1,845 research outputs found

    Endo-microscopy beyond the Abbe and Nyquist limits

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    For several centuries, far-field optical microscopy has remained a key instrument in many scientific disciplines including physical, chemical and biomedical research. Nonetheless, far-field imaging has many limitations: the spatial resolution is controlled by the diffraction of light and the imaging speed follows Nyquist-Shannon sampling theorem. The recent development of super-resolution techniques has pushed the limits of spatial resolution. However, these methods typically require complicated setups, long acquisition time and are still not applicable for deep-tissue bioimaging. Here we report imaging through an ultra-thin fiber probe with a spatial resolution beyond the Abbe limit and a temporal resolution beyond the Nyquist limit simultaneously in a simple and compact setup. We use the random nature of mode coupling in a multimode fiber, the sparsity constraint and compressive sensing reconstruction. The new approach of super-resolution endo-microscopy does not use any specific properties of the fluorescent label such as depletion or stochastic activation of the molecular fluorescent state and therefore could be used for label-free imaging. We demonstrate a spatial resolution more than 2 times better than the diffraction limit and an imaging speed 20 times faster than the Nyquist limit. The proposed approach could significantly expand the realm of the application of nanoscopy for bioimaging.Comment: 22 pages, 6 figures, supplementary materials include

    Spectral-domain optical coherence reflectometric sensor for highly sensitive molecular detection

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    We describe what we believe to be a novel use of spectral-domain optical coherence reflectometry (SD-OCR) for highly sensitive molecular detection in real time. The SD-OCR sensor allows identification of a sensor surface of interest in an OCR depth scan and monitoring the phase alteration due to molecular interaction at that surface with subnanometer optical thickness sensitivity. We present subfemtomole detection sensitivity for etching of Si

    Robustness of Light-Transport Processes to Bending Deformations in Graded-Index Multimode Waveguides

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    Light transport through a multimode optical waveguide undergoes changes when subjected to bending deformations. We show that optical waveguides with a perfectly parabolic refractive index profile are almost immune to bending, conserving the structure of propagation-invariant modes. Moreover, we show that changes to the transmission matrix of parabolic-index fibers due to bending can be expressed with only two free parameters, regardless of how complex a particular deformation is. We provide detailed analysis of experimentally measured transmission matrices of a commercially available graded-index fiber as well as a gradient-index rod lens featuring a very faithful parabolic refractive index profile. Although parabolic-index fibers with a sufficiently precise refractive index profile are not within our reach, we show that imaging performance with standard commercially available graded-index fibers is significantly less influenced by bending deformations than step-index types under the same conditions. Our work thus predicts that the availability of ultraprecise parabolic-index fibers will make endoscopic applications with flexible probes feasible and free from extremely elaborate computational challenges

    High resolution combined molecular and structural optical imaging of colorectal cancer in a xenograft mouse model

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    With the emergence of immunotherapies for cancer treatment, there is a rising clinical need to visualize the tumor microenvironment (TME) non-invasively in detail, which could be crucial to predict the efficacy of therapy. Nuclear imaging techniques enable whole-body imaging but lack the required spatial resolution. Conversely, near-infrared immunofluorescence (immuno-NIRF) is able to reveal tumor cells and/or other cell subsets in the TME by targeting the expression of a specific membrane receptor with fluorescently labeled monoclonal antibodies (mAb). Optical coherence tomography (OCT) provides three-dimensional morphological imaging of tissues without exogenous contrast agents. The combination of the two allows molecular and structural contrast at a resolution of ~15 µm, allowing for the specific location of a cell-type target with immuno-NIRF as well as revealing the three-dimensional architectural context with OCT. For the first time, combined immuno-NIRF and OCT of a tumor is demonstrated in situ in a xenograft mouse model of human colorectal cancer, targeted by a clinically-safe fluorescent mAb, revealing unprecedented details of the TME. A handheld scanner for ex vivo examination and an endoscope designed for imaging bronchioles in vivo are presented. This technique promises to complement nuclear imaging for diagnosing cancer invasiveness, precisely determining tumor margins, and studying the biodistribution of newly developed antibodies in high detail

    Spectral-domain optical coherence phase and multiphoton microscopy

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    We describe simultaneous quantitative phase contrast and multiphoton fluorescence imaging by combined spectral-domain optical coherence phase and multiphoton microscopy. The instrument employs two light sources for efficient optical coherence microscopic and multiphoton imaging and can generate structural and functional images of transparent specimens in the epidirection. Phase contrast imaging exhibits spatial and temporal phase stability in the subnanometer range. We also demonstrate the visualization of actin filaments in a fixed cell specimen, which is confirmed by simultaneous multiphoton fluorescence imaging. © 2007 Optical Society of America

    Focus-extension by depth-encoded synthetic aperture in Optical Coherence Tomography

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    We present a novel method to extend the depth-of-focus of Optical Coherence Tomography (OCT). OCT is an interferometric imaging technique that provides depth-resolved scattering information. The axial resolution in OCT is provided by the coherence gate and is invariant over the full image depth. The lateral resolution is determined by the beam parameters such as wavelength and numerical aperture. The Rayleigh range determines the depth range over which the lateral resolution can be maintained. The lateral resolution is often sacrificed to maintain relatively long Rayleigh range. In this study, we propose to use a depth-encoded synthetic aperture detection scheme to extend the depth range over which a sharp focus can be maintained beyond the Rayleigh range. An annular phase plate is inserted into the light path in the sample arm, which gives rise to three separate images in a single B-scan, corresponding to three different optical path length encoded apertures. These three images are coherently summed after phase-manipulation to reconstruct a new image with a lateral resolution that is maintained over a five times larger depth range. © 2013 Optical Society of America
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