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Sample records for multiphoton jaynes-cummings model

  1. Generalized Jaynes-Cummings model as a quantum search algorithm

    SciTech Connect

    Romanelli, A.

    2009-07-15

    We propose a continuous time quantum search algorithm using a generalization of the Jaynes-Cummings model. In this model the states of the atom are the elements among which the algorithm realizes the search, exciting resonances between the initial and the searched states. This algorithm behaves like Grover's algorithm; the optimal search time is proportional to the square root of the size of the search set and the probability to find the searched state oscillates periodically in time. In this frame, it is possible to reinterpret the usual Jaynes-Cummings model as a trivial case of the quantum search algorithm.

  2. Oscillator-like coherent states for the Jaynes-Cummings Model

    NASA Technical Reports Server (NTRS)

    Berubelauziere, Y.; Hussin, V.; Nieto, Michael M.

    1995-01-01

    A new way of diagonalizing the Jaynes-Cummings Hamiltonian is proposed, which allows the definition of annihilation operators and coherent states for this model. Mean values and dispersions over these states are computed and interpreted.

  3. From the Jaynes-Cummings-Hubbard to the Dicke model

    NASA Astrophysics Data System (ADS)

    Schmidt, S.; Blatter, G.; Keeling, J.

    2013-11-01

    We discuss the Jaynes-Cummings-Hubbard model describing the superfluid-Mott insulator transition of polaritons (i.e., dressed photon-qubit states) in coupled qubit-cavity arrays in the crossover from strong to weak correlations. In the strongly correlated regime the phase diagram and the elementary excitations of lattice polaritons near the Mott lobes are calculated analytically using a slave-boson theory (SBT). The opposite regime of weakly interacting polariton superfluids is described by a weak-coupling mean-field theory for a generalized multi-mode Dicke model. We show that a remarkable relation between the two theories exists in the limit of large photon bandwidth and large negative detuning, i.e., when the nature of polariton quasiparticles becomes qubit-like. In this regime, the weak-coupling theory predicts the existence of a single Mott lobe with a change of the universality class of the phase transition at the tip of the lobe, in perfect agreement with the SBT. Moreover, the spectra of low energy excitations, i.e., the sound velocity of the Goldstone mode and the gap of the amplitude mode match exactly as calculated from both theories.

  4. Grassmann phase space theory and the Jaynes-Cummings model

    NASA Astrophysics Data System (ADS)

    Dalton, B. J.; Garraway, B. M.; Jeffers, J.; Barnett, S. M.

    2013-07-01

    The Jaynes-Cummings model of a two-level atom in a single mode cavity is of fundamental importance both in quantum optics and in quantum physics generally, involving the interaction of two simple quantum systems—one fermionic system (the TLA), the other bosonic (the cavity mode). Depending on the initial conditions a variety of interesting effects occur, ranging from ongoing oscillations of the atomic population difference at the Rabi frequency when the atom is excited and the cavity is in an n-photon Fock state, to collapses and revivals of these oscillations starting with the atom unexcited and the cavity mode in a coherent state. The observation of revivals for Rydberg atoms in a high-Q microwave cavity is key experimental evidence for quantisation of the EM field. Theoretical treatments of the Jaynes-Cummings model based on expanding the state vector in terms of products of atomic and n-photon states and deriving coupled equations for the amplitudes are a well-known and simple method for determining the effects. In quantum optics however, the behaviour of the bosonic quantum EM field is often treated using phase space methods, where the bosonic mode annihilation and creation operators are represented by c-number phase space variables, with the density operator represented by a distribution function of these variables. Fokker-Planck equations for the distribution function are obtained, and either used directly to determine quantities of experimental interest or used to develop c-number Langevin equations for stochastic versions of the phase space variables from which experimental quantities are obtained as stochastic averages. Phase space methods have also been developed to include atomic systems, with the atomic spin operators being represented by c-number phase space variables, and distribution functions involving these variables and those for any bosonic modes being shown to satisfy Fokker-Planck equations from which c-number Langevin equations are often

  5. Strong coupling expansion for the Bose-Hubbard and Jaynes-Cummings lattice models.

    PubMed

    Heil, Christoph; von der Linden, Wolfgang

    2012-07-25

    A strong coupling expansion based on the Kato-Bloch perturbation theory, which has recently been proposed by Eckardt et al (2009 Phys. Rev. B 79 195131) and Teichmann et al (2009 Phys. Rev. B 79 224515), is implemented in order to study various aspects of the Bose-Hubbard and Jaynes-Cummings lattice models. The approach, which allows us to generate numerically all diagrams up to a desired order in the interaction strength, is generalized for disordered systems and for the Jaynes-Cummings lattice model. Results for the Bose-Hubbard and Jaynes-Cummings lattice models will be presented and compared with results from the variational cluster approach and density matrix renormalization group. Our focus will be on the Mott insulator to superfluid transition.

  6. Berry phase in a two-atom Jaynes-Cummings model with Kerr medium

    NASA Astrophysics Data System (ADS)

    Bu, Shen-Ping; Zhang, Guo-Feng; Liu, Jia; Chen, Zi-Yu

    2008-12-01

    The Jaynes-Cummings model (JCM) is an very important model for describing interaction between quantized electromagnetic fields and atoms in cavity quantum electrodynamics (QED). This model is generalized in many different directions since it predicts many novel quantum effects that can be verified by modern physics experimental technologies. In this paper, the Berry phase and entropy of the ground state for arbitrary photon number n of a two-atom Jaynes-Cummings model with Kerr-like medium are investigated. It is found that there is some correspondence between their images, especially the existence of a curve in the Δ-ɛ plane along which the energy, Berry phase and entropy all reach their special values. So it is available for detecting entanglement by applying Berry phase.

  7. A generalized Jaynes-Cummings model: The relativistic parametric amplifier and a single trapped ion

    SciTech Connect

    Ojeda-Guillén, D.; Mota, R. D.; Granados, V. D.

    2016-06-15

    We introduce a generalization of the Jaynes-Cummings model and study some of its properties. We obtain the energy spectrum and eigenfunctions of this model by using the tilting transformation and the squeezed number states of the one-dimensional harmonic oscillator. As physical applications, we connect this new model to two important and novelty problems: the relativistic parametric amplifier and the quantum simulation of a single trapped ion.

  8. Inhibition of atomic dipole collapses by squeezed light: a Jaynes-Cummings model treatment

    NASA Astrophysics Data System (ADS)

    Ben-Aryeh, Y.; Miller, C. A.; Risken, H.; Schleich, W.

    1992-06-01

    We investigate the collapse of the atomic dipole caused by a squeezed vacuum in an ideal one-mode cavity. The difference between the collapse times of the two quadrature components of the dipole moments is increasing with increasing squeezing parameter. This phenomenon predicted by a hamiltonian Jaynes-Cummings model is similar to the inhibition and enhancement of atomic phase decay predicted by Gardiner for a markovian system.

  9. Exact non-Markovian master equation for the spin-boson and Jaynes-Cummings models

    NASA Astrophysics Data System (ADS)

    Ferialdi, L.

    2017-02-01

    We provide the exact non-Markovian master equation for a two-level system interacting with a thermal bosonic bath, and we write the solution of such a master equation in terms of the Bloch vector. We show that previous approximated results are particular limits of our exact master equation. We generalize these results to more complex systems involving an arbitrary number of two-level systems coupled to different thermal baths, providing the exact master equations also for these systems. As an example of this general case we derive the master equation for the Jaynes-Cummings model.

  10. Mean-field and quantum-fluctuation dynamics in the driven dispersive Jaynes-Cummings model

    NASA Astrophysics Data System (ADS)

    Mavrogordatos, Th.; Szafulski, P.; Ginossar, E.; Szymańska, M. H.

    2016-12-01

    In this work we investigate the regime of amplitude bistability in the driven dissipative Jaynes-Cummings (JC) model. We study the semiclassical equation dynamics in contrast to entangled cavity-photon and qubit quantum trajectories, discussing our results in the context of an out-of-equilibrium first order quantum dissipative phase transition for a single JC resonator. Finally, we compare the switching process between metastable states for the two system degrees of freedom by examining a single realization of the random qubit vector in the Bloch sphere next to the intracavity amplitude quasi distributions at given time instants.

  11. Integrability and superintegrability of the generalized n-level many-mode Jaynes-Cummings and Dicke models

    SciTech Connect

    Skrypnyk, T.

    2009-10-15

    We analyze symmetries of the integrable generalizations of Jaynes-Cummings and Dicke models associated with simple Lie algebras g and their reductive subalgebras g{sub K}[T. Skrypnyk, 'Generalized n-level Jaynes-Cummings and Dicke models, classical rational r-matrices and nested Bethe ansatz', J. Phys. A: Math. Theor. 41, 475202 (2008)]. We show that their symmetry algebras contain commutative subalgebras isomorphic to the Cartan subalgebras of g, which can be added to the commutative algebras of quantum integrals generated with the help of the quantum Lax operators. We diagonalize additional commuting integrals and constructed with their help the most general integrable quantum Hamiltonian of the generalized n-level many-mode Jaynes-Cummings and Dicke-type models using nested algebraic Bethe ansatz.

  12. A classical simulation of nonlinear Jaynes-Cummings and Rabi models in photonic lattices.

    PubMed

    Rodríguez-Lara, B M; Soto-Eguibar, Francisco; Cárdenas, Alejandro Zárate; Moya-Cessa, H M

    2013-05-20

    The interaction of a two-level atom with a single-mode quantized field is one of the simplest models in quantum optics. Under the rotating wave approximation, it is known as the Jaynes-Cummings model and without it as the Rabi model. Real-world realizations of the Jaynes-Cummings model include cavity, ion trap and circuit quantum electrodynamics. The Rabi model can be realized in circuit quantum electrodynamics. As soon as nonlinear couplings are introduced, feasible experimental realizations in quantum systems are drastically reduced. We propose a set of two photonic lattices that classically simulates the interaction of a single two-level system with a quantized field under field nonlinearities and nonlinear couplings as long as the quantum optics model conserves parity. We describe how to reconstruct the mean value of quantum optics measurements, such as photon number and atomic energy excitation, from the intensity and from the field, such as von Neumann entropy and fidelity, at the output of the photonic lattices. We discuss how typical initial states involving coherent or displaced Fock fields can be engineered from recently discussed Glauber-Fock lattices. As an example, the Buck-Sukumar model, where the coupling depends on the intensity of the field, is classically simulated for separable and entangled initial states.

  13. Fock-space localization of polaritons in the Jaynes-Cummings dimer model

    NASA Astrophysics Data System (ADS)

    Shapourian, Hassan; Sadri, Darius

    2016-01-01

    We present a method to study the semiclassical dynamics of the Jaynes-Cummings dimer model, describing two coupled cavities, each containing a two-level system (qubit). We develop a Fock-space WKB approach in the polariton basis where each site is treated exactly while the intersite polariton hopping is treated semiclassically. We show that the self-trapped states can be viewed as Fock-space localized states. We find that this picture yields the correct critical value of interaction strength at which the delocalization-localization transition occurs. Moreover, the validity of our WKB approach is supported by showing that the quantum spectrum can be derived from a set of Bohr-Sommerfeld quantization conditions and by confirming that the quantum eigenstates are consistent with the classical orbital motion in the polariton band picture. The underlying idea of our method is quite general and can be applied to other interacting spin-boson models.

  14. Quantum Entanglement in Double Quantum Systems and Jaynes-Cummings Model.

    PubMed

    Jakubczyk, Paweł; Majchrowski, Klaudiusz; Tralle, Igor

    2017-12-01

    In the paper, we proposed a new approach to producing the qubits in electron transport in low-dimensional structures such as double quantum wells or double quantum wires (DQW). The qubit could arise as a result of quantum entanglement of two specific states of electrons in DQW structure. These two specific states are the symmetric and antisymmetric (with respect to inversion symmetry) states arising due to tunneling across the structure, while entanglement could be produced and controlled by means of the source of nonclassical light. We examined the possibility to produce quantum entanglement in the framework of Jaynes-Cummings model and have shown that at least in principle, the entanglement can be achieved due to series of "revivals" and "collapses" in the population inversion due to the interaction of a quantized single-mode EM field with a two-level system.

  15. Equivalent spin-orbit interaction in the two-polariton Jaynes-Cummings-Hubbard model

    PubMed Central

    Li, C.; Zhang, X. Z.; Song, Z.

    2015-01-01

    A cavity quantum electrodynamics (cavity-QED) system combines two or more distinct quantum components, exhibiting features not seen in the individual systems. In this work, we study the one-dimensional Jaynes-Cummings-Hubbard model in the two-excitation (two-polariton) subspace. We find that the centre momentum of two-excitation induces a magnetic flux piercing the equivalent Hamiltonian Hk in the invariant subspace with momentum k, which can be described as a 4-leg ladder in the auxiliary space. Furthermore, it is shown that the system in π-centre-momentum subspace is equivalent to a lattice system for spin-1 particle with spin-orbit coupling. On the basis of this concise description, a series of bound-pair eigenstates which display long-range polaritonic entanglement is presented as a simple application. PMID:26159665

  16. Effects of spin-orbit coupling on Jaynes-Cummings and Tavis-Cummings models

    NASA Astrophysics Data System (ADS)

    Zhu, Chuanzhou; Dong, Lin; Pu, Han

    2016-11-01

    We consider ultracold atoms inside a ring optical cavity that supports a single plane-wave mode. The cavity field, together with an external coherent laser field, drives a two-photon Raman transition between two internal pseudospin states of the atom. This gives rise to an effective coupling between atom's pseudospin and external center-of-mass (COM) motion. For the case of a single atom inside the cavity, We show how the spin-orbit coupling modifies the static and dynamic properties of the Jaynes-Cummings (JC) model. In the case of many atoms in thermodynamic limit, we show that the spin-orbit coupling modifies the Dicke superradiance phase transition boundary and the non-superradiant normal phase may become reentrant in some regimes.

  17. Quantum revivals of a non-Rabi type in a Jaynes-Cummings model

    NASA Astrophysics Data System (ADS)

    Ozhigov, Yu. I.; Skovoroda, N. A.; Victorova, N. B.

    2016-11-01

    We study full revivals (e.g., the reappearance in the unitary evolution) of quantum states in the Jaynes-Cummings model with the rotating wave approximation. We prove that in the case of a zero detuning in subspaces generated by two adjacent pairs of energy levels, full revival does not exist for any values of the parameters. In contrast, the set of parameters that allows full revival is everywhere dense in the set of all parameters in the case of a nonzero detuning. The nature of these revivals differs from Rabi oscillations for a single pair of energy levels. In more complex subspaces, the presence of full revival reduces to particular cases of the tenth Hilbert problem for rational solutions of systems of nonlinear algebraic equations, which has no algorithmic solution in the general case. Non-Rabi revivals become partial revivals in the case where the rotating wave approximation is rejected.

  18. A note on approximate teleportation of an unknown atomic state in the two-photon Jaynes-Cummings model

    NASA Astrophysics Data System (ADS)

    dSouza, A. D.; Cardoso, W. B.; Avelar, A. T.; Baseia, B.

    2009-04-01

    We consider recent schemes [J.M. Liu, B. Weng, Physica A 367 (2006) 215] to teleport unknown atomic states and superposition of zero- and two-photon states using the two-photon Jaynes-Cummings model. Here we do the same using the “full two-photon Jaynes-Cumming”, valid for arbitrary average number of photons. The success probability and fidelity of this teleportation are also considered.

  19. A semi-classical study of the Jaynes-Cummings model

    NASA Astrophysics Data System (ADS)

    Babelon, O.; Cantini, L.; Douçot, B.

    2009-07-01

    We consider the Jaynes-Cummings model of a single quantum spin s coupled to a harmonic oscillator in a parameter regime where the underlying classical dynamics exhibits an unstable equilibrium point. This state of the model is relevant to the physics of cold atom systems, in non-equilibrium situations obtained by fast sweeping through a Feshbach resonance. We show that in this integrable system with two degrees of freedom, for any initial condition close to the unstable point, the classical dynamics is controlled by a singularity of the focus-focus type. In particular, it displays the expected monodromy, which forbids the existence of global action-angle coordinates. Explicit calculations of the joint spectrum of conserved quantities reveal the monodromy at the quantum level, as a dislocation in the lattice of eigenvalues. We perform a detailed semi-classical analysis of the associated eigenstates. Whereas most of the levels are well described by the usual Bohr-Sommerfeld quantization rules, properly adapted to polar coordinates, we show how these rules are modified in the vicinity of the critical level. The spectral decomposition of the classically unstable state is computed, and is found to be dominated by the critical WKB states. This provides a useful tool with which to analyze the quantum dynamics starting from this particular state, which exhibits an aperiodic sequence of solitonic pulses with a rather well defined characteristic frequency.

  20. Parity Deformed Jaynes-Cummings Model: “Robust Maximally Entangled States”

    PubMed Central

    Dehghani, A.; Mojaveri, B.; Shirin, S.; Faseghandis, S. Amiri

    2016-01-01

    The parity-deformations of the quantum harmonic oscillator are used to describe the generalized Jaynes-Cummings model based on the λ-analog of the Heisenberg algebra. The behavior is interestingly that of a coupled system comprising a two-level atom and a cavity field assisted by a continuous external classical field. The dynamical characters of the system is explored under the influence of the external field. In particular, we analytically study the generation of robust and maximally entangled states formed by a two-level atom trapped in a lossy cavity interacting with an external centrifugal field. We investigate the influence of deformation and detuning parameters on the degree of the quantum entanglement and the atomic population inversion. Under the condition of a linear interaction controlled by an external field, the maximally entangled states may emerge periodically along with time evolution. In the dissipation regime, the entanglement of the parity deformed JCM are preserved more with the increase of the deformation parameter, i.e. the stronger external field induces better degree of entanglement. PMID:27917882

  1. Parity Deformed Jaynes-Cummings Model: “Robust Maximally Entangled States”

    NASA Astrophysics Data System (ADS)

    Dehghani, A.; Mojaveri, B.; Shirin, S.; Faseghandis, S. Amiri

    2016-12-01

    The parity-deformations of the quantum harmonic oscillator are used to describe the generalized Jaynes-Cummings model based on the λ-analog of the Heisenberg algebra. The behavior is interestingly that of a coupled system comprising a two-level atom and a cavity field assisted by a continuous external classical field. The dynamical characters of the system is explored under the influence of the external field. In particular, we analytically study the generation of robust and maximally entangled states formed by a two-level atom trapped in a lossy cavity interacting with an external centrifugal field. We investigate the influence of deformation and detuning parameters on the degree of the quantum entanglement and the atomic population inversion. Under the condition of a linear interaction controlled by an external field, the maximally entangled states may emerge periodically along with time evolution. In the dissipation regime, the entanglement of the parity deformed JCM are preserved more with the increase of the deformation parameter, i.e. the stronger external field induces better degree of entanglement.

  2. Dark-polariton bound pairs in the modified Jaynes-Cummings-Hubbard model

    NASA Astrophysics Data System (ADS)

    Maggitti, A.; Radonjić, M.; Jelenković, B. M.

    2016-01-01

    We investigate a one-dimensional modified Jaynes-Cummings-Hubbard chain of N identical QED cavities with nearest-neighbor photon tunneling and periodic boundary conditions. Each cavity contains an embedded three-level atom which is coupled to a cavity mode and an external classical control field. In the case of two excitations and common large detuning of two Raman-resonant fields, we show the emergence of two different species of dark-polariton bound pairs (DPBPs) that are mutually localized in their relative spatial coordinates. Due to the high degree of controllability, we show the appearance of either one or two DPBPs, having the energies within the energy gaps between three bands of mutually delocalized eigenstates. Interestingly, in a different parameter regime with negatively detuned Raman fields, we find that the ground state of the system is a DPBP which can be utilized for the photon storage, retrieval, and controllable state preparation. Moreover, we propose an experimental realization of our model system.

  3. Exact treatment of the Jaynes-Cummings model under the action of an external classical field

    SciTech Connect

    Abdalla, M. Sebawe; Khalil, E.M.; Obada, A.S.-F.

    2011-09-15

    We consider the usual Jaynes-Cummings model (JCM), in the presence of an external classical field. Under a certain canonical transformation for the Pauli operators, the system is transformed into the usual JCM. Using the equations of motion in the Heisenberg picture, exact solutions for the time-dependent dynamical operators are obtained. In order to calculate the expectation values of these operators, the wave function has been constructed. It has been shown that the classical field augments the atomic frequency {omega}{sub 0} and mixes the original atomic states. Changes of squeezing from one quadrature to another is also observed for a strong value of the coupling parameter of the classical field. Furthermore, the system in this case displays partial entanglement and the state of the field losses its purity. - Highlights: > The time-dependent JCM, in the presence of the classical field, is still one of the essential problems in the quantum optics. > A new approach is applied through a certain canonical transformation. > The classical field augments the atomic frequency {omega}{sub 0} and mixes the original atomic states.

  4. Exact mapping of the 2+1 Dirac oscillator onto the Jaynes-Cummings model: Ion-trap experimental proposal

    SciTech Connect

    Bermudez, A.; Martin-Delgado, M. A.; Solano, E.

    2007-10-15

    We study the dynamics of the 2+1 Dirac oscillator exactly and find spin oscillations due to a Zitterbewegung of purely relativistic origin. We find an exact mapping of this quantum-relativistic system onto a Jaynes-Cummings model, describing the interaction of a two-level atom with a quantized single-mode field. This equivalence allows us to map a series of quantum optical phenomena onto the relativistic oscillator and vice versa. We make a realistic experimental proposal, in reach with current technology, for studying the equivalence of both models using a single trapped ion.

  5. Entanglement and the Jaynes-Cummings model with Rydberg-dressed atoms

    NASA Astrophysics Data System (ADS)

    Biedermann, Grant

    2016-05-01

    Controlling quantum entanglement between parts of a many-body system is the key to unlocking the power of quantum information processing for applications such as quantum computation, high-precision sensing, and simulation of many-body physics. Spin degrees of freedom of ultracold neutral atoms in their ground electronic state provide a natural platform given their long coherence times and our ability to control them with magneto-optical fields, but creating strong coherent coupling between spins has been challenging. We demonstrate for the first time a strong and tunable Rydberg-dressed interaction between spins of individually trapped cesium atoms with energy shifts of order 1 MHz in units of Planck's constant. We spectroscopically demonstrate that this system is isomorphic to a Jaynes-Cummings Hamiltonian, and observe the √{ N} nonlinearity of the Jaynes-Cummings ladder with a single symmetric Rydberg excitation. This interaction enables a ground-state spin-flip blockade, whereby simultaneous hyperfine spin flips of two atoms are blockaded due to their mutual interaction. We employ this spin-flip blockade to rapidly produce single-step Bell-state entanglement between atoms. This work was supported by the Laboratory Directed Research and Development program at Sandia National Laboratories and through the National Science Foundation's Center for Quantum Information and Control NSF-1212445.

  6. On the relationship between the classical Dicke-Jaynes-Cummings-Gaudin model and the nonlinear Schroedinger equation

    SciTech Connect

    Du, Dianlou; Geng, Xue

    2013-05-15

    In this paper, the relationship between the classical Dicke-Jaynes-Cummings-Gaudin (DJCG) model and the nonlinear Schroedinger (NLS) equation is studied. It is shown that the classical DJCG model is equivalent to a stationary NLS equation. Moreover, the standard NLS equation can be solved by the classical DJCG model and a suitably chosen higher order flow. Further, it is also shown that classical DJCG model can be transformed into the classical Gaudin spin model in an external magnetic field through a deformation of Lax matrix. Finally, the separated variables are constructed on the common level sets of Casimir functions and the generalized action-angle coordinates are introduced via the Hamilton-Jacobi equation.

  7. Enhanced spin squeezing and quantum entanglement near the critical point of the Jaynes-Cummings-Dicke model

    NASA Astrophysics Data System (ADS)

    Bhattacherjee, Aranya B.; Sharma, Deepti

    2017-04-01

    We investigate spin squeezing (SS) and the quantum Fisher information (QFI) for the Jaynes-Cummings-Dicke (JCD) model in a two-component atomic Bose-Einstein condensate (BEC) inside an optical cavity. Analytical expressions for spin squeezing and the reciprocal of the quantum Fisher information per particle (RMQFI) are derived using the frozen spin approximation. It is shown that in the superradiant phase near the critical point, maximum squeezing and maximum quantum entanglement occur and thus the critical point emerges as a useful resource for precision measurements. In the presence of decoherence and particle loss, we show that gradually with time, even though the ability of squeezing and entanglement generation are weakened, yet significant amounts are still present which can be relevant to quantum information processing and precision spectroscopy.

  8. Amplitude-Squared Squeezing in the m-PHOTON Jaynes-Cummings Model with Squeezed Field Input

    NASA Astrophysics Data System (ADS)

    Mir, Mubeen A.; Razmi, M. S. K.

    Amplitude-squared (AS) squeezing has been investigated for the m-photon Jaynes-Cummings model assuming the field to be initially in the squeezed states. The role played by intensity-dependent coupling has also been discussed. It has been shown that for the large initial average photon number (bar {n}) with odd values of m, AS squeezing revokes permanently whereas with even values it recurs periodically. As m increases the revocation is hastened and the duration of occurrence decreases. Higher values of m for the initial field in a squeezed vacuum state can make one of the quadrature permanently squeezed. The AS squeezing behavior for two initial states of the atom, i.e., ground state versus excited state is also compared.

  9. Fifty years of Jaynes-Cummings physics

    NASA Astrophysics Data System (ADS)

    Greentree, Andrew D.; Koch, Jens; Larson, Jonas

    2013-11-01

    This special issue commemorates the 50th anniversary of the seminal paper published by E T Jaynes and F W Cummings [1], the fundamental model which they introduced and now carries their names, and celebrates the remarkable host of exciting research on Jaynes-Cummings physics throughout the last five decades. The Jaynes-Cummings model has been taking the prominent stance as the 'hydrogen atom of quantum optics' [2]. Generally speaking, it provides a fundamental quantum description of the simplest form of coherent radiation-matter interaction. The Jaynes-Cummings model describes the interaction between a single electromagnetic mode confined to a cavity, and a two-level atom. Energy is exchanged between the field and the atom, which leads directly to coherent population oscillations (Rabi oscillations) and superposition states (dressed states). Being exactly solvable, the Jaynes-Cummings model serves as a most useful toy model, and as such it is a textbook example of the physicists' popular strategy of simplifying a complex problem to its most elementary constituents. Thanks to the simplicity of the Jaynes-Cummings model, this caricature of coherent light-matter interactions has never lost its appeal. The Jaynes-Cummings model is essential when discussing experiments in quantum electrodynamics (indeed the experimental motivation of the Jaynes-Cummings model was evident already in the original paper, dealing as it does with the development of the maser), and it has formed the starting point for much fruitful research ranging from ultra-cold atoms to cavity quantum electrodynamics. In fact, Jaynes-Cummings physics is at the very heart of the beautiful experiments by S Haroche and D Wineland, which recently earned them the 2012 Nobel Prize in physics. Indeed, as with most significant models in physics, the model is invoked in settings that go far beyond its initial framework. For example, recent investigations involving multi-level atoms, multiple atoms [3, 4], multiple

  10. "Twisted" rational r-matrices and the algebraic Bethe ansatz: Applications to generalized Gaudin models, Bose-Hubbard dimers, and Jaynes-Cummings-Dicke-type models

    NASA Astrophysics Data System (ADS)

    Skrypnyk, T. V.

    2016-10-01

    We construct quantum integrable systems associated with the Lie algebra gl( n) and non-skew-symmetric "shifted and twisted" rational r-matrices. The obtained models include Gaudin-type models with and without an external magnetic field, n-level ( n-1)-mode Jaynes-Cummings-Dicke-type models in the Λ-configuration, a vector generalization of Bose-Hubbard dimers, etc. We diagonalize quantum Hamiltonians of the constructed integrable models using a nested Bethe ansatz.

  11. A transparent mechanism of Q function splitting in a Jaynes-Cummings model with intensity-dependent level shift

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Xu, Chang; Ren, Zhongzhou

    2015-10-01

    We investigate the tripartite relationship between the collapse and revival, the Q function splitting and the energy level structure in the Jaynes-Cummings (JC) model with an intensity-dependent level shift whose magnitude is tuned to give rise to periodic collapse and revivals. We show that this constitutes a clearer demonstration of the mechanism of Q function splitting and its relation with the collapse and revival than the standard JC model itself. The eigenstates form two groups, both of which form equidistant ladders with differing energy intervals. This structure gives rise to the periodic splitting and reunion of the Q function. Only when the reunion happens, a non-vanishing mutual interference between the two groups is possible and gives rise to observable Rabi oscillations. The possibility of observing the phenomena using a Rubidium atom in a cavity is also discussed. We believe the present work could contribute to the understanding of the collapse and revival and the Q function-splitting phenomena.

  12. A classical simulation of nonlinear Jaynes-Cummings and Rabi models in photonic lattices: comment.

    PubMed

    Lo, C F

    2014-01-27

    Recently Rodriguez-Lara et al. [Opt. Express 21(10), 12888 (2013)] proposed a classical simulation of the dynamics of the nonlinear Rabi model by propagating classical light fields in a set of two photonic lattices. However, the nonlinear Rabi model has already been rigorously proven to be undefined by Lo [Quantum Semiclass. Opt. 10, L57 (1998)]. Hence, the proposed classical simulation is actually not applicable to the nonlinear Rabi model and the simulation results are completely invalid.

  13. Atomic Dipole Squeezing in the Correlated Two-Mode Two-Photon Jaynes-Cummings Model

    NASA Technical Reports Server (NTRS)

    Dong, Zhengchao; Zhao, Yonglin

    1996-01-01

    In this paper, we study the atomic dipole squeezing in the correlated two-mode two-photon JC model with the field initially in the correlated two-mode SU(1,1) coherent state. The effects of detuning, field intensity and number difference between the two field modes are investigated through numerical calculation.

  14. ELECTROMAGNETISM, OPTICS, ACOUSTICS, HEAT TRANSFER, CLASSICAL MECHANICS, AND FLUID DYNAMICS: Entropy and Entanglement in Master Equation of Effective Hamiltonian for Jaynes-Cummings Model

    NASA Astrophysics Data System (ADS)

    Hessian, H. A.; Mohammed, F. A.; Mohamed, A.-B. A.

    2009-04-01

    In this paper, we analytically solve the master equation for Jaynes-Cummings model in the dispersive regime including phase damping and the field is assumed to be initially in a superposition of coherent states. Using an established entanglement measure based on the negativity of the eigenvalues of the partially transposed density matrix we find a very strong sensitivity of the maximally generated entanglement to the amount of phase damping. Qualitatively this behavior is also reflected in alternative entanglement measures, but the quantitative agreement between different measures depends on the chosen noise model. The phase decoherence for this model results in monotonic increase in the total entropy while the atomic sub-entropy keeps its periodic behaviour without any effect.

  15. (p,q) deformations and (p,q)-vector coherent states of the Jaynes-Cummings model in the rotating wave approximation

    SciTech Connect

    Ben Geloun, Joseph; Govaerts, Jan; Hounkonnou, M. Norbert

    2007-03-15

    Classes of (p,q) deformations of the Jaynes-Cummings model in the rotating wave approximation are considered. Diagonalization of the Hamiltonian is performed exactly, leading to useful spectral decompositions of a series of relevant operators. The latter include ladder operators acting between adjacent energy eigenstates within two separate infinite discrete towers, except for a singleton state. These ladder operators allow for the construction of (p,q)-deformed vector coherent states. Using (p,q) arithmetics, explicit and exact solutions to the associated moment problem are displayed, providing new classes of coherent states for such models. Finally, in the limit of decoupled spin sectors, our analysis translates into (p,q) deformations of the supersymmetric harmonic oscillator, such that the two supersymmetric sectors get intertwined through the action of the ladder operators as well as in the associated coherent states.

  16. ELECTROMAGNETISM, OPTICS, ACOUSTICS, HEAT TRANSFER, CLASSICAL MECHANICS, AND FLUID DYNAMICS: Properties of Linear Entropy in k-Photon Jaynes-Cummings Model with Stark Shift and Kerr-Like Medium

    NASA Astrophysics Data System (ADS)

    Liao, Qing-Hong; Ashfaq Ahmad, Muhammad; Wang, Yue-Yuan; Liu, Shu-Tian

    2010-05-01

    The time evolution of the linear entropy of an atom in k-photon Jaynes-Cummings model is investigated taking into consideration Stark shift and Kerr-like medium. The effect of both the Stark shift and Kerr-like medium on the linear entropy is analyzed using a numerical technique for the field initially in coherent state and in even coherent state. The results show that the presence of the Kerr-like medium and Stark shift has an important effect on the properties of the entropy and entanglement. It is also shown that the setting of the initial state plays a significant role in the evolution of the linear entropy and entanglement.

  17. Demonstration of the Jaynes-Cummings ladder with Rydberg-dressed atoms

    DOE PAGES

    Lee, Jongmin; Martin, Michael J.; Jau, Yuan-Yu; ...

    2017-04-06

    Here, we observe the nonlinearity of the Jaynes-Cummings (JC) ladder in the Autler-Townes spectroscopy of the hyperfine ground states for a Rydberg-dressed two-atom system. The role of the two-level system in the JC model is played by the presence or absence of a collective Rydberg excitation, and the bosonic mode manifests as the number n of single-atom spin flips, symmetrically distributed between the atoms. We also measure the normal-mode splitting and √ n nonlinearity as a function of detuning and Rabi frequency, thereby experimentally establishing the isomorphism with the JC model.

  18. Cavity losses for the dissipative Jaynes Cummings Hamiltonian beyond rotating wave approximation

    NASA Astrophysics Data System (ADS)

    Scala, M.; Militello, B.; Messina, A.; Maniscalco, S.; Piilo, J.; Suominen, K.-A.

    2007-11-01

    A microscopic derivation of the master equation for the Jaynes-Cummings model with cavity losses is given, taking into account the terms in the dissipator which vary with frequencies of the order of the vacuum Rabi frequency. Our approach allows us to single out physical contexts wherein the usual phenomenological dissipator turns out to be fully justified and constitutes an extension of our previous analysis (Scala et al 2007 Phys. Rev. A 75 013811), where a microscopic derivation was given in the framework of the rotating wave approximation.

  19. Quantum phase transition in a multiconnected superconducting Jaynes-Cummings lattice

    NASA Astrophysics Data System (ADS)

    Seo, Kangjun; Tian, Lin

    2015-05-01

    The connectivity and tunability of superconducting qubits and resonators provide us with an appealing platform to study the many-body physics of microwave excitations. Here we present a multiconnected Jaynes-Cummings lattice model which is symmetric with respect to the nonlocal qubit-resonator couplings. Our calculation shows that this model exhibits a Mott insulator-superfluid-Mott insulator phase transition at commensurate fillings, featured by symmetric quantum critical points. Phase diagrams in the grand canonical ensemble are also derived, which confirm the incompressibility of the Mott insulator phase. Different from a general-purposed quantum computer, it only requires two operations to demonstrate this phase transition: the preparation and the detection of commensurate many-body ground state. We discuss the realization of these operations in a superconducting circuit.

  20. Quantum Phase Transition in the Finite Jaynes-Cummings Lattice Systems

    NASA Astrophysics Data System (ADS)

    Hwang, Myung-Joong; Plenio, Martin B.

    2016-09-01

    Phase transitions are commonly held to occur only in the thermodynamical limit of a large number of system components. Here, we exemplify at the hand of the exactly solvable Jaynes-Cummings (JC) model and its generalization to finite JC lattices that finite component systems of coupled spins and bosons may exhibit quantum phase transitions (QPTs). For the JC model we find a continuous symmetry-breaking QPT, a photonic condensate with a macroscopic occupation as the ground state, and a Goldstone mode as a low-energy excitation. For the two site JC lattice we show analytically that it undergoes a Mott-insulator to superfluid QPT. We identify as the underlying principle of the emergence of finite system QPTs the combination of increasing atomic energy and increasing interaction strength between the atom and the bosonic mode, which allows for the exploration of an increasingly large portion of the infinite dimensional Hilbert space of the bosonic mode. This suggests that finite system phase transitions will be present in a broad range of physical systems.

  1. Quantum and classical chaos in kicked coupled Jaynes-Cummings cavities

    SciTech Connect

    Hayward, A. L. C.; Greentree, Andrew D.

    2010-06-15

    We consider two Jaynes-Cummings cavities coupled periodically with a photon hopping term. The semiclassical phase space is chaotic, with regions of stability over some ranges of the parameters. The quantum case exhibits dynamic localization and dynamic tunneling between classically forbidden regions. We explore the correspondence between the classical and quantum phase space and propose an implementation in a circuit QED system.

  2. Reconstruction of the Jaynes-Cummings field state of ionic motion in a harmonic trap

    NASA Astrophysics Data System (ADS)

    Lv, Dingshun; An, Shuoming; Um, Mark; Zhang, Junhua; Zhang, Jing-Ning; Kim, M. S.; Kim, Kihwan

    2017-04-01

    A quantum state is fully characterized by its density matrix or equivalently by its quasiprobabilities in phase space. A scheme to identify the quasiprobabilities of a quantum state is an important tool in the recent development of quantum technologies. One of the most fundamental interaction models in quantum optics is the so-called Jaynes-Cummings model (JCM), which has been massively studied theoretically and experimentally. However, the expected essential dynamics of the field states under the resonant JCM has not been observed experimentally due to the lack of a proper reconstruction scheme. In this paper, we further develop a highly efficient vacuum measurement scheme and study the JCM dynamics in a trapped ion system with the capability of the vacuum measurement to reconstruct its quasiprobability Q function, which is a preferred choice to study the core of the dynamics of a quantum state in phase space. During the JCM dynamics, the Gaussian peak of the initial coherent state bifurcates and rotates around the origin of phase space. They merge at the so-called revival time at the other side of phase space. The measured Q function agrees with the theoretical prediction. Moreover, we reconstruct the Wigner function by deconvoluting the Q function and observe the quantum interference in the Wigner function at half of the revival time, where the vibrational state becomes nearly disentangled from the internal energy states and forms a superposition of two composite states. The scheme can be applied to other physical setups including cavity or circuit-QED and optomechanical systems.

  3. High-fidelity readout in circuit quantum electrodynamics using the Jaynes-Cummings nonlinearity.

    PubMed

    Reed, M D; DiCarlo, L; Johnson, B R; Sun, L; Schuster, D I; Frunzio, L; Schoelkopf, R J

    2010-10-22

    We demonstrate a qubit readout scheme that exploits the Jaynes-Cummings nonlinearity of a superconducting cavity coupled to transmon qubits. We find that, in the strongly driven dispersive regime of this system, there is the unexpected onset of a high-transmission "bright" state at a critical power which depends sensitively on the initial qubit state. A simple and robust measurement protocol exploiting this effect achieves a single-shot fidelity of 87% using a conventional sample design and experimental setup, and at least 61% fidelity to joint correlations of three qubits.

  4. Comment on "Thermal-light-induced dynamics: Coherence and revivals in V -type and molecular Jaynes-Cummings systems"

    NASA Astrophysics Data System (ADS)

    Dodin, Amro; Brumer, Paul

    2017-06-01

    Recent numerical and analytical results have been obtained for the dynamics of a V -type system, and of a model molecular system, interacting with the thermal states of a cavity with a single mode or with a few discrete modes [D. Avisar and A. D. Wilson-Gordon, Phys. Rev. A 93, 033843 (2016), 10.1103/PhysRevA.93.033843]. The authors speculate that these results may be relevant to excitation with natural incoherent radiation, such as sunlight, which has a continuous spectrum. We claim that this is incorrect, as are their comments about prior work on natural incoherent radiation that does properly deal with a continuous spectrum. Specifically, while their results obtained for the Jaynes-Cummings systems may be of interest for excitation by thermal states of cavities with a few modes, the discrete nature of their field modes produces dynamics that are fundamentally different from those induced by natural sunlight. Hence, we show here that the criticisms leveled in their paper regarding prior treatments that dealt with the continuous spectrum of natural incoherent radiation, as well as their speculation that excitation with continuous-mode thermal radiation can induce long-lived molecular coherences, are incorrect.

  5. Transition from Jaynes-Cummings to Autler-Townes ladder in a quantum dot-microcavity system

    NASA Astrophysics Data System (ADS)

    Hopfmann, Caspar; Carmele, Alexander; Musiał, Anna; Schneider, Christian; Kamp, Martin; Höfling, Sven; Knorr, Andreas; Reitzenstein, Stephan

    2017-01-01

    We study experimentally and theoretically a coherently driven strongly coupled quantum dot-microcavity system. Our focus is on physics of the unexplored intermediate excitation regime where the resonant laser field dresses a strongly coupled single exciton-photon (polariton) system resulting in a ladder of laser-dressed Jaynes-Cummings states. In that case, both the coupling of the emitter to the confined light field of the microcavity and to the light field of the external laser are equally important, as proved by observation of injection pulling of the polariton branches by an external laser. This intermediate interaction regime is of particular interest since it connects the purely quantum mechanical Jaynes-Cummings ladder and the semiclassical Autler-Townes ladder. Exploring the driving strength dependence of the mutually coupled system we establish the maximum in the resonance fluorescence signal to be a robust fingerprint of the intermediate regime and observe signatures indicating the laser-dressed Jaynes-Cummings ladder. In order to address the underlying physics we excite the coupled system via the matter component of fermionic nature undergoing saturation—in contrast to commonly used cavity-mediated excitation.

  6. Climbing the Jaynes-Cummings ladder and observing its nonlinearity in a cavity QED system.

    PubMed

    Fink, J M; Göppl, M; Baur, M; Bianchetti, R; Leek, P J; Blais, A; Wallraff, A

    2008-07-17

    The field of cavity quantum electrodynamics (QED), traditionally studied in atomic systems, has gained new momentum by recent reports of quantum optical experiments with solid-state semiconducting and superconducting systems. In cavity QED, the observation of the vacuum Rabi mode splitting is used to investigate the nature of matter-light interaction at a quantum-mechanical level. However, this effect can, at least in principle, be explained classically as the normal mode splitting of two coupled linear oscillators. It has been suggested that an observation of the scaling of the resonant atom-photon coupling strength in the Jaynes-Cummings energy ladder with the square root of photon number n is sufficient to prove that the system is quantum mechanical in nature. Here we report a direct spectroscopic observation of this characteristic quantum nonlinearity. Measuring the photonic degree of freedom of the coupled system, our measurements provide unambiguous spectroscopic evidence for the quantum nature of the resonant atom-field interaction in cavity QED. We explore atom-photon superposition states involving up to two photons, using a spectroscopic pump and probe technique. The experiments have been performed in a circuit QED set-up, in which very strong coupling is realized by the large dipole coupling strength and the long coherence time of a superconducting qubit embedded in a high-quality on-chip microwave cavity. Circuit QED systems also provide a natural quantum interface between flying qubits (photons) and stationary qubits for applications in quantum information processing and communication.

  7. Reply to "Comment on `Thermal-light-induced dynamics: Coherence and revivals in V -type and molecular Jaynes-Cummings systems' "

    NASA Astrophysics Data System (ADS)

    Avisar, David; Wilson-Gordon, A. D.

    2017-06-01

    We recently presented an extended Jaynes-Cummings model for the interaction of a realistic molecular system of two Born-Oppenheimer potential energy surfaces and a quantized electromagnetic field [Avisar and Wilson-Gordon, Phys. Rev. A 93, 033843 (2016), 10.1103/PhysRevA.93.033843]. We studied the interaction of this molecular model, and also a prototype V -type system, with single-mode and multimode thermal states of the field, characterized by low and high average photon number n ¯. Among our results, we showed that the three-mode thermal state of the field induces excited-state material coherence and that a thermal state of high n ¯ can induce "coherentlike" collapse and revival patterns. The preceding Comment by Dodin and Brumer [Phys. Rev. A 95, 067801 (2017), 10.1103/PhysRevA.95.067801] criticizes our work for allegedly drawing conclusions regarding sunlight-induced dynamics from our results, and for unjustified citation of previous work. However, we think the Comment fails to represent the contents of our paper, and we therefore reply to it. We show it is based on misinterpretation of our paper.

  8. Dynamics of single photon transport in a one-dimensional waveguide two-point coupled with a Jaynes-Cummings system

    PubMed Central

    Wang, Yuwen; Zhang, Yongyou; Zhang, Qingyun; Zou, Bingsuo; Schwingenschlogl, Udo

    2016-01-01

    We study the dynamics of an ultrafast single photon pulse in a one-dimensional waveguide two-point coupled with a Jaynes-Cummings system. We find that for any single photon input the transmissivity depends periodically on the separation between the two coupling points. For a pulse containing many plane wave components it is almost impossible to suppress transmission, especially when the width of the pulse is less than 20 times the period. In contrast to plane wave input, the waveform of the pulse can be modified by controlling the coupling between the waveguide and Jaynes-Cummings system. Tailoring of the waveform is important for single photon manipulation in quantum informatics. PMID:27653770

  9. Characteristic-function approach to the Jaynes-Cummings-model revivals

    NASA Astrophysics Data System (ADS)

    Pimenta, Hudson; James, Daniel F. V.

    2016-11-01

    A two-level system interacting with an electromagnetic mode experiences inversion collapses and revivals. They are an indirect signature of the field quantization and also hold information about the mode. Thus, they may be harnessed for quantum-state reconstruction. In this work, we investigate the inversion via the characteristic function of the field mode photon-number distribution. The characteristic function is the spectral representation of the photon-number probability distribution. Exploiting the characteristic function periodicity, we find that the inversion can be understood as the result of interference between a set of structures akin to a free quantum-mechanical wave packet, with each structure corresponding to a snapshot of this packet for different degrees of dispersion. The Fourier representation of each packet Fourier determines the photon-number distribution. We also derive an integral equation whose solution yields the underlying packets. This approach allows the retrieval of the field photon-number distribution directly from the inversion under fairly general conditions and paves the way for a partial tomography technique.

  10. Entanglement transfer from two-mode continuous variable SU(2) cat states to discrete qubits systems in Jaynes-Cummings Dimers

    PubMed Central

    Ran, Du; Hu, Chang-Sheng; Yang, Zhen-Biao

    2016-01-01

    We study the entanglement transfer from a two-mode continuous variable system (initially in the two-mode SU(2) cat states) to a couple of discrete two-state systems (initially in an arbitrary mixed state), by use of the resonant Jaynes-Cummings (JC) interaction. We first quantitatively connect the entanglement transfer to non-Gaussianity of the two-mode SU(2) cat states and find a positive correlation between them. We then investigate the behaviors of the entanglement transfer and find that it is dependent on the initial state of the discrete systems. We also find that the largest possible value of the transferred entanglement exhibits a variety of behaviors for different photon number as well as for the phase angle of the two-mode SU(2) cat states. We finally consider the influences of the noise on the transferred entanglement. PMID:27553881

  11. Squeezing of Atomic Variables in the One-Photon and Two-Photon Jaynes-Cummings Model

    DTIC Science & Technology

    1989-06-01

    of Chemistry University of hester Pennsylvania State University Roches ew York 14627 University Park, Pennsylvania 16802 r. G. Rubloff Dr. Roald ... Hoffmann IBM Department of Chemistry Thomas J. Watson Research Center Cornell University P.O. Box 218 Ithaca, New York 14853 Yorktown Heights, New York

  12. Effects of the Stark Shift on the Evolution of the Field Entropy and Entanglement in the Two-Photon Jaynes-Cummings Model

    NASA Technical Reports Server (NTRS)

    Fang, Mao Fa

    1996-01-01

    The evolution of the field entropy in the two-photon JCM in the presence of the Stark shift is investigated, and the effects of the dynamic Stark shift on the evolution of the field entropy and entanglement between the atom and field, are examined. The results show that the dynamic Stark shift plays an important role in the evolution of the field entropy in two-photon processes.

  13. Separation of variables in anisotropic models: anisotropic Rabi and elliptic Gaudin model in an external magnetic field

    NASA Astrophysics Data System (ADS)

    Skrypnyk, T.

    2017-08-01

    We study the problem of separation of variables for classical integrable Hamiltonian systems governed by non-skew-symmetric non-dynamical so(3)\\otimes so(3) -valued elliptic r-matrices with spectral parameters. We consider several examples of such models, and perform separation of variables for classical anisotropic one- and two-spin Gaudin-type models in an external magnetic field, and for Jaynes-Cummings-Dicke-type models without the rotating wave approximation.

  14. General integrable n-level, many-mode Janes-Cummings-Dicke models and classical r-matrices with spectral parameters

    SciTech Connect

    Skrypnyk, T. E-mail: tskrypnyk@imath.kiev.ua

    2015-02-15

    Using the technique of classical r-matrices and quantum Lax operators, we construct the most general form of the quantum integrable “n-level, many-mode” spin-boson Jaynes-Cummings-Dicke-type hamiltonians describing an interaction of a molecule of N n-level atoms with many modes of electromagnetic field and containing, in general, additional non-linear interaction terms. We explicitly obtain the corresponding quantum Lax operators and spin-boson analogs of the generalized Gaudin hamiltonians and prove their quantum commutativity. We investigate symmetries of the obtained models that are associated with the geometric symmetries of the classical r-matrices and construct the corresponding algebra of quantum integrals. We consider in detail three classes of non-skew-symmetric classical r-matrices with spectral parameters and explicitly obtain the corresponding quantum Lax operators and Jaynes-Cummings-Dicke-type hamiltonians depending on the considered r-matrix.

  15. A simple model of multiphoton micromachining in silk hydrogels

    SciTech Connect

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

    2016-06-13

    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.

  16. A simple model of multiphoton micromachining in silk hydrogels

    NASA Astrophysics Data System (ADS)

    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.

  17. Violation of the quantum regression theorem and the Leggett-Garg inequality in an exactly solvable model

    NASA Astrophysics Data System (ADS)

    Ban, Masashi

    2017-08-01

    Violation of the quantum regression theorem and the Leggett-Garg inequality is studied by means of the exactly solvable multi-mode Jaynes-Cummings model. An exact expression of a two-time correlation function is compared with that derived by the quantum regression theorem. It is found that the quantum regression theorem is not valid even if the reduced time evolution of the qubit is Markovian. Furthermore, it is shown that if the quantum regression theorem is applied in this model, the Leggett-Garg inequality is satisfied while it is violated by the exact correlation function.

  18. Particle modeling of microplasma generated by resonance enhanced multiphoton ionization

    NASA Astrophysics Data System (ADS)

    Tholeti, Siva Sashank

    Resonance-enhanced multiphoton ionization (REMPI) is a technique applied to the spectroscopy of atoms. The REMPI technique typically involves a resonant single or multiple photon absorption to an electronically excited intermediate state followed by another photon which ionizes the atom. Rayleigh scattering of REMPI plasma has given rise to a non-intrusive, time accurate measurement of electron formation and loss, which lead to many applications viz. trace species detection and micro-plasma diagnostics. It is very important to quantify the expansion process and the evolution of energy of electrons and ions. The operation scale of this process is in microns and non continuum nature of the process lead to the use of PIC/MCC scheme to compu- tationally model REMPI technique. This work attempts to understand and analyze the processes taking place during the expansion of REMPI plasma computationally using the PIC/MCC scheme. One dimensional and two dimensional approximations are considered to analyze the REMPI plasma expansion in Argon gas generated by a laser with a focal shape of a prolate ellipsoid. The expansion of the plasma is found to be very sensitive to the initial velocity distribution of the electrons. REMPI plasma expansion is shown to be ambipolar in nature, with the radial expansion more predominant than axial expansion, hence requiring the 2D model. Electron energy distribution functions(EEDFs) are found at various radial locations along with the corresponding mean energies. The deviation of the EEDFs from that of equilibrium Maxwell-Boltzmann energy distribution is presented both qualitatively and quanti- tatively, indicating the predominant processes at various instances in time.

  19. Eigenvalue-based determinants for scalar products and form factors in Richardson-Gaudin integrable models coupled to a bosonic mode

    NASA Astrophysics Data System (ADS)

    Claeys, Pieter W.; De Baerdemacker, Stijn; Van Raemdonck, Mario; Van Neck, Dimitri

    2015-10-01

    Starting from integrable su(2) (quasi-)spin Richardson-Gaudin (RG) XXZ models we derive several properties of integrable spin models coupled to a bosonic mode. We focus on the Dicke-Jaynes-Cummings-Gaudin models and the two-channel (p + ip)-wave pairing Hamiltonian. The pseudo-deformation of the underlying su(2) algebra is here introduced as a way to obtain these models in the contraction limit of different RG models. This allows for the construction of the full set of conserved charges, the Bethe ansatz state, and the resulting RG equations. For these models an alternative and simpler set of quadratic equations can be found in terms of the eigenvalues of the conserved charges. Furthermore, the recently proposed eigenvalue-based determinant expressions for the overlaps and form factors of local operators are extended to these models, linking the results previously presented for the Dicke-Jaynes-Cummings-Gaudin models with the general results for RG XXZ models.

  20. Quantum Rabi Model with Trapped Ions

    PubMed Central

    Pedernales, J. S.; Lizuain, I.; Felicetti, S.; Romero, G.; Lamata, L.; Solano, E.

    2015-01-01

    We propose the quantum simulation of the quantum Rabi model in all parameter regimes by means of detuned bichromatic sideband excitations of a single trapped ion. We show that current setups can reproduce, in particular, the ultrastrong and deep strong coupling regimes of such a paradigmatic light-matter interaction. Furthermore, associated with these extreme dipolar regimes, we study the controlled generation and detection of their entangled ground states by means of adiabatic methods. Ion traps have arguably performed the first quantum simulation of the Jaynes-Cummings model, a restricted regime of the quantum Rabi model where the rotating-wave approximation holds. We show that one can go beyond and experimentally investigate the quantum simulation of coupling regimes of the quantum Rabi model that are difficult to achieve with natural dipolar interactions. PMID:26482660

  1. Quantum Rabi Model with Trapped Ions.

    PubMed

    Pedernales, J S; Lizuain, I; Felicetti, S; Romero, G; Lamata, L; Solano, E

    2015-10-20

    We propose the quantum simulation of the quantum Rabi model in all parameter regimes by means of detuned bichromatic sideband excitations of a single trapped ion. We show that current setups can reproduce, in particular, the ultrastrong and deep strong coupling regimes of such a paradigmatic light-matter interaction. Furthermore, associated with these extreme dipolar regimes, we study the controlled generation and detection of their entangled ground states by means of adiabatic methods. Ion traps have arguably performed the first quantum simulation of the Jaynes-Cummings model, a restricted regime of the quantum Rabi model where the rotating-wave approximation holds. We show that one can go beyond and experimentally investigate the quantum simulation of coupling regimes of the quantum Rabi model that are difficult to achieve with natural dipolar interactions.

  2. Multi-photon signals from composite models at LHC

    NASA Astrophysics Data System (ADS)

    Freitas, A.; Schwaller, P.

    2011-01-01

    We analyze the collider signals of composite scalars that emerge in certain little Higgs models and models of vectorlike confinement. Similar to the decay of the pion into photon pairs, these scalars mainly decay through anomaly-induced interactions into electroweak gauge bosons, leading to a distinct signal with three or more photons in the final state. We study the standard model backgrounds for these signals, and find that the LHC can discover these models over a large range of parameter space with 30 fb-1 at 14 TeV. An early discovery at the current 7 TeV run is possible in some regions of parameter space. We also discuss possibilities to measure the spin of the particles in the γγ and Zγ decay channels.

  3. In vivo imaging of spinal cord in contusion injury model mice by multi-photon microscopy

    NASA Astrophysics Data System (ADS)

    Oshima, Y.; Horiuchi, H.; Ogata, T.; Hikita, A.; Miura, H.; Imamura, T.

    2014-03-01

    Fluorescent imaging technique is a promising method and has been developed for in vivo applications in cellular biology. In particular, nonlinear optical imaging technique, multi-photon microscopy has make it possible to analyze deep portion of tissues in living animals such as axons of spinal code. Traumatic spinal cord injuries (SCIs) are usually caused by contusion damages. Therefore, observation of spinal cord tissue after the contusion injury is necessary for understanding cellular dynamics in response to traumatic SCI and development of the treatment for traumatic SCI. Our goal is elucidation of mechanism for degeneration of axons after contusion injuries by establishing SCI model and chronic observation of injured axons in the living animals. Firstly we generated and observed acute SCI model by contusion injury. By using a multi-photon microscope, axons in dorsal cord were visualized approximately 140 micron in depth from the surface. Immediately after injury, minimal morphological change of spinal cord was observed. At 3 days after injury, spinal cord was swelling and the axons seem to be fragmented. At 7 days after injury, increased degradation of axons could be observed, although the image was blurred due to accumulation of the connective tissue. In the present study, we successfully observed axon degeneration after the contusion SCI in a living animal in vivo. Our final goal is to understand molecular mechanisms and cellular dynamics in response to traumatic SCIs in acute and chronic stage.

  4. Quantum Rabi model in a superfluid Bose-Einstein condensate

    NASA Astrophysics Data System (ADS)

    Felicetti, S.; Romero, G.; Solano, E.; Sabín, C.

    2017-09-01

    We propose a quantum simulation of the quantum Rabi model in an atomic quantum dot, which is a single atom in a tight optical trap coupled to the quasiparticle modes of a superfluid Bose-Einstein condensate. This widely tunable setup allows us to simulate the ultrastrong coupling regime of light-matter interaction in a system which enjoys an amenable characteristic time scale, paving the way for an experimental analysis of the transition between the Jaynes-Cummings and the quantum Rabi dynamics using cold-atom systems. Our scheme can be naturally extended to simulate multiqubit quantum Rabi models. In particular, we discuss the appearance of effective two-qubit interactions due to phononic exchange, among other features.

  5. Z 2-graded classical r-matrices and algebraic Bethe ansatz: applications to integrable models of quantum optics and nuclear physics

    NASA Astrophysics Data System (ADS)

    Skrypnyk, T.

    2016-09-01

    We consider quantum integrable models based on the Lie algebra gl(n) and non-skew-symmetric classical r-matrices associated with Z 2-gradings of gl(n) of the following type: {gl}(n)={gl}{(n)}\\bar{0}+{gl}{(n)}\\bar{1}, where {gl}{(n)}\\bar{0}={gl}({n}1)\\oplus {gl}(n-{n}1). Among the considered models are Gaudin-type models with an external magnetic field, used in nuclear physics to produce proton-neutron Bardeen-Cooper-Schrieer-type models, n-level many-mode Jaynes-Cummings-Dicke-type models of quantum optics, matrix generalization of Bose-Hubbard dimers, etc. We diagonalize the constructed models by means of the ‘generalized’ nested Bethe ansatz.

  6. Modeling molecule-plasmon interactions using quantized radiation fields within time-dependent electronic structure theory

    SciTech Connect

    Nascimento, Daniel R.; DePrince, A. Eugene

    2015-12-07

    We present a combined cavity quantum electrodynamics/ab initio electronic structure approach for simulating plasmon-molecule interactions in the time domain. The simple Jaynes-Cummings-type model Hamiltonian typically utilized in such simulations is replaced with one in which the molecular component of the coupled system is treated in a fully ab initio way, resulting in a computationally efficient description of general plasmon-molecule interactions. Mutual polarization effects are easily incorporated within a standard ground-state Hartree-Fock computation, and time-dependent simulations carry the same formal computational scaling as real-time time-dependent Hartree-Fock theory. As a proof of principle, we apply this generalized method to the emergence of a Fano-like resonance in coupled molecule-plasmon systems; this feature is quite sensitive to the nanoparticle-molecule separation and the orientation of the molecule relative to the polarization of the external electric field.

  7. A phasor approach analysis of multiphoton FLIM measurements of three-dimensional cell culture models

    NASA Astrophysics Data System (ADS)

    Lakner, P. H.; Möller, Y.; Olayioye, M. A.; Brucker, S. Y.; Schenke-Layland, K.; Monaghan, M. G.

    2016-03-01

    Fluorescence lifetime imaging microscopy (FLIM) is a useful approach to obtain information regarding the endogenous fluorophores present in biological samples. The concise evaluation of FLIM data requires the use of robust mathematical algorithms. In this study, we developed a user-friendly phasor approach for analyzing FLIM data and applied this method on three-dimensional (3D) Caco-2 models of polarized epithelial luminal cysts in a supporting extracellular matrix environment. These Caco-2 based models were treated with epidermal growth factor (EGF), to stimulate proliferation in order to determine if FLIM could detect such a change in cell behavior. Autofluorescence from nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) in luminal Caco-2 cysts was stimulated by 2-photon laser excitation. Using a phasor approach, the lifetimes of involved fluorophores and their contribution were calculated with fewer initial assumptions when compared to multiexponential decay fitting. The phasor approach simplified FLIM data analysis, making it an interesting tool for non-experts in numerical data analysis. We observed that an increased proliferation stimulated by EGF led to a significant shift in fluorescence lifetime and a significant alteration of the phasor data shape. Our data demonstrates that multiphoton FLIM analysis with the phasor approach is a suitable method for the non-invasive analysis of 3D in vitro cell culture models qualifying this method for monitoring basic cellular features and the effect of external factors.

