Extracellular vesicles (EVs) are complex biological nanoparticles endogenously secreted by all eukaryotic cells. EVs carry a specific molecular cargo of proteins, lipids, and nucleic acids derived from cells of origin and play a significant role in the physiology and pathology of cells, organs, and organisms. Upon release, they may be found in different body fluids that can be easily accessed via noninvasive methodologies. Due to the unique information encoded in their molecular cargo, they may reflect the state of the parent cell and therefore EVs are recognized as a rich source of biomarkers for early diagnostics involving liquid biopsy. However, body fluids contain a mixture of EVs released by different types of healthy and diseased cells, making the detection of the EVs of interest very challenging. Recent research efforts have been focused on the detection and characterization of diagnostically relevant subpopulations of EVs, with emphasis on label-free methods that simplify sample preparation and are free of interfering signals. Therefore, in this paper, we review the recent progress of the label-free optical methods employed for the detection, counting, and morphological and chemical characterization of EVs. We will first briefly discuss the biology and functions of EVs, and then introduce different optical label-free techniques for rapid, precise, and nondestructive characterization of EVs such as nanoparticle tracking analysis, dynamic light scattering, atomic force microscopy, surface plasmon resonance spectroscopy, Raman spectroscopy, and SERS spectroscopy. In the end, we will discuss their applications in the detection of neurodegenerative diseases and cancer and provide an outlook on the future impact and challenges of these technologies to the field of liquid biopsy via EVs.

中文翻译：

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细胞外囊泡光学无标记表征的最新进展

细胞外囊泡 (EVs) 是由所有真核细胞内源性分泌的复杂生物纳米颗粒。EV 携带源自细胞的蛋白质、脂质和核酸的特定分子货物，并在细胞、器官和生物体的生理学和病理学中发挥重要作用。释放后，它们可能存在于易于获取的不同体液中通过非侵入性方法。由于其分子货物中编码的独特信息，它们可能反映了母细胞的状态，因此 EV 被认为是涉及液体活检的早期诊断的丰富生物标志物来源。然而，体液包含由不同类型的健康和患病细胞释放的 EV 的混合物，这使得检测感兴趣的 EV 非常具有挑战性。最近的研究工作集中在检测和表征与诊断相关的 EV 亚群，重点是简化样品制备和无干扰信号的无标记方法。因此，在本文中，我们回顾了用于 EV 检测、计数以及形态学和化学表征的无标记光学方法的最新进展。我们将首先简要讨论 EV 的生物学和功能，然后介绍用于快速、精确和无损表征 EV 的不同光学无标记技术，例如纳米粒子跟踪分析、动态光散射、原子力显微镜、表面等离子体共振光谱、拉曼光谱和 SERS 光谱。最后，我们将讨论它们在检测神经退行性疾病和癌症中的应用，并展望这些技术对液体活检领域的未来影响和挑战 表面等离子共振光谱、拉曼光谱和 SERS 光谱。最后，我们将讨论它们在检测神经退行性疾病和癌症中的应用，并展望这些技术对液体活检领域的未来影响和挑战 表面等离子共振光谱、拉曼光谱和 SERS 光谱。最后，我们将讨论它们在检测神经退行性疾病和癌症中的应用，并展望这些技术对液体活检领域的未来影响和挑战通过电动汽车。