This PDF file contains the front matter associated with SPIE Proceedings Volume 10380, including the Title Page, Copyright information, Table of Contents, and Conference Committee listing.

Sphingomyelin(SM) is specifically enriched in the plasma membrane of mammalian cells. Its molecular structure is compose by N-acyl-Derythro-sphingosylphosphorylcholine. The function of the SM related to membrane signaling and protein trafficking are relied on the interactions of the SM, cations, cholesterol and proteins. In this report, the interaction of three different nature SMs, cations and cholesterol at air/aqueous interfaces studied by high-resolution broadband sum frequency vibrational spectroscopy, respectively. Our results shed lights on understanding the relationship between SMs monolayer, cholesterol and Cations.

Two-dimensional materials have attracted significant interest recently for their unique optical properties compared to their bulk counterparts. Specifically, the family of transition metal dichalcogenides (TMD), such as MoS2 and WS2, have large second order nonlinear susceptibility. Extraordinary second harmonic generation and sum frequency generation have been observed. Here we investigate the second order nonlinearity of 2D materials, including TMD layered materials with dopants and defects. Experimental results and preliminary theoretical analysis will be discussed.

We demonstrate the simultaneous generation of multicolor femtosecond laser pulses in a 0.5 mm Type I BBO crystal from 1028 nm fundamental and weak near-IR supercontinuum of a Yb:KGW ultrafast Yb based laser. The multicolor broadband laser pulses observed are attributed to cascaded four-wave mixing (CFWM) processes. A set of spatially separated CFWM sideband signals with second harmonic-generation and sum-frequency-generation pulses are arose from the interaction between the two pulses intersect at a certain angle. The CFWM sideband signals can be changed by rotating the BBO crystal to achieve the phase matching condition and adjusting the time delay between the two incident pulses to change the time overlapping.

We presented a broadly tunable, power scalable, multi-line, ultrafast source. The source is based on combining principles of pulse division with the phenomenon of the soliton self-frequency shift. By using this system, interferometric pulse recombination is demonstrated showing that the source can decouple the generally limiting relationship between output power and center wavelength in soliton self-frequency shift based optical sources. Broadly tunable multi-color soliton self-frequency shifted pulses are experimentally demonstrated. Simultaneous dual-polarization second harmonic generation was performed with the source, demonstrating one novel imaging methodology that the source can enable.

Ultrashort pulsed mode-locked lasers with exceptional performance qualities (e.g. short temporal widths or high peak powers) are desired for applications ranging from biomedical imaging to materials processing. Despite rapid progress in source development, evidence suggests that performance limits anticipated theoretically have not yet been reached. In this talk, we review recent progress and help resolve the discrepancy by presenting a limit to mode-locked laser performance based on the route taken to reach the desired steady-state pulse solution instead of on the pulse solution itself. Furthermore, we introduce an iteratively seeded method of mode-locking that allows this limit to be surmounted.

SLAC recently launched the ultrafast electron diffraction and microscopy (UED/UEM) Initiative, with the goal to develop the world’s leading ultrafast electron scattering instruments, which are complementary with x-ray free-electron lasers such as LCLS and LCLS-II. The first step of the Initiative is a MeV UED system which is now actively supporting an ultrafast science program, and at the same time serving as a testbed for instrumentation development. In this talk, design of the SLAC MeV UED system will be briefly introduced. Key machine performance parameters will be reviewed, including machine stability and reproducibility, as well as reciprocal-space and temporal resolution. Ultrafast dynamics from a variety of samples, including 2D materials, thin nanofilms, nanoparticles, and gas-phase molecules have been studied using this machine. Selected ultrafast science experiment results will be presented. In the meantime, much R&D efforts have been devoted for novel machine capabilities to enable new science opportunities. For example, we have experimentally demonstrated a femtosecond MeV electron microdiffraction, which is capable to resolve local structure from single crystal of μm lateral size with 100 fs root-mean-square temporal resolution. Future developments include 10-fs temporal resolution UED, THz pumping capability, etc. We will also discuss R&D towards the next step of the Initiative, which is to develop key technologies for future UEM with unprecedented combined spatial-temporal resolution. This R&D will focus on a superconducting radio-frequency photocathode gun, which features high accelerating field hence high beam brightness, excellent energy stability, and outstanding flexibility in bunch length from picosecond to a hundred picoseconds.

