Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “single molecule techniques”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Scalable Parallel Measurement of Individual Nitrogen-Vacancy Centers

The nitrogen-vacancy (NV) center in diamond is a solid-state spin defect that has been widely adopted for quantum sensing and quantum information processing applications. Typically, experiments are performed either with a single isolated NV center or with an unresolved ensemble of many NV centers, resulting in a trade-off between measurement speed and spatial resolution or control over individual defects. In this work, we introduce an experimental platform that bypasses this trade-off by addressing multiple optically resolved NV centers in parallel. We perform charge- and spin-state manipulations selectively on multiple NV centers from within a larger set, and we manipulate and measure the electronic spin states of over 100 NV centers in parallel. We show that the high signal-to-noise ratio of the measurements enables the detection of shot-to-shot pairwise correlations between the spin states of 108 NV centers, corresponding to the simultaneous measurement of 5778 unique correlation coefficients. We discuss how our platform can be scaled to parallel experiments with thousands of individually resolved NV centers. These results enable parallelized high-throughput sensing experiments that retain the spatial resolution of single defects and will, thereby, help to unlock advances in applications such as single-molecule NMR and characterization of integrated circuits. In addition, our approach to multiplexing provides a natural platform for the application of recently developed correlated sensing techniques.

NV centers↗
DOE OSTI2022

State-selective probing of CO 2 autoionizing inner valence Rydberg states with attosecond extreme ultraviolet four-wave-mixing spectroscopy

Nonlinear spectroscopies can disentangle spectra that are congested due to inhomogeneous broadening. Here, in conjunction with theoretical calculations, attosecond extreme ultraviolet (XUV) four-wave-mixing (FWM) spectroscopy is utilized to probe the dynamics of autoionizing inner valence excited Rydberg states of the polyatomic molecule, CO 2 . This tabletop nonlinear technique employs a short attosecond XUV pulse train and two noncollinear, few-cycle near-infrared pulses to generate background-free XUV wave-mixing signals. FWM emission is observed from the n=5-7 states of the Henning sharp ndσ g Rydberg series that converges to the ionic $\widetilde{B}$ 2 Σ$^{+}_{u}$ state. However, these transient emission signals decay with lifetimes of 33 ± 6, 53 ± 2, and 94 ± 2 fs, respectively, which calculations show are consistent with the lifetimes of the short-lived n=6-8 members of the nsσ g character Henning diffuse Rydberg series. The oscillator strengths of transitions between states involved in all possible resonant FWM processes are calculated, verifying that the nonlinear spectra are dominated by pathways described by an initial excitation to the diffuse nsσ g Rydberg series and emission from the sharp ndσ g Rydberg series. The results substantiate not only that attosecond XUV FWM spectroscopy produces rigorous and meaningful measurements of ultrafast dynamics in polyatomic systems, but also that nonlinear spectroscopic techniques are versatile tools to selectively probe dynamics that are otherwise difficult to access.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Unraveling the Dynamics of Nucleosome Arrays

The organization of genomic DNA into chromatin is a fundamental determinant of genome stability, regulation, and cellular function. Nucleosomes, the basic repeating units of chromatin, assemble into higher-order structures whose organization and heterogeneity remain difficult to characterize using conventional ensemble-averaged techniques. A key need in the field is the development of experimental approaches capable of directly visualizing nucleosome assemblies and their structural variability at the single-molecule level. This LDRD Lab-Wide project focused on establishing and evaluating atomic force microscopy (AFM)–based approaches for the characterization of nucleosome assemblies. The work emphasized experimental workflows for preparing, imaging, and assessing multi-nucleosome systems, rather than isolated single nucleosomes. Through method development and exploratory measurements, the project demonstrated the feasibility of applying scanning probe microscopy to investigate chromatin-relevant assemblies and provided preliminary insight into the strengths and limitations of this approach for future quantitative studies. Results and lessons learned from this effort were disseminated to the broader scientific community through multiple national conference presentations, helping to position LLNL for continued work in chromatin and genome organization research.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Two-dimensional phase cartography for high-harmonic spectroscopy

