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.

Abstract. The Maxwell stress tensor method is used to calculate the optical forces acting upon a glass nanosphere in the proximity of gold nanoantenna structures in normal and total internal reflection case. The angle dependance of optical forces over a full range of angles leads to a conclusion that total internal reflection incidence does not bring any particular advantage to trapping efficiency. Multiple trapping sites are found with similar trapping properties for the normal and the total internal reflection case, respectively. The issue of convective heating, which might oppose the optical forces and optical trapping in particular, is also discussed.

No abstract

The cell selective introduction of therapeutic agents remains a challenging problem. Here we demonstrate spatially controlled cavitation instigated by laser-induced breakdown of an optically trapped single gold nanoparticle of diameter 100 nm. The energy breakdown threshold of the gold nanoparticle with a single nanosecond laser pulse at 532 nm is three orders of magnitude lower than water, which leads to nanocavitation allowing single cell transfection. We quantify the shear stress to cells from the expanding bubble and optimize the pressure to be in the range of 1-10 kPa for transfection. The transfection of genes and injection of therapeutic agents into individual mammalian cells are among the most important research tools in modern molecular biology [1]. The use of acoustic bubbles in the proximity of cells oscillated by ultrasonic irradiation (insonation) can lead to enhanced membrane permeabilization of cells, and is known as sonoporation. Acoustic streaming, shock waves, and liquid microjets associated with the dynamics of cavitation bubble are implicated in gene and drug delivery into cells [2]. This approach, however, often leads to nonuniform and sporadic molecular uptake that lacks cell selectivity and suffers from a significant loss of cell viability. Recently a suite of optical methods in the domain of cavitation-based therapies has provided the potential of sterility, reconfigurability, and single cell selectivity [3]. Laser-induced breakdown (LIB) of a liquid medium containing cells, has demonstrated cell lysis, necrosis or membrane permeabilization, with the outcome dependent upon the hydrodynamic shear stress to cells caused by the expanding bubble [4]. However, the relatively high energy deposition required for this process resulted in a much larger cavitation bubble (typically >200 μm in diameter) compared to the typical cell size that effectively reduces cell viability and has been detrimental to allow its wider usage.More spatially controlled cavitation may be achieved by optically trapping particles for subsequent LIB instead of the surrounding liquid [5]. Optical tweezers allow the positioning of individual nanoparticles or microparticles at a desired location within the buffer medium. Therefore, using this tool for LIB offers additional degrees of freedom-the particle material, its size, and the LIB position relative to cells or tissues. We have shown that the LIB of trapped polystyrene nanoparticles significantly reduced the energy required for cavitation [6,7]. This leads to the permeabilization of cell membranes and transfection of cells in a targeted area in the absence of a lysis zone of cells.Gold nanoparticle clusters have played a key role in this field, through antibody binding and sequestration with subsequent irradiation by nanosecond or femtosecond laser pulses [8][9][10]. A unique interaction of gold nanoparticles with light, known as surface plasmon resonance, can lead to strong absorption of light for heat generation. However, the introduction of gold nanoparticles in the c...

Optical fiber bundle microendoscopes are widely used for visualizing hard-to-reach areas of the human body. These ultrathin devices often forgo tunable focusing optics because of size constraints and are therefore limited to two-dimensional (2D) imaging modalities. Ideally, microendoscopes would record 3D information for accurate clinical and biological interpretation, without bulky optomechanical parts. Here, we demonstrate that the optical fiber bundles commonly used in microendoscopy are inherently sensitive to depth information. We use the mode structure within fiber bundle cores to extract the spatio-angular description of captured light rays—the light field—enabling digital refocusing, stereo visualization, and surface and depth mapping of microscopic scenes at the distal fiber tip. Our work opens a route for minimally invasive clinical microendoscopy using standard bare fiber bundle probes. Unlike coherent 3D multimode fiber imaging techniques, our incoherent approach is single shot and resilient to fiber bending, making it attractive for clinical adoption.