arXiv subjects

Dashan Dong

Publications and source records attributed to Dashan Dong.

8 recordsLinked to original sources

arXiv2026

Mid-wave infrared photothermal microscopy for molecular and metabolic imaging in deep tissues and spheroids

High-resolution chemical imaging within deep tissues and intact spheroids remains a grand challenge. Here, we introduce mid-wave infrared photothermal (MWIP) microscopy operating in the underexplored 2000-2500 nm spectral window for submicron-resolution molecular and metabolic imaging in intact tumor spheroids and deep tissues. A dark-field photothermal detection scheme significantly suppresses water background and enhances contrast. By accessing strong carbon-hydrogen combination absorptions, a detection limit of 0.12% for dimethyl sulfoxide is achieved, comparable to stimulated Raman scattering microscopy. Depth-resolved imaging of endogenous biomolecules up to 500 micrometers in excised mouse skin and brain tissues is demonstrated. MWIP further enables depth-resolved tracking of transdermal drug transport via carbon-deuterium overtone absorption. Using deuterium metabolic probes, fatty-acid metabolism is imaged at 200 micrometers deep within intact tumor spheroids through carbon-deuterium overtone and combination bands. Collectively, MWIP offers a platform for functional imaging of 3D biological systems in their native environments.

physics.optics↗

arXiv2026

Chem-SIM: Super-resolution Chemical Imaging via Photothermal Modulation of Structured-Illumination Fluorescence

Structured illumination microscopy (SIM) has attained high spatiotemporal delineation of subcellular architecture, yet offers limited insight into chemical composition. We develop Chem-SIM, a structured-illumination fluorescence detected mid-infrared photothermal microscopy, for super-resolved chemical imaging of microorganisms and mammalian cells. Poisson maximum-likelihood demodulation and spectral normalization across wavenumber recover the weak IR-induced fluorescence intensity change under low photon budgets and convert the fluorescence intensity modulation to chemical fingerprints. Photothermal gating further rejects water backgrounds in aqueous samples, while the IR pump maintains cellular activity at near-physiological temperature. Chem-SIM preserves full vibrational fingerprints, achieves SIM-grade lateral resolution in a high-throughput camera-based format. Here, we show that this platform distinguishes stationary- from log-phase bacteria through chemical content mapping, reports deuterated fatty-acid incorporation in ovarian cancer cells, and resolves lipid-droplet dynamics in live cells, establishing a high-throughput route to super-resolved imaging of organelle chemistry, metabolism, and dynamics.

physics.optics↗

arXiv2025

Mid-Infrared Photothermal Relaxation Intensity Diffraction Tomography for Video-rate Volumetric Chemical Imaging

Three-dimensional molecular imaging of living cells is essential for unraveling cellular metabolism and response to therapies. However, existing volumetric methods, including fluorescence microscopy and quantitative phase imaging, either require fluorescent labels or lack chemical specificity. Mid-infrared (mid-IR) photothermal microscopy provides label-free spectroscopic contrast with sub-micrometer resolution but is limited by slow acquisition rates, precluding 3D live-cell studies. Here, we present a photothermal relaxation intensity diffraction tomography (PRIDT) system that encodes mid-IR absorption induced refractive index change via a photothermal relaxation scheme and recovers it through intensity diffraction tomography. PRIDT achieves video-rate volumetric chemical imaging with up to 15 Hz per wavelength and offers lateral and axial resolutions of 264 nm and 1.12 um over a volumetric field of view of 50x50x10 um3. We showcase high-speed PRIDT imaging of protein and lipid metabolism in ovarian cancer cells and lipid-droplet dynamics in live cells. PRIDT opens new avenues for rapid, quantitative, three-dimensional molecular imaging in living systems.

