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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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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Adaptive optical correction for in vivo two-photon fluorescence microscopy with neural fields

Adaptive optics restore ideal imaging performance in complex samples by measuring and correcting optical aberrations but often require custom-built microscopes with carefully aligned wavefront sensing/shaping devices and can be susceptible to sample motion. Here we describe NeAT, a computational framework using neural fields for adaptive optics two-photon fluorescence microscopy. NeAT estimates wavefront aberration and recovers sample structure from a 3D image stack without requiring external datasets for training. Incorporating motion correction in learning and correcting conjugation errors commonly found in commercial microscopes, NeAT is designed for deployment in biological laboratories for in vivo imaging. We validate NeAT’s performance using a custom-built microscope with a wavefront sensor under varying signal-to-noise ratios, aberration and motion conditions. With a commercial microscope, we demonstrate real-time aberration correction for in vivo morphological and functional imaging in the living mouse brain, with NeAT improving the signal and accuracy of glutamate and calcium imaging of synapses and neurons.

Kang, Iksung↗
DOE OSTI2022

Hierarchical deep reinforcement learning reveals a modular mechanism of cell movement

Time-lapse images of cells and tissues contain rich information about dynamic cell behaviours, which reflect the underlying processes of proliferation, differentiation and morphogenesis. However, we lack computational tools for effective inference. Here we exploit deep reinforcement learning (DRL) to infer cell–cell interactions and collective cell behaviours in tissue morphogenesis from three-dimensional (3D) time-lapse images. We use hierarchical DRL (HDRL), known for multiscale learning and data efficiency, to examine cell migrations based on images with a ubiquitous nuclear label and simple rules formulated from empirical statistics of the images. When applied to Caenorhabditis elegans embryogenesis, HDRL reveals a multiphase, modular organization of cell movement. Imaging with additional cellular markers confirms the modular organization as a novel migration mechanism, which we term sequential rosettes. Furthermore, HDRL forms a transferable model that successfully differentiates sequential rosettes-based migration from others. Our study demonstrates a powerful approach to infer the underlying biology from time-lapse imaging without prior knowledge.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

VitroJet: new features and case studies

Single-particle cryo-electron microscopy has become a widely adopted method in structural biology due to many recent technological advances in microscopes, detectors and image processing. Before being able to inspect a biological sample in an electron microscope, it needs to be deposited in a thin layer on a grid and rapidly frozen. The VitroJet was designed with this aim, as well as avoiding the delicate manual handling and transfer steps that occur during the conventional grid-preparation process. Since its creation, numerous technical developments have resulted in a device that is now widely utilized in multiple laboratories worldwide. It features plasma treatment, low-volume sample deposition through pin printing, optical ice-thickness measurement and cryofixation of pre-clipped Autogrids through jet vitrification. This paper presents recent technical improvements to the VitroJet and the benefits that it brings to the cryo-EM workflow. A wide variety of applications are shown: membrane proteins, nucleosomes, fatty-acid synthase, Tobacco mosaic virus, lipid nanoparticles, tick-borne encephalitis viruses and bacteriophages. These case studies illustrate the advancement of the VitroJet into an instrument that enables accurate control and reproducibility, demonstrating its suitability for time-efficient cryo-EM structure determination.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Ultra-high Information-content Chemical Imaging with Broadband Coherent Anti-Stokes Raman and Two-photon Fluorescence Lifetime Microscopy

Raman fingerprint spectroscopy and fluorescence lifetime imaging are emerging tools for studying metabolic profiles of biological specimens. While Raman fingerprint spectroscopy detects intrinsic molecular vibrations that reflect the molecular composition and chemical environment of a sample, fluorescence lifetime imaging measures changes in the excited-state lifetime of fluorophores that are sensitive to their microenvironments. Here, we present a multimodal imaging platform combining broadband coherent anti-Stokes Raman scattering (BCARS) and two-photon fluorescence lifetime imaging (2p-FLIM) microscopy that can acquire biologically relevant Raman fingerprint spectra and fluorescence lifetime signals in vivo and simultaneously. The tremendous chemical information obtained from spatially co-registered BCARS and 2p-FLIM images allows us to characterize the subtle differences between sub-cellular compartments and verify the potential false-positive results generated by fluorescence imaging alone. This is demonstrated by directly comparing the BCARS, 2p-FLIM, and two-photon excitation fluorescence(TPEF) signals simultaneously obtained from the same dye-stained organelle in the live, intact C. elegans expressing a green fluorescent protein (GFP) marker. In this work, we introduce the BCARS/2p-FLIM/TPEF setup scheme, the image acquisition steps, data processing, and representative results showing that the cross-modality imaging method enables rigorous characterization and in vivo detection at sub-cellular resolution. Furthermore, this protocol provides a framework for simultaneous chemical and fluorescence lifetime imaging to improve the accuracy of biological interpretation in complex living systems.

