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Sample records for act intravital multiphoton

  1. From morphology to biochemical state – intravital multiphoton fluorescence lifetime imaging of inflamed human skin

    Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Getova, Valentina; Niemeyer, Verena; Zens, Katharina; Unnerstall, Tim R.; Feger, Julia S.; Fallah, Mohammad A.; Metze, Dieter; Ständer, Sonja; Luger, Thomas A.; Koenig, Karsten; Mess, Christian; Schneider, Stefan W.

    2016-03-01

    The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients’ bedsides. These ‘optical biopsies’ generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy.

  2. Correlating Intravital Multi-Photon Microscopy to 3D Electron Microscopy of Invading Tumor Cells Using Anatomical Reference Points

    Karreman, Matthia A.; Mercier, Luc; Schieber, Nicole L.; Shibue, Tsukasa; Schwab, Yannick; Goetz, Jacky G.

    2014-01-01

    Correlative microscopy combines the advantages of both light and electron microscopy to enable imaging of rare and transient events at high resolution. Performing correlative microscopy in complex and bulky samples such as an entire living organism is a time-consuming and error-prone task. Here, we investigate correlative methods that rely on the use of artificial and endogenous structural features of the sample as reference points for correlating intravital fluorescence microscopy and electr...

  3. Correlating intravital multi-photon microscopy to 3D electron microscopy of invading tumor cells using anatomical reference points.

    Matthia A Karreman

    Full Text Available Correlative microscopy combines the advantages of both light and electron microscopy to enable imaging of rare and transient events at high resolution. Performing correlative microscopy in complex and bulky samples such as an entire living organism is a time-consuming and error-prone task. Here, we investigate correlative methods that rely on the use of artificial and endogenous structural features of the sample as reference points for correlating intravital fluorescence microscopy and electron microscopy. To investigate tumor cell behavior in vivo with ultrastructural accuracy, a reliable approach is needed to retrieve single tumor cells imaged deep within the tissue. For this purpose, fluorescently labeled tumor cells were subcutaneously injected into a mouse ear and imaged using two-photon-excitation microscopy. Using near-infrared branding, the position of the imaged area within the sample was labeled at the skin level, allowing for its precise recollection. Following sample preparation for electron microscopy, concerted usage of the artificial branding and anatomical landmarks enables targeting and approaching the cells of interest while serial sectioning through the specimen. We describe here three procedures showing how three-dimensional (3D mapping of structural features in the tissue can be exploited to accurately correlate between the two imaging modalities, without having to rely on the use of artificially introduced markers of the region of interest. The methods employed here facilitate the link between intravital and nanoscale imaging of invasive tumor cells, enabling correlating function to structure in the study of tumor invasion and metastasis.

  4. Intravital multiphoton tomography as a novel tool for non-invasive in vivo analysis of human skin affected with atopic dermatitis

    Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Niemeyer, Verena; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.

    2010-02-01

    Atopic Dermatitis (AD) is an inflammatory disease of human skin. Its pathogenesis is still unknown; however, dysfunctions of the epidermal barrier and the immune response are regarded as key factors for the development of AD. In our study we applied intravital multiphoton tomography (5D-IVT), equipped with a spectral-FLIM module for in-vivo and ex-vivo analysis of human skin affected with AD. In addition to the morphologic skin analysis, FLIM technology gain access to the metabolic status of the epidermal cells referring to the NADH specific fluorescence lifetime. We evaluated a characteristic 5D-IVT skin pattern of AD in comparison to histological sections and detected a correlation with the disease activity measured by SCORAD. FLIM analysis revealed a shift of the mean fluorescence lifetime (taum) of NADH, indicating an altered metabolic activity. Within an ex-vivo approach we have investigated cryo-sections of human skin with or without barrier defects. Spectral-FLIM allows the detection of autofluorescent signals that reflect the pathophysiological conditions of the defect skin barrier. In our study the taum value was shown to be different between healthy and affected skin. Application of the 5D-IVT allows non-invasive in-vivo imaging of human skin with a penetration depth of 150 μm. We could show that affected skin could be distinguished from healthy skin by morphological criteria, by FLIM and by spectral-FLIM. Further studies will evaluate the application of the 5D-IVT technology as a diagnostic tool and to monitor the therapeutic efficacy.

  5. Intravital multiphoton imaging of the selective uptake of water-dispersible quantum dots into sinusoidal liver cells.

    Liang, Xiaowen; Grice, Jeffrey E; Zhu, Yian; Liu, David; Sanchez, Washington Y; Li, Zhen; Crawford, Darrell H G; Le Couteur, David G; Cogger, Victoria C; Liu, Xin; Xu, Zhi Ping; Roberts, Michael S

    2015-04-01

    Although many studies reporting the organ-level biodistribution of nanoparticles (NPs) in animals, very few have addressed the fate of NPs in organs at the cellular level. The liver appears to be the main organ for accumulation of NPs after intravenous injection. In this study, for the first time, the in vivo spatiotemporal disposition of recently developed mercaptosuccinic acid (MSA)-capped cadmium telluride/cadmium sulfide (CdTe/CdS) quantum dots (QDs) is explored in rat liver using multiphoton microscopy (MPM) coupled with fluorescence lifetime imaging (FLIM), with subcellular resolution (∼1 μm). With high fluorescence efficiency and largely improved stability in the biological environment, these QDs show a distinct distribution pattern in the liver compared to organic dyes, rhodamine 123 and fluorescein. After intravenous injection, fluorescent molecules are taken up by hepatocytes and excreted into the bile, while negatively charged QDs are retained in the sinusoids and selectively taken up by sinusoidal cells (Kupffer cells and liver sinusoidal endothelial cells), but not by hepatocytes within 3 h. The results could help design NPs targeting the specific types of liver cells and choose the fluorescent markers for appropriate cellular imaging. PMID:25504510

  6. Intravital microscopy

    Masedunskas, Andrius; Milberg, Oleg; Porat-Shliom, Natalie; Sramkova, Monika; Wigand, Tim; Amornphimoltham, Panomwat; Weigert, Roberto

    2012-01-01

    Intravital microscopy is an extremely powerful tool that enables imaging several biological processes in live animals. Recently, the ability to image subcellular structures in several organs combined with the development of sophisticated genetic tools has made possible extending this approach to investigate several aspects of cell biology. Here we provide a general overview of intravital microscopy with the goal of highlighting its potential and challenges. Specifically, this review is geared...

  7. Deep insights: intravital imaging with two-photon microscopy.

    Schießl, Ina Maria; Castrop, Hayo

    2016-09-01

    Intravital multiphoton microscopy is widely used to assess the structure and function of organs in live animals. Although different tissues vary in their accessibility for intravital multiphoton imaging, considerable progress has been made in the imaging quality of all tissues due to substantial technical improvements in the relevant imaging components, such as optics, excitation laser, detectors, and signal analysis software. In this review, we provide an overview of the technical background of intravital multiphoton microscopy. Then, we note a few seminal findings that were made through the use of multiphoton microscopy. Finally, we address the technical limitations of the method and provide an outlook for how these limitations may be overcome through future technical developments. PMID:27352273

  8. Intravital multiphoton tomography as an appropriate tool for non-invasive in vivo analysis of human skin affected with atopic dermatitis

    Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Mess, Christian; Dimitrova, Valentina; Schwarz, Martin; Riemann, Iris; Niemeyer, Verena; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.

    2011-03-01

    Increasing incidence of inflammatory skin diseases such as Atopic Dermatitis (AD) has been noted in the past years. According to recent estimations around 15% of newborn subjects are affected with a disease severity that requires medical treatment. Although its pathogenesis is multifactorial, recent reports indicate that an impaired physical skin barrier predispose for the development of AD. The major part of this barrier is formed by the stratum corneum (SC) wherein corneocytes are embedded in a complex matrix of proteins and lipids. Its components were synthesized in the stratum granulosum (SG) and secreted via lamellar bodies at the SC/SG interface. Within a clinical in vivo study we focused on the skin metabolism at the SC/SG interface in AD affected patients in comparison to healthy subjects. Measurement of fluorescence life-time of NADH provides access to the metabolic state of skin. Due to the application of a 5D intravital tomographic skin analysis we facilitate the non-invasive investigation of human epidermis in the longitudinal course of AD therapy. We could ascertain by blinded analysis of 40 skin areas of 20 patients in a three month follow-up that the metabolic status at the SC/SG interface was altered in AD compromised skin even in non-lesional, apparent healthy skin regions. This illustrates an impaired skin barrier formation even at non-affected skin of AD subjects appearing promotive for the development of acute skin inflammation. Therefore, our findings allow a deeper understanding of the individual disease development and the improved management of the therapeutic intervention in clinical application.

  9. Microbial pathogenesis revealed by intravital microscopy: pros, cons and cautions.

    Stolp, Bettina; Melican, Keira

    2016-07-01

    Intravital multiphoton imaging allows visualization of infections and pathogenic mechanisms within intact organs in their physiological context. Today, most organs of mice and rats are applicable to in vivo or ex vivo imaging, opening completely new avenues for many researchers. Advances in fluorescent labeling of pathogens and infected cells, as well as improved small animal models for human pathogens, led to the increased application of in vivo imaging in infectious diseases research in recent years. Here, we review the latest literature on intravital or ex vivo imaging of viral and bacterial infections and critically discuss requirements, benefits and drawbacks of applied animal models, labeling strategies, and imaged organs. PMID:26938770

  10. Fluorescent Tobacco mosaic virus-Derived Bio-Nanoparticles for Intravital Two-Photon Imaging

    Niehl, Annette; Appaix, Florence; Boscá, Sonia; van der Sanden, Boudewijn; Nicoud, Jean-François; Bolze, Frédéric; Heinlein, Manfred

    2016-01-01

    Multi-photon intravital imaging has become a powerful tool to investigate the healthy and diseased brain vasculature in living animals. Although agents for multi-photon fluorescence microscopy of the microvasculature are available, issues related to stability, bioavailability, toxicity, cost or chemical adaptability remain to be solved. In particular, there is a need for highly fluorescent dyes linked to particles that do not cross the blood brain barrier (BBB) in brain diseases like tumor or stroke to estimate the functional blood supply. Plant virus particles possess a number of distinct advantages over other particles, the most important being the multi-valency of chemically addressable sites on the particle surface. This multi-valency, together with biological compatibility and inert nature, makes plant viruses ideal carriers for in vivo imaging agents. Here, we show that the well-known Tobacco mosaic virus is a suitable nanocarrier for two-photon dyes and for intravital imaging of the mouse brain vasculature. PMID:26793221

  11. Highly resolved intravital striped-illumination microscopy of germinal centers.

    Cseresnyes, Zoltan; Oehme, Laura; Andresen, Volker; Sporbert, Anje; Hauser, Anja E; Niesner, Raluca

    2014-01-01

    Monitoring cellular communication by intravital deep-tissue multi-photon microscopy is the key for understanding the fate of immune cells within thick tissue samples and organs in health and disease. By controlling the scanning pattern in multi-photon microscopy and applying appropriate numerical algorithms, we developed a striped-illumination approach, which enabled us to achieve 3-fold better axial resolution and improved signal-to-noise ratio, i.e. contrast, in more than 100 µm tissue depth within highly scattering tissue of lymphoid organs as compared to standard multi-photon microscopy. The acquisition speed as well as photobleaching and photodamage effects were similar to standard photo-multiplier-based technique, whereas the imaging depth was slightly lower due to the use of field detectors. By using the striped-illumination approach, we are able to observe the dynamics of immune complex deposits on secondary follicular dendritic cells - on the level of a few protein molecules in germinal centers. PMID:24748007

  12. Multiphoton processes: conference proceedings

    The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base

  13. Multiphoton processes: conference proceedings

    Lambropoulos, P.; Smith, S.J. (eds.)

    1984-01-01

    The chapters of this volume represent the invited papers delivered at the conference. They are arranged according to thermatic proximity beginning with atoms and continuing with molecules and surfaces. Section headings include multiphoton processes in atoms, field fluctuations and collisions in multiphoton process, and multiphoton processes in molecules and surfaces. Abstracts of individual items from the conference were prepared separately for the data base. (GHT)

  14. Multiphoton bibliography, 1980

    This bibliography expands the collection of references appearing in multiphoton bibliography 1970-76, edited by J.H. Eberly and B. Karczewski, and the multiphoton bibliographies 1977, 1978, and 1979, edited by J.H. Eberly, J.W. Gallagher and E.C. Beaty. Items are included based on a list of words and phrases (e.g., multiphoton, intense field, strong field, multiple photon, 2-photon, 3-photon, etc.) or their equivalents appearing in an article's title or abstract

  15. Multiphoton ionization of atoms

    The paper is devoted to the analysis of high intensity effects which result from multiphoton ionization of atoms in a high laser intensity, ranging from 1010 to 1015 W cm-2. Resonant multiphoton ionization of atoms, the production of multiply charged ions, and electron energy spectra, are all discussed. (U.K.)

  16. Fluorescein Derivatives in Intravital Fluorescence Imaging

    Michael S. Roberts

    2013-08-01

    Full Text Available Intravital fluorescence microscopy enables the direct imaging of fluorophores in vivo and advanced techniques such as fluorescence lifetime imaging (FLIM enable the simultaneous detection of multiple fluorophores. Consequently, it is now possible to record distribution and metabolism of a chemical in vivo and to optimise the delivery of fluorophores in vivo. Recent clinical applications with fluorescein and other intravital fluorescent stains have occurred in neurosurgery, dermatology [including photodynamic therapy (PDT] and endomicroscopy. Potential uses have been identified in periodontal disease, skin graft and cancer surgery. Animal studies have demonstrated that diseased tissue can be specifically stained with fluorophore conjugates. This review focuses on the fluorescein derived fluorophores in common clinical use and provides examples of novel applications from studies in tissue samples.

  17. MULTIPHOTON IONIZATION OF ATOMS

    Mainfray, G.

    1985-01-01

    Multiphoton ionization of one-electron atoms, such as atomic hydrogen and alkaline atoms, is well understood and correctly described by rigorous theoretical models. The present paper will be devoted to collisionless multiphoton ionization of many-electron atoms as rare gases. It induces removal of several electrons and the production of multiply charged ions. Up to Xe5+ ions are produced in Xe atoms. Doubly charged ions can be produced, either by simultaneous excitation of two electrons, or b...

  18. Multiphoton Squeezed States

    YANGXiao-Xue; WUYing

    2003-01-01

    We present analytical results for the multiphoton squeezed states defined through nonlinear quadrature-dependent Bogoliubov transformations. These analytical results turn a nonlinear problem into an essentially linear one and they can be utilized to express explicitly the mean walues and deviations of the quadrature operators and the photon variables under the multiphoton states in terms of those quantities averaged over the standard squeezed states which only involves the quadrature-independent Bogoliubov transformation.

  19. Multiphoton Squeezed States

    YANG Xiao-Xue; WU Ying

    2003-01-01

    We present analytical results for the multiphoton squeezed states defined through nonlinear quadraturedependent Bogoliubov transformations. These analytical results turn a nonlinear problem into an essentially linear one and they can be utilized to express explicitly the mean values and deviations of the quadrature operators and the photon variables under the multiphoton states in terms of those quantities averaged over the standard squeezed states which only involves the quadrature-independent Bogoliubov transformation.

  20. Multiphoton ionization of atoms

    This article provides an overview of the current understanding of multiphoton ionization of atoms. It begins with an introductory section to explain the background of the subject. Then the article develops the three topics which have been central themes of discussion in multiphoton ionization of atoms these past few years: multiply charged ion production, very high order harmonic generation, and above-threshold ionization, a name given to the absorption of a very large number of photons by an already ionized electron. A large part of the review is devoted to some theoretical aspects of multiphoton ionization of atoms and especially non-perturbative theories. Finally the article considers the very near future prospects of laser-electron interactions and more generally laser-matter interactions at 1018 -1019 W cm-2, an intensity range now within reach due to new short pulse laser technology. (author)

  1. Multiphoton microscopy in neuroscience

    Denk, Winfried

    2002-06-01

    The study of the nervous system requires to an exceptional extent observation of and experimentation on intact tissue. There, in particular, high-resolution optical microscopy benefits from the inherent advantages of multi-photon fluorescence excitation. Several cases will be presented from a number of different tissues and organisms, where multi-photon excited laser scanning fluorescence microscopy has been an essential experimental tool. Those examples include the discovery of biochemical coincidence detection in synaptic spines and the clarification of the underlying mechanism; the observation of sensory evoked dendritic signaling in intact animals and the observation of light induced calcium signals in the intact retina. Recently a fiber coupled two-photon microscopy has been developed that allows the imaging in moving animal.

  2. Clinical multiphoton FLIM tomography

    König, Karsten

    2012-03-01

    This paper gives an overview on current clinical high resolution multiphoton fluorescence lifetime imaging in volunteers and patients. Fluorescence lifetime imaging (FLIM) in Life Sciences was introduced in Jena/Germany in 1988/89 based on a ZEISS confocal picosecond dye laser scanning microscope equipped with a single photon counting unit. The porphyrin distribution in living cells and living tumor-bearing mice was studied with high spatial, temporal, and spectral resolution. Ten years later, time-gated cameras were employed to detect dental caries in volunteers based on one-photon excitation of autofluorescent bacteria with long fluorescence lifetimes. Nowadays, one-photon FLIM based on picosecond VIS laser diodes are used to study ocular diseases in humans. Already one decade ago, first clinical twophoton FLIM images in humans were taken with the certified clinical multiphoton femtosecond laser tomograph DermaInspectTM. Multiphoton tomographs with FLIM modules are now operating in hospitals at Brisbane, Tokyo, Berlin, Paris, London, Modena and other European cities. Multiple FLIM detectors allow spectral FLIM with a temporal resolution down to 20 ps (MCP) / 250 ps (PMT) and a spectral resolution of 10 nm. Major FLIM applications include the detection of intradermal sunscreen and tattoo nanoparticles, the detection of different melanin types, the early diagnosis of dermatitis and malignant melanoma, as well as the measurement of therapeutic effects in pateints suffering from dermatitis. So far, more than 1,000 patients and volunteers have been investigated with the clinical multiphoton FLIM tomographs DermaInspectTM and MPTflexTM.

  3. Intravital Microscopy for THz-Bio Analysis

    Kim, Pilhan

    Intravital microscopy is a high-resolution imaging technique to observe biological phenomena in living organisms. It often also stated as in vivo microscopy. Literal meaning of in vivo is "within the living" and there is another term, ex vivo of which literal meaning is "out of the living". Both terms are commonly used to describe the status of sample at the moment of biological manipulations or investigations are done. In vivo study is a form of research using whole living organism in experiment to investigate a certain biological phenomenon in its natural environment, whereas ex vivo study uses non-living subjects such as tissues or organs dissected from dead animal. In addition, in vitro of which literal meaning is "within the glass" is another commonly used term. In vitro study is a form of research using small living subject such as cell in a controlled environment such as petri dish or test tube. Cell culture, the process of growing cells in a petri dish, is the most common form of in vitro study. Figure 1 summarizes the status of samples for biological study categorized by in vivo, in vitro and ex vivo.

  4. Multiphoton ionization of polarized atoms

    A theory is derived for the multiphoton ionization of polarized atoms. The angular distributions of the differential and total ionization probabilities are studied for various polarizations of the electromagnetic radiation. The circular dichroism is also studied. The multiphoton ionization of oriented s-state atoms near a resonance is studied separately. Some relevant experiments which might be carried out are discussed

  5. Multiphoton ionization of polarized atoms

    A theory of multiphoton ionization of polarized atoms is developed. The angular dependences of the different and total ionization probabilities for various polarizations of the radiation and the circular dichroism effect are investigated. Multiphoton ionization of oriented in the s-states near resonance is considered separately

  6. Microhemodynamic parameters quantification from intravital microscopy videos

    Blood flow and blood–endothelium interactions correspond with the genesis of cardiovascular diseases. Therefore, quantitative analysis of blood flow dynamics at the microcirculation level is of special interest. Regulatory mechanisms mediated by blow flow have been studied in detail using in vitro approaches. However, these mechanisms have not been fully validated in vivo due to technical limitations that arise when quantifying microhemodynamics with the required level of detail. Intravital microscopy combined with high-speed video recordings has been used for the analysis of blood flow in small blood vessels of chronic and acute experimental tissue preparations. This tool can be used to study the interaction between the flowing blood and the vessel walls of arterioles and venules with sufficient temporal and spatial resolution. Our objective was to develop a simple and robust cross-correlation algorithm for the automatic analysis of high-speed video recordings of microcirculatory blood flow. The algorithm was validated using in vitro and in vivo systems. Results indicate that the algorithm's ability to estimate the velocity of local red blood cells as a function of blood vessel radius is highly accurate. They thereby suggest that the algorithm could be used to explore dynamic changes in blood flow under different experimental conditions including a wide range of flow rates and hematocrit levels. The algorithm can also be used to measure volumetric flow rates, radial velocity profiles, wall shear rate, and wall shear stress. Several applications are presently explored, including the analysis of velocity profiles in the branches of arterial bifurcations. This work demonstrates the robustness of the cross-correlation technique in various flow conditions and elucidates its potential application for in vivo determination of blood flow dynamics in the microcirculation. (paper)

  7. Intravital Microscopy for Imaging the Tumor Microenvironment in Live Mice.

    Naumenko, Victor; Jenne, Craig; Mahoney, Douglas J

    2016-01-01

    The development of intravital microscopy has provided unprecedented capacity to study the tumor microenvironment in live mice. The dynamic behavior of cancer, stromal, vascular, and immune cells can be monitored in real time, in situ, in both primary tumors and metastatic lesions, allowing treatment responses to be observed at single cell resolution and therapies tracked in vivo. These features provide a unique opportunity to elucidate the cellular mechanisms underlying the biology and treatment of cancer. We describe here a method for imaging the microenvironment of subcutaneous tumors grown in mice using intravital microscopy. PMID:27581025

  8. Calculation of multiphoton ionization processes

    Chang, T. N.; Poe, R. T.

    1976-01-01

    We propose an accurate and efficient procedure in the calculation of multiphoton ionization processes. In addition to the calculational advantage, this procedure also enables us to study the relative contributions of the resonant and nonresonant intermediate states.

  9. Phase modulated multiphoton microscopy

    Karki, Khadga Jung; Pullerits, Tonu

    2015-01-01

    We show that the modulation of the phases of the laser beams of ultra-short pulses leads to modulation of the two photon fluorescence intensity. The phase modulation technique when used in multi-photon microscopy can improve the signal to noise ratio. The technique can also be used in multiplexing the signals in the frequency domain in multi-focal raster scanning microscopy. As the technique avoids the use of array detectors as well as elaborate spatiotemporal multiplexing schemes it provides a convenient means to multi-focal scanning in axial direction. We show examples of such uses. Similar methodology can be used in other non-linear scanning microscopies, such as second or third harmonic generation microscopy.

  10. Multiphoton ionization of Uracil

    Prieto, Eladio; Martinez, Denhi; Guerrero, Alfonso; Alvarez, Ignacio; Cisneros, Carmen

    2016-05-01

    Multiphoton ionization and dissociation of Uracil using a Reflectron time of flight spectrometer was performed along with radiation from the second harmonic of a Nd:YAG laser. Uracil is one of the four nitrogen bases that belong to RNA. The last years special interest has been concentrated on the study of the effects under UV radiation in nucleic acids1 and also in the role that this molecule could have played in the origin and development of life on our planet.2 The MPI mass spectra show that the presence and intensity of the resulting ions strongly depend on the density power. The identification of the ions in the mass spectra is presented. The results are compared with those obtained in other laboratories under different experimental conditions and some of them show partial agreement.3 The present work was supported by CONACYT-Mexico Grant 165410 and DGAPA UNAM Grant IN101215 and IN102613.

  11. Intravital Fluorescence Videomicroscopy to Study Tumor Angiogenesis and Microcirculation

    Peter Vajkoczy

    2000-01-01

    Full Text Available Angiogenesis and microcirculation play a central role in growth and metastasis of human neoplasms, and, thus, represent a major target for novel treatment strategies. Mechanistic analysis of processes involved in tumor vascularization, however, requires sophisticated in vivo experimental models and techniques. Intravital microscopy allows direct assessment of tumor angiogenesis, microcirculation and overall perfusion. Its application to the study of tumor-induced neovascularization further provides information on molecular transport and delivery, intra- and extravascular cell-to-cell and cell-tomatrix interaction, as well as tumor oxygenation and metabolism. With the recent advances in the field of bioluminescence and fluorescent reporter genes, appropriate for in vivo imaging, the intravital fluorescent microscopic approach has to be considered a powerful tool to study microvascular, cellular and molecular mechanisms of tumor growth.

  12. Intravital FRET: Probing Cellular and Tissue Function in Vivo.

    Radbruch, Helena; Bremer, Daniel; Mothes, Ronja; Günther, Robert; Rinnenthal, Jan Leo; Pohlan, Julian; Ulbricht, Carolin; Hauser, Anja E; Niesner, Raluca

    2015-01-01

    The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo-ratiometrically and time-resolved by fluorescence lifetime imaging-and show their concrete application in the context of neuroinflammation in adult mice. PMID:26006244

  13. Intravital FRET: Probing Cellular and Tissue Function in Vivo

    Helena Radbruch; Daniel Bremer; Ronja Mothes; Robert Günther; Jan Leo Rinnenthal; Julian Pohlan; Carolin Ulbricht; Hauser, Anja E.; Raluca Niesner

    2015-01-01

    The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context o...

  14. Intravital microscopy to image membrane trafficking in live rats

    Masedunskas, Andrius; Sramkova, Monika; Parente, Laura; Weigert, Roberto

    2013-01-01

    Intravital microscopy (IVM) is a powerful tool that enables imaging various biological processes in live animals. Here, we describe a series of procedures designed to image subcellular structures, such as endsosomes and secretory vesicles in the salivary glands (SGs) of live rats. To this aim, we used fluorescently labeled molecules and/or fluorescently-tagged proteins that were transiently transfected in the live animal.

  15. Multiphotons and Photon-Jets

    Toro, Natalia; Yavin, Itay(Perimeter Institute for Theoretical Physics, Waterloo, ON, Canada)

    2012-01-01

    We discuss an extension of the Standard Model with a new vector-boson decaying predominantly into a multi-photon final state through intermediate light degrees of freedom. The model has a distinctive phase in which the photons are collimated. As such, they would fail the isolation requirements of standard multi-photon searches, but group naturally into a novel object, the photon-jet. Once defined, the photon-jet object facilitates more inclusive searches for similar phenomena. We present a co...

  16. Intravital FRET: Probing Cellular and Tissue Function in Vivo

    Helena Radbruch

    2015-05-01

    Full Text Available The development of intravital Förster Resonance Energy Transfer (FRET is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice.

  17. Compact non-contact total emission detection for in vivo multiphoton excitation microscopy.

    Combs, C A; Smirnov, A; Glancy, B; Karamzadeh, N S; Gandjbakhche, A H; Redford, G; Kilborn, K; Knutson, J R; Balaban, R S

    2014-02-01

    We describe a compact, non-contact design for a total emission detection (c-TED) system for intra-vital multiphoton imaging. To conform to a standard upright two-photon microscope design, this system uses a parabolic mirror surrounding a standard microscope objective in concert with an optical path that does not interfere with normal microscope operation. The non-contact design of this device allows for maximal light collection without disrupting the physiology of the specimen being examined. Tests were conducted on exposed tissues in live animals to examine the emission collection enhancement of the c-TED device compared to heavily optimized objective-based emission collection. The best light collection enhancement was seen from murine fat (5×-2× gains as a function of depth), whereas murine skeletal muscle and rat kidney showed gains of over two and just under twofold near the surface, respectively. Gains decreased with imaging depth (particularly in the kidney). Zebrafish imaging on a reflective substrate showed close to a twofold gain throughout the entire volume of an intact embryo (approximately 150 μm deep). Direct measurement of bleaching rates confirmed that the lower laser powers, enabled by greater light collection efficiency, yielded reduced photobleaching in vivo. The potential benefits of increased light collection in terms of speed of imaging and reduced photo-damage, as well as the applicability of this device to other multiphoton imaging methods is discussed. PMID:24251437

  18. Multi-photon excitation microscopy

    Faretta Mario; Vicidomini Giuseppe; Bianchini Paolo; Diaspro Alberto; Ramoino Paola; Usai Cesare

    2006-01-01

    Abstract Multi-photon excitation (MPE) microscopy plays a growing role among microscopical techniques utilized for studying biological matter. In conjunction with confocal microscopy it can be considered the imaging workhorse of life science laboratories. Its roots can be found in a fundamental work written by Maria Goeppert Mayer more than 70 years ago. Nowadays, 2PE and MPE microscopes are expected to increase their impact in areas such biotechnology, neurobiology, embryology, tissue engine...

  19. Intravital microscopy of subpleural alveoli via transthoracic endoscopy

    Schwenninger, David; Runck, Hanna; Schumann, Stefan; Haberstroh, Jörg; Meissner, Sven; Koch, Edmund; Guttmann, Josef

    2011-04-01

    Transfer of too high mechanical energy from the ventilator to the lung's alveolar tissue is the main cause for ventilator-induced lung injury (VILI). To investigate the effects of cyclic energy transfer to the alveoli, we introduce a new method of transthoracic endoscopy that provides morphological as well as functional information about alveolar geometry and mechanics. We evaluate the new endoscopic method to continuously record images of focused subpleural alveoli. The method is evaluated by using finite element modeling techniques and by direct observation of subpleural alveoli both in isolated rat lungs as well as in intact animals (rats). The results confirm the overall low invasiveness of the endoscopic method insofar as the mechanical influences on the recorded alveoli are only marginal. It is, hence, a suited method for intravital microscopy in the rat model as well as in larger animals.

  20. Multiphoton quantum optics and quantum state engineering

    We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms that are relevant for the conceptual investigations as well as for the practical applications of forefront aspects of modern quantum mechanics. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromagnetic field, either in discrete or in continuous variables, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information

  1. Multiphoton quantum optics and quantum state engineering

    Dell' Anno, Fabio [Dipartimento di Fisica ' E. R. Caianiello' , Universita degli Studi di Salerno, CNISM and CNR-INFM Coherentia, and INFN Sezione di Napoli, Gruppo Collegato di Salerno, Via S. Allende, I-84081 Baronissi (Saudi Arabia) (Italy)]. E-mail: dellanno@sa.infn.it; De Siena, Silvio [Dipartimento di Fisica ' E. R. Caianiello' , Universita degli Studi di Salerno, CNISM and CNR-INFM Coherentia, and INFN Sezione di Napoli, Gruppo Collegato di Salerno, Via S. Allende, I-84081 Baronissi (SA) (Italy)]. E-mail: desiena@sa.infn.it; Illuminati, Fabrizio [Dipartimento di Fisica ' E. R. Caianiello' , Universita degli Studi di Salerno, CNISM and CNR-INFM Coherentia, and INFN Sezione di Napoli, Gruppo Collegato di Salerno, Via S. Allende, I-84081 Baronissi (SA) (Italy)]. E-mail: illuminati@sa.infn.it

    2006-05-15

    We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms that are relevant for the conceptual investigations as well as for the practical applications of forefront aspects of modern quantum mechanics. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromagnetic field, either in discrete or in continuous variables, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information.

  2. Intravital microscopy as a tool to study drug delivery in preclinical studies

    Amornphimoltham, Panomwat; Masedunskas, Andrius; Weigert, Roberto

    2010-01-01

    The technical developments in the field of non-linear microscopy have made intravital microscopy one of the most successful techniques for studying physiological and pathological processes in live animals. Intravital microscopy has been utilized to address many biological questions in basic research and is now a fundamental tool for preclinical studies, with an enormous potential for clinical applications. The ability to dynamically image cellular and subcellular structures combined with the ...

  3. Multiphoton spectroscopy in heavy elements

    Solarz, R.W.; Paisner, J.A.; Worden, E.F.

    1977-05-03

    Some recently discovered regularities in the spectra of heavy elements which are also applicable to the analysis of the spectra of lighter atoms are described. It is pointed out that stepwise resonant multiphoton methods are irreplaceable tools in the study of high lying states in a complex atomic system. Systematic applications of these methods has permitted regularities to be observed which also hold for the lighter elements. It is noted that greatly increased understanding of the excited state structure of heavy atoms is not possible. 8 references. (JFP)

  4. Multiphoton dissociation of polyatomic molecules

    The dynamics of infrared multiphoton excitation and dissociation of SF6 was investigated under collision free conditions by a crossed laser-molecular beam method. In order to understand the excitation mechanism and to elucidate the requirements of laser intensity and energy fluence, a series of experiments were carried out to measure the dissociation yield dependences on energy fluence, vibrational temperature of SF6, the pulse duration of the CO2 laser and the frequency in both one and two laser experiments. Translational energy distributions of the SF5 dissociation product measured by time of flight and angular distributions and the dissociation lifetime of excited SF6 as inferred from the observation of secondary dissociation of SF5 into SF4 and F during the laser pulse suggest that the dynamics of dissociation of excited molecules is dominated by complete energy randomization and rapid intramolecular energy transfer on a nanosecond timescale, and can be adequately described by RRKM theory. An improved phenomenological model including the initial intensity dependent excitation, a rate equation describing the absorption and stimulated emission of single photons, and the unimolecular dissociation of excited molecules is constructed based on available experimental results. The model shows that the energy fluence of the laser determines the excitation of molecules in the quasi-continuum and the excess energy with which molecules dissociate after the laser pulse. The role played by the laser intensity in multiphoton dissociation is more significant than just that of overcoming the intensity dependent absorption in the lowest levels. 63 references

  5. Structure of multiphoton quantum optics. II. Bipartite systems, physical processes, and heterodyne squeezed states

    Dell'Anno, F; Illuminati, F; Anno, Fabio Dell'; Siena, Silvio De; Illuminati, Fabrizio

    2004-01-01

    Extending the scheme developed for a single mode of the electromagnetic field in the preceding paper ``Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states'', we introduce two-mode nonlinear canonical transformations depending on two heterodyne mixing angles. They are defined in terms of hermitian nonlinear functions that realize heterodyne superpositions of conjugate quadratures of bipartite systems. The canonical transformations diagonalize a class of Hamiltonians describing non degenerate and degenerate multiphoton processes. We determine the coherent states associated to the canonical transformations, which generalize the non degenerate two--photon squeezed states. Such heterodyne multiphoton squeezed are defined as the simultaneous eigenstates of the transformed, coupled annihilation operators. They are generated by nonlinear unitary evolutions acting on two-mode squeezed states. They are non Gaussian, highly non classical, entangled states. For a quadratic nonline...

  6. Multiphoton microscopy: An introduction to gastroenterologists

    Hye Jin Cho; Hoon Jai Chun; Eun Sun Kim; Bong Rae Cho

    2011-01-01

    Multiphoton microscopy, relying on the simultaneous absorption of two or more photons by a fluorophore, has come to occupy a prominent place in modern biomedical research with its ability to allow real-time observation of a single cell and molecules in intact tissues. Multiphoton microscopy exhibits nonlinear optical contrast properties, which can make it possible to provide an exceptionally large depth penetration with less phototoxicity. This system becomes more and more an inspiring tool for a non-invasive imaging system to realize "optical biopsy" and to examine the functions of living cells. In this review, we briefly present the physical principles and properties of multiphoton microscopy as well as the current applications in biological fields. In addition, we address what we see as the future potential of multiphoton microscopy for gastroenterologic research.

  7. Multiphoton Quantum Optics and Quantum State Engineering

    Dell'Anno, F; Illuminati, F; 10.1016/j.physrep.2006.01.004

    2009-01-01

    We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states...

  8. MULTI-PHOTON PHOSPHOR FEASIBILITY RESEARCH

    R. Graham; W. Chow

    2003-05-01

    Development of multi-photon phosphor materials for discharge lamps represents a goal that would achieve up to a doubling of discharge (fluorescent) lamp efficacy. This report reviews the existing literature on multi-photon phosphors, identifies obstacles in developing such phosphors, and recommends directions for future research to address these obstacles. To critically examine issues involved in developing a multi-photon phosphor, the project brought together a team of experts from universities, national laboratories, and an industrial lamp manufacturer. Results and findings are organized into three categories: (1) Multi-Photon Systems and Processes, (2) Chemistry and Materials Issues, and (3) Concepts and Models. Multi-Photon Systems and Processes: This category focuses on how to use our current understanding of multi-photon phosphor systems to design new phosphor systems for application in fluorescent lamps. The quickest way to develop multi-photon lamp phosphors lies in finding sensitizer ions for Gd{sup 3+} and identifying activator ions to red shift the blue emission from Pr{sup 3+} due to the {sup 1}S{sub 0} {yields} {sup 1}I{sub 6} transition associated with the first cascading step. Success in either of these developments would lead to more efficient fluorescent lamps. Chemistry and Materials Issues: The most promising multi-photon phosphors are found in fluoride hosts. However, stability of fluorides in environments typically found in fluorescent lamps needs to be greatly improved. Experimental investigation of fluorides in actual lamp environments needs to be undertaken while working on oxide and oxyfluoride alternative systems for backup. Concepts and Models: Successful design of a multi-photon phosphor system based on cascading transitions of Gd{sup 3+} and Pr{sup 3+} depends critically on how the former can be sensitized and the latter can sensitize an activator ion. Methods to predict energy level diagrams and Judd-Ofelt parameters of multi-photon

  9. Differential Multiphoton Laser Scanning Microscopy

    Field, Jeffrey J.; Sheetz, Kraig E.; Chandler, Eric V.; Hoover, Erich E.; Young, Michael D.; Ding, Shi-you; Sylvester, Anne W.; Kleinfeld, David; Squier, Jeff A.

    2016-01-01

    Multifocal multiphoton microscopy (MMM) in the biological and medical sciences has become an important tool for obtaining high resolution images at video rates. While current implementations of MMM achieve very high frame rates, they are limited in their applicability to essentially those biological samples that exhibit little or no scattering. In this paper, we report on a method for MMM in which imaging detection is not necessary (single element point detection is implemented), and is therefore fully compatible for use in imaging through scattering media. Further, we demonstrate that this method leads to a new type of MMM wherein it is possible to simultaneously obtain multiple images and view differences in excitation parameters in a single shot.

  10. ATOMS INTERACTING WITH ELECTROMAGNETIC FIELDS, MULTIPHOTON IONIZATION

    Mainfray, G

    1982-01-01

    The non linear interaction between an intense laser radiation and atoms leads to ionization through the absorption of N photons from the laser radiation via laser-induced virtual states. The multiphoton ionization rate varies as a function of the laser intensity I as IN. We discuss the two most important effects which govern multiphoton ionization processes : resonance effects and laser-coherence effects. In a moderate laser intensity range (107 - 109 W cm-2) corresponding to the two, three o...

  11. Quantum electrodynamic perspective on multiphoton ionization

    A fully quantum nonperturbative method is developed to describe multiphoton ionization in intense fields. It is shown that, treating the radiation field with quantum electrodynamic (QED) theory enables the authors to obtain the above-threshold ionization energy distribution spectrum in analytical form firstly. Moreover, in addition to the well-known semiclassical theory, the framework presented here, derived from a QED perspective, provides a new picture of the multiphoton ionization

  12. Multiphoton Quantum Optics and Quantum State Engineering

    Dell'Anno, F.; Siena, S; Illuminati, F.

    2007-01-01

    We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously ...

  13. Multiphoton excitation spectra in biological samples

    Dickinson, Mary E.; Simbuerger, Eva; Zimmermann, Bernhard; Waters, Christopher W.; Fraser, Scott E.

    2003-01-01

    Multiphoton microscopy is becoming a popular mode of live and fixed cell imaging. This mode of imaging offers several advantages due to the fact that fluorochrome excitation is a nonlinear event resulting in excitation only at the plane of focus. Multiphoton excitation is enhanced by the use of ultrafast lasers emitting in the near IR, offering better depth penetration coupled with efficient excitation. Because these lasers, such as titanium:sapphire lasers, offer tunable output it is possibl...

  14. Multiphoton ionization of uranium hexafluoride

    Multiphoton ionization (MPI) time-of-flight mass spectroscopy (TOFMS) and photoelectron spectroscopy (PES) studies of UF6 are reported using focused light from the Nd:YAG laser fundamental (λ=1064 nm) and its harmonics (λ=532, 355, or 266 nm), as well as other wavelengths provided by a tunable dye laser. The MPI mass spectra are dominated by the singly and multiply charged uranium ions rather than by the UF+x fragment ions, even at the lowest laser power densities at which signal could be detected. In general, the doubly charged uranium ion (U2+) intensity is much greater than that of the singly charged uranium ion (U+). For the case of the tunable dye laser experiments, the Un+ (n=1--4) wavelength dependence is relatively unstructured and does not show observable resonance enhancement at known atomic uranium excitation wavelengths. The MPI-PES studies reveal only very slow electrons (≤0.5 eV) for all wavelengths investigated. The dominance of the U2+ ion, the absence or very small intensities of UF+x (x=1--3) fragments, the unstructured wavelength dependence, and the preponderance of slow electrons all indicate that mechanisms may exist other than ionization of bare U atoms following the stepwise photodissociation of F atoms from the parent molecule. The data also argue against stepwise photodissociation of UF+x (x=5,6) ions. Neither of the traditional MPI mechanisms (''neutral ladder'' or the ''ionic ladder'') are believed to adequately describe the ionization phenomena observed. We propose that the multiphoton excitation of UF6 under these experimental conditions results in a highly excited molecule, superexcited UF6**

  15. Multiphoton ionization and multiphoton resonances in the tunneling regime

    The rate of ionization of an atom of helium, argon, or hydrogen exposed to an intense monochromatic laser field and the quasienergy spectrum of their dressed states are studied for values of the Keldysh parameter between 1 and 0.6 and wavelengths between 390 and 1300 nm. The calculations are carried out within the non-Hermitian Floquet theory. Resonances with intermediate excited states significantly affect ionization from the dressed ground state at all the intensities and all the wavelengths considered. The dressed excited states responsible for these structures are large-α0 states akin to the Kramers-Henneberger states of the high-frequency Floquet theory. Within the single-active-electron approximation, these large-α0 states become species independent at sufficiently high intensity or sufficiently long wavelength. Apart for the resonance structures arising from multiphoton coupling with excited states, the ab initio Floquet ionization rate is in excellent agreement with the predictions of two different calculations in the strong field approximation, one based on a length-gauge formulation of this approximation and one based on a velocity-gauge formulation. The calculations also confirm the validity of the ω2 expansion as an alternative to the strong field approximation for taking into account the nonadiabaticity of the ionization process in intense low-frequency laser fields.

  16. Multiphoton ionization of uranium hexafluoride

    Armstrong, D. P.; Harkins, D. A.; Compton, R. N.; Ding, D.

    1994-01-01

    Multiphoton ionization (MPI) time-of-flight mass spectroscopy (TOFMS) and photoelectron spectroscopy (PES) studies of UF6 are reported using focused light from the Nd:YAG laser fundamental (λ=1064 nm) and its harmonics (λ=532, 355, or 266 nm), as well as other wavelengths provided by a tunable dye laser. The MPI mass spectra are dominated by the singly and multiply charged uranium ions rather than by the UF+x fragment ions, even at the lowest laser power densities at which signal could be detected. In general, the doubly charged uranium ion (U2+) intensity is much greater than that of the singly charged uranium ion (U+). For the case of the tunable dye laser experiments, the Un+ (n=1-4) wavelength dependence is relatively unstructured and does not show observable resonance enhancement at known atomic uranium excitation wavelengths. The MPI-PES studies reveal only very slow electrons (≤0.5 eV) for all wavelengths investigated. The dominance of the U2+ ion, the absence or very small intensities of UF+x (x=1-3) fragments, the unstructured wavelength dependence, and the preponderance of slow electrons all indicate that mechanisms may exist other than ionization of bare U atoms following the stepwise photodissociation of F atoms from the parent molecule. The data also argue against stepwise photodissociation of UF+x (x=5,6) ions. Neither of the traditional MPI mechanisms (``neutral ladder'' or the ``ionic ladder'') are believed to adequately describe the ionization phenomena observed. We propose that the multiphoton excitation of UF6 under these experimental conditions results in a highly excited molecule, superexcited UF6**. The excitation of highly excited UF6** is proposed to be facilitated by the well known ``giant resonance,'' whose energy level lies in the range of 12-14 eV above that of ground state UF6. The highly excited molecule then primarily dissociates, via multiple channels, into Un+, UF+x, fluorine atoms, and ``slow'' electrons, although dissociation

  17. Multiphoton ionization of H- and He in intense laser fields

    The recently proposed R-matrix-Floquet theory of multiphoton processes has been used to calculate multiphoton ionization rates for the two-electron systems H- and He in intense laser fields. The theory is nonperturbative and includes electron-electron correlations. Results are presented for total and partial multiphoton ionization rates and novel nonperturbative correlation effects are discussed

  18. Multiphoton ionization of atomic cesium

    We describe experimental studies of resonantly enhanced multiphoton ionization (MPI) of cesium atoms in the presence and absence of an external electric field. In the zero-field studies, photoelectron angular distributions for one- and two-photon resonantly enhanced MPI are compared with the theory of Tang and Lambropoulos. Deviations of experiment from theory are attributed to hyperfine coupling effects in the resonant intermediate state. The agreement between theory and experiment is excellent. In the absence of an external electric field, signal due to two-photon resonant three-photon ionization of cesium via np states is undetectable. Application of an electric field mixes nearby nd and ns levels, thereby inducing excitation and subsequent ionization. Signal due to two-photon excitation of ns levels in field-free experiments is weak due to their small photoionization cross section. An electric field mixes nearby np levels which again allows detectable photoionization signal. For both ns and np states the field induced MPI signal increases as the square of the electric field for a given principal quantum number and increases rapidly with n for a given field strength. Finally, we note that the classical two-photon field-ionization threshold is lower for the case in which the laser polarization and the electric field are parallel than it is when they are perpendicular. 22 references, 11 figures

  19. Clinical multiphoton and CARS microscopy

    Breunig, H. G.; Weinigel, M.; Darvin, M. E.; Lademann, J.; König, K.

    2012-03-01

    We report on clinical CARS imaging of human skin in vivo with the certified hybrid multiphoton tomograph CARSDermaInspect. The CARS-DermaInspect provides simultaneous imaging of non-fluorescent intradermal lipid and water as well as imaging of two-photon excited fluorescence from intrinsic molecules. Two different excitation schemes for CARS imaging have been realized: In the first setup, a combination of fs oscillator and optical parametric oscillator provided fs-CARS pump and Stokes pulses, respectively. In the second setup a fs oscillator was combined with a photonic crystal fiber which provided a broadband spectrum. A spectral range out of the broadband-spectrum was selected and used for CARS excitation in combination with the residual fs-oscillator output. In both setups, in addition to CARS, single-beam excitation was used for imaging of two-photon excited fluorescence and second harmonic generation signals. Both CARS-excitation systems were successfully used for imaging of lipids inside the skin in vivo.

  20. Models for multiphoton ionization processes

    Using the Fourier transform method, several analytical models for multiphoton processes have been developed, which emphasize the non-perturbative regime of C-C transitions. It was found that the population trapping of continuum-continuum (C-C) transitions can occurs under general conditions: for two continua with energy-dependent matrix elements, and for an infinite number of structureless continua with coupled bands. A above-threshold ionization model with two-frequency smooth pulses for hydrogenic atom was first proposed. This model give a simple form for analytical solutions if an ionization threshold is negligible. The results predict that (a) there is no trapping or saturation of the bound-continuum transition and that the ionization rate is independent of the redistribution among the continua for the C-C matrix element chosen; (b) There are peak switch in photoelectron energy spectra which depends on not only redistribution laser intensity, but also the pulses shape and their overlap in time, as well as the coupling between the bound state and continua; (c) peaks about the ionization energy in the photoelectron spectra are symmetric and only appear during the ionization process; (d) as the laser intensity is increased, the total angular photoelectrons distribution peak strongly in forward and backward direction of the redistribution laser polarization; and the minima of this distribution are not zero for higher laser intensity. The photon spectrum is also investigated

  1. Infrared multiphoton absorption and decomposition

    The discovery of infrared laser induced multiphoton absorption (IRMPA) and decomposition (IRMPD) by Isenor and Richardson in 1971 generated a great deal of interest in these phenomena. This interest was increased with the discovery by Ambartzumian, Letokhov, Ryadbov and Chekalin that isotopically selective IRMPD was possible. One of the first speculations about these phenomena was that it might be possible to excite a particular mode of a molecule with the intense infrared laser beam and cause decomposition or chemical reaction by channels which do not predominate thermally, thus providing new synthetic routes for complex chemicals. The potential applications to isotope separation and novel chemistry stimulated efforts to understand the underlying physics and chemistry of these processes. At ICOMP I, in 1977 and at ICOMP II in 1980, several authors reviewed the current understandings of IRMPA and IRMPD as well as the particular aspect of isotope separation. There continues to be a great deal of effort into understanding IRMPA and IRMPD and we will briefly review some aspects of these efforts with particular emphasis on progress since ICOMP II. 31 references

  2. Optical physics enables advances in multiphoton imaging

    Since the initial images were taken using a multiphoton imaging technique the method has rapidly established itself as the preferred method for imaging deeply into biological samples with micron resolution in three dimensions. Multiphoton imaging has thus enabled researchers in the life sciences to undertake studies that had previously been believed to be impossible without significantly perturbing the sample. Many of these experiments have only been realized due to close cooperation between optical physicists, from a range of disciplines, and the biomedical researchers. This paper will provide a general review of the current state of the field demonstrating how the various aspects of the physics development have brought the multiphoton technique to its current position at the forefront of biological microscopy. (topical review)

  3. A pragmatic guide to multiphoton microscope design

    Young, Michael D.; Field, Jeffrey J.; Sheetz, Kraig E.; Bartels, Randy A.; Squier, Jeff

    2016-01-01

    Multiphoton microscopy has emerged as a ubiquitous tool for studying microscopic structure and function across a broad range of disciplines. As such, the intent of this paper is to present a comprehensive resource for the construction and performance evaluation of a multiphoton microscope that will be understandable to the broad range of scientific fields that presently exploit, or wish to begin exploiting, this powerful technology. With this in mind, we have developed a guide to aid in the design of a multiphoton microscope. We discuss source selection, optical management of dispersion, image-relay systems with scan optics, objective-lens selection, single-element light-collection theory, photon-counting detection, image rendering, and finally, an illustrated guide for building an example microscope.

  4. Multiphoton microscopy in defining liver function

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  5. Multiphoton polymerization using optical trap assisted nanopatterning

    Leitz, Karl-Heinz; Tsai, Yu-Cheng; Flad, Florian; Schäffer, Eike; Quentin, Ulf; Alexeev, Ilya; Fardel, Romain; Arnold, Craig B.; Schmidt, Michael

    2013-06-01

    In this letter, we show the combination of multiphoton polymerization and optical trap assisted nanopatterning (OTAN) for the additive manufacturing of structures with nanometer resolution. User-defined patterns of polymer nanostructures are deposited on a glass substrate by a 3.5 μm polystyrene sphere focusing IR femtosecond laser pulses, showing minimum feature sizes of λ/10. Feature size depends on the applied laser fluence and the bead surface spacing. A finite element model describes the intensity enhancement in the microbead focus. The results presented suggest that OTAN in combination with multiphoton processing is a viable technique for additive nanomanufacturing with sub-diffraction-limited resolution.

  6. Structure of multiphoton quantum optics. II. Bipartite systems, physical processes, and heterodyne squeezed states

    Extending the scheme developed for a single mode of the electromagnetic field in the preceding paper [F. Dell'Anno, S. De Siena, and F. Illuminati, Phys. Rev. A 69, 033812 (2004)], we introduce two-mode nonlinear canonical transformations depending on two heterodyne mixing angles. They are defined in terms of Hermitian nonlinear functions that realize heterodyne superpositions of conjugate quadratures of bipartite systems. The canonical transformations diagonalize a class of Hamiltonians describing nondegenerate and degenerate multiphoton processes. We determine the coherent states associated with the canonical transformations, which generalize the nondegenerate two-photon squeezed states. Such heterodyne multiphoton squeezed states are defined as the simultaneous eigenstates of the transformed, coupled annihilation operators. They are generated by nonlinear unitary evolutions acting on two-mode squeezed states. They are non-Gaussian, highly nonclassical, entangled states. For a quadratic nonlinearity the heterodyne multiphoton squeezed states define two-mode cubic phase states. The statistical properties of these states can be widely adjusted by tuning the heterodyne mixing angles, the phases of the nonlinear couplings, as well as the strength of the nonlinearity. For quadratic nonlinearity, we study the higher-order contributions to the susceptibility in nonlinear media and we suggest possible experimental realizations of multiphoton conversion processes generating the cubic-phase heterodyne squeezed states

  7. Structure of multiphoton quantum optics. II. Bipartite systems, physical processes, and heterodyne squeezed states

    dell'Anno, Fabio; de Siena, Silvio; Illuminati, Fabrizio

    2004-03-01

    Extending the scheme developed for a single mode of the electromagnetic field in the preceding paper [F. Dell’Anno, S. De Siena, and F. Illuminati, Phys. Rev. A 69, 033812 (2004)], we introduce two-mode nonlinear canonical transformations depending on two heterodyne mixing angles. They are defined in terms of Hermitian nonlinear functions that realize heterodyne superpositions of conjugate quadratures of bipartite systems. The canonical transformations diagonalize a class of Hamiltonians describing nondegenerate and degenerate multiphoton processes. We determine the coherent states associated with the canonical transformations, which generalize the nondegenerate two-photon squeezed states. Such heterodyne multiphoton squeezed states are defined as the simultaneous eigenstates of the transformed, coupled annihilation operators. They are generated by nonlinear unitary evolutions acting on two-mode squeezed states. They are non-Gaussian, highly nonclassical, entangled states. For a quadratic nonlinearity the heterodyne multiphoton squeezed states define two-mode cubic phase states. The statistical properties of these states can be widely adjusted by tuning the heterodyne mixing angles, the phases of the nonlinear couplings, as well as the strength of the nonlinearity. For quadratic nonlinearity, we study the higher-order contributions to the susceptibility in nonlinear media and we suggest possible experimental realizations of multiphoton conversion processes generating the cubic-phase heterodyne squeezed states.

  8. MULTIPLE IONIZATION OF ATOMS THROUGH MULTIPHOTON ABSORPTION

    L'Huillier, A

    1987-01-01

    We review the main aspects of multiple ionization of rare gases in strong laser fields (above 1012W.cm-2). We discuss the mechanisms responsible for the multi-electron ejection : inner-shell ionization or outer-shell ionization, one-step or multi-step. We show the differences between one-photon and multi-photon multiple ionization.

  9. Route to Direct Multiphoton Multiple Ionization

    Lambropoulos, P; Papamihail, K G

    2011-01-01

    We address the concept of direct multiphoton multiple ionization in atoms exposed to intense, short wavelength radiation and explore the conditions under which such processes dominate over the sequential. Their contribution is shown to be quite robust, even under intensity fluctuations and interaction volume integration, and reasonable agreement with experimental data is also found.

  10. Route to direct multiphoton multiple ionization

    We address the concept of direct multiphoton multiple ionization in atoms exposed to intense, short-wavelength radiation and explore the conditions under which such processes dominate over the sequential. Their contribution is shown to be quite robust, even under intensity fluctuations and interaction volume integration, and reasonable agreement with experimental data is also found.

  11. Multi-Photon Interference and Temporal Distinguishability of Photons

    Ou, Z. Y.

    2007-01-01

    A number of recent interference experiments involving multiple photons are reviewed. These experiments include generalized photon bunching effects, generalized Hong-Ou-Mandel interference effects and multi-photon interferometry for demonstrations of multi-photon de Broglie wavelength. The multi-photon states used in these experiments are from two pairs of photons in parametric down-conversion. We find that the size of the interference effect in these experiments, characterized by the visibili...

