Stimulated Raman scattering microscopy with phase-controlled light focusing and aberration correction for rapid and label-free, volumetric deep tissue imaging

We report a novel stimulated Raman scattering(SRS)microscopy technique featuring phase-controlled light focusing and aberration corrections for rapid,deep tissue 3D chemical imaging with subcellular resolution.To accomplish phasecontrolled SRS(PC-SRS),we utilize a single spatial light modulator to electronically tune the axial positioning of both the shortened-length Bessel pump and the focused Gaussian Stokes beams,enabling z-scanning-free optical sectioning in the sample.By incorporating Zernike polynomials into the phase patterns,we simultaneously correct the system aberrations at two separate wavelengths(~240 nm difference),achieving a~3-fold enhancement in signal-to-noise ratio over the uncorrected imaging system.PC-SRS provides>2-fold improvement in imaging depth in various samples(e.g.,polystyrene bead phantoms,porcine brain tissue)as well as achieves SRS 3D imaging speed of~13 Hz per volume for real-time monitoring of Brownian motion of polymer beads in water,superior to conventional point-scanning SRS 3D imaging.We further utilize PC-SRS to observe the metabolic activities of the entire tumor liver in living zebrafish in cellsilent region,unraveling the upregulated metabolism in liver tumor compared to normal liver.This work shows that PCSRS provides unprecedented insights into morpho-chemistry,metabolic and dynamic functioning of live cells and tissue in real-time at the subcellular level.

Focusing on the tetra-partite synapse in Parkinson’s disease research using human patient-derived neurons

Parkinson’s disease(PD)was first described as a neurological disease by Dr.James Parkinson in 1817 as a“shaking palsy”.Since that time,much more is known about the pathophysiology of PD yet the disease is still uncurable.The hallmark of the disease is often considered Lewy body neural inclusions in the substantia nigra pars compacta and other brain areas,although not all patients have these inclusions.The patients exhibit massive neuronal cell loss in the substantia nigra pars compacta,which is associated with the motor symptoms of tremor,bradykinesia,rigidity,and postural instability.PD is the second most common neurodegenerative disease after Alzheimer’s disease with a prevalence of around 1%of individuals over the age of 60.

Three-dimensional isotropic microfabrication in glass using spatiotemporal focusing of high-repetition-rate femtosecond laser pulses

To improve the processing efficiency and extend the tuning range of 3D isotropic fabrication,we apply the simultaneous spatiotemporal focusing(SSTF)technique to a high-repetition-rate femtosecond(fs)fiber laser system.In the SSTF scheme,we propose a pulse compensation scheme for the fiber laser with a narrow spectral bandwidth by building an extra-cavity pulse stretcher.We further demonstrate truly 3D isotropic microfabrication in photosensitive glass with a tunable resolution ranging from 8μm to 22μm using the SSTF of fs laser pulses.Moreover,we systematically investigate the influences of pulse energy,writing speed,processing depth,and spherical aberration on the fabrication resolution.As a proof-of-concept demonstration,the SSTF scheme was further employed for the fs laser-assisted etching of complicated glass microfluidic structures with 3D uniform sizes.The developed technique can be extended to many applications such as advanced photonics,3D biomimetic printing,micro-electromechanical systems,and lab-on-a-chips.

Spectra-assisted laser focusing in quantitative analysis of laser-induced breakdown spectroscopy for copper alloys

Laser-induced breakdown spectroscopy(LIBS)is a capable technique for elementary analysis,while LIBS quantitation is still under development.In quantitation,precise laser focusing plays an important role because it ensures the distance between the laser and samples.In the present work,we employed spectral intensity as a direct way to assist laser focusing in LIBS quantitation for copper alloys.It is found that both the air emission and the copper line could be used to determine the position of the sample surface by referencing the intensity maximum.Nevertheless,the fine quantitation was only realized at the position where the air emission(e.g.O(I)777.4 nm)reached intensity maximum,and also in this way,a repeatable quantitation was successfully achieved even after 120 days.The results suggested that the LIBS quantitation was highly dependent on the focusing position of the laser,and spectra-assisted focusing could be a simple way to find the identical condition for different samples’detection.In the future,this method might be applicable in field measurements for LIBS analysis of solids.