  8. Dirac bi-spinor entanglement under local noise and its simulation by Jaynes-Cummings interactions

    NASA Astrophysics Data System (ADS)

    Bittencourt, Victor A. S. V.; Bernardini, Alex E.

    2017-08-01

    A description of the effects of the local noise on the quantum entanglement constraining the internal degrees of freedom of Dirac bi-spinor structures driven by arbitrary Poincaré invariant potentials is proposed. Given that the Dirac equation dynamics including external potentials can be simulated by a suitable four level trapped ion setup, quantum entanglement of two-qubit ionic states with quantum numbers related to the total angular momentum and to its projection onto the direction of the external magnetic field (used for lift the ions degeneracy), are recovered by means of a suitable ansatz. This formalism allows the inclusion of noise effects, which leads to disentanglement in the four level trapped ion quantum system. Our results indicate the role of interactions in bi-spinor entanglement, as well as the description of disentanglement in ionic states under local noises. For a state prepared initially in one of the ionic levels, local noise induces entanglement sudden death followed by sudden revivals driven by the noiseless dynamics of the state. Residual quantum correlations are observed in the intervals where such state is separable. Schrödinger cat and Werner states partially loose their initial entanglement content due to the interaction with the noisy environment but presenting entanglement oscillations without sudden death. Because Dirac equation describes low energy excitations of mono layer and bi-layer graphene, the formalism can also be applied to compute, for instance, electron-hole or electron/electron entanglement in various circumstances.

  9. Multi-photon microscopy of tobacco-exposed organotypic skin models

    NASA Astrophysics Data System (ADS)

    Dao, Belinda; Yamazaki, Alissa; Sun, Chung Ho; Wang, Zifu; Pham, Nguyen; Oldham, Michael; Wong, Brian J. F.

    2006-02-01

    Cigarette smoking is the most preventable cause of death in the United States. Researchers have extensively studied smoking in regards to its association with cancer, cardiovascular, and pulmonary disease. In contrast, the impact of cigarette smoking on skin has received much less attention. To provide a better understanding of the effect of cigarette smoking on the human dermal layer, this study used multi-photon microscopy (MPM) to examine collagen in organotypic skin models exposed to cigarette smoke condensate (CSC). Adult and neonatal organotypic tissue-engineered artificial skin models (RAFTs) were constructed and exposed to varying concentrations of CSC. Imaging of the RAFTs was performed using MPM and second-harmonic generation signals (SHG), which allowed for collagen structure to be viewed and analyzed as well as for collagen density to be assessed from derived depth-dependent decay (DDD) values. RAFT contraction as related to exposure concentration was monitored as well. Results indicated a dose dependent between contraction rates and CSC concentration. Collagen structure showed more preservation of its original structure at a greater depth in RAFTs with higher concentrations of CSC. No clear trends could be drawn from analysis of derived DDD values.

  10. Multiphoton in vivo imaging of amyloid in animal models of Alzheimer’s disease

    PubMed Central

    Dong, Jinghui; Revilla-Sanchez, Raquel; Moss, Stephen; Haydon, Philip G.

    2011-01-01

    Amyloid-beta (Aβ) deposition is a defining feature of Alzheimer’s disease (AD). The toxicity of Aβ aggregation is thought to contribute to clinical deficits including progressive memory loss and cognitive dysfunction. Therefore, Aβ peptide has become the focus of many therapeutic approaches for the treatment of AD due to its central role in the development of neuropathology of AD. In the past decade, taking the advantage of multiphoton microscopy and molecular probes for amyloid peptide labeling, the dynamic progression of Aβ aggregation in amyloid plaques and cerebral amyloid angiopathy has been monitored in real time in transgenic mouse models of AD. Moreover, amyloid plaque-associated alterations in the brain including dendritic and synaptic abnormalities, changes of neuronal and astrocytic calcium homeostasis, microglial activation and recruitment in the plaque location have been extensively studied. These studies provide remarkable insight to understand the pathogenesis and pathogenicity of amyloid plaques in the context of AD. The ability to longitudinally image plaques and related structures facilitates the evaluation of therapeutic approaches targeting toward the clearance of plaques. PMID:20398680

  11. Multimodal imaging of vocal fold scarring in a rabbit model by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Kazarine, Alexei; Bouhabel, Sarah; Douillette, Annie H.; Kost, Karen; Li-Jessen, Nicole Y. K.; Mongeau, Luc; Wiseman, Paul W.

    2017-02-01

    Vocal fold scarring as a result of injury or disease can lead to voice disorders which can significantly affect the quality of life. During the scarring process, the normally elastic tissue of the vocal fold lamina propria is replaced by a much stiffer collagen-based fibrotic tissue, which impacts the fold's ability to vibrate. Surgical removal of this tissue is often ineffective and can result in further scarring. Injectable biomaterials, a form of tissue engineering, have been proposed as a potential solution to reduce existing scars or prevent scarring altogether. In order to properly evaluate the effectiveness of these new materials, multiphoton microscopy emerges as an effective tool due to its intrinsic multiple label free contrast mechanisms that highlight extracellular matrix elements. In this study, we evaluate the spatial distribution of collagen and elastin fibers in a rabbit model using second harmonic generation (SHG), third harmonic generation (THG) and two photon autofluorescence (TPAF) applied to unlabeled tissue sections. In comparison to traditional methods that rely on histological staining or immunohistochemistry, SHG, THG and TPAF provide a more reliable detection of these native proteins. The evaluation of collagen levels allows us to follow the extent of scarring, while the presence of elastin fibers is thought to be indicative of the level of healing of the injured fold. Using these imaging modalities, we characterize the outcome of injectable biomaterial treatments in order to direct future treatments for tissue engineering.

  12. Multiphoton Assisted Recombination

    NASA Astrophysics Data System (ADS)

    Shuman, E. S.; Jones, R. R.; Gallagher, T. F.

    2008-12-01

    We have observed multiphoton assisted recombination in the presence of a 38.8 GHz microwave field. Stimulated emission of up to ten microwave photons results in energy transfer from continuum electrons, enabling recombination. The maximum electron energy loss is far greater than the 2Up predicted by the standard “simpleman’s” model. The data are well reproduced by both an approximate analytic expression and numerical simulations in which the combined Coulomb and radiation fields are taken into account.

  13. The Multiphoton Interaction of Lambda Model Atom and Two-Mode Fields

    NASA Technical Reports Server (NTRS)

    Liu, Tang-Kun

    1996-01-01

    The system of two-mode fields interacting with atom by means of multiphotons is addressed, and the non-classical statistic quality of two-mode fields with interaction is discussed. Through mathematical calculation, some new rules of non-classical effects of two-mode fields which evolue with time, are established.

  14. Modeling extracellular matrix (ECM) alterations in ovarian cancer by multiphoton excited fabrication of stromal models (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Campagnola, Paul J.; Ajeti, Visar; Lara, Jorge; Eliceiri, Kevin W.; Patankar, Mansh

    2016-04-01

    A profound remodeling of the extracellular matrix (ECM) occurs in human ovarian cancer but it unknown how this affects tumor growth, where this understanding could lead to better diagnostics and therapeutic approaches. We investigate the role of these ECM alterations by using multiphoton excited (MPE) polymerization to fabricate biomimetic models to investigate operative cell-matrix interactions in invasion/metastasis. First, we create nano/microstructured gradients mimicking the basal lamina to study adhesion/migration dynamics of ovarian cancer cells of differing metastatic potential. We find a strong haptotactic response that depends on both contact guidance and ECM binding cues. While we found enhanced migration for more invasive cells, the specifics of alignment and directed migration also depend on cell polarity. We further use MPE fabrication to create collagen scaffolds with complex, 3D submicron morphology. The stromal scaffold designs are derived directly from "blueprints" based on SHG images of normal, high risk, and malignant ovarian tissues. The models are seeded with different cancer cell lines and this allows decoupling of the roles of cell characteristics (metastatic potential) and ECM structure and composition (normal vs cancer) on adhesion/migration dynamics. We found the malignant stroma structure promotes enhanced migration and proliferation and also cytoskeletal alignment. Creating synthetic models based on fibers patterns further allows decoupling the topographic roles of the fibers themselves vs their alignment within the tissue. These models cannot be synthesized by other conventional fabrication methods and we suggest the MPE image-based fabrication method will enable a variety of studies in cancer biology.

  15. In vivo three-dimensional optical coherence tomography and multiphoton microscopy in a mouse model of ovarian neoplasia

    NASA Astrophysics Data System (ADS)

    Watson, Jennifer M.; Marion, Samuel L.; Rice, Photini Faith; Bentley, David L.; Besselsen, David; Utzinger, Urs; Hoyer, Patricia B.; Barton, Jennifer K.

    2013-03-01

    Our goal is to use optical coherence tomography (OCT) and multiphoton microscopy (MPM) to detect early tumor development in a mouse model of ovarian neoplasia. We hope to use information regarding early tumor development to create a diagnostic test for high-risk patients. In this study we collect in vivo images using OCT, second harmonic generation and two-photon excited fluorescence from non-vinylcyclohexene diepoxide (VCD)-dosed and VCD-dosed mice. VCD causes follicular apoptosis (simulating menopause) and leads to tumor development. Using OCT and MPM we visualized the ovarian microstructure and were able to see differences between non-VCD-dosed and VCD-dosed animals. This leads us to believe that OCT and MPM may be useful for detecting changes due to early tumor development.

  16. Multiphoton processes: conference proceedings

    SciTech Connect

    Lambropoulos, P.; Smith, S.J.

    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)

  17. MULTI-PHOTON PHOSPHOR FEASIBILITY RESEARCH

    SciTech Connect

    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

  18. Kinetic modeling of evolution of 3 + 1:Resonance enhanced multiphoton ionization plasma in argon at low pressures

    SciTech Connect

    Tholeti, Siva Sashank; Alexeenko, Alina A.; Shneider, Mikhail N.

    2014-06-15

    We present numerical kinetic modeling of generation and evolution of the plasma produced as a result of resonance enhanced multiphoton ionization (REMPI) in Argon gas. The particle-in-cell/Monte Carlo collision (PIC/MCC) simulations capture non-equilibrium effects in REMPI plasma expansion by considering the major collisional processes at the microscopic level: elastic scattering, electron impact ionization, ion charge exchange, and recombination and quenching for metastable excited atoms. The conditions in one-dimensional (1D) and two-dimensional (2D) formulations correspond to known experiments in Argon at a pressure of 5 Torr. The 1D PIC/MCC calculations are compared with the published results of local drift-diffusion model, obtained for the same conditions. It is shown that the PIC/MCC and diffusion-drift models are in qualitative and in reasonable quantitative agreement during the ambipolar expansion stage, whereas significant non-equilibrium exists during the first few 10 s of nanoseconds. 2D effects are important in the REMPI plasma expansion. The 2D PIC/MCC calculations produce significantly lower peak electron densities as compared to 1D and show a better agreement with experimentally measured microwave radiation scattering.

  19. A novel model for ectopic, chronic, intravital multiphoton imaging of bone marrow vasculature and architecture in split femurs

    PubMed Central

    Bălan, Mirela; Kiefer, Friedemann

    2015-01-01

    Creating a model for intravital visualization of femoral bone marrow, a major site of hematopoiesis in adult mammalian organisms, poses a serious challenge, in that it needs to overcome bone opacity and the inaccessibility of marrow. Furthermore, meaningful analysis of bone marrow developmental and differentiation processes requires the repetitive observation of the same site over long periods of time, which we refer to as chronic imaging. To surmount these issues, we developed a chronic intravital imaging model that allows the observation of split femurs, ectopically transplanted into a dorsal skinfold chamber of a host mouse. Repeated, long term observations are facilitated by multiphoton microscopy, an imaging technique that combines superior imaging capacity at greater tissue depth with low phototoxicity. The transplanted, ectopic femur was stabilized by its sterile environment and rapidly connected to the host vasculature, allowing further development and observation of extended processes. After optimizing transplant age and grafting procedure, we observed the development of new woven bone and maturation of secondary ossification centers in the transplanted femurs, preceded by the sprouting of a sinusoidal-like vascular network, which was almost entirely composed of femoral endothelial cells. After two weeks, the transplant was still populated with stromal and haematopoietic cells belonging both to donor and host. Over this time frame, the transplant partially retained myeloid progenitor cells with single and multi-lineage differentiation capacity. In summary, our model allowed repeated intravital imaging of bone marrow angiogenesis and hematopoiesis. It represents a promising starting point for the development of improved chronic optical imaging models for femoral bone marrow. PMID:28243515

  20. Examination of diagnostic features in multiphoton microscopy and optical coherence tomography images of ovarian tumorigenesis in a mouse model

    NASA Astrophysics Data System (ADS)

    Watson, Jennifer M.

    Ovarian cancer is a deadly disease owing to the non-specific symptoms and suspected rapid progression, leading to frequent late stage detection and poor prognosis. Medical imaging methods such as CT, MRI and ultrasound as well as serum testing for cancer markers have had extremely poor performance for early disease detection. Due to the poor performance of available screening methods, and the impracticality and ineffectiveness of taking tissue biopsies from the ovary, women at high risk for developing ovarian cancer are often advised to undergo prophylactic salpingo-oophorectomy. This surgery results in many side effects and is most often unnecessary since only a fraction of high risk women go on to develop ovarian cancer. Better understanding of the early development of ovarian cancer and characterization of morphological changes associated with early disease could lead to the development of an effective screening test for women at high risk. Optical imaging methods including optical coherence tomography (OCT) and multiphoton microscopy (MPM) are excellent tools for studying disease progression owing to the high resolution and depth sectioning capabilities. Further, these techniques are excellent for optical biopsy because they can image in situ non-destructively. In the studies described in this dissertation OCT and MPM are used to identify cellular and tissue morphological changes associated with early tumor development in a mouse model of ovarian cancer. This work is organized into three specific aims. The first aim is to use the images from the MPM phenomenon of second harmonic generation to quantitatively examine the morphological differences in collagen structure in normal mouse ovarian tissue and mouse ovarian tumors. The second aim is to examine the differences in endogenous two-photon excited fluorescence in normal mouse ovarian tissue and mouse ovarian tumors. The third and final aim is to identify changes in ovarian microstructure resulting from early

  1. Principles of multiphoton microscopy.

    PubMed

    Dunn, Kenneth W; Young, Pamela A

    2006-01-01

    Multiphoton fluorescence microscopy is a powerful, important tool in biomedical research that offers low photon toxicity and higher spatial and temporal resolution than other in vivo imaging modalities. The capability to collect images hundreds of micrometers into biological tissues provides an invaluable tool for studying cellular and subcellular processes in the context of tissues and organs in living animals. Multiphoton microscopy is based upon two-photon excitation of fluorescence that occurs only in a sub-femtoliter volume at the focus; by scanning the focus through a sample, 2- and 3-dimensional images can be collected. The complex 3-dimensional organization of the kidney makes it especially appropriate for multiphoton microscopic analysis, which has been used to characterize numerous aspects of renal physiology and pathophysiology in living rats and mice. However, the ability to collect fluorescence images deep into biological tissues raises unique problems not encountered in other forms of optical microscopy, including issues of probe access, and tissue optics. Future improvements in multiphoton fluorescence microscopy will involve optimizing objectives for the unique characteristics of multiphoton fluorescence imaging, improving the speed at which images may be collected and extending the depth to which imaging may be conducted. Copyright 2006 S. Karger AG, Basel.

  2. Spectral classification of coupling regimes in the quantum Rabi model

    NASA Astrophysics Data System (ADS)

    Rossatto, Daniel Z.; Villas-Bôas, Celso J.; Sanz, Mikel; Solano, Enrique

    2017-07-01

    The quantum Rabi model is in the scientific spotlight due to the recent theoretical and experimental progress. Nevertheless, a full-fledged classification of its coupling regimes remains as a relevant open question. We propose a spectral classification dividing the coupling regimes into three regions based on the validity of perturbative criteria on the quantum Rabi model, which allows us the use of exactly solvable effective Hamiltonians. These coupling regimes are (i) the perturbative ultrastrong coupling regime which comprises the Jaynes-Cummings model, (ii) a region where nonperturbative ultrastrong and nonperturbative deep strong coupling regimes coexist, and (iii) the perturbative deep strong coupling regime. We show that this spectral classification depends not only on the ratio between the coupling strength and the natural frequencies of the unperturbed parts, but also on the energy to which the system can access. These regimes additionally discriminate the completely different behaviors of several static physical properties, namely the total number of excitations, the photon statistics of the field, and the cavity-qubit entanglement. Finally, we explain the dynamical properties which are traditionally associated with the deep strong coupling regime, such as the collapses and revivals of the state population, in the frame of the proposed spectral classification.

  3. Multiphoton polymerization using optical trap assisted nanopatterning

    NASA Astrophysics Data System (ADS)

    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.

  4. Analog quantum simulation of the Rabi model in the ultra-strong coupling regime.

    PubMed

    Braumüller, Jochen; Marthaler, Michael; Schneider, Andre; Stehli, Alexander; Rotzinger, Hannes; Weides, Martin; Ustinov, Alexey V

    2017-10-03

    The quantum Rabi model describes the fundamental mechanism of light-matter interaction. It consists of a two-level atom or qubit coupled to a quantized harmonic mode via a transversal interaction. In the weak coupling regime, it reduces to the well-known Jaynes-Cummings model by applying a rotating wave approximation. The rotating wave approximation breaks down in the ultra-strong coupling regime, where the effective coupling strength g is comparable to the energy ω of the bosonic mode, and remarkable features in the system dynamics are revealed. Here we demonstrate an analog quantum simulation of an effective quantum Rabi model in the ultra-strong coupling regime, achieving a relative coupling ratio of g/ω ~ 0.6. The quantum hardware of the simulator is a superconducting circuit embedded in a cQED setup. We observe fast and periodic quantum state collapses and revivals of the initial qubit state, being the most distinct signature of the synthesized model.An analog quantum simulation scheme has been explored with a quantum hardware based on a superconducting circuit. Here the authors investigate the time evolution of the quantum Rabi model at ultra-strong coupling conditions, which is synthesized by slowing down the system dynamics in an effective frame.

  5. Simultaneous optical coherence and multiphoton microscopy of skin-equivalent tissue models

    NASA Astrophysics Data System (ADS)

    Barton, Jennifer K.; Tang, Shuo; Lim, Ryan; Tromberg, Bruce J.

    2007-07-01

    Three-layer skin-equivalent models (rafts) were created consisting of a collagen/fibroblast layer and an air-exposed keratinocyte layer. Rafts were imaged with a tri-modality microscope including optical coherence (OC), two-photon excited fluorescence (TPEF), and second harmonic generation (SHG) channels. Some rafts were stained with Hoechst 33343 or rhodamine 123, and some were exposed to dimethyl sulfoxide (DMSO). OC microscopy revealed signal in cell cytoplasm and nuclear membranes, and a characteristic texture in the collagen/fibroblast layer. TPEF showed signal in cell cytoplasm and from collagen, and stained specimens revealed cell nuclei or mitochondria. There was little SHG in the keratinocyte layer, but strong signal from collagen bundles. Endogenous signals were severely attenuated in DMSO treated rafts; stained samples revealed shrunken and distorted cell structure. OC, TPEF, and SHG can provide complementary and non-destructive information about raft structure and effect of chemical agents.

  6. Parity oscillations and photon correlation functions in the Z2-U (1 ) Dicke model at a finite number of atoms or qubits

    NASA Astrophysics Data System (ADS)

    Yi-Xiang, Yu; Ye, Jinwu; Zhang, CunLin

    2016-08-01

    Four standard quantum optics models, that is, the Rabi, Dicke, Jaynes-Cummings, and Tavis-Cummings models, were proposed by physicists many decades ago. Despite their relative simple forms and many previous theoretical works, their physics at a finite N , especially inside the superradiant regime, remain unknown. In this work, by using the strong-coupling expansion and exact diagonalization (ED), we study the Z2-U(1 ) Dicke model with independent rotating-wave coupling g and counterrotating-wave coupling g' at a finite N . This model includes the four standard quantum optics models as its various special limits. We show that in the superradiant phase, the system's energy levels are grouped into doublets with even and odd parity. Any anisotropy β =g'/g ≠1 leads to the oscillation of parities in both the ground and excited doublets as the atom-photon coupling strength increases. The oscillations will be pushed to the infinite coupling strength in the isotropic Z2 limit β =1 . We find nearly perfect agreement between the strong-coupling expansion and the ED in the superradiant regime when β is not too small. We also compute the photon correlation functions, squeezing spectrum, and number correlation functions that can be measured by various standard optical techniques.

  7. Quantum-optical model for the dynamics of high-order-harmonic generation

    NASA Astrophysics Data System (ADS)

    Gombkötő, Ákos; Czirják, Attila; Varró, Sándor; Földi, Péter

    2016-07-01

    We investigate a two-level atom in the field of a strong laser pulse. The resulting time-dependent polarization is the source of a radiation the frequency components of which are essentially harmonics of the driving field's carrier frequency. The time evolution of this secondary radiation is analyzed in terms of the expectation values of the photon-number operators for a large number of electromagnetic modes that are initially in the vacuum state. Our method is based on a multimode version of the Jaynes-Cummings-Paul model and can be generalized to different radiating systems as well. We show that, after the exciting pulse, the final distribution of the photon numbers is close to the conventional (Fourier-transform-based) power spectrum of the secondary radiation. The details of the high-order-harmonic spectra (HHG spectra) are also analyzed; for many-cycle excitations a clear physical interpretation is given in terms of the Floquet quasienergies. A first step towards the determination of the photon statistics of the high-order-harmonic modes reveals states with slightly super-Poissonian distribution.

  8. Clinical multiphoton FLIM tomography

    NASA Astrophysics Data System (ADS)

    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.

  9. High speed multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Li, Yongxiao; Brustle, Anne; Gautam, Vini; Cockburn, Ian; Gillespie, Cathy; Gaus, Katharina; Lee, Woei Ming

    2016-12-01

    Intravital multiphoton microscopy has emerged as a powerful technique to visualize cellular processes in-vivo. Real time processes revealed through live imaging provided many opportunities to capture cellular activities in living animals. The typical parameters that determine the performance of multiphoton microscopy are speed, field of view, 3D imaging and imaging depth; many of these are important to achieving data from in-vivo. Here, we provide a full exposition of the flexible polygon mirror based high speed laser scanning multiphoton imaging system, PCI-6110 card (National Instruments) and high speed analog frame grabber card (Matrox Solios eA/XA), which allows for rapid adjustments between frame rates i.e. 5 Hz to 50 Hz with 512 × 512 pixels. Furthermore, a motion correction algorithm is also used to mitigate motion artifacts. A customized control software called Pscan 1.0 is developed for the system. This is then followed by calibration of the imaging performance of the system and a series of quantitative in-vitro and in-vivo imaging in neuronal tissues and mice.

  10. Photophysics of infrared multiphoton excitation in thiophosgene

    SciTech Connect

    Brenner, D.M.; Spencer, M.N.; Steinfeld, J.I.

    1983-01-01

    IR multiphoton absorption (IRMPA) in thiophosgene has been studied by IR-visible double resonance. In particular, the probability of absorption has been measured in both collision-free (molecular beam) and collision-perturbed environments by monitoring the depopulation of the ground state level (000000). Although no evidence for true multiphoton absorption is found, a number of important observations have been made. (1) No correlation exists between the IRMPA spectrum under collision-free conditions and the low energy IR absorption spectrum. (2) Homogeneous depletion of rotational populations occurs at all CO/sub 2/-laser frequencies. (3) Bottlenecks to absorption do not occur in the pumped-mode ladder. (4) The probability of absorption depends inversely on pressure and is affected dramatically by long-range collisions. These results are interpreted in the framework of an optical Bloch equation model.

  11. Transverse correlations in multiphoton entanglement

    NASA Astrophysics Data System (ADS)

    Wen, Jianming; Rubin, Morton H.; Shih, Yanhua

    2007-10-01

    We have analyzed the transverse correlation in multiphoton entanglement. The generalization of quantum ghost imaging is extended to the N -photon state. The Klyshko’s two-photon advanced-wave picture is generalized to the N -photon case.

  12. Transverse correlations in multiphoton entanglement

    SciTech Connect

    Wen Jianming; Rubin, Morton H.; Shih Yanhua

    2007-10-15

    We have analyzed the transverse correlation in multiphoton entanglement. The generalization of quantum ghost imaging is extended to the N-photon state. The Klyshko's two-photon advanced-wave picture is generalized to the N-photon case.

  13. Multiphoton ionization of Uracil

    NASA Astrophysics Data System (ADS)

    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.

  14. Video-rate resonant scanning multiphoton microscopy

    PubMed Central

    Kirkpatrick, Nathaniel D.; Chung, Euiheon; Cook, Daniel C.; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L.; Padera, Timothy P.; Fukumura, Dai; Jain, Rakesh K.

    2013-01-01

    The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion and metastasis of tumor cells, the dynamics of immune cell trafficking to and within tumors, and gene expression in tumors. However, traditional multiphoton microscopy suffers from inherently slow imaging rates—only a few frames per second, thus unable to capture more rapid events such as blood flow, lymphatic flow, and cell movement within vessels. Here, we report the development and implementation of a video-rate multiphoton microscope (VR-MPLSM) based on resonant galvanometer mirror scanning that is capable of recording at 30 frames per second and acquiring intravital multispectral images. We show that the design of the system can be readily implemented and is adaptable to various experimental models. As examples, we demonstrate the utility of the system to directly measure flow within tumors, capture metastatic cancer cells moving within the brain vasculature and cells in lymphatic vessels, and image acute responses to changes in a vascular network. VR-MPLSM thus has the potential to further advance intravital imaging and provide new insight into the biology of the tumor microenvironment. PMID:24353926

  15. Multiphoton tomography of astronauts

    NASA Astrophysics Data System (ADS)

    König, Karsten; Weinigel, Martin; Pietruszka, Anna; Bückle, Rainer; Gerlach, Nicole; Heinrich, Ulrike

    2015-03-01

    Weightlessness may impair the astronaut's health conditions. Skin impairments belong to the most frequent health problems during space missions. Within the Skin B project, skin physiological changes during long duration space flights are currently investigated on three European astronauts that work for nearly half a year at the ISS. Measurements on the hydration, the transepidermal water loss, the surface structure, elasticity and the tissue density by ultrasound are conducted. Furthermore, high-resolution in vivo histology is performed by multiphoton tomography with 300 nm spatial and 200 ps temporal resolution. The mobile certified medical tomograph with a flexible 360° scan head attached to a mechano-optical arm is employed to measure two-photon autofluorescence and SHG in the volar forearm of the astronauts. Modification of the tissue architecture and of the fluorescent biomolecules NAD(P)H, keratin, melanin and elastin are detected as well as of SHG-active collagen. Thinning of the vital epidermis, a decrease of the autofluoresence intensity, an increase in the long fluorescence lifetime, and a reduced skin ageing index SAAID based on an increased collagen level in the upper dermis have been found. Current studies focus on recovery effects.

  16. Multiphoton Effects in Rutile.

    NASA Astrophysics Data System (ADS)

    Royce, Gerald A.

    Multiphoton effects are investigated in crystalline rutile TiO(,2) using Nd:YAG laser photons. The 1.06 micron laser is operated in Q-switched mode with intensities up to 1.4 x 10('6) watts/cm('2) on the rutile crystal. Photoconductivity measurements provide data indicating a mixture of modes for electrons to be photoionized. Assuming aluminum impurity as the contributing sites, the first order photionization cross section is found to be 1.5 x 10('-26) cm('2) and second order cross section is found to be 7.7 x 10('-51) cm('4)-s. No appreciable change in cross section is observed for circular versus linear polarization of the laser. Observations of the photo-emission of the laser illuminated crystal provide radiative relaxation times on the order of 100 nanoseconds with emission peaks at 4500 and 5000 angstroms plus a near infrared continuum out to 1 micron. The thermoluminescence of rutile shows a number of trapping levels between 0.4 and 0.8 eV below the conduction band. These are attributed to an aluminum impurity.

  17. Quantitative multiphoton imaging

    NASA Astrophysics Data System (ADS)

    König, Karsten; Weinigel, Martin; Breunig, Hans Georg; Uchugonova, Aisada

    2014-02-01

    Certified clinical multiphoton tomographs for label-free multidimensional high-resolution in vivo imaging have been introduced to the market several years ago. Novel tomographs include a flexible 360° scan head attached to a mechanooptical arm for autofluorescence and SHG imaging as well as a CARS module. Non-fluorescent lipids and water, mitochondrial fluorescent NAD(P)H, fluorescent elastin, keratin, and melanin as well as SHG-active collagen can be imaged in vivo with submicron resolution in human skin. Sensitive and rapid detectors allow single photon counting and the construction of 3D maps where the number of detected photons per voxel is depicted. Intratissue concentration profiles from endogenous as well exogenous substances can be generated when the number of detected photons can be correlated with the number of molecules with respect to binding and scattering behavior. Furthermore, the skin ageing index SAAID based on the ratio elastin/collagen as well as the epidermis depth based on the onset of SHG generation can be determined.

  18. Multimodal multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Légaré, François; Pfeffer, Christian P.; Ganikhanov, Feruz

    2009-02-01

    Multiphoton microscopy is a powerful technique for high spatial resolution thick tissue imaging. In its simple version, it uses a high repetition rate femtosecond oscillator laser source focussed and scanned across biological sample that contains fluorophores. However, not every biological structure is inherently fluorescent or can be stained without causing biochemical changes. To circumvent these limitations, other non-invasive nonlinear optical imaging approaches are currently being developed and investigated with regard to different applications. These techniques are: (1) second harmonic generation (SHG), (2) third harmonic generation (THG), and (3) coherent anti-Stokes Raman scattering (CARS) microscopy. The main advantage of the above mentioned techniques is that they derive their imaging contrast from optical nonlinearities that do not involve fluorescence process. As a particular application example we investigated collagen arrays. We show that combining SHG-THG-CARS onto a single imaging platform provides complementary information about the sub-micron architecture of the tissue. SHG microscopy reveals the fibrillar architecture of collagen arrays and confirm a rather high degree of heterogeneity of χ(2) within the focal volume, THG highlights the boundaries between the collagen sheets, and CH2 spectroscopic contrast with CARS.

  19. The implementation of universal quantum memory and gates based on large-scale diamond surface

    NASA Astrophysics Data System (ADS)

    Qi, Xiao-Ning; Zhang, Yong

    2016-08-01

    Nitrogen-vacancy (NV) centers implanted beneath the diamond surface have been demonstrated to be effective in the processing of controlling and reading-out. In this paper, NV center entangled with the fluorine nuclei collective ensemble is simplified to Jaynes-Cummings (JC) model. Based on this system, we discussed the implementation of quantum state storage and single-qubit quantum gate.

  20. Advances in multiphoton microscopy technology

    PubMed Central

    Hoover, Erich E.; Squier, Jeff A.

    2013-01-01

    Multiphoton microscopy has enabled unprecedented dynamic exploration in living organisms. A significant challenge in biological research is the dynamic imaging of features deep within living organisms, which permits the real-time analysis of cellular structure and function. To make progress in our understanding of biological machinery, optical microscopes must be capable of rapid, targeted access deep within samples at high resolution. In this Review, we discuss the basic architecture of a multiphoton microscope capable of such analysis and summarize the state-of-the-art technologies for the quantitative imaging of biological phenomena. PMID:24307915

  1. Modeling of the initiation and evolution of a laser-ionized column in the lower atmosphere - 314.5 nm wavelength resonant multiphoton ionization of naturally occurring argon

    NASA Technical Reports Server (NTRS)

    Fetzer, G. J.; Stockley, J. E.

    1992-01-01

    A 3+1 resonant multiphoton ionization process in naturally occurring argon is studied at 314.5 nm as a candidate for providing a long ionized channel through the atmosphere. Results are presented which indicate peak electron densities up to 10 exp 8/cu cm can be created using laser intensities on the order of 10 exp 8 W/sq cm.

  2. High-intensity laser heating in liquids: Multiphoton absorption

    SciTech Connect

    Longtin, J.P.; Tien, C.L.

    1995-12-31

    At high laser intensities, otherwise transparent liquids can absorb strongly by the mechanism of multiphoton absorption, resulting in absorption and heating several orders of magnitude greater than classical, low-intensity mechanisms. The use of multiphoton absorption provides a new mechanism for strong, controlled energy deposition in liquids without bulk plasma formation, shock waves, liquid ejection, etc., which is of interest for many laser-liquid applications, including laser desorption of liquid films, laser particle removal, and laser water removal from microdevices. This work develops a microscopically based model of the heating during multiphoton absorption in liquids. The dependence on pulse duration, intensity, wavelength, repetition rate, and liquid properties is discussed. Pure water exposed to 266 nm laser radiation is investigated, and a novel heating mechanism for water is proposed that uses multiple-wavelength laser pulses.

  3. Multiphoton tomography for tissue engineering

    NASA Astrophysics Data System (ADS)

    König, Karsten

    2008-02-01

    Femtosecond laser multiphoton tomography has been employed in the field of tissue engineering to perform 3D high-resolution imaging of the extracellular matrix proteins elastin and collagen as well as of living cells without any fixation, slicing, and staining. Near infrared 80 MHz picojoule femtosecond laser pulses are able to excite the endogenous fluorophores NAD(P)H, flavoproteins, melanin, and elastin via a non-resonant two-photon excitation process. In addition, collagen can be imaged by second harmonic generation. Using a two-PMT detection system, the ratio of elastin to collagen was determined during optical sectioning. A high submicron spatial resolution and 50 picosecond temporal resolution was achieved using galvoscan mirrors and piezodriven focusing optics as well as a time-correlated single photon counting module with a fast microchannel plate detector and fast photomultipliers. Multiphoton tomography has been used to optimize the tissue engineering of heart valves and vessels in bioincubators as well as to characterize artificial skin. Stem cell characterization and manipulation are of major interest for the field of tissue engineering. Using the novel sub-20 femtosecond multiphoton nanoprocessing laser microscope FemtOgene, the differentiation of human stem cells within spheroids has been in vivo monitored with submicron resolution. In addition, the efficient targeted transfection has been demonstrated. Clinical studies on the interaction of tissue-engineered products with the natural tissue environment can be performed with in vivo multiphoton tomograph DermaInspect.

  4. Multiphoton microscopy in life sciences.

    PubMed

    König, K

    2000-11-01

    Near infrared (NIR) multiphoton microscopy is becoming a novel optical tool of choice for fluorescence imaging with high spatial and temporal resolution, diagnostics, photochemistry and nanoprocessing within living cells and tissues. Three-dimensional fluorescence imaging based on non-resonant two-photon or three-photon fluorophor excitation requires light intensities in the range of MW cm(-2) to GW cm(-2), which can be derived by diffraction limited focusing of continuous wave and pulsed NIR laser radiation. NIR lasers can be employed as the excitation source for multifluorophor multiphoton excitation and hence multicolour imaging. In combination with fluorescence in situ hybridization (FISH), this novel approach can be used for multi-gene detection (multiphoton multicolour FISH). Owing to the high NIR penetration depth, non-invasive optical biopsies can be obtained from patients and ex vivo tissue by morphological and functional fluorescence imaging of endogenous fluorophores such as NAD(P)H, flavin, lipofuscin, porphyrins, collagen and elastin. Recent botanical applications of multiphoton microscopy include depth-resolved imaging of pigments (chlorophyll) and green fluorescent proteins as well as non-invasive fluorophore loading into single living plant cells. Non-destructive fluorescence imaging with multiphoton microscopes is limited to an optical window. Above certain intensities, multiphoton laser microscopy leads to impaired cellular reproduction, formation of giant cells, oxidative stress and apoptosis-like cell death. Major intracellular targets of photodamage in animal cells are mitochondria as well as the Golgi apparatus. The damage is most likely based on a two-photon excitation process rather than a one-photon or three-photon event. Picosecond and femtosecond laser microscopes therefore provide approximately the same safe relative optical window for two-photon vital cell studies. In labelled cells, additional phototoxic effects may occur via

  5. Multiphoton imaging of cardiovascular structures

    NASA Astrophysics Data System (ADS)

    Schenke-Layland, Katja; Opitz, Florian; Riemann, Iris; Stock, Ulrich A.; Konig, Karsten

    2004-09-01

    Near infrared (NIR) femtosecond laser imaging systems represent a novel and very promising diagnostic technology for non-invasive cross-sectional analysis of living biological tissues. In this study 3D multiphoton imaging with submicron resolution has been performed for non-invasive analysis of living native and tissue-engineered (TE) heart valves and blood vessels. High-resolution autofluorescence and second harmonic generation (SHG) images of collagenous structures and elastic fibers were demonstrated using multiphoton excitation at two different wavelengths. Non-invasive optical sections have been obtained without the need of staining or embedding. The quality of the resulting three-dimensional images allowed exact differentiation between collagenous structures and elastic fibers. These experimental results are very encouraging for NIR femtosecond laser scanning microscopy as a useful tool for future non-destructive monitoring and characterization of vital and intact TE cardiovascular structures.

  6. Compact clinical high-NA multiphoton endoscopy

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; Fischer, Peter; Kellner-Höfer, Marcel; Bückle, Rainer; König, Karsten

    2012-02-01

    Multiphoton imaging methods are excellent for non-invasive imaging of living tissue without any need of additional contrast agents. The increasing demand for endoscopic techniques has forced the development of multiphoton endoscopes for imaging of areas with reduced accessibility like chronic wounds. Gradient index (GRIN) lenses can miniaturize the bulky distal focusing optics of conventional tomographs to a diameter of less than 1.4 mm and a numerical aperture (NA) of 0.8. We combined a high NA clinical multiphoton endoscope with existing multiphoton tomographs like the DermaInspect® and the MPTflex® to enable the examination of wound healing processes.

  7. Multiphoton microscopy of atheroslcerotic plaques

    NASA Astrophysics Data System (ADS)

    Lilledahl, Magnus B.; de Lange Davies, Catharina; Haugen, Olav A.; Svaasand, Lars O.

    2007-02-01

    Multiphoton microscopy is a techniques that fascilitates three dimensional imaging of intact, unstained tissue. Especially connective tissue has a relatively strong nonlinear optical response and can easily be imaged. Atherosclerosis is a disease where lipids accumulate in the vessel wall and there is a thickening of the intima by growth of a cap of connective tissue. The mechanical strength of this fibrous cap is of clinically importance. If the cap ruptures a thrombosis forms which can block a coronary vessel and therby causing myocardial infarction. Multiphoton microscopy can be used to image the fibrous cap and thereby determine the thickness of the cap and the structure of the connective fibres. This could possibly be developed into a diagnostic and clincal tool to monitor the vulnerability of a plaque and also to better understand the development of a plaque and effects of treatment. We have collected multiphoton microscopy images from atherosclerotic plaque in human aorta, both two photon excited fluorescens and second harmonic generated signal. The feasability of using this technique to determine the state of the plaque is explored.

  8. Quantum Dynamical Model of Laser/Surface-Induced Predissociation: Multiphoton-Multiphonon Processes and Photon/Phonon-Dressed States.

    DTIC Science & Technology

    1981-02-01

    Landau - Zener form), is studied. The optimal detunings for the enhancement of LSSPD are shown by the numerical results of a set of coupled generalized...induced damping factor (level width), the field detuning, and the phase detuning ( Landau - Zener form), is studied. The optimal detunings for the enhancement...the phase detuning obtained by the usual Landau - Zener model, i.e., W2 c(R)-W1 2 R)-iw 2 .c(t. 17 There are some important features of the above

  9. Correlated multiphoton holes: absence of multiphoton coincidence events.

    PubMed

    Afek, I; Ambar, O; Silberberg, Y

    2010-08-27

    We generate bipartite states of light which exhibit an absence of multiphoton coincidence events between two modes amid a constant background flux. These "correlated photon holes" are produced by mixing a coherent state and relatively weak spontaneous parametric down-conversion by using a balanced beam splitter. Correlated holes with arbitrarily high photon numbers may be obtained by adjusting the relative phase and amplitude of the inputs. We measure states of up to five photons and verify their nonclassicality. The scheme provides a route for observation of high-photon-number nonclassical correlations without requiring intense quantum resources.

  10. Multiphoton excited fluorescence spectroscopy of biomolecular systems

    NASA Astrophysics Data System (ADS)

    Birch, David J. S.

    2001-09-01

    Recent work on the emerging application of multiphoton excitation to fluorescence studies of biomolecular dynamics and structure is reviewed. The fundamental principles and experimental techniques of multiphoton excitation are outlined, fluorescence lifetimes, anisotropy and spectra in membranes, proteins, hydrocarbons, skin, tissue and metabolites are featured, and future opportunities are highlighted.

  11. Multi-Photon Fluorescence Microscopy: Behavior of Biological Specimens Under High Intensity Illumination

    DTIC Science & Technology

    2000-07-01

    used in these types of microscopy. We have used maize leaf protoplast as a model system to evaluate the photo-induced response of living sample under...to fluorescence emission, second harmonic generation was observed in the maize protoplasts. Keywords: Multi-photon fluorescence microscopy, photon...damage, cell damage, high intensity illumination, maize 1. INTRODUCTION Multi-photon fluorescence microscopy has been cited for its advantage in the

  12. Phase-imprinted multiphoton subradiant states

    NASA Astrophysics Data System (ADS)

    Jen, H. H.

    2017-08-01

    We propose to generate the multiphoton subradiant states and investigate their fluorescences in an array of two-level atoms. These multiphoton states are created initially from the timed Dicke states. Then we can use either a Zeeman or Stark field gradient pulse to imprint linearly increasing phases on the atoms, and this phase-imprinting process unitarily evolves the system to the multiphoton subradiant states. The fluorescence engages a long-range dipole-dipole interaction which originates from a system-reservoir coupling in the dissipation. We locate some of the subradiant multiphoton states from the eigenmodes and show that an optically thick atomic array is best for the preparation of the state with the most reduced decay rate. This phase-imprinting process enables quantum-state engineering of the multiphoton subradiant states and realizes a potential quantum storage of the photonic qubits in the two-level atoms.

  13. Intensity dependence of multiphoton dissociation in formaldehyde

    NASA Astrophysics Data System (ADS)

    Koren, G.

    1980-01-01

    The paper reports a new intensity-dependent measurement of multiple-photon dissociation (MPD) in H2CO, HDCO, and D2CO gases using an intense pulsed CO2 TEA laser. In this measurement the energy and duration of the laser pulses are constant, and the intensity is varied by irradiating the sample with concave mirrors of different focal lengths. A model calculation is used to analyze and fit the MPD data of HDCO and D2CO which assumes that dissociation is obtained by a repeated mechanism in which coherent multiphoton excitation (CME) of the molecule to high vibration-rotation states is followed by intramolecular transfer of the excitation energy (ITEE) to the other molecule modes. It is concluded that the results are consistent with the absorption of 14 plus or minus 4 and 17 plus or minus 5 photons per molecule of HDCO and D2CO, respectively.

  14. High-resolution multiphoton cryomicroscopy.

    PubMed

    König, Karsten; Uchugonova, Aisada; Breunig, Hans Georg

    2014-03-15

    An ultracompact high-resolution multiphoton cryomicroscope with a femtosecond near infrared fiber laser has been utilized to study the cellular autofluorescence during freezing and thawing of cells. Cooling resulted in an increase of the intracellular fluorescence intensity followed by morphological modifications at temperatures below -10 °C, depending on the application of the cryoprotectant DMSO and the cooling rate. Furthermore, fluorescence lifetime imaging revealed an increase of the mean lifetime with a decrease in temperature. Non-destructive, label-free optical biopsies of biomaterial in ice can be obtained with sub-20 mW mean powers.

  15. Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in new mouse models with fluorescent lineage tags.

    PubMed

    Hackl, Matthias J; Burford, James L; Villanueva, Karie; Lam, Lisa; Suszták, Katalin; Schermer, Bernhard; Benzing, Thomas; Peti-Peterdi, János

    2013-12-01

    Podocytes are critical in the maintenance of a healthy glomerular filter; however, they have been difficult to study in the intact kidney because of technical limitations. Here we report the development of serial multiphoton microscopy (MPM) of the same glomeruli over several days to visualize the motility of podocytes and parietal epithelial cells (PECs) in vivo. In podocin-GFP mice, podocytes formed sporadic multicellular clusters after unilateral ureteral ligation and migrated into the parietal Bowman's capsule. The tracking of single cells in podocin-confetti mice featuring cell-specific expression of CFP, GFP, YFP or RFP revealed the simultaneous migration of multiple podocytes. In phosphoenolpyruvate carboxykinase (PEPCK)-GFP mice, serial MPM found PEC-to-podocyte migration and nanotubule connections. Our data support a highly dynamic rather than a static nature of the glomerular environment and cellular composition. Future application of this new approach should advance our understanding of the mechanisms of glomerular injury and regeneration.

  16. Two-color multiphoton emission from nanotips

    NASA Astrophysics Data System (ADS)

    Cheng-Wei Huang, Wayne; Becker, Maria; Beck, Joshua; Batelaan, Herman

    2017-02-01

    Two-color multiphoton emission from polycrystalline tungsten nanotips has been demonstrated using two-color laser fields. The two-color photoemission is assisted by a three-photon multicolor quantum channel, which leads to a twofold increase in quantum efficiency. Weak-field control of two-color multiphoton emission was achieved by changing the efficiency of the quantum channel with pulse delay. The result of this study complements two-color tunneling photoemission in strong fields, and has potential applications for nanowire-based photonic devices. Moreover, the demonstrated two-color multiphoton emission may be important for realizing ultrafast spin-polarized electron sources via optically injected spin current.

  17. Multiphoton cryo microscope with sample temperature control

    NASA Astrophysics Data System (ADS)

    Breunig, H. G.; Uchugonova, A.; König, K.

    2013-02-01

    We present a multiphoton microscope system which combines the advantages of multiphoton imaging with precise control of the sample temperature. The microscope provides online insight in temperature-induced changes and effects in plant tissue and animal cells with subcellular resolution during cooling and thawing processes. Image contrast is based on multiphoton fluorescence intensity or fluorescence lifetime in the range from liquid nitrogen temperature up to +600°C. In addition, micro spectra from the imaged regions can be recorded. We present measurement results from plant leaf samples as well as Chinese hamster ovary cells.

  18. Multiphoton fluorescence lifetime imaging of human hair.

    PubMed

    Ehlers, Alexander; Riemann, Iris; Stark, Martin; König, Karsten

    2007-02-01

    In vivo and in vitro multiphoton imaging was used to perform high resolution optical sectioning of human hair by nonlinear excitation of endogenous as well as exogenous fluorophores. Multiphoton fluorescence lifetime imaging (FLIM) based on time-resolved single photon counting and near-infrared femtosecond laser pulse excitation was employed to analyze the various fluorescent hair components. Time-resolved multiphoton imaging of intratissue pigments has the potential (i) to identify endogenous keratin and melanin, (ii) to obtain information on intrahair dye accumulation, (iii) to study bleaching effects, and (iv) to monitor the intratissue diffusion of pharmaceutical and cosmetical components along hair shafts.

  19. Phase matching alters spatial multiphoton processes in dense atomic ensembles.

    PubMed

    Leszczyński, Adam; Parniak, Michał; Wasilewski, Wojciech

    2017-01-09

    Multiphoton processes in dense atomic vapors such as four-wave mixing or coherent blue light generation are typically viewed from single-atom perspective. Here we study the surprisingly important effect of phase matching near two-photon resonances that arises due to spatial extent of the atomic medium within which the multiphoton process occurs. The non-unit refractive index of the atomic vapor may inhibit generation of light in nonlinear processes, significantly shift the efficiency maxima in frequencies and redirect emitted beam. We present these effects on an example of four-wave mixing in dense rubidium vapors in a double-ladder configuration. By deriving a simple theory that takes into account essential spatial properties of the process, we give precise predictions and confirm their validity in the experiment. The model allows us to improve on the geometry of the experiment and engineer more efficient four-wave mixing.

  20. Multiphoton microscopy: an introduction to gastroenterologists.

    PubMed

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

    2011-10-28

    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.

  1. Microbeam-integrated multiphoton imaging system

    PubMed Central

    Bigelow, Alan W.; Geard, Charles R.; Randers-Pehrson, Gerhard; Brenner, David J.

    2008-01-01

    Multiphoton microscopy has been added to the array of imaging techniques at the endstation for the Microbeam II cell irradiator at Columbia University’s Radiological Research Accelerator Facility (RARAF). This three-dimensional (3D), laser-scanning microscope functions through multiphoton excitation, providing an enhanced imaging routine during radiation experiments with tissuelike samples, such as small living animals and organisms. Studies at RARAF focus on radiation effects; hence, this multiphoton microscope was designed to observe postirradiation cellular dynamics. This multiphoton microscope was custom designed into an existing Nikon Eclipse E600-FN research fluorescence microscope on the irradiation platform. Design details and biology applications using this enhanced 3D-imaging technique at RARAF are reviewed. PMID:19123569

  2. Differential Multiphoton Laser Scanning Microscopy

    PubMed Central

    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. PMID:27390511

  3. Differential Multiphoton Laser Scanning Microscopy

    SciTech Connect

    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.

    2012-01-01

    Multifocal multiphoton laser scanning microscopy (mfMPLSM) in the biological and medical sciences has the potential to become a ubiquitous tool for obtaining high-resolution images at video rates. While current implementations of mfMPLSM 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 mfMPLSM in which whole-field detection with a single detector, rather than detection with a matrix of detectors, such as a charge-coupled device (CCD) camera, is implemented. This advance makes mfMPLSM fully compatible for use in imaging through scattering media. Further, we demonstrate that this method makes it possible to simultaneously obtain multiple images and view differences in excitation parameters in a single scan of the specimen.

  4. Mechanisms of Multiphoton Dissociation of Molecular Ions.

    DTIC Science & Technology

    1981-04-30

    dissociation energy and are thus re- Thus, some small fraction of all ions produced in our moved from the beam by unimolecular decomposition. source probably...AD-A099 121 SRI INTERNATIONAL MENLO PARK CA F/6 7/5 MECHANISMS OF MULTIPHOTON DISSOCIATION OF MOLECULAR IONS, U) APR 81 M J COGGIOLA. J R PETERSON, P...Final Report MECHANISMS OF MULTIPHOTON DISSOCIATION OF MOLECULAR IONS By: Michael J. Coggiola, Project Leader James R. Peterson, Project Supervisor

  5. Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in novel mouse models with fluorescent lineage tags

    PubMed Central

    Hackl, Matthias J.; Burford, James L.; Villanueva, Karie; Lam, Lisa; Suszták, Katalin; Schermer, Bernhard; Benzing, Thomas; Peti-Peterdi, János

    2014-01-01

    Podocytes are critical in the maintenance of a healthy glomerular filter, however they have been difficult to study in the intact kidney due to technical limitations. Here we report the development of serial multiphoton microscopy (MPM) of the same glomeruli over several days to visualize the motility of podocytes and parietal epithelial cells (PEC) in vivo. In Podocin-GFP mice podocytes formed sporadic multi-cellular clusters after unilateral ureteral ligation (UUO) and migrated into the parietal Bowman’s capsule. The tracking of single cells in Podocin-confetti mice featuring cell-specific expression of CFP, GFP, YFP, or RFP revealed the simultaneous migration of multiple podocytes. In PEPCK-GFP mice serial MPM found PEC-to-podocyte migration and nanotubule connections. Our data support the highly dynamic rather than static nature of the glomerular environment and cellular composition. Future application of this new approach promises to advance our understanding of the mechanisms of glomerular injury and regeneration. PMID:24270544

  6. Multiphoton ionization of uranium hexafluoride

    NASA Astrophysics Data System (ADS)

    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

  7. Multiphoton fluorescent images with a spatially varying background signal: a ML deconvolution method.

    PubMed

    Crivaro, M; Enjieu-Kadji, H; Hatanaka, R; Nakauchi, S; Bosch, J; Judin, J; Riera, J; Kawashima, R

    2011-06-01

    By means of multiphoton laser scanning microscopy, neuroscientists can look inside the brain deeper than has ever been possible before. Multiphoton fluorescent images, as all optical images, suffer from degradation caused by a variety of sources (e.g. light dispersion and absorption in the tissue, laser fluctuations, spurious photodetection and staining deficiency). From a modelling perspective, such degradations can be considered the sum of stochastic noise and a background signal. Among the methods proposed in the literature to perform image deconvolution in either confocal or multiphoton fluorescent microscopy, Vicidomini et al. (2009) were the first to incorporate models for noise (a Poisson process) and background signal (spatially constant) in the context of regularized inverse problems. Unfortunately, the so-called split-gradient deconvolution method (SGM) they used did not consider possible spatial variations in the background signal. In this paper, we extend the SGM by adding a maximum-likelihood estimation step for the determination of a spatially varying background signal. We demonstrate that the assumption of a constant background is not always valid in multiphoton laser microscopy and by using synthetic and actual multiphoton fluorescent images, we evaluate the face of validity of the proposed method, and compare its accuracy with the previously introduced SGM algorithm.

  8. Multi-photon excitation microscopy

    PubMed Central

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

    2006-01-01

    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 engineering, materials science where imaging can be coupled to the possibility of using the microscopes in an active way, too. As well, 2PE implementations in noninvasive optical bioscopy or laser-based treatments point out to the relevance in clinical applications. Here we report about some basic aspects related to the phenomenon, implications in three-dimensional imaging microscopy, practical aspects related to design and realization of MPE microscopes, and we only give a list of potential applications and variations on the theme in order to offer a starting point for advancing new applications and developments. PMID:16756664

  9. Multi-photon excitation microscopy.

    PubMed

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

    2006-06-06

    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 engineering, materials science where imaging can be coupled to the possibility of using the microscopes in an active way, too. As well, 2PE implementations in noninvasive optical bioscopy or laser-based treatments point out to the relevance in clinical applications. Here we report about some basic aspects related to the phenomenon, implications in three-dimensional imaging microscopy, practical aspects related to design and realization of MPE microscopes, and we only give a list of potential applications and variations on the theme in order to offer a starting point for advancing new applications and developments.

  10. Multi-Photon Quantum Interferometry

    NASA Astrophysics Data System (ADS)

    Bouwmeester, Dirk

    2007-06-01

    Based on the investigation of multi-photon entanglement, as produced by stimulated parametric down-conversion, a technique is presented to create heralded ``noon'' states. The relevance for interferometry will be discussed. Furthermore we explored the use of photon-number resolving detectors in Mach-Zehnder type of interferometers. Our current detectors can distinguish 0, 1, 2, to7, photon impacts. Although the overall collection and detection efficiency of photons is well below unity (about 0.3) the photon number resolving property is still very useful if combined with coherent input states since those state are eigenstates of the photon annihilation operator. First we analyze the coherent state interferometer with a single photon-number resolving detector, revealing the strong non-linear response of an interferometer in the case of Fock-state projection. Second, we use two such detectors together with a Baysian phase estimation strategy to demonstrate that it is possible to achieve the standard quantum limit independently from the true value of the phase shift. This protocol is unbiased and saturates the Cramer-Rao phase uncertainty bound and, therefore, is an optimal phase estimation strategy. As a final topic it will be shown how quantum interferometry combined with micromechanical structures can be used to investigate quantum superpositions and quantum decoherence of macroscopic objects.

  11. Clinical multiphoton and CARS microscopy

    NASA Astrophysics Data System (ADS)

    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.

  12. Multiphoton fluorescence microscopy in biology

    NASA Astrophysics Data System (ADS)

    Heikal, Ahmed A.; Webb, Watt W.

    2002-11-01

    The inherent advantages of nonlinear excitation make multiphoton fluorescence microscopy (MPFM) awell-suited imaging technique for extracting valuable information from turbid and thick biological samples. These advantages include high three-dimensional spatial resolution, large penetration depth, minimum out-of-focus cellular photodamage, and high signal-to-noise contrast. We have investigated the nonlinear spectroscopy of biologically important molecules such as NADH, flavins, and intrinsically fluorescent proteins. Fundamental understanding of the molecular spectroscopy and dynamics of these biomolecules is essential for advancing their applications in biological research. MPFM has been utilized for monitoring a large spectrum of biological processes including metabolic activity and exocytosis. We will discuss two-photon (2P) redox fluorescence microscopy of NADH, which gives a quantitative measure of the respiratory chain activity, thus allowing functional imaging of energy metabolism in neurons and native brain tissue. Finally, a rational design strategy, based on donor-acceptor-donor configuration, will be elucidated for fluorescent probes with large 2P-excitation cross-section. These dyes are water-soluble, yet possess a high affinity to organic phases with site-specific labeling and Ca+2 sensitivity (Kd ~ 350 nM). A brief account on the biological application of nanocrystals and second harmonic imaging will be reviewed.

  13. Visualizing the podocyte with multiphoton microscopy

    PubMed Central

    Khoury, Charbel C.; Khayat, Mark F.; Yeo, Tet-Kin; Pyagay, Petr E.; Wang, Amy; Asuncion, Allan M.; Sharma, Kumar; Yu, Weiming; Chen, Sheldon

    2012-01-01

    The podocyte is a highly specialized kidney glomerular epithelial cell that plays an essential role in glomerular filtration and is believed to be the target of numerous glomerular diseases leading to proteinuria. Despite the leaps in our understanding of podocyte biology, new methodologies are needed to facilitate research into the cell. Multiphoton microscopy (MPM) was used to image the nephrin knockout/green fluorescent protein (GFP) knock-in heterozygote (Nphs1tm1Rkl/J) mouse. The nephrin promoter restricts GFP expression to the podocytes that fluoresce green under excitation. From the exterior of an intact kidney, MPM can peer into the renal parenchyma and visualize the podocytes that outline the globular shape of the glomeruli. Details as fine as the podocyte’s secondary processes can be resolved. In contrast, podocytes exhibit no fluorescence in the wildtype mouse and are invisible to MPM. Phenotypically, there are no significant differences between wildtype and Nphs1tm1Rkl/J mice in body weight, urinary albumin excretion, creatinine clearance, or glomerular depth. Interestingly, the glomeruli are closer to the kidney capsule in female mice, making the gender the preferred choice for MPM. For the first time, green fluorescent podocytes in a mouse model free of confounding phenotypes can be visualized unequivocally and in the “positive” by MPM, facilitating intravital studies of the podocyte. PMID:23022193

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

    NASA Astrophysics Data System (ADS)

    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.

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

    SciTech Connect

    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.

  16. Phase sensitive demodulation in multiphoton microscopy.

    PubMed

    Fisher, Walt G; Piston, David W; Wachter, Eric A

    2002-06-01

    Multiphoton laser scanning microscopy offers advantages in depth of penetration into intact samples over other optical sectioning techniques. To achieve these advantages it is necessary to detect the emitted light without spatial filtering. In this nondescanned (nonconfocal) approach, ambient room light can easily contaminate the signal, forcing experiments to be performed in absolute darkness. For multiphoton microscope systems employing mode-locked lasers, signal processing can be used to reduce such problems by taking advantage of the pulsed characteristics of such lasers. Specifically, by recovering fluorescence generated at the mode-locked frequency, interference from stray light and other ambient noise sources can be significantly reduced. This technology can be adapted to existing microscopes by inserting demodulation circuitry between the detector and data collection system. The improvement in signal-to-noise ratio afforded by this approach yields a more robust microscope system and opens the possibility of moving multiphoton microscopy from the research lab to more demanding settings, such as the clinic.

  17. A pragmatic guide to multiphoton microscope design

    PubMed Central

    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. PMID:27182429

  18. Multiphoton microscopy in defining liver function

    NASA Astrophysics Data System (ADS)

    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.

  19. Polarization phenomena in multiphoton ionization of atoms.

    NASA Technical Reports Server (NTRS)

    Jacobs, V. L.

    1973-01-01

    The theory of multiphoton ionization for an atomic system of arbitrary complexity is developed using a density matrix formalism. An expression is obtained which determines the differential N-photon ionization cross section as a function of the polarization states of the target atom and the incident radiation. The parameters which characterize the photo-electron angular distribution are related to the general reduced matrix elements for the N-photon transition. Two-photon ionization of unpolarized atoms is treated as an illustration of the use of the theory. The dependence of the multiphoton ionization cross section on the polarization state of the incident radiation, which has been observed in two- and three-photon ionization of Cs, is accounted for by the theory. Finally, the photoelectron spin polarization produced by the multiphoton ionization of unpolarized atoms, like the analogous polarization resulting from single-photon ionization, is found to depend on the circular polarization of the incident radiation.

  20. Polarization phenomena in multiphoton ionization of atoms

    NASA Technical Reports Server (NTRS)

    Jacobs, V. L.

