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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.

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13 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Integrative Quantitative-Phase and Airy Light-Sheet Imaging

Light-sheet microscopy enables considerable speed and phototoxicity gains, while quantitative-phase imaging confers label-free organelle recognition and metabolic information that are inaccessible by conventional methods. We report the fusion of these two modalities onto a standard inverted microscope that retains compatibility with microfluidics. We describe the utilization of an accelerating Airy-beam light-sheet yielding identical imaging areas with interferometry, and an application in unmasking the effects of cellular noise on metabolic compartmentalization.

Biological sciences, Biological techniques, Micros↗
DOE OSTI2024

A Semi‐Automated, High‐Throughput Approach for the Synthesis and Identification of Highly Photo‐Cytotoxic Iridium Complexes

Abstract The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein, we apply combinatorial synthesis to build a library of 90 iridium(III) complexes (81 of which are new) over two synthesise‐and‐test cycles, with the aim of identifying potential agents for photodynamic therapy. We demonstrate the power of this approach by identifying highly active complexes that are well‐tolerated in the dark but display very low nM phototoxicity against cancer cells. To build a detailed structure–activity relationship for this class of compounds we have used density functional theory (DFT) calculations to determine some key electronic parameters and study correlations with the experimental data. Finally, we present an optimised semi‐automated synthesise‐and‐test protocol to obtain multiplex data within 72 hours.

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

Fusing Quantitative-Phase Imaging with Airy Light- Sheet Microscopy

We report the integration of quantitative-phase imaging (QPI) with light-sheet (LS) fluorescent microscopy on to a standard inverted microscope that retains compatibility with microfluidics. QPI enables label-free imaging and number-density quantification of single cells and their organelles. Conversely, LS yields considerable speed and phototoxicity gains in quantifying the 4D dynamics of gene-encoded fluorescent biomarkers. We will detail the system design that relied on spatial light interferometry for QPI and an accelerating Airy- beam light-sheet for fluorescence, its performance, as well as results of a representative multivariate imaging analysis of single-cell metabolism.

imaging, lattice light sheet, Yarrowia lipolytica,↗
DOE OSTI2024

A Semi‐Automated, High‐Throughput Approach for the Synthesis and Identification of Highly Photo‐Cytotoxic Iridium Complexes

Abstract The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there is increasing interest in developing workflows that allow for the rapid synthesis and evaluation of libraries of compounds with the aim of identifying leads for further drug development. Herein, we apply combinatorial synthesis to build a library of 90 iridium(III) complexes (81 of which are new) over two synthesise‐and‐test cycles, with the aim of identifying potential agents for photodynamic therapy. We demonstrate the power of this approach by identifying highly active complexes that are well‐tolerated in the dark but display very low nM phototoxicity against cancer cells. To build a detailed structure–activity relationship for this class of compounds we have used density functional theory (DFT) calculations to determine some key electronic parameters and study correlations with the experimental data. Finally, we present an optimised semi‐automated synthesise‐and‐test protocol to obtain multiplex data within 72 hours.

Kench, Timothy↗
DOE OSTI2023

Scattered–light–sheet microscopy with sub–cellular resolving power

Since its first demonstration over 100 years ago, scattering-based light-sheet microscopy has recently re-emerged as a key modality in label-free tissue imaging and cellular morphometry; however, scattering-based light-sheet imaging with subcellular resolution remains an unmet target to date. This is because related approaches inevitably superimpose speckle or granular intensity modulation on to the native subcellular features. Here, we addressed this challenge by deploying a time-averaged pseudo-thermalized light-sheet illumination. While pseudo-thermalizing the illumination sheet increased its lateral dimensions, we achieved subcellular resolving power at ultralow irradiance levels after image deconvolution. We validated this approach by imaging cytosolic carbon depots in yeast and bacteria with increased specificity and no staining. Altogether, we expect this scattering-based light-sheet microscopy approach will advance live single-cell imaging investigations by conferring low-irradiance and label-free operation towards eradicating phototoxicity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Dual-Color Optical Recording of Bioelectric Potentials by Polymer Electrochromism

