“Digital microfluidic biochip (DMFB)” emanates as one of the most promising technologies in the discipline of “Lab-on-a-Chip (LoC)” environment, which encompasses several application areas like biology, electronics, chemistry, etc., by replacing the conventional laboratory equipment. The geometry of digital microfluidic biochips is realized on a 2D grid with regular three-, four- and six-sided polygons. In this paper, we address the structural and behavioural aspects of the architectures as mentioned earlier and throwing sight to the enhancement of two primary modular operations such as droplet routing and mixing. Furthermore, a complete and tangible comparative study is performed efficiently based on these three design methodologies. © 2021, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.