Generation of Higher Terahertz Harmonics in Nonlinear Paraelectrics under Focusing in a Wide Temperature Range

It is theoretically investigated the generation of higher harmonics of two-dimensional and three-dimensional terahertz electromagnetic beams in nonlinear crystals. The attention is paid to crystalline paraelectrics like SrTiO3 under the temperatures 60 - 200 K, these crystals possess the cubic nonlinearity. The bias electric field is applied to provide the dominating quadratic nonlinearity. The initial focusing of the beams not only increases the efficiency of generation of higher harmonics, but alto makes possible to select maxima of different higher harmonics at some distances from the input. At lower temperatures the nonlinearity behaves at smaller input amplitudes, whereas at higher temperatures the harmonic generation can be observed at higher frequencies up to 1.5 THz. In three-dimensional beams the peak amplitudes of higher harmonics can be bigger than in two-dimensional beams, but the ratios of these peak values to the maximum values of the focused first harmonic are smaller than in two-dimensional beams.

Propagation and focusing characteristics of the Bessel-Gaussian beam with the spiral phase term of new power-exponent-phase

A new type of beam called the NPEP-BG(a Bessel-Gaussian(BG)beam with a spiral phase term of a new powerexponent-phase(NPEP))is theoretically studied in this paper.The results show that the number of singularities of the phase and side lobes of the intensity of this beam were equal to the topological charges(TCs)and the beam has the characteristics of self-healing during propagation.The NPEP-BG beam combined the partial characteristics of the new power-exponentphase vortex(NPEPV)and the Bessel-Gaussian beam.At the focus of the beam,the characteristic like a perfect vortex beam was present,in which the focal radius is stable and independent of the topological charge.There are multi-focal spots around a ring in the focal plane,meaning that the NPEP-BG beam has a potential for application in multi-particle manipulation.

NUMERICAL INVESTIGATION OF TOROIDAL SHOCK WAVES FOCUSING USING DISCONTINUOUS GALERKIN FINITE ELEMENT METHOD

A numerical simulation of the toroidal shock wave focusing in a co-axial cylindrical shock tube is inves- tigated by using discontinuous Galerkin （DG） finite element method to solve the axisymmetric Euler equations. For validating the numerical method, the shock-tube problem with exact solution is computed, and the computed results agree well with the exact cases. Then, several cases with higher incident Mach numbers varying from 2.0 to 5.0 are simulated. Simulation results show that complicated flow-field structures of toroidal shock wave diffraction, reflection, and focusing in a co-axial cylindrical shock tube can be obtained at different incident Mach numbers and the numerical solutions appear steep gradients near the focusing point, which illustrates the DG method has higher accuracy and better resolution near the discontinuous point. Moreover, the focusing peak pres- sure with different grid scales is compared.

DETONATION INITIATION INDUCED BY FLAME IMPLOSION AND SHOCK WAVE FOCUSING

Computational simulations on structurally different detonation generator are carried out to study the phenomena,the mechanism and the gas dynamics characteristics of flame implosion and shock wave focusing.Two-dimensional axisymmetric and unsteady Navier-Stokes equations are numerically solved and detailed chemical reaction kinetics of hydrogen/air mixture is used.The simulation results show that the laminar flame generated by low energy spark in the jet flame burner is accelerated under the narrow channel,the jet flame impinging on the axis strengthens shock wave and the shock wave enhances flame acceleration.Under the function of multiple shock waves and flame,a number of hot spots appear between the wave and the surface.The spots enlarge rapidly,thus forming an over-drive detonation with high pressure,and then declining to stable detonation.Through calculation and analysis,the length of detonation initiation and stable detonation are obtained,thus providing the useful information for further experimental investigations.

Acoustic focusing effect of composite metamaterial column in air

The acoustic focusing effect of metamaterial has a wide range of applications in medicine,acoustic imaging,signal detection,etc.This paper presents an acoustic metamaterial applied to the acoustic focusing effect.The formation of acousticmetamaterial is designed into a cylindrical structure with three layers of ludox,cork and fluid rubber,which can produce a focusingphenomenon when acoustic waves propagate in air.For these strange phenomena,a scientific description is given theorietically.It can also be concluded that when the frequency of the incident acoustic wave increases?the number of peripheral bandsoutside the focusing poles will increase periodically.Besides,there are numerous groups of multipolar focusing phenomena inhigh frequency.The design of this acoustic metamaterial is successful through theorietical and experimental verification,therefore,it can be applied to acoustic communication and test.

