Cancer cell migration and invasion, which are involved in tumour metastasis, are hard to predict and control. Numerous studies have demonstrated that physical cues influence cancer cell migration and affect tumour metastasis. In this study, we proposed the use of a microchannel chip equipped with a number of vertical constrictions to produce periodic compression forces on cells passing through narrow channels. The chip with repeated vertical confinement was applied on adherent MHCC-97L liver cancer cells and suspended OCI-AML leukaemia cells to determine the migration ability of these cancer cells. Given the stimulation of the periodic mechanical confinement on-chip, the migration ability of cancer cells was promoted. Moreover, the migration speed increased as the stimulation was enhanced. Both AFM nanoindentation and optical stretching tests on cancer cells were performed to measure their mechanical property. After confinement stimulation, the cancer cells possessed higher deformability and lower stiffness than non-stimulating cells. The confinement stimulation altered the cell cytoskeleton, which governs the migration speed. This phenomenon was determined through gene expression analysis. The proposed on-chip cell migration assays will help characterise the migration property of cancer cells and benefit the development of new therapeutic strategies for metastasis.
Single-cell culture represents the most straightforward method for investigating cellular heterogeneity. In this paper, we present a novel microfluidic platform that can individually array and culture hundreds of cells under chemical and electrical stimuli for week-scale characterization. Single cells can be deterministically and gently captured in a microchamber array on the proposed platform. The size of the microchamber can be adjusted to fit different cell culture times, and this characteristic enables remarkable scalability. Transparent indium tin oxide microelectrodes were integrated with the single-cell array platform for on-chip electrical stimuli. The platform exhibited nearly 90% single-cell efficiency and facilitated week-scale clonal expansion of different types of single cells. Chemical and electrical stimuli affected proliferation and differentiation of MC 3T3-E1 cells were examined on the chip prototype that contained 416 (32 rows × 13 columns) microchambers, and each microchamber had 1 mm diameter. By tracking clonal expansion of cells under chemical/electrical stimuli for relatively long periods, the proposed platform can facilitate the screening of the cell subpopulation with a favorable growth phenotype for drug testing and cell therapy.
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