Ultrafast electron diffraction (UED) has the potential to capture changes in the structure of isolated molecules on the natural spatial and temporal scale of chemical reactions, that is, sub-Angstrom changes in the atomic positions that happen on femtosecond time scales. UED has the advantage that electron sources can easily reach sub-Angstrom spatial resolution, but so far femtosecond resolution had not been available for gas phase experiments due to the challenges in delivering short enough electron pulses on a gas target and the velocity mismatch between laser and electron pulses. Recently, we have used relativistic electron pulses at MeV energy to solve these challenges and reach femtosecond resolution. We have, for the first time, imaged coherent nuclear motion in a molecule with UED. In a proof-of-principle experiment, we captured the motion of a laser-excited vibrational wavepacket in iodine molecules. We are currently performing experiments in more complex molecules to capture laser-induced dissociation and conformational changes. We have also developed a table top 100 keV source that relies on a pulse compressor to deliver femtosecond electron pulses on a target and uses a tilted laser pulse to compensate for the velocity mismatch between the laser and the electrons. This source has a high repetition rate that will complement the high temporal resolution of the relativistic source.

Recently ultrafast electron diffraction and microscopy have reached unprecedented temporal resolution, and transient structures with atomic precision have been observed in various reactions. It is anticipated that these extraordinary advances will soon allow direct observation of electronic motions during chemical reactions. We therefore performed a series of theoretical investigations and simulations to investigate the imaging of electronic motions in atoms and molecules by ultrafast electron diffraction. Three prototypical electronic motions were considered for hydrogen atoms. For the case of a breathing mode, the electron density expands and contracts periodically, and we show that the time-resolved scattering intensities reflect such changes of the charge radius. For the case of a wiggling mode, the electron oscillates from one side of the nucleus to the other, and we show that the diffraction images exhibit asymmetric angular distributions. The last case is a hybrid mode that involves both breathing and wiggling motions. Owing to the demonstrated ability of ultrafast electrons to image these motions, we have proposed to image a coherent population transfer in lithium atoms using currently available femtosecond electron pulses. A frequency-swept laser pulse adiabatically drives the valence electron of a lithium atom from the 2s to 2p orbitals, and a time-delayed electron pulse maps such motion. Our simulations show that the diffraction images reflect this motion both in the scattering intensities and the angular distributions.

The nonequilibrium dynamics of carriers in semiconductors plays a major role in the performance and efficiency of the electronic and photovoltaic devices. In this study, we use the scanning ultrafast electron microscopy (SUEM) technique to study the surface photovoltage dynamics in doped silicon samples. We observe that the optical excitation of lightly doped n-type and p-type silicon as well as heavily doped n-type silicon increases the electron density on the surface. In contrast, the optical excitation of heavily doped p-type silicon increases the hole density on the surface. Furthermore, we show that the rise and the decay timescales of these events strongly depend on the doping concentration.

In an effort to solve the crystallization problem in crystallography, we have been engaged in developing a method termed “serial single molecule electron diffraction imaging” (SS-EDI). The unique features of SS-EDI are superfluid helium droplet cooling and field-induced orientation: together the two features constitute a molecular goniometer. Unfortunately, the helium atoms surrounding the sample molecule also contribute to a diffraction background. In this report, we analyze the properties of a superfluid helium droplet beam and its doping statistics, and demonstrate the feasibility of overcoming the background issue by using the velocity slip phenomenon of a pulsed droplet beam. Electron diffraction profiles and pair correlation functions of ferrocene-monomer-doped droplets and iodine-nanocluster-doped droplets are presented. The timing of the pulsed electron gun and the effective doping efficiency under different dopant pressures can both be controlled for size selection. This work clears any doubt of the effectiveness of superfluid helium droplets in SS-EDI, thereby advancing the effort in demonstrating the “proof-of-concept” one step further.