Three-dimensional spatial multi-point uniform light focusing through scattering media based on feedback wavefront shaping

We use feedback wavefront shaping technology to realize the multi-point uniform light focusing in three-dimensional(3D) space through scattering media only by loading the optimal mask once.General 3D spatial focusing needs to load the optimal mask multiple times to realize the spatial movement of the focal point and the uniformity of multi-point focusing cannot be guaranteed.First,we investigate the effects of speckle axial correlation and different axial distances on 3D spatial multi-point uniform focusing and propose possible solutions.Then we use our developed non-dominated sorting genetic algorithm suitable for 3D spatial focusing(S-NSGA) to verify the experiment of multi-point focusing in 3D space.This research is expected to have potential applications in the fields of optical manipulation and optogenetics.

Physical Investigation of Directional Wave Focusing and Breaking Waves in Wave Basin

An experimental scheme for the generation of directional focusing waves in a wave basin is established in this paper. The effects of the directional range, frequency width and center frequency on the wave focusing are studied. The distribution of maximum amplitude and the evolution of time series and spectra during wave packet propagation and the variation of water surface parameters are extensively investigated. The results reveal that the characteristics of focusing waves are significantly influenced by wave directionality and that the breaking criteria for directional waves are distinctly different from those for unidirectional waves.

Efficient Focusing Models for Generation of Freak Waves

Four focusing models for generation of freak waves are presented. An extreme wave focusing model is presented on the basis of the enhanced High-Order Spectral （HOS） method and the importance of the nonlinear wave-wave interaction is evaluated by comparison of the calculated results with experimental and theoretical data. Based on the modification of the Longuet-Higgins model, four wave models for generation of freak waves （a. extreme wave model ＋ random wave model; b. extreme wave model ＋ regular wave model; e. phase interval modulation wave focusing model; d. number modulation wave focusing model with the same phase） are proposed. By use of different energy distribution techniques in the four models, freak wave events are obtained with different Hmax/Hs in finite space and time.

Tight Focusing Properties of Radially Polarized Gaussian Beams with Pair of Vortices

The tight focusing properties of a radially polarized Gaussian beam with a nested pair of vortices having a radial wave front distribution are investigated theoretically by the vector diffraction theory. The results show that the optical intensity in the focal region can be altered considerably by changing the location of the vortices nested in a radially polarized Gaussian beam. It is noted that focal evolution from one annular focal pattern to a highly confined focal spot in the transverse direction is observed corresponding to the change in the location of the optical vortices in the input plane. It is also observed that the generated focal hole or spot lead to a focal shift along the optical axis remarkably under proper radial phase modulation. Hence the proposed system may be applied to construct tunable optical traps for both high and low refractive index particles.

Light Focusing through Scattering Media by Particle Swarm Optimization

We demonstrate light focusing through scattering media by introducing particle swarm optimization for modulat- ing the phase wavefront. Light refocusing is simulated numerically based on the angular spectrum method and the circular Gaussian distribution model of the scattering media. Experimentally, a spatial light modulator is used to control the phase of incident light, so as to make the scattered light converge to a focus. The influence of divided segments of input light and the effect of the number of iterations on light intensity enhancement are investigated. Simulation results are found to be in good agreement with the theoretical analysis for light refocusing.

A method of laser focusing control in microlaser-induced breakdown spectroscopy

This paper presents a method for the automatic adjustment of the laser defocusing amount in micro-laser-induced breakdown spectroscopy. A microscopic optical imaging system consisting of a CCD camera and a 20× objective lens was adopted to realize the method. The real-time auto-focusing of the system was achieved by detecting the effective pixels of the light spot generated by the laser pointer. The focusing accuracy of the method could achieve 3 μm. The element concentrations of Mn and Ni in low-alloy steels were analyzed at a crater diameter of about 35 μm using the presented method. After using the presented method, the determination coefficients of Mn and Ni both exceeded 0.997, with the root-mean-square errors being 0.0133 and 0.0395, respectively. Scanning analysis was performed on the inclined plane and the curved surface by means of focusing control and non-focusing control. Ten characteristic spectral lines of Fe were selected as the analysis lines. With the focusing control, the average relative standard deviations obtained on the inclined plane and curved surface were both less than 5%, and much less than the values without focusing control, 14.6% and 40.39%.