    1973-01-01

    The theory of multiphoton ionization for an atomic system of arbitrary complexity is developed using a density matrix formalism. An expression is obtained which determines the differential N-photon ionization cross section as a function of the polarization states of the target atom and the incident radiation. The parameters which characterize the photoelectron angular distribution are related to the general reduced matrix elements for the N-photon transition. Two-photon ionization of unpolarized atoms is treated as an illustration of the use of the theory. The dependence of the multiphoton ionization cross section on the polarization state of the incident radiation, which has been observed in two- and three-photon ionization of Cs, is accounted for by the theory. Finally, the photoelectron spin polarization produced by the multiphoton ionization of unpolarized atoms, like the analogous polarization resulting from single-photon ionization, is found to depend on the circular polarization of the incident radiation.

  1. A pragmatic guide to multiphoton microscope design.

    PubMed

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

    2015-06-30

    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.

  2. Multiphoton absorption in amyloid protein fibres

    NASA Astrophysics Data System (ADS)

    Hanczyc, Piotr; Samoc, Marek; Norden, Bengt

    2013-12-01

    Fibrillization of peptides leads to the formation of amyloid fibres, which, when in large aggregates, are responsible for diseases such as Alzheimer's and Parkinson's. Here, we show that amyloids have strong nonlinear optical absorption, which is not present in native non-fibrillized protein. Z-scan and pump-probe experiments indicate that insulin and lysozyme β-amyloids, as well as α-synuclein fibres, exhibit either two-photon, three-photon or higher multiphoton absorption processes, depending on the wavelength of light. We propose that the enhanced multiphoton absorption is due to a cooperative mechanism involving through-space dipolar coupling between excited states of aromatic amino acids densely packed in the fibrous structures. This finding will provide the opportunity to develop nonlinear optical techniques to detect and study amyloid structures and also suggests that new protein-based materials with sizable multiphoton absorption could be designed for specific applications in nanotechnology, photonics and optoelectronics.

  3. Design and development of compact multiphoton microscopes

    NASA Astrophysics Data System (ADS)

    Mehravar, SeyedSoroush

    A compact multi-photon microscope (MPM) was designed and developed with the use of low-cost mode-locked fiber lasers operating at 1040nm and 1560nm. The MPM was assembled in-house and the system aberration was investigated using the optical design software: Zemax. A novel characterization methodology based on 'nonlinear knife-edge' technique was also introduced to measure the axial, lateral resolution, and the field curvature of the multi-photon microscope's image plane. The field curvature was then post-corrected using data processing in MATLAB. A customized laser scanning software based on LabVIEW was developed for data acquisition, image display and controlling peripheral electronics. Finally, different modalities of multi-photon excitation such as second- and third harmonic generation, two- and three-photon fluorescence were utilized to study a wide variety of samples from cancerous cells to 2D-layered materials.

  4. New developments in multimodal clinical multiphoton tomography

    NASA Astrophysics Data System (ADS)

    König, Karsten

    2011-03-01

    80 years ago, the PhD student Maria Goeppert predicted in her thesis in Goettingen, Germany, two-photon effects. It took 30 years to prove her theory, and another three decades to realize the first two-photon microscope. With the beginning of this millennium, first clinical multiphoton tomographs started operation in research institutions, hospitals, and in the cosmetic industry. The multiphoton tomograph MPTflexTM with its miniaturized flexible scan head became the Prism-Award 2010 winner in the category Life Sciences. Multiphoton tomographs with its superior submicron spatial resolution can be upgraded to 5D imaging tools by adding spectral time-correlated single photon counting units. Furthermore, multimodal hybrid tomographs provide chemical fingerprinting and fast wide-field imaging. The world's first clinical CARS studies have been performed with a hybrid multimodal multiphoton tomograph in spring 2010. In particular, nonfluorescent lipids and water as well as mitochondrial fluorescent NAD(P)H, fluorescent elastin, keratin, and melanin as well as SHG-active collagen have been imaged in patients with dermatological disorders. Further multimodal approaches include the combination of multiphoton tomographs with low-resolution imaging tools such as ultrasound, optoacoustic, 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 (malignant melanoma), optimization of treatment strategies (wound healing, dermatitis), and cosmetic research including long-term biosafety tests of ZnO sunscreen nanoparticles and the measurement of the stimulated biosynthesis of collagen by anti-ageing products.

  5. Human bladder cancer diagnosis using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sushmita; Wysock, James S.; Ng, Casey K.; Akhtar, Mohammed; Perner, Sven; Lee, Ming-Ming; Rubin, Mark A.; Maxfield, Frederick R.; Webb, Watt W.; Scherr, Douglas S.

    2009-02-01

    At the time of diagnosis, approximately 75% of bladder cancers are non-muscle invasive. Appropriate diagnosis and surgical resection at this stage improves prognosis dramatically. However, these lesions, being small and/or flat, are often missed by conventional white-light cystoscopes. Furthermore, it is difficult to assess the surgical margin for negativity using conventional cystoscopes. Resultantly, the recurrence rates in patients with early bladder cancer are very high. This is currently addressed by repeat cystoscopies and biopsies, which can last throughout the life of a patient, increasing cost and patient morbidity. Multiphoton endoscopes offer a potential solution, allowing real time, noninvasive biopsies of the human bladder, as well as an up-close assessment of the resection margin. While miniaturization of the Multiphoton microscope into an endoscopic format is currently in progress, we present results here indicating that Multiphoton imaging (using a bench-top Multiphoton microscope) can indeed identify cancers in fresh, unfixed human bladder biopsies. Multiphoton images are acquired in two channels: (1) broadband autofluorescence from cells, and (2) second harmonic generation (SHG), mostly by tissue collagen. These images are then compared with gold standard hematoxylin/eosin (H&E) stained histopathology slides from the same specimen. Based on a "training set" and a very small "blinded set" of samples, we have found excellent correlation between the Multiphoton and histopathological diagnoses. A larger blinded analysis by two independent uropathologists is currently in progress. We expect that the conclusion of this phase will provide us with diagnostic accuracy estimates, as well as the degree of inter-observer heterogeneity.

  6. Multiphoton flow cytometry strategies and applications.

    PubMed

    Tkaczyk, Eric R; Tkaczyk, Alan H

    2011-10-01

    A handful of research teams around the world have recently begun to utilize multiphoton techniques in cytometry, especially for in vivo applications. These approaches offer similar enhancements to flow cytometry as the multiphoton phenomenon brought to the field of microscopy at the turn of the 20th century, with at least six advantages over single-photon excitation. Here, we review the published literature on multiphoton cytometry in vivo or in vitro from the initial experiments in 1999 to present. Multiphoton cytometry instrumentation set-ups vary from adapted multiphoton microscopy to a dedicated system, with laser pulse power and repetition rate serving as important variables. Two-beam geometry enables quantitation of cell size. Labeling strategies include conjugated fluorophore targeting, with folate and/or dendrimer platforms. With two-color measurement, ratiometric labeling is also possible, where one dye serves as a trigger to indicate the amount of excitation a cell receives, and another informs of cellular function. With two-color labeling, geometric fluorophore distribution proves important in theory and experiment for detection sensitivity curves and detected event intensity correlation. The main biological achievements to date using this young technology are reviewed, with emphasis on real-time monitoring of minute-by-minute and long-term cell dynamics as well as the clinically significant surveillance of circulating tumor cells. For this goal, minimally invasive two-photon flow cytometry with a fiber probe may overcome the primary issue of sample volume. The technique of multicolor, multiphoton flow cytometry greatly enhances the capabilities of flow cytometry to investigate the dynamics of circulating cells in cancer and other important diseases, and may in the future benefit from advances in microscopy such as super-resolution imaging, coherent control, and bioluminescence. Copyright © 2011 International Society for Advancement of Cytometry.

  7. Classical-driving-assisted entanglement dynamics control

    NASA Astrophysics Data System (ADS)

    Zhang, Ying-Jie; Han, Wei; Xia, Yun-Jie; Fan, Heng

    2017-04-01

    We propose a scheme of controlling entanglement dynamics of a quantum system by applying the external classical driving field for two atoms separately located in a single-mode photon cavity. It is shown that, with a judicious choice of the classical-driving strength and the atom-photon detuning, the effective atom-photon interaction Hamiltonian can be switched from Jaynes-Cummings model to anti-Jaynes-Cummings model. By tuning the controllable atom-photon interaction induced by the classical field, we illustrate that the evolution trajectory of the Bell-like entanglement states can be manipulated from entanglement-sudden-death to no-entanglement-sudden-death, from no-entanglement-invariant to entanglement-invariant. Furthermore, the robustness of the initial Bell-like entanglement can be improved by the classical driving field in the leaky cavities. This classical-driving-assisted architecture can be easily extensible to multi-atom quantum system for scalability.

  8. Quantum cryptography with perfect multiphoton entanglement.

    PubMed

    Luo, Yuhui; Chan, Kam Tai

    2005-05-01

    Multiphoton entanglement in the same polarization has been shown theoretically to be obtainable by type-I spontaneous parametric downconversion (SPDC), which can generate bright pulses more easily than type-II SPDC. A new quantum cryptographic protocol utilizing polarization pairs with the detected type-I entangled multiphotons is proposed as quantum key distribution. We calculate the information capacity versus photon number corresponding to polarization after considering the transmission loss inside the optical fiber, the detector efficiency, and intercept-resend attacks at the level of channel error. The result compares favorably with all other schemes employing entanglement.

  9. Zeno physics in ultrastrong-coupling circuit QED

    SciTech Connect

    Lizuain, I.; Casanova, J.; Muga, J. G.; Garcia-Ripoll, J. J.; Solano, E.

    2010-06-15

    We study the Zeno and anti-Zeno effects in a superconducting qubit interacting strongly and ultrastrongly with a microwave resonator. Using a model of a frequently measured two-level system interacting with a quantized mode, we predict different behaviors and total control of the Zeno times depending on whether the rotating-wave approximation can be applied in the Jaynes-Cummings model. As an example, we show the dependence of our results with the properties of the initial field states.

  10. Strong light-matter coupling in the presence of lasing

    NASA Astrophysics Data System (ADS)

    Gies, C.; Gericke, F.; Gartner, P.; Holzinger, S.; Hopfmann, C.; Heindel, T.; Wolters, J.; Schneider, C.; Florian, M.; Jahnke, F.; Höfling, S.; Kamp, M.; Reitzenstein, S.

    2017-08-01

    The regime of strong light-matter coupling is typically associated with weak excitation. With current realizations of cavity-QED systems, strong coupling may persevere even at elevated excitation levels sufficient to cross the threshold to lasing. In the presence of stimulated emission, the vacuum-Rabi doublet in the emission spectrum is modified and the established criterion for strong coupling no longer applies. We provide a generalized criterion for strong coupling and the corresponding emission spectrum, which includes the influence of higher Jaynes-Cummings states. The applicability is demonstrated in a theory-experiment comparison of a few-emitter quantum-dot-micropillar laser as a particular realization of the driven dissipative Jaynes-Cummings model. Furthermore, we address the question if and for which parameters true single-emitter lasing can be achieved and provide evidence for the coexistence of strong coupling and lasing in our system in the presence of background emitter contributions.

  11. Studies on wide-field-of-view multiphoton imaging using the flexible clinical multiphoton tomograph MPTflex

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; Fischer, Peter; Kellner-Höfer, Marcel; Bückle, Rainer; König, Karsten

    2012-03-01

    Multiphoton imaging systems are capable of high-resolution 3-D image acquisition of deep tissue. A first commercially available CE-certified biomedical system for subcelluar resolution of human skin has been launched by JenLab company with the DermaInspectR in 2002. The demand for more flexibility caused the development of the MPTflexR, which provides an increased flexibility and accessibility especially for clinical and cosmetic examinations. However the high resolution of clinical multiphoton tomographs are adherent with a small field-of-view (FOV) of about 360×360μm2. Especially time-consuming is the relocation of areas of interest (AOI) like lesions, sweat glands or hair shafts during a multiphoton examination. This limitation can be be overcome by macroscopic large-area (wide-field-ofview) multiphoton tomography, which is tested first within this work.

  12. Intravital multiphoton imaging of mouse tibialis anterior muscle

    PubMed Central

    Lau, Jasmine; Goh, Chi Ching; Devi, Sapna; Keeble, Jo; See, Peter; Ginhoux, Florent; Ng, Lai Guan

    2016-01-01

    ABSTRACT Intravital imaging by multiphoton microscopy is a powerful tool to gain invaluable insight into tissue biology and function. Here, we provide a step-by-step tissue preparation protocol for imaging the mouse tibialis anterior skeletal muscle. Additionally, we include steps for jugular vein catheterization that allow for well-controlled intravenous reagent delivery. Preparation of the tibialis anterior muscle is minimally invasive, reducing the chances of inducing damage and inflammation prior to imaging. The tibialis anterior muscle is useful for imaging leukocyte interaction with vascular endothelium, and to understand muscle contraction biology. Importantly, this model can be easily adapted to study neuromuscular diseases and myopathies. PMID:28243520

  13. Circular Dichroism in Multiphoton Ionization of Resonantly Excited He^{+} Ions.

    PubMed

    Ilchen, M; Douguet, N; Mazza, T; Rafipoor, A J; Callegari, C; Finetti, P; Plekan, O; Prince, K C; Demidovich, A; Grazioli, C; Avaldi, L; Bolognesi, P; Coreno, M; Di Fraia, M; Devetta, M; Ovcharenko, Y; Düsterer, S; Ueda, K; Bartschat, K; Grum-Grzhimailo, A N; Bozhevolnov, A V; Kazansky, A K; Kabachnik, N M; Meyer, M

    2017-01-06

    Intense, circularly polarized extreme-ultraviolet and near-infrared (NIR) laser pulses are combined to double ionize atomic helium via the oriented intermediate He^{+}(3p) resonance state. Applying angle-resolved electron spectroscopy, we find a large photon helicity dependence of the spectrum and the angular distribution of the electrons ejected from the resonance by NIR multiphoton absorption. The measured circular dichroism is unexpectedly found to vary strongly as a function of the NIR intensity. The experimental data are well described by theoretical modeling and possible mechanisms are discussed.

  14. Circular Dichroism in Multiphoton Ionization of Resonantly Excited He+ Ions

    NASA Astrophysics Data System (ADS)

    Ilchen, M.; Douguet, N.; Mazza, T.; Rafipoor, A. J.; Callegari, C.; Finetti, P.; Plekan, O.; Prince, K. C.; Demidovich, A.; Grazioli, C.; Avaldi, L.; Bolognesi, P.; Coreno, M.; Di Fraia, M.; Devetta, M.; Ovcharenko, Y.; Düsterer, S.; Ueda, K.; Bartschat, K.; Grum-Grzhimailo, A. N.; Bozhevolnov, A. V.; Kazansky, A. K.; Kabachnik, N. M.; Meyer, M.

    2017-01-01

    Intense, circularly polarized extreme-ultraviolet and near-infrared (NIR) laser pulses are combined to double ionize atomic helium via the oriented intermediate He+(3 p ) resonance state. Applying angle-resolved electron spectroscopy, we find a large photon helicity dependence of the spectrum and the angular distribution of the electrons ejected from the resonance by NIR multiphoton absorption. The measured circular dichroism is unexpectedly found to vary strongly as a function of the NIR intensity. The experimental data are well described by theoretical modeling and possible mechanisms are discussed.

  15. Synchronization between uncertain nonidentical networks with quantum chaotic behavior

    NASA Astrophysics Data System (ADS)

    Li, Wenlin; Li, Chong; Song, Heshan

    2016-11-01

    Synchronization between uncertain nonidentical networks with quantum chaotic behavior is researched. The identification laws of unknown parameters in state equations of network nodes, the adaptive laws of configuration matrix elements and outer coupling strengths are determined based on Lyapunov theorem. The conditions of realizing synchronization between uncertain nonidentical networks are discussed and obtained. Further, Jaynes-Cummings model in physics are taken as the nodes of two networks and simulation results show that the synchronization performance between networks is very stable.

  16. Experimental observation of multiphoton Thomson scattering

    NASA Astrophysics Data System (ADS)

    Yan, Wenchao; Golovin, Grigory; Fruhling, Colton; Haden, Daniel; Zhang, Ping; Zhang, Jun; Zhao, Baozhen; Liu, Cheng; Chen, Shouyuan; Banerjee, Sudeep; Umstadter, Donald

    2016-10-01

    With the advent of high-power lasers, several multiphoton processes have been reported involving electrons in strong fields. For electrons that were initially bound to atoms, both multiphoton ionization and scattering have been reported. However, for free electrons, only low-order harmonic generation has been observed until now. This limitation stems from past difficulty in achieving the required ultra-high-field strengths in scattering experiments. Highly relativistic laser intensities are required to reach the multiphoton regime of Thomson scattering, and generate high harmonics from free electrons. The scaling parameter is the normalized vector potential (a0). Previous experiments have observed phenomena in the weakly relativistic case (a0 >> 1). In ultra-intense fields (a0 >>1), the anomalous electron trajectory is predicted to produce a spectrum characterized by the merging of multiple high-order harmonic generation into a continuum. This may be viewed as the multiphoton Thomson scattering regime analogous to the wiggler of a synchrotron. Thus, the light produced reflects the electrons behavior in an ultra-intense lase field. We discuss the first experiments in the highly relativistic case (a0 15). This material is based upon work supported by NSF No. PHY-153700; US DOE, Office of Science, BES, # DE-FG02-05ER15663; AFOSR # FA9550-11-1-0157; and DHS DNDO # HSHQDC-13-C-B0036.

  17. Multiphoton microscopy imaging of developing tooth germs.

    PubMed

    Pan, Pei-Yu; Chen, Rung-Shu; Ting, Chih-Liang; Chen, Wei-Liang; Dong, Chen-Yuan; Chen, Min-Huey

    2014-01-01

    Traditionally, tooth germ is observed by histological investigation with hematoxylin and eosin stain and information may loss during the process. The purpose of this study is to use multiphoton laser fluorescence microscopy to observe the developing tooth germs of mice for building up the database of the images of tooth germs and compare with those from conventional histological analysis. Tooth germs were isolated from embryonic and newborn mice with age of Embryonic Day 14.5 and Postnatal Days 1, 3, 5, and 7. Comparison of the images of tooth germ sections in multiphoton microscopy with the images of histology was performed for investigating the molar tooth germs. It was found that various signals arose from different structures of tooth germs. Pre-dentin and dentin have strong second-harmonic generation signals, while ameloblasts and enamel tissues were shown with strong autofluorescence signals. In this study, a novel multiphoton microscopy database of images from developing tooth germs in mice was set up. We confirmed that multiphoton laser microscopy is a powerful tool for investigating the development of tooth germ and is worthy for further application in the study of tooth regeneration. Copyright © 2012. Published by Elsevier B.V.

  18. The Infrared Multiphoton Dissociation of Three Nitrolkanes.

    DTIC Science & Technology

    1986-01-24

    eam experiment, using infrared multiphoton dissociation where the concept of temperature has no place, can be quantitatively related to pyrolysis ...respectively. This large release of translational energy is suggested to be due to the nature of the transition state mechanical barrier which is largely...to pyrolysis experiments which are conducted under collisional, thermal conditions and measure phenomenological quantities such as activation energies

  19. Multiphoton ionization studies of xenon clusters

    SciTech Connect

    Echt, O.; Cook, M.C.; Castleman, A.W.

    1987-04-03

    Non-resonant multiphoton ionization of xenon clusters has revealed the same magic numbers as found in the case of electron-impact ionization. Large dissociation rates are found for the trimer through pentamer ion, measured on a time scale of approx 10/sup -7/ s after ionization.

  20. Multiphoton microscopy as a diagnostic imaging modality for lung cancer

    NASA Astrophysics Data System (ADS)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Peters, Rachel M.; Weiss, Robert S.; Webb, Watt W.

    2010-02-01

    Lung cancer is the leading killer among all cancers for both men and women in the US, and is associated with one of the lowest 5-year survival rates. Current diagnostic techniques, such as histopathological assessment of tissue obtained by computed tomography guided biopsies, have limited accuracy, especially for small lesions. Early diagnosis of lung cancer can be improved by introducing a real-time, optical guidance method based on the in vivo application of multiphoton microscopy (MPM). In particular, we hypothesize that MPM imaging of living lung tissue based on twophoton excited intrinsic fluorescence and second harmonic generation can provide sufficient morphologic and spectroscopic information to distinguish between normal and diseased lung tissue. Here, we used an experimental approach based on MPM with multichannel fluorescence detection for initial discovery that MPM spectral imaging could differentiate between normal and neoplastic lung in ex vivo samples from a murine model of lung cancer. Current results indicate that MPM imaging can directly distinguish normal and neoplastic lung tissues based on their distinct morphologies and fluorescence emission properties in non-processed lung tissue. Moreover, we found initial indication that MPM imaging differentiates between normal alveolar tissue, inflammatory foci, and lung neoplasms. Our long-term goal is to apply results from ex vivo lung specimens to aid in the development of multiphoton endoscopy for in vivo imaging of lung abnormalities in various animal models, and ultimately for the diagnosis of human lung cancer.

  1. Multiphoton amplification processes and quantum-path interferences in a coherently driven atomic vapor

    SciTech Connect

    Fernandez-Soler, J.J.; Font, J.L.; Vilaseca, R.; Gauthier, Daniel J.; Kul'minskii, A.

    2003-10-01

    We develop a theoretical model of two-photon amplification in laser-driven potassium atoms and use it to analyze the recent experiments reported by Pfister et al. [Phys. Rev. A 60, R4249 (1999)]. The model takes into account most of the essential factors influencing the amplification process, including the atomic hyperfine structure (which makes multiphoton emission possible) and the simultaneous interaction with intense drive and probe beams with arbitrary detunings. We determine the origin and analyze the properties of different multiphoton gain resonances that appear in the light-matter interaction. In particular, the influence of the drive and probe field amplitudes and detunings on the strength and frequency of the two-photon amplification resonance is studied in detail, showing clearly the differences with respect to the behavior of single-photon or other multiphoton amplification processes. In addition, we investigate interferences between different quantum pathways originating from the hyperfine structure and determine the conditions under which they can enhance or suppress multiphoton resonances. The predictions of the model are in good agreement with the observations, indicating that it can be used to understand recent experiments on two-photon lasing reported by Pfister et al. [Phys. Rev. Lett. 86, 4512 (2001)].

  2. Multiphoton imaging of renal regulatory mechanisms.

    PubMed

    Peti-Peterdi, János; Toma, Ildikó; Sipos, Arnold; Vargas, Sarah L

    2009-04-01

    Most physiological functions of the kidneys, including the clearance of metabolic waste products, maintenance of body fluid, electrolyte homeostasis, and blood pressure, are achieved by complex interactions between multiple renal cell types and previously inaccessible structures in many organ parts that have been difficult to study. Multiphoton fluorescence microscopy offers a state-of-the-art imaging technique for deep optical sectioning of living tissues and organs with minimal deleterious effects. Dynamic regulatory processes and multiple functions in the intact kidney can be quantitatively visualized in real time, noninvasively, and with submicron resolution. This article reviews innovative multiphoton imaging technologies and their applications that provided the most complex, immediate, and dynamic portrayal of renal function-clearly depicting as well as analyzing the components and mechanisms involved in renal (patho)physiology.

  3. Collective multiphoton blockade in cavity quantum electrodynamics

    NASA Astrophysics Data System (ADS)

    Zhu, C. J.; Yang, Y. P.; Agarwal, G. S.

    2017-06-01

    We present a study of collective multiphoton blockade in coherently driven atoms in a single-mode cavity. Considering two atoms strongly coupled to an optical cavity, we show that the two-photon blockade with two-photon antibunching, and the three-photon blockade with three-photon antibunching can be observed simultaneously. The three-photon blockade probes both dressed states in the two-photon and three-photon spaces. The two-photon and three-photon blockades strongly depend on the location of the two atoms in the strong-coupling regime. The asymmetry in the atom-cavity coupling constants opens pathways for multiphoton blockade which is also shown to be sensitive to the atomic decay and pumping strengths. The work presented here predicts many quantum statistical features due to the collective behavior of atoms and can be useful to generate nonclassical photon pairs.

  4. In vivo multiphoton tomography of skin cancer

    NASA Astrophysics Data System (ADS)

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

    2006-02-01

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

  5. Multiphoton tomography to detect chemo- and biohazards

    NASA Astrophysics Data System (ADS)

    König, Karsten

    2015-03-01

    In vivo high-resolution multiphoton/CARS tomography provides optical biopsies with 300 nm lateral resolution with chemical fingerprints. Thousands of volunteers and patients have been investigated for early cancer diagnosis, evaluation of anti-ageing cosmetic products, and changes of cellular metabolism by UV exposure and decreased oxygen supply. The skin as the outermost and largest organ is also the major target of CB agents. Current UV-based sensors are useful for bio-aerosol sensing but not for evaluating exposed in vivo skin. Here we evaluate the use of 4D multiphoton/CARS tomographs based on near infrared femtosecond laser radiation, time-correlated single photon counting (FLIM) and white light generation by photonic crystal fibers to detect bio- and chemohazards in human in vivo skin using twophoton fluorescence, SHG, and Raman signals.

  6. Multiphoton adiabatic passage for atom optics applications

    SciTech Connect

    Demeter, Gabor; Djotyan, Gagik P.

    2009-04-15

    We study the force exerted on two-level atoms by short, counterpropagating laser pulses. When the counterpropagating pulses overlap each other partially, multiphoton adiabatic processes are possible in several configurations, which amplify the force exerted on the atoms. We investigate the practical usefulness of such multiphoton adiabatic transitions for the manipulation of the atoms' mechanical state. In particular, we compare the efficiency of a pair of constant frequency, oppositely detuned laser pulses and that of a pair of frequency-chirped pulses. We also consider the case of prolonged exposure to a sequence of laser pulses for a duration that is comparable to or much larger than the spontaneous lifetime of the atoms. We use numerical methods to calculate the reduction of the force and the heating of the atomic ensemble when spontaneous emission cannot be neglected during the interaction. In addition, we derive simple approximate formulas for the force and the heating, and compare them to the numerical results.

  7. Multiphoton tomography of intratissue tattoo nanoparticles

    NASA Astrophysics Data System (ADS)

    König, Karsten

    2012-02-01

    Most of today's intratissue tattoo pigments are unknown nanoparticles. So far, there was no real control of their use due to the absence of regulations. Some of the tattoo pigments contain carcinogenic amines e.g. azo pigment Red 22. Nowadays, the European Union starts to control the administration of tattoo pigments. There is an interest to obtain information on the intratissue distribution, their interaction with living cells and the extracellular matrix, and the mechanisms behind laser tattoo removal. Multiphoton tomographs are novel biosafety and imaging tools that can provide such information non-invasively and without further labeling. When using the spectral FLIM module, spatially-resolved emission spectra, excitation spectra, and fluorescence lifetimes can pr provided. Multiphoton tomographs are used by all major cosmetic comapanies to test the biosafety of sunscreen nanoparticles.

  8. Gene inactivation by multiphoton-targeted photochemistry

    PubMed Central

    Berns, Michael W.; Wang, Zifu; Dunn, Andrew; Wallace, Vincent; Venugopalan, Vasan

    2000-01-01

    Multiphoton-targeted photochemistry was used to selectively inactivate the expression of genes in vertebrate cells. A membrane permeable DNA-associating vital dye, ethidium bromide monoacetate (visible wavelength single photon absorption peak at 530 nm) was used to photosensitize chromosomes in dividing cells. A 100-ps infrared laser beam operating at 1.06 microns was focused onto a selected region of a mitotic chromosome corresponding to the sites of the nucleolar (ribosomal) genes. Individual cells followed through mitosis demonstrated a reduction in the number of nucleoli formed in daughter cells that corresponded to the number of nucleolar genes sites irradiated. These results demonstrate the ability to selectively manipulate genes by using the focal point specificity characteristic of multiphoton microscopy. This technique should have wide biotechnology applications both in vitro and in vivo. PMID:10944219

  9. Clinical multiphoton endoscopy with FLIM capability

    NASA Astrophysics Data System (ADS)

    Weinigel, Martin; Breunig, Hans Georg; Fischer, Peter; Kellner-Höfer, Marcel; Bückle, Rainer; König, Karsten

    2013-02-01

    Multiphoton endoscopy can be applied for intra-corporeal imaging as well as to examine otherwise hard-to-access tissue areas like chronic wounds. Using high-NA (NA = 0.8) gradient-index (GRIN) lens-based endoscopes with a diameter of 1.4 mm and effective lengths of 7 mm and 20 mm, respectively, two-photon excitation of endogenous fluorophores and second-harmonic generation (SHG) is used for multimodal in vivo imaging of human skin. A further imaging modality is fluorescence lifetime imaging (FLIM) which allows functional imaging to investigate the healing mechanism of chronic wounds and the corresponding cell metabolism. We performed first in vivo measurements using FLIM endoscopy with the medically-certified multiphoton tomograph MPTflex® in combination with a computer-controlled motorized scan head and a GRIN-lens endoscope.

  10. Assessing and benchmarking multiphoton microscopes for biologists

    PubMed Central

    Corbin, Kaitlin; Pinkard, Henry; Peck, Sebastian; Beemiller, Peter; Krummel, Matthew F.

    2017-01-01

    Multiphoton microscopy has become staple tool for tracking cells within tissues and organs due to superior depth of penetration, low excitation volumes, and reduced phototoxicity. Many factors, ranging from laser pulse width to relay optics to detectors and electronics, contribute to the overall ability of these microscopes to excite and detect fluorescence deep within tissues. However, we have found that there are few standard ways already described in the literature to distinguish between microscopes or to benchmark existing microscopes to measure the overall quality and efficiency of these instruments. Here, we discuss some simple parameters and methods that can either be used within a multiphoton facility or by a prospective purchaser to benchmark performance. This can both assist in identifying decay in microscope performance and in choosing features of a scope that are suited to experimental needs. PMID:24974026

  11. Assessing and benchmarking multiphoton microscopes for biologists.

    PubMed

    Corbin, Kaitlin; Pinkard, Henry; Peck, Sebastian; Beemiller, Peter; Krummel, Matthew F

    2014-01-01

    Multiphoton microscopy has become staple tool for tracking cells within tissues and organs due to superior depth of penetration, low excitation volumes, and reduced phototoxicity. Many factors, ranging from laser pulse width to relay optics to detectors and electronics, contribute to the overall ability of these microscopes to excite and detect fluorescence deep within tissues. However, we have found that there are few standard ways already described in the literature to distinguish between microscopes or to benchmark existing microscopes to measure the overall quality and efficiency of these instruments. Here, we discuss some simple parameters and methods that can either be used within a multiphoton facility or by a prospective purchaser to benchmark performance. This can both assist in identifying decay in microscope performance and in choosing features of a scope that are suited to experimental needs. © 2014 Elsevier Inc. All rights reserved.

  12. Studies of atmospheric molecules by multiphoton spectroscopy

    SciTech Connect

    Johnson, P.M.

    1991-10-01

    Carbon dioxide presents a great challenge to spectroscopy because of its propensity toward dissociation in all of its excited states. Multiphoton ionization spectroscopy is usually not applicable to the study of dissociating molecules because the dissociation competes effectively with ionization, resulting in no signal. We reasoned, however, that with high enough laser fluence, ionization could compete with dissociation in the longer lived states, exposing them for study from the continuous spectral background resulting from rapidly dissociating states. We describe the various spectroscopic and photophysical effects found through the multiphoton ionization and multiphoton photoelectron spectra. A recently developed variant of threshold ionization spectroscopy, usually called ZEKE, has shown a great deal of usefulness in providing the same information as traditional photoelectron spectroscopy but with higher resolution and much better signal-to-noise when using standard laboratory lasers. Threshold ionization techniques locate the states of an ion by scanning a light source across the ionization continuum of a neutral and somehow detecting when electrons are produced with no kinetic energy. We chose to develop our capabilities in threshold ionization spectroscopy using aromatic molecules because of their importance and because their electronic structure allows a pump-probe type of excitation scheme which avoids the use of vacuum ultraviolet laser beams. Among aromatics, the azines are noted for their small S{sub 1}-T{sub 1} energy gap which give them unique and interesting photophysical properties. We have continued our work on the multiphoton spectrum of metastable nitrogen produced by an electric discharge in supersonic beam. We have been able to assign more of the lines and simulated their rotational structure but many peaks remain unassigned.

  13. Unified approach to multiphoton coherent states

    NASA Astrophysics Data System (ADS)

    Shanta, P.; Chaturvedi, S.; Srinivasan, V.; Agarwal, G. S.; Mehta, C. L.

    1994-03-01

    We obtain a large class of multiphoton annihilation operator (F) eigenstates by constructing an operator G° such that [F,G°]=1. We show that almost all known coherent states, including the squeezed states and other nonclassical states such as the cat and the kitten states follow from our approach. Further, we show that all of them can be expressed as an exponential operator acting on the vacuum of the operator F. The technique can be easily generalized to deformed bosons.

  14. Multiphoton spectroscopy of human skin in vivo

    NASA Astrophysics Data System (ADS)

    Breunig, Hans G.; Weinigel, Martin; König, Karsten

    2012-03-01

    In vivo multiphoton-intensity images and emission spectra of human skin are reported. Optical sections from different depths of the epidermis and dermis have been measured with near-infrared laser-pulse excitation. While the intensity images reveal information on the morphology, the spectra show emission characteristics of main endogenous skin fluorophores like keratin, NAD(P)H, melanin, elastin and collagen as well as of second harmonic generation induced by the excitation-light interaction with the dermal collagen network.

  15. First multiphoton tomography of brain in man

    NASA Astrophysics Data System (ADS)

    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.

  16. Superresolving multiphoton interferences with independent light sources.

    PubMed

    Oppel, S; Büttner, T; Kok, P; von Zanthier, J

    2012-12-07

    We propose to use multiphoton interferences from statistically independent light sources in combination with linear optical detection techniques to enhance the resolution in imaging. Experimental results with up to five independent thermal light sources confirm this approach to improve the spatial resolution. Since no involved quantum state preparation or detection is required, the experiment can be considered an extension of the Hanbury Brown-Twiss experiment for spatial intensity correlations of order N>2.

  17. Multiphoton imaging of renal tissues in vitro.

    PubMed

    Peti-Peterdi, János

    2005-06-01

    The highly inhomogeneous and light-scattering structure of living renal tissue makes the application of conventional imaging techniques more difficult compared with other parenchymal organs. On the other hand, key physiological processes of the kidney, such as regulation of glomerular filtration, hemodynamics, concentration, and dilution, involve complex interactions between multiple cell types and otherwise inaccessible structures that necessitate visual approaches. An ideal solution is multiphoton excitation fluorescence microscopy, a state-of-the-art imaging technique superior for deep optical sectioning of living tissue samples. Here, we review the basics and advantages of multiphoton microscopy and provide examples for its application in renal physiology using dissected cortical and medullary tissues in vitro. In combination with microperfusion techniques, the major functions of the juxtaglomerular apparatus, tubuloglomerular feedback and renin release, can be studied with high spatial and temporal resolution. Salt-dependent changes in macula densa cell volume, vasoconstriction of the afferent arteriole, and activity of an intraglomerular precapillary sphincter composed of renin granular cells are visualized in real time. Release and tissue activity of renin can be studied on the individual granule level. Imaging of the living inner medulla shows how interstitial cells interconnect cells of the vasa recta, loop of Henle, and collecting duct. In summary, multiphoton microscopy is an exciting new optical sectioning technique that has great potential for numerous future developments and is ideal for applications that require deep optical sectioning of living tissue samples.

  18. Live cell imaging by multifocal multiphoton microscopy.

    PubMed

    Straub, M; Lodemann, P; Holroyd, P; Jahn, R; Hell, S W

    2000-10-01

    Multifocal multiphoton microscopy (MMM) permits parallel multiphoton excitation by scanning an array of high numerical aperture foci across a plane in the sample. MMM is particularly suitable for live cell investigations since it combines advantages of standard multiphoton microscopy such as optical sectioning and suppression of out-of-focus phototoxicity with high recording speeds. Here we describe several applications of MMM to live cell imaging using the neuroendocrine cell line PC12 and bovine chromaffin cells. Stainings were performed with the acidophilic dye acridine orange and the lipophilic dyes FM1-43 and Fast DiA as well as by transfection of the cells with GFP. In both bovine chromaffin and PC12 cells structural elements of nuclear chromatin and the 3-D distribution of acidic organelles inside the cells were visualized. In PC12 cells differentiated by nerve growth factor examples of neurites were monitored. Stainings of membranes were used to reconstruct the morphology of cells and neurites in three dimensions by volume-rendering and by isosurface plots. 3-D reconstructions were composed from stacks of about 50 images each with a diameter of 30-100 microm that were acquired within a few seconds. We conclude that MMM proves to be a technically simple and very effective method for fast 3-D live cell imaging at high resolution.

  19. In vivo multiphoton nanosurgery on cortical neurons.

    PubMed

    Sacconi, Leonardo; O'Connor, Rodney P; Jasaitis, Audrius; Masi, Alessio; Buffelli, Mario; Pavone, Francesco S

    2007-01-01

    Two-photon microscopy has been used to perform high spatial resolution imaging of spine plasticity in the intact neocortex of living mice. Multiphoton absorption has also been used as a tool for the selective disruption of cellular structures in living cells and simple organisms. In this work, we exploit the spatial localization of multiphoton excitation to perform selective lesions on the neuronal processes of cortical neurons in living mice expressing fluorescent proteins. Neurons are irradiated with a focused, controlled dose of femtosecond laser energy delivered through cranial optical windows. The morphological consequences are then characterized with time lapse 3-D two-photon imaging over a period of minutes to days after the procedure. This methodology is applied to dissect single dendrites with submicrometric precision without causing any visible collateral damage to the surrounding neuronal structures. The spatial precision of this method is demonstrated by ablating individual dendritic spines, while sparing the adjacent spines and the structural integrity of the dendrite. The combination of multiphoton nanosurgery and in vivo imaging in mammals represents a promising tool for neurobiology and neuropharmacology research.

  20. Optimization-based wavefront sensorless adaptive optics for multiphoton microscopy.

    PubMed

    Antonello, Jacopo; van Werkhoven, Tim; Verhaegen, Michel; Truong, Hoa H; Keller, Christoph U; Gerritsen, Hans C

    2014-06-01

    Optical aberrations have detrimental effects in multiphoton microscopy. These effects can be curtailed by implementing model-based wavefront sensorless adaptive optics, which only requires the addition of a wavefront shaping device, such as a deformable mirror (DM) to an existing microscope. The aberration correction is achieved by maximizing a suitable image quality metric. We implement a model-based aberration correction algorithm in a second-harmonic microscope. The tip, tilt, and defocus aberrations are removed from the basis functions used for the control of the DM, as these aberrations induce distortions in the acquired images. We compute the parameters of a quadratic polynomial that is used to model the image quality metric directly from experimental input-output measurements. Finally, we apply the aberration correction by maximizing the image quality metric using the least-squares estimate of the unknown aberration.

  1. Plasma induced by resonance enhanced multiphoton ionization in inert gas

    SciTech Connect

    Shneider, Mikhail N.; Zhang Zhili; Miles, Richard B.

    2007-12-15

    We present a detailed model for the evolution of resonance enhanced multiphoton ionization (REMPI) produced plasma during and after the ionizing laser pulse in inert gas (argon, as an example) at arbitrary pressures. Our theory includes the complete process of the REMPI plasma generation and losses, together with the changing gas thermodynamic parameters. The model shows that the plasma expansion follows a classical ambipolar diffusion and that gas heating results in a weak shock or acoustic wave. The gas becomes involved in the motion not only from the pressure gradient due to the heating, but also from the momentum transfer from the charged particles to gas atoms. The time dependence of the total number of electrons computed in theory matches closely with the results of coherent microwave scattering experiments.

  2. Multiphoton spectroscopy of Rydberg states of small molecules

    SciTech Connect

    Pratt, Stephen T.; McCormack, E. F.; Dehmer, Joseph L.; Dehmer, Patricia M.

    1990-09-01

    Multiphoton ionization techniques provide a versatile means for studying highly excited states of atoms and molecules and provide a valuable complement to traditional techniques based on single-photon absorption and ionization studies. In this paper we present the results of new multiphoton ionization studies of molecular nitrogen and molecular oxygen that serve to illustrate the power of these techniques. 30 refs., 3 figs.

  3. Applying phasor approach analysis of multiphoton FLIM measurements to probe the metabolic activity of three-dimensional in vitro cell culture models

    PubMed Central

    Lakner, Pirmin H.; Monaghan, Michael G.; Möller, Yvonne; Olayioye, Monilola A.; Schenke-Layland, Katja

    2017-01-01

    Fluorescence lifetime imaging microscopy (FLIM) can measure and discriminate endogenous fluorophores present in biological samples. This study seeks to identify FLIM as a suitable method to non-invasively detect a shift in cellular metabolic activity towards glycolysis or oxidative phosphorylation in 3D Caco-2 models of colorectal carcinoma. These models were treated with potassium cyanide or hydrogen peroxide as controls, and epidermal growth factor (EGF) as a physiologically-relevant influencer of cell metabolic behaviour. Autofluorescence, attributed to nicotinamide adenine dinucleotide (NADH), was induced by two-photon laser excitation and its lifetime decay was analysed using a standard multi-exponential decay approach and also a novel custom-written code for phasor-based analysis. While both methods enabled detection of a statistically significant shift of metabolic activity towards glycolysis using potassium cyanide, and oxidative phosphorylation using hydrogen peroxide, employing the phasor approach required fewer initial assumptions to quantify the lifetimes of contributing fluorophores. 3D Caco-2 models treated with EGF had increased glucose consumption, production of lactate, and presence of ATP. FLIM analyses of these cultures revealed a significant shift in the contribution of protein-bound NADH towards free NADH, indicating increased glycolysis-mediated metabolic activity. This data demonstrate that FLIM is suitable to interpret metabolic changes in 3D in vitro models. PMID:28211922

  4. Applying phasor approach analysis of multiphoton FLIM measurements to probe the metabolic activity of three-dimensional in vitro cell culture models.

    PubMed

    Lakner, Pirmin H; Monaghan, Michael G; Möller, Yvonne; Olayioye, Monilola A; Schenke-Layland, Katja

    2017-02-13

    Fluorescence lifetime imaging microscopy (FLIM) can measure and discriminate endogenous fluorophores present in biological samples. This study seeks to identify FLIM as a suitable method to non-invasively detect a shift in cellular metabolic activity towards glycolysis or oxidative phosphorylation in 3D Caco-2 models of colorectal carcinoma. These models were treated with potassium cyanide or hydrogen peroxide as controls, and epidermal growth factor (EGF) as a physiologically-relevant influencer of cell metabolic behaviour. Autofluorescence, attributed to nicotinamide adenine dinucleotide (NADH), was induced by two-photon laser excitation and its lifetime decay was analysed using a standard multi-exponential decay approach and also a novel custom-written code for phasor-based analysis. While both methods enabled detection of a statistically significant shift of metabolic activity towards glycolysis using potassium cyanide, and oxidative phosphorylation using hydrogen peroxide, employing the phasor approach required fewer initial assumptions to quantify the lifetimes of contributing fluorophores. 3D Caco-2 models treated with EGF had increased glucose consumption, production of lactate, and presence of ATP. FLIM analyses of these cultures revealed a significant shift in the contribution of protein-bound NADH towards free NADH, indicating increased glycolysis-mediated metabolic activity. This data demonstrate that FLIM is suitable to interpret metabolic changes in 3D in vitro models.

  5. Visualization of in vivo thromboprophylactic and thrombolytic efficacy of enoxaparin in laser-induced vascular endothelial injury model using multiphoton microscopy

    PubMed Central

    Tanaka, Koji; Koike, Yuhki; Matsushita, Kohei; Okigami, Masato; Toiyama, Yuji; Kawamura, Mikio; Saigusa, Susumu; Okugawa, Yoshinaga; Inoue, Yasuhiro; Uchida, Keiichi; Araki, Toshimitsu; Mohri, Yasuhiko; Mizoguchi, Akira; Kusunoki, Masato

    2015-01-01

    Enoxaparin is used postoperatively for the prevention of venous thromboembolism. In vitro studies and clinical trials have demonstrated the anticoagulant and antithrombotic efficacy of enoxaparin. In this study, we visualised thromboprophylactic and thrombolytic efficacy of enoxaparin in a laser-induced thrombus formation model in vivo using two-photon laser-scanning microscopy (TPLSM). Thrombus was induced by the selective irradiation of vascular endothelium in arterioles of the cecum of green fluorescent protein transgenic mice. The thromboprophylactic and thrombolytic efficacy of enoxaparin was visualised in vivo real-time using TPLSM. Platelet adhesion, aggregation, and platelet-dependent thrombus formation were observed in the laser-induced thrombus formation model with reproducibility. Laser-induced thrombus formation was significantly inhibited by enoxaparin pretreatment as the thromboprophylactic agent, as compared with control. The mean thrombus volumes were 652 microcubic meters in mice pretreated with enoxaparin and 8906 microcubic meter in control mice. Enoxaparin reduced the volume of laser-induced thrombus when using it as a thrombolytic agent. The mean rate of reduction was 59 percent. In a lipopolysaccharide-induced sepsis model, thromboprophylactic efficacy of enoxaparin was also observed in vivo in real-time. In vivo thromboprophylactic and thrombolytic efficacy of enoxaparin can be visualised at the single platelet level in the laser-induced endothelium injury model using TPLSM. PMID:25755830

  6. Some simple mechanisms of multiphoton excitation in many - level systems

    NASA Astrophysics Data System (ADS)

    Donley, E. A.; Marquardt, R.; Quack, M.; Stohner, J.; Thanopulos, I.; Wallenborn, E.-U.

    Results are reported on coherent monochromatic multiphoton excitation in many-level systems, which are representative for some of the basic mechanisms for atomic and molecular multiphoton processes. Numerical solutions are discussed that use the Floquet and quasiresonant approximations in the framework of the URIMIR program package. The excitation schemes include direct three-photon excitation, two-photon excitation with diagonal coupling, Göppert-Mayer-type two-photon processes, multiphoton excitation with off-resonant intermediates, and practically irreversible coherent excitation into dense spectral structures. Several interesting phenomena are observed, such as nonlinear line shifts and broadenings of multiphoton resonances of relevance for multiphoton spectroscopy and almost constant intermediate population inversions, potentially useful for laser design. The accurate numerical results are compared with approximate solutions from perturbation theory, and with simple analytical solutions from Rabi-type formulae.

  7. Multiphoton intravital microscopy setup to visualize the mouse mammary gland

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Herrera Torres, Ana M.; Masedunskas, Andrius; Baratti, Mariana O.; de Thomaz, Andre A.; Pelegati, Vitor B.; Carvalho, Hernandes F.; Cesar, Carlos L.

    2013-06-01

    Recently, light microscopy-based techniques have been extended to live mammalian models leading to the development of a new imaging approach called intravital microscopy (IVM). Although IVM has been introduced at the beginning of the last century, its major advancements have occurred in the last twenty years with the development of non-linear microscopy that has enabled performing deep tissue imaging. IVM has been utilized to address many biological questions in basic research and is now a fundamental tool that provide information on tissues such as morphology, cellular architecture, and metabolic status. IVM has become an indispensable tool in numerous areas. This study presents and describes the practical aspects of IVM necessary to visualize epithelial cells of live mouse mammary gland with multiphoton techniques.

  8. Search for Multiphoton Signatures of a Higgs Boson

    SciTech Connect

    Atramentov, Oleksiy Vladimirovich

    2006-07-01

    In this thesis we describe a search for a fermiophobic Higgs boson in 3γ+X events. The study has been performed on 0.83 fb-1 of data collected with the D0 detector that resides at one of the interaction regions of the Tevatron collider, the world's highest energy accelerator. This study was motivated by a fairly recent phenomenological paper [33] where it was noticed that in certain class of models (2HDM Type I and THM) the multi-photon final states like this one become detectable at the luminosity that has been collected by the D0 experiment by 2006. The mechanism that permits such final state becomes available when the conventional higgs production mechanism (higgs strahlung) are suppressed. This leads to the fact that Higgs boson with mass (mhf < 90 GeV/c2) lower than the current limit has not been excluded.

  9. Multi-photon absorption limits to heralded single photon sources

    PubMed Central

    Husko, Chad A.; Clark, Alex S.; Collins, Matthew J.; De Rossi, Alfredo; Combrié, Sylvain; Lehoucq, Gaëlle; Rey, Isabella H.; Krauss, Thomas F.; Xiong, Chunle; Eggleton, Benjamin J.

    2013-01-01

    Single photons are of paramount importance to future quantum technologies, including quantum communication and computation. Nonlinear photonic devices using parametric processes offer a straightforward route to generating photons, however additional nonlinear processes may come into play and interfere with these sources. Here we analyse spontaneous four-wave mixing (SFWM) sources in the presence of multi-photon processes. We conduct experiments in silicon and gallium indium phosphide photonic crystal waveguides which display inherently different nonlinear absorption processes, namely two-photon (TPA) and three-photon absorption (ThPA), respectively. We develop a novel model capturing these diverse effects which is in excellent quantitative agreement with measurements of brightness, coincidence-to-accidental ratio (CAR) and second-order correlation function g(2)(0), showing that TPA imposes an intrinsic limit on heralded single photon sources. We build on these observations to devise a new metric, the quantum utility (QMU), enabling further optimisation of single photon sources. PMID:24186400

  10. Multiphoton quantum interference in a multiport integrated photonic device.

    PubMed

    Metcalf, Benjamin J; Thomas-Peter, Nicholas; Spring, Justin B; Kundys, Dmytro; Broome, Matthew A; Humphreys, Peter C; Jin, Xian-Min; Barbieri, Marco; Kolthammer, W Steven; Gates, James C; Smith, Brian J; Langford, Nathan K; Smith, Peter G R; Walmsley, Ian A

    2013-01-01

    Increasing the complexity of quantum photonic devices is essential for many optical information processing applications to reach a regime beyond what can be classically simulated, and integrated photonics has emerged as a leading platform for achieving this. Here we demonstrate three-photon quantum operation of an integrated device containing three coupled interferometers, eight spatial modes and many classical and nonclassical interferences. This represents a critical advance over previous complexities and the first on-chip nonclassical interference with more than two photonic inputs. We introduce a new scheme to verify quantum behaviour, using classically characterised device elements and hierarchies of photon correlation functions. We accurately predict the device's quantum behaviour and show operation inconsistent with both classical and bi-separable quantum models. Such methods for verifying multiphoton quantum behaviour are vital for achieving increased circuit complexity. Our experiment paves the way for the next generation of integrated photonic quantum simulation and computing devices.

  11. Multi-photon absorption limits to heralded single photon sources

    NASA Astrophysics Data System (ADS)

    Husko, Chad A.; Clark, Alex S.; Collins, Matthew J.; de Rossi, Alfredo; Combrié, Sylvain; Lehoucq, Gaëlle; Rey, Isabella H.; Krauss, Thomas F.; Xiong, Chunle; Eggleton, Benjamin J.

    2013-11-01

    Single photons are of paramount importance to future quantum technologies, including quantum communication and computation. Nonlinear photonic devices using parametric processes offer a straightforward route to generating photons, however additional nonlinear processes may come into play and interfere with these sources. Here we analyse spontaneous four-wave mixing (SFWM) sources in the presence of multi-photon processes. We conduct experiments in silicon and gallium indium phosphide photonic crystal waveguides which display inherently different nonlinear absorption processes, namely two-photon (TPA) and three-photon absorption (ThPA), respectively. We develop a novel model capturing these diverse effects which is in excellent quantitative agreement with measurements of brightness, coincidence-to-accidental ratio (CAR) and second-order correlation function g(2)(0), showing that TPA imposes an intrinsic limit on heralded single photon sources. We build on these observations to devise a new metric, the quantum utility (QMU), enabling further optimisation of single photon sources.

  12. Pulse front adaptive optics in multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    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.

  13. Electron Vortices in Femtosecond Multiphoton Ionization

    NASA Astrophysics Data System (ADS)

    Pengel, D.; Kerbstadt, S.; Johannmeyer, D.; Englert, L.; Bayer, T.; Wollenhaupt, M.

    2017-02-01

    Multiphoton ionization of potassium atoms with a sequence of two counter-rotating circularly polarized femtosecond laser pulses produces vortex-shaped photoelectron momentum distributions in the polarization plane describing Archimedean spirals. The pulse sequences are produced by polarization shaping and the three-dimensional photoelectron distributions are tomographically reconstructed from velocity map imaging measurements. We show that perturbative ionization leads to electron vortices with c6 rotational symmetry. A change from c6 to c4 rotational symmetry of the vortices is demonstrated for nonperturbative interaction.

  14. Complex effective Hamiltonian approach for ir multiphoton dissociation

    NASA Astrophysics Data System (ADS)

    Flosnik, Thomas M.; Wyatt, Robert E.

    1989-11-01

    A complex effective Hamiltonian (CEH) approach is formulated in the semiclassical (quantum-molecule-classical-field) representation for the study of ir multiphoton-dissociation processes. This formulation enables one to evaluate the dissociation dynamics in terms of the discrete states only. The effects of the bound-continuum-state interactions are manifested in the CEH matrix by the addition of level shifts and imaginary decay widths to the unperturbed bound-state energies and bound-bound dipole-coupling elements. The periodicity of the CEH matrix in time is preserved, allowing the use of Floquet theory to exactly evaluate the time development of the system. This CEH formulation requires that transitions between continuum states can be safely ignored, that the bound-continuum dipole couplings vary slowly with the continuum state energy ɛ, and that time t is sufficiently long. High field intensities also tend to make these requirements more stringent. It is found that the CEH matrix in the semiclassical representation can be asymmetric with respect to the level shifts and decay widths. For the ir multiphoton dissociation of a nonrotating model diatomic molecule in the ground electronic state, a rather truncated form of the CEH is tested against a discretized continuum plus optical potential method. Despite the high field intensity and relatively short laser pulse used in these tests, the results indicate that this CEH method works well provided the bound-continuum dipole-coupling elements vary slowly with ɛ. As can be expected, the validity of the CEH is limited when the bound-continuum dipole couplings vary strongly with ɛ, which is the case with our model diatomic molecule. The nature of the bound-continuum interactions can apparently have considerable effect on the dissociation dynamics.

  15. Multiphoton and tunneling ionization probability of atoms and molecules in an intense laser field

    NASA Astrophysics Data System (ADS)

    Zhao, Song-Feng; Liu, Lu; Zhou, Xiao-Xin

    2014-02-01

    We theoretically studied ionization of atoms exposed to an intense laser field by using three different methods, i.e., the numerical solution of the single-active-electron approximation based time-dependent Schrödinger equation (SAE-TDSE), the Perelomov-Popov-Terent'ev (PPT) model, and the Ammosov-Delone-Krainov (ADK) model. The ionization of several linear molecules in a strong laser field is also investigated with the molecular ADK (MO-ADK) and the molecular PPT (MO-PPT) model. We show that the ionization probability from the PPT and the MO-PPT model agrees well with the corresponding SAE-TDSE result in both the multiphoton and tunneling ionization regimes. By considering the volume effect of the laser field, the ionization signal obtained from the PPT and the MO-PPT model fits well the experimental data in the whole range of the multiphoton and tunneling ionization regimes. However, both the ADK and MO-ADK models seriously underestimate the ionization probabilities (or signals) in the multiphoton regime.

  16. Efficient Multiphoton Generation in Waveguide Quantum Electrodynamics.

    PubMed

    González-Tudela, A; Paulisch, V; Kimble, H J; Cirac, J I

    2017-05-26

    Engineering quantum states of light is at the basis of many quantum technologies such as quantum cryptography, teleportation, or metrology among others. Though, single photons can be generated in many scenarios, the efficient and reliable generation of complex single-mode multiphoton states is still a long-standing goal in the field, as current methods either suffer from low fidelities or small probabilities. Here we discuss several protocols which harness the strong and long-range atomic interactions induced by waveguide QED to efficiently load excitations in a collection of atoms, which can then be triggered to produce the desired multiphoton state. In order to boost the success probability and fidelity of each excitation process, atoms are used to both generate the excitations in the rest, as well as to herald the successful generation. Furthermore, to overcome the exponential scaling of the probability of success with the number of excitations, we design a protocol to merge excitations that are present in different internal atomic levels with a polynomial scaling.

  17. Ultrafast Multiphoton Thermionic Photoemission from Graphite

    NASA Astrophysics Data System (ADS)

    Tan, Shijing; Argondizzo, Adam; Wang, Cong; Cui, Xuefeng; Petek, Hrvoje

    2017-01-01

    Electronic heating of cold crystal lattices in nonlinear multiphoton excitation can transiently alter their physical and chemical properties. In metals where free electron densities are high and the relative fraction of photoexcited hot electrons is low, the effects are small, but in semimetals, where the free electron densities are low and the photoexcited densities can overwhelm them, the intense femtosecond laser excitation can induce profound changes. In semimetal graphite and its derivatives, strong optical absorption, weak screening of the Coulomb potential, and high cohesive energy enable extreme hot electron generation and thermalization to be realized under femtosecond laser excitation. We investigate the nonlinear interactions within a hot electron gas in graphite through multiphoton-induced thermionic emission. Unlike the conventional photoelectric effect, within about 25 fs, the memory of the excitation process, where resonant dipole transitions absorb up to eight quanta of light, is erased to produce statistical Boltzmann electron distributions with temperatures exceeding 5000 K; this ultrafast electronic heating causes thermionic emission to occur from the interlayer band of graphite. The nearly instantaneous thermalization of the photoexcited carriers through Coulomb scattering to extreme electronic temperatures characterized by separate electron and hole chemical potentials can enhance hot electron surface femtochemistry, photovoltaic energy conversion, and incandescence, and drive graphite-to-diamond electronic phase transition.

  18. Multiphoton tomography of the human eye

    NASA Astrophysics Data System (ADS)

    König, Karsten; Batista, Ana; Hager, Tobias; Seitz, Berthold

    2017-02-01

    Multiphoton tomography (MPT) is a novel label-free clinical imaging method for non-invasive tissue imaging with high spatial (300 nm) and temporal (100 ps) resolutions. In vivo optical histology can be realized due to the nonlinear excitation of endogenous fluorophores and second-harmonic generation (SHG) of collagen. Furthermore, optical metabolic imaging (OMI) is performed by two-photon autofluorescence lifetime imaging (FLIM). So far, applications of the multiphoton tomographs DermaInspect and MPTflex were limited to dermatology. Novel applications include intraoperative brain tumor imaging as well as cornea imaging. In this work we describe two-photon imaging of ex vivo human corneas unsuitable for transplantation. Furthermore, the cross-linking (CXL) process of corneal collagen based on UVA exposure and 0.1 % riboflavin was studied. The pharmacokinetics of the photosensitizer could be detected with high spatial resolution. Interestingly, an increase in the stromal autofluorescence intensity and modifications of the autofluorescence lifetimes were observed in the human corneal samples within a few days following CXL.

  19. Development of an applicator for multiphoton PDT

    NASA Astrophysics Data System (ADS)

    Graschew, Georgi; Bastian, Matthias; Rakowsky, Stefan; Roelofs, Theo A.; Balanos, Evangelos; Schlag, Peter M.; Steinmeyer, Gunter; Elsaesser, Thomas

    2004-09-01

    Multiphoton excitation of photosensitizers for laser induced fluorescence diagnosis (LIFD) and photodynamic therapy (PDT) of tumors has the advantage of greater tissue penetration due to the longer wavelength of irradiation. However, multiphoton LIFD and PDT are presently not clinically applicable as there are no applicators available for the delivery of the pulsed laser radiation to the operating room. As an approach, in this contribution the beam delivery through photonic crystal fibers has been investigated. Pulses of a Ti:sapphire laser of 100 fs pulse duration and an average power of 150 mW have been transported through such a fiber of 25 m length and the resulting pulses show the absence of nonlinear contributions but still a broadening of the pulse to 2 ps due to the dispersion of the fiber. It is planned to compensate this broadening by a grating in front of the fiber. Alternatively, the transport of laser radiation of 150 fs and 100 mW through a mirror-joint-arm used for conventional CO2 lasers has been tested showing no broadening of the laser pulses. Two-photon photodynamic activity of mTHPC-CMPEG4 shall serve as a test of the laser light transport system.

  20. Efficient Multiphoton Generation in Waveguide Quantum Electrodynamics

    NASA Astrophysics Data System (ADS)

    González-Tudela, A.; Paulisch, V.; Kimble, H. J.; Cirac, J. I.

    2017-05-01

    Engineering quantum states of light is at the basis of many quantum technologies such as quantum cryptography, teleportation, or metrology among others. Though, single photons can be generated in many scenarios, the efficient and reliable generation of complex single-mode multiphoton states is still a long-standing goal in the field, as current methods either suffer from low fidelities or small probabilities. Here we discuss several protocols which harness the strong and long-range atomic interactions induced by waveguide QED to efficiently load excitations in a collection of atoms, which can then be triggered to produce the desired multiphoton state. In order to boost the success probability and fidelity of each excitation process, atoms are used to both generate the excitations in the rest, as well as to herald the successful generation. Furthermore, to overcome the exponential scaling of the probability of success with the number of excitations, we design a protocol to merge excitations that are present in different internal atomic levels with a polynomial scaling.

