Stoyan Tanev

Brian C. Wilson

Valery V. Tuchin

Dennis Matthews

Biophotonics

A new 3D simulation method based on the finite-difference time domain (FDTD) approach in combination with Fourier optic techniques is applied to the modeling of optical phase contrast microscope (OPCM) imaging of gold nanoparticles (NPs) in singe biological cells. We consider a realistic size 3D cell model at optical immersion conditions, that is, when the refractive index values of the cytoplasm and of the extracellular medium are equal. For the first time, an FDTD-based OPCM model is applied to visualize the presence of a cluster of gold NPs in the cytoplasm at both resonant and nonresonant conditions. The results demonstrate the capability to model OPCM image enhancement by optically controlling the resonant properties of the NPs. Our research study extends the applicability of the FDTD modeling approach into a new biomedical optics research area.

James Pond

Paul Paddon

A New 3D Simulation Method for the Construction of Optical Phase Contrast Images of Gold Nanoparticle Clusters in Biological Cells

A 3-chip CCD imaging system has been developed for quantitative in vivo fluorescence imaging. This incorporates a ratiometric algorithm to correct for the effects of tissue optical absorption and scattering, imaging  “geometry” and tissue autofluorescence background. The performance was characterized, and the algorithm was validated in tissue-simulating optical phantoms for quantitative measurement of the fluorescent molecule protoporphyrin IX (PpIX). The technical feasibility to use this system for fluorescence-guided surgical resection of malignant brain tumor tissue was assessed in an animal model in which PpIX was induced exogenously in the tumor cells by systemic administration of aminolevulinic acid (ALA).

Eduardo H. Moriyama

Anthony Kim

Arjen Bogaards

Lothar Lilge

A Ratiometric Fluorescence Imaging System for Surgical Guidance

Delta-aminolevulinic acid/protoporphyrin IX is applied for fluorescent tumor detection in the upper part of gastrointestinal tract. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. In such way, 1D detection and 2D visualization of the lesions' fluorescence are received, and both advantages and limitations of these methodologies are discussed in relation to their clinical applicability. Comparison of the spectra received from normal mucosa, inflammatory, and tumor areas is applied to evaluate the feasibility for development of simple but effective algorithm based on dimensionless ratio of the fluorescence signals at 560 and 635 nm, for differentiation of normal/abnormal gastrointestinal tissues.

Ekaterina Borisova

Borislav Vladimirov

Latchezar Avramov

5-ALA Mediated Fluorescence Detection of Gastrointestinal Tumors

Autonomic dysreflexia (AD) is an inappropriate response of the sympathetic nervous system that commonly occurs when individuals with spinal cord injury (SCI), at or above the sixth thoracic (T6) vertebra, are subjected to a noxious stimulus below the level of injury. An AD event can be put into motion by something as simple as an ingrown toenail or a full bladder, with symptoms ranging from headache, high blood pressure, and even stroke. We have characterized the onset of AD and resulting autonomic events in an individual with SCI using a fiberoptic-based probe. Two probes were located above and below the injury level, on the subjects forearm and thigh, respectively, and were connected to a dual channel spectrophotometer. Oxygen saturation was calculated using the reflectance spectra and an algorithm based on melanin and hemoglobin absorption. We noticed that during an AD event the amount of oxygen in the skin below the injury level dropped by as much as 40%, while above the injury level, skin oxygenation remained constant. In addition, we found that the level of skin perspiration below the level of injury increased significantly. We hypothesize that the combination of AD-related ischemia with pressure-related ischemia and increased perspiration places individuals with spinal cord injury level at T6 or above at an elevated risk for developing a pressure sore below the injury site.

J. C. Ramella-Roman

J. M. Hidler

The Impact of Autonomic Dysreflexia on Blood Flow and Skin Response in Individuals with Spinal Cord Injury

The spectral properties of novel styryl dyes developed for the biomacromolecules (such as DNA) detection and imaging were investigated. The energy structures of dye molecules were examined. The spectral data prove that dyes aggregate and interact with DNA. The essential increase of the fluorescence intensity of dyes in the presence of DNA was observed. The photostability and phototoxic influence on the DNA of several styryl dyes were studied by analyzing absorption, fluorescence, and phosphorescence spectra of these dyes and dye-DNA systems. Changes of the optical density value of dye-DNA solutions caused by the irradiation were fixed in the DNA and dye absorption wavelength regions. Fluorescence emission of dye-DNA complexes upon two-photon excitation at wavelength 1064&#x2009;nm with the 20-nanosecond pulsed YAG:<svg     style="vertical-align:-0.16379pt;width:34.625px;" id="M1" height="16.049999" version="1.1" viewBox="0 0 34.625 16.049999" width="34.625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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</svg> laser and at 840&#x2009;nm with the 90 famtosecond pulsed Ti:sapphire laser was registered. The values of two-photon absorption cross-sections of dye-DNA complexes were evaluated.