Numerical Study of Two-Dimensional Focusing Waves

Two-dimensional focusing waves are generated and investigated by numerical method. The numerical model is developed by introducing the wave maker boundary on the high-order spectral （HOS） method proposed by Dommermuth and Yue in 1987 and verified by theoretical and experimental data. Some cases of focusing waves considering different parameters such as assumed focusing amplitudes, frequency bandwidth, central frequency and frequency spectrum are generated. Characteristics of the focusing wave including surface elevations, the maximum crest, shift of focusing points and frequency spectra are discussed. The results show that the focusing wave characteristics are strongly affected by focusing amplitudes, frequency bandwidth, central frequency and frequency spectrum.

Stochastic focusing search:a novel optimization algorithm for real-parameter optimization

A novel optimization algorithm called stochastic focusing search （SFS） for the real-parameter optimization is proposed. The new algorithm is a swarm intelligence algorithm, which is based on simulating the act of human randomized searching, and the human searching behaviors. The algorithm＇s performance is studied using a challenging set of typically complex functions with comparison of differential evolution （DE） and three modified particle swarm optimization （PSO） algorithms, and the simulation results show that SFS is competitive to solve most parts of the benchmark problems and will become a promising candidate of search algorithms especially when the existing algorithms have some difficulties in solving certain problems.

Femtosecond electron pulse compression by using the time focusing technique in ultrafast electron diffraction

We present a new model of an electron gun for generating subrelativistic femtosecond （fs） electron pulses. The basic idea is to utilize a dc acceleration stage combined with a time focusing region, the time focusing electrode generates an electron energy chirp for bunching at the target. Without considering the space charge effects, simulations of the electron gun were carried out under the conditions of different dc voltages and various slopes of the voltage added on the time focusing electrode. Tracing and simulating large numbers of photoelectrons through Monte-Carlo and finite difference methods, the electron pulses with 1 ps can be compressed to 55 fs, which will allow significant advances in the field of ultrafast diagnosis.

Numerical simulation of flow focusing pattern and morphological changes in two-phase flow inside nozzle

The flow focusing nozzle is a new type of nozzle that performs effective atomization of the discrete phase by means of high-speed motion of the continuous phase.The flow pattern and its morphological changes have a significant effect on the atomization, but the influence of different parameters on the morphological change of the flow pattern remains unclear.The flow focusing pattern and morphological changes in the two-phase flow inside the nozzle were simulated numerically, based on the volume of fluid method.The results demonstrate that the ratio of the nozzle-to-capillary distance and capillary diameter, the gas–liquid velocity ratio, and capillary diameter have significant effects on the flow pattern.When the ratio of the nozzle-to-capillary distance H and capillary diameter D increases, or the capillary diameter D increases, the flow pattern tends to transform into a laminar form; however, when the gas–liquid velocity ratio V increases, the flow pattern tends to transform into a turbulence form.Furthermore, we define the cone-shaped expansion rate, cone-shaped focusing rate,and cone angle in order to study the morphological changes in the cone shape inside the nozzle.The results indicate that the morphological change of the cone shape and flow pattern transformation is interrelated.When the cone shape tends to be unstable, the flow pattern changes towards flow blurring, whereas, a stable cone indicates that the flow tends to exhibit a droplet pattern.

Focusing phenomenon and near-trapped modes of SH waves

In this study, the null-field boundary integral equation method （BIEM） and the image method are used to solve the SH wave scattering problem containing semi-circular canyons and circular tunnels. To fully utilize the analytical property of Circular geometry, the polar coordinates are used to expand the closed-form fundamental solution to the degenerate kernel, and the Fourier series is also introduced to represent the boundary density. By collocating boundary points to match boundary condition on the boundary, a linear algebraic system is constructed. The unknown coefficients in the algebraic system can be easily determined. In this way, a semi-analytical approach is developed. Following the experience of near-trapped modes in water wave problems of the full plane, the focusing phenomenon and near-trapped modes for the SH wave problem of the half-plane are solved, since the two problems obey the same mathematical model. In this study, it is found that the SH wave problem containing two semi-circular canyons and a circular tunnel has the near-trapped mode and the focusing phenomenon for a special incident angle and wavenumber. In this situation, the amplification factor for the amplitude of displacement is over 300.