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.

Intracellular delivery of functional materials holds great promise in biologic research and therapeutic applications but poses challenges to existing techniques, including the reliance on exogenous vectors and lack of selectivity. To address these problems, we propose a vector-free approach that utilizes millimeter-sized iron rods or spheres driven by magnetic forces to selectively deform targeted cells, which in turn generates transient disruption in cell membranes and enables the delivery of foreign materials into cytosols. A range of functional materials with the size from a few nanometers to hundreds of nanometers have been successfully delivered into various types of mammalian cells in situ with high efficiency and viability and minimal undesired effects. Mechanistically, material delivery is mediated by force-induced transient membrane disruption and restoration, which depend on actin cytoskeleton and calcium signaling. When used for siRNA delivery, CXCR4 is effectively silenced and cell migration and proliferation are significantly inhibited. Remarkably, cell patterns with various complexities are generated, demonstrating the unique ability of our approach in selectively delivering materials into targeted cells in situ. In summary, we have developed a magnetic force-driven intracellular delivery method with in situ selectivity, which may have tremendous applications in biology and medicine.

This paper comprehensively reviews the literature related to disaster relief supply management in recent years by taking the perspectives of three critical decision-making issues, i.e., coordination issues, facility location decisions, and inventory decisions. For each decision-making issue discussed, we clarify the barriers of current research papers and identify the major challenges and critical factors that should be considered. In the following, we present the perspectives on the road of coordination between multiple relief actors, characterize the location decisions of relief facilities with a variety of optimization objectives, and emphasize the importance of relief supply varieties and critical factors in the decisions of disaster relief inventories. Future research directions are recommended for further discussions.