Microfluidics-based devices: New tools for studying cancer and cancer stem cell migration

Abstract

Cell movement is highly sensitive to stimuli from the extracellular matrix and media. Receptors on the plasma membrane in cells can activate signal transduction pathways that change the mechanical behavior of a cell by reorganizing motion-related organelles. Cancer cells change their migration mechanisms in response to different environments more robustly than noncancer cells. Therefore, therapeutic approaches to immobilize cancer cells via inhibition of the related signal transduction pathways rely on a better understanding of cell migration mechanisms. In recent years, engineers have been working with biologists to apply microfluidics technology to study cell migration. As opposed to conventional cultures on dishes, microfluidics deals with the manipulation of fluids that are geometrically constrained to a submillimeter scale. Such small scales offer a number of advantages including cost effectiveness, low consumption of reagents, high sensitivity, high spatiotemporal resolution, and laminar flow. Therefore, microfluidics has a potential as a new platform to study cell migration. In this review, we summarized recent progress on the application of microfluidics in cancer and other cell migration researches. These studies have enhanced our understanding of cell migration and cancer invasion as well as their responses to subtle variations in their microenvironment. We hope that this review will serve as an interdisciplinary guidance for both biologists and engineers as they further develop the microfluidic toolbox toward applications in cancer research.

Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging

“…Due to a limitation in visual inspection and geometrical manipulation, conventional migration assays 5 are restricted to quantifying overall cell populations. In contrast, microfluidic devices permit single cell analysis because of compatibility with modern microscopy and control over microenvironment [6][7][8][9] .…”

“…Due to a limitation in visual inspection and geometrical manipulation, conventional migration assays 5 are restricted to quantifying overall cell populations. In contrast, microfluidic devices permit single cell analysis because of compatibility with modern microscopy and control over microenvironment [6][7][8][9] .We present a method for detailed characterization of BTSC migration using compartmentalizing microfluidic devices. These PDMS-made devices cast the tissue culture environment into three connected compartments: seeding chamber, receiving chamber and bridging microchannels.…”

Covalently immobilized biomolecule gradient on hydrogel surface using a gradient generating microfluidic device for a quantitative mesenchymal stem cell study

“…Recently, many efforts have been spent to use microfluidic technology to generate biomolecule gradients with advantages of reproducibility, high-throughput, and high precision. [4][5][6][7] However, current microfluidic approaches for cell study focus on culturing cells on glass or plastic substrates with gradients of diffusible proteins or surface-bound biomolecules. [8][9][10][11] In native tissues, cells always interact with the surrounding microenvironment with various biophysical properties.…”

A novel microfluidic platform for studying mammalian cell chemotaxis in different oxygen environments under zero-flow conditions

“…To better reproduce physiological and pathological phenomena in a microfluidic device, researchers have made great efforts to mimic cellular microenvironments. [25][26][27][28] Many microfluidic-based devices designed to explore the effect of oxygen tension on cell migration have been reported. [29][30][31][32][33][34][35][36] In one example, a three-dimensional microfluidic cell culture system featuring a controlled hypoxia environment was developed, a central 3D gel region acting as an external cellular matrix, and peripheral gas channel on each side establishing oxygen environment.…”