A variety of imaging and analytical methods have been developed to study nanoparticles in cells. Each has its benefits, limitations, and varying degrees of expense and difficulties in implementation. High-resolution analytical scanning transmission electron microscopy (HRSTEM) has the unique ability to image local cellular environments adjacent to a nanoparticle at near atomic resolution and apply analytical tools to these environments such as energy dispersive spectroscopy and electron energy loss spectroscopy. These tools can be used to analyze particle location, translocation and potential reformation, ion dispersion, and in vivo synthesis of second-generation nanoparticles. Such analyses can provide in depth understanding of tissue-particle interactions and effects that are caused by the environmental "invader" nanoparticles. Analytical imaging can also distinguish phases that form due to the transformation of "invader" nanoparticles in contrast to those that are triggered by a response mechanism, including the commonly observed iron biomineralization in the form of ferritin nanoparticles. The analyses can distinguish ion species, crystal phases, and valence of parent nanoparticles and reformed or in vivo synthesized phases throughout the tissue. This article will briefly review the plethora of methods that have been developed over the last 20 years with an emphasis on the state-of-the-art techniques used to image and analyze nanoparticles in cells and highlight the sample preparation necessary for biological thin section observation in a HRSTEM. Specific applications that provide visual and chemical mapping of the local cellular environments surrounding parent nanoparticles and second-generation phases are demonstrated, which will help to identify novel nanoparticle-produced adverse effects and their associated mechanisms.

中文翻译：

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通过高级分析成像技术对纳米材料的组织特异性 - 综述。

已经开发了多种成像和分析方法来研究细胞中的纳米粒子。每种方法都有其优点、局限性以及不同程度的费用和实施难度。高分辨率分析型扫描透射电子显微镜 (HRSTEM) 具有以接近原子分辨率对邻近纳米粒子的局部细胞环境进行成像的独特能力，并将分析工具应用于这些环境，例如能量色散谱和电子能量损失谱。这些工具可用于分析粒子的位置、易位和潜在的重组、离子分散以及第二代纳米粒子的体内合成。这种分析可以深入了解由环境“入侵者”纳米粒子引起的组织-粒子相互作用和影响。分析成像还可以区分由于“入侵者”纳米粒子的转变而形成的相，与由响应机制触发的相形成对比，包括常见的铁蛋白纳米粒子形式的铁生物矿化。分析可以区分离子种类、晶相和母体纳米粒子的价态，以及整个组织中的重组或体内合成相。本文将简要回顾过去 20 年来开发的大量方法，重点介绍用于对细胞中的纳米粒子进行成像和分析的最先进技术，并重点介绍生物薄片观察所需的样品制备在 HRSTEM 中。