  12. Real-time intravital imaging of pH variation associated with osteoclast activity.

    Maeda, Hiroki; Kowada, Toshiyuki; Kikuta, Junichi; Furuya, Masayuki; Shirazaki, Mai; Mizukami, Shin; Ishii, Masaru; Kikuchi, Kazuya

    2016-08-01

    Intravital imaging by two-photon excitation microscopy (TPEM) has been widely used to visualize cell functions. However, small molecular probes (SMPs), commonly used for cell imaging, cannot be simply applied to intravital imaging because of the challenge of delivering them into target tissues, as well as their undesirable physicochemical properties for TPEM imaging. Here, we designed and developed a functional SMP with an active-targeting moiety, higher photostability, and a fluorescence switch and then imaged target cell activity by injecting the SMP into living mice. The combination of the rationally designed SMP with a fluorescent protein as a reporter of cell localization enabled quantitation of osteoclast activity and time-lapse imaging of its in vivo function associated with changes in cell deformation and membrane fluctuations. Real-time imaging revealed heterogenic behaviors of osteoclasts in vivo and provided insights into the mechanism of bone resorption. PMID:27272564

  13. Intravital two-photon microscopy of immune cell dynamics in corneal lymphatic vessels.

    Philipp Steven

    Full Text Available BACKGROUND: The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. METHODOLOGY/PRINCIPAL FINDINGS: We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM. Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. CONCLUSIONS: To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible

  14. Intravital imaging reveals angiotensin II–induced transcytosis of albumin by podocytes

    Schießl, Ina Maria; Hammer, Anna; Kattler, Veronika; Gess, Bernhard; Theilig, Franziska; Witzgall, Ralph; Castrop, Hayo

    2016-01-01

    Albuminuria is a hallmark of kidney disease of various etiologies and usually caused by deterioration of glomerular filtration barrier integrity. We recently showed that angiotensin II (Ang II) acutely increases albumin filtration in the healthy kidney. Here, we used intravital microscopy to assess the effects of Ang II on podocyte function in rats. Acute infusion of 30, 60, or 80 ng/kg per minute Ang II enhanced the endocytosis of albumin by activation of the type 1 Ang II receptor and ...

  15. Intravital immunofluorescence for visualizing the microcirculatory and immune microenvironments in the mouse ear dermis

    Kilarski, Witold W.; Güç, Esra; Teo, Jeremy C. M.; Oliver, S. Ryan; Lund, Amanda W.; Swartz, Melody A.

    2013-01-01

    Visualizing the dynamic behaviors of immune cells in living tissue has dramatically increased our understanding of how cells interact with their surroundings, contributing important insights into mechanisms of leukocyte trafficking, tumor cell invasion, and T cell education by dendritic cells, among others. Despite substantial advances with various intravital imaging techniques including two-photon microscopy and the generation of multitudes of reporter mice, there is a growing need to assess...

  16. Morphology and hemodynamics during vascular regeneration in critically ischemic murine skin studied by intravital microscopy techniques

    Schweizer, R.; Merz, K.; Schlosser, S; Spanholtz, T; Contaldo, C; Stein, J V; Enzmann, V; Giovanoli, P.; Erni, D; Plock, J A

    2011-01-01

    BACKGROUND: With the understanding of angiogenesis and arteriogenesis, new theories about the orchestration of these processes have emerged. The aim of this study was to develop an in vivo model that enables visualization of vascular regenerating mechanisms by intravital microscopy techniques in collateral arteriolar flap vascularity. METHODS: A dorsal skin flap (15 × 30 mm) was created in mice and fixed into a skinfold chamber to allow for assessment of morphology and microhemodynamics by ...

  17. Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy

    Masedunskas, Andrius; Sramkova, Monika; Parente, Laura; Sales, Katiuchia Uzzun; Amornphimoltham, Panomwat; Thomas H Bugge; Weigert, Roberto

    2011-01-01

    The regulation and the dynamics of membrane trafficking events have been studied primarily in in vitro models that often do not fully reflect the functional complexity found in a living multicellular organism. Here we used intravital microscopy in the salivary glands of live rodents to investigate regulated exocytosis, a fundamental process in all of the secretory organs. We found that β-adrenergic stimulation elicits exocytosis of large secretory granules, which gradually collapse with the a...

  18. Intravital Microscopy Reveals Differences in the Kinetics of Endocytic Pathways between Cell Cultures and Live Animals

    Roberto Weigert; Myo-Pale' Aye; Kamil Rechache; Natalie Porat-Shliom; Andrius Masedunskas

    2012-01-01

    Intravital microscopy has enabled imaging of the dynamics of subcellular structures in live animals, thus opening the door to investigating membrane trafficking under physiological conditions. Here, we sought to determine whether the architecture and the environment of a fully developed tissue influences the dynamics of endocytic processes. To this aim, we imaged endocytosis in the stromal cells of rat salivary glands both in situ and after they were isolated and cultured on a solid surface. ...

  19. Probing the role of the actin cytoskeleton during regulated exocytosis by intravital microscopy

    Milberg, Oleg; Tora, Muhibullah; Shitara, Akiko; Masedunskas, Andrius; Weigert, Roberto

    2014-01-01

    The actin cytoskeleton plays a fundamental role in controlling several steps during regulated exocytosis. Here we describe a combination of procedures that are aimed at studying the dynamics and the mechanism of the actin cytoskeleton in the salivary glands of live rodents, a model for exocrine secretion. Our approach relies on intravital microscopy, an imaging technique that enables imaging biological events in live animals at a subcellular resolution, and it is complemented by the use of ph...

  20. Intravital microscopy: a novel tool to study cell biology in living animals

    Weigert, Roberto; Sramkova, Monika; Parente, Laura; Masedunskas, Andrius

    2010-01-01

    Intravital microscopy encompasses various optical microscopy techniques aimed at visualizing biological processes in live animals. In the last decade, the development of non-linear optical microscopy resulted in an enormous increase of in vivo studies, which have addressed key biological questions in fields such as neurobiology, immunology and tumor biology. Recently, few studies have shown that subcellular processes can be imaged dynamically in the live animal at a resolution comparable to t...

  1. Intravital Microscopy for Imaging Subcellular Structures in Live Mice Expressing Fluorescent Proteins

    Masedunskas, Andrius; Porat-Shliom, Natalie; Tora, Muhibullah; Milberg, Oleg; Weigert, Roberto

    2013-01-01

    Here we describe a procedure to image subcellular structures in live rodents that is based on the use of confocal intravital microscopy. As a model organ, we use the salivary glands of live mice since they provide several advantages. First, they can be easily exposed to enable access to the optics, and stabilized to facilitate the reduction of the motion artifacts due to heartbeat and respiration. This significantly facilitates imaging and tracking small subcellular structures. Second, most o...

  2. Multiphoton ionization with femtosecond laser pulses

    There are a number of reasons to use subpicosecond pulses in multiphoton ionization experiments. Pulses with shorter risetimes make it possible to study processes with higher rates before one runs into the problem of depletion of target atoms. Furthermore, the momentum of the electron does not change between the point of ionization and the detector if the pulse expires before the electron has time to sample the spatial inhomogeneity of the light intensity. This makes it possible to identify the intensity at which an electron was formed from the energy with which it reaches the detector. Yet another advantage is the fact that the primary ionization products are subject to the ionizing radiation for only a short amount of time, thus reducing the probability of sequential ionization as compared to direct processes. In this paper the experimental results on the multiphoton ionization of xenon with pulses of 100 fs, that were obtained during the preceding year at ENSTA, Palaiseau, will be presented

  3. Multiphoton ionization/dissociation of osmium tetroxide

    The mechanisms leading to laser multiphoton ionization and dissociation (MPI/MPD) of osmium tetroxide (OsO4) have been investigated from measurements of the kinetic energies of product ions (Os+, Os2+, OsO+, O2+, O+) and photoelectrons as a function of the laser wavelength. Neutral channels, intermediate to the dominant Os+ ionization channel, such as OsO4→OsO4-n+nO are examined using resonance-enhanced multiphoton ionization (REMPI) of the fast O atoms. Equipartition of the available photon energy among the fragments is observed. The wavelength dependence of the Os+ ion signal suggests that one or more of the steps leading to Os+ ions involve molecular ions and/or excited neutral atoms. The observed preponderance of very slow (2+ is shown to result primarily from REMPI of Os+

  4. In vivo multiphoton tomography of skin cancer

    König, Karsten; Riemann, Iris; Ehlers, Alexander; Buckle, Rainer; Dimitrow, Enrico; Kaatz, Martin; Fluhr, Joachim; Elsner, Peter

    2006-02-01

    The multiphoton tomograph DermaInspect was used to perform first clinical studies on the early non-invasive detection of skin cancer based on non-invasive optical sectioning of skin by two-photon autofluorescence and second harmonic generation. In particular, deep-tissue pigmented lesions -nevi- have been imaged with intracellular resolution using near infrared (NIR) femtosecond laser radiation. So far, more than 250 patients have been investigated. Cancerous tissues showed significant morphological differences compared to normal skin layers. In the case of malignant melanoma, the occurrence of luminescent melanocytes has been detected. Multiphoton tomography will become a novel non-invasive method to obtain high-resolution 3D optical biopsies for early cancer detection, treatment control, and in situ drug screening.

  5. Multiphoton processes in isolated atoms and molecules

    The theory of coherent excitation of a multilevel quantum mechanical system is developed. Damping of the system is taken into account by the use of a density matrix formalism. General properties of the wave function and/or the density matrix are discussed. The physical implications for the behavior of the system are described, together with possible applications of the formalism, including the infrared multiphoton excitation of molecules, and optical pumping in alkali atoms. Experimental results are presented on the infrared multiphoton dissociation of molecules, followed by a discussion of the general features of this process. The experimental results were obtained using a crossed laser and molecular beam method, and the emphasis is on determining the properties of the dissociating molecule and the dissociation products. The dissociation process is shown to be described very well by the standard statistical theory (RRKM theory) of unimolecular reactions, a brief presentation of which is also included

  6. Medium-induced multi-photon radiation

    MA, Hao; Salgado, Carlos A.; Tywoniuk, Konrad

    2011-01-01

    We study the spectrum of multi-photon radiation off a fast quark in medium in the BDMPS/ASW approach. We reproduce the medium-induced one-photon radiation spectrum in dipole approximation, and go on to calculate the two-photon radiation in the Moli\\`{e}re limit. We find that in this limit the LPM effect holds for medium-induced two-photon ladder emission.

  7. How periodic orbit bifurcations drive multiphoton ionization

    Huang, S.; Chandre, C; Uzer, T.

    2006-01-01

    The multiphoton ionization of hydrogen by a strong bichromatic microwave field is a complex process prototypical for atomic control research. Periodic orbit analysis captures this complexity: Through the stability of periodic orbits we can match qualitatively the variation of experimental ionization rates with a control parameter, the relative phase between the two modes of the field. Moreover, an empirical formula reproduces quantum simulations to a high degree of accuracy. This quantitative...

  8. Medium-induced multi-photon radiation

    Ma Hao; Salgado, Carlos A [Departamento de Fisica de PartIculas, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Tywoniuk, Konrad [Lund University (Sweden)

    2011-01-01

    We study the spectrum of multi-photon radiation off a fast quark in medium in the BDMPS/ASW approach. We reproduce the medium-induced one-photon radiation spectrum in dipole approximation, and go on to calculate the two-photon radiation in the Moliere limit. We find that in this limit the LPM effect holds for medium-induced two-photon ladder emission.

  9. Multiphoton microscopy with near infrared contrast agents

    Yazdanfar, Siavash; Joo, Chulmin; Zhan, Chun; Berezin, Mikhail Y.; Akers, Walter J.; Achilefu, Samuel

    2010-05-01

    While multiphoton microscopy (MPM) has been performed with a wide range of excitation wavelengths, fluorescence emission has been limited to the visible spectrum. We introduce a paradigm for MPM of near-infrared (NIR) fluorescent molecular probes via nonlinear excitation at 1550 nm. This all-NIR system expands the range of available MPM fluorophores, virtually eliminates background autofluorescence, and allows for use of fiber-based, turnkey ultrafast lasers developed for telecommunications.

  10. Fundamental studies of molecular multiphoton ionization

    For several years the authors have performed fundamental studies of molecular multiphoton ionization (MPI). We will present a potpourri of techniques and results chosen to illustrate the interesting complexities of molecular MPI. Techniques used include time-of-flight mass spectroscopy, photoelectron spectroscopy, supersonic expansion cooling of molecular beams, harmonic generation, two-color laser MPI, and polarization spectroscopy. Whenever possible the relevance of these results to resonance ionization spectroscopy schemes will be delineated. 23 references, 10 figures

  11. First multiphoton tomography of brain in man

    König, Karsten; Kantelhardt, Sven R.; Kalasauskas, Darius; Kim, Ella; Giese, Alf

    2016-03-01

    We report on the first two-photon in vivo brain tissue imaging study in man. High resolution in vivo histology by multiphoton tomography (MPT) including two-photon FLIM was performed in the operation theatre during neurosurgery to evaluate the feasibility to detect label-free tumor borders with subcellular resolution. This feasibility study demonstrates, that MPT has the potential to identify tumor borders on a cellular level in nearly real-time.

  12. Optimizing Fluorescence Collection Efficiency in Multiphoton Microscopy

    Zinter, Joseph P.

    Over the past 20 years multiphoton microscopy has established itself as the premier modality for high resolution (techniques result from the use of longer wavelength excitation light (˜700--1000 nm), enabling deeper tissue penetration, and the spatially and temporally localized generation of fluorescence inherent in two-photon excitation, which virtually eliminates out-of-focus fluorescence. Imaging depths of ˜500 mum are now considered common practice, however, as the technique continues to increase in popularity and utility significant efforts are being made to maximize imaging depth. These efforts can be compartmentalized into those aimed at increasing fluorescence excitation and those attempting to maximize fluorescence collection. Progress has been made in increasing fluorescence excitation efficiency, however these approaches require costly and complicated optical instrumentation, and are often deemed impractical. Efforts targeted at increasing fluorescence collection efficiency have been limited due to the complexity of describing the ensemble of scattered fluorescent photons emerging from a sample and propagating through a microscope objective and the subsequent fluorescence collection pathway of a multiphoton microscope. Since there is no analytic solution for these fluorescent photon distributions as a function of imaging depth in the relevant, non-diffusive multiphoton imaging range, numerical techniques are required. Here is presented the first computational model of fluorescence propagation through the complete fluorescence collection pathway of a multiphoton microscope. Monte Carlo simulations were used to model the propagation of fluorescence as a function of imaging depth in a scattering sample with physiologically accurate optical properties, and to determine the collected and transmitted fluorescent fraction through the Olympus 20X 0.95NA microscope objective, one of the highest performance and most commonly used objectives for multiphoton

  13. The multiphoton ionization of uranium hexafluoride

    Multiphoton ionization (MPI) time-of-flight mass spectroscopy and photoelectron spectroscopy studies of UF6 have been conducted using focused light from the Nd:YAG laser fundamental (λ = 1064 nm) and its harmonics (λ = 532, 355, or 266 nm), as well as other wavelengths provided by a tunable dye laser. The MPI mass spectra are dominated by the singly and multiply charged uranium ions rather than by the UFx+ fragment ions. The laser power dependence of Un+ ion signals indicates that saturation can occur for many of the steps required for their ionization. The doubly-charged uranium ion (U2+) intensity is much greater than that of the singly-charged uranium ion (U+). For the case of the tunable dye laser experiments, the Un+ (n=1-4) wavelength dependence is relatively unstructured and does not show observable resonance enhancement at known atomic uranium excitation wavelengths. The dominance of the U2+ ion and the absence or very small intensities of UFx+ fragments, along with the unstructured wavelength dependence, indicate that mechanisms may exist other than ionization of bare U atoms after the stepwise photodissociation of F atoms from the parent molecule. The data argue against step-wise photodissociation of UFx+ (x = 5,6) ions. Neither the neutral ladder nor the ion ladder mechanisms adequately describe the ionization phenomena observed. These results suggest an alternate mechanism which better explains the multiphoton excitation and dissociative ionization of UF6. It is likely that the multiphoton excitation of UF6 under these experimental conditions results in a superexcited molecule, UF6**, which primarily dissociates into Un+ (through multiple channels), fluorine atoms, and slow electrons. The excitation of such superexcited molecules may be facilitated by the existence of a previously reported giant resonance at 12-14 eV

  14. Pulse front adaptive optics in multiphoton microscopy

    Sun, B.; Salter, P. S.; Booth, M. J.

    2016-03-01

    The accurate focusing of ultrashort laser pulses is extremely important in multiphoton microscopy. Using adaptive optics to manipulate the incident ultrafast beam in either the spectral or spatial domain can introduce significant benefits when imaging. Here we introduce pulse front adaptive optics: manipulating an ultrashort pulse in both the spatial and temporal domains. A deformable mirror and a spatial light modulator are operated in concert to modify contours of constant intensity in space and time within an ultrashort pulse. Through adaptive control of the pulse front, we demonstrate an enhancement in the measured fluorescence from a two photon microscope.

  15. Intense-field multiphoton ionization of helium

    The dynamics of multiphoton ionization of helium are investigated through numerical integration of the two-electron time-dependent Schroedinger equation. Using this work as a benchmark, a new single-active-electron model is introduced that gives agreement with He ionization rates to within a few per cent on average, and gives good agreement with He harmonic generation spectra over a laser intensity range of 0.5x1014 to 8.0x1014 W cm-2, and frequencies corresponding to four- and five-photon ionization. (author). Letter-to-the-editor

  16. Intravital and post-mortem CT examinations of cerebral gunshot injuries

    The value of CT was assessed in 24 patients who died of cerebral gun-shot injuries and in two patients with more recent injuries in order to reconstruct the mode of injury and for adding forensic information. The post-mortem and intravital appearances are described and are compared with ultrasound rotation compound scans of the isolated brains. CT showed good agreement with pathological findings. Ultrasound produced images with an accuracy between CT and photographs of the brain specimen. Both methods are regarded as valuable additions to the pathological and forensic information concerning gunshot injuries. (orig.)

  17. The infrared multiphoton dissociation of three nitrolkanes

    Wodtke, A. M.; Hintsa, E. J.; Lee, Y. T.

    1986-01-01

    Infrared multiphoton dissociation in a molecular beam has been studied in order to elucidate the collision free, 'thermal' chemistry and dynamics of nitromethane, nitroethane and 2-nitropropane. The isomerization of CH3NO2 to CH3ONO was observed by detecting the CH3O and NO products from the dissociation of the very internally hot, isomerized nitromethane. A novel application of RRKM theory was used to estimate the barrier height to isomerization at 55.5 kcal/mol. The barrier height determination method was tested and found to give excellent results by applying it to the determintaion of the barrier height to HONO elimination from nitroethane, a value which is well known from activation energy measurements. The method was then applied to the case of HONO elimination from 2-nitropropane and it appears that there is good to believe that the barrier height is 3-5 kcal/mol lower in 2-nitropropane than in nitroethane. The success of this method for determining barrier heights shows how a microscopic molecular beam experiment, using infrared multiphoton dissociation where the concept of temperature has no place, can be quantitatively related to pyrolysis experiments which are conducted under collisional, thermal conditions and measure phenomenological quantities such as activation energies.

  18. Single- and multiphoton ionization processes in molecules

    This dissertation is theoretical in nature and can be separated into two main areas: (1) single- and multiphoton ionization studies of a novel photoelectron effect, and (2) single-photon ionization studies of simple clusters as models for adsorbate photoemission. The first area centers on the phenomenon of circular dichroism in photoelectron angular distributions (CDAD). CDAD is shown to exist from oriented linear molecules, adsorbed atoms, and aligned atoms and molecules in the gas phase. The calculations presented here are the first to demonstrate the experimental feasability of CDAD studies. CDAD is shown to be a measureable effect which exists because the photoelectron collection direction can break the symmetry of these otherwise highly symmetric systems. As a direct results of the work presented here, CDAD has now been observed experimentally. Coupled with resonantly enhanced multiphoton ionization (REMPI), CDAD is shown to be a powerful probe of unknown alignment in gas phase atomic and molecular samples. The second area of research focuses on the simple oriented molecules NiCO and NiN2 as models for the corresponding adsorbate systems. These simple models provide insight into features observed in the experimental angle-resolved photoemission spectra

  19. Multiphoton ionization of large water clusters

    Water clusters are multimers of water molecules held together by hydrogen bonds. In the present work, multiphoton ionization in the UV range coupled with time of flight mass spectrometry has been applied to water clusters with up to 160 molecules in order to obtain information on the electronic states of clusters of different sizes up to dimensions that can approximate the bulk phase. The dependence of ion intensities of water clusters and their metastable fragments produced by laser ionization at 355 nm on laser power density indicates a (3+1)-photon resonance-enhanced multiphoton ionization process. It also explains the large increase of ionization efficiency at 355 nm compared to that at 266 nm. Indeed, it was found, by applying both nanosecond and picosecond laser ionization with the two different UV wavelengths, that no water cluster sequences after n = 9 could be observed at 266 nm, whereas water clusters up to m/z 2000 Th in reflectron mode and m/z 3000 Th in linear mode were detected at 355 nm. The agreement between our findings on clusters of water, especially true in the range with n > 10, and reported data for liquid water supports the hypothesis that clusters above a critical dimension can approximate the liquid phase. It should thus be possible to study clusters just above 10 water molecules, for getting information on the bulk phase structure

  20. Multimodal optoacoustic and multiphoton fluorescence microscopy

    Sela, Gali; Razansky, Daniel; Shoham, Shy

    2013-03-01

    Multiphoton microscopy is a powerful imaging modality that enables structural and functional imaging with cellular and sub-cellular resolution, deep within biological tissues. Yet, its main contrast mechanism relies on extrinsically administered fluorescent indicators. Here we developed a system for simultaneous multimodal optoacoustic and multiphoton fluorescence 3D imaging, which attains both absorption and fluorescence-based contrast by integrating an ultrasonic transducer into a two-photon laser scanning microscope. The system is readily shown to enable acquisition of multimodal microscopic images of fluorescently labeled targets and cell cultures as well as intrinsic absorption-based images of pigmented biological tissue. During initial experiments, it was further observed that that detected optoacoustically-induced response contains low frequency signal variations, presumably due to cavitation-mediated signal generation by the high repetition rate (80MHz) near IR femtosecond laser. The multimodal system may provide complementary structural and functional information to the fluorescently labeled tissue, by superimposing optoacoustic images of intrinsic tissue chromophores, such as melanin deposits, pigmentation, and hemoglobin or other extrinsic particle or dye-based markers highly absorptive in the NIR spectrum.

  1. Multiphoton imaging with a nanosecond supercontinuum source

    Lefort, Claire; O'Connor, Rodney P.; Blanquet, Véronique; Baraige, Fabienne; Tombelaine, Vincent; Lévêque, Philippe; Couderc, Vincent; Leproux, Philippe

    2016-03-01

    Multiphoton microscopy is a well-established technique for biological imaging of several kinds of targets. It is classically based on multiphoton processes allowing two means of contrast simultaneously: two-photon fluorescence (TPF) and second harmonic generation (SHG). Today, the quasi exclusive laser technology used in that aim is femtosecond titanium sapphire (Ti: Sa) laser. We experimentally demonstrate that a nanosecond supercontinuum laser source (STM-250-VIS-IR-custom, Leukos, France; 1 ns, 600-2400 nm, 250 kHz, 1 W) allows to obtain the same kind of image quality in the case of both TPF and SHG, since it is properly filtered. The first set of images concerns the muscle of a mouse. It highlights the simultaneous detection of TPF and SHG. TPF is obtained thanks to the labelling of alpha-actinin with Alexa Fluor® 546 by immunochemistry. SHG is created from the non-centrosymmetric organization of myosin. As expected, discs of actin and myosin are superimposed alternatively. The resulting images are compared with those obtained from a standard femtosecond Ti: Sa source. The physical parameters of the supercontinuum are discussed. Finally, all the interest of using an ultra-broadband source is presented with images obtained in vivo on the brain of a mouse where tumor cells labeled with eGFP are grafted. Texas Red® conjugating Dextran is injected into the blood vessels network. Thus, two fluorophores having absorption wavelengths separated by 80 nm are imaged simultaneously with a single laser source.

  2. Intravital imaging of the effects of 5-fluorouracil on the murine liver microenvironment using 2-photon laser scanning microscopy

    OKIGAMI, MASATO; TANAKA, KOJI; INOUE, YASUHIRO; SAIGUSA, SUSUMU; OKUGAWA, YOSHINAGA; TOIYAMA, YUJI; MOHRI, YASUHIKO; KUSUNOKI, MASATO

    2016-01-01

    5-fluorouracil (5FU) is often used in the treatment of colorectal cancer. 5FU improves the median overall and disease-free survival rates and reduces recurrence rates in patients who have undergone curative surgical resection. However, in the adjuvant setting, whether 5FU eradicates clinically undetectable micrometastases in target organs such as the liver, or whether 5-FU inhibits the adhesion of circulating tumor cells has not yet been established. In the present study, 5FU was administered following the inoculation of red fluorescent protein-expressing HT29 cells into green fluorescent protein (GFP)-transgenic nude mice to examine its inhibitory effect. 2-photon laser scanning microscopy was performed at selected time points for time-series imaging of liver metastasis of GFP-transgenic mice. The cell number in vessels was quantified to evaluate the response of the tumor microenvironment to chemotherapy. HT29 cells were visualized in hepatic sinusoids at the single-cell level. A total of 2 hours after the injection (early stage), time-series imaging revealed that the number of caught tumor cells gradually reduced over time. In the 5FU treatment group, no significant difference was observed in the cell number in the early stage. One week after the injection (late stage), a difference in morphology was observed. The results of the present study indicated that 5FU eradicated clinically undetectable micrometastases in liver tissues by acting as a cytotoxic agent opposed to preventing adhesion. The present study indicated that time-series intravital 2-photon laser scanning microscopic imaging of metastatic tumor xenografts may facilitate the screening and evaluation of novel chemotherapeutic agents with less interindividual variability. PMID:27073493

  3. Self-organized pattern formation in laser-induced multiphoton ionization in fused silica

    Buschlinger, Robert; Peschel, Ulf

    2013-01-01

    We use finite difference time domain modelling to investigate plasma generation in bulk silica induced by multi-photon absorption of intense laser light. Plasma generation is found to be extremely amplified around nanometer-sized inhomogeneities as present in glasses. Each inhomogeneity acts as the seed of a plasma structure growing against the direction of light propagation. Plasma structures originating from randomly distributed inhomogeneities are found to interact strongly and to organize in regularly spaced planes oriented perpendicularly to the laser polarization. We discuss similarities between our results and nanogratings in fused silica written by laser beams with spatially homogeneous as well as radial and azimuthal polarization.

  4. Tumor Vascularity Assessed By Magnetic Resonance Imaging and Intravital Microscopy Imaging

    Jon-Vidar Gaustad

    2008-04-01

    Full Text Available Gadopentetate dimeglumine (Gd-DTPA-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI is considered to be a useful method for characterizing the vascularity of tumors. However, detailed studies of experimental tumors comparing DCE-MRI-derived parametric images with images of the morphology and function of the microvascular network have not been reported. In this communication, we describe a novel MR-compatible mouse dorsal window chamber and report comparative DCE-MRI and intravital microscopy studies of A-07-GFP tumors xenografted to BALB/c nu/nu mice. Blood supply time (BST images (i.e., images of the time from when arterial blood enters a tumor through the supplying artery until it reaches a vessel segment within the tumor and morphologic images of the microvascular network were produced by intravital microscopy. Images of E·F (E is the initial extraction fraction of Gd-DTPA and F is perfusion were produced by subjecting DCE-MRI series to Kety analysis. The E·F images mirrored the morphology (microvascular density and the function (BST of the microvascular networks well. Tumor regions showing high E·F values colocalized with tumor regions showing high microvascular density and low BST values. Significant correlations were found between E·F and microvascular density and between E·F and BST, both within and among tumors.

  5. High resolution intravital imaging of subcellular structures of mouse abdominal organs using a microstage device.

    Cao, Liqin; Kobayakawa, Satoru; Yoshiki, Atsushi; Abe, Kuniya

    2012-01-01

    Intravital imaging of brain and bone marrow cells in the skull with subcellular resolution has revolutionized neurobiology, immunology and hematology. However, the application of this powerful technology in studies of abdominal organs has long been impeded by organ motion caused by breathing and heartbeat. Here we describe for the first time a simple device designated 'microstage' that effectively reduces organ motions without causing tissue lesions. Combining this microstage device with an upright intravital laser scanning microscope equipped with a unique stick-type objective lens, the system enables subcellular-level imaging of abdominal organs in live mice. We demonstrate that this technique allows for the quantitative analysis of subcellular structures and gene expressions in cells, the tracking of intracellular processes in real-time as well as three-dimensional image construction in the pancreas and liver of the live mouse. As the aforementioned analyses based on subcellular imaging could be extended to other intraperitoneal organs, the technique should offer great potential for investigation of physiological and disease-specific events of abdominal organs. The microstage approach adds an exciting new technique to the in vivo imaging toolbox. PMID:22479464

  6. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Laura Sarah Sasportas

    Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  7. Intravital imaging of hair-cell development and regeneration in the zebrafish

    Hernan Lopez-Schier

    2013-10-01

    Full Text Available Direct videomicroscopic visualization of organ formation and regeneration in toto is a powerful strategy to study cellular processes that often cannot be replicated in vitro. Intravital imaging aims at quantifying changes in tissue architecture or subcellular organization over time during organ development, regeneration or degeneration. A general feature of this approach is its reliance on the optical isolation of defined cell types in the whole animals by transgenic expression of fluorescent markers. Here we describe a simple and robust method to analyze sensory hair-cell development and regeneration in the zebrafish lateral line by high-resolution intravital imaging using laser-scanning confocal microscopy (LSCM and selective plane illumination microscopy (SPIM. The main advantage of studying hair-cell regeneration in the lateral line is that it occurs throughout the life of the animal, which allows its study in the most natural context. We detail protocols to achieve continuous videomicroscopy for up to 68 hours, enabling direct observation of cellular behavior, which can provide a sensitive assay for the quantitative classification of cellular phenotypes and cell-lineage reconstruction. Modifications to this protocol should facilitate pharmacogenetic assays to identify or validate otoprotective or reparative drugs for future clinical strategies aimed at preserving aural function in humans.

  8. Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy

    Miller, Mark J.; Wei, Sindy H.; Cahalan, Michael D.; Parker, Ian

    2003-03-01

    The recirculation of T cells between the blood and secondary lymphoid organs requires that T cells are motile and sensitive to tissue-specific signals. T cell motility has been studied in vitro, but the migratory behavior of individual T cells in vivo has remained enigmatic. Here, using intravital two-photon laser microscopy, we imaged the locomotion and trafficking of naïve CD4+ T cells in the inguinal lymph nodes of anesthetized mice. Intravital recordings deep within the lymph node showed T cells flowing rapidly in the microvasculature and captured individual homing events. Within the diffuse cortex, T cells displayed robust motility with an average velocity of 11 μm·min1. T cells cycled between states of low and high motility roughly every 2 min, achieving peak velocities >25 μm·min1. An analysis of T cell migration in 3D space revealed a default trafficking program analogous to a random walk. Our results show that naïve T cells do not migrate collectively, as they might under the direction of pervasive chemokine gradients. Instead, they appear to migrate as autonomous agents, each cell taking an independent trafficking path. Our results call into question the role of chemokine gradients for basal T cell trafficking within T cell areas and suggest that antigen detection may result from a stochastic process through which a random walk facilitates contact with antigen-presenting dendritic cells.

  9. R-matrix Floquet theory of molecular multiphoton processes: II. Multiphoton ionization of H2

    Multiphoton ionization rates for H2 immersed in an intense linearly polarized laser field are calculated using the recently developed R-matrix Floquet theory of molecular multiphoton processes. We assume that the H2 molecule is aligned along the laser polarization direction and we adopt the fixed-nuclei approximation, in which the motion of the target electrons is calculated in the laser field and in the field of the nuclei, which are assumed to be fixed in space. An accurate multi-state wavefunction is employed to calculate one-, two- and four-photon ionization rates for H2 at several internuclear separations over a range of frequencies and intensities. Analysis of the ionization rates reveals the important role played both by resonances corresponding to Rydberg bound states converging to the H2+ ion ground state and by doubly excited states converging to the H2+ ion first excited state. These resonances give rise to resonant enhanced multiphoton ionization peaks in many of the ionization rates studied in this paper, and their possible role in controlling the vibrational population of the final H2+ ion is discussed. (author)

  10. In vivo multiphoton tomography of inflammatory tissue and melanoma

    Riemann, Iris; Dimitrow, Enrico; Kaatz, Martin; Fluhr, Joachim; Elsner, Peter; Kobow, Jens; Konig, Karsten

    2005-04-01

    Multiphoton optical tomography provides the capability of non-invasive optical sectioning of skin with high spatial and intracellular resolution as well as high NIR (near infrared) light penetration into pigmented skin areas. The imaging system DermaInspect based on femtosecond laser pulses was used to perform multiphoton optical tomography in clinical studies. Patients with abnormal pigmented tissues were imaged in vivo. After the multiphoton imaging procedure, biopsies were taken, imaged again and further processed with standard histological methods. We report on preliminary results. The visualization of pigmented cell clusters based on non-linear luminescence using the novel multiphoton device was possible. These clusters could be clearly distinguished from non-pigmented cells. Cancerous tissues showed significant differences in the cell structure of the epidermal layers. The system DermaInspect might become a high resolution diagnostic tool for melanoma diagnostics.

  11. Multiphoton imaging with high peak power VECSELs

    Mirkhanov, Shamil; Quarterman, Adrian H.; Swift, Samuel; Praveen, Bavishna B.; Smyth, Conor J. C.; Wilcox, Keith G.

    2016-03-01

    Multiphoton imaging (MMPI) has become one of thee key non-invasive light microscopy techniques. This technique allows deep tissue imaging with high resolution and less photo-damage than conventional confocal microscopy. MPI is type of laser-scanning microscopy that employs localized nonlinear excitation, so that fluorescence is excited only with is scanned focal volume. For many years, Ti: sapphire femtosecond lasers have been the leading light sources for MPI applications. However, recent developments in laser sources and new types of fluorophores indicate that longer wavelength excitation could be a good alternative for these applications. Mode-locked VECSEELs have the potential to be low cost, compact light sources for MPI systems, with the additional advantage of broad wavelength coverage through use of different semiconductor material systems. Here, we use a femtosecond fibber laser to investigate the effect average power and repetition rate has on MPI image quality, to allow us to optimize our mode-locked VVECSELs for MPI.

  12. Multi-photon entanglement in high dimensions

    Malik, Mehul; Huber, Marcus; Krenn, Mario; Fickler, Robert; Zeilinger, Anton

    2015-01-01

    Entanglement lies at the heart of quantum mechanics $-$ as a fundamental tool for testing its deep rift with classical physics, while also providing a key resource for quantum technologies such as quantum computation and cryptography. In 1987 Greenberger, Horne, and Zeilinger realized that the entanglement of more than two particles implies a non-statistical conflict between local realism and quantum mechanics. The resulting predictions were experimentally confirmed by entangling three photons in their polarization. Experimental efforts since have singularly focused on increasing the number of particles entangled, while remaining in a two-dimensional space for each particle. Here we show the experimental generation of the first multi-photon entangled state where both $-$ the number of particles and the number of dimensions $-$ are greater than two. Interestingly, our state exhibits an asymmetric entanglement structure that is only possible when one considers multi-particle entangled states in high dimensions....

  13. Multi-photon entanglement in high dimensions

    Malik, Mehul; Erhard, Manuel; Huber, Marcus; Krenn, Mario; Fickler, Robert; Zeilinger, Anton

    2016-04-01

    Forming the backbone of quantum technologies today, entanglement has been demonstrated in physical systems as diverse as photons, ions and superconducting circuits. Although steadily pushing the boundary of the number of particles entangled, these experiments have remained in a two-dimensional space for each particle. Here we show the experimental generation of the first multi-photon entangled state where both the number of particles and dimensions are greater than two. Two photons in our state reside in a three-dimensional space, whereas the third lives in two dimensions. This asymmetric entanglement structure only appears in multiparticle entangled states with d > 2. Our method relies on combining two pairs of photons, high-dimensionally entangled in their orbital angular momentum. In addition, we show how this state enables a new type of ‘layered’ quantum communication protocol. Entangled states such as these serve as a manifestation of the complex dance of correlations that can exist within quantum mechanics.

  14. Lippmann-Schwinger description of multiphoton ionization

    Ivanov, I A

    2005-01-01

    We outline a formalism and develop a computational procedure to treat the process of multiphoton ionization (MPI) of atomic targets in strong laser fields. We treat the MPI process nonperturbatively as a decay phenomenon by solving a coupled set of the integral Lippmann-Schwinger equations. As basic building blocks of the theory we use a complete set of field-free atomic states, discrete and continuous. This approach should enable us to provide both the total and differential cross-sections of MPI of atoms with one or two electrons. As an illustration, we apply the proposed procedure to a simple model of MPI from a square well potential and to the hydrogen atom.

  15. Multiphoton dissociative ionization of molecular deuterium

    The kinetic energy spectra of deuterium ions produced from D2 arising from collision-free subpicosecond irradiation at 248 nm with intensities spanning the 10/sup 13/--10/sup 16/-W/cm2 range have been measured by time-of-flight analysis. The behaviors of the kinetic energy distributions of the fragments and the relative abundances of atomic (D+) and molecular (D2+) ions reveal the presence of two mechanisms of multiphoton dissociative ionization. Calibration of the energy scale for D+ is facilitated by comparison with He/sup 2+/. For intensities in the 10/sup 13/--10/sup 15/-W/cm2 region, intermediate three-photon resonances and the optical Stark shift play important roles. At an intensity /similar to/0/sup 16/ W/cm2, a direct transition from the molecular ground state to the dissociative ionic level appears as a significant channel. No evidence of direct double ionization was observed

  16. Soliton dynamics in the multiphoton plasma regime

    Husko, Chad A; Colman, Pierre; Zheng, Jiangjun; De Rossi, Alfredo; Wong, Chee Wei; 10.1038/srep01100

    2013-01-01

    Solitary waves have consistently captured the imagination of scientists, ranging from fundamental breakthroughs in spectroscopy and metrology enabled by supercontinuum light, to gap solitons for dispersionless slow-light, and discrete spatial solitons in lattices, amongst others. Recent progress in strong-field atomic physics include impressive demonstrations of attosecond pulses and high-harmonic generation via photoionization of free-electrons in gases at extreme intensities of 1014 Wcm2. Here we report the first phase-resolved observations of femtosecond optical solitons in a semiconductor microchip, with multiphoton ionization at picojoule energies and 1010 Wcm2 intensities. The dramatic nonlinearity leads to picojoule observations of free-electron-induced blue-shift at 1016 cm3 carrier densities and self-chirped femtosecond soliton acceleration. Furthermore, we evidence the time-gated dynamics of soliton splitting on-chip, and the suppression of soliton recurrence due to fast free-electron dynamics. Thes...

  17. Methods in Mammary Gland Development and Cancer: the second ENDBC meeting - intravital imaging, genomics, modeling and metastasis

    Stingl, John; Matthew J Smalley; Glukhova, Marina A.; Bentires-Alj, Mohamed

    2010-01-01

    The second meeting of the European Network for Breast Development and Cancer (ENBDC) on 'Methods in Mammary Gland Development and Cancer' was held in April 2010 in Weggis, Switzerland. The focus was on genomics and bioinformatics, extracellular matrix and stroma-epithelial cell interactions, intravital imaging, the search for metastasis founder cells and mouse models of breast cancer.

  18. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    Taejun Wang; Won Hyuk Jang; Seunghun Lee; Yoon, Calvin J.; Jun Ho Lee; Bumju Kim; Sekyu Hwang; Chun-Pyo Hong; Yeoreum Yoon; Gilgu Lee; Viet-Hoan Le; Seoyeon Bok; G-One Ahn; Jaewook Lee; Yong Song Gho

    2016-01-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetra...

  19. Multifocal multiphoton microscopy based on multianode photomultiplier tubes

    Kim, Ki Hean; Buehler, Christof; Bahlmann, Karsten; Ragan, Timothy; Lee, Wei-Chung A.; Nedivi, Elly; Heffer, Erica L.; Fantini, Sergio; So, Peter T. C.

    2007-01-01

    Multifocal multiphoton microscopy (MMM) enhances imaging speed by parallelization. It is not well understood why the imaging depth of MMM is significantly shorter than conventional single-focus multiphoton microscopy (SMM). In this report, we show that the need for spatially resolved detectors in MMM results in a system that is more sensitive to the scattering of emission photons with reduced imaging depth. For imaging depths down to twice the scattering mean free path length of emission phot...

  20. Multiphoton spectral microscopy for imaging and quantification of tissue glycation

    Tseng, Jo-Ya; Ghazaryan, Ara A.; Lo, Wen; Chen, Yang-Fang; Hovhannisyan, Vladimir; Chen, Shean-Jen; Tan, Hsin-Yuan; Dong, Chen-Yuan

    2010-01-01

    Tissue glycation from diabetes and aging can result in complications such as renal failure, blindness, nerve damage and vascular diseases. In this work, we applied multiphoton microscopy for imaging and characterizing the extent of tissue glycation. The characteristic features of multiphoton autofluorescence (MPAF) and second harmonic generation (SHG) images as well as MPAF spectra of glycated bovine skin, cornea and aorta were acquired. The analysis of MPAF intensity change accompanying the ...

  1. Advances in multi-photon processes and spectroscopy, v.3

    Lin, Sheng H

    1987-01-01

    In view of the rapid growth in both experimental and theoretical studies of multiphoton processes and multiphoton spectroscopy of atoms, ions, and molecules in chemistry, physics, biology and material sciences, this series contains review papers exploring the growth. They are readable not only by active researchers in these areas but also by those who are not experts in the field but intend to enter the field.

  2. Multiphoton above threshold effects in strong-field fragmentation

    Madsen, C. B.; Anis, F; Madsen, L. B.; Esry, B. D.

    2012-01-01

    We present a study of multiphoton dissociative ionization from molecules. By solving the time-dependent Schr\\"{o}dinger equation for H$_2^+$ and projecting the solution onto double continuum scattering states, we observe the correlated electron-nuclear ionization dynamics in detail. We show --- for the first time --- how multiphoton structure prevails as long as the energies of all fragments are accounted for. Our current work provides a new avenue to analyze strong-field fragmentation that l...

  3. Advances in multi-photon processes and spectroscopy, v.2

    Lin, Sheng H

    1986-01-01

    This volume focuses on the recent rapid growth in both experimental and theoretical studies of multiphoton processes and multiphoton spectroscopy of atoms, ions and molecules in chemistry, physics, biology, material sciences, It contains papers readable by active researchers and by those who intend to enter it. Theory and experiment are equally emphasized, and each review article is written in a self-contained manner by experts in the field so that readers learn the subject without much preparation.

  4. Integrated intravital microscopy and mathematical modeling to optimize nanotherapeutics delivery to tumors

    Anne L. van de Ven

    2012-03-01

    Full Text Available Inefficient vascularization hinders the optimal transport of cell nutrients, oxygen, and drugs to cancer cells in solid tumors. Gradients of these substances maintain a heterogeneous cell-scale microenvironment through which drugs and their carriers must travel, significantly limiting optimal drug exposure. In this study, we integrate intravital microscopy with a mathematical model of cancer to evaluate the behavior of nanoparticle-based drug delivery systems designed to circumvent biophysical barriers. We simulate the effect of doxorubicin delivered via porous 1000 x 400 nm plateloid silicon particles to a solid tumor characterized by a realistic vasculature, and vary the parameters to determine how much drug per particle and how many particles need to be released within the vasculature in order to achieve remission of the tumor. We envision that this work will contribute to the development of quantitative measures of nanoparticle design and drug loading in order to optimize cancer treatment via nanotherapeutics.

  5. Intravital Microscopy Reveals Differences in the Kinetics of Endocytic Pathways between Cell Cultures and Live Animals

    Roberto Weigert

    2012-11-01

    Full Text Available Intravital microscopy has enabled imaging of the dynamics of subcellular structures in live animals, thus opening the door to investigating membrane trafficking under physiological conditions. Here, we sought to determine whether the architecture and the environment of a fully developed tissue influences the dynamics of endocytic processes. To this aim, we imaged endocytosis in the stromal cells of rat salivary glands both in situ and after they were isolated and cultured on a solid surface. We found that the internalization of transferrin and dextran, two molecules that traffic via distinct mechanisms, is substantially altered in cultured cells, supporting the idea that the three dimensional organization of the tissue and the cues generated by the surrounding environment strongly affect membrane trafficking events.

  6. Combined application of dynamic light scattering imaging and fluorescence intravital microscopy in vascular biology

    The dynamic light scattering imaging (DLSI) system combined with the conventional fluorescence intravital microscope (FIM) has been applied for the examination of blood and lymph vessels in the mouse ear in vivo. While the CCD camera can be shared by both techniques the combined application of DLSI and FIM allows rapid switching between the modalities. In current study temporal speckles fluctuations are used for rendering blood vessels structure and monitoring blood perfusion with the higher spatial resolution, whereas FIM provides the images of lymphatic vessels. The results clearly demonstrate that combined application of DLSI and FIM approaches provides synchronic in vivo images of blood and lymph vessels with higher contrast and specificity. The use of this new dual-modal diagnostic system is particularly important and has a great potential to significantly expand the capabilities of vascular diagnostics providing synchronic in vivo images of blood and lymph vessels

  7. A Novel Model of Intravital Platelet Imaging Using CD41-ZsGreen1 Transgenic Rats

    Mizuno, Makoto; Tomizawa, Atsuyuki; Ohno, Kousaku; Jakubowski, Joseph A.; Sugidachi, Atsuhiro

    2016-01-01

    Platelets play pivotal roles in both hemostasis and thrombosis. Although models of intravital platelet imaging are available for thrombosis studies in mice, few are available for rat studies. The present effort aimed to generate fluorescent platelets in rats and assess their dynamics in a rat model of arterial injury. We generated CD41-ZsGreen1 transgenic rats, in which green fluorescence protein ZsGreen1 was expressed specifically in megakaryocytes and thus platelets. The transgenic rats exhibited normal hematological and biochemical values with the exception of body weight and erythroid parameters, which were slightly lower than those of wild-type rats. Platelet aggregation, induced by 20 μM ADP and 10 μg/ml collagen, and blood clotting times were not significantly different between transgenic and wild-type rats. Saphenous arteries of transgenic rats were injured with 10% FeCl3, and the formation of fluorescent thrombi was evaluated using confocal microscopy. FeCl3 caused time-dependent increases in the mean fluorescence intensity of injured arteries of vehicle-treated rats. Prasugrel (3 mg/kg, p.o.), administered 2 h before FeCl3, significantly inhibited fluorescence compared with vehicle-treated rats (4.5 ± 0.4 vs. 14.9 ± 2.4 arbitrary fluorescence units at 30 min, respectively, n = 8, P = 0.0037). These data indicate that CD41-ZsGreen1 transgenic rats represent a useful model for intravital imaging of platelet-mediated thrombus formation and the evaluation of antithrombotic agents. PMID:27128503

  8. Impact of rapamycin on phenotype and tolerogenic function of dendritic cells via intravital optical imaging

    Luo, Meijie; Zhang, Zhihong

    2014-03-01

    Rapamycin (RAPA) as a unique tolerance-promoting therapeutic drug is crucial to successful clinical organ transplantation. DC (Dendritic cells) play a critical role in antigen presentation to T cells to initiate immune responses involved in tissue rejection. Although the influence of RAPA on DC differentiation and maturation had been reported by some research groups, it is still controversial and unclear right now. In addition, it is also lack of study on investigating the role of DC in DTH reaction via intravital optical imaging. Herein, we investigated the effect of rapamycin on phenotype and function of bone marrow monocyte-derived DC both in vitro and in vivo. In vitro experiments by flow cytometry (FACS) showed that DC displayed decreased cell size and lower expression levels of surface molecule CD80 induced by RAPA; Furthermore, the phagocytic ability to OVA of DC was inhibited by RAPA started from 1 h to 2 h post co-incubation, but recovered after 4 h; In addition, the capacity of DC to activate naïve OT-II T cell proliferation was also inhibited at 3 day post co-incubation, but had no effect at 5 day, the data indicated this effect was reversible when removing the drug. More importantly, the DC-T interaction was monitored both in vitro and in intravital lymph node explant, and showed that RAPA-DC had a significant lower proportion of long-lived (>15min) contacts. Thus, RAPA displayed immunosuppressive to phenotypic and functional maturation of DC, and this phenomenon induced by RAPA may favorable in the clinical organ transplantation in future.

  9. Automated filtering of intrinsic movement artifacts during two-photon intravital microscopy.

    Denis Soulet

    Full Text Available In vivo imaging using two-photon microscopy is an essential tool to explore the dynamic of physiological events deep within biological tissues for short or extended periods of time. The new capabilities offered by this technology (e.g. high tissue penetrance, low toxicity have opened a whole new era of investigations in modern biomedical research. However, the potential of using this promising technique in tissues of living animals is greatly limited by the intrinsic irregular movements that are caused by cardiac and respiratory cycles and muscular and vascular tone. Here, we show real-time imaging of the brain, spinal cord, sciatic nerve and myenteric plexus of living mice using a new automated program, named Intravital_Microscopy_Toolbox, that removes frames corrupted with motion artifacts from time-lapse videos. Our approach involves generating a dissimilarity score against precalculated reference frames in a specific reference channel, thus allowing the gating of distorted, out-of-focus or translated frames. Since the algorithm detects the uneven peaks of image distortion caused by irregular animal movements, the macro allows a fast and efficient filtering of the image sequence. In addition, extra features have been implemented in the macro, such as XY registration, channel subtraction, extended field of view with maximum intensity projection, noise reduction with average intensity projections, and automated timestamp and scale bar overlay. Thus, the Intravital_Microscopy_Toolbox macro for ImageJ provides convenient tools for biologists who are performing in vivo two-photon imaging in tissues prone to motion artifacts.

  10. A Novel Model of Intravital Platelet Imaging Using CD41-ZsGreen1 Transgenic Rats.

    Makoto Mizuno

    Full Text Available Platelets play pivotal roles in both hemostasis and thrombosis. Although models of intravital platelet imaging are available for thrombosis studies in mice, few are available for rat studies. The present effort aimed to generate fluorescent platelets in rats and assess their dynamics in a rat model of arterial injury. We generated CD41-ZsGreen1 transgenic rats, in which green fluorescence protein ZsGreen1 was expressed specifically in megakaryocytes and thus platelets. The transgenic rats exhibited normal hematological and biochemical values with the exception of body weight and erythroid parameters, which were slightly lower than those of wild-type rats. Platelet aggregation, induced by 20 μM ADP and 10 μg/ml collagen, and blood clotting times were not significantly different between transgenic and wild-type rats. Saphenous arteries of transgenic rats were injured with 10% FeCl3, and the formation of fluorescent thrombi was evaluated using confocal microscopy. FeCl3 caused time-dependent increases in the mean fluorescence intensity of injured arteries of vehicle-treated rats. Prasugrel (3 mg/kg, p.o., administered 2 h before FeCl3, significantly inhibited fluorescence compared with vehicle-treated rats (4.5 ± 0.4 vs. 14.9 ± 2.4 arbitrary fluorescence units at 30 min, respectively, n = 8, P = 0.0037. These data indicate that CD41-ZsGreen1 transgenic rats represent a useful model for intravital imaging of platelet-mediated thrombus formation and the evaluation of antithrombotic agents.

  11. Molecular detection by multiphoton photoionization: Final report, 1 November 1985-1 November 1986

    This paper discusses the use of multiphoton ionization techniques to detection molecules at a sensitivity approaching one-molecule/cm3. Multiphoton fragmentation processes and ion spectroscopy are discussed. 10 refs., 3 figs

  12. High-resolution multimodal clinical multiphoton tomography of skin

    König, Karsten

    2011-03-01

    This review focuses on multimodal multiphoton tomography based on near infrared femtosecond lasers. Clinical multiphoton tomographs for 3D high-resolution in vivo imaging have been placed into the market several years ago. The second generation of this Prism-Award winning High-Tech skin imaging tool (MPTflex) was introduced in 2010. The same year, the world's first clinical CARS studies have been performed with a hybrid multimodal multiphoton tomograph. In particular, non-fluorescent lipids and water as well as mitochondrial fluorescent NAD(P)H, fluorescent elastin, keratin, and melanin as well as SHG-active collagen has been imaged with submicron resolution in patients suffering from psoriasis. Further multimodal approaches include the combination of multiphoton tomographs with low-resolution wide-field systems such as ultrasound, optoacoustical, OCT, and dermoscopy systems. Multiphoton tomographs are currently employed in Australia, Japan, the US, and in several European countries for early diagnosis of skin cancer, optimization of treatment strategies, and cosmetic research including long-term testing of sunscreen nanoparticles as well as anti-aging products.

  13. The multiphoton ionization of uranium hexafluoride

    Multiphoton ionization (MPI) time-of-flight mass spectroscopy and photoelectron spectroscopy studies of UF6 have been conducted using focused light from the Nd:YAG laser fundamental (λ=1064 nm) and its harmonics (λ=532, 355, or 266 nm), as well as other wavelengths provided by a tunable dye laser. The MPI mass spectra are dominated by the singly and multiply charged uranium ions rather than by the UFx+ fragment ions even at the lowest laser power densities at which signal could be detected. The laser power dependence of Un+ ions signals indicates that saturation can occur for many of the steps required for their ionization. In general, the doubly-charged uranium ion (U2+) intensity is much greater than that of the singly-charged uranium ion (U+). For the case of the tunable dye laser experiments, the Un+ (n = 1- 4) wavelength dependence is relatively unstructured and does not show observable resonance enhancement at known atomic uranium excitation wavelengths. The dominance of the U2+ ion and the absence or very small intensities of UFx+ fragments, along with the unsaturated wavelength dependence, indicate that mechanisms may exist other than ionization of bare U atoms after the stepwise photodissociation of F atoms from the parent molecule

  14. Selective enhancement of resonant multiphoton ionization with strong laser fields

    Li, Min; Luo, Siqiang; Zhou, Yueming; Zhang, Qingbin; Lan, Pengfei; Lu, Peixiang

    2015-01-01

    High-resolution photoelectron momentum distributions of Xe atom ionized by 800-nm linearly polarized laser fields have been traced at intensities from 1.1*1013 W/cm2 to 3.5*1013 W/cm2 using velocity-map imaging techniques. At certain laser intensities, the momentum spectrum exhibits a distinct double-ring structure for low-order above-threshold ionization, which appears to be absent at lower or higher laser intensities. By investigating intensity-resolved photoelectron energy spectrum, we find that this double-ring structure originates from resonant multiphoton ionization involving multiple Rydberg states of atoms. Varying the laser intensity, we can selectively enhance multiphoton excitation of atomic Rydberg populations. The photoelectron angular distributions of multiphoton resonance are also investigated for the low-order above threshold ionization.

  15. Dynamic resonances and tunnelling in the multiphoton ionization of argon

    We present results of wavepacket simulations for multiphoton ionization in argon. A single active electron model is applied to estimate the single-electron ionization rates and photoelectron energy distributions for λ = 390 nm light with intensities up to I = 2 x 1014 W cm-2. The multiphoton ionization rates are compared with R-matrix Floquet calculations and found to be in very good agreement. The photoelectron energy distribution is used to study the nature of ionization at the higher intensities. Our results are consistent with recent calculations and experiments which show the imprint of the tunnelling process in the multiphoton regime. For few-cycle intense pulses, we find that the strong modulation of intensity and increased bandwidth leads to dynamic mixing of the 3d and 5s resonances.

  16. Intravital two-photon microscopy for studying the uptake and trafficking of fluorescently conjugated molecules in live rodents

    Masedunskas, Andrius; Weigert, Roberto

    2008-01-01

    Here we describe an experimental system based on intravital two-photon microscopy for studying endocytosis in live animals. The rodent submandibular glands were chosen as model organs since they can be exposed easily, imaged without compromising their function and, furthermore, they are amenable to pharmacological and genetic manipulations. We show that the fibroblasts within the stroma of the glands readily internalize systemically injected molecules such as fluorescently conjugated dextran ...

  17. Treadmill exercise induces neutrophil recruitment into muscle tissue in a reactive oxygen species-dependent manner. An intravital microscopy study.

    Albená Nunes-Silva

    Full Text Available Intense exercise is a physiological stress capable of inducing the interaction of neutrophils with muscle endothelial cells and their transmigration into tissue. Mechanisms driving this physiological inflammatory response are not known. Here, we investigate whether production of reactive oxygen species is relevant for neutrophil interaction with endothelial cells and recruitment into the quadriceps muscle in mice subjected to the treadmill fatiguing exercise protocol. Mice exercised until fatigue by running for 56.3±6.8 min on an electric treadmill. Skeletal muscle was evaluated by intravital microscopy at different time points after exercise, and then removed to assess local oxidative stress and histopathological analysis. We observed an increase in plasma lactate and creatine kinase (CK concentrations after exercise. The numbers of monocytes, neutrophils, and lymphocytes in blood increased 12 and 24 hours after the exercise. Numbers of rolling and adherent leukocytes increased 3, 6, 12, and 24 hours post-exercise, as assessed by intravital microscopy. Using LysM-eGFP mice and confocal intravital microscopy technology, we show that the number of transmigrating neutrophils increased 12 hours post-exercise. Mutant gp91phox-/- (non-functional NADPH oxidase mice and mice treated with apocynin showed diminished neutrophil recruitment. SOD treatment promoted further adhesion and transmigration of leukocytes 12 hours after the exercise. These findings confirm our hypothesis that treadmill exercise increases the recruitment of leukocytes to the postcapillary venules, and NADPH oxidase-induced ROS plays an important role in this process.