The magnetic field associated with a picosecond intense electron pulse is shown to switch locally the magnetization of extended films and nanostructures and to ignite locally spin waves excitations. Also topologically protected magnetic textures such as skyrmions can be imprinted swiftly in a sample with a residual Dzyaloshinskii-Moriya spin-orbital coupling. Characteristics of the created excitations such as the topological charge or the width of the magnon spectrum can be steered via the duration and the strength of the electron pulses. The study points to a possible way for a spatiotemporally controlled generation of magnetic and skyrmionic excitations.

A rotational wave packet (RWP) can be created when a molecule is nonresonantly excited by laser pulses with durations much shorter than the molecular rotational periods. More interestingly, a unidirectional molecular rotation at THz frequency can be initiated by optical kicking. Such phenomenon has attracted many interests in the fields of molecular deflection, generation of molecular vortices, and etc. However, a comprehensive physical picture of the spatiotemporal evolution of the impulsively excited molecular unidirectional rotation has lacked for more than 10 years since its first observation. Here, we directly visualize the spatiotemporal evolution of an impulsively created unidirectional spinning molecular RWP using the coincidence Coulomb explosion imaging technique (CCEIT) in an intense ultrafast laser field for the first time [1]. Both the experimental results and the numerical simulations show rich dynamical information. Depending on the timing or polarization of the pump pulses, the well-confined cigar- or disk-shaped RWP can be impulsively kicked to rotate clockwise or counterclockwise which afterwards disperses and exhibits field-free revivals owing to the time-dependent beating of the coherently populated rotational states. Very recently, the rotational echo of an impulsively excited RWP has been visualized using the CCEIT [2]. The quantum and classical dynamics of the echo phenomena will be discussed. These results will improve the understanding in other fields of physics and trigger the developments in many applications. Refs: [1] K. Lin et al., PRA 92, 013410 (2015). [2] K. Lin et al., PRX 6, 041056 (2016).

Chloride level in sweat is a major diagnostic criterion for cystic fibrosis (CF) and many other health conditions. In an effort to develop a low cost, point-of-care sweat diagnostics system for chloride concentration measurement, we demonstrated a smartphone-based chloridometer to measure sweat chloride by using our recently developed fluorescence chloride sensor. We characterized the performance of our device to validate its clinical potential. The study indicates that our smartphone-based chloridometer may potentially advance the point-of-care diagnostic system by reducing cost and improving diagnostic accuracy.

The turbidity of biological tissue due to fundamental light-tissue interactions has been a long-standing challenge in biomedical optical technologies. Implanting fibrous optical waveguide into tissue and organ for light delivery and collection is one of the most effective way for alleviate this problem. In this manuscript, by taking advantage of the favorable designability and processibility of citrate-based synthetic polymers, two bio-elastomers with distinct optical properties but matched mechanical properties and similar biodegradation profiles were developed. Combining with an efficient two-step fabrication method, we created a new biodegradable and biocompatible step-index optical fiber. Benefited from this step-index structure and high tunability of citrate-based bio-elastomers, our optical fiber not only demonstrated outstanding optical performance (0.4dB/cm loss), but also had favorable mechanical and biodegradable properties. Apart from the fabrication and characterization of our optical fiber, we successfully demonstrated the functionalities of multimode fiber imaging, deep tissue light delivery and in vivo fluorescence detection of our newly designed optical fiber. We believe the flexible, biodegradable and low loss optical fiber designed in our work offers a valuable tool for optical applications including imaging, detecting, sensing, optogenetic stimulation, and treatment to target regions underneath deep tissue.

The unique spatial distribution of corneal elasticity is shown by the nonhomogeneous structure of the cornea. It is critical to understanding how biomechanics control corneal stability and refraction and one way to do this job is non-invasive measurement of this distribution. Femtosecond laser pulses have the ability to induce optical breakdown and produced cavitation in the anterior and posterior cornea. A confocal ultrasonic transducer applied 6.5 ms acoustic radiation forcechirp bursts to the bubble at 1.5 MHz while monitoring bubble position using pulse-echoes at 20 MHz. The laser induced breakdown spectroscopy (LIBS) were measured in the anterior and posterior cornea with the plasmas that induced by the same femtosecond laser to see whether the laser induced plasmas signals will show relationship to Young’s modulus.

