Dror Fixler

Bar Ilan University, Gan, Tel Aviv, Israel

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Publications (73)202.22 Total impact

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    ABSTRACT: A critical challenge arising during a surgical procedure for tumor removal is the determination of the tumor margins. Gold nanorods (GNRs) conjugated to epidermal growth factor receptors (EGFR) (GNRs-EGFR) are long being used in the detection of cancerous cells as the expression of EGFR dramatically increases once the tissue becomes cancerous. Optical techniques for the identification of these GNRs-EGFR in tumor are intensively developed based on the unique scattering and absorption properties of the GNRs. In this study we investigate the distribution of the GNRs in tissue sections presenting squamous cell carcinoma (SCC) to evaluate the SCC margins. Air scanning electron microscopy (airSEM), a novel, high resolution microscopy is used, enabling to localize and actually visualize nanoparticles on the tissue. The airSEM pictures presented a gradient of GNRs from the tumor to normal epithelium, spread in an area of 1mm, suggesting tumor margins of 1mm. Diffusion reflection (DR) measurements, performed in a resolution of 1mm, of human oral SCC have shown a clear difference between the DR profiles of the healthy epithelium and the tumor itself.
    No preview · Article · Jan 2016 · ACS Nano
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    ABSTRACT: Optical methods for detecting physiological state based on light-tissue interaction are noninvasive, inexpensive, simplistic, and thus very useful. The blood vessels in human tissue are the main cause of light absorbing and scattering. Therefore, the effect of blood vessels on light-tissue interactions is essential for optically detecting physiological tissue state, such as oxygen saturation, blood perfusion and blood pressure. We have previously suggested a new theoretical and experimental method for measuring the full scattering profile, which is the angular distribution of light intensity, of cylindrical tissues. In this work we will present experimental measurements of the full scattering profile of heterogenic cylindrical phantoms that include blood vessels. We show, for the first time that the vessel diameter influences the full scattering profile, and found higher reflection intensity for larger vessel diameters accordance to the shielding effect. For an increase of 60% in the vessel diameter the light intensity in the full scattering profile above 90° is between 9% to 40% higher, depending on the angle. By these results we claim that during respiration, when the blood-vessel diameter changes, it is essential to consider the blood-vessel diameter distribution in order to determine the optical path in tissues. A CT scan of the measured silicon-based phantoms. The phantoms contain the same blood volume in different blood-vessel diameters.
    No preview · Article · Dec 2015 · Journal of Biophotonics
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    Said Abu-Ghosh · Dror Fixler · Zvy Dubinsky · David Iluz
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    ABSTRACT: 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.
    Full-text · Article · Dec 2015 · Bioresource Technology
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    ABSTRACT: In this study, we developed a highly sensitive dual-mode imaging system using gold nanoparticles (GNPs) conjugated to various fluorophores in solid phantoms. The system consists of fluorescence-lifetime imaging microscopy (FLIM) for surface imaging, diffusion reflection (DR) for deep-tissue imaging (up to 1 cm), and metal-enhanced fluorescence (MEF). We detected quenching in the fluorescent intensity (FI) for the conjugation of both gold nanospheres (GNS) and gold nanorods (GNRs) to Fluorescein, which has an excitation peak at a wavelength shorter than the surface plasmon resonance (SPR) of both types of GNPs. Enhanced FI was detected in conjugation to Rhodamine B (RhB) and Sulforhodamine B (SRB), both with excitation peaks in the SPR regions of the GNPs. The enhanced FI was detected both in solution and in solid phantoms by the FLIM measurements. DR measurements detected the presence of GNRs within the solid phantoms by recording the dropped rates of light scattering in wavelengths corresponding to the absorption spectra of the GNRs. With the inclusion of MEF, this promising dual-mode imaging technique enables efficient and sensitive molecular and functional imaging.[Figure not available: see fulltext.] © 2015 Tsinghua University Press and Springer-Verlag Berlin Heidelberg
    No preview · Article · Nov 2015 · Nano Research
  • Idit Feder · Hamootal Duadi · Dror Fixler
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    ABSTRACT: Optical methods for monitoring physiological tissue state are important and useful because they are non-invasive and sensitive. Experimental measurements of the full scattering profile of circular phantoms are presented. We report, for the first time, an experimental observation of a typical reflected light intensity behavior for a circular structure characterized by the isobaric point. We previously suggested a new theoretically method for measuring the full scattering profile, which is the angular distribution of light intensity, of cylindrical tissues. In this work we present that the experimental result match the simulation results. We show the isobaric point at 105° for a cylindrical phantom with a 7mm diameter, while for a 16mm diameter phantom the isobaric point is at 125°. Furthermore, the experimental work present a new crossover point of the full scattering profiles of subjects with different diameters of the cylindrical tissues.
