Single-cell isolation is a truly transformative tool for the understanding of biological systems. It allows single-cell molecular analyses and considers the heterogeneity of cell populations, which is of particular relevance for the diagnosis and treatment of evolving diseases and for personalized medicine. Single-cell isolation is also a key process in cell line development, where it is used to obtain stable and high producing clonally-derived cell lines, thus contributing to the efficiency, safety and reproducible quality of the drug produced. High producing clonally-derived cell lines are however rare events and their identification is a time-consuming process that requires the screening of thousands of clones. Therefore, there is an unmet need for a device that would allow the fast and efficient isolation of single cells, while preserving their integrity and providing an insurance of their clonality. We proposed earlier an impedance based pipetting technology for isolation of single cells (Bonzon et al., 2020), with initial validations for state-of-the-art stem cell in-vitro and in-vivo assays (Muller et al., 2020). Here, we present the transition from this pioneering technology developed in an academic setting into an automated instrument, called DispenCell-S1, allowing for traceable isolation of single cells. We developed and validated models predicting the performances for 96-well plates single-cell isolation. This resulted in a time of dispense down to 3 min and a plate filling rate up to 96%. Finally, we obtained an impedance signal reliability for proof of single particle isolation of 99% with beads and ranging from 93 to 95% with CHO cells.

中文翻译：

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可追溯的基于阻抗的单细胞移液，从研究装置到强大而快速的自动化机器人：DispenCell-S1。

单细胞分离是理解生物系统的真正变革性工具。它允许进行单细胞分子分析并考虑细胞群的异质性，这对于不断发展的疾病的诊断和治疗以及个性化医疗特别重要。单细胞分离也是细胞系开发的关键过程，用于获得稳定和高产的克隆衍生细胞系，从而有助于生产药物的效率、安全性和可重复的质量。然而，高产的克隆衍生细胞系是罕见的事件，它们的鉴定是一个耗时的过程，需要筛选数千个克隆。因此，需要一种能够快速有效地分离单细胞的装置，同时保持它们的完整性并为其克隆性提供保险。我们早些时候提出了一种基于阻抗的移液技术，用于分离单细胞（Bonzon 等人，2020），并初步验证了最先进的干细胞体外和体内测定（Muller 等人，2020） ）。在这里，我们展示了从这种在学术环境中开发的开创性技术到称为 DispenCell-S1 的自动化仪器的转变，该仪器允许对单细胞进行可追溯的分离。我们开发并验证了预测 96 孔板单细胞分离性能的模型。这导致分配时间降至 3 分钟，板填充率高达 96%。最后，我们获得了阻抗信号可靠性，证明使用珠子的单粒子分离率为 99%，使用 CHO 细胞的单粒子分离率范围为 93% 至 95%。