Publications by authors named "Dvir Yelin"

40 Publications

Imaging the dynamics and microstructure of fibrin clot polymerization in cardiac surgical patients using spectrally encoded confocal microscopy.

Am J Hematol 2021 May 10. Epub 2021 May 10.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

During cardiac surgery with cardiopulmonary bypass (CPB), altered hemostatic balance may disrupt fibrin assembly, predisposing patients to perioperative hemorrhage. We investigated the utility of a novel device termed spectrally-encoded confocal microscopy (SECM) for assessing fibrin clot polymerization following heparin and protamine administration in CPB patients. SECM is a novel, high-speed optical approach to visualize and quantify fibrin clot formation in three dimensions with high spatial resolution (1.0 μm) over a volumetric field-of-view (165 × 4000 × 36 μm). The measurement sensitivity of SECM was first determined using plasma samples from normal subjects spiked with heparin and protamine. Next, SECM was performed in plasma samples from patients on CPB to quantify the extent to which fibrin clot dynamics and microstructure were altered by CPB exposure. In spiked samples, prolonged fibrin time (4.4 ± 1.8 to 49.3 ± 16.8 min, p < 0.001) and diminished fibrin network density (0.079 ± 0.010 to 0.001 ± 0.002 A.U, p < 0.001) with increasing heparin concentration were reported by SECM. Furthermore, fibrin network density was not restored to baseline levels in protamine-treated samples. In CPB patients, SECM reported lower fibrin network density in protaminized samples (0.055 ± 0.01 A.U. [Arbitrary units]) vs baseline values (0.066 ± 0.009 A.U.) (p = 0.03) despite comparable fibrin time (baseline = 6.0 ± 1.3, protamine = 6.4 ± 1.6 min, p = 0.5). In these patients, additional metrics including fibrin heterogeneity, length and straightness were quantified. Note, SECM revealed that following protamine administration with CPB exposure, fibrin clots were more heterogeneous (baseline = 0.11 ± 0.02 A.U, protamine = 0.08 ± 0.01 A.U, p = 0.008) with straighter fibers (baseline = 0.918 ± 0.003A.U, protamine = 0.928 ± 0.0006A.U. p < 0.001). By providing the capability to rapidly visualize and quantify fibrin clot microstructure, SECM could furnish a new approach for assessing clot stability and hemostasis in cardiac surgical patients.
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http://dx.doi.org/10.1002/ajh.26217DOI Listing
May 2021

Formation of large intracellular actin networks following plasmonic cell fusion.

IEEE Trans Nanobioscience 2021 May 5;PP. Epub 2021 May 5.

Following fusion between two or more individual cells, the resulting cellular entity must undergo extensive restructuring of its plasma membrane and cytoskeleton in order to maintain its mechanical and physiological function. In artificial cell fusion that is executed by external triggering, such restructuring could be problematic due to the absence of preconditioning biological signals. In this work we study the reorganization of the actin filaments in adenocarcinoma cells that were fused using plasmonic triggering, i.e. the irradiation by resonant femtosecond laser pulses of cells specifically targeted by gold nanoparticles. Time-lapse confocal microscopy of the fusing cells has revealed the formation of large-scale actin networks that preserve the local orientations of the original actin cytoskeletons. The results confirm the local nature of the plasmonic interactions that were confined to the cells' plasma membranes and would help studying the development and dynamics of actin networks by offering a relatively stable, living cellular environment that supports large-scale actin growth.
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http://dx.doi.org/10.1109/TNB.2021.3077638DOI Listing
May 2021

Rapid imaging of tympanic membrane vibrations in humans.

Biomed Opt Express 2020 Nov 19;11(11):6470-6479. Epub 2020 Oct 19.

Department of Biomedical Engineering, Technion-Israel institute of Technology, Haifa 3200003, Israel.

Functional imaging of the human ear is an extremely challenging task because of its minute anatomic structures and nanometer-scale motion in response to sound. Here, we demonstrate noninvasive functional imaging of the human tympanic membrane under various acoustic excitations, and identify unique vibration patterns that vary between human subjects. By combining spectrally encoded imaging with phase-sensitive spectral-domain interferometry, our system attains high-resolution functional imaging of the two-dimensional membrane surface, within a fraction of a second, through a handheld imaging probe. The detailed physiological data acquired by the system would allow measuring a wide range of clinically relevant parameters for patient diagnosis, and provide a powerful new tool for studying middle and inner ear physiology.
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http://dx.doi.org/10.1364/BOE.402097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687925PMC
November 2020

Plasmonic targeting of cancer cells in a three-dimensional natural hydrogel.

