Nanoscale chemical imaging with structured X-ray illumination.

High-resolution imaging with compositional and chemical sensitivity is crucial for a wide range of scientific and engineering disciplines. Although synchrotron X-ray imaging through spectromicroscopy has been tremendously successful and broadly applied, it encounters challenges in achieving enhanced detection sensitivity, satisfactory spatial resolution, and high experimental throughput simultaneously. In this work, based on structured illumination, we develop a single-pixel X-ray imaging approach coupled with a generative image reconstruction model for mapping the compositional heterogeneity with nanoscale resolvability. This method integrates a full-field transmission X-ray microscope with an X-ray fluorescence detector and eliminates the need for nanoscale X-ray focusing and raster scanning. We experimentally demonstrate the effectiveness of our approach by imaging a battery sample composed of mixed cathode materials and successfully retrieving the compositional variations of the imaged cathode particles. Bridging the gap between structural and chemical characterizations using X-rays, this technique opens up vast opportunities in the fields of biology, environmental, and materials science, especially for radiation-sensitive samples.

What are the advantages of ghost imaging? Multiplexing for x-ray and electron imaging.

Ghost imaging, Fourier transform spectroscopy, and the newly developed Hadamard transform crystallography are all examples of multiplexing measurement strategies. Multiplexed experiments are performed by measuring multiple points in space, time, or energy simultaneously. This contrasts to the usual method of systematically scanning single points. How do multiplexed measurements work and when they are advantageous? Here we address these questions with a focus on applications involving x-rays or electrons. We present a quantitative framework for analyzing the expected error and radiation dose of different measurement scheme that enables comparison. We conclude that in very specific situations, multiplexing can offer improvements in resolution and signal-to-noise. If the signal has a sparse representation, these advantages become more general and dramatic, and further less radiation can be used to complete a measurement.

Laguerre-Gaussian Mode Laser Heater for Microbunching Instability Suppression in Free-Electron Lasers.

Microbunching instability (MBI) driven by beam collective effects is known to be detrimental to high-brightness storage rings, linacs, and free-electron lasers (FELs). One known way to suppress this instability is to induce a small amount of energy spread to an electron beam by a laser heater. The distribution of the induced energy spread greatly affects MBI suppression and can be controlled by shaping the transverse profile of the heater laser. Here, we present the first experimental demonstration of effective MBI suppression using a LG_{01} transverse laser mode and compare the improved results with respect to traditional Gaussian transverse laser mode at the Linac Coherent Light Source. The effects on MBI suppression are characterized by multiple downstream measurements, including longitudinal phase space analysis and coherent radiation spectroscopy. We also discuss the role of LG_{01} shaping in soft x-ray self-seeded FEL emission, one of the most advanced operation modes of a FEL for which controlled suppression of MBI is critical.

Attosecond transient absorption spooktroscopy: a ghost imaging approach to ultrafast absorption spectroscopy.

The recent demonstration of isolated attosecond pulses from an X-ray free-electron laser (XFEL) opens the possibility for probing ultrafast electron dynamics at X-ray wavelengths. An established experimental method for probing ultrafast dynamics is X-ray transient absorption spectroscopy, where the X-ray absorption spectrum is measured by scanning the central photon energy and recording the resultant photoproducts. The spectral bandwidth inherent to attosecond pulses is wide compared to the resonant features typically probed, which generally precludes the application of this technique in the attosecond regime. In this paper we propose and demonstrate a new technique to conduct transient absorption spectroscopy with broad bandwidth attosecond pulses with the aid of ghost imaging, recovering sub-bandwidth resolution in photoproduct-based absorption measurements.

Erratum: Luan, E.X.; Shoman, H.; Ratner, D.M.; Cheung, K.C.; Chrostowski, L. Silicon Photonic Biosensors Using Label-Free Detection. Sensors 2018, 18, 3519.

The authors wish to make the following corrections in their published paper in Sensors [...].

Silicon Photonic Biosensors Using Label-Free Detection.

Thanks to advanced semiconductor microfabrication technology, chip-scale integration and miniaturization of lab-on-a-chip components, silicon-based optical biosensors have made significant progress for the purpose of point-of-care diagnosis. In this review, we provide an overview of the state-of-the-art in evanescent field biosensing technologies including interferometer, microcavity, photonic crystal, and Bragg grating waveguide-based sensors. Their sensing mechanisms and sensor performances, as well as real biomarkers for label-free detection, are exhibited and compared. We also review the development of chip-level integration for lab-on-a-chip photonic sensing platforms, which consist of the optical sensing device, flow delivery system, optical input and readout equipment. At last, some advanced system-level complementary metal-oxide semiconductor (CMOS) chip packaging examples are presented, indicating the commercialization potential for the low cost, high yield, portable biosensing platform leveraging CMOS processes.

