Li Mingsheng, Xiao Sheng, Ni Hongli, Ding Guangrui, Yuan Yuhao, Marar Carolyn, Mertz Jerome, Cheng Ji-Xin
Department of Electrical and Computer Engineering, Boston University, Boston, MA, USA.
Photonics Center, Boston University, Boston, MA, USA.
Nat Commun. 2025 Jul 2;16(1):6065. doi: 10.1038/s41467-025-61332-w.
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.
由于反射模式下灵敏度较差以及在微米尺度上分辨率较低，体内红外光谱面临挑战。为了突破这一障碍，我们报告了一种斜向光热显微镜（OPTM），以实现对活体对象进行亚微米分辨率的超灵敏红外光谱成像。传统的光热测量仅通过一个光阑捕获一小部分探测光子来提取光热信号。相反，OPTM使用放置在样品表面的差分分裂探测器来收集多500倍的光子，并通过平衡检测将激光噪声抑制12倍。凭借其提高的灵敏度，OPTM能够对皮肤进行低剂量红外成像而不会造成光损伤。展示了对小鼠和人类皮肤下代谢标志物的深度分辨体内OPTM成像。此外，我们证明了在小鼠和人类皮肤内对局部药物含量进行体内OPTM跟踪。总体而言，OPTM为体内和原位分子分析提供了一个高度灵敏的成像平台。