    No preview · Article · Aug 2015 · Biomedical Optics Express
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    Said Abu-Ghosh · Dror Fixler · Zvy Dubinsky · David Iluz
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    ABSTRACT: Under specific conditions, flashing light enhances the photosynthesis rate in comparison to continuous illumination. Here we show that a combination of flashing light and continuous background light with the same integrated photon dose as continuous or flashing light alone can be used to significantly enhance photosynthesis and increase microalgae growth. To test this hypothesis, the green microalga Dunaliella salina was exposed to three different light regimes: continuous light, flashing light, and concomitant application of both. Algal growth was compared under three different integrated light quantities; low, intermediate, and moderately high. Under the combined light regime, there was a substantial increase in all algal growth parameters, with an enhanced photosynthesis rate, within 3days. Our strategy demonstrates a hitherto undescribed significant increase in photosynthesis and algal growth rates, which is beyond the increase by flashing light alone. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jul 2015 · Bioresource Technology
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    ABSTRACT: In this study, we report a potential noninvasive technique for the detection of vulnerable plaques using scatter analyses with flow cytometry (FCM) method combined with the diffusion reflection (DR) method. The atherosclerotic plaques are commonly divided into two major categories: stable and vulnerable. The vulnerable plaques are rich with inflammatory cells, mostly macrophages (MΦ), which release enzymes that break down collagen in the cap. The detection method is based on uptake of gold nanorods (GNR) by MΦ. The GNR have unique optical properties that enable their detection using the FCM method, based on their scattering properties, and using the DR method, based on their unique absorption properties. This work demonstrates that after GNR labeling of MΦ, 1) the FCM scatter values increased up to 3.7-fold with arbitrary intensity values increasing from 1,110 to 4,100 and 2) the DR slope changed from an average slope of 0.196 (MΦ only) to an average slope of 0.827 (MΦ labeled with GNR) (P<0.001 for both cases). The combination of FCM and DR measurements provides a potential novel, highly sensitive, and noninvasive method for the identification of atherosclerotic vulnerable plaques, aimed to develop a potential tool for in vivo tracking.
    Full-text · Article · Jul 2015 · International Journal of Nanomedicine
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    ABSTRACT: The composition of atherosclerotic (AS) plaques is crucial concerning rupture, thrombosis and clinical events. Two plaque types are distinguished: stable and vulnerable plaques. Vulnerable plaques are rich in inflammatory cells, mostly only M1 macrophages, and are highly susceptible to rupture. These plaques represent a high risk particularly with the standard invasive diagnosis by coronary angiography. So far there are no non-invasive low-risk clinical approaches available to detect and distinguish AS plaque types in vivo. The perspective review introduces a whole work-flow for a novel approach for non-invasive detection and classification of AS plaques using the diffusion reflection method with gold nanoparticle loaded macrophages in combination with flow and image cytometric analysis for quality assurance. Classical biophotonic methods for AS diagnosis are summarized. Phenotyping of monocytes and macrophages are discussed for specific subset labelling by nanomaterials, as well as existing studies and first experimental proofs of concept for the novel approach are shown. In vitro and in vivo detection of NP loaded macrophages (MΦ). Different ways of MΦ labelling include (1) in vitro labelling in suspension (whole blood or buffy coat) or (2) labelling of short-term MΦ cultures with re-injection of MΦ-NP into the animal to detect migration of the cells in the plaques and (3) in vivo injection of NP into the organism. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Full-text · Article · Jun 2015 · Journal of Biophotonics
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    ABSTRACT: Sonochemistry has become a well-known technique for fabricating nanomaterials. Since one of the advantages of nanomaterials is that they have higher chemical activities compared with particles in the bulk form, efforts are being made to produce nano organic compounds with enhanced biological activities that could be exploited in the medical area. This study uses the sonication technique to prepare nano Vitamin B12 and nano Penicillin, and demonstrates their enhanced biological and pharmacological activity. The size and morphology of the nano Penicillin and nano Vitamin B12 were investigated using electron microscopy as well as dynamic light scattering techniques. The sizes of Penicillin and Vitamin B12 nanoparticles (NPs) were found to be 70 and 120-180 nm, respectively. The bactericidal effect of nano Penicillin was studied and found to be higher than that of the bulk form. Reducing the size of Vitamin B12 resulted in their enhanced antioxidative activity as observed using the electron paramagnetic spectroscopy technique. The penetration depth of these organic NPs can be detected by an optical iterative method. It is believed that nano organic drugs fabrication will have a great impact on the medical field.
