Multiphotonics has attracted a lot of interest over recent years thanks to the advantages it provides in microscopic bioimaging. These include an intrinsic three-dimensional resolution, increased penetration depth in tissues and reduced photodamages. To take full benefits of multiphotonics, the design of dedicated probes having very large nonlinear optical responses (such as two-photon absorption (2PA) or second-harmonic generation (SHG) cross-sections) is highly desirable as it opens the way to improved sensitivity, faster scanning speed as well as selective photo-addressing [1a]. As an illustration, examples of multiphotonics probes designed for bioimaging and sensing purposes (pH imaging, subcellular imaging, membrane dynamics, real-time monitoring of neuronal activity, heavy metals detection in effluents….) will be presented [1b-f]. Two-photon activatable phototriggers have also been developed for synchronous photoinitiation of reductive bioprocesses [1a] as well as antenna systems for efficient uncaging of neurotransmitters [2]. 

Nanoparticles offer major potential as they can afford potentially extremely bright nano-objects with large nonlinear responses. In particular luminescent semiconductor-based nanoparticles (i.e., quantum dots QDs) have been shown to be of interest for 2PEF bioimaging [3]. QDs with large 2PA responses however raise critical toxicity and biodegradability issues inspiring us to develop biocompatible and ecofriendly alternatives. With this aim in mind, we have developed two bottom-up routes towards fully-organic nanoemitters. The first route led to soft tunable organic nanodots (ONDs), having radius of a few nm, which outcome QDs in terms of 1P and 2P brightness [4a], and allow fast excitation energy transfer [4b]. ONDs have proven of major interest for in vivo bio-imaging [4c] as well as for detection of explosives by 2PE [4b]. The second route is based on the spontaneous assembly in water of insoluble dyes. From specifically-designed dyes, we elaborated, via a simple, fast and green protocol, Fluorescent Organic Nanoparticles (FONs), typically 10-50 nm in radius, showing extremely high one- and two-photon brightness (up to 108 M-1cm-1 and 106 GM) [5]. Their color, biocompatibility and colloidal stability can be tuned thanks to a subtle bottom-up strategy, yielding biocompatible ultrasensitive nanotracers for in vivo angiography [5a]. As a result, hyperbright NIR-emitting molecular-based FONs (thus named HiFONs) have been successfully applied to imaging in cells as well as to single particle tracking in water [5b].

References

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[2] S. Picard, E. Cueto-Diaz, E. Genin, G. Clermont, F. Acher, D. Ogden, M. Blanchard-Desce, Chem. Comm., 2013, 49, 10805-10807; E. J. Cueto Díaz, S. Picard, V. Chevasson, J. Daniel, V. Hugues, O. Mongin, E. Genin, M. Blanchard-Desce, Org. Lett. 2015, 17, 102-105.

[3] D. R. Larson, W. R. Zipfel, R. M. Williams, S. W. Clark, M. P. Bruchez, F. W. Wise and W. W. Webb, Science 2003, 300, 1434-1437.

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[5] a) V. Parthasarathy, S. Fery-Forgues, E. Campioli, G. Recher, F. Terenziani and M. Blanchard-Desce, Small, 2011, 7, 3219-3229; b) E. Genin, Z. Gao, J. A. Varela, J. Daniel, T. Bsaibess, I. Gosse, L. Groc, L. Cognet and M. Blanchard-Desce, Adv. Mater. 2014, 26, 2258-2261.