Fully-Automated On-Chip Multi-Cell Arraying with Deterministic Quantities

Microfluidic devices for cell immobilization have significantly advanced the biological analysis at the single-cell level. However, the previous research on immobilization of multiple single cells, especially with deterministic quantities, is insufficient. In this paper, we proposed a novel microfluidic device based on the passive hydrodynamics and the uniform geometric design principle, which can array different numbers of cells in every capture cavity. The capture cavities could be stretched to accommodate more cells, and the trapping force was adjusted by modifying the related geometric parameters of the inside channel. The whole procedure was monitored and further automatized by integrating computer vision technology under a microscope. On the proposed integrated on-chip platform, we realized full-automated arraying of a single cell, two cells, and three cells on a single chip, achieving success rates up to 95%, 75%, and 72%, respectively. As a primary experimental demonstration, the cell viability test of arraying multiple cells with different quantities showed excellent biocompatibility and no significant association between trapping quantity and cell survivability. We envision that the proposed quantity-controllable, high-efficiency microfluidic devices for multiple cell arraying could be a powerful platform for an in-depth study of cell heterogeneity and cell communication between multiple cells. Note to Practitioners - This article is motivated by the biomedical applications of multi-cell arraying. The designed microfluidic devices employ passive hydrodynamics, and the capture cavities are stretched to accommodate different numbers of cells. The whole arraying procedures are automatized using computer vision technology. Simulations and experiments demonstrate the high efficiency, controllability of the cell quantity, and excellent biocompatibility.