When the characteristic length of a material shrink to 1 nm scale, many distinct physical phenomena, such as quantum confinement, enhanced many-body interactions, strong van der Waals inter-material couplings and ultrafast charge separation, will appear. To investigate the related fascinating low-dimensional physics, we need a tool to quantitatively link the atomic structures to the physical properties of these very small nano-materials. In this talk, I will introduce our recently developed in-situ TEM + high-sensitive ultrafast nano-optical spectroscopy technique, which combines capability of structural characterization in TEM and property characterization in ultrafast nano-optical spectroscopy on the same individual nano-materials. Several examples of using this technique to study the 1D carbon nanotube and 2D atomic layered systems will be demonstrated.

We present pump-probe and Raman measurements on individual plasmonic nano-junctions. The time-resolved measurements reveal differences between capacitive and conductive junctions, and paint a detailed picture of the ultrafast electrodynamics of the nano-junction. The insights gleaned from these measurements help interpret the ultrafast response of single molecules placed in the junction.

Triplet excitons (TE), bound electron-hole pairs with unity spin and long lifetime, form the basis for exploitation in applications including singlet oxygen generation, photodynamic therapy, and photochemical upconversion. As a result, an emerging theme in the realm of nanostructured inorganic semiconductors is the extraction of their transiently stored potential in the form of molecular triplet excited states. In some instances, the efficiency of the triplet energy transfer process approaches unity, leading to generation of surface-bound triplets with lifetimes on the millisecond time scale. These observations are mostly limited to molecular or reduced-dimensional structures, and most typically are pursued in solution phase. While organic-inorganic perovskites have attracted substantial attention for application to optoelectronics, the generation of TEs from the broad perovskite family (i.e., both 3D and lower-dimensional frameworks) remains largely unexplored. In the present work, efficient TE generation on picosecond time scales in a 2D perovskite (CH3NH3)2Pb(SCN)2I2 is demonstrated using static and transient spectroscopic techniques.

Ultrafast pump-probe microscopy enables visualization of non-fluorescent materials in biological tissue, such as melanin and hemoglobin. Whereas transient absorption has been primarily a physical chemistry technique, used to gain insight into molecular and electronic structure, pump-probe microscopy represents a paradigm shift in translating transient absorption into an analytical technique, which can clearly resolve pigments with nearly indistinguishable linear absorption spectra. Extending this technique to other important targets, such as mitochondrial respiratory chain hemes, will require new laser sources and new data processing techniques to estimate heme content from the pump-probe response. We will present recent developments on both of these fronts. The laser system we have developed to elicit a pump probe response of respiratory chain hemes is based on an amplified Yb:fiber ultrafast laser that uses modest spectral broadening followed by sum frequency generation to produce a tunable pulse pair in the visible region. Wavelength tuning is accomplished by changing quasi-phase matching conditions. We will present preliminary imaging data in addition to discussing management of sample heating problems that arise from performing transient absorption measurements at the high repetition rates needed for imaging microscopy. In the second part of the talk, we will present the use of regularized and non-negative least squares fitting, along with feature-preserving noise removal to estimate composition of a pixel from its pump-probe response.

Foerster (or fluorescence) resonance energy transfer (FRET) is a powerful tool for investigating protein-protein interactions, in both living cells and in controlled environments. A typical hetero-FRET pair consists of a donor and acceptor tethered together with a linker. The corresponding energy transfer efficiency of a hetero-FRET pair probe depends upon the donor-acceptor distance, relative dipole orientation, and spectral overlap. Because of the sensitivity of the energy transfer efficiency on the donor-acceptor distance, FRET is often referred to as a “molecular ruler”. Time-resolved fluorescence approach for measuring the excited-state lifetime of the donor and acceptor emissions is one of the most reliable approaches for quantitative assessment of the energy transfer efficiency in hetero-FRET pairs. In this contribution, we provide an analytical kinetics model that describes the excited-state depopulation of a FRET probe as a means to predicts the time-resolved fluorescence profile as a function of excitation and detection wavelengths. In addition, we used this developed kinetics model to simulate the time-dependence of the excited-state population of both the donor and acceptor. These results should serve as a guide for our ongoing studies of newly developed hetero-FRET sensors (mCerulean3–linker–mCitrine) that are designed specifically for in vivo studies of macromolecular crowding. The same model is applicable to other FRET pairs with the careful consideration of their steady-state spectroscopy and the experimental design for wavelength- dependence of the fluorescence lifetime measurements.