Nanoscale 2018 Sep;10(37):17807-17813

Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel.

Using specifically designed gold nanoparticles and local laser irradiation, individual cells and small cell clusters could be targeted on a microscopic scale with minimal toxicity to nearby tissue. To date, most scientific studies and technological demonstrations of this approach were conducted on two-dimensional cultures, while most feasibility tests and preclinical trials were conducted using animal models. For bridging the gap between two-dimensional cell cultures and animal experiments, we propose and demonstrate the use of a natural hydrogel for studying the effect of intense, ultrashort laser pulses on a gold nanoparticle targeted tissue. Using illumination parameters comparable to those used with two-dimensional cultures, we show the complete eradication of multilayered cell colonies comprising normal fibroblasts and malignant epithelial cells co-cultured on a hydrogel scaffold. By evaluating the extent of cell damage for various pulse durations at off-resonance irradiation, we find that the observed damage mechanism was dominated by rapid thermal transitions around the gold nanospheres, rather than by photoionization. The work provides a new tool for understanding the complex pulse-particle-tissue interactions and demonstrates the important role of nanoparticle mediated cavitation bubbles in a thick, multilayered tissue.
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http://dx.doi.org/10.1039/c8nr03391aDOI Listing
September 2018

Measuring blood oxygen saturation along a capillary vessel in human.

Biomed Opt Express 2017 Nov 30;8(11):5342-5348. Epub 2017 Oct 30.

Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 3200003, Israel.

Measuring oxygen saturation in capillary vessels could provide valuable information on oxygen transport and tissue viability. Most spectroscopic measurement techniques, however, lack the spatial resolution to account for the small vessel dimensions within a scattering tissue and the steep gradients of oxygen saturation levels. Here, we developed a noninvasive technique for image-guided confocal measurement of the optical absorption spectrum from a small region that is comparable in size to the cross section of a single capillary vessel. A wide range of oxygen saturation levels were measured in a single capillary in a human volunteer, with blood deoxygenation rates of 7.1% per hundred microns. The technique could help in studying oxygen exchange dynamics in tissues and could play a key role in future clinical diagnosis and therapeutic applications that require localized functional tissue inspection.
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http://dx.doi.org/10.1364/BOE.8.005342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695974PMC
November 2017

Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration.

J Tissue Eng Regen Med 2018 04 8;12(4):1049-1061. Epub 2018 Jan 8.

The Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.

Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi-synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo-patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser-ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo-patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process.
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http://dx.doi.org/10.1002/term.2606DOI Listing
April 2018

In vivo noninvasive microscopy of human leucocytes.

Sci Rep 2017 10 12;7(1):13031. Epub 2017 Oct 12.

Department of Biomedical Engineering, Technion-Israel institute of Technology, Haifa, Israel.

Leucocytes play a key role in our immune system, protecting the body against infections using a wide range of biological mechanisms. Effective imaging and identification of leucocytes within the blood stream in patients is challenging, however, because of their low volume fraction in the blood, the high tissue scattering and the rapid blood flow. Spectrally encoded flow cytometry (SEFC) has recently been demonstrated effective for label-free high-resolution in vivo imaging of blood cells using an optical probe that does not require mechanical scanning. Here, we use SEFC to noninvasively image leucocytes at different imaging depths within small vessels in human volunteers, and identify visual differences in cell brightness and nuclei shapes, that would help distinguish between the two most abundant leucocyte types. The observed differences match the in vitro characteristics of isolated granulocytes and mononuclear cells. The results prove the potential of the system for conducting differential leucocyte count and as an effective research tool for studying the function and distribution of leucocytes in humans.
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http://dx.doi.org/10.1038/s41598-017-13555-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5638923PMC
October 2017

Measuring sickle cell morphology during blood flow.

Biomed Opt Express 2017 Mar 28;8(3):1996-2003. Epub 2017 Feb 28.

