Yang Yang, Pang Wei, Zhang Hongxiang, Cui Weiwei, Jin Ke, Sun Chongling, Wang Yanyan, Zhang Lin, Ren Xiubao, Duan Xuexin
State Key Laboratory of Precision Measuring Technology and Instruments, Tianjin University, Tianjin, 300072 China.
Tianjin Medical University Cancer Institute & Hospital, Tianjin Medical University, Tianjin, 300072 China.
Microsyst Nanoeng. 2022 Aug 4;8:88. doi: 10.1038/s41378-022-00424-9. eCollection 2022.
At the single-cell level, cellular parameters, gene expression and cellular function are assayed on an individual but not population-average basis. Essential to observing and analyzing the heterogeneity and behavior of these cells/clusters is the ability to prepare and manipulate individuals. Here, we demonstrate a versatile microsystem, a stereo acoustic streaming tunnel, which is triggered by ultrahigh-frequency bulk acoustic waves and highly confined by a microchannel. We thoroughly analyze the generation and features of stereo acoustic streaming to develop a virtual tunnel for observation, pretreatment and analysis of cells for different single-cell applications. 3D reconstruction, dissociation of clusters, selective trapping/release, in situ analysis and pairing of single cells with barcode gel beads were demonstrated. To further verify the reliability and robustness of this technology in complex biosamples, the separation of circulating tumor cells from undiluted blood based on properties of both physics and immunity was achieved. With the rich selection of handling modes, the platform has the potential to be a full-process microsystem, from pretreatment to analysis, and used in numerous fields, such as in vitro diagnosis, high-throughput single-cell sequencing and drug development.
在单细胞水平上，细胞参数、基因表达和细胞功能是在个体而非群体平均水平上进行测定的。观察和分析这些细胞/细胞簇的异质性和行为的关键在于制备和操控单个细胞的能力。在此，我们展示了一种多功能微系统——立体声表面流通道，它由超高频体声波触发，并被微通道高度限制。我们深入分析了立体声表面流的产生和特性，以开发一个虚拟通道，用于不同单细胞应用的细胞观察、预处理和分析。展示了3D重建、细胞簇解离、选择性捕获/释放、原位分析以及单细胞与条形码凝胶珠配对。为了进一步验证该技术在复杂生物样本中的可靠性和稳健性，基于物理和免疫特性从未稀释血液中分离出循环肿瘤细胞。凭借丰富的处理模式选择，该平台有潜力成为一个从预处理到分析的全流程微系统，并应用于众多领域，如体外诊断、高通量单细胞测序和药物开发。
