A5052711606- Advanced Fluorescence Microscopy Techniques
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Optical Coherence Tomography Applications
- Photoacoustic and Ultrasonic Imaging
- Image Processing Techniques and Applications
- Gene Regulatory Network Analysis
- Digital Holography and Microscopy
- Gene expression and cancer classification
- Quantum Dots Synthesis And Properties
- Orbital Angular Momentum in Optics
- Neonatal Respiratory Health Research
- Chalcogenide Semiconductor Thin Films
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- Random lasers and scattering media
- Advanced biosensing and bioanalysis techniques
- Advanced Biosensing Techniques and Applications
- Advanced Electron Microscopy Techniques and Applications
- Cancer Cells and Metastasis
- Gut microbiota and health
- Molecular Biology Techniques and Applications
- Pregnancy and preeclampsia studies
- Lattice Boltzmann Simulation Studies
Arizona State University
2019-2025
Center for Theoretical Biological Physics
2022-2023
University of Colorado Anschutz Medical Campus
2015-2020
University of Colorado Denver
2014-2020
Lung Institute
2020
Children's Hospital Colorado
2020
University of Denver
2016
Los Alamos National Laboratory
2010-2015
Center for Integrated Nanotechnologies
2010-2015
Colorado State University
2010-2012
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations individual the variability present in population. Here we integrated Human Lung Cell Atlas (HLCA), combining 49 respiratory system into single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents consensus re-annotation with...
We present an oblique plane microscope (OPM) that uses a bespoke glass-tipped tertiary objective to improve the resolution, field of view, and usability over previous variants. Owing its high numerical aperture optics, this achieves lateral axial resolutions are comparable square illumination mode lattice light-sheet microscopy, but in user friendly versatile format. Given performance, we demonstrate high-resolution imaging clathrin-mediated endocytosis, vimentin, endoplasmic reticulum,...
ABSTRACT Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture variability present in population, these must include diverse demographics such as age ethnicity from both healthy diseased individuals. The growth size number single-cell datasets, combined with recent advances computational techniques, for first time makes it possible generate comprehensive large-scale through integration multiple datasets. Here, we integrated Human...
Significance Systems biology seeks to combine experiments with computation predict biological behaviors. However, despite tremendous data and knowledge, models make less-accurate predictions compared other fields. By analyzing single-cell, single-molecule measurements of mRNA during yeast stress response, we explore why how the shapes experimental distributions control prediction accuracy. We show asymmetric long tails cause standard modeling approaches yield excellent fits but meaningless...
Linear structured illumination microscopy (SIM) is a super-resolution technique that does not impose photophysics requirements on fluorescent samples. Multicolor SIM implementations typically rely liquid crystal silicon (LCoS) spatial light modulators (SLM's) for patterning the excitation light, but digital micromirror devices (DMD's) are promising alternative, owing to their lower cost and higher speed. However, existing coherent DMD use only single wavelength of limited by lack efficient...
Antenatal factors, such as chorioamnionitis, preeclampsia, and postnatal injury, are associated with an increased risk for bronchopulmonary dysplasia (BPD) pulmonary hypertension (PH) after preterm birth. IGF-1 (insulin-like growth factor-1) is markedly decreased in normal infants, but whether treatment can prevent BPD or PH unknown.
We present a high-resolution miniature, light-weight fluorescence microscope with electrowetting lens and onboard CMOS for high resolution volumetric imaging structured illumination rejection of out-of-focus scattered light. The miniature (SIMscope3D) delivers light using coherent fiber bundle to obtain optical sectioning an axial 18 µm. Volumetric eGFP labeled cells in fixed mouse brain tissue at depths up 260 µm is demonstrated. functionality SIMscope3D provide background free 3D shown by...
Abstract Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy CLD lungs to identify molecular characteristics that may account worse COVID-19 outcomes in patients diseases. We observe a similar cellular distribution relative expression SARS-CoV-2 entry factors control lungs. AT2 express higher levels genes linked directly efficiency...
