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

Abstract

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%.