Development of microfluidic alginate microbead generator tunable by pulsed airflow injection for the microencapsulation of cells

Recently, microbead generation and microencapsulation of cells using microfluidic technology have been actively pursued for various applications. However, most of the proposed systems are not only technically demanding, but might also be harmful to the encapsulated cells. To tackle these issues, this study reports a microfluidic alginate microbead generator consisting of a polydimethylsiloxane (PDMS) microfluidic chip and an integrated quartz microcapillary tube. The working principle is based on the use of a pulsed airflow to segment a continuous alginate suspension flow to form suspension fragments in a microchannel and then alginate microbeads when they were delivered out the microfluidic system to a sterile calcium chloride solution through a microcapillary tube. In this study, the alginate suspension fragments with varied sizes in the microchannel can be generated either by modulating the alginate suspension flow rate or the pulsation frequency of airflow injection. By fine tuning the size of them, the alginate microbeads can be generated in a size-controllable manner. Results showed that alginate microbeads with the size ranging from 150 to 370 mu m in diameter can be generated at the suspension flow rate and airflow injection frequency ranges of 2-4 mu l/min and 0.6-35 Hz, respectively. Besides, the alginate microbeads generated by the system were tested with excellent size uniformity (CV: 3.1-5.1%). Moreover, its application for the microencapsulation of chondrocytes in alginate microbeads was also demonstrated with high cell viability (96 +/- A 2%). As a whole, the proposed device has paved an alternative route to perform alginate microbead generation or microencapsulation of cells in a simple, continuous, controllable, uniform, cell friendly, and less contaminated manner.