Faculty of Biomedical Engineering, Technion - IIT, Haifa, Israel.

During a sickle cell crisis in sickle cell anemia patients, deoxygenated red blood cells may change their mechanical properties and block small blood vessels, causing pain, local tissue damage, and possibly organ failure. Measuring the structural and morphological changes in sickle cells is important for understanding the factors contributing to vessel blockage and for developing an effective treatment. In this work, we image blood cells from sickle cell anemia patients using spectrally encoded flow cytometry, and analyze the interference patterns between reflections from the cell membranes. Using a numerical simulation for calculating the interference pattern obtained from a model of a red blood cell, we propose an analytical expression for the three-dimensional shape of characteristic sickle cells and compare our results to a previously suggested model. Our imaging approach offers new means for analyzing the morphology of sickle cells, and could be useful for studying their unique physiological and biomechanical properties.
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http://dx.doi.org/10.1364/BOE.8.001996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480593PMC
March 2017

hematocrit measurement using spectrally encoded flow cytometry.

Biomed Opt Express 2016 Oct 27;7(10):4327-4334. Epub 2016 Sep 27.

Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel.

Measuring key physiological parameters of small blood samples extracted from patients could be useful for real-time clinical diagnosis at the point of care. An important parameter required from all blood tests is the blood hematocrit, a measure of the fractional volume occupied by the red cells within the blood. In this work, we present a method for evaluation of hematocrit based on the data acquired using spectrally encoded flow cytometry. Analysis of the reflectance confocal images of blood within a flow chamber resulted in an error as low as 1.7% in the measured hematocrit. The technique could be used as part of an diagnostic system that measures important blood parameters at the point of care.
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http://dx.doi.org/10.1364/BOE.7.004327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102548PMC
October 2016

Experimental Proof for the Role of Nonlinear Photoionization in Plasmonic Phototherapy.

Nano Lett 2016 07 8;16(7):4601-7. Epub 2016 Jun 8.

Faculty of Biomedical Engineering, Technion, Israel Institute of Technology , Technion City, Haifa, 3200003, Israel.

Targeting individual cells within a heterogeneous tissue is a key challenge in cancer therapy, encouraging new approaches for cancer treatment that complement the shortcomings of conventional therapies. The highly localized interactions triggered by focused laser beams promise great potential for targeting single cells or small cell clusters; however, most laser-tissue interactions often involve macroscopic processes that may harm healthy nearby tissue and reduce specificity. Specific targeting of living cells using femtosecond pulses and nanoparticles has been demonstrated promising for various potential therapeutic applications including drug delivery via optoporation, drug release, and selective cell death. Here, using an intense resonant femtosecond pulse and cell-specific gold nanorods, we show that at certain irradiation parameters cell death is triggered by nonlinear plasmonic photoionization and not by thermally driven processes. The experimental results are supported by a physical model for the pulse-particle-medium interactions. A good correlation is found between the calculated total number and energy of the generated free electrons and the observed cell death, suggesting that femtosecond photoionization plays the dominant role in cell death.
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http://dx.doi.org/10.1021/acs.nanolett.6b01901DOI Listing
July 2016

Spectral imaging using forward-viewing spectrally encoded endoscopy.

Biomed Opt Express 2016 Feb 8;7(2):392-8. Epub 2016 Jan 8.

Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel.

Spectrally encoded endoscopy (SEE) enables miniature, small-diameter endoscopic probes for minimally invasive imaging; however, using the broadband spectrum to encode space makes color and spectral imaging nontrivial and challenging. By careful registration and analysis of image data acquired by a prototype of a forward-viewing dual channel spectrally encoded rigid probe, we demonstrate spectral and color imaging within a narrow cylindrical lumen. Spectral imaging of calibration cylindrical test targets and an ex-vivo blood vessel demonstrates high-resolution spatial-spectral imaging with short (10 μs/line) exposure times.
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http://dx.doi.org/10.1364/BOE.7.000392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771457PMC
February 2016

Reflectance confocal microscopy of red blood cells: simulation and experiment.

Biomed Opt Express 2015 Nov 9;6(11):4335-43. Epub 2015 Oct 9.

Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel.

