Microfluidic Bioreactors for Cellular Microarrays

Living cell microarrays have been combined with microfluidic bioreactors, which provide multiple advantages for multiplex dynamic analyses and high-throughput screening. In the last decade, many developments in this new field have been introduced. The technology has evolved from fixed cell analysis towards living single-cell dynamic systems’ biology and high content analyses. The aim of this review is to provide an updated overview of the developments of living cellular microarrays in microfluidic bioreactors. Cell arrays in microfluidic bioreactors constructed with adherent mammalian cells are compared to non-adherent cells (mainly microbial cells). An overview is given on the design and construction of these microfluidic devices with a particular focus on cell patterning techniques. Cell patterning on adhesive micropatterns using techniques such as microcontact printing, microfluidic patterning, dip-pen nanolithography and polymer pen lithography as well as photo-patterning and laser-patterning strategies are discussed. Additionally, developments in mechanical cell patterning methods and robotic cell printing are reviewed. Two-dimensional (2D) as well as recently developed 3D cell arraying are discussed. Finally, cell array microfluidic setups and operation for single-cell types versus cell population variants are illustrated and compared on the basis of some illustrative examples in the field of drug screening, cytotoxicity evaluation, and basic cellular and microbiology research.