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用于高通量和选择性包封单个靶细胞的微流控装置。

Microfluidic device for the high-throughput and selective encapsulation of single target cells.

机构信息

Life Science Technology Research & Development Dept., Application Technology Research & Development Div., Technology Development Laboratories, Sony Corporation, Tokyo, Japan.

出版信息

Lab Chip. 2024 May 28;24(11):2958-2967. doi: 10.1039/d4lc00037d.

DOI:10.1039/d4lc00037d
PMID:38722067
Abstract

Droplet-based microfluidic technologies for encapsulating single cells have rapidly evolved into powerful tools for single-cell analysis. In conventional passive single-cell encapsulation techniques, because cells arrive randomly at the droplet generation section, to encapsulate only a single cell with high precision, the average number of cells per droplet has to be decreased by reducing the average frequency at which cells arrive relative to the droplet generation rate. Therefore, the encapsulation efficiency for a given droplet generation rate is very low. Additionally, cell sorting operations are required prior to the encapsulation of target cells for specific cell type analysis. To address these challenges, we developed a cell encapsulation technology with a cell sorting function using a microfluidic chip. The microfluidic chip is equipped with an optical detection section to detect the optical information of cells and a sorting section to encapsulate cells into droplets by controlling a piezo element, enabling active encapsulation of only the single target cells. For a particle population including both targeted and non-targeted particles arriving at an average frequency of up to 6000 particles per s, with an average number of particles per droplet of 0.45, our device maintained a high purity above 97.9% for the single-target-particle droplets and achieved an outstanding throughput, encapsulating up to 2900 single target particles per s. The proposed encapsulation technology surpasses the encapsulation efficiency of conventional techniques, provides high efficiency and flexibility for single-cell research, and shows excellent potential for various applications in single-cell analysis.

摘要

基于液滴的微流控技术已迅速发展成为单细胞分析的强大工具。在传统的被动单细胞包封技术中,由于细胞随机到达液滴生成部分,因此要高精度地包封单个细胞,必须通过降低细胞相对于液滴生成率的到达频率来减少每个液滴中的平均细胞数。因此,给定的液滴生成率的封装效率非常低。此外,在对目标细胞进行特定细胞类型分析之前,需要进行细胞分选操作。为了解决这些挑战,我们使用微流控芯片开发了一种具有细胞分选功能的细胞包封技术。微流控芯片配备了一个光学检测部分,用于检测细胞的光学信息和一个分选部分,通过控制压电元件将细胞包封成液滴,从而能够主动包封仅单个目标细胞。对于包括靶向和非靶向颗粒的颗粒群体,平均到达频率高达每秒 6000 个颗粒,每个液滴中的平均颗粒数为 0.45,我们的设备保持了超过 97.9%的单目标颗粒液滴的高纯度,并实现了高达每秒 2900 个单目标颗粒的出色吞吐量。所提出的封装技术超过了传统技术的封装效率,为单细胞研究提供了高效率和灵活性,并在单细胞分析的各种应用中显示出了巨大的潜力。

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Microfluidic device for the high-throughput and selective encapsulation of single target cells.用于高通量和选择性包封单个靶细胞的微流控装置。
Lab Chip. 2024 May 28;24(11):2958-2967. doi: 10.1039/d4lc00037d.
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High-throughput deterministic single-cell encapsulation and droplet pairing, fusion, and shrinkage in a single microfluidic device.在单个微流控装置中实现高通量确定性单细胞封装以及液滴配对、融合和收缩。
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Encapsulation of single cells on a microfluidic device integrating droplet generation with fluorescence-activated droplet sorting.在微流控装置上将单细胞包封,该装置集成了液滴生成与荧光激活液滴分选。
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High throughput single cell counting in droplet-based microfluidics.基于液滴的微流控中的高通量单细胞计数。
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