    Preview · Article · May 2015 · International Journal of Nanomedicine
  • Hamootal Duadi · Dror Fixler
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    ABSTRACT: Light reflectance and transmission from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph (PPG) and reflectance pulse oximeter. Incident light on the skin travels into the underlying layers and is in part reflected back to the surface, in part transferred and in part absorbed. Most methods of near infrared (NIR) spectroscopy focus on the volume reflectance from a semi-infinite sample, while very few measure transmission. We have previously shown that examining the full scattering profile (angular distribution of exiting photons) provides more comprehensive information when measuring from a cylindrical tissue. Furthermore, an isobaric point was found which is not dependent on changes in the reduced scattering coefficient. The angle corresponding to this isobaric point depends on the tissue diameter. We investigated the role of multiple scattering and absorption on the full scattering profile of a cylindrical tissue. First, we define the range in which multiple scattering occurs for different tissue diameters. Next, we examine the role of the absorption coefficient in the attenuation of the full scattering profile. We demonstrate that the absorption linearly influences the intensity at each angle of the full scattering profile and, more importantly, the absorption does not change the position of the isobaric point. The findings of this work demonstrate a realistic model for optical tissue measurements such as NIR spectroscopy, PPG, and pulse oximetery.
    No preview · Article · May 2015 · Journal of Biomedical Optics
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    Said Abu-Ghosh · Dror Fixler · Zvy Dubinsky · David Iluz
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    ABSTRACT: An energy-input analysis of the life-cycle of microalgal cultivation systems was performed to study the oil-rich biomass production from fast-growing microalgae, for biodiesel production purposes. We estimated and compared the energy demands for the algal biomass cultivation in open-ponds (OP) with that required in closed-system photobioreactors (PBR) based on the new technologies. We also present the best microalgal candidates that show the highest biomass productivity and lipid yield indoors (laboratory scale), and discuss their potential to be used for full-scale biodiesel production. The results show that the energy requirements are highly dependent on the final mass concentration and/or using industrial wastes, with PBR cultivation being the largest energy consumer. Our offered scenario to minimize energy inputs and to increase algal-oil yields considers the most ideal cases, which could be the most promising model for energy-efficient biofuel production. Although biodiesel production by any of these systems is still not economically competitive with fossil fuel, recent suggestions on how to increase the efficiency of both systems are discussed, based on our energy-input assessment, with a critical evaluation of all stages for large-scale production of oil-rich microalgal biomass.