  18. Advances in multi-photon processes and spectroscopy, v.5

    Lin, Sheng H

    1989-01-01

    In view of the rapid growth in both experimental and theoretical studies of multiphoton processes and multiphoton spectroscopy of atoms, ions and molecules in many interdisciplinary fields, an Advanced Series that contains review papers readable not only to active researchers in these areas but also to those who are not experts in the field but intend to enter the field is very necessary. This series attempts to serve this purpose. Each review article is written in a self-contained manner by the experts in the area so that the readers can grasp the knowledge in the area without too much prepar

  19. Unambiguous atomic Bell measurement assisted by multiphoton states

    Torres, Juan Mauricio; Bernád, József Zsolt; Alber, Gernot

    2016-05-01

    We propose and theoretically investigate an unambiguous Bell measurement of atomic qubits assisted by multiphoton states. The atoms interact resonantly with the electromagnetic field inside two spatially separated optical cavities in a Ramsey-type interaction sequence. The qubit states are postselected by measuring the photonic states inside the resonators. We show that if one is able to project the photonic field onto two coherent states on opposite sites of phase space, an unambiguous Bell measurement can be implemented. Thus, our proposal may provide a core element for future components of quantum information technology such as a quantum repeater based on coherent multiphoton states, atomic qubits and matter-field interaction.

  20. Quantum cryptography with entangled multiphotons of the same polarization

    Multiphoton entanglement in the same polarization has been theoretically shown to be obtainable by type-I spontaneous parametric down-conversion (SPDC), which can generate bright pulses more easily than type-II SPDC. A quantum cryptographic protocol utilizing photon number coding of the detected type-I entangled multiphotons is described. The information capacity versus photon number is calculated after considering the transmission loss inside the optical fiber and the detector efficiency, considering possible attacks to the scheme. The result thus achieved compares very favorably with all other schemes employing entanglement

  1. Effect of multiphoton ionization on performance of crystalline lens.

    Gupta, Pradeep Kumar; Singh, Ram Kishor; Strickland, D; Campbell, M C W; Sharma, R P

    2014-12-15

    This Letter presents a model for propagation of a laser pulse in a human crystalline lens. The model contains a transverse beam diffraction effect, laser-induced optical breakdown for the creation of plasma via a multiphoton ionization process, and the gradient index (GRIN) structure. Plasma introduces the nonlinearity in the crystalline lens which affects the propagation of the beam. The multiphoton ionization process generates plasma that changes the refractive index and hence leads to the defocusing of the laser beam. The Letter also points out the relevance of the present investigation to cavitation bubble formation for restoring the elasticity of the eyes. PMID:25502994

  2. Observation of detection-dependent multi-photon coherence times

    Ra, Young-Sik; Tichy, Malte C.; Lim, Hyang-Tag;

    2013-01-01

    which the multi-photon coherence time, defined by the width of the interference signal, depends on the number of interfering photons and on the measurement scheme chosen to detect the particles. A theoretical analysis reveals that all multi-photon interferences with more than two particles feature this...... dependence, which can be attributed to higher-order effects in the mutual indistinguishability of the particles. As a striking consequence, a single, well-defined many-particle quantum state can exhibit qualitatively different degrees of interference, depending on the chosen observable. Therefore, optimal...... sensitivity in many-particle quantum interferometry can only be achieved by choosing a suitable detection scheme....

  3. Quantitative studies of multiphoton ionization using tunable VUV radiation

    The storage ring free electron laser makes studies of multiphoton ionization in the vacuum ultraviolet possible. At relatively low laser intensities one can study two-photon resonant three-photon ionization of atoms in a regime where perturbation theory works well. In this regime cross sections for the multiphoton processes can be measured accurately and then used for sensitive, quantitative detection of atoms. At higher intensities higher-order processes such as multiple ionization can take place. The tunability, variable pulse length, and well characterized spatial distribution of the FEL is important in unraveling the mechanisms of these processes

  4. Nanosecond Versus, Picosecond Molecular Multiphoton Fragmentation of Ketene and Cyclohexane

    Castillejo, M.; Martín, M; de Nalda, R.

    1998-01-01

    Multiphoton dissociation of ketene was studied at 290.5 nm after irradiation of the first excited singlet state with two different laser pulsewidths of 4 ns and 10 ps. Analysis of the photofragment fluorescence spectra in the two time domains sheds light on the mechanisms that are responsible for the production of the observed CH(A2Δ),  (B2Σ−) and C2(d3Πg) photofragments. Multiphoton ionization of cyclohexane induced by a visible laser at 581 nm and its second harmonic at 290.5 nm was measure...

  5. Multiphoton above threshold effects in strong-field fragmentation

    Madsen, C B; Madsen, L B; Esry, B D

    2012-01-01

    We present a study of multiphoton dissociative ionization from molecules. By solving the time-dependent Schr\\"{o}dinger equation for H$_2^+$ and projecting the solution onto double continuum scattering states, we observe the correlated electron-nuclear ionization dynamics in detail. We show --- for the first time --- how multiphoton structure prevails as long as the energies of all fragments are accounted for. Our current work provides a new avenue to analyze strong-field fragmentation that leads to a deeper understanding of the correlated molecular dynamics.

  6. Multiphoton above threshold effects in strong-field fragmentation

    B Madsen, C; Anis, F; B Madsen, L;

    2012-01-01

    We present a study of multiphoton dissociative ionization from molecules. By solving the time-dependent Schrödinger equation for H2+ and projecting the solution onto double continuum scattering states, we observe the correlated electron-nuclear ionization dynamics in detail. We show—for the first...... time—how multiphoton structure prevails as long as one accounts for the energies of all the fragments. Our current work provides a new avenue to analyze strong-field fragmentation that leads to a deeper understanding of the correlated molecular dynamics....

  7. Optical clearing and multiphoton imaging of paraffin-embedded specimens

    Wilson, Jesse W.; Degan, Simone; Fischer, Martin C.; Warren, Warren S.

    2013-02-01

    New labeling, imaging, or analysis tools could provide new retrospective insights when applied to archived, paraffin-embedded samples. Deep-tissue multiphoton microscopy of paraffin-embedded specimens is achieved using optical clearing with mineral oil. We tested a variety of murine tissue specimens including skin, lung, spleen, kidney, and heart, acquiring multiphoton autofluorescence and second-harmonic generation, and pump-probe images This technique introduces the capability for non-destructive 3-dimensional microscopic imaging of existing archived pathology specimens, enabling retrospective studies.

  8. Multiphoton Coherent Manipulation in Large Spin Qubits

    Chiorescu, Irinel

    2009-03-01

    Manipulation of quantum information allows certain algorithms to be performed at unparalleled speeds. Photons are an ideal choice to manipulate qubits as they interact with quantum systems in predictable ways. They are a versatile tool for manipulating, reading/coupling qubits and for encoding/transferring quantum information over long distances. Spin-based qubits have well known behavior under photon driving and can be potentially operated up to room temperature. When diluted enough to avoid uncontrolled spin-spin interactions, a variety of spin qubits show long coherence times, e.g. the nitrogen vacancies in pure diamonds (1,2), nitrogen atoms trapped in a C60 cage (3), Ho3+ and Cr5+ ions (4,5) and molecular magnets (6,7). We have used large spin Mn2+ ions (S=5/2) to realize a six level system that can be operated by means of single as well as multi-photon coherent Rabi oscillations (8). This spin system has a very small anisotropy whose effect can be tuned in-situ to turn the system into a multi-level harmonic system. This offer new ways of manipulating, reading and resetting a spin qubit. Decoherence effects are strongly reduced by the quasi-isotropic electron interaction with the crystal field and with the 55Mn nuclear spins. [0pt] 1. R. Hanson et al., Science 320, 352 (2008). [0pt] 2. M.V. Gurudev Dutt et al., Science 316, 1312 (2007). [0pt] 3. G.W. Morley et al., Phys. Rev. Lett. 98, 220501 (2007). [0pt] 4. S. Bertaina et al., Nat. Nanotech. 2, 39 (2007). [0pt] 5. S. Nellutla et al., Phys. Rev. Lett. 99, 137601 (2007). [0pt] 6. A. Ardavan et al., Phys. Rev. Lett. 98, 057201 (2007). [0pt] 7. S. Bertaina et al., Nature 453, 203,(2008). [0pt] 8. S. Bertaina et al., submitted.

  9. Parallelized TCSPC for dynamic intravital fluorescence lifetime imaging: quantifying neuronal dysfunction in neuroinflammation.

    Jan Leo Rinnenthal

    Full Text Available Two-photon laser-scanning microscopy has revolutionized our view on vital processes by revealing motility and interaction patterns of various cell subsets in hardly accessible organs (e.g. brain in living animals. However, current technology is still insufficient to elucidate the mechanisms of organ dysfunction as a prerequisite for developing new therapeutic strategies, since it renders only sparse information about the molecular basis of cellular response within tissues in health and disease. In the context of imaging, Förster resonant energy transfer (FRET is one of the most adequate tools to probe molecular mechanisms of cell function. As a calibration-free technique, fluorescence lifetime imaging (FLIM is superior for quantifying FRET in vivo. Currently, its main limitation is the acquisition speed in the context of deep-tissue 3D and 4D imaging. Here we present a parallelized time-correlated single-photon counting point detector (p-TCSPC (i for dynamic single-beam scanning FLIM of large 3D areas on the range of hundreds of milliseconds relevant in the context of immune-induced pathologies as well as (ii for ultrafast 2D FLIM in the range of tens of milliseconds, a scale relevant for cell physiology. We demonstrate its power in dynamic deep-tissue intravital imaging, as compared to multi-beam scanning time-gated FLIM suitable for fast data acquisition and compared to highly sensitive single-channel TCSPC adequate to detect low fluorescence signals. Using p-TCSPC, 256×256 pixel FLIM maps (300×300 µm(2 are acquired within 468 ms while 131×131 pixel FLIM maps (75×75 µm(2 can be acquired every 82 ms in 115 µm depth in the spinal cord of CerTN L15 mice. The CerTN L15 mice express a FRET-based Ca-biosensor in certain neuronal subsets. Our new technology allows us to perform time-lapse 3D intravital FLIM (4D FLIM in the brain stem of CerTN L15 mice affected by experimental autoimmune encephalomyelitis and, thereby, to truly quantify

  10. Intravital placenta imaging reveals microcirculatory dynamics impact on sequestration and phagocytosis of Plasmodium-infected erythrocytes.

    Luciana Vieira de Moraes

    2013-01-01

    Full Text Available Malaria in pregnancy is exquisitely aggressive, causing a range of adverse maternal and fetal outcomes prominently linked to Plasmodium-infected erythrocyte cytoadherence to fetal trophoblast. To elucidate the physiopathology of infected erythrocytes (IE sequestration in the placenta we devised an experimental system for intravital placental examination of P. berghei-infected mice. BALB/c females were mated to C57Bl/6 CFP+ male mice and infected with GFP+ P. berghei IE, and at gestational day 18, placentas were exposed for time-lapse imaging acquisition under two-photon microscopy. Real-time images and quantitative measurements revealed that trophoblast conformational changes transiently restrain blood flow in the mouse placental labyrinth. The complex dynamics of placental microcirculation promotes IE accumulation in maternal blood spaces with low blood flow and allows the establishment of stable IE-trophoblast contacts. Further, we show that the fate of sequestered IE includes engulfment by both macrophagic and trophoblastic fetal-derived cells. These findings reinforce the current paradigm that IE interact with the trophoblast and provide definitive evidence on two novel pathogenesis mechanisms: (1 trophoblast layer controls placental microcirculation promoting IE sequestration; and (2 fetal-derived placental cells engulf sequestered IE.

  11. Intravital spectral imaging as a tool for accurate measurement of vascularization in mice

    Tsatsanis Christos

    2010-10-01

    Full Text Available Abstract Background Quantitative determination of the development of new blood vessels is crucial for our understanding of the progression of several diseases, including cancer. However, in most cases a high throughput technique that is simple, accurate, user-independent and cost-effective for small animal imaging is not available. Methods In this work we present a simple approach based on spectral imaging to increase the contrast between vessels and surrounding tissue, enabling accurate determination of the blood vessel area. This approach is put to test with a 4T1 breast cancer murine in vivo model and validated with histological and microvessel density analysis. Results We found that one can accurately measure the vascularization area by using excitation/emission filter pairs which enhance the surrounding tissue's autofluorescence, significantly increasing the contrast between surrounding tissue and blood vessels. Additionally, we found excellent correlation between this technique and histological and microvessel density analysis. Conclusions Making use of spectral imaging techniques we have shown that it is possible to accurately determine blood vessel volume intra-vitally. We believe that due to the low cost, accuracy, user-independence and simplicity of this technique, it will be of great value in those cases where in vivo quantitative information is necessary.

  12. Intra-vital microscopy of lung tissue: A simulation based analysis of the image formation

    Gaertner, Maria; Schirrmann, Kerstin; Schnabel, Christian; Meissner, Sven; Kertzscher, Ulrich; Kirsten, Lars; Koch, Edmund

    2013-06-01

    In the course of pulmonary research, understanding alveolar tissue dynamics plays a critical role in the treatment of patients suffering from acute lung diseases. As a gold standard technique for monitoring micro scale changes of lung tissue, real-time intra-vital microscopy (IVM) has been established to evaluate the behavior of the alveolar tissue. To allow profound qualitative and quantitative conclusions, characteristic features of the obtained images have to be thoroughly understood. These factors are strongly influenced by the imaging setup and physiological condition of the lung. To circumvent misinterpretations, a ray-tracing approach has been applied in this study using an idealized geometry of the mouse lung parenchyma deduced from optical coherence tomography (OCT) as a complementary imaging technique. Basic features of IVM images are double ring structures and disappearing of alveoli related to liquid infiltration. Ray propagation analysis reveals the formation of these features by two major reflection processes: partial reflection and total internal reflection. The results give rise to quantification errors of the alveolar area related to reflexes misinterpreted as alveolar borders and should further be used to yield a correction factor for future IVM lung tissue studies.

  13. Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study

    Rafael Simas

    2012-01-01

    Full Text Available OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage

  14. Advances in time-dependent methods for multiphoton processes

    This paper discusses recent theoretical results on above threshold ionization harmonic generation and high-frequency, high intensity suppression of ionization. These studies of multiphoton processes in atoms and molecules for short, intense pulsed optical lasers have been carried out using techniques which involve the explicit solution of the time-dependent Schroedinger equation. 43 refs., 5 figs

  15. Multiphoton ionization of magnesium via an autoionizing state

    N.J. van Druten; R. Trainham; H.G. Muller

    1994-01-01

    Multiphoton single and double ionization of magnesium was studied by measuring electron energy spectra and ion mass spectra using 1-ps laser pulses in the 580-595-nm wavelength and 1012-1013-W/cm2 intensity range. In single ionization the (3p)2 1S doubly excited autoionizing state, resonant at the f

  16. All short pulse multiphoton ionization is resonant ionization

    Energy resolved photoelectron spectra of multiphoton ionization taken with a 300 fs laser pulse at 616 nm shows that the ionization probability is highly structured as a function of laser intensity. The spectrum is consistent with all of the ionization occurring at intensity resonances

  17. Multi-photon Absorption in Optical Pumping of Rubidium

    Xu, Xinyi

    2015-01-01

    In optical pumping of rubidium, a new kind of absorption occurs with a higher amplitude of radio frequency current. From measurement of the corresponding magnetic field value where this absorption occurs, there is a conclusion that it is multi-photon absorption. Both the degeneracy and energy of photons contribute to the intensity.

  18. Multi-photon Rabi model: Generalized parity and its applications

    Quantum multi-photon spin–boson model is considered. We solve an operator Riccati equation associated with that model and present a candidate for a generalized parity operator allowing to transform spin–boson Hamiltonian to a block-diagonal form what indicates an existence of the related symmetry of the model.

  19. On a Jaynes-Cummings type model with multiphoton transitions

    The authors present a quantum electrodynamic model, soluble in the dipole and rotating wave approximation, for a three-level atom interacting with a two-mode resonant radiation field through the multiphoton transition mechanism. Population dynamics and photon statistics in this Jaynes-Cummings type model are examined. (author)

  20. Landau-Dykhne approximation for multiphoton dipole-forbidden transitions

    A two-level system in a monochromatic laser field is considered in the Landau-Dykhne approximation under the violation of dipole selection rules. An analytic expression is obtained for the rate of transitions. The multiphoton and tunneling limits are found

  1. Influence of Heat-radiating on Multi-photon Compton Scattering High-energy Electron

    HAO Dong-shan; WANG Xin-min

    2007-01-01

    Using the model of the inverse Compton scattering between high-energy electrons and heat-radiation photons, the influence of heat-radiating photons on multi-photon Compton scattering high-energy electrons is studied . The results show that the energy loss, power loss, light resistance and light pressure of the high-energy electron formed by heat radiating are all proportional to the temperature T4 of the vacuum cavity of the electron,the Lorentz factor γ2 of the high-energy electrons, the scattering section of the electron and the number of photons acting at the same time with high-energy electrons. A good method for lessening the energy loss of the high-energy electron by using the one-photon Compton scattering between high-energy electrons and heat radiation photons is proposed.

  2. Multiphoton dynamics of qutrits in the ultrastrong coupling regime with a quantized photonic field

    Multiphoton resonant excitation of a three-state quantum system (a qutrit) with a single-mode photonic field is considered in the ultrastrong coupling regime, when the qutrit–photonic field coupling rate is comparable to appreciable fractions of the photon frequency. For ultrastrong couplings, the obtained solutions of the Schrödinger equation that reveal multiphoton Rabi oscillations in qutrits with the interference effects leading to the collapse and revival of atomic excitation probabilities at the direct multiphoton resonant transitions

  3. Hamiltonian models of multiphoton processes and four--photon squeezed states via nonlinear canonical transformations

    De Siena, Silvio; Di Lisi, Antonio; Illuminati, Fabrizio

    2002-01-01

    We introduce nonlinear canonical transformations that yield effective Hamiltonians of multiphoton down conversion processes, and we define the associated non-Gaussian multiphoton squeezed states as the coherent states of the multiphoton Hamiltonians. We study in detail the four-photon processes and the associated non-Gaussian four-photon squeezed states. The realization of squeezing, the behavior of the field statistics, and the structure of the phase space distributions show that these state...

  4. Multiphoton dynamics of qutrits in the ultrastrong coupling regime with a quantized photonic field

    Avetissian, H. K., E-mail: avetissian@ysu.am; Avetissian, A. K.; Mkrtchian, G. F. [Yerevan State University 0025, Center of Strong Fields Physics (Armenia); Kibis, O. V. [Novosibirsk State Technical University, Department of Applied and Theoretical Physics (Russian Federation)

    2015-12-15

    Multiphoton resonant excitation of a three-state quantum system (a qutrit) with a single-mode photonic field is considered in the ultrastrong coupling regime, when the qutrit–photonic field coupling rate is comparable to appreciable fractions of the photon frequency. For ultrastrong couplings, the obtained solutions of the Schrödinger equation that reveal multiphoton Rabi oscillations in qutrits with the interference effects leading to the collapse and revival of atomic excitation probabilities at the direct multiphoton resonant transitions.

  5. Multiphoton Rabi Oscillations of Correlated Electrons in Strong Field Nonsequential Double Ionization

    Qing, Liao; Cheng, Huang; Peixiang, Lu

    2011-01-01

    With quantum calculations, we have investigated the multiphoton nonsequential double ionization of helium atoms in intense laser fields at ultraviolet wavelengths. Very surprisingly, we find a so-far unobserved double-circle structure in the correlated electron momentum spectra. The double-circle structure essentially reveals multiphoton Rabi oscillations of two electrons, which are strongly supported by the oscillating population of a certain doubly excited state and by the oscillating double ionization signals. This two-electron multiphoton Rabi effect provides profound understandings of electronic correlations and complicated multiphoton phenomena and is expected to be a new tool for broad applications, such as quantum coherent control.

  6. Multiphoton Rabi oscillations of correlated electrons in strong-field nonsequential double ionization

    With quantum calculations, we have investigated the multiphoton nonsequential double ionization of helium atoms in intense laser fields at ultraviolet wavelengths. Very surprisingly, we found a so-far unobserved double-circle structure in the correlated electron momentum spectra. The double-circle structure essentially reveals multiphoton Rabi oscillations of two electrons, which are strongly supported by the oscillating population of a certain doubly excited state and by the oscillating double ionization signals. This two-electron multiphoton Rabi effect provides a profound understanding of electronic correlations and complicated multiphoton phenomena and is expected to be a new tool for broad applications, such as quantum coherent control. (paper)

  7. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G.-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-06-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.

  8. Multiphoton Imaging of Ultrasound Bioeffects in the Murine Brain

    Raymond, Scott; Skoch, Jesse; Bacskai, Brian; Hynynen, Kullervo

    2006-05-01

    The purpose of this study was to demonstrate the feasibility of multiphoton imaging in the murine brain during exposure to ultrasound. Our experimental setup coupled ultrasound through the ventral surface of the mouse while allowing imaging through a cranial window from the dorsal surface. Field attenuation was estimated by scanning the field after insertion of a freshly sacrificed mouse; beam profile and peak position were preserved, suggesting adequate targeting for imaging experiments. C57 mice were imaged with a Biorad multiphoton microscope while being exposed to ultrasound (f = 1.029 MHz, peak pressure ˜ 200 kPa, average power ˜ 0.18 W) with IV injection of Optison. We observed strong vasoconstriction coincident with US and Optison, as well as permeabilization of the blood-brain barrier.

  9. Experimental Resonance Enhanced Multiphoton Ionization (REMPI) studies of small molecules

    Dehmer, J. L.; Dehmer, P. M.; Pratt, S. T.; Ohalloran, M. A.; Tomkins, F. S.

    1987-01-01

    Resonance enhanced multiphoton ionization (REMPI) utilizes tunable dye lasers to ionize an atom or molecule by first preparing an excited state by multiphoton absorption and then ionizing that state before it can decay. This process is highly selective with respect to both the initial and resonant intermediate states of the target, and it can be extremely sensitive. In addition, the products of the REMPI process can be detected as needed by analyzing the resulting electrons, ions, fluorescence, or by additional REMPI. This points to a number of exciting opportunities for both basic and applied science. On the applied side, REMPI has great potential as an ultrasensitive, highly selective detector for trace, reactive, or transient species. On the basic side, REMPI affords an unprecedented means of exploring excited state physics and chemistry at the quantum-state-specific level. An overview of current studies of excited molecular states is given to illustrate the principles and prospects of REMPI.

  10. High-order multiphoton ionization photoelectron spectroscopy of NO

    Photoelectron energy and angular distributions of NO following three different high-order multiphoton ionization (MPI) schemes have been measured. The 3+3 resonantly enhanced multiphoton ionization (REMPI) via the A2Σ+ (v=0) level yielded a distribution of electron energies corresponding to all accessible vibrational levels (v+=0--6) of the nascent ion. Angular distributions of electrons corresponding to v+=0 and v+=3 were significantly different. The 3+2 REMPI via the A2Σ+ (v=1) level produced only one low-energy electron peak (v+=1). Nonresonant MPI at 532 nm yielded a distribution of electron energies corresponding to both four- and five-photon ionization. Prominent peaks in the five-photon photoelectron spectrum (PES) suggest contributions from near-resonant states at the three-photon level

  11. Microwave multiphoton ionization and excitation of helium Rydberg atoms

    We study experimentally and theoretically the detailed field-amplitude dependence of the multiphoton ionization and excitation probability of highly excited n03S helium atoms in a 9.924-GHz linearly polarized microwave electric field. For ionization, with principal quantum numbers in the range n0=25--32, we use a quasistatic analysis that employs integration of the time-dependent Schroedinger equation using basis states of the static field Hamiltonian. The calculated results are used to interpret the observed ionization threshold structure. For excitation, the results of n03S→n03L, L>2 excitation experiments are explained quantitatively and precisely using a theory of multiphoton resonances. We present maps of quasienergy levels that allow the study of the dynamics of the field-switching transients. These transient effects are analyzed along the lines of standard atomic collision theory and are shown to determine the shape of the observed resonances

  12. Theoretical aspects of multiphoton ionization with many resonant excited states

    The variety of the parameters involved in multi-color multi-step ionization makes it a formidable job to obtain a theoretically comprehensible overview of the process. We examine these parameters of such processes as well as commonly used assumptions in theoretical investigations of multiphoton ionization with many resonantly excited levels. The density matrix formalism is adequate to treat resonant multiphoton ionization when the number of the resonant levels involved is not too large, solving the resonantly coupled states separately beyond the lowest order perturbation theory, while the rest of the states are treated perturbatively. An example of such formalism is given for a four-level system ionized with three lasers each of which resonantly couples the adjacent pairs of the atomic states.

  13. A simple model of multiphoton micromachining in silk hydrogels

    Applegate, Matthew B.; Alonzo, Carlo; Georgakoudi, Irene; Kaplan, David L.; Omenetto, Fiorenzo G.

    2016-06-01

    High resolution three-dimensional voids can be directly written into transparent silk fibroin hydrogels using ultrashort pulses of near-infrared (NIR) light. Here, we propose a simple finite-element model that can be used to predict the size and shape of individual features under various exposure conditions. We compare predicted and measured feature volumes for a wide range of parameters and use the model to determine optimum conditions for maximum material removal. The simplicity of the model implies that the mechanism of multiphoton induced void creation in silk is due to direct absorption of light energy rather than diffusion of heat or other photoproducts, and confirms that multiphoton absorption of NIR light in silk is purely a 3-photon process.

  14. Does Infrared Multiphoton Dissociation of Vinyl Chloride Yield Cold Vinylidene?

    Fernando, Ravin; Qu, Chen; Bowman, Joel M; Field, Robert W; Suits, Arthur G

    2015-07-01

    Velocity map imaging of the infrared multiphoton dissociation of vinyl chloride shows the formation of HCl in rotational levels below J = 10 that are associated with the three-center elimination pathway. The total translational energy release is observed to peak at 3-5 kcal/mol, which is consistent with the low reverse barrier predicted for the formation of HCl with vinylidene coproducts. Direct dynamics trajectory studies from the three-center transition state reproduce the observed distributions and show that the associated vinylidene is formed with only modest rotational excitation, precluding Coriolis-induced mixing among the excited vibrational levels of acetylene that would lead to distribution of vinylidene character into many vibrationally mixed acetylene vibrational levels. The results suggest that infrared multiphoton dissociation of vinyl chloride is an efficient route to synthesis of stable, cold vinylidene. PMID:26266719

  15. Characteristics of subgingival calculus detection by multiphoton fluorescence microscopy

    Tung, Oi-Hong; Lee, Shyh-Yuan; Lai, Yu-Lin; Chen, How-Foo

    2011-06-01

    Subgingival calculus has been recognized as a major cause of periodontitis, which is one of the main chronic infectious diseases of oral cavities and a principal cause of tooth loss in humans. Bacteria deposited in subgingival calculus or plaque cause gingival inflammation, function deterioration, and then periodontitis. However, subgingival calculus within the periodontal pocket is a complicated and potentially delicate structure to be detected with current dental armamentaria, namely dental x-rays and dental probes. Consequently, complete removal of subgingival calculus remains a challenge to periodontal therapies. In this study, the detection of subgingival calculus employing a multiphoton autofluorescence imaging method was characterized in comparison with a one-photon confocal fluorescence imaging technique. Feasibility of such a system was studied based on fluorescence response of gingiva, healthy teeth, and calculus with and without gingiva covered. The multiphoton fluorescence technology perceived the tissue-covered subgingival calculus that cannot be observed by the one-photon confocal fluorescence method.

  16. Individual bioaerosol particle discrimination by multi-photon excited fluorescence

    Kiselev, Denis; Bonacina, Luigi; Wolf, Jean-Pierre

    2011-01-01

    Femtosecond laser induced multi-photon excited fluorescence (MPEF) from individual airborne particles is tested for the first time for discriminating bioaerosols. The fluorescence spectra, analysed in 32 channels, exhibit a composite character originating from simultaneous two-photon and three-photon excitation at 790 nm. Simulants of bacteria aggregates (clusters of dyed polystyrene microspheres) and different pollen particles (Ragweed, Pecan, Mulberry) are clearly discriminated by their MPE...

  17. Relaxation channels of multi-photon excited xenon clusters

    Serdobintsev, P. Yu.; Melnikov, A. S. [Institute of Nanobiotechnologies, Peter the Great St.Petersburg Polytechnic University, Saint Petersburg 195251 (Russian Federation); Department of Physics, St. Petersburg State University, Saint Petersburg 198904 (Russian Federation); Rakcheeva, L. P., E-mail: lida@nanobio.spbstu.ru; Murashov, S. V.; Khodorkovskii, M. A. [Institute of Nanobiotechnologies, Peter the Great St.Petersburg Polytechnic University, Saint Petersburg 195251 (Russian Federation); Lyubchik, S. [REQUIMTE, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica 2829-516 (Portugal); Timofeev, N. A.; Pastor, A. A. [Department of Physics, St. Petersburg State University, Saint Petersburg 198904 (Russian Federation)

    2015-09-21

    The relaxation processes of the xenon clusters subjected to multi-photon excitation by laser radiation with quantum energies significantly lower than the thresholds of excitation of atoms and ionization of clusters were studied. Results obtained by means of the photoelectron spectroscopy method showed that desorption processes of excited atoms play a significant role in the decay of two-photon excited xenon clusters. A number of excited states of xenon atoms formed during this process were discovered and identified.

  18. Dark gamma-ray bursts: possible role of multiphoton processes

    Perel'man, Mark E

    2009-01-01

    The absence of optical afterglow at some gamma-ray bursts (so called dark bursts) requires analyses of physical features of this phenomenon. It is shown that such singularity can be connected with multiphoton processes of frequencies summation in the Rayleigh- Jeans part of spectra, their pumping into higher frequencies. It can be registered most probably on young objects with still thin plasma coating, without further thermalization, i.e. soon after a prompt beginning of the explosive activity.

  19. Imaging carious dental tissues with multiphoton fluorescence lifetime imaging microscopy

    Lin, Po-Yen; Lyu, Hong-Chou; Hsu, Chin-Ying Stephen; Chang, Chia-Seng; Kao, Fu-Jen

    2010-01-01

    In this study, multiphoton excitation was utilized to image normal and carious dental tissues noninvasively. Unique structures in dental tissues were identified using the available multimodality (second harmonic, autofluorescence, and fluorescence lifetime analysis) without labeling. The collagen in dentin exhibits a strong second harmonic response. Both dentin and enamel emit strong autofluorescence that reveals in detail morphological features (such as dentinal tubules and enamel rods) and,...

  20. Multiphoton ionization and stabilization of helium in superintense xuv fields

    Sørngård, S. A.; Askeland, S.; Nepstad, R.; Førre, M.

    2011-01-01

    Multiphoton ionization of helium is investigated in the superintense field regime, with particular emphasis on the role of the electron-electron interaction in the ionization and stabilization dynamics. To accomplish this, we solve ab initio the time-dependent Schr\\"odinger equation with the full electron-electron interaction included. By comparing the ionization yields obtained from the full calculations with corresponding results of an independent-electron model, we come to the somewhat cou...

  1. Multiphoton ionization and stabilization of helium in superintense xuv fields

    Sørngård, Stian Astad; Askeland, Sigurd; Nepstad, Raymond; Førre, Morten

    2011-01-01

    Multiphoton ionization of helium is investigated in the superintense field regime, with particular emphasis on the role of the electron-electron interaction in the ionization and stabilization dynamics. To accomplish this, we solve ab initio the time-dependent Schr¨odinger equation with the full electron-electron interaction included. By comparing the ionization yields obtained from the full calculations with the corresponding results of an independent-electron model, we come to t...

  2. Multiphoton resonance ionization for hydrogen atom in laser field

    The Schroedinger equation of hydrogen atom in laser field is expanded by Floquet wave and can be solved by the iterative method. The atomic ionization by laser field is a complex eigenvalue problem, which is formed from differential equation and boundary condition. Then the formula of the multiphoton resonance ionization in a linear polarization laser field was obtained and it is compared with the experiment

  3. Tagging multiphoton ionization events by two-dimensional photoelectron spectroscopy

    de Groot, Mattijs; Broos, Jaap; Buma, Wybren Jan

    2007-01-01

    Two-dimensional photoelectron spectroscopy has been used to supply process-specific labels to multiphoton ionization events. Employing these tags, the authors can construct excitation and photoelectron spectra along predefined excitation routes in the neutral manifold and ionization routes to the ionic manifold from one single two-dimensional photoelectron spectrum. These results offer a novel way to elucidate the vibronic and dynamic properties of excited and ionic states. (c) 2007 American ...

  4. CHIRAL MULTIPHOTON ABSORPTION AND INVERSE SKIN EFFECT IN WLAN SYSTEMS

    Héctor Torres Silva; Mario Zamorano Lucero

    2005-01-01

    A model formed by chiral bioplasma with a set of macromolecules of DNA, which represents the human head inner structure, makes possible to analyze its behavior, when it is radiated by a microwave electromagnetic field from cellular phones and WLAN's at frequencies of 2.4 and 5.2 GHz is presented. The finite difference time domain, FDTD, numeric technique is used under multiphoton regime deduced from Maxwell equations. The numerical results of the Specific Absorption Rate, SAR, show the SAR be...

  5. Multiphoton ionization mass spectrometry of nitrated polycyclic aromatic hydrocarbons.

    Tang, Yuanyuan; Imasaka, Tomoko; Yamamoto, Shigekazu; Imasaka, Totaro

    2015-08-01

    In order to suppress the fragmentation and improve the sensitivity for determination of nitrated polycyclic aromatic hydrocarbons (NPAHs), the mechanism of multiphoton ionization was studied for the following representative NPAHs, 9-nitroanthracene, 3-nitrofluoranthene, and 1-nitropyrene. The analytes were extracted from the PM2.5 on the sampling filter ultrasonically, and were measured using gas chromatography/multiphoton ionization/time-of-flight mass spectrometry with a femtosecond tunable laser in the range from 267 to 405 nm. As a result, a molecular ion was observed as the major ion and fragmentation was suppressed at wavelengths longer than 345 nm. Furthermore, the detection limit measured at 345 nm was measured to be the subpicogram level. The organic compounds were extracted from a 2.19 mg sample of particulate matter 2.5 (PM2.5), and the extract was subjected to multiphoton ionization mass spectrometry after gas chromatograph separation. The background signals were drastically suppressed at 345 nm, and the target NPAHs, including 9-nitroanthracene and 1-nitropyrene, were detected, and their concentrations were determined to be 5 and 3 pg/m(3), respectively. PMID:26048831

  6. Multiphoton ionization studies of laser induced chemistry in clusters

    Three examples are presented where multiphoton ionization mass spectrometry is used to study photochemistry in clusters. In the first, NO+(N2O3)m and NO2+(N2O3)m are made by 226nm multiphoton ionization of the clusters produced in an expansion of NO/CH4/Ar with a trace of H2O. Second, H3O+(H2O)n and CH3OH2+(CH3OH)n are observed when sufficiently large clusters of NO(H2O)m and NO(CH3OH)m are ionized, suggesting laser initiation of intracluster charge transfer reactions in these systems. Thirdly, multiphoton ionization of mixed expansions of NO and Fe(CO)5 leads to the production of (Fe)m+, (Fe)m+(CO)n, Fe+(NO)(CO), Fe+NO, and FeO+. The mechanisms for formation of these species will be discussed and analogies drawn between intracluster and collisional chemistry. copyright 1997 American Institute of Physics

  7. Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source.

    Lefort, Claire; O'Connor, Rodney P; Blanquet, Véronique; Magnol, Laetitia; Kano, Hideaki; Tombelaine, Vincent; Lévêque, Philippe; Couderc, Vincent; Leproux, Philippe

    2016-07-01

    Multicolor multiphoton microscopy is experimentally demonstrated for the first time on a spectral bandwidth of excitation of 300 nm (full width half maximum) thanks to the implementation a nanosecond supercontinuum (SC) source compact and simple with a low repetition rate. The interest of such a wide spectral bandwidth, never demonstrated until now, is highlighted in vivo: images of glioma tumor cells stably expressing eGFP grafted on the brain of a mouse and its blood vessels network labelled with Texas Red(®) are obtained. These two fluorophores have a spectral bandwidth covering the whole 300 nm available. In parallel, a similar image quality is obtained on a sample of mouse muscle in vitro when excited with this nanosecond SC source or with a classical high rate, femtosecond and quasi monochromatic laser. This opens the way for (i) a simple and very complete biological characterization never performed to date with multiphoton processes, (ii) multiple means of contrast in nonlinear imaging allowed by the use of numerous fluorophores and (iii) other multiphoton processes like three-photon ones. PMID:26872004

  8. Record Multiphoton Absorption Cross-Sections by Dendrimer Organometalation.

    Simpson, Peter V; Watson, Laurance A; Barlow, Adam; Wang, Genmiao; Cifuentes, Marie P; Humphrey, Mark G

    2016-02-12

    Large increases in molecular two-photon absorption, the onset of measurable molecular three-photon absorption, and record molecular four-photon absorption in organic π-delocalizable frameworks are achieved by incorporation of bis(diphosphine)ruthenium units with alkynyl linkages. The resultant ruthenium alkynyl-containing dendrimers exhibit strong multiphoton absorption activity through the biological and telecommunications windows in the near-infrared region. The ligated ruthenium units significantly enhance solubility and introduce fully reversible redox switchability to the optical properties. Increasing the ruthenium content leads to substantial increases in multiphoton absorption properties without any loss of optical transparency. This significant improvement in multiphoton absorption performance by incorporation of the organometallic units into the organic π-framework is maintained when the relevant parameters are scaled by molecular weights or number of delocalizable π-electrons. The four-photon absorption cross-section of the most metal-rich dendrimer is an order of magnitude greater than the previous record value. PMID:26797727

  9. Multiphoton imaging of excised normal skin and keloid scar: preliminary investigations

    Brewer, Michael B.; Yeh, Alvin T.; Torkian, Behrooz; Sun, Chung-Ho; Tromberg, Bruce J.; Wong, Brian J.

    2004-07-01

    Wound healing is a physiologic process that acts to repair disruptions in the continuity of tissue caused by injury or surgical incision. Keloids and hypertrophic scars are forms of aberrant wound healing, which are characterized by the overproduction of collagen, resulting in an excessive amount of scar tissue. Keloid tumors, by definition, grow outside the boundary of the original tissue damage. Multiphoton microscopy (MPM) is an imaging technique which allows imaging of living specimens, without the use of fixation or stains. Images of collagen fibers are produced by the second harmonic signal intensity generated by endogenous fluorescence through excitation by infrared laser light. A postauricular keloid tumor was excised from a patient. The tissue was dissected, and a portion was imaged using MPM. Normal skin tissue was isolated from a patient undergoing a facelift. A portion of this tissue was also dissected and imaged using MPM. MPM images were taken using a 63X water immersion objective lens on a two-photon microscope and a titanium-sapphire laser. Images were taken beginning at the surface of the tissue and moving in at intervals of 200 nm to a final depth of 30 μm. The two-photon images were used to reconstruct three-dimensional representations of the collagen matrix within the tissues, which are readily contrasted. Density of the collagen within each tissue was also ascertained using depth dependant decay of the image intensity. Multiphoton imaging was successfully used to image the collagen matrix of normal skin and a keloid scar, demonstrating differences in their microstructures.

  10. Generation of Multi-Photon Cluster States through the Cavity Input-Output Process

    We propose a scheme to generate the multi-photon cluster states via the cavity input-output process and the single-bit rotations. The method can be generalized to construct a series of multi-photon graph states, and the successful probability is close to unity in the ideal condition

  11. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining. PMID:26830089

  12. Spatiotemporal Analyses of Osteogenesis and Angiogenesis via Intravital Imaging in Cranial Bone Defect Repair.

    Huang, Chunlan; Ness, Vincent P; Yang, Xiaochuan; Chen, Hongli; Luo, Jiebo; Brown, Edward B; Zhang, Xinping

    2015-07-01

    Osteogenesis and angiogenesis are two integrated components in bone repair and regeneration. A deeper understanding of osteogenesis and angiogenesis has been hampered by technical difficulties of analyzing bone and neovasculature simultaneously in spatiotemporal scales and in 3D formats. To overcome these barriers, a cranial defect window chamber model was established that enabled high-resolution, longitudinal, and real-time tracking of angiogenesis and bone defect healing via multiphoton laser scanning microscopy (MPLSM). By simultaneously probing new bone matrix via second harmonic generation (SHG), neovascular networks via intravenous perfusion of fluorophore, and osteoblast differentiation via 2.3-kb collagen type I promoter-driven GFP (Col2.3GFP), we examined the morphogenetic sequence of cranial bone defect healing and further established the spatiotemporal analyses of osteogenesis and angiogenesis coupling in repair and regeneration. We showed that bone defect closure was initiated in the residual bone around the edge of the defect. The expansion and migration of osteoprogenitors into the bone defect occurred during the first 3 weeks of healing, coupled with vigorous microvessel angiogenesis at the leading edge of the defect. Subsequent bone repair was marked by matrix deposition and active vascular network remodeling within new bone. Implantation of bone marrow stromal cells (BMSCs) isolated from Col2.3GFP mice further showed that donor-dependent bone formation occurred rapidly within the first 3 weeks of implantation, in concert with early angiogenesis. The subsequent bone wound closure was largely host-dependent, associated with localized modest induction of angiogenesis. The establishment of a live imaging platform via cranial window provides a unique tool to understand osteogenesis and angiogenesis in repair and regeneration, enabling further elucidation of the spatiotemporal regulatory mechanisms of osteoprogenitor cell interactions with host bone

  13. Microstructure imaging of human rectal mucosa using multiphoton microscopy

    Liu, N R; Chen, J X; Zhuo, S M; Zheng, L Q; Jiang, X S [Institute of Laser and Optoelectronics Technology, Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou (China); Chen, G [Department of Pathology, Fujian Provincial Tumor Hospital, Fuzhou (China); Yan, J, E-mail: chenjianxin@fjnu.edu.cn, E-mail: ynjun@yahoo.com [Department of Surgery, Fujian Provincial Tumor Hospital, Fuzhou (China)

    2011-01-01

    Multiphoton microscopy (MPM) has high resolution and sensitivity. In this study, MPM was used to image microstructure of human rectal mucosa. The morphology and distribution of the main components in mucosa layer, absorptive cells and goblet cells in the epithelium, abundant intestinal glands in the lamina propria and smooth muscle fibers in the muscularis mucosa were clearly monitored. The variations of these components were tightly relevant to the pathology in gastrointestine system, especially early rectal cancer. The obtained images will be helpful for the diagnosis of early colorectal cancer.

  14. Non-perturbative methods applied to multiphoton ionization

    The use of non-perturbative methods in the treatment of atomic ionization is discussed. Particular attention is given to schemes of the type proposed by Keldysh where multiphoton ionization and tunnel auto-ionization occur for high intensity fields. These methods are shown to correspond to a certain type of expansion of the T-matrix in the intra-atomic potential; in this manner a criterium concerning the range of application of these non-perturbative schemes is suggested. A brief comparison between the ionization rate of atoms in the presence of linearly and circularly polarized light is presented. (Author)

  15. Multiphoton ionization of magnesium via an autoionizing state

    Druten, van, N.J.; Trainham, R.; Muller, H.G.

    1994-01-01

    Multiphoton single and double ionization of magnesium was studied by measuring electron energy spectra and ion mass spectra using 1-ps laser pulses in the 580-595-nm wavelength and 1012-1013-W/cm2 intensity range. In single ionization the (3p)2 1S doubly excited autoionizing state, resonant at the four-photon level, is found to play an important role. Single ionization leaving the Mg+ ion in the 3p excited state is strongly enhanced when resonant with the (3p)2 1S state. The amount of above t...

  16. Partitioning of the linear photon momentum in multiphoton ionization

    Smeenk, C; Zhou, B; Mysyrowicz, A; Villeneuve, D M; Staudte, A; Corkum, P B

    2011-01-01

    The balance of the linear photon momentum in multiphoton ionization is studied experimentally. In the experiment argon and neon atoms are singly ionized by circularly polarized laser pulses with a wavelength of 800 nm and 1400 nm in the intensity range of 10^{14} - 10^{15} W/cm^2. The photoelectrons are measured using velocity map imaging. We find that the photoelectrons carry linear momentum corresponding to the photons absorbed above the field free ionization threshold. Our finding has implications for concurrent models of the generation of terahertz radiation in filaments.

  17. Circular dichroism in XUV + IR multiphoton ionization of atoms

    Circular dichroism (CD) is theoretically considered for two-colour multiphoton ionization of arbitrary atomic subshells. In particular, p-subshell ionization is analysed and compared with s-subshell ionization. Simple analytical expressions for the CD are obtained for both s- and p-subshell ionization. The calculations performed for Ne(2p) ionization by an extreme ultraviolet pulse in the presence of an infrared laser pulse show that the CD in this case is appreciably larger than in previously discussed s-shell ionization. It makes this case favourable for applications as a sensitive tool for measuring the helicity of short-wavelength free-electron laser beams. (paper)

  18. NON-PERTURBATIVE METHODS APPLIED TO MULTIPHOTON IONIZATION

    Brandi, H.; Davidovich, L.; Zagury, N.

    1982-01-01

    We discuss the use of non-perturbative methods in the treatment of atomic ionization. Particular attention is given to schemes of the type proposed by Keldysh where multiphoton ionization and tunnel auto-ionization occur for high intensity fields. These methods are shown to correspond to a certain type of expansion of the T-matrix in the intra-atomic potential, in this manner a criterium concerning the range of application of these non-perturbative scheme is suggested. A brief comparison betw...

  19. Multiphoton production at high energies in the Standard Model, 1

    Mahlon, G

    1993-01-01

    We examine multiphoton production in the electroweak sector of the Standard Model in the high energy limit using the equivalence theorem in combination with spinor helicity techniques. We obtain recursion relations for currents consisting of a charged scalar, spinor, or vector line that radiates $n$ photons. Closed form solutions to these recursion relations for arbitrary $n$ are presented for the cases of like-helicity and one unlike-helicity photon production. We apply the currents singly and in pairs to obtain amplitudes for processes involving the production of $n$ photons with up to two unlike helicities from a pair of charged particles. The replacement of one or more photons by transversely polarized

  20. Multiphoton double ionization via field-independent resonant excitation

    The double ionization of xenon in the multiphoton regime has been studied at two wavelengths (0.77 and 0.79 μm) using an electron-ion coincidence technique and an intensity binned ion ratio method. Sharp resonant structures in the electron energy distribution correlated with the doubly charged ion, as well as a wavelength dependence of the Xe2+/Xe+ ratio provides new insights. A mechanism involving the shelving of population in Rydberg states followed by excitation of a core electron is proposed

  1. Advances in multi-photon processes and spectroscopy v.22

    Lin, S H; Fujimura, Y

    2014-01-01

    This volume presents the recent progress and perspective in multi-photon processes and spectroscopy of atoms, ions, molecules and solids. The subjects in the series cover the experimental and theoretical investigations in the interdisciplinary research fields of natural science including chemistry, physics, bioscience and material science. Contents:Theoretical Foundations for Exploring Quantum Optimal Control of Molecules (Tak-San Ho, Herschel Rabitz and Shih-I Chu)Intramolecular Nuclear Flux Densities (I Barth, C Daniel, E Gindensperger, J Manz, J F Pérez-To

  2. Simultaneous three-dimensional optical coherence tomography and intravital microscopy for imaging subpleural pulmonary alveoli in isolated rabbit lungs

    Meissner, Sven; Knels, Lilla; Krueger, Alexander; Koch, Thea; Koch, Edmund

    2009-09-01

    There is a growing interest in analyzing lung mechanics at the level of the alveoli in order to understand stress-related pathogenesis and possibly avoid ventilator associated lung injury. Emerging quantitative models to simulate fluid mechanics and the associated stresses and strains on delicate alveolar walls require realistic quantitative input on alveolar geometry and its dynamics during ventilation. Here, three-dimensional optical coherence tomography (OCT) and conventional intravital microscopy are joined in one setup to investigate the geometric changes of subpleural alveoli during stepwise pressure increase and release in an isolated and perfused rabbit lung model. We describe good qualitative agreement and quantitative correlation between the OCT data and video micrographs. Our main finding is the inflation and deflation of individual alveoli with noticeable hysteresis. Importantly, this three-dimensional geometry data can be extracted and converted into input data for numerical simulations.

  3. Holographic intravital microscopy for 2-D and 3-D imaging intact circulating blood cells in microcapillaries of live mice

    Kim, Kyoohyun; Park, Inwon; Kim, Pilhan; Park, YongKeun

    2016-01-01

    Intravital microscopy is an essential tool that reveals behaviours of live cells under conditions close to natural physiological states. So far, although various approaches for imaging cells in vivo have been proposed, most require the use of labelling and also provide only qualitative imaging information. Holographic imaging approach based on measuring the refractive index distributions of cells, however, circumvent these problems and offer quantitative and label-free imaging capability. Here, we demonstrate in vivo two- and three-dimensional holographic imaging of circulating blood cells in intact microcapillaries of live mice. The measured refractive index distributions of blood cells provide morphological and biochemical properties including three-dimensional cell shape, haemoglobin concentration, and haemoglobin contents at the individual cell level. With the present method, alterations in blood flow dynamics in live healthy and sepsis-model mouse were also investigated.

  4. Contribution of laser Doppler flowmetry with venoarteriolar reflex, cold, and rewarming testing, and intravital capillaroscopy to diagnose Raynaud's phenomenon

    Zeman J

    2014-05-01

    Full Text Available Jan Zeman,1 Oksana Turyanytsya,1 Vojtĕch Kapsa,2 Mojmír Eliáš3 1Department of Clinical Cardiology and Angiology, Hospital Bulovka, 2Charles University in Prague, Faculty of Mathematics and Physics, 3Kooperativa a.s., Pobrezni, Prague, Czech Republic Background: The early differential diagnosis of Raynaud’s phenomenon (RP is crucial for the prognosis and therapy of these patients. In our microcirculatory laboratory, we use intravital capillaroscopy (IC, plethysmography (P, and laser Doppler flowmetry (LDF for examining acrosyndromes. We combine LDF with venoarteriolar reflex test, cold test, and rewarming test to achieve more reliable diagnoses of acrosyndromes. Patients and methods: We examined LDF and IC according to a strict protocol using a battery of tests (venoarteriolar reflex test, cold test, rewarming test applied to five different groups of people and compared their results: healthy controls, primary Raynaud’s phenomenon (PRP, systemic scleroderma, vibration white finger, and peripheral artery occlusive disease. Our tests included 340 individuals (72 patients plus 268 controls. Results: Although all tests provided some differences between controls and patients, only the rewarming test offered significant results for differential diagnoses. Conclusion: IC and LDF combined with the battery of tests (venoarteriolar reflex test, cold test, rewarming test under standard conditions can be used as reliable tools to distinguish between PRP and some types of secondary RP (especially in the case of systemic scleroderma, vibration white fingers, or peripheral artery occlusive disease; RPs with organic occlusions of the small arteries causing the diseases. Our methodology can help to distinguish between other types of RP, as well. Keywords: Raynaud’s phenomenon, acrosyndrome, laser Doppler flowmetry, intravital capillaroscopy, scleroderma, vibration white finger, peripheral artery occlusive disease

  5. Multiphoton Microscopy of Nonfluorescent Nanoparticles In Vitro and In Vivo.

    Dietzel, Steffen; Hermann, Stefanie; Kugel, Yan; Sellner, Sabine; Uhl, Bernd; Hirn, Stephanie; Krombach, Fritz; Rehberg, Markus

    2016-06-01

    Nanotechnology holds great promise for a plethora of potential applications. The interaction of engineered nanomaterials with living cells, tissues, and organisms is, however, only partly understood. Microscopic investigations of nano-bio interactions are mostly performed with a few model nanoparticles (NPs) which are easy to visualize, such as fluorescent quantum dots. Here the possibility to visualize nonfluorescent NPs with multiphoton excitation is investigated. Signals from silver (Ag), titanium dioxide (TiO2 ), and silica (SiO2 ) NPs in nonbiological environments are characterized to determine signal dependency on excitation wavelength and intensity as well as their signal stability over time. Ag NPs generate plasmon-induced luminescence decaying over time. TiO2 NPs induce photoluminescent signals of variable intensities and in addition strong third harmonic generation (THG). Optimal settings for microscopic detection are determined and then applied for visualization of these two particle types in living cells, in murine muscle tissue, and in the murine blood stream. Silica NPs produce a THG signal, but in living cells it cannot be discriminated sufficiently from endogenous cellular structures. It is concluded that multiphoton excitation is a viable option for studies of nano-bio interactions not only for fluorescent but also for some types of nonfluorescent NPs. PMID:27120195

  6. Dynamics of rotationally-resolved multiphoton ionization processes in molecules

    This dissertation presents the results of studies of several rotationally-resolved resonance enhanced multiphoton ionization (REMPI) processes in some simple molecular systems. The objective of these studies is to quantitatively identify the underlying dynamics of this highly state-specific process which utilizes the narrow bandwidth radiation of a laser to ionize a molecule by first preparing an excited state via multiphoton absorption and subsequently ionization that state before it can decay. Coupled with high-resolution photoelectron spectroscopy, REMPI is clearly an important probe of molecular excited states and their photoionization dynamics. A key feature of these studies is that they are carried out using accurate Hartree-Fock orbitals to describe the photoelectron orbitals of the molecular ions. Studies reported here include investigations of (i) ionic rotational branching ratios and their energy dependence for REMPI via the A2Σ+(3sσ) and D2Σ+(3pσ) states of NO, (ii) the influence of angular momentum constraints on branching ratios at low photoelectron energies for REMPI via low-J levels of the resonant intermediate state, (iii) the strong dependence of photoelectron angular distributions on final ionic rotational state and on the alignment in REMPI of the A2Σ+ state of NO, (iv) vibrational state dependence of ionic rotational branching ratios arising from rapid orbital evolution in resonant states (v) the influence of rovibronic interactions on the rotational branching ratios seen in REMPI via the D2Σ+(3pσ) state of NO

  7. Dynamics of single and multiphoton ionization processes in molecules

    Single-photon and resonant multiphoton ionization studies, which can now be carried out using synchrotron radiation and lasers, respectively, are providing important dynamical information on molecular photoionization. The author studied the underlying dynamical features of these ionization processes using Hartree-Fock continuum orbitals generated using the iterative Schwinger variational method for solving the photoelecttron collisional equations. The single-photon studies examine the important role that shape and autoionizing resonances play in molecular photoionization, while the multiphoton studies investigate the ionization dynamics of exited electronic states. The subtle nature of shape resonances was demonstrated in polyatomic systems such as C2H2 and C2N2, where the possibility of multiple resonances in a single channel is observed. Molecular autoionizing resonances are known to dominate regions of the photoionization spectra. The author adapted and applied a generalization of the Fano treatment for autoionization to molecular systems. Results for H2 and C2H2 autoionizing resonances are presented and discussed

  8. Multiphoton ionization and stabilization of helium in superintense xuv fields

    Sørngård, S A; Nepstad, R; Førre, M

    2011-01-01

    Multiphoton ionization of helium is investigated in the superintense field regime, with particular emphasis on the role of the electron-electron interaction in the ionization and stabilization dynamics. To accomplish this, we solve ab initio the time-dependent Schr\\"odinger equation with the full electron-electron interaction included. By comparing the ionization yields obtained from the full calculations with corresponding results of an independent-electron model, we come to the somewhat counterintuitive conclusion that the single-particle picture breaks down at superstrong field strengths. We explain this finding from the perspective of the so-called Kramers-Henneberger frame, the reference frame of a free (classical) electron moving in the field. The breakdown is tied to the fact that shake-up and shake-off processes cannot be properly accounted for in commonly used independent-electron models. In addition, we see evidence of a change from the multiphoton to the shake-off ionization regime in the energy di...

  9. Resonant enhanced multiphoton ionization studies of atomic oxygen

    Dixit, S. N.; Levin, D.; Mckoy, V.

