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Xinyan Teng

Publications and source records attributed to Xinyan Teng.

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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

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

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

Self-Supervised Elimination of Non-Independent Noise in Hyperspectral Imaging

Hyperspectral imaging has been widely used for spectral and spatial identification of target molecules, yet often contaminated by sophisticated noise. Current denoising methods generally rely on independent and identically distributed noise statistics, showing corrupted performance for non-independent noise removal. Here, we demonstrate Self-supervised PErmutation Noise2noise Denoising (SPEND), a deep learning denoising architecture tailor-made for removing non-independent noise from a single hyperspectral image stack. We utilize hyperspectral stimulated Raman scattering and mid-infrared photothermal microscopy as the testbeds, where the noise is spatially correlated and spectrally varied. Based on single hyperspectral images, SPEND permutates odd and even spectral frames to generate two stacks with identical noise properties, and uses the pairs for efficient self-supervised noise-to-noise training. SPEND achieved an 8-fold signal-to-noise improvement without having access to the ground truth data. SPEND enabled accurate mapping of low concentration biomolecules in both fingerprint and silent regions, demonstrating its robustness in sophisticated cellular environments.

eess.IV