  1. Multiphoton imaging with a nanosecond supercontinuum source

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  2. Sub-cycle dynamics of multiphoton ionization

    NASA Astrophysics Data System (ADS)

    Telnov, Dmitry A.; Nasiri Avanaki, K.; Chu, Shih-I.

    2014-05-01

    Sub-cycle oscillatory structures are revealed in calculated time-dependent multiphoton ionization rates. Both atomic and molecular targets manifest multiple ionization bursts per one optical cycle of the laser field. Using the accurate and efficient time-dependent generalized pseudospectral method to solve the time-dependent Schrödinger equation, we have performed calculations on H, He+, H2+,and HHe2+, for the laser fields with several intensities and wavelengths in the near-infrared range (750 nm to 1064 nm). The sub-cycle structures appear a universal feature of multiphoton ionization and become well pronounced for sufficiently strong laser fields depending on the target atom or molecule. Analysis of the electron density distributions on the sub-femtosecond time scale shows several time moments per optical cycle (not necessarily corresponding to the peak values of the laser field) when significant portions of the electron density move away from the nucleus giving rise to the bursts in the ionization rate. The nature of the phenomenon can be related to ionization through different pathways, including direct ionization as well as population of the excited states by the laser field with subsequent ionization at later times. This work is partially supported by DOE.

  3. Multifocal multiphoton microscopy with adaptive optical correction

    NASA Astrophysics Data System (ADS)

    Coelho, Simao; Poland, Simon; Krstajic, Nikola; Li, David; Monypenny, James; Walker, Richard; Tyndall, David; Ng, Tony; Henderson, Robert; Ameer-Beg, Simon

    2013-02-01

    Fluorescence lifetime imaging microscopy (FLIM) is a well established approach for measuring dynamic signalling events inside living cells, including detection of protein-protein interactions. The improvement in optical penetration of infrared light compared with linear excitation due to Rayleigh scattering and low absorption have provided imaging depths of up to 1mm in brain tissue but significant image degradation occurs as samples distort (aberrate) the infrared excitation beam. Multiphoton time-correlated single photon counting (TCSPC) FLIM is a method for obtaining functional, high resolution images of biological structures. In order to achieve good statistical accuracy TCSPC typically requires long acquisition times. We report the development of a multifocal multiphoton microscope (MMM), titled MegaFLI. Beam parallelization performed via a 3D Gerchberg-Saxton (GS) algorithm using a Spatial Light Modulator (SLM), increases TCSPC count rate proportional to the number of beamlets produced. A weighted 3D GS algorithm is employed to improve homogeneity. An added benefit is the implementation of flexible and adaptive optical correction. Adaptive optics performed by means of Zernike polynomials are used to correct for system induced aberrations. Here we present results with significant improvement in throughput obtained using a novel complementary metal-oxide-semiconductor (CMOS) 1024 pixel single-photon avalanche diode (SPAD) array, opening the way to truly high-throughput FLIM.

  4. Multiphoton imaging for assessing renal disposition in acute kidney injury

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

    2016-11-01

    Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

  5. Nonperturbative multiphoton processes and electron-positron pair production

    SciTech Connect

    Hatsagortsyan, K. Z.; Mueller, C.; Keitel, C. H.

    2006-04-07

    Various regimes of pair production in laser fields are analyzed. Particularly, the question of the observability of pair production in a nonperturbative multiphoton regime is discussed. A simple heuristic method is employed which gives order-of-magnitude estimates for probabilities of multiphoton processes and allows to describe its main features. The method is initially probed upon the known process of pair production in a Coulomb and a strong laser field. Then it is applied to the nonperturbative multiphoton regime of the pair production process in a standing laser wave.

  6. Nonperturbative multiphoton processes and electron-positron pair production

    NASA Astrophysics Data System (ADS)

    Hatsagortsyan, K. Z.; Müller, C.; Keitel, C. H.

    2006-04-01

    Various regimes of pair production in laser fields are analyzed. Particularly, the question of the observability of pair production in a nonperturbative multiphoton regime is discussed. A simple heuristic method is employed which gives order-of-magnitude estimates for probabilities of multiphoton processes and allows to describe its main features. The method is initially probed upon the known process of pair production in a Coulomb and a strong laser field. Then it is applied to the nonperturbative multiphoton regime of the pair production process in a standing laser wave.

  7. Multiphoton entanglement through a Bell-multiport beam splitter

    SciTech Connect

    Lim Yuanliang; Beige, Almut

    2005-06-15

    Multiphoton entanglement is an important resource for linear optics quantum computing. Here we show that a wide range of highly entangled multiphoton states, including W-states, can be prepared by interfering single photons inside a Bell multiport beam splitter and using postselection. A successful state preparation is indicated by the collection of one photon per output port. An advantage of the Bell multiport beam splitter is that it redirects the photons without changing their inner degrees of freedom. The described setup can therefore be used to generate polarization, time-bin, and frequency multiphoton entanglement, even when using only a single photon source.

  8. Calculations of photoelectron momentum distributions and energy spectra at strong-field multiphoton ionization of sodium

    NASA Astrophysics Data System (ADS)

    Bunjac, Andrej; Popović, Duška B.; Simonović, Nenad S.

    2017-08-01

    Multiphoton ionization of sodium by a femtosecond laser pulse of 760 nm wavelength and different peak intensities is studied by inspecting the photoelectron angular and momentum distributions and the energy spectra. For this purpose a single-electron model of the atom interacting with the electromagnetic field is used, and the distributions are determined by calculating the evolution of the electron wave function. Beside the most prominent distribution maxima related to the four-photon ionization, the five-photon (above-threshold) ionization peaks are observed. Substructures in the main (nonresonant) maximum in the photoelectron spectra at the four-photon ionization are related to the resonantly enhanced multiphoton ionization via intermediate 4 s, 4 f, 5 p, 5 f and 6 p states.

  9. Statistical properties of multiphoton time-dependent three-boson coupled oscillators

    SciTech Connect

    Abdalla, M. Sebawe; Perina, Jan; Krepelka, Jaromir

    2006-06-15

    We investigate the quantum statistics of three time-dependent coupled oscillators in the presence of multiphoton processes. The system is connected with the two-atom multiphoton Tavis-Cummings model. The solution of the Heisenberg equations of the motion is obtained in a compact form. We assume that the modes are initially prepared in coherent states, and we discuss nonclassical phenomena (squeezing and sub-Poissonian behavior). Further, we examine the joint quasi-distribution functions as well as photon-number distribution and its factorial moments. The system has shown that the nonclassical effect is apparent in compound modes (1,3) and (2,3). Moreover, the superstructure phenomenon is observed when the photon transition is increased.

  10. Multiphoton fluorescence imaging of NADH to quantify metabolic changes in epileptic tissue in vitro

    NASA Astrophysics Data System (ADS)

    Chia, Thomas H.; Zinter, Joseph; Spencer, Dennis D.; Williamson, Anne; Levene, Michael J.

    2007-02-01

    A powerful advantage of multiphoton microscopy is its ability to image endogenous fluorophores such as the ubiquitous coenzyme NADH in discrete cellular populations. NADH is integral in both oxidative and non-oxidative cellular metabolism. NADH loses fluorescence upon oxidation to NAD +; thus changes in NADH fluorescence can be used to monitor metabolism. Recent studies have suggested that hypo metabolic astrocytes play an important role in cases of temporal lobe epilepsy (TLE). Current theories suggest this may be due to defective and/or a reduced number of mitochondria or dysfunction of the neuronal-astrocytic metabolic coupling. Measuring NADH fluorescence changes following chemical stimulation enables the quantification of the cellular distribution of metabolic anomalies in epileptic brain tissue compared to healthy tissue. We present what we believe to be the first multiphoton microscopy images of NADH from the human brain. We also present images of NADH fluorescence from the hippocampus of the kainate-treated rat TLE model. In some experiments, human and rat astrocytes were selectively labeled with the fluorescent dye sulforhodamine 101 (SR101). Our results demonstrate that multiphoton microscopy is a powerful tool for assaying the metabolic pathologies associated with temporal lobe epilepsy in humans and in rodent models.

  11. Spectroscopic characterization of oral epithelial dysplasia and squamous cell carcinoma using multiphoton autofluorescence micro-spectroscopy.

    PubMed

    Pal, Rahul; Edward, Kert; Ma, Liang; Qiu, Suimin; Vargas, Gracie

    2017-07-05

    Multiphoton autofluorescence microscopy (MPAM) has shown potential in identifying features that are directly related to tissue microstructural and biochemical changes throughout epithelial neoplasia. In this study, we evaluate the autofluorescence spectral characteristics of neoplastic epithelium in dysplasia and oral squamous cell carcinoma (OSCC) using multiphoton autofluorescence spectroscopy (MPAS) in an in vivo hamster model of oral neoplasia in order to identify unique signatures that could be used to delineate normal oral mucosa from neoplasia. A 9,10-dimethyl-1,2-benzanthracene (DMBA) hamster model of oral precancer and OSCC was used for in vivo MPAM and MPAS. Multiphoton Imaging and spectroscopy were performed with 780 nm excitation while a bandpass emission 450-650 nm was used for MPAM. Autofluorescence spectra was collected in the spectral window of 400-650 nm. MPAS with fluorescence excitation at 780 nm revealed an overall red shift of a primary blue-green peak (480-520 nm) that is attributed to NADH and FAD. In the case of oral squamous cell carcinoma (OSCC) and some high-grade dysplasia an additional prominent peak at 635 nm, attributed to PpIX was observed. The fluorescence intensity at 635 nm and an intensity ratio of the primary blue-green peak versus 635 nm peak, showed statistically significant difference between control and neoplastic tissue. Neoplastic transformation in the epithelium is known to alter the intracellular homeostasis of important tissue metabolites such as NADH, FAD, and PpIX, which was observed by MPAS in their native environment. A combination of deep tissue microscopy owing to higher penetration depth of multiphoton excitation and depth resolved spectroscopy could prove to be invaluable in identification of cytologic as well as biomolecular spectral characteristic of oral epithelial neoplasia. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Multiphoton imaging of biological samples during freezing and heating

    NASA Astrophysics Data System (ADS)

    Breunig, H. G.; Uchugonova, A.; König, K.

    2014-02-01

    We applied multiphoton microscopic imaging to observe freezing and heating effects in plant- and animal cell samples. The experimental setups consisted of a multiphoton imaging system and a heating and cooling stage which allows for precise temperature control from liquid nitrogen temperature (-196°C 77 K) up to +600°C (873 K) with heating/freezing rates between 0.01 K/min and 150 K/min. Two multiphoton imaging systems were used: a system based on a modified optical microscope and a flexible mobile system. To illustrate the imaging capabilities, plant leafs as well as animal cells were microscopically imaged in vivo during freezing based on autofluorescence lifetime and intensity of intrinsic molecules. The measurements illustrate the usefulness of multiphoton imaging to investigate freezing effects on animal and plant cells.

  13. Rotational averaging of multiphoton absorption cross sections

    NASA Astrophysics Data System (ADS)

    Friese, Daniel H.; Beerepoot, Maarten T. P.; Ruud, Kenneth

    2014-11-01

    Rotational averaging of tensors is a crucial step in the calculation of molecular properties in isotropic media. We present a scheme for the rotational averaging of multiphoton absorption cross sections. We extend existing literature on rotational averaging to even-rank tensors of arbitrary order and derive equations that require only the number of photons as input. In particular, we derive the first explicit expressions for the rotational average of five-, six-, and seven-photon absorption cross sections. This work is one of the required steps in making the calculation of these higher-order absorption properties possible. The results can be applied to any even-rank tensor provided linearly polarized light is used.

  14. Rotational averaging of multiphoton absorption cross sections.

    PubMed

    Friese, Daniel H; Beerepoot, Maarten T P; Ruud, Kenneth

    2014-11-28

    Rotational averaging of tensors is a crucial step in the calculation of molecular properties in isotropic media. We present a scheme for the rotational averaging of multiphoton absorption cross sections. We extend existing literature on rotational averaging to even-rank tensors of arbitrary order and derive equations that require only the number of photons as input. In particular, we derive the first explicit expressions for the rotational average of five-, six-, and seven-photon absorption cross sections. This work is one of the required steps in making the calculation of these higher-order absorption properties possible. The results can be applied to any even-rank tensor provided linearly polarized light is used.

  15. Multi-photon entanglement in high dimensions

    NASA Astrophysics Data System (ADS)

    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.

  16. Multiphoton double ionization of the He atom

    NASA Astrophysics Data System (ADS)

    Li, Y.; Pindzola, M. S.

    2016-05-01

    Time-dependent close-coupling (TDCC) calculations are made for the multiphoton double ionization of the He atom under the influence of a fast pulse XUV laser. One set of TDCC calculations employs l1m1l2m2 coupling on a 2D (r1 ,r2) numerical lattice, a second set of TDCC calculations employs m1m2 coupling on a 4D (r1 ,θ1 ,r2 ,θ2) numerical lattice, and a third set of TDCC calculations employs m1m2 coupling on a 4D (ρ1 ,z1 ,ρ2 ,z2) numerical lattice. Studies are made to see which TDCC method is the most efficient at explaining measurements as the number of photons absorbed is increased. Work supported in part by Grants from NASA, NSF, and DOE.

  17. REVIEW ARTICLE Multiphoton polymerization of hybrid materials

    NASA Astrophysics Data System (ADS)

    Farsari, Maria; Vamvakaki, Maria; Chichkov, Boris N.

    2010-12-01

    Multiphoton polymerization has been developed as a direct laser writing technique for the preparation of complex 3D structures with resolution beyond the diffraction limit of light. The combination of two or more hybrid materials with different functionalities in the same system has allowed the preparation of structures with advanced properties and functions. Furthermore, the surface functionalization of the 3D structures opens new avenues for their applications in a variety of nanobiotechnological fields. This paper describes the principles of 2PP and the experimental set-up used for 3D structure fabrication. It also gives an overview of the materials that have been employed in 2PP so far and depicts the perspectives of this technique in the development of new active components.

  18. Evaluation of Barrett esophagus by multiphoton microscopy.

    PubMed

    Chen, Jianxin; Wong, Serena; Nathanson, Michael H; Jain, Dhanpat

    2014-02-01

    Multiphoton microscopy (MPM) based on 2-photon excitation fluorescence and second-harmonic generation allows simultaneous visualization of cellular details and extracellular matrix components of fresh, unfixed, and unstained tissue. Portable multiphoton microscopes, which could be placed in endoscopy suites, and multiphoton endomicroscopes are in development, but their clinical utility is unknown. To examine fresh, unfixed endoscopic biopsies obtained from the distal esophagus and gastroesophageal junction to (1) define the MPM characteristics of normal esophageal squamous mucosa and gastric columnar mucosa, and (2) evaluate whether diagnosis of intestinal metaplasia/Barrett esophagus (BE) could be made reliably with MPM. The study examined 35 untreated, fresh biopsy specimens from 25 patients who underwent routine upper endoscopy. A Zeiss LSM 710 Duo microscope (Carl Zeiss, Thornwood, New York) coupled to a Spectra-Physics (Mountain View, California) Tsunami Ti:sapphire laser was used to obtain a MPM image within 4 hours of fresh specimen collection. After obtaining MPM images, the biopsy specimens were placed in 10% buffered formalin and submitted for routine histopathologic examination. Then, the MPM images were compared with the findings in the hematoxylin-eosin-stained, formalin-fixed, paraffin-embedded sections. The MPM characteristics of the squamous, gastric-type columnar and intestinal-type columnar epithelium were analyzed. In biopsies with discrepancy between MPM imaging and hematoxylin-eosin-stained sections, the entire tissue block was serially sectioned and reevaluated. A diagnosis of BE was made when endoscopic and histologic criteria were satisfied. Based on effective 2-photon excitation fluorescence of cellular reduced pyridine nucleotides and flavin adenine dinucleotide and lack of 2-photon excitation fluorescence of mucin and cellular nuclei, MPM could readily identify and distinguish among squamous epithelial cells, goblet cells, gastric

  19. Dynamics of cluster dissociation following multiphoton ionization

    SciTech Connect

    Castleman, A.W.

    1986-01-01

    A major advance in the study of unimolecular dissociation and the spectroscopy of clusters has become available through the use of multiphoton ionization coupled with a reflectron introduced into the drift region of a time-of-flight mass spectrometer. Using single and two-color tunable pulsed lasers, the excess energy introduced into a cluster can be well controlled. The power of this method is demonstrated by the results of recent investigations of hydrogen-bonded clusters which, following ionization, lead to an internal ion-molecule reaction, and cluster fragmentation. The role of dissociation and the influence of the thermochemical stability of cluster ions in effecting the appearance of magic numbers in certain cluster distributions is discussed. The application of this method in determining ionization potentials of probe molecules following successive clustering with a solvent species is also presented.

  20. Point spread function engineering with multiphoton SPIFI

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

    MultiPhoton SPatIal Frequency modulated Imaging (MP-SPIFI) has recently demonstrated the ability to simultaneously obtain super-resolved images in both coherent and incoherent scattering processes -- namely, second harmonic generation and two-photon fluorescence, respectively.1 In our previous analysis, we considered image formation produced by the zero and first diffracted orders from the SPIFI modulator. However, the modulator is a binary amplitude mask, and therefore produces multiple diffracted orders. In this work, we extend our analysis to image formation in the presence of higher diffracted orders. We find that tuning the mask duty cycle offers a measure of control over the shape of super-resolved point spread functions in an MP-SPIFI microscope.

  1. Multiphoton microscopy of cleared mouse organs

    NASA Astrophysics Data System (ADS)

    Parra, Sonia G.; Chia, Thomas H.; Zinter, Joseph P.; Levene, Michael J.

    2010-05-01

    Typical imaging depths with multiphoton microscopy (MPM) are limited to less than 300 μm in many tissues due to light scattering. Optical clearing significantly reduces light scattering by replacing water in the organ tissue with a fluid having a similar index of refraction to that of proteins. We demonstrate MPM of intact, fixed, cleared mouse organs with penetration depths and fields of view in excess of 2 mm. MPM enables the creation of large 3-D data sets with flexibility in pixel format and ready access to intrinsic fluorescence and second-harmonic generation. We present high-resolution images and 3-D image stacks of the brain, small intestine, large intestine, kidney, lung, and testicle with image sizes as large as 4096×4096 pixels.

  2. Intravital multiphoton microscopy for imaging hepatobiliary function

    NASA Astrophysics Data System (ADS)

    Li, Feng-Chieh; Sun, Tzu-Lin; Lee, Hsuan-Shu; Yang, Shu-Mei; Dong, Chen-Yuan

    2007-07-01

    Liver is the chemical factory in body responsible for important functions such as metabolism and detoxification. When liver can not be regenerated in time to amend damages that has occurred, failure of hepatic functions can result. Traditionally, the study of liver pathology has depended on histological techniques, but such methods are limited to ex-vivo observation. In order to study hepatic metabolism in vivo, we have designed a hepatic imaging chamber made of biocompatible titanium alloy (6V4Al-Ti, ELI grade). In combination with multiphoton and second harmonic generation microscopy, our approach allows the intravital observation of hepatic intravital activities to be achieved. Processes such as hepatic metabolism and disease progression can be studied using this methodology.

  3. Multiphoton nanosurgery in cells and tissues

    NASA Astrophysics Data System (ADS)

    Riemann, Iris; Anhut, Tiemo; Stracke, Frank; Le Harzic, Ronan; Koenig, Karsten

    2005-04-01

    Multiphoton Microscopy with a femtosecond pulsed Ti:sapphire laser in the near infrared (NIR) enables the user not only to image cells and tissues with a subcellular resolution but also to perform highly precise nanosurgery. Intratissue compartments, single cells and even cell organelles like mitochondria, membranes or chromosomes can be manipulated and optically knocked out. Working at transient TW/cm2 laser intensities, single cells of tumor-sphaeroids were eliminated efficiently inside the sphaeroid without damaging the neighbour cells. Also single organelles of cells inside tissues could be optically knocked out with the nanoscalpel without collateral damage. Tissue structures inside a human tooth have been ablated with sizes below 1 μm. This method may become a useful instrument for nano-manipulating and surgery in several fields of science, including targeted transfection.

  4. Rapid mesoscale multiphoton microscopy of human skin

    PubMed Central

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

    2016-01-01

    We present a multiphoton microscope designed for mesoscale imaging of human skin. The system is based on two-photon excited fluorescence and second-harmonic generation, and images areas of ~0.8x0.8 mm2 at speeds of 0.8 fps (800x800 pixels; 12 frame averages) for high signal-to-noise ratio, with lateral and axial resolutions of 0.5µm and 3.3µm, respectively. The main novelty of this instrument is the design of the scan head, which includes a fast galvanometric scanner, optimized relay optics, a beam expander and high NA objective lens. Computed aberrations in focus are below the Marechal criterion of 0.07λ rms for diffraction-limited performance. We demonstrate the practical utility of this microscope by ex-vivo imaging of wide areas in normal human skin. PMID:27895980

  5. First-principles calculation of multiphoton absorption cross section of α-quartz under femtosecond laser irradiation

    NASA Astrophysics Data System (ADS)

    Yu, Dong; Jiang, Lan; Wang, Feng; Qu, Liangti; Lu, Yongfeng

    2016-05-01

    Time-dependent density functional theory-based first-principles calculations have been used to study the ionization process and electron excitation. The results show that the number of excited electrons follows the power law σ k I k at peak intensities of I < 5 × 1013 W/cm2, indicating that the multiphoton ionization plays a key role. The multiphoton absorption cross section of α-quartz σ k is further calculated to be 3.54 × 1011 cm-3 ps-1 (cm2/TW)6. Using the plasma model, the theoretical results of the damage threshold fluences are consistent with the experimental data, which validates the calculated value of multiphoton absorption cross section. By employing the calculated cross section value in the plasma model, the damage threshold fluences are theoretically estimated, being consistent with the experimental data, which validates the calculated value of multiphoton absorption cross section. The preliminary multiscale model shows great potential in the simulation of laser processing.

  6. Studies of atmospheric molecules by multiphoton spectroscopy

    NASA Astrophysics Data System (ADS)

    Johnson, P. M.

    1990-12-01

    Resonance ionization processes can play an important role in understanding molecules important in combustion processes. They are a reflection of the dynamic as well as the static properties of atomic and molecular species. Due to the sequential or quasisequential nature of photon absorption in resonant multiphoton events, the lifetimes of the intermediate states play an essential role in the overall cross-sections if they are short enough to be competitive with subsequent photon interactions. In molecules, this is particularly important because there are many dissociative and other radiationless pathways which can contribute to a competitive channel. Under those conditions it should be possible to obtain information about the nature of the dynamics of the intermediate state from the multiphoton ionization process. This will involve looking at not only the ionization cross-section but also other observables such as the kinetic energy of the ejected electrons and possibly the distribution of fragment ions produced in the ionization event. Whether the ionization amplitude is affected or not, the time scales of the dynamic events which alter the ionization path can vary over a large range from the femtoseconds of dissociation to the microseconds of some radiationless transitions in large molecules. When the competing channel has a time scale shorter than the laser pulse length, the kinetics of the ionization are intimately tied into the precise nature of the laser pulse. For time scales longer than the laser pulse, pump-probe ionization schemes in which one laser prepares a state while another does the ionization provide a particularly simple method for investigating the dynamics of the intermediate state. Here the author discusses examples from each of these regimes. CO2 and pyrazine are examined.

  7. Multiphoton Photochemical and Collisional Effects during Oxygen Atom Flame Detection.

    DTIC Science & Technology

    1984-10-01

    multiphoton ionization (MPI), 3𔃾’ 5 the latter allo referred to as optogalvanic detection. In the case of the oxv en atoms, however, direct...multiphoton induced photolysis of the fuel and oxidizer parent molecules followed by a 0 atom two-photon resonant formation of a microplasma . In the...of nonlinearity. A microplasma is not surprising since the absorption of the third photon ionizes the 0 atoms4 and the temperature in the focal

  8. Multiphoton lasing in atomic potassium: Steady-state and dynamic behavior

    SciTech Connect

    Font, J. L.; Fernandez-Soler, J. J.; Vilaseca, R.; Gauthier, Daniel J.

    2005-12-15

    We show theoretically that it is possible to generate laser light based on two-photon and other high-order multiphoton processes when an atomic beam of optically driven potassium atoms crosses a high-finesse optical cavity. We use a rigorous model that takes into account all the atomic substates involved in the optical interactions and is valid for any drive and lasing field intensities. The polarizations of the drive and lasing fields are assumed to be fixed. Stable and unstable laser emission branches are obtained, which are represented as a function of cavity detuning and are analyzed in terms of the fundamental quantum processes yielding them. Closed-curve laser-emission profiles are obtained for multiphoton lasing based on processes involving more than one lasing photon. Two-photon laser emission branches show relatively long segments of stationary emission, combined in general with some segments of nonstationary emission, or with segments of mixture with three-photon emission processes. Rayleigh and hyper-Rayleigh processes can become simultaneously resonant, entailing in such case a large and fast transfer of population from the atomic initial ground sublevel to other ground sublevels with different z components of the total angular momentum. They could be useful in generating multiphoton correlated field states. In all cases the largest laser emission intensities are obtained from the highest-order processes, rather than the lowest. These results open the way to the understanding of experiments performed in the past years and suggest possibilities for more efficient and varied types of multiphoton laser operation.

  9. Assessment of multiphoton absorption in inert gases for the measurement of gas temperatures.

    PubMed

    Bednar, Natalie J; Walewski, Joachim W; Sanders, Scott T

    2006-03-01

    A spatially resolved optical technique to measure gas temperature was assessed. The technique relies on multiphoton absorption in inert gases. In contrast to laser-induced fluorescence, absorption is insensitive to collisional deactivation, and, in contrast to one-photon absorption, multiphoton absorption only occurs around the focus point of a typical laser beam. Multiphoton absorption features both the merits of being insensitive to quenching and of being a spatially resolved technique. In a case study we assessed two-photon absorption in xenon upon exciting the 5p6 1S0-->5p56p[5/2]2 transition in xenon at a wavelength of 256 nm. The amount of light absorbed by xenon is related to the number density of the gas, and if the gas pressure is known then the gas temperature can be inferred from the number density. Two-photon absorbance was measured as a function of xenon number density and was used to validate a theoretical model of the absorption process. We discuss the circumnavigation of experimental challenges in applying this technique and analyze its precision in terms of the inferred gas temperature.

  10. Intrinsic Indicator of Photodamage during Label-Free Multiphoton Microscopy of Cells and Tissues

    PubMed Central

    Andresen, Elisabeth F.; Geiger, Kathrin D.; Koch, Edmund; Schackert, Gabriele; Steiner, Gerald; Kirsch, Matthias

    2014-01-01

    Multiphoton imaging has evolved as an indispensable tool in cell biology and holds prospects for clinical applications. When addressing endogenous signals such as coherent anti-Stokes Raman scattering (CARS) or second harmonic generation, it requires intense laser irradiation that may cause photodamage. We report that increasing endogenous fluorescence signal upon multiphoton imaging constitutes a marker of photodamage. The effect was studied on mouse brain in vivo and ex vivo, on ex vivo human brain tissue samples, as well as on glioblastoma cells in vitro, demonstrating that this phenomenon is common to a variety of different systems, both ex vivo and in vivo. CARS microscopy and vibrational spectroscopy were used to analyze the photodamage. The development of a standard easy-to-use model that employs rehydrated cryosections allowed the characterization of the irradiation-induced fluorescence and related it to nonlinear photodamage. In conclusion, the monitoring of endogenous two-photon excited fluorescence during label-free multiphoton microscopy enables to estimate damage thresholds ex vivo as well as detect photodamage during in vivo experiments. PMID:25343251

  11. Investigation of depilatory mechanism by use of multiphoton fluorescent microscopy

    NASA Astrophysics Data System (ADS)

    Lin, Chiao-Ying; Lee, Gie-ne; Jee, Shiou-Hwa; Dong, Chen-Yuan; Lin, Sung-Jan

    2007-07-01

    Transdermal drug delivery provides a non-invasive route of drug administration, and can be a alternative method to oral delivery and injection. The stratum corneum (SC) of skin acts as the main barrier to transdermal drug delivery. Studies suggest that depilatory enhances permeability of drug through the epidermis. However, transdermal delivery pathway and mechanism are not completely understood. Previous studies have found that depilatory changes the keratinocytes of epidermis, and cause the protein in combination with lipid extraction of SC to become disordered. Nevertheless, those studies did not provide images of those processes. The aim of this study is to characterize the penetration enhancing effect of depilatory agent and the associated structural alterations of stratum corneum. Fresh human foreskin is treated by a depilatory agent for 10 minutes and then subjected to the treatment of fluorescent model drugs of hydrophilic rhodamine and hydrophobic rhodamine-RE. The penetration of model drugs is imaged and quantified by multiphoton microscopy. Our results showed that the penetration of both hydrophilic and hydrophobic agents can be enhanced and multifocal detachment of surface corneocytes is revealed. Nile red staining revealed, instead of a regular motar distribution of lipid around the brick of corneocytes, a disorganized and homogenized pattern of lipid distribution. We concluded that depilatory agents enhance drug penetration by disrupting both the cellular integrity of corneocytes and the regular packing of intercellular lipid of stratum corneum.

  12. High-efficiency multiphoton boson sampling

    NASA Astrophysics Data System (ADS)

    Wang, Hui; He, Yu; Li, Yu-Huai; Su, Zu-En; Li, Bo; Huang, He-Liang; Ding, Xing; Chen, Ming-Cheng; Liu, Chang; Qin, Jian; Li, Jin-Peng; He, Yu-Ming; Schneider, Christian; Kamp, Martin; Peng, Cheng-Zhi; Höfling, Sven; Lu, Chao-Yang; Pan, Jian-Wei

    2017-06-01

    Boson sampling is considered as a strong candidate to demonstrate 'quantum computational supremacy' over classical computers. However, previous proof-of-principle experiments suffered from small photon number and low sampling rates owing to the inefficiencies of the single-photon sources and multiport optical interferometers. Here, we develop two central components for high-performance boson sampling: robust multiphoton interferometers with 99% transmission rate and actively demultiplexed single-photon sources based on a quantum dot-micropillar with simultaneously high efficiency, purity and indistinguishability. We implement and validate three-, four- and five-photon boson sampling, and achieve sampling rates of 4.96 kHz, 151 Hz and 4 Hz, respectively, which are over 24,000 times faster than previous experiments. Our architecture can be scaled up for a larger number of photons and with higher sampling rates to compete with classical computers, and might provide experimental evidence against the extended Church-Turing thesis.

  13. A large area liquid scintillation multiphoton detector

    NASA Astrophysics Data System (ADS)

    Bharadwaj, V. K.; Cain, M. P.; Caldwell, D. O.; Denby, B. H.; Eisner, A. M.; Joshi, U. P.; Kennett, R. G.; Lu, A.; Morrison, R. J.; Pfost, D. R.; Stuber, H. R.; Summers, D. J.; Yellin, S. J.; Appel, J. A.

    1985-01-01

    A 60 layer lead-liquid scintillator shower detector, which we call the SLIC, has been used for multiphoton detection in the Fermilab tagged photon spectrometer. The detector has an unimpeded active area which is 2.44 m by 4.88 m and is segmented, by means of teflon coated channels, into 3.17 cm wide strips. The 60 layers in depth are broken into three directions of alternating readouts so that three position coordinates are determined for each shower. At present the readouts are made by 334 photomultiplier tubes coupled to BBQ doped wavelength shifter bars which integrate the entire depth of the detector. It is relatively straightforward to increase the number of readouts to include longitudinal segmentation and to increase the segmentation of the outer region which are at present read out two strips to a readout. The energy and position resolutions of isolated showers are about {12%}/{√E} and 3 mm., respectively. The SLIC has been used to study the K-π+π0 decay of the D 0 [1], as well as for electron and muon identification in ψ → e +e - and ψ → μ+μ- plus π0 identification in γp → ψχ [8].

  14. Soliton dynamics in the multiphoton plasma regime

    PubMed Central

    Husko, Chad A.; Combrié, Sylvain; Colman, Pierre; Zheng, Jiangjun; De Rossi, Alfredo; Wong, Chee Wei

    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 W/cm2. Here we report the first phase-resolved observations of femtosecond optical solitons in a semiconductor microchip, with multiphoton ionization at picojoule energies and 1010 W/cm2 intensities. The dramatic nonlinearity leads to picojoule observations of free-electron-induced blue-shift at 1016 cm−3 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. These observations in the highly dispersive slow-light media reveal a rich set of physics governing ultralow-power nonlinear photon-plasma dynamics.

  15. Multiphoton excitation of fluorescent DNA base analogs.

    PubMed

    Katilius, Evaldas; Woodbury, Neal W

    2006-01-01

    Multiphoton excitation was used to investigate properties of the fluorescent DNA base analogs, 2-aminopurine (2AP) and 6-methylisoxanthopterin (6MI). 2-aminopurine, a fluorescent analog of adenine, was excited by three-photon absorption. Fluorescence correlation measurements were attempted to evaluate the feasibility of using three-photon excitation of 2AP for DNA-protein interaction studies. However, high excitation power and long integration times needed to acquire high signal-to-noise fluorescence correlation curves render three-photon excitation FCS of 2AP not very useful for studying DNA base dynamics. The fluorescence properties of 6-methylisoxanthopterin, a guanine analog, were investigated using two-photon excitation. The two-photon absorption cross-section of 6MI was estimated to be about 2.5 x 10(-50) cm(4)s (2.5 GM units) at 700 nm. The two-photon excitation spectrum was measured in the spectral region from 700 to 780 nm; in this region the shape of the two-photon excitation spectrum is very similar to the shape of single-photon excitation spectrum in the near-UV spectral region. Two-photon excitation of 6MI is suitable for fluorescence correlation measurements. Such measurements can be used to study DNA base dynamics and DNA-protein interactions over a broad range of time scales.

  16. The multiphoton ionization of uranium hexafluoride

    SciTech Connect

    Armstrong, D.P. . UEO Enrichment Technical Operations Div.)

    1992-05-01

    Multiphoton ionization (MPI) time-of-flight mass spectroscopy and photoelectron spectroscopy studies of UF{sub 6} have been conducted using focused light from the Nd:YAG laser fundamental ({lambda}=1064 nm) and its harmonics ({lambda}=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{sub x}{sup +} fragment ions even at the lowest laser power densities at which signal could be detected. The laser power dependence of U{sup n+} ions signals indicates that saturation can occur for many of the steps required for their ionization. In general, the doubly-charged uranium ion (U{sup 2+}) intensity is much greater than that of the singly-charged uranium ion (U{sup +}). For the case of the tunable dye laser experiments, the U{sup n+} (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 U{sup 2+} ion and the absence or very small intensities of UF{sub x}{sup +} 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.

  17. Continuous-variable entanglement via multiphoton catalysis

    NASA Astrophysics Data System (ADS)

    Hu, Liyun; Liao, Zeyang; Zubairy, M. Suhail

    2017-01-01

    We theoretically investigate the performance of multiphoton catalysis applied on the two-mode squeezed state by examining the entropy of entanglement, logarithmic negativity, Eistein-Podolsky-Rosen (EPR), and Hillery-Zubairy (HZ) correlations, and the fidelity of teleportation. It is found that the entanglement increases with the number of catalysis operations if the squeezing parameter is low initially. Our comparisons show that the HZ correlation presents a better performance than the EPR correlation for detecting the entanglement, and the improvement of HZ correlation definitely results in the improvement of entropy of entanglement rather than negativity; the region of enhanced EPR correlation is a subregion of all other entanglement properties. In addition, we consider the performances of the fidelity by comparing such operations applied before or after the amplitude damping channel. It is shown that the catalysis operation of m =n =1 before the channel presents the best performance in the initial-low squeezing regime. This may provide a useful insight for a long-distance quantum communication.

  18. Infrared multiphoton dissociation for quantitative shotgun proteomics.

    PubMed

    Ledvina, Aaron R; Lee, M Violet; McAlister, Graeme C; Westphall, Michael S; Coon, Joshua J

    2012-05-15

    We modified a dual-cell linear ion trap mass spectrometer to perform infrared multiphoton dissociation (IRMPD) in the low-pressure trap of a dual-cell quadrupole linear ion trap (dual-cell QLT) and perform large-scale IRMPD analyses of complex peptide mixtures. Upon optimization of activation parameters (precursor q-value, irradiation time, and photon flux), IRMPD subtly, but significantly, outperforms resonant-excitation collisional-activated dissociation (CAD) for peptides identified at a 1% false-discovery rate (FDR) from a yeast tryptic digest (95% confidence, p = 0.019). We further demonstrate that IRMPD is compatible with the analysis of isobaric-tagged peptides. Using fixed QLT rf amplitude allows for the consistent retention of reporter ions, but necessitates the use of variable IRMPD irradiation times, dependent upon precursor mass to charge (m/z). We show that IRMPD activation parameters can be tuned to allow for effective peptide identification and quantitation simultaneously. We thus conclude that IRMPD performed in a dual-cell ion trap is an effective option for the large-scale analysis of both unmodified and isobaric-tagged peptides.

  19. Infrared Multiphoton Dissociation for Quantitative Shotgun Proteomics

    PubMed Central

    Ledvina, Aaron R.; Lee, M. Violet; McAlister, Graeme C.; Westphall, Michael S.; Coon, Joshua J.

    2012-01-01

    We modified a dual-cell linear ion trap mass spectrometer to perform infrared multiphoton dissociation (IRMPD) in the low pressure trap of a dual-cell quadrupole linear ion trap (dual cell QLT) and perform large-scale IRMPD analyses of complex peptide mixtures. Upon optimization of activation parameters (precursor q-value, irradiation time, and photon flux), IRMPD subtly, but significantly outperforms resonant excitation CAD for peptides identified at a 1% false-discovery rate (FDR) from a yeast tryptic digest (95% confidence, p = 0.019). We further demonstrate that IRMPD is compatible with the analysis of isobaric-tagged peptides. Using fixed QLT RF amplitude allows for the consistent retention of reporter ions, but necessitates the use of variable IRMPD irradiation times, dependent upon precursor mass-to-charge (m/z). We show that IRMPD activation parameters can be tuned to allow for effective peptide identification and quantitation simultaneously. We thus conclude that IRMPD performed in a dual-cell ion trap is an effective option for the large-scale analysis of both unmodified and isobaric-tagged peptides. PMID:22480380

  20. High-resolution multimodal clinical multiphoton tomography of skin

    NASA Astrophysics Data System (ADS)

    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.

  1. Metrology of Multiphoton Microscopes Using Second Harmonic Generation Nanoprobes.

    PubMed

    Mahou, Pierre; Malkinson, Guy; Chaudan, Élodie; Gacoin, Thierry; Beaurepaire, Emmanuel; Supatto, Willy

    2017-09-19

    In multiphoton microscopy, the ongoing trend toward the use of excitation wavelengths spanning the entire near-infrared range calls for new standards in order to quantify and compare the performances of microscopes. This article describes a new method for characterizing the imaging properties of multiphoton microscopes over a broad range of excitation wavelengths in a straightforward and efficient manner. It demonstrates how second harmonic generation (SHG) nanoprobes can be used to map the spatial resolution, field curvature, and chromatic aberrations across the microscope field of view with a precision below the diffraction limit and with unique advantages over methods based on fluorescence. KTiOPO4 nanocrystals are used as SHG nanoprobes to measure and compare the performances over the 850-1100 nm wavelength range of several microscope objectives designed for multiphoton microscopy. Finally, this approach is extended to the post-acquisition correction of chromatic aberrations in multicolor multiphoton imaging. Overall, the use of SHG nanoprobes appears as a uniquely suited method to standardize the metrology of multiphoton microscopes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Dissociation dynamics of methanol clusters following multiphoton ionization

    SciTech Connect

    Morgan, S.; Castleman, A.W. Jr. )

    1989-06-01

    Following multiphoton ionization (MPI), neutral methanol clusters are found to undergo a well-known ion-molecule reaction which leads to the production of protonated clusters. Evaporative dissociation rates of the cluster ions are measured for sizes ranging from the dimer to the 21-mer following MPI. There is a general trend of the rates decreasing with time after the initial ionization event in accordance with the evaporative ensemble model. Rates measured at long times after ionization display a consistent trend of increasing with cluster size. These findings are shown to be in accord with statistical considerations of evaporative unimolecular dissociation. Collision-induced-dissociation cross sections are found to generally increase with size; the finding of a local minimum in the value for H{sup +}(CH{sub 3}OH){sub 3} is in agreement with predictions of its structure. Finally, through a combination of unimolecular evaporative and collision-induced-dissociation processes, as many as five methanol monomers are found to be lost from a cluster as small as H{sup +} (CH{sub 3}OH){sub 7}.

  3. Intravital Multiphoton Imaging of the Kidney: Tubular Structure and Metabolism.

    PubMed

    Small, David M; Sanchez, Washington Y; Gobe, Glenda C

    2016-01-01

    Multiphoton microscopy (MPM) allows the visualization of dynamic pathophysiological events in real time in live animals. Intravital imaging can be applied to investigate novel mechanisms and treatments of different forms of kidney disease as well as improve our understanding of normal kidney physiology. Using rodent models, in conjunction with endogenous fluorescence and infused exogenous fluorescent dyes, measurement can be made of renal processes such as glomerular permeability, juxtaglomerular apparatus function, interactions of the tubulointerstitium, tubulovascular interactions, vascular flow rate, and the renin-angiotensin-aldosterone system. Subcellular processes including mitochondrial dynamics, reactive oxygen species production, cytosolic ion concentrations, and death processes of apoptosis and necrosis can also be seen and measured by MPM. The current methods chapter presents an overview of MPM with a focus on techniques for intravital kidney imaging and gives examples of instances where intravital MPM has been utilized to study renal pathophysiology. Suggestions are provided for MPM methods within the confines of intravital microscopy and selected kidney structure. MPM is undoubtedly a powerful new technique for application in experimental nephrology, and we believe it will continue to create new paradigms for understanding and treating kidney disease.

  4. Strong-field Breit-Wheeler pair production in short laser pulses: Identifying multiphoton interference and carrier-envelope-phase effects

    NASA Astrophysics Data System (ADS)

    Jansen, Martin J. A.; Müller, Carsten

    2016-03-01

    The creation of electron-positron pairs by the strong-field Breit-Wheeler process in intense short laser pulses is investigated in the framework of laser-dressed quantum electrodynamics. Regarding laser field parameters in the multiphoton regime, special attention is brought to the energy spectrum of the created particles, which can be reproduced and explained by means of an intuitive model. The model is based on the probabilities of multiphoton events driven by the spectral components of the laser pulse. It allows us, in particular, to identify interferences between different pair production channels which exhibit a characteristic dependence on the laser carrier-envelope phase.

  5. Vibrational resonance enhanced broadband multiphoton absorption in a triphenylamine derivative

    SciTech Connect

    Lu Changgui; Cui Yiping; Huang Wei; Yun Binfeng; Wang Zhuyuan; Hu Guohua; Cui Jing; Lu Zhifeng; Qian Ying

    2007-09-17

    Multiphoton absorption of 2,5-bis[4-(2-N,N-diphenylaminostyryl)phenyl]-1,3,4-oxadiazole was experimentally studied by using femtosecond laser pulses. This material demonstrates a very broad multiphoton absorption band of around 300 nm width with two peaks of 1250 and 1475 nm. The first peak results from the three-photon absorption process while the second is attributed to the vibrational resonance enhanced four-photon absorption process. Combination of these two processes provides a much broader multiphoton absorption band. In this letter, the analytical solution to nonlinear transmission of a three-photon absorption process is also given when the incident beam has a Gaussian transverse spatial profile.

  6. A review of biomedical multiphoton microscopy and its laser sources

    NASA Astrophysics Data System (ADS)

    Lefort, Claire

    2017-10-01

    Multiphoton microscopy (MPM) has been the subject of major development efforts for about 25 years for imaging biological specimens at micron scale and presented as an elegant alternative to classical fluorescence methods such as confocal microscopy. In this topical review, the main interests and technical requirements of MPM are addressed with a focus on the crucial role of excitation source for optimization of multiphoton processes. Then, an overview of the different sources successfully demonstrated in literature for MPM is presented, and their physical parameters are inventoried. A classification of these sources in function with their ability to optimize multiphoton processes is proposed, following a protocol found in literature. Starting from these considerations, a suggestion of a possible identikit of the ideal laser source for MPM concludes this topical review. Dedicated to Martin.

  7. Coherence-Gated Sensorless Adaptive Optics Multiphoton Retinal Imaging

    PubMed Central

    Cua, Michelle; Wahl, Daniel J.; Zhao, Yuan; Lee, Sujin; Bonora, Stefano; Zawadzki, Robert J.; Jian, Yifan; Sarunic, Marinko V.

    2016-01-01

    Multiphoton microscopy enables imaging deep into scattering tissues. The efficient generation of non-linear optical effects is related to both the pulse duration (typically on the order of femtoseconds) and the size of the focused spot. Aberrations introduced by refractive index inhomogeneity in the sample distort the wavefront and enlarge the focal spot, which reduces the multiphoton signal. Traditional approaches to adaptive optics wavefront correction are not effective in thick or multi-layered scattering media. In this report, we present sensorless adaptive optics (SAO) using low-coherence interferometric detection of the excitation light for depth-resolved aberration correction of two-photon excited fluorescence (TPEF) in biological tissue. We demonstrate coherence-gated SAO TPEF using a transmissive multi-actuator adaptive lens for in vivo imaging in a mouse retina. This configuration has significant potential for reducing the laser power required for adaptive optics multiphoton imaging, and for facilitating integration with existing systems. PMID:27599635

  8. Coherence-Gated Sensorless Adaptive Optics Multiphoton Retinal Imaging

    NASA Astrophysics Data System (ADS)

    Cua, Michelle; Wahl, Daniel J.; Zhao, Yuan; Lee, Sujin; Bonora, Stefano; Zawadzki, Robert J.; Jian, Yifan; Sarunic, Marinko V.

    2016-09-01

    Multiphoton microscopy enables imaging deep into scattering tissues. The efficient generation of non-linear optical effects is related to both the pulse duration (typically on the order of femtoseconds) and the size of the focused spot. Aberrations introduced by refractive index inhomogeneity in the sample distort the wavefront and enlarge the focal spot, which reduces the multiphoton signal. Traditional approaches to adaptive optics wavefront correction are not effective in thick or multi-layered scattering media. In this report, we present sensorless adaptive optics (SAO) using low-coherence interferometric detection of the excitation light for depth-resolved aberration correction of two-photon excited fluorescence (TPEF) in biological tissue. We demonstrate coherence-gated SAO TPEF using a transmissive multi-actuator adaptive lens for in vivo imaging in a mouse retina. This configuration has significant potential for reducing the laser power required for adaptive optics multiphoton imaging, and for facilitating integration with existing systems.

  9. Coherence-Gated Sensorless Adaptive Optics Multiphoton Retinal Imaging.

    PubMed

    Cua, Michelle; Wahl, Daniel J; Zhao, Yuan; Lee, Sujin; Bonora, Stefano; Zawadzki, Robert J; Jian, Yifan; Sarunic, Marinko V

    2016-09-07

    Multiphoton microscopy enables imaging deep into scattering tissues. The efficient generation of non-linear optical effects is related to both the pulse duration (typically on the order of femtoseconds) and the size of the focused spot. Aberrations introduced by refractive index inhomogeneity in the sample distort the wavefront and enlarge the focal spot, which reduces the multiphoton signal. Traditional approaches to adaptive optics wavefront correction are not effective in thick or multi-layered scattering media. In this report, we present sensorless adaptive optics (SAO) using low-coherence interferometric detection of the excitation light for depth-resolved aberration correction of two-photon excited fluorescence (TPEF) in biological tissue. We demonstrate coherence-gated SAO TPEF using a transmissive multi-actuator adaptive lens for in vivo imaging in a mouse retina. This configuration has significant potential for reducing the laser power required for adaptive optics multiphoton imaging, and for facilitating integration with existing systems.

  10. Spectroscopic analysis of keratin endogenous signal for skin multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Pena, A.-M.; Strupler, M.; Boulesteix, T.; Schanne-Klein, M.-C.

    2005-08-01

    We recorded one-photon excited fluorescence (1PEF) and two-photon excited fluorescence (2PEF) spectra of purified keratin from human epidermis, and determined the action cross section of this endogenous chromophore. We used this spectroscopic analysis to analyse multiphoton images of skin biopsies and assign the intrinsic fluorescence signals in the epidermis. We observed a good agreement between in situ and in vitro 2PEF spectra of keratin. This study provides a comprehensive characterization of the 2PEF signal of the keratins from the epidermis, and will be of practical interest for multiphoton imaging of the skin.

  11. Multiphoton microscopic imaging of human normal and cancerous oesophagus tissue.

    PubMed

    Chen, W S; Wang, Y; Liu, N R; Zhang, J X; Chen, R

    2014-01-01

    In this paper, microstructures of human oesophageal submucosa are evaluated using multiphoton microscopy, based on two-photon excited fluorescence and second harmonic generation. The content and distribution of collagen, elastic fibers and cancer cells in normal and cancerous submucosa layer have been distinctly obtained and briefly discussed. The variation of these components is very relevant to the pathology in oesophagus, especially in early oesophageal cancer. Our results further indicate that the multiphoton microscopy technique has the potential application in vivo in clinical diagnosis and monitoring of early oesophageal cancer. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.

  12. Unambiguous atomic Bell measurement assisted by multiphoton states

    NASA Astrophysics Data System (ADS)

    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.

  13. In vivo multiphoton microscopy beyond 1 mm in the brain

    NASA Astrophysics Data System (ADS)

    Miller, David R.; Medina, Flor A.; Hassan, Ahmed; Perillo, Evan P.; Hagan, Kristen; Kazmi, S. M. Shams; Zemelman, Boris V.; Dunn, Andrew K.

    2017-02-01

    We perform high-resolution, non-invasive, in vivo deep-tissue imaging of the mouse neocortex using multiphoton microscopy with a high repetition rate optical parametric amplifier laser source tunable between λ=1,100 and 1,400 nm. We demonstrate an imaging depth of 1,200 μm in vasculature and 1,160 μm in neurons. We also demonstrate deep-tissue imaging using Indocyanine Green (ICG), which is FDA approved and a promising route to translate multiphoton microscopy to human applications.

  14. Multiphoton autofluorescence spectral analysis for fungus imaging and identification

    NASA Astrophysics Data System (ADS)

    Lin, Sung-Jan; Tan, Hsin-Yuan; Kuo, Chien-Jui; Wu, Ruei-Jr; Wang, Shiou-Han; Chen, Wei-Liang; Jee, Shiou-Hwa; Dong, Chen-Yuan

    2009-07-01

    We performed multiphoton imaging on fungi of medical significance. Fungal hyphae and spores of Aspergillus flavus, Micosporum gypseum, Micosoprum canis, Trichophyton rubrum, and Trichophyton tonsurans were found to be strongly autofluorescent but generate less prominent second harmonic signal. The cell wall and septum of fungal hyphae can be easily identified by autofluorescence imaging. We found that fungi of various species have distinct autofluorescence characteristics. Our result shows that the combination of multiphoton imaging and spectral analysis can be used to visualize and identify fungal species. This approach may be developed into an effective diagnostic tool for fungal identification.

  15. MULTIPHOTON IMAGING CAN BE USED FOR MICROSCOPIC EXAMINATION OF INTACT HUMAN GASTROINTESTINAL MUCOSA EX VIVO

    PubMed Central

    Rogart, Jason N.; Nagata, Jun; Loeser, Caroline S.; Roorda, Robert D.; Aslanian, Harry; Robert, Marie E.; Zipfel, Warren R.; Nathanson, Michael H.

    2008-01-01

    Background & Aims The ability to observe cellular and subcellular detail during routine endoscopy is a major goal in the development of new endoscopic imaging techniques. Multiphoton microscopy, which relies on nonlinear infared optical processes, has the potential to identify cellular details by excitation of endogenous fluorescent molecules. We examined the feasibility of using multiphoton microscopy to characterize mucosal histology in the human gastrointestinal tract. Methods A multiphoton microscope was used to determine the optimal excitation wavelength for examination of gastrointestinal mucosa. Fresh, unfixed, and unstained biopsy specimens obtained during routine endoscopy in human subjects were then examined by confocal microscopy and multiphoton microscopy. Multiphoton images also were compared to standard H&E images obtained from paired biopsy specimens. A prototype miniaturized multiphoton probe was used to examine intact rat colon. Results Peak multiphoton autofluorescence intensity was detected in mucosa excited at 735 nm. Multiphoton microscopic examination of unstained biopsy specimens revealed improved cellular detail relative to either unstained or stained specimens examined by confocal imaging. Resolution of structures such as epithelial nuclei, goblet cells, and interstitial fibers and cells was comparable to what was obtained using standard H&E histology. Similar findings were observed when using a prototype miniaturized multiphoton probe. Conclusions Multiphoton microscopy can be used to examine gastrointestinal mucosa at the cellular level, without the need for fluorescent dyes. The construction of a multiphoton endomicroscope could therefore provide a practical means of performing “virtual biopsies” during the course of routine endoscopy, with advantages over currently available endomicroscopy technologies. PMID:18065276

  16. Resonant single-photon and multiphoton coherent transitions in a detuned regime

    NASA Astrophysics Data System (ADS)

    Bertaina, S.; Martens, M.; Egels, M.; Barakel, D.; Chiorescu, I.

    2015-07-01

    We performed quantum manipulations of the multilevel spin system S =5 /2 of a Mn2 + ion, by means of a two-tone pulse drive. The detuning between the excitation and readout radio frequency pulses allows one to select the number of photons involved in a Rabi oscillation as well as increase the frequency of this nutation. Thus detuning can lead to a resonant multiphoton process. Our analytical model for a two-photon process as well as a numerical generalization fit well the experimental findings, with implications for the use of multilevel spin systems as tunable solid state qubits.

  17. FAST TRACK COMMUNICATION: \\ {P}\\ {T}-symmetry, Cartan decompositions, Lie triple systems and Krein space-related Clifford algebras

    NASA Astrophysics Data System (ADS)

    Günther, Uwe; Kuzhel, Sergii

    2010-10-01

    Gauged \\ {P}\\ {T} quantum mechanics (PTQM) and corresponding Krein space setups are studied. For models with constant non-Abelian gauge potentials and extended parity inversions compact and noncompact Lie group components are analyzed via Cartan decompositions. A Lie-triple structure is found and an interpretation as \\ {P}\\ {T}-symmetrically generalized Jaynes-Cummings model is possible with close relation to recently studied cavity QED setups with transmon states in multilevel artificial atoms. For models with Abelian gauge potentials a hidden Clifford algebra structure is found and used to obtain the fundamental symmetry of Krein space-related J-self-adjoint extensions for PTQM setups with ultra-localized potentials.

  18. Physics and Probability

    NASA Astrophysics Data System (ADS)

    Grandy, W. T., Jr.; Milonni, P. W.

    2004-12-01

    Preface; 1. Recollection of an independent thinker Joel A. Snow; 2. A look back: early applications of maximum entropy estimation to quantum statistical mechanics D. J. Scalapino; 3. The Jaynes-Cummings revival B. W. Shore and P. L. Knight; 4. The Jaynes-Cummings model and the one-atom-master H. Walther; 5. The Jaynes-Cummings model is alive and well P. Meystre; 6. Self-consistent radiation reaction in quantum optics - Jaynes' influence and a new example in cavity QED J. H. Eberly; 7. Enhancing the index of refraction in a nonabsorbing medium: phaseonium versus a mixture of two-level atoms M. O. Scully, T. W. Hänsch, M. Fleischhauer, C. H. Keitel and Shi-Yao Zhu; 8. Ed Jaynes' steak dinner problem II Michael D. Crisp; 9. Source theory of vacuum field effects Peter W. Milonni; 10. The natural line shape Edwin A. Power; 11. An operational approach to Schrödinger's cat L. Mandel; 12. The classical limit of an atom C. R. Stroud, Jr.; 13. Mutual radiation reaction in spontaneous emission Richard J. Cook; 14. A model of neutron star dynamics F. W. Cummings; 15. The kinematic origin of complex wave function David Hestenes; 16. On radar target identification C. Ray Smith; 17. On the difference in means G. Larry Bretthorst; 18. Bayesian analysis, model selection and prediction Arnold Zellner and Chung-ki Min; 19. Bayesian numerical analysis John Skilling; 20. Quantum statistical inference R. N. Silver; 21. Application of the maximum entropy principle to nonlinear systems far from equilibrium H. Haken; 22. Nonequilibrium statistical mechanics Baldwin Robertson; 23. A backward look to the future E. T. James; Appendix. Vita and bibliography of Edwin T. Jaynes; Index.

  19. Advances in renal (patho)physiology using multiphoton microscopy.

    PubMed

    Sipos, A; Toma, I; Kang, J J; Rosivall, L; Peti-Peterdi, J

    2007-11-01

    Multiphoton excitation fluorescence microscopy is a state-of-the-art confocal imaging technique ideal for deep optical sectioning of living tissues. It is capable of performing ultrasensitive, quantitative imaging of organ functions in health and disease with high spatial and temporal resolution which other imaging modalities cannot achieve. For more than a decade, multiphoton microscopy has been successfully used with various in vitro and in vivo experimental approaches to study many functions of different organs, including the kidney. This study focuses on recent advances in our knowledge of renal (patho)physiological processes made possible by the use of this imaging technology. Visualization of cellular variables like cytosolic calcium, pH, cell-to-cell communication and signal propagation, interstitial fluid flow in the juxtaglomerular apparatus (JGA), real-time imaging of tubuloglomerular feedback (TGF), and renin release mechanisms are reviewed. A brief summary is provided of kidney functions that can be measured by in vivo quantitative multiphoton imaging including glomerular filtration and permeability, concentration, dilution, and activity of the intrarenal renin-angiotensin system using this minimally invasive approach. New visual data challenge a number of existing paradigms in renal (patho)physiology. Also, quantitative imaging of kidney function with multiphoton microscopy has tremendous potential to eventually provide novel non-invasive diagnostic and therapeutic tools for future applications in clinical nephrology.

  20. Advances in time-dependent methods for multiphoton processes

    SciTech Connect

    Kulander, K.C.; Schafer, K.J.; Krause, J.L.

    1990-09-01

    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.

  1. A multiphoton microscope platform for imaging the mouse eye

    PubMed Central

    Masihzadeh, Omid; Lei, Tim C.; Ammar, David A.; Kahook, Malik Y.

    2012-01-01

    Purpose To demonstrate the ability of multiphoton microscopy to obtain full three-dimensional high-resolution images of the intact mouse eye anterior chamber without need for enucleation. Methods A custom multiphoton microscope was constructed and optimized for deep tissue imaging. Simultaneous two-photon autofluorescence (2PAF) and second harmonic generation (SHG) imaging were performed. A mouse holder and stereotaxic platform were designed to access different parts of the eye for imaging. A reservoir for keeping the eye moist was used during imaging sessions. Results Non-invasive multiphoton images deep inside the anterior chamber of the mouse eye were obtained without the need for enucleation. The iris, corneal epithelium and endothelium, trabecular meshwork region and conjunctiva were visualized by the 2PAF and SHG signals. Identification of the anatomy was achieved by the intrinsic properties of the native tissue without any exogenous labeling. Images as deep as 600 microns into the eye were clearly demonstrated. Full three-dimensional image reconstructions of the entire anterior chamber were performed and analyzed using custom software. Conclusions Multiphoton imaging is a highly promising tool for ophthalmic research. We have demonstrated the ability to image the entire anterior chamber of the mouse eye in its native state. These results provide a foundation for future in vivo studies of the eye. PMID:22815637

  2. Controlling the transmitted information of a multi-photon interacting with a single-Cooper pair box

    SciTech Connect

    Kadry, Heba Abdel-Aty, Abdel-Haleem Zakaria, Nordin; Cheong, Lee Yen

    2014-10-24

    We study a model of a multi-photon interaction of a single Cooper pair box with a cavity field. The exchange of the information using this system is studied. We quantify the fidelity of the transmitted information. The effect of the system parameters (detuning parameter, field photons, state density and mean photon number) in the fidelity of the transmitted information is investigated. We found that the fidelity of the transmitted information can be controlled using the system parameters.

