Recent developments in microfluidic devices, nanoparticle chemistry, fluorescent microscopy, and biochemical techniques such as genetic identification and antibody capture have provided easier and more sensitive platforms for detecting and diagnosing diseases as well as providing new fundamental insight into disease progression. These advancements have led to the development of new technology and assays capable of easy and early detection of pathogenicity as well as the enhancement of the drug discovery and development pipeline. While some studies have focused on treatment, many of these technologies have found initial success in laboratories as a precursor for clinical applications. This review highlights the current and future progress of microfluidic techniques geared toward the timely and inexpensive diagnosis of disease including technologies aimed at high-throughput single cell analysis for drug development. It also summarizes novel microfluidic approaches to characterize fundamental cellular behavior and heterogeneity.
Even though the majority of breast cancers respond well to primary therapy, a large percentage of patients relapse with metastatic disease, for which there is no treatment. In metastasis, a tumor sheds a small number of cancerous cells, termed circulating tumor cells (CTCs), into the local vasculature, from where they spread throughout the body to form new tumors. As CTCs move through the circulatory system, they experience physiological forces not present in the initial tumor environment, namely, fluid shear stress (FSS). Evidence suggests that CTCs respond to FSS by adopting a more aggressive phenotype; however, to date single-cell morphological changes have not been quantified to support this observation. Furthermore, the methodology of previous studies involves inducing FSS by flowing cells through the tubing, which lacks a precise and tunable control of FSS. Here, a microfluidic approach is used for isolating and characterizing the biophysical response of single breast cancer cells to conditions experienced in the circulatory system during metastasis. To evaluate the single-cell response of multiple breast cancer types, two model circulating tumor cell lines, MDA-MB-231 and MCF7, were challenged with FSS at precise magnitudes and durations. As expected, both MDA-MB-231 and MCF7 cells exhibited greater deformability due to increasing duration and magnitudes of FSS. However, wide variations in single-cell responses were observed. MCF7 cells were found to rapidly deform but reach a threshold value after 5 min of FSS, while MDA-MB-231 cells were observed to deform at a slower rate but with a larger threshold of deformation. This behavioral diversity suggests the presence of distinct cell subpopulations with different phenotypes.
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