Amihai Meiri

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. The inter-particle plasmon resonance pattern of the highly concentrated GNR leads to an extension and a red-shift (Δλ) in the absorption spectrum of the concentrated GNR. Dark-field microscopy was used in order to measure the expected Δλ in different GNR concentrations in vitro. Double-wavelength DR measurements of tissue-like phantoms and tumor bearing mice containing different GNR concentrations are presented. We show that the DR profile of the highly concentrated GNR directly correlate with the spectral extension and red-shift. This presented work suggests that wavelength dependent DR method can serve as a promising tool for real-time superficial tumor detection.

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. We excite the temporal flickering of the scattered light from gold nanoparticle that labels a biological sample. By preforming temporal spectral analysis of the received spatial image and by inspecting the proper spectral component corresponding to the modulation frequency, we separate the signal from the wide spread spectral noise (lock-in amplification).

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. In this paper we present the use of a nonlinear image decomposition algorithm termed K-factor, which reduces an image into a nonlinear set of contrast-ordered decompositions whose joint product reassembles the original image. The K-factor technique, when implemented on raw data prior to localization, can improve the localization accuracy of standard existing methods, and also enable the localization of overlapping particles, allowing the use of increased fluorophore activation density, and thereby increased data collection speed. Numerical simulations of fluorescence data with random probe positions, and especially at high densities of activated fluorophores, demonstrate an improvement of up to 85% in the localization precision compared to single fitting techniques. Implementing the proposed concept on experimental data of cellular structures yielded a 37% improvement in resolution for the same super-resolution image acquisition time, and a decrease of 42% in the collection time of super-resolution data with the same resolution.

Uniformly Immobilizing Gold Nanorods on a Glass Substrate

The goal of this paper is to immobilize gold nanoparticles uniformly on a glass substrate. In order to attach gold-nanorods (GNRs) to an area of a few squared microns surface of glass substrate without preliminary coating of the GNR, 3-(Mercaptopropyl)trimethoxysilane molecules were used as linker while using different methods. These methods included placing the glass slide and the GNR (1) inside a tube without any motion; (2) inside a shaker; (3) in a fan setup. The fan setup included a tube containing the GNR solution and the glass slide at a vertical position, when the fan blows above the tube, producing turbulations in the liquid. Each method was evaluated according to the density and the homogeneousness of the GNR monolayer on the surface. The uniformity of the monolayer was demonstrated using AFM images of different areas on the slides, and the effectiveness of the protocol was demonstrated by calculating the average density of the GNR on the surface using image processing and analysis software. It was found that while both the shaker and the fan setups improved the monolayer density, the fan setup improved the density by a factor of more than two than the density found using the shaker.

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. The proposed method enables the simultaneous superresolved imaging of different areas of interest within biological sample and also the spatial separation of GNPs at sub-diffraction distances, making it a useful tool in the study of intracellular trafficking pathways in living 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., Au on top of a Si layer). The device may exhibits a wide range of plasmonic resonance according to external photonic radiation. The second type of device involves the usage of sub micron superparamagnetic particles located on a suitable structuring grid, that according to the angle of the external magnetic field allows control of the length of the structuring grid and therefore control the diffraction order of each wavelength.

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. The method has two steps; the first is the imaging of gold nanoparticles that labels targets of interest inside biological cells using a lock-in technique that enables the separation of the signal from the wide spread spectral noise. The second step is the application of the K-factor nonlinear image decomposition algorithm on the obtained image, which improves the localization accuracy that can reach 5nm and enables the localization of overlapping particles at minimal distances that are closer by 65% than conventional methods.

Multilayer photonic logic gate integrated into microelectronic chip

An all-optical XOR gate was designed to take advantage of the previously unused silicon dioxide (SiO2) interconnect layers in a microelectronic chip. The device relies on the coupling of modes between parallel waveguides and the interaction of the modes with the metal interconnects of a silicon chip to obtain a phase difference between input arms. When the signals from the two input arms interfere, the result is a logic XOR operation due to the phase difference. The design was numerically implemented, and a contrast of 18.7 dB was obtained with a 13.2-μm-long logic gate.

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%. The algorithm was tested both on simulated data and experimentally.

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. The structure of such a memory cell, implemented by utilization of two proposed XOR gates, configured to perform the NOT function, is shown. The unique structure of the proposed device allows us to significantly reduce sensitivity to process variations and therefore makes it possible to utilize the memory cell in state-of-the-art nanoscale processes. The proposed memory can be integrated with conventional electronics on the same VLSI chip.