  3. Multiphoton absorption in graphene and metal-organic frameworks

    NASA Astrophysics Data System (ADS)

    Weiqiang, Chen

    Materials possessing large multiphoton absorption are of direct relevance to both photonics applications and materials physics. In this dissertation, we present our investigations into two novel materials: namely, (1) graphene and (2) metal-organic frameworks (MOFs). The dissertation divides into two parts. The first part of the dissertation reports our systematical Z-scan measurements onto two-photon absorption (2PA) in graphene in the spectral range of 435-1100 nm with femtosecond laser pulses. We report that the measured 2PA coefficients of graphene in the near-infrared (NIR) range of 800-1100 nm can be explained by a theoretical model based on the optical transitions near the Dirac point (K point). We also determine the 2PA coefficients of graphene in the visible spectrum (435-700 nm) and observe an enhancement induced by the excitonic Fano resonance at the saddle point (M point). By applying the second-order, time-dependent perturbation theory on interband transitions among three states near the saddle point, we develop a semi-empirical model to take excitons in graphene into consideration. And the model is in agreement with the photon-energy dependence of the observed 2PA spectrum with a scaling factor of B = (1 5) x 102 cm/MW/eV5. Our results verify, for the first time, that the excitonic Fano resonance plays an important role for the 2PA of graphene in the visible spectrum. Besides, we also detail our measurements on the spectral dependence of one-photon absorption (1PA) saturation in graphene over the visible-NIR range. A quadratic photon energy dependence of the measured saturation intensity/fluence is observed over the investigated spectral range. The underlying photo-dynamics is discussed. In the second part of the dissertation, we investigate multiphoton excited photoluminescence (MEPL) from three solid-state crystals of metal-organic frameworks (MOFs): (1) [Zn2(trans,trans-4,4 stilbenedicarboxylic acid (SDC))2(trans, trans-9, 10-bis (4-pyridylethenyl

  4. Nonequilibrium Quantum Simulation in Circuit QED

    NASA Astrophysics Data System (ADS)

    Raftery, James John

    Superconducting circuits have become a leading architecture for quantum computing and quantum simulation. In particular, the circuit QED framework leverages high coherence qubits and microwave resonators to construct systems realizing quantum optics models with exquisite precision. For example, the Jaynes-Cummings model has been the focus of significant theoretical interest as a means of generating photon-photon interactions. Lattices of such strongly correlated photons are an exciting new test bed for exploring non-equilibrium condensed matter physics such as dissipative phase transitions of light. This thesis covers a series of experiments which establish circuit QED as a powerful tool for exploring condensed matter physics with photons. The first experiment explores the use of ultra high speed arbitrary waveform generators for the direct digital synthesis of complex microwave waveforms. This new technique dramatically simplifies the classical control chain for quantum experiments and enables high bandwidth driving schemes expected to be essential for generating interesting steady-states and dynamical behavior. The last two experiments explore the rich physics of interacting photons, with an emphasis on small systems where a high degree of control is possible. The first experiment realizes a two-site system called the Jaynes-Cummings dimer, which undergoes a self-trapping transition where the strong photon-photon interactions block photon hopping between sites. The observation of this dynamical phase transition and the related dissipation-induced transition are key results of this thesis. The final experiment augments the Jaynes-Cummings dimer by redesigning the circuit to include in-situ control over photon hopping between sites using a tunable coupler. This enables the study of the dimer's localization transition in the steady-state regime.

  5. Non-invasive short-term assessment of retinoids effects on human skin in vivo using multiphoton microscopy.

    PubMed

    Tancrède-Bohin, E; Baldeweck, T; Decencière, E; Brizion, S; Victorin, S; Parent, N; Faugere, J; Souverain, L; Bagot, M; Pena, A-M

    2015-04-01

    The occlusive patch test developed for assessing topical retinoids activity in human skin has been extended as a short-term screening protocol for anti-ageing agents. In this model, biopsies are performed at the end of the occlusion period for morphological and immuno-histochemistry analysis. Multiphoton microscopy is a recent non-invasive imaging technique that combined with image processing tools allows the in vivo quantification of human skin modifications. To validate with gold standards of anti-ageing that are retinoids, the relevance of multiphoton microscopy for kinetic and quantitative assessment in this model. Twenty women, aged 50-65 years, were enrolled. Retinol 0.3% (RO) and Retinoic acid 0.025% (RA) were applied to the dorsal photo-damaged side of their forearm under occlusive patches for 12 days. A patch alone was applied to a third area as control. Evaluation was performed at day D0, D12 (end of treatment), D18 and D32 using multiphoton microscopy. Epidermal thickness, normalized area of the dermal-epidermal junction (DEJ) and melanin density were estimated using 3D image processing tools. Main significant results are: Epidermal thickening at D12, D18 and D32 with RO and at D12, D18 with RA vs. baseline and vs. Increased DEJ undulation at D32 with RO and at D12 with RA vs. baseline and vs. Decreased melanin content with RO (at D12 and D18 vs. baseline and at D32 vs. baseline and vs. control) and with RA (at D12 vs. baseline). This study shows that multiphoton microscopy associated to specific 3D image processing tools allows cutaneous effects induced by topical retinoids in this in vivo model to be non-invasively detected, quantified and followed over time. This innovative approach could be applied to the evaluation of other active compounds. © 2014 European Academy of Dermatology and Venereology.

  6. Enhancement of transmission rates in quantum memory channels with damping.

    PubMed

    Benenti, Giuliano; D'Arrigo, Antonio; Falci, Giuseppe

    2009-07-10

    We consider the transfer of quantum information down a single-mode quantum transmission line. Such a quantum channel is modeled as a damped harmonic oscillator, the interaction between the information carriers -a train of N qubits- and the oscillator being of the Jaynes-Cummings kind. Memory effects appear if the state of the oscillator is not reset after each channel use. We show that the setup without resetting is convenient in order to increase the transmission rates, both for the transfer of quantum and classical private information. Our results can be applied to the micromaser.

  7. Transient Sub-Poissonian Distribution for Single-Mode Lasers

    NASA Technical Reports Server (NTRS)

    Zang, J. Y.; Gu, Q.; Tian, L. K.

    1996-01-01

    In this paper, the transient photon statistics for single-mode lasers is investigated by making use of the theory of quantum electrodynamics. By taking into account of the transitive time l,we obtain the master equation for Jaynes-Cummings model. The relation between the Mandel factor and the time is obtained by directly solving the master equation. The result shows that a transient phenomenon from the transient super-Poissonian distribution to the transient sub-Poissonian distribution occurs for single-mode lasers. In addition, the influences of the thermal light field and the cavity loss on the transient sub-Poissonian distribution are also studied.

  8. Bosonic quasideterminants and eigenvalue problems of generalized spin-orbit operators

    SciTech Connect

    Ben Geloun, Joseph; Hounkonnou, M. Norbert

    2008-02-15

    This paper deals with an extension of the applications of the paper by Gelfand and Retakh [Funct. Anal. Appl. 25, 91 (1991)] on quasideterminant (QsD) algebraic method to eigenvalue problems in quantum mechanics. Using relevant identities on the free 1-mode bosonic algebra, we build characteristic QsDs associated with generalized spin-orbit Hamiltonians with a well defined representation which allows us to explicitly and straightforwardly compute analytical expressions of eigenenergies. Specific instances are provided on f-deformed generalized Jaynes-Cummings models and other Hamiltonian classes widely used in condensed matter physics.

  9. Measuring and using non-Markovianity

    NASA Astrophysics Data System (ADS)

    Pineda, Carlos; Gorin, Thomas; Davalos, David; Wisniacki, Diego A.; García-Mata, Ignacio

    2016-02-01

    We construct measures for the non-Markovianity of quantum evolution with a physically meaningful interpretation. We first provide a general setting in the framework of channel capacities and propose two families of meaningful quantitative measures, based on the largest revival of a channel capacity, avoiding some drawbacks of other non-Markovianity measures. We relate the proposed measures to the task of information screening. This shows that the non-Markovianity of a quantum process may be used as a resource. Under these considerations, we analyze two paradigmatic examples, a qubit in a quantum environment with classically mixed dynamics and the Jaynes-Cummings model.

  10. Elimination of the A-square problem from cavity QED.

    PubMed

    Vukics, András; Griesser, Tobias; Domokos, Peter

    2014-02-21

    We generalize the Power-Zineau-Woolley transformation to obtain a canonical Hamiltonian of cavity quantum electrodynamics for arbitrary geometry of boundaries. This Hamiltonian is free from the A-square term and the instantaneous Coulomb interaction between distinct atoms. The single-mode models of cavity QED (Dicke, Tavis-Cummings, Jaynes-Cummings) are justified by a term by term mapping to the proposed microscopic Hamiltonian. As one straightforward consequence, the basis of no-go argumentations concerning the Dicke phase transition with atoms in electromagnetic fields dissolves.

  11. Rabi splitting in a quantum well system with Rashba spin-orbital coupling

    NASA Astrophysics Data System (ADS)

    Ma, Wenjie; Wang, Zhihai; Zhu, Hongbo

    2017-01-01

    We study the Rabi splitting phenomenon in a quantum well system with Rashba spin-orbital coupling where the spin degree of freedom is driven weakly by an external field. The dynamics of the system can be described by the Jaynes-Cummings model. As we increase the strength of spin-orbital coupling, the system undergoes an energy-level crossing which does not occure in the traditional cavity and circuit QED setups. We find that the intuitive rotating wave approximation in the driving Hamiltonian is ineffective when the energy-level crossing occurs. We also give a physical understanding based on the dressed-state representation.

  12. Acousto-optic multiphoton laser scanning microscopy and multiphoton photon counting spectroscopy: Applications and implications for optical neurobiology

    NASA Astrophysics Data System (ADS)

    Iyer, Vijay

    Multiphoton excitation of molecular probes has become an important tool in experimental neurobiology owing to the intrinsic optical sectioning and low light scattering it affords. Using molecular functional indicators, multiphoton excitation allows physiological signals within single neurons to be observed from within living brain tissue. Ideally, it would be possible to record from multiple sites located throughout the elaborately branching dendritic arbors, in order to study the correlations of structure and function both within and across experiments. However, existing multiphoton microscope systems based on scanning mirrors do not allow optical recordings to be obtained from more than a handful of sites simultaneously at the high rates required to capture the fast physiological signals of interest (>100Hz for Ca2+ signals, >1kHz for membrane potential transients). In order to overcome this limitation, two-dimensional acousto-optic deflection was employed, to allow an ultrafast laser beam suited for multiphoton excitation to be rapidly repositioned with low latency (˜15mus). This supports a random-access scanning mode in which the beam can repeatedly visit a succession of user-selected sites of interest within the microscope's field-of-view at high rates, with minimal sacrifice of pixel dwell time. This technique of acousto-optic multiphoton laser scanning microscope (AO-MPLSM) was demonstrated to allow the spatial profile of signals arising in response to physiological stimulation to be rapidly mapped. Means to compensate or avoid problems of dispersion which have hampered AO-MPLSM in the past are presented, with the latter being implemented. Separately, the combination of photon counting detection with multiphoton excitation, termed generally multiphoton photon counting spectroscopy (MP-PCS), was also considered, with particular emphasis on the technique of fluorescence correlation spectroscopy (FCS). MP-PCS was shown to allow information about molecular

  13. Intact corneal stroma visualization of GFP mouse revealed by multiphoton imaging.

    PubMed

    Lo, Wen; Teng, Shu-Wen; Tan, Hsin-Yuan; Kim, Ki Hean; Chen, Hsiao-Ching; Lee, Hsuan-Shu; Chen, Yang-Fan; So, Peter T C; Dong, Chen-Yuan

    2006-12-01

    The aim of this work is to demonstrate that multiphoton microscopy is a preferred technique to investigate intact cornea structure without slicing and staining. At the micron resolution, multiphoton imaging can provide both large morphological features and detailed structure of epithelium, corneal collagen fibril bundles and keratocytes. A large area multiphoton cross-section across an intact eye excised from a GFP mouse was obtained by a homebuilt multiphoton microscope. The broadband multiphoton fluorescence (435-700 nm) and second harmonic generation (SHG, 360-400 nm) signals were generated by the 760 nm output of a femtosecond titanium-sapphire laser. A water immersion objective (Fluor, 40X, NA 0.8; Nikon) was used to facilitate imaging the curve ocular surface. The multiphoton image over entire cornea provides morphological information of epithelial cells, keratocytes, and global collagen orientation. Specifically, our planar, large area multiphoton image reveals a concentric pattern of the stroma collagen, indicative of the laminar collagen organization throughout the stroma. In addition, the green fluorescence protein (GFP) labeling contributed to fluorescence contrast of cellular area and facilitated visualizing of inactive keratocytes. Our results show that multiphoton imaging of GFP labeled mouse cornea manifests both morphological significance and structural details. The second harmonic generation imaging reveals the collagen orientation, while the multiphoton fluorescence imaging indicates morphology and distribution of cells in cornea. Our results support that multiphoton microscopy is an appropriate technology for further in vivo investigation and diagnosis of cornea. Copyright (c) 2006 Wiley-Liss, Inc.

  14. In vivo multiphoton imaging of the cornea: polarization-resolved second harmonic generation from stromal collagen

    NASA Astrophysics Data System (ADS)

    Latour, G.; Gusachenko, I.; Kowalczuk, L.; Lamarre, I.; Schanne-Klein, M.-C.

    2012-03-01

    Multiphoton microscopy provides specific and contrasted images of unstained collagenous tissues such as tendons or corneas. Polarization-resolved second harmonic generation (SHG) measurements have been implemented in a laserscanning multiphoton microscope. Distortion of the polarimetric response due to birefringence and diattenuation during propagation of the laser excitation has been shown in rat-tail tendons. A model has been developed to account for these effects and correct polarization-resolved SHG images in thick tissues. This new modality is then used in unstained human corneas to access two quantitative parameters: the fibrils orientation within the collagen lamellae and the ratio of the main second-order nonlinear tensorial components. Orientation maps obtained from polarization resolution of the trans-detected SHG images are in good agreement with the striated features observed in the raw images. Most importantly, polarization analysis of the epi-detected SHG images also enables to map the fibrils orientation within the collagen lamellae while epi-detected SHG images of corneal stroma are spatially homogenous and do not enable direct visualization of the fibrils orientation. Depth profiles of the polarimetric SHG response are also measured and compared to models accounting for orientation changes of the collagen lamellae within the focal volume. Finally, in vivo polarization-resolved SHG is performed in rat corneas and structural organization of corneal stroma is determined using epi-detected signals.

  15. Full analysis of multi-photon pair effects in spontaneous parametric down conversion based photonic quantum information processing

    NASA Astrophysics Data System (ADS)

    Takeoka, Masahiro; Jin, Rui-Bo; Sasaki, Masahide

    2015-04-01

    In spontaneous parametric down conversion (SPDC) based quantum information processing (QIP) experiments, there is a tradeoff between the coincidence count rates (i.e. the pumping power of the SPDC), which limits the rate of the protocol, and the visibility of the quantum interference, which limits the quality of the protocol. This tradeoff is mainly caused by the multi-photon pair emissions from the SPDCs. In theory, the problem is how to model the experiments without truncating these multi-photon emissions while including practical imperfections. In this paper, we establish a method to theoretically simulate SPDC-based QIPs which fully incorporates the effect of multi-photon emissions and various practical imperfections. The key ingredient in our method is the application of the characteristic function formalism which has been used in continuous variable QIPs. We apply our method to three examples, the Hong-Ou-Mandel interference and the Einstein-Podolsky-Rosen interference experiments, and the concatenated entanglement swapping protocol. For the first two examples, we show that our theoretical results quantitatively agree with the recent experimental results. Also we provide the closed expressions for these interference visibilities with the full multi-photon components and various imperfections. For the last example, we provide the general theoretical form of the concatenated entanglement swapping protocol in our method and show the numerical results up to five concatenations. Our method requires only a small computational resource (a few minutes by a commercially available computer), which was not possible in the previous theoretical approach. Our method will have applications in a wide range of SPDC-based QIP protocols with high accuracy and a reasonable computational resource.

  16. Multiphoton absorption is probably not the primary threshold damage mechanism for femtosecond laser pulse exposures in the retinal pigment epithelium

    NASA Astrophysics Data System (ADS)

    Glickman, Randolph D.; Johnson, Thomas E.

    2004-07-01

    Laser induced breakdown has the lowest energy threshold in the femtosecond domain, and is responsible for production of threshold ocular lesions. It has been proposed that multiphoton absorption may also contribute to ultrashort-pulse tissue damage, based on the observation that 33 fs, 810 nm pulse laser exposures caused more DNA breakage in cultured, primary RPE cells, compared to CW laser exposures delivering the same average power. Subsequent studies, demonstrating two-photon excitation of fluorescence in isolated RPE melanosomes, appeared to support the role of multiphoton absorption, but mainly at suprathreshold irradiance. Additional experiments have not found a consistent difference in the DNA strand breakage produced by ultrashort and CW threshold exposures. DNA damage appears to be dependent on the amount of melanin pigmentation in the cells, rather than the pulsewidth of the laser; current studies have found that, at threshold, CW and ultrashort pulse laser exposures produce almost identical amounts of DNA breakage. A theoretical analysis suggest that the number of photons delivered to the RPE melanosome during a single 33-fsec pulse at the ED50 irradiance is insufficient to produce multiphoton excitation. This result appears to exclude the melanosome as a locus for two- or three-photon excitation; however, a structure with a larger effective absorption cross-section than the melanosome may interact with the laser pulses. One possibility is that the nuclear chromatin acts as a unit absorber of photons resulting in DNA damage, but this does not explain the near equivalence of ultrashort and CW exposures in the comet assay model. This equivalence indicated that multiphoton absorption is not a major contributor to the ultrashort pulse laser damage threshold in the near infrared.

  17. Video-rate resonant scanning multiphoton microscopy: An emerging technique for intravital imaging of the tumor microenvironment.

    PubMed

    Kirkpatrick, Nathaniel D; Chung, Euiheon; Cook, Daniel C; Han, Xiaoxing; Gruionu, Gabriel; Liao, Shan; Munn, Lance L; Padera, Timothy P; Fukumura, Dai; Jain, Rakesh K

    2012-01-01

    The abnormal tumor microenvironment fuels tumor progression, metastasis, immune suppression, and treatment resistance. Over last several decades, developments in and applications of intravital microscopy have provided unprecedented insights into the dynamics of the tumor microenvironment. In particular, intravital multiphoton microscopy has revealed the abnormal structure and function of tumor-associated blood and lymphatic vessels, the role of aberrant tumor matrix in drug delivery, invasion and metastasis of tumor cells, the dynamics of immune cell trafficking to and within tumors, and gene expression in tumors. However, traditional multiphoton microscopy suffers from inherently slow imaging rates-only a few frames per second, thus unable to capture more rapid events such as blood flow, lymphatic flow, and cell movement within vessels. Here, we report the development and implementation of a video-rate multiphoton microscope (VR-MPLSM) based on resonant galvanometer mirror scanning that is capable of recording at 30 frames per second and acquiring intravital multispectral images. We show that the design of the system can be readily implemented and is adaptable to various experimental models. As examples, we demonstrate the utility of the system to directly measure flow within tumors, capture metastatic cancer cells moving within the brain vasculature and cells in lymphatic vessels, and image acute responses to changes in a vascular network. VR-MPLSM thus has the potential to further advance intravital imaging and provide new insight into the biology of the tumor microenvironment.

  18. Hybrid Multiphoton Volumetric Functional Imaging of Large Scale Bioengineered Neuronal Networks

    PubMed Central

    Paluch, Shir; Dvorkin, Roman; Brosh, Inbar; Shoham, Shy

    2014-01-01

    Planar neural networks and interfaces serve as versatile in vitro models of central nervous system physiology, but adaptations of related methods to three dimensions (3D) have met with limited success. Here, we demonstrate for the first time volumetric functional imaging in a bio-engineered neural tissue growing in a transparent hydrogel with cortical cellular and synaptic densities, by introducing complementary new developments in nonlinear microscopy and neural tissue engineering. Our system uses a novel hybrid multiphoton microscope design combining a 3D scanning-line temporal-focusing subsystem and a conventional laser-scanning multiphoton microscope to provide functional and structural volumetric imaging capabilities: dense microscopic 3D sampling at tens of volumes/sec of structures with mm-scale dimensions containing a network of over 1000 developing cells with complex spontaneous activity patterns. These developments open new opportunities for large-scale neuronal interfacing and for applications of 3D engineered networks ranging from basic neuroscience to the screening of neuroactive substances. PMID:24898000

  19. Characterizing liver capsule microstructure via in situ bulge test coupled with multiphoton imaging.

    PubMed

    Jayyosi, C; Coret, M; Bruyère-Garnier, K

    2016-02-01

    The characterization of biological tissue at the microscopic scale is the starting point of many applications in tissue engineering and especially in the development of structurally based constitutive models. In the present study, focus is made on the liver capsule, the membrane encompassing hepatic parenchyma, which takes a huge part in liver mechanical properties. An in situ bulge test experiment under a multiphoton microscope has been developed to assess the microstructure changes that arise with biaxial loading. Multiphoton microscopy allows to observe the elastin and collagen fiber networks simultaneously. Thus a description of the microstructure organization of the capsule is given, characterizing the shapes, geometry and arrangement of fibers. The orientation of fibers is calculated and orientation distribution evolution with loading is given, in the case of an equibiaxial and two non equibiaxial loadings, thanks to a circular and elliptic set up of the bulge test. The local strain fields have also been computed, by the mean of a photobleaching grid, to get an idea of what the liver capsule might experience when subjected to internal pressure. Results show that strain fields present some heterogeneity due to anisotropy. Reorientation occurs in non equibiaxial loadings and involves fibers layers from the inner to the outer surface as expected. Although there is a fiber network rearrangement to accommodate with loading in the case of equibiaxial loading, there is no significant reorientation of the main fibers direction of the different layers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Hybrid multiphoton volumetric functional imaging of large-scale bioengineered neuronal networks

    NASA Astrophysics Data System (ADS)

    Dana, Hod; Marom, Anat; Paluch, Shir; Dvorkin, Roman; Brosh, Inbar; Shoham, Shy

    2014-06-01

    Planar neural networks and interfaces serve as versatile in vitro models of central nervous system physiology, but adaptations of related methods to three dimensions (3D) have met with limited success. Here, we demonstrate for the first time volumetric functional imaging in a bioengineered neural tissue growing in a transparent hydrogel with cortical cellular and synaptic densities, by introducing complementary new developments in nonlinear microscopy and neural tissue engineering. Our system uses a novel hybrid multiphoton microscope design combining a 3D scanning-line temporal-focusing subsystem and a conventional laser-scanning multiphoton microscope to provide functional and structural volumetric imaging capabilities: dense microscopic 3D sampling at tens of volumes per second of structures with mm-scale dimensions containing a network of over 1,000 developing cells with complex spontaneous activity patterns. These developments open new opportunities for large-scale neuronal interfacing and for applications of 3D engineered networks ranging from basic neuroscience to the screening of neuroactive substances.

  1. Chronic imaging of amyloid plaques in the live mouse brain using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Bacskai, Brian J.; Kajdasz, Stephen T.; Christie, R. H.; Zipfel, Warren R.; Williams, Rebecca M.; Kasischke, Karl A.; Webb, Watt W.; Hyman, B. T.

    2001-04-01

    Transgenic mice expressing the human Amyloid Precursor Protein (APP) develop amyloid plaques as they age. These plaques resemble those found in the human disease. Multiphoton laser scanning microscopy combined with a novel surgical approach was used to measure amyloid plaque dynamics chronically in the cortex of living transgenic mice. Thioflavine S (thioS) was used as a fluorescent marker of amyloid deposits. Multiphoton excitation allowed visualization of amyloid plaques up to 200 micrometers deep into the brain. The surgical site could be imaged repeatedly without overt damage to the tissue, and individual plaques within this volume could be reliably identified over periods of several days to several months. On average, plaque sizes remained constant over time, supporting a model of rapid deposition, followed by relative stability. Alternative reporters for in vivo histology include thiazine red, and FITC-labeled amyloid-(Beta) peptide. We also present examples of multi-color imaging using Hoechst dyes and FITC-labeled tomato lectin. These approaches allow us to observe cell nuclei or microglia simultaneously with amyloid-(Beta) deposits in vivo. Chronic imaging of a variety of reporters in these transgenic mice should provide insight into the dynamics of amyloid-(Beta) activity in the brain.

  2. Multiphoton fluorescence microscopic imaging through double-layer turbid tissue media

    NASA Astrophysics Data System (ADS)

    Deng, Xiaoyuan; Gan, Xiaosong; Gu, Min

    2002-04-01

    Image formation in multiphoton fluorescence microscopy through double-layer turbid tissue media is investigated using Monte Carlo simulation. With the help of the concept of the effective point spread function, the relationship of image resolution and signal level to the thickness and scattering properties of the double-layer turbid media under single-, two-, and three-photon excitation is revealed. Results show that for a double-layer turbid medium of a given thickness, small particles in the top layer result in a quicker degradation of signal level than large particles in the top layer. This model is then applied to study the penetration depth of multiphoton fluorescence microscopy through human skin tissue which exhibits a layered structure. It is predicated that using 3p excitation leads to a signal level up to two orders of magnitude higher than that under 2p excitation, while diffraction-limited image resolution can be maintained for skin tissue of thickness up to 500 μm.

  3. Multiphoton microscopy and microspectroscopy for diagnostics of inflammatory and neoplastic lung

    NASA Astrophysics Data System (ADS)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Flanders, James; Southard, Teresa L.; Weiss, Robert S.; Webb, Watt W.

    2012-03-01

    Limitations of current medical procedures for detecting early lung cancers inspire the need for new diagnostic imaging modalities for the direct microscopic visualization of lung nodules. Multiphoton microscopy (MPM) provides for subcellular resolution imaging of intrinsic fluorescence from unprocessed tissue with minimal optical attenuation and photodamage. We demonstrate that MPM detects morphological and spectral features of lung tissue and differentiates between normal, inflammatory and neoplastic lung. Ex vivo MPM imaging of intrinsic two-photon excited fluorescence was performed on mouse and canine neoplastic, inflammatory and tumor-free lung sites. Results showed that MPM detected microanatomical differences between tumor-free and neoplastic lung tissue similar to standard histopathology but without the need for tissue processing. Furthermore, inflammatory sites displayed a distinct red-shifted fluorescence compared to neoplasms in both mouse and canine lung, and adenocarcinomas displayed a less pronounced fluorescence emission in the 500 to 550 nm region compared to adenomas in mouse models of lung cancer. These spectral distinctions were also confirmed by two-photon excited fluorescence microspectroscopy. We demonstrate the feasibility of applying MPM imaging of intrinsic fluorescence for the differentiation of lung neoplasms, inflammatory and tumor-free lung, which motivates the application of multiphoton endoscopy for the in situ imaging of lung nodules.

  4. Setup and use of a two-laser multiphoton microscope for multichannel intravital fluorescence imaging

    PubMed Central

    Entenberg, David; Wyckoff, Jeffrey; Gligorijevic, Bojana; Roussos, Evanthia T; Verkhusha, Vladislav V; Pollard, Jeffrey W; Condeelis, John

    2014-01-01

    Characterizing biological mechanisms dependent upon the interaction of many cell types in vivo requires both multiphoton microscope systems capable of expanding the number and types of fluorophores that can be imaged simultaneously while removing the wavelength and tunability restrictions of existing systems, and enhanced software for extracting critical cellular parameters from voluminous 4D data sets. We present a procedure for constructing a two-laser multiphoton microscope that extends the wavelength range of excitation light, expands the number of simultaneously usable fluorophores and markedly increases signal to noise via ‘over-clocking’ of detection. We also utilize a custom-written software plug-in that simplifies the quantitative tracking and analysis of 4D intravital image data. We begin by describing the optics, hardware, electronics and software required, and finally the use of the plug-in for analysis. We demonstrate the use of the setup and plug-in by presenting data collected via intravital imaging of a mouse model of breast cancer. The procedure may be completed in ~24 h. PMID:21959234

  5. Multiphoton photochemistry of red fluorescent proteins in solution and live cells.

    PubMed

    Drobizhev, Mikhail; Stoltzfus, Caleb; Topol, Igor; Collins, Jack; Wicks, Geoffrey; Mikhaylov, Alexander; Barnett, Lauren; Hughes, Thomas E; Rebane, Aleksander

    2014-08-07

    Genetically encoded fluorescent proteins (FPs), and biosensors based on them, provide new insights into how living cells and tissues function. Ultimately, the goal of the bioimaging community is to use these probes deep in tissues and even in entire organisms, and this will require two-photon laser scanning microscopy (TPLSM), with its greater tissue penetration, lower autofluorescence background, and minimum photodamage in the out-of-focus volume. However, the extremely high instantaneous light intensities of femtosecond pulses in the focal volume dramatically increase the probability of further stepwise resonant photon absorption, leading to highly excited, ionizable and reactive states, often resulting in fast bleaching of fluorescent proteins in TPLSM. Here, we show that the femtosecond multiphoton excitation of red FPs (DsRed2 and mFruits), both in solution and live cells, results in a chain of consecutive, partially reversible reactions, with individual rates driven by a high-order (3-5 photon) absorption. The first step of this process corresponds to a three- (DsRed2) or four-photon (mFruits) induced fast isomerization of the chromophore, yielding intermediate fluorescent forms, which then subsequently transform into nonfluorescent products. Our experimental data and model calculations are consistent with a mechanism in which ultrafast electron transfer from the chromophore to a neighboring positively charged amino acid residue triggers the first step of multiphoton chromophore transformations in DsRed2 and mFruits, consisting of decarboxylation of a nearby deprotonated glutamic acid residue.

  6. Characteristics of subgingival calculus detection by multiphoton fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    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.

  7. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  8. Hybrid label-free multiphoton and optoacoustic microscopy (MPOM)

    NASA Astrophysics Data System (ADS)

    Soliman, Dominik; Tserevelakis, George J.; Omar, Murad; Ntziachristos, Vasilis

    2015-07-01

    Many biological applications require a simultaneous observation of different anatomical features. However, unless potentially harmful staining of the specimens is employed, individual microscopy techniques do generally not provide multi-contrast capabilities. We present a hybrid microscope integrating optoacoustic microscopy and multiphoton microscopy, including second-harmonic generation, into a single device. This combined multiphoton and optoacoustic microscope (MPOM) offers visualization of a broad range of structures by employing different contrast mechanisms and at the same time enables pure label-free imaging of biological systems. We investigate the relative performance of the two microscopy modalities and demonstrate their multi-contrast abilities through the label-free imaging of a zebrafish larva ex vivo, simultaneously visualizing muscles and pigments. This hybrid microscopy application bears great potential for developmental biology studies, enabling more comprehensive information to be obtained from biological specimens without the necessity of staining.

  9. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    PubMed Central

    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

    2016-01-01

    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 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. PMID:27283889

  10. 48-channel coincidence counting system for multiphoton experiment

    NASA Astrophysics Data System (ADS)

    Zhang, Chen; Li, Wei; Hu, Yi; Yang, Tao; Jin, Ge; Jiang, Xiao

    2016-11-01

    In this paper, we demonstrate a coincidence counting system with 48 input channels which is aimed to count all coincidence events, up to 531 441 kinds, in a multiphoton experiment. Using the dynamic delay adjusting inside the Field Programmable Gate Array, the alignment of photon signals of 48 channels is achieved. After the alignment, clock phase shifting is used to sample signal pulses. Logic constraints are used to stabilize the pulse width. The coincidence counting data stored in a 1G bit external random access memory will be sent to the computer to analyze the amount of 2-, 3-, 4-, 5-, and 6-fold coincidence events. This system is designed for multiphoton entanglement experiments with multiple degrees of freedom of photons.

  11. Multiphoton imaging of freezing and heating effects in plant leaves.

    PubMed

    Breunig, Hans Georg; Tümer, Fatma; König, Karsten

    2013-08-01

    Thermally-induced changes in Arabidopsis thaliana leaves were investigated with a novel cryo microscope by multiphoton, fluorescence lifetime and spectral imaging as well as micro spectroscopy. Samples were excited with fs pulses in the near-infrared range and cooled/heated in a cryogenic chamber. The results show morphological changes in the chloroplast distribution as well as a shift from chlorophyll to cell-wall fluorescence with decreasing temperature. At temperatures below -40 °C, also second harmonic generation was observed. The measurements illustrate the suitability of multiphoton imaging to investigate thermally-induced changes at temperatures used for cryopreservation as well as for basic investigations of thermal effects on plant tissue in general.

  12. Characteristics of subgingival calculus detection by multiphoton fluorescence microscopy.

    PubMed

    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.

  13. Nanoscale hydroxyl radical generation from multiphoton ionization of tryptophan.

    PubMed

    Bisby, Roger H; Crisostomo, Ana G; Botchway, Stanley W; Parker, Anthony W

    2009-01-01

    Exposure of solutions containing both tryptophan and hydrogen peroxide to a pulsed ( approximately 180 fs) laser beam at 750 nm induces luminescence characteristic of 5-hydroxytryptophan. The results indicate that 3-photon excitation of tryptophan results in photoionization within the focal volume of the laser beam. The resulting hydrated electron is scavenged by hydrogen peroxide to produce the hydroxyl radical. The latter subsequently reacts with tryptophan to form 5-hydroxytryptophan. The involvement of hydroxyl radicals is confirmed by the use of ethanol and nitrous oxide as scavengers and their effects on the fluorescence yield in this system. It is postulated that such multiphoton ionization of tryptophanyl residues in cellular proteins may contribute to the photodamage observed during imaging of cells and tissues using multiphoton microscopy.

  14. Towards in vivo breast skin characterization using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Batista, Ana; Uchugonova, Aisada; Breunig, Hans Georg; König, Karsten

    2017-02-01

    Breast cancer, the most common type of cancer in women worldwide, as well as its treatment (e.g. radiation therapy) can affect the human skin. Multiphoton imaging could provide new insights into these skin alterations non-invasively and with high-resolution. As a preparation for a later investigation involving patients, areas of the breast and forearm skin of healthy volunteers were imaged using the clinically certified multiphoton imaging tomograph MPTflex based on endogenous skin autofluorescence and second-harmonic signals. Depth-resolved image stacks were acquired in consecutive weeks to explore the influence of hormonal variations on the skin properties. Both breasts were considered and up to three different areas were imaged per session. Acquisition parameters were optimized to minimize artifacts caused by breathing-motion. As a first result, skin properties, such as the epidermal thickness, appear to be influenced by hormonal variations.

  15. Differentiation of highly metastatic nasopharyngeal carcinoma cells using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhan, Zhenlin; Sun, Zhenzhen; Li, Jingwen; Ye, Qing; Zhuo, Shuangmu; Xie, Shusen

    2016-10-01

    The primary hypothesis tested in the study was that nasopharyngeal carcinoma (NPC) cells at different stage of invasion and metastasis can be differentiated using multiphoton microscopy (MPM). CNE1 and CNE2Z cells were cultured and used in this study. The activity of cell migration and invasion was measured using Transwell assays. At the same time, the morphologic features were quantified from the multiphoton images. The measurements of Transwell migration and invasion showed that the invasion and migration of CNE2Z cells were significantly enhanced when compared with that of CNE1 cells. Also, statistically significant differences in the morphologic features were found between two kinds of cancer cells. In conclusion, it is feasible to use MPM to differentiate cancer cells with different stage of invasion and metastasis.

  16. Differentiation of normal and cancerous lung tissues by multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Li, Feng-Chieh; Wu, Ruei-Jhih; Hovhannisyan, Vladimir A.; Lin, Wei-Chou; Lin, Sung-Jan; So, Peter T. C.; Dong, Chen-Yuan

    2009-07-01

    We utilize multiphoton microscopy for the label-free diagnosis of noncancerous, lung adenocarcinoma (LAC), and lung squamous cell carcinoma (SCC) tissues from humans. Our results show that the combination of second-harmonic generation (SHG) and multiphoton excited autofluorescence (MAF) signals may be used to acquire morphological and quantitative information in discriminating cancerous from noncancerous lung tissues. Specifically, noncancerous lung tissues are largely fibrotic in structure, while cancerous specimens are composed primarily of tumor masses. Quantitative ratiometric analysis using MAF to SHG index (MAFSI) shows that the average MAFSI for noncancerous and LAC lung tissue pairs are 0.55+/-0.23 and 0.87+/-0.15, respectively. In comparison, the MAFSIs for the noncancerous and SCC tissue pairs are 0.50+/-0.12 and 0.72+/-0.13, respectively. Our study shows that nonlinear optical microscopy can assist in differentiating and diagnosing pulmonary cancer from noncancerous tissues.

  17. Multiphoton Imaging of Ultrasound Bioeffects in the Murine Brain

    NASA Astrophysics Data System (ADS)

    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.

  18. Multiphoton tomography of skin tumors after ALA application

    NASA Astrophysics Data System (ADS)

    Riemann, Iris; Ehlers, Alexander; Dill-Müller, Dorothee; Martin, Sven; König, Karsten

    2007-02-01

    In skin, the most common form of cancer is the basal cell carcinoma, affecting about 800.000 people in US each year. One of the treatments is photodynamic therapy (PDT) with a topical application of 5-aminolevulinic acid (ALA) derivates. These photosensitizers accumulate mainly in cancerous cells and can be activated by light resulting in a destruction of the cells. We performed multiphoton tomography based on near-infrared (NIR) femtosecond laser pulses on skin biopsies in order to study the biosynthesis of protoporphyrine IX and the effect of treatment with submicron resolution. The fluorescence of the photosensitizer was excited using two-photon processes and monitored through the epidermis towards the basal layer. In comparison with normal skin the cancerous cells showed different morphology and fluorescence behavior. Multiphoton tomography might become a useful tool for high resolution imaging of cancerous tissue and to evaluate the therapeutical effects.

  19. Multiphoton fluorescence and second harmonic generation microscopy for imaging keratoconus

    NASA Astrophysics Data System (ADS)

    Sun, Yen; Lo, Wen; Lin, Sung-Jan; Lin, Wei-Chou; Jee, Shiou-Hwa; Tan, Hsin-Yuan; Dong, Chen-Yuan

    2006-02-01

    The purpose of this study is to assess the possible application of multiphoton fluorescence and second harmonic generation (SHG) microscopy for imaging the structural features of keratoconus cornea and to evaluate its potential as being a clinical in vivo monitoring technique. Using the near-infrared excitation source from a titanium-sapphire laser pumped by a diode-pumped, solid state (DPSS) laser system, we can induce and simultaneously acquire multiphoton autofluorescence and SHG signals from the cornea specimens with keratoconus. A home-modified commercial microscope system with specified optical components is used for optimal signal detection. Keratoconus cornea button from patient with typical clinical presentation of keratoconus was obtained at the time of penetrating keratoplasty. The specimen was also sent for the histological examination as comparison. In all samples of keratoconus, destruction of lamellar structure with altered collagen fiber orientation was observed within whole layer of the diseased stromal area. In addition, the orientation of the altered collagen fibers within the cone area shows a trend directing toward the apex of the cone, which might implicate the biomechanical response of the keratoconus stroma to the intraocular pressure. Moreover, increased autofluorescent cells were also found in the cone area, with increased density as one approaches the apical area. In conclusion, multiphoton autofluorescence and SHG microscopy non-invasively demonstrated the morphological features of keratoconus cornea, especially the structural alternations of the stromal lamellae. We believe that in the future the multiphoton microscopy can be applied in vivo as an effective, non-invasive diagnostic and monitoring technique for keratoconus.

  20. Relaxation channels of multi-photon excited xenon clusters

    SciTech Connect

    Serdobintsev, P. Yu.; Melnikov, A. S.; Rakcheeva, L. P. Murashov, S. V.; Khodorkovskii, M. A.; Lyubchik, S.; Timofeev, N. A.; Pastor, A. A.

    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.

  1. Relaxation channels of multi-photon excited xenon clusters.

    PubMed

    Serdobintsev, P Yu; Rakcheeva, L P; Murashov, S V; Melnikov, A S; Lyubchik, S; Timofeev, N A; Pastor, A A; Khodorkovskii, M A

    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. Adaptive optics improves multiphoton super-resolution imaging.

    PubMed

    Zheng, Wei; Wu, Yicong; Winter, Peter; Fischer, Robert; Nogare, Damian Dalle; Hong, Amy; McCormick, Chad; Christensen, Ryan; Dempsey, William P; Arnold, Don B; Zimmerberg, Joshua; Chitnis, Ajay; Sellers, James; Waterman, Clare; Shroff, Hari

    2017-09-01

    We improve multiphoton structured illumination microscopy using a nonlinear guide star to determine optical aberrations and a deformable mirror to correct them. We demonstrate our method on bead phantoms, cells in collagen gels, nematode larvae and embryos, Drosophila brain, and zebrafish embryos. Peak intensity is increased (up to 40-fold) and resolution recovered (up to 176 ± 10 nm laterally, 729 ± 39 nm axially) at depths ∼250 μm from the coverslip surface.

  3. Multiphoton laser lithography for the fabrication of plasmonic components

    NASA Astrophysics Data System (ADS)

    Passinger, Sven; Koch, Jürgen; Kiyan, Roman; Reinhardt, Carsten; Chichkov, Boris N.

    2006-08-01

    In this contribution, we demonstrate multi-photon femtosecond laser lithography for the fabrication and rapid prototyping of plasmonic components. Using this technology different dielectric and metallic SPP-structures can be fabricated in a low-cost and time-efficient way. Resolution limits of this technology will be discussed. Investigations of the optical properties of the fabricated SPP-structures by far-field leakage radiation microscopy will be reported.

  4. Multi-Photon Micro-Spectroscopy of Biological Specimens

    DTIC Science & Technology

    2000-07-01

    Arabidopsis thaliana and maize stem sections were used to demonstrate the feasibility of multi- photon fluorescence micro-spectroscopy at subcellular...Micro-spectroscopy, multi-photon fluorescence spectroscopy, second harmonic generation, plant tissues, stem, chloroplast, protoplast, maize , Arabidopsis...thaliana and stem slices of maize (Zea mays) were used as samples to address these issues in a set-up for micro-spectroscopy. 2. MATERIALS AND METHODS

  5. Relaxation channels of multi-photon excited xenon clusters

    NASA Astrophysics Data System (ADS)

    Serdobintsev, P. Yu.; Rakcheeva, L. P.; Murashov, S. V.; Melnikov, A. S.; Lyubchik, S.; Timofeev, N. A.; Pastor, A. A.; Khodorkovskii, M. A.

    2015-09-01

    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.

  6. Laser-Based Multiphoton Excitation Processes in Combustion Diagnostics

    DTIC Science & Technology

    1990-07-01

    5 B. O-Atons ..... C. N- and C-Atoms . ...... o.18 IV. CONCLUSION .................................................... 18 REFERENCES ...Flame atomic species have be detected, as such, with resonant. multiphoton optogal,,anic spectroscopy. - In general, the term optogalvanic loosely refers ... jet burner system was fabricated from a Swagelock 0.635-cm stainless steel terminator fitting through which a 0.5 mm hole was drilled. The burner tip

  7. Multiphoton in vivo imaging with a femtosecond semiconductor disk laser

    PubMed Central

    Voigt, Fabian F.; Emaury, Florian; Bethge, Philipp; Waldburger, Dominik; Link, Sandro M.; Carta, Stefano; van der Bourg, Alexander; Helmchen, Fritjof; Keller, Ursula

    2017-01-01

    We use an ultrafast diode-pumped semiconductor disk laser (SDL) to demonstrate several applications in multiphoton microscopy. The ultrafast SDL is based on an optically pumped Vertical External Cavity Surface Emitting Laser (VECSEL) passively mode-locked with a semiconductor saturable absorber mirror (SESAM) and generates 170-fs pulses at a center wavelength of 1027 nm with a repetition rate of 1.63 GHz. We demonstrate the suitability of this laser for structural and functional multiphoton in vivo imaging in both Drosophila larvae and mice for a variety of fluorophores (including mKate2, tdTomato, Texas Red, OGB-1, and R-CaMP1.07) and for endogenous second-harmonic generation in muscle cell sarcomeres. We can demonstrate equivalent signal levels compared to a standard 80-MHz Ti:Sapphire laser when we increase the average power by a factor of 4.5 as predicted by theory. In addition, we compare the bleaching properties of both laser systems in fixed Drosophila larvae and find similar bleaching kinetics despite the large difference in pulse repetition rates. Our results highlight the great potential of ultrafast diode-pumped SDLs for creating a cost-efficient and compact alternative light source compared to standard Ti:Sapphire lasers for multiphoton imaging. PMID:28717563

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

    PubMed

    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.

  9. Application of multiphoton ionization mass spectrometry: protected dideoxyribonucleotides

    NASA Astrophysics Data System (ADS)

    Lindner, J.; Grotemeyer, J.

    1991-08-01

    This work demonstrates how IR-laser desorption of neutral molecules followed by resonantly enhanced multiphoton ionization can be employed to determine the molecular weight, base sequence of synthetic protected dinucleotides. All sixteen possible combinations of isomeric deoxyribodinucleotides which contain the phosphotriester linkage used in oligonucleotide synthesis have been investigated. The positively charged molecular ion was detected for each dinucleotide at low laser powers at an ionizing wavelength of 242.5 nm. In addition, fragment ions reflecting the primary structure were observed in the soft ionization mode. In the hard ionization mode intensive low mass fragment ions are formed by multiphoton absorption of the molecular ion. In this way the nucleic base composition of the dideoxyribonucleotide can be determined. Fragments containing the 5' end are preferentially detected indicating the high UV absorptivity of the aromatic protective function located at the 5' end. Beside absorption cross-sections, the stability of the N-glycosidic bond between the ribose, the nucleic base affects the intensity of both parent and daughter ions. By assigning the fragment ions generated by multiphoton absorption it is possible to distinguish isomeric sequences of these deoxyribodinucleotides. The influence of the type of the nucleobase and the position of the nucleoside with respect to the phosphate linkage on the relative intensities of the fragment ions are discussed.

  10. Non-invasive multiphoton imaging of extracellular matrix structures

    PubMed Central

    Schenke-Layland, Katja

    2015-01-01

    Multiphoton microscopy has become a powerful method for the artifact-free, nondestructive evaluation of deep-tissue cells and extracellular matrix (ECM) structures in their native environment. By interacting with highly non-centrosymmetric molecular assemblies such as fibrillar collagen, the non-linear process called second harmonic generation (SHG) has also proven to be an important diagnostic tool for the visualization of ECM compartments in situ with submicron resolution without the need for tissue processing. This review reports on applications of multiphoton-induced autofluorescence and SHG microscopy to identify collagen and elastic fiber orientation in native, tissue-engineered and processed, as well as healthy and diseased, tissues and organs. SHG signal profiling was used to quantify ECM damage in various cardiovascular and exocrine tissues, as well as cartilage. These novel imaging modalities open the general possibility of high-resolution in situ and more important in vivo imaging of ECM structures, cells and intracellular organelles in living intact tissues. Heart valve leaflets have a unique extracellular matrix that is organized in distinct layers, which can be non-destructively visualized by multiphoton imaging. PMID:19343671

  11. Differentiation of normal and cancerous lung tissues by multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Chun-Chin; Li, Feng-Chieh; Wu, Ruei-Jr; Hovhannisyan, Vladimir A.; Lin, Wei-Chou; Lin, Sung-Jan; So, Peter T. C.; Dong, Chen-Yuan

    2010-02-01

    In this work, we utilized multiphoton microscopy for the label-free diagnosis of non-cancerous, lung adenocarcinoma (LAC), and lung squamous cell carcinoma (SCC) tissues from human. Our results show that the combination of second harmonic generation (SHG) and multiphoton excited autofluorescence (MAF) signals may be used to acquire morphological and quantitative information in discriminating cancerous from non-cancerous lung tissues. Specifically, non-cancerous lung tissues are largely fibrotic in structure while cancerous specimens are composed primarily of tumor masses. Quantitative ratiometric analysis using MAF to SHG index (MAFSI or SAAID) shows that the average MAFSI for noncancerous and LAC lung tissue pairs are 0.55 +/-0.23 and 0.87+/-0.15 respectively. In comparison, the MAFSIs for the noncancerous and SCC tissue pairs are 0.50+/-0.12 and 0.72+/-0.13 respectively. Intrinsic fluorescence ratio (FAD/NADH) of SCC and non-cancerous tissues are 0.40+/-0.05 and 0.53+/-0.05 respectively, the redox ratio of SCC diminishes significantly, indicating that increased cellular metabolic activity. Our study shows that nonlinear optical microscopy can assist in differentiating and diagnosing pulmonary cancer from non-cancerous tissues. With additional development, multiphoton microscopy may be used for the clinical diagnosis of lung cancers.

  12. Wavelength Scaling of High Harmonic Generation Close to the Multiphoton Ionization Regime

    NASA Astrophysics Data System (ADS)

    Lai, Chien-Jen; Cirmi, Giovanni; Hong, Kyung-Han; Moses, Jeffrey; Huang, Shu-Wei; Granados, Eduardo; Keathley, Phillip; Bhardwaj, Siddharth; Kärtner, Franz X.

    2013-08-01

    We study the wavelength scaling of high harmonic generation efficiency with visible driver wavelengths in the transition between the tunneling and the multiphoton ionization regimes where the Keldysh parameter is around unity. Our experiment shows a less dramatic wavelength scaling of efficiency than the conventional case for near- and mid-IR driver wavelengths, and it is well explained by a generalized three-step model for increased Keldysh parameters that employs complex ionization times in addition to the nonadiabatic ionization. The complex ionization time is critical to avoid the divergence when replacing the quasistatic ionization model by the more general nonadiabatic ionization model. Together, the two modifications present a consistent description of the influence of the atomic potential on the rescattering process in the intermediate Keldysh regime.

  13. Phonon-dressed Mollow triplet in the regime of cavity quantum electrodynamics: excitation-induced dephasing and nonperturbative cavity feeding effects.

    PubMed

    Roy, C; Hughes, S

    2011-06-17

    We study the resonance fluorescence spectra of a driven quantum dot placed inside a high-Q semiconductor cavity and interacting with an acoustic phonon bath. The dynamics is calculated using a time-convolutionless master equation in the polaron frame. We predict pronounced spectral broadening of the Mollow sidebands through off-resonant cavity emission which, for small cavity-coupling rates, increases quadratically with the Rabi frequency in direct agreement with recent experiments using semiconductor micropillars [S. M. Ulrich et al., preceding Letter, Phys. Rev. Lett. 106, 247402 (2011)]. We also demonstrate that, surprisingly, phonon coupling actually helps resolve signatures of the elusive second rungs of the Jaynes-Cummings ladder states via off-resonant cavity feeding. Both multiphonon and multiphoton effects are shown to play a qualitatively important role on the fluorescence spectra.

  14. Probing spin-orbit-interaction-induced electron dynamics in the carbon atom by multiphoton ionization

    NASA Astrophysics Data System (ADS)

    Rey, H. F.; van der Hart, H. W.

    2014-09-01

    We use R-matrix theory with time dependence (RMT) to investigate multiphoton ionization of ground-state atomic carbon with initial orbital magnetic quantum number ML=0 and ML=1 at a laser wavelength of 390 nm and peak intensity of 1014W/cm2. Significant differences in ionization yield and ejected-electron momentum distribution are observed between the two values for ML. We use our theoretical results to model how the spin-orbit interaction affects electron emission along the laser polarization axis. Under the assumption that an initial C atom is prepared at zero time delay with ML=0, the dynamics with respect to time delay of an ionizing probe pulse modeled by using RMT theory is found to be in good agreement with available experimental data.

  15. Caught in the Act: Intravital Multiphoton Microscopy of Host-Pathogen Interactions

    PubMed Central

    Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.

    2009-01-01

    Intravital multiphoton microscopy provides a unique opportunity to discover and characterize biological phenomena in the natural context of living organisms. Here we provide an overview of multiphoton microscopy with particular attention to its application for studying host-pathogen interactions. PMID:19154984

  16. Multi-Photon Fluorescence Spectroscopy of Fluorescent Bio-Probes and Bio-Molecules

    DTIC Science & Technology

    2000-07-01

    the set-up of a multi-photon fluorescence microscope. The information can also be useful in the detection of multi-photon fluorescence in bio -chip...technology. In addition, we have investigated a few highly fluorescent bio -molecules commonly found in plant cells.

  17. Optimization of multi-photon event discrimination levels using Poisson statistics

    NASA Astrophysics Data System (ADS)

    Soukka, Juri M.; Virkki, Arho; Hänninen, Pekka E.; Soini, Juhani T.

    2004-01-01

    In applications where random multi-photon events must be distinguishable from the background, detection of the signals must be based on either analog current measurement or photon counting and multi-level discrimination of single and multi-photon events. In this paper a novel method for optimizing photomultiplier (PMT) pulse discrimination levels in single- and multi-photon counting is demonstrated. This calibration method is based on detection of photon events in coincidence to short laser pulses. The procedure takes advantage of Poisson statistics of single- and mult-iphoton signals and it is applicable to automatic calibration of photon counting devices on production line. Results obtained with a channel photomultiplier (CPM) are shown. By use of three parallel discriminators and setting the discriminator levels according to the described method resulted in a linear response over wide range of random single- and multi-photon signals.

  18. Label-free in vivo imaging of Drosophila melanogaster by multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Lin, Chiao-Ying; Hovhannisyan, Vladimir; Wu, June-Tai; Lin, Sung-Jan; Lin, Chii-Wann; Chen, Jyh-Horng; Dong, Chen-Yuan

    2008-02-01

    The fruit fly Drosophila melanogaster is one of the most valuable organisms in genetic and developmental biology studies. Drosophila is a small organism with a short life cycle, and is inexpensive and easy to maintain. The entire genome of Drosophila has recently been sequenced (cite the reference). These advantages make fruit fly an attractive model organism for biomedical researches. Unlike humans, Drosophila can be subjected to genetic manipulation with relative ease. Originally, Drosophila was mostly used in classical genetics studies. In the model era of molecular biology, the fruit fly has become a model organ for developmental biology researches. In the past, numerous molecularly modified mutants with well defined genetic defects affecting different aspects of the developmental processes have been identified and studied. However, traditionally, the developmental defects of the mutant flies are mostly examined in isolated fixed tissues which preclude the observation of the dynamic interaction of the different cell types and the extracellular matrix. Therefore, the ability to image different organelles of the fruit fly without extrinsic labeling is invaluable for Drosophila biology. In this work, we successfully acquire in vivo images of both developing muscles and axons of motor neurons in the three larval stages by using the minimially invasive imaging modality of multiphoton (SHG) microscopy. We found that while SHG imaging is useful in revealing the muscular architecture of the developing larva, it is the autofluorescence signal that allows label-free imaging of various organelles to be achieved. Our results demonstrate that multiphoton imaging is a powerful technique for investigation the development of Drosophila.

  19. Von Neumann entropy and phase distribution of two mode parametric amplifier interacting with a single atom

    SciTech Connect

    Sebawe Abdalla, M. . E-mail: m.sebawe@physics.org; Obada, A.-S.F.; Abdel-Aty, M.

    2005-08-01

    In the present article, we introduce a Hamiltonian model that consists of two modes of the field in a perfect cavity to interact with a single two-level atom. The interaction between the fields has been taken into account and considered to be in the parametric amplifier form. The model in one hand can be regarded as a generalization of the Jaynes-Cummings model (JCM), however, in the other hand it can be considered as a generalization of the parametric amplifier model. Under a certain condition the exact solution to the Schroedinger equation is obtained. Employing this solution and for chosen values of different parameters we discuss numerically the atomic occupation probabilities as well as the degree of entanglement through the entropy of the field. The system shows superstructure phenomenon similar to that appeared from the effect of the Kerr-like medium on the Jaynes-Cummings model. The von Neumann entropy and phase distribution for both two-mode correlated and uncorrelated coherent states cases are also considered.

  20. Control of multiphoton molecular excitation with shaped femtosecond laser pulses

    NASA Astrophysics Data System (ADS)

    Xu, Bingwei

    The work presented in this dissertation describes the use of shaped femtosecond laser pulses to control the outcome of nonlinear optical process and thus to achieve the selectivity for multiphoton molecular transitions. This research could lead to applications in various fields including nonlinear optical spectroscopy, chemical identification, biological imaging, communications, photodynamic therapy, etc. In order to realize accurate pulse shaping of the femtosecond laser pulses, it is essential to measure and correct the spectral phase distortion of such pulses. A method called multiphoton intrapulse interference phase scan is used to do so throughout this dissertation. This method is highly accurate and reproducible, and has been proved in this work to be compatible with any femtosecond pulses regardless of bandwidth, intensity and repetition rate of the laser. The phase control of several quasi-octave laser sources is demonstrated in this dissertation, with the generation of 4.3 fs and 5.9 fs pulses that reach the theoretically predicted transform-limited pulse duration. The excellent phase control achieved also guarantees the reproducibility for selective multiphoton excitations by accurate phase and/or amplitude shaping. Selective two-photon excitation, stimulated Raman scattering and coherent anti-Stokes Raman scattering with a single broadband laser source are demonstrated in this dissertation. Pulse shaping is used to achieve a fast and robust approach to measure the two-photon excitation spectrum from fluorescent molecules, which provide important information for two-photon biological imaging. The selective excitation concept is also applied in the field of remote chemical identification. Detection of characteristic Raman lines for several chemicals using a single beam coherent anti-Stokes Raman scattering spectroscopy from a 12 meter standoff distance is shown, providing a promising approach to standoff detection of chemicals, hazardous contaminations

  1. Simultaneous Measurement of Neural Spike Recordings and Multi-Photon Calcium Imaging in Neuroblastoma Cells

    PubMed Central

    Kim, Suhwan; Jung, Unsang; Baek, Juyeong; Kang, Shinwon; Kim, Jeehyun

    2012-01-01

    This paper proposes the design and implementation of a micro-electrode array (MEA) for neuroblastoma cell culturing. It also explains the implementation of a multi-photon microscope (MPM) customized for neuroblastoma cell excitation and imaging under ambient light. Electrical signal and fluorescence images were simultaneously acquired from the neuroblastoma cells on the MEA. MPM calcium images of the cultured neuroblastoma cell on the MEA are presented and also the neural activity was acquired through the MEA recording. A calcium green-1 (CG-1) dextran conjugate of 10,000 D molecular weight was used in this experiment for calcium imaging. This study also evaluated the calcium oscillations and neural spike recording of neuroblastoma cells in an epileptic condition. Based on our observation of neural spikes in neuroblastoma cells with our proposed imaging modality, we report that neuroblastoma cells can be an important model for epileptic activity studies. PMID:23202210

  2. Freeform multiphoton excited microfabrication for biological applications using a rapid prototyping CAD-based approach

    NASA Astrophysics Data System (ADS)

    Cunningham, Lawrence P.; Veilleux, Matthew P.; Campagnola, Paul J.

    2006-09-01

    Multiphoton excited polymerization has attracted increasing attention as a powerful 3 dimensional nano/microfabrication tool. The nonlinear excitation confines the fabrication region to the focal volume allowing the potential to achieve freeform fabrication with submicron capabilities. We report the adaptation and use of a computer aided design (CAD) approach, based on rapid prototyping software, which exploits this potential for fabricating with protein and polymers in biologically compatible aqueous environments. 3D structures are drawn in the STL format creating a solid model that can be sliced, where the individual sections are then serially fabricated without overwriting previous layers. The method is shown for potential biological applications including microfluidics, cell entrapment, and tissue engineering.

  3. Mesenchymal stem cell interactions with 3D ECM modules fabricated via multiphoton excited photochemistry.

    PubMed

    Su, Ping-Jung; Tran, Quyen A; Fong, Jimmy J; Eliceiri, Kevin W; Ogle, Brenda M; Campagnola, Paul J

    2012-09-10

    To understand complex micro/nanoscale ECM stem cell interactions, reproducible in vitro models are needed that can strictly recapitulate the relative content and spatial arrangement of native tissue. Additionally, whole ECM proteins are required to most accurately reflect native binding dynamics. To address this need, we use multiphoton excited photochemistry to create 3D whole protein constructs or "modules" to study how the ECM governs stem cell migration. The constructs were created from mixtures of BSA/laminin (LN) and BSA alone, whose comparison afforded studying how the migration dynamics are governed from the combination of morphological and ECM cues. We found that mesenchymal stem cells interacted for significantly longer durations with the BSA/LN constructs than pure BSA, pointing to the importance of binding cues of the LN. Critical to this work was the development of an automated system with feedback based on fluorescence imaging to provide quality control when synthesizing multiple identical constructs.

  4. Quantitative characterization of articular cartilage using Mueller matrix imaging and multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Ellingsen, Pa˚L. Gunnar; Lilledahl, Magnus Borstad; Aas, Lars Martin Sandvik; Davies, Catharina De Lange; Kildemo, Morten

    2011-11-01

    The collagen meshwork in articular cartilage of chicken knee is characterized using Mueller matrix imaging and multiphoton microscopy. Direction and degree of dispersion of the collagen fibers in the superficial layer are found using a Fourier transform image-analysis technique of the second-harmonic generated image. Mueller matrix images are used to acquire structural data from the intermediate layer of articular cartilage where the collagen fibers are too small to be resolved by optical microscopy, providing a powerful multimodal measurement technique. Furthermore, we show that Mueller matrix imaging provides more information about the tissue compared to standard polarization microscopy. The combination of these techniques can find use in improved diagnosis of diseases in articular cartilage, improved histopathology, and additional information for accurate biomechanical modeling of cartilage.

