Photothermal therapies of nanophotohyperthermia and nanophotothermolysis utilize the light absorptive properties of nanoparticles to create heat and free radicals in a small localized region. Conjugating nanoparticles with various biomolecules allows for targeted delivery to specific tissues or even specific cells, cancerous cells being of particular interest. Previous studies have investigated nanoparticles at visible and infrared wavelengths where surface plasmon resonance leads to unique absorption characteristics. However, issues such as poor penetration depth of the visible light through biological tissues limits the effectiveness of delivery by noninvasive means. In other news, various nanoparticles have been investigated as contrast agents for traditional X-ray procedures, utilizing the strong absorption characteristics of the nanoparticles to enhance contrast of the detected X-ray image. Using X-rays to power photothermal therapies has three main advantages over visiblespectra wavelengths: the high penetration depth of X-rays through biological media makes noninvasive treatments very feasible; the high energy of individual photons means nanoparticles can be heated to desired temperatures with lower beam intensities, or activated to produce the free radicals; and X-ray sources are already common throughout the medical industry, making future implementation on existing equipment possible. This paper uses Lorenz-Mie theory to investigate the light absorption properties of various size gold nanoparticles over photon energies in the 1-100 keV range. These absorption values are then plugged into a thermal model to determine the temperatures reached by the nanoparticles for X-ray exposures of differing time and intensity. The results of these simulations are discussed in relation to the effective implementation of nanophotohyperthermia and nanophotothermolysis treatments.
Nanodrugs selectively delivered to a tumor site can be activated by radiation for drug release, or nanoparticles (NPs) can be used as a drug themselves by producing biological damage in cancer cells through thermal, mechanical ablations or charged particle emission. Radio-frequency (RF) waves have an excellent ability to penetrate into the human body without causing healthy tissue damage, which provides a great opportunity to activate/heat NPs delivered inside the body as a contrast agent for diagnosis and treatment purposes. However the heating of NPs in the RF range of the spectrum is controversial in the research community because of the low power load of RF waves and low absorption of NPs in the RF range. To resolve these weaknesses in the RF activation of NPs and dramatically increase absorption of contrast agents in tumor, we suggest aggregating the nanoclusters inside or on the surface of the cancer cells. We simulate space distribution of temperature changes inside and outside metal and dielectric nanopraticles/nanoclusters, determine the number of nanoparticles needed to form a cluster, and estimate the thermal damage area produced in surrounding medium by nanopraticles/nanoclusters heated in the RF field.
The use of nanoparticles in medical applications has been gaining momentum as antibody-conjugated nanoparticles are
becoming more and more feasible as a means of targeted delivery of various therapies. Irradiating nanoparticles with
light of strongly-absorbed wavelengths allows them to act as heat generation sites. Two therapies utilize these
nanoparticle heat sources to kill the target cells: nanophotohyperthermia, which heats the particles just enough to disrupt
cell function and trigger cell death; and nanophotothermolysis, which heats the particles to such extremes as to destroy
the cell membrane. The use of optical wavelengths in the range of 750-1100 nm has been to capitalize on the "optical
transparency window" of biotissues between the absorption peaks of hemoglobin in the visible end and water in the
near-IR. However, further research has shown that a plasmon resonance can greatly affect the absorption characteristics
of nanoparticles at the plasmon resonant frequency, allowing for increased absorption characteristics at desirable
wavelengths. Thus, other transparency windows may find use in a similar manner, such as nanoparticle heating by RF
waves. This paper presents the modeling of 3D thermal fields around nanoparticle absorbers in bone tissue for various
frequencies. A comparison of the heating effectiveness across multiple wavelengths is discussed for application to
nanophotothermolysis and nanophotohyperthermia treatments in or near biological hard tissue.