    1987-01-01

    In resonant enhanced multiphoton ionization (REMPI), an atom absorbs several photons making a transition to a resonant intermediate state and subsequently ionizing out of it. With currently available tunable narrow-band lasers, the extreme sensitivity of REMPI to the specific arrangement of levels can be used to selectively probe minute amounts of a single species (atom) in a host of background material. Determination of the number density of atoms from the observed REMPI signal requires a knowledge of the multiphoton ionization cross sections. The REMPI of atomic oxygen was investigated through various excitation schemes that are feasible with available light sources. Using quantum defect theory (QDT) to estimate the various atomic parameters, the REMPI dynamics in atomic oxygen were studied incorporating the effects of saturation and a.c. Stark shifts. Results are presented for REMPI probabilities for excitation through various 2p(3) (4S sup o) np(3)P and 2p(3) (4S sup o) nf(3)F levels.

  10. Multiphoton ionization and stabilization of helium in superintense xuv fields

    Multiphoton ionization of helium is investigated in the superintense field regime, with particular emphasis on the role of the electron-electron interaction in the ionization and stabilization dynamics. To accomplish this, we solve ab initio the time-dependent Schroedinger equation with the full electron-electron interaction included. By comparing the ionization yields obtained from the full calculations with the corresponding results of an independent-electron model, we come to the somewhat counterintuitive conclusion that the single-particle picture breaks down at superstrong field strengths. We explain this finding from the perspective of the so-called Kramers-Henneberger frame, the reference frame of a free (classical) electron moving in the field. The breakdown is tied to the fact that shake-up and shake-off processes cannot be properly accounted for in commonly used independent-electron models. In addition, we see evidence of a change from the multiphoton to the shake-off ionization regime in the energy distributions of the electrons. From the angular distribution, it is apparent that the correlation is an important factor even in this regime.

  11. Ultrafast multiphoton transient absorption of {beta}-carotene

    Buckup, Tiago [Philipps University Marburg, Department of Chemistry, D-35043 Marburg (Germany); Ruprecht-Karls University Heidelberg, Physical-Chemistry Institute, D-69120 (Germany); Weigel, Alexander; Hauer, Juergen [Philipps University Marburg, Department of Chemistry, D-35043 Marburg (Germany); Motzkus, Marcus, E-mail: Marcus.Motzkus@pci.uni-heidelberg.de [Philipps University Marburg, Department of Chemistry, D-35043 Marburg (Germany); Ruprecht-Karls University Heidelberg, Physical-Chemistry Institute, D-69120 (Germany)

    2010-07-19

    Multiphoton spectroscopy is able to directly excite electronic states, which are one-photon forbidden. Under single photon conditions, such one-photon forbidden states are exclusively populated via internal relaxation. Hence, transient absorption with two-photon excitation has the potential of clarifying complex relaxation networks by using aimed excitation. In this work we exploited ultrafast two-photon spectroscopy to investigate the excitation of dark states of {beta}-carotene in solution. After direct excitation of the vibronic manifold of S{sub 1}(2A{sub g}{sup -}) from S{sub 0} via two-photon transition, the characteristic internal conversion via hot-S{sub 1} {yields} S{sub 1} {yields} S{sub 0} was observed in the respective spectral region. Additional slow dynamics in the blue-wing of excited-state absorption (ESA) and in the NIR were detected, which is not directly observable with one-photon excitation transient absorption. These features are associated here to resonant multiphoton processes, which lead simultaneously to ultrafast intersystem crossing between singlet and triplet systems as well as to excitation of doublet states. Furthermore, we identify a 340-400 fs relaxation component in the near-infrared region after two-photon resonant excitation and discuss the role of additional dark states (3A{sub g}{sup -} and 1B{sub u}{sup -}) in this process.

  12. The cross-over from tunnelling to multiphoton ionization of atoms

    Klaiber, Michael

    2016-01-01

    We present a theory illuminating the cross-over from strong-field tunnelling ionization to weak-field multiphoton ionization in the interaction of a classical laser field with a hydrogen atom. A simple formula is derived in which the ionization amplitude appears as a product of two separate amplitudes. The first describes the initial polarization of the atom by virtual multiphoton absorption and the second the subsequent tunnelling out of the polarized atom. Tunnelling directly from the ground state and multiphoton absorption without tunnelling appear naturally as the limits of the theory.

  13. Effects of laser radiation parameters of the infrared multiphoton dissociation of protonated trichloroethylene

    The favorable properties of the infrared multiphoton absorption and dissociation of trichloroethylene-H, (C2 HCl3), by TEA-CO2 laser radiation and rapid isotopic exchange between this molecule and water, indicate that it can be a promising further candidate for the final enrichment of heavy water (> 98% D2 O), by laser method. We present the results obtained in the isotopic selectivity of multiphoton absorption measurements and in the study of the pulse energy and frequency laser radiation influence on the infrared multiphoton dissociation of C2 HCl3 in isotopic mixture with C2 DCl3. (Author)

  14. Multiphoton imaging with a novel compact diode-pumped Ti:sapphire oscillator

    König, Karsten; Andersen, Peter E.; Le, Tuan; Breunig, Hans Georg

    2015-01-01

    Multiphoton laser scanning microscopy commonly relies on bulky and expensive femtosecond lasers. We integrated a novel minimal-footprint Ti:sapphire oscillator, pumped by a frequency-doubled distributed Bragg reflector tapered diode laser, into a clinical multiphoton tomograph and evaluated its...... imaging capability using different biological samples, i.e. cell monolayers, corneal tissue, and human skin. With the novel laser, the realization of very compact Ti:sapphire-based systems for high-quality multiphoton imaging at a significantly size and weight compared to current systems will become...

  15. Generating Nanostructures with Multiphoton Absorption Polymerization using Optical Trap Assisted Nanopatterning

    Tsai, Yu-Cheng; Leitz, Karl-Heinz; Fardel, Romain; Schmidt, Michael; Arnold, Craig B.

    The need to generate sub 100 nm features is of interest for a variety of applications including optics, optoelectronics, and plasmonics. To address this requirement, several advanced optical lithography techniques have been developed based on either multiphoton absorption polymerization or near-field effects. In this paper, we combine strengths from multiphoton absorption and near field using optical trap assisted nanopatterning (OTAN). A Gaussian beam is used to position a microsphere in a polymer precursor fluid near a substrate. An ultrafast laser is focused by that microsphere to induce multiphoton polymerization in the near field, leading additive direct-write nanoscale processing.

  16. Hamiltonian formulation for the theory of multiphoton processes in atoms based on the first principles--

    Bakasov, A.A. (Joint Institute for Nuclear Research, Head Post Office, P.O. Box 79, Moscow (SU))

    1989-07-01

    A Hamiltonian is derived on the basis of the first principles of quantum electrodynamics. The Hamiltonian is seen to describe two- and multiphoton processes. A problem of consequent derivation and microscopic substantiation of models of multiphoton processes widely used in quantum optics is solved. The first correction to the Pauli equation is obtained. The constant of interaction of a two-level atom with two photons is given in an explicit form. A method of calculating interaction constants for multilevel atoms with multiphoton transitions is presented. Other results obtained on the basis of the developed approach are discussed.

  17. Hamiltonian models of multiphoton processes and four--photon squeezed states via nonlinear canonical transformations

    De Siena, S; Illuminati, F; Siena, Silvio De; Lisi, Antonio Di; Illuminati, Fabrizio

    2002-01-01

    We introduce nonlinear canonical transformations that yield effective Hamiltonians of multiphoton down conversion processes, and we define the associated non-Gaussian multiphoton squeezed states as the coherent states of the multiphoton Hamiltonians. We study in detail the four-photon processes and the associated non-Gaussian four-photon squeezed states. The realization of squeezing, the behavior of the field statistics, and the structure of the phase space distributions show that these states realize a natural four-photon generalization of the two-photon squeezed states.

  18. Fringe-free, Background-free, Collinear Third Harmonic Generation FROG Measurements for Multiphoton Microscopy

    Chadwick, R; Spahr, E; Squier, J A; Durfee, C G; Walker, B C; Fittinghoff, D N

    2006-07-21

    Collinear pulse measurement tools useful at the full numerical aperture (NA) of multiphoton microscope objectives are a necessity for a quantitative characterization of the femtosecond pulses focused by these systems. In this letter, we demonstrate a simple new technique, for characterizing the pulse at the focus in a multiphoton microscope. This technique, a background-free, fringe-free, form of frequency-resolved optical gating, uses the third harmonic signal generated from a glass coverslip. Here it is used to characterize 100 fs pulses (typical values for a multiphoton microscope) at the focus of a 0.65 NA objective.

  19. Aqueous multiphoton lithography with multifunctional silk-centred bio-resists

    Sun, Yun-Lu; Li, Qi; Sun, Si-Ming; Huang, Jing-Chun; Zheng, Bo-Yuan; Chen, Qi-Dai; Shao, Zheng-Zhong; Sun, Hong-Bo

    2015-10-01

    Silk and silk fibroin, the biomaterial from nature, nowadays are being widely utilized in many cutting-edge micro/nanodevices/systems via advanced micro/nanofabrication techniques. Herein, for the first time to our knowledge, we report aqueous multiphoton lithography of diversiform-regenerated-silk-fibroin-centric inks using noncontact and maskless femtosecond laser direct writing (FsLDW). Initially, silk fibroin was FsLDW-crosslinked into arbitrary two/three-dimensional micro/nanostructures with good elastic properties merely using proper photosensitizers. More interestingly, silk/metal composite micro/nanodevices with multidimension-controllable metal content can be FsLDW-customized through laser-induced simultaneous fibroin oxidation/crosslinking and metal photoreduction using the simplest silk/Ag+ or silk/[AuCl4]- aqueous resists. Noticeably, during FsLDW, fibroin functions as biological reductant and matrix, while metal ions act as the oxidant. A FsLDW-fabricated prototyping silk/Ag microelectrode exhibited 104-Ω-1 m-1-scale adjustable electric conductivity. This work not only provides a powerful development to silk micro/nanoprocessing techniques but also creates a novel way to fabricate multifunctional metal/biomacromolecule complex micro/nanodevices for applications such as micro/nanoscale mechanical and electrical bioengineering and biosystems.

  20. Super-resolving multi-photon interferences with independent light sources

    Oppel, Steffen; Kok, Pieter; von Zanthier, Joachim

    2012-01-01

    Multi-photon interferences with indistinguishable photons from independent light sources are at the focus of current research owing to their potential in optical quantum computing, creating remote entanglement for quantum computation and communication, and quantum metrology. The paradigmatic states for multi-photon interference are the highly entangled NOON states, which can be used to achieve increased resolution in spectroscopy, interferometry, lithography, and microscopy. Multi-photon interferences from independent, uncorrelated emitters can also lead to enhanced resolution in metrology and imaging. So far, such interferences have been observed with maximally two independent emitters. Here, we report multi-photon interferences with up to five independent emitters, displaying interference patterns equivalent to those of NOON states. Experimental results with independent thermal light sources confirm this NOON-like modulation. The experiment is an extension of the landmark measurement by Hanbury Brown and Tw...

  1. Multiphoton ionization of CF3I clusters by ultraviolet laser radiation

    The results of the investigation of the multiphoton ionization of (CF3I)n clusters by ultraviolet laser radiation are reported. The yields of the I2+ and I+ ions, which are the products of the multiphoton ionization, have been measured as functions of the intensity of the ultraviolet radiation at the wavelengths of 308 and 232.5 nm. The degree of multiphoton ionization has been determined and appears to depend on the wavelength of radiation. The velocity distributions of the products have been measured in detail for various wavelengths and various polarizations of radiation. The anisotropy parameters of the velocity distributions of the produced ions and their kinetic energy have been determined. After analysis of the data, a mechanism of the multiphoton ultraviolet ionization of the clusters under investigation has been proposed. This mechanism depends on the used wavelengths.

  2. Intensity and Polarization Effects in Short-Pulse Multiphoton Ionization of Xenon

    KANG Hui-Peng; WANG Chuan-Liang; LIN Zhi-Yang; CHEN Yong-Ju; WU Ming-Yan; QUAN Wei; LIU Hong-Ping; LIU Xiao-Jun

    2011-01-01

    @@ We present photoelectron spectra (PES) of xenon subject to ultrashort intense laser pulses at 400nm.The intensity-dependent PES exhibit the dominance of ac-Stark-shifted multiphoton resonances in a multiphoton ionization process.A distinct difference in the spectra with different laser polarization states (i.e., linearly and circularly polarized states) is revealed and can be understood in terms of the quantum selection rule, whichrestricts the angular momentum of states that may shift into multiphoton resonances.Furthermore, the intensity dependence of the resonance-enhanced electron yield is analyzed in the context of multiphoton Landau-Zener theory.The model calculation results considering the focal volume effect are in good agreement with the experimental observation.

  3. Intensity and Polarization Effects in Short-Pulse Multiphoton Ionization of Xenon

    We present photoelectron spectra (PES) of xenon subject to ultrashort intense laser pulses at 400 nm. The intensity-dependent PES exhibit the dominance of ac-Stark-shifted multiphoton resonances in a multiphoton ionization process. A distinct difference in the spectra with different laser polarization states (i.e., linearly and circularly polarized states) is revealed and can be understood in terms of the quantum selection rule, which restricts the angular momentum of states that may shift into multiphoton resonances. Furthermore, the intensity dependence of the resonance-enhanced electron yield is analyzed in the context of multiphoton Landau-Zener theory. The model calculation results considering the focal volume effect are in good agreement with the experimental observation. (atomic and molecular physics)

  4. Wavelength scaling of high-harmonic generation efficiency close to the multiphoton ionization regime

    Lai, Chien-Jen; Cirmi, Giovanni; Huang, Shu-Wei; Granados, Eduardo; Hong, Kyung-Han; Moses, Jeffrey; Keathley, Philip; Bhardwaj, Siddharth; Kaertner, Franz

    2013-01-01

    Our experiment shows a less dramatic wavelength scaling of high harmonic generation efficiency between the tunneling and the multiphoton ionization regimes, which can be explained by a modified three-step model with complex ionization time.

  5. Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states

    Dell'Anno, F; Illuminati, F; Anno, Fabio Dell'; Siena, Silvio De; Illuminati, Fabrizio

    2004-01-01

    We introduce a formalism of nonlinear canonical transformations for general systems of multiphoton quantum optics. For single-mode systems the transformations depend on a tunable free parameter, the homodyne local oscillator angle; for n-mode systems they depend on n heterodyne mixing angles. The canonical formalism realizes nontrivial mixings of pairs of conjugate quadratures of the electromagnetic field in terms of homodyne variables for single-mode systems; and in terms of heterodyne variables for multimode systems. In the first instance the transformations yield nonquadratic model Hamiltonians of degenerate multiphoton processes and define a class of non Gaussian, nonclassical multiphoton states that exhibit properties of coherence and squeezing. We show that such homodyne multiphoton squeezed states are generated by unitary operators with a nonlinear time evolution that realizes the homodyne mixing of a pair of conjugate quadratures. Tuning of the local oscillator angle allows to vary at will the statist...

  6. Properties of Differential Scattering Section Based on Multi-photon Nonlinear Compton Effect

    2002-01-01

    Properties of damping electrons in collision with photons based on multi-photon nonlinear Compton effect are investigated. The expressions of the differential scattering section are derived. Several useful conclusions are drawn.

  7. Simultaneous imaging of GFP, CFP and collagen in tumors in vivo using multiphoton microscopy

    Segall Jeffrey E

    2005-05-01

    Full Text Available Abstract Background The development of multiphoton laser scanning microscopy has greatly facilitated the imaging of living tissues. However, the use of genetically encoded fluorescent proteins to distinguish different cell types in living animals has not been described at single cell resolution using multiphoton microscopy. Results Here we describe a method for the simultaneous imaging, by multiphoton microscopy, of Green Fluorescent Protein, Cyan Fluorescent Protein and collagen in vivo in living tumors. This novel method enables: 1 the simultaneous visualization of overall cell shape and sub-cellular structures such as the plasma membrane or proteins of interest in cells inside living animals, 2 direct comparison of the behavior of single cells from different cell lines in the same microenvironment in vivo. Conclusion Using this multi-fluor, multiphoton technique, we demonstrate that motility and metastatic differences between carcinoma cells of differing metastatic potential can be imaged in the same animal simultaneously at sub-cellular resolution.

  8. Dynamics of multi-photon photoluminescence in gold nanoantennas

    Biagioni, P; Huang, J -S; Kern, J; Duò, L; Hecht, B; Finazzi, M; Cerullo, G

    2011-01-01

    We perform a combined study of the degree of nonlinearity and the temporal dynamics of multiphoton-excited photoluminescence (MPPL) in gold nanoantennas. At variance with standard gold two-photon photoluminescence (TPPL), the large photoluminescence enhancement in resonant nanostructures is sometimes found to involve more than two absorbed photons per emitted photon. By two-pulse correlation measurements of TPPL and MPPL we are able to address the particular dynamics of these mechanisms. Our data give direct evidence for the two-step model that has been proposed for gold TPPL and suggest that MPPL is characterized by very similar dynamics. Interestingly, for resonant antennas we observe a reduced MPPL relaxation time compared to off-resonant antennas.

  9. Clinical multiphoton tomography and clinical two-photon microendoscopy

    König, Karsten; Bückle, Rainer; Weinigel, Martin; Elsner, Peter; Kaatz, Martin

    2009-02-01

    We report on applications of high-resolution clinical multiphoton tomography based on the femtosecond laser system DermaInspectTM with its flexible mirror arm in Australia, Asia, and Europe. Applications include early detection of melanoma, in situ tracing of pharmacological and cosmetical compounds including ZnO nanoparticles in the epidermis and upper dermis, the determination of the skin aging index SAAID as well as the study of the effects of anti-aging products. In addition, first clinical studies with novel rigid high-NA two-photon 1.6 mm GRIN microendoscopes have been conducted to study the effect of wound healing in chronic wounds (ulcus ulcera) as well as to perform intrabody imaging with subcellular resolution in small animals.

  10. Reassignment of scattered emission photons in multifocal multiphoton microscopy.

    Cha, Jae Won; Singh, Vijay Raj; Kim, Ki Hean; Subramanian, Jaichandar; Peng, Qiwen; Yu, Hanry; Nedivi, Elly; So, Peter T C

    2014-01-01

    Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously scanning multiple foci across different regions of specimen. The use of imaging detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to-noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly recovered using multianode photomultiplier tubes (MAPMT). In this design, however, emission photons scattered to neighbor anodes are encoded by the foci scan location resulting in ghost images. The crosstalk between different anodes is currently measured a priori, which is cumbersome as it depends specimen properties. Here, we present the photon reassignment method for MMM, established based on the maximum likelihood (ML) estimation, for quantification of crosstalk between the anodes of MAPMT without a priori measurement. The method provides the reassignment of the photons generated by the ghost images to the original spatial location thus increases the SNR of the final reconstructed image. PMID:24898470

  11. Tunneling dynamics in multiphoton ionization and attoclock calibration

    Klaiber, M; Keitel, C H

    2014-01-01

    The intermediate domain of strong-field ionization between the tunneling and the multiphoton regimes is investigated using the strong field approximation and the imaginary-time method. An intuitive model for the dynamics is developed which describes the ionization process within a nonadiabatic tunneling picture with a coordinate dependent electron energy during the under-the-barrier motion. The nonadiabatic effects in the elliptically polarized laser field induce a transversal momentum shift of the tunneled electron wave packet at the tunnel exit, a delayed appearance in the continuum as well as a shift of the tunneling exit towards the ionic core. The latter significantly modifies the Coulomb focusing during the electron excursion in the laser field after exiting the ionization tunnel. We show that nonadiabatic effects are especially large when the Coulomb field of the ionic core is taken into account during the under-the-barrier motion. The simpleman model modified with these nonadiabatic corrections provid...

  12. Multiphoton ionization of acetone-water clusters at 355 nm

    WANG Reng; KONG Xiang-he; ZHANG Shu-dong; ZHANG Xia; FAN Xing-yan; ZHAO Shu-yan

    2006-01-01

    @@ The multiphoton ionization of acetone-water clusters were detected at 355 nm laser wavelength by using the time of flight mass spectrometer(TOF-MS).The experiments show that all products are protonated.Three main products such as (CH3COCH3)n-(H2O)n-2H+,(CH3COCH3)n-(H2O)n-1H+ and (CH3COCH3)n-(H2O)nH+ are concluded from the results.In order to study the equilibrium structures of the (CH3COCH3)n-(H2O)n-2H+,the ab-initio calculation is used on them.The experiment is even done when the volume rate of acetone to water is 1:2.

  13. Multiphoton production at high energies in the Standard Model, 2

    Mahlon, G

    1993-01-01

    We examine multiphoton production in the electroweak sector of the Standard Model in the high energy limit using the equivalence theorem in combination with spinor helicity techniques. We utilize currents consisting of a charged scalar, spinor, or vector line that radiates $n$ photons. Only one end of the charged line is off shell in these currents, which are known for the cases of like-helicity and one unlike-helicity photons. We obtain a wide variety of helicity amplitudes for processes involving two pairs of charged particles by considering combinations of four currents. We examine the situation with respect to currents which have both ends of the charged line off-shell, and present solutions for the case of like-helicity photons. These new currents may be combined with two of the original currents to produce additional amplitudes involving Higgs, longitudinal $Z$ or neutrino pairs.

  14. Quadrature-dependent Bogoliubov transformations and multiphoton squeezed states

    De Siena, S; Illuminati, F; Siena, Silvio De; Lisi, Antonio Di; Illuminati, Fabrizio

    2001-01-01

    We introduce a linear, canonical transformation of the fundamental single--mode field operators $a$ and $a^{\\dagger}$ that generalizes the linear Bogoliubov transformation familiar in the construction of the harmonic oscillator squeezed states. This generalization is obtained by adding to the linear transformation a nonlinear function of any of the fundamental quadrature operators $X_{1}$ and $X_{2}$, making the original Bogoliubov transformation quadrature--dependent. Remarkably, the conditions of canonicity do not impose any constraint on the form of the nonlinear function, and lead to a set of nontrivial algebraic relations between the $c$--number coefficients of the transformation. We examine in detail the structure and the properties of the new quantum states defined as eigenvectors of the transformed annihilation operator $b$. These eigenvectors define a class of multiphoton squeezed states. The structure of the uncertainty products and of the quasiprobability distributions in phase space shows that bes...

  15. Monitoring wound healing by multiphoton tomography/endoscopy

    König, Karsten; Weinigel, Martin; Bückle, Rainer; Kaatz, Martin; Hipler, Christina; Zens, Katharina; Schneider, Stefan W.; Huck, Volker

    2015-02-01

    Certified clinical multiphoton tomographs are employed to perform rapid label-free high-resolution in vivo histology. Novel tomographs include a flexible 360° scan head attached to a mechano-optical arm for autofluorescence and SHG imaging as well as rigid two-photon GRIN microendoscope. Mitochondrial fluorescent NAD(P)H, fluorescent elastin, keratin, and melanin as well as SHG-active collagen can be imaged with submicron resolution in human skin. The system was employed to study the healing of chronic wounds (venous leg ulcer) and acute wounds (curettage of actinic or seborrheic keratosis) on a subcellular level. Furthermore, a flexible sterile foil as interface between wound and focusing optic was tested.

  16. Reassignment of Scattered Emission Photons in Multifocal Multiphoton Microscopy

    Cha, Jae Won; Singh, Vijay Raj; Kim, Ki Hean; Subramanian, Jaichandar; Peng, Qiwen; Yu, Hanry; Nedivi, Elly; So, Peter T. C.

    2014-06-01

    Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously scanning multiple foci across different regions of specimen. The use of imaging detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to-noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly recovered using multianode photomultiplier tubes (MAPMT). In this design, however, emission photons scattered to neighbor anodes are encoded by the foci scan location resulting in ghost images. The crosstalk between different anodes is currently measured a priori, which is cumbersome as it depends specimen properties. Here, we present the photon reassignment method for MMM, established based on the maximum likelihood (ML) estimation, for quantification of crosstalk between the anodes of MAPMT without a priori measurement. The method provides the reassignment of the photons generated by the ghost images to the original spatial location thus increases the SNR of the final reconstructed image.

  17. Picosecond multiphoton ionization of atomic and molecular clusters

    High peak-power picosecond laser pulses have been used for the first time to effect nonresonant or resonant multiphoton ionization (MPI) of clusters generated in a supersonic nozzle expansion. The resulting ions are subsequently detected and characterized by time-of-flight mass spectroscopy. Specifically, we present results involving MPI of clusters of xenon and nitric oxide. Previous MPI studies of many molecular clusters using nanosecond lasers have not been successful in observing the parent ion, presumably due to fast dissociation channels. It is proposed that the present technique is a new and rather general ionization source for cluster studies which is complementary to electron impact but may, in addition, provide unique spectroscopic or dynamical information. 23 refs., 5 figs

  18. Partial indistinguishability theory for multi-photon experiments in multiport devices

    Shchesnovich, V. S.

    2014-01-01

    We generalize an approach for description of multi-photon experiments with multi-port unitary linear optical devices, initiated in \\textit{Phys. Rev. A \\textbf{89}, 022333 (2014)} for the case of single photons in mixed spectral states, to arbitrary (multi-photon) input and arbitrary photon detectors. We give a physical interpretation of a non-negative definite Hermitian matrix, the matrix of a quadratic form giving output probabilities, as the partial indistinguishability matrix. We show tha...

  19. Multiphoton Rabi Oscillations of Correlated Electrons in Strong Field Nonsequential Double Ionization

    Qing, Liao; Yueming, Zhou; Cheng, Huang; Peixiang, Lu

    2011-01-01

    With quantum calculations, we have investigated the multiphoton nonsequential double ionization of helium atoms in intense laser fields at ultraviolet wavelengths. Very surprisingly, we find a so-far unobserved double-circle structure in the correlated electron momentum spectra. The double-circle structure essentially reveals multiphoton Rabi oscillations of two electrons, which are strongly supported by the oscillating population of a certain doubly excited state and by the oscillating doubl...

  20. Multiphoton atom ionization in a field of an ultrashort laser pulse

    Closed analytical expressions for the probability of the multiphoton atoms and ions ionization under effect of the alternating current filed applicable for any value of Keldysh parameter are obtained through imaginary time method. Dependence of the ionization probability and photoelectron pulse spectrum on the ultrashort laser pulse form is considered. The formulae obtained may be used in the theory of the semiconductor multiphoton ionization by the laser pulse field

  1. Enabling Multiphoton and Second Harmonic Generation Imaging in Paraffin-Embedded and Histologically Stained Sections

    Monaghan, Michael G.; Kroll, Sebastian; Brucker, Sara Y.; Schenke-Layland, Katja

    2016-01-01

    Nonlinear microscopy, namely multiphoton imaging and second harmonic generation (SHG), is an established noninvasive technique useful for the imaging of extracellular matrix (ECM). Typically, measurements are performed in vivo on freshly excised tissues or biopsies. In this article, we describe the effect of rehydrating paraffin-embedded sections on multiphoton and SHG emission signals and the acquisition of nonlinear images from hematoxylin and eosin (H&E)-stained sections before and after a...

  2. Multiphoton dissociation and thermal unimolecular reactions induced by infrared lasers

    Multiphoton dissociation (MPD) of ethyl chloride was studied using a tunable 3.3 μm laser to excite CH stretches. The absorbed energy increases almost linearly with fluence, while for 10 μm excitation there is substantial saturation. Much higher dissociation yields were observed for 3.3 μm excitation than for 10 μm excitation, reflecting bottlenecking in the discrete region of 10 μm excitation. The resonant nature of the excitation allows the rate equations description for transitions in the quasicontinuum and continuum to be extended to the discrete levels. Absorption cross sections are estimated from ordinary ir spectra. A set of cross sections which is constant or slowly decreasing with increasing vibrational excitation gives good fits to both absorption and dissociation yield data. The rate equations model was also used to quantitatively calculate the pressure dependence of the MPD yield of SF6 caused by vibrational self-quenching. Between 1000-3000 cm-1 of energy is removed from SF6 excited to approx. > 60 kcal/mole by collision with a cold SF6 molecule at gas kinetic rate. Calculation showed the fluence dependence of dissociation varies strongly with the gas pressure. Infrared multiphoton excitation was applied to study thermal unimolecular reactions. With SiF4 as absorbing gas for the CO2 laser pulse, transient high temperature pulses were generated in a gas mixture. IR fluorescence from the medium reflected the decay of the temperature. The activation energy and the preexponential factor of the reactant dissociation were obtained from a phenomenological model calculation. Results are presented in detail

  3. High-order multiphoton ionization of the noble gases

    Ionization of an atom by the absorption of several photons from a strong electromagnetic field is considered. Specifically, the absolute yield of multiply charged ions of the noble gases, argon, krypton, and xenon produced using a well-characterized, tunable picosecond dye laser is reported as a function of both laser intensity and frequency. Theoretical models are developed to provide a quantitative interpretation of the data. The experiments were designed to investigate the influence of intermediate atomic states on the multiphoton ionization probability at intensities such that the strength of the applied field approached that of the internal atomic field. This was accomplished by measuring the ion yield over a broad range of laser intensity, 1012 ≤ I ≤ 4 x 1014 Wcm2 and frequency. The laser wavelength was varied between 570 and 620 nm and the second harmonic, 285 to 310 nm. Enhancement of the yield of singly-charged krypton ions by two orders of magnitude by three-photon resonant, four-photon ionization was observed at intensities nearly two orders of magnitude above previous results. A model which considers only two atomic levels coupled by the strong field is presented and is found to be in good agreement with the experimental results. Measured values of the three-photon Rabi rate to, and the photoionization cross sections of, several excited states of Kr I are reported. In addition, even at intensities exceeding 1013 Wcm2, it was possible to find frequencies at which no resonant enhancement of the ionization probability could be observed. Charge states as high as Ar4+, Kr5+ and Xe6+ produced by this non-resonant multiphoton ionization were observed at the highest intensities. 102 refs., 50 figs., 5 tabs

  4. Data-adaptive image-denoising for detecting and quantifying nanoparticle entry in mucosal tissues through intravital 2-photon microscopy

    Torsten Bölke

    2014-11-01

    Full Text Available Intravital 2-photon microscopy of mucosal membranes across which nanoparticles enter the organism typically generates noisy images. Because the noise results from the random statistics of only very few photons detected per pixel, it cannot be avoided by technical means. Fluorescent nanoparticles contained in the tissue may be represented by a few bright pixels which closely resemble the noise structure. We here present a data-adaptive method for digital denoising of datasets obtained by 2-photon microscopy. The algorithm exploits both local and non-local redundancy of the underlying ground-truth signal to reduce noise. Our approach automatically adapts the strength of noise suppression in a data-adaptive way by using a Bayesian network. The results show that the specific adaption to both signal and noise characteristics improves the preservation of fine structures such as nanoparticles while less artefacts were produced as compared to reference algorithms. Our method is applicable to other imaging modalities as well, provided the specific noise characteristics are known and taken into account.

  5. Reduction of Tubular Flow Rate as a Mechanism of Oliguria in the Early Phase of Endotoxemia Revealed by Intravital Imaging.

    Nakano, Daisuke; Doi, Kent; Kitamura, Hiroaki; Kuwabara, Takashige; Mori, Kiyoshi; Mukoyama, Masashi; Nishiyama, Akira

    2015-12-01

    Urine output is widely used as a criterion for the diagnosis of AKI. Although several potential mechanisms of septic AKI have been identified, regulation of urine flow after glomerular filtration has not been evaluated. This study evaluated changes in urine flow in mice with septic AKI. The intratubular urine flow rate was monitored in real time by intravital imaging using two-photon laser microscopy. The tubular flow rate, as measured by freely filtered dye (FITC-inulin or Lucifer yellow), time-dependently declined after LPS injection. At 2 hours, the tubular flow rate was slower in mice injected with LPS than in mice injected with saline, whereas BP and GFR were similar in the two groups. Importantly, fluorophore-conjugated LPS selectively accumulated in the proximal tubules that showed reduced tubular flow at 2 hours and luminal obstruction with cell swelling at 24 hours. Delipidation of LPS or deletion of Toll-like receptor 4 in mice abolished these effects, whereas neutralization of TNF-α had little effect on LPS-induced tubular flow retention. Rapid intravenous fluid resuscitation within 6 hours improved the tubular flow rate only when accompanied by the dilation of obstructed proximal tubules with accumulated LPS. These findings suggest that LPS reduces the intratubular urine flow rate during early phases of endotoxemia through a Toll-like receptor 4-dependent mechanism, and that the efficacy of fluid resuscitation may depend on the response of tubules with LPS accumulation. PMID:25855781

  6. Discharge and Multiphoton Ionization in the Focus of Powerful Lasers

    The paper gives a review of the most interesting physical results obtained in recent years during studies of the development of light sparks and multiphoton ionization of atoms. The processes taking place in light sparks - the avalanche ionization of gases in a laser focus - are considered. The basic features of light sparks, determined by the focal length of the lens and the power of the laser beam, are indicated. All sparks can be classed as ''short'' or ''long''. In ''short'' sparks the discharge plasma can extend across the laser beam, and a large part of the light energy is absorbed in it. In ''long'' sparks, produced with lenses of long focal length and high power lasers, only a small fraction of the energy goes into the plasma. ''Short'' sparks propagate in the direction of the laser, while ''long'' sparks propagate along a straight line in two opposite directions. The sparks are characterized by a striated structure. This structure is apparently due not only to the characteristics of the plasma produced, but also to the space-time structure of the laser radiation.. Thus, the production of a light spark is much more complicated than was assumed in earlier theoretical works. In ''short'' laser sparks produced with a lens of short focal length, high temperatures are reached (approx. 106 degrees), so that they can be regarded as high-temperature explosions. To understand the processes taking place in the spark, it is important to consider the following stages:' 'the formation of a fast photo-ionization corona, the production of a shock-wave fireball, the separation of,the shock wave from the fireball, the production of two-layer structure in the shock wave and, finally, the formation of long- lived decaying plasma. At lower pressures there is no avalanche ionization, and ionization is due mainly to the multiphoton photo-effect. The first results on multiphoton ionization of atoms by a strong changing field of laser radiation were presented at the Yugoslav

  7. CHIRAL MULTIPHOTON ABSORPTION AND INVERSE SKIN EFFECT IN WLAN SYSTEMS

    Héctor Torres Silva

    2005-12-01

    Full Text Available A model formed by chiral bioplasma with a set of macromolecules of DNA, which represents the human head inner structure, makes possible to analyze its behavior, when it is radiated by a microwave electromagnetic field from cellular phones and WLAN's at frequencies of 2.4 and 5.2 GHz is presented. The finite difference time domain, FDTD, numeric technique is used under multiphoton regime deduced from Maxwell equations. The numerical results of the Specific Absorption Rate, SAR, show the SAR behavior in function of input power and the chirality factor. The main conclusions of our work are: a the microwave absorption from cellular phones or WLAN's is enhanced, compared with classical models, when values of the normalized chiral factor are of order of one which appear under multiphoton regime ; b a phenomena like an “inverse skin effect” in 5.2 GHz, with respect to a 2.4 GHz source, was observed. c In the metamaterial region we show that the absorption rate always is positive.Un modelo formado por bioplasma quiral con un conjunto de macromoléculas de ADN, que representa la estructura interna de la cabeza humana, hace posible analizar su comportamiento, cuando es irradiada por campos electromagnéticos de microondas de teléfonos celulares o sistemas WLAN a frecuencias de 2.4 y 5.2 GHz. El método de diferencias finitas en el dominio del tiempo, FDTD, en régimen de multifotones deducido de las ecuaciones de Maxwell es usado. Los resultados numéricos de la taza de absorción específica SAR, muestran el comportamiento de la SAR en función de la potencia de entrada y del factor quiral. Las principales conclusiones de nuestro trabajo son: a la absorción de microondas es aumentada comparada con modelos clásicos, cuando valores del factor quiral normalizado son del orden de la unidad, que aparecen bajo régimen multifotónico; b Un fenómeno de efecto pelicular inverso en 5.2 GHz con respecto a una fuente de 2.4 GHz fue observado; c En la regi

  8. Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states

    We introduce a formalism of nonlinear canonical transformations for general systems of multiphoton quantum optics. For single-mode systems the transformations depend on a tunable free parameter, the homodyne local-oscillator angle; for n-mode systems they depend on n heterodyne mixing angles. The canonical formalism realizes nontrivial mixing of pairs of conjugate quadratures of the electromagnetic field in terms of homodyne variables for single-mode systems, and in terms of heterodyne variables for multimode systems. In the first instance the transformations yield nonquadratic model Hamiltonians of degenerate multiphoton processes and define a class of non-Gaussian, nonclassical multiphoton states that exhibit properties of coherence and squeezing. We show that such homodyne multiphoton squeezed states are generated by unitary operators with a nonlinear time evolution that realizes the homodyne mixing of a pair of conjugate quadratures. Tuning of the local-oscillator angle allows us to vary at will the statistical properties of such states. We discuss the relevance of the formalism for the study of degenerate (up-)down-conversion processes. In a companion paper [F. Dell'Anno, S. De Siena, and F. Illuminati, 69, 033813 (2004)], we provide the extension of the nonlinear canonical formalism to multimode systems, we introduce the associated heterodyne multiphoton squeezed states, and we discuss their possible experimental realization

  9. Structure of multiphoton quantum optics. I. Canonical formalism and homodyne squeezed states

    dell'Anno, Fabio; de Siena, Silvio; Illuminati, Fabrizio

    2004-03-01

    We introduce a formalism of nonlinear canonical transformations for general systems of multiphoton quantum optics. For single-mode systems the transformations depend on a tunable free parameter, the homodyne local-oscillator angle; for n -mode systems they depend on n heterodyne mixing angles. The canonical formalism realizes nontrivial mixing of pairs of conjugate quadratures of the electromagnetic field in terms of homodyne variables for single-mode systems, and in terms of heterodyne variables for multimode systems. In the first instance the transformations yield nonquadratic model Hamiltonians of degenerate multiphoton processes and define a class of non-Gaussian, nonclassical multiphoton states that exhibit properties of coherence and squeezing. We show that such homodyne multiphoton squeezed states are generated by unitary operators with a nonlinear time evolution that realizes the homodyne mixing of a pair of conjugate quadratures. Tuning of the local-oscillator angle allows us to vary at will the statistical properties of such states. We discuss the relevance of the formalism for the study of degenerate (up-)down-conversion processes. In a companion paper [ F. Dell’Anno, S. De Siena, and F. Illuminati, 69, 033813 (2004) ], we provide the extension of the nonlinear canonical formalism to multimode systems, we introduce the associated heterodyne multiphoton squeezed states, and we discuss their possible experimental realization.

  10. Label-free detection of breast masses using multiphoton microscopy.

    Xiufeng Wu

    Full Text Available Histopathology forms the gold standard for the diagnosis of breast cancer. Multiphoton microscopy (MPM has been proposed to be a potentially powerful adjunct to current histopathological techniques. A label-free imaging based on two- photon excited fluorescence and second-harmonic generation is developed for differentiating normal breast tissues, benign, as well as breast cancer tissues. Human breast biopsies (including human normal breast tissues, benign as well as breast cancer tissues that are first imaged (fresh, unfixed, and unstained with MPM and are then processed for routine H-E histopathology. Our results suggest that the MPM images, obtained from these unprocessed biopsies, can readily distinguish between benign lesions and breast cancers. In the tissues of breast cancers, MPM showed that the tumor cells displayed marked cellular and nuclear pleomorphism. The tumor cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, infiltrated into disrupted connective tissue, leading to the loss of second-harmonic generation signals. For breast cancer, MPM diagnosis was 100% correct because the tissues of breast cancers did not have second-harmonic generation signals in MPM imaging. On the contrary, in benign breast masses, second-harmonic generation signals could be seen easily in MPM imaging. These observations indicate that MPM could be an important potential tool to provide label-free noninvasive diagnostic impressions that can guide surgeon in biopsy and patient management.

  11. Superresolved multiphoton microscopy with spatial frequency-modulated imaging.

    Field, Jeffrey J; Wernsing, Keith A; Domingue, Scott R; Allende Motz, Alyssa M; DeLuca, Keith F; Levi, Dean H; DeLuca, Jennifer G; Young, Michael D; Squier, Jeff A; Bartels, Randy A

    2016-06-14

    Superresolved far-field microscopy has emerged as a powerful tool for investigating the structure of objects with resolution well below the diffraction limit of light. Nearly all superresolution imaging techniques reported to date rely on real energy states of fluorescent molecules to circumvent the diffraction limit, preventing superresolved imaging with contrast mechanisms that occur via virtual energy states, including harmonic generation (HG). We report a superresolution technique based on spatial frequency-modulated imaging (SPIFI) that permits superresolved nonlinear microscopy with any contrast mechanism and with single-pixel detection. We show multimodal superresolved images with two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) from biological and inorganic media. Multiphoton SPIFI (MP-SPIFI) provides spatial resolution up to 2η below the diffraction limit, where η is the highest power of the nonlinear intensity response. MP-SPIFI can be used to provide enhanced resolution in optically thin media and may provide a solution for superresolved imaging deep in scattering media. PMID:27231219

  12. Photoionization of excited molecular states using multiphoton excitation techniques

    Photoelectron spectra are reported for three photon resonant, four photon ionization of H2 via the B 1Σ/sub u/+, v = 7 (J = 2,4) and C 1π/sub u'/, v = 0-4 (J = 1) levels and of N2 via the o31π/sub u'/, v = 1,2, b 1π/sub u'/, v = 3-5, and c 1π/sub u'/, v = 0 levels. The results reflect both the spectroscopy and the dynamics of photoionization of excited molecular states and are discussed in terms of the selection rules for photoionization and the relative probabilities of photoionization from Rydberg and valence states. In some cases, in accordance with the Franck-Condon principle, the results demonstrate that resonant multiphoton ionization through Rydberg states may be a powerful technique for the production of electronic, vibrational, and rotational state selected ions. However, in other cases, systematic departures from Franck-Condon factors are observed, which reflect the more subtle dynamics of excited state photoionization. 23 references, 6 figures, 2 tables

  13. Photoionization of excited molecular states using multiphoton excitation techniques

    Dehmer, Patricia M. [Argonne National Laboratory (ANL), Argonne, IL (United States); Pratt, Stephen T. [Argonne National Laboratory (ANL), Argonne, IL (United States); Dehmer, Joseph L. [Argonne National Laboratory (ANL), Argonne, IL (United States)

    1984-01-01

    Photoelectron spectra are reported for three photon resonant, four photon ionization of H₂ via the B ¹Σu⁺, v = 7 (J = 2,4) and C ¹Πu v = 0-4 (J = 1) levels and of N₂ via the o₃ ¹Πu, v = 1,2, b ¹Πu, v = 3-5, and c ¹Πu, v = 0 levels. The results reflect both the spectroscopy and the dynamics of photoionization of excited molecular states and are discussed in terms of the selection rules for photoionization and the relative probabilities of photoionization from Rydberg and valence states. In some cases, in accordance with the Franck-Condon principle, the results demonstrate that resonant multiphoton ionization through Rydberg states may be a powerful technique for the production of electronic, vibrational, and rotational state selected ions. However, in other cases, systematic departures from Franck-Condon factors are observed, which reflect the more subtle dynamics of excited state photoionization.

  14. Multi-photon Resonance Phenomena Using Laguerre-Gaussian Beams

    Kazemi, Seyedeh Hamideh

    2016-01-01

    We study the influence of Laguerre-Gaussian (LG) and Gaussian fields on the linewidth of the optical spectrum of multi-photon resonance phenomena. First, we investigate the dependence of the steady-state coherence on the laser profile in a two-level system. Thanks to the LG field, the linewidth of the one-photon optical pumping peak is explicitly narrower than for a Gaussian field. We then investigate the atomic coherence in a two-level pump-probe atomic system and show that using the LG fields, a narrower two-photon absorption peak can be obtained compared to the usual Gaussian ones. In next section, we investigate the effect of the laser profiles on the coherent population trapping in the $\\Lambda$-type molecular open systems. It is shown that, comparing with the the Gaussian fields, the LG fields reduce the linewidth of the optical spectrum. In addition, for a laser-driven four-level atomic system we study the effect of laser profiles on the Autler-Townes doublet structure in the absorption spectrum. We al...

  15. Security of quantum key distribution with multiphoton components

    Yin, Hua-Lei; Fu, Yao; Mao, Yingqiu; Chen, Zeng-Bing

    2016-07-01

    Most qubit-based quantum key distribution (QKD) protocols extract the secure key merely from single-photon component of the attenuated lasers. However, with the Scarani-Acin-Ribordy-Gisin 2004 (SARG04) QKD protocol, the unconditionally secure key can be extracted from the two-photon component by modifying the classical post-processing procedure in the BB84 protocol. Employing the merits of SARG04 QKD protocol and six-state preparation, one can extract secure key from the components of single photon up to four photons. In this paper, we provide the exact relations between the secure key rate and the bit error rate in a six-state SARG04 protocol with single-photon, two-photon, three-photon, and four-photon sources. By restricting the mutual information between the phase error and bit error, we obtain a higher secure bit error rate threshold of the multiphoton components than previous works. Besides, we compare the performances of the six-state SARG04 with other prepare-and-measure QKD protocols using decoy states.

  16. Quantum Decoherence for Multi-Photon Entangled States

    SUN Yan-Hua; ZHU Xia; KUANG Le-Man

    2005-01-01

    @@ We investigate quantum decoherence of the multi-photon entangled state |ψNm> = Nm[cosγ|N- m>1|m>2 +eiθm sinγ|m>1|N - m>2]. When the entangled channel |ψNm> is embedded in an environment, the channel decoheres and becomes a mixed state governed by a master equation. We calculate thelinear entropy and the relative entropy of entanglement, which describe the mixedness and the amount of entanglement for the mixed state, respectively. We show that quantum decoherence weakens the amount of entanglement and enhances the mixedness with the time evolution. It is indicated that the relative entropy of entanglement depends on not only the initial entanglement angle and the decohering parameter, but also the number of photons in each mode. In particular, we find that the decohering speed depends on the number-difference of photons in the two modes. The larger the number-difference of photons is, the higher the decohering speed.

  17. Multiphoton Ionization Detection in Collinear Laser Spectroscopy of Isolde Beams

    2002-01-01

    The experiments using the multiphoton ionization technique have been continued in the beginning of 1990 with stable beam tests on the modified apparatus and with another radioactive beam time on Yb. Higher laser power and an increased vacuum in the ionization region (see figure) yielded a further gain in sensitivity, mainly due to the better suppression of the background ions produced in rest gas collisions. For even Yb isotopes we have now reached a detection efficiency of $\\epsilon$~=~1~x~10$^{-5}$ ions per incoming atom at a background count rate of 30~ions from a beam of 5~x~10$^9$. This sensitivity was high enough for spectroscopy on $^{157}$Yb, where the typical ISOLDE yield of 5~x~10$^7$Yb ions is covered by an isobaric contamination of more than 10$^{10}$ ions. Measurements have also been performed on $^{175}$Yb. These give the first precise value for the magnetic moment of this isotope, $\\mu$~=~0.766(8)$ mu _{N} $, which agrees rather well with the magnetic moment of the isotone $^{177}$Hf. The isoto...

  18. Multiphoton imaging the disruptive nature of sulfur mustard lesions

    Werrlein, Robert J.; Braue, Catherine R.; Dillman, James F.

    2005-03-01

    Sulfur mustard [bis-2-chloroethyl sulfide] is a vesicating agent first used as a weapon of war in WWI. It causes debilitating blisters at the epidermal-dermal junction and involves molecules that are also disrupted by junctional epidermolysis bullosa (JEB) and other blistering skin diseases. Despite its recurring use in global conflicts, there is still no completely effective treatment. We have shown by imaging human keratinocytes in cell culture and in intact epidermal tissues that the basal cells of skin contain well-organized molecules (keratins K5/K14, α6β4 integrin, laminin 5 and α3β1 integrin) that are early targets of sulfur mustard. Disruption and collapse of these molecules is coincident with nuclear displacement, loss of functional asymmetry, and loss of polarized mobility. The progression of this pathology precedes basal cell detachment by 8-24 h, a time equivalent to the "clinical latent phase" that defines the extant period between agent exposure and vesication. Our images indicate that disruption of adhesion-complex molecules also impairs cytoskeletal proteins and the integration of structures required for signal transduction and tissue repair. We have recently developed an optical system to test this hypothesis, i.e., to determine whether and how the early disruption of target molecules alters signal transduction. This environmentally controlled on-line system provides a nexus for real-time correlation of imaged lesions with DNA microarray analysis, and for using multiphoton microscopy to facilitate development of more effective treatment strategies.

  19. Multiphoton ionization of pyrrole-water mixed clusters

    2001-01-01

    Multiphoton ionization of the hydrogen-bonded pyrrole-water clusters ( C4H5 N)n H2O)m is studied with a reflectron—time of flight mass spectrometer at 355 nm. With increasing partial concentration of pyrrole in a gas mixture source, a series of poly-pyrrole-water binary-mixed cluster ions can be observed, including unprotonated cluster ions [(C4H5N)x (H2O)y]* , protonated cluster ions [(C4H5N)x (H2O)yH]* and dehydrogenated cluster ions [ ( C4 H4 N) ( C4 H5 N) x ( H2O) y ] + . Ab initio calculations of their structures, bond strengths, charge distributions and re action energies are carried out. Stable structures of these clusters are obtained from the calculations. A probable forma tion mechanism of the cluster ions [(C4H5N)x(H2O)y] + , [(C4H5N)x (H2O)y]H+ and [(C4H4N) (C4H5N)x (H2O)y]-is supposed to be the ionization of clusters followed by dissociation.

  20. Materials characterization using ion bombardment and multiphoton resonance ionization

    The combination of energetic ion bombardment with multiphoton resonance ionization (MPRI) spectroscopy has proven to be an important advancement in surface science. The goal of this project is continuing the development of MPRI of desorbed neutrals as a surface analytical tool. The method for accomplishing this is a detailed examination of the factors which govern a measurement and the implementation of the optimum experimental approach. Initially, a review of the progress in laser post-ionization of desorbed neutral particles is presented. This is followed by a description of the newly redesigned instrument, emphasizing detailed characterization of the high current ion source and the reflecting time-of-flight mass spectrometer. Using the new apparatus, the quantitative aspects of the measurement are examined and the fractions of desorbed ions and neutrals are determined using several matrices. The In concentration in a set of silicon wafers is measured, yielding a detection limit of 9 parts-per-trillion. Finally, the prospects for employing this experiment for measuring the half-life of the rare double beta decay of 136Xe to 136Ba are assessed

  1. Tunneling dynamics in multiphoton ionization and attoclock calibration.

    Klaiber, Michael; Hatsagortsyan, Karen Z; Keitel, Christoph H

    2015-02-27

    The intermediate domain of strong-field ionization between the tunneling and multiphoton regimes is investigated using the strong-field approximation and the imaginary-time method. An intuitive model for the dynamics is developed which describes the ionization process within a nonadiabatic tunneling picture with a coordinate dependent electron energy during the under-the-barrier motion. The nonadiabatic effects in the elliptically polarized laser field induce a transversal momentum shift of the tunneled electron wave packet at the tunnel exit and a delayed appearance in the continuum as well as a shift of the tunneling exit towards the ionic core. The latter significantly modifies the Coulomb focusing during the electron excursion in the laser field after exiting the ionization tunnel. We show that nonadiabatic effects are especially large when the Coulomb field of the ionic core is taken into account during the under-the-barrier motion. The simple man model modified with these nonadiabatic corrections provides an intuitive background for exact theories and has direct implications for the calibration of the attoclock technique. PMID:25768761

  2. Development of resonance-enhanced multiphoton ionization system

    Radiation and Photochemistry Division has developed a Molecular Beam-Resonance Enhanced Multiphoton Ionization-Time-of-Flight spectrometer, a highly sensitive and selective analytical detection system, for investigation of photodissociation dynamics of isolated molecules. In this system, the molecular beam is intersected in the extraction region of a Wiley-McLaren type Time-of-Flight mass spectrometer by the photolysis laser beam, propagating perpendicular to both the molecular beams and the Time-of-Flight tube. The probe (ionization) laser beam counter propagating to the photolysis beam, ionizes the stable products and the radicals produced on photodissociation. The important features of the system, namely, the resolution and the detection limit, have been determined from the studies of aniline molecular beam, generated by seeding 1% aniline in helium. For the present configuration, using one metre long flight tube, the resolution has been found to be about 400, and detection limit is better than 106 species per cm3. The integrity of the set-up is obtained from the photodissociation dynamics studies of bromoform. (author)

  3. Characterization of powdered epidermal vaccine delivery with multiphoton microscopy

    Multiphoton laser scanning microscopy (MPLSM) has been adapted to non-invasively characterize hand-held powdered epidermal vaccine delivery technology. A near infrared femtosecond pulsed laser, wavelength at approximately 920 nm, was used to evoke autofluorescence of endogenous fluorophores within ex vivo porcine and human skin. Consequently, sub cellular resolution three-dimensional images of stratum corneum and viable epidermal cells were acquired and utilized to observe the morphological deformation of these cells as a result of micro-particle penetration. Furthermore, the distributional pattern of micro-particles within the specific skin target volume was quantified by measuring the penetration depth as revealed by serial optical sections in the axial plane obtained with MPLSM. Additionally, endogenous fluorescence contrast images acquired at the supra-basal layer reveal cellular structures that may pertain to dendritic Langerhans cells of the epidermis. These results show that MPLSM has advantages over conventional histological approaches, since three-dimensional functional images with sub-cellular spatial resolution to depths beyond the epidermis can be acquired non-invasively. Accordingly, we propose that MPLSM is ideal for investigations of powdered epidermal vaccine delivery

  4. Superresolved multiphoton microscopy with spatial frequency-modulated imaging

    Field, Jeffrey J.; Wernsing, Keith A.; Domingue, Scott R.; Allende Motz, Alyssa M.; DeLuca, Keith F.; Levi, Dean H.; DeLuca, Jennifer G.; Young, Michael D.; Squier, Jeff A.; Bartels, Randy A.

    2016-05-26

    Superresolved far-field microscopy has emerged as a powerful tool for investigating the structure of objects with resolution well below the diffraction limit of light. Nearly all superresolution imaging techniques reported to date rely on real energy states of fluorescent molecules to circumvent the diffraction limit, preventing superresolved imaging with contrast mechanisms that occur via virtual energy states, including harmonic generation (HG). We report a superresolution technique based on spatial frequency-modulated imaging (SPIFI) that permits superresolved nonlinear microscopy with any contrast mechanism and with single-pixel detection. We show multimodal superresolved images with two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) from biological and inorganic media. Multiphoton SPIFI (MP-SPIFI) provides spatial resolution up to 2..eta.. below the diffraction limit, where ..eta.. is the highest power of the nonlinear intensity response. MP-SPIFI can be used to provide enhanced resolution in optically thin media and may provide a solution for superresolved imaging deep in scattering media.

  5. The polarization effect of a laser in multiphoton Compton scattering

    Liang, Guo-Hua; Lü, Qing-Zheng; Teng, Ai-Ping; Li, Ying-Jun

    2014-05-01

    The multiphoton Compton scattering in a high-intensity laser beam is studied by using the laser-dressed quantum electrodynamics (QED) method, which is a non-perturbative theory for the interaction between a plane electromagnetic field and a charged particle. In order to analyze in the real experimental condition, a Lorentz transformation for the cross section of this process is derived between the laboratory frame and the initial rest frame of electrons. The energy of the scattered photon is analyzed, as well as the cross sections for different laser intensities and polarizations and different electron velocities. The angular distribution of the emitted photon is investigated in a special velocity of the electron, in which for a fixed number of absorbed photons, the electron energy will not change after the scattering in the lab frame. We obtain the conclusion that higher laser intensities suppress few-laser-photon absorption and enhance more-laser-photon absorption. A comparison between different polarizations is also made, and we find that the linearly polarized laser is more suitable to generate nonlinear Compton scattering.

  6. The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: An intravital microscopy study in mice

    The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases

  7. Stabilizing 3D in vivo intravital microscopy images with an iteratively refined soft-tissue model for immunology experiments.