Chirality plays a fundamental role in biomedical fields; many drugs, enzymes, and biomolecules cannot function unless their chiralities are correct. Since the conformation of a molecule, as well as the chirality, is very sensitive to the local microenvironment, it is vital to characterize molecular chirality without altering the surrounding conditions. To determine the chirality in materials, optical activity is the most common way. In linear optics, optical rotatory dispersion and circular-dichroism are the two well-developed methods for probing chirality. However, their weak contrast, poor optical sectioning, and low penetration depth constrain its application to study chirality in tissues and real bio-samples. Therefore, previous research has been mostly limited to surfaces or solutions. In contrast to linear optics, there are several nonlinear optical activity effects in chiral materials, such as vibrational circular dichroism, Raman optical activity, two-photon absorption circular dichroism, and second-harmonic generation circular-dichroism (SHG-CD). The last one is the most studied nonlinear chiral effect since it shows significantly improved chiral contrast. An additional advantage of SHG-CD is its intrinsic optical sectioning due to nonlinearity. When combined with an infrared excitation, SHG-CD has been demonstrated to provide high penetration depth for three-dimensional imaging. However, in recent studies, the signal origin of SHG-CD in biological tissue is ambiguous, since not only chirality, but also the anisotropy of molecules contribute to SHG-CD response. It will be of great importance to find an experimental skill that can distinguish the contribution between these two mechanisms. Here we studied SHG-CD of collagen, which is the most abundant protein in human body. Inspired by linear CD where resonant wavelength is required to reveal chirality, we have carried out nonlinear microspectroscopy measurement and shown that when the excitation meets the resonant band of collagen, chirality-induced SHG-CD is strongly enhanced and can be easily identified versus the anisotropy-induced contribution. By slowly heating up the sample, we have further verified that there is a wavelength-independent anisotropy contribution of SHG-CD vanishing at around 40 – 50 degree Celsius, while the resonance-enhanced chirality component of SHG-CD remains until temperature rise to 60 degree. Our results feature the first quantitative identification of chirality-induced SHG-CD in an intact biological tissue, and will be a critical step toward nonlinear chiral microscopy.

The need for ultrathin fiber-based devices that can deliver light to confined places in order to perform imaging and/or laser ablation of a desired target has been a research area of significant interest. The current endoscopic devices are based on distal optics and scanning mechanisms to focus and scan the light in the end of the fiber. The distal components are limiting factors for decreasing the size of the device. However, using wavefront shaping techniques, lensless focusing and scanning of a laser focus spot through the fiber can be achieved, enabling a smaller endoscopic tool. In our case, a high power focus spot is created by wavefront shaping of the light through a multicore fiber (MCF), providing the possibility of two-photon fluorescence (TPF) imaging. Femtosecond laser ablation through the endoscopic device can be also a powerful tool for a range of applications. Therefore, we investigate limitations in the maximum peak power that can be delivered through the MCF due to nonlinear effects induced in the fiber cores in the ablation peak power regime. After characterizing the capabilities of our system, we demonstrate that femtosecond pulsed laser ablation can be performed through the MCF.

We demonstrate a sum frequency generation (SFG) holographic imaging method by integrating the capabilities of holography and SFG spectroscopy. SFG can probe the molecular vibrational resonance in non-centrosymmetric media. Holographic recording can capture both the amplitude and the phase of the SFG signal, thus leading to label-free spectroscopic three-dimensional imaging.

We investigate the utility of non-degenerate 2-photon excitation (ND-2PE) as a strategy for extending the 2-photon imaging depth. For the ND-2PE scheme, two pulsed, synchronized laser sources of different wavelength each provide a photon for the 2-photon absorption process. By independently tuning their wavelengths, we are able to tune the excitation to tissue transparency windows while maintaining resonant fluorescence excitation. These transparency windows reduce excitation power loss resulting from scattering. In addition, by having two sources we are able to displace the beams in space except at their common focus; thus, reducing background fluorescence excitation. Finally, we show that ND-2PE inherently results in increased 2-photon absorption cross sections, resulting in increased fluorescence intensity. By combining beam displacement, tissue transparency and increased absorption cross sections, we achieve increased imaging depths as compared to degenerate 2-photon excitation with commonly used fluorophores.