Extremely nonlinear spectroscopy based on high-order-harmonic generation has become a powerful investigation method for attosecond dynamics in gas and solid targets. In particular, the phase of harmonic emission was shown to carry profound insight into atomic and molecular structure and dynamics. However, current techniques offer phase measurements only along specific directions, thus providing partial characterization. Here we report on a new approach combining optical and quantum interferometers measuring along two dimensions the intensity and phase of harmonic emission from aligned molecules in the exact same experimental conditions. This two-dimensional cartography technique measures the phase with no arbitrary offset and no uncertainty on its sign. Measurements along different dimensions can be combined in two ways: either a single mapping or a redundant mapping allowing high-precision phase recovery using a Shack–Hartmann-like algorithm. We demonstrate both methods in a nitrogen test case, which allows disentangling structural and dynamical effects. Two-dimensional phase cartography paves the way to high-resolution high-harmonic spectroscopy for applications such as quantum orbital tomography and attosecond charge migration in molecules.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2024

Towards interpretable Cryo-EM: disentangling latent spaces of molecular conformations

Molecules are essential building blocks of life and their different conformations (i.e., shapes) crucially determine the functional role that they play in living organisms. Cryogenic Electron Microscopy (cryo-EM) allows for acquisition of large image datasets of individual molecules. Recent advances in computational cryo-EM have made it possible to learn latent variable models of conformation landscapes. However, interpreting these latent spaces remains a challenge as their individual dimensions are often arbitrary. The key message of our work is that this interpretation challenge can be viewed as an Independent Component Analysis (ICA) problem where we seek models that have the property of identifiability. That means, they have an essentially unique solution, representing a conformational latent space that separates the different degrees of freedom a molecule is equipped with in nature. Thus, we aim to advance the computational field of cryo-EM beyond visualizations as we connect it with the theoretical framework of (nonlinear) ICA and discuss the need for identifiable models, improved metrics, and benchmarks. Moving forward, we propose future directions for enhancing the disentanglement of latent spaces in cryo-EM, refining evaluation metrics and exploring techniques that leverage physics-based decoders of biomolecular systems. Moreover, we discuss how future technological developments in time-resolved single particle imaging may enable the application of nonlinear ICA models that can discover the true conformation changes of molecules in nature. The pursuit of interpretable conformational latent spaces will empower researchers to unravel complex biological processes and facilitate targeted interventions. This has significant implications for drug discovery and structural biology more broadly. More generally, latent variable models are deployed widely across many scientific disciplines. Thus, the argument we present in this work has much broader applications in AI for science if we want to move from impressive nonlinear neural network models to mathematically grounded methods that can help us learn something new about nature.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Experimental determination of the magnetic anisotropy in five-coordinated Co( II ) field-induced single molecule magnets

Magnetic anisotropy of the central metal atom is a crucial property of single molecule magnets (SMMs). Small structural changes can alter the magnetic properties, and accurate experimental methods to investigate magnetic anisotropy are therefore critical. Here, we investigate two five-coordinated Co( II ) SMMs, [CoCl 2 Cltpy] (1) and [CoBr 2 Cltpy] (2) (Cltpy = 4′-chloro-2,2′:6′,2′′-terpyridine), through multiple techniques. Ab initio theoretical calculations performed on the two compounds show that both possess axial magnetic anisotropy with the magnetic easy axis pointing towards one of the terminal halogen atoms. Theoretical calculations on SMMs are typically done on isolated molecular species, and to validate this approximation the magnetic anisotropy was further studied through experimental techniques. EPR measurements confirm an axial anisotropy of 1, and magnetic measurements provide experimental Zero-Field Splitting (ZFS) parameters, showing that the values from theoretical calculations are slightly overestimated. The X-ray electron density determined from 20 K single-crystal synchrotron X-ray diffraction data provides estimated d-orbital populations also suggesting axial magnetic anisotropy in both systems, and furthermore suggesting a more pronounced axiality in 1 compared to 2. This is in good agreement with the results obtained from both magnetic measurements and theoretical calculations. The magnetic anisotropy of 1 is quantified experimentally through polarized powder neutron diffraction via the site susceptibility method, confirming an axial magnetic anisotropy of the compound. A slight deviation in the easy axis direction is observed between experimental and theoretical results. This, together with the overestimation of the ZFS parameters from theoretical calculations, shows that experimental investigation of the magnetic anisotropy of SMMs is of high relevance. Magnetic anisotropy of the central metal atom is a crucial property of single molecule magnets (SMMs).