  5. Angular distribution of electrons in multiphoton ionisation of polarised Lithium atoms

    NASA Astrophysics Data System (ADS)

    Klimova, Yu. A.; Marmo, S. I.; Meremianin, A. V.

    2013-09-01

    The asymmetry of the angular distributions of photoelectrons in the photoionisation of polarised alkali atoms is investigated. The general formulas for the amplitude of the multiphoton ionisation of np-states are given. In these formulas the dynamical and kinematical factors are explicitly separated. Our calculations within Fues model potential approach demonstrate that, under the experimental conditions essentially similar to those employed in [M. Schuricke, Ganjun Zhu, J. Steinmann, K. Simeonidis, I. Ivanov, A. Kheifets, A.N. Grum-Grzhimailo, K. Bartschat, A. Dorn, J. Ullrich, Phys. Rev. A 83 (2011) 023413(11)], the relative magnitude of the linear magnetic dichroism in three-photon ionisation of Li can be as large as 30%.

  6. Simultaneous measurement of neural spike recordings and multi-photon calcium imaging in neuroblastoma cells.

    PubMed

    Kim, Suhwan; Jung, Unsang; Baek, Juyeong; Kang, Shinwon; Kim, Jeehyun

    2012-11-08

    This paper proposes the design and implementation of a micro-electrode array (MEA) for neuroblastoma cell culturing. It also explains the implementation of a multi-photon microscope (MPM) customized for neuroblastoma cell excitation and imaging under ambient light. Electrical signal and fluorescence images were simultaneously acquired from the neuroblastoma cells on the MEA. MPM calcium images of the cultured neuroblastoma cell on the MEA are presented and also the neural activity was acquired through the MEA recording. A calcium green-1 (CG-1) dextran conjugate of 10,000 D molecular weight was used in this experiment for calcium imaging. This study also evaluated the calcium oscillations and neural spike recording of neuroblastoma cells in an epileptic condition. Based on our observation of neural spikes in neuroblastoma cells with our proposed imaging modality, we report that neuroblastoma cells can be an important model for epileptic activity studies.

  7. Dataset on coherent control of fields and induced currents in nonlinear multiphoton processes in a nanosphere

    PubMed Central

    McArthur, Duncan; Hourahine, Ben; Papoff, Francesco

    2015-01-01

    We model a scheme for the coherent control of light waves and currents in metallic nanospheres which applies independently of the nonlinear multiphoton processes at the origin of waves and currents. Using exact mathematical formulae, we calculate numerically with a custom fortran code the effect of an external control field which enable us to change the radiation pattern and suppress radiative losses or to reduce absorption, enabling the particle to behave as a perfect scatterer or as a perfect absorber. Data are provided in tabular, comma delimited value format and illustrate narrow features in the response of the particles that result in high sensitivity to small variations in the local environment, including subwavelength spatial shifts. PMID:26601699

  8. Five-Photon Absorption and Selective Enhancement of Multiphoton Absorption Processes.

    PubMed

    Friese, Daniel H; Bast, Radovan; Ruud, Kenneth

    2015-05-20

    We study one-, two-, three-, four-, and five-photon absorption of three centrosymmetric molecules using density functional theory. These calculations are the first ab initio calculations of five-photon absorption. Even- and odd-order absorption processes show different trends in the absorption cross sections. The behavior of all even- and odd-photon absorption properties shows a semiquantitative similarity, which can be explained using few-state models. This analysis shows that odd-photon absorption processes are largely determined by the one-photon absorption strength, whereas all even-photon absorption strengths are largely dominated by the two-photon absorption strength, in both cases modulated by powers of the polarizability of the final excited state. We demonstrate how to selectively enhance a specific multiphoton absorption process.

  9. Five-Photon Absorption and Selective Enhancement of Multiphoton Absorption Processes

    PubMed Central

    2015-01-01

    We study one-, two-, three-, four-, and five-photon absorption of three centrosymmetric molecules using density functional theory. These calculations are the first ab initio calculations of five-photon absorption. Even- and odd-order absorption processes show different trends in the absorption cross sections. The behavior of all even- and odd-photon absorption properties shows a semiquantitative similarity, which can be explained using few-state models. This analysis shows that odd-photon absorption processes are largely determined by the one-photon absorption strength, whereas all even-photon absorption strengths are largely dominated by the two-photon absorption strength, in both cases modulated by powers of the polarizability of the final excited state. We demonstrate how to selectively enhance a specific multiphoton absorption process. PMID:26120588

  10. Fluorescence relaxation in 3D from diffraction-limited sources of PAGFP or sinks of EGFP created by multiphoton photoconversion.

    PubMed

    Calvert, P D; Peet, J A; Bragin, A; Schiesser, W E; Pugh, E N

    2007-01-01

    The relaxation of fluorescence from diffraction-limited sources of photoactivatable green fluorescent protein (PAGFP) or sinks of photobleached enhanced GFP (EGFP) created by multiphoton photo-conversion was measured in solutions of varied viscosity (eta), and in live, spherical Chinese hamster ovary (CHO) cells. Fluorescence relaxation was monitored with the probing laser fixed, or rapidly scanning along a line bisected by the photoconversion site. Novel solutions to several problems that hamper the study of PAGFP diffusion after multiphoton photoconversion are presented. A theoretical model of 3D diffusion in a sphere from a source in the shape of the measured multiphoton point-spread function was applied to the fluorescence data to estimate the apparent diffusion coefficient, D(ap). The model incorporates two novel features that make it of broad utility. First, the model includes the no-flux boundary condition imposed by cell plasma membranes, allowing assessment of potential impact of this boundary on estimates of D(ap). Second, the model uses an inhomogeneous source term that, for the first time, allows analysis of diffusion from sources produced by multiphoton photoconversion pulses of varying duration. For diffusion in aqueous solution, indistinguishable linear relationships between D(ap) and eta(-1) were obtained for the two proteins: for PAGFP, D(aq)= 89 +/- 2.4 microm2 s(-1) (mean +/- 95% confidence interval), and for EGFP D(aq)= 91 +/- 1.8 microm2 s(-1). In CHO cells, the application of the model yielded D(ap)= 20 +/- 3 microm2 s(-1) (PAGFP) and 19 +/- 2 microm2 s(-1) (EGFP). Furthermore, the model quantitatively predicted the decline in baseline fluorescence that accompanied repeated photobleaching cycles in CHO cells expressing EGFP, supporting the hypothesis of fluorophore depletion as an alternative to the oft invoked 'bound fraction' explanation of the deviation of the terminal fluorescence recovery from its pre-bleach baseline level. Nonetheless

  11. Imaging photoelectron circular dichroism of chiral molecules by femtosecond multiphoton coincidence detection.

    PubMed

    Lehmann, C Stefan; Ram, N Bhargava; Powis, Ivan; Janssen, Maurice H M

    2013-12-21

    Here, we provide a detailed account of novel experiments employing electron-ion coincidence imaging to discriminate chiral molecules. The full three-dimensional angular scattering distribution of electrons is measured after photoexcitation with either left or right circular polarized light. The experiment is performed using a simplified photoelectron-photoion coincidence imaging setup employing only a single particle imaging detector. Results are reported applying this technique to enantiomers of the chiral molecule camphor after three-photon ionization by circularly polarized femtosecond laser pulses at 400 nm and 380 nm. The electron-ion coincidence imaging provides the photoelectron spectrum of mass-selected ions that are observed in the time-of-flight mass spectra. The coincident photoelectron spectra of the parent camphor ion and the various fragment ions are the same, so it can be concluded that fragmentation of camphor happens after ionization. We discuss the forward-backward asymmetry in the photoelectron angular distribution which is expressed in Legendre polynomials with moments up to order six. Furthermore, we present a method, similar to one-photon electron circular dichroism, to quantify the strength of the chiral electron asymmetry in a single parameter. The circular dichroism in the photoelectron angular distribution of camphor is measured to be 8% at 400 nm. The electron circular dichroism using femtosecond multiphoton excitation is of opposite sign and about 60% larger than the electron dichroism observed before in near-threshold one-photon ionization with synchrotron excitation. We interpret our multiphoton ionization as being resonant at the two-photon level with the 3s and 3p Rydberg states of camphor. Theoretical calculations are presented that model the photoelectron angular distribution from a prealigned camphor molecule using density functional theory and continuum multiple scattering X alpha photoelectron scattering calculations

  12. Multi-photon UV photolysis of gaseous polycyclic aromatic hydrocarbons: Extinction spectra and dynamics

    NASA Astrophysics Data System (ADS)

    Walsh, A. J.; Ruth, A. A.; Gash, E. W.; Mansfield, M. W. D.

    2013-08-01

    The extinction spectra of static naphthalene and static biphenylene vapor, each buffered with a noble gas at room temperature, were measured as a function of time in the region between 390 and 850 nm after UV multi-photon laser photolysis at 308 nm. Employing incoherent broadband cavity enhanced absorption spectroscopy (IBBCEAS), the spectra were found to be unstructured with a general lack of isolated features suggesting that the extinction was not solely based on absorption but was in fact dominated by scattering from particles formed in the photolysis of the respective polycyclic aromatic hydrocarbon. Following UV multi-photon photolysis, the extinction dynamics of the static (unstirred) closed gas-phase system exhibits extraordinary quasi-periodic and complex oscillations with periods ranging from seconds to many minutes, persisting for up to several hours. Depending on buffer gas type and pressure, several types of dynamical responses could be generated (classified as types I, II, and III). They were studied as a function of temperature and chamber volume for different experimental conditions and possible explanations for the oscillations are discussed. A conclusive model for the observed phenomena has not been established. However, a number of key hypotheses have made based on the measurements in this publication: (a) Following the multi-photon UV photolysis of naphthalene (or biphenylene), particles are formed on a timescale not observable using IBBCEAS. (b) The observed temporal behavior cannot be described on basis of a chemical reaction scheme alone. (c) The pressure dependence of the system's responses is due to transport phenomena of particles in the chamber. (d) The size distribution and the refractive indices of particles are time dependent and evolve on a timescale of minutes to hours. The rate of particle coagulation, involving coalescent growth and particle agglomeration, affects the observed oscillations. (e) The walls of the chamber act as a sink

  13. Multi-photon UV photolysis of gaseous polycyclic aromatic hydrocarbons: Extinction spectra and dynamics

    SciTech Connect

    Walsh, A. J.; Gash, E. W.; Mansfield, M. W. D.; Ruth, A. A.

    2013-08-07

    The extinction spectra of static naphthalene and static biphenylene vapor, each buffered with a noble gas at room temperature, were measured as a function of time in the region between 390 and 850 nm after UV multi-photon laser photolysis at 308 nm. Employing incoherent broadband cavity enhanced absorption spectroscopy (IBBCEAS), the spectra were found to be unstructured with a general lack of isolated features suggesting that the extinction was not solely based on absorption but was in fact dominated by scattering from particles formed in the photolysis of the respective polycyclic aromatic hydrocarbon. Following UV multi-photon photolysis, the extinction dynamics of the static (unstirred) closed gas-phase system exhibits extraordinary quasi-periodic and complex oscillations with periods ranging from seconds to many minutes, persisting for up to several hours. Depending on buffer gas type and pressure, several types of dynamical responses could be generated (classified as types I, II, and III). They were studied as a function of temperature and chamber volume for different experimental conditions and possible explanations for the oscillations are discussed. A conclusive model for the observed phenomena has not been established. However, a number of key hypotheses have made based on the measurements in this publication: (a) Following the multi-photon UV photolysis of naphthalene (or biphenylene), particles are formed on a timescale not observable using IBBCEAS. (b) The observed temporal behavior cannot be described on basis of a chemical reaction scheme alone. (c) The pressure dependence of the system's responses is due to transport phenomena of particles in the chamber. (d) The size distribution and the refractive indices of particles are time dependent and evolve on a timescale of minutes to hours. The rate of particle coagulation, involving coalescent growth and particle agglomeration, affects the observed oscillations. (e) The walls of the chamber act as a sink

  14. Multiphoton ionization of ions, neutrals, and clusters. Progress report

    SciTech Connect

    Wessel, J.

    1991-06-28

    Scientific results are summarized from a three year research program on multiphoton ionization in aromatic molecules, clusters, and their ions. As originally proposed, the studies elucidated a new cluster ionization mechanism, characterized properties of long range intermolecular interactions, and investigated electronic transitions of aromatic cations cooled in a supersonic beam. The studies indicate that the new cluster ionization mechanism is highly efficient and dominates conventional 1 + 1 resonant ionization. In the case of the dimer of the large aromatic molecule fluorene, the results suggest that excimer formation competes with a direct ionization process. Highly selective excitonic spectra have been identified for several cluster species.

  15. Anomalous multiphoton photoelectric effect in ultrashort time scales.

    PubMed

    Kupersztych, J; Raynaud, M

    2005-09-30

    In a multiphoton photoelectric process, an electron needs to absorb a given number of photons to escape the surface of a metal. It is shown for the first time that this number is not a constant depending only on the characteristics of the metal and light, but varies with the interaction duration in ultrashort time scales. The phenomenon occurs when electromagnetic energy is transferred, via ultrafast excitation of electron collective modes, to conduction electrons in a duration less than the electron energy damping time. It manifests itself through a dramatic increase of electron production.

  16. Microstructure imaging of human rectal mucosa using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Liu, N. R.; Chen, G.; Chen, J. X.; Yan, J.; Zhuo, S. M.; Zheng, L. Q.; Jiang, X. S.

    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.

  17. Compact diode laser source for multiphoton biological imaging

    PubMed Central

    Niederriter, Robert D.; Ozbay, Baris N.; Futia, Gregory L.; Gibson, Emily A.; Gopinath, Juliet T.

    2016-01-01

    We demonstrate a compact, pulsed diode laser source suitable for multiphoton microscopy of biological samples. The center wavelength is 976 nm, near the peak of the two-photon cross section of common fluorescent markers such as genetically encoded green and yellow fluorescent proteins. The laser repetition rate is electrically tunable between 66.67 kHz and 10 MHz, with 2.3 ps pulse duration and peak powers >1 kW. The laser components are fiber-coupled and scalable to a compact package. We demonstrate >600 μm depth penetration in brain tissue, limited by laser power. PMID:28101420

  18. Multi-photon microscope driven by novel green laser pump

    NASA Astrophysics Data System (ADS)

    Marti, Dominik; Djurhuus, Martin; Jensen, Ole Bjarlin; Andersen, Peter E.

    2016-03-01

    Multi-photon microscopy is extensively used in research due to its superior possibilities when compared to other microscopy modalities. The technique also has the possibility to advance diagnostics in clinical applications, due to its capabilities complementing existing technology in a multimodal system. However, translation is hindered due to the high cost, high training demand and large footprint of a standard setup. We show in this article that minification of the setup, while also reducing cost and complexity, is indeed possible without compromising on image quality, by using a novel diode laser replacing the commonly used conventional solid state laser as the pump for the femtosecond system driving the imaging.

  19. Multiphoton laser direct writing of two-dimensional silver structures.

    PubMed

    Baldacchini, Tommaso; Pons, Anne-Cécile; Pons, Josefina; Lafratta, Christopher; Fourkas, John; Sun, Yong; Naughton, Michael

    2005-02-21

    We report a novel and efficient method for the laser direct writing of two-dimensional silver structures. Multiphoton absorption of a small fraction of the output of a Ti:sapphire oscillator is sufficient to photoreduce silver nitrate in a thin film of polyvinylpyrrolidone that has been spin-coated on a substrate. The polymer can then be washed away, leaving a pattern consisting of highly interconnected silver nanoparticles. We report the characterization of the silver patterns using scanning electron and atomic force microscopies, and demonstrate the application of this technique in the creation of diffraction gratings.

  20. Visualization of hepatobiliary excretory function by intravital multiphoton microscopy.

    PubMed

    Liu, Yuan; Chen, Hsiao-Ching; Yang, Shu-Mei; Sun, Tzu-Lin; Lo, Wen; Chiou, Ling-Ling; Huang, Guan Tarn; Dong, Chen-Yuan; Lee, Hsuan-Shu

    2007-01-01

    Intravital imaging of hepatobiliary excretion is vital for elucidating liver metabolism. In this work, we describe a novel method to observe the intravital dynamics of the uptake, processing, and excretion of an organic anion, 6-carboxyfluorescein diacetate (6-CFDA) in the hepatobiliary system. This is achieved by the use of multiphoton microscopy and an intravital hepatic imaging chamber. The high-quality images show sequential uptake and processing of 6-CFDA from the hepatocytes and the subsequent excretion into bile canaliculi within approximately 50 min. This is a promising technique to study intravital hepatic physiology and metabolism.

  1. Volumetric display with holographic multi-photon excitations

    NASA Astrophysics Data System (ADS)

    Hayasaki, Yoshio; Kumagai, Kota

    2016-10-01

    We developed a volumetric display with holographic two- and multi-photon excitations using a computer-generated hologram displayed on a liquid crystal spatial light modulator. The holographic technique has advantages of increasing the number of voxels of the volumetric graphics per unit time, increasing the total input energy to the volumetric display because the maximum energy incident at a point in the display material is limited by the damage threshold, and controlling the size, shape and spatial position of voxels. We demonstrated a volumetric display with stacked multi-color fluorescence plates.

  2. The nature of multiphoton fluorescence from red blood cells

    NASA Astrophysics Data System (ADS)

    Saytashev, Ilyas; Murphy, Michael; Osseiran, Sam; Spence, Dana M.; Evans, Conor L.; Dantus, Marcos

    2016-03-01

    We report on the nature of multiphoton excited fluorescence observed from human erythrocytes (red blood cells RBC's) and their "ghosts" following 800nm sub-15 fs excitation. The detected optical signal is assigned as two-photon excited fluorescence from hemoglobin. Our findings are supported by wavelength-resolved fluorescence lifetime decay measurements using time-correlated single photon counting system from RBC's, their ghosts as well as in vitro samples of various fluorophores including riboflavin, NADH, NAD(P)H, hemoglobin. We find that low-energy and short-duration pulses allow two-photon imaging of RBC's, but longer more intense pulses lead to their destruction.

  3. Quantum Radiation Reaction Effects in Multiphoton Compton Scattering

    SciTech Connect

    Di Piazza, A.; Hatsagortsyan, K. Z.; Keitel, C. H.

    2010-11-26

    Radiation reaction effects in the interaction of an electron and a strong laser field are investigated in the realm of quantum electrodynamics. We identify the quantum radiation reaction with the multiple photon recoils experienced by the laser-driven electron due to consecutive incoherent photon emissions. After determining a quantum radiation dominated regime, we demonstrate how in this regime quantum signatures of the radiation reaction strongly affect multiphoton Compton scattering spectra and that they could be measurable in principle with presently available laser technology.

  4. Inherent contradictions in the tunneling-multiphoton dichotomy

    SciTech Connect

    Reiss, H. R.

    2007-03-15

    Strong-field phenomena are currently described as being multiphoton or tunneling, based on whether the Keldysh parameter {gamma} is greater than or less than unity. There are disqualifying features in this categorization. It is specific to the length gauge, dependent on only one intensity parameter, and backward in the sense that ionization with {gamma}>>1 can occur only by tunneling, and ionization with {gamma}<<1 must be over the barrier, and hence is not achieved by tunneling. As {gamma} becomes smaller, ionization becomes increasingly distant from tunneling, and eventually reaches conditions where the dipole approximation fails and there is no meaningful scalar-potential diagram at all.

  5. Combining multiphoton and CARS microscopy for skin imaging

    NASA Astrophysics Data System (ADS)

    Breunig, H. G.; Weinigel, M.; Kellner-Höfer, M.; Bückle, R.; Darvin, M. E.; Lademann, J.; König, K.

    2013-02-01

    Microscopic imaging based on multiphoton fluorescence, second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) imaging has been realized in one common platform which is appropriate for use in hospitals. The different optical modalities non-invasively provide in vivo images from human skin with subcellular resolution, at different depths based on endogenous fluorescent, SHG-active molecules as well as non-fluorescent molecules with vibrational resonances at 2845 cm-1, in particular lipids. An overview of the system employing a Ti:sapphire laser and photonic crystal fiber to generate the excitation light as well as several imaging examples are presented.

  6. Multiphoton ionization of ions, neutrals, and clusters. Final report

    SciTech Connect

    Wessel, J.

    1995-12-28

    A multiyear research program investigating molecular detection methods based on multiphoton spectroscopy has been completed under DOE sponsorship. A number of new laser-based spectroscopic methods were developed and applied to a variety of aromatic hydrocarbons, including monomer and cluster species. The objectives of sensitivities approaching single molecule detection combined with high selectivity were achieved. This report references the status of the field at the beginning of this work and summarizes the significant progress during the period from 1987 onward. Detailed scientific findings from the studies are presented in the published literature referenced throughout this report.

  7. Multiphoton dissociation and thermal unimolecular reactions induced by infrared lasers. [REAMPA code

    SciTech Connect

    Dai, H.L.

    1981-04-01

    Multiphoton dissociation (MPD) of ethyl chloride was studied using a tunable 3.3 ..mu..m laser to excite CH stretches. The absorbed energy increases almost linearly with fluence, while for 10 ..mu..m excitation there is substantial saturation. Much higher dissociation yields were observed for 3.3 ..mu..m excitation than for 10 ..mu..m excitation, reflecting bottlenecking in the discrete region of 10 ..mu..m excitation. The resonant nature of the excitation allows the rate equations description for transitions in the quasicontinuum and continuum to be extended to the discrete levels. Absorption cross sections are estimated from ordinary ir spectra. A set of cross sections which is constant or slowly decreasing with increasing vibrational excitation gives good fits to both absorption and dissociation yield data. The rate equations model was also used to quantitatively calculate the pressure dependence of the MPD yield of SF/sub 6/ caused by vibrational self-quenching. Between 1000-3000 cm/sup -1/ of energy is removed from SF/sub 6/ excited to approx. > 60 kcal/mole by collision with a cold SF/sub 6/ molecule at gas kinetic rate. Calculation showed the fluence dependence of dissociation varies strongly with the gas pressure. Infrared multiphoton excitation was applied to study thermal unimolecular reactions. With SiF/sub 4/ as absorbing gas for the CO/sub 2/ laser pulse, transient high temperature pulses were generated in a gas mixture. IR fluorescence from the medium reflected the decay of the temperature. The activation energy and the preexponential factor of the reactant dissociation were obtained from a phenomenological model calculation. Results are presented in detail. (WHK)

  8. Nonlinear microwave photon occupancy of a driven resonator strongly coupled to a transmon qubit

    NASA Astrophysics Data System (ADS)

    Suri, B.; Keane, Z. K.; Bishop, Lev S.; Novikov, S.; Wellstood, F. C.; Palmer, B. S.

    2015-12-01

    We measure photon occupancy in a thin-film superconducting lumped element resonator coupled to a transmon qubit at 20 mK and find a nonlinear dependence on the applied microwave power. The transmon-resonator system was operated in the strong dispersive regime, where the ac Stark shift (2 χ ) due to a single microwave photon present in the resonator was larger than the linewidth (Γ ) of the qubit transition. When the resonator was coherently driven at 5.474 325 GHz, the transition spectrum of the transmon at 4.982 GHz revealed well-resolved peaks, each corresponding to an individual photon number-state of the resonator. From the relative peak heights we obtain the occupancy of the photon states and the average photon occupancy n ¯ of the resonator. We observe a nonlinear variation of n ¯ with the applied drive power Prf for n ¯<5 and compare our results to numerical simulations of the system-bath master equation in the steady state, as well as to a semiclassical model for the resonator that includes the Jaynes-Cummings interaction between the transmon and the resonator. We find good quantitative agreement using both models and analysis reveals that the nonlinear behavior is principally due to shifts in the resonant frequency caused by a qubit-induced Jaynes-Cummings nonlinearity.

  9. High-precision force sensing using a single trapped ion

    PubMed Central

    Ivanov, Peter A.; Vitanov, Nikolay V.; Singer, Kilian

    2016-01-01

    We introduce quantum sensing schemes for measuring very weak forces with a single trapped ion. They use the spin-motional coupling induced by the laser-ion interaction to transfer the relevant force information to the spin-degree of freedom. Therefore, the force estimation is carried out simply by observing the Ramsey-type oscillations of the ion spin states. Three quantum probes are considered, which are represented by systems obeying the Jaynes-Cummings, quantum Rabi (in 1D) and Jahn-Teller (in 2D) models. By using dynamical decoupling schemes in the Jaynes-Cummings and Jahn-Teller models, our force sensing protocols can be made robust to the spin dephasing caused by the thermal and magnetic field fluctuations. In the quantum-Rabi probe, the residual spin-phonon coupling vanishes, which makes this sensing protocol naturally robust to thermally-induced spin dephasing. We show that the proposed techniques can be used to sense the axial and transverse components of the force with a sensitivity beyond the range, i.e. in the (xennonewton, 10−27). The Jahn-Teller protocol, in particular, can be used to implement a two-channel vector spectrum analyzer for measuring ultra-low voltages. PMID:27306426

  10. Characterization of dermal structural assembly in normal and pathological connective tissues by intrinsic signal multiphoton optical microscopy

    NASA Astrophysics Data System (ADS)

    Lyubovitsky, Julia G.; Xu, Xiaoman; Sun, Chung-ho; Andersen, Bogi; Krasieva, Tatiana B.; Tromberg, Bruce J.

    2008-02-01

    Employing a reflectance multi-photon microscopy (MPM) technique, we developed novel method to quantitatively study the three-dimensional assembly of structural proteins within bulk of dermal ECMs. Using a structurally simplified model of skin with enzymatically dissected epidermis, we find that low resolution MPM clearly discriminates between normal and pathological dermis. High-resolution images revealed that the backscattered MPM signals are affected by the assembly of collagen fibrils and fibers within this system. Exposure of tissues to high concentrations of potentially denaturing chemicals also resulted in the reduction of SHG signals from structural proteins which coincided with the appearance of aggregated fluorescent structures.

  11. Three-dimensional multiphoton autofluorescence spectral imaging of live tissues

    NASA Astrophysics Data System (ADS)

    Palero, Jonathan A.; de Bruijn, Henriëtte S.; van der Ploeg van den Heuvel, Angélique; Sterenborg, Henricus J. C. M.; Gerritsen, Hans C.

    2006-04-01

    We combined a homebuilt multiphoton microscope and a prism-CCD based spectrograph to develop a spectral imaging system capable of imaging deep into live tissues. The spectral images originate from the two-photon autofluorescence of the tissue and second harmonic signal from the collagen fibers. A highly penetrating near-infrared light is used to excite the endogenous fluorophores via multiphoton excitation enabling us to produce high quality images deep into the tissue. We were able to produce 100-channel (330 nm to 600 nm) autofluorescence spectral images of live skin tissues in less than 2 minutes for each xy-section. The spectral images rendered in RGB (real) colors showed green hair shafts, blue cells, and purple collagen. Analysis on the optical signal degradation with increasing depth of the collagen second-harmonic signal showed 1) exponential decay behavior of the intensity and 2) linear broadening of the spectrum. This spectral imaging system is a promising tool for both in biological applications and biomedical applications such as optical biopsy.

  12. Superpenetration optical microscopy by iterative multiphoton adaptive compensation technique

    PubMed Central

    Tang, Jianyong; Germain, Ronald N.; Cui, Meng

    2012-01-01

    Biological tissues are rarely transparent, presenting major challenges for deep tissue optical microscopy. The achievable imaging depth is fundamentally limited by wavefront distortions caused by aberration and random scattering. Here, we report an iterative wavefront compensation technique that takes advantage of the nonlinearity of multiphoton signals to determine and compensate for these distortions and to focus light inside deep tissues. Different from conventional adaptive optics methods, this technique can rapidly measure highly complicated wavefront distortions encountered in deep tissue imaging and provide compensations for not only aberration but random scattering. The technique is tested with a variety of highly heterogeneous biological samples including mouse brain tissue, skull, and lymph nodes. We show that high quality three-dimensional imaging can be realized at depths beyond the reach of conventional multiphoton microscopy and adaptive optics methods, albeit over restricted distances for a given correction. Moreover, the required laser excitation power can be greatly reduced in deep tissues, deviating from the power requirement of ballistic light excitation and thus significantly reducing photo damage to the biological tissue. PMID:22586078

  13. Multiphoton imaging: a view to understanding sulfur mustard lesions

    NASA Astrophysics Data System (ADS)

    Werrlein, Robert J. S.; Madren-Whalley, Janna S.

    2003-07-01

    It is well known that topical exposure to sulfur mustard (SM) produces persistent, incapacitating blisters of the skin. However, the primary lesions effecting epidermal-dermal separation and disabling of mechanisms for cutaneous repair remain uncertain. Immunofluorescent staining plus multiphoton imaging of human epidermal tissues and keratinocytes exposed to SM (400 μM x 5 min)have revealed that SM disrupts adhesion-complex molecules which are also disrupted by epidermolysis bullosa-type blistering diseases of the skin. Images of keratin-14 showed early, progressive, postexposure collapse of the K5/K14 cytoskeleton that resulted in ventral displacement of the nuclei beneath its collapsing filaments. This effectively corrupted the dynamic filament assemblies that link basal-cell nuclei to the extracellular matrix via α6β4-integrin and laminin-5. At 1 h postexposure, there was disruption in the surface organization of α6β4 integrins, associated displacement of laminin-5 anchoring sites and a concomitant loss of functional asymmetry. Accordingly, our multiphoton images are providing compelling evidence that SM induces prevesicating lesions that disrupt the receptor-ligand organization and cytoskeletal systems required for maintaining dermal-epidermal attachment, signal transduction, and polarized mobility.

  14. Rigid and high NA multiphoton fluorescence GRIN-endoscopes

    NASA Astrophysics Data System (ADS)

    Schenkl, Selma; Ehlers, Alexander; Le Harzic, Ronan; Stark, Martin; Riemann, Iris; Messerschmidt, Bernhard; Kaatz, Martin; König, Karsten

    2007-07-01

    Multiphoton autofluorescence imaging offers minimal-invasive examination of cells without the need of staining and complicated confocal detection systems. Therefore, it is especially interesting for non-invasive clinical diagnostics. To extend this sophisticated technique from superficial regions to deep lying cell layers, internal body parts and specimens difficult of access, the bulky optics need to be reduced in diameter. This is done by tiny GRIN-optics, based on a radial gradient in the reflective index. Of especial interest for multi-photon applications is the newly developed GRIN-lens assembly with increased numerical aperture. High resolution images of plant tissue, hair and cells show the improved image quality,compared to classical GRIN-lenses. The rigid GRIN-endoscopes are already applied in wound healing studies. Here, the GRIN-lenses with diameters smaller than 3 mm enter small skin depressions. They reproduce the focus of a conventional laser scanning tomograph tens of mm apart in the specimen under study. We present first clinical measurements of elastin and SHG of collagen of in-vivo human skin of venous ulcers (ulcer curis).

  15. Resonant enhanced multiphoton ionization studies of atomic oxygen

    NASA Technical Reports Server (NTRS)

    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.

  16. Multibeam multifocal multiphoton photon counting imaging in scattering media

    NASA Astrophysics Data System (ADS)

    Hoover, Erich E.

    Multiphoton microscopy is an invaluable technique for the neurological community, allowing for deep explorations within highly scattering tissues such as the brain. However, prior to this research multiphoton microscopy was limited in its ability to rapidly construct volumetric images deep within scattering specimens. This work establishes a technique that permits such exploration through the application of multiple beams separated in both space and time, where signal photons corresponding to those beams are demultiplexed through the use of a field programmable gate array. With this system a number of improvements are provided to research in scattering media, including the coveted ability to perform photon-counting imaging with multiple beams. The ability to perform these measurements with multiple beams permits unique quantitative measurements of fluorophores within living specimens, allowing new research into dynamic three-dimensional behavior occurring within the brain. Additionally, the ability to perform multimodal measurements without filtering allows for unique avenues of research where the harmonic generation is indistinguishable from the two-photon excited fluorescence. These improvements provide neuroscience researchers with a large assortment of technological tools that will permit them to perform numerous novel experiments within the brain and other highly-scattering specimens, which should one day lead to significant advances in our understanding of complex neuronal activity.

  17. Bleed-through and photobleaching correction in multiphoton FRET microscopy

    NASA Astrophysics Data System (ADS)

    Elangovan, Masilamani; Periasamy, Ammasi

    2001-04-01

    Fluorescence resonance energy transfer (FRET) microscopy provides a tool to visualize the protein with high spatial and temporal resolution. In multi-photon FRET microscopy one experiences considerably less photobleaching compared to one-photon excitation since the illumination is the diffraction limited spot and the excitation is infrared-pulsed laser light. Because of the spectral overlap involved in the selection of the fluorophore pair for FRET imaging, the spectral bleed-through signal in the FRET channel is unavoidable. We describe in this paper the development of dedicated software to correct the bleed-through signal due to donor and acceptor fluorophore molecules. We used living cells expressed with BFP-RFP (DsRed)-C/EBP(alpha) proteins in the nucleus. We acquired images of different combinations like donor alone, acceptor alone, and both acceptor and donor under similar conditions. We statistically evaluated the percentage of bleed-through signal from one channel to the other based on the overlap areas of the spectra. We then reconstructed the images after applying the correction. Characterization of multi-photon FRET imaging system taking into account the intensity, dwell time, concentration of fluorophore pairs, objective lens and the excitation wavelength are described in this paper.

  18. Multi-photon photoelectron spectromicroscopy of supported polystyrene spheres

    NASA Astrophysics Data System (ADS)

    Lilienkamp, Gerhard; Lindla, Florian; Senft, Christoph; Daum, Winfried

    2008-08-01

    Multi-photon photoemission excited by 100 fs, 400 nm laser pulses leads to an unexpected high contrast in photoelectron images of polystyrene spheres on a platinum substrate. The total, energy-integrated photoelectron yield shows clear signatures of two-photon photoemission from the substrate while photoemission from polystyrene is dominated by one-photon processes for low laser power and multi-photon processes for higher laser power. For excitation with UV light from a conventional Hg arc lamp, we observe a marked energy shift of the photoelectron spectrum of polystyrene with respect to that of the substrate. This shift is related to the different surface potentials of the conductive substrate and the dielectric spheres in the strong electric field of the objective lens of the microscope. Laser illumination causes photoconductivity in polystyrene by efficient two-photon excitation of long-lived states and induces a shifting of the surface potential of the polystyrene spheres. Pump-probe experiments support our conclusion that photoemission from polystyrene takes place from these long-lived intermediate states via a one-photon process for sufficiently low laser power. We suggest that photoelectron spectromicroscopy might be useful as a non-scanning method for fast height profiling of supported dielectric structures.

  19. The effect of radial polarization in multiphoton lithography

    NASA Astrophysics Data System (ADS)

    Lin, Le; Zheng, Mei-Ling; Dong, Xian-Zi; Duan, Xuan-Ming; Zhao, Zhen-Sheng

    2015-10-01

    Considering the axially symmetric polarization and intensity distribution, radially polarized (RP) laser beam has comparatively higher axial component of electric field and smaller size of focal spot compared to linearly polarized (LP) laser. In this study, the effect of radial polarization on multiphoton fabrication has been studied, and polymer spots and lines are chosen as the study objects of 2D micro/nano structures of multiphoton lithography. These structures were fabricated with IP-L, a commercial negative photoresist, by RP fs-pulse laser beam which was tightly focused by an objective lens with high numerical aperture. Multiple experimental conditions, such as fabrication power, exposure time and scanning velocity, were verified in order to observe the structural variation of these polymer structures. On the basis of measurement from images of the scanning electron microscope, the transverse and longitudinal sizes of polymer spots and lines could be analyzed, and the relationship between the aspect ratio (AR) and the above experimental conditions could be acquired. The statistical results agree with our predictions that the RP laser beam can significantly reduce the AR, and the AR in RP laser fabrication has little correlation with conditions besides fabrication power, such as exposure time and scanning velocity.

  20. In vivo multiphoton endoscopy of endogenous skin fluorophores

    NASA Astrophysics Data System (ADS)

    Ehlers, Alexander; Schenkl, Selma; Riemann, Iris; Messerschmidt, Bernhard; Kaatz, Martin; Bückle, Rainer; König, Karsten

    2007-02-01

    Multiphoton tomography offers a painless method to examine patients under natural physiological conditions in vivo. Multiphoton excitation induces a weak autofluorescence of naturally endogenous fluorescent bio-molecules, such as flavines, NAD(P)H, metal-free porphyrines, components of lipofuscin, elastin and keratin. Additionally, collagen can be detected by second harmonic generation (SHG). Due to the nonlinearity, the effects occur only in a very tight focus, where the photon density is high enough. This leads to high axial and lateral resolution of <1μm without any need of a confocal detection and avoids out-of-focus damage. The limited depth range, given by the working distance of the focusing optics, is overcome with a gradient index-lens (GRIN-lens) based endoscope. In this work we present the first results of clinical applications in vivo of gradient-index lens endoscopes. Images of e.g. elastin and collagen (SHG) in the dermal layer of human skin are presented.

  1. In vivo multiphoton imaging of the eyelid skin

    NASA Astrophysics Data System (ADS)

    Batista, Ana; Breunig, Hans Georg; Uchugonova, Aisada; König, Karsten

    2017-02-01

    Multiphoton tomography (MPT) has become an important imaging method for non-invasive and high-resolution imaging of the skin in vivo. Due to the nonlinear excitation, by using near-infrared (NIR) light, 3D information is intrinsically provided. In combination with fluorescence lifetime imaging (FLIM), it is possible to obtain both structural and metabolic data. Human in vivo measurements are usually limited to easily accessible regions. However, often imaging of specific body parts such as the eyelid are of interest for cosmetic reasons. By using the clinically certified multiphoton imaging tomograph MPTflex this demand can be fulfilled. An articulated mirror arm and scan-detector head enable imaging at otherwise difficult-to-access areas. We show the characterization of the epidermal and upper dermal layers of the eyelid skin of human volunteers in vivo based on endogenous autofluorescence intensity, lifetime, and second-harmonic generation signals. Skin properties such as the epidermal thickness were also assessed. Furthermore, the influence of an anti-aging cream on the eyelid and forearm skin was investigated. Changes of the skin epidermis autofluorescence lifetime were observed after two-weeks long application of an anti-aging cream. The SHG-to-AF aging index of dermis (SAAID) increased during that time.

  2. Photoelectron circular dichroism in the multiphoton ionization by short laser pulses. I. Propagation of single-active-electron wave packets in chiral pseudo-potentials

    SciTech Connect

    Artemyev, Anton N.; Müller, Anne D.; Demekhin, Philipp V.; Hochstuhl, David

    2015-06-28

    A theoretical method to study the angle-resolved multiphoton ionization of polyatomic molecules is developed. It is based on the time-dependent formulation of the Single Center (TDSC) method and consists in the propagation of single-active-electron wave packets in the effective molecular potentials in the presence of intense laser pulses. For this purpose, the time-dependent Schrödinger equation for one electron, moving in a molecular field and interacting with an arbitrary laser pulse, is solved in spherical coordinates by an efficient numerical approach. As a test, the method is applied to the one- and two-photon ionizations of a model methane-like chiral system by circularly polarized short intense high-frequency laser pulses. Thereby, we analyze the photoelectron circular dichroism (PECD) in the momentum distribution. The considered model application illustrates the capability of the TDSC method to study multiphoton PECD in fixed-in-space and randomly oriented chiral molecules.

  3. Photoelectron circular dichroism in the multiphoton ionization by short laser pulses. I. Propagation of single-active-electron wave packets in chiral pseudo-potentials

    NASA Astrophysics Data System (ADS)

    Artemyev, Anton N.; Müller, Anne D.; Hochstuhl, David; Demekhin, Philipp V.

    2015-06-01

    A theoretical method to study the angle-resolved multiphoton ionization of polyatomic molecules is developed. It is based on the time-dependent formulation of the Single Center (TDSC) method and consists in the propagation of single-active-electron wave packets in the effective molecular potentials in the presence of intense laser pulses. For this purpose, the time-dependent Schrödinger equation for one electron, moving in a molecular field and interacting with an arbitrary laser pulse, is solved in spherical coordinates by an efficient numerical approach. As a test, the method is applied to the one- and two-photon ionizations of a model methane-like chiral system by circularly polarized short intense high-frequency laser pulses. Thereby, we analyze the photoelectron circular dichroism (PECD) in the momentum distribution. The considered model application illustrates the capability of the TDSC method to study multiphoton PECD in fixed-in-space and randomly oriented chiral molecules.

  4. Feasible quantum engineering of quantum multiphoton superpositions

    NASA Astrophysics Data System (ADS)

    Stobińska, Magdalena

    2015-02-01

    We examine an experimental setup implementing a family of quantum non-Gaussian filters. The filters can be applied to an arbitrary two-mode input state. We assume realistic photodetection in the filtering process and explore two different models of inefficient detections: a beam splitter of a small reflectivity located in front of a perfect detector and a Weierstrass transform applied to the unperturbed measurement outcomes. We explicitly give an operator which describes the coherent action of the filters in the realistic experimental conditions. The filtered states may find applications in quantum metrology, quantum communication and other quantum tasks.

  5. Water-Soluble Quantum Dots for Multiphoton Fluorescence Imaging in Vivo

    NASA Astrophysics Data System (ADS)

    Larson, Daniel R.; Zipfel, Warren R.; Williams, Rebecca M.; Clark, Stephen W.; Bruchez, Marcel P.; Wise, Frank W.; Webb, Watt W.

    2003-05-01

    The use of semiconductor nanocrystals (quantum dots) as fluorescent labels for multiphoton microscopy enables multicolor imaging in demanding biological environments such as living tissue. We characterized water-soluble cadmium selenide-zinc sulfide quantum dots for multiphoton imaging in live animals. These fluorescent probes have two-photon action cross sections as high as 47,000 Goeppert-Mayer units, by far the largest of any label used in multiphoton microscopy. We visualized quantum dots dynamically through the skin of living mice, in capillaries hundreds of micrometers deep. We found no evidence of blinking (fluorescence intermittency) in solution on nanosecond to millisecond time scales.

  6. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo.

    PubMed

    Larson, Daniel R; Zipfel, Warren R; Williams, Rebecca M; Clark, Stephen W; Bruchez, Marcel P; Wise, Frank W; Webb, Watt W

    2003-05-30

    The use of semiconductor nanocrystals (quantum dots) as fluorescent labels for multiphoton microscopy enables multicolor imaging in demanding biological environments such as living tissue. We characterized water-soluble cadmium selenide-zinc sulfide quantum dots for multiphoton imaging in live animals. These fluorescent probes have two-photon action cross sections as high as 47,000 Goeppert-Mayer units, by far the largest of any label used in multiphoton microscopy. We visualized quantum dots dynamically through the skin of living mice, in capillaries hundreds of micrometers deep. We found no evidence of blinking (fluorescence intermittency) in solution on nanosecond to millisecond time scales.

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

    SciTech Connect

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2015-12-01

    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 possible.

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

    NASA Astrophysics Data System (ADS)

    Chia, Thomas H.

    Multiphoton microscopy is a laser-scanning fluorescence imaging method with extraordinary potential. We describe three innovative multiphoton microscopy techniques across various disciplines. Traditional in vivo fluorescence microscopy of the mammalian brain has a limited penetration depth (<400 microm). We present a method of imaging 1 mm deep into mouse neocortex by using a glass microprism to relay the excitation and emission light. This technique enables simultaneous imaging of multiple cortical layers, including layer V, at an angle typical of slice preparations. At high-magnification imaging using an objective with 1-mm of coverglass correction, resolution was sufficient to resolve dendritic spines on layer V GFP neurons. Functional imaging of blood flow at various neocortical depths is also presented, allowing for quantification of red blood cell flux and velocity. Multiphoton fluorescence lifetime imaging (FLIM) of NADH reveals information on neurometabolism. NADH, an intrinsic fluorescent molecule and ubiquitous metabolic coenzyme, has a lifetime dependent on enzymatic binding. A novel NADH FLIM algorithm is presented that produces images showing spatially distinct NADH fluorescence lifetimes in mammalian brain slices. This program provides advantages over traditional FLIM processing of multi-component lifetime data. We applied this technique to a GFP-GFAP pilocarpine mouse model of temporal lobe epilepsy. Results indicated significant changes in the neurometabolism of astrocytes and neuropil in the cell and dendritic layers of the hippocampus when compared to control tissue. Data obtained with NADH FLIM were subsequently interpreted based on the abnormal activity reported in epileptic tissue. Genuine U.S. Federal Reserve Notes have a consistent, two-component intrinsic fluorescence lifetime. This allows for detection of counterfeit paper money because of its significant differences in fluorescence lifetime when compared to genuine paper money. We used

  11. Design and commissioning of a directly coupled in-vivo multiphoton microscope for skin imaging in humans and large animals

    NASA Astrophysics Data System (ADS)

    Mulholland, William J.; Kendall, Mark A.

    2004-02-01

    The application of near infrared multiphoton excitation to the laser-scanning microscope was first conceived by Denk, Strickler and Webb in 1990. Since then, advances in design have seen the multiphoton laser scanning microscope (MPLSM) applied to a wide range of biological research areas, including skin imaging and vaccine delivery. The technique has the attributes of low phototoxicity, high-resolution functional imaging to depths in scattered tissues. These characteristics have encouraged engineers and scientists to develop in-vivo imaging systems. For these applications, laser excitation pulses can be delivered to the sample through optical fibers. Although this solution provides a number of advantages relating to movement and flexibility of the site of interest relative to the laser source, the peak powers that can be delivered down the fiber are limited. We report on the design and commissioning of a directly coupled in-vivo MPM system, optimised for the imaging of epidermal vaccines delivered to a range of biological models and humans. Specifically, we seek to apply the system to visualise in-vivo, the influence of hand-held, helium powered needle-free systems on skin cells. A standard Nikon E600FN microscope, dissected above the optical plane was cantilevered from a vibration isolated table using rigid support arms. The modified microscope was coupled to an infrared optimised Bio-Rad Radiance 2100MP, multiphoton dedicated laser scanning control and image acquisition system. Femtosecond laser pulses were provided by a 10W Verdi pumped Mira Ti:Sapphire laser, from Coherent Inc. The microscope was modified such that the transmission half may be selectively attached for conventional imaging with ex-vivo and cell culture samples, or removed for in-vivo imaging of skin sites on the body of humans and large animals. Optical performance of the system, and aspects of its design and commissioning are discussed in this paper.

  12. Advanced multiphoton methods for in vitro and in vivo functional imaging of mouse retinal neurons (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Cohen, Noam; Schejter, Adi; Farah, Nairouz; Shoham, Shy

    2016-03-01

    Studying the responses of retinal ganglion cell (RGC) populations has major significance in vision research. Multiphoton imaging of optogenetic probes has recently become the leading approach for visualizing neural populations and has specific advantages for imaging retinal activity during visual stimulation, because it leads to reduced direct photoreceptor excitation. However, multiphoton retinal activity imaging is not straightforward: point-by-point scanning leads to repeated neural excitation while optical access through the rodent eye in vivo has proven highly challenging. Here, we present two enabling optical designs for multiphoton imaging of responses to visual stimuli in mouse retinas expressing calcium indicators. First, we present an imaging solution based on Scanning Line Temporal Focusing (SLITE) for rapidly imaging neuronal activity in vitro. In this design, we scan a temporally focused line rather than a point, increasing the scan speed and reducing the impact of repeated excitation, while maintaining high optical sectioning. Second, we present the first in vivo demonstration of two-photon imaging of RGC activity in the mouse retina. To obtain these cellular resolution recordings we integrated an illumination path into a correction-free imaging system designed using an optical model of the mouse eye. This system can image at multiple depths using an electronically tunable lens integrated into its optical path. The new optical designs presented here overcome a number of outstanding obstacles, allowing the study of rapid calcium- and potentially even voltage-indicator signals both in vitro and in vivo, thereby bringing us a step closer toward distributed monitoring of action potentials.

  13. Molecular photoelectron angular distribution rotations in multi-photon resonant ionization of H{sub 2}{sup +} by circularly polarized ultraviolet laser pulses

    SciTech Connect

    Yuan, Kai-Jun Chelkowski, Szczepan; Bandrauk, André D.

    2015-04-14

    We study effects of pulse durations on molecular photoelectron angular distributions (MPADs) in ultrafast circular polarization ultraviolet resonant ionization processes. Simulations performed on aligned H{sub 2}{sup +} by numerically solving time dependent Schrödinger equations show rotations of MPADs with respect to the molecular symmetry axes. It is found that in multi-photon resonant ionization processes, rotation angles are sensitive to pulse durations, which we attribute to the coherent resonant excitation between the ground state and the intermediate excited electronic state induced by Rabi oscillations. Multi-photon nonresonant and single photon ionization processes are simulated and compared which exhibit a constant rotation angle. An asymmetry parameter is introduced to describe the pulse duration sensitivity by perturbation theory models. Influence of pulse frequency detunings on MPADs is also investigated where oscillations of rotations are absent at long pulse durations due to nonresonance excitation.

  14. Multiphoton fluorescence recovery after photobleaching: Advancements for novel in vivo applications

    NASA Astrophysics Data System (ADS)

    Sullivan, Kelley Diane

    Multiphoton fluorescence recovery after photobleaching (MP-FRAP) is a laser microscopy technique used to probe the transport properties of macromolecules in biological systems. MP-FRAP utilizes two-photon fluorescence and photobleaching to produce a three-dimensionally resolved diffusion coefficient for an ensemble of molecules in the region of the two-photon focal volume. This thesis describes two fundamental improvements to the MP-FRAP technique, which are vital steps to enable MP-FRAP to be applied to the complex in vivo environment. In Chapter 1, we lay the groundwork for our discussion of these advancements by introducing the MP-FRAP technique and the physics upon which it is based. We begin with a description of fluorescence and diffusion and discuss their importance in biomedical research. Next, we describe how two-photon fluorescence and photobleaching are applied to a diffusing system to measure the diffusion coefficient via fluorescence recovery after photobleaching (FRAP). Then, we take the reader through the evolution of FRAP, which leads to the application of two- photon fluorescence and photobleaching to produce MP-FRAP. Along the way, we highlight applications and advancements of the FRAP techniques, and introduce fluorescence correlation spectroscopy, a popular complement to FRAP. In Chapter 2, we collect the experimental methods for the studies presented in Chapters 3 and 4. We begin with an in-depth discussion of our work to build and troubleshoot our MP-FRAP apparatus, followed by a detailed description of our data analysis protocol. Next, we delve into the specific methods for producing computer generated data and fits, as well as in vitro and in vivo experimental data, for our work in Chap. 3 on improving MP-FRAP to measure diffusion in the presence of convective flow. We end with a description of the Monte Carlo algorithm we developed for our work in Chap. 4 to model diffusion and multiphoton fluorescence recovery after photobleaching in the

  15. Resonance Enhanced Multi-photon Spectroscopy of DNA

    NASA Astrophysics Data System (ADS)

    Ligare, Marshall Robert

    For over 50 years DNA has been studied to better understand its connection to life and evolution. These past experiments have led to our understanding of its structure and function in the biological environment but the interaction of DNA with UV radiation at the molecular level is still not very well understood. Unique mechanisms in nucleobase chromaphores protect us from adverse chemical reactions after UV absorption. Studying these processes can help develop theories for prebiotic chemistry and the possibility of alternative forms of DNA. Using resonance enhanced multi-photon spectroscopic techniques in the gas phase allow for the structure and dynamics of individual nucleobases to be studied in detail. Experiments studying different levels of structure/complexity with relation to their biological function are presented. Resonant IR multiphoton dissociation spectroscopy in conjunction with molecular mechanics and DFT calculations are used to determine gas phase structures of anionic nucleotide clusters. A comparison of the identified structures with known biological function shows how the hydrogen bonding of the nucleotides and their clusters free of solvent create favorable structures for quick incorporation into enzymes such as DNA polymerase. Resonance enhanced multi-photon ionization (REMPI) spectroscopy techniques such as resonant two photon ionization (R2PI) and IR-UV double resonance are used to further elucidate the structure and excited state dynamics of the bare nucleobases thymine and uracil. Both exhibit long lived excited electronic states that have been implicated in DNA photolesions which can ultimately lead to melanoma and carcinoma. Our experimental data in comparison with many quantum chemical calculations suggest a new picture for the dynamics of thymine and uracil in the gas phase. A high probability of UV absorption from a vibrationally hot ground state to the excited electronic state shows that the stability of thymine and uracil comes from

  16. High-throughput multiphoton-induced three-dimensional ablation and imaging for biotissues

    PubMed Central

    Lin, Chun-Yu; Li, Pei-Kao; Cheng, Li-Chung; Li, Yi-Cheng; Chang, Chia-Yuan; Chiang, Ann-Shyn; Dong, Chen Yuan; Chen, Shean-Jen

    2015-01-01

    In this study, a temporal focusing-based high-throughput multiphoton-induced ablation system with axially-resolved widefield multiphoton excitation has been successfully applied to rapidly disrupt biotissues. Experimental results demonstrate that this technique features high efficiency for achieving large-area laser ablation without causing serious photothermal damage in non-ablated regions. Furthermore, the rate of tissue processing can reach around 1.6 × 106 μm3/s in chicken tendon. Moreover, the temporal focusing-based multiphoton system can be efficiently utilized in optical imaging through iterating high-throughput multiphoton-induced ablation machining followed by widefield optical sectioning; hence, it has the potential to obtain molecular images for a whole bio-specimen. PMID:25780739

  17. Multiphoton Processes: ICOMP VIII: 8th International Conference, AIP Conference Proceedings, No. 525 [APCPCS

    SciTech Connect

    DiMauro, L.F.; Freeman, R.R.; Kulander, K.C.

    2000-12-31

    Topics include: atoms in strong fields; stabilization; double ionization and multi-electron calculations; high-order harmonics; molecules in strong fields; multiphoton processes in clusters; coherent control; light sources; and relativistic effects.

  18. Invited review article: Imaging techniques for harmonic and multiphoton absorption fluorescence microscopy.

    PubMed

    Carriles, Ramón; Schafer, Dawn N; Sheetz, Kraig E; Field, Jeffrey J; Cisek, Richard; Barzda, Virginijus; Sylvester, Anne W; Squier, Jeffrey A

    2009-08-01

    We review the current state of multiphoton microscopy. In particular, the requirements and limitations associated with high-speed multiphoton imaging are considered. A description of the different scanning technologies such as line scan, multifoci approaches, multidepth microscopy, and novel detection techniques is given. The main nonlinear optical contrast mechanisms employed in microscopy are reviewed, namely, multiphoton excitation fluorescence, second harmonic generation, and third harmonic generation. Techniques for optimizing these nonlinear mechanisms through a careful measurement of the spatial and temporal characteristics of the focal volume are discussed, and a brief summary of photobleaching effects is provided. Finally, we consider three new applications of multiphoton microscopy: nonlinear imaging in microfluidics as applied to chemical analysis and the use of two-photon absorption and self-phase modulation as contrast mechanisms applied to imaging problems in the medical sciences.

  19. Invited Review Article: Imaging techniques for harmonic and multiphoton absorption fluorescence microscopy

    PubMed Central

    Carriles, Ramón; Schafer, Dawn N.; Sheetz, Kraig E.; Field, Jeffrey J.; Cisek, Richard; Barzda, Virginijus; Sylvester, Anne W.; Squier, Jeffrey A.

    2009-01-01

    We review the current state of multiphoton microscopy. In particular, the requirements and limitations associated with high-speed multiphoton imaging are considered. A description of the different scanning technologies such as line scan, multifoci approaches, multidepth microscopy, and novel detection techniques is given. The main nonlinear optical contrast mechanisms employed in microscopy are reviewed, namely, multiphoton excitation fluorescence, second harmonic generation, and third harmonic generation. Techniques for optimizing these nonlinear mechanisms through a careful measurement of the spatial and temporal characteristics of the focal volume are discussed, and a brief summary of photobleaching effects is provided. Finally, we consider three new applications of multiphoton microscopy: nonlinear imaging in microfluidics as applied to chemical analysis and the use of two-photon absorption and self-phase modulation as contrast mechanisms applied to imaging problems in the medical sciences. PMID:19725639

  20. High-throughput multiphoton-induced three-dimensional ablation and imaging for biotissues.

    PubMed

    Lin, Chun-Yu; Li, Pei-Kao; Cheng, Li-Chung; Li, Yi-Cheng; Chang, Chia-Yuan; Chiang, Ann-Shyn; Dong, Chen Yuan; Chen, Shean-Jen

    2015-02-01

    In this study, a temporal focusing-based high-throughput multiphoton-induced ablation system with axially-resolved widefield multiphoton excitation has been successfully applied to rapidly disrupt biotissues. Experimental results demonstrate that this technique features high efficiency for achieving large-area laser ablation without causing serious photothermal damage in non-ablated regions. Furthermore, the rate of tissue processing can reach around 1.6 × 10(6) μm(3)/s in chicken tendon. Moreover, the temporal focusing-based multiphoton system can be efficiently utilized in optical imaging through iterating high-throughput multiphoton-induced ablation machining followed by widefield optical sectioning; hence, it has the potential to obtain molecular images for a whole bio-specimen.

  1. Multiphoton FLIM: a reliable FRET detection tool in cell biological applications

    NASA Astrophysics Data System (ADS)

    Krishnan, Ramanujan V.; Biener, Eva; Centonze, Victoria E.; Gertler, Arieh; Herman, Brian A.

    2004-06-01

    Fluorescence lifetime imaging microscopy (FLIM) using multiphoton excitation is emerging as a reliable quantitative tool for measuring fluorescence resonance energy transfer (FRET) in living cells. By virtue of being free from spectroscopic artifacts encountered in conventional FRET detection methods, multiphoton FLIM methods offer the advantages of high spatial and temporal resolution, faster data acquisition and data analysis. We compare the FRET results obtained by two different methods namely (i) multiphoton excitation lifetime-based FRET and (ii) single photon excitation intensity-based acceptor photobleaching FRET. Using the same biological samples, we apply these two different methods in understanding the growth hormone receptor dimerization kinetics at the cell surface of human embryonic kidney cells. We conclude that the multiphoton FLIM using the streak-camera approach provides the best ability to monitor FRET in dynamic situations where high temporal and spatial resolution are required with minimal photodamage/phototoxicity.

  2. Live-Animal Imaging of Renal Function by Multiphoton Microscopy

    PubMed Central

    Dunn, Kenneth W.; Sutton, Timothy A.; Sandoval, Ruben M.

    2015-01-01

    Intravital microscopy, microscopy of living animals, is a powerful research technique that combines the resolution and sensitivity found in microscopic studies of cultured cells with the relevance and systemic influences of cells in the context of the intact animal. The power of intravital microscopy has recently been extended with the development of multiphoton fluorescence microscopy systems capable of collecting optical sections from deep within the kidney at subcellular resolution, supporting high-resolution characterizations of the structure and function of glomeruli, tubules, and vasculature in the living kidney. Fluorescent probes are administered to an anesthetized, surgically prepared animal, followed by image acquisition for up to 3 hr. Images are transferred via a high-speed network to specialized computer systems for digital image analysis. This general approach can be used with different combinations of fluorescent probes to evaluate processes such as glomerular permeability, proximal tubule endocytosis, microvascular flow, vascular permeability, mitochondrial function, and cellular apoptosis/necrosis. PMID:23042524

  3. Multiphoton autofluorescence lifetime imaging of induced pluripotent stem cells

    NASA Astrophysics Data System (ADS)

    Uchugonova, Aisada

    2017-06-01

    The multiphoton fluorescence lifetime imaging tomograph MPTflex with its flexible 360-deg scan head, articulated arm, and tunable femtosecond laser source was employed to study induced pluripotent stem cell (iPS) cultures. Autofluorescence (AF) lifetime imaging was performed with 250-ps temporal resolution and submicron spatial resolution using time-correlated single-photon counting. The two-photon excited AF was based on the metabolic coenzymes NAD(P)H and flavin adenine dinucleotide/flavoproteins. iPS cells generated from mouse embryonic fibroblasts (MEFs) and cocultured with growth-arrested MEFs as feeder cells have been studied. Significant differences on AF lifetime signatures were identified between iPS and feeder cells as well as between their differentiating counterparts.

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

    PubMed

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

    2014-06-05

    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.

  5. Reassignment of Scattered Emission Photons in Multifocal Multiphoton Microscopy

    PubMed Central

    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

  6. Resonance Enhanced Multiphoton Ionization (rempi) Spectroscopy of Weakly Bound Complexes

    NASA Astrophysics Data System (ADS)

    Muzangwa, Lloyd; Nyambo, Silver; Uhler, Brandon; Reid, Scott A.