Measuring the morphology of red blood cells is important for clinical diagnosis, providing valuable indications on a patient's health. In this work, we have simulated the appearance of normal red blood cells under a reflectance confocal microscope and discovered unique relations between the morphological parameters and the resulting characteristic interference patterns of the cell. The simulation results showed good agreement with in vitro reflectance confocal images of red blood cells, acquired using spectrally encoded flow cytometry that imaged the cells in a linear flow without artificial staining. By matching the simulated patterns to confocal images of the cells, this method could be used for measuring cell morphology in three dimensions and for studying their physiology.
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http://dx.doi.org/10.1364/BOE.6.004335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646543PMC
November 2015

In-situ architectures designed in 3D cell-laden hydrogels using microscopic laser photolithography.

Adv Mater 2015 Mar 5;27(11):1933-8. Epub 2015 Feb 5.

Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, 32000, Israel.

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http://dx.doi.org/10.1002/adma.201404185DOI Listing
March 2015

Spectral imaging using single-axis spectrally dispersed illumination.

Opt Lett 2014 Sep;39(17):5177-9

Spectral imaging is a powerful tool for a wide variety of applications; however, low imaging rates and signal-to-noise ratios (SNRs) often limit its use for many biomedical applications. Here, we present a technique for spectral imaging using a unique two-dimensional illumination pattern having spectral dispersion in one axis. The method, which is called spectrally dispersed illumination spectral imaging (SDISI), allows high-speed, high-resolution acquisition of spectral data from specimens that often cannot tolerate high illumination intensities or require fast imaging for avoiding motion artifacts. The technique is demonstrated by capturing spectral data cubes of the finger of a human volunteer using short exposure durations and a high (33.5 dB) SNR.
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http://dx.doi.org/10.1364/OL.39.005177DOI Listing
September 2014

Miniature forward-viewing spectrally encoded endoscopic probe.

Opt Lett 2014 Aug;39(16):4871-4

Spectrally encoded endoscopy is a promising technique for minimally invasive imaging, allowing high-quality imaging through small diameter probes that do not require rapid mechanical scanning. A novel optical configuration that employs broadband visible light and dual-channel imaging is used to demonstrate a miniature forward-viewing probe having a high number of resolvable points, low speckle contrast, negligible backreflections, and high signal-to-noise ratio. The system would be most suitable for imaging through narrow ducts and vessels for clinical diagnosis at hard-to-reach locations in the body.
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http://dx.doi.org/10.1364/OL.39.004871DOI Listing
August 2014

Measuring blood velocity using correlative spectrally encoded flow cytometry.

Opt Lett 2014 Aug;39(15):4424-6

Spectrally encoded flow cytometry (SEFC) is a promising technique for imaging blood in the microcirculation. Yet, the dependency of one of the axes of the image on time prevents effective quantification of essential clinical parameters. Here, we address this challenge by splitting the optical path in an SEFC system into two parallel imaging lines, followed by straightforward data analysis for recovering the flow speed from the multiplexed data. The method is demonstrated by measuring the flow velocity of latex beads and blood cells in vitro. The system allows real-time velocity measurements of up to 11.7  mm/s at high spatial resolution, and could be integrated into existing SEFC systems for effectively measuring blood parameters in small capillary vessels.
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http://dx.doi.org/10.1364/OL.39.004424DOI Listing
August 2014

Phase-sensitive imaging of tissue acoustic vibrations using spectrally encoded interferometry.

Opt Express 2013 Aug;21(17):19681-9

Acoustic vibrations in tissue are often difficult to image, requiring high-speed scanning, high sensitivity and nanometer-scale axial resolution. Here we use spectrally encoded interferometry to measure the vibration pattern of two-dimensional surfaces, including the skin of a volunteer, at nanometric resolution, without the need for rapid lateral scanning and with no prior knowledge of the driving acoustic waveform. Our results demonstrate the feasibility of this technique for measuring tissue biomechanics using simple and compact imaging probes.
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http://dx.doi.org/10.1364/OE.21.019681DOI Listing
August 2013

High levels of reactive oxygen species in gold nanoparticle-targeted cancer cells following femtosecond pulse irradiation.

Sci Rep 2013 ;3:2146

Department of Biomedical Engineering, Technion-Israel Institute of Technology, 32000, Haifa, Israel.