Optical recording based on voltage-sensitive fluorescent reporters allows for spatial flexibility of measuring from desired cells, but photobleaching and phototoxicity of the fluorescent labels often limit their sensitivity and recording duration. Voltage-dependent optical absorption, rather than fluorescence, of electrochromic materials, would overcome these limitations to achieve long-term optical recording of bioelectrical signals. Electrochromic materials such as PEDOT:PSS possess the property that an applied voltage can either increase or decrease the light absorption depending on the wavelength. In this work, we harness this anticorrelated light absorption at two different wavelengths to significantly improve the signal detection. With dual-color detection, electrical activity from cells produces signals of opposite polarity, while artifacts, mechanical motions, and technical noises are uncorrelated or positively correlated. Using this technique, we are able to optically record cardiac action potentials with a high signal-to-noise ratio, 10 kHz sampling rate, >15 min recording duration, and no time-dependent degradation of the signal. Furthermore, we can reliably perform multiple recording sessions from the same culture for over 25 days.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Site-specific photo-crosslinking in a double crossover DNA tile facilitated by squaraine dye aggregates: advancing thermally stable and uniform DNA nanostructures

We investigated the role of dichloro-squaraine (SQ) dye aggregates in facilitating thymine–thymine interstrand photo-crosslinking within double crossover (DX) tiles, to develop thermally stable and structurally uniform two-dimensional (2D) DNA-based nanostructures. By strategically incorporating SQ modified thymine pairs, we enabled site-selective [2 + 2] photocycloaddition under 310 nm UV light. Strong dye–dye interactions, particularly through the formation of aggregates, facilitated covalent bond formation between proximal thymines. To evaluate the impact of dye aggregation on crosslinking efficiency, ten DX tile variants with varying SQ-modified thymine positions were tested. Our results demonstrated that SQ dye aggregates significantly enhanced crosslinking, driven by precise SQ-modified thymine dimer placement within the DNA tiles. Analytical techniques, including denaturing PAGE and UV-visible spectroscopy, validated successful crosslinking in DNA tiles with multiple SQ-modified thymine pairs. This non-phototoxic method offers a potential route for creating thermally stable, homogeneous higher-order DNA–dye assemblies with potential applications in photoactive and exciton-based fields such as optoelectronics, nanoscale computing, and quantum computing. Furthermore, the insights from this study establish a foundation for further exploration of advanced DNA–dye systems, enabling the design of next-generation DNA nanostructures with enhanced functional properties.

2D DNA template↗
DOE OSTI2026

Enabling robust, stable, and accurate nonlinear optical measurements from squeezed light generated in hot rubidium vapor

The feasibility of nonlinear optical (NLO) imaging and spectroscopy using low intensity quantum states of light including entangled photon and squeezed light sources, such as those driven by two-photon absorption (TPA), has been a topic of ongoing debate. An unambiguous identification of the appreciable quantum advantage in such quantum light applications could enable NLO imaging of biological samples without photodegradation and phototoxicity. Recently, we have constructed a two-mode squeezed light source based on four-wave mixing in 85Rb vapor, which is capable of 7.9 dB of intensity-difference squeezing (IDS), corresponding to 8.7 dB upon electronic noise correction. In this talk, we discuss the stability of our system, including implementation details on achieving and maintaining 8.7 dB of IDS for several hours, and ensuring the two spatially multimode beams are properly overlapped in a sample with minimal optical loss.

