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

Fuente: arXiv
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Main Authors: Li, Mingsheng, Yuan, Yuhao, Ding, Guangrui, Ni, Hongli, Gao, Biwen, Dong, Dashan, He, Qinshu, He, Hongjian, Teng, Xinyan, Sun, Yuwei, Sun, Dingcheng, Xia, Qing, Pham, Thao, Cheng, Ji-Xin
Format: Preprint
Published: 2026
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author Li, Mingsheng
Yuan, Yuhao
Ding, Guangrui
Ni, Hongli
Gao, Biwen
Dong, Dashan
He, Qinshu
He, Hongjian
Teng, Xinyan
Sun, Yuwei
Sun, Dingcheng
Xia, Qing
Pham, Thao
Cheng, Ji-Xin
author_facet Li, Mingsheng
Yuan, Yuhao
Ding, Guangrui
Ni, Hongli
Gao, Biwen
Dong, Dashan
He, Qinshu
He, Hongjian
Teng, Xinyan
Sun, Yuwei
Sun, Dingcheng
Xia, Qing
Pham, Thao
Cheng, Ji-Xin
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2603_05785
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Mid-wave infrared photothermal microscopy for molecular and metabolic imaging in deep tissues and spheroids
Li, Mingsheng
Yuan, Yuhao
Ding, Guangrui
Ni, Hongli
Gao, Biwen
Dong, Dashan
He, Qinshu
He, Hongjian
Teng, Xinyan
Sun, Yuwei
Sun, Dingcheng
Xia, Qing
Pham, Thao
Cheng, Ji-Xin
Optics
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.
title Mid-wave infrared photothermal microscopy for molecular and metabolic imaging in deep tissues and spheroids
topic Optics
url https://arxiv.org/abs/2603.05785