Verily Life Sciences LLC, 249 E. Grand Avenue, South San Francisco, CA 94080, USA.
Lab Chip. 2021 Oct 26;21(21):4262-4273. doi: 10.1039/d1lc00493j.
Droplet microfluidics is a commercially successful technology, widely used in single cell sequencing and droplet PCR. Combining droplet making with droplet sorting has also been demonstrated, but so far found limited use, partly due to difficulties in scaling manufacture with injection molded plastics. We introduce a droplet sorting system with several new elements, including: 1) an electrode design combining metallic and ionic liquid parts, 2) a modular, multi-sorting fluidic design with features for keeping inter-droplet distances constant, 3) using timing parameters calculated from fluorescence or scatter signal triggers to precisely actuate dozens of sorting electrodes, 4) droplet collection techniques, including ability to collect a single droplet, and 5) a new emulsion breaking method to collect aqueous samples for downstream analysis. We use these technologies to build a fluorescence based cell sorter that can sort with high (>90%) purity. We also show that these microfluidic designs can be translated into injection molded thermoplastic, suitable for industrial production. Finally, we tally the advantages and limitations of these devices.
液滴微流控技术是一种商业上成功的技术，广泛应用于单细胞测序和液滴 PCR。将液滴生成与液滴分选相结合也已经得到了证明，但到目前为止，这种方法的应用有限，部分原因是注塑塑料制造的规模化存在困难。我们引入了一种具有多个新元素的液滴分选系统，包括：1）一种结合金属和离子液体部分的电极设计，2）一种模块化、多分选的流体设计，具有保持液滴间距离恒定的特点，3）使用从荧光或散射信号触发计算的定时参数来精确驱动数十个分选电极，4）液滴收集技术，包括收集单个液滴的能力，以及 5）一种新的乳液破坏方法，用于收集用于下游分析的水性样品。我们使用这些技术构建了一种基于荧光的细胞分选器，能够以高（>90%）纯度进行分选。我们还表明，这些微流控设计可以转化为注塑热塑性塑料，适用于工业生产。最后，我们总结了这些设备的优缺点。