Slavensky, Hannah H. [Aarhus Univ. (Denmark)] (ORC↗
DOE OSTI2022

Hole in one: Pathways to deterministic single-acceptor incorporation in Si(100)-2 x 1

We report that stochastic incorporation kinetics can be a limiting factor in the scalability of semiconductor fabrication technologies using atomic-precision techniques. While these technologies have recently been extended from donors to acceptors, the extent to which kinetics will impact single-acceptor incorporation has yet to be assessed. To identify the precursor molecule and dosing conditions that are promising for deterministic incorporation, we develop and apply an atomistic model for the single-acceptor incorporation rates of several recently demonstrated molecules: diborane (B 2 H 6 ), boron trichloride (BCl 3 ), and aluminum trichloride in both monomer (AlCl 3 ) and dimer forms (Al 2 Cl 6 ). While all three precursors can realize single-acceptor incorporation, we predict that diborane is unlikely to realize deterministic incorporation, boron trichloride can realize deterministic incorporation with modest heating (50 °C), and aluminum trichloride can realize deterministic incorporation at room temperature. We conclude that both boron and aluminum trichloride are promising precursors for atomic-precision single-acceptor applications, with the potential to enable the reliable production of large arrays of single-atom quantum devices.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2021

Structural Insights into the Vapochromic Behavior of Pt- and Pd-Based Compounds

Anionic complexes having vapochromic behavior are investigated: [K(H 2 O)][M(ppy)(CN) 2 ], [K(H 2 O)][M(bzq)(CN) 2 ], and [Li(H 2 O) n ][Pt(bzq)(CN) 2 ], where ppy = 2-phenylpyridinate, bzq = 7,8-benzoquinolate, and M = Pt(II) or Pd(II). These hydrated potassium/lithium salts exhibit a change in color upon being heated to 380 K, and they transform back into the original color upon absorption of water molecules from the environment. The challenging characterization of their structure in the vapochromic transition has been carried out by combining several experimental techniques, despite the availability of partially ordered and/or impure crystalline material. Room-temperature single-crystal and powder X-ray diffraction investigation revealed that [K(H 2 O)][Pt(ppy)(CN) 2 ] crystallizes in the Pbca space group and is isostructural to [K(H 2 O)][Pd(ppy)(CN) 2 ]. Variable-temperature powder X-ray diffraction allowed the color transition to be related to changes in the diffraction pattern and the decrease in sample crystallinity. Water loss, monitored by thermogravimetric analysis, occurs in two stages, well separated for potassium Pt compounds and strongly overlapped for potassium Pd compounds. Furthermore, the local structure of potassium compounds was monitored by in situ pair distribution function (PDF) measurements, which highlighted changes in the intermolecular distances due to a rearrangement of the crystal packing upon vapochromic transition.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Selective photo-excitation of molecules enabled by stimulated Raman pre-excitation

Double resonance excitation, where the energies of vibrational and electronic molecular transitions are combined in a single, sequential excitation process, was introduced in the 1970s but has only been recently applied to microscopy due to the immense progress in Raman spectroscopy. The value of the technique is in combining the chemical selectivity of IR or Raman excitation with the much larger cross-sections of electronic transitions. Recently, it has been shown to be particularly suited for the detection and identification of chromophores at low concentrations and in the presence of spectral crosstalk. However, despite its low quantum yield per pulse sequence, we believe the technique has potential for selective photochemical transformations. There are some cases (e.g., the selective excitation of optogenetic switches) where the low yield may be overcome by repeated excitations to build up biochemically relevant concentrations. Here we show that double resonance excitation using general, non-resonant Raman pre-excitation is a viable candidate for selectively promoting molecules to chemically active energy levels. Further, the use of non-resonant Raman pre-excitation is less constraining than resonant Raman (used in previous double resonance microscopy works) since the choice of Raman pump-Stokes frequencies may be rather freely chosen.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Atomic Force Microscopy to Characterize Antimicrobial Peptide-Induced Defects in Model Supported Lipid Bilayers

