The limited penetration of photons in biological tissue restricts the deep-tissue detection and imaging application. The micro-scale spatially offset Raman spectroscopy (micro-SORS) with an optical fiber probe, colleting photons from deeper regions by offsetting the position of laser excitation from the collection optics in a range of hundreds of microns, shows great potential to be integrated with endoscopy for inside-body noninvasive detection by circumventing this restriction, particularly with the combination of surface-enhanced Raman spectroscopy (SERS). However, a detailed tissue penetration study of micro-SORS in combination with SERS is still lacking. Herein, we compared the signal decay of enhanced Raman nanotags through the tissue phantom of agarose gel and the biological tissue of porcine muscle in the near-infrared (NIR) region using a portable Raman spectrometer with a micro-SORS probe (2.1mm in diameter) and a conventional hand-held probe (9.7mm in diameter). Two kinds of Raman nanotags were prepared from gold nanorods decorated with the nonresonant (4-nitrobenzenethiol) or resonant Raman reporter molecules (IR-780 iodide). The SERS measurements show that the penetration depths of two Raman nanotags are both over 2cm in agarose gel and 3mm in porcine muscle. The depth could be improved to over 4cm in agarose gel and 5mm in porcine tissue when using the micro-SORS system. This demonstrates the superiority of optical-fiber micro-SORS system over the conventional Raman detection for the detection of nanotags in deeper layers in the turbid medium and biological tissue, offering the possibility of combining the micro-SORS technique with SERS for noninvasive in vivo endoscopy-integrated clinical application.

中文翻译：

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表面增强微尺度空间偏移拉曼光谱在混浊凝胶和生物组织中的光学穿透

光子在生物组织中的有限穿透限制了深层组织检测和成像应用。带有光纤探针的微尺度空间偏移拉曼光谱 (micro-SORS) 通过偏移收集光学器件的激光激发位置在数百微米范围内从较深区域收集光子，显示出与集成的巨大潜力通过规避这一限制，特别是结合表面增强拉曼光谱 (SERS) 进行体内无创检测的内窥镜检查。然而，仍然缺乏与 SERS 结合的 micro-SORS 的详细组织穿透研究。在此处，毫米直径）和一个传统的手持式探头（9.7毫米直径）。两种拉曼纳米标签由装饰有非共振（4-硝基苯硫醇）或共振拉曼报告分子（IR-780 碘化物）的金纳米棒制备。SERS 测量表明，两个拉曼纳米标签的穿透深度均超过 2厘米琼脂糖凝胶和 3毫米猪肌肉。深度可以提高到4以上厘米琼脂糖凝胶和 5使用 micro-SORS 系统时，猪组织中的 mm。这证明了光纤微SORS系统在检测浑浊介质和生物组织中较深层纳米标签方面优于传统拉曼检测的优越性，为将微SORS技术与SERS相结合实现无创性提供了可能性体内内窥镜一体化临床应用。