V. M. Yashchuk

S. M. Yarmoluk

V. Yu. Kudrya

M. Yu. Losytskyy

V. P. Tokar

V. M. Kravchenko

V. B. Kovalska

A. O. Balanda

D. V. Kryvorotenko

Optical Biomedical Diagnostics: Sensors with Optical Response Based on Two-Photon Excited Luminescent Dyes for Biomolecules Detection

The technique of variable-angle total internal reflection fluorescence microscopy (TIRFM) and its application to nanotomography of cell surfaces are described. Present applications include (1) 3D imaging of chromosomes in their metaphase to demonstrate axial resolution in the nanometre range, (2) measurements of cell-substrate topology, which upon cholesterol depletion shows some loosening of cell-substrate contacts, and (3) measurements of cell topology upon photodynamic therapy (PDT), which demonstrate cell swelling and maintenance of focal contacts. The potential of the method for in vitro diagnostics, but also some requirements and limitations are discussed.

Michael Wagner

Petra Weber

Wolfgang S. L. Strauss

Henri-Pierre Lassalle

Herbert Schneckenburger

Nanotomography of Cell Surfaces with Evanescent Fields

The objective of this research program is to develop a novel, noninvasive, 
low-cost infrared
(8–12?<svg style="vertical-align:-3.56265pt;width:9.5625px;" id="M1" height="12.175" version="1.1" viewBox="0 0 9.5625 12.175" width="9.5625" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D707" d="M538 96q-38 -45 -84 -76.5t-71 -31.5q-44 0 -15 117q12 49 18 89h-2q-99 -128 -163 -178q-36 -28 -70 -28q-26 0 -44 38h-2q-16 -69 -16 -129q0 -43 11 -75.5t24 -42.5l1 -6q-7 -12 -24.5 -23t-37.5 -11q-40 0 -40 76q0 52 35 202l94 407l78 24l5 -5q-32 -122 -72 -310&#xA;q-7 -33 0 -55t25 -22q36 0 105.5 75t107.5 145l32 146l75 26h10q-50 -197 -78 -347q-7 -38 6 -38q7 0 31 17t47 39z" /></g></svg>m spectral range) imaging technique that would improve upon current methods using nanostructured core/shell magnetic/noble 
metal-based imaging and therapies. The biocompatible magnetic nanoparticles are able to produce heat under AC magnetic field. This thermal radiation propagates along the tissue by thermal conduction reaching the medium's (tissue's) surface. The surface temperature distribution is acquired by a thermal camera and can be analyzed to retrieve and reconstruct nanoparticles' temperature and location within the tissue. The technique may function as a diagnostic tool thanks to the ability of specific bioconjugation of these nanoparticles to tumor's outer surface markers. Hence, by applying a magnetic field, we could cause a selective elevation of temperature of the targeted nanoparticles up to <svg style="vertical-align:-0.20473pt;width:24.625px;" id="M2" height="13.1875" version="1.1" viewBox="0 0 24.625 13.1875" width="24.625" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.875)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g><g transform="matrix(.012,-0,0,-.012,8.225,4.712)"><path id="x2218" d="M326 255q0 -56 -41 -96t-99 -40t-99 40t-41 96t41 96t99 40t99 -40t41 -96zM274 255q0 38 -25.5 65t-62.5 27t-62.5 -27t-25.5 -65t25.5 -65t62.5 -27t62.5 27t25.5 65z" /></g><g transform="matrix(.017,-0,0,-.017,13.262,12.875)"><path id="x43" d="M614 175l29 -10q-33 -109 -57 -154q-121 -26 -184 -26q-90 0 -160.5 29t-112.5 77t-63.5 105.5t-21.5 119.5q0 157 108 253t277 96q36 0 71.5 -5t69 -13.5t36.5 -8.5q15 -102 20 -150l-29 -8q-20 79 -66.5 114t-128.5 35q-119 0 -187.5 -86t-68.5 -207&#xA;q0 -140 73.5 -227.5t188.5 -87.5q73 0 119.5 37.5t86.5 116.5z" /></g></svg>, which detects the tumor. Furthermore, elevating the temperature over <svg style="vertical-align:-0.20473pt;width:32.787498px;" id="M3" height="13.1875" version="1.1" viewBox="0 0 32.787498 13.1875" width="32.787498" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.875)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g><g transform="matrix(.017,-0,0,-.017,8.222,12.875)"><use xlink:href="#x35" /></g><g transform="matrix(.012,-0,0,-.012,16.375,4.712)"><use xlink:href="#x2218" /></g><g transform="matrix(.017,-0,0,-.017,21.412,12.875)"><use xlink:href="#x43" /></g></svg> and up to <svg style="vertical-align:-0.20473pt;width:40.950001px;" id="M4" height="13.1875" version="1.1" viewBox="0 0 40.950001 13.1875" width="40.950001" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.875)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g><g transform="matrix(.017,-0,0,-.017,8.222,12.875)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,16.381,12.875)"><use xlink:href="#x30" /></g><g transform="matrix(.012,-0,0,-.012,24.538,4.712)"><use xlink:href="#x2218" /></g><g transform="matrix(.017,-0,0,-.017,29.575,12.875)"><use xlink:href="#x43" /></g></svg> stimulates a thermo ablating interaction which causes a 
localized irreversible damage to the cancerous site with no harm  to the surrounding tissue. While functioning as a diagnostic tool, this procedure may serve as a targeted therapeutic tool under thermal feedback control as well.