    Gómez-Conde, Iván; Caetano, Susana S; Tadokoro, Carlos E; Olivieri, David N

    2015-09-01

    We describe a set of new algorithms and a software tool, StabiTissue, for stabilizing in vivo intravital microscopy images that suffer from soft-tissue background movement. Because these images lack predetermined anchors and are dominated by noise, we use a pixel weighted image alignment together with a correction for nonlinear tissue deformations. We call this correction a poor man׳s diffeomorphic map since it ascertains the nonlinear regions of the image without resorting to a full integral equation method. To determine the quality of the image stabilization, we developed an ensemble sampling method that quantifies the coincidence between image pairs from randomly distributed image regions. We obtain global stabilization alignment through an iterative constrained simulated annealing optimization procedure. To show the accuracy of our algorithm with existing software, we measured the misalignment error rate in datasets taken from two different organs and compared the results to a similar and popular open-source solution. Present open-source stabilization software tools perform poorly because they do not treat the specific needs of the IV-2pM datasets with soft-tissue deformation, speckle noise, full 5D inter- and intra-stack motion error correction, and undefined anchors. In contrast, the results of our tests demonstrate that our method is more immune to noise and provides better performance for datasets' possessing nonlinear tissue deformations. As a practical application of our software, we show how our stabilization improves cell tracking, where the presence of background movement would degrade track information. We also provide a qualitative comparison of our software with other open-source libraries/applications. Our software is freely available at the open source repository http://sourceforge.net/projects/stabitissue/. PMID:26232672

  8. Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution

    Dachs Gabi U

    2004-11-01

    Full Text Available Abstract Background Electroporation is currently receiving much attention as a way to increase drug and DNA delivery. Recent studies demonstrated the feasibility of electrogene therapy using a range of therapeutic genes for the treatment of experimental tumors. However, the transfection efficiency of electroporation-assisted DNA delivery is still low compared to viral methods and there is a clear need to optimize this approach. In order to optimize treatment, knowledge about spatial and time dependency of gene expression following delivery is of utmost importance in order to improve gene delivery. Intravital microscopy of tumors growing in dorsal skin fold window chambers is a useful method for monitoring gene transfection, since it allows non-invasive dynamic monitoring of gene expression in tumors in a live animal. Methods Intravital microscopy was used to monitor real time spatial distribution of the green fluorescent protein (GFP and time dependence of transfection efficiency in syngeneic P22 rat tumor model. DNA alone, liposome-DNA complexes and electroporation-assisted DNA delivery using two different sets of electric pulse parameters were compared. Results Electroporation-assisted DNA delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz was superior to other methods and resulted in 22% increase in fluorescence intensity in the tumors up to 6 days post-transfection, compared to the non-transfected area in granulation tissue. Functional GFP was detected within 5 h after transfection. Cells expressing GFP were detected throughout the tumor, but not in the surrounding tissue that was not exposed to electric pulses. Conclusions Intravital microscopy was demonstrated to be a suitable method for monitoring time and spatial distribution of gene expression in experimental tumors and provided evidence that electroporation-assisted gene delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz is an effective method, resulting in early onset and homogenous

  9. Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution

    Electroporation is currently receiving much attention as a way to increase drug and DNA delivery. Recent studies demonstrated the feasibility of electrogene therapy using a range of therapeutic genes for the treatment of experimental tumors. However, the transfection efficiency of electroporation-assisted DNA delivery is still low compared to viral methods and there is a clear need to optimize this approach. In order to optimize treatment, knowledge about spatial and time dependency of gene expression following delivery is of utmost importance in order to improve gene delivery. Intravital microscopy of tumors growing in dorsal skin fold window chambers is a useful method for monitoring gene transfection, since it allows non-invasive dynamic monitoring of gene expression in tumors in a live animal. Intravital microscopy was used to monitor real time spatial distribution of the green fluorescent protein (GFP) and time dependence of transfection efficiency in syngeneic P22 rat tumor model. DNA alone, liposome-DNA complexes and electroporation-assisted DNA delivery using two different sets of electric pulse parameters were compared. Electroporation-assisted DNA delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz was superior to other methods and resulted in 22% increase in fluorescence intensity in the tumors up to 6 days post-transfection, compared to the non-transfected area in granulation tissue. Functional GFP was detected within 5 h after transfection. Cells expressing GFP were detected throughout the tumor, but not in the surrounding tissue that was not exposed to electric pulses. Intravital microscopy was demonstrated to be a suitable method for monitoring time and spatial distribution of gene expression in experimental tumors and provided evidence that electroporation-assisted gene delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz is an effective method, resulting in early onset and homogenous distribution of gene expression in the syngeneic P22 rat tumor model

  10. A Fluorescent Polymer Probe with High Selectivity toward Vascular Endothelial Cells for and beyond Noninvasive Two-Photon Intravital Imaging of Brain Vasculature.

    Mettra, B; Appaix, F; Olesiak-Banska, J; Le Bahers, T; Leung, A; Matczyszyn, K; Samoc, M; van der Sanden, B; Monnereau, C; Andraud, C

    2016-07-13

    A chromophore-engineering strategy that relies on the introduction of a ground-state distortion in a quadrupolar chromophore was used to obtain a quasi-quadrupolar chromophore with red emission and large two-photon absorption (2PA) cross-section in polar solvents. This molecule was functionalized with water-solubilizing polymer chains. It constitutes not only a remarkable contrast agent for intravital two-photon microscopy of the functional cerebral vasculature in a minimally invasive configuration but presents intriguing endothelial staining ability that makes it a valuable probe for premortem histological staining. PMID:27267494

  11. What ticks do under your skin: two-photon intravital imaging of Ixodes scapularis feeding in the presence of the lyme disease spirochete.

    Bockenstedt, Linda K; Gonzalez, David; Mao, Jialing; Li, Ming; Belperron, Alexia A; Haberman, Ann

    2014-03-01

    Lyme disease, due to infection with the Ixodes-tick transmitted spirochete Borrelia burgdorferi, is the most common tick-transmitted disease in the northern hemisphere. Our understanding of the tick-pathogen-vertebrate host interactions that sustain an enzootic cycle for B. burgdorferi is incomplete. In this article, we describe a method for imaging the feeding of Ixodes scapularis nymphs in real-time using two-photon intravital microscopy and show how this technology can be applied to view the response of Lyme borrelia in the skin of an infected host to tick feeding. PMID:24600332

  12. Theory of Multiphoton Multielectron Ionization of Xenon under Strong 93-eV Radiation

    We present a theoretical interpretation of recent experimental results on multiphoton multiple ionization of xenon by soft-x-ray radiation of photon energy ∼93 eV and intensity up to 1016 W/cm2[A. A Sorokin et al., Phys. Rev. Lett. 99, 213002 (2007)]. The data are interpreted within multiphoton perturbation theory, taking into account the spatiotemporal distribution of the radiation. Multiphoton cross sections have been obtained through a technique of scaling, with occasional adjustment to the data, provided the two prove to be compatible. Whatever discrepancies between theory and experiment persist can be reasonably attributed to some uncertainty in the experimental conditions and possibly to the value of some cross sections, without, however, any evidence for nonperturbative behavior

  13. Prolate spheroidal coordinates for calculations of rates for multiphoton ionization of H2+

    The validity of using the spheroidal coordinates in the problem of multiphoton ionization of H2+ is investigated in conjunction with a method that is highly efficient in the calculation of rates for multiphoton ionization of H atom in the nonperturbative intensities of laser by resuming the Rayleigh-Schroedinger perturbation series. This method takes advantages of the separability of the Hamiltonian, which in turn enables us to calculate rates of multiphoton ionization for more complex atoms or molecules. We utilize the efficiency to apply this method to the case of H2+ and compare the results to those of H atom. This method turns out to be as efficient as in the H atom calculation over a finite range of frequencies in contrast with the failure for very high or low frequencies and the reason of which are also discussed.

  14. Distinguishing human normal or cancerous esophagus tissue ex vivo using multiphoton microscopy

    Application of multiphoton microscopy (MPM) to clinical cancer research has greatly developed over the last few years. In this paper, we mainly focus on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) for investigating esophageal cancer. We chiefly discuss the SHG/TPEF image and spectral characteristics of normal and cancerous esophagus submucosa with the combined multi-channel imaging mode and Lambda mode of a multiphoton microscope (LSM 510 META). Great differences can be detected, such as collagen content and morphology, glandular-shaped cancer cells, TPEF/SHG intensity ratio, and so on, which demonstrate that the multiphoton imaging technique has the potential ability for minimally-invasive early cancer diagnosis. (paper)

  15. The effect laser pulse width on the multi-photon ionization efficiency

    We studied the variation of the multi-photon ionization efficiencies of atoms as a function of the laser pulse width under the condition of constant pulse energy. The density-matrix calculation showed that long pulses were preferred for efficient ionization whenever the lifetimes of the levels involved in the transition were longer than the pulse widths. Also, it was demonstrated that the atomic and the laser parameters, such as transition cross-sections, laser pulse widths, and lifetimes affect the optimal excitation rate of the transition for efficient multi-photon ionization

  16. Demonstration of structural alterations in experimental corneal infectious model using multiphoton microscopy

    Lo, Wen; Tan, Hsin-Yuan; Chang, Yuh-Ling; Sun, Yen; Lin, Sung-Jan; Jee, Shiou-Hwa; Dong, Chen-Yuan

    2007-02-01

    The aim of this study is to assess the application of multiphoton autofluorescence and second harmonic generation (SHG) microscopy for investigating the structural alterations and the pattern of microbial spreading during corneal infectious process in an in vitro organ culture model. The autofluorescence spectrum derived from pathogens allows us to monitoring the pattern of microbial spreading within corneal lamellae. In addition, the destruction and regeneration of second harmonic generating collagen during infectious process can also be monitored in a non-invasive fashion. Therefore we propose that multiphoton microscopy may potentially be applied as an effective monitoring tool for corneal infection studies.

  17. Multiphoton atom ionization on the field of an ultrashort laser pulse

    One derived closed analytical expressions for probability of multiphoton ionization of atoms and ions under the effect of alternating electrical field applicable for arbitrary values of Keldysh parameter. One studies dependences of ionization probability and pulsed spectrum of photoelectrons on the shape of ultrashort laser pulse. One studied in detail examples of various type pulsed fields. One studied interference effect in energy spectrum of photoelectrons at atom ionization by general periodical field. One discusses field of application for adiabatic approximation in theory of multiphoton ionization

  18. Integral-equation approach to multiphoton ionization by intense fields. II. Application to H and H-

    We have developed an integral-equation method for treating multiphoton ionization of atomic systems irradiated by intense fields. We have applied this method to the calculation of partial rates for multiphoton detachment of H- (into specific continuum channels) by a laser operating at frequencies of 0.2 and 0.5 eV. Nonperturbative features are seen at intensities above about 5 x 10/sup 10/ W/cm2. We have also applied the method to hydrogen, to the determination of the field-induced width in the ground-state energy (the total ionization rate)

  19. Coherent Phase Control of Multiphoton Ionization in Three-Level Ladder-Type System

    ZHANG Shi-An; CHEN Yu-Ting; WANG Zu-Geng; SUN Zhen-Rong

    2009-01-01

    We present the theoretical investigation of photoelectron spectroscopy resulting from the strong field induced multiphoton ionization in a typical three-level ladder-style system.Our theoretical results show that the photoelectron spectral structure can be alternatively steered by spectral phase modulation.This physical mechanism for strong field quantum control is explicitly exploited by the time-dependent dressed state population.It is concluded that the phase-shaped laser pulses can be used to selectively manipulate the multiphoton ionization process in complicated quantum systems.

  20. Fermi-coupled spherically adapted effective states in the collisionless multiphoton excitation of SF6

    A calculation method for the collisionless multiphoton excitation of SF6 by intense CO2 laser light up to a chain of parallel nν3, (n - 1)ν3 + ν2 + ν6 ... vibrational-rotational ladders linked by Fermi interaction is described. Spherically adapted effective states suitable to the purpose are defined, and matrix elements for multiphoton excitation in the rotating wave approximation effective hamiltonian formalism are given in this basis. The method is aimed at the investigation of population transfer between the cited parallel vibrational ladders, and is suitable for computer-calculation programmation. (orig.)

  1. Fermi-coupled spherically adapted effective states in the collisionless multiphoton excitation of SF 6

    Di Lauro, C.; Lattanzi, F.

    1982-10-01

    A calculation method for the collisionless multiphoton excitation of SF 6 by intense CO 2 laser light up to a chain of parallel nv3, ( n - 1) v3 + v2 + v6 … vibrational-rotational ladders linked by Fermi interaction is described. Spherically adapted effective states suitable to the purpose are defined, and matrix elements for multiphoton excitation in the rotatingwave approximation effective hamiltonian formalism are given in this basis. The method is aimed at the investigation of population transfer between the cited parallel vibrational ladders, and is suitable for computer-calculation programmation.

  2. Large field of view multiphoton microscopy of human skin

    Balu, Mihaela; Mikami, Hideharu; Hou, Jue; Potma, Eric O.; Tromberg, Bruce J.

    2016-03-01

    Clinical examination crucially relies on the ability to quickly examine large tissue areas and rapidly zoom in to regions of interest. Skin lesions often show irregularity in color and appearance in general, especially when they start to progress towards malignancy. Large field of view (FOV) and automatic translation of the imaging area are critical in the assessment of the entire lesion. Imaging of limited FOVs of the lesion can easily result in false negative diagnosis. We present a multiphoton microscope based on two-photon excited fluorescence and second-harmonic generation that images FOVs of about 0.8 mm2 (without stitching adjacent FOVs) at speeds of 10 frames/second (800 x 800 pixels) with lateral and axial resolutions of 0.5 μm and 2.5 μm, respectively. The main novelty of this instrument is the design of the scan head, which includes a fast galvanometric scanner, relay optics, a beam expander and a high NA objective lens. We optimized the system based on the Olympus 25x, 1.05NA water immersion lens, that features a long working distance of 1 mm. Proper tailoring of the beam expander, which consists of the scan and tube lens elements, enables scaling of the FOV. The design criteria include a flat wavefront of the beam, minimum field curvature, and suppressed spherical aberrations. All aberrations in focus are below the Marechal criterion of 0.07λ rms for diffraction-limited performance. We demonstrate the practical utility of this microscope by ex-vivo imaging of wide FOVs in normal human skin.

  3. Infrared multiphoton dissociation processes of some halogenated hydrocarbons

    We review our studies on mechanisms and dynamics of infrared multiphoton dissociation of CF3CHClF, C2HCl3, CBrF2CHClF, CBrF2CHBrF, CBrF2CBrClF, and c-C4F8 using a photofragmentation translational spectroscopy and ab initio MO calculations. In the case of CF3CHClF, three-centered HCl elimination and C-Cl bond rupture occurred competitively as primary dissociation processes. The center-of-mass translational energy distribution of the products produced by the HCl elimination indicates that an exit barrier of several kcal/mol exists in the potential energy surface of the reaction. In the case of C2HCl3, three- and four-centered eliminations of HCl occurred competitively. Halogenated ethanes containing bromine atoms dissociated through a C-Br bond rupture channel. The halogenated ethyl radicals produced by the C-Br bond ruptures subsequently dissociated through a C-halogen bond rupture channel. The translational energy distributions for the C-halogen bond ruptures observed are almost consistent with those calculated by RRKM theory. In the case of c-C4F8, dissociation of c-C4F8 to two C2F4 molecules was observed as a primary process. About 30% of the exit barrier for this reaction is converted to the translational energy of the products. This indicates that the dissociation proceeds through a loose transition state. This conclusion is supported by the transition state structure calculated by an ab initio MO method. (author)

  4. High-intensity multiphoton ionization of H2

    A tunable, high-intensity picosecond-dye-laser system has been employed with electron energy analysis to investigate the dynamics of (3+1) resonance-enhanced multiphoton ionization via various vibrational levels of the B 1Σu+ and C 1Πu electronic states in H2. At the intensities studied [(0.2--6)x1013 W/cm2], we find evidence for production of molecular ions in various vibrational levels; at the lower intensities the population distribution of final vibrational states varies with wavelength in a manner consistent with resonant enhancement at the three-photon level, followed by ionization into a vibrational level of H2+ roughly predictable by a Franck-Condon analysis of ionization out of the C state. At higher intensities, there is a shift to increased population of lower vibrational states of H2+, consistent with an ac Stark shift of the correspondingly lower vibrational levels of the C state into resonance with the three-photon energy of the laser. Clear evidence of direct dissociation of H2 followed by single-photon ionization of the excited H atom is observed as well. Above-threshold ionization of these two processes occurs readily. We also find that dissociative ionization is an increasingly important ionization pathway as the wavelength is increased. Finally, we see evidence of a fourth ionization pathway, which we tentatively assign to photoionization into a transient bound state created by the avoided crossing of the first repulsive electronic state of H2+, |2pσu,n right-angle, with the single-photon-dressed ground state of H2+, |1sσg,n+1 right-angle

  5. Visualizing the Acute Effects of Vascular-Targeted Therapy In Vivo Using Intravital Microscopy and Magnetic Resonance Imaging: Correlation with Endothelial Apoptosis, Cytokine Induction, and Treatment Outcome

    Mukund Seshadri

    2007-02-01

    Full Text Available The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA were investigated in vivo using intravital microscopy (IVM and magnetic resonance imaging (MRI. Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p. and correlated with induction of tumor necrosis factor-α (TNF-α, endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-α. Parallel contrast-enhanced MRI studies showed a ~ 4-fold increase in longitudinal relaxation rates (ΔR1, indicative of increased contrast agent accumulation within the tumor. Dualimmunostained tumor sections (CD31/TdT revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in ΔR1 and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome.

  6. Multiphoton spectroscopy of autoionising states and AC Stark shifts in strontium atoms

    The paper reports and discusses recent data on multiphoton ionisation of strontium, with emphasis on resonant multi photon ionisation. A theoretical framework is described for interpretation of the results, along with a description of the experiment. The results are presented as discussed with respect to the AC stark shifts of two-photon resonance, and configuration mixing for autoionising states. (U.K.)

  7. Ion beam studies of surfaces by multiphoton resonance ionization of sputtered neutrals

    Ionization of neutral atoms sputtered from ion bombarded solids by multiphoton resonance ionization has been recently demonstrated. The ionization efficiency is several orders of magnitude greater than other post-ionization methods. This approach should find applications in the characterization of the chemistry and structure of solid surfaces and in the trace analysis of a wide variety of materials. (author)

  8. Clinical combination of multiphoton tomography and high frequency ultrasound imaging for evaluation of skin diseases

    König, K.; Speicher, M.; Koehler, M. J.; Scharenberg, R.; Elsner, P.; Kaatz, M.

    2010-02-01

    For the first time, high frequency ultrasound imaging, multiphoton tomography, and dermoscopy were combined in a clinical study. Different dermatoses such as benign and malign skin cancers, connective tissue diseases, inflammatory skin diseases and autoimmune bullous skin diseases have been investigated with (i) state-of-the-art and highly sophisticated ultrasound systems for dermatology, (ii) the femtosecond-laser multiphoton tomograph DermaInspectTM and (iii) dermoscopes. Dermoscopy provides two-dimensional color imaging of the skin surface with a magnification up to 70x. Ultrasound images are generated from reflections of the emitted ultrasound signal, based on inhomogeneities of the tissue. These echoes are converted to electrical signals. Depending on the ultrasound frequency the penetration depth varies from about 1 mm to 16 mm in dermatological application. The 100-MHz-ultrasound system provided an axial resolution down to 16 μm and a lateral resolution down to 32 μm. In contrast to the wide-field ultrasound images, multiphoton tomography provided horizontal optical sections of 0.36×0.36 mm2 down to 200 μm tissue depth with submicron resolution. The autofluorescence of mitochondrial coenzymes, melanin, and elastin as well as the secondharmonic- generation signal of the collagen network were imaged. The combination of ultrasound and multiphoton tomography provides a novel opportunity for diagnostics of skin disorders.

  9. Multiphoton lonization Spectrum of Nitrogen Oxide by D~2∑←X2П

    2003-01-01

    The resonance-enhanced multiphoton ionization (REMPI) spectrum of NO has been obtained. The spectral lines can be attributed to NO D2∑←X2П transitions. NO molecules are ionized via the resonant intermediate D2∑ states and by (3+2) REMPI process.

  10. Extension of the sum rule for the transition rates between multiplets to the multiphoton case

    Solovyev, D; Volotka, A; Plunien, G

    2010-01-01

    The sum rule for the transition rates between the components of two multiplets, known for the one-photon transitions, is extended to the multiphoton transitions in hydrogen and hydrogen-like ions. As an example the transitions 3p-2p, 4p-3p and 4d-3d are considered. The numerical results are compared with previous calculations.

  11. Temporal shaping of nanosecond CO2 laser pulses in multiphoton saturable absorbers

    It was shown that substantial temporal distortion of nanosecond 10.6 μm laser pulses occurs in traversing multiphoton saturable absorbers. The risetime and pulse delay effects appear to depend both on fluence and wavelength, and to be qualitatively consistent with predictions of a simple two-level absorption model

  12. Potential of ultraviolet widefield imaging and multiphoton microscopy for analysis of dehydroergosterol in cellular membranes

    Wüstner, Daniel; Brewer, Jonathan R.; Bagatolli, Luis;

    2011-01-01

    Dehydroergosterol (DHE) is an intrinsically fluorescent sterol with absorption/emission in the ultraviolet (UV) region and biophysical properties similar to those of cholesterol. We compared the potential of UV-sensitive low-light-level wide-field (UV-WF) imaging with that of multiphoton (MP) exc...

  13. Multiphoton Ionization Spectrum of Nitrogen Oxide by D2∑←X2∏

    Lianshui Zhang; Guiyin Zhang; Xiaodong Yang; Bo Sun; Xiaohui Zhao

    2003-01-01

    The resonance-enhanced multiphoton ionization (REMPI) spectrum of NO has been obtained. The spectral lines can be attributed to NO D2∑←X2∏ transitions. NO molecules are ionized via the resonant intermediate D2∑ states and by (3+2) REMPI process.

  14. Very low energy photoelectron spectroscopy in multiphoton ionization of H2

    Bordas, C.; Dyer, M.; Helm, H.

    1994-01-01

    We apply a novel photoelectron imaging spectrometer [1] to the energy and angular analysis of photoelectrons resulting from resonantly enhanced multiphoton ionization of H2. Photoelectron images with well resolved individual rotational structure of the resulting H2+ ion are obtained, demonstrating the capability of this technique for analyzing photoelectrons in the meV energy range.

  15. Electron-Nuclear Energy Sharing in Above-Threshold Multiphoton Dissociative Ionization of H2

    Wu, J.; Kunitski, M.; Pitzer, M.;

    2013-01-01

    We report experimental observation of the energy sharing between electron and nuclei in above-threshold multiphoton dissociative ionization of H2 by strong laser fields. The absorbed photon energy is shared between the ejected electron and nuclei in a correlated fashion, resulting in multiple...... diagonal lines in their joint energy spectrum governed by the energy conservation of all fragment particles....

  16. Nanoparticle-assisted-multiphoton microscopy for in vivo brain imaging of mice

    Qian, Jun

    2015-03-01

    Neuro/brain study has attracted much attention during past few years, and many optical methods have been utilized in order to obtain accurate and complete neural information inside the brain. Relying on simultaneous absorption of two or more near-infrared photons by a fluorophore, multiphoton microscopy can achieve deep tissue penetration and efficient light detection noninvasively, which makes it very suitable for thick-tissue and in vivo bioimaging. Nanoparticles possess many unique optical and chemical properties, such as anti-photobleaching, large multiphoton absorption cross-section, and high stability in biological environment, which facilitates their applications in long-term multiphoton microscopy as contrast agents. In this paper, we will introduce several typical nanoparticles (e.g. organic dye doped polymer nanoparticles and gold nanorods) with high multiphoton fluorescence efficiency. We further applied them in two- and three-photon in vivo functional brain imaging of mice, such as brain-microglia imaging, 3D architecture reconstruction of brain blood vessel, and blood velocity measurement.

  17. Multi-photon entanglement and applications in quantum information

    In this thesis, two new linear optics networks are introduced and their application for several quantum information tasks is presented. Spontaneous parametric down conversion, is used in different configurations to provide the input states for the networks. The first network is a new design of a controlled phase gate which is particularly interesting for applications in multi-photon experiments as it constitutes an improvement of former realizations with respect to stability and reliability. This is explicitly demonstrated by employing the gate in four-photon experiments. In this context, a teleportation and entanglement swapping protocol is performed in which all four Bell states are distinguished by means of the phase gate. A similar type of measurement applied to the subsystem parts of two copies of a quantum state, allows further the direct estimation of the state's entanglement in terms of its concurrence. Finally, starting from two Bell states, the controlled phase gate is applied for the observation of a four photon cluster state. The analysis of the results focuses on measurement based quantum computation, the main usage of cluster states. The second network, fed with the second order emission of non-collinear type ii spontaneous parametric down conversion, constitutes a tunable source of a whole family of states. Up to now the observation of one particular state required one individually tailored setup. With the network introduced here many different states can be obtained within the same arrangement by tuning a single, easily accessible experimental parameter. These states exhibit many useful properties and play a central role in several applications of quantum information. Here, they are used for the solution of a four-player quantum Minority game. It is shown that, by employing four-qubit entanglement, the quantum version of the game clearly outperforms its classical counterpart. Experimental data obtained with both networks are utilized to demonstrate

  18. Ex vivo applications of multiphoton microscopy in urology

    Jain, Manu; Mukherjee, Sushmita

    2016-03-01

    Background: Routine urological surgery frequently requires rapid on-site histopathological tissue evaluation either during biopsy or intra-operative procedure. However, resected tissue needs to undergo processing, which is not only time consuming but may also create artifacts hindering real-time tissue assessment. Likewise, pathologist often relies on several ancillary methods, in addition to H&E to arrive at a definitive diagnosis. Although, helpful these techniques are tedious and time consuming and often show overlapping results. Therefore, there is a need for an imaging tool that can rapidly assess tissue in real-time at cellular level. Multiphoton microscopy (MPM) is one such technique that can generate histology-quality images from fresh and fixed tissue solely based on their intrinsic autofluorescence emission, without the need for tissue processing or staining. Design: Fresh tissue sections (neoplastic and non-neoplastic) from biopsy and surgical specimens of bladder and kidney were obtained. Unstained deparaffinized slides from biopsy of medical kidney disease and oncocytic renal neoplasms were also obtained. MPM images were acquired using with an Olympus FluoView FV1000MPE system. After imaging, fresh tissues were submitted for routine histopathology. Results: Based on the architectural and cellular details of the tissue, MPM could characterize normal components of bladder and kidney. Neoplastic tissue could be differentiated from non-neoplastic tissue and could be further classified as per histopathological convention. Some of the tumors had unique MPM signatures not otherwise seen on H&E sections. Various subtypes of glomerular lesions were identified as well as renal oncocytic neoplasms were differentiated on unstained deparaffinized slides. Conclusions: We envision MPM to become an integral part of regular diagnostic workflow for rapid assessment of tissue. MPM can be used to evaluate the adequacy of biopsies and triage tissues for ancillary studies

  19. Multi-photon entanglement and applications in quantum information

    Schmid, Christian I.T.

    2008-05-30

    In this thesis, two new linear optics networks are introduced and their application for several quantum information tasks is presented. Spontaneous parametric down conversion, is used in different configurations to provide the input states for the networks. The first network is a new design of a controlled phase gate which is particularly interesting for applications in multi-photon experiments as it constitutes an improvement of former realizations with respect to stability and reliability. This is explicitly demonstrated by employing the gate in four-photon experiments. In this context, a teleportation and entanglement swapping protocol is performed in which all four Bell states are distinguished by means of the phase gate. A similar type of measurement applied to the subsystem parts of two copies of a quantum state, allows further the direct estimation of the state's entanglement in terms of its concurrence. Finally, starting from two Bell states, the controlled phase gate is applied for the observation of a four photon cluster state. The analysis of the results focuses on measurement based quantum computation, the main usage of cluster states. The second network, fed with the second order emission of non-collinear type ii spontaneous parametric down conversion, constitutes a tunable source of a whole family of states. Up to now the observation of one particular state required one individually tailored setup. With the network introduced here many different states can be obtained within the same arrangement by tuning a single, easily accessible experimental parameter. These states exhibit many useful properties and play a central role in several applications of quantum information. Here, they are used for the solution of a four-player quantum Minority game. It is shown that, by employing four-qubit entanglement, the quantum version of the game clearly outperforms its classical counterpart. Experimental data obtained with both networks are utilized to

  20. ACT Test

    ... ACT. It is important to evaluate how the person is responding to this ACT lower limit and to the amount of heparin ... to determine someone's heparin anticoagulant requirements, stabilize the person, and then change the monitoring tool. The ACT may be influenced by a person's platelet count ...

  1. Ultrafast dynamics of multiphoton photoemisssion from gold and carrier-envelope phase sensitivity

    Full text: 'Multiphoton-induced photoelectron emission from gold was investigated using ultrashort pulses to assess additional effects influencing its carrier-envelope phase dependence. The third-order interferometric autocorrelation showed short side-wings indicating ultrafast hot electron dynamics reducing the phase contrast.' The application of carrier-envelope (CE) phase controlled waveforms proved to be an essential tool in experimental attosecond science. However, the currently used f-to-2f technique for CE phase stabilization is not capable of precisely tracking carrier-envelope phase drifts in an amplified laser system. Therefore, direct CE phase measurement methods raised interest in the past year or so and some experiments were also carried out based on physical effects that could hold promise of forming a basis for a compact, direct, single-shot CE phase detector. Three effects were studied in detail. The first is based on the so-called stereo-ATI setup, which has the inherent drawbacks of drawing on a gas-phase interaction and the need for spectrally selecting high-energy electrons for high contrast. Two other methods were demonstrated with solid-state devices but both lack the desired high signal contrast expected in terms of the CE phase. According to simulations, multi-photon-induced photoelectron emission from a gold surface should result in an overall yield of electrons that has a high CE phase sensitivity; as much as 40 % modulation depth is expected when applying 5-fs pulses. The experimentally observed sensitivity was, however, below the percent level. The measurements to be presented were aiming at investigating the reasons for this discrepancy. While standard tests, such as the laser intensity and the polarization dependence of the emission process with few-cycle pulses did not yield anything unexpected, time-resolved measurements brought some new insight. They were carried out with a Michelson interferometer, the output of which was used to

  2. ACTS 2014

    Co-curator of ACTS 2014 together with Rasmus Holmboe, Judith Schwarzbart and Sanne Kofoed. ACTS is the Museum of Contemporary Art’s international bi-annual festival. ACTS was established in 2011 and, while the primary focus is on sound and performance art, it also looks toward socially oriented art....... For the 2014 festival, the museum has entered into a collaboration with the Department for Performance Design at Roskilde University – with continued focus on sound and performance art, and social art in public spaces. With ACTS, art moves out of its usual exhibition space and instead utilizes the...... city, its various possibilities and public spaces as a stage. ACTS takes place in and around the museum and diverse locations in Roskilde city. ACTS is partly curated by the museum staff and partly by guest curators. ACTS 2014 is supported by Nordea-fonden and is a part of the project The Museum goes...

  3. Sequential multiphoton multiple ionization of Ar and Xe by X-ray free electron laser pulses at SACLA

    We have investigated multiphoton multiple ionization of Ar and Xe atoms irradiated by intense X-ray pulses using the new X-ray free electron laser facility SACLA. The experimental results are compared with theoretical results.

  4. Combination of an optical parametric oscillator and quantum-dots 655 to improve imaging depth of vasculature by intravital multicolor two-photon microscopy.

    Ricard, Clément; Lamasse, Lisa; Jaouen, Alexandre; Rougon, Geneviève; Debarbieux, Franck

    2016-06-01

    Simultaneous imaging of different cell types and structures in the mouse central nervous system (CNS) by intravital two-photon microscopy requires the characterization of fluorophores and advances in approaches to visualize them. We describe the use of a two-photon infrared illumination generated by an optical parametric oscillator (OPO) on quantum-dots 655 (QD655) nanocrystals to improve resolution of the vasculature deeper in the mouse brain both in healthy and pathological conditions. Moreover, QD655 signal can be unmixed from the DsRed2, CFP, EGFP and EYFP fluorescent proteins, which enhances the panel of multi-parametric correlative investigations both in the cortex and the spinal cord. PMID:27375951

  5. Periodicity in tumor vasculature targeting kinetics of ligand-functionalized nanoparticles studied by dynamic contrast enhanced magnetic resonance imaging and intravital microscopy

    Hak, Sjoerd; Cebulla, Jana; Huuse, Else Marie;

    2014-01-01

    because angiogenesis plays an important role in various pathologies, but also since endothelial cell surface receptors are directly accessible for relatively large circulating nanoparticles. Typically, nanoparticle targeting towards these receptors is studied by analyzing the contrast distribution on...... kinetics. These kinetics will not only depend on nanoparticle characteristics, but also on receptor binding and recycling. In this study, we monitored the in vivo targeting kinetics of αvβ3-integrin specific nanoparticles with intravital microscopy and dynamic contrast enhanced magnetic resonance imaging...... periodicity in the accumulation kinetics of αvβ3-integrin targeted nanoparticles and hypothesize that this periodicity is caused by receptor binding, internalization and recycling dynamics. Taken together, this demonstrates that our experimental approach provides new insights in in vivo nanoparticle targeting...

  6. In vivo 3D measurement of moxifloxacin and gatifloxacin distributions in the mouse cornea using multiphoton microscopy

    Seunghun Lee; Jun Ho Lee; Jin Hyoung Park; Yeoreum Yoon; Wan Kyun Chung; Hungwon Tchah; Myoung Joon Kim; Ki Hean Kim

    2016-01-01

    Moxifloxacin and gatifloxacin are fourth-generation fluoroquinolone antibiotics used in the clinic to prevent or treat ocular infections. Their pharmacokinetics in the cornea is usually measured from extracted ocular fluids or tissues, and in vivo direct measurement is difficult. In this study multiphoton microscopy (MPM), which is a 3D optical microscopic technique based on multiphoton fluorescence, was applied to the measurement of moxifloxacin and gatifloxacin distribution in the cornea. I...

  7. High-fidelity spatially resolved multiphoton counting for quantum imaging applications

    Chrapkiewicz, Radoslaw; Banaszek, Konrad

    2015-01-01

    We present a method for spatially resolved multiphoton counting based on an intensified camera with the retrieval of multimode photon statistics fully accounting for non-linearities in the detection process. The scheme relies on one-time quantum tomographic calibration of the detector. Faithful, high-fidelity reconstruction of single- and two-mode statistics of multiphoton states is demonstrated for coherent states and their statistical mixtures. The results consistently exhibit classical values of Mandel and Fano parameters in contrast to raw statistics of camera photo-events. Detector operation is reliable for illumination levels up to the average of one photon per an event area, substantially higher than in previous approaches to characterize quantum statistical properties of light with spatial resolution.

  8. Label-free identification of intestinal metaplasia in the stomach using multiphoton microscopy

    Wu, G.; Wei, J.; Zheng, Z.; Ye, J.; Zeng, S.

    2014-06-01

    The early diagnosis of intestinal metaplasia (IM) in the stomach together with effective therapeutic interventions is crucial to reducing the mortality-rates of the patients associated with gastric cancer. However, it is challenging during conventional white-light endoscopy, and histological analysis remains the ‘gold standard’ for the final diagnosis. Here, we describe a label-free imaging method, multiphoton microscopy (MPM), for the identification of IM in the stomach. It was found that multiphoton imaging provides cellular and subcellular details to the identification of IM from normal gastric tissues. In particular, there is significant difference in the population density of goblet cells between normal and IM gastric tissues, providing substantial potential to become a quantitative intrinsic marker for in vivo clinical diagnosis of early gastric lesions. To our knowledge, this is the first demonstration of the potential of MPM for the identification of IM.

  9. On the effect of Coulomb interaction on the multiphoton ionization probability

    The nonresonant multiphoton ionization problem is considered in the case of one-dimensional Coulomb potential. The continuous spectrum wave function in the presence of electromagnetic field and Coulomb interaction is calculated in the quasiclassical approximation. The Coulomb interaction is taken into account by the use of the perturbation theory in that part of action which arises due to interaction with an electromagnetic field. Criteria of this approximation validity are found and it is shown that such an approach allows the process of nonresonant multiphoton ionization to be described in the field range εa (εa is the characteristic atomic field) for arbitrary values of the adiabaticity parameter γ. Within the range γ>>1 the Coulomb factor in the ionization probability is independing of the field strength and has to be taken into account

  10. Stepwise multi-photon activation fluorescence reveals a new method of melanoma imaging for dermatologists

    Lai, Zhenhua; Lian, Christine; Ma, Jie; Yu, Jingyi; Gu, Zetong; Rajadhyaksha, Milind; DiMarzio, Charles A.

    2014-02-01

    Previous research has shown that the stepwise multi-photon activated fluorescence (SMPAF) of melanin, activated by a continuous-wave (CW) mode near infrared (NIR) laser, is a low cost and reliable method of detecting melanin. SMPAF images of melanin in a mouse hair and a formalin fixed mouse melanoma were compared with conventional multiphoton fluorescence microscopy (MPFM) images and confocal reflectance microscopy (CRM) images, all of which were acquired at an excitation wavelength of 920 nm, to further prove the effectiveness of SMPAF in detecting melanin. SMPAF images add specificity for melanin detection to MPFM images and CRM images. Melanin SMPAF can be a promising technology to enable melanoma imaging for dermatologists.

  11. Multiphoton ionization of the hydrogen atom exposed to circularly or linearly polarized laser pulses

    This paper studies the multiphoton ionization of the hydrogen atom exposed to the linearly or circularly polarized laser pulses by solving the time-dependent Schrödinger equation. It finds that the ratio of the ionization probabilities by linearly and circularly polarized laser pulses varies with the numbers of absorbing photons. With the same laser intensity, the circularly polarized laser pulse favors to ionize the atom with more ease than the linearly polarized laser pulse if only two or three photons are necessary to be absorbed. For the higher order multiphoton ionization, the linearly polarized laser pulse has the advantage over circularly polarized laser pulse to ionize the atom. (atomic and molecular physics)

  12. Absolute density-profile tomography of molecular beams using multiphoton ionization

    We describe an approach for the absolute density measurement of rotationally symmetric molecular beams via multiphoton ionization. This simple single-projection tomographic technique requires only knowledge of the spatial intensity profile and ionization characteristics of the focused laser beam that probes the pulsed molecular jet. Multiphoton ionization (MPI) of a xenon beam allowed tomographic reconstruction of a two-dimensional density profile with a peak density of (4.2±0.4)x1018 m-3, which was compared with the theoretical predictions of the sudden freeze model. An analytic solution to the Abel transform is derived for Gaussian projected density profiles which greatly simplifies the reconstruction of the absolute radial density. MPI is sufficiently general that this technique can be readily applied to atomic beams with a broad range of chemistries.

  13. Multiphoton ionization studies of benzene in tetramethylsilane and n-pentane solutions

    The multiphoton ionization spectra of dilute solutions (approx. -3 M) of benzene in tetramethylsilane (TMSi) and n-pentane (n-Pt) have been measured using linearly polarized light over the laser excitation wavelength (λ/sub exc/) region from 360 to 560 nm. Spectra measured with circularly polarized light are also reported for 460 <λ/sub exc/<540 nm. The order of the multiphoton ionization mechanisms that occur in different λ/sub exc/ regions has been determined, and their importance is discussed together with the observed polarization behavior. The polarization ratio and the ''apparent'' order of the ionization process were found to depend on the laser intensity. The ionization threshold of benzene in TMSi was estimated to lie between 6.6 and 5.9 eV, while in n-Pt between 7.36 and 6.8 eV

  14. Deep inner-shell multiphoton ionization by intense x-ray free-electron laser pulses

    Fukuzawa, H; Motomura, K; Mondal, S; Nagaya, K; Wada, S; Liu, X -J; Feifel, R; Tachibana, T; Ito, Y; Kimura, M; Sakai, T; Matsunami, K; Hayashita, H; Kajikawa, J; Johnsson, P; Siano, M; Kukk, E; Rudek, B; Erk, B; Foucar, L; Robert, E; Miron, C; Tono, K; Inubushi, Y; Hatsui, T; Yabashi, M; Yao, M; Santra, R; Ueda, K

    2012-01-01

    We have investigated multiphoton multiple ionization dynamics of argon and xenon atoms using a new x-ray free electron laser (XFEL) facility, SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan, and identified that highly charged Xe ions with the charge state up to +26 are produced predominantly via four-photon absorption as well as highly charged Ar ions with the charge state up to +10 are produced via two-photon absorption at a photon energy of 5.5 keV. The absolute fluence of the XFEL pulse, needed for comparison between theory and experiment, has been determined using two-photon processes in the argon atom with the help of benchmark ab initio calculations. Our experimental results, in combination with a newly developed theoretical model for heavy atoms, demonstrate the occurrence of multiphoton absorption involving deep inner shells.

  15. Photoelectron circular dichroism of bicyclic ketones from multiphoton ionization with femtosecond laser pulses.

    Lux, Christian; Wollenhaupt, Matthias; Sarpe, Cristian; Baumert, Thomas

    2015-01-12

    Photoelectron circular dichroism (PECD) is a CD effect up to the ten-percent regime and shows contributions from higher-order Legendre polynomials when multiphoton ionization is compared to single-photon ionization. We give a full account of our experimental methodology for measuring the multiphoton PECD and derive quantitative measures that we apply on camphor, fenchone and norcamphor. Different modulations and amplitudes of the contributing Legendre polynomials are observed despite the similarity in chemical structure. In addition, we study PECD for elliptically polarized light employing tomographic reconstruction methods. Intensity studies reveal dissociative ionization as the origin of the observed PECD effect, whereas ionization of the intermediate resonance is dominating the signal. As a perspective, we suggest to make use of our tomographic data as an experimental basis for a complete photoionization experiment and give a prospect of PECD as an analytic tool. PMID:25492564

  16. Non-perturbative calculations for the multiphoton ionization of hydrogen and lithium atoms

    Multiphoton ionization rates for the Hydrogen atom are calculated by direct solution of the time-dependent Schrodinger equation for several intensities at a photon energy of 5.0 eV (KrF laser). Ionization rates for linear polarized light are extracted front the time evolution of the ground state on a 2d cylindrical coordinate lattice, while rates for circular polarized light are extracted from calculations on a 3d Cartesian coordinate lattice. Multiphoton ionization rates for the Lithium atom are calculated in the frozen-core TDHF approximation for a variety of intensities and photon frequencies. The time-dependent equation for the valence HF orbital is solved on a 2d cylindrical coordinate lattice using both fixed and variable grid spacings. The non-perturbative results for both atoms are in sharp contrast to perturbation theory predictions

  17. Multiphoton single ionization of two-electron systems in intense laser fields

    Multiphoton single-ionization of a two-electron system (He and He-like ions) in intense circularly polarized laser field is reported in a relativistic field theoretic method. Coulomb-correction factor is introduced to estimate the effect of the Coulomb field of the residual ion on the rate. Antisymmetric wave function is considered both in the initial and in the final state. The spin-specific currents are calculated. Angular asymmetry in current generation is noted with the change in the spin direction of the ionized electron. Coulomb-corrected relativistic-result for total rate is compared with the Coulomb-corrected nonrelativistic KFR rate. At the high-intensity regime nonrelativistic rate overestimates the relativistic rate. Formation of orthopositronium and parapositronium from positronium negative ion by multiphoton ionization is discussed.

  18. Comparison of multiphoton and collisional ionization in high intensity laser-plasma interactions

    Recent multiphoton ionization experiments, have shown that the tunneling ionization theories for complex atoms of Ammosov, et al. are valid in the regime where n* > 2 and the Keldysh tunneling parameter, γ, is less than 1. n* = Z (Eh/Eion)0.5 with Eh the ionization potential of hydrogen, and Eion that of the charge state of interest. γ = (Eion/2Φpond)0.5 where Φpond is the pondermotive potential of the laser. In high intensity laser-plasma and laser-solid interaction, tunneling ionization due to the laser field may become a dominant ionization channel. The authors discuss the laser and plasma characteristics required for multiphoton ionization to become the dominant ionization process and the effects this has on high intensity, laser-plasma and laser-solid interactions

  19. Laser-assisted multiphoton ionization of a hydrogen atom by electron impact

    Deb, S Ghosh; Sinha, C

    2008-01-01

    The dynamics of the electron impact multiphoton ionization of a hydrogen atom in the presence of an intense laser field has been studied theoretically, with a view to comparing (qualitatively) the results with the recent kinematically complete experiments of Horr et al [ Phys. Rev. Lett., vol. 94, 153201, (2005) ] for the He target. Significant laser modifications are noted in the present doubly (DDCS) and the fully differential cross sections (TDCS). For most of the explored kinematics (chosen in accordance with the experiment), the present binary peak intensity of the laser-assisted TDCS is significantly enhanced with respect to the field free ones, in agreement with the experiment but in contradiction with the existing first order theories. Importance of the multiphoton effects are also studied.

  20. High laser bandwidth single colour multiphoton ionization spectroscopy of uranium by galvanic detection

    The uranium single colour multiphoton ionization spectrum, with high laser bandwidth excitation, was measured, in the spectral range of R6G, using the fast pulsed (∝10-9s) optogalvanic signal generated by photoionization in the dark space of a hollow cathode discharge. Results indicate that this spectrum is dense in the 570 to 610 nm spectral range. A list of the 74 most intense lines is given. The results of a try at explaining these lines by a three photon resonant or quasi-resonant scheme, using known levels of uranium, are presented. The multiphoton ionization line at 591.54 nm is a special case which is discussed more thoroughly. (orig.)

  1. Multiphoton ionization (MPI) spectroscopy of tungsten hexafluoride: Experimental observation of Molecular spectrum using MPI

    In general, multiphoton ionization (MPI) spectroscopy of metal complexes shows the dissociation and ionization of the compounds. Well-structured molecular ionization spectrum is not observed yet for metal complexes by use of the multiphoton ionization technique. Tungsten hexafluoride was selected to get a molecular spectrum with MPI technique because it had a very high dissociation energy that might suppress facile photofragmentation. Also, WF6 has high vapor pressure(>1,000 torr at 300 K), which means heating is not required to get enough sample concentration in the molecular beam. The electronic absorption spectrum and the electron impact spectrum of WF6 were previously studied. The assignment of WF6 spectrum obtained by MPI can be compared with those published results. Experimentally, we observed the molecular MPI spectra of WF6 and the clear assignments are not easy with current results as well as previous works.

  2. Label-free identification of intestinal metaplasia in the stomach using multiphoton microscopy

    The early diagnosis of intestinal metaplasia (IM) in the stomach together with effective therapeutic interventions is crucial to reducing the mortality-rates of the patients associated with gastric cancer. However, it is challenging during conventional white-light endoscopy, and histological analysis remains the ‘gold standard’ for the final diagnosis. Here, we describe a label-free imaging method, multiphoton microscopy (MPM), for the identification of IM in the stomach. It was found that multiphoton imaging provides cellular and subcellular details to the identification of IM from normal gastric tissues. In particular, there is significant difference in the population density of goblet cells between normal and IM gastric tissues, providing substantial potential to become a quantitative intrinsic marker for in vivo clinical diagnosis of early gastric lesions. To our knowledge, this is the first demonstration of the potential of MPM for the identification of IM. (letters)

  3. Compact Coding Using Multi-Photon Tolerant Quantum Protocols for Quantum Communication

    Hajj, Rasha El; Chan, Kam Wai Clifford

    2016-01-01

    This paper presents a new encryption scheme called Compact Coding that encodes information in time, phase, and intensity domains, simultaneously. While these approaches have previously been used one at a time, the proposed scheme brings to bear for the first time their strengths simultaneously leading to an increase in the secure information transfer rate. The proposed scheme is applicable to both optical fibers and free space optics, and can be considered as an alternative to polarization coding. This paper applies the proposed compact coding scheme to multi-photon tolerant quantum protocols in order to produce quantum-level security during information transfer. We present the structure of the proposed coding scheme in a multi-photon environment and address its operation.

  4. Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

    Zhou, Yi; Chen, Zhifen; Kang, Deyong; li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2016-01-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections.

  5. In Vivo Multiphoton NADH Fluorescence Reveals Depth-Dependent Keratinocyte Metabolism in Human Skin

    Balu, Mihaela; Mazhar, Amaan; Hayakawa, Carole K.; Mittal, Richa; Krasieva, Tatiana B.; Konig, Karsten; Venugopalan, Vasan; Tromberg, Bruce J.

    2013-01-01

    We employ a clinical multiphoton microscope to monitor in vivo and noninvasively the changes in reduced nicotinamide adenine dinucleotide (NADH) fluorescence of human epidermal cells during arterial occlusion. We correlate these results with measurements of tissue oxy- and deoxyhemoglobin concentration during oxygen deprivation using spatial frequency domain imaging. During arterial occlusion, a decrease in oxyhemoglobin corresponds to an increase in NADH fluorescence in the basal epidermal c...

  6. Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy

    Raub, CB; Putnam, AJ; Tromberg, BJ; George, SC

    2010-01-01

    Cellularized collagen gels are a common model in tissue engineering, but the relationship between the microstructure and bulk mechanical properties is only partially understood. Multiphoton microscopy (MPM) is an ideal non-invasive tool to examine collagen microstructure, cellularity and crosslink content in these gels. In order to identify robust image parameters that characterize microstructural determinants of the bulk elastic modulus, we performed serial MPM and mechanical tests on acellu...

  7. Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy

    Raub, Christopher B.; Suresh, Vinod; Krasieva, Tatiana; Lyubovitsky, Julia; Mih, Justin D.; Putnam, Andrew J.; Tromberg, Bruce J.; George, Steven C.

    2006-01-01

    Multiphoton microscopy of collagen hydrogels produces second harmonic generation (SHG) and two-photon fluorescence (TPF) images, which can be used to noninvasively study gel microstructure at depth (∼1 mm). The microstructure is also a primary determinate of the mechanical properties of the gel; thus, we hypothesized that bulk optical properties (i.e., SHG and TPF) could be used to predict bulk mechanical properties of collagen hydrogels. We utilized polymerization temperature (4–37°C) and gl...

  8. Multiphoton-double-ionization probability linearly depends on laser intensity: Experimental studies of barium

    Bondar, I. I.; Suran, V. V.; Bondar, D. I.

    2013-01-01

    Despite inherently complex multiphoton dynamics, our observations show that Ba double ionization with an infrared laser (8800-8920 cm^{-1}) resembles a single-photon process; namely, its probability is proportional to the laser intensity. In this regime, single-electron ionization is due to a four-photon resonant transition through the highly perturbed state 6p^2 1D_2, whereas double ionization is realized by the two-electron mechanism. Furthermore, we argue that these conclusions are valid f...

  9. Study on multiphoton ionization mass spectra of 3-picoline in femtosecond laser field

    Using 800 nm femtosecond laser as excitation source, the processes and mechanism of multiphoton ionization and dissociation of 3-picoline is studied, and find the process is ionization before dissociation, the possible dissociation channels are analyzed. At B3LYP/6-311 G + + (d, p) level, we calculate the energy of every dissociation channel, the result is consistent with the laser power index of ions based on the experiment. (authors)

  10. Non-descanned multifocal multiphoton microscopy with a multianode photomultiplier tube

    Jae Won Cha; Yew, Elijah Y. S.; Daekeun Kim; Jaichandar Subramanian; Elly Nedivi; So, Peter T. C.

    2015-01-01

    Multifocal multiphoton microscopy (MMM) improves imaging speed over a point scanning approach by parallelizing the excitation process. Early versions of MMM relied on imaging detectors to record emission signals from multiple foci simultaneously. For many turbid biological specimens, the scattering of emission photons results in blurred images and degrades the signal-to-noise ratio (SNR). We have recently demonstrated that a multianode photomultiplier tube (MAPMT) placed in a descanned config...

  11. Ionization and fragmentation of C-60 via multiphoton-multiplasmon excitation

    Hunsche, S; Starczewski, Tomas; L'Huillier, Anne; Persson, Anders; Wahlström, Claes-Göran; vandenHeuvell, B. V. L; Svanberg, Sune

    1996-01-01

    We study the intensity dependence of ionization and fragmentation of buckminsterfullerene (C-60) in strong laser fields. Our data provide strong evidence that at intensities less than or similar to 10(14) W/cm(2) these processes occur predominantly via multiphoton excitation of the 20 eV plasmon resonance of C-60 At least two plasmons have to be created to initiate fragmentation or multiple ionization.

  12. Laser-assisted multiphoton ionization of a hydrogen atom by electron impact

    Deb, S. Ghosh; S Roy; Sinha, C.

    2008-01-01

    The dynamics of the electron impact multiphoton ionization of a hydrogen atom in the presence of an intense laser field has been studied theoretically, with a view to comparing (qualitatively) the results with the recent kinematically complete experiments of Horr et al [ Phys. Rev. Lett., vol. 94, 153201, (2005) ] for the He target. Significant laser modifications are noted in the present doubly (DDCS) and the fully differential cross sections (TDCS). For most of the explored kinematics (chos...

  13. Resonance-enhanced multiphoton ionization spectroscopy oflaser-ablated copper atoms

    Andrejeva, Anna; Harris, Joe P.; Wright, Timothy G.

    2014-01-01

    Resonance-enhanced multiphoton ionization (REMPI) spectra of laser-ablated copper atoms entrainedin a supersonic free jet expansion are reported. Depending on the ionization scheme employed, andthe conditions under which the copper atoms are produced, very different spectra are produced, whichare discussed. In some circumstances, high proportions of metastable atoms survive the ablation andexpansion process and are clearly seen in the spectra. The spectroscopic transitions for the observedlin...

  14. Femtosecond time-resolved wave packet motion in molecular multiphoton ionization and fragmentation

    Baumert, Thomas,; Bühler, B; Grosser, M.; Thalweiser, Rainer; Weiss, V.; Wiedenmann, Ernst; Gerber, Gustav

    1991-01-01

    The dynamics of molecular multiphoton ionization and fragmentation of a diatomic molecule (Na_2) have been studied in molecular beam experiments. Femtosecond laser pulses from an amplified colliding-pulse mode-locked (CPM) ring dye laser are employed to induce and probe the molecular transitions. The final continuum states are analyzed by photoelectron spectroscopy, by ion mass spectrometry and by measuring the kinetic energy of the formed ionic fragments. Pump-probe spectra emplo...

  15. Alignment dependent enhancement of the photo-electron cutoff for multi-photon ionization of molecules

    Smeenk, C.T.L.; Arissian, L; Sokolov, A. V.; Spanner, M.; Lee, K F; Staudte, A.; Villeneuve, D. M.; Corkum, P B

    2013-01-01

    The multiphoton ionization rate of molecules depends on the alignment of the molecular axis with respect to the ionizing laser polarization. By studying molecular frame photo-electron angular distributions from N$_2$, O$_2$ and benzene, we illustrate how the angle-dependent ionization rate affects the photo-electron cutoff energy. We find alignment can enhance the high energy cutoff of the photo-electron spectrum when probing along a nodal plane or when ionization is otherwise suppressed. Thi...

  16. Femtosecond time-resolved molecular multiphoton ionization: the Na_2 system

    Baumert, Thomas,; Grosser, M.; Thalweiser, Rainer; Gerber, Gustav

    1991-01-01

    We report here the first experimental study of femtosecond time-resolved molecular multiphoton ionization. Femtosecond pump-probe techniques are combined with time-of-flight spectroscopy to measure transient ionization spectra of Na_2 in a molecular-beam experiment. The wave-packet motions in different molecular potentials show that incoherent contributions from direct photoionization of a singly excited state and from excitation and autoionization of a bound doubly excited molecu...

  17. The Application of Resonance-Enhanced Multiphoton Ionization Technique in Gas Chromatography Mass Spectrometry

    2014-01-01

    Gas chromatography resonance-enhanced multiphoton ionization time-of-flight mass spectrometry (GC/REMPI-TOFMS) using a nanosecond laser has been applied to analyze the 16 polycyclic aromatic hydrocarbons (PAHs). The excited-state lifetime, absorption characters, and energy of electronic states of the 16 PAHs were investigated to optimize the ionization yield. A river water sample pretreated by means of solid phase extraction was analyzed to evaluate the performance of the analytical instrumen...

  18. Studies of multiphoton ionization schemes for RIMS of La and Ba

    Multiphoton ionization (MPI) with tunable dye lasers has the potential to selectively ionize La in the presence of Ba and attain very high sensitivity. The objective of the work was to study MPI processes of Ba and La and select suitable schemes for selective ionization of La in the presence of Ba. The spectral region 520 to 610 nm was chosen because of reported strong radiative transitions in this region, and its applicability to high repetition rate Cu vapour lasers. (author)

  19. Time-resolved two-color photoacoustic and multiphoton ionization spectroscopy of aniline

    Moll, D. J.; G R Parker; Kuppermann, Aron

    1984-01-01

    The multiphoton ionization and photoacoustic signals from aniline have been detected as a function of time delay between two laser pulses of different wavelength. The first pulse excited the S0 → S1 0–0 transition. The second pulse either excited S1 to a higher singlet state, or a triplet state produced by intersystem crossing to a higher triplet state, depending on the time delay between pulses. Both ionization and dissociation processes are observed. By varying the conditions of excitation ...

