Plasmonic nanoparticles (e.g., gold, silver) have attracted much attention for biological sensing and imaging as promising nanoprobes. Practical biomedical applications demand small gold nanoparticles (Au NPs) with a comparable size to quantum dots and fluorescent proteins. Very small nanoparticles with a size below the Rayleigh limit (usually <30–40 nm) are hard to see by light scattering using a dark-field microscope, especially within a cellular medium. A photothermal microscope is able to detect very small nanoparticles, down to a few nanometers, but the imaging speed is usually too slow (minutes to hours) to image living cell processes. Here an absorption modulated scattering microscopy (AMSM) method is presented, which allows for the imaging of sub-10 nm Au NPs within a cellular medium. The unique physical mechanism of AMSM offers the remarkable ability to remove the light scattering background of the cellular component. In addition to having a sensitivity comparable to that of photothermal microscopy, AMSM has a much higher imaging speed, close to the video rate (20 fps), which allows for the dynamic tracking of small nanoparticles in living cells. This AMSM method might be a valuable tool for living cell imaging, using sub-10 nm Au NPs as biological probes, and thereby unlocking many new applications, such as single molecule labeling and the dynamic tracking of molecular interactions.

中文翻译：

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在无背景散射的细胞介质中亚 10 nm 等离子体纳米粒子的视频速率成像

等离子体纳米颗粒（例如金、银）作为有前景的纳米探针在生物传感和成像领域引起了广泛关注。实际的生物医学应用需要尺寸与量子点和荧光蛋白相当的小型金纳米粒子（Au NP）。使用暗视野显微镜很难通过光散射看到尺寸低于瑞利极限（通常<30-40 nm）的非常小的纳米颗粒，尤其是在细胞介质中。光热显微镜能够检测非常小的纳米颗粒，小至几纳米，但成像速度通常太慢（几分钟到几小时），无法对活细胞过程进行成像。这里提出了一种吸收调制散射显微镜 (AMSM) 方法，该方法可以对细胞介质内的亚 10 nm Au NP 进行成像。AMSM 独特的物理机制提供了去除细胞成分的光散射背景的卓越能力。除了具有与光热显微镜相当的灵敏度外，AMSM 还具有更高的成像速度，接近视频速率 (20 fps)，从而可以动态跟踪活细胞中的小纳米颗粒。这种 AMSM 方法可能是活细胞成像的一个有价值的工具，使用亚 10 nm Au NP 作为生物探针，从而解锁许多新的应用，例如单分子标记和分子相互作用的动态跟踪。