Allen, Harry [ORNL] (ORCID:0000000190253914)↗
DOE OSTI2021

Airy light-sheet Raman imaging

Light-sheet fluorescence microscopy has greatly improved the speed and overall photostability of optically sectioning cellular and multi-cellular specimens. Similar gains have also been conferred by light-sheet Raman imaging; these schemes, however, rely on diffraction limited Gaussian beams that hinder the uniformity and size of the imaging field-of-view, and, as such, the resulting throughput rates. Here, we demonstrate that a digitally scanned Airy beam increases the Raman imaging throughput rates by more than an order of magnitude than conventional diffraction-limited beams. Overall, this, spectrometer-less, approach enabled 3D imaging of microparticles with high contrast and 1 µm axial resolution at 300 msec integration times per plane and orders of magnitude lower irradiation density than coherent Raman imaging schemes. We detail the apparatus and its performance, as well as its compatibility with fluorescence light-sheet and quantitative-phase imaging towards rapid and low phototoxicity multimodal imaging.

47 OTHER INSTRUMENTATION↗
DOE OSTI2024

Infrared quantum ghost imaging of living and undisturbed plants

Quantum ghost imaging (QGI) is a method that measures absorption at extremely low light intensities. Nondegenerate QGI probes a sample at one wavelength while forming an image with correlated photons at a different wavelength. This spectral separation alleviates the need for imaging detectors with high sensitivity in the near-infrared (NIR) region, thereby reducing the required illumination intensity. Using NCam, a single-photon detector, we demonstrated nondegenerate QGI with unprecedented sensitivity and contrast, obtaining images of living plants with less than 1% light transmission. The plants experienced 3aW/cm 2 of light during imaging, orders of magnitude below starlight. This realization of QGI expands the method to extremely low-light bioimaging and imaging of light-sensitive samples, where minimizing illumination intensity is crucial to prevent phototoxicity or sample degradation.

47 OTHER INSTRUMENTATION↗
DOE OSTI2021

Deep learning classification of lipid droplets in quantitative phase images

We report the application of supervised machine learning to the automated classification of lipid droplets in label-free, quantitative-phase images. By comparing various machine learning methods commonly used in biomedical imaging and remote sensing, we found convolutional neural networks to outperform others, both quantitatively and qualitatively. We describe our imaging approach, all implemented machine learning methods, and their performance with respect to computational efficiency, required training resources, and relative method performance measured across multiple metrics. Overall, our results indicate that quantitative-phase imaging coupled to machine learning enables accurate lipid droplet classification in single living cells. As such, the present paradigm presents an excellent alternative of the more common fluorescent and Raman imaging modalities by enabling label-free, ultra-low phototoxicity, and deeper insight into the thermodynamics of metabolism of single cells.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Integrated imaging assembly and method for using

Certain disclosed embodiments concern an integrated imaging system that combined light-sheet microscopy, which enables considerable speed and phototoxicity gains, with quantitative-phase imaging. A method for using such imaging systems also is disclosed. In an exemplary embodiment, an integrated imaging system was used for multivariate investigation of live-cells in microfluidics.

Vasdekis, Andreas E.↗
DOE OSTI2020

Sparse and Random Sampling Techniques for High-Resolution, Full-Field, BSS-Based Structural Dynamics Identification from Video

Video-based techniques for identification of structural dynamics have the advantage that they are very inexpensive to deploy compared to conventional accelerometer or strain gauge techniques. When structural dynamics from video is accomplished using full-field, high-resolution analysis techniques utilizing algorithms on the pixel time series such as principal components analysis and solutions to blind source separation the added benefit of high-resolution, full-field modal identification is achieved. An important property of video of vibrating structures is that it is particularly sparse. Typically video of vibrating structures has a dimensionality consisting of many thousands or even millions of pixels and hundreds to thousands of frames. However the motion of the vibrating structure can be described using only a few mode shapes and their associated time series. As a result, emerging techniques for sparse and random sampling such as compressive sensing should be applicable to performing modal identification on video. This work presents how full-field, high-resolution, structural dynamics identification frameworks can be coupled with compressive sampling. The techniques described in this work are demonstrated to be able to recover mode shapes from experimental video of vibrating structures when 70% to 90% of the frames from a video captured in the conventional manner are removed.

47 OTHER INSTRUMENTATION↗