For the printing industry to grow and for companies in the field to remain competitive, there is a drive toward enhancing research and development so that costs of inks and substrates can be minimized. This paper details one of the first studies into the importance of liquid droplet size for applying wettability science to the development of inks and substrates using a newly developed picoliter droplet dispensing system (PDDS). Differences between using microliter, mu L (0.2-5 mu L), and picoliter, pL (15-380 pL), droplets for wettability analysis is considered, showing the importance of using pL droplets within the development of inks and substrates for printing applications. This is due to differences in contact angle being up to 40 degrees when comparing results from pL- and mu L-sized water-based droplets. Wetting, absorption, and evaporation behavior of different droplet sizes are also discussed with specific consideration to the use of wettability science for ink development and the development of inkjet printing substrates. A newly developed commercially available water-based blue ink and a commercially available water-based black ink are studied using pL experimentation to show how pL-sized droplets for inkjet wettability analysis is the optimum volume range to ensure optimized inkjet printing analysis and development.