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Ultrafast Nano-Biophotonics

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Nano-Optics: Principles Enabling Basic Research and Applications

Abstract

In the quest for the next generation of imaging bio-markers, successful probes have to prove to be non toxic, bright, stable against long term excitation, and able to generate a sharp contrast against background fluorescence. Harmonics-generating Nanocrystals (HN) appeared recently as a novel labelling method with unprecedented wavelength flexibility, enabled by the non-resonant nature of the harmonics generation process. In particular, imaging using frequency doubling nanocrystals (i.e. nanodoublers), such as iron iodate, potassium niobate, barium ferrite (BFO) and KTP, has been demonstrated with laser sources in the near-infrared (800 nm) and infrared (1.55 μm) regions. The latter allows deeper penetration depth in tissues, thus especially promising for in vivo applications. The phase-coherent optical response of HN can also be exploited to fully characterize the excitation laser pulse in the focal spot of a high-NA objective with nanometric resolution.

HN have been used for the first time to monitor the evolution and differentiation of embryonic stem cells (ESC) by second harmonic microscopy imaging. The potential of this approach was made evident for tissue-regeneration studies, by capturing high-speed movies of ESC-derived cardiomyocytes autonomously beating within a cluster. HNs were also applied to cancer research: BFO nanoparticles were functionalized to selectively target human lung cancer cells and to serve both for cancer diagnostics and therapy (commonly referred to as “theranostics”).

Although significant progress has recently been achieved in the quest for better bio-markers, such as the above mentioned HN, the ultimate goal would be the use of no external probe for achieving “label-free” imaging. In the last decade coherent control with optimally tailored ultrashort laser pulses revolutionized molecular spectroscopy. Here, we show that playing with quantum interference between reaction pathways, it was possible to discriminate nearly identical cellular vitamins and identify selectively proteins (antibodies) in blood serum. Immunoglobulins G and M, as well as albumin, could be directly be quantified in blood serum label-free, yielding the first “Quantum Control Based Bio-assays”.

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Acknowledgements

The authors gratefully acknowledge the collaborators at the Universities of Geneva and Lyon, in particular L. Bonacina, F. Courvoisier, L. Guyon, V. Boutou, E. Salmon, J. Yu, G. Mejean, J. Kasparian, C. Kasparian, A. Rondi, S. Afonina, J. Extermann, P. Bejot, S. Weber, D. Kiselev, J. Gateau, S. Hermelin and M. Moret, as well as H. Rabitz and his group at Princeton, particularly M. Roth and J. Roslund, and all the collaborators of the NAMDIATREAM consortium.

We also acknowledge the financial support of the Swiss National Science Foundation (contracts No. 2000021-111688 and No 200020-124689), the Swiss NCCR MUST, and European FP7 project NAMDIATREAM (NMP-2009-4.0-3-246479).

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Wolf, JP. (2017). Ultrafast Nano-Biophotonics. In: Di Bartolo, B., Collins, J., Silvestri, L. (eds) Nano-Optics: Principles Enabling Basic Research and Applications. NATO Science for Peace and Security Series B: Physics and Biophysics. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0850-8_8

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