Simulation-based method for optimum microfluidic sample dilution using weighted mix-split of droplets

Digital microfluidics has recently emerged as an effective technology in providing inexpensive but reliable solutions to various biomedical and healthcare applications. On-chip dilution of a fluid sample to achieve a desired concentration is an important problem in the context of droplet-based microfluidic systems. Existing dilution algorithms deploy a sequence of balanced mix-split steps, where two unit-volume droplets of different concentrations are mixed, followed by a balanced-split operation to obtain two equal-sized droplets. In this study, the authors study the problem of generating dilutions using a combination of (1 : 1) and (1:2) mix/split operations, called weighted dilution (WD), and present a layout architecture to implement such WD-steps. The authors also describe a simulation based method to find the optimal mix-split steps for generating a dilution under various criteria such as minimisation of waste, sample, or buffer droplets. The sequences can be stored in a look-up table a priori, and used later in real time for fast generation of actuation sequences. Compared with the balanced (1:1) model, the proposed WD scheme reduces the number of mix-split steps by around 22%, and the number of waste droplets, by 18%.