Prediction and control of number of cells in microdroplets by stochastic modeling

Manipulation and encapsulation of cells in microdroplets has found many applications in various fields such as clinical diagnostics, pharmaceutical research, and regenerative medicine. The control over the number of cells in individual droplets is important especially for microfluidic and bioprinting applications. There is a growing need for modeling approaches that enable control over a number of cells within individual droplets. In this study, we developed statistical models based on negative binomial regression to determine the dependence of number of cells per droplet on three main factors: cell concentration in the ejection fluid, droplet size, and cell size. These models were based on experimental data obtained by using a microdroplet generator, where the presented statistical models estimated the number of cells encapsulated in droplets. We also propose a stochastic model for the total volume of cells per droplet. The statistical and stochastic models introduced in this study are adaptable to various cell types and cell encapsulation technologies such as microfluidic and acoustic methods that require reliable control over number of cells per droplet provided that settings and interaction of the variables is similar.
W. H. Coulter Foundation; Center for Integration of Medicine and Innovative Technology under U.S. Army Medical Research Acquisition Activity; NIH; U.S. Army Medical Research & Materiel Command (USAMRMC); Telemedicine & Advanced Technology Research Center (TATRC), at Fort Detrick, MD; National Science Foundation under NSF CAREER