Cancer cells could be locally damaged using specifically targeted gold nanoparticles and laser pulse irradiation, while maintaining minimum damage to nearby, particle-free tissue. Here, we show that in addition to the immediate photothermal cell damage, high concentrations of reactive oxygen species (ROS) are formed within the irradiated cells. Burkitt lymphoma B cells and epithelial breast cancer cells were targeted by antibody-coated gold nanospheres and irradiated by a few resonant femtosecond pulses, resulting in significant elevation of intracellular ROS which was characterized and quantified using time-lapse microscopy of different fluorescent markers. The results suggest that techniques that involve targeting of various malignancies using gold nanoparticles and ultrashort pulses may be more effective and versatile than previously anticipated, allowing diverse, highly specific set of tools for local cancer therapy.
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http://dx.doi.org/10.1038/srep02146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701901PMC
September 2013

Optically induced cell fusion using bispecific nanoparticles.

Small 2013 Nov 21;9(22):3771-7. Epub 2013 Jun 21.

Department of Biomedical Engineering, Technion-Israel Institute of Technology, 32000 Haifa, Israel.

Redirecting the immune system to eliminate tumor cells is a promising alternative to traditional cancer therapies, most often requiring direct interaction between an immune system effector cell and its target. Herein, a novel approach for selective attachment of malignant cells to antigen-presenting cells by using bispecific nanoparticles is presented. The engaged cell pairs are then irradiated by a sequence of resonant femtosecond pulses, which results in widespread cell fusion and the consequent formation of hybrid cells. The dual role of gold nanoparticles as conjugating agents and fusion promoters offers a simple yet effective means for specific fusion between different cells. This technology could be useful for a variety of in vitro and in vivo applications that call for selective fusion between cells within a large heterogenic cell population.
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http://dx.doi.org/10.1002/smll.201300696DOI Listing
November 2013

High-speed interferometric spectrally encoded flow cytometry.

Opt Lett 2012 Dec;37(24):5154-6

Faculty of Biomedical Engineering, Technion—Israel Institute of Technology, Haifa 32000, Israel.

Spectrally encoded flow cytometry (SEFC) is a promising technique for noninvasive in vivo microscopy of blood cells. Here, we introduce a novel SEFC system for label-free confocal imaging of blood cells flowing at velocities of up to 10  mm/s within 65 μm-diameter vessels. The new system employs interferometric Fourier-domain detection and a high-speed wavelength-swept source, allowing 100 kHz line rate, sufficient for sampling the rapidly flowing cells 80 μm below the tissue surface. The large data sets obtained by this technique would improve diagnosis accuracy, reduce imaging time, and open new possibilities for noninvasive monitoring of blood in patients.
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http://dx.doi.org/10.1364/OL.37.005154DOI Listing
December 2012

Dual-channel spectrally encoded endoscopic probe.

Biomed Opt Express 2012 Aug 16;3(8):1855-64. Epub 2012 Jul 16.

High quality imaging through sub-millimeter endoscopic probes provides clinicians with valuable diagnostics capabilities in hard to reach locations within the body. Spectrally encoded endoscopy (SEE) has been shown promising for such task; however, challenging probe fabrication and high speckle noise had prevented its testing in in vivo studies. Here we demonstrate a novel miniature SEE probe which incorporates some of the recent progress in spectrally encoded technology into a compact and robust endoscopic system. A high-quality miniature diffraction grating was fabricated using automated femtosecond laser cutting from a large bulk grating. Using one spectrally encoded channel for imaging and a separate channel for incoherent illumination, the new system has large depth of field, negligible back reflections and well controlled speckle noise which depends on the core diameter of the illumination fiber. Moreover, by using a larger imaging channel, higher groove density grating, shorter wavelength and broader spectrum, the new endoscopic system now allow significant improvements in almost all imaging parameter compared to previous systems, through an ultra-miniature endoscopic probe.
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http://dx.doi.org/10.1364/BOE.3.001855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409704PMC
August 2012

Controlled release of Rituximab from gold nanoparticles for phototherapy of malignant cells.

J Control Release 2012 Sep 1;162(2):303-9. Epub 2012 Jul 1.

Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.

