Microfluidics Cell Loading-Dock System: Ordered Cellular Array for Dynamic Lymphocyte-Communication Study
Microfluidics Cell Loading-Dock System: Ordered Cellular Array for Dynamic Lymphocyte-Communication Study
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DOI：
10.1002/adbi.201700085
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发表时间：
2017-10-01
影响因子：
4.1
通讯作者：
Qin, Lidong
中科院分区：
文献类型：
--
作者：
Li, Ying;Jang, Joon Hee;Qin, Lidong
建立一个高通量的研究平台，探索多个淋巴细胞（>2个细胞）之间的相互作用，并回收感兴趣的细胞用于下游分析，仍然是一个巨大的挑战。这项研究展示了一种微流体细胞加载-对接系统（Cell-Dock），可将多个细胞封闭在1D，2D和3D腔室中，具有高通量和效率以及单细胞准确性。一个，三个和五个电池系统的负载效率分别达到95%，85%和74%。Cell-Dock系统提供精确和动态的细胞堆积模型，以促进淋巴细胞相互作用研究。结果表明，单个自然杀伤（NK）细胞可能独立发挥作用，而不是在特定的微环境中协同裂解靶细胞。此外，强/弱NK细胞基于其芯片上的细胞毒性被检索，并且进行mRNA测序以找到“连环杀伤”的可能机制，这是一个重要但未解决的问题。本研究发现，较强的NK细胞过度表达多个参与细胞毒性的基因，并且粘附分子（包括众所周知的ICAM 1和很少报道的B4 GALT 1）可能在NK细胞溶解的调节中起重要作用。
It remains a great challenge to establish a high-throughput platform that can explore the interactions among multiple lymphocytes (>2 cells) and retrieve the interested cells for downstream analysis. This study demonstrates a microfluidics cell loading-dock system (Cell-Dock) to enclose multiple cells in 1D, 2D, and 3D chambers with high throughput and efficiency and single-cell accuracy. The loading efficiencies of 95%, 85%, and 74% for one-, three-, and five-cell systems are achieved, respectively. The Cell-Dock system provides precise and dynamic cell packing models to facilitate lymphocyte-interaction studies. The results demonstrate that individual natural killer (NK) cells may function independently rather than cooperate to lyse target cells in the defined microenvironment. Furthermore, the strong/weak NK cells are retrieved based on their on-chip cytotoxicity and mRNA sequencing is conducted to find the possible mechanisms for "serial killing," an important but unsolved issue. This study finds that the stronger NK cells overexpress multiple genes involved in cytotoxicity and adhesion molecules (including the well-known ICAM1 and seldom reported B4GALT1) might play important roles in the regulation of NK cytolysis.