    Full-text · Article · Apr 2015 · Applied Energy
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    ABSTRACT: This paper introduces a theoretical and practical model for reconstructing the scattering properties of a participating media. Our theory is based on a robust generalization of the Gerchberg-Saxton (G-S) algorithm. At the end of this algorithm the reduced scattering coefficient μ's of a given substance, can be estimated from the standard deviation (STD) of the retrieved phase of the remitted light. We use the theory to compute the phase's STD that directly correlated to the optical properties for different types of milk components, and we derive a novel appearance model for milk parameterized by the lactose and protein contents. Our results show that we are able to detect the possibility of lactose and milk proteins' quantitative signature by the G-S optical tool, en route to the design of a novel milk-content-monitoring tool. Sketch of the experimental setup for light intensity measurements and reduced scattering coefficient reconstruction. The samples were prepared from various milk components: whey protein, sodium casienate and lactose, at different concentrations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    No preview · Article · Apr 2015 · Journal of Biophotonics
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    ABSTRACT: Nanocomposites as multifunctional agents are capable of combing imaging and cell biology technologies. The conventional methods used for validation of the conjugation process of nanoparticles (NPs) to fluorescent molecules such as spectroscopy analysis and surface potential measurements, are not sufficient. In this paper we present a new and highly sensitive procedure that uses the combination of (1) fluorescence spectrum, (2) fluorescence lifetime, and (3) steady state fluorescence polarization measurements. We characterize and analyze gold NPs with Lucifer yellow (LY) surface coating as a model. We demonstrate the ability to differentiate between LY-GNP (the conjugated complex) and a mixture of coated NP and free dyes. We suggest the approach for neuroscience applications where LY is used for detecting and labeling cells, studying morphology and intracellular communications. Histograms of Fluorescence lifetime imaging (FLIM) of free LY dye (Left) in comparison to the conjugated dye to gold nanoparticles, LY-GNP (Middle) enable the differentiation between LY-GNP (the conjugated complex) and a mixture of coated NP and free dyes (Right).
    No preview · Article · Apr 2015 · Journal of Biophotonics
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    ABSTRACT: Several approaches for optimization of fluorescence lifetime imaging microscopy (FLIM) system have been recently suggested. This paper discusses the influences of photons losses on the optimization of FLIM systems based time-correlated single photon counting (TCSPC) technique, considering the limitations associated with detecting the required amount of photons by the system. The fluorescence intensity (FI) and fluorescence lifetime (FLT) were measured in different operating regimes of the imaging system. The relation between parameters such as excitation power, detector gain, laser repetition rate, is also analyzed. Based on data acquisition limitations of typical TCSPC systems, we discuss the considerations for choosing the correct system parameters, which would most influence the accuracy of FLIM experiments. A simple scheme for optimization of FLIM systems for different types of fluorescent samples is finally suggested. - See more at: http://eurekaselect.com/128060#sthash.1W1q4fyI.dpuf
    Full-text · Article · Feb 2015 · Behaviour and Information Technology
  • D. Fixler · I. Yariv
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    ABSTRACT: In recent years, infiltrating materials into the human body has become a great challenge many researches are facing. In medicine and cosmetics today, there are materials which are administrated to patients by injection only. The main challenge with topical medication is penetrating the skin barrier. The skin is an effective barrier between the body and the outside environment, which prevents foreign materials entering the body easily. However, reducing the size of the desired materials might help their skin penetration ability. Recently nanoparticles (NPs) are being evaluated for use in many fields like chemistry, biology, medicine, physics and optics. The technique used in this work for forming organic NPs (ONPs) is the application of sonic waves to an aqueous solution, known as sonochemistry. To investigate the physical penetration depth of ONPs into the human body, we first developed a novel optical technique for detecting NPs within tissues. The detection of NPs is done by the extraction and investigation of the reemitted light phase.
    No preview · Article · Jan 2015
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    ABSTRACT: Determining the physical penetration depth of nanoparticles (NPs) into tissues is a challenge that many researchers have been facing in recent years. This paper presents a new noninvasive method for detecting NPs in tissue using an optical iterative technique based on the Gerchberg-Saxton (G-S) algorithm. At the end of this algorithm the reduced scattering coefficient (µs'), of a given substance, can be estimated from the standard deviation (STD) of the retrieved phase of the remitted light. Presented in this paper are the results of a tissue simulation which indicate a linear ratio between the STD and the scattering components. A linear ratio was also observed in the tissue-like phantoms and in ex vivo experiments with and without NPs (Gold nanorods and nano Methylene Blue). The proposed technique is the first step towards determining the physical penetration depth of NPs.