Synthetic Macromolecular Antibiotic Platform for Inhalable Therapy against Aerosolized Intracellular Alveolar Infections.

Lung-based intracellular bacterial infections remain one of the most challenging infectious disease settings. For example, the current standard for treating Franciscella tularensis pneumonia (tularemia) relies on administration of oral or intravenous antibiotics that poorly achieve and sustain pulmonary drug bioavailability. Inhalable antibiotic formulations are approved and in clinical development for upper respiratory infections, but sustained drug dosing from inhaled antibiotics against alveolar intracellular infections remains a current unmet need. To provide an extended therapy against alveolar intracellular infections, we have developed a macromolecular therapeutic platform that provides sustained local delivery of ciprofloxacin with controlled dosing profiles. Synthesized using RAFT polymerization, these macromolecular prodrugs characteristically have high drug loading (16-17 wt % drug), tunable hydrolysis kinetics mediated by drug linkage chemistry (slow-releasing alkyllic vs fast-releasing phenolic esters), and, in general, represent new fully synthetic nanotherapeutics with streamlined manufacturing profiles. In aerosolized and completely lethal F.t. novicida mouse challenge models, the fast-releasing ciprofloxacin macromolecular prodrug provided high cure efficiencies (75% survival rate under therapeutic treatment), and the importance of release kinetics was demonstrated by the inactivity of the similar but slow-releasing prodrug system. Pharmacokinetics and biodistribution studies further demonstrated that the efficacious fast-releasing prodrug retained drug dosing in the lung above the MIC over a 48 h period with corresponding Cmax/MIC and AUC0-24h/MIC ratios being greater than 10 and 125, respectively; the thresholds for optimal bactericidal efficacy. These findings identify the macromolecular prodrug platform as a potential therapeutic system to better treat alveolar intracellular infections such as F. tularensis, where positive patient outcomes require tailored antibiotic pharmacokinetic and treatment profiles.

Sub-wavelength grating for enhanced ring resonator biosensor.

While silicon photonic resonant cavities have been widely investigated for biosensing applications, enhancing their sensitivity and detection limit continues to be an area of active research. Here, we describe how to engineer the effective refractive index and mode profile of a silicon-on-insulator (SOI) waveguide using sub-wavelength gratings (SWG) and report on its observed performance as a biosensor. We designed a 30 µm diameter SWG ring resonator and fabricated it using Ebeam lithography. Its characterization resulted in a quality factor, Q, of 7 · 103, bulk sensitivity Sb = 490 nm/RIU, and system limit of detection sLoD = 2 · 10-6 RIU. Finally we employ a model biological sandwich assay to demonstrate its utility for biosensing applications.

X-ray absorption spectroscopy using a self-seeded soft X-ray free-electron laser.

X-ray free electron lasers (XFELs) enable unprecedented new ways to study the electronic structure and dynamics of transition metal systems. L-edge absorption spectroscopy is a powerful technique for such studies and the feasibility of this method at XFELs for solutions and solids has been demonstrated. However, the required x-ray bandwidth is an order of magnitude narrower than that of self-amplified spontaneous emission (SASE), and additional monochromatization is needed. Here we compare L-edge x-ray absorption spectroscopy (XAS) of a prototypical transition metal system based on monochromatizing the SASE radiation of the linac coherent light source (LCLS) with a new technique based on self-seeding of LCLS. We demonstrate how L-edge XAS can be performed using the self-seeding scheme without the need of an additional beam line monochromator. We show how the spectral shape and pulse energy depend on the undulator setup and how this affects the x-ray spectroscopy measurements.

Femtosecond photodissociation dynamics of 1,4-diiodobenzene by gas-phase X-ray scattering and photoelectron spectroscopy.

We present a multifaceted investigation into the initial photodissociation dynamics of 1,4-diiodobenzene (DIB) following absorption of 267 nm radiation. We combine ultrafast time-resolved photoelectron spectroscopy and X-ray scattering experiments performed at the Linac Coherent Light Source (LCLS) to study the initial electronic excitation and subsequent rotational alignment, and interpret the experiments in light of Complete Active Space Self-Consistent Field (CASSCF) calculations of the excited electronic landscape. The initially excited state is found to be a bound 1B1 surface, which undergoes ultrafast population transfer to a nearby state in 35 ± 10 fs. The internal conversion most likely leads to one or more singlet repulsive surfaces that initiate the dissociation. This initial study is an essential and prerequisite component of a comprehensive study of the complete photodissociation pathway(s) of DIB at 267 nm. Assignment of the initially excited electronic state as a bound state identifies the mechanism as predissociative, and measurement of its lifetime establishes the time between excitation and initiation of dissociation, which is crucial for direct comparison of photoelectron and scattering experiments.