Iddo M. Gescheit

Moshe Ben-David

Israel Gannot

A Proposed Method for Thermal Specific Bioimaging and Therapy Technique for Diagnosis and Treatment of Malignant Tumors by Using Magnetic Nanoparticles

We review our work developing optical waveguide-based evanescent field sensors for the label-free, specific detection of biological molecules. Using high-index-contrast silicon photonic wire waveguides of submicrometer dimension, we demonstrate ultracompact and highly sensitive molecular sensors compatible with commercial spotting apparatus and microfluidic-based analyte delivery systems. We show that silicon photonic wire waveguides support optical modes with strong evanescent field at the waveguide surface, leading to strong interaction with surface bound molecules for sensitive response. Furthermore, we present new sensor geometries benefiting from the very small bend radii achievable with these high-index-contrast waveguides to extend the sensing path length, while maintaining compact size. We experimentally demonstrate the sensor performance by monitoring the adsorption of protein molecules on the waveguide surface and by tracking small refractive index changes of bulk solutions.

A. Densmore

D.-X. Xu

S. Janz

P. Waldron

J. Lapointe

T. Mischki

G. Lopinski

A. Del&#226;ge

J. H. Schmid

P. Cheben

Sensitive Label-Free Biomolecular Detection Using Thin  Silicon Waveguides

We present experimental results on optical properties of cranial bone controlled by administration of propylene glycol and glycerol. Both transmittance and reflectance spectra of human and porcine cranial bone in vitro were measured. For estimation of absorption and reduced scattering coefficients of the bone, the inverse adding-doubling method was used. The decrease of reflectance of the samples under action of the immersion agents was demonstrated. The experiments have shown that administration of the immersion liquids allows for effective controlling of tissue optical characteristics that makes bone more transparent, thereby increasing the ability of light penetration through the tissue. The presented results can be used in developing of functional imaging techniques, including OCT.

Elina A. Genina

Alexey N. Bashkatov

Optical Clearing of Cranial Bone

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Published Special Issues

Advances in Optical Technologies

Biophotonics

Biophotonics

Articles

Biophotonics

A New 3D Simulation Method for the Construction of Optical Phase Contrast Images of Gold Nanoparticle Clusters in Biological Cells

A Ratiometric Fluorescence Imaging System for Surgical Guidance

5-ALA Mediated Fluorescence Detection of Gastrointestinal Tumors

The Impact of Autonomic Dysreflexia on Blood Flow and Skin Response in Individuals with Spinal Cord Injury

Optical Biomedical Diagnostics: Sensors with Optical Response Based on Two-Photon Excited Luminescent Dyes for Biomolecules Detection

Nanotomography of Cell Surfaces with Evanescent Fields

A Proposed Method for Thermal Specific Bioimaging and Therapy Technique for Diagnosis and Treatment of Malignant Tumors by Using Magnetic Nanoparticles

Sensitive Label-Free Biomolecular Detection Using Thin Silicon Waveguides

Optical Clearing of Cranial Bone