Design and proof-of-concept of a micropillar-based microfluidic chip for trapping and culture of single cells

Abstract

Single-cell analysis provides a groundbreaking avenue for exploring cell-to-cell variation, the heterogeneity of cell responses to stimuli, and the impact of DNA sequence variations on cell phenotypes. A crucial facet of this analytical approach involves the refinement of techniques for effective single-cell trapping and sustained culture. This study introduces a microfluidic platform based on micropillars for hydrodynamic trapping and prolonged cultivation of individual cells. The proposed biochip design, termed three-micropillars based microfluidic (3µPF) structure, incorporates interleaved trap units, each featuring three-micropillars based microfluidic structure strategically designated to trap single cells, enhance the surface area of cells exposed to the culture medium, and enable dynamic culture, continuous waste removal. This configuration aims to mitigate adverse effects associated with bioparticle collisions compared to conventional trap units. The study employs finite element method to conduct a comprehensive numerical investigation into the operational mechanism of the microfluidic device. The simulation results show that the filled trap unit demonstrates a low-velocity magnitude, reducing shear stress on cells and facilitating extended culture. The hydrodynamic single-cell trap mechanism of the proposed device was also verified. The insights derived from this work are pivotal for optimizing the device and guiding future experimental examinations, thus contributing significantly to the progression of single-cell analysis techniques.