  20. Multiphoton imaging to identify grana, stroma thylakoid, and starch inside an intact leaf

    Chen, Mei-Yu; Zhuo, Guan-Yu; Chen, Kuan-Chieh; Wu, Pei-Chun; Hsieh, Tsung-Yuan; Liu, Tzu-Ming; Chu, Shi-Wei

    2014-01-01

    Background Grana and starch are major functional structures for photosynthesis and energy storage of plant, respectively. Both exhibit highly ordered molecular structures and appear as micrometer-sized granules inside chloroplasts. In order to distinguish grana and starch, we used multiphoton microscopy, with simultaneous acquisition of two-photon fluorescence (2PF) and second harmonic generation (SHG) signals. SHG is sensitive to crystallized structures while 2PF selectively reveals the dist...

  1. Continuum generation in ultra high numerical aperture fiber with application to multiphoton microscopy

    Sayler, Nicholas

    Nonlinear microscopy benefits from broadband laser sources, enabling efficient excitation of an array of fluorophores, for example. This work demonstrates broadening of a narrow band input pulse (6 nm to 40 nm) centered at 1040 nm with excellent shot-to-shot stability. In a preliminary demonstration, multiphoton imaging with pulses from the fiber is performed. In particular second harmonic imaging of corn starch is performed.

  2. Resonantly enhanced multiphoton ionization and third-harmonic generation in krypton and xenon

    Multiphoton ionization (MPI) and third-harmonic generation (THG) in gaseous krypton and xenon have been studied using multiple laser photons resonant with numerous atomic energy levels of the target gas. The MPI and THG were studied concurrently in a high-pressure ionization cell with a vacuum ultraviolet (Vuv) radiation detector. Mass-resolved MPI and photoelectron spectra were recorded at low pressure (-4 torr) using the time-of-flight (TOF) mass spectrometer and double focusing spherical energy analyzer

  3. Study on multiphoton ionization dissociation processes of ethyl iodide at 800 nm laser radiation

    Multiphoton ionization-dissociation (MPID) process of ethyl iodide are studied at 800 nm femto-second laser, and time-of-flight mass spectrometer of ethyl iodide are obtained. The result of laser power index shows that the parent-ion mainly undergoes the 3 + 3 resonant enhanced multiphoton ionization (REMPI) process. The percentage of part fragment ions to the total ion current and the laser intensity dependence of the molecule are measured. Based on the experiment results, the multiphoton ionization- dissociation mechanism of ethyl iodide is discussed. The conclusion is that most of ion fragments are produced by C2H5I+ dissociation, this is consistent with the parent-ion dissociation staircase. The two possible dissociation channels of parent-ion are analyzed, but the C-I dissociation is the main channel. We also use Gaussian 03 calculated the energy change of the two channels with B3LYP/3-21G basis set, the theoretical results further demonstrated the experiment. (authors)

  4. Live-cell multiphoton fluorescence correlation spectroscopy with an improved large Stokes shift fluorescent protein

    Guan, Yinghua; Meurer, Matthias; Raghavan, Sarada; Rebane, Aleksander; Lindquist, Jake R.; Santos, Sofia; Kats, Ilia; Davidson, Michael W.; Mazitschek, Ralph; Hughes, Thomas E.; Drobizhev, Mikhail; Knop, Michael; Shah, Jagesh V.

    2015-01-01

    We report an improved variant of mKeima, a monomeric long Stokes shift red fluorescent protein, hmKeima8.5. The increased intracellular brightness and large Stokes shift (∼180 nm) make it an excellent partner with teal fluorescent protein (mTFP1) for multiphoton, multicolor applications. Excitation of this pair by a single multiphoton excitation wavelength (MPE, 850 nm) yields well-separable emission peaks (∼120-nm separation). Using this pair, we measure homo- and hetero-oligomerization interactions in living cells via multiphoton excitation fluorescence correlation spectroscopy (MPE-FCS). Using tandem dimer proteins and small-molecule inducible dimerization domains, we demonstrate robust and quantitative detection of intracellular protein–protein interactions. We also use MPE-FCCS to detect drug–protein interactions in the intracellular environment using a Coumarin 343 (C343)-conjugated drug and hmKeima8.5 as a fluorescence pair. The mTFP1/hmKeima8.5 and C343/hmKeima8.5 combinations, together with our calibration constructs, provide a practical and broadly applicable toolbox for the investigation of molecular interactions in the cytoplasm of living cells. PMID:25877871

  5. Multiphoton effects in laser-assisted ionization of a helium atom by electron impact

    The dynamics of the electron impact multiphoton ionization of a He atom in the presence of an intense laser field (nγe, 2e) is studied theoretically for laser polarization (||l) and perpendicular to the incident momentum. The triple differential (TDCS) as well as the double differential (DDCS) cross sections are studied for the coplanar asymmetric geometry. The results are compared with the only available kinematically complete experiment at high incident energy (1000 eV). Significant laser modification (enhancement) is noted due to multiphoton effects in the present binary and recoil peak intensities of the TDCS for both the geometries, in qualitative agreement with the experiment. In the single photon case, the net effect of the laser field is to suppress the field free (FF) TDCS as well as the DDCS in the zeroth order approximation of the ejected electron wave function (CV), while in the first order (MCV), the cross sections are found to be enhanced. The CV multiphoton cross sections obey the famous Kroll Watson (KW) sum rule while the latter does not hold good in the corresponding MCV approximation. (authors)

  6. Intrinsic indicator of photodamage during label-free multiphoton microscopy of cells and tissues.

    Roberta Galli

    Full Text Available Multiphoton imaging has evolved as an indispensable tool in cell biology and holds prospects for clinical applications. When addressing endogenous signals such as coherent anti-Stokes Raman scattering (CARS or second harmonic generation, it requires intense laser irradiation that may cause photodamage. We report that increasing endogenous fluorescence signal upon multiphoton imaging constitutes a marker of photodamage. The effect was studied on mouse brain in vivo and ex vivo, on ex vivo human brain tissue samples, as well as on glioblastoma cells in vitro, demonstrating that this phenomenon is common to a variety of different systems, both ex vivo and in vivo. CARS microscopy and vibrational spectroscopy were used to analyze the photodamage. The development of a standard easy-to-use model that employs rehydrated cryosections allowed the characterization of the irradiation-induced fluorescence and related it to nonlinear photodamage. In conclusion, the monitoring of endogenous two-photon excited fluorescence during label-free multiphoton microscopy enables to estimate damage thresholds ex vivo as well as detect photodamage during in vivo experiments.

  7. Real-time digital signal processing in multiphoton and time-resolved microscopy

    Wilson, Jesse W.; Warren, Warren S.; Fischer, Martin C.

    2016-03-01

    The use of multiphoton interactions in biological tissue for imaging contrast requires highly sensitive optical measurements. These often involve signal processing and filtering steps between the photodetector and the data acquisition device, such as photon counting and lock-in amplification. These steps can be implemented as real-time digital signal processing (DSP) elements on field-programmable gate array (FPGA) devices, an approach that affords much greater flexibility than commercial photon counting or lock-in devices. We will present progress toward developing two new FPGA-based DSP devices for multiphoton and time-resolved microscopy applications. The first is a high-speed multiharmonic lock-in amplifier for transient absorption microscopy, which is being developed for real-time analysis of the intensity-dependence of melanin, with applications in vivo and ex vivo (noninvasive histopathology of melanoma and pigmented lesions). The second device is a kHz lock-in amplifier running on a low cost (50-200) development platform. It is our hope that these FPGA-based DSP devices will enable new, high-speed, low-cost applications in multiphoton and time-resolved microscopy.

  8. 多焦点多光子显微技术及其研究进展%Multifocal Multiphoton Microscopy and Its Research Progress

    刘立新

    2011-01-01

    Multifocal multiphoton microscopy ( MMM) can greatly improve the utilization of the excitation light and imaging speed, and it can also acquire three-dimensional fluorescence microscopic images by multiphoton excitation with the advantages of high speed, reduced photobleaching and photodamage, enhanced penetration depth and high signal to noise ratio. The realization and research progresses of multifocal multiphoton microscopy are discussed in detail, which include simultaneous time- and spectrum-resolved multifocal multiphoton microscopy(STSR-MMM) , multifocal multiphoton microscopy based on time-correlated single photon counting( TCSPC-MMM ) , multifocal multiphoton microscopy using a field of view zoom scanning protocol and stochastic scanning multifocal multiphoton microscopy (SS-MMM) , etc.%多焦点多光子显微技术(multifocal multiphoton microscopy,MMM)提高了激发光能的利用率和成像速度,可以实现样品的三维快速多光子激发荧光显微成像,并具有对活体样品损伤小,成像深度大,图像信噪比高等优点.详细阐述了MMM的实现方法及其研究进展,包括同时时间和光谱分辨的MMM(simultaneous time- and spectrum-resolved multifocal multiphoton microscopy,STSR-MMM)、基于时间相关单光子计数技术的MMM( multifocal multiphoton microscopy based on time-correlated single photon counting,TCSPC-MMM)、基于随机扫描的MMM(stochastic scanning multifocal multiphoton microscopy,SS-MMM)、基于固定光路系统的变视场扫描的MMM等技术.

  9. Modified method for intravital-fluorescent microscopy for on-line measurement of vasomotion in cutaneous microcirculation of mice in vivo

    The purpose of this study was establishing of the suitable method for long term investigations of changes of the blood vessel diameter up to 60 min continuous measurements with the main aim to be detected possible changes in low frequency component of vasomotion at cutaneous microcirculation of mice in vivo without using anesthetized animals. For investigation of micro-circulatory changes of blood vessel diameter, it is necessary to be used as high as possible quality video images with high resolution (1591x1061 pixels) - at this time the best method for this purpose is intravital microscopy, with high magnification and high resolution this method allows to be observed blood vessels from 5 to 100 μm - and also to be determined blood vessel wall and surrounded blood vessel cells. In this investigation BALB/c mice were used, and a Dorsal Skin-fold Chamber (DSC), were surgically implanted 4 days before the experiment. Intravital video-microscopy measurements of vasomotion in vivo were realized by 3CCD-camera, SONY Inc. and Nikon Inc. microscopy system. Fluorescence signal from the blood vessel, were enhanced by using DVS-3000 system (Hamamatsu Inc.) Vasomotion or temporal changes of the blood vessel diameter was measured by High-speed Digital Machine Vision System CV-2100 (KEYENCE Inc.), using an edge-gap detection algorithm (with a sampling time 389 ms), for on-line calculating the outer diameter of the blood vessels by means of fluorescence-image visualization (with precision 0.5 μm), after caudal vein injection of (from 50h150 μl per 25g animal) Fluorescein Isothiocyanate (FITC)-labeled Dextrans from 60-250 kDa concentration 2.5% in PBS solution pH=7.5. First part of this study was set up the intensity of the fluorescence using different concentrations and molecular weight Dextrans for visualization of the blood plasma with enough high intensity and as low as possible effects on the blood viscosity. Set up of the edge finding algorithm from off-line calculations

  10. Book Act

    Kivland, Sharon

    2014-01-01

    Book Act was a new project by AMBruno, initiated by Sophie Loss, in which artist book-makers performed and embodied the concept or essence of their books through the medium of film or performance. The exhibition at The Tetley, Leeds, comprised the originating books and corresponding video work, with live performances on Sunday 9 March 2014. Book Act took place during the 17th International Contemporary Artists' Book Fair (7th to 9th March) and the exhibition continued until 26th March 2014.

  11. Novel techniques with multiphoton microscopy: Deep-brain imaging with microprisms, neurometabolism of epilepsy, and counterfeit paper money detection

    Chia, Thomas H.

    Multiphoton microscopy is a laser-scanning fluorescence imaging method with extraordinary potential. We describe three innovative multiphoton microscopy techniques across various disciplines. Traditional in vivo fluorescence microscopy of the mammalian brain has a limited penetration depth (counterfeit paper money because of its significant differences in fluorescence lifetime when compared to genuine paper money. We used scanning multiphoton laser excitation to sample a ˜4 mm2 region from 54 genuine Reserve Notes. Three types of counterfeit samples were tested. Four out of the nine counterfeit samples fit to a one-component decay. Five out of nine counterfeit samples fit to a two-component model, but are identified as counterfeit due to significant deviations in the longer lifetime component compared to genuine bills.

  12. Remote z-scanning with a macroscopic voice coil motor for fast 3D multiphoton laser scanning microscopy.

    Rupprecht, Peter; Prendergast, Andrew; Wyart, Claire; Friedrich, Rainer W

    2016-05-01

    There is a high demand for 3D multiphoton imaging in neuroscience and other fields but scanning in axial direction presents technical challenges. We developed a focusing technique based on a remote movable mirror that is conjugate to the specimen plane and translated by a voice coil motor. We constructed cost-effective z-scanning modules from off-the-shelf components that can be mounted onto standard multiphoton laser scanning microscopes to extend scan patterns from 2D to 3D. Systems were designed for large objectives and provide high resolution, high speed and a large z-scan range (>300 μm). We used these systems for 3D multiphoton calcium imaging in the adult zebrafish brain and measured odor-evoked activity patterns across >1500 neurons with single-neuron resolution and high signal-to-noise ratio. PMID:27231612

  13. Inhibition of Tumor Growth, Angiogenesis, and Microcirculation by the Novel Flk-1 Inhibitor SU5416 as Assessed by Intravital Multi-fluorescence Videomicroscopy

    Peter Vajkoczy

    1999-04-01

    Full Text Available Vascular endothelial growth factor (VEGF plays a fundamental role in mediating tumor angiogenesis and tumor growth. Here we investigate the direct effect of a novel small molecule inhibitor of the Flk-1-mediated signal transduction pathway of VEGF, SU5416, on tumor angiogenesis and microhemodynamics of an experimental glioblastoma by using intravital multifluorescence videomicroscopy. SU5416 treatment significantly suppressed tumor growth. In parallel, SU5416 demonstrated a potent antiangiogenic activity, resulting in a significant reduction of both the total and functional vascular density of the tumor microvasculature, which indicates an impaired vascularization as well as significant perfusion failure in treated tumors. This malperfusion was not compensated for by changes in vessel diameter or recruitment of nonperfused vessels. Analyses of the tumor microcirculation revealed significant microhemodynamic changes after angiogenesis blockage such as a higher red blood cell velocity and blood flow in remnant tumor vessels when compared with controls. Our results demonstrate that the novel antiangiogenic concept of targeting the tyrosine kinase of Flk-1/KDR by means of a small molecule inhibitor represents an efficient strategy to control growth and progression of angiogenesis-dependent tumors. This study provides insight into microvascular consequences of Flk-1/KDR targeting in vivo and may have important implications for the future treatment of angiogenesis-dependent neoplasms.

  14. Calculations of hydrogen atom multiphoton energy level shifts, transition amplitudes and ionization probabilities

    Analyses of the resonant multiphoton ionization of atoms require knowledge of ac Stark energy shifts and of multiphoton, bound-to-bound state, transition amplitudes. In this paper, we consider the three-photon photoionization of hydrogen atoms at frequencies that are at and surrounding the two-photon 1s to 2s resonance. AC energy shift sums of both the 1s and 2s states are calculated as a function of the laser frequency along with two-photon 1s → 2s resonant transition amplitude sums. These quantities are calculated using an extended version of a method, which has often been employed in a variety of ways, of calculating these sums by expressing them in terms of solutions to a variety of differential equations that are derived from the different sums being evaluated. We demonstrate how exact solutions are obtained to these differential equations, which lead to exact evaluations of the corresponding sums. A variety of different cases are analysed, some involving analytic continuation, some involving real number analysis and some involving complex number analysis. A dc Stark sum calculation of the 2s state is carried out to illustrate the case where analytic continuation, pole isolation and pole subtraction are required and where the calculation can be carried out analytically; the 2s state, ac Stark shift sum calculations involve a case where no analytic continuation is required, but where the solution to the differential equation produces complex numbers owing to the finite photoionization lifetime of the 2s state. Results from these calculations are then used to calculate three-photon ionization probabilities of relevance to an analysis of the multiphoton ionization data published by Kyrala and Nichols (1991 Phys. Rev. A 44, R1450)

  15. Wavelength-dependent collective effects in the multiphoton ionization of atomic deuterium

    This paper presents the results of an experimental investigation into collective effects in the transient plasma formed by multiphoton ionization of atomic deuterium with a pulsed laser. The laser wavelength is varied in a narrow range around 243 nm, so that the photoionization is resonant with the metastable 2S1/2 state. The ion yield, the ion time-of-flight spectra, and the yield of Lyman-α photons have been measured as a function of laser intensity (from 1 to 340 MW/cm2) and laser detuning around the 1S1/2-2S1/2 two-photon resonance. During and shortly after the laser pulse, collective effects resulting from the mutual interaction of the photoelectrons and the ions affect the spatial and temporal distribution of the ions. Because of the near-degeneracy of the 2S1/2, 2P1/2, and 2P3/2 states, the resonant multiphoton ionization is affected by the Stark mixing of these states in the collective field. As a result, the time-dependent yields of ions and of Lyman-α photons are modulated by the interplay of the multiphoton ionization of the atoms and the collective effects in the plasma. From the measurements it is deduced that collective effects are important above a critical charge density of 3x108 ions/cm3. An asymmetry is observed in the line profile of the total ion yield as a function of laser detuning. This asymmetry is interpreted to be due to the effect of the collective field upon the intermediate resonant 2S1/2 state of the photoionization process

  16. Multiphoton imaging of quantum dot bioconjugates in cultured cells following Nd:YLF laser excitation

    Serrano, Elba E.; Knight, V. B.

    2005-04-01

    Quantum dot bioconjugates offer unprecedented opportunities for monitoring biological processes and molecular interactions in cells, tissues, and organs. We are interested in developing applications that permit investigation of physiological processes and cytoskeletal organization in live cells, and allow imaging of complex organs, such as the auditory and vestibular sensory structures of the inner ear. Multiphoton microscopy is a powerful technique for acquiring images from deep within a sample while reducing phototoxic effects of laser light exposure on cells. Previous studies have established that a solid-state Nd:YLF laser can be used to acquire two-photon and three-photon images from live cells while minimizing phototoxic side effects (Wokosin et al., 1996, Bioimaging, 4:208-214; Squirrell et al., 1999, Nature Biotechnology, 8:763-767). We present here the results of experiments using an all-solid-state Nd:YLF 1047 nm femtosecond laser (Microlase DPM1000) source to excite quantum dot bioconjugates. Cells were labeled with Qdot (Quantum Dot Corporation) bioconjugates or with Alexa Fluor (Molecular Probes) bioconjugates and then imaged with a BioRad 1024 confocal microscope configured for multiphoton imaging using internal or external (non-descanned) detectors. Results demonstrate that the Nd:YLF laser can be used to stimulate fluorescence emission of quantum dots and Alexa Fluor bioconjugates in cultured amphibian (Xenopus) and mammalian (rat, chinese hamster) cells. We conclude that the Nd:YLF laser is a viable excitation source that extends the applicability of quantum dots for investigation of biological processes using multiphoton microscopy.

  17. Multiphoton ionization of a metastable hydrogen atom by electron and positron impact and charge asymmetry

    Charge asymmetry is studied theoretically for multiphoton ionization (nγ e±, e e±) of a hydrogen atom from its metastable (2S) state using coplanar geometry. The external laser field is chosen to be single-mode, spatially homogeneous, linearly polarized with laser intensity that is quite high by laboratory standards. The continuum states of the impinging electron (e) or positron (e+) are represented by plane wave Volkov states, while the wavefunctions for the ejected electron and the scattered electron/positron are chosen to be of Coulomb-Volkov type. The dressed wavefunction for the metastable (2S) hydrogen is constructed in the framework of degenerate perturbation theory. Charge asymmetry is noted in the triple differential cross sections (TDCS) of the two projectiles both in the field-free (FF) and laser-assisted situations. The positron binary peak intensity is much higher than that of the electron, while the reverse is true for the recoil peak. As for the laser modifications, the single-photon TDCS exhibits a distinct four lobed structure in contrast to the FF (two lobed) and is highly suppressed w.r.t. the latter, while the multiphoton TDCS usually tends to approach the FF (with some exceptions), obeying the famous Kroll-Watson (KW) sum rule for both projectiles. For e+ impact, the electron capture to the continuum (ECC) effect is also studied (for the symmetric geometry), where enhancement is noted in both the single and multiphoton ECC peaks thereby deviating from the KW sum rules.

  18. Design, Fabrication and Computational Characterization of a 3D Micro-Valve Built by Multi-Photon Polymerization

    Stratos Galanopoulos

    2014-08-01

    Full Text Available We report on the design, modeling and fabrication by multi-photon polymerization of a complex medical fluidic device. The physical dimensions of the built micro-valve prototype are compared to those of its computer-designed model. Important fabrication issues such as achieving high dimensional resolution and ability to control distortion due to shrinkage are presented and discussed. The operational performance of both multi-photon and CAD-created models under steady blood flow conditions was evaluated and compared through computational fluid dynamics analysis.

  19. Resonant multiphoton ionization of the 1s state of a hydrogen atom in a strong laser field

    The process of resonant multiphoton ionization of hydrogen atom in the main state 1s is studied by the method of direct numerical integration of the Schroedinger nonstationary equation for quantum system in the field of an electromagnetic wave. A nonmonotonous dependence of photoionization probability on radiation intensity is found. It is ascertained that multiphoton resonances between the main and one of excited (Rydberg) atomic states induced by laser radiation field correspond to ionization minima. It is shown that ionization suppression occurs as a result of the Rydberg states restructuring in a strong field, being accompanied by effective Raman transitions binding the totality of the close-by Rydberg states

  20. Waveguide-integrated single- and multi-photon detection at telecom wavelengths using superconducting nanowires

    Ferrari, Simone; Kahl, Oliver [Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe 76132 (Germany); Kovalyuk, Vadim [Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe 76132 (Germany); Department of Physics, Moscow State Pedagogical University, Moscow 119992 (Russian Federation); Goltsman, Gregory N. [Department of Physics, Moscow State Pedagogical University, Moscow 119992 (Russian Federation); National Research University Higher School of Economics, 20 Myasnitskaya Ulitsa, Moscow 101000 (Russian Federation); Korneev, Alexander [Department of Physics, Moscow State Pedagogical University, Moscow 119992 (Russian Federation); Moscow Institute of Physics and Technology (State University), Moscow 141700 (Russian Federation); Pernice, Wolfram H. P., E-mail: wolfram.pernice@kit.edu [Institute of Nanotechnology, Karlsruhe Institute of Technology, Karlsruhe 76132 (Germany); Department of Physics, University of Münster, 48149 Münster (Germany)

    2015-04-13

    We investigate single- and multi-photon detection regimes of superconducting nanowire detectors embedded in silicon nitride nanophotonic circuits. At near-infrared wavelengths, simultaneous detection of up to three photons is observed for 120 nm wide nanowires biased far from the critical current, while narrow nanowires below 100 nm provide efficient single photon detection. A theoretical model is proposed to determine the different detection regimes and to calculate the corresponding internal quantum efficiency. The predicted saturation of the internal quantum efficiency in the single photon regime agrees well with plateau behavior observed at high bias currents.

  1. Ionisation of hydrogen-like atoms by a multiphoton absorption process

    The general expression for the amplitude of the probability of ionisation by a multiphoton absorption process is derived. Its non-relativistic limit is taken and the bipolar approximation is used for calculating the ionisation cross-section of hydrogen-like atoms. This latter involves the summation over intermediate virtual states by means of: a) a recursion relationship concerning angular functions, b) a particular technique which when applied to radial functions makes it possible to solve a system of inhomogeneous first-order differential equations. (authors)

  2. Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy

    Vinegoni, C; Luo, W; Marks, D L; Ralston, T; Tan, W

    2005-01-01

    An integrated microscope that combines different optical techniques for simultaneous imaging is demonstrated. The microscope enables spectral-domain optical coherence microscopy based on optical backscatter, and multi-photon microscopy for the detection of two-photon fluorescence and second harmonic generation signals. The unique configuration of this integrated microscope allows for the simultaneous acquisition of both anatomical (structural) and functional imaging information with particular emphasis for applications in the fields of tissue engineering and cell biology. In addition, the contemporary analysis of the spectroscopic features can enhance contrast by differentiating among different tissue components.

  3. Multiphoton ionization/dissociation of cyclopentanone at the lower Rydberg states

    The 2-photon excitation of the 3p and 3d Rydberg states in jet-cooled cyclopentanone has been investigated by resonance enhanced multiphoton ionization (REMPI) in a time of flight mass spectrometer. The three 3px,y,z components are clearly resolved while the case for the 3di excitations is obscure due to the S1 one-photon resonance. The ns laser induced mass spectra are characteristic of hard ionization while the fs laser induced mass spectrum is very similar to the Electron Impact one

  4. Multiphoton ionization/dissociation of cyclopentanone at the lower Rydberg states

    Philis, John G.; Kosmidis, Constantine; Tzallas, Paraskevas

    1998-12-01

    The 2-photon excitation of the 3p and 3d Rydberg states in jet-cooled cyclopentanone has been investigated by resonance enhanced multiphoton ionization (REMPI) in a time of flight mass spectrometer. The three 3px,y,z components are clearly resolved while the case for the 3di excitations is obscure due to the S1 one-photon resonance. The ns laser induced mass spectra are characteristic of hard ionization while the fs laser induced mass spectrum is very similar to the Electron Impact one.

  5. In vivo stepwise multi-photon activation fluorescence imaging of melanin in human skin

    Lai, Zhenhua; Gu, Zetong; Abbas, Saleh; Lowe, Jared; Sierra, Heidy; Rajadhyaksha, Milind; DiMarzio, Charles

    2014-03-01

    The stepwise multi-photon activated fluorescence (SMPAF) of melanin is a low cost and reliable method of detecting melanin because the activation and excitation can be a continuous-wave (CW) mode near infrared (NIR) laser. Our previous work has demonstrated the melanin SMPAF images in sepia melanin, mouse hair, and mouse skin. In this study, we show the feasibility of using SMPAF to detect melanin in vivo. in vivo melanin SMPAF images of normal skin and benign nevus are demonstrated. SMPAF images add specificity for melanin detection than MPFM images and CRM images. Melanin SMPAF is a promising technology to enable early detection of melanoma for dermatologists.

  6. Spin-statistic selection rules for multiphoton transitions: Application to helium atoms

    Zalialiutdinov, T.; Solovyev, D.; Labzowsky, L.; Plunien, G.

    2016-01-01

    A theoretical investigation of the three-photon transition rates 2 1P1→2 1S0,1 1S0 and 2 3P2→2 1S0,1 1S0 for the helium atom is presented. Photon energy distributions and precise values of the nonrelativistic transition rates are obtained with employment of correlated wave functions of the Hylleraas type. The possible experiments for the tests of the Bose-Einstein statistics for multiphoton systems are discussed.

  7. Spin-Statistic Selection Rules for Multiphoton Transitions: Application to Helium Atom

    Zalialiutdinov, T; Labzowsky, L; Plunien, G

    2016-01-01

    A theoretical investigation of the three-photon transition rates $ 2^1P_1\\rightarrow 2^1S_0\\;,1^1S_0 $ and $ 2^3P_2\\rightarrow 2^1S_0\\;,1^1S_0 $ for the helium atom is presented. Photon energy distributions and precise values of the nonrelativistic transition rates are obtained with employment of correlated wave functions of the Hylleraas type. The possible experiments for the tests of the Bose-Einstein statistics for multiphoton systems are discussed.

  8. Single ionization of atoms in intense laser pulses: Evolution from multiphoton to tunnel ionization

    Rudenko, A.; Zrost, K.; Ergler, T.; Feuerstein, B.; de Jesus, V.; Schröter, C; Moshammer, R.; Ullrich, J.

    2005-01-01

    We present results of high resolution fully differential measurements on single ionization of He, Ne, and Ar by 7-25 fs linearly polarized 800nm laser pulses at intensities of up to 2.1015 W/cm2. Using a 'Reaction-Microscope' we were able to trace signatures of multiphoton ionization deep into the tunnelling regime. Surprisingly, in the low-energy electron spectra we observed several features (absence of the ponderomotive shifts, splitting of the peaks, their degeneration for few-cycle laser ...

  9. Optical-optical double-resonant multiphoton ionization spectra of Rydberg states of nitrogen dioxide

    Zhang Gui-Yin; Zhang Lian-Shui; Sun Bo; Han Xiao-Feng; Yu Wei

    2005-01-01

    The optical-optical double-resonant multiphoton ionization(OODR-MPI) technique has been applied to the study of the Rydberg states of nitrogen dioxide. The results show that ,althougy the OODR-MPI spectra of NO2 are composed of regular progression bands at different pump laser intensities, their ionization pathways are different.The NO2 mollecule is ionized through the (3+1+1)double-resonant process as the pump laser intensity is in a high value, or else it is through the (1+2+1)rpocess.The final resonant states in the two ionizing processes have been attributed to different Rydberg states.

  10. Spin-Other-Orbit Effect in Two-Mode Multiphoton Ionization

    李晓峰; 高靓辉; 王兵兵; 傅盘铭; D. S. Guo; R. R. Freeman

    2002-01-01

    A previously unknown "spin-other-orbit" effect of photon modes is predicted by solving a Schrodinger-like equation for a non-relativistic electron interacting with a two-mode intense photon field propagating in two perpendicular directions. A multiphoton ionization experiment to test this effect is suggested. Transition rates which manifest this effect to be measured in the experiment are calculated and presented graphically. A detailed comparison between this effect and the well-known spin-other-orbit effect of electrons is included.

  11. Compressor optimization with compressor-based multiphoton intrapulse interference phase scan (MIIPS).

    Hou, B; Easter, J H; Nees, J A; He, Z; Thomas, A G R; Krushelnick, K

    2012-04-15

    The multiphoton intrapulse interference phase scan (MIIPS) technique is modified to optimize the compressor settings of a chirped pulse amplification (CPA) laser system. Here, we use the compressor itself to perform the phase scan inherent in MIIPS measurement . A frequency-resolved optical gating measurement shows that the pulse duration of the compressor optimized using the modified MIIPS technique is 33.8 fs with a 2.24 rad temporal phase variation above 2% intensity. The measured time-bandwidth product is 0.60, which is close to that of transform-limited Gaussian pulse (0.44). PMID:22513694

  12. Multiphoton resonant ionization of hydrogen atom exposed to two-colour laser pulses

    Wang Pei-Jie; Fang Yan

    2008-01-01

    This paper studies the multiphoton resonant ionization by two-colour laser pulses in the hydrogen atom by solving the time-dependent Schr(o)dinger equation.By fixing the parameters of fundamental laser field and scanning the frequency of second laser field,it finds that the ionization probability shows several resonance peaks and is also much larger than the linear superposition of probabilities by applying two lasers separately.The enhancement of the ionization happens when the system is resonantly pumped to the excited states by absorbing two or more colour photons non-sequentially.

  13. Multiphoton Ionization of Formaldehyde: Observation of 3py and 3pz Rydberg States

    Bomse, D. S.; Dougal, S.

    1987-01-01

    Multiphoton ionization (MPI) of CH2O and CD2O is reported for dye laser wavelengths between 445 and 470 nm. The ionization pathway starts with three-photon resonant absorption to 3py and 3pz Rydberg states. One or two additional photons are required, depending on wavelength, to reach threshold. MPI spectra agree well with VUV absorption measurements of the same Rydberg levels. MPI yields are small and photoacoustic measurements imply the initial three-photon excitation has low probability. Tr...

  14. A NEW TECHNIQUE TO STUDY RYDBERG STATES BY MULTIPHOTON IONIZATION SPECTROSCOPY

    Verma, R.; Chanda, A.

    1987-01-01

    A new technique to study the Rydberg states of the Ba atom has been developed. In this technique a Multiphoton Ionization signal is detected by selective excitation of the ground state ion (6s) to an excited state (6p), which results in a collimated Amplified Spontaneous Emission (ASE) signal at the 6p→5d transition of Ba*. Discrete Rydberg states, 6snℓ (ℓ=0,2), as well as autoionizing Rydberg states, 5dnℓ (ℓ=0,2) and 6pnℓ (ℓ=0,2) are observed by this novel but very simple method.

  15. Resonantly Enhanced Multi-Photon Ionization Spectrum of the Neutral Green Fluorescent Protein Chromophore

    greenwood, jason; Miles, Jordan; De Camillis, Simone; Mulholland, Peter; Zhang, Lijuan; Parkes, Michael A.; Hailes, Helen C.; Fielding, Helen H.

    2014-01-01

    The photophysics of the green fluorescent protein is governed by the electronic structure of the chromophore at the heart of its β-barrel protein structure. We present the first two-color, resonance-enhanced, multiphoton ionization spectrum of the isolated neutral chromophore in vacuo with supporting electronic structure calculations. We find the absorption maximum to be 3.65 ± 0.05 eV (340 ± 5 nm), which is blue-shifted by 0.5 eV (55 nm) from the absorption maximum of the protein in its neut...

  16. Intense-field multiphoton ionization of a two-electron atom

    Multiphoton ionization of helium at high laser intensities has been investigated by direct numerical integration of the full time-dependent two-electron Schrodinger equation on a Cray T3D. At field intensities above 4 x 1014 W cm-2, two-photon ionization occurs in a few field periods, and double ionization and high harmonic generation are prominent. We present calculations of double ionization yields, investigate the sensitivity of double ionization to the electron-electron electrostatic repulsion, and present evidence of unexpected non-exponential behaviour in ionization decay rates. (Author)

  17. Two-Electron Effects in the Multiphoton Ionization of Magnesium with 400 nm 150 fs Pulses

    Xenakis, D; Karapanagioti, N. E.; Charalambidis, D.; Bachau, H.; Cormier, E

    1999-01-01

    The multiphoton ionization and photoelectron spectra of magnesium were studied at laser intensities of up to 6x10^{13} Wcm^{-2} using 150 fs laser pulses of a wavelength of 400 nm. The results indicated that a variety of different ionization mechanisms played a role in both types of spectra. A theoretical model describing the processes is presented and the routes to ionization are identified. The work demonstrates the significance of the two-electron nature of the atom in interpreting the exp...

  18. Multiphoton ionization through the triplet states of Mg by linearly and circularly polarized laser pulses

    Buica, Gabriela; 10.1103/PhysRevA.79.013419

    2013-01-01

    We theoretically study multiphoton ionization through the triplet states of Mg by linearly polarized (LP) and circularly polarized (CP) fs laser pulses. After the construction of the atomic basis using the frozen-core Hartree-Fock potential (FCHFP) as well as the model potential (MP) approaches for both singlet and triplet series which show rather good agreements with the existing data in terms of state energies and dipole matrix elements, we solve time-dependent Schr\\"{o}dinger equations with $3s3p$ $^{3}P_{1}$ as an initial state, and calculate the total ionization yield and photoelectron energy spectra (PES).

  19. The Effect of the Argon Carrier Gas in the Multiphoton Dissociation-Ionization of Tetracene

    Carmen Cisneros; Ignacio ÃÂlvarez; Alfonso Guerrero; Alejandro San Román; Juan Carlos Poveda

    2008-01-01

    The multiphoton dissociation-ionization of tetracene at 355 nm using 6.5 nanosecond laser pulses, with and without argon as a carrier gas (CG), has been studied and compared. Ion fragments were analyzed in a time-of-flight mass spectrometer and separated according to their mass-to-charge ratio (m/z). The results show that the dynamic of photodissociation at ~1010 W⋅cm-2 intensities is strongly influenced by the CG. The suppression of fragmentation channels primarily those relating to the...

  20. Multiphoton resonant ionization of hydrogen atom exposed to two-colour laser pulses

    This paper studies the multiphoton resonant ionization by two-colour laser pulses in the hydrogen atom by solving the time-dependent Schrodinger equation. By fixing the parameters of fundamental laser field and scanning the frequency of second laser field, it finds that the ionization probability shows several resonance peaks and is also much larger than the linear superposition of probabilities by applying two lasers separately. The enhancement of the ionization happens when the system is resonantly pumped to the excited states by absorbing two or more colour photons non-sequentially. (atomic and molecular physics)

  1. Electron spectroscopy study of single and double multiphoton ionization of strontium by visible picosecond laser light

    Petite, G.; Agostini, P.

    1986-01-01

    Multiphoton single and double ionization of strontium was studied using electron spectroscopy techniques. Both a picosecond, frequency doubled Nd : Yag Laser and a picosecond rhodamine 6G Dye Laser were used, with intensities ranging from 1011 W . cm- 2 to a few 10 12 W . cm-2. Single MPI was shown to produce ions in both the ground state (3 photon) and several low lying excited states, through a four photon process. Two and three photon resonances were observed, on singly and doubly excited ...

  2. New electronic states of NH and ND observed by resonance enhanced multiphoton ionization spectroscopy

    Johnson, Russell D., III; Hudgens, Jeffrey W.

    1990-01-01

    Resonance Enhanced MultiPhoton Ionization (REMPI) spectra of NH and ND, which reveal four new electronic states are presented. Transitions from NH a 1 delta to 3s and 3p Rydberg states in both NH and ND have been observed and rotationally analyzed. The transitions were observed in the wavelength range of 258 to 288 nm. The state assignments are: e 1 pi (3s sigma) at 82857/cm, f 1 pi (3p sigma) at 86378/cm, g 1 delta (3p pi) at 88141/cm and h 1 sigma (3p pi) at 89151/cm.

  3. Signatures of tunneling and multiphoton ionization by short-laser pulses: The partial-wave distribution

    Arbó, Diego G.; Lemell, Christoph; Burgdörfer, Joachim

    2015-09-01

    We analyze the two-dimensional angular momentum-energy distribution of electrons emitted from argon by short laser pulses. We identify characteristic features of both multiphoton and tunneling ionization in the partial-wave distribution for Keldysh parameters close to unity. We observe a remarkable degree of quantum-classical correspondence in the photoinization process which becomes even more pronounced after intensity averaging over the focal volume. We derive an energy-dependent cut-off for the highest angular momentum accessible within the framework of the strong-field approximation, which accurately reproduces the partial wave distributions found from solutions of the time-dependent Schrödinger equation.

  4. Multiphoton imaging to distinguish grana and starch inside an intact leaf

    Chen, Mei-Yu; Zhuo, Guan-Yu; Chen, Po-Fu; Wu, Pei-Chun; Liu, Tzu-Ming; Chu, Shi-Wei

    2013-02-01

    We have demonstrated a straightforward and noninvasive method to identify the distribution of grana and starch within an intact leaf. Grana and starch are the major functional structures for photosynthesis and energy storage of plant, respectively. Both exhibit highly ordered molecular structures and appear as micrometer-sized granules inside chloroplasts. In order to distinguish grana and starch, we used multiphoton microscopy, with simultaneous acquisition of two photon fluorescence (2PF) and second harmonic generation (SHG) signals. Consequently, SHG is found on both grana and starch while 2PF from chlorophyll indicates the identity of grana.

  5. Multiphoton Ionization of Xenon at the LCLS Free-Electron Laser

    Rudek, B.; Rolles, D.; Rudenko, A.; Epp, S.; Foucar, L.; Erk, B.; R. Hartmann; Kimmel, N; Holl, P.; Reich, C.; Strüder, L.; Hirsemann, H.; Ueda, K.; Simon, M.; Berrah, N.

    2012-01-01

    With the first X-ray free-electron laser (FEL), the Linac Coherent Light Source (LCLS), multiphoton ionization has been pushed to a new regime, where atoms and molecules are not just ionized by a series of valence ionizations but "from the inside out". At unprecedented high intensities and short pulse durations in the soft X-ray regime, a series of inner-shell photoionizations followed by cascades of Auger decays was observed to lead to highly charged final states in rare gases such as Ne, Ar...

  6. Waveguide-integrated single- and multi-photon detection at telecom wavelengths using superconducting nanowires

    We investigate single- and multi-photon detection regimes of superconducting nanowire detectors embedded in silicon nitride nanophotonic circuits. At near-infrared wavelengths, simultaneous detection of up to three photons is observed for 120 nm wide nanowires biased far from the critical current, while narrow nanowires below 100 nm provide efficient single photon detection. A theoretical model is proposed to determine the different detection regimes and to calculate the corresponding internal quantum efficiency. The predicted saturation of the internal quantum efficiency in the single photon regime agrees well with plateau behavior observed at high bias currents

  7. Direct detection of atomic ions from molecular photofragmentation during nonresonant multiphoton ionization of sputtered species

    The photoionization of sputtered Cu, Al, and Ru atoms and dimers was investigated by measuring velocity distributions using both resonant and nonresonant photoionization. Nonresonant ionization produced an atomic distribution that peaked at the same velocity as the respective dimer distribution, indicating that virtually all the nonresonant atomic ion signal is from photofragmented dimers. Various mechanisms of dimer photofragmentation are discussed. Domination of the atomic photoion channel by molecule fragmentation appears to be a general phenomenon that must be accounted for in all gas-phase multiphoton nonresonant ionization experiments at easily achievable laser power densities (≤ 109 W/cm2)

  8. 3D super-resolved in vitro multiphoton microscopy by saturation of excitation

    Nguyen, Anh Dung; Bouwens, Arno; Vanholsbeeck, Frédérique; Egrise, Dominique; Van Simayes, Gaetan; Emplit, Philippe; Goldman, Serge; Gorza, Simon-Pierre

    2015-01-01

    We demonstrate a significant resolution enhancement beyond the conventional limit in multiphoton microscopy (MPM) using saturated excitation of fluorescence. Our technique achieves super-resolved imaging by temporally modulating the excitation laser-intensity and demodulating the higher harmonics from the saturated fluorescence signal. The improvement of the lateral and axial resolutions is measured on a sample of fluorescent microspheres. While the third harmonic already provides an enhanced resolution, we show that a further improvement can be obtained with an appropriate linear combination of the demodulated harmonics. Finally, we present in vitro imaging of fluorescent microspheres incorporated in HeLa cells to show that this technique performs well in biological samples.

  9. Preparation of multi-photon Fock states and quantum entanglement properties in circuit QED

    We demonstrate the controllable generation of multi-photon Fock states in circuit quantum electrodynamics (circuit QED). The external bias flux regulated by a counter can effectively adjust the bias time on each superconducting flux qubit so that each flux qubit can pass in turn through the circuit cavity and thereby avoid the effect of decoherence. We further investigate the quantum correlation dynamics of coupling superconducting qubits in a Fock state. The results reveal that the lower the photon number of the light field in the number state, the stronger the interaction between qubits is, then the more beneficial to maintaining entanglement between qubits it will be. (general)

  10. Imaging NO elimination in the infrared multiphoton dissociation of nitroalkanes and alkyl nitrites

    Fernando, Ravin; Ariyasingha, Nuwandi M.; Suits, Arthur G.

    2016-02-01

    We present a DC slice imaging study of the decomposition of C2, C3 and C4 nitroalkanes and alkyl nitrites, focusing on the NO elimination channel, possibly a minor pathway. Infrared multiphoton dissociation (IRMPD) is used to induce dissociation on the ground electronic state under collisionless conditions. The channels that produced NO as a product were studied and compared among the target molecules to gain a better understanding of the isomerization of the nitroalkanes prior to dissociation. Trends in the total translational energy and NO rotational temperatures obtained from the images are discussed.

  11. Deep Inner-Shell Multiphoton Ionization by Intense X-Ray Free-Electron Laser Pulses

    Fukuzawa, H; Son, S.-K.; Kimura, M; Sakai, T; Matsunami, K; Hayashita, H.; Kajikawa, J.; Johnsson, P.; Siano, M.; Kukk, E.; Rudek, B.; Erk, B.; Motomura, K.; Foucar, L.; Robert, E.

    2013-01-01

    We have investigated multiphoton multiple ionization dynamics of argon and xenon atoms using a new x-ray free electron laser (XFEL) facility, SPring-8 Angstrom Compact free electron LAser (SACLA) in Japan, and identified that highly charged Xe ions with the charge state up to +26 are produced predominantly via four-photon absorption as well as highly charged Ar ions with the charge state up to +10 are produced via two-photon absorption at a photon energy of 5.5 keV. The absolute fluence of th...

  12. Relationship between resolution enhancement and multiphoton absorption rate in quantum lithography

    Tsang, Mankei

    2007-01-01

    The proposal of quantum lithography [Boto et al., Phys. Rev. Lett. 85, 2733 (2000)] is studied via a rigorous formalism. It is shown that, contrary to Boto et al.'s heuristic claim, the multiphoton absorption rate of a (|N,0>+|0,N>) quantum state is actually lower than that of a classical state with otherwise identical parameters. The proof-of-concept experiment of quantum lithography [D'Angelo et al., Phys. Rev. Lett. 87, 013602 (2001)] is also analyzed in terms of the proposed formalism, an...

  13. Multi-Photon Quantum Key Distribution Based on Double-Lock Encryption

    Chan, Kam Wai Clifford; Rifai, Mayssaa El; Verma, Pramode K.; Kak, Subhash; Chen, Yuhua

    2015-01-01

    This paper presents a multi-stage, multi-photon quantum key distribution protocol based on the double-lock cryptography. It exploits the asymmetry in the detection strategies between the legitimate users and the eavesdropper. The security analysis of the protocol is presented with coherent states under the intercept-resend attack, the photon number splitting attack, and the man-in-the-middle attack. It is found that the mean photon number can be much larger than one. This complements the rece...

  14. Histology in vivo: chemical contrast combined with clinical multimodal multiphoton tomography

    Weinigel, Martin; Breunig, Hans Georg; Koenig, Karsten

    2015-03-01

    Label-free multiphoton tomography based on two-photon autofluorescence, fluorescence lifetime, and second harmonic generation imaging can be supplemented by coherent anti-Stokes Raman scattering. We present a compact, mobile and flexible clinical tomograph equipped with a novel detector design with multiple miniaturized detectors for individual acquisition of all four contrast mechanisms. Imaging of endogenous fluorophores, SHG-active collagen as well as nonfluorescent lipids in human skin in vivo is possible with this clinical tomograph paving the way towards in vivo histology.

  15. Multiphoton ionisation and dissociation of NO 2 by 50 fs laser pulses

    Singhal, R. P.; Kilic, H. S.; Ledingham, K. W. D.; Kosmidis, C.; McCanny, T.; Langley, A. J.; Shaikh, W.

    1996-04-01

    Multiphoton ionisation and dissociation of NO 2 has been studied experimentally at 375 nm for laser pulse widths of 10 ns and 50 fs. The parent NO 2 ion peak is not seen in the ns data. In all spectra, the main peak observed is due to the ionisation of the NO molecule which results from the dissociation of excited NO 2 formed after absorbing a 375 nm photon. The intensity dependencies of both NO and NO 2 ion peaks have also been measured. The data has been analysed within the context of a rate equation model using published cross-sections and dissociation rates except for the two-photon ionisation cross-section for NO 2 which was chosen to reproduce the NO 2/NO ion signal ratios at 50 fs. The rate equation model provides a good description of the complete set of data. Indirectly, it may be concluded that coherence effects do not play an important role in the multiphoton excitation/ionisation of NO 2. The data also rules out the importance of above-ionisation dissociation in NO 2 — a conclusion which is consistent with previous data at 496 and 248 nm for laser pulse widths ⩾ 300 fs.

  16. Stepwise multiphoton activation fluorescence reveals a new method of melanin detection

    Lai, Zhenhua; Kerimo, Josef; Mega, Yair; DiMarzio, Charles A.

    2013-06-01

    The stepwise multiphoton activated fluorescence (SMPAF) of melanin, activated by a continuous-wave mode near infrared (NIR) laser, reveals a broad spectrum extending from the visible spectra to the NIR and has potential application for a low-cost, reliable method of detecting melanin. SMPAF images of melanin in mouse hair and skin are compared with conventional multiphoton fluorescence microscopy and confocal reflectance microscopy (CRM). By combining CRM with SMPAF, we can locate melanin reliably. However, we have the added benefit of eliminating background interference from other components inside mouse hair and skin. The melanin SMPAF signal from the mouse hair is a mixture of a two-photon process and a third-order process. The melanin SMPAF emission spectrum is activated by a 1505.9-nm laser light, and the resulting spectrum has a peak at 960 nm. The discovery of the emission peak may lead to a more energy-efficient method of background-free melanin detection with less photo-bleaching.

  17. Secure satellite communication using multi-photon tolerant quantum communication protocol

    Darunkar, Bhagyashri; Punekar, Nikhil; Verma, Pramode K.

    2015-09-01

    This paper proposes and analyzes the potential of a multi-photon tolerant quantum communication protocol to secure satellite communication. For securing satellite communication, quantum cryptography is the only known unconditionally secure method. A number of recent experiments have shown feasibility of satellite-aided global quantum key distribution (QKD) using different methods such as: Use of entangled photon pairs, decoy state methods, and entanglement swapping. The use of single photon in these methods restricts the distance and speed over which quantum cryptography can be applied. Contemporary quantum cryptography protocols like the BB84 and its variants suffer from the limitation of reaching the distances of only Low Earth Orbit (LEO) at the data rates of few kilobits per second. This makes it impossible to develop a general satellite-based secure global communication network using the existing protocols. The method proposed in this paper allows secure communication at the heights of the Medium Earth Orbit (MEO) and Geosynchronous Earth Orbit (GEO) satellites. The benefits of the proposed method are two-fold: First it enables the realization of a secure global communication network based on satellites and second it provides unconditional security for satellite networks at GEO heights. The multi-photon approach discussed in this paper ameliorates the distance and speed issues associated with quantum cryptography through the use of contemporary laser communication (lasercom) devices. This approach can be seen as a step ahead towards global quantum communication.

  18. Role of quantum trajectory in high-order harmonic generation in the Keldysh multiphoton regime.

    Li, Peng-Cheng; Jiao, Yuan-Xiang; Zhou, Xiao-Xin; Chu, Shih-I

    2016-06-27

    We present a systematic study of spectral and temporal structure of high-order harmonic generation (HHG) by solving accurately the time-dependent Schrödinger equation for a hydrogen atom in the multiphoton regime where the Keldysh parameter is greater unity. Combining with a time-frequency transform and an extended semiclassical analysis, we explore the role of quantum trajectory in HHG. We find that the time-frequency spectra of the HHG plateau near cutoff exhibit a decrease in intensity associated with the short- and long-trajectories when the ionization process is pushed from the multiphoton regime into the tunneling regime. This implies that the harmonic emission spectra in the region of the HHG plateau near and before the cutoff are suppressed. To see the generality of this prediction, we also present a time-dependent density-functional theoretical study of the effect of correlated multi-electron responses on the spectral and temporal structure of the HHG plateau of the Ar atom. PMID:27410589

  19. Femtosecond Laser-Induced Upconversion Luminescence in Rare-Earth Ions by Nonresonant Multiphoton Absorption.

    Yao, Yunhua; Xu, Cheng; Zheng, Ye; Yang, Chengshuai; Liu, Pei; Jia, Tianqing; Qiu, Jianrong; Sun, Zhenrong; Zhang, Shian

    2016-07-21

    The upconversion luminescence of rare-earth ions has attracted considerable interest because of its important applications in photoelectric conversion, color display, laser device, multiplexed biolabeling, and security printing. Previous studies mainly explored the upconversion luminescence generation through excited state absorption, energy transfer upconversion, and photon avalanche under the continuous wave laser excitation. Here, we focus on the upconversion luminescence generation through a nonresonant multiphoton absorption by using the intense femtosecond pulsed laser excitation and study the upconversion luminescence intensity control by varying the femtosecond laser phase and polarization. We show that the upconversion luminescence of rare-earth ions under the intense femtosecond laser field excitation is easy to be obtained due to the nonresonant multiphoton absorption through the nonlinear interaction between light and matter, which is not available by the continuous wave laser excitation in previous works. We also show that the upconversion luminescence intensity can be effectively controlled by varying the femtosecond pulsed laser phase and polarization, which can open a new technological opportunity to generate and control the upconversion luminescence of rare-earth ions and also can be further extended to the relevant application areas. PMID:27367751

  20. Multiphoton photochemistry of red fluorescent proteins in solution and live cells.

    Drobizhev, Mikhail; Stoltzfus, Caleb; Topol, Igor; Collins, Jack; Wicks, Geoffrey; Mikhaylov, Alexander; Barnett, Lauren; Hughes, Thomas E; Rebane, Aleksander

    2014-08-01

    Genetically encoded fluorescent proteins (FPs), and biosensors based on them, provide new insights into how living cells and tissues function. Ultimately, the goal of the bioimaging community is to use these probes deep in tissues and even in entire organisms, and this will require two-photon laser scanning microscopy (TPLSM), with its greater tissue penetration, lower autofluorescence background, and minimum photodamage in the out-of-focus volume. However, the extremely high instantaneous light intensities of femtosecond pulses in the focal volume dramatically increase the probability of further stepwise resonant photon absorption, leading to highly excited, ionizable and reactive states, often resulting in fast bleaching of fluorescent proteins in TPLSM. Here, we show that the femtosecond multiphoton excitation of red FPs (DsRed2 and mFruits), both in solution and live cells, results in a chain of consecutive, partially reversible reactions, with individual rates driven by a high-order (3-5 photon) absorption. The first step of this process corresponds to a three- (DsRed2) or four-photon (mFruits) induced fast isomerization of the chromophore, yielding intermediate fluorescent forms, which then subsequently transform into nonfluorescent products. Our experimental data and model calculations are consistent with a mechanism in which ultrafast electron transfer from the chromophore to a neighboring positively charged amino acid residue triggers the first step of multiphoton chromophore transformations in DsRed2 and mFruits, consisting of decarboxylation of a nearby deprotonated glutamic acid residue. PMID:25004113

  1. Evidence for excitation of fluorescence in RPE melanin by multiphoton absorption

    Glickman, Randolph D.; Rockwell, Benjamin A.; Noojin, Gary D.; Stolarski, David J.; Denton, Michael L.

    2002-06-01

    Previously, we reported that ultrashort, near infrared (NIR) laser pulses caused more DNA breakage in cultured retinal pigment epithelial (RPE) cells than did CW, NIR laser radiation delivering a similar radiant exposure. We hypothesized that this difference was due to multiphoton absorption in an intracellular chromophore such as the RPE melanin. We investigated two-photon excitation of fluorescence in a suspension of isolated bovine RPE melanosomes exposed to a 1-KHz train of approximately 50- fsec laser pulses at 810 nm from a Ti:Sapphire laser, and compared this to the fluorescence excited by CW exposures at 406 nm from a Krypton ion laser. Fluorescence was measured with a PC-based spectrometer. The CW sources excited fluorescence with a peak at 525 nm. The fluorescence intensity depended on the irradiance of the sample, as well as the melanosome concentration. Peak fluorescence was obtained with a suspension of ~2 x 107 melanin granules/ml. The 810-nm, ultrashort pulses also excited fluorescence, but with a broader, lower-amplitude peak. The weaker fluorescence signal excited by the 810-nm ultrashort pulse laser for a given melanosome concentration, compared to 406-nm CW excitation, is possibly due to the smaller two- photon absorption cross-section. These results indicate the involvement of multiphoton absorption in DNA damage.

  2. High-resolution multiphoton optical tomography of tissues: an in vitro and in vivo study

    Riemann, Iris; Schenke-Layland, Katja; Ehlers, Alexander; Dimitrow, Enrico; Kaatz, Martin; Elsner, Peter; Martin, Sven; König, Karsten

    2006-03-01

    Multiphoton optical tomography based on NIR (near-infrared) femtosecond laser pulses provides non-invasive optical sectioning of skin with high spatial intracellular resolution and high tissue penetration. The imaging system DermaInspect was used to perform this technology in clinical studies in vivo on patients with suspicious melanoma. Pigmented cell clusters based on non-linear luminescence were clearly distinguished from non-pigmented cells in the epidermis using the autofluorescence of endogenous fluorophores like NAD(P)H, flavins, keratin, elastin, collagen and melanin. Some of the investigated tissues showed differences in the structure of the epidermal layers and the presence of dendritic cells compared to normal skin. Multiphoton laser microscopy was used to visualize extracellular matrix (ECM) structures of native and tissueengineered heart valves. The quality of the resulting 3-D images allowed an exact differentiation between collagenous and elastic fibers. The analysis of heart valve tissues of patients with cardiomyopathy revealed a dramatic loss of its capability to generate SH (second harmonic), indicating a structural deformation of the collagenous fibers, which was virtually impossible to obtain by routine histological or immunohistological staining. These results indicate that NIR femtosecond laser scanning systems can be employed as novel non-invasive optical technology for 3-D resolved ECM component imaging and in vitro and in vivo tissue diagnosis.

