Microfluidic and cross-linking methods for encapsulation of living cells and bacteria - A review

Highlights: • Flow-focusing enables high bead production frequency and narrow size distribution. • Co-flow exhibits simple fabrication and generates large microbeads. • Thermal cross-linking enables fast gelation and produces beads of adequate strength. • Ionically cross-linked beads can be mechanically enhanced using polymer blends. • Photo cross-linked beads show high mechanical strength and long-term cell viability. -- Abstract: Microencapsulation of living cells is a field that has been heavily investigated by many researchers over the past two decades. Numerous experimental setups have been developed to encapsulate living cells in microbeads using different microfluidic devices and materials. Previous studies have investigated different microfluidic devices and materials for use in cancer treatment, drug delivery, environmental remediation, food production, and cell culture contexts. Some of the current challenges to these setups are maintaining reasonable levels of cell viability, cell leaching, nutrient and oxygen diffusion, and ensuring uniform microbead shape and size distribution. Addressing these issues and identifying the most reproducible and convenient setup enables researchers to efficiently encapsulate living cells and further advance the biomedical field. The efficiency of microencapsulation in terms of cell viability and uniform microbead shape and size distribution are directly related to the type of device used and the cross-linking method applied. Hence, the focus of this review is to assess the effects of using T-junction, flow-focusing, and co-flow microfluidic devices as well as thermal, ionic, and photo cross-linking methods for the microencapsulation of living cells. Recent applications of bacteria microencapsulation using microfluidic systems since 2017 are presented.