A valve‐based microfluidic device for on‐chip single cell treatments

Yue Sun, Bo Cai, Xiaoyun Wei, Zixiang Wang, Lang Rao, Qian‐Fang Meng, Qingquan Liao, Wei Liu, Shishang Guo, Xingzhong Zhao

Electrophoresis · 2018 · 22 citations · 40 references

TL;DR

Single-cell assays are increasingly important for uncovering cellular mechanisms and heterogeneity, yet existing microfluidic devices often damage cells with hydraulic forces or fail to immobilize cells while delivering reagents. The study introduces a two-layer pneumatic valve-based platform that simultaneously immobilizes and treats single cells on-chip, allowing non‑destructive collection for downstream analysis. The platform encapsulates target cells in sodium alginate droplets that solidify into hydrogel beads whose size is tuned by flow rates, and integrated pneumatic valves regulate fluid resistance to capture and release the beads on‑chip. Proof‑of‑concept experiments showed live/dead staining of single cells on the device, indicating its potential for biochemical assays in single‑cell manipulation.

Abstract

Abstract Assays toward single‐cell analysis have attracted the attention in biological and biomedical researches to reveal cellular mechanisms as well as heterogeneity. Yet nowadays microfluidic devices for single‐cell analysis have several drawbacks: some would cause cell damage due to the hydraulic forces directly acting on cells, while others could not implement biological assays since they could not immobilize cells while manipulating the reagents at the same time. In this work, we presented a two‐layer pneumatic valve‐based platform to implement cell immobilization and treatment on‐chip simultaneously, and cells after treatment could be collected non‐destructively for further analysis. Target cells could be encapsulated in sodium alginate droplets which solidified into hydrogel when reacted with Ca 2+ . The size of hydrogel beads could be precisely controlled by modulating flow rates of continuous/disperse phases. While regulating fluid resistance between the main channel and passages by the integrated pneumatic valves, on‐chip capture and release of hydrogel beads was implemented. As a proof of concept for on‐chip single‐cell treatments, we showed cellular live/dead staining based on our devices. This method would have potential in single cell manipulation for biochemical cellular assays.

References

40