Releasing drug molecules at their targets with high spatial and temporal accuracy could aid numerous clinical applications which require low systemic damage and low side effects. Nano-carriers of drugs are an attractive solution for such task, allowing specific accumulation in tumors and gradual release of their payload. Here, we utilize gold nanospheres conjugated to Rituximab, an anti-CD20 monoclonal antibody-based drug, for carrying and releasing the drug upon irradiation of specifically tailored femtosecond laser pulses. The released anti-CD20 molecules retain their functionality and ability of triggering the complement-dependent cytotoxicity. This effect comes in addition to cell necrosis caused by the plasmonic nanometric shock waves emanating from the nanospheres and rupturing the plasma membranes. Main advantages of the presented technique include high spatial and temporal resolution, low toxicity and high repeatability and consistency due to the morphological stability of the nanospheres.
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http://dx.doi.org/10.1016/j.jconrel.2012.06.030DOI Listing
September 2012

Noninvasive imaging of flowing blood cells using label-free spectrally encoded flow cytometry.

Biomed Opt Express 2012 Jun 21;3(6):1455-64. Epub 2012 May 21.

Optical microscopy of blood cells in vivo provides a unique opportunity for clinicians and researchers to visualize the morphology and dynamics of circulating cells, but is usually limited by the imaging speed and by the need for exogenous labeling of the cells. Here we present a label-free approach for in vivo flow cytometry of blood using a compact imaging probe that could be adapted for bedside real-time imaging of patients in clinical settings, and demonstrate subcellular resolution imaging of red and white blood cells flowing in the oral mucosa of a human volunteer. By analyzing the large data sets obtained by the system, valuable blood parameters could be extracted and used for direct, reliable assessment of patient physiology.
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http://dx.doi.org/10.1364/BOE.3.001455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370984PMC
June 2012

Optical nanomanipulations of malignant cells: controlled cell damage and fusion.

Small 2012 Jun 19;8(11):1732-9. Epub 2012 Mar 19.

Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.

Specifically targeting and manipulating living cells is a key challenge in biomedicine and in cancer research in particular. Several studies have shown that nanoparticles irradiated by intense lasers are capable of conveying damage to nearby cells for various therapeutic and biological applications. In this work ultrashort laser pulses and gold nanospheres are used for the generation of localized, nanometric disruptions on the membranes of specifically targeted cells. The high structural stability of the nanospheres and the resonance pulse irradiation allow effective means for controlling the induced nanometric effects. The technique is demonstrated by inducing desired death mechanisms in epidermoid carcinoma and Burkitt lymphoma cells, and initiating efficient cell fusion between various cell types. Main advantages of the presented approach include low toxicity, high specificity, and high flexibility in the regulation of cell damage and cell fusion, which would allow it to play an important role in various future clinical and scientific applications.
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http://dx.doi.org/10.1002/smll.201102304DOI Listing
June 2012

Spectrally encoded spectral imaging.

Opt Express 2011 Mar;19(7):6913-22

Department of Biomedical Engineering, Technion-Israel Institute of Technology, Technion City, Haifa, Israel.

Spectral imaging, i.e. the acquisition of the spectrum emitted from each sample location, is a powerful tool for a wide variety of applications in science and technology. For biomedical applications, spectral imaging is important for accurate analysis of a biological specimen and for assisting clinical diagnosis, however it could be challenging mainly due to the typically low damage thresholds and strict time constraints. Here, we present a fiber-based technique termed spectrally encoded spectral imaging (SESI), in which a fully emitted spectrum is captured from each resolvable point of a specimen using an additional lateral scanning of the spectrally encoded line. The technique is demonstrated by capturing spectral data cubes of a color print and of a green leaf, and its potential advantage in signal-to-noise ratio is theoretically discussed. Using a miniaturized grating-lens configuration, SESI could be conducted endoscopically, allowing minimally invasive color and spectral imaging in remote locations of the body.
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http://dx.doi.org/10.1364/OE.19.006913DOI Listing
March 2011

Dispersion management for controlling image plane in Fourier-domain spectrally encoded endoscopy.

Opt Express 2011 Feb;19(5):4777-85

Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.