Stimulated X-ray Raman scattering - a critical assessment of the building block of nonlinear X-ray spectroscopy.

With the invention of femtosecond X-ray free-electron lasers (XFELs), studies of light-induced chemical reaction dynamics and structural dynamics reach a new era, allowing for time-resolved X-ray diffraction and spectroscopy. To ultimately probe coherent electron and nuclear dynamics on their natural time and length scales, coherent nonlinear X-ray spectroscopy schemes have been proposed. In this contribution, we want to critically assess the experimental realisation of nonlinear X-ray spectroscopy at current-day XFEL sources, by presenting first experimental attempts to demonstrate stimulated resonant X-ray Raman scattering in molecular gas targets.

Nanostructured glycopolymer augmented liposomes to elucidate carbohydrate-mediated targeting.

Carbohydrate receptors on alveolar macrophages are attractive targets for receptor-mediated delivery of nanostructured therapeutics. In this study, we employed reversible addition fragmentation chain transfer polymerization to synthesize neoglycopolymers, consisting of mannose- and galactose methacrylate-based monomers copolymerized with cholesterol methacrylate for use in functional liposome studies. Glycopolymer-functional liposomes were employed to elucidate macrophage mannose receptor (CD206) and macrophage galactose-type lectin (CD301) targeting in both primary macrophage and immortal macrophage cell lines. Expression of CD206 and CD301 was observed to vary significantly between cell lines (murine alveolar macrophage, murine bone marrow-derived macrophage, RAW264.7, and MH-S), which has significant implications in in vitro targeting and uptake studies. Synthetic glycopolymers and glycopolymer augmented liposomes demonstrated specific receptor-mediated uptake in a manner dependent on carbohydrate receptor expression. These results establish a platform capable of probing endogenous carbohydrate receptor-mediated targeting via glycofunctional nanomaterials.

Optical laser systems at the Linac Coherent Light Source.

Ultrafast optical lasers play an essential role in exploiting the unique capabilities of recently commissioned X-ray free-electron laser facilities such as the Linac Coherent Light Source (LCLS). Pump-probe experimental techniques reveal ultrafast dynamics in atomic and molecular processes and reveal new insights in chemistry, biology, material science and high-energy-density physics. This manuscript describes the laser systems and experimental methods that enable cutting-edge optical laser/X-ray pump-probe experiments to be performed at LCLS.

Damage threshold of platinum coating used for optics for self-seeding of soft X-ray free electron laser.

We investigated the experimental damage threshold of platinum coating on a silicon substrate illuminated by soft x-ray radiation at grazing incidence angle of 2 degrees. The coating was the same as the blazed grating used for the soft X-ray self-seeding optics of the Linac Coherent Light Source free electron laser. The irradiation condition was chosen such that the absorbed dose was similar to the maximum dose expected for the grating. The expected dose was simulated by solving the Helmholtz equation in non-homogenous media. The experiment was performed at 900 eV photon energy for both single pulse and multi-shot conditions. We have not observed single shot damage. This corresponds to a single shot damage threshold being higher than 3 J/cm(2). The multiple shot damage threshold measured for 10 shots and about 600 shots was determined to be 0.95 J/cm(2) and 0.75 J/cm(2) respectively. The damage threshold occurred at an instantaneous dose which is higher that the melt dose of platinum.

Performance of ultra-thin SOI-based resonators for sensing applications.

This work presents simulation and experimental results of ultra-thin optical ring resonators, having larger Evanescent Field (EF) penetration depths, and therefore larger sensitivities, as compared to conventional Silicon-on-Insulator (SOI)-based resonator sensors. Having higher sensitivities to the changes in the refractive indices of the cladding media is desirable for sensing applications, as the interactions of interest take place in this region. Using ultra-thin waveguides (<100 nm thick) shows promise to enhance sensitivity for both bulk and surface sensing, due to increased penetration of the EF into the cladding. In this work, the designs and characterization of ultra-thin resonator sensors, within the constraints of a multi-project wafer service that offers three waveguide thicknesses (90 nm, 150 nm, and 220 nm), are presented. These services typically allow efficient integration of biosensors with on-chip detectors, moving towards the implementation of lab-on-chip (LoC) systems. Also, higher temperature stability of ultra-thin resonator sensors were characterized and, in the presence of intentional environmental (temperature) fluctuations, were compared to standard transverse electric SOI-based resonator sensors.

Phage lambda capsids as tunable display nanoparticles.

