On-Chip Sample Preparation with Multiple Dilutions Using Digital Microfluidics

Abstract

In many biochemical protocols, solution preparation is a preprocessing step for mixing two or more fluids in a given ratio. Dilution of a biochemical sample/reagent is the special case of mixing or solution preparation where only two different type of fluids, one of which is a buffer solution, are mixed at a certain ratio corresponding to the desired concentration factor. Bioassays implemented on digital micro fluidic biochips may require several different concentration values of the same sample/reagent. In this paper, we present a scheme in which a set of different target droplets (with concentration values ranged between 0\% and 100\%) can be produced with an acceptable error bound in minimum mix-split steps. The method does not require any intermediate storage since, at each step, the current droplet is mixed only with the sample (with 100% concentration) or with the buffer (with 0% concentration) droplet. The problem of generating multiple target concentrations has been formulated based on a binary de Bruijn graph. The proposed technique outperforms the existing single target based methods in terms of both the number of mix-split steps and the number of waste droplets. This in turn, reduces the execution time, the number of electrode actuations, and sample/reagent requirement. A digital micro fluidic platform can also be easily designed to implement such on-chip sample preparation.