Cell migration with microfluidic chips

Abstract

Cell migration plays a pivotal role in various physiological and pathological processes including angiogenesis, cancer metastasis, wound healing, inflammation, and embryogenesis. For cell migration in vitro , the conventional cell migration assays like the Boyden chamber and wound-healing assays are unable to meet the requirements of high-throughput, and are incapable of integrating complex environmental factors to comprehensively consider multi-parameters factors, such as cell matrix and concentration gradient, particularly those effecting cell migration. In contrast, microfluidic chips have the potential to take these challenges by allowing for precise and simultaneous control of multiple environmental factors mimicking in vivo environment of cells. Microfluidic devices successfully produce accurately controllable fluid and stable concentration gradient quickly, and manipulate gradients spatially and temporally. In addition, microfluidic devices enables accurate and reliable cell migration assay on real-time observation with limited amounts of reagents. It has exhibited tremendous potential due to its miniaturization, integration, high-throughput and high-precision. Owing to these particular advantages, over the past few years, a number of microfluidic chips combining two-dimensional (2D) and three-dimensional (3D) cell cultures have already been widely used in cell migration assays, demonstrating that microfluidic technology has significant implications for cell biology and cell-based assays. The microfluidic chips for cell migration assay using 2D platform could be classified into wound-healing and non-wound assays. Wound edges could be attained though a laminar flow of trypsin solution or removing solid barrier. After wound formed, cell migration could be detected and monitored using electric cell-substrate impedance sensing. Non-wound assays include chemotaxis and electrotaxis. The in vivo microenvironment is characterized by a 3D scaffold and multiple cell types. Therefore, increasing microfluidic devices with a 3D cell culture system have been developed for cell chemotaxis. These chips embed cells in a structure manufactured using agarose, collagen and hydrogel that mimics the extracellular matrix (ECM) of structural proteins found in real and living tissues. Various microfluidic devices with a 3D cell culture model can present cell-matrix and cell-cell interactions and provide reliable analysis platform for cell migration. Briefly, 2D and 3D microfludic chip-based models for concentration gradients, chemotaxis, electrotaxis and cells interactions have beneficial effects on cell migration assays. As a breakthrough to conventional methods, those microfluidic chip-based cell migration assays really promote the advanced progress in the area of cell biology and biomedicine. In this review, we describe the characterization of cell migration assays in microfluidic systems, highlight latest advances of the microfluidic device for researching in cell migration, focusing on both 2D and 3D cell cultures, and discuss advantages and disadvantages of this rapidly developed analysis technology.