State Key Laboratory of Precision Measurement Technology and Instruments, Tsinghua University, Beijing 100084, China.
Center for Biosystems Dynamics Research (BDR), RIKEN, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
Sensors (Basel). 2018 Oct 29;18(11):3672. doi: 10.3390/s18113672.
Single-cell capture plays an important role in single-cell manipulation and analysis. This paper presents a microfluidic device for deterministic single-cell trapping based on the hydrodynamic trapping mechanism. The device is composed of an S-shaped loop channel and thousands of aligned trap units. This arrayed structure enables each row of the device to be treated equally and independently, as it has row periodicity. A theoretical model was established and a simulation was conducted to optimize the key geometric parameters, and the performance was evaluated by conducting experiments on MCF-7 and Jurkat cells. The results showed improvements in single-cell trapping ability, including loading efficiency, capture speed, and the density of the patterned cells. The optimized device can achieve a capture efficiency of up to 100% and single-cell capture efficiency of up to 95%. This device offers 200 trap units in an area of 1 mm², which enables 100 single cells to be observed simultaneously using a microscope with a 20× objective lens. One thousand cells can be trapped sequentially within 2 min; this is faster than the values obtained with previously reported devices. Furthermore, the cells can also be recovered by reversely infusing solutions. The structure can be easily extended to a large scale, and a patterned array with 32,000 trap sites was accomplished on a single chip. This device can be a powerful tool for high-throughput single-cell analysis, cell heterogeneity investigation, and drug screening.
单细胞捕获在单细胞操作和分析中起着重要作用。本文提出了一种基于流体动力捕获机制的微流控器件，用于确定性单细胞捕获。该器件由 S 形环道和数千个对准的捕获单元组成。这种阵列结构使得器件的每一行都可以平等且独立地处理，因为它具有行周期性。建立了理论模型并进行了模拟以优化关键几何参数，并通过 MCF-7 和 Jurkat 细胞进行实验评估了性能。结果表明，单细胞捕获能力得到了提高，包括加载效率、捕获速度和图案化细胞的密度。优化后的设备可实现高达 100%的捕获效率和高达 95%的单细胞捕获效率。该设备在 1mm²的区域内提供 200 个捕获单元，可使用 20×物镜的显微镜同时观察 100 个单细胞。一千个细胞可以在 2 分钟内顺序捕获；这比以前报道的设备获得的值更快。此外，细胞也可以通过反向注入溶液来回收。该结构可以很容易地扩展到大规模，并且在单个芯片上完成了具有 32000 个捕获位点的图案化阵列。该设备可以成为高通量单细胞分析、细胞异质性研究和药物筛选的有力工具。