Spectrally encoded endoscopy (SEE) uses single optical fiber and miniature diffractive optics to allow imaging through a miniature probe. Utilizing Fourier-domain interferometry, SEE was shown capable of video-rate three-dimensional imaging, albeit at limited depth of field due to the limited spectral resolution of the detection spectrometer. We show that by using dispersion management at the reference arm of the interferometer, the tilt and curvature of the field of view could be adjusted without modifying the endoscopic probe itself. By controlling the group velocity dispersion, this technique is demonstrated useful for imaging specimen regions which reside outside the system's depth of field. This approach could be used to improve usability, functionality and image quality of SEE without affecting probe size and flexibility.
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http://dx.doi.org/10.1364/OE.19.004777DOI Listing
February 2011

Multiple-channel spectrally encoded imaging.

Opt Express 2010 Jul;18(14):14745-51

Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.

Spectrally encoded endoscopy (SEE) uses miniature diffractive optics to encode space with wavelength, allowing video-rate three-dimensional imaging through sub-millimeter, flexible endoscopic probes. Here we present a new approach for SEE in which the illumination and the collection channels are separated in space, and spectral encoding is present only in the collection channel. Bench-top experiments using spatially incoherent white light illumination reveal significant improvement in image quality and considerable reduction of speckle noise compared to conventional techniques, and show that the new system is capable of high sensitivity fluorescence imaging of single cells. The presented new approach would allow improved functionality and usability of SEE.
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http://dx.doi.org/10.1364/OE.18.014745DOI Listing
July 2010

Flow cytometry using spectrally encoded confocal microscopy.

Opt Lett 2010 Jul;35(13):2218-20

Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.

Flow cytometry techniques often rely on detecting fluorescence from single cells flowing through the cross section of a laser beam, providing invaluable information on vast numbers of cells. Such techniques, however, are often limited in their ability to resolve clusters of cells or parallel cell flow through large vessels. We present a confocal imaging technique that images unstained cells flowing in parallel through a wide channel, using spectrally encoded reflectance confocal microscopy that does not require mechanical scanning. Images of red blood cells from our system are compared to conventional transmission microscopy, and imaging of flowing red blood cells in vitro is experimentally demonstrated.
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http://dx.doi.org/10.1364/OL.35.002218DOI Listing
July 2010

Theoretical analysis of spectrally encoded endoscopy.

Opt Express 2009 Dec;17(26):24045-59

Department of Biomedical Engineering, Technion-Israel Institute of Technology, 32000 Haifa, Israel.

Using a single optical fiber and miniature distal optics, spectrally-encoded endoscopy (SEE) has been demonstrated as a promising, three-dimensional endoscopic imaging method with a large number of resolvable points and high frame rates. We present a detailed theoretical study of the SEE prototype system and probe. Several key imaging parameters of SEE are thoroughly derived and formulated, including the three-dimensional point-spread function and field of view, as well as the system's optical aberrations and fundamental limits. We find that the point-spread function of the SEE system maintains a unique relation between its transverse and axial shapes, discuss the asymmetry of the volumetric field of view, determine that the number of lateral resolvable points is nearly twice than what was previously accepted, and derive an expression for the upper limit for the total number of resolvable points in the cross-sectional image plane.
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http://dx.doi.org/10.1364/OE.17.024045DOI Listing
December 2009

Spectrally-encoded color imaging.

Opt Express 2009 Aug;17(17):15239-47

Harvard Medical School and Wellman center for Photomedicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.

Spectrally-encoded endoscopy (SEE) is a technique for ultraminiature endoscopy that encodes each spatial location on the sample with a different wavelength. One limitation of previous incarnations of SEE is that it inherently creates monochromatic images, since the spectral bandwidth is expended in the spatial encoding process. Here we present a spectrally-encoded imaging system that has color imaging capability. The new imaging system utilizes three distinct red, green, and blue spectral bands that are configured to illuminate the grating at different incident angles. By careful selection of the incident angles, the three spectral bands can be made to overlap on the sample. To demonstrate the method, a bench-top system was built, comprising a 2400-lpmm grating illuminated by three 525-microm-diameter beams with three different spectral bands. Each spectral band had a bandwidth of 75 nm, producing 189 resolvable points. A resolution target, color phantoms, and excised swine small intestine were imaged to validate the system's performance. The color SEE system showed qualitatively and quantitatively similar color imaging performance to that of a conventional digital camera.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852249PMC
http://dx.doi.org/10.1364/oe.17.015239DOI Listing
August 2009