Xu, Haoyu [Georgia Institute of Technology, Atlant↗
DOE OSTI2026

Quantum correlation imaging via X-ray parametric down-conversion

Quantum imaging leverages correlations between pairs of photons and has the potential to obtain image information beyond what classical sources provide. Extending this approach to the X-ray regime has been limited by low photon-pair generation rates and the lack of suitable detectors. Here, we demonstrate X-ray coincidence imaging using spontaneous parametric down-conversion (SPDC) and a pixelated area detector with time- and energy-resolved capabilities. This configuration enables simultaneous detection of correlated X-ray photon pairs and coincidence-based imaging of test objects, including a biological specimen. The increased coincidence rate and spatially resolved detection establish a basis for future quantum-enhanced and low-dose X-ray imaging.

Goodrich, Justin C. [Brookhaven National Laborator↗
DOE OSTI2025

SwinCell: a 3D transformer and flow-based framework for improved cell segmentation

Segmentation of three-dimensional (3D) cellular images is fundamental for studying and understanding cell structure and function. However, 3D cellular segmentation is challenging, particularly for dense cells and tissues. This challenge arises mainly from the complex contextual information within 3D images, anisotropic properties, and the sensitivity to internal cellular structures, which often lead to incorrect segmentation. In this work, we introduce SwinCell, a 3D transformer-based framework that leverages Swin-transformer to predict flow and differentiate individual cell instances. We demonstrate SwinCell’s utility in the segmentation of nuclei, colon tissue cells, and densely cultured cells. SwinCell strikes a balance between maintaining detailed local feature recognition and understanding broader contextual information. Through extensive testing with both public and in-house 3D cell imaging datasets, SwinCell shows utility in segmenting dense cells, making it a valuable tool for 3D segmentation in cellular analysis that could expedite research in cell biology and tissue engineering.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Selecting XFEL single-particle snapshots by geometric machine learning

A promising new route for structural biology is single-particle imaging with an X-ray Free-Electron Laser (XFEL). This method has the advantage that the samples do not require crystallization and can be examined at room temperature. However, high-resolution structures can only be obtained from a sufficiently large number of diffraction patterns of individual molecules, so-called single particles. Here, we present a method that allows for efficient identification of single particles in very large XFEL datasets, operates at low signal levels, and is tolerant to background. This method uses supervised Geometric Machine Learning (GML) to extract low-dimensional feature vectors from a training dataset, fuse test datasets into the feature space of training datasets, and separate the data into binary distributions of “single particles” and “non-single particles.” As a proof of principle, we tested simulated and experimental datasets of the Coliphage PR772 virus. We created a training dataset and classified three types of test datasets: First, a noise-free simulated test dataset, which gave near perfect separation. Second, simulated test datasets that were modified to reflect different levels of photon counts and background noise. These modified datasets were used to quantify the predictive limits of our approach. Third, an experimental dataset collected at the Stanford Linear Accelerator Center. The single-particle identification for this experimental dataset was compared with previously published results and it was found that GML covers a wide photon-count range, outperforming other single-particle identification methods. Moreover, a major advantage of GML is its ability to retrieve single particles in the presence of structural variability.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2025

Ultracold cryogenic TEM with liquid helium and high stability

Cryogenic transmission electron microscopy has revolutionized structural biology and materials science. To image below liquid nitrogen temperatures, various liquid helium stages have been constructed but have proven to be complex and unstable, making high-resolution imaging challenging. This problem is even more pronounced in side-entry specimen holders common on modern transmission electron microscopes. Here, we introduce an ultracold liquid helium transmission electron microscope side-entry specimen holder, featuring continuous cryogen flow and vibration decoupling. This instrument is compatible with modern aberration-corrected microscopes and achieves sub-25 K base temperature, ±2 mK thermal stability over many hours, and atomic resolution—setting the stage for a new era of cryogenic electron microscopy.