  3. Label-free monitoring of colorectal adenoma-carcinoma sequence based on multiphoton microscopy

    Chen, J. X.; Li, H. S.; Chen, Z. F.; Feng, C. Y.; Yang, Y. H.; Jiang, W. Z.; Guan, G. X.; Zhu, X. Q.; Zhuo, S. M.; Xu, J.

    2014-06-01

    The monitoring and evaluation of colorectal adenoma-carcinoma sequence during endoscopy are important for endoscopic resection of precursor lesions to disrupt the adenoma-carcinoma sequence and halt progression to invasive neoplastic disease. In this study, multiphoton microscopy (MPM) was used to identify different stages during the development of colorectal adenocarcinoma including adenoma with low-grade and high-grade dysplasia, and adenocarcinoma invading the submucosa. It was found that by combining two-photon excited fluorescence (TPEF) imaging and second harmonic generation (SHG) imaging, MPM can reveal the morphological changes of the epithelial cells and glands, identify the invasive position and depth of atypical glands and quantitatively describe the change of the cellular nucleus and the nuclear-to-cytoplasmic ratio during the stepwise progression of colorectal adenocarcinoma. These are important pathological findings for pathologists when diagnosing colorectal lesions. With the advancement of a compact and flexible multiphoton endoscope for in vivo imaging and clinical applications, MPM has the potential to provide immediate histological diagnosis for the monitoring and evaluation of the colorectal adenoma-carcinoma sequence during endoscopy.

  4. Single- and Multi-Photon Events with Missing Energy in $e^+ e^-$ Collisions at LEP

    Achard, P; Aguilar-Benítez, M; Alcaraz, J; Alemanni, G; Allaby, James V; Aloisio, A; Alviggi, M G; Anderhub, H; Andreev, V P; Anselmo, F; Arefev, A; Azemoon, T; Aziz, T; Bagnaia, P; Bajo, A; Baksay, G; Baksay, L; Baldew, S V; Banerjee, S; Banerjee, Sw; Barczyk, A; Barillère, R; Bartalini, P; Basile, M; Batalova, N; Battiston, R; Bay, A; Becattini, F; Becker, U; Behner, F; Bellucci, L; Berbeco, R; Berdugo, J; Berges, P; Bertucci, B; Betev, B L; Biasini, M; Biglietti, M; Biland, A; Blaising, J J; Blyth, S C; Bobbink, Gerjan J; Böhm, A; Boldizsar, L; Borgia, B; Bottai, S; Bourilkov, D; Bourquin, Maurice; Braccini, S; Branson, J G; Brochu, F; Burger, J D; Burger, W J; Cai, X D; Capell, M; Cara Romeo, G; Carlino, G; Cartacci, A M; Casaus, J; Cavallari, F; Cavallo, N; Cecchi, C; Cerrada, M; Chamizo-Llatas, M; Chang, Y H; Chemarin, M; Chen, A; Chen, G; Chen, G M; Chen, H F; Chen, H S; Chiefari, G; Cifarelli, Luisa; Cindolo, F; Clare, I; Clare, R; Coignet, G; Colino, N; Costantini, S; de la Cruz, B; Cucciarelli, S; van Dalen, J A; De Asmundis, R; Déglon, P L; Debreczeni, J; Degré, A; Dehmelt, K; Deiters, K; Della Volpe, D; Delmeire, E; Denes, P; De Notaristefani, F; De Salvo, A; Diemoz, M; Dierckxsens, M; Dionisi, C; Dittmar, M; Doria, A; Dova, M T; Duchesneau, D; Duda, M; Echenard, B; Eline, A; El-Hage, A; El-Mamouni, H; Engler, A; Eppling, F J; Extermann, P; Falagán, M A; Falciano, S; Favara, A; Fay, J; Fedin, O; Felcini, M; Ferguson, T; Fesefeldt, H S; Fiandrini, E; Field, J H; Filthaut, F; Fisher, P H; Fisher, W; Fisk, I; Forconi, G; Freudenreich, Klaus; Furetta, C; Galaktionov, Yu; Ganguli, S N; García-Abia, P; Gataullin, M; Gentile, S; Giagu, S; Gong, Z F; Grenier, G; Grimm, O; Grünewald, M W; Guida, M; van Gulik, R; Gupta, V K; Gurtu, A; Gutay, L J; Haas, D; Hatzifotiadou, D; Hebbeker, T; Hervé, A; Hirschfelder, J; Hofer, H; Hohlmann, M; Holzner, G; Hou, S R; Hu, Y; Jin, B N; Jones, L W; de Jong, P; Josa-Mutuberria, I; Käfer, D; Kaur, M; Kienzle-Focacci, M N; Kim, J K; Kirkby, Jasper; Kittel, E W; Klimentov, A; König, A C; Kopal, M; Koutsenko, V F; Kräber, M H; Krämer, R W; Krüger, A; Kunin, A; Ladrón de Guevara, P; Laktineh, I; Landi, G; Lebeau, M; Lebedev, A; Lebrun, P; Lecomte, P; Lecoq, P; Le Coultre, P; Le Goff, J M; Leiste, R; Levtchenko, M; Levchenko, P M; Li, C; Likhoded, S; Lin, C H; Lin, W T; Linde, Frank L; Lista, L; Liu, Z A; Lohmann, W; Longo, E; Lü, Y S; Luci, C; Luminari, L; Lustermann, W; Ma Wen Gan; Malgeri, L; Malinin, A; Maña, C; Mans, J; Martin, J P; Marzano, F; Mazumdar, K; McNeil, R R; Mele, S; Merola, L; Meschini, M; Metzger, W J; Mihul, A; Milcent, H; Mirabelli, G; Mnich, J; Mohanty, G B; Muanza, G S; Muijs, A J M; Musicar, B; Musy, M; Nagy, S; Natale, S; Napolitano, M; Nessi-Tedaldi, F; Newman, H; Nisati, A; Novák, T; Nowak, H; Ofierzynski, R A; Organtini, G; Pal, I; Palomares, C; Paolucci, P; Paramatti, R; Passaleva, G; Patricelli, S; Paul, T; Pauluzzi, M; Paus, C; Pauss, Felicitas; Pedace, M; Pensotti, S; Perret-Gallix, D; Petersen, B; Piccolo, D; Pierella, F; Pioppi, M; Piroué, P A; Pistolesi, E; Plyaskin, V; Pohl, M; Pozhidaev, V; Pothier, J; Prokofev, D; Prokofiev, D O; Quartieri, J; Rahal-Callot, G; Rahaman, M A; Raics, P; Raja, N; Ramelli, R; Rancoita, P G; Ranieri, R; Raspereza, A V; Razis, P A; Ren, D; Rescigno, M; Reucroft, S; Riemann, S; Riles, K; Roe, B P; Romero, L; Rosca, A; Rosenbleck, C; Rosier-Lees, S; Roth, S; Rubio, J A; Ruggiero, G; Rykaczewski, H; Sakharov, A; Saremi, S; Sarkar, S; Salicio, J; Sánchez, E; Schäfer, C; Shchegelskii, V; Schopper, Herwig Franz; Schotanus, D J; Sciacca, C; Servoli, L; Shevchenko, S; Shivarov, N; Shoutko, V; Shumilov, E; Shvorob, A V; Son, D; Souga, C; Spillantini, P; Steuer, M; Stickland, D P; Stoyanov, B; Strässner, A; Sudhakar, K; Sultanov, G G; Sun, L Z; Sushkov, S; Suter, H; Swain, J D; Szillási, Z; Tang, X W; Tarjan, P; Tauscher, Ludwig; Taylor, L; Tellili, B; Teyssier, D; Timmermans, C; Ting, Samuel C C; Ting, S M; Tonwar, S C; Tóth, J; Tully, C; Tung, K L; Ulbricht, J; Valente, E; Van de Walle, R T; Vásquez, R; Veszpremi, V; Vesztergombi, G; Vetlitskii, I; Vicinanza, D; Viertel, Gert M; Villa, S; Vivargent, M; Vlachos, S; Vodopyanov, I; Vogel, H; Vogt, H; Vorobev, I; Vorobyov, A A; Wadhwa, M; Wang, Q; Wang, X L; Wang, Z M; Weber, M; Wienemann, P; Wilkens, H; Wynhoff, S; Xia, L; Xu, Z Z; Yamamoto, J; Yang, B Z; Yang, C G; Yang, H J; Yang, M; Yeh, S C; Zalite, A; Zalite, Yu; Zhang, Z P; Zhao, J; Zhu, G Y; Zhu, R Y; Zhuang, H L; Zichichi, A; Zimmermann, B; Zöller, M

    2004-01-01

    Single- and multi-photon events with missing energy are selected in 619/pb of data collected by the L3 detector at LEP at centre-of-mass energies between 189GeV and 209GeV. The cross sections of the process e^+e^- -> nu nu gamma (gamma) are found to be in agreement with the Standard Model expectations, and the number of light neutrino species is determined, including lower energy data, to be N_nu = 2.98 +/- 0.05 +/- 0.04. Selection results are also given in the form of tables which can be used to test future models involving single- and multi-photon signatures at LEP. These final states are also predicted by models with large extra dimensions and by several supersymmetric models. No evidence for such models is found. Among others, lower limits between 1.5TeV and 0.65TeV are set, at 95% confidence level, on the new scale of gravity for the number of extra dimensions between 2 and 8.

  5. Single- and multiphoton events with missing energy in $e^{+} e^{-}$ collisions at LEP

    Achard, P; Aguilar-Benítez, M; Alcaraz, J; Alemanni, G; Allaby, James V; Aloisio, A; Alviggi, M G; Anderhub, H; Andreev, V P; Anselmo, F; Arefev, A; Azemoon, T; Aziz, T; Bagnaia, P; Bajo, A; Baksay, G; Baksay, L; Baldew, S V; Banerjee, S; Banerjee, Sw; Barczyk, A; Barillère, R; Bartalini, P; Basile, M; Batalova, N; Battiston, R; Bay, A; Becattini, F; Becker, U; Behner, F; Bellucci, L; Berbeco, R; Berdugo, J; Berges, P; Bertucci, B; Betev, B L; Biasini, M; Biglietti, M; Biland, A; Blaising, J J; Blyth, S C; Bobbink, G J; Böhm, A; Boldizsar, L; Borgia, B; Bottai, S; Bourilkov, D; Bourquin, M; Braccini, S; Branson, J G; Brochu, F; Burger, J D; Burger, W J; Cai, X D; Capell, M; Carlino, G; Cartacci, A; Casaus, J; Cavallari, F; Cavallo, N; Cecchi, C; Cerrada, M; Chamizo-Llatas, M; Chang, Y H; Chemarin, M; Chen, A; Chen, G; Chen, G M; Chen, H F; Chen, H S; Chiefari, G; Cifarelli, L; Cindolo, F; Clare, I; Clare, R; Coignet, G; Colino, N; Costantini, S; Cucciarelli, S; De Salvo, A; De Notaristefani, F; Debreczeni, J; Deglon, P; Degré, A; Dehmelt, K; Deiters, K; Delmeire, E; Denes, P; Diemoz, M; Dierckxsens, M; Dionisi, C; Dittmar, M; Doria, A; Dova, M T; Duchesneau, D; Duda, M; Echenard, B; El-Hage, A; El-Mamouni, H; Eline, A; Engler, A; Eppling, F J; Extermann, P; Falagán, M A; Falciano, S; Favara, A; Fay, J; Fedin, O; Felcini, M; Ferguson, T; Fesefeldt, H S; Fiandrini, E; Field, J H; Filthaut, F; Fisher, P H; Fisher, W; Fisk, I; Forconi, G; Freudenreich, Klaus; Furetta, C; Galaktionov, Yu; Ganguli, S N; García-Abia, P; Gataullin, M; Gentile, S; Giagu, S; Gong, Z F; Grenier, G; Grimm, O; Grünewald, M W; Guida, M; Gupta, V K; Gurtu, A; Gutay, L J; Haas, D; Hatzifotiadou, D; Hebbeker, T; Hervé, A; Hirschfelder, J; Hofer, H; Hohlmann, M; Holzner, G; Hou, S R; Hu, Y; Jin, B N; Jones, L W; Josa-Mutuberria, I; Käfer, D; Kaur, M; Kienzle-Focacci, M N; Kim, J K; Kirkby, Jasper; Kittel, E W; Klimentov, A; König, A C; Kopal, M; Koutsenko, V F; Kraber, M; Krämer, R W; Krüger, A; Kunin, A; Laktineh, I; Landi, G; Le Coultre, P; Le Goff, J M; Lebeau, M; Lebedev, A; Lebrun, P; Lecomte, P; Lecoq, P; Leiste, R; Levtchenko, M; Levchenko, P M; Li, C; Likhoded, S; Lin, C H; Lin, W T; Linde, Frank L; Lista, L; Liu, Z A; Lohmann, W; Longo, E; Lü, Y S; Luci, C; Luminari, L; Lustermann, W; Ma W G; Malgeri, L; Malinin, A; Maña, C; Mans, J; Martin, J P; Marzano, F; Mazumdar, K; McNeil, R R; Mele, S; Merola, L; Meschini, M; Metzger, W J; Mihul, A; Milcent, H; Mirabelli, G; Mnich, J; Mohanty, G B; Muanza, G S; Muijs, A J M; Musicar, B; Musy, M; Nagy, S; Napolitano, M; Natale, S; Nessi-Tedaldi, F; Newman, H; Nisati, A; Novák, T; Nowak, H; Ofierzynski, R A; Organtini, G; Pal, I; Palomares, C; Paolucci, P; Paramatti, R; Passaleva, G; Patricelli, S; Paul, T; Pauluzzi, M; Paus, C; Pauss, F; Pedace, M; Pensotti, S; Perret-Gallix, D; Petersen, B; Piccolo, D; Pierella, F; Pioppi, M; Piroué, P A; Pistolesi, E; Plyaskin, V; Pohl, M; Pozhidaev, V; Pothier, J; Prokofev, D; Prokofiev, D O; Quartieri, J; Rahal-Callot, G; Rahaman, M A; Raics, P; Raja, N; Ramelli, R; Rancoita, P G; Ranieri, R; Raspereza, A V; Razis, P; Ren, D; Rescigno, M; Reucroft, S; Riemann, S; Riles, K; Roe, B P; Romeo, G C; Romero, L; Rosca, A; Rosenbleck, C; Rosier-Lees, S; Roth, S; Rubio, J A; Ruggiero, G; Rykaczewski, H; Sakharov, A; Salicio, J; Sánchez, E; Saremi, S; Sarkar, S; Schäfer, C; Shchegelskii, V; Schopper, Herwig Franz; Schotanus, D J; Sciacca, C; Servoli, L; Shevchenko, S; Shivarov, N; Shoutko, V; Shumilov, E; Shvorob, A; Son, D; Souga, C; Spillantini, P; Steuer, M; Stickland, D P; Stoyanov, B; Strässner, A; Sudhakar, K; Sultanov, G G; Sun, L Z; Sushkov, S; Suter, K; Swain, J D; Szillási, Z; Tang, X W; Tarjan, P; Tauscher, L; Taylor, L; Tellili, B; Teyssier, D; Timmermans, C; Ting, Samuel C C; Ting, S M; Tonwar, S C; Tóth, J; Tully, C; Tung, K L; Ulbricht, J; Valente, E; Van de Walle, R T; Vásquez, R; Veszpremi, V; Vesztergombi, G; Vetlitskii, I; Vicinanza, D; Viertel, G; Villa, S; Vivargent, M; Vlachos, S; Vodopyanov, I; Vogel, H; Vogt, H; Vorobev, I; Vorobyov, A A; Wadhwa, M; Wang, Q; Wang, X L; Wang, Z M; Weber, M; Wienemann, P; Wilkens, H; Wynhoff, S; Xia, L; Xu, Z Z; Yamamoto, J; Yang, B Z; Yang, C G; Yang, H J; Yang, M; Yeh, S C; Zalite, A; Zalite, Yu; Zhang, Z P; Zhao, J; Zhu, G Y; Zhu, R Y; Zhuang, H L; Zichichi, A; Zimmermann, B; Zöller, M; De Asmundis, R; De Guevara, P L; de Jong, P; de la Cruz, B; Della Volpe, D; van Dalen, J A; van Gulik, R

    2004-01-01

    Single- and multiphoton events with missing energy are selected in 619 pb/sup -1/ of data collected by the L3 detector at LEP at centre- of-mass energies between 189 and 209 GeV. The cross sections of the process e^{+}e^{-} to nu nu gamma ( gamma ) are found to be in agreement with the standard model expectations, and the number of light neutrino species is determined, including lower energy data, to be N/sub nu /=2.98+or-0.05+or-0.04. Selection results are given in the form of tables which can be used to test future models involving single- and multiphoton signatures at LEP. These final states are also predicted by models with large extra dimensions and by several supersymmetric models. No evidence for such models is found. Among others, lower limits between 1.5 and 0.65 TeV are set, at 95% confidence level, on the new scale of gravity for the number of extra dimensions between 2 and 6.

  6. Insights on proximity effect and multiphoton induced luminescence from gold nanospheres in far field optical microscopy

    Borglin, Johan [Biomedical Photonics Group, Department of Chemistry and Molecular Biology, University of Gothenburg, Kemivägen 10, 412 96 Gothenburg (Sweden); Department of Physics, University of Gothenburg, Kemivägen 10, 412 96 Gothenburg (Sweden); Guldbrand, Stina [Department of Physics, University of Gothenburg, Kemivägen 10, 412 96 Gothenburg (Sweden); Evenbratt, Hanne [Pharmaceutical Technology, Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Kemigården 4, 412 96 Gothenburg (Sweden); Kirejev, Vladimir; Ericson, Marica B., E-mail: marica.ericson@chem.gu.se [Biomedical Photonics Group, Department of Chemistry and Molecular Biology, University of Gothenburg, Kemivägen 10, 412 96 Gothenburg (Sweden); Grönbeck, Henrik [Department of Applied Physics, Chalmers University of Technology, Kemivägen 9, 412 96 Gothenburg (Sweden)

    2015-12-07

    Gold nanoparticles can be visualized in far-field multiphoton laser-scanning microscopy (MPM) based on the phenomena of multiphoton induced luminescence (MIL). This is of interest for biomedical applications, e.g., for cancer diagnostics, as MPM allows for working in the near-infrared (NIR) optical window of tissue. It is well known that the aggregation of particles causes a redshift of the plasmon resonance, but its implications for MIL applying far-field MPM should be further exploited. Here, we explore MIL from 10 nm gold nanospheres that are chemically deposited on glass substrates in controlled coverage gradients using MPM operating in NIR range. The substrates enable studies of MIL as a function of inter-particle distance and clustering. It was shown that MIL was only detected from areas on the substrates where the particle spacing was less than one particle diameter, or where the particles have aggregated. The results are interpreted in the context that the underlying physical phenomenon of MIL is a sequential two-photon absorption process, where the first event is driven by the plasmon resonance. It is evident that gold nanospheres in this size range have to be closely spaced or clustered to exhibit detectable MIL using far-field MPM operating in the NIR region.

  7. Insights on proximity effect and multiphoton induced luminescence from gold nanospheres in far field optical microscopy

    Gold nanoparticles can be visualized in far-field multiphoton laser-scanning microscopy (MPM) based on the phenomena of multiphoton induced luminescence (MIL). This is of interest for biomedical applications, e.g., for cancer diagnostics, as MPM allows for working in the near-infrared (NIR) optical window of tissue. It is well known that the aggregation of particles causes a redshift of the plasmon resonance, but its implications for MIL applying far-field MPM should be further exploited. Here, we explore MIL from 10 nm gold nanospheres that are chemically deposited on glass substrates in controlled coverage gradients using MPM operating in NIR range. The substrates enable studies of MIL as a function of inter-particle distance and clustering. It was shown that MIL was only detected from areas on the substrates where the particle spacing was less than one particle diameter, or where the particles have aggregated. The results are interpreted in the context that the underlying physical phenomenon of MIL is a sequential two-photon absorption process, where the first event is driven by the plasmon resonance. It is evident that gold nanospheres in this size range have to be closely spaced or clustered to exhibit detectable MIL using far-field MPM operating in the NIR region

  8. Multi-photon creation and single-photon annihilation of electron-positron pairs

    In this thesis we study multi-photon e+e- pair production in a trident process, and singlephoton e+e- pair annihilation in a triple interaction. The pair production is considered in the collision of a relativistic electron with a strong laser beam, and calculated within the theory of laser-dressed quantum electrodynamics. A regularization method is developed systematically for the resonance problem arising in the multi-photon process. Total production rates, positron spectra, and relative contributions of different reaction channels are obtained in various interaction regimes. Our calculation shows good agreement with existing experimental data from SLAC, and adds further insights into the experimental findings. Besides, we study the process in a manifestly nonperturbative domain, whose accessibility to future all-optical experiments based on laser acceleration is shown. In the single-photon e+e- pair annihilation, the recoil momentum is absorbed by a spectator particle. Various kinematic configurations of the three incoming particles are examined. Under certain conditions, the emitted photon exhibits distinct angular and polarization distributions which could facilitate the detection of the process. Considering an equilibrium relativistic e+e- plasma, it is found that the single-photon process becomes the dominant annihilation channel for plasma temperatures above 3 MeV. Multi-particle correlation effects are therefore essential for the e+e- dynamics at very high density. (orig.)

  9. Multi-photon creation and single-photon annihilation of electron-positron pairs

    Hu, Huayu

    2011-04-27

    In this thesis we study multi-photon e{sup +}e{sup -} pair production in a trident process, and singlephoton e{sup +}e{sup -} pair annihilation in a triple interaction. The pair production is considered in the collision of a relativistic electron with a strong laser beam, and calculated within the theory of laser-dressed quantum electrodynamics. A regularization method is developed systematically for the resonance problem arising in the multi-photon process. Total production rates, positron spectra, and relative contributions of different reaction channels are obtained in various interaction regimes. Our calculation shows good agreement with existing experimental data from SLAC, and adds further insights into the experimental findings. Besides, we study the process in a manifestly nonperturbative domain, whose accessibility to future all-optical experiments based on laser acceleration is shown. In the single-photon e{sup +}e{sup -} pair annihilation, the recoil momentum is absorbed by a spectator particle. Various kinematic configurations of the three incoming particles are examined. Under certain conditions, the emitted photon exhibits distinct angular and polarization distributions which could facilitate the detection of the process. Considering an equilibrium relativistic e{sup +}e{sup -} plasma, it is found that the single-photon process becomes the dominant annihilation channel for plasma temperatures above 3 MeV. Multi-particle correlation effects are therefore essential for the e{sup +}e{sup -} dynamics at very high density. (orig.)

  10. Use of multiphoton microscopy to diagnose liver cancer and lung metastasis in an orthotopic rat model.

    Yan, Jun; Zhuo, Shuangmu; Chen, Gang; Tan, Changjun; Zhu, Weifeng; Lu, Jianping; Fan, Jia; Chen, Jianxin; Zhou, Jian

    2012-01-01

    Liver or lung biopsy for suspicious lesions has several disadvantages such as bleeding, bile leak or pneumothorax, needle track seeding, and time-consuming histopathological procedure. The ability to directly observe cellular and subcellular details and then perform "optical biopsy" is a major goal in the development of new interventional techniques. Multiphoton microscopy (MPM) enables real-time noninvasive visualization of tissue architecture and cell morphology in live tissue. We performed a study to evaluate whether MPMcan make real-time optical diagnosis for liver cancer and lung metastasis using an orthotopic rat model with Morris hepatoma. We found that real-time high-resolution MPMimaging could clearly show tissue architecture and cell morphology. In the normal liver tissue, MPMimaging clearly revealed the blood-filled sinusoids and cords of hepatocytes. In the cancerous tissue, MPMimaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. MPMimages were comparable to golden standard hematoxylin-eosin staining images. Moreover, MPMimaging had deep penetration with the capability of optical sectioning. In short, MPMcan make real-time optical diagnosis for liver cancer and lung metastasis. This study provides the groundwork for further using multiphoton endoscopy to perform real-time noninvasive "optical biopsy" for liver cancer and lung metastasis in the near future. PMID:22331704

  11. Tunable fibre-coupled multiphoton microscopy with a negative curvature fibre.

    Sherlock, Ben; Yu, Fei; Stone, Jim; Warren, Sean; Paterson, Carl; Neil, Mark A A; French, Paul M W; Knight, Jonathan; Dunsby, Chris

    2016-07-01

    Negative curvature fibre (NCF) guides light in its core by inhibiting the coupling of core and cladding modes. In this work, an NCF was designed and fabricated to transmit ultrashort optical pulses for multiphoton microscopy with low group velocity dispersion (GVD) at 800 nm. Its attenuation was measured to be power of ∼20 mW and pulse repetition rate of 80 MHz, the NCF enabled pulses with a duration of pulse widths were maintained to within 10% of low power values up to the maximum fibre output power achievable with the laser system used of 278 mW at 700 nm, 808 mW at 800 nm and 420 mW at 860 nm. When coupled to a multiphoton microscope, it enabled imaging of ex vivo tissue using excitation wavelengths from 740 nm to 860 nm without any need for adjustments to the set-up. PMID:26989868

  12. Preparation of metallo-dielectric photonic crystals by multi-photon direct laser writing

    Kuebler, Stephen M.; Tal, Amir; Chen, Yun-Sheng

    2008-02-01

    Metallo-dielectric photonic crystals (MDPCs) can exhibit intriguing and potentially useful optical properties, including ultra-wide photonic bandgaps, engineered thermal emission, and negative refractive index. But access to such materials has been limited by the lack of suitable methods for their preparation. We have developed a route to three-dimensional (3D) MDPCs that involves fabricating a polymeric pre-form by multi-photon direct laser writing and then conformally depositing metal onto the pre-form by electroless metallization. We use the approach to prepare silver- and copper-plated "woodpile" PCs having face-centered tetragonal symmetry and unit-cell period of several micrometers. The resulting 3D metallized structures exhibit mid-infrared reflectance that is consistent with theory and experimental observations obtained for MDPCs prepared by other routes. These data indicate that multi-photon direct laser writing coupled with electroless metallization is a viable route to complex 3D MDPCs of many symmetries and basis sets and provides a path for integrating such structures with other micron-scale optical elements.

  13. Multiphoton microscopy as a diagnostic tool for pathological analysis of sentinel lymph nodes

    Lemiere, J.; Douady, J.; Estève, F.; Salameire, D.; Lantuejoul, S.; Lorimier, P.; Ricard, C.; van der Sanden, B.; Vial, J.-C.

    2009-02-01

    Multiphoton microscopy has shown a powerful potential for biomedical in vivo and ex vivo analysis of tissue sections and explants. Studies were carried out on several animal organs such as brain, arteries, lungs, and kidneys. One of the current challenges is to transfer to the clinic the knowledge and the methods previously developed in the labs at the preclinical level. For tumour staging, physicians often remove the lymph nodes that are localized at the proximity of the lesion. In case of breast cancer or melanoma, sentinel lymph node protocol is performed: pathologists randomly realize an extensive sampling of formol fixed nodes. However, the duration of this protocol is important and its reliability is not always satisfactory. The aim of our study was to determine if multiphoton microscopy would enable the fast imaging of lymph nodes on important depths, with or without exogenous staining. Experiments were first conducted on pig lymph nodes in order to test various dyes and to determine an appropriate protocol. The same experiments were then performed on thin slices of human lymph nodes bearing metastatic melanoma cells. We obtained relevant images with both endofluorescence plus second-harmonic generation and xanthene dyes. They show a good contrast between tumour and healthy cells. Furthermore, images of pig lymph nodes were recorded up to 120μm below the surface. This new method could then enable a faster diagnosis with higher efficiency for the patient. Experiments on thicker human lymph nodes are currently underway in order to validate these preliminary results.

  14. Characterization of multiphoton photoacoustic spectroscopy for subsurface brain tissue diagnosis and imaging

    Dahal, Sudhir; Cullum, Brian M.

    2016-04-01

    The development and demonstration of a multiphoton photoacoustic imaging technique capable of providing high spatial resolution chemical images of subsurface tissue components as deep as 1.4 cm below the tissue surface is described. By combining multiphoton excitation in the diagnostic window (650 to 1100 nm), with ultrasonic detection of nonradiative relaxation events, it is possible to rapidly reconstruct three-dimensional, chemical specific, images of samples underneath overlying structures as well as chemical species of the same material. Demonstration of this technique for subsurface tissue differentiation is shown, with the ability to distinguish between grade III astrocytoma tissue and adjacent healthy tissue in blind studies. By employing photoacoustic signal detection, the high nonradiative relaxation rates of most biological tissue components (>90%) and the minimal signal attenuation of the resulting ultrasound compensate for excitation efficiency losses associated with two-photon absorption. Furthermore, the two-photon absorption process results in a highly localized excitation volume (ca., 60 μm). Characterization of the probing depth, spatial resolution, and ability to image through overlying structures is also demonstrated in this paper using tissue phantoms with well-characterized optical scattering properties, mimicking those of tissues.

  15. Development and characterization of non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) for brain tumor margining

    Dahal, Sudhir

    During tumor removal surgery, due to the problems associated with obtaining high-resolution, real-time chemical images of where exactly the tumor ends and healthy tissue begins (tumor margining), it is often necessary to remove a much larger volume of tissue than the tumor itself. In the case of brain tumor surgery, however, it is extremely unsafe to remove excess tissue. Therefore, without an accurate image of the tumor margins, some of the tumor's finger-like projections are inevitably left behind in the surrounding parenchyma to grow again. For this reason, the development of techniques capable of providing high-resolution real-time images of tumor margins up to centimeters below the surface of a tissue is ideal for the diagnosis and treatment of tumors, as well as surgical guidance during brain tumor excision. A novel spectroscopic technique, non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), is being developed with the capabilities of obtaining high-resolution subsurface chemical-based images of underlying tumors. This novel technique combines the strengths of multiphoton tissue spectroscopy and photoacoustic spectroscopy into a diagnostic methodology that will, ultimately, provide unparalleled chemical information and images to provide the state of sub-surface tissues. The NMPPAS technique employs near-infrared light (in the diagnostic window) to excite ultraviolet and/or visible light absorbing species deep below the tissue's surface. Once a multiphoton absorption event occurs, non-radiative relaxation processes generates a localized thermal expansion and subsequent acoustic wave that can be detected using a piezoelectric transducer. Since NMPPAS employs an acoustic detection modality, much deeper diagnoses can be performed than that is possible using current state of the art high-resolution chemical imaging techniques such as multiphoton fluorescence spectroscopy. NMPPAS was employed to differentiate between excised brain tumors (astrocytoma III

  16. Quantitative evaluation of the effect of multiphoton ionization in laser Thomson scattering diagnostics of low-temperature plasmas

    Kono, Akihiro; Matsuda, Yukitaka; Okada, Ken; Aramaki, Mitsutoshi

    2011-10-01

    Laser Thomson scattering technique allows one very high spatial-resolution measurements of electron density and temperature as required in diagnostics of microplasmas or measurement of regions very close to the wall. In such high-resolution measurements, laser energy density in the scattering volume must be very high for obtaining sufficient amount of scattering photons; therefore, electron production via multiphoton ionization by the laser beam may significantly affect Thomson scattering due to plasma electrons. In order to clarify the effect of multiphoton ionization in Thomson scattering diagnostics, we have been measuring absolute efficiency of multiphoton ionization caused by frequency-doubled Nd:YAG laser for various gases including rare gases, N2, O2, CF4 and SF6. It has been found that electrons produced via multiphoton ionization can reach a significant fraction of plasma electrons even at low pressures, depending on the gas species and laser focusing conditions. Details will be given in the presentation, including simulation results about how the escape of photoelectrons from the scattering volume affects the situation.

  17. “Single Shot” Laser Multiphoton Ionization Detection of UF5 Following the 266 nm Photodissociation of UF6

    Chou, J. S.; Sumida, D.; Stuke, M.; Wittig, C

    1982-01-01

    By using laser multiphoton ionization and a time-of-flight mass filter, we have detected nascent UF5 from the 266 nm laser photodissociation of UF6, following a single laser firing. The method can be used to monitor these species under conditions wherein isotopically selective excitation is responsible for the dissociation of UF6.

  18. In vivo 3D measurement of moxifloxacin and gatifloxacin distributions in the mouse cornea using multiphoton microscopy

    Lee, Seunghun; Lee, Jun Ho; Park, Jin Hyoung; Yoon, Yeoreum; Chung, Wan Kyun; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

    2016-05-01

    Moxifloxacin and gatifloxacin are fourth-generation fluoroquinolone antibiotics used in the clinic to prevent or treat ocular infections. Their pharmacokinetics in the cornea is usually measured from extracted ocular fluids or tissues, and in vivo direct measurement is difficult. In this study multiphoton microscopy (MPM), which is a 3D optical microscopic technique based on multiphoton fluorescence, was applied to the measurement of moxifloxacin and gatifloxacin distribution in the cornea. Intrinsic multiphoton fluorescence properties of moxifloxacin and gatifloxacin were characterized, and their distributions in mouse cornea in vivo were measured by 3D MPM imaging. Both moxifloxacin and gatifloxacin had similar multiphoton spectra, while moxifloxacin had stronger fluorescence than gatifloxacin. MPM imaging of mouse cornea in vivo showed (1) moxifloxacin had good penetration through the superficial corneal epithelium, while gatifloxacin had relatively poor penetration, (2) both ophthalmic solutions had high intracellular distribution. In vivo MPM results were consistent with previous studies. This study demonstrates the feasibility of MPM as a method for in vivo direct measurement of moxifloxacin and gatifloxacin in the cornea.

  19. Comparison of analytical and Monte Carlo calculations of multi-photon effects in bremsstrahlung emission by high-energy electrons

    Mangiarotti, Alessio; Sona, Pietro; Ballestrero, Sergio;

    2012-01-01

    Approximate analytical calculations of multi-photon effects in the spectrum of total radiated energy by high-energy electrons crossing thin targets are compared to the results of Monte Carlo type simulations. The limits of validity of the analytical expressions found in the literature are establi...

  20. Verification Results of Jet Resonance-enhanced Multiphoton Ionization as a Real-time PCDD/F Emission Monitor

    The Jet REMPI (Resonance Enhanced Multiphoton Ionization) monitor was tested on a hazardous waste firing boiler for its ability to determine concentrations of polychlorinated dibenzodioxins and dibenzofurans (PCDDs/Fs). Jet REMPI is a real time instrument capable of highly selec...

  1. Statistical analysis on activation and photo-bleaching of step-wise multi-photon activation fluorescence of melanin

    Gu, Zetong; Lai, Zhenhua; Zhang, Xi; Yin, Jihao; DiMarzio, Charles A.

    2015-03-01

    Melanin is regarded as the most enigmatic pigments/biopolymers found in most organisms. We have shown previously that melanin goes through a step-wise multi-photon absorption process after the fluorescence has been activated with high laser intensity. No melanin step-wise multi-photon activation fluorescence (SMPAF) can be obtained without the activation process. The step-wise multi-photon activation fluorescence has been observed to require less laser power than what would be expected from a non-linear optical process. In this paper, we examined the power dependence of the activation process of melanin SMPAF at 830nm and 920nm wavelengths. We have conducted research using varying the laser power to activate the melanin in a point-scanning mode for multi-photon microscopy. We recorded the fluorescence signals and position. A sequence of experiments indicates the relationship of activation to power, energy and time so that we can optimize the power level. Also we explored regional analysis of melanin to study the spatial relationship in SMPAF and define three types of regions which exhibit differences in the activation process.

  2. Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein.

    Devender Kumar

    2015-12-01

    Full Text Available Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration.

  3. Imaging photoelectron circular dichroism of chiral molecules by femtosecond multiphoton coincidence detection

    Lehmann, C. Stefan; Ram, N. Bhargava; Janssen, Maurice H. M., E-mail: m.h.m.janssen@vu.nl [LaserLaB Amsterdam, VU University Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam (Netherlands); Powis, Ivan [School of Chemistry, University of Nottingham, Nottingham NG7 2RD (United Kingdom)

    2013-12-21

    Here, we provide a detailed account of novel experiments employing electron-ion coincidence imaging to discriminate chiral molecules. The full three-dimensional angular scattering distribution of electrons is measured after photoexcitation with either left or right circular polarized light. The experiment is performed using a simplified photoelectron-photoion coincidence imaging setup employing only a single particle imaging detector. Results are reported applying this technique to enantiomers of the chiral molecule camphor after three-photon ionization by circularly polarized femtosecond laser pulses at 400 nm and 380 nm. The electron-ion coincidence imaging provides the photoelectron spectrum of mass-selected ions that are observed in the time-of-flight mass spectra. The coincident photoelectron spectra of the parent camphor ion and the various fragment ions are the same, so it can be concluded that fragmentation of camphor happens after ionization. We discuss the forward-backward asymmetry in the photoelectron angular distribution which is expressed in Legendre polynomials with moments up to order six. Furthermore, we present a method, similar to one-photon electron circular dichroism, to quantify the strength of the chiral electron asymmetry in a single parameter. The circular dichroism in the photoelectron angular distribution of camphor is measured to be 8% at 400 nm. The electron circular dichroism using femtosecond multiphoton excitation is of opposite sign and about 60% larger than the electron dichroism observed before in near-threshold one-photon ionization with synchrotron excitation. We interpret our multiphoton ionization as being resonant at the two-photon level with the 3s and 3p Rydberg states of camphor. Theoretical calculations are presented that model the photoelectron angular distribution from a prealigned camphor molecule using density functional theory and continuum multiple scattering X alpha photoelectron scattering calculations

  4. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  5. Imaging normal and cancerous human gastric muscular layer in transverse and longitudinal sections by multiphoton microscopy.

    Zhou, Yi; Kang, Deyong; Yang, Zhenrong; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Zhou, Yongjian; Chen, Jianxin

    2016-07-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) has been widely used for imaging microstructure of biological tissues. In this article, we used MPM to investigate the microstructure changes of normal and cancerous human gastric muscular layer in transverse and longitudinal sections. The results displayed different patterns of microstructure changes of smooth muscular tissue, cell morphology and interstitial fibers in transverse and longitudinal sections, being similar to standard histopathological images but without the need for tissue processing. Our study demonstrated that MPM can bring more detailed complementary information on tissue architecture through observing transverse and longitudinal sections of tissues, which are the important pathological information when the pathologists diagnose the gastrointestinal lesions. These observations indicate that MPM could be an important potential tool to provide real-time pathological diagnosis for gastric cancer in the future. SCANNING 38:357-364, 2016. © 2015 Wiley Periodicals, Inc. PMID:26435529

  6. Spatiotemporal control of degenerate multiphoton fluorescence microscopy with delay-tunable femtosecond pulse pairs

    Das, Dhiman; Bhattacharyya, Indrajit; Goswami, Debabrata

    2016-07-01

    Selective excitation of a particular fluorophore in an ensemble of different fluorophores with overlapping fluorescence spectra is shown to be dependent on the time delay of femtosecond pulse pairs in multiphoton fluorescence microscopy. In particular, the two-photon fluorescence behavior of the Texas Red and DAPI dye pair inside Bovine Pulmonary Artery Endothelial (BPAE) cells depends strongly on the center wavelength of the laser, as well as the delay between two identical laser pulses in one-color femtosecond pulse-pair excitation scheme. Thus, we present a novel design concept using pairs of femtosecond pulses at different central wavelengths and tunable pulse separations for controlling the image contrast between two spatially and spectrally overlapping fluorophores. This femtosecond pulse-pair technique is unique in utilizing the variation of dye dynamics inside biological cells as a contrast mode in microscopy of different fluorophores.

  7. Robert Feulgen Prize Lecture. Laser tweezers and multiphoton microscopes in life sciences.

    König, K

    2000-08-01

    Near infrared (NIR) laser microscopy enables optical micromanipulation, piconewton force determination, and sensitive fluorescence studies by laser tweezers. Otherwise, fluorescence images with high spatial and temporal resolution of living cells and tissues can be obtained via non-resonant fluorophore excitation with multiphoton NIR laser scanning microscopes. Furthermore, NIR femtosecond laser pulses at TW/cm2 intensities can be used to realize non-invasive contact-free surgery of nanometer-sized structures within living cells and tissues. Applications of these novel versatile NIR laser-based tools for the determination of motility forces, coenzyme and chlorophyll imaging, three-dimensional multigene detection, non-invasive optical sectioning of tissues ("optical biopsy"), functional protein imaging, and nanosurgery of chromosomes are described. PMID:11052257

  8. Flame temperature measurements by radar resonance-enhanced multiphoton ionization of molecular oxygen.

    Wu, Yue; Sawyer, Jordan; Zhang, Zhili; Adams, Steven F

    2012-10-01

    Here we report nonintrusive local rotational temperature measurements of molecular oxygen, based on coherent microwave scattering (radar) from resonance-enhanced multiphoton ionization (REMPI) in room air and hydrogen/air flames. Analyses of the rotational line strengths of the two-photon molecular oxygen C(3)Π(v=2)←X(3)Σ(v'=0) transition have been used to determine the hyperfine rotational state distribution of the ground X(3)Σ(v'=0) state. Rotationally resolved 2+1 REMPI spectra of the molecular oxygen C(3)Π(v=2)←X(3)Σ(v'=0) transition at different temperatures were obtained experimentally by radar REMPI. Rotational temperatures have been determined from the resulting Boltzmann plots. The measurements in general had an accuracy of ~±60 K in the hydrogen/air flames at various equivalence ratios. Discussions about the decreased accuracy for the temperature measurement at elevated temperatures have been presented. PMID:23033104

  9. Laser and molecules: the season of multiphoton in Frascati in the years 70 and 80

    This paper consists of a historical review of the research activities going on at the end of the ‘70 and beginning of the ’80 at ENEA Frascati Research Centre on the topic of infrared laser molecule interactions in the gas phase. Main goal of the studies was the implementation of isotopically selective multiphoton dissociation. The activity, conducted in an extended framework of fruitful international cooperation, ranged from fundamental research addressed to the understanding of the mechanism of the excitation process in climbing the vibro-rotational ladder, to applicative consequences in the realization of process prototypes (laser, reactors) suitable to successive commercialization. The entire activity successively pushed the laboratory development in the ’90 both on fundamental research themes (like the high resolution IR spectroscopy and the study of molecular clusters in ultracold supersonic beams) and on other applicative fields, like laser driven nano-technologies and lidar systems

  10. Smart microscope: an adaptive optics learning system for aberration correction in multiphoton confocal microscopy.

    Albert, O; Sherman, L; Mourou, G; Norris, T B; Vdovin, G

    2000-01-01

    Off-axis aberrations in a beam-scanning multiphoton confocal microscope are corrected with a deformable mirror. The optimal mirror shape for each pixel is determined by a genetic learning algorithm, in which the second-harmonic or two-photon fluorescence signal from a reference sample is maximized. The speed of the convergence is improved by use of a Zernike polynomial basis for the deformable mirror shape. This adaptive optical correction scheme is implemented in an all-reflective system by use of extremely short (10-fs) optical pulses, and it is shown that the scanning area of an f:1 off-axis parabola can be increased by nine times with this technique. PMID:18059779

  11. Aromatic C-H bond activation revealed by infrared multiphoton dissociation spectroscopy.

    Jašíková, Lucie; Hanikýřová, Eva; Schröder, Detlef; Roithová, Jana

    2012-04-01

    Metal-oxide cations are models of catalyst mediating the C-H bond activation of organic substrates. One of the most powerful reagents suggested in the gas phase is based on CuO(+) . Here, we describe the activation of the aromatic C-H bonds of phenanthroline in its complex with CuO(+) . The reaction sequence starts with a hydrogen atom abstraction by the oxygen atom from the 2-position of the phenanthroline ring, followed by OH migration to the ring. Using infrared multiphoton spectroscopy, it is shown that the reaction can be energetically facilitated by additional coordination of a water ligand to the copper ion. As the reaction is intramolecular, a spectroscopic characterization of the product is mandatory in order to unambiguously address the reaction mechanism. PMID:22689621

  12. Resonance-Enhanced Multiphoton Ionization Mass Spectrometry (REMPI-MS): Applications for Process Analysis

    Streibel, Thorsten; Zimmermann, Ralf

    2014-06-01

    Process analysis is an emerging discipline in analytical sciences that poses special requirements on analytical techniques, especially when conducted in an online manner. Mass spectrometric methods seem exceedingly suitable for this task, particularly if a soft ionization method is applied. Resonance-enhanced multiphoton ionization (REMPI) in combination with time-of-flight mass spectrometry (TOFMS) provides a selective and sensitive means for monitoring (poly)aromatic compounds in process flows. The properties of REMPI and various variations of the ionization process are presented. The potential of REMPI for process analysis is highlighted with several examples, and drawbacks of the method are also noted. Applications of REMPI-TOFMS for the detection and monitoring of aromatic species in a large variety of combustion processes comprising flames, vehicle exhaust, and incinerators are discussed. New trends in technical development and combination with other analytical methods are brought forward.

  13. Engineering entangled microwave photon states through multiphoton interactions between two cavity fields and a superconducting qubit

    Zhao, Yan-Jun; Wang, Changqing; Zhu, Xiaobo; Liu, Yu-xi

    2016-01-01

    It has been shown that there are not only transverse but also longitudinal couplings between microwave fields and a superconducting qubit with broken inversion symmetry of the potential energy. Using multiphoton processes induced by longitudinal coupling fields and frequency matching conditions, we design a universal algorithm to produce arbitrary superpositions of two-mode photon states of microwave fields in two separated transmission line resonators, which are coupled to a superconducting qubit. Based on our algorithm, we analyze the generation of evenly-populated states and NOON states. Compared to other proposals with only single-photon process, we provide an efficient way to produce entangled microwave photon states when the interactions between superconducting qubits and microwave fields are in the strong and ultrastrong regime. PMID:27033558

  14. Visualization of dermal alteration in skin lesions with discoid lupus erythematosus by multiphoton microscopy

    Discoid lupus erythematosus (DLE) is a chronic dermatological disease which lacks valid methods for early diagnosis and therapeutic monitoring. Considering the collagen and elastin disorder due to mucin deposition of DLE, multiphoton microscopy (MPM) imaging techniques were employed to obtain high-resolution collagen and elastin images from the dermis. The content and distribution of collagen and elastin were quantified to characterize the dermal pathological status of skin lesions with DLE in comparison with normal skin. Our results showed a significant difference between skin lesions with DLE and normal skin in terms of the morphological structure of collagen and elastin in the dermis, demonstrating the possibility of MPM for noninvasively tracking the pathological process of DLE even in its early stages and evaluating the therapeutic efficacy at the molecular level. (paper)

  15. Electron spectroscopy of He and NO using electron impact and multiphoton ionisation

    This thesis describes two experimental studies which are intended to contribute to our knowledge of the structure of molecules and the decay dynamics of excited molecular states. The two studies have in common that they are both concerned with ionisation processes, in which an accurately known amount of energy is transferred to the target, and energy analysis of the ejected electrons is made. Ionisation is caused either by scattering electrons off the molecules (chapter 2: electron impact ionisation) or by a simultaneous absorption of several photons (chapter 3: multiphoton ionisation). In chapter 2 an electron impact ionisation experiment on Helium is described in which the kinematics of both the scattered and the ejected electrons is fully determined ((e,2e) experiment). (Auth.)

  16. Optical properties of multicoated CdSe/CdS/ZnS quantum dots for multiphoton applications

    CdSe-core CdS/Cd0.5Zn0.5S/ZnS multishell quantum dots (QDs) were synthesized by using the successive ion layer adsorption and reaction method, and their optical properties were characterized experimentally. Based on probability calculations of the time-dependent Schroedinger equation, a kinetic Monte Carlo method was used to simulate and analyse the absorption and spontaneous emission spectra of multiphoton-excited QDs. It has been shown that the blue shift of the photoluminescence peak of the core CdSe QD after coating is most probably due to the Zn diffusion during the synthesis of the ZnS coating layer

  17. Multi-Photon Multi-Channel Interferometry for Quantum Information Processing

    Dhand, Ish

    2016-01-01

    This thesis reports advances in the theory of design, characterization and simulation of multi-photon multi-channel interferometers. I advance the design of interferometers through an algorithm to realize an arbitrary discrete unitary transformation on the combined spatial and internal degrees of freedom of light. This procedure effects an arbitrary $n_{s}n_{p}\\times n_{s}n_{p}$ unitary matrix on the state of light in $n_{s}$ spatial and $n_{p}$ internal modes. I devise an accurate and precise procedure for characterizing any multi-port linear optical interferometer using one- and two-photon interference. Accuracy is achieved by estimating and correcting systematic errors that arise due to spatiotemporal and polarization mode mismatch. Enhanced accuracy and precision are attained by fitting experimental coincidence data to a curve simulated using measured source spectra. The efficacy of our characterization procedure is verified by numerical simulations. I develop group-theoretic methods for the analysis and ...

  18. Four-dimensional multiphoton microscopy with time-correlated single-photon counting.

    Schönle, A; Glatz, M; Hell, S W

    2000-12-01

    We report on the implementation of fluorescence-lifetime imaging in multiphoton excitation microscopy that uses PC-compatible modules for time-correlated single-photon counting. Four-dimensional data stacks are produced with each pixel featuring fluorescence-decay curves that consist of as many as 4096 bins. Fluorescence lifetime(s) and their amplitude(s) are extracted by statistical methods at each pixel or in arbitrarily defined regions of interest. When employing an avalanche photodiode the width of the temporal response function is 420 ps. Although this response confines the temporal resolution to values greater than several hundreds of picoseconds, the lifetime precision is determined by the signal-to-noise ratio and can be in the range of tens of picosconds. Lifetime changes are visualized in pulsed-laser-deposited fluorescent layers as well as in cyan fluorescent proteins that transfer energy to yellow fluorescent proteins in live mammalian cells. PMID:18354639

  19. Influence of laser intensity on the double-resonance multiphoton ionization process of NO molecule

    Guiyin Zhang; Yidong Jin

    2008-01-01

    The analytic forrnula of the ionization efficiency in the process of double resonance enhanced multi-photon ionization (DREMPI) is derived from the dynamic rate equation about the interaction of photon and material. Based on rids formula, the ionization efficiency arid the laser power index versus laser intensity in the DREMPI process of NO molecule, via A2∑ and S2∑ intermediate resonant states, is numerically sinnllated. It is shown that the ionization efficiency of NO molecule increases with the laser intensity until getting saturation, while the laser power index decreases with the enhancement of the laser intensity arid changes to zero at last. The variation of the laser power index with the laser intensity indicates that the ionization efficiency reaches saturation in the one, two, and three excitation steps respectively. It is also found that the narrower the laser pulse duration is, the higher becomes the laser intensity for saturation.

  20. Superresolving Imaging of Irregular Arrays of Thermal Light Sources using Multiphoton Interferences

    Classen, Anton; Giebel, Sebastian; Schneider, Raimund; Bhatti, Daniel; Mehringer, Thomas; von Zanthier, Joachim

    2016-01-01

    We propose to use multiphoton interferences of photons emitted from statistically independent thermal light sources in combination with linear optical detection techniques to reconstruct, i.e., image, arbitrary source geometries in one dimension with subclassical resolution. The scheme is an extension of earlier work [Phys. Rev. Lett. 109, 233603 (2012)] where N regularly spaced sources in one dimension were imaged by use of the Nth-order intensity correlation function. Here, we generalize the scheme to reconstruct any number of independent thermal light sources at arbitrary separations in one dimension exploiting intensity correlation functions of order $m \\geq 3$. We present experimental results confirming the imaging protocol and provide a rigorous mathematical proof for the obtained subclassical resolution.

  1. Chiral asymmetry in the multiphoton ionization of methyloxirane using femtosecond electron-ion coincidence imaging.

    Rafiee Fanood, Mohammad M; Powis, Ivan; Janssen, Maurice H M

    2014-12-11

    Multiphoton photoelectron circular dichroism (MP-PECD) has been observed as an asymmetry in the angular distribution of photoelectrons emitted in the ionization of pure enantiomers of the small chiral molecule methyloxirane using a femtosecond laser operated at 420 nm. Energetically, this requires the uptake of four photons. By switching the laser between left- and right-circular polarization, and observing the differences in the full three-dimensional electron momentum distribution recorded in an electron-ion coincidence technique, the chiral (odd) terms in the angular distribution expression can be isolated. Electron events can additionally be filtered by coincident ion mass, providing mass-tagged electron distributions and quantitative measures of the MP-PECD asymmetry that help characterize the different ionization channels. For the production of ground state parent cation, the magnitude of the mean chiral asymmetry is measured to be 4.7%, with a peak magnitude exceeding 10% PMID:25402546

  2. Multiphoton ionization and dissociation of CH3I at 266 and 355 nm

    Li Li; Xianghe Kong; Shudong Zhang

    2007-01-01

    The mechanisms of multiphoton ionization (MPI) and dissociation of CH3I have been studied using timeof-flight (TOF) mass spectrometer at 266 and 355 nm. MPI mass spectrum at 266 nm consists mostly of fragment ions. This is consistent with a neutral-fragment photoionization mechanism in which rapid one-photon dissociation occurs from the repulsive potential energy surface followed by MPI of neutral photofragments. The observation of parent ions at 355-nm excitation is indicative of parent-ionic ladder mechanism in which the parent ions are produced directly by two-photon excitation resonantly excited to Rydberg C state and then ionized through additional one-photon absorption to produce CH3I+. Fragment ions are produced by dissociation of CH3I+.

  3. A time-dependent variational approach to multiphoton ionization of H atoms in intense laser fields

    We present calculations using a variational method for the time-dependent Schrodinger equation for the study of multiphoton ionization of H atoms in intense laser fields. The trial wavefunction is chosen to be an anisotropic Gaussian wavepacket and the case of linear polarization of the laser field is considered. We report on ionization rates as a function of laser intensity (in the range 1015-1016W cm2) and frequency (corresponding to ionization by three or more photons) and momentum-dependent electron spectra. Comparison is made with results obtained when the trial wavefunction is an isotropic Gaussian wavepacket and with large-scale numerical calculations. The present method gives reliable results for non-resonant ionization in the limit of high field intensity as well as in the low-frequency limit. The electron momentum distributions are singly peaked and provide a qualitative picture of the ionization process at high field strengths. (author)

  4. Electron impact ionization and multiphoton ionization of doped superfluid helium droplets: A comparison.

    He, Yunteng; Zhang, Jie; Kong, Wei

    2016-02-28

    We compare characteristics of electron impact ionization (EI) and multiphoton ionization (MPI) of doped superfluid helium droplets using the same droplet source. Selected dopant ion fragments from the two ionization schemes demonstrate different dependence on the doping pressure, which could be attributed to the different ionization mechanisms. While EI directly ionizes helium atoms in a droplet therefore has higher yields for bigger droplets (within a limited size range), MPI is insensitive to the helium in a droplet and is only dependent on the number of dopant molecules. The optimal timing of the ionization pulse also varies with the doping pressure, implying a velocity slip among different sized droplets. Calculations of the doping statistics and ionization probabilities qualitatively agree with the experimental data. Our results offer a word of caution in interpreting the pressure and timing dependence of superfluid helium droplets, and we also devise a scheme in achieving a high degree of doping while limiting the contribution of dopant clusters. PMID:26931697

  5. Coulomb asymmetry and sub-cycle electron dynamics in multiphoton multiple ionization of H2

    We present a systematic study of the molecular-frame photo-electron angular distributions produced by multiphoton double ionization of H2 using circularly polarized 800 nm, femtosecond laser pulses. We compare experimental results to numerical results obtained from a reduced-dimensionality time-dependent Schrödinger equation (TDSE) model. In addition, we implement a TDSE-like version of the strong-field approximation to isolate the effect of the parent ion’s Coulomb potential on the continuum electron in our simulations. Thereby we identify the contributions of the parent ion potential, and light induced sub-optical cycle electron dynamics on the observable energy and angular distributions.

