In a similar fashion to diffusers or other highly scattering media, multimode fibres deliver coherent light signals in the form of apparently random speckled patterns. In contrast to other optically random environments, multimode fibres feature remarkably faithful cylindrical symmetry. Our experimental studies challenge the commonly held notion that classifies multimode fibres as unpredictable optical systems. Instead, we demonstrate that commercially available multimode fibres are capable of performing as extremely precise optical components. We show that, with a sufficiently accurate theoretical model, light propagation within straight or even significantly deformed segments of multimode fibres may be predicted up to distances in excess of hundreds of millimetres. Harnessing this newly discovered predictability in imaging, we demonstrate the unparalleled power of multimode fibre-based endoscopes, which offer exceptional performance both in terms of resolution and instrument footprint. These results thus pave the way for numerous exciting applications, including high-quality imaging deep inside motile organisms.T he theoretical description of light transport processes within ideal multimode fibres (MMFs) has been developed for over half a century 1-4 . This elaborate theoretical model is, however, frequently considered inadequate to describe real-life MMFs, which are manufactured by drawing melted silica preforms. Such fibres are commonly seen as unreliable, and the inherent randomization of light propagating through them is typically attributed to undetectable deviations from the ideal fibre structure. It is a commonly held belief that this additional chaos is unpredictable and that its influence grows with the length of the fibre. Despite this, light transport through MMFs remains deterministic.The prospect of deterministic light propagation within MMFs has only recently been used through methods of digital holography and by adopting the concept of empirical measurement of the transformation matrix (TM) 5-11 . This technique, developed in studies of light propagation through highly turbid media 12-17 , has opened a new window of opportunity for MMFs to become extremely narrow and minimally invasive endoscopes, allowing sub-micrometre resolution imaging in deep regions of sensitive tissues 9,18 .However attractive, this technology suffers from several major limitations, the most critical being the lack of flexible operation. Any bending or looping of the fibre results in changes to its TM, rendering the imaging heavily impaired. All current methods exploiting MMFs for imaging require open optical access to the distal end of the fibre during the time-consuming measurement of the TM. Furthermore, this characterization must be repeated upfront for every intended configuration (deformation) and any axial distance of the focal plane behind the fibre before the system can be used for imaging 7,19 . The necessity to determine the TM empirically is therefore a major bottleneck of the technology, and it would be immense...

We present a generic technique allowing size-based all-optical sorting of gold nanoparticles. Optical forces acting on metallic nanoparticles are substantially enhanced when they are illuminated at a wavelength near the plasmon resonance, as determined by the particle's geometry. Exploiting these resonances, we realize sorting in a system of two counter-propagating evanescent waves, each at different wavelengths that selectively guide nanoparticles of different sizes in opposite directions. We validate this concept by demonstrating bidirectional sorting of gold nanoparticles of either 150 or 130 nm in diameter from those of 100 nm in diameter within a mixture.

Achieving intravital optical imaging with diffraction-limited spatial resolution of deep-brain structures represents an important step toward the goal of understanding the mammalian central nervous system1–4. Advances in wavefront-shaping methods and computational power have recently allowed for a novel approach to high-resolution imaging, utilizing deterministic light propagation through optically complex media and, of particular importance for this work, multimode optical fibers (MMFs)5–7. We report a compact and highly optimized approach for minimally invasive in vivo brain imaging applications. The volume of tissue lesion was reduced by more than 100-fold, while preserving diffraction-limited imaging performance utilizing wavefront control of light propagation through a single 50-μm-core MMF. Here, we demonstrated high-resolution fluorescence imaging of subcellular neuronal structures, dendrites and synaptic specializations, in deep-brain regions of living mice, as well as monitored stimulus-driven functional Ca2+ responses. These results represent a major breakthrough in the compromise between high-resolution imaging and tissue damage, heralding new possibilities for deep-brain imaging in vivo.

Sub-diffraction microscopy enables bio-imaging with unprecedented clarity. However, most super-resolution methods require complex, costly purpose-built systems, involve image post-processing and struggle with sub-diffraction imaging in 3D. Here, we realize a conceptually different super-resolution approach which circumvents these limitations and enables 3D sub-diffraction imaging on conventional confocal microscopes. We refer to it as super-linear excitation-emission (SEE) microscopy, as it relies on markers with super-linear dependence of the emission on the excitation power. Super-linear markers proposed here are upconversion nanoparticles of NaYF 4 , doped with 20% Yb and unconventionally high 8% Tm, which are conveniently excited in the near-infrared biological window. We develop a computational framework calculating the 3D resolution for any viable scanning beam shape and excitation-emission probe profile. Imaging of colominic acid-coated upconversion nanoparticles endocytosed by neuronal cells, at resolutions twice better than the diffraction limit both in lateral and axial directions, illustrates the applicability of SEE microscopy for sub-cellular biology.