    2012-06-01

    We have recently implemented Resonance Enhanced Multiphoton Ionization (REMPI) spectroscopy in our laboratory as a spectroscopic probe of transient species. We will report on initial gas-phase studies of the spectra of weakly bound van der Waals and halogen bonded complexes involving aromatic organic donors. The complexes are formed in the rarified environment of a supersonic molecular beam, which is skimmed prior to passing into the differentially pumped flight tube of a linear time-of-flight mass spectrometer. Ionization is initiated both by 1+1 and 1+1' REMPI schemes; the latter is used to minimize fragmentation. Our initial studies have examined van der Waals and halogen bonded complexes involving the phenol and toluene chromophores. Progress in the coupling of a discharge source into this apparatus will also be discussed.

  7. Multi-Photon Absorption in Metal-Organic Frameworks.

    PubMed

    Medishetty, Raghavender; Nemec, Lydia; Nalla, Venkatram; Henke, Sebastian; Samoc, Marek; Reuter, Karsten; Fischer, Roland A

    2017-09-12

    Multi-photon absorption (MPA) is among the most prominent nonlinear optical (NLO) effects and has applications, for example in telecommunications, defense, photonics and bio-medicines. Established MPA materials include dyes, quantum dots, organometallics and conjugated polymers, most often dispersed in solution. We demonstrate how metal-organic frameworks (MOFs), a novel NLO solid-state materials class, can be designed for exceptionally strong MPA behavior. MOFs consisting of zirconium- and hafnium-oxo-clusters and featuring a chromophore linker based on the tetraphenylethene (TPE) molecule exhibit record high two-photon absorption (2PA) cross section values, up to 3600 GM. The unique modular building-block principle of MOFs allows enhancing and optimizing their MPA properties in a theory guided approach by combining tailored charge polarization, conformational strain, three-dimensional arrangement and alignment of the chromophore linkers in the crystal. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Performance evaluation of a sensorless adaptive optics multiphoton microscope.

    PubMed

    Skorsetz, Martin; Artal, Pablo; Bueno, Juan M

    2016-03-01

    A wavefront sensorless adaptive optics technique was combined with a custom-made multiphoton microscope to correct for specimen-induced aberrations. A liquid-crystal-on-silicon (LCoS) modulator was used to systematically generate Zernike modes during image recording. The performance of the instrument was evaluated in samples providing different nonlinear signals and the benefit of correcting higher order aberrations was always noticeable (in both contrast and resolution). The optimum aberration pattern was stable in time for the samples here involved. For a particular depth location within the sample, the wavefront to be precompensated was independent on the size of the imaged area (up to ∼ 360 × 360 μm(2)). The mode combination optimizing the recorded image depended on the Zernike correction control sequence; however, the final images hardly differed. At deeper locations, a noticeable dominance of spherical aberration was found. The influence of other aberration terms was also compared to the effect of the spherical aberration.

  9. Molecule-specific darkfield and multiphoton imaging using gold nanocages

    NASA Astrophysics Data System (ADS)

    Powless, Amy J.; Jenkins, Samir V.; McKay, Mary Lee; Chen, Jingyi; Muldoon, Timothy J.

    2015-03-01

    Due to their robust optical properties, biological inertness, and readily adjustable surface chemistry, gold nanostructures have been demonstrated as contrast agents in a variety of biomedical imaging applications. One application is dynamic imaging of live cells using bioconjugated gold nanoparticles to monitor molecule trafficking mechanisms within cells; for instance, the regulatory pathway of epidermal growth factor receptor (EGFR) undergoing endocytosis. In this paper, we have demonstrated a method to track endocytosis of EGFR in MDA-MB-468 breast adenocarcinoma cells using bioconjugated gold nanocages (AuNCs) and multiphoton microscopy. Dynamic imaging was performed using a time series capture of 4 images every minute for one hour. Specific binding and internalization of the bioconjugated AuNCs was observed while the two control groups showed non-specific binding at fewer surface sites, leading to fewer bound AuNCs and no internalization.

  10. Multimodal optoacoustic and multiphoton microscopy of human carotid atheroma.

    PubMed

    Seeger, Markus; Karlas, Angelos; Soliman, Dominik; Pelisek, Jaroslav; Ntziachristos, Vasilis

    2016-09-01

    Carotid artery atherosclerosis is a main cause of stroke. Understanding atherosclerosis biology is critical in the development of targeted prevention and treatment strategies. Consequently, there is demand for advanced tools investigating atheroma pathology. We consider hybrid optoacoustic and multiphoton microscopy for the integrated and complementary interrogation of plaque tissue constituents and their mutual interactions. Herein, we visualize human carotid plaque using a hybrid multimodal imaging system that combines optical resolution optoacoustic (photoacoustic) microscopy, second and third harmonic generation microscopy, and two-photon excitation fluorescence microscopy. Our data suggest more comprehensive insights in the pathophysiology of atheroma formation and destabilization, by enabling congruent visualization of structural and biological features critical for the atherosclerotic process and its acute complications, such as red blood cells and collagen.

  11. Clinical multiphoton tomography and clinical two-photon microendoscopy

    NASA Astrophysics Data System (ADS)

    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.

  12. In vivo multiphoton tomography in skin aging studies

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

    High-resolution clinical multiphoton tomography based on the femtosecond laser system DermaInspect has been performed on hundreds of patients and volunteers in Australia, Asia, and Europe. The system enables the in vivo detection of the elastin and the collagen network as well as the imaging of melanin clusters in aging spots. The epidermis-dermis junction can be detected with submicron resolution. One major applications of this novel HighTech imaging tool is the determination of the skin aging index SAAID as well as the study of the effects of anti-aging products. In particular, the stimulated biosynthesis of collagen can be investigated over long periods of time. The system with its sub-500 nm lateral resolution is able to image age-related modifications of the extracellular matrix on the level of a single elastin fiber.

  13. Monitoring wound healing by multiphoton tomography/endoscopy

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2011-01-01

    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, despite their very similar spectral profiles, can be differentiated by lifetime analysis. Specifically, the carious dental tissue exhibits a greatly reduced autofluorescence lifetime, which result is consistent with the degree of demineralization, determined by micro-computed tomography. Our findings suggest that two-photon excited fluorescence lifetime imaging may be a promising tool for diagnosing and monitoring dental caries. PMID:21326645

  15. Wavefront sensorless adaptive optics temporal focusing-based multiphoton microscopy

    PubMed Central

    Chang, Chia-Yuan; Cheng, Li-Chung; Su, Hung-Wei; Hu, Yvonne Yuling; Cho, Keng-Chi; Yen, Wei-Chung; Xu, Chris; Dong, Chen Yuan; Chen, Shean-Jen

    2014-01-01

    Temporal profile distortions reduce excitation efficiency and image quality in temporal focusing-based multiphoton microscopy. In order to compensate the distortions, a wavefront sensorless adaptive optics system (AOS) was integrated into the microscope. The feedback control signal of the AOS was acquired from local image intensity maximization via a hill-climbing algorithm. The control signal was then utilized to drive a deformable mirror in such a way as to eliminate the distortions. With the AOS correction, not only is the axial excitation symmetrically refocused, but the axial resolution with full two-photon excited fluorescence (TPEF) intensity is also maintained. Hence, the contrast of the TPEF image of a R6G-doped PMMA thin film is enhanced along with a 3.7-fold increase in intensity. Furthermore, the TPEF image quality of 1μm fluorescent beads sealed in agarose gel at different depths is improved. PMID:24940539

  16. Wavefront sensorless adaptive optics temporal focusing-based multiphoton microscopy.

    PubMed

    Chang, Chia-Yuan; Cheng, Li-Chung; Su, Hung-Wei; Hu, Yvonne Yuling; Cho, Keng-Chi; Yen, Wei-Chung; Xu, Chris; Dong, Chen Yuan; Chen, Shean-Jen

    2014-06-01

    Temporal profile distortions reduce excitation efficiency and image quality in temporal focusing-based multiphoton microscopy. In order to compensate the distortions, a wavefront sensorless adaptive optics system (AOS) was integrated into the microscope. The feedback control signal of the AOS was acquired from local image intensity maximization via a hill-climbing algorithm. The control signal was then utilized to drive a deformable mirror in such a way as to eliminate the distortions. With the AOS correction, not only is the axial excitation symmetrically refocused, but the axial resolution with full two-photon excited fluorescence (TPEF) intensity is also maintained. Hence, the contrast of the TPEF image of a R6G-doped PMMA thin film is enhanced along with a 3.7-fold increase in intensity. Furthermore, the TPEF image quality of 1μm fluorescent beads sealed in agarose gel at different depths is improved.

  17. Multiphoton Rabi oscillations between highly excited Stark states of potassium

    SciTech Connect

    He Yonglin

    2011-11-15

    We have applied a nonperturbative resonant theory to study the Rabi frequency of microwave multiphoton transitions between two Rydberg states of potassium in a static electric field. The Stark electric dipole moments used to calculate the Rabi frequency are determined by the Stark states' wave functions, which are obtained by the diagonalization method. The frequencies of the Rabi oscillations are in good agreement with either experimental ones or ones calculated by the time-dependent close-coupling method and the Floquet theory. Furthermore, we are able to show that the size of avoided crossings between the (n+2)s and (n,3) states can be predicted from the Stark electric dipole moment and the difference of the two Stark states' energy at a given resonance.

  18. Suppression of multiphoton intrashell resonances in Li Rydberg atoms

    SciTech Connect

    Waheed, A.; Fregenal, D.; Frette, O.; Foerre, M.; Hjertaker, B. T.; Preclikova, J.; Horsdal, E.; Pilskog, I.

    2011-06-15

    Multiphoton intrashell transitions in strongly driven Li (n=25) Rydberg atoms are studied experimentally. Orthogonal dc electric and magnetic fields lift the degeneracy of the n shell and define the eccentricity e of the initial coherent elliptic states, which are formed by laser excitation and subsequent adiabatic transformation. The intrashell transitions are driven by a time-harmonic electric field linearly polarized parallel to the major axis of the ellipse. N-photon resonances with N=1-9 are studied as a function of e. All resonances with N{>=}3 are suppressed at certain e values in between 0 and 1. A similar system was analyzed by Yabuzaki et al. [Phys. Rev. A 10, 1955 (1974)] who found a simple pattern of suppressions that applies also for the present experiments. The results of these experimentally confirm that each time N is increased by two, an additional suppression is observed.

  19. Features of multiphoton-stimulated bremsstrahlung in a quantized field

    NASA Astrophysics Data System (ADS)

    Burenkov, Ivan A.; Tikhonova, Olga V.

    2010-12-01

    The process of absorption and emission of external field quanta by a free electron during the scattering on a potential centre is investigated in the case of interaction with a quantized electromagnetic field. The analytical expression for differential cross-sections and probabilities of different multiphoton channels are obtained. We demonstrate that in the case of a non-classical 'squeezed vacuum' initial field state the probability for the electron to absorb a large number of photons appears to be larger by several orders of magnitude in comparison to the classical field and leads to the formation of the high-energy plateau in the electron energy spectrum. The generalization of the Marcuse effect to the case of the quantized field is worked out. The total probability of energy absorption by electron from the non-classical light is analysed.

  20. Design of a fiber-optic multiphoton microscopy handheld probe

    PubMed Central

    Zhao, Yuan; Sheng, Mingyu; Huang, Lin; Tang, Shuo

    2016-01-01

    We have developed a fiber-optic multiphoton microscopy (MPM) system with handheld probe using femtosecond fiber laser. Here we present the detailed optical design and analysis of the handheld probe. The optical systems using Lightpath 352140 and 352150 as objective lens were analyzed. A custom objective module that includes Lightpath 355392 and two customized corrective lenses was designed. Their performances were compared by wavefront error, field curvature, astigmatism, F-θ error, and tolerance in Zemax simulation. Tolerance analysis predicted the focal spot size to be 1.13, 1.19 and 0.83 µm, respectively. Lightpath 352140 and 352150 were implemented in experiment and the measured lateral resolution was 1.22 and 1.3 µm, respectively, which matched with the prediction. MPM imaging by the handheld probe were conducted on leaf, fish scale and rat tail tendon. The MPM resolution can potentially be improved by the custom objective module. PMID:27699109

  1. In vivo multiphoton imaging of bile duct ligation

    NASA Astrophysics Data System (ADS)

    Liu, Yuan; Li, Feng-Chieh; Chen, Hsiao-Chin; Chang, Po-shou; Yang, Shu-Mei; Lee, Hsuan-Shu; Dong, Chen-Yuan

    2008-02-01

    Bile is the exocrine secretion of liver and synthesized by hepatocytes. It is drained into duodenum for the function of digestion or drained into gallbladder for of storage. Bile duct obstruction is a blockage in the tubes that carry bile to the gallbladder and small intestine. However, Bile duct ligation results in the changes of bile acids in serum, liver, urine, and feces1, 2. In this work, we demonstrate a novel technique to image this pathological condition by using a newly developed in vivo imaging system, which includes multiphoton microscopy and intravital hepatic imaging chamber. The images we acquired demonstrate the uptake, processing of 6-CFDA in hepatocytes and excretion of CF in the bile canaliculi. In addition to imaging, we can also measure kinetics of the green fluorescence intensity.

  2. Evaluating thermal damage induced by pulsed light with multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Gong, Wei; Xie, Shusen; Huang, Yimei

    2009-02-01

    Nonablative skin remodeling is a new light treatment approach for photodamaged skin. Compared to ablative CO2 or Er:YAG laser resurfacing, dermabrasion, and chemical peels, the clinical objective of nonablative skin remodeling is to maximize thermal damage to upper dermis while minimizing injury to the epidermis and surrounding tissue, consequently decreasing potential complications and shortening long recuperation periods. Histological analysis of preoperative and postoperative biopsies using H&E or special stains has indicated the dermal thermal injury, which resulting in collagen denaturation, is the most important mechanism of nonablative skin remodeling for improving skin situation. And the extent of improvement of skin situation corresponded to the formation of a new band of dense, compact collagen bundles in the papillary dermis. The diversity of individual skin condition influences the choice of pulsed light treatment parameters, and further influences the degree of dermal thermal damage, thus the efficacy of nonablative skin remodeling remains unstable. Recently, multiphoton microscopy has show a promising application for monitoring skin thermal damage, because collagen could produce strong second harmonic generation (SHG). And SHG intensity is presumably proportional to the percentage of collagen in dermis. In this paper, the auto-fluorescence (AF) intensity and SHG intensity of mice skin irradiated by pulsed Nd:YAG laser were measured and imaged with multiphoton microscope, and the results show the ratio of SHG to AF decreases with the increase of irradiation exposure dose, and could be a quantitative technique to assess dermal thermal damage, and could further benefit the choice of light treatment parameters.

  3. Multi-Photon Absorption Spectra: A Comparison Between Transmittance Change and Fluorescence Methods

    DTIC Science & Technology

    2015-05-21

    AFRL-OSR-VA-TR-2015-0134 multi-photon absorption spectra Cleber Mendonca INSTITUTO DE FISICA DE SAO CARLOS Final Report 05/21/2015 DISTRIBUTION A...multi-photon absorption spectra: a comparison between transmittance change and fluorescence methods 5a. CONTRACT NUMBER Award No: FA9550-12-1-0028...presents the progress we have made on the project Determination of multi-photon absorption spectra: a comparison between transmittance change and

  4. High (1 GHz) repetition rate compact femtosecond laser: A powerful multiphoton tool for nanomedicine and nanobiotechnology

    NASA Astrophysics Data System (ADS)

    Ehlers, A.; Riemann, I.; Martin, S.; Le Harzic, R.; Bartels, A.; Janke, C.; König, K.

    2007-07-01

    Multiphoton tomography of human skin and nanosurgery of human chromosomes have been performed with a 1GHz repetition rate laser by the use of the commercially available femtosecond multiphoton laser tomograph DermaInspect as well as a compact galvoscanning microscope. We performed the autofluorescence tomography up to 100μm in the depth of human skin. Submicron cutting lines and hole drillings have been conducted on labeled human chromosomes.

  5. High-Resolution Spectroscopy and Dynamics of Multiphoton Processes in Atoms and Molecules.

    DTIC Science & Technology

    1985-06-13

    perform photoion-photoelectron coincidence studies using a resonance lamp , is presently operated Independently of the photoelectron spectrometer. The mass...photoionization of excited states of atomic carbon. Atomic carbon in both the 3 p ground state and the 1D excited state was prepared by UV multiphoton...34 Gordon Conference on UV /Visible Multiphoton Ionization and Dissociation Processes, 12-16 July 1982 (no abstract available). 5. P. M. Dehmer, "VUV

  6. In vivo multiphoton microscopy of deep tissue with gradient index lenses

    NASA Astrophysics Data System (ADS)

    Levene, Michael J.; Dombeck, Daniel A.; Williams, Rebecca M.; Skoch, Jesse; Hickey, Gregory A.; Kasischke, Karl A.; Molloy, Raymond P.; Ingelsson, Martin; Stern, Edward A.; Klucken, Jochen; Bacskai, Brian J.; Zipfel, Warren R.; Hyman, Bradley T.; Webb, Watt W.

    2004-06-01

    Gradient index lenses enable multiphoton microscopy of deep tissues in the intact animal. In order to assess their applicability to clinical research, we present in vivo multiphoton microscopy with gradient index lenses in brain regions associated with Alzheimer's disease and Parkinson's disease in both transgenic and wild-type mice. We also demonstrate microscopy of ovary in wild type mouse using only intrinsic fluorescence and second harmonic generation, signal sources which may prove useful for both the study and diagnosis of cancer.

  7. In vivo multiphoton microscopy associated to 3D image processing for human skin characterization

    NASA Astrophysics Data System (ADS)

    Baldeweck, T.; Tancrède, E.; Dokladal, P.; Koudoro, S.; Morard, V.; Meyer, F.; Decencière, E.; Pena, A.-M.

    2012-03-01

    Multiphoton microscopy has emerged in the past decade as a promising non-invasive skin imaging technique. The aim of this study was to assess whether multiphoton microscopy coupled to specific 3D image processing tools could provide new insights into the organization of different skin components and their age-related changes. For that purpose, we performed a clinical trial on 15 young and 15 aged human female volunteers on the ventral and dorsal side of the forearm using the DermaInspectR medical imaging device. We visualized the skin by taking advantage of intrinsic multiphoton signals from cells, elastic and collagen fibers. We also developed 3D image processing algorithms adapted to in vivo multiphoton images of human skin in order to extract quantitative parameters in each layer of the skin (epidermis and superficial dermis). The results show that in vivo multiphoton microscopy is able to evidence several skin alterations due to skin aging: morphological changes in the epidermis and modifications in the quantity and organization of the collagen and elastic fibers network. In conclusion, the association of multiphoton microscopy with specific image processing allows the three-dimensional organization of skin components to be visualized and quantified thus providing a powerful tool for cosmetic and dermatological investigations.

  8. Improving signal levels in intravital multiphoton microscopy using an objective correction collar

    NASA Astrophysics Data System (ADS)

    Muriello, Pamela A.; Dunn, Kenneth W.

    2008-04-01

    Multiphoton microscopy has enabled biologists to collect high-resolution images hundreds of microns into biological tissues, including tissues of living animals. While the depth of imaging exceeds that possible from any other form of light microscopy, multiphoton microscopy is nonetheless generally limited to depths of less than a millimeter. Many of the advantages of multiphoton microscopy for deep tissue imaging accrue from the unique nature of multiphoton fluorescence excitation. However, the quadratic relationship between illumination level and fluorescence excitation makes multiphoton microscopy especially susceptible to factors that degrade the illumination focus. Here we examine the effect of spherical aberration on multiphoton microscopy in fixed kidney tissues and in the kidneys of living animals. We find that spherical aberration, as evaluated from axial asymmetry in the point-spread function, can be corrected by adjustment of the correction collar of a water immersion objective lens. Introducing a compensatory positive spherical aberration into the imaging system decreases the depth-dependence of signal levels in images collected from living animals, increasing signal by up to 50%.

  9. Use of multi-photon laser-scanning microscopy to describe the distribution of xenobiotic chemicals in fish early life stages.

    PubMed

    Hornung, Michael W; Cook, Philip M; Flynn, Kevin M; Lothenbach, Doug B; Johnson, Rodney D; Nichols, John W

    2004-03-30

    To better understand the mechanisms by which persistent bioaccumulative toxicants (PBTs) produce toxicity during fish early life stages (ELS), dose-response relationships need to be understood in relation to the dynamic distribution of chemicals in sensitive tissues. In this study, a multi-photon laser scanning microscope (MPLSM) was used to determine the multi-photon excitation spectra of several polyaromatic hydrocarbons (PAHs) and to describe chemical distribution among tissues during fish ELS. The multi-photon excitation spectra revealed intense fluorescent signal from the model fluorophore, pentamethyl-difluoro-boro-indacene (BODIPY), less signal from benzo[a]pyrene and fluoranthene, and no detectable signal from pyrene. The imaging method was tested by exposing newly fertilized medaka (Oryzias latipes) eggs to BODIPY or fluoranthene for 6 h, followed by transfer to clean media. Embryos and larvae were then imaged through 5 days post-hatch. The two test chemicals partitioned similarly throughout development and differences in fluorescence intensity among tissues were evident to a depth of several hundred microns. Initially, the most intense signal was observed in the oil droplet within the yolk, while a moderate signal was seen in the portion of the yolk containing the yolk-platelets. As embryonic development progressed, the liver biliary system, gall bladder, and intestinal tract accumulated strong fluorescent signal. After hatch, once the gastrointestinal tract was completely developed, most of the fluorescent signal was cleared. The MPLSM is a useful tool to describe the tissue distribution of fluorescent PBTs during fish ELS.

  10. Multiphoton Absorption Order of CsPbBr3 As Determined by Wavelength-Dependent Nonlinear Optical Spectroscopy.

    PubMed

    Saouma, Felix O; Stoumpos, Constantinos C; Kanatzidis, Mercouri G; Kim, Yong Soo; Jang, Joon I

    2017-10-05

    CsPbBr3 is a direct-gap semiconductor where optical absorption takes place across the fundamental bandgap, but this all-inorganic halide perovskite typically exhibits above-bandgap emission when excited over an energy level, lying above the conduction-band minimum. We probe this bandgap anomaly using wavelength-dependent multiphoton absorption spectroscopy and find that the fundamental gap is strictly two-photon forbidden, rendering it three-photon absorption (3PA) active. Instead, two-photon absorption (2PA) commences when the two-photon energy is resonant with the optical gap, associated with the level causing the anomaly. We determine absolute nonlinear optical dispersion over this 3PA-2PA region, which can be explained by two-band models in terms of the optical gap. The polarization dependence of 3PA and 2PA is also measured and explained by the relevant selection rules. CsPbBr3 is highly luminescent under multiphoton absorption at room temperature with marked polarization and wavelength dependence at the 3PA-2PA crossover and therefore has potential for nonlinear optical applications.

  11. Theoretical description of circular dichroism in photoelectron angular distributions of randomly oriented chiral molecules after multi-photon photoionization

    NASA Astrophysics Data System (ADS)

    Goetz, R. E.; Isaev, T. A.; Nikoobakht, B.; Berger, R.; Koch, C. P.

    2017-01-01

    Photoelectron circular dichroism refers to the forward/backward asymmetry in the photoelectron angular distribution with respect to the propagation axis of circularly polarized light. It has recently been demonstrated in femtosecond multi-photon photoionization experiments with randomly oriented camphor and fenchone molecules [C. Lux et al., Angew. Chem., Int. Ed. 51, 4755 (2012) and C. S. Lehmann et al., J. Chem. Phys. 139, 234307 (2013)]. A theoretical framework describing this process as (2+1) resonantly enhanced multi-photon ionization is constructed, which consists of two-photon photoselection from randomly oriented molecules and successive one-photon ionization of the photoselected molecules. It combines perturbation theory for the light-matter interaction with ab initio calculations for the two-photon absorption and a single-center expansion of the photoelectron wavefunction in terms of hydrogenic continuum functions. It is verified that the model correctly reproduces the basic symmetry behavior expected under exchange of handedness and light helicity. When applied to fenchone and camphor, semi-quantitative agreement with the experimental data is found, for which a sufficient d wave character of the electronically excited intermediate state is crucial.

  12. Multiphoton excited fabrication of collagen matrixes cross-linked by a modified benzophenone dimer: bioactivity and enzymatic degradation.

    PubMed

    Basu, Swarna; Cunningham, Lawrence P; Pins, George D; Bush, Katie A; Taboada, Rosa; Howell, Amy R; Wang, Jun; Campagnola, Paul J

    2005-01-01

    Multiphoton excited (MPE) photochemistry is used to fabricate model tissue engineering scaffolds directly from types I, II, and IV collagen. A modified benzophenone dimer (BPD) provides the photoactivation and becomes incorporated into the resulting collagen matrixes. Unlike xanthene photochemistries, the benzophenone dimer can be used in acidic environments, where most forms of collagen have the greatest solubility. The minimum feature sizes are investigated by using two- and three-photon excitation, where the latter provides for superior "resolution" and suggests that collagen structures can be fabricated on the size scales of focal contacts. The resulting structures display excellent retention of bioactivity as evidenced by highly specific cell adhesion as well as immunofluorescence labeling. Structural and chemical aspects of the collagen matrixes are probed through measuring the enzymatic degradation through specific and nonspecific proteases, as the resulting relative rates are consistent with the activity of these enzymes. The degradation rates can also be controlled through varying the cross-link density in the matrixes, which is achieved through tuning the exposure dose during the fabrication process. The degradation rates are also found to be consistent with swelling/shrinking measurements and thus the average mesh size of the matrixes. In all cases the enzymatic degradations are well-fit single exponentials, suggesting that the matrixes can be fabricated with a priori knowledge of their structural properties. These results coupled with the resulting bioactivity suggest that the multiphoton fabrication process may be a powerful tool for the creation of cell-sized tissue engineering scaffolds.

  13. Image segmentation for integrated multiphoton microscopy and reflectance confocal microscopy imaging of human skin in vivo

    PubMed Central

    Chen, Guannan; Lui, Harvey

    2015-01-01

    Background Non-invasive cellular imaging of the skin in vivo can be achieved in reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM) modalities to yield complementary images of the skin based on different optical properties. One of the challenges of in vivo microscopy is the delineation (i.e., segmentation) of cellular and subcellular architectural features. Methods In this work we present a method for combining watershed and level-set models for segmentation of multimodality images obtained by an integrated MPM and RCM imaging system from human skin in vivo. Results Firstly, a segmentation model based on watershed is introduced for obtaining the accurate structure of cell borders from the RCM image. Secondly,, a global region based energy level-set model is constructed for extracting the nucleus of each cell from the MPM image. Thirdly, a local region-based Lagrange Continuous level-set approach is used for segmenting cytoplasm from the MPM image. Conclusions Experimental results demonstrated that cell borders from RCM image and boundaries of cytoplasm and nucleus from MPM image can be obtained by our segmentation method with better accuracy and effectiveness. We are planning to use this method to perform quantitative analysis of MPM and RCM images of in vivo human skin to study the variations of cellular parameters such as cell size, nucleus size and other mophormetric features with skin pathologies. PMID:25694949

  14. Multiphoton microscopy and image guided light activated therapy using nanomaterials (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Prasad, Paras N.

    2017-02-01

    This talk will focus on design and applications of nanomaterials exhibiting strong multiphoton upconversion for multiphoton microscopy as well as for image-guided and light activated therapy .1-3 Such processes can occur by truly nonlinear optical interactions proceeding through virtual intermediate states or by stepwise coupled linear excitations through real intermediate states. Multiphoton processes in biocompatible multifunctional nanoparticles allow for 3D deep tissue imaging. In addition, they can produce in-situ photon conversion of deep tissue penetrating near IR light into a needed shorter wavelength light for photo-activated therapy at a targeted site, thus overcoming the limited penetration of UV or visible light into biological media. We are using near IR emitters such as silicon quantum dots which also exhibit strong multiphoton excitation for multiphoton microscopy. Another approach involves nonlinear nanocrystals such as ZnO which can produce four wave mixing, sum frequency generation as well as second harmonic generation to convert a deep tissue penetrating Near IR light at the targeted biological site to a desired shorter wavelength light suitable for bio imaging or activation of a therapy. We have utilized this approach to activate a photosensitizer for photodynamic therapy. Yet another type of upconversion materials is rare-earth ion doped optical nanotransformers which transform a Near IR (NIR) light from an external source by sequential single photon absorption, in situ and on demand, to a needed wavelength. Applications of these nanotransformers in multiphoton photoacoustic imaging will also be presented. An exciting direction pursued by us using these multiphoton nanoparticles, is functional imaging of brain. Simultaneously, they can effect optogenetics for regioselective stimulation of neurons for providing an effective intervention/augmentation strategy to enhance the cognitive state and lead to a foundation for futuristic vision of super

  15. In vivo non-invasive multiphoton tomography of human skin

    NASA Astrophysics Data System (ADS)

    König, Karsten; Riemann, Iris; Ehlers, Alexander; Le Harzic, Ronan

    2005-10-01

    High resolution non-invasive 3D imaging devices are required to detect pathogenic microorganisms such as Anthrax spores, bacteria, viruses, fungi and chemical agents entering biological tissues such as the epidermis. Due to the low light penetration depth and the biodamage potential, ultraviolet light sources can not be employed to realize intratissue imaging of bio- and chemohazards. We report on the novel near infrared laser technology multiphoton tomography and the high resolution 4D imaging tool DermaInspect for non-invasive detection of intratissue agents and their influence on cellular metabolism based on multiphoton autofluorescence imaging (MAI) and second harmonic generation (SHG). Femtosecond laser pulses in the spectral range of 750 nm to 850 nm have been used to image in vivo human skin with subcellular spatial and picosecond temporal resolution. The non-linear induced autofluorescence of both, skin tissues and microorganisms, originates mainly from naturally endogenous fluorophores/protein structures like NAD(P)H, flavins, keratin, collagen, elastin, porphyrins and melanin. Bacteria emit in the blue/green spectral range due to NAD(P)H and flavoproteins and, in certain cases, in the red spectral range due to the biosynthesis of Zn-porphyrins, coproporphyrin and protoporphyrin. Collagen and exogenous non-centrosymmetric molecules can be detected by SHG signals. The system DermaInspect consists of a wavelength-tunable compact 80/90 MHz Ti:sapphire laser, a scan module with galvo scan mirrors, piezo-driven objective, fast photon detector and time-resolved single photon counting unit. It can be used to perform optical sectioning and 3D autofluorescence lifetime imaging (τ-mapping) with 1 μm spatial resolution and 270 ps temporal resolution. The parameter fluorescence lifetime depends on the type of fluorophore and its microenvironment and can be used to distinguish bio- and chemohazards from cellular background and to gain information for pathogen

  16. Quantification of aortic and cutaneous elastin and collagen morphology in Marfan syndrome by multiphoton microscopy.

    PubMed

    Cui, Jason Z; Tehrani, Arash Y; Jett, Kimberly A; Bernatchez, Pascal; van Breemen, Cornelis; Esfandiarei, Mitra

    2014-09-01

    In a mouse model of Marfan syndrome, conventional Verhoeff-Van Gieson staining displays severe fragmentation, disorganization and loss of the aortic elastic fiber integrity. However, this method involves chemical fixatives and staining, which may alter the native morphology of elastin and collagen. Thus far, quantitative analysis of fiber damage in aorta and skin in Marfan syndrome has not yet been explored. In this study, we have used an advanced noninvasive and label-free imaging technique, multiphoton microscopy to quantify fiber fragmentation, disorganization, and total volumetric density of aortic and cutaneous elastin and collagen in a mouse model of Marfan syndrome. Aorta and skin samples were harvested from Marfan and control mice aged 3-, 6- and 9-month. Elastin and collagen were identified based on two-photon excitation fluorescence and second-harmonic-generation signals, respectively, without exogenous label. Measurement of fiber length indicated significant fragmentation in Marfan vs. control. Fast Fourier transform algorithm analysis demonstrated markedly lower fiber organization in Marfan mice. Significantly reduced volumetric density of elastin and collagen and thinner skin dermis were observed in Marfan mice. Cutaneous content of elastic fibers and thickness of dermis in 3-month Marfan resembled those in the oldest control mice. Our findings of early signs of fiber degradation and thinning of skin dermis support the potential development of a novel non-invasive approach for early diagnosis of Marfan syndrome.

  17. Open-ended response theory with polarizable embedding: multiphoton absorption in biomolecular systems.

    PubMed

    Steindal, Arnfinn Hykkerud; Beerepoot, Maarten T P; Ringholm, Magnus; List, Nanna Holmgaard; Ruud, Kenneth; Kongsted, Jacob; Olsen, Jógvan Magnus Haugaard

    2016-10-12

    We present the theory and implementation of an open-ended framework for electric response properties at the level of Hartree-Fock and Kohn-Sham density functional theory that includes effects from the molecular environment modeled by the polarizable embedding (PE) model. With this new state-of-the-art multiscale functionality, electric response properties to any order can be calculated for molecules embedded in polarizable atomistic molecular environments ranging from solvents to complex heterogeneous macromolecules such as proteins. In addition, environmental effects on multiphoton absorption (MPA) properties can be studied by evaluating single residues of the response functions. The PE approach includes mutual polarization effects between the quantum and classical parts of the system through induced dipoles that are determined self-consistently with respect to the electronic density. The applicability of our approach is demonstrated by calculating MPA strengths up to four-photon absorption for the green fluorescent protein. We show how the size of the quantum region, as well as the treatment of the border between the quantum and classical regions, is crucial in order to obtain reliable MPA predictions.

  18. In vivo optical imaging of cancer metastasis using multiphoton microscopy: a short review

    PubMed Central

    Tanaka, Koji; Toiyama, Yuji; Okugawa, Yoshinaga; Okigami, Masato; Inoue, Yasuhiro; Uchida, Keiichi; Araki, Toshimitsu; Mohri, Yasuhiko; Mizoguchi, Akira; Kusunoki, Masato

    2014-01-01

    Intravital (in vivo) microscopy using fluorescently-tagged proteins is a valuable tool for imaging the expression of a specific protein, its subcellular location and the dynamics of specific cell populations in living animals. Recently, multiphoton microscopy including two-photon laser scanning microscopy (TPLSM) has been used in the field of tumor biology due to its ability to image target organs at higher magnification and at deeper depths from the tissue surface for longer time periods. We developed a method of in vivo real-time imaging for tumor metastasis using TPLSM with an organ stabilizing system, which allow us to observe not only a single tumor cell and its microenvironment for a long time, but also to observe the same organ of the same mouse at multiple time points in preclinical models. Here, we presented in vivo real-time images of 1) tumor cell arrest, 2) tumor cell-platelet interaction, 3) tumor cell-leukocyte interaction, and 4) metastatic colonization at the secondary organs as representative steps of metastatic process of experimental liver metastasis models using TPLSM. PMID:24936213

  19. Combining large area fluorescence with multiphoton microscopy for improved detection of oral epithelial neoplasia (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

    2016-03-01

    Volumetric Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia representing the complex microstructural organization of mucosa, potentially providing high specificity for detection of neoplasia, but is limited by small imaging area. Large area fluorescence methods on the other hand show high sensitivity appropriate for screening but are hampered by low specificity. In this study, we apply MPAM-SHGM following guidance from large area fluorescence, by either autofluorescence or a targeted metabolic fluorophore, as a potentially clinically viable approach for detection of oral neoplasia. Sites of high neoplastic potentially were identified by large area red/green autofluorescence or by a fluorescently labelled deoxy-glucose analog, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) to highlight areas of high glucose uptake across the buccal pouch of a hamster model for OSCC. Follow-up MPAM-SHGM was conducted on regions of interests (ROIs) to assess whether microscopy would reveal microscopic features associated with neoplasia to confirm or exclude large area fluorescence findings. Parameters for analysis included cytologic metrics, 3D epithelial connective tissue interface metrics (MPAM-SHGM) and intensity of fluorescence (widefield). Imaged sites were biopsied and processed for histology and graded by a pathologist. A small sample of human ex vivo tissues were also imaged. A generalized linear model combining image metrics from large area fluorescence and volumetric MPAM-SHGM indicated the ability to delineate normal and inflammation from neoplasia.

  20. Multiphoton microscopy, fluorescence lifetime imaging and optical spectroscopy for the diagnosis of neoplasia

    NASA Astrophysics Data System (ADS)

    Skala, Melissa Caroline

    2007-12-01

    Cancer morbidity and mortality is greatly reduced when the disease is diagnosed and treated early in its development. Tissue biopsies are the gold standard for cancer diagnosis, and an accurate diagnosis requires a biopsy from the malignant portion of an organ. Light, guided through a fiber optic probe, could be used to inspect regions of interest and provide real-time feedback to determine the optimal tissue site for biopsy. This approach could increase the diagnostic accuracy of current biopsy procedures. The studies in this thesis have characterized changes in tissue optical signals with carcinogenesis, increasing our understanding of the sensitivity of optical techniques for cancer detection. All in vivo studies were conducted on the dimethylbenz[alpha]anthracene treated hamster cheek pouch model of epithelial carcinogenesis. Multiphoton microscopy studies in the near infrared wavelength region quantified changes in tissue morphology and fluorescence with carcinogenesis in vivo. Statistically significant morphological changes with precancer included increased epithelial thickness, loss of stratification in the epithelium, and increased nuclear diameter. Fluorescence changes included a statistically significant decrease in the epithelial fluorescence intensity per voxel at 780 nm excitation, a decrease in the fluorescence lifetime of protein-bound nicotinamide adenine dinucleotide (NADH, an electron donor in oxidative phosphorylation), and an increase in the fluorescence lifetime of protein-bound flavin adenine dinucleotide (FAD, an electron acceptor in oxidative phosphorylation) with precancer. The redox ratio (fluorescence intensity of FAD/NADH, a measure of the cellular oxidation-reduction state) did not significantly change with precancer. Cell culture experiments (MCF10A cells) indicated that the decrease in protein-bound NADH with precancer could be due to increased levels of glycolysis. Point measurements of diffuse reflectance and fluorescence spectra in

  1. Femtosecond laser pulse optimization for multiphoton cytometry and control of fluorescence

    NASA Astrophysics Data System (ADS)

    Tkaczyk, Eric Robert

    This body of work encompasses optimization of near infrared femtosecond laser pulses both for enhancement of flow cytometry as well as adaptive pulse shaping to control fluorescence. A two-photon system for in vivo flow cytometry is demonstrated, which allows noninvasive quantification of circulating cell populations in a single live mouse. We monitor fluorescently-labeled red blood cells for more than two weeks, and are also able to noninvasively measure circulation times of two distinct populations of breast cancer cells simultaneously in a single mouse. We build a custom laser excitation source in the form of an extended cavity mode-locked oscillator, which enables superior detection in whole blood or saline of cell lines expressing fluorescent proteins including the green fluorescent protein (GFP), tdTomato and mPlum. A mathematical model explains unique features of the signals. The ability to distinguish different fluorescent species is central to simultaneous measurement of multiple molecular targets in high throughput applications including the multiphoton flow cytometer. We demonstrate that two dyes which are not distinguishable to one-photon measurements can be differentiated and in fact quantified in mixture via phase-shaped two-photon excitation pulses found by a genetic algorithm. We also selectively enhance or suppress two-photon fluorescence of numerous common dyes with tailored pulse shapes. Using a multiplicative (rather than ratiometric) fitness parameter, we are able to control the fluorescence while maintaining a strong signal. With this method, we control the two-photon fluorescence of the blue fluorescent protein (BFP), which is of particular interest in investigations of protein-protein interactions, and has frustrated previous attempts of control. Implementing an acousto-optic interferometer, we use the same experimental setup to measure two-photon excitation cross-sections of dyes and prove that photon-photon interferences are the

  2. Multiphoton Imaging of the Glomerular Permeability of Angiotensinogen

    PubMed Central

    Nakano, Daisuke; Kobori, Hiroyuki; Burford, James L.; Gevorgyan, Haykanush; Seidel, Saskia; Hitomi, Hirofumi; Nishiyama, Akira

    2012-01-01

    Patients and animals with renal injury exhibit increased urinary excretion of angiotensinogen. Although increased tubular synthesis of angiotensinogen contributes to the increased excretion, we do not know to what degree glomerular filtration of systemic angiotensinogen, especially through an abnormal glomerular filtration barrier, contributes to the increase in urinary levels. Here, we used multiphoton microscopy to visualize and quantify the glomerular permeability of angiotensinogen in the intact mouse and rat kidney. In healthy mice and Munich-Wistar-Frömter rats at the early stage of glomerulosclerosis, the glomerular sieving coefficient of systemically infused Atto565-labeled human angiotensinogen (Atto565-hAGT), which rodent renin cannot cleave, was only 25% of the glomerular sieving coefficient of albumin, and its urinary excretion was undetectable. In a more advanced phase of kidney disease, the glomerular permeability of Atto565-hAGT was slightly higher but still very low. Furthermore, unlike urinary albumin, the significantly higher urinary excretion of endogenous rat angiotensinogen did not correlate with either the Atto565-hAGT or Atto565-albumin glomerular sieving coefficients. These results strongly suggest that the vast majority of urinary angiotensinogen originates from the tubules rather than glomerular filtration. PMID:22997258

  3. Multiphoton imaging of the glomerular permeability of angiotensinogen.

    PubMed

    Nakano, Daisuke; Kobori, Hiroyuki; Burford, James L; Gevorgyan, Haykanush; Seidel, Saskia; Hitomi, Hirofumi; Nishiyama, Akira; Peti-Peterdi, Janos

    2012-11-01

    Patients and animals with renal injury exhibit increased urinary excretion of angiotensinogen. Although increased tubular synthesis of angiotensinogen contributes to the increased excretion, we do not know to what degree glomerular filtration of systemic angiotensinogen, especially through an abnormal glomerular filtration barrier, contributes to the increase in urinary levels. Here, we used multiphoton microscopy to visualize and quantify the glomerular permeability of angiotensinogen in the intact mouse and rat kidney. In healthy mice and Munich-Wistar-Frömter rats at the early stage of glomerulosclerosis, the glomerular sieving coefficient of systemically infused Atto565-labeled human angiotensinogen (Atto565-hAGT), which rodent renin cannot cleave, was only 25% of the glomerular sieving coefficient of albumin, and its urinary excretion was undetectable. In a more advanced phase of kidney disease, the glomerular permeability of Atto565-hAGT was slightly higher but still very low. Furthermore, unlike urinary albumin, the significantly higher urinary excretion of endogenous rat angiotensinogen did not correlate with either the Atto565-hAGT or Atto565-albumin glomerular sieving coefficients. These results strongly suggest that the vast majority of urinary angiotensinogen originates from the tubules rather than glomerular filtration.

  4. Security of quantum key distribution with multiphoton components

    PubMed Central

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

    2016-01-01

    Most qubit-based quantum key distribution (QKD) protocols extract the secure key merely from single-photon component of the attenuated lasers. However, with the Scarani-Acin-Ribordy-Gisin 2004 (SARG04) QKD protocol, the unconditionally secure key can be extracted from the two-photon component by modifying the classical post-processing procedure in the BB84 protocol. Employing the merits of SARG04 QKD protocol and six-state preparation, one can extract secure key from the components of single photon up to four photons. In this paper, we provide the exact relations between the secure key rate and the bit error rate in a six-state SARG04 protocol with single-photon, two-photon, three-photon, and four-photon sources. By restricting the mutual information between the phase error and bit error, we obtain a higher secure bit error rate threshold of the multiphoton components than previous works. Besides, we compare the performances of the six-state SARG04 with other prepare-and-measure QKD protocols using decoy states. PMID:27383014

  5. In vivo multiphoton imaging of immune cell dynamics.

    PubMed

    Okada, Takaharu; Takahashi, Sonoko; Ishida, Azusa; Ishigame, Harumichi

    2016-11-01

    Multiphoton imaging has been utilized to analyze in vivo immune cell dynamics over the last 15 years. Particularly, it has deepened the understanding of how immune responses are organized by immune cell migration and interactions. In this review, we first describe the following technical advances in recent imaging studies that contributed to the new findings on the regulation of immune responses and inflammation. Improved multicolor imaging of immune cell behavior has revealed that their interactions are spatiotemporally coordinated to achieve efficient and long-term immunity. The use of photoactivatable and photoconvertible fluorescent proteins has increased duration and volume of cell tracking, even enabling the analysis of inter-organ migration of immune cells. In addition, visualization of immune cell activation using biosensors for intracellular calcium concentration and signaling molecule activities has started to give further mechanistic insights. Then, we also introduce recent imaging analyses of interactions between immune cells and non-immune cells including endothelial, fibroblastic, epithelial, and nerve cells. It is argued that future imaging studies that apply updated technical advances to analyze interactions between immune cells and non-immune cells will be important for thorough physiological understanding of the immune system.

  6. Identification of intramural metastasis in esophageal cancer using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Kang, Deyong; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, jiangbo; Chen, Jianxin

    2017-02-01

    Intramural metastasis (IM) of esophageal cancer is defined as metastasis from a primary lesion to the esophageal wall without intraepithelial cancer extension. Esophageal cancer with IM is more common and such cases indicate a poor prognosis. In esophageal surgery, if curative resection is possible, the complete removal of both primary tumor and associated IMs is required. Therefore, accurate diagnosis of IMs in esophageal cancer prior to surgery is of particular importance. Multiphoton microscopy (MPM) with subcellular resolution is well-suited for deep tissue imaging since many endogenous fluorophores of fresh biological tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Here, a study to identify IM in fresh tissue section using MPM is reported. In this study, the morphological and spectral differences between IM and surrounding tissue are described. These results show that MPM has the ability to accurately identify IM in esophageal tissues. With improvement of the penetration depth of MPM and the development of multiphton microendoscope, MPM may be a promising imaging technique for preoperative diagnosis of IMs in esophageal cancer in the future.

  7. Multiphoton imaging the disruptive nature of sulfur mustard lesions

    NASA Astrophysics Data System (ADS)

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

    2005-03-01

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

  8. Superresolved multiphoton microscopy with spatial frequency-modulated imaging

    PubMed Central

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

    2016-01-01

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

  9. Compact fixed wavelength femtosecond oscillators for multi-photon imaging

    NASA Astrophysics Data System (ADS)

    Hakulinen, T.; Klein, J.; Zadoyan, R.; Baldacchini, T.; Franke, T.

    2015-03-01

    In recent years two-photon microscopy with fixed-wavelength has raised increasing interest in life-sciences: Two-photon (2P) absorption spectra of common dyes are broader than single-photon ones. Therefore, excitation of several dyes simultaneously with a single IR laser wavelength is feasible and could be seen as an advantage in 2P microscopy. We used pulsed fixed-wavelength infrared lasers with center wavelength at 1040 nm, for two-photon microscopy in a variety of biologically relevant samples, among these a mouse brain sample, a mouse artery (within the animal, acute preparation), and a preparation of mouse bladder. The 1040 nm laser proved to be efficient not only in exciting fluorescence from yellow fluorescent protein (YFP) and red fluorescent dyes, but also for second harmonic generation (SHG) signals from muscle tissue and collagen. With this work we demonstrate that economical, small-footprint fixedwavelength lasers can present an interesting alternative to tunable lasers that are commonly used in multiphoton microscopy.

  10. In vivo multiphoton microscopy of deep brain tissue.

    PubMed

    Levene, Michael J; Dombeck, Daniel A; Kasischke, Karl A; Molloy, Raymond P; Webb, Watt W

    2004-04-01

    Although fluorescence microscopy has proven to be one of the most powerful tools in biology, its application to the intact animal has been limited to imaging several hundred micrometers below the surface. The rest of the animal has eluded investigation at the microscopic level without excising tissue or performing extensive surgery. However, the ability to image with subcellular resolution in the intact animal enables a contextual setting that may be critical for understanding proper function. Clinical applications such as disease diagnosis and optical biopsy may benefit from minimally invasive in vivo approaches. Gradient index (GRIN) lenses with needle-like dimensions can transfer high-quality images many centimeters from the object plane. Here, we show that multiphoton microscopy through GRIN lenses enables minimally invasive, subcellular resolution several millimeters in the anesthetized, intact animal, and we present in vivo images of cortical layer V and hippocampus in the anesthetized Thy1-YFP line H mouse. Microangiographies from deep capillaries and blood vessels containing fluorescein-dextran and quantum dot-labeled serum in wild-type mouse brain are also demonstrated.

  11. The multiphoton ionization of uranium hexafluoride. Revision 1

    SciTech Connect

    Armstrong, D.P.

    1992-05-01

    Multiphoton ionization (MPI) time-of-flight mass spectroscopy and photoelectron spectroscopy studies of UF{sub 6} have been conducted using focused light from the Nd:YAG laser fundamental ({lambda}=1064 nm) and its harmonics ({lambda}=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{sub x}{sup +} fragment ions even at the lowest laser power densities at which signal could be detected. The laser power dependence of U{sup n+} ions signals indicates that saturation can occur for many of the steps required for their ionization. In general, the doubly-charged uranium ion (U{sup 2+}) intensity is much greater than that of the singly-charged uranium ion (U{sup +}). For the case of the tunable dye laser experiments, the U{sup n+} (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 U{sup 2+} ion and the absence or very small intensities of UF{sub x}{sup +} 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.

  12. Dissecting multi-photon resonances at the large hadron collider

    NASA Astrophysics Data System (ADS)

    Allanach, B. C.; Bhatia, D.; Iyer, Abhishek M.

    2017-09-01

    We examine the phenomenology of the production, at the 13 TeV Large Hadron Collider (LHC), of a heavy resonance X, which decays via other new on-shell particles n into multi-(i.e. three or more) photon final states. In the limit that n has a much smaller mass than X, the multi-photon final state may dominantly appear as a two-photon final state because the γ s from the n decay are highly collinear and remain unresolved. We discuss how to discriminate this scenario from X → γ γ : rather than discarding non-isolated photons, it is better to relax the isolation criteria and instead form photon jets substructure variables. The spins of X and n leave their imprint upon the distribution of pseudo-rapidity gap Δ η between the apparent two-photon states. Depending on the total integrated luminosity, this can be used in many cases to claim discrimination between the possible spin choices of X and n, although the case where X and n are both scalar particles cannot be discriminated from the direct X → γ γ decay in this manner. Information on the mass of n can be gained by considering the mass of each photon jet.

  13. Characterization of multiphoton emission from aggregated gold nano particles

    NASA Astrophysics Data System (ADS)

    Eguchi, Akira; Lu, Phat; Kim, Youngsik; Milster, Tom D.

    2016-09-01

    Although gold nanoparticles (GNPs) are promising probes for biological imaging because of their attracting optical properties and bio-friendly nature, properties of the multi-photon (MP) emission from GNP aggregates produced by a short-wave infrared (SWIR) laser have not been examined. In this paper, characterization of MP emission from aggregated 50 nm GNPs excited by a femtosecond (fs) laser at 1560 nm is discussed with respect to aggregate structures. The key technique in this work is single particle spectroscopy. A pattern matching technique is applied to correlate MP emission and SEM images, which includes an optimization processes to maximize cross correlation coefficients between a binary microscope image and a binary SEM image with respect to xy displacement, image rotation angle, and image magnification. Once optimization is completed, emission spots are matched to the SEM image, which clarifies GNP ordering and emission properties of each aggregate. Correlation results showed that GNP aggregates have stronger MP emission than single GNPs. By combining the pattern matching technique with spectroscopy, MP emission spectrum is characterized for each GNP aggregate. A broad spectrum in the visible region and near infrared (NIR) region is obtained from GNP dimers, unlike previously reported surface plasmon enhanced emission spectrum.

  14. Guided Homing of Cells in Multi-Photon Microfabricated Bioscaffolds.

    PubMed

    Skylar-Scott, Mark A; Liu, Man-Chi; Wu, Yuelong; Dixit, Atray; Yanik, Mehmet Fatih

    2016-05-01

    Tissues contain exquisite vascular microstructures, and patterns of chemical cues for directing cell migration, homing, and differentiation for organ development and function. 3D microfabrication by multi-photon photolithography is a flexible, high-resolution tool for generating 3D bioscaffolds. However, the combined fabrication of scaffold microstructure simultaneously with patterning of cues to create both geometrically and chemically defined microenvironments remains to be demonstrated. This study presents a high-speed method for micron-resolution fabrication of scaffold microstructure and patterning of protein cues simultaneously using native scaffold materials. By the simultaneous microfabrication of arbitrary microvasculature geometries, and patterning selected regions of the microvasculature with the homing ligand P-selectin, this study demonstrates adhesion, rolling, and selective homing of cells in defined 3D regions. This novel ability to generate high-resolution geometries replete with patterned cues at high speed enables the construction of biomimetic microenvironments for complex 3D assays of cellular behavior. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Characterization of powdered epidermal vaccine delivery with multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Mulholland, William J.; Kendall, Mark A. F.; White, Nick; Bellhouse, Brian J.

    2004-11-01

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

  16. Spectroscopic analysis of skin intrinsic signals for multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Pena, Ana-Maria; Strupler, Mathias; Boulesteix, Thierry; Senni, Karim; Godeau, Gaston; Beaurepaire, Emmanuel; Schanne-Klein, Marie-Claire

    2006-02-01

    We recorded multiphoton images of human skin biopsies using endogenous sources of nonlinear optical signals. We detected simultaneously two-photon excited fluorescence (2PEF) from intrinsic fluorophores and second harmonic generation (SHG) from collagen. We observed SHG from fibrillar collagens in the dermis, whereas no SHG was detectable from the non fibrillar type IV collagen in the basal laminae. We compared these distinct behaviours of collagens I and IV in SHG microscopy to polarization-resolved surface SHG experiments on thin films of collagens I and IV molecules. We observed similar signals for both types of molecular films, except for the chiroptical contributions which are present only for collagen I and enhance the signal typically by a factor of 2. We concluded that SHG microscopy is a sensitive probe of the micrometer-scale structural organization of collagen in biological tissues. In order to elucidate the origin of the endogenous fluorescence signals, we recorded 2PEF spectra at various positions in the skin biopsies, and compared these data to in vitro spectroscopic analysis. In particular, we studied the keratin fluorescence and determined its 2PEF action cross section. We observed a good agreement between 2PEF spectra recorded in the keratinized upper layers of the epidermis and in a solution of purified keratin. Finally, to illustrate the capabilities of this technique, we recorded 2PEF/SHG images of skin biopsies obtained from patients of various ages.

  17. The analysis of aging skin based on multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Wu, Shulian; Li, Hui; Zhang, Xiaoman; Li, Zhifang; Xu, Shufei

    2010-11-01

    Aging is a very important issue not only in dermatology, but also in cosmetic science. Cutaneous aging involves both chronological and photoaging aging process. The chronological aging is induced with the passage of time. And the photoaging skin is the extrinsic aging caused by sun exposure. The aim of this study is to use multiphoton microscopy (MPM) in vivo to assess intrinsic-age-related and photo-age-related difference. The changes of dermal collagen are measured in quantitively. The algorithm that we used automatically produced the transversal dermal map from MPM. Others, the texture of dermis are analyzed by Fourier transform and Gray Level Co-occurrence Matrix. And the object extraction in textured images is proposed based on the method in object edge extraction, and the aim of it is to detect the object hidden in the skin texture in difference aging skin. The result demonstrates that the approach is effective in detecting the object in epidermis and dermis textured image in different aging skin. It could help to further understand the aging mechanism.

  18. Direct trabecular meshwork imaging in porcine eyes through multiphoton gonioscopy

    NASA Astrophysics Data System (ADS)

    Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.

    2013-03-01

    The development of technologies to characterize the ocular aqueous outflow system (AOS) is important for the understanding of the pathophysiology of glaucoma. Multiphoton microscopy (MPM) offers the advantage of high-resolution, label-free imaging with intrinsic image contrast because the emitted signals result from the specific biomolecular content of the tissue. Previous attempts to use MPM to image the murine irido-corneal region directly through the sclera have suffered from degradation in image resolution due to scattering of the focused laser light. As a result, transscleral MPM has limited ability to observe fine structures in the AOS. In this work, the porcine irido-corneal angle was successfully imaged through the transparent cornea using a gonioscopic lens to circumvent the highly scattering scleral tissue. The resulting high-resolution images allowed the detailed structures in the trabecular meshwork (TM) to be observed. Multimodal imaging by two-photon autofluorescence and second harmonic generation allowed visualization of different features in the TM without labels and without disruption of the TM or surrounding tissues. MPM gonioscopy is a promising noninvasive imaging tool for high-resolution studies of the AOS, and research continues to explore the potential for future clinical applications in humans.

  19. Superresolved multiphoton microscopy with spatial frequency-modulated imaging

    SciTech Connect

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

    2016-05-26

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

  20. Label-free imaging of cortical structures with multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Wang, Shu; Chen, Xiuqiang; Wu, Weilin; Chen, Zhida; Lin, Ruolan; Lin, Peihua; Wang, Xingfu; Fu, Yu Vincent; Chen, Jianxin

    2017-02-01

    Cortical structures in the central nervous system exhibit an ordered laminar organization. Defined cell layers are significant to our understanding of brain structure and function. In this work, multiphoton microscopy (MPM) based on second harmonic generation (SHG) and two-photon excited fluorescence (TPEF), which was applied for qualitatively visualizing the structure of cerebral and cerebellar cortex from the fresh, unfixed, and unstained specimen. MPM is able to effectively identify neurons and neurites in cerebral cortex, as well as glial cells, Purkinje cells, and granule cells in cerebellar cortex at subcellular resolution. In addition, the use of automated image processing algorithms can quantify the circularity of neurons and the density distribution of neurites based on the intrinsic nonlinear optical contrast, further providing quantitative characteristics for automatically analyzing the laminar structure of cortical structures. These results suggest that with the development of the feasibility of two-photon fiberscopes and microendoscope probes, the combined MPM and image analysis holds potential to provide supplementary information to augment the diagnostic accuracy of neuropathology and in vivo identification of various neurological illnesses in clinic.

  1. Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage

    NASA Astrophysics Data System (ADS)

    Wachsmann-Hogiu, Sebastian; Krakow, Deborah; Kirilova, Veneta T.; Cohn, Daniel H.; Bertolotto, Cristina; Acuna, Dora; Fang, Qiyin; Krivorov, Nikola; Farkas, Daniel L.

    2005-03-01

    It has recently been shown that mutations in Filamin A and B genes produce a large spectrum of skeletal disorders in developing fetuses. However, high-resolution optical microscopy in cartilage growth plate using fluorescent antibody assays, which should elucidate molecular aspects of these disorders, is extremely difficult due to the high level of autofluoresce in this tissue. We apply multiphoton, confocal, lifetime and spectral microscopy to (i) image and characterize autofluorophores in chondrocytes and subtract their contributions to obtain a corrected antibody-marker fluorescence signal, and (ii) measure the interaction between Filamin A and B proteins by detecting the fluorescence resonance energy transfer (FRET) between markers of the two proteins. Taking advantage of the different fluorescence spectra of the endogenous and exogenous markers, we can significantly reduce the autofluorescence background. Preliminary results of the FRET experiments suggest no interaction between Filamin A and B proteins. However, developing of new antibodies targeting the carboxy-terminal immunoglobulin-like domain may be necessary to confirm this result.

  2. Multiphoton catalysis with coherent state input: nonclassicality and decoherence

    NASA Astrophysics Data System (ADS)

    Hu, Li-Yun; Wu, Jia-Ni; Liao, Zeyang; Zubairy, M. Suhail

    2016-09-01

    We propose a scheme to generate a new kind of non-Gaussian state—the Laguerre polynomial excited coherent state (LPECS)—by using multiphoton catalysis with coherent state input. The nonclassical properties of the LPECS are studied in terms of nonclassical depth, Mandel’s parameter, second-order correlation, quadrature squeezing, and the negativity of the Wigner function (WF). It is found that the LPECS is highly nonclassical and its nonclassicality depends on the amplitude of the coherent state, the catalysis photon number, and the parameters of the unbalanced beam splitter (BS). In particular, the maximum degree of squeezing can be enhanced by increasing the catalysis photon number. In addition, we examine the effect of decoherence using the WF, which shows that the negative region, the characteristic time of decoherence, and the structure of the WF are affected by catalysis photon number and the parameters of the unbalanced BS. Our work provides general analysis on how to prepare polynomial quantum states, which may be useful in the fields of quantum information and quantum computation.

