Dror Fixler

Synthetic aperture superresolution by speckle pattern projection

We propose a method for increasing the resolution of an aperture limited optical system by illuminating the input with a speckle pattern. The high resolution of the projected speckle pattern demodulates the high frequencies of the sample and permits its passage through the system aperture. A decoding provides the superresolved image. The speckle pattern can be generated in a simple manner in contrast with other structured light superresolution methods. The method is demonstrated in microscopy test images.

In‐vivo Tumor detection using diffusion reflection measurements of targeted gold nanorods – a quantitative study

The ability to quantitatively and non-invasively detect nanoparticles has important implications on their development as an in-vivo cancer diagnostic tool. The Diffusion Reflection (DR) method is a simple, non-invasive imaging technique which has been proven useful for the investigation of tissues optical parameters. In this study, Monte Carlo (MC) simulations, tissue-like phantom experiments and in-vivo measurements of the reflected light intensity from tumor bearing mice are presented. Following intravenous injection of antibody conjugated poly (ethylene glycol)-coated (PEGylated) gold nanorods (GNR) to tumor-bearing mice, accumulation of GNR in the tumor was clearly detected by the DR profile of the tumor. The ability of DR measurements to quantitate in-vivo the concentration of the GNR in the tumor was demonstrated and validated with Flame Atomic Absorption spectroscopy results. With GNR as absorbing contrast agents, DR has important potential applications in the image guided therapy of superficial tumors such as head and neck cancer, breast cancer and melanoma.

A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods

This paper presents a new method for cancer detection based on diffusion reflection measurements. This method enables discrimination between cancerous and noncancerous tissues due to the intense light absorption of gold nanorods (GNRs), which are selectively targeted to squamous cell carcinoma head and neck cancer cells. Presented in this paper are tissue-like phantom and in vivo results that demonstrate the high sensitivity of diffusion reflection measurements to the absorption differences between the GNR-targeted cancerous tissue and normal, noncancerous tissue. This noninvasive and nonionizing optical detection method provides a highly sensitive, simple, and inexpensive tool for cancer detection.

Reflected light intensity profile of two-layer tissues: phantom experiments

Experimental measurements of the reflected light intensity from two-layer phantoms are presented. We report, for the first time, an experimental observation of a typical reflected light intensity behavior for the two-layer structure characterized by two different slopes in the reflected light profile of the irradiated tissue. The point in which the first slope changes to the second slope, named as the crossover point, depends on the upper layer thickness as well as on the ratio between the absorption coefficients of the two layers. Since similar experiments from one-layer phantoms present a monotonic decay behavior, the existence and the location of the crossover point can be used as a diagnostic fingerprint for two-layer tissue structures. This pertains to two layers with greater absorptivity in the upper layer, which is the typical biological case in tissues like skin.

Linear optics based nanoscopy

Classically, optical systems are considered to have a fundamental resolution limit due to wave nature of light. This article presents a novel method for observing sub-wavelength features in a conventional optical microscope using linear optics. The operation principle is based on a random and time varying flow of nanoparticles moving in proximity to the inspected sample. Those particles excite the evanescent waves and couple them into harmonic waves. The sub-wavelength features are encoded and later on digitally decoded by proper image processing of a sequence of images. The achievable final resolution limit corresponds to the size of the nanoparticles. Experimental proof of principle validation of the technique is reported.

Errata: Subcutaneous gold nanorods detection with diffusion reflection measurement

Abstract. The ability to quantitatively and noninvasively detect nanoparticles nearby the skin surface has important implications on their development as an in vivo cancer diagnostic tool. The diffusion reflection (DR) method is a simple, noninvasive imaging technique which has been proven useful for the investigation of the optical parameters of the tissue. A new method is presented for the measurements of gold nanorod (GNR) concentration in tissue-like phantoms, based on DR measurement and intense light absorption of GNR. Monte Carlo simulations and tissue-like phantom measurements of the reflected light intensity are presented. The ability to extract optical properties of phantoms and their GNR concentrations from DR measurements is demonstrated, followed by a discussion about the best mathematical model for light propagation in tissues, based on the diffusion theory.

Flashing light in microalgae biotechnology

Flashing light can enhance photosynthesis and improve the quality and quantity of microalgal biomass, as it can increase the products of interest by magnitudes. Therefore, the integration of flashing light effect into microalgal cultivation systems should be considered. However, microalgae require a balanced mix of the light/dark cycle for higher growth rates, and respond to light intensity differently according to the pigments acquired or lost during the growth. This review highlights recently published results on flashing light effect on microalgae and its applications in biotechnology, as well as the recently developed bioreactors designed to fulfill this effect. It also discusses how this knowledge can be applied in selecting the optimal light frequencies and intensities with specific technical properties for increasing biomass production and/or the yield of the chemicals of interest by microalgae belonging to different genera.

Gold nanorods as absorption contrast agents for the noninvasive detection of arterial vascular disorders based on diffusion reflection measurements.

In this study we report the use of gold nanorods (GNRs) as absorption contrast agents in the diffusion reflection (DR) method for the in vivo detection of atherosclerotic injury. The early detection and characterization of atherosclerotic vascular disease is considered to be one of the greatest medical challenges today. We show that macrophage cells, which are major components of unstable active atherosclerotic plaques, uptake gold nanoparticles, resulting in a change in the optical properties of tissue-like phantoms and a unique DR profile. In vivo DR measurements of rats that underwent injury of the carotid artery showed a clear difference between the DR profiles of the injured compared with healthy arteries. The results suggest that DR measurements following GNRs administration represent a potential novel method for the early detection of atherosclerotic vascular disease.

In vivo tumor detection using polarization and wavelength reflection characteristics of gold nanorods.

This paper presents a novel concept involving sensing the back-reflected and absorbed light at two polarization states and at several wavelengths from gold nanorods (GNRs). While the GNRs are flowing in the bloodstream the reflected light has a high degree of polarization and only one resonance wavelength. When the GNRs are located in a tumor the reflected light has a low degree of polarization and two resonance wavelengths are detected. Such characteristics can assist in detecting a tumor in passive targeting and without labeling it.

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.