Small extracellular vesicles (sEVs), a form of extracellular vesicles, are lipid bilayered structures released by all cells. Large-scale studies on sEVs from clinical samples are necessary, but a major obstacle is the lack of rapid, reproducible, efficient, and low-cost methods to enrich sEVs. Acoustic microfluidics have the advantage of being label-free and biocompatible, which have been reported to successfully enrich sEVs. In this paper, we present a highly efficient acoustic microfluidic trap that can offer low and large volume compatible ways of enriching sEVs from biological fluids by flexible structure design. It uses the idea of pre-loading larger seed particles in the acoustic trap to enable sub-micron particle capturing. The microfluidic chip is actuated using a piezoelectric plate transducer attached to a silicon-glass bonding plate with circular cavities. Each cavity works as a resonant unit, excited at the frequency of both the half wave resonance in the main plane and inverted quarter wave resonance in the depth direction, which has the ability to strongly trap seed particles at the center, thereby improving the subsequent nanoparticle capture efficiency. Mean trapping efficiencies of 35.62% and 64.27% were obtained using 60 nm and 100 nm nanobeads, respectively. By the use of this technology, we have successfully enriched sEVs from cell culture conditioned media and blood plasma at a flow rate of 10 μL min⁻¹. The isolated sEV subpopulations are characterized by NTA and TEM, and their protein cargo is determined by WB. This acoustic trapping chip provides a rapid and robust method to enrich sEVs from biofluids with high reproducibility and sufficient quantities. Therefore, it can serve as a new tool for biological and clinical research such as cancer diagnosis and drug delivery.

中文翻译：

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使用声阱从生物液体中富集小细胞外囊泡

小细胞外囊泡（sEV）是细胞外囊泡的一种形式，是所有细胞释放的脂质双层结构。对临床样本中的 sEV 进行大规模研究是必要的，但主要障碍是缺乏快速、可重复、高效且低成本的方法来富集 sEV。声学微流体具有无标记和生物相容性的优点，据报道可以成功丰富 sEV。在本文中，我们提出了一种高效的声学微流体陷阱，它可以提供小体积和大体积兼容的方式，通过灵活的结构设计从生物流体中富集 sEV。它利用在声阱中预加载较大种子颗粒的想法来实现亚微米颗粒捕获。微流控芯片使用连接到具有圆形空腔的硅玻璃接合板上的压电板传感器来驱动。每个空腔作为一个谐振单元，在主平面的半波谐振和深度方向的倒四分之一波谐振的频率下激发，具有将种子粒子强烈捕获在中心的能力，从而提高后续纳米粒子的捕获能力。捕获效率。使用 60 nm 和 100 nm 纳米珠的平均捕获效率分别为 35.62% 和 64.27%。通过使用这项技术，我们成功地以10 μL min ^-1的流速从细胞培养条件培养基和血浆中富集了sEV 。分离的 sEV 亚群通过 NTA 和 TEM 进行表征，其蛋白质货物通过 WB 测定。这种声学捕获芯片提供了一种快速、稳健的方法，以高重现性和足够的数量从生物流体中富集 sEV。因此，它可以作为癌症诊断和药物输送等生物学和临床研究的新工具。