Antimicrobial peptides (AMPs) interact with bacterial cell membranes through a variety of mechanisms, causing changes extending from nanopore formation to microscale membrane lysis, eventually leading to cell death. Several AMPs also disrupt mammalian cell membranes, despite their significantly different lipid composition and such collateral hemolytic damage hinders the potential therapeutic applicability of the AMP as an anti-microbial. Elucidating the mechanisms underlying the AMP–membrane interactions is challenging due to the variations in the chemical and structural features of the AMPs, the complex compositional variations of cell membranes and the inadequacy of any single experimental technique to comprehensively probe them. (1) Background: Atomic Force Microscopy (AFM) imaging can be used in combination with other techniques to help understand how AMPs alter the orientation and structural organization of the molecules within cell membranes exposed to AMPs. The structure, size, net charge, hydrophobicity and amphipathicity of the AMPs affect how they interact with cell membranes of differing lipid compositions. (2) Methods: Our study examined two different types of AMPs, a 20-amino acid, neutral, α-helical (amphipathic) peptide, alamethicin, and a 13-amino acid, non-α-helical cationic peptide, indolicidin (which intramolecularly folds, creating a hydrophobic core), for their interactions with supported lipid bilayers (SLBs). Robust SLB model membranes on quartz supports, incorporating predominantly anionic lipids representative of bacterial cells, are currently not available and remain to be developed. Therefore, the SLBs of zwitterionic egg phosphatidylcholine (PC), which represents the composition of a mammalian cell membrane, was utilized as the model membrane. This also allows for a comparison with the results obtained from the Quartz Crystal Microbalance with Dissipation (QCM-D) experiments conducted for these peptides interacting with the same zwitterionic SLBs. Further, in the case of alamethicin, because of its neutrality, the lipid charge may be less relevant for understanding its membrane interactions. (3) Results: Using AFM imaging and roughness analysis, we found that alamethicin produced large, unstable defects in the membrane at 5 µM concentrations, and completely removed the bilayer at 10 µM. Indolicidin produced smaller holes in the bilayer at 5 and 10 µM, although they were able to fill in over time. The root-mean-square (RMS) roughness values for the images showed that the surface roughness caused by visible defects peaked after peptide injection and gradually decreased over time. (4) Conclusions: AFM is useful for helping to uncover the dynamic interactions between different AMPs and cell membranes, which can facilitate the selection and design of more efficient AMPs for use in therapeutics and antimicrobial applications.

Swana, Kathleen W.↗
DOE OSTI2022

Comprehensive single-shot biophysical cytometry using simultaneous quantitative phase imaging and Brillouin spectroscopy

Abstract Single-cell analysis, or cytometry, is a ubiquitous tool in the biomedical sciences. Whereas most cytometers use fluorescent probes to ascertain the presence or absence of targeted molecules, biophysical parameters such as the cell density, refractive index, and viscosity are difficult to obtain. In this work, we combine two complementary techniques—quantitative phase imaging and Brillouin spectroscopy—into a label-free image cytometry platform capable of measuring more than a dozen biophysical properties of individual cells simultaneously. Using a geometric simplification linked to freshly plated cells, we can acquire the cellular diameter, volume, refractive index, mass density, non-aqueous mass, fluid volume, dry volume, the fractional water content of cells, both by mass and by volume, the Brillouin shift, Brillouin linewidth, longitudinal modulus, longitudinal viscosity, the loss modulus, and the loss tangent, all from a single acquisition, and with no assumptions of underlying parameters. Our methods are validated across three cell populations, including a control population of CHO-K1 cells, cells exposed to tubulin-disrupting nocodazole, and cells under hypoosmotic shock. Our system will unlock new avenues of research in biophysics, cell biology, and medicine.

Steelman, Zachary A.↗
DOE OSTI2022

Triplet-pair spin signatures from macroscopically aligned heteroacenes in an oriented single crystal

The photo-driven process of singlet fission generates coupled triplet pairs (TT) with fundamentally intriguing and potentially useful properties. The quintet 5 TT 0 sublevel is particularly interesting for quantum information because it is highly entangled, is addressable with microwave pulses, and could be detected using optical techniques. Previous theoretical work on a model Hamiltonian and nonadiabatic transition theory, called the JDE model, has determined that this sublevel can be selectively populated if certain conditions are met. Among the most challenging, the molecules within the dimer undergoing singlet fission must have their principal magnetic axes parallel to one another and to an applied Zeeman field. Here, we present time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy of a single crystal sample of a tetracenethiophene compound featuring arrays of dimers aligned in this manner, which were mounted so that the orientation of the field relative to the molecular axes could be controlled. The observed spin sublevel populations in the paired TT and unpaired (T+T) triplets are consistent with predictions from the JDE model, including preferential 5 TT 0 formation at z ‖ B 0 , with one caveat—two 5 TT spin sublevels have little to no population. This may be due to crossings between the 5 TT and 3 TT manifolds in the field range investigated by TR-EPR, consistent with the intertriplet exchange energy determined by monitoring photoluminescence at varying magnetic fields.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

A simple technique to classify diffraction data from dynamic proteins according to individual polymorphs

One often observes small but measurable differences in the diffraction data measured from different crystals of a single protein. These differences might reflect structural differences in the protein and may reveal the natural dynamism of the molecule in solution. Partitioning these mixed-state data into single-state clusters is a critical step that could extract information about the dynamic behavior of proteins from hundreds or thousands of single-crystal data sets. Mixed-state data can be obtained deliberately (through intentional perturbation) or inadvertently (while attempting to measure highly redundant single-crystal data). To the extent that different states adopt different molecular structures, one expects to observe differences in the crystals; each of the polystates will create a polymorph of the crystals. After mixed-state diffraction data have been measured, deliberately or inadvertently, the challenge is to sort the data into clusters that may represent relevant biological polystates. Here, this problem is addressed using a simple multi-factor clustering approach that classifies each data set using independent observables, thereby assigning each data set to the correct location in conformational space. This procedure is illustrated using two independent observables, unit-cell parameters and intensities, to cluster mixed-state data from chymotrypsinogen (ChTg) crystals. It is observed that the data populate an arc of the reaction trajectory as ChTg is converted into chymotrypsin.