42 ENGINEERING↗
DOE OSTI2021

Bi-terminal pegylated integrin-binding peptides and methods of use thereof

The present invention provides bi-terminal PEGylated peptide conjugates that target an integrin such as αvβ6 integrin. In particular embodiments, the peptide conjugates of the present invention further comprise a biological agent such as an imaging agent or a therapeutic agent, e.g., covalently attached to one of the PEG moieties. The peptide conjugates of the present invention are particularly useful for imaging a tumor, organ, or tissue and for treating integrin-mediated diseases and disorders such as cancer, inflammatory diseases, autoimmune diseases, chronic fibrosis, chronic obstructive pulmonary disease (COPD), lung emphysema, and chronic wounding skin disease. Compositions and kits containing the peptide conjugates of the present invention find utility in a wide range of applications including, e.g., in vivo imaging and immunotherapy.

Hausner, Sven H.↗
DOE OSTI2022

Bi-terminal pegylated integrin-binding peptides and methods of use thereof

The present invention provides bi-terminal PEGylated peptide conjugates that target an integrin such as αvβ6 integrin. In particular embodiments, the peptide conjugates of the present invention further comprise a biological agent such as an imaging agent or a therapeutic agent, e.g., covalently attached to one of the PEG moieties. The peptide conjugates of the present invention are particularly useful for imaging a tumor, organ, or tissue and for treating integrin-mediated diseases and disorders such as cancer, inflammatory diseases, autoimmune diseases, chronic fibrosis, chronic obstructive pulmonary disease (COPD), lung emphysema, and chronic wounding skin disease. Compositions and kits containing the peptide conjugates of the present invention find utility in a wide range of applications including, e.g., in vivo imaging and immunotherapy.

Hausner, Sven H.↗
DOE OSTI2026

Development of high throughput light-sheet fluorescence lifetime imaging microscopy for 3D functional imaging of metabolic pathways in plant and microorganisms (Final Technical Report)

This research program will enable new biochemical contrast in the nanosecond lifetime domain through use of the recently demonstrated electro-optic fluorescence lifetime imaging technique (EO-FLIM) for wide-field lifetime imaging. The Stanford/Stanford Linear Accelerator Center multidisciplinary collaboration -- physics, applied physics, and structural biology -- will develop a light-sheet fluorescence lifetime imaging microscope for functional studies of microbial and plant metabolic pathways and dynamic interactions between plants and microorganisms in the rhizosphere. The proposed approach overcomes the imaging time bottleneck associated with existing fluorescence lifetime imaging methods. Initial demonstrations have shown a factor of 100,000 improvement in photon throughput compared to existing methods. High photon efficiency allowed the first wide-field fluorescence lifetime imaging of single molecules. Recent work has improved the technique’s repetition rate to enable compatibility with mode-locked lasers and demonstrated the combination of wide-field fluorescence lifetime imaging with super-resolution localization microscopy, observations of single molecule dynamics, and observation of donor lifetime quenching in single-molecule imaging. These results were achieved on standard camera sensors and would not have been possible with other wide-field approaches. The throughput and photon economy of the EO-FLIM method enables new BER-relevant imaging opportunities. In particular, scanned single- and two-photon light-sheet excitation will be used to achieve volumetric imaging with time-domain contrast.

47 OTHER INSTRUMENTATION↗
DOE OSTI2021

Integrated multi-wavelength microscope combining TIRFM and IRM modalities for imaging cellulases and other processive enzymes

We describe a multimodal microscope for visualizing processive enzymes moving on immobilized substrates. The instrument combines interference reflection microscopy (IRM) with multi-wavelength total internal reflectance fluorescence microscopy (TIRFM). The microscope can localize quantum dots with a precision of 2.8 nm at 100 frames/s, and was used to image the dynamics of the cellulase, Cel7a interacting with surface-immobilized cellulose. The instrument, which was built with off-the-shelf components and is controlled by custom software, is suitable for tracking other degradative enzymes such as collagenases, as well as motor proteins moving along immobilized tracks.

