Manipulation of close-packed hydrogel microbeads in microscale channels: A review on fundamentals and biomedical applications

The microscale operation of close-packed hydrogel microbead suspensions (CPHMSs) has attracted widespread attention due to their advantages in reducing randomness and avoiding the challenges of density matching in applications spanning from single-cell sequencing, tissue engineering to drug carrier fabrication, etc. In this paper, the fundamentals, technologies, and applications of CPHMSs are reviewed. Preparation methods of CPHMSs and the fundamentals of flow and rheological properties of CPHMSs are first discussed. Then, a brief overview of the technological development of microscale manipulation of CPHMSs is presented, including pairing, mixing, co-encapsulation, and 3D printing of CPHMSs. Furthermore, a review on the applications of CPHMS manipulation in several fields such as single-cell sequencing and preparation of topological hydrogels is presented. The technical challenges that need to be further addressed on CPHMS manipulation are also outlined.