Nanoparticle technologies provide a powerful tool for the development of reagents for use in both therapeutic and diagnostic, or "theragnostic" biomedical applications. Two broad classes of particles are under development, viral and synthetic systems, each with their respective strengths and limitations. Here we adapt the phage lambda system to construct modular "designer" nanoparticles that blend these two approaches. We have constructed a variety of modified "decoration" proteins that allow site-specific modification of the shell with both protein and nonproteinaceous ligands including small molecules, carbohydrates, and synthetic display ligands. We show that the chimeric proteins can be used to simultaneously decorate the shell in a tunable surface density to afford particles that are physically homogeneous and that can be manufactured to display a variety of ligands in a defined composition. These designer nanoparticles set the stage for development of lambda as a theragnostic nanoparticle system.

Identifying human milk glycans that inhibit norovirus binding using surface plasmon resonance.

Human milk glycans inhibit binding between norovirus and its host glycan receptor; such competitive inhibition by human milk glycans is associated with a reduced risk of infection. The relationship between the presence of specific structural motifs in the human milk glycan and its ability to inhibit binding by specific norovirus strains requires facile, accurate and miniaturized-binding assays. Toward this end, a high-throughput biosensor platform was developed based on surface plasmon resonance imaging (SPRi) of glycan microarrays. The SPRi was validated, and its utility was tested, by measuring binding specificities between defined human milk glycan epitopes and the capsids of two common norovirus strains, VA387 and Norwalk. Human milk oligosaccharide (HMOS)-based neoglycoconjugates, including chemically derived neoglycoproteins and oligosaccharide-glycine derivatives, were used to represent polyvalent glycoconjugates and monovalent oligosaccharides, respectively, in human milk. SPRi binding results established that the glycan motifs that bind norovirus capsids depend upon strain; VA387 capsid interacts with two neoglycoproteins, whereas Norwalk capsid binds to a different set of HMOS motifs in the form of both polyvalent neoglycoproteins and monovalent oligosaccharides. SPRi competitive binding assays further demonstrated that specific norovirus-binding glycans are able to inhibit norovirus capsid binding to their host receptors. A polyvalent neoglycoconjugate with clustered carbohydrate moieties is required for the inhibition of VA387 capsid binding to host receptor glycans, whereas both monovalent oligosaccharides and polyvalent neoglycoconjugates are able to inhibit Norwalk capsid binding to its host receptor. Binding of HMOS and HMOS-based neoglycoconjugates to norovirus capsids depends upon the specific strain characteristics, implying that HMOS and their polyvalent derivatives are potential anti-adhesive agents for norovirus prophylaxis.

Silicon photonic micro-disk resonators for label-free biosensing.

Silicon photonic biosensors are highly attractive for multiplexed Lab-on-Chip systems. Here, we characterize the sensing performance of 3 µm TE-mode and 10 µm dual TE/TM-mode silicon photonic micro-disk resonators and demonstrate their ability to detect the specific capture of biomolecules. Our experimental results show sensitivities of 26 nm/RIU and 142 nm/RIU, and quality factors of 3.3x10(4) and 1.6x10(4) for the TE and TM modes, respectively. Additionally, we show that the large disks contain both TE and TM modes with differing sensing characteristics. Finally, by serializing multiple disks on a single waveguide bus in a CMOS compatible process, we demonstrate a biosensor capable of multiplexed interrogation of biological samples.

Conformationally constrained functional peptide monolayers for the controlled display of bioactive carbohydrate ligands.

In this study, we employed thiolated peptides of the conformationally constrained, strongly helicogenic α-aminoisobutyric acid (Aib) residue to prepare self-assembled monolayers (SAMs) on gold surfaces. Electrochemistry and infrared reflection absorption spectroscopy support the formation of very well packed Aib-peptide SAMs. The immobilized peptides retain their helical structure, and the resulting SAMs are stabilized by a network of intermolecular H bonds involving the NH groups adjacent to the Au surface. Binary SAMs containing a synthetically defined glycosylated mannose-functionalized Aib-peptide as the second component display similar features, thereby providing reproducible substrates suitable for the controlled display of bioactive carbohydrate ligands. The efficiency of such Aib-based SAMs as a biomolecular recognition platform was evidenced by examining the mannose-concanavalin A interaction via surface plasmon resonance biosensing.

Capturing dynamical correlations using implicit neural representations.

Understanding the nature and origin of collective excitations in materials is of fundamental importance for unraveling the underlying physics of a many-body system. Excitation spectra are usually obtained by measuring the dynamical structure factor, S(Q, ω), using inelastic neutron or x-ray scattering techniques and are analyzed by comparing the experimental results against calculated predictions. We introduce a data-driven analysis tool which leverages 'neural implicit representations' that are specifically tailored for handling spectrographic measurements and are able to efficiently obtain unknown parameters from experimental data via automatic differentiation. In this work, we employ linear spin wave theory simulations to train a machine learning platform, enabling precise exchange parameter extraction from inelastic neutron scattering data on the square-lattice spin-1 antiferromagnet La2NiO4, showcasing a viable pathway towards automatic refinement of advanced models for ordered magnetic systems.