On-Chip Disassembling of Cell-Aggregates for Seamless Single-Cell Analysis and Homogeneous Treatment

We present an on-chip disassembling of cell-aggregates, emerging target in on-chip cell analysis. Unlike existing microfluidic methods, our proposed method can be applied to various platforms for single-cell analysis. The uniquely designed tube-like microfluidic chip which has the constriction channels is installed into the microfluidic device utilizing the sheath flow technology. Thus, the target cell-aggregates are aligned and disassembled at the center of the microchannel by designed fluidic force with just flowing. In this paper, we demonstrated the on-chip disassembling of 500 μm-spheroids and obtained the cell suspensions containing over 87% single-cells. We also applied the designed chip to the seamless and homogeneous treatment of the disassembled cells with two types of lipid-based nanoparticles (LNPs) containing different plasmid DNAs (pDNAs). We confirmed the floating cell-aggregates were effectively disassembled by the fabricated microfluidic chip. Additionally, the seamless manner also enhanced each cellular uptake of LNPs even in the case of co-transfection of pDNAs because of the homogeneous cell-LNP interactions.