36 MATERIALS SCIENCE↗
DOE OSTI2022

Methods to Calculate Electronic Excited-State Dynamics for Molecules on Large Metal Clusters with Many States: Ensuring Fast Overlap Calculations and a Robust Choice of Phase

Here, we present an efficient set of methods for propagating excited-state dynamics involving a large number of configuration interaction singles (CIS) or Tamm-Dancoff approximation (TDA) single-reference excited states. Specifically, (i) following Head-Gordon et al., we implement an exact evaluation of the overlap of singly-excited CIS/TDA electronic states at different nuclear geometries using a biorthogonal basis and (ii) we employ a unified protocol for choosing the correct phase for each adiabat at each geometry. For many-electron systems, the combination of these techniques significantly reduces the computational cost of integrating the electronic Schrodinger equation and imposes minimal overhead on top of the underlying electronic structure calculation. As a demonstration, we calculate the electronic excited-state dynamics for a hydrogen molecule scattering off a silver metal cluster, focusing on high-lying excited states, where many electrons can be excited collectively and crossings are plentiful. Interestingly, we find that the high-lying, plasmon-like collective excitation spectrum changes with nuclear dynamics, highlighting the need to simulate non-adiabatic nuclear dynamics and plasmonic excitations simultaneously. In the future, the combination of methods presented here should help theorists build a mechanistic understanding of plasmon-assisted charge transfer and excitation energy relaxation processes near a nanoparticle or metal surface.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Structure evolution of single-site Pt in a metal–organic framework

Heterogeneous single-metal-site catalyst or single-atom catalyst research has grown rapidly due to the accessibility of modern characterization techniques that can provide invaluable information at the atomic-scale. Herein, we study the structural evolution of isolated single Pt sites incorporated in a metal–organic framework containing bipyridine functional groups using in situ diffuse reflectance infrared Fourier transform spectroscopy with CO as the probe molecule. The structure and electronic properties of the isolated Pt sites are further corroborated by x-ray photoelectron spectroscopy and aberration-corrected scanning transmission electron microscopy. Here, we find the prerequisite of high temperature He treatment for Pt activation and CO insertion and inquire into the structural transformation of Pt site process by dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance spectroscopy.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Quantum interferometry and pathway selectivity in the nonlinear response of photosynthetic excitons

We propose a time–frequency resolved spectroscopic technique which employs nonlinear interferometers to study exciton–exciton scattering in molecular aggregates. A higher degree of control over the contributing Liouville pathways is obtained as compared to classical light. We show how the nonlinear response can be isolated from the orders-of-magnitude stronger linear background by either phase matching or polarization filtering. Both arise due to averaging the signal over a large number of noninteracting, randomly oriented molecules. We apply our technique to the Frenkel exciton model which excludes charge separation for the photosystem II reaction center. We show how the sum of the entangled photon frequencies can be used to select two-exciton resonances, while their delay times reveal the single-exciton levels involved in the optical process.

Science & Technology - Other Topics↗
DOE OSTI2023

Mid-infrared spectroscopy with a broadly tunable thin-film lithium niobate optical parametric oscillator

Mid-infrared spectroscopy, an important technique for sensing molecules, has encountered barriers from sources either limited in tuning range or excessively bulky for widespread use. We present a compact, efficient, and broadly tunable optical parametric oscillator surmounting these challenges. Leveraging dispersion-engineered thin-film lithium niobate-on-sapphire photonics and a singly resonant cavity allows broad, controlled tuning over an octave from 1.5–3.3 µm. The device generates >25mW of mid-infrared light at 3.2 µm with 15% conversion efficiency. The ability to precisely control the device’s mid-infrared emission enables spectroscopy of methane and ammonia, demonstrating our approach’s relevance for sensing. Our work signifies an important advance in nonlinear photonics miniaturization, bringing practical field applications of high-speed, broadband mid-infrared spectroscopy closer to reality.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