Exploring the influence of silicon oxide microchips shape on cellular uptake using imaging flow cytometry

Abstract

Nano- and micro-carriers of therapeutic molecules offer numerous advantages for drug delivery, and the shape of these</p><p>particles plays a vital role in their biodistribution and their interaction with cells. However, analysing how microparticles</p><p>are taken up by cells presents methodological challenges. Qualitative methods like microscopy provide detailed imaging</p><p>but are time-consuming, whereas quantitative methods such as flow cytometry enable high-throughput analysis but struggle</p><p>to differentiate between internalised and surface-bound particles. Instead, imaging flow cytometry combines the best of</p><p>both worlds, offering high-resolution imaging with the efficiency of flow cytometry, allowing for quantitative analysis at the</p><p>single-cell level. This study focuses on fluorescently labelled silicon oxide microchips of various morphologies but related</p><p>surface areas and volumes: rectangular cuboids and apex-truncated square pyramid microchips fabricated using photolithography</p><p>techniques, offering a reliable basis for comparison with the more commonly studied spherical particles. Imaging</p><p>flow cytometry was utilised to evaluate the effect of particle shape on cellular uptake using RAW 264.7 cells and revealed</p><p>phagocytosis of particles with all shapes. Increasing the particle dose enhanced the uptake, while macrophage stimulation had</p><p>minimal effect. Using a ratio particle:cell of 10:1 cuboids and spheres showed an uptake rate of approximately 50%, in terms</p><p>of the percentage of cells with internalised particles, and the average number of particles taken up per cell ranging from about</p><p>1–1.5 particle/cell for all the different shapes. This study indicates how differently shaped micro-carriers offer insights into</p><p>particle uptake variations, demonstrating the potential of non-spherical micro-carriers for precise drug delivery applications.