Yossef Danan

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).

A Photonic 1 × 4 Power Splitter Based on Multimode Interference in Silicon–Gallium-Nitride Slot Waveguide Structures

In this paper, a design for a 1 × 4 optical power splitter based on the multimode interference (MMI) coupler in a silicon (Si)–gallium nitride (GaN) slot waveguide structure is presented—to our knowledge, for the first time. Si and GaN were found as suitable materials for the slot waveguide structure. Numerical optimizations were carried out on the device parameters using the full vectorial-beam propagation method (FV-BPM). Simulation results show that the proposed device can be useful to divide optical signal energy uniformly in the C-band range (1530–1565 nm) into four output ports with low insertion losses (0.07 dB).

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.

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.

Silicon-coated gold nanoparticles nanoscopy

Abstract. This paper presents a method for modifying the point spread function (PSF) into a doughnut-like shape, through the utilization of the plasma dispersion effect (PDE) of silicon-coated gold nanoparticles. This modified PSF has spatial components smaller than the diffraction limit, and by scanning the sample with it, super-resolution can be achieved. The sample is illuminated using two laser beams. The first is the pump, with a wavelength in the visible region that creates a change in the refractive index of the silicon coating due to the PDE. This creates a change in the localized surface plasmon resonance wavelength. Since the pump beam has a Gaussian profile, the high intensity areas of the beam experience the highest refractive index change. When the second beam (i.e., the probe) illuminates the sample with a near-infrared wavelength, this change in the refractive index is transformed into a change in the PSF profile. The ordinary Gaussian shape is transformed into a doughnut shape, with higher spatial frequencies, which enables one to achieve super-resolution by scanning the specimen using this PSF. This is a step toward the creation of a nonfluorescent nanoscope.

Improved Margins Detection of Regions Enriched with Gold Nanoparticles inside Biological Phantom

Utilizing the surface plasmon resonance (SPR) effect of gold nanoparticles (GNPs) enables their use as contrast agents in a variety of biomedical applications for diagnostics and treatment. These applications use both the very strong scattering and absorption properties of the GNPs due to their SPR effects. Most imaging methods use the light-scattering properties of the GNPs. However, the illumination source is in the same wavelength of the GNPs’ scattering wavelength, leading to background noise caused by light scattering from the tissue. In this paper we present a method to improve border detection of regions enriched with GNPs aiming for the real-time application of complete tumor resection by utilizing the absorption of specially targeted GNPs using photothermal imaging. Phantoms containing different concentrations of GNPs were irradiated with a continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms. By modulating the laser illumination, and use of a simple post processing, the border location was identified at an accuracy of better than 0.5 mm even when the surrounding area got heated. This work is a continuation of our previous research.

Targeted Magnetic Nanoparticles for Mechanical Lysis of Tumor Cells by Low-Amplitude Alternating Magnetic Field

Currently available cancer therapies can cause damage to healthy tissue. We developed a unique method for specific mechanical lysis of cancer cells using superparamagnetic iron oxide nanoparticle rotation under a weak alternating magnetic field. Iron oxide core nanoparticles were coated with cetuximab, an anti-epidermal growth factor receptor antibody, for specific tumor targeting. Nude mice bearing a head and neck tumor were treated with cetuximab-coated magnetic nanoparticles (MNPs) and then received a 30 min treatment with a weak external alternating magnetic field (4 Hz) applied on alternating days (total of seven treatments, over 14 days). This treatment, compared to a pure antibody, exhibited a superior cell death effect over time. Furthermore, necrosis in the tumor site was detected by magnetic resonance (MR) images. Thermal camera images of head and neck squamous cell carcinoma cultures demonstrated that cell death occurred purely by a mechanical mechanism.

Decoupling and tuning the light absorption and scattering resonances in metallic composite nanostructures

Utilizing the localized surface plasmon resonance (LSPR) effect of metallic nanoparticles enables their usage as contrast agents in a variety of applications for medical diagnostics and treatment. Those applications can use both the very strong absorption and scattering properties of the metallic nanoparticle due to their LSPR effects. There are certain applications where domination of the scattering over absorption or vice versa would be an advantage. However, the scattering and absorption resonance peaks have practically the same spectral location for solid noble metal nanoparticles at a certain domination of one over the other. In this paper we present gold nanoparticles coated with silicon that switches the order between the scattering and the absorption magnitude at the resonance peak by up to 34% in scattering-absorption ratio and tune the plasmon resonance over the spectrum by up to 56nm. This is obtained by modifying the refractive index of the silicon coating of the nanoparticle by illuminating it with a pumping light due to the plasma dispersion effect in silicon.

Temporally flickering nanoparticles for compound cellular imaging and super resolution

This work presents the use of flickering nanoparticles for imaging biological samples. The method has high noise immunity, and it enables the detection of overlapping types of GNPs, at significantly sub-diffraction distances, making it attractive for super resolving localization microscopy techniques. The method utilizes a lock-in technique at which the imaging of the sample is done using a time-modulated laser beam that match the number of the types of gold nanoparticles (GNPs) that label a given sample, and resulting in the excitation of the temporal flickering of the scattered light at known temporal frequencies. The final image where the GNPs are spatially separated is obtained using post processing where the proper spectral components corresponding to the different modulation frequencies are extracted. This allows the simultaneous super resolved imaging of multiple types of GNPs that label targets of interest within biological samples. Additionally applying the post-processing algorithm of the K-factor image decomposition algorithm can further improve the performance of the proposed approach.

Design of tunable thermo-optic C-band filter based on coated silicon slab

Optical filters are required to have narrow band-pass filtering in the spectral C-band for applications such as signal tracking, sub-band filtering or noise suppression. These requirements lead to a variety of filters such as Mach-Zehnder interferometer inter-leaver in silica, which offer thermo-optic effect for optical switching, however, without proper thermal and optical efficiency. In this paper we propose tunable thermo-optic filtering device based on coated silicon slab resonator with increased Q-factor for the C-band optical switching. The device can be designed either for long range wavelength tuning of for short range with increased wavelength resolution. Theoretical examination of the thermal parameters affecting the filtering process is shown together with experimental results. Proper channel isolation with an extinction ratio of 20dBs is achieved with spectral bandpass width of 0.07nm.