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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. 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.

  10. 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.

  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 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.

  13. 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

  14. 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...

  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. 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

  11. 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 ...

  12. 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...

  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. 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

  19. 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

  20. 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

  1. 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.

  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. 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.

  9. 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.

  10. 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.

  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. 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...

  14. 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. ...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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 ...

  20. 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

  1. 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 ...

  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. 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

  5. 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.

  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. 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

  10. 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.

  11. 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.

  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. 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

  15. 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.

  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. 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.

  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. 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.

  1. 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.

  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. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  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. 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....

  12. 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.

  13. 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.

  14. 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

  15. 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.

  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. 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...

  19. 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...

  20. 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...

  1. 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 ...

  2. 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.

  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. 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.

  5. 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.

  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. 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.

  8. 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.

  9. 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

  10. 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.

  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. 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.

  15. 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.

  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. 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

  19. 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....

  20. 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

  1. 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...

  2. 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.

  3. 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....

  4. 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

  5. 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.

  6. 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

  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 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.

  11. 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.

  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. 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

  15. 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

  16. 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

  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. 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.

  4. 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...

  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. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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...

  17. 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...

  18. 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

  19. 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 ...

  20. 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...

  1. 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.

  2. 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.

  3. 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,...

  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. 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

  6. 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

  7. 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

  8. 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

  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. 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

  11. 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

  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. 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)

  14. 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...

  15. 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.

  16. 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)

  17. 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...

  18. 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

  19. 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

  20. 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.

  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. 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.

  3. 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.

  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. 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

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. 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

  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. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  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. 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.

  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. 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...

  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. 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...

  8. 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...

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  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. 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...

  18. 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...

  19. 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

  20. 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...

  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. 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...