Droplet Generation and Manipulation in Microfluidics: A Comprehensive Overview of Passive and Active Strategies.

Droplet-based microfluidics (DBM) has emerged as a powerful tool for a wide range of biochemical applications, from single-cell analysis and drug screening to diagnostics and tissue engineering. This review provides a comprehensive overview of the latest advancements in droplet generation and trapping techniques, highlighting both passive and active approaches. Passive methods-such as co-flow, cross-flow, and flow-focusing geometries-rely on hydrodynamic instabilities and capillary effects, offering simplicity and integration with compact devices, though often at the cost of tunability. In contrast, active methods exploit external fields-electric, magnetic, thermal, or mechanical-to enable on-demand droplet control, allowing for higher precision and throughput. Furthermore, we explore innovative trapping mechanisms such as hydrodynamic resistance networks, microfabricated U-shaped wells, and anchor-based systems that enable precise spatial immobilization of droplets. In the final section, we also examine active droplet sorting strategies, including electric, magnetic, acoustic, and thermal methods, as essential tools for downstream analysis and high-throughput workflows. These manipulation strategies facilitate in situ chemical and biological analyses, enhance experimental reproducibility, and are increasingly adaptable to industrial-scale applications. Emphasis is placed on the design flexibility, scalability, and biological compatibility of each method, offering critical insights for selecting appropriate techniques based on experimental needs and operational constraints.