  3. Label-Free Detection of Breast Masses Using Multiphoton Microscopy

    PubMed Central

    Lu, Jianping; Zhu, Weifeng; Qiu, Jingting; Chen, Jianxin; Xie, Shusen; Zhuo, Shuangmu; Yan, Jun

    2013-01-01

    Histopathology forms the gold standard for the diagnosis of breast cancer. Multiphoton microscopy (MPM) has been proposed to be a potentially powerful adjunct to current histopathological techniques. A label-free imaging based on two- photon excited fluorescence and second-harmonic generation is developed for differentiating normal breast tissues, benign, as well as breast cancer tissues. Human breast biopsies (including human normal breast tissues, benign as well as breast cancer tissues ) that are first imaged (fresh, unfixed, and unstained) with MPM and are then processed for routine H-E histopathology. Our results suggest that the MPM images, obtained from these unprocessed biopsies, can readily distinguish between benign lesions and breast cancers. In the tissues of breast cancers, MPM showed that the tumor cells displayed marked cellular and nuclear pleomorphism. The tumor cells, characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio, infiltrated into disrupted connective tissue, leading to the loss of second-harmonic generation signals. For breast cancer, MPM diagnosis was 100% correct because the tissues of breast cancers did not have second-harmonic generation signals in MPM imaging. On the contrary, in benign breast masses, second-harmonic generation signals could be seen easily in MPM imaging. These observations indicate that MPM could be an important potential tool to provide label-free noninvasive diagnostic impressions that can guide surgeon in biopsy and patient management. PMID:23755295

  4. Multiphoton gonioscopy to image the trabecular meshwork of porcine eyes

    NASA Astrophysics Data System (ADS)

    Masihzadeh, Omid; Ammar, David A.; Kahook, Malik Y.; Gibson, Emily A.; Lei, Tim C.

    2013-03-01

    The aqueous outflow system (AOS), including the trabecular meshwork (TM), the collector channels (CC) and the Schlemm's canal (SC), regulates intraocular pressure (IOP) through the drainage of the aqueous humor (AH). Abnormal IOP elevation leads to increased pressure stress to retinal ganglion cells, resulting in cell loss that can ultimately lead to complete loss of eyesight. Therefore, development of imaging tools to detect abnormal structural and functional changes of the AOS is important in early diagnosis and prevention of glaucoma. Multiphoton microscopy (MPM), including twophoton autofluorescence (TPAF) and second harmonic generation (SHG), is a label-free microscopic technique that allows molecular specific imaging of biological tissues like the TM. Since the TM and other AOS structures are located behind the highly scattering scleral tissue, transscleral imaging of the TM does not provide enough optical resolution. In this work, a gonioscopic lens is used to allow direct optical access of the TM through the cornea for MPM imaging. Compared to transscleral imaging, the acquired MPM images show improved resolution as individual collagen fiber bundles of the TM can be observed. MPM gonioscopy may have the potential to be developed as a future clinical imaging tool for glaucoma diagnostics.

  5. Optical visualization of Alzheimer’s pathology via multiphoton-excited intrinsic fluorescence and second harmonic generation

    PubMed Central

    Kwan, Alex C.; Duff, Karen; Gouras, Gunnar K.; Webb, Watt W.

    2010-01-01

    Intrinsic optical emissions, such as autofluorescence and second harmonic generation (SHG), are potentially useful for functional fluorescence imaging and biomedical disease diagnosis for neurodegenerative diseases such as Alzheimer’s disease (AD). Here, using multiphoton and SHG microscopy, we identified sources of intrinsic emissions in ex vivo, acute brain slices from AD transgenic mouse models. We observed autofluorescence and SHG at senile plaques as well as characterized their emission spectra. The utility of intrinsic emissions was demonstrated by imaging senile plaque autofluorescence in conjunction with SHG from microtubule arrays to assess the polarity of microtubules near pathological lesions. Our results suggest that tissues from AD transgenic models contain distinct intrinsic emissions, which can provide valuable information about the disease mechanisms. PMID:19259208

  6. Application of Multiphoton Microscopy in Dermatological Studies: a Mini-Review

    PubMed Central

    Yew, Elijah; Rowlands, Christopher

    2014-01-01

    This review summarizes the historical and more recent developments of multiphoton microscopy, as applied to dermatology. Multiphoton microscopy offers several advantages over competing microscopy techniques: there is an inherent axial sectioning, penetration depths that compete well with confocal microscopy on account of the use of near-infrared light, and many two-photon contrast mechanisms, such as second-harmonic generation, have no analogue in one-photon microscopy. While the penetration depths of photons into tissue are typically limited on the order of hundreds of microns, this is of less concern in dermatology, as the skin is thin and readily accessible. As a result, multiphoton microscopy in dermatology has generated a great deal of interest, much of which is summarized here. The review covers the interaction of light and tissue, as well as the various considerations that must be made when designing an instrument. The state of multiphoton microscopy in imaging skin cancer and various other diseases is also discussed, along with the investigation of aging and regeneration phenomena, and finally, the use of multiphoton microscopy to analyze the transdermal transport of drugs, cosmetics and other agents is summarized. The review concludes with a look at potential future research directions, especially those that are necessary to push these techniques into widespread clinical acceptance. PMID:25075226

  7. Visualizing dynamics of sub-hepatic distribution of nanoparticles using intravital multiphoton fluorescence microscopy.

    PubMed

    Cheng, Shih-Hsun; Li, Feng-Chieh; Souris, Jeffrey S; Yang, Chung-Shi; Tseng, Fan-Gang; Lee, Hsuan-Shu; Chen, Chin-Tu; Dong, Chen-Yuan; Lo, Leu-Wei

    2012-05-22

    Nanoparticles that do not undergo renal excretion or in vivo degradation into biocompatible debris often accumulate in the reticuloendothelial system, also know as the mononuclear phagocyte system, with undesired consequences that limit their clinical utility. In this work, we report the first application of intravital multiphoton fluorescence microscopy to dynamically track the hepatic metabolism of nanoparticles with subcellular resolution in real time. Using fluorescently labeled mesoporous silica nanoparticles (MSNs) in mice as a prototypical model, we observed significant hepatocyte uptake of positively charged, but not negatively charged, moieties. Conversely, in vivo imaging of negatively charged, but not positively charged, MSNs reveals an overwhelming propensity for the former's rapid uptake by Kupffer cells in liver sinusoids. Since the only prerequisite for these studies was that nanoparticles are fluorescently labeled and not of a specific composition or structure, the techniques we present can readily be extended to a wide variety of nanoparticle structures and surface modifications (e.g., shape, charge, hydrophobicity, PEGylation) in the preclinical assessment and tailoring of their hepatotoxicities and clearances.

  8. The skin immune atlas: three-dimensional analysis of cutaneous leukocyte subsets by multiphoton microscopy.

    PubMed

    Tong, Philip L; Roediger, Ben; Kolesnikoff, Natasha; Biro, Maté; Tay, Szun S; Jain, Rohit; Shaw, Lisa E; Grimbaldeston, Michele A; Weninger, Wolfgang

    2015-01-01

    Site-specific differences in skin response to pathogens and in the course of cutaneous inflammatory diseases are well appreciated. The composition and localization of cutaneous leukocytes has been studied extensively using histology and flow cytometry. However, the precise three-dimensional (3D) distribution of distinct immune cell subsets within skin at different body sites requires visualization of intact living skin. We used intravital multiphoton microscopy in transgenic reporter mice in combination with quantitative flow cytometry to generate a 3D immune cell atlas of mouse skin. The 3D location of innate and adaptive immune cells and site-specific differences in the densities of macrophages, T cells, and mast cells at four defined sites (ear, back, footpad, and tail) is presented. The combinatorial approach further demonstrates an as yet unreported age-dependent expansion of dermal gamma-delta T cells. Localization of dermal immune cells relative to anatomical structures was also determined. Although dendritic cells were dispersed homogeneously within the dermis, mast cells preferentially localized to the perivascular space. Finally, we show the functional relevance of site-specific mast cell disparities using the passive cutaneous anaphylaxis model. These approaches are applicable to assessing immune cell variations and potential functional consequences in the setting of infection, as well as the pathogenesis of inflammatory skin conditions.

  9. Multi-photon Imaging of Actin Filament Formation and Mitochondrial Energetics of Human ACBT Gliomas

    PubMed Central

    Hwang, Yu-Jer; Kolettis, Nomiki; Yang, Miso; Gillard, Elizabeth R.; Sanchez, Edgar; Sun, Chung-ho; Tromberg, Bruce J.; Krasieva, Tatiana B.; Lyubovitsky, Julia G.

    2011-01-01

    We studied the three-dimensional (3D) distribution of actin filaments and mitochondria in relation to ACBT glioblastoma cells migration. We embedded the cells in the spheroid form within collagen hydrogels and imaged them by in-situ multi-photon microscopy (MPM). The static 3D overlay of the distribution of actin filaments and mitochondria provided a greater understanding of cell-to-cell and cell-to-substrate interactions and morphology. While imaging mitochondria to obtain ratiometric redox index based on cellular fluorescence from reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD) we observed differential sensitivity of the migrating ACBT glioblastoma cells to femtosecond laser irradiation employed in MPM. We imaged actin-GFP fluorescence in live ACBT glioma cells and for the first time observed dynamic modulation of the pools of actin during migration in 3D. The MPM imaging, which probes cells directly within the 3D cancer models, could potentially aid in working out a link between the functional performance of mitochondria, actin distribution and cancer invasiveness. PMID:21143483

  10. Analyses of cryogenic samples using ion-induced desorption and multiphoton resonance ionization.

    PubMed

    Ervin, M H; Wood, M C; Winograd, N

    1993-02-15

    In this study, ion-beam-induced desorption with multiphoton resonance ionization detection of desorbed neutral molecules is used to characterize frozen aqueous solutions. This type of matrix is of particular importance since it serves as a model for biological matrices. The time-of-flight mass spectrum, obtained in this way for a millimolar tryptophan/H2O solution, is virtually identical to that for a submonolayer of tryptophan on a silicon wafer. The tryptophan signal from a frozen solution is demonstrated to have a linear dependence on concentration by using 4,4'-biphenyldiol as an internal standard. A detection limit of 2 x 10(-6) M is also demonstrated. Since our ion beam samples one layer of 0.1 cm2 and we assume 10(15) molecules/cm2 of ice, this concentration corresponds to approximately 4 x 10(6) molecules/layer. It is also shown that the signal exhibits an exponential decay with primary ion dose due to the accumulation of primary ion damage in the near-surface molecules.

  11. Peak-power dependence of rovibronic populations below the quasicontinuum during IR multiphoton absorption

    SciTech Connect

    Brenner, D M

    1981-01-01

    Experimental studies on IR multiphoton absorption and dissociation have generally provided insight only into the relationship of IR laser characteristics such as power, wavelength, and mode structure to the observables dissociation yields, average number of photons absorbed, and product energy distribution. As a result, theoretical modeling of absorption at levels below the quasicontinuum has been based on facts somewhat removed from the actual phenomenon of interest. The experiments presented here provide information on the unperturbed rotational/vibrational populations of levels subsequent to IR excitation at levels below 4000 cm/sup -1/ of energy. The experiment makes use of molecular beam techniques in conjunction with IR-visible double resonance. A CO/sub 2/ laser of known pulse duration prepares vibrationally excited thiophosgene, Cl/sub 2/C = S. The absorbing transition is 2 ..nu../sub 4/. A tunable nitrogen-pumped dye laser scans the visible excitation spectrum to probe the perturbed rotational-vibrational populations of the pumped mode. Because the electronic transition is electric dipole forbidden, combination hot bands having the appropriate quantum numbers of the ground state are used in the analysis.

  12. Adhesion and migration of ovarian cancer cells on crosslinked laminin fibers nanofabricated by multiphoton excited photochemistry

    PubMed Central

    Chen, Xiyi; Brewer, Molly A.; Zou, Changping; Campagnola, Paul J.

    2013-01-01

    Ovarian cancer is the deadliest gynecological cancer, which may arise in part due to the concurrent invasion and metastasis of high grade tumors. It is thus crucial to gain insight into the adhesion and migration mechanisms in vivo, as this may ultimately lead to new treatment/detection options. To explore this possibility, we have used multiphoton excited photochemistry (MPE) to synthesize models of the ovarian basal lamina consisting of crosslinked laminin nanofibers to quantify the adhesion/migration dynamics. The nanostructured laminin patterns permit the systematic comparison of total migration, directed migration, adhesion, and morphology of “normal” immortalized human ovarian epithelial cells (IOSE) and three lines of varying metastatic potential (OVCA433, SKOV-3.ip1, and HEY-1 cells). We find that the migration of all the cell lines is directed by the crosslinked fibers, and that the contact guidance enhances the total migration rates relative to monolayers. These rates increase with increasing metastatic potential, and the more invasive cells are less rigid and more weakly adhered to the nanofibers. The extent of directed migration also depends on the cell polarity and focal adhesion expression. For the invasive cells, these findings are similar to the integrin-independent ameboid-like migration seen for polar cells in collagen gels. Collectively, the results suggest that contact mediated migration as well as decreased adhesion may be operative in metastasis of ovarian cancer in vivo. PMID:20023757

  13. Directed Self-Assembly of Block Copolymers in 3D Templates Fabricated by Multiphoton Lithography

    NASA Astrophysics Data System (ADS)

    Singer, Jonathan; Thomas, Edwin

    2012-02-01

    Confinement of block-copolymers (BCP) within physical templates has been used as a method to both enhance the microdomain order and manipulate the morphology. Previous investigations have focused on 1D or quasi-2D templates (e.g. trenches, cylindrical pores) patterned at a variety of length scales. We have sought to employ the nearly-arbitrary structural fabrication afforded by multiphoton direct write lithography (MPL) to extend these stereolithographic control techniques to 3D directed assembly. Complex architectures, for example those formed by large scale lithographic techniques such as interference lithography or self-assembly, can be broken down into simplifier component structures: e.g. multibranch junctions, bends, and symmetric or asymmetric connecting pores. By utilizing MPL, we can fabricate model geometries possessing these features written in photoresist at various scales. We then infiltrate these structures with PS-PDMS BCP and observe the resulting morphology by SEM from focused ion beam cross-sections, allowing development of design rules that may be applied towards progressively more complex templates and the fabrication of 3D hierarchical structures with highly ordered and novel domain features spanning from the micron to the 10 nm scale.

  14. Resonant IR multi-photon dissociation spectroscopy of a trapped and sympathetically cooled biomolecular ion species.

    PubMed

    Wellers, Ch; Borodin, A; Vasilyev, S; Offenberg, D; Schiller, S

    2011-11-14

    In this work we demonstrate vibrational spectroscopy of polyatomic ions that are trapped and sympathetically cooled by laser-cooled atomic ions. We use the protonated dipeptide tryptophan-alanine (HTyrAla(+)) as a model system, cooled by barium ions to less than 800 mK secular temperature. The spectroscopy is performed on the fundamental vibrational transition of a local vibrational mode at 2.74 μm using a continuous-wave optical parametric oscillator (OPO). Resonant IR multi-photon dissociation spectroscopy (R-IRMPD) (without the use of a UV laser) generates charged molecular fragments, which are sympathetically cooled and trapped, and subsequently released from the trap and counted. We measured the cross section for R-IRMPD under conditions of low intensity, and found it to be approximately two orders smaller than the vibrational excitation cross section. The observed rotational bandwidth of the vibrational transition is larger than the one expected from the combined effects of 300 K black-body temperature, conformer-dependent line shifts, and intermolecular vibrational relaxation broadening (J. Stearns et al., J. Chem. Phys., 2007, 127, 154322-154327). This indicates that as the internal energy of the molecule grows, an increase of the rotational temperature of the molecular ions well above room temperature (up to on the order of 1000 K), and/or an appreciable shift of the vibrational transition frequency (approx. 6-8 cm(-1)) occurs.

  15. Comparison of infrared multiphoton dissociation and collision-induced dissociation of supercharged peptides in ion traps.

    PubMed

    Madsen, James A; Brodbelt, Jennifer S

    2009-03-01

    The number and types of diagnostic ions obtained by infrared multiphoton dissociation (IRMPD) and collision-induced dissociation (CID) were evaluated for supercharged peptide ions created by electrospray ionization of solutions spiked with m-nitrobenzyl alcohol. IRMPD of supercharged peptide ions increased the sequence coverage compared with that obtained by CID for all charge states investigated. The number of diagnostic ions increased with the charge state for IRMPD; however, this trend was not consistent for CID because the supercharged ions did not always yield the greatest number of diagnostic ions. Significantly different fragmentation pathways were observed for the different charge states upon CID or IRMPD with the latter yielding far more immonium ions and often fewer uninformative ammonia, water, and phosphoric acid neutral losses. Pulsed-Q dissociation resulted in an increase in the number of internal product ions, a decrease in sequence-informative ions, and reduced overall ion abundances. The enhanced sequence coverage afforded by IRMPD of supercharged ions was demonstrated for a variety of model peptides, as well as for a tryptic digest of cytochrome c.

  16. In vivo multiphoton and second harmonic generation microscopy of epithelial carcinogenesis

    NASA Astrophysics Data System (ADS)

    Vargas, Gracie; Shilagard, Tuya; Sun, Ju; Motamedi, Massoud

    2006-02-01

    Multiphoton microscopy and second harmonic generation microscopy were used to image epithelial changes in a hamster model for oral malignant transformation. In vivo imaging was performed to characterize morphometric alterations in normal and precancerous regions. Morphometric measurements such as cell nucleus area and epithelial thicknesses obtained from MPM-SHGM were in excellent agreement with histology obtained after in vivo imaging. MPM-SHGM was highly sensitive to spectroscopic and architectural alterations throughout carcinogenesis, showing statistically significant changes in morphology. MPM revealed hyperkeratosis, nuclear enlargement/crowding in dysplasia, and immune cell infiltration. SHGM revealed alterations in submucosal architecture, with a decrease in SHG density evident during early stages of precancer. By combining MPM with SHGM, the basement membrane could be identified in normal, hyperplasia, and dysplasia samples and in some cases of early invasion. The combined technique of MPM-SHGM has the potential to serve as an adjunct to biopsy for assessing precancerous changes and will be investigated further for that purpose. Additionally, the method can provide spatiotemporal assessment of early neoplastic changes in order to elucidate the stages of transformation in vivo and could be used to assess therapeutic efficacy of agents being tested for the treatment of epithelial precancers/cancer.

  17. Evaluation of endogenous species involved in brain tumors using multiphoton photoacoustic spectroscopy

    NASA Astrophysics Data System (ADS)

    Dahal, Sudhir; Cullum, Brian M.

    2013-05-01

    It has been shown that using non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), excised brain tumor (grade III astrocytoma) and healthy tissue can be differentiated from each other, even in neighboring biopsy samples[1, 2]. Because of this, this powerful technique offers a great deal of potential for use as a surgical guidance technique for tumor margining with up to cellular level spatial resolution[3]. NMPPAS spectra are obtained by monitoring the non-radiative relaxation pathways via ultrasonic detection, following two-photon excitation with light in the optical diagnostic window (740nm-1100nm). Based upon significant differences in the ratiometric absorption of the tissues following 970nm and 1100nm excitation, a clear classification of the tissue can be made. These differences are the result of variations in composition and oxidation state of certain endogenous biochemical species between healthy and malignant tissues. In this work, NADH, NAD+ and ATP were measured using NMPPAS in model gelatin tissue phantoms to begin to understand which species might be responsible for the observed spectral differences in the tissue. Each species was placed in specific pH environments to provide control over the ratio of oxidized to reduced forms of the species. Ratiometric analyses were then conducted to account for variability caused due to instrumental parameters. This paper will discuss the potential roles of each of the species for tumor determination and their contribution to the spectral signature.

  18. Multi-photon microfabrication of three-dimensional capillary-scale vascular networks

    NASA Astrophysics Data System (ADS)

    Skylar-Scott, Mark A.; Liu, Man-Chi; Wu, Yuelong; Yanik, Mehmet Fatih

    2017-02-01

    Biomimetic models of microvasculature could enable assays of complex cellular behavior at the capillary-level, and enable efficient nutrient perfusion for the maintenance of tissues. However, existing three-dimensional printing methods for generating perfusable microvasculature with have insufficient resolution to recapitulate the microscale geometry of capillaries. Here, we present a collection of multiphoton microfabrication methods that enable the production of precise, three-dimensional, branched microvascular networks in collagen. When endothelial cells are added to the channels, they form perfusable lumens with diameters as small as 10 μm. Using a similar photochemistry, we also demonstrate the micropatterning of proteins embedded in microfabricated collagen scaffolds, producing hybrid scaffolds with both defined microarchitecture with integrated gradients of chemical cues. We provide examples for how these hybrid microfabricated scaffolds could be used in angiogenesis and cell homing assays. Finally, we describe a new method for increasing the micropatterning speed by synchronous laser and stage scanning. Using these technologies, we are working towards large-scale (>1 cm), high resolution ( 1 μm) scaffolds with both microarchitecture and embedded protein cues, with applications in three-dimensional assays of cellular behavior.

  19. Possibility of efficient generation of multiphoton entangled states using a one-dimensional nonlinear photonic crystal

    SciTech Connect

    Dong Yunxia; Zhang Xiangdong

    2010-03-15

    A rigorous quantum theory for the generation of multiphoton entangled states based on two consecutive three-frequency interactions of waves in a one-dimensional nonlinear photonic crystal is developed using the field expansion and differentiation methods. The three-photon correlation coefficient and the average photon numbers generated in the structure are calculated. All order expansion terms are included in the calculation. The generation conditions for multiphoton entangled states in such a structure are also analyzed. It is shown that the created photons in the present structures obey the super-Poisson statistics at the interacting frequencies and are in a multiparticle entangled state. This means the nonlinear photonic crystal can be applied as a highly efficient source of an entangled multiphoton for highly integrated all-optical circuits.

  20. Label-free multiphoton imaging and photoablation of preinvasive cancer cells

    NASA Astrophysics Data System (ADS)

    Zhuo, Shuangmu; Chen, Jianxin; Wu, Guizhu; Zhu, Xiaoqin; Jiang, Xingshan; Xie, Shusen

    2012-01-01

    Detection and treatment of early lesions in epithelial tissue offer several possibilities for curing cancer, but it is challenging. Here, we present an optical technique, the combination of multiphoton imaging and absorption, to label-freely detect and ablate preinvasive cancer cells in epithelial tissue. We find that multiphoton imaging can label-freely visualize the principal features of nuclear atypia associated with epithelial precancerous lesions, and the spatial localization of multiphoton absorption can perform targeted ablation of preinvasive cancer cells with micrometer-sized volume precision. These results indicate that this optical technique has the capability to label-freely visualize and remove preinvasive cancer cells in epithelial tissue. This study highlights the potential of this technique as a "seek-and-treat" tool for early lesions in epithelial tissue.

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

    NASA Astrophysics Data System (ADS)

    Liu, N. R.; Chen, G. N.; Wu, S. S.; Chen, R.

    2014-02-01

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

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

    SciTech Connect

    Makris, M. G.; Lambropoulos, P.; Mihelic, A.

    2009-01-23

    We present a theoretical interpretation of recent experimental results on multiphoton multiple ionization of xenon by soft-x-ray radiation of photon energy {approx}93 eV and intensity up to 10{sup 16} W/cm{sup 2}[A. A Sorokin et al., Phys. Rev. Lett. 99, 213002 (2007)]. The data are interpreted within multiphoton perturbation theory, taking into account the spatiotemporal distribution of the radiation. Multiphoton cross sections have been obtained through a technique of scaling, with occasional adjustment to the data, provided the two prove to be compatible. Whatever discrepancies between theory and experiment persist can be reasonably attributed to some uncertainty in the experimental conditions and possibly to the value of some cross sections, without, however, any evidence for nonperturbative behavior.

  3. Ultrafast pulse-pair control in multiphoton fluorescence laser-scanning microscopy.

    PubMed

    De, Arijit Kumar; Goswami, Debabrata

    2009-01-01

    In multiphoton fluorescence laser-scanning microscopy, ultrafast laser pulses [i.e., light pulses having pulse width multiphoton absorption cross-sections of common fluorophores. Because of the broad overlapping two-photon absorption spectra of fluorophores and the large spectral bandwidth of a short pulse, simultaneous excitation of many fluorophores is common, which justifies a persistent demand for selective excitation of individual fluorophores. We describe the use of pulse-pair excitation with possibilities of controlling molecular fluorescence in laser-scanning microscopy and compare it with coherent control using pulse sequence [De and Goswami, "Coherent control in multiphoton fluorescence imaging," Proc. SPIE 7183, 71832B (2009)].

  4. Three-dimensional tooth imaging using multiphoton and second harmonic generation microscopy

    NASA Astrophysics Data System (ADS)

    Chen, Min-Huey; Chen, Wei-Liang; Sun, Yen; Fwu, Peter Tramyeon; Lin, Ming-Gu; Dong, Chen-Yuan

    2007-02-01

    Detailed morphological and cellular information relating to the human tooth have traditionally been obtained through histological studies that required decalcification, staining, and fixation. With the recent invention of multiphoton microscopy, it has become possible to acquire high resolution images without histological procedures. Using an epiilluminated multiphoton microscope, we obtained two-photon excited autofluorescence and second harmonic generation (SHG) images of ex vivo human tooth. By combining these two imaging modalities we obtained submicron resolution images of the enamel, dentin, and the periodontal ligaments. The enamel emits endogenous two-photon autofluorescence. The structure of the dentin is visible from both the autofluorescence and second harmonic generation signals. The periodontal ligament composed mostly of collagen can be visualized by SHG imaging. We also constructed three dimensional images of the enamel, dentin, and periodontal ligament. The effectiveness of using multiphoton and second harmonic generation microscopy to obtain structural information of teeth suggest its potential use in dental diagnostics.

  5. Kerr nonlinearity and multi-photon absorption in germanium at mid-infrared wavelengths

    NASA Astrophysics Data System (ADS)

    Sohn, B.-U.; Monmeyran, C.; Kimerling, L. C.; Agarwal, A. M.; Tan, D. T. H.

    2017-08-01

    Multiphoton absorption coefficients and nonlinear refractive indices of germanium in the near and mid-infrared (2-5 μm) are reported. The nonlinear coefficients are measured by open and closed aperture Z-scan with 150 fs pulses at a repetition rate of 1 kHz. The nonlinear refractive index of Ge has a peak value of 9.1 ×10-5cm2/GW at a wavelength of 3 μm. The effect of free electrons generated by multiphoton absorption is discussed by investigating the variation of multiphoton absorption coefficients at different input powers. Kramers-Kronig relations are also discussed with regard to the relationship between nonlinear refractive index and two photon absorption coefficient.

  6. In vivo microscopy of the mouse brain using multiphoton laser scanning techniques

    NASA Astrophysics Data System (ADS)

    Yoder, Elizabeth J.

    2002-06-01

    The use of multiphoton microscopy for imaging mouse brain in vivo offers several advantages and poses several challenges. This tutorial begins by briefly comparing multiphoton microscopy with other imaging modalities used to visualize the brain and its activity. Next, an overview of the techniques for introducing fluorescence into whole animals to generate contrast for in vivo microscopy using two-photon excitation is presented. Two different schemes of surgically preparing mice for brain imaging with multiphoton microscopy are reviewed. Then, several issues and problems with in vivo microscopy - including motion artifact, respiratory and cardiac rhythms, maintenance of animal health, anesthesia, and the use of fiducial markers - are discussed. Finally, examples of how these techniques have been applied to visualize the cerebral vasculature and its response to hypercapnic stimulation are provided.

  7. Two-photon imaging of intact living plants during freezing with a flexible multiphoton tomograph

    NASA Astrophysics Data System (ADS)

    Breunig, H. G.; König, K.

    2015-02-01

    We describe the combination of a flexible multiphoton tomograph (MPTflex) with a heating and cooling stage. The stage allows temperature control in the range of (-196 °C) (77 K) to +600 °C (873 K) with selectable heating/freezing rates between 0.01 K min-1 and 150 K min-1. To illustrate the imaging capabilities of the combined system, fluorescence intensity and lifetime of intrinsic molecules from a plant leaf were imaged with submicron resolution during freezing in vivo without detaching the leaf from the plant. An increase of fluorescence intensity and decay times with decreasing temperature was observed. The measurements illustrate the usefulness of multiphoton imaging as a non-invasive online tool to investigate temperature-induced effects. The flexible multiphoton tomograph with its adjustable mechano-optical arm and scan head allows imaging at otherwise hardly accessible sample regions.

  8. Real-time optical diagnosis of gastric cancer with serosal invasion using multiphoton imaging

    PubMed Central

    Yan, Jun; Zheng, Yu; Zheng, Xiaoling; Liu, Zhangyuanzhu; Liu, Wenju; Chen, Dexin; Dong, Xiaoyu; Li, Kai; Liu, Xiumin; Chen, Gang; Lu, Jianping; Chen, Jianxin; Zhuo, Shuangmu; Li, Guoxin

    2016-01-01

    A real-time optical biopsy, which could determine tissue histopathology, would be of extraordinary benefit to staging laparoscopy for gastric cancer with serosal invasion (T4) that requires downstage treatment. We investigated the feasibility of using multiphoton imaging to perform a real-time optical diagnosis of gastric cancer with or without serosal invasion. First, a pilot study was performed to establish the optical diagnostic features of gastric cancer with or without serosal invasion using multiphoton imaging compared with hematoxylin-eosin staining and Masson’s trichrome staining. Second, a blinded study was performed to compare the diagnostic sensitivity, specificity, and accuracy of multiphoton imaging and endoscopic ultrasonography (EUS) for T4 gastric cancer. In the pilot study, multiphoton imaging revealed collagen loss and degradation and cellular and nuclear pleomorphism in gastric cancer with serosal invasion. The collagen content in gastric cancer with or without serosal invasion was 0.36 ± 0.18 and 0.79 ± 0.16 (p < 0.001), respectively. In the blinded study, the sensitivity, specificity, and accuracy of EUS and multiphoton imaging for T4 gastric cancer were 70% and 90% (p = 0.029), 66.67% and 96.67% (p = 0.003), and 68.33% and 93.33% (p = 0.001), respectively. It is feasible to use multiphoton imaging to make a real-time optical diagnosis of gastric cancer with or without serosal invasion. PMID:27499365

  9. Multiphoton imaging reveals that nanosecond pulsed electric fields collapse tumor and normal vascular perfusion in human glioblastoma xenografts

    PubMed Central

    Bardet, Sylvia M.; Carr, Lynn; Soueid, Malak; Arnaud-Cormos, Delia; Leveque, Philippe; O’Connor, Rodney P.

    2016-01-01

    Despite the biomedical advances of the last century, many cancers including glioblastoma are still resistant to existing therapies leaving patients with poor prognoses. Nanosecond pulsed electric fields (nsPEF) are a promising technology for the treatment of cancer that have thus far been evaluated in vitro and in superficial malignancies. In this paper, we develop a tumor organoid model of glioblastoma and apply intravital multiphoton microscopy to assess their response to nsPEFs. We demonstrate for the first time that a single 10 ns, high voltage electric pulse (35–45 kV/cm), collapses the perfusion of neovasculature, and also alters the diameter of capillaries and larger vessels in normal tissue. These results contribute to the fundamental understanding of nsPEF effects in complex tissue environments, and confirm the potential of nsPEFs to disrupt the microenvironment of solid tumors such as glioblastoma. PMID:27698479

  10. Comparison of HORACE and PHOTOS Algorithms for Multi-Photon Emission in the Context of the W Boson Mass Measurement

    DOE PAGES

    Kotwal, Ashutosh V.; Jayatilaka, Bodhitha

    2016-01-01

    W boson mass measurement is sensitive to QED radiative corrections due to virtual photon loops and real photon emission. The largest shift in the measured mass, which depends on the transverse momentum spectrum of the charged lepton from the boson decay, is caused by the emission of real photons from the final-state lepton. There are a number of calculations and codes available to model the final-state photon emission. We perform a detailed study, comparing the results from HORACE and PHOTOS implementations of the final-state multiphoton emission in the context of a direct measurement ofW boson mass at Tevatron. Mass fitsmore » are performed using a simulation of the CDF II detector.« less

  11. Comparison of HORACE and PHOTOS Algorithms for Multi-Photon Emission in the Context of the W Boson Mass Measurement

    SciTech Connect

    Kotwal, Ashutosh V.; Jayatilaka, Bodhitha

    2016-01-01

    W boson mass measurement is sensitive to QED radiative corrections due to virtual photon loops and real photon emission. The largest shift in the measured mass, which depends on the transverse momentum spectrum of the charged lepton from the boson decay, is caused by the emission of real photons from the final-state lepton. There are a number of calculations and codes available to model the final-state photon emission. We perform a detailed study, comparing the results from HORACE and PHOTOS implementations of the final-state multiphoton emission in the context of a direct measurement ofW boson mass at Tevatron. Mass fits are performed using a simulation of the CDF II detector.

  12. Rapid diagnosis of liver fibrosis using multimodal multiphoton nonlinear optical microspectroscopy imaging.

    PubMed

    Lee, Jang Hyuk; Kim, Jong Chul; Tae, Giyoong; Oh, Myoung-Kyu; Ko, Do-Kyeong

    2013-07-01

    A multimodal multiphoton nonlinear optical (NLO) microspectroscopy imaging system was developed using a femtosecond laser and a photonic crystal fiber. Coherent anti-Stokes Raman scattering (CARS) microspectroscopy was combined with two-photon excitation fluorescence and second-harmonic generation microscopy in one platform and the system was applied to diagnose liver fibrosis. Normal and liver fibrosis tissues were clearly distinguished with the great difference from CARS spectra as well as multimodal multiphoton NLO images. We expect the system to be a rapid diagnosis tool for liver fibrosis at tissue level with label-free imaging of significant biochemical components.

  13. Diagrammatic analysis of multiphoton processes in a ladder-type three-level atomic system

    SciTech Connect

    Noh, Heung-Ryoul; Moon, Han Seb

    2011-11-15

    We present a diagrammatic method for complete characterization of multiphoton processes in three-level atomic systems. By considering the interaction routes of the coupling and probe photons for a ladder-type, three-level, noncycling (or cycling) atomic system, we are able to completely discriminate between the pure one-photon and the pure two-photon resonance effects, and the effect of their combination in electromagnetically induced transparency (EIT) using our diagrammatic method. We show that the proposed diagrammatic method is very useful for the analysis of multiphoton processes in ladder-type EIT.

  14. Multiphoton adaptation of a commercial low-cost confocal microscope for live tissue imaging.

    PubMed

    Mancuso, James J; Larson, Adam M; Wensel, Theodore G; Saggau, Peter

    2009-01-01

    The Nikon C1 confocal laser scanning microscope is a relatively inexpensive and user-friendly instrument. We describe a straightforward method to convert the C1 for multiphoton microscopy utilizing direct coupling of a femtosecond near-infrared laser into the scan head and fiber optic transmission of emission light to the three-channel detector box. Our adapted system can be rapidly switched between confocal and multiphoton mode, requires no modification to the original system, and uses only a few custom-made parts. The entire system, including scan mirrors and detector box, remain under the control of the user-friendly Nikon EZ-C1 software without modification.

  15. Switching the vibrational excitation of a polyatomic ion in multi-photon strong field ionization

    NASA Astrophysics Data System (ADS)

    Liu, Yuzhu; Gerber, Thomas; Radi, Peter; Sych, Yaroslav; Knopp, Gregor

    2014-08-01

    The multiphoton ionization (MPI) of CH3I has been investigated by angular resolved photoelectron spectroscopy as a function of femtosecond laser excitation intensity. A sudden change in the electron kinetic energy is observed above a specific field strength. The multiphoton excitation at a fixed wavelength of 800 nm becomes vibronically resonant due to Stark shifting of intermediate Rydberg state levels. The present letter gives an experimental evidence for ultrafast optical control of the vibrational excitation in a polyatomic ion by adjusting the intensity of a femtosecond laser pulse.

  16. Suppression of Multiphoton Resonances in Driven Quantum Systems via Pulse Shape Optimization

    NASA Astrophysics Data System (ADS)

    Gagnon, Denis; Fillion-Gourdeau, François; Dumont, Joey; Lefebvre, Catherine; MacLean, Steve

    2017-08-01

    This Letter demonstrates control over multiphoton absorption processes in driven two-level systems, which include, for example, superconducting qubits or laser-irradiated graphene, through spectral shaping of the driving pulse. Starting from calculations based on Floquet theory, we use differential evolution, a general purpose optimization algorithm, to find the Fourier coefficients of the driving function that suppress a given multiphoton resonance in the strong field regime. We show that the suppression of the transition probability is due to the coherent superposition of high-order Fourier harmonics which closes the dynamical gap between the Floquet states of the two-level system.

  17. Reversed interplay of quantum interference and which-way information in multiphoton entangled states

    NASA Astrophysics Data System (ADS)

    Ra, Young-Sik; Tichy, Malte C.; Lim, Hyang-Tag; Gneiting, Clemens; Mølmer, Klaus; Buchleitner, Andreas; Kim, Yoon-Ho

    2017-08-01

    We report experimental studies of quantum interference of multiphoton states impinging on a two-port balanced beam splitter. When the distinguishability between the two input paths is increased, we observe a reduction followed by a resurgence of the interference visibility in multiphoton coincidence detection. We ascribe this unusual behavior to the competition among contributions from distinct number state components of the interfering fields. Our results suggest that wave-particle duality gives rise to a wide range of largely unexplored phenomena in multiparticle interference.

  18. Resonance enhanced multiphoton ionization spectroscopy of carbonyl sulphide

    NASA Astrophysics Data System (ADS)

    Morgan, Ross A.; Orr-Ewing, Andrew J.; Ascenzi, Daniela; Ashfold, Michael N. R.; Buma, Wybren Jan; Scheper, Connie R.; de Lange, Cornelis A.

    1996-08-01

    Rydberg excited states of the OCS molecule in the energy range 70500-86000 cm-1 have been investigated via the two and three photon resonance enhancements they provide in the mass resolved multiphoton ionization (MPI) spectrum of a jet-cooled sample of the parent molecule. Spectral interpretation has been assisted by companion measurements of the kinetic energies of the photoelectrons that accompany the various MPI resonances. The present study supports the earlier conclusions of Weinkauf and Boesl [J. Chem. Phys. 98, 4459 (1993)] regarding five Rydberg origins in the 70500-73000 cm-1 energy range, attributable to, respectively, states of 3Π, 1Π, 3Δ, 1Δ and 1Σ+ symmetry arising from the 4pλ←3π orbital promotion. We also identify a further 21 Rydberg origins at higher energies. These partition into clumps with quantum defects ca. 3.5 and 4.5, which we associate with the orbital promotions npλ←3π (n=5,6), and others with near integer quantum defect which are interpretable in terms of excitation to s,d and (possibly) f Rydberg orbitals. We also identify MPI resonances attributable to CO(X 1Σ+) fragments and to S atoms in both their ground (3P) and excited (1D) electronic states. Analysis of the former resonances confirms that the CO(X) fragments resulting from one photon dissociation of OCS at excitation wavelengths ca. 230 nm are formed with a highly inverted, bimodal rotational state population distribution, whilst the latter are consistent with previous reports of the wavelength dependence for forming ground and excited state S atoms in the near uv photolysis of OCS.

  19. Large field of view multiphoton microscopy of human skin

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  20. In Vivo Multiphoton Microscopy of Basal Cell Carcinoma

    PubMed Central

    Balu, Mihaela; Zachary, Christopher B.; Harris, Ronald M.; Krasieva, Tatiana B.; König, Karsten; Tromberg, Bruce J.; Kelly, Kristen M.

    2015-01-01

    Importance Basal cell carcinomas (BCCs) are diagnosed by clinical evaluation, which can include dermoscopic evaluation, biopsy, and histopathologic examination. Recent translation of multiphoton microscopy (MPM) to clinical practice raises the possibility of noninvasive, label-free in vivo imaging of BCCs that could reduce the time from consultation to treatment. Objectives To demonstrate the capability of MPM to image in vivo BCC lesions in human skin, and to evaluate if histopathologic criteria can be identified in MPM images. Design, Setting, and Participants Imaging in patients with BCC was performed at the University of California–Irvine Health Beckman Laser Institute & Medical Clinic, Irvine, between September 2012 and April 2014, with a clinical MPM-based tomograph. Ten BCC lesions were imaged in vivo in 9 patients prior to biopsy. The MPM images were compared with histopathologic findings. Main Outcomes and Measures MPM imaging identified in vivo and noninvasively the main histopathologic feature of BCC lesions: nests of basaloid cells showing palisading in the peripheral cell layer at the dermoepidermal junction and/or in the dermis. Results The main MPM feature associated with the BCC lesions involved nests of basaloid cells present in the papillary and reticular dermis. This feature correlated well with histopathologic examination. Other MPM features included elongated tumor cells in the epidermis aligned in 1 direction and parallel collagen and elastin bundles surrounding the tumors. Conclusions and Relevance This study demonstrates, in a limited patient population, that noninvasive in vivo MPM imaging can provide label-free contrast that reveals several characteristic features of BCC lesions. Future studies are needed to validate the technique and correlate MPM performance with histopathologic examination. PMID:25909650

  1. Multi-photon resonance phenomena using Laguerre-Gaussian beams

    NASA Astrophysics Data System (ADS)

    Hamideh Kazemi, Seyedeh; Mahmoudi, Mohammad

    2016-12-01

    We study the influence of laser profile on the linewidth of the optical spectrum of multi-photon resonance phenomena. First, we investigate the dependence of the absorption spectrum on the laser profile in a two-level system. Thanks to the Laguerre-Gaussian field, the linewidth of the one-photon optical pumping and two-photon absorption peaks are explicitly narrower than that obtained with a Gaussian field. In the next section, it is shown that, compared to the Gaussian fields, the Laguerre-Gaussian ones reduce the linewidth of the optical spectrum in the coherent population trapping. Interestingly, it turns out that the use of a Laguerre-Gaussian beam makes the linewidth of the spectrum narrower as compared with a Gaussian one in Doppler-broadened electromagnetically induced transparency. Moreover, we study the effect of the laser profile on the Autler-Townes doublet structure in the absorption spectrum for a laser-driven four-level atomic system. We also consider the different values of the Laguerre-Gaussian mode beam waist, and, perhaps more remarkably, we find that for the small waist values, the Autler-Townes doublet can be removed and a prominent narrow central peak appears in the absorption spectrum. Finally, we investigate the effect of the laser profile on the linewidth of the sub-natural three-photon absorption peak of double dark resonance. The differences in the linewidth are quite large, offering potential applications in metrology and isotope separation methods. Our results can be used for super ultra-high resolution laser spectroscopy and to improve the resolution of the technology of isotope/isomer separation and photo-biology even at essential overlap of the spectra of the different particles.

  2. a UV+VUV Multiphoton Ionization Scheme for OH Radicals

    NASA Astrophysics Data System (ADS)

    Beames, Joseph M.; Liu, Fang; Lester, Marsha I.

    2012-06-01

    OH radicals are of significant atmospheric interest as a dominant oxidizing agent in day-time tropospheric chemistry. In this study, a 1+1' multiphoton ionization (MPI) scheme is employed to record rotationally-resolved spectra of OH radicals via the A^2Σ^+ resonant intermediate state. UV excitation is used to prepare OH A^2Σ^+(v=1, {J}, F_i), which is subsequently ionized by a second photon of fixed frequency VUV (118.3 nm), generated by tripling the 355 nm output of a Nd:YAG laser. The mass-selected OH^+ ion signal from 1+1' MPI is detected using time-of flight mass spectrometry and compared with the laser-induced fluorescence (LIF) signal arising from OH A^2Σ^+-X^2π(1,0) excitation. The MPI signal is observed over a range of UV+VUV total energies, corresponding to various OH A^2Σ^+ (v=1, {J}, F_i) intermediate states, with relative intensities that differ considerably from LIF. The ion signal is enhanced relative to LIF at combined UV + VUV photon energies consistent with an autoionizing 3{d} Rydberg state that converges on the OH^+ A^3π ion core; direct ionization into OH^+ X^3Σ^- is forbidden in a one-photon electric-dipole transition from OH A^2Σ^+. The MPI intensities have been quantified relative to LIF over the OH A^2Σ^+-X^2π(1,0) region such that this scheme is now applicable for quantitative state-selective detection of OH X^2π. J. M. Beames, F. Liu, M. I. Lester and C. Murray, J. Chem. Phys. 134, 241102 (2011). J. D. Barr, A. De Fanis, J. M. Dyke, S. D. Gamblin, N. Hooper, A. Morris, S. Stranges, J. B. West, and T. G. Wright, J. Chem. Phys. 110, 345 (1999).

  3. Label-free in vivo in situ diagnostic imaging by cellular metabolism quantification with a flexible multiphoton endomicroscope (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Leclerc, Pierre; Hage, Charles-Henri; Fabert, Marc; Brevier, Julien; O'Connor, Rodney P.; Bardet-Coste, Sylvia M.; Habert, Rémi; Braud, Flavie; Kudlinski, Alexandre; Louradour, Frederic

    2017-02-01

    Multiphoton microscopy is a cutting edge imaging modality leading to increasing advances in biology and also in the clinical field. To use it at its full potential and at the very heart of clinical practice, there have been several developments of fiber-based multiphoton microendoscopes. The application for those probes is now limited by few major restrictions, such as the difficulty to collect autofluorescence signals from tissues and cells theses being inherently weak (e.g. the ones from intracellular NADH or FAD metabolites). This limitation reduces the usefulness of microendoscopy in general, effectively restraining it to morphological imaging modality requiring staining of the tissues. Our aim is to go beyond this limitation, showing for the first time label-free cellular metabolism monitoring, in vivo in situ in real time. The experimental setup is an upgrade of a recently published one (Ducourthial et.al, Scientific Reports, 2016) where femtosecond pulse fiber delivery is further optimized thank's to a new transmissive-GRISM-based pulse stretcher permitting high energy throughput and wide bandwidth. This device allows fast sequential operation with two different excitation wavelengths for efficient two-photon excited NADH and FAD autofluorescence endoscopic detection (i.e. 860 nm for FAD and 760 nm for NADH), enabling cellular optical redox ratio quantification at 8 frames/s. The obtained results on cell models in vitro and also on animal models in vivo (e.g. neurons of a living mouse) prove that we accurately assess the level of NADH and FAD at subcellular resolution through a 3-meters-long fiber with our miniaturized probe (O.D. =2.2 mm).

  4. Simulation of multi-photon emission isotopes using time-resolved SimSET multiple photon history generator

    SciTech Connect

    Chiang, Chih-Chieh; Lin, Hsin-Hon; Lin, Chang-Shiun; Chuang, Keh-Shih; Jan, Meei-Ling

    2015-07-01

    Abstract-Multiple-photon emitters, such as In-111 or Se-75, have enormous potential in the field of nuclear medicine imaging. For example, Se-75 can be used to investigate the bile acid malabsorption and measure the bile acid pool loss. The simulation system for emission tomography (SimSET) is a well-known Monte Carlo simulation (MCS) code in nuclear medicine for its high computational efficiency. However, current SimSET cannot simulate these isotopes due to the lack of modeling of complex decay scheme and the time-dependent decay process. To extend the versatility of SimSET for simulation of those multi-photon emission isotopes, a time-resolved multiple photon history generator based on SimSET codes is developed in present study. For developing the time-resolved SimSET (trSimSET) with radionuclide decay process, the new MCS model introduce new features, including decay time information and photon time-of-flight information, into this new code. The half-life of energy states were tabulated from the Evaluated Nuclear Structure Data File (ENSDF) database. The MCS results indicate that the overall percent difference is less than 8.5% for all simulation trials as compared to GATE. To sum up, we demonstrated that time-resolved SimSET multiple photon history generator can have comparable accuracy with GATE and keeping better computational efficiency. The new MCS code is very useful to study the multi-photon imaging of novel isotopes that needs the simulation of lifetime and the time-of-fight measurements. (authors)

  5. Three dimensional multiphoton imaging of fresh and whole mount developing mouse mammary glands

    PubMed Central

    2013-01-01

    Background The applications of multiphoton microscopy for deep tissue imaging in basic and clinical research are ever increasing, supplementing confocal imaging of the surface layers of cells in tissue. However, imaging living tissue is made difficult by the light scattering properties of the tissue, and this is extraordinarily apparent in the mouse mammary gland which contains a stroma filled with fat cells surrounding the ductal epithelium. Whole mount mammary glands stained with Carmine Alum are easily archived for later reference and readily viewed using bright field microscopy to observe branching architecture of the ductal network. Here, we report on the advantages of multiphoton imaging of whole mount mammary glands. Chief among them is that optical sectioning of the terminal end bud (TEB) and ductal epithelium allows the appreciation of abnormalities in structure that are very difficult to ascertain using either bright field imaging of the stained gland or the conventional approach of hematoxylin and eosin staining of fixed and paraffin-embedded sections. A second advantage is the detail afforded by second harmonic generation (SHG) in which collagen fiber orientation and abundance can be observed. Methods GFP-mouse mammary glands were imaged live or after whole mount preparation using a Zeiss LSM510/META/NLO multiphoton microscope with the purpose of obtaining high resolution images with 3D content, and evaluating any structural alterations induced by whole mount preparation. We describe a simple means for using a commercial confocal/ multiphoton microscope equipped with a Ti-Sapphire laser to simultaneously image Carmine Alum fluorescence and collagen fiber networks by SHG with laser excitation set to 860 nm. Identical terminal end buds (TEBs) were compared before and after fixation, staining, and whole mount preparation and structure of collagen networks and TEB morphologies were determined. Flexibility in excitation and emission filters was explored

  6. Non-invasive in vivo characterization of skin wound healing using label-free multiphoton microscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Jones, Jake D.; Majid, Fariah; Ramser, Hallie; Quinn, Kyle P.

    2017-02-01

    Non-healing ulcerative wounds, such as diabetic foot ulcers, are challenging to diagnose and treat due to their numerous possible etiologies and the variable efficacy of advanced wound care products. Thus, there is a critical need to develop new quantitative biomarkers and diagnostic technologies that are sensitive to wound status in order to guide care. The objective of this study was to evaluate the utility of label-free multiphoton microscopy for characterizing wound healing dynamics in vivo and identifying potential differences in diabetic wounds. We isolated and measured an optical redox ratio of FAD/(NADH+FAD) autofluorescence to provide three-dimensional maps of local cellular metabolism. Using a mouse model of wound healing, in vivo imaging at the wound edge identified a significant decrease in the optical redox ratio of the epidermis (p≤0.0103) between Days 3 through 14 compared to Day 1. This decrease in redox ratio coincided with a decrease in NADH fluorescence lifetime and thickening of the epithelium, collectively suggesting a sensitivity to keratinocyte hyperproliferation. In contrast to normal wounds, we have found that keratinocytes from diabetic wounds remain in a proliferative state at later time points with a lower redox ratio at the wound edge. Microstructural organization and composition was also measured from second harmonic generation imaging of collagen and revealed differences between diabetic and non-diabetic wounds. Our work demonstrates label-free multiphoton microscopy offers potential to provide non-invasive structural and functional biomarkers associated with different stages of skin wound healing, which may be used to detect delayed healing and guide treatment.

  7. Temperature alters solute transport in growth plate cartilage measured by in vivo multiphoton microscopy

    PubMed Central

    Serrat, Maria A.; Williams, Rebecca M.; Farnum, Cornelia E.

    2009-01-01

    Solute delivery to avascular cartilaginous plates is critical to bone elongation, and impaired transport of nutrients and growth factors in cartilage matrix could underlie many skeletal abnormalities. Advances in imaging technology have revolutionized our ability to visualize growth plates in vivo, but quantitative methods are still needed. We developed analytical standards for measuring solute delivery, defined by amount and rate of intravenous tracer entry, in murine growth plates using multiphoton microscopy. We employed an acute temperature model because of its well-established impact on bone circulation and tested the hypothesis that solute delivery changes positively with limb temperature when body core and respiration are held constant (36°C, 120 breaths/min). Tibial growth plates were surgically exposed in anesthetized 5-wk-old mice, and their hindlimbs were immersed in warm (36°C) or cool (23°C) saline (n = 6/group). After 30 min of thermal equilibration, we administered an intracardiac injection of fluorescein (50 μl, 0.5%) and captured sequentially timed growth plate images spanning 10 min at standardized depth. Absolute growth plate fluorescence was normalized to vascular concentrations for interanimal comparisons. As predicted, more fluorescein infiltrated growth plates at 36°C, with standardized values nearly double those at 23°C. Changing initial limb temperature did not alter baseline values, suggesting a sustained response period. These data validate the sensitivity of our system and have relevance to strategies for enhancing localized delivery of therapeutic agents to growth plates of children. Applications of this technique include assessment of solute transport in models of growth plate dysfunction, particularly chondrodysplasias with matrix irregularities. PMID:19372302

  8. Semiclassical analysis of long-wavelength multiphoton processes: The Rydberg atom

    SciTech Connect

    Vela-Arevalo, Luz V.; Fox, Ronald F.

    2004-06-01

    We study the problem of multiphoton processes for intense, long-wavelength irradiation of atomic and molecular electrons. An exact, nonperturbative approach is applied to the standard vector potential coupling Hamiltonian for a three-dimensional hydrogenlike atom in a microwave field treated semiclassically. Multiphoton probability exchange is calculated in both the velocity and the length gauges, by applying the Goeppert-Mayer gauge transformation. The expansion of the time-dependent solution in terms of Floquet states delineates the mechanism of multiphoton transitions. A detailed analysis of the Floquet states and quasienergies as functions of the field parameters allows us to describe the relation between avoided quasienergy crossings and multiphoton probability exchange. We formulate analytical expressions for the variation of quasienergies and Floquet states with respect to the field parameters, and demonstrate that avoided quasienergy crossings are accompanied by dramatic changes in the Floquet states. Analysis of the Floquet states, for small values of the field strength, yields selection rules for the avoided quasienergy crossings. In the case of strong fields, the simultaneous choice of frequency and strength of the field producing an avoided crossing results in improved ionization probability.

  9. Higher multipole contributions to the probability of multiphoton ionization of polarized atoms

    SciTech Connect

    Marmo, S.I.; Ovsyannikov, V.D.

    1995-08-01

    Analytic expressions are derived for invariant atomic parameters that determine the dependence of the multiphoton ionization cross section on polarization multipoles of an initial state. Cross sections for the two-photon ionization of hydrogen and alkali metal atoms from the polarized P and D states are calculated numerically. 19 refs., 2 figs., 1 tab.

  10. Electron-nuclear energy sharing in above-threshold multiphoton dissociative ionization of H2.

    PubMed

    Wu, J; Kunitski, M; Pitzer, M; Trinter, F; Schmidt, L Ph H; Jahnke, T; Magrakvelidze, M; Madsen, C B; Madsen, L B; Thumm, U; Dörner, R

    2013-07-12

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

  11. Detection of the multiphoton signals in stained tissue using nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Zeng, Yaping; Xu, Jian; Kang, Deyong; Lin, Jiangbo; Chen, Jianxin

    2016-10-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) imaging, has become a powerful, important tool for tissue imaging at the molecular level. Recently, MPM is also used to image hematoxylin and eosin (H and E)-stained sections in cancer diagnostics. However, several studies have showed that the MPM images of tissue stained with H and E are significantly different from unstained tissue sections. Our aim was to detect of the multiphoton signals in stained tissue by using MPM. In this paper, MPM was used to image histological sections of esophageal invasive carcinoma tissues stained with H, E, H and E and fresh tissue. To detect of the multiphoton signals in stained tissue, the emission spectroscopic of tissue stained with H, E, H and E were obtained. For comparison, the fresh tissues were also investigated. Our results showed that the tissue stained with H, E, H and E could be detected by their TPEF signals. While the tissue stained with H and fresh tissue could be detected by their TPEF and SHG signals. In this work, we detect of the multiphoton signals in stained tissue. These findings will be useful for choosing suitable staining method so to improve the quality of MPM imaging in the future.

  12. tritium isotope separation by CO 2 laser-induced multiphoton dissociation of CTF 3

    NASA Astrophysics Data System (ADS)

    Makide, Yoshihiro; Hagiwara, Satoru; Tominaga, Takeshi; Takeuchi, Kazuo; Nakane, Ryohei

    1981-08-01

    Isotope separation of tritium at ppm concentration level was achieved by CO 2 laser-induced multiphoton dissociation of CTF 3 in CHF 3 with single-step separation factors exceeding 500. The effects of laser frequency, pulse energy, pulse duration, irradiation geometry, tritium concentration, sample pressure, and buffer gas were investigated.

  13. Multiphoton imaging microscopy at deeper layers with adaptive optics control of spherical aberration

    NASA Astrophysics Data System (ADS)

    Bueno, Juan M.; Skorsetz, Martin; Palacios, Raquel; Gualda, Emilio J.; Artal, Pablo

    2014-01-01

    Despite the inherent confocality and optical sectioning capabilities of multiphoton microscopy, three-dimensional (3-D) imaging of thick samples is limited by the specimen-induced aberrations. The combination of immersion objectives and sensorless adaptive optics (AO) techniques has been suggested to overcome this difficulty. However, a complex plane-by-plane correction of aberrations is required, and its performance depends on a set of image-based merit functions. We propose here an alternative approach to increase penetration depth in 3-D multiphoton microscopy imaging. It is based on the manipulation of the spherical aberration (SA) of the incident beam with an AO device while performing fast tomographic multiphoton imaging. When inducing SA, the image quality at best focus is reduced; however, better quality images are obtained from deeper planes within the sample. This is a compromise that enables registration of improved 3-D multiphoton images using nonimmersion objectives. Examples on ocular tissues and nonbiological samples providing different types of nonlinear signal are presented. The implementation of this technique in a future clinical instrument might provide a better visualization of corneal structures in living eyes.

  14. The layered resolved microstructure and spectroscopy of mouse oral mucosa using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhuo, Shuangmu; Chen, Jianxin; Jiang, Xingshan; Xie, Shusen; Chen, Rong; Cao, Ning; Zou, Qilian; Xiong, Shuyuan

    2007-08-01

    The layered-resolved microstructure and spectroscopy of mouse oral mucosa are obtained using a combination of multiphoton imaging and spectral analysis with different excitation wavelengths. In the keratinizing layer, the keratinocytes microstructure can be characterized and the keratinizing thickness can be measured. The keratin fluorescence signal can be further characterized by emission maxima at 510 nm. In the epithelium, the cellular microstructure can be quantitatively visualized with depth and the epithelium thickness can be determined by multiphoton imaging excited at 730 nm. The study also shows that the epithelial spectra excited at 810 nm, showing a combination of NADH and FAD fluorescence, can be used for the estimation of the metabolic state in epithelium. Interestingly, a second-harmonic generation (SHG) signal from DNA was observed for the first time within the epithelial layer in backscattering geometry and provides the possibility of analyzing the chromatin structure. In the stroma, the combination of multiphoton imaging and spectral analysis excited at 850 nm in tandem can obtain quantitative information regarding the biomorphology and biochemistry of stroma. Specifically, the microstructure of collagen, minor salivary glands and elastic fibers, and the optical property of the stroma can be quantitatively displayed. Overall, these results suggest that the combination of multiphoton imaging and spectral analysis with different excitation wavelengths has the potential to provide important and comprehensive information for early diagnosis of oral cancer.

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

    NASA Astrophysics Data System (ADS)

    Qian, Jun

    2015-03-01

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

  16. Resonance enhanced multiphoton ionization spectra of molecules and molecular fragments. Technical report, January 1990--December 1990

    SciTech Connect

    1997-07-01

    The objective of our effort is to carry out theoretical studies of resonance enhanced multiphoton ionization processes in molecules and molecular fragments. These studies are designed to provide a quantitatively robust analysis and prediction of key spectral features of interest in several ongoing experimental studies and applications of this technique.

  17. Experimental measurements of multiphoton enhanced air breakdown by a subthreshold intensity excimer laser

    NASA Astrophysics Data System (ADS)

    Way, Jesse; Hummelt, Jason; Scharer, John

    2009-10-01

    This work presents density, spectroscopic temperature, and shockwave measurements of laser induced breakdown plasma in atmospheric air by subthreshold intensity (5.5×109 W/cm2) 193 nm laser radiation. Using molecular spectroscopy and two-wavelength interferometry, it is shown that substantial ionization (>1016 cm-3) occurs that is not predicted by collisional cascade (CC) breakdown theory. While the focused laser irradiance is three orders of magnitude below the theoretical collisional breakdown threshold, the substantial photon energy at 193 nm (6.42 eV/photon) compared with the ionization potential of air (15.6 eV) significantly increases the probability of multiphoton ionization effects. By spectroscopically monitoring the intensity of the N2+ first negative system (B Σu+2-X Σg+2) vibrational bandhead (v'=0,v″=0) at low pressure (20 Torr) where multiphoton effects are dominant, it is shown that two photon excitation, resonant enhanced multiphoton ionization is the primary mechanism for quantized ionization of N2 to the N2+(B Σu+2) state. This multiphoton effect then serves to amplify the collisional breakdown process at higher pressures by electron seeding, thereby reducing the threshold intensity from that required via CC processes for breakdown and producing high density laser formed plasmas.

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Simultaneous resonant enhanced multiphoton ionization and electron avalanche ionization in gas mixtures

    SciTech Connect

    Shneider, Mikhail N.; Zhang Zhili; Miles, Richard B.

    2008-07-15

    Resonant enhanced multiphoton ionization (REMPI) and electron avalanche ionization (EAI) are measured simultaneously in Ar:Xe mixtures at different partial pressures of mixture components. A simple theory for combined REMPI+EAI in gas mixture is developed. It is shown that the REMPI electrons seed the avalanche process, and thus the avalanche process amplifies the REMPI signal. Possible applications are discussed.