09 BIOMASS FUELS↗
DOE OSTI2020

Small animal PET: a review of what we have done and where we are going

Abstract Small animal research is an essential tool in studying both pharmaceutical biodistribution and disease progression over time. Furthermore, through the rapid development of in vivo imaging technology over the last few decades, small animal imaging (also referred to as preclinical imaging) has become a mainstay for all fields of biologic research and a center point for most preclinical cancer research. Preclinical imaging modalities include optical, MRI and MRS, microCT, small animal PET, ultrasound, and photoacoustic, each with their individual strengths. The strong points of small animal PET are its translatability to the clinic; its quantitative imaging capabilities; its whole-body imaging ability to dynamically trace functional/biochemical processes; its ability to provide useful images with only nano- to pico- molar concentrations of administered compounds; and its ability to study animals serially over time. This review paper gives an overview of the development and evolution of small animal PET imaging. It provides an overview of detector designs; system configurations; multimodality PET imaging systems; image reconstruction and analysis tools; and an overview of research and commercially available small animal PET systems. It concludes with a look toward developing technologies/methodologies that will further enhance the impact of small animal PET imaging on medical research in the future.

Engineering↗
DOE OSTI2023

Multimodal single-Cell/ Particle imaging and engineering for energy conversion in bacteria (Final Technical Report)

Hybrid inorganic-microbial systems have emerged as a potentially transformative approach to combine the light-harvesting capability of inorganic semiconductors and the ability of microbes to orchestrate complex chemical transformations. The objective of this collaborative research is to combine quantum materials synthesis, bacterial synthetic biology, and multimodal single-entity imaging to quantitatively study how hybrid QD-bacteria systems convert light to value chemicals at the single-to-sub cell level, with the ultimate goal of gaining insights to guide the engineering of QDs and bacterial genetics for more efficient bioenergy conversion. The final technical report summarizes our achievements toward this objective.

09 BIOMASS FUELS↗
DOE OSTI2025

HAMscope: a snapshot Hyperspectral Autofluorescence Miniscope for real-time molecular imaging

We introduce HAMscope, a compact, snapshot hyperspectral autofluorescence miniscope that enables real-time, label-free molecular imaging in a wide range of biological systems. By integrating a thin polymer diffuser into a widefield miniscope, HAMscope spectrally encodes each frame and employs a probabilistic deep learning framework to reconstruct 30-channel hyperspectral stacks (452-703 nm) or directly infer molecular composition maps from single images. A scalable multi-pass U-Net architecture with transformer-based attention and per pixel uncertainty estimation enables high spatio-spectral fidelity (mean absolute error ∼0.0048) at video rates. While initially demonstrated in plant systems, including lignin, chlorophyll, and suberin imaging in intact poplar and cork tissues, the platform is readily adaptable to other applications such as neural activity mapping, metabolic profiling, and histopathology. We show that the system generalizes to out-of-distribution tissue types and supports direct molecular mapping without the need for spectral unmixing. HAMscope establishes a general framework for compact, uncertainty-aware spectral imaging that combines minimal optics with advanced deep learning, offering broad utility for real-time biochemical imaging across neuroscience, environmental monitoring, and biomedicine.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Synthetic Promoter Screening Using Poplar Mesophyll Protoplast Transformation

Plant protoplasts are useful to study both transcriptional regulation and protein subcellular localization in rapid screens. Protoplast transformation can be used in automated platforms for design-build-test cycles of plant promoters, including synthetic promoters. A notable application of protoplasts comes from recent successes in dissecting synthetic promoter activity with poplar mesophyll protoplasts. For this purpose, we constructed plasmids with TurboGFP driven by a synthetic promoter together with TurboRFP constitutively controlled by a 35S promoter, to monitor transformation efficiency, allowing versatile screening of high numbers of cells by monitoring green fluorescent protein expression in transformed protoplasts. Herein, we introduce a protocol for poplar mesophyll protoplast isolation followed by protoplast transformation and image analysis for the selection of valuable synthetic promoters.

59 BASIC BIOLOGICAL SCIENCES↗