Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy
Abstract In vivo IR spectroscopy faces challenges due to poor sensitivity in reflection mode and low resolution at micrometer scale. To break this barrier, we report an oblique photothermal microscope (OPTM) to enable ultrasensitive IR spectroscopic imaging of live subjects at sub-micron resolution....
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61332-w |
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| author | Mingsheng Li Sheng Xiao Hongli Ni Guangrui Ding Yuhao Yuan Carolyn Marar Jerome Mertz Ji-Xin Cheng |
| author_facet | Mingsheng Li Sheng Xiao Hongli Ni Guangrui Ding Yuhao Yuan Carolyn Marar Jerome Mertz Ji-Xin Cheng |
| author_sort | Mingsheng Li |
| collection | DOAJ |
| description | Abstract In vivo IR spectroscopy faces challenges due to poor sensitivity in reflection mode and low resolution at micrometer scale. To break this barrier, we report an oblique photothermal microscope (OPTM) to enable ultrasensitive IR spectroscopic imaging of live subjects at sub-micron resolution. Classic photothermal measurement captures only a small fraction of probe photons through an iris to extract the photothermal signal. Instead, OPTM uses a differential split detector placed on the sample surface to collect 500-fold more photons and suppress the laser noise by 12 fold via balanced detection. Leveraging its improved sensitivity, OPTM enables low-dose IR imaging of skin without photodamage. Depth-resolved in vivo OPTM imaging of metabolic markers beneath mouse and human skin is shown. Furthermore, we demonstrate in vivo OPTM tracking of topical drug contents within mouse and human skin. Collectively, OPTM presents a highly sensitive imaging platform for in vivo and in situ molecular analysis. |
| format | Article |
| id | doaj-art-4eaa868199724d7292c1510cc3d3d807 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4eaa868199724d7292c1510cc3d3d8072025-08-20T03:37:38ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61332-wUltrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopyMingsheng Li0Sheng Xiao1Hongli Ni2Guangrui Ding3Yuhao Yuan4Carolyn Marar5Jerome Mertz6Ji-Xin Cheng7Department of Electrical and Computer Engineering, Boston UniversityDepartment of Electrical and Computer Engineering, Boston UniversityDepartment of Electrical and Computer Engineering, Boston UniversityDepartment of Electrical and Computer Engineering, Boston UniversityDepartment of Electrical and Computer Engineering, Boston UniversityPhotonics Center, Boston UniversityPhotonics Center, Boston UniversityDepartment of Electrical and Computer Engineering, Boston UniversityAbstract In vivo IR spectroscopy faces challenges due to poor sensitivity in reflection mode and low resolution at micrometer scale. To break this barrier, we report an oblique photothermal microscope (OPTM) to enable ultrasensitive IR spectroscopic imaging of live subjects at sub-micron resolution. Classic photothermal measurement captures only a small fraction of probe photons through an iris to extract the photothermal signal. Instead, OPTM uses a differential split detector placed on the sample surface to collect 500-fold more photons and suppress the laser noise by 12 fold via balanced detection. Leveraging its improved sensitivity, OPTM enables low-dose IR imaging of skin without photodamage. Depth-resolved in vivo OPTM imaging of metabolic markers beneath mouse and human skin is shown. Furthermore, we demonstrate in vivo OPTM tracking of topical drug contents within mouse and human skin. Collectively, OPTM presents a highly sensitive imaging platform for in vivo and in situ molecular analysis.https://doi.org/10.1038/s41467-025-61332-w |
| spellingShingle | Mingsheng Li Sheng Xiao Hongli Ni Guangrui Ding Yuhao Yuan Carolyn Marar Jerome Mertz Ji-Xin Cheng Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy Nature Communications |
| title | Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy |
| title_full | Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy |
| title_fullStr | Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy |
| title_full_unstemmed | Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy |
| title_short | Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy |
| title_sort | ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy |
| url | https://doi.org/10.1038/s41467-025-61332-w |
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