  6. Resonant and nonresonant multiphoton ionization processes in the mass spectrometry of explosives.

    Hamachi, Akifumi; Okuno, Tomoya; Imasaka, Tomoko; Kida, Yuichiro; Imasaka, Totaro

    2015-03-01

    Multiphoton ionization processes were studied for three types of explosives using a line-tunable ultraviolet femtosecond laser. When peroxides such as triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD) were ionized through a nonresonant two-photon process, a molecular ion was dominantly observed by reducing the excess energy remaining in the ion. However, an aromatic nitro compound such as 2,4,6-trinitrotoluene (TNT) produced large signals arising from molecular and fragment ions by resonant two-photon ionization. In addition, only fragment ions were produced from a nonaromatic nitro compound such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), even when a resonant two-photon ionization process was employed, suggesting that a further reduction in excess energy would be necessary if a molecular ion were to be observed. PMID:25622138

  7. The Effect of the Argon Carrier Gas in the Multiphoton Dissociation-Ionization of Tetracene

    Carmen Cisneros

    2008-10-01

    Full Text Available The multiphoton dissociation-ionization of tetracene at 355 nm using 6.5 nanosecond laser pulses, with and without argon as a carrier gas (CG, has been studied and compared. Ion fragments were analyzed in a time-of-flight mass spectrometer and separated according to their mass-to-charge ratio (m/z. The results show that the dynamic of photodissociation at ~1010 W⋅cm-2 intensities is strongly influenced by the CG. The suppression of fragmentation channels primarily those relating to the formation of the CHm+ (m = 2, 4, C2H4+ and C5H4+2 ions. CH5+ and CH6+ were observed which have not been reported before in photodissociation tetracene experiments.

  8. Multiphoton Ionization Time-of-Flight Mass Spectrometry for the Detection of Bioactive Lignan.

    Uchimura, Tomohiro; Tokumoto, Goro; Batnyam, Onon; Chou, Chih-Wei; Fujita, Satoshi

    2016-01-01

    Multiphoton ionization time-of-flight mass spectrometry (MPI-TOFMS) combined with a pulsed laser for sample vaporization was developed for the detection of a low-volatile compound in a solution. A solution containing Taiwanin A ((3E,4E)-3,4-bis(1,3-benzodioxol-5-ylmethylene)dihydro-2(3H)-furanone), which is a lignan that has an anticancer effect, was employed in the present study. Consequently, Taiwanin A could be detected by irradiating a laser pulse for vaporization to an inlet nozzle, rather than by heating. Therefore, the present method could be effective for detecting compounds with lower volatilities in a liquid sample. PMID:26860576

  9. The Application of Resonance-Enhanced Multiphoton Ionization Technique in Gas Chromatography Mass Spectrometry

    Adan Li

    2014-01-01

    Full Text Available Gas chromatography resonance-enhanced multiphoton ionization time-of-flight mass spectrometry (GC/REMPI-TOFMS using a nanosecond laser has been applied to analyze the 16 polycyclic aromatic hydrocarbons (PAHs. The excited-state lifetime, absorption characters, and energy of electronic states of the 16 PAHs were investigated to optimize the ionization yield. A river water sample pretreated by means of solid phase extraction was analyzed to evaluate the performance of the analytical instrument. The results suggested that REMPI is superior to electron impact ionization method for soft ionization and suppresses the background signal due to aliphatic hydrocarbons. Thus, GC/REMPI-TOFMS is a more reliable method for the determination of PAHs present in the environment.

  10. Spatiotemporal steering of photoelectron emission in multiphoton above-threshold ionization

    Gong, Xiaochun; Liu, Mingming; Song, Qiying; Lin, Kang; Ji, Qinying; Zhang, Wenbin; Ma, Junyang; Lu, Peifen; Liu, Yunquan; He, Feng; Zeng, Heping; Yang, Weifeng; Wu, Jian

    2016-01-01

    We experimentally demonstrate spatiotemporal steering of photoelectron emission in multiphoton above-threshold single ionization of atoms exposed to a phase-controlled orthogonally polarized two-color (OTC) laser pulse. Spatial and energy resolved photoelectron angular distributions are measured as a function of the laser phase, allowing us to look into the fine structures and emission dynamics. The slow and fast photoelectrons, distinguished by the energy larger or smaller than 2Up with Up being the ponderomotive energy of a free electron in the laser field, have distinct spatiotemporal dependences of the laser waveform. The phase-of-phase of the slow electron oscillates as functions of both the energy and emission direction, however, the fast electron present rather flat phase structure which merely depends on its emission direction. Three-dimensional generalized quantum trajectory Monte Carlo simulations are performed to explore the sub-cycle dynamics of the electron emission in the phase-controlled OTC pu...

  11. Three-Dimensional Organic Microlasers with Low Lasing Thresholds Fabricated by Multiphoton Lithography

    Chen, Vincent W; Lafargue, Clement; Mansfield, Eric S; Yom, Jeannie; Johnstone, Luke; Hales, Joel M; Bittner, Stefan; Charpignon, Severin; Ulbricht, David; Lautru, Joseph; Denisyuk, Igor; Zyss, Joseph; Perry, Joseph W; Lebental, Melanie

    2014-01-01

    Cuboid-shaped organic microcavities containing a pyrromethene laser dye and supported upon a photonic crystal have been investigated as an approach to reducing the lasing threshold of the cavities. Multiphoton lithography facilitated fabrication of the cuboid cavities directly on the substrate or on the decoupling structure, while similar structures were fabricated on the substrate by UV lithography for comparison. Significant reduction of the lasing threshold by up to a factor of 4 has been observed for cavities supported by the photonic crystal relative to those fabricated on the substrate. The lasing mode spectra of the cuboid microresonators provide strong evidence showing that the lasing modes are localized in the horizontal plane, with the shape of an inscribed diamond.

  12. Non-dipole effects in multiphoton ionization of hydrogen atom in short superintense laser fields

    The development of novel light sources has enabled the realization of high-precision experiments investigating various non-linear processes in the dynamics of atomic, molecular, and ionic systems interacting with high intense laser pulses. At high intensities or short wavelengths, the analysis of these experiments would definitely require a reliable non-perturbative solution of the time-dependent Schroedinger or Dirac equation. These solutions should consider both the temporal and the spatial intensity variations of the laser pulse.We have solved the non-relativistic time dependent Schroedinger equation for a ground state hydrogen atom interacting with short intense spatially and temporally resolved laser fields corresponding to the multiphoton ATI regime for a monochromatic source with λ= 800 nm. We shall analyse the effects of the A2 term and the corresponding orders of the multipolar expansion of the transition matrix.

  13. Entanglement of molecular-orientation, rotational and orbital degrees of freedom in multiphoton orientational wave packets

    Mainos, C.; Dutier, G.; Grucker, J.; Perales, F.; Baudon, J.; Ducloy, M.

    2008-02-01

    Multiphoton orientational wave packets induced by short resonant polarized laser pulses in a rotationally-frozen interacting molecule contain relevant information. The entanglement of the orbital, rotational and orientational degrees of freedom shows a strong dependence on the polarization state of the absorbed photons and the space orientation of the interacting molecule and enables one to assign the orbital state of the excited molecular electron, to measure the space orientation of the interacting molecule from the orientational recurrences, to relate the measured temporal widths to the angular momentum photon state and the coherence of the laser pulse, to obtain information on the ground rotational state, or to measure the effective temperature of an isotropic molecular assembly. The space orientation of a small number of independent molecules can be distinguished from their distinct orientational dependence in the formation of the individual orientational wave packets.

  14. Time and spectrum-resolving multiphoton correlator for 300–900 nm

    Johnsen, Kelsey D.; Thibault, Marilyne; Jennewein, Thomas [Institute for Quantum Computing and Department for Physics and Astronomy, University of Waterloo, 200 University Ave. West, Waterloo, Ontario N2L 3G1 (Canada); Kolenderski, Piotr, E-mail: kolenderski@fizyka.umk.pl [Institute for Quantum Computing and Department for Physics and Astronomy, University of Waterloo, 200 University Ave. West, Waterloo, Ontario N2L 3G1 (Canada); Faculty of Physics, Astronomy and Informatics, Institute of Physics, Nicolaus Copernicus University, Grudziadzka 5, 87-100 Torun (Poland); Scarcella, Carmelo; Tosi, Alberto [Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Piazza Leonardo da Vinci 32, I-20133 Milano (Italy)

    2014-10-14

    We demonstrate a single-photon sensitive spectrometer in the visible range, which allows us to perform time-resolved and multi-photon spectral correlation measurements at room temperature. It is based on a monochromator composed of two gratings, collimation optics, and an array of single photon avalanche diodes. The time resolution can reach 110 ps and the spectral resolution is 2 nm/pixel, limited by the design of the monochromator. This technique can easily be combined with commercial monochromators and can be useful for joint spectrum measurements of two photons emitted in the process of parametric down conversion, as well as time-resolved spectrum measurements in optical coherence tomography or medical physics applications.

  15. Multiphoton dissociation/ionisation of dimethyl sulphide (CH3SCH3) at 355 and 532 nm

    Rajesh K Vatsa; Chiranjib Majumder; Onnattu D Jayakumar; Shailendra K Kulshreshtha; Jai P Mittal

    2001-04-01

    Multiphoton dissociation/ionization has been studied for CH3SCH3 at 355 and 532 nm using a time-of-flight mass spectrometer. The major ion signals observed at 355 nm are C+, CH$_{3}^{+}$, HCS+, CH2S+, CH3S+ and CH3SCH$_{3}^{+}$. Power dependence studies at 355 nm show a (2 + 1) REMPI process for the formation of parent ion. Peaks at / = 46, 47 and 61 show two-photon laser power dependence whereas / = 15 and 45 peaks show four-photon dependence. However, in 532 nm photoionisation, no parent ion signal is observed. A peak at / = 35 corresponding to SH$_{3}^{+}$ has been observed. SH$_{3}^{+}$ has been suggested to originate from CH3SCH$_{2}^{+}$ via a cyclic transition state. Photoionisation results of CH3SCH3 have been compared with those of CH3SSCH3, at these two wavelengths.

  16. Multi-photon quantum interference in a multi-port integrated photonic device

    Metcalf, Benjamin J; Spring, Justin B; Kundys, Dmytro; Broome, Matthew A; Humphreys, Peter; Jin, Xian-Min; Barbieri, Marco; Kolthammer, W Steven; Gates, James C; Smith, Brian J; Langford, Nathan K; Smith, Peter G R; Walmsley, Ian A

    2012-01-01

    Increasing the complexity of quantum photonic devices is essential for many optical information processing applications to reach a regime beyond what can be classically simulated, and integrated photonics has emerged as a leading platform for achieving this. Here, we demonstrate three-photon quantum operation of an integrated device containing three coupled interferometers, eight spatial modes and many classical and nonclassical interferences. This represents a critical advance over previous complexities and the first on-chip nonclassical interference with more than two photonic inputs. We introduce a new scheme to verify quantum behaviour, using classically characterised device elements and hierarchies of photon correlation functions. We accurately predict the device's quantum behaviour and show operation inconsistent with both classical and bi-separable quantum models. Such methods for verifying multiphoton quantum behaviour are vital for achieving increased circuit complexity. Our experiment paves the way ...

  17. High-order harmonic generation and multi-photon ionization of Na2 in laser fields

    Zhang Yan-Ping; Zhang Feng-Shou; Meng Ke-Lai; Xiao Guo-Qing

    2007-01-01

    In this paper high-order harmonic generation (HHG) spectra and the ionization probabilities of various charge states of small cluster Na2 in the multiphoton regimes are calculated by using time-dependent local density approximation (TDLDA) for one-colour (1064 nm) and two-colour (1064 nm and 532 nm) ultrashort (25 fs) laser pulses. HHG spectra of Na2 have not the large extent of plateaus due to pronounced collective effects of electron dynamics. In addition, the two-colour laser field can result in the breaking of the symmetry and generation of the even order harmonic such as the second order harmonic. The results of ionization probabilities show that a two-colour laser field can increase the ionization probability of higher charge state.

  18. Engineering entangled microwave photon states through multiphoton interactions between two cavity fields and a superconducting qubit

    Zhao, Yan-Jun; Wang, Changqing; Zhu, Xiaobo; Liu, Yu-Xi

    2016-04-01

    It has been shown that there are not only transverse but also longitudinal couplings between microwave fields and a superconducting qubit with broken inversion symmetry of the potential energy. Using multiphoton processes induced by longitudinal coupling fields and frequency matching conditions, we design a universal algorithm to produce arbitrary superpositions of two-mode photon states of microwave fields in two separated transmission line resonators, which are coupled to a superconducting qubit. Based on our algorithm, we analyze the generation of evenly-populated states and NOON states. Compared to other proposals with only single-photon process, we provide an efficient way to produce entangled microwave photon states when the interactions between superconducting qubits and microwave fields are in the strong and ultrastrong regime.

  19. The stepwise multi-photon activation fluorescence guided ablation of melanin

    Lai, Zhenhua; Gu, Zetong; DiMarzio, Charles

    2015-02-01

    Previous research has shown that the stepwise multi-photon activation fluorescence (SMPAF) of melanin, activated and excited by a continuous-wave (CW) mode near infrared (NIR) laser, is a low-cost and reliable method for detecting melanin. We have developed a device utilizing the melanin SMPAF to guide the ablation of melanin with a 975 nm CW laser. This method provides the ability of targeting individual melanin particles with micrometer resolution, and enables localized melanin ablation to be performed without collateral damage. Compared to the traditional selective photothermolysis, which uses pulsed lasers for melanin ablation, this method demonstrates higher precision and lower cost. Therefore, the SMPAF guided selective ablation of melanin is a promising tool of melanin ablation for both medical and cosmetic purposes.

  20. 2010 MULTIPHOTON PROCESSES GORDON RESEARCH CONFERENCE, JUNE 6-11, 2010, TILTON, NH

    Mette Gaarde

    2010-06-11

    The Gordon Research Conference on Multiphoton Processes will be held for the 15th time in 2010. The meeting continues to evolve as it embraces both the rapid technological and intellectual growth in the field as well as the multi-disciplinary expertise of the participants. This time the sessions will focus on: (1) Ultrafast coherent control; (2) Free-electron laser experiments and theory; (3) Generation of harmonics and attosecond pulses; (4) Ultrafast imaging; (5) Applications of very high intensity laser fields; (6) Strong-field processes in molecules and solids; (7) Attosecond science; and (8) Controlling light. The scientific program will blur traditional disciplinary boundaries as the presenters and discussion leaders involve chemists, physicists, and optical engineers, representing both experiment and theory. The broad range of expertise and different perspectives of attendees should provide a stimulating and unique environment for solving problems and developing new ideas in this rapidly evolving field.

  1. Generation of multiphoton entangled quantum states by means of integrated frequency combs.

    Reimer, Christian; Kues, Michael; Roztocki, Piotr; Wetzel, Benjamin; Grazioso, Fabio; Little, Brent E; Chu, Sai T; Johnston, Tudor; Bromberg, Yaron; Caspani, Lucia; Moss, David J; Morandotti, Roberto

    2016-03-11

    Complex optical photon states with entanglement shared among several modes are critical to improving our fundamental understanding of quantum mechanics and have applications for quantum information processing, imaging, and microscopy. We demonstrate that optical integrated Kerr frequency combs can be used to generate several bi- and multiphoton entangled qubits, with direct applications for quantum communication and computation. Our method is compatible with contemporary fiber and quantum memory infrastructures and with chip-scale semiconductor technology, enabling compact, low-cost, and scalable implementations. The exploitation of integrated Kerr frequency combs, with their ability to generate multiple, customizable, and complex quantum states, can provide a scalable, practical, and compact platform for quantum technologies. PMID:26965623

  2. Performing high-quality multi-photon experiments with parametric down-conversion

    We demonstrate entanglement swapping of polarization entangled photons using an interferometric Bell-state measurement operating at the theoretical limit of 50% efficiency capable of identifying two of the four Bell states. Our experiment represents the highest quality of entanglement swapping so far, with the correlations of the final entangled states showing an overlap fidelity with the ideal Bell states of F = 0.892, and a violation Bell's inequality for both swapped entangled states. In order to achieve this high-quality operation we have optimized various experimental error sources of our setup including the quality of optical elements, as well as the constraints due to the coherence and the group-velocity mismatch of the pump and down-conversion photons. Our results are relevant for experiments that involve interferences of independent photons and pulsed multi-photon states, such as in quantum computing, quantum metrology and quantum communication with quantum repeaters.

  3. Circular dichroism in hydrogen multiphoton ionization by a bichromatic field of frequencies {omega} and 3{omega}

    Fifirig, Magda [Department of Chemistry, University of Bucharest, Bucharest (Romania); Cionga, Aurelia [Institute of Space Sciences, Bucharest-Magurele (Romania)

    2002-02-28

    The dichroic effects in the multiphoton ionization of the ground state hydrogen atom by a coherent superposition of a laser beam and its third harmonic, are studied via perturbative calculations. The final state of the photoelectrons, which has the energy E=E{sub 1}+3(h/2{pi}){omega} (E{sub 1} the ground state energy and {omega} the laser frequency), is reached by two interfering quantum paths: (a) absorption of one harmonic photon and (b) absorption of three laser photons. In the chosen regime of field intensities, the radiative corrections to the absorption of one harmonic photon may be disregarded. Our numerical results illustrate the influence of the laser frequency, of the relative intensity and of the harmonic phase upon the dichroic signal. (author)

  4. Nonadiabatic geometric phases of multiphoton transitions in dissipative systems and spin-j systems

    We present new developments in nonadiabatic geometric phases along two lines for systems undergoing changes of quantum state in intense fields. We first present a geometric representation of the non-Hermitian Schrodinger equation and introduce the notion of a complex multiphoton Aharonov-Anandan (AA) phase associated with dissipative two-level systems driven by periodic fields. The concept is further extended to include field modulation effects. We then develop the AA phase for spin-j systems in periodic fields and find conditions for cyclic evolution for general multi-level systems. In both cases, generalizations of the Floquet formalism lead to general analytical expressions for geometric phases that can be tested by experiments. 16 refs., 5 figs

  5. Laser-manipulated the multiphoton transitions of a harmonically trapped particle

    Chen Qiong; Hai Kuo; Hai Wen-Hua

    2007-01-01

    A single particle magneto-confined in a one-dimensional (1D) quantum wire experiences a harmonic potential,and imposing a sharply focused laser beam on an appropriate site shapes a δ potential. The theoretical investigation has demonstrated that for a sufficiently strong δ pulse the quantum motional stationary state of the particle is one of the eigenstatss of the free harmonic oscillator, and it is determined by the site of the laser beam uniquely, namely a quantum state is admissible if and only if the laser site is one of its nodes. The numerical computation shows that all the nodes of the lower energy states with quantum numbers n ≤ 20, except the coordinate origin, are mutually different.So we can manipulate the multiphoton transitions between the quantum states by adjusting the position of the laser δpulse and realize the transition from an unknown higher excitation state to a required lower energy state.

  6. Multiphoton dissociation and thermal unimolecular reactions induced by infrared lasers. [REAMPA code

    Dai, H.L.

    1981-04-01

    Multiphoton dissociation (MPD) of ethyl chloride was studied using a tunable 3.3 ..mu..m laser to excite CH stretches. The absorbed energy increases almost linearly with fluence, while for 10 ..mu..m excitation there is substantial saturation. Much higher dissociation yields were observed for 3.3 ..mu..m excitation than for 10 ..mu..m excitation, reflecting bottlenecking in the discrete region of 10 ..mu..m excitation. The resonant nature of the excitation allows the rate equations description for transitions in the quasicontinuum and continuum to be extended to the discrete levels. Absorption cross sections are estimated from ordinary ir spectra. A set of cross sections which is constant or slowly decreasing with increasing vibrational excitation gives good fits to both absorption and dissociation yield data. The rate equations model was also used to quantitatively calculate the pressure dependence of the MPD yield of SF/sub 6/ caused by vibrational self-quenching. Between 1000-3000 cm/sup -1/ of energy is removed from SF/sub 6/ excited to approx. > 60 kcal/mole by collision with a cold SF/sub 6/ molecule at gas kinetic rate. Calculation showed the fluence dependence of dissociation varies strongly with the gas pressure. Infrared multiphoton excitation was applied to study thermal unimolecular reactions. With SiF/sub 4/ as absorbing gas for the CO/sub 2/ laser pulse, transient high temperature pulses were generated in a gas mixture. IR fluorescence from the medium reflected the decay of the temperature. The activation energy and the preexponential factor of the reactant dissociation were obtained from a phenomenological model calculation. Results are presented in detail. (WHK)

  7. Coherent Control of Multiphoton Transitions in the Gas and Condensed Phases with Shaped Ultrashort Pulses

    Controlling laser-molecule interactions has become an integral part of developing devices and applications in spectroscopy, microscopy, optical switching, micromachining and photochemistry. Coherent control of multiphoton transitions could bring a significant improvement of these methods. In microscopy, multi-photon transitions are used to activate different contrast agents and suppress background fluorescence; coherent control could generate selective probe excitation. In photochemistry, different dissociative states are accessed through two, three, or more photon transitions; coherent control could be used to select the reaction pathway and therefore the yield-specific products. For micromachining and processing a wide variety of materials, femtosecond lasers are now used routinely. Understanding the interactions between the intense femtosecond pulse and the material could lead to technologically important advances. Pulse shaping could then be used to optimize the desired outcome. The scope of our research program is to develop robust and efficient strategies to control nonlinear laser-matter interactions using ultrashort shaped pulses in gas and condensed phases. Our systematic research has led to significant developments in a number of areas relevant to the AMO Physics group at DOE, among them: generation of ultrashort phase shaped pulses, coherent control and manipulation of quantum mechanical states in gas and condensed phases, behavior of isolated molecules under intense laser fields, behavior of condensed phase matter under intense laser field and implications on micromachining with ultrashort pulses, coherent control of nanoparticles their surface plasmon waves and their nonlinear optical behavior, and observation of coherent Coulomb explosion processes at 1016 W/cm2. In all, the research has resulted in 36 publications (five journal covers) and nine invention disclosures, five of which have continued on to patenting

  8. Analysis of pesticides by gas chromatography/multiphoton ionization/mass spectrometry using a femtosecond laser

    Highlights: → Gas chromatography/multiphoton ionization/time-of-flight mass spectrometry was utilized for analysis. → A standard mixture sample containing 49 pesticides and 4 real samples were measured. → Third-harmonic emission of a Ti:sapphire laser (100 fs) was employed as an ionization source. → Most of the pesticides were softly ionized by the femtosecond laser. → Three pesticides were found, although some of them were not detected by GC/EI/MS-MS. - Abstract: Gas chromatography/multiphoton ionization/time-of-flight mass spectrometry (GC/MPI/TOFMS) was utilized for analysis of a standard mixture sample containing 49 pesticides and 4 real samples using the third-harmonic emission (267 nm) of a femtosecond Ti:sapphire laser (100 fs) as the ionization source. A sample of a standard mixture of n-alkane was also measured for calibration of the retention time indices of the pesticides. Two photons are required for the excitation of n-alkane due to an absorption band located in the far ultraviolet region (140 nm). The n-alkane molecule in the excited state was subsequently ionized either directly or by absorbing another photon because of a high ionization potential. Due to a large excess of energy, the molecular ion was decomposed and formed many fragment ions. Compared to n-alkanes, most of the pesticides were softly ionized by the femtosecond laser; one photon was used for excitation and another was used for the subsequent ionization. The pesticides with no conjugated double bond had a lower ionization efficiency. The present analytical instrument was applied to several samples prepared from a variety of vegetables and a single fruit after pretreatment with solid-phase extraction. Three pesticides were found in these samples, although some of them were not detected by conventional GC/EI/MS-MS due to insufficient sensitivity and selectivity.

  9. Multiphoton ionization in a short-range potential: A nonperturbative approach

    We introduce an alternative approach to the study of multiphoton ionization. The approach is based on consideration of the relative frequency instead of the relative field strength of the applied laser field as a small parameter (or, equivalently, a large number of photons). The choice is based on the characteristics of present-day lasers. We apply our approach specifically to an electron bound by a δ-function potential. In order to show a simpler situation first, we start by applying our analysis to the time-independent tunneling problem from such a potential due to an external electrostatic field. For this problem, we derive from first principles the well-known ionization rate for tunneling. Next, we derive with the same general formalism an analytical formula, asymptotic in the number of photons, for the multiphoton ionization rate, under strong field conditions, of an electron confined by a δ-function potential. We also obtain the ionization rate from a numerical solution of the corresponding equations. The comparison with the analytical expression is very good, even for a small number of photons. Our approach puts the results of Perelomov, Popov, and Terentev (Zh. Eksp. Teor. Fiz. 50, 1393 (1966) [Sov. Phys. JETP 23, 924 (1966)]) on a rigorous basis as well as extending them to a wider range of parameters. To cover analytically the few-photon case, we also develop a perturbation theory in the relative field strength to calculate the ionization rate. This perturbative approach has the advantage over the conventional Rayleigh-Schroedinger theory in that it effectively takes into account the continuum without having to deal with it directly. The comparison with the numerical results is also very good

  10. Determination of triacetone triperoxide using ultraviolet femtosecond multiphoton ionization time-of-flight mass spectrometry

    Highlights: • A UV ultrashort laser pulse was useful for ionization of triacetone triperoxide. • A molecular ion was strongly enhanced in multiphoton ionization mass spectrometry. • Triacetone triperoxide in the human blood was measured without any interferences. • An organic compound of phorone was formed in the human blood from acetone. - Abstract: Triacetone triperoxide (TATP), an explosive compound, was measured using gas chromatography combined with multiphoton ionization time-of-flight mass spectrometry (GC/MPI-TOFMS). By decreasing the pulse width of a femtosecond laser from 80 to 35 fs, a molecular ion was drastically enhanced and was measured as one of the major ions in the mass spectrum. The detection limits obtained using the molecular (M·+) and fragment (C2H3O+) ions were similar or slightly superior to those obtained using conventional mass spectrometry based on electron and chemical ionization. In order to improve the reliability, an isotope of TATP, i.e., TATP-d18, was synthesized and used as an internal standard in the trace analysis of TATP in a sample of human blood. TATP could be identified in a two-dimensional display, even though numerous interfering compounds were present in the sample. Acetone, which is frequently used as a solvent in sampling TATP, produced a chemical species with a retention time nearly identical to that of TATP and provided a C2H3O+ fragment ion that was employed for measuring a chromatogram of TATP in conventional MS. This compound, the structure of which was assigned as phorone, was clearly differentiated from TATP based on a molecular ion observable in MPI-TOFMS

  11. Label-free in vivo imaging of Drosophila melanogaster by multiphoton microscopy

    Lin, Chiao-Ying; Hovhannisyan, Vladimir; Wu, June-Tai; Lin, Sung-Jan; Lin, Chii-Wann; Chen, Jyh-Horng; Dong, Chen-Yuan

    2008-02-01

    The fruit fly Drosophila melanogaster is one of the most valuable organisms in genetic and developmental biology studies. Drosophila is a small organism with a short life cycle, and is inexpensive and easy to maintain. The entire genome of Drosophila has recently been sequenced (cite the reference). These advantages make fruit fly an attractive model organism for biomedical researches. Unlike humans, Drosophila can be subjected to genetic manipulation with relative ease. Originally, Drosophila was mostly used in classical genetics studies. In the model era of molecular biology, the fruit fly has become a model organ for developmental biology researches. In the past, numerous molecularly modified mutants with well defined genetic defects affecting different aspects of the developmental processes have been identified and studied. However, traditionally, the developmental defects of the mutant flies are mostly examined in isolated fixed tissues which preclude the observation of the dynamic interaction of the different cell types and the extracellular matrix. Therefore, the ability to image different organelles of the fruit fly without extrinsic labeling is invaluable for Drosophila biology. In this work, we successfully acquire in vivo images of both developing muscles and axons of motor neurons in the three larval stages by using the minimially invasive imaging modality of multiphoton (SHG) microscopy. We found that while SHG imaging is useful in revealing the muscular architecture of the developing larva, it is the autofluorescence signal that allows label-free imaging of various organelles to be achieved. Our results demonstrate that multiphoton imaging is a powerful technique for investigation the development of Drosophila.

  12. Density matrix equation analysis of optical–optical double-resonance multiphoton ionization probability

    An analytical formula of the optical–optical double-resonance multi-photon ionization (OODR-MPI) probability is derived from the time-dependent density-matrix equations that describe the interaction of photon and material. Based on the formula, the variation of the multiphoton ionization (MPI) probability with laser resonance detuning, Rabi frequency, laser pulse duration and ionization rate is investigated theoretically. It is shown that the MPI probability will decrease with the increase of laser resonance detuning, to some extent, to zero. The influence of the pump laser resonance detuning on the ionization probability is more important with respect to the probe laser. It not only influences Rabi frequency for saturation, but also the saturation value of MPI probability. The MPI probability will increase with Rabi frequency, laser pulse duration and ionization rate. It is also found that though the variation of the populations in the ground, the first and the second resonance states is different at the beginning of laser radiation, but they will still decrease to zero as the time goes on. It is then that the ionization probability gets the maximum value. Thus long laser pulse duration and high laser intensity are in favor for improving the MPI probability. These theoretical research results can provide a useful guide for the practical application of OODR-MPI spectroscopy. - Highlights: • An analytical expression of OODR-MPI probability has been derived. • MPI probability decreases with the increase of laser resonance detuning. • The influence of pump laser on the MPI probability is larger than probe laser. • Larger laser pulse duration and intensity are in favor of higher MPI probability

  13. Coherent control of multiphoton dynamics and high-order-harmonic generation driven by two frequency-comb fields with a relative envelope delay

    Zhao, Di; Jiang, Chen-Wei; Li, Fu-li

    2016-07-01

    We present a theoretical investigation of the coherent control of multiphoton dynamics and a high-order-harmonic generation (HHG) process driven by two frequency-comb fields, via the interference of multiphoton transition paths by tuning the relative envelope delay between fields. The many-mode Floquet theorem is employed to provide a nonperturbative and exact treatment of the interaction between a quantum system and frequency-comb laser fields. The case of two frequency-comb fields with the same repetition frequency and the carrier frequencies of fundamental and second harmonics, respectively, is considered. Due to the coupling of the second harmonic controlling the frequency-comb laser field, multiphoton transitions involving both fundamental- and second-harmonic photons occur. Different multiphoton transition paths can be superpositioned when the matching condition for carrier-envelope-phase shifts is satisfied, offering the possibility of coherent control of HHG power spectra via the interference of paths by tuning the relative envelope delay between fields. The calculated HHG power spectra present both sub-cycle oscillation and multi-cycle modulation behavior when the relative envelope delay is varied. It is also found that, under the condition of multiphoton resonance, the HHG power spectra can be further enhanced by about 10 times via the interference of multiphoton transition paths by tuning the relative envelope delay.

  14. Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability.

    Tozer, G M; Prise, V E; Wilson, J; Cemazar, M; Shan, S; Dewhirst, M W; Barber, P R; Vojnovic, B; Chaplin, D J

    2001-09-01

    The tumor vascular effects of the tubulin destabilizing agent disodium combretastatinA-4 3-O-phosphate (CA-4-P) were investigated in the rat P22 tumor growing in a dorsal skin flap window chamber implanted into BD9 rats. CA-4-P is in clinical trial as a tumor vascular targeting agent. In animal tumors, it can cause the shut-down of blood flow, leading to extensive tumor cell necrosis. However, the mechanisms leading to vascular shut-down are still unknown. Tumor vascular effects were visualized and monitored on-line before and after the administration of two doses of CA-4-P (30 and 100 mg/kg) using intravital microscopy. The combined effect of CA-4-P and systemic nitric oxide synthase (NOS) inhibition using N(omega)-nitro-L-arginine (L-NNA) was also assessed, because this combination has been shown previously to have a potentiating effect. The early effect of CA-4-P on tumor vascular permeability to albumin was determined to assess whether this could be involved in the mechanism of action of the drug. Tumor blood flow reduction was extremely rapid after CA-4-P treatment, with red cell velocity decreasing throughout the observation period and dropping to blood flow reduction was very different for NOS inhibition and CA-4-P. That of NOS inhibition could be explained by a decrease in vessel diameter, which was most profound on the arteriolar side of the tumor circulation. In contrast, the effects of CA-4-P resembled an acute inflammatory reaction resulting in a visible loss of a large proportion of the smallest blood vessels. There was some return of visible vasculature at 1 h after treatment, but the blood in these vessels was static or nearly so, and many of the vessels were distended. The hematocrit within larger draining tumor venules tended to increase at early times after CA-4-P, suggesting fluid loss from the blood. The stacking of red cells to form rouleaux was also a common feature, coincident with slowing of blood flow; and these two factors would lead to an

  15. Detection and mapping of trace explosives on surfaces under ambient conditions using multiphoton electron extraction spectroscopy (MEES).

    Tang, Shisong; Vinerot, Nataly; Fisher, Danny; Bulatov, Valery; Yavetz-Chen, Yehuda; Schechter, Israel

    2016-08-01

    Multiphoton electron extraction spectroscopy (MEES) is an analytical method in which UV laser pulses are utilized for extracting electrons from solid surfaces in multiphoton processes under ambient conditions. Counting the emitted electrons as a function of laser wavelength results in detailed spectral features, which can be used for material identification. The method has been applied to detection of trace explosives on a variety of surfaces. Detection was possible on dusty swabs spiked with explosives and also in the standard dry-transfer contamination procedure. Plastic explosives could also be detected. The analytical limits of detection (LODs) are in the sub pmole range, which indicates that MEES is one of the most sensitive detection methods for solid surface under ambient conditions. Scanning the surface with the laser allows for its imaging, such that explosives (as well as other materials) can be located. The imaging mode is also useful in forensic applications, such as detection of explosives in human fingerprints. PMID:27216679

  16. Imaging the morphological change of tissue structure during the early phase of esophageal tumor progression using multiphoton microscopy

    Xu, Jian; Kang, Deyong; Xu, Meifang; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2012-12-01

    Esophageal cancer is a common malignancy with a very poor prognosis. Successful strategies for primary prevention and early detection are critically needed to control this disease. Multiphoton microscopy (MPM) is becoming a novel optical tool of choice for imaging tissue architecture and cellular morphology by two-photon excited fluorescence. In this study, we used MPM to image microstructure of human normal esophagus, carcinoma in situ (CIS), and early invasive carcinoma in order to establish the morphological features to differentiate these tissues. The diagnostic features such as the appearance of cancerous cells, the significant loss of stroma, the absence of the basement membrane were extracted to distinguish between normal and cancerous esophagus tissue. These results correlated well with the paired histological findings. With the advancement of clinically miniaturized MPM and the multi-photon probe, combining MPM with standard endoscopy will therefore allow us to make a real-time in vivo diagnosis of early esophageal cancer at the cellular level.

  17. Multiphoton Double Ionization of Ar in Intense Extreme Ultraviolet Laser Fields Studied by Shot-by-Shot Photoelectron Spectroscopy

    Photoelectron spectroscopy has been performed to study the multiphoton double ionization of Ar in an intense extreme ultraviolet laser field (hν∼21 eV, ∼5 TW/cm2), by using a free electron laser (FEL). Three distinct peaks identified in the observed photoelectron spectra clearly show that the double ionization proceeds sequentially via the formation of Ar+: Ar+hν→Ar++e- and Ar++2hν→Ar2++e-. Shot-by-shot recording of the photoelectron spectra allows simultaneous monitoring of FEL spectrum and the multiphoton process for each FEL pulse, revealing that the two-photon ionization from Ar+ is significantly enhanced by intermediate resonances in Ar+.

  18. An apparatus for isotopic ratio measurement in UF5 formed by infrared multiphoton dissociation of UF6 in molecular beam

    A Separation factor was measured in isotopically selective infrared multiphoton dissociation (IRMPD) of supercooled UF6 in a supersonic expansion by multiphoton ionization (MPI) and time-of-flight mass spectrometry (TOFMS). A pulsed free-jet nozzle was used to generate a UF6-molecular beam seeded in Ar (∼10-7 Torr in UF6 partial pressure). Two-frequency p-H2 Raman laser beams around 16 μm were used for the dissociation of UF6 under collisionless conditions in the molecular beam where the flow velocity for UF6 is about 500 m/s. The 235U/238U isotopic ratios in nascent UF5 photoproducts were determined by selective MPI of UF5 at 532 nm followed by TOFMS with a mass resolution as high as 1200. A separation factor of about 2 was observed under the experimental conditions chosen for the demonstration of this method. (author)

  19. Theoretical description of circular dichroism in photoelectron angular distributions of randomly oriented chiral molecules after multi-photon photoionization

    Goetz, R E; Nikoobakht, B; Berger, R; Koch, C P

    2016-01-01

    Photoelectron circular dichroism refers to the forward/backward asymmetry in the photoelectron angular distribution with respect to the propagation axis of circularly polarized light. It has recently been demonstrated in femtosecond multi-photon photoionization experiments with randomly oriented camphor and fenchone molecules [C. Lux et al., Angew. Chem. Int. Ed. 51, 5001 (2012);C. S. Lehmann et al., J. Chem. Phys. 139, 234307 (2013)]. A theoretical framework describing this process as (2+1) resonantly enhanced multi-photon ionization is constructed, which consists of two-photon photoselection from randomly oriented molecules and successive one-photon ionisation of the photoselected molecules. It combines perturbation theory for the light-matter interaction with ab initio calculations for the two-photon absorption and a single-center expansion of the photoelectron wavefunction in terms of hydrogenic continuum functions. It is verified that the model correctly reproduces the basic symmetry behavior expected un...

  20. Interband photorefractive effect in beta-BBO crystal due to multiphoton excitation by intense ultrashort optical pulses.

    Xu, Shixiang; Cai, Hua; Zeng, Heping

    2007-08-20

    This paper presents the first experimental observation of interband photo- refractive (PR) effects in beta-BBO crystal due to multiphoton excitation with intense ultrashort pulses. In order to fully characterize the PR effects, a sensitive intracavity scheme is developed to magnify the dynamics of nonlinear lenses induced by the PR effects. The reproducible PR phenomena depend strongly on the power, wavelength, and spatial intensity profile of the intense laser pulses and the electro-optic coefficient of the optical materials. Its response time is from tens of seconds to several minutes. The results may be very helpful for us to find a solution to overcome the deleterious influence of multiphoton induced photo-charges on nonlinear optical frequency conversions, e.g. optical parametric chirped pulse amplification. PMID:19547410

  1. Molecular photoelectron angular distribution rotations in multi-photon resonant ionization of H2+ by circularly polarized ultraviolet laser pulses

    We study effects of pulse durations on molecular photoelectron angular distributions (MPADs) in ultrafast circular polarization ultraviolet resonant ionization processes. Simulations performed on aligned H2+ by numerically solving time dependent Schrödinger equations show rotations of MPADs with respect to the molecular symmetry axes. It is found that in multi-photon resonant ionization processes, rotation angles are sensitive to pulse durations, which we attribute to the coherent resonant excitation between the ground state and the intermediate excited electronic state induced by Rabi oscillations. Multi-photon nonresonant and single photon ionization processes are simulated and compared which exhibit a constant rotation angle. An asymmetry parameter is introduced to describe the pulse duration sensitivity by perturbation theory models. Influence of pulse frequency detunings on MPADs is also investigated where oscillations of rotations are absent at long pulse durations due to nonresonance excitation

  2. Revival-collapse phenomenon in the quadrature squeezing of the multiphoton intensity-dependent Jaynes Cummings model

    El-Orany, Faisal A. A.

    2006-12-01

    For the multiphoton intensity-dependent Jaynes Cummings model (JCM) described by a two-level atom interacting with a radiation field, we prove that there is a relationship between the atomic inversion and the quadrature squeezing. We give the required condition to obtain best information from this relation. Also we show that this relation is only sensitive to large values of the detuning parameter. Furthermore, we discuss briefly such relation for the off-resonance standard JCM.

  3. Revival-collapse phenomenon in the quadrature squeezing of the multiphoton intensity-dependent Jaynes-Cummings model

    El-Orany, Faisal A A

    2009-01-01

    For multiphoton intensity-dependent Jaynes-Cummings model (JCM), which is described by two-level atom interacting with a radiation field, we prove that there is a relationship between the atomic inversion and the quadrature squeezing. We give the required condition to obtain best information from this relation. Also we show that this relation is only sensitive to large values of the detuning parameter. Furthermore, we discuss briefly such relation for the off-resonance standard JCM.

  4. S-matrix analysis of vibrational and alignment effects in intense-field multiphoton ionization of molecules

    Requate, A.

    2007-03-15

    Theoretical analysis of the vibrational excitation of small molecules during multiphoton ionization in intense laser fields of optical and infrared frequencies. Analysis of the alignment dependence of the electron impact ionization of diatomic molecules in the presence of an intense laser field as the final step in the process of Nonsequential Double Ionization. Quantum mechanical description using S-matrix theory in Strong Field Approximation (SFA), i.e. beyond perturbation theory. (orig.)

  5. Light-induced temperature jump causes power-dependent ultrafast kinetics of electrons generated in multiphoton ionization of liquid water

    Crowell, Robert A.; Lian, Rui; Shkrob, Ilya A.; Qian, Jun; Oulianov, Dmitri A.; Pommeret, Stanislas

    2004-01-01

    Picosecond geminate recombination kinetics for electrons generated by multiphoton ionization of liquid water become power dependent when the radiance of the excitation light is greater than 0.3-0.5 TW/cm^2 (the terawatt regime). To elucidate the mechanism of this power dependence, tri- 400 nm photon ionization of water has been studied using pump-probe laser spectroscopy on the pico- and femtosecond time scales. We suggest that the observed kinetic transformations are caused by a rapid temper...

  6. S-matrix analysis of vibrational and alignment effects in intense-field multiphoton ionization of molecules

    Theoretical analysis of the vibrational excitation of small molecules during multiphoton ionization in intense laser fields of optical and infrared frequencies. Analysis of the alignment dependence of the electron impact ionization of diatomic molecules in the presence of an intense laser field as the final step in the process of Nonsequential Double Ionization. Quantum mechanical description using S-matrix theory in Strong Field Approximation (SFA), i.e. beyond perturbation theory. (orig.)

  7. Resonance-enhanced multiphoton ionization photoelectron spectroscopy of Rydberg states of N2O below the X ionization limit

    Scheper, C.R.; Kuijt, J.; Buma, W.J.; Lange

    1998-01-01

    A three-photon resonance-enhanced multiphoton ionization spectroscopic study on N2O is carried out in the spectral range from 80 000 cm - 1 up to the lowest ionization limit at 103 963 cm - 1. High-resolution photoelectron spectroscopy is used to identify and characterize the observed excited states. Eighteen origins are reported which have either not been assigned before or are reassigned now. Moreover, the photoelectron spectra taken at higher-lying resonances often show extensive vibronic ...

  8. Relativistic theory of the above-threshold multiphoton ionization of hydrogen-like atoms in the ultrastrong laser fields

    Avetissian, H. K.; Markossian, A. G.; Mkrtchian, G. F.

    1999-01-01

    The relativistic theory of above-threshold ionization (ATI) of hydrogen-like atoms in ultrastrong radiation fields, taking into account the photoelectron induced rescattering in the continuum spectrum is developed. It is shown that the contribution of the latter in the multiphoton ionization probability even in the Born approximation by Coulomb field is of the order of ATI probability in the scope of Keldysh-Faisal-Reiss ansatz.

  9. In vivo measurements of cutaneous melanin across spatial scales: Using multiphoton microscopy and spatial frequency domain spectroscopy

    Saager, RB; Balu, M; Crosignani, V; Sharif, A; Durkin, AJ; Kelly, KM; Tromberg, BJ

    2015-01-01

    © 2015 The Authors. The combined use of nonlinear optical microscopy and broadband reflectance techniques to assess melanin concentration and distribution thickness in vivo over the full range of Fitzpatrick skin types is presented. Twelve patients were measured using multiphoton microscopy (MPM) and spatial frequency domain spectroscopy (SFDS) on both dorsal forearm and volar arm, which are generally sun-exposed and non-sun-exposed areas, respectively. Both MPM and SFDS measured melanin volu...

  10. Controlling the transmitted information of a multi-photon interacting with a single-Cooper pair box

    We study a model of a multi-photon interaction of a single Cooper pair box with a cavity field. The exchange of the information using this system is studied. We quantify the fidelity of the transmitted information. The effect of the system parameters (detuning parameter, field photons, state density and mean photon number) in the fidelity of the transmitted information is investigated. We found that the fidelity of the transmitted information can be controlled using the system parameters

  11. Controlling the transmitted information of a multi-photon interacting with a single-Cooper pair box

    Kadry, Heba, E-mail: hkadry1@yahoo.com; Abdel-Aty, Abdel-Haleem, E-mail: hkadry1@yahoo.com; Zakaria, Nordin, E-mail: hkadry1@yahoo.com [Computer and Information Science Department, Universiti Teknologi Petronas, Seri Iskandar, 31750 Tronoh, Perak (Malaysia); Cheong, Lee Yen [Fundamental and Applied Science Department, Universiti Teknologi Petronas, Seri Iskandar, 31750 Tronoh, Perak (Malaysia)

    2014-10-24

    We study a model of a multi-photon interaction of a single Cooper pair box with a cavity field. The exchange of the information using this system is studied. We quantify the fidelity of the transmitted information. The effect of the system parameters (detuning parameter, field photons, state density and mean photon number) in the fidelity of the transmitted information is investigated. We found that the fidelity of the transmitted information can be controlled using the system parameters.

  12. Multiphoton Ca2+ production occurring before the onset of Ca+ saturation: is it a fingerprint of direct double ionization?

    Singly and doubly charged Ca ions have been produced by multiphoton excitation of Ca vapour with 5 ns, low intensity (≤3 x 1011 W cm-2) dye-laser pulses in the 675-685 nm wavelength range, including the four-photon 4s21S0 → 4p21S0 excitation. The intensity and wavelength dependence of the ion yields was recorded as well as the fluorescence emission from excited states of the Ca ion in an effort to identify the excitation pathways leading to single and double ionization. Unambiguous evidence for the absorption of at least two photons above the first ionization threshold was recorded, in agreement with earlier results for Mg and Sr obtained under similar conditions. However, certain characteristics of the process differ significantly from those of the earlier results, despite the apparent similarity in both the atomic structure and the excitation scheme. The most striking and unexpected finding is that for a certain wavelength, the Ca2+ yield is observable well before the saturation intensity of Ca+ and, moreover, it grows with intensity and saturates in parallel with the Ca+ yield. Possible mechanisms behind this outcome are discussed in detail as well as their implications for the multiphoton multiple ionization of complex atoms. Our tentative conclusion is that the occurrence of doubly charged ion production before the singly charged ion saturation should not be considered as 'synonymous' with direct (or non-sequential) multiphoton double ionization.

  13. Effect of the odd-photon destructive interference on laser-induced transparency and multiphoton excitation and ionization in rubidium

    We report experimental results on two-color multiphoton ionization and four-wave-mixing production under conditions where one form of laser-induced transparency (LIT) occurs. Under the conditions of LIT, multiphoton-ionization line shapes obtained by tuning one laser through a two-photon resonance exhibit a pronounced Autler-Townes splitting at low concentrations, when a second laser couples the two-photon state to a third level. In this concentration region we observed a four-wave-mixing field that increased quadratically with concentration. As the concentration is increased the Autler-Townes splitting starts to decrease, and disappears completely as a critical concentration is reached. Simultaneously, the four-wave-mixing field intensity starts to level off and finally becomes concentration independent. These observations are explained in terms of odd-photon destructive interference between different excitation pathways. In rubidium, we demonstrate that above concentrations of n≅5x1014 cm-3 the four-wave-mixing field is concentration independent and the multiphoton-ionization line shape shows no Autler-Townes splitting, and the width of the line shape is determined by the laser bandwidth. The results presented here demonstrate that destructive interference significantly limits the high-efficiency and high-intensity nonlinear optical generation promised in early studies on LIT, at least for the multimode laser system used in the present experiment. copyright 1996 The American Physical Society

  14. Atomic Energy Commission Act, 2000 (Act 588)

    Act 588 of the Republic of Ghana entitled, Atomic Energy Commission Act, 2000, amends and consolidates the Atomic Energy Commission Act, 204 of 1963 relating to the establishment of the Atomic Energy Commission. Act 588 makes provision for the Ghana Atomic Energy Commission to establish more institutes for the purpose of research in furtherance of its functions and also promote the commercialization of its research and development results. (E.A.A.)

  15. Multimodal microscopy and the stepwise multi-photon activation fluorescence of melanin

    Lai, Zhenhua

    The author's work is divided into three aspects: multimodal microscopy, stepwise multi-photon activation fluorescence (SMPAF) of melanin, and customized-profile lenses (CPL) for on-axis laser scanners, which will be introduced respectively. A multimodal microscope provides the ability to image samples with multiple modalities on the same stage, which incorporates the benefits of all modalities. The multimodal microscopes developed in this dissertation are the Keck 3D fusion multimodal microscope 2.0 (3DFM 2.0), upgraded from the old 3DFM with improved performance and flexibility, and the multimodal microscope for targeting small particles (the "Target" system). The control systems developed for both microscopes are low-cost and easy-to-build, with all components off-the-shelf. The control system have not only significantly decreased the complexity and size of the microscope, but also increased the pixel resolution and flexibility. The SMPAF of melanin, activated by a continuous-wave (CW) mode near-infrared (NIR) laser, has potential applications for a low-cost and reliable method of detecting melanin. The photophysics of melanin SMPAF has been studied by theoretical analysis of the excitation process and investigation of the spectra, activation threshold, and photon number absorption of melanin SMPAF. SMPAF images of melanin in mouse hair and skin, mouse melanoma, and human black and white hairs are compared with images taken by conventional multi-photon fluorescence microscopy (MPFM) and confocal reflectance microscopy (CRM). SMPAF images significantly increase specificity and demonstrate the potential to increase sensitivity for melanin detection compared to MPFM images and CRM images. Employing melanin SMPAF imaging to detect melanin inside human skin in vivo has been demonstrated, which proves the effectiveness of melanin detection using SMPAF for medical purposes. Selective melanin ablation with micrometer resolution has been presented using the Target system

  16. Multiphoton microscopy, fluorescence lifetime imaging and optical spectroscopy for the diagnosis of neoplasia

    Skala, Melissa Caroline

    2007-12-01

    Cancer morbidity and mortality is greatly reduced when the disease is diagnosed and treated early in its development. Tissue biopsies are the gold standard for cancer diagnosis, and an accurate diagnosis requires a biopsy from the malignant portion of an organ. Light, guided through a fiber optic probe, could be used to inspect regions of interest and provide real-time feedback to determine the optimal tissue site for biopsy. This approach could increase the diagnostic accuracy of current biopsy procedures. The studies in this thesis have characterized changes in tissue optical signals with carcinogenesis, increasing our understanding of the sensitivity of optical techniques for cancer detection. All in vivo studies were conducted on the dimethylbenz[alpha]anthracene treated hamster cheek pouch model of epithelial carcinogenesis. Multiphoton microscopy studies in the near infrared wavelength region quantified changes in tissue morphology and fluorescence with carcinogenesis in vivo. Statistically significant morphological changes with precancer included increased epithelial thickness, loss of stratification in the epithelium, and increased nuclear diameter. Fluorescence changes included a statistically significant decrease in the epithelial fluorescence intensity per voxel at 780 nm excitation, a decrease in the fluorescence lifetime of protein-bound nicotinamide adenine dinucleotide (NADH, an electron donor in oxidative phosphorylation), and an increase in the fluorescence lifetime of protein-bound flavin adenine dinucleotide (FAD, an electron acceptor in oxidative phosphorylation) with precancer. The redox ratio (fluorescence intensity of FAD/NADH, a measure of the cellular oxidation-reduction state) did not significantly change with precancer. Cell culture experiments (MCF10A cells) indicated that the decrease in protein-bound NADH with precancer could be due to increased levels of glycolysis. Point measurements of diffuse reflectance and fluorescence spectra in

  17. Tunable Fabrication of Molybdenum Disulfide Quantum Dots for Intracellular MicroRNA Detection and Multiphoton Bioimaging.

    Dai, Wenhao; Dong, Haifeng; Fugetsu, Bunshi; Cao, Yu; Lu, Huiting; Ma, Xinlei; Zhang, Xueji

    2015-09-01

    Molybdenum disulfide (MoS2 ) quantum dots (QDs) (size MoS2 QDs has not been investigated in great detail. Here, a facile and efficient approach for synthesis of controllable-size MoS2 QDs with excellent photoluminescence (PL) by using a sulfuric acid-assisted ultrasonic route is developed for this investigation. Various MoS2 structures including monolayer MoS2 flake, nanoporous MoS2 , and MoS2 QDs can be yielded by simply controlling the ultrasonic durations. Comprehensive microscopic and spectroscopic tools demonstrate that the MoS2 QDs have uniform lateral size and possess excellent excitation-independent blue PL. The as-generated MoS2 QDs show high quantum yield of 9.65%, long fluorescence lifetime of 4.66 ns, and good fluorescent stability over broad pH values from 4 to 10. Given the good intrinsic optical properties and large surface area combined with excellent physiological stability and biocompatibility, a MoS2 QDs-based intracellular microRNA imaging analysis system is successfully constructed. Importantly, the MoS2 QDs show good performance as multiphoton bioimaging labeling. The proposed synthesis strategy paves a new way for facile and efficient preparing MoS2 QDs with tunable-size for biomedical imaging and optoelectronic devices application. PMID:26033986

  18. Investigation of signal-to-noise ratio in frequency-domain multiphoton fluorescence lifetime imaging microscopy.

    Zhang, Yide; Khan, Aamir A; Vigil, Genevieve D; Howard, Scott S

    2016-07-01

    Multiphoton microscopy (MPM) combined with fluorescence lifetime imaging microscopy (FLIM) has enabled three-dimensional quantitative molecular microscopy in vivo. The signal-to-noise ratio (SNR), and thus the imaging rate of MPM-FLIM, which is fundamentally limited by the shot noise and fluorescence saturation, has not been quantitatively studied yet. In this paper, we investigate the SNR performance of the frequency-domain (FD) MPM-FLIM with two figures of merit: the photon economy in the limit of shot noise, and the normalized SNR in the limit of saturation. The theoretical results and Monte Carlo simulations find that two-photon FD-FLIM requires 50% fewer photons to achieve the same SNR as conventional one-photon FLIM. We also analytically show that the MPM-FD-FLIM can exploit the DC and higher harmonic components generated by nonlinear optical mixing of the excitation light to improve SNR, reducing the required number of photons by an additional 50%. Finally, the effect of fluorophore saturation on the experimental SNR performance is discussed. PMID:27409702

  19. Simultaneous multiple-excitation multiphoton microscopy yields increased imaging sensitivity and specificity

    Brinkman Brendan C

    2011-03-01

    Full Text Available Abstract Background Multiphoton microscopy (MPM offers many advantages over conventional wide-field and confocal laser scanning microscopy (CLSM for imaging biological samples such as 3D resolution of excitation, reduced phototoxicity, and deeper tissue imaging. However, adapting MPM for critical multi-color measurements presents a challenge because of the largely overlapping two-photon absorption (TPA peaks of common biological fluorophores. Currently, most multi-color MPM relies on the absorbance at one intermediate wavelength of multiple dyes, which introduces problems such as decreased and unequal excitation efficiency across the set of dyes. Results Here we describe an MPM system incorporating two, independently controlled sources of two-photon excitation whose wavelengths are adjusted to maximally excite one dye while minimally exciting the other. We report increased signal-to-noise ratios and decreased false positive emission bleed-through using this novel multiple-excitation MPM (ME-MPM compared to conventional single-excitation MPM (SE-MPM in a variety of multi-color imaging applications. Conclusions Similar to the tremendous gain in popularity of CLSM after the introduction of multi-color imaging, we anticipate that the ME-MPM system will further increase the popularity of MPM. In addition, ME-MPM provides an excellent tool to more rapidly design and optimize pairs of fluorescence probes for multi-color two-photon imaging, such as CFP/YFP or GFP/DsRed for CLSM.

  20. Label-free identification of the hippocampus and surrounding structures by multiphoton microscopy

    Wang, Shu; Jiang, Liwei; Du, Huiping; Wang, Xingfu; Zheng, Liqin; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin

    2016-05-01

    The hippocampus is one of the essential neuroanatomical substrates and plays an important role in different neurological illnesses. In this work, multiphoton microscopy (MPM) based on intrinsic nonlinear optical processes two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), was applied to label-freely detect the entire hippocampus and surrounding structures in high-magnification imaging, as well as acquire large-scale MPM images at subcellular resolution. It was found that MPM has the capability to identify cornu ammonis, dentate gyrus (DG), alveus, and fimbria of the entire hippocampus, choroid plexus in lateral ventricles, and white matter tracts. MPM also can be used to quantitatively describe the differences of the cellular nucleus in the cornu ammonis and the DG, further identify the morphological features of hippocampal subfields. In addition, the surrounding structures of the hippocampus including the lateral ventricles and white matter serve as useful information to determine the position of the hippocampus. Our results suggest that with the development of the clinical feasibility of two-photon fiberscopes and microendoscope probes, MPM has the potential for in vivo intraoperative identification and monitoring of hippocampus-related lesions without the need for tissue labelling or fluorescent markers.