There have been increasing interests in nonlinear optical imaging technology, especially in biomedical and material research fields, where higher spatial resolution, better sensitivity, deeper penetration and faster data acquisition are always desired. Most recent examples include fluorescence microscopy, coherent Raman and nonlinear wave mixing imaging. In this talk, we will present our recent progresses on deep tissue fluorescence super-resolution and non-labeling chiral sum frequency generation imaging by utilizing optical field engineering mechanism.

Observing the fast dynamics of specific molecules or targets in three-dimensional (3D) space and time inside a crowded and complex environment, such as living cells or tissues, remain one of the grand open challenges in modern science. Harmonic holography tackle this challenge by combining the 3D imaging capability of holography with the ultrafast, coherent optical contrast offered by second-harmonic radiating imaging probes (SHRIMPs). Similar to fluorescence, the second-harmonic signal emitted from SHRIMPs provides a color contrast against the uninterested background scattering, which can be efficiently suppressed by an optical filter. We review the latest developments in SHRIMPs and harmonic holography and discuss their further applications in fluidics and biofluidics.

Analysis of effectiveness of the staphylococcal infections treatment in the tonsils is carried out using Raman spectroscopy method. Spectral changes were established in the treatment of palatine tonsils with the antibiotic Amoksiklav. It was shown that when the antibiotic dosage is 500mg / 10ml, the lines disappear at wave numbers 735 cm^-1 and 783 cm^-1, 986 cm^-1, and 1633 cm^-1, corresponding to adenine, cytosine, proteins, and amide I, which indicates the effectiveness of treatment.

The paper presents the results of a comparative analysis by the method of Raman spectroscopy of the joint hyaline cartilage of adults and children. Differences in the spectral characteristics of the surface of articular cartilage are shown. New optical coefficients have been introduced, which make it possible to evaluate the age-related changes in cartilaginous tissue.

In this study, we performed studies longitudinal sections of long bones of rats by Raman spectroscopy in the simulation reduction of bone mineral density in the animals. The main spectral characteristics of different sections of longitudinal sections of rat humerus are determined. Optical criteria have been introduced to identify bone tissue with reduced mineral density.

The results of application of the Raman spectroscopy method for the estimation of alternative sources for the production of bone spongy implants using the "Lioplast" technology, namely, the femoral heads resected in the operation of hip replacement surgery, are presented. It is shown that Raman spectroscopy can be used to estimate the component composition of the surface of bone implants during their processing. Comparing different sources of sponge bone production, no significant differences were found, but there are differences in the ratio of the intensities of the Raman peaks at wave numbers 1555 cm^-1 and 1665 cm^-1 corresponding to amide II and amide I, and also in the intensity of Raman peaks at wave numbers of 959 cm^-1 (РО₄ ^3- (ν₁)) and 1068 cm^-1 (СO₃ ^2- (ν₁) B-type substitution).

We present results of experimental and numerical investigation of supercontinuum generation in polarization maintaining photonic crystal fiber (PCF) using chirped femtosecond pulses. The initial unchirped pump pulse source was a mode-locked Yb:KGW laser generating 52 nJ energy 110 fs duration pulses at 1030 nm with 76 MHz repetition rate. The nonlinear medium was a 32 cm long polarization maintaining PCF manufactured by NKT Photonics A/S. We demonstrated the influence of pump pulse chirp on spectral characteristics of supercontinuum. We showed that by chirping pump pulses positively or negatively one can obtain broader supercontinuum spectrum than in case of unchirped pump pulses at the same peak power. Moreover, the extension can be controlled by changing the amount of pump pulse chirp. In our case the supercontinuum spectrum width was extended by up to 115 nm (at maximum chirp value of +10500 fs² that we could achieve in our setup) compared to the case of unchirped pump at the same peak power.