    Preview · Article · Nov 2014 · Biomedical Optics Express
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    Dror Fixler · Tsviya Nayhoz · Krishanu Ray
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    ABSTRACT: In this paper we report the optical properties of fluorescein-conjugated gold nanoparticles (GNPs) in solid phantoms using diffusion reflection (DR) and fluorescence lifetime imaging microscopy (FLIM). The GNPs attached with fluorescein in solution were studied by fluorescence correlation spectroscopy. The intensity decays were recorded to reveal the fluorescence lifetime of fluorescein while in the near-field vicinity of the GNPs. The DR method was used to explore the solid phantoms containing GNPs, indicating the light propagation from the surface of solid phantoms. The resulting DR slopes of the reflected intensity showed the higher the GNP concentration, the bigger the slope. Fluorescence intensity, lifetime, and anisotropy images of solid phantoms were investigated by FLIM. The exploration of optical properties and molecular imaging combined with DR and FLIM methods is a new approach that has not been established until now. The combined DR-FLIM technique is expected to provide discrimination based on unique spectroscopic fingerprints of GNPs that could be utilized for cell imaging. This paper includes a combined study with a variety of methods, which may lead to multimodal imaging for surfaces (by FLIM) and deep penetration (up to cm by the DR) together.
    Preview · Article · Sep 2014
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    Lior Turgeman · Dror Fixler
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    ABSTRACT: Recent developments in the field of fluorescence lifetime imaging microscopy (FLIM) techniques allow the use of high repetition rate light sources in live cell experiments. For light sources with a repetition rate of 20-100 MHz, the time-correlated single photon counting (TCSPC) FLIM systems suffer serious dead time related distortions, known as "inter-pulse pile-up". The objective of this paper is to present a new method to quantify the level of signal distortion in TCSPC FLIM experiments, in order to determine the most efficient laser repetition rate for different FLT ranges. Optimization of the F -value, which is the relation between the relative standard deviation (RSD) in the measured FLT to the RSD in the measured fluorescence intensity (FI), allows quantification of the level of FI signal distortion, as well as determination of the correct FLT of the measurement. It is shown that by using a very high repetition rate (80 MHz) for samples characterized by high real FLT's (4-5 ns), virtual short FLT components are added to the FLT histogram while a F -value that is higher than 1 is obtained. For samples characterized with short real FLT's, virtual long FLT components are added to the FLT histogram with the lower repetition rate (20-50 MHz), while by using a higher repetition rate (80 MHz) the "inter-pulse pile-up" is eliminated as the F -value is close to 1. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
    Full-text · Article · Jun 2014 · Journal of Biophotonics
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    ABSTRACT: 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 (ASVD) 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 (GNPs), 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.
    Full-text · Article · Apr 2014 · Nano Letters
  • D Fixler · R Ankri · I Kaplan · I Novikov · A Hirshberg
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    ABSTRACT: Intraoperative detection of residual disease in oral cancer may reduce the high rate of recurrences. The aim of the present study was to evaluate the detection sensitivity of diffusion reflection (DR) measurements of bioconjugated gold nanorods (GNRs) to cancerous sites in a rat model of oral squamous cell carcinoma. We used hyperspectral spectroscopy and DR measurements of GNRs bioconjugated to slide specimens of rat tongues where squamous carcinoma was induced by 4NQO (4-nitroquinoline-N-oxide). Wistar-derived male rats were used: 6 were sacrificed at wk 32 to 37 following 4NQO administration (experimental rats), as were 2 control rats at wk 32 and 36. The detection results were compared with histopathology: 19 sites of cancerous changes were identified microscopically (11 invasive cancer and 8 carcinoma in situ [CIS]). The GNRs attached selectively to areas of carcinomatous changes with an intensity exceeding 17 intensity units at 780 nm (overall specificity, 97%; overall sensitivity, 87%) when the hyperspectral spectroscopy system was used. The resulting DR slopes of the reflected intensity showed an increase of >80% in areas of invasive cancer and an increase of >30% in the CIS sites. The resulting intensity units of the hyperspectral spectroscopy system in the invasive cancer significantly exceed those of the CIS (t test, p = .0002; Mann-Whitney, p = .0024). The results demonstrate a great potential of the direct DR scanning as a new and simple tool for detecting residual disease intraoperatively.
    No preview · Article · Apr 2014 · Journal of dental research