et Pharmacologie, UMR 7213 Université de Strasbourg-CNRS, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch Graffenstaden cedex, France Received: February 12, 2013. Accepted: March 11, 2013. Two-photon Excited Microscopy (TPEM) and Electron Microscopy (EM) became in the past few years routine techniques for biological research, available in most imaging platforms, allowing in depth studies at organ or cellular level with TPEM and subcellular level with EM. Recently the combination of these two techniques is of growing empha- sis, allowing the acquisition at these two scales on the same sample. The development of this correlative technique pointed out the necessity to engineer new dyes allowing the induction of contrast in both methods on the same system. We describe here the preparation and characterization of core shell iron oxide nanoparticles (for EM contrast) conjugated to new functionalized two-photon sensitive fluorescent dyes (for TPEM con- trast). These dyes showed astonishing contrast in EM and TPEM on HeLa cell cultures. Keywords: Correlative light-electron microscopy- Two-photon microscopy- Electron microscopy- Core shell iron oxide nanoparticle- Diketodipyrrolopyrrole- Fluorescent Dyes- Multimodal fluorophore.