Review of 3D cell culture with analysis in microfluidic systems

A review with 105 references that analyzes the emerging research area of 3D cell culture in microfluidic platforms with integrated detection schemes. Over the last several decades a central focus of cell culture has been the development of better in vivo mimics. This has led to the evolution from planar cell culture to cell culture on 3D scaffolds, and the incorporation of cell scaffolds into microfluidic devices. Specifically, this review explores the incorporation of suspension culture, hydrogels scaffolds, paper-based scaffolds, and fiber-based scaffolds into microfluidic platforms. In order to decrease analysis time, simplify sample preparation, monitor key signaling pathways involved in cell-to-cell communication or cell growth, and combat the limitations of sample volume/ dilution seen in traditional assays, researchers have also started to focus on integrating detection schemes into the cell culture devices. This review will highlight the work that has been performed towards combining these techniques and will discuss potential future directions. It is clear that microfluidic-based 3D cell culture coupled with quantitative analysis can greatly improve our ability to mimic and understand in vivo systems.