Biological hard tissues, such as those found in bone and teeth, are complex tissues that build a strong mineral structure
over an organic matrix framework. The laser-matter interaction for bone hard tissues holds great interest to laser surgery
and laser dentistry; the use of short/ultrashort pulses, in particular, shows interesting behaviors not seen in continuous
wave lasers. High laser energy densities in ultrashort pulses can be focused on a small irradiated surface (spot diameter is
10-50 μm) leading to rapid temperature rise and thermal ablation of the bone tissue. Ultrashort pulses, specifically those
in the picosecond and femtosecond ranges, impose several challenges in modeling bone tissue response. In the present
paper we perform time-dependent thermal simulations of short and ultrashort pulse laser-bone interactions in singlepulse
and multipulse (set of ultrashort pulses) modes of laser heating. A comparative analysis for both radiation modes is
discussed for laser heating of different types of the solid bone on the nanosecond, picosecond and femtosecond time
scales. It is shown that ultrashort laser pulses with high energy densities can ablate bone tissue without heating tissues
bordering the ablation creator. This reaction is particularly desirable as heat accumulation and thermal damage are the
main factors affecting tissue regrowth rates, and thus patient recovery times.
Nanoparticles are being researched as a noninvasive method for selectively killing cancer cells. With particular antibody
coatings on nanoparticles, they attach to the abnormal cells of interest (cancer or otherwise). Once attached,
nanoparticles can be heated with UV/visible/IR or RF pulses, heating the surrounding area of the cell to the point of
death. Researchers often use single-pulse or multipulse lasers when conducting nanoparticle ablation research. In the
present paper, we are conducting an analysis to determine if the multipulse mode has any advantage in heating of
spherical metal nanoparticles (such as accumulative heating effect). The laser heating of nanoparticles is very sensitive
to the time structure of the incident pulsed laser radiation, the time interval between the pulses, and the number of pulses
used in the experiments. We perform time-dependent simulations and detailed analyses of the different nonstationary
pulsed laser-nanoparticle interaction modes, and show the advantages and disadvantages of multipulse (set of short
pulses) and single-pulse laser heating of nanoparticles. A comparative analysis for both radiation modes (single-pulse
and multipulse) are discussed for laser heating of metal nanotargets on nanosecond, picosecond and femtosecond time
scales to make recommendations for efficient laser heating of nanomaterials in the experiments.
A simple focusing device is proposed for de Broglie matter waves—a diffractive lens, based on the optical effect of diffractive multifocal focusing of radiation. This matter-wave lens consists of two coaxial circular apertures in which the second aperture of smaller diameter is located where the Fresnel number of the first aperture is unity. It is shown that diffraction of a de Broglie matter wave by a system of two pinholes on an optical axis exhibits the multifocal focusing effect of matter waves in the near-field (Fresnel) zone, which creates a very intense, spatially localized beam of atoms. Theoretical predictions for the focusing efficiency of a neutral atomic beam by the diffractive lens are as follows. The spot diameter is ~0.1 µm, the ratio of focal and incident intensities is ~15, the focal length of the diffractive lens is in the range ~0.13 to 6 cm, the focusing depth is in the range ~15 to 30 cm, and the energy transmitting efficiency is ~30 %. For the relatively large diameters of the pinholes, 5.0 µm, the proposed configuration acts as a matter-wave lens with a large focal length and a long focusing depth.
Diffraction of a de Broglie matter wave by a system of two pinholes on an optical axis exhibits the multifocal focusing effect of matter waves in the near-field (Fresnel zone). The focusing, defocusing and refocusing phenomenon results from periodic phase changes at singular points, which are observed for the even Fresnel numbers, where the intensity is zero and the phase is undefined. As an on-axis observation point passes through a singular point, the nature of the wave in the neighborhood of the axis changes from that of a diverging wave to that of a converging wave, i.e., the wave refocuses. The amplitudes of the oscillations in the intensity and phase of the de Broglie wave depend on the ratio of the radii of the two apertures in the system. This effect of diffractive multifocal focusing of de Broglie waves can be used for designing a diffractive lens for matter-wave beams.
