Waste-aware single-target dilution of a biochemical fluid using digital microfluidic biochips

A key challenge in design automation of digital microfluidic biochips is to carry out on-chip dilution/mixing of biochemical samples/reagents for achieving a desired concentration factor (CF). In a bioassay, reducing the waste is crucial because the management of waste droplets is cumbersome and expensive; transporting them to the waste reservoir and washing their pathways to clean contaminated regions and remove the residue left by them may increase assay completion time. The existing dilution algorithms attempt to reduce the number of mix-split steps required in the process but focus little on the minimization of sample requirement or waste droplets. In this work, we characterize the underlying combinatorial properties of waste generation and identify the inherent limitations of two earlier mixing algorithms two WayMix (Thies et al., Natural Computing, 2008) [11] and DMRW (Roy et al., TCAD, 2010) [12] in addressing this issue. Based on these properties, we design an improved dilution/mixing algorithm (IDMA) that optimizes the usage of intermediate droplets generated during the dilution process, which in turn, reduces the demand of sample/reagent and production of waste. The algorithm terminates in O(d) steps for producing a target CF with a maximum error of 1/2(d+1), where d is the an accuracy level of the desired CF. Based on simulation results for all CF values, ranging from 1/1024 to 1023/1024 using a sample (100% concentration) and a buffer solution (0% concentration), we present an integrated scheme of choosing the best waste-aware dilution algorithm among four approaches such as two WayMix, DMRW, REMIA (Huang et al., ICCