Integration of high-resolution imaging through scattering medium into a disposable micro-endoscope via projection of 2D spots-array.

The objective of this research includes integration of high-resolution imaging through scattering medium, such as blood, into a disposable micro-endoscope. A fiber laser integrated into the micro-endoscope as part of its illumination channel, allows to project a tunable array of spots of light onto an object, that is located behind the scattering medium. We have a laser fiber as part of the illumination channel of a disposable micro-endoscope.

S194-Imaging through scattering media by 3D spatial filtering embedded into micro-endoscope.

Background: The main objective is related to the capability of integrating into minimally invasive and ultra-thin disposable micro-endoscopic tool, a modality of realizing high-resolution imaging through scattering medium such as blood while performing medical procedure. In this research we aim for the first time to present a time-multiplexing super-resolving approach exhibiting enhanced focus sensitivity, generated by 3D spatial filtering, for significant contrast increase in images collected through scattering medium.

Method: Our innovative method of imaging through scattering media provides imaging of only one specific object plane in scattering medium's volume while suppressing the noise coming from all other planes.

Imaging of nanoparticle dynamics in live and apoptotic cells using temporally-modulated polarization.

Gold nanoparticles are widely exploited in phototherapy. Owing to their biocompatibility and their strong visible-light surface plasmonic resonance, these particles also serve as contrast agents for cell image enhancement and super-resolved imaging. Yet, their optical signal is still insufficiently strong for many important real-life applications.

Interference based localization of single emitters.

The ability to localize precisely a single optical emitter is important for particle tracking applications and super resolution microscopy. It is known that for a traditional microscope the ability to localize such an emitter is limited by the photon count. Here we analyze the ability to improve such localization by imposing interference fringes.

Phase retrieval deblurring for imaging of dense object within a low scattering soft biological tissue.

Tissues are characterized by a strong scattering of visible optical radiation, which prevents one from achieving deep-tissue imaging. We propose a computational imaging technique for the inference of specific macroscopic, spatial phase distribution features of the scattering media. The spatial phase distribution is reconstructed from several defocused intensity images.

K-factor image deshadowing for three-dimensional fluorescence microscopy.

The ability to track single fluorescent particles within a three dimensional (3D) cellular environment can provide valuable insights into cellular processes. In this paper, we present a modified nonlinear image decomposition technique called K-factor that reshapes the 3D point spread function (PSF) of an XYZ image stack into a narrow Gaussian profile. The method increases localization accuracy by ~60% with compare to regular Gaussian fitting, and improves minimal resolvable distance between overlapping PSFs by ~50%.

Cellular superresolved imaging of multiple markers using temporally flickering nanoparticles.

In this paper we present a technique aimed for simultaneous detection of multiple types of gold nanoparticles (GNPs) within a biological sample, using lock-in detection. We image the sample using a number of modulated laser beams that correspond to the number of GNP species that label a given sample. The final image where the GNPs are spatially separated is obtained computationally.

Increased localization precision by interference fringe analysis.

We report a novel optical single-emitter-localization methodology that uses the phase induced by path length differences in a Mach-Zehnder interferometer to improve localization precision. Using information theory, we demonstrate that the localization capability of a modified Fourier domain signal generated by photon interference enables a more precise localization compared to a standard Gaussian intensity distribution of the corresponding point-spread function. The calculations were verified by numerical simulations and an exemplary experiment, where the centers of metal nanoparticles were localized to a precision of 3 nm.

Superresolved labeling nanoscopy based on temporally flickering nanoparticles and the K-factor image deshadowing.

Localization microscopy provides valuable insights into cellular structures and is a rapidly developing field. The precision is mainly limited by additive noise and the requirement for single molecule imaging that dictates a low density of activated emitters in the field of view. In this paper we present a technique aimed for noise reduction and improved localization accuracy.

Cellular imaging using temporally flickering nanoparticles.

Utilizing the surface plasmon resonance effect in gold nanoparticles enables their use as contrast agents in a variety of applications for compound cellular imaging. However, most techniques suffer from poor signal to noise ratio (SNR) statistics due to high shot noise that is associated with low photon count in addition to high background noise. We demonstrate an effective way to improve the SNR, in particular when the inspected signal is indistinguishable in the given noisy environment.

Fast wide-field photothermal and quantitative phase cell imaging with optical lock-in detection.

We present a fast, wide-field holography system for detecting photothermally excited gold nanospheres with combined quantitative phase imaging. An interferometric photothermal optical lock-in approach (POLI) is shown to improve SNR for detecting nanoparticles (NPs) on multiple substrates, including a monolayer of NPs on a silanized coverslip, and NPs bound to live cells. Furthermore, the set up allowed for co-registered quantitative phase imaging (QPI) to be acquired in an off-axis holographic set-up.

Improved localization accuracy in stochastic super-resolution fluorescence microscopy by K-factor image deshadowing.

Localization of a single fluorescent particle with sub-diffraction-limit accuracy is a key merit in localization microscopy. Existing methods such as photoactivated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) achieve localization accuracies of single emitters that can reach an order of magnitude lower than the conventional resolving capabilities of optical microscopy. However, these techniques require a sparse distribution of simultaneously activated fluorophores in the field of view, resulting in larger time needed for the construction of the full image.

Comparative review of interferometric detection of plasmonic nanoparticles.

Noble metal nanoparticles exhibit enhanced scattering and absorption at specific wavelengths due to a localized surface plamson resonance. This unique property can be exploited to enable the use of plasmonic nanoparticles as contrast agents in optical imaging. A range of optical techniques have been developed to detect nanoparticles in order to implement imaging schemes.

Photonic XOR with inherent loss compensation mechanism for memory cell implementation in a standard nanoscale very large-scale integrated fabrication process.

A multilayer photonic XOR gate is presented. The XOR is implemented by the interconnect layers of a microelectronic chip and is suitable for fabrication in a standard VLSI fabrication process. The proposed device features an inherent insertion loss compensation mechanism by utilization of nanometric holes, making it possible to implement an optic memory cell without the need of additional complex compensation devices.

Intercoupling surface plasmon resonance and diffusion reflection measurements for real-time cancer detection.

Spatial diffusion reflection (DR) measurements of gold nanorods (GNR) were recently suggested as a simple and highly sensitive non-invasive and non-ionizing method for real-time cancer detection. In this paper we demonstrate that wavelength dependent DR measurements enable the spectral red-shift observation of highly concentrated GNR. By conjugating targeting moieties to the GNR, large density of GNR can specifically home onto cancer cells.

Sub-micron particle based structures as reconfigurable photonic devices controllable by external photonic and magnetic fields.

In this paper we present the configurations of two nanometer scale structures--one of them optically controllable and the second one magnetically controllable. The first involves an array of nanoparticles that are made up of two layers (i.e.