Myelin, the insulating sheath around axons, supports axon function. An important question is impact of mild myelin disruption. In absence protein proteolipid (PLP1), generated but with age, axonal function/maintenance disrupted. Axon disruption occurs in Plp1-null mice as early 2 months cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase oligodendrocyte density olfactory bulb and rostral corpus callosum that increased during...
Structured illumination microscopy (SIM) achieves superresolution in fluorescence imaging through patterned and computational image reconstruction, yet current methods require bulky, costly modulation optics high-precision optical alignment, thus hindering the widespread implementation of SIM. To address this challenge, work demonstrates how nano-optical metasurfaces, rationally designed to tailor far-field wavefront at sub-wavelength dimensions, hold great potential as ultrathin,...
Biological images captured by microscopes are characterized heterogeneous signal-to-noise ratios (SNRs) due to spatially varying photon emission across the field of view convoluted with camera noise. State-of-the-art unsupervised structured illumination microscopy (SIM) reconstruction methods, commonly implemented in Fourier domain, often do not accurately model this Such methods therefore suffer from high-frequency artifacts, user-dependent choices smoothness constraints making assumptions...
Abstract In biological imaging, there is a demand for cost-effective, high-resolution techniques to study dynamic intracellular processes. Structured illumination microscopy (SIM) ideal achieving high axial and lateral resolution in live samples due its optical sectioning low phototoxicity. However, conventional SIM systems remain expensive complex. We introduce openSIMMO, an open-source, fully-automated module compatible with commercial microscopes, supporting dual-color excitation. Our...
Bacterial counts from native environments, such as soil or the animal gut, often show substantial variability across replicate samples. This heterogeneity is typically attributed to genetic environmental factors. A common approach estimating bacterial populations involves successive dilution and plating, followed by multiplying colony method, however, overestimates in population because it conflates inherent uncertainty drawing a subsample total with sample arising biological origins. In...
Here, we present a modification to single-molecule fluorescence in situ hybridization that enables quantitative detection and analysis of small RNA (sRNA) expressed bacteria. We show short (∼200 nucleotide) nucleic acid targets can be detected when the background unbound singly dye-labeled DNA oligomers is reduced through with set complementary labeled quencher. By neutralizing from probes, were able significantly reduce number false positives, allowing for accurate quantification sRNA...
We have studied isolated semiconductor nanocrystal quantum dots (QDs) and small clusters of QDs by single-molecule time-correlated single-photon counting, from which fluorescence intensity trajectories, autocorrelation functions, decay histograms, lifetime-intensity distributions been constructed. These measurements confirm that QD exhibit unique behavior not observed in QDs. In particular, the a short-lifetime component their is correlated with low cluster. A model based on nonradiative...
Retinal vasculature develops in a highly orchestrated three-dimensional (3-D) sequence. The stages of retinal vascularization are susceptible to oxygen perturbations. We demonstrate that optical tissue clearing intact rat retinas and light-sheet microscopy provides rapid 3-D characterization vascular complexity during development. Compared with flat mount preparations dissect the retina primarily image outermost layers, cleared imaged using fluorescence display changes rapidly without need...
Optical tissue clearing has revolutionized researchers' ability to perform fluorescent measurements of molecules, cells, and structures within intact tissue. One common complication all optically cleared is a spatially heterogeneous refractive index, leading light scattering first-order defocus. We designed C-DSLM (cleared digital scanned light-sheet microscopy) as low-cost method intended automatically generate in-focus images demonstrate the flexibility power by quantifying features in...
The complex motility of bacteria, ranging from single-swimmer behaviors such as chemotaxis to collective dynamics, including biofilm formation and active matter phenomena, is driven by their microscale propellers. Despite extensive study swimming flagellated the hydrodynamic properties helical-shaped propellers have never been directly measured. primary challenges studying are 1) small size fast, correlated motion, 2) necessity controlling fluid flow at microscale, 3) isolating influence a...