Layout-Aware Mixture Preparation of Biochemical Fluids on Application-Specific Digital Microfluidic Biochips

Abstract

The recent proliferation of digital microfluidic (DMF) biochips has enabled rapid on-chip implementation of many biochemical laboratory assays or protocols. Sample preprocessing, which includes dilution and mixing of reagents, plays an important role in the preparation of assays. The automation of sample preparation on a digital microfluidic platform often mandates the execution of a mixing algorithm, which determines a sequence of droplet mix-split steps (usually represented as a mixing graph). However, the overall cost and performance of on-chip mixture preparation not only depends on the mixing graph but also on the resource allocation and scheduling strategy, for instance, the placement of boundary reservoirs or dispensers, mixer modules, storage units, and physical design of droplet-routing pathways. In this article, we first present a new mixing algorithm based on a number-partitioning technique that determines a layout-aware mixing tree corresponding to a given target ratio of a number of fluids. The mixing graph produced by the proposed method can be implemented on a chip with a fewer number of crossovers among droplet-routing paths as well as with a reduced reservoir-to-mixer transportation distance. Second, we propose a routing-aware resource-allocation scheme that can be used to improve the performance of a given mixing algorithm on a chip layout. The design methodology is evaluated on various test cases to demonstrate its effectiveness in mixture preparation with the help of two representative mixing algorithms. Simulation results show that on average, the proposed scheme can reduce the number of crossovers among droplet-routing paths by 89.7% when used in conjunction with the new mixing algorithm, and by 75.4% when an earlier algorithm [Thies et al. 2008] is used.