physics.optics↗

arXiv2025

Transfer-Function Approach to Substrate-Enhanced Diffraction Tomography

Forward and backward scattering provide complementary volumetric and interfacial information, yet conventional three-dimensional (3D) imaging typically accesses only one. In this Letter, we present a substrate-enhanced diffraction tomography approach that simultaneously recovers both channels under multi-angle epi-illumination.This geometry captures one forward- and two backward-scattering bands in axially symmetric Fourier regions, where their complementary coverage enables phase-absorption separation in a non-Hermitian spectrum. Explicit 3D transfer functions are derived for both channels, and an axial Kramers-Kronig relation is established to incorporate substrate-induced boundary conditions in a unified framework. Our results establish a label-free, high-resolution 3D imaging modality that surpasses the limits of existing methods.

physics.optics↗

arXiv2025

FILM: Mapping organellar metabolism by mid-infrared photothermal modulated fluorescence

Metabolism unfolds within specific organelles in eukaryotic cells. Lysosomes are highly metabolically active organelles, and their metabolic states dynamically influence signal transduction, cellular homeostasis, and organismal physiopathology. Despite the significance of lysosomal metabolism, a method for its in vivo measurement is currently lacking. Here, we report optical boxcar-enhanced, fluorescence-detected mid-infrared photothermal microscopy, together with AI-assisted data denoising and spectral deconvolution, to map metabolic activity and composition of individual lysosomes in living cells and organisms. Using this method, we uncovered lipolysis and proteolysis heterogeneity across lysosomes within the same cell, as well as early-onset lysosomal dysfunction during organismal aging. Additionally, we discovered organelle-level metabolic changes associated with diverse lysosomal storage diseases. This method holds the broad potential to profile metabolic fingerprints of individual organelles within their native context and quantitatively assess their dynamic changes under different physiological and pathological conditions, providing a high-resolution chemical cellular atlas.

physics.bio-ph↗

arXiv2024

Mid-infrared Energy Deposition Spectroscopy

Photothermal microscopy is an emerging tool for measuring light-matter interactions with single-molecule sensitivity. It is generally believed that the spectral acquisition speed in photothermal microscopy is limited by the slow thermal diffusion process. Here, we demonstrate mid-infrared energy deposition (MIRED) spectroscopy, which offers both microsecond-scale temporal resolution and sub-micron spatial resolution. In this approach, the photothermal process is optically probed while the infrared pulses from a quantum cascade laser array are rapidly tuned. Based on Newton's law, the energy deposition corresponds to the first derivative of local temperature rise over time and provides the instantaneous infrared absorption. By employing time-resolved measurement of transient energy deposition, the upper limit for spectrum encoding shifts to the vibrational relaxation level, which occurs on the picosecond scale. This method significantly increases the detection bandwidth while maintaining the sensitivity and resolution advantages of photothermal detection.

physics.optics↗

arXiv2022

A Multislice computational model for birefringent scattering

Modeling optical field propagation in highly scattering and birefringent medium is of important interest to many photonic research branches. Despite the existence of numerical electromagnetic simulation tools and beam propagation method frameworks, there has been a lack of an analytical model including the full tensor nature of birefringence, which is an essential forward-propagation tool for applications requiring efficiently iterative regularization and end-to-end designs. Here, we present an analytical tool for modeling field propagation in a birefringent scattering medium by including a full set of field tensor elements and multiple scattering characteristics. Birefringence-controlled field propagation experiments were successfully carried out to validate the proposed model.

physics.optics↗

arXiv2015

Super-resolution deep imaging with hollow Bessel beam STED microscopy

Stimulated emission depletion (STED) microscopy has become a powerful imaging and localized excitation method beating the diffraction barrier for improved lateral spatial resolution in cellular imaging, lithography, etc. Due to specimen-induced aberrations and scattering distortion, it has been a great challenge for STED to maintain consistent lateral resolution deeply inside the specimens. Here we report on a deep imaging STED microscopy by using Gaussian beam for excitation and hollow Bessel beam for depletion (GB-STED). The proposed scheme shows the improved imaging depth up to ~155μm in solid agarose sample, ~115μm in PDMS and ~100μm in phantom of gray matter in brain tissue with consistent super resolution, while the standard STED microscopy shown a significantly reduced lateral resolution at the same imaging depth. The results indicate the excellent imaging penetration capability of GB-STED, making it a promising tool for deep 3D imaging optical nanoscopy and laser fabrication.

physics.optics↗