A simple focusing device is proposed for de Broglie matter-waves - a diffractive lens, based on the optical effect of
diffractive multifocal focusing of radiation. This matter-wave lens consists of two co-axial circular apertures in which
the second aperture of smaller diameter is located where the Fresnel number of the first aperture is unity. It is shown that
diffraction of a de Broglie matter wave by a system of two pinholes on an optical axis exhibits the multifocal focusing
effect of matter waves in the near-field (Fresnel) zone. The focusing, defocusing and refocusing phenomenon is
explained as resulting from periodic phase changes at singular points, which are points where the intensity is zero and
the phase is undefined. It is shown that the proposed matter-wave lens could create a very intense, spatially-localized
beam of atoms. Theoretical predictions for the focusing efficiency of a neutral atomic beam by the diffractive lens are:
the spot diameter is ~ 0.1 &mgr;m, the ratio of focal and incident intensities is ~ 15, the focal length of the diffractive lens is
in the range ~ 0.13.6 cm, the focusing depth is in the range ~ 15.30 cm, and the energy transmitting efficiency is ~
30%. For the relatively-large diameters of the pinholes, ⩾ 5.0 &mgr;m, the proposed configuration acts as a matter-wave lens
with a large focal length and a long focusing depth.
A promising avenue in the development of pulsed chemical HF/DF lasers and amplifiers is the utilization of a photonbranched
chain reaction initiated in a two-phase active medium, i.e., a medium containing a working gas and
ultradispersed passivated metal particles. These particles are evaporated under the action of IR laser radiation, which
results in the appearance of free atoms, their diffusion into the gas, and the development of the photon-branching process.
The key obstacle here is the formation a relatively-large volume (in excess of 103 cm3) of the stable active medium, and
filling this volume homogeneously for a short time with a sub-micron monodispersed metal aerosol, which has specified
properties. In this manuscript, results are presented for an extensive study of a gas-dispersed component of a H2-F2 laser
active medium, including novel techniques for the formation of a two-phase active medium with specified properties;
aerosol optics; degradation of the dispersed component; and beam stability of a chemically-active aerosol. These results
should help lead the way to creating powerful, reliable and inexpensive self-contained pulsed sources of coherent
radiation with high energy, high laser beam quality, and the possibility of scaling up the output energy.
A new mechanism is proposed for selective laser killing of abnormal cells by laser thermal explosion of single
nanoparticles - "nano-bombs" - delivered to the cells. Thermal explosion of the nanoparticles is realized when the heat
generates within the strongly-absorbing target more rapidly than the heat can diffuse away. On the basis of simple
energy balance, it is shown that the lower level of the threshold energy density of a single laser pulse required for
thermal explosion of solid gold nanospehere is about 40 mJ/cm2, which is well below the safety standard for medical
lasers (100 mJ/cm2) for healthy tissue and cells. The nanoparticle's explosion energy density can be reduced further (up
to 11 mJ/cm2) by using gold nanorods due to higher plasmon-resonance absorption efficiency of nanorods. Additionally,
the nanorods optical resonance lies in the near-IR region, where biological tissue transmissivity is the highest. Here, the
effective therapeutic effect for cancer cell killing can be achieved due to nonlinear phenomena, which accompany the
thermal explosion of the nanoparticles: generation of the strong shock wave with supersonic expansion of dense vapor in
the cell volume, producing sound waves and optical plasma.
The problem of correct measurement of human eye aberrations is very important with the rising widespread of a surgical procedure for reducing refractive error in the eye, so called, LASIK (laser-assisted in situ keratomileusis). In this paper we show capabilities to measure aberrations by means of the aberrometer built in our lab together with Active Optics Ltd. We discuss the calibration of the aberrometer and show invalidity to use for the ophthalmic calibration purposes the analytical equation based on thin lens formula. We show that proper analytical equation suitable for calibration should have dependence on the square of the distance increment and we illustrate this both by experiment and by Zemax Ray tracing modeling. Also the error caused by inhomogeneous intensity distribution of the beam imaged onto the aberrometer's Shack-Hartmann sensor is discussed.
In this presentation a model of human eye based on bimorph flexible mirror is introduced. We demonstrate experimental data of reproducing low- and high-order aberrations typical for human eye with RMS error about 5%. The presented temporal spectra of measured human eye aberrations have the main power within the range of 10 Hz. We discuss the possibility to reproduce it with our eye model. We show invalidity for the ophthalmic calibration purposes to use analytical equation based on thin lens formula. We show that proper analytical equation suitable for calibration should have dependence on the square of the distance increment and we illustrate this both by experiment and by Zemax Ray tracing modeling.
In this presentation a dynamic model of human eye based on bimorph flexible mirror is introduced. We demonstrate experimental data of reproducing low- and high-order aberrations typical for human eye with RMS error about 5% and discuss possibility to reproduce their time-tracings.
Background and Objective: The application of nanotechnology for laser thermal-based killing of abnormal cells (e.g. cancer cells) targeted with absorbing nanoparticles (e.g. gold solid nanospheres, nanoshells, or rod) is becoming an extensive area of research. We develop an approach to enhance the efficiency of selective nanophotothermolysis of cancer cells through laser-induced synergistic effects around gold nanoparticles aggregated in nanoclusters on cell membrane.
Study Design/Materials and Methods: A concept of selective target damages by laser-induced synergistic interaction of optical, thermal, and acoustic fields around clustered nanoparticles is presented with focus on overlapping bubbles from nanoparticles aggregated on cell's membrane. The experimental verification of this concept in vitro was performed by the use a tunable laser pulses (420-570 nm, 8-12 ns, 0.1-300 μJ, laser flux of 0.1-10 J/cm2) for irradiation of MDA-MB-231 breast cancer cells targeted with primary antibodies to which selecttively 40-nm gold nanoparticles were attached by the means of secondary antibodies. The photothermal, electron and atomic force microscopes in combination with viability test (annexin -V-Propidium iodide) were employed to study the nanoparticle's spatial organization, the dynamics of microbubble formations around the particle's clusters, and cells damage.
Results: An aggregation of nanoparticles on cell membrane was observed with simultaneous increase bubble formation phenomena, and red-shifted absorption due to plasmon-plasmon resonances into nanoclusters. It led to a significant enhancement, at least two orders of magnitude, of the efficiency of selectively killing cancer cells with nanosecond laser pulses.
Conclusion: Described approach allows using relatively small nanoparticles which would be easier delivery to target site with further creation of nanoclusters with larger sizes which provide more profound thermal and related phenomena leading to more efficient laser killing of cancer cells. This nanocluster model might be promising also for treatment or modification different targets (e.g. bacteria, virus, vascular lesions, fat, etc.) as well as teh use different type energy deposition (focused ultrasound, microwave, magnetic field, etc.).
The problem of correct eye aberrations measurement is very important with the rising widespread of a surgical procedure for reducing refractive error in the eye, so called, LASIK (laser-assisted in situ keratomileusis). The double-pass technique commonly used for measuring aberrations of a human eye involves some uncertainties. One of them is loosing the information about odd human eye aberrations. We report about investigations of the applicability limit of the double-pass measurements depending upon the aberrations status introduced by human eye and actual size of the entrance pupil. We evaluate the double-pass effects for various aberrations and different pupil diameters. It is shown that for small pupils the double-pass effects are negligible. The testing and alignment of aberrometer was performed using the schematic eye, developed in our lab. We also introduced a model of human eye based on bimorph flexible mirror. We perform calculations to demonstrate that our schematic eye is capable of reproducing spatial-temporal statistics of aberrations of living eye with normal vision or even myopic or hypermetropic or with high aberrations ones.
In the present report we propose an innovative concept for effective diffractive wave guiding of optical (infrared, visible and X-rays) beams based on the effect of diffractive multifocal focusing of radiation (DMFR). The optical DMFR effect, predicted earlier by theory, on a bicomponent diffraction system, has recently been confirmed experimentally. The bicomponent diffraction system consists of two plane screens with circular apertures, which are located in the first open Fresnel zone of each other along optical axes. It was shown that the diffraction picture in the focal planes of such a system represents a bright narrow peak at the center for open odd Fresnel zones, whose intensity can exceed by six times the value of the intensity of the incident spherical wave. We propose to utilize the DMRF effect for multi-component system of pinholes, positioned along the optical axis, and design a new diffractive photonic-crystal-like fiber (wave-guide), in which space localization of an electromagnetic field is rigidly fixed for given values of the wavelength and the pinhole diameter. Thus, such a diffractive photonic crystal has an internal periodic macrostructure, but it differs from a traditional photonic crystal in that the forbidden zones are formed in a natural way as a result of the diffraction off the pinhole system.
In the present report a novel diffractive technique for effective optical pumping of power chemical lasers by external coherent radiation is proposed. This technique utilizes a bicomponent diffraction system coupled structurally to the unstable telescopic cavity of the laser. The space localization of the electromagnetic field inside the proposed optical scheme represents a periodic structure of diffractive maxima in the near field-zone and a narrow paraxial diffraction channel with high intensity in the far-field zone. In the Fresnel diffraction zone, the optical effect of multifocal diffractive focusing of the radiation is observed. Here the intensity in the central peaks can exceed by a factor of six (for spherical waves) to ten (for plane waves) the value of the incident wave intensity. The diffractive focusing of the input radiation opens the possibility to create a narrow diffraction initiation channel inside the laser cavity with a given space distribution and a high intensity. This technique provides a high efficiency for optical pumping and makes it possible to get a huge value of the laser energy gain. Calculations show that the ignition of laser-chemical reactions in the diffraction initiation channel under the condition of diffractive focusing of input radiation allows the laser energy to reach a gain of up to 109.
The possible construction of a self-contained and compact pulsed chemical HF-laser based on an auto-wave photon-branched chain reaction initiated in a gaseous disperse medium composed of H2-F2-O2-He and Al particles by focused external IR radiation is studied theoretically. It is shown that minimization of the parameters of the main pulsed HF-laser units are achievable due to both the effect of ignition of the laser-chemical reaction in an auto-wave regime under the condition of external beam focusing and the effect of a huge laser energy gain of 1011. These effects provide strong reduction of the input pulse energy necessary for initiation, down to ~10-8 J, and make it possible to construct a self-contained laser with kilojoule output energy per pulse, which can be initiated by a small sub-microjoule master oscillator powered by an accumulator. Due to an increase in the general pressure of the working gases, up to P = 2.3 bar, and optimization of the parameters of the dispersed component (Al particles with a radius of r0 = 0.09 μm and a concentration of N0 = 1.4×109 cm-3), and the composition of the working mixture, the HF-laser system will ensure an output energy up to ~ 1.5 kJ in a pulse, produced in a small volume of ~ 2 L of active medium.
A huge energy gain is predicted theoretically in a pulsed chemical laser-amplifier based on a photon-branched chain reaction initiated in a gaseous dispersed medium composed of H2-F2-O2-He and Al particles by focused external infrared radiation. It is shown that this effect is due to the possibility of ignition of the laser-chemical reaction in an initial small focal volume of the active medium. It then spreads out of this minimal volume spontaneously in the auto-wave regime without external power sources and subsequently fills the entire volume of the laser cavity with a high intensive electromagnetic field as self-supporting cylindrical photon-branching zones formed by the paths of the rays inside the unstable telescopic cavity. Calculations show that the ignition of an auto-wave photon-branched chain reaction under the condition of external signal focusing reduces strongly the input pulse energy necessary for initiation up to ~ 10-8 J, and thereby allows a huge value of the energy gain of ~ 1011. The predicted effect of this huge laser energy gain should make it possible to construct a self-contained laser, which can be initiated by a very weak source signal.
In the present report we discuss new physical principles for creating super-high-energy pulsed HF lasers and amplifiers based on a photon-branched chain reaction (PBCR). In the proposed mechanism, no external energy is consumed. We also formulate the demands for constructing lasers of this type. It is shown that a multi-pass optical scheme of a pulsed chemical HF laser allows for the initiation of an auto-wave PBCR by external radiation. Self-supporting cylindrical zones of photon branching sequentially initiated by multiple reflections by the mirrors of an unstable telescopic cavity. Such cylindrical zones of photon branching can be considered as amplifying cascades enclosed by each other. The energy emitted by each subsequent amplifying cascade considerably exceeds the energy of the previous cascade, and the number of such cascades is determined by the cavity parameters: the diameters of the mirrors, the radius of curvature of the mirrors and the diameter of the input hole for the master oscillator. Thus, this multi-pass optical scheme allows for an effective scaling of the laser output energy up to extreme high values, even for a rather small working volume of the laser. We have conducted a parametrical study of the main laser units and we offer a specific design for a self-contained pulsed HF laser with multi-mega-joule output energy in a pulse. Also, a brief historical review of chemical lasers and the idea of a PBCR is presented in this report.
It is shown theoretically and experimentally that when a Gaussian beam illuminates a bicomponent diffraction system with small Fresnel numbers, consisting of two plane screens with circular apertures on given optical axes, in a near zone of the second screen the effect of diffractive multifocal focusing of radiation is observed. In this case, the diffraction picture from the second screen in the focal planes represents the circular nonlocal bands of the Fresnel zones with a bright narrow peak at the center, whose intensity can exceed by six times the value of the incident wave intensity. The proposed diffractive method allows the focusing of the wide-aperture beams without using classical refraction elements such as lenses and prisms, and it is applicable to both low-intensive and high-power radiation. The energy efficiency of diffractive focusing of Gaussian beams is as high as 70%. Such a method can improve the energy efficiency of the fiber coupling of diode lasers and can increase the intensity of radiation on a fiber exit up to a factor of ten.
The new optical effect of a diffractive multifocal focussing of radiation, predicted by the theory, on a bicomponent diffraction system with small Fresnel numbers, consisting of two plane screens with circular apertures on a given optical axes, is confirmed experimentally. Is shown, that the diffraction picture in the focal planes of such system represents the circular nonlocal bands of the Fresnel zones with a bright narrow peak at the center, whose intensity in the experiment can exceed by six to ten times the value of the incident plane wave intensity. Experimentally is established, that the diffractive multifocal focusing of a radiation on a real screens with axial circular apertures, whose diameters exceed a radiation wavelength, is insensitive to the 'rough' external conditions: to a thickness of screens, to the irregularities of edges and non-ideal form of apertures, to a heterogeneity of initial distribution of an incident wave intensity, to changes in the medium of the wave propagation.
This course will provide training in computational problem-solving techniques used to understand and predict properties of nanoscale systems for nanomedicine applications. We will focus on applications in cancer discovery and treatment using nanoparticles. The nanodrug, selectively delivered to the tumor site, can be activated by radiation for a strong drug release, or nanoparticles can be used as a drug themselves by producing biological damage through thermal and mechanical ablations or charged particle emission. The nanodrug design includes the physical properties like material, optical, thermal, etc., and morphological properties (shape, size and structure) of nanoparticles. Emphasis of this course will be placed on how to use simulations effectively to predict plasmonic properties that occur at the nanoparticles, and compute the optical properties of normal and cancerous cell organelles for the selective nanophototherapy applications. As a result of these simulations we will predict the optimal wavelength of radiation and the size of nanoparticles of given material for nanodrug design in cancer therapy and diagnostics.