Abstract
To understand the burgeoning challenges of metastasis, a microchannel of 35 μm diameter, constricted to 7 μm for a distance of 200 μm in a total length of 3 mm, was designed and fabricated using a mask aligner made of polydimethylsiloxane (PDMS) to mimic in vivo capillaries. A thin glass cover-slide was mounted on top to monitor the motion of single or aggregated malignant HeLa cells (size 17–30 μm) microscopically through the constricted microchannel at a constant flow rate of 30 μl/h. Quantitative deconvolution of high-speed videographs of a single cell of 30 μm revealed cellular deformation while passing through constriction, having elongation index, average transit velocity and entry time of 2.67, 18 mm/s and 5.1 ms, respectively. Morphological analysis of live and apoptotic cells by dual staining with Acridine Orange/Ethidium Bromide demonstrated retention of a significant viable cell population after exit through the constriction and a viability index of 50% was quantified by dye exclusion assay. The cumulative data for microfluidic parameters, morphology and relevant metastatic MMP2 gene expression efficiency measured by real-time polymerase chain reaction revealed retention of virulence potency that could possibly cause metastasis, would be beneficial in developing futuristic MEMS device for cancer theranostics.
Highlights
Even in this modern era of cancer therapeutics, scientists and oncologists have not been able to resolve the mystery of metastatic cancer, which causes high mortality worldwide
In the past few decades, several efforts have been made to elucidate the role of circulating tumour cells (CTCs) in seeding metastasis, where two or more CTCs form clusters, and these clusters are reported to be strong initiators of metastasis compared with singlets[6,14,15,16]
The precise width and length of the constricted section were ascertained by Field emission scanning electron microscopy (FESEM) analysis and were found to be 6.18 and 200.28 μm, respectively, as shown in Fig. 2c and d
Summary
Even in this modern era of cancer therapeutics, scientists and oncologists have not been able to resolve the mystery of metastatic cancer, which causes high mortality worldwide. It is often challenging to study the behaviour of CTCs in real conditions, constricted microfluidic channels with a width smaller than the diameter of the cells are often fabricated using standard microfabrication techniques, as they are efficient in providing an environment to mimic in vivo capillaries[20]. The main objective of this work was to elucidate the flow behaviour of metastatic cancer cells experimentally, similar to CTCs, evaluating the flow dynamics and viability indices of cancer cells in a constricted microchannel. HeLa cells were allowed to pass through the constricted channels of width 7 μm for a distance of 200 μm at a constant peristaltic flow rate (30 μl/h) Physical parameters such as entry time, transit velocity and elongation index of a single HeLa cell were evaluated using representative images deconvoluted from high-speed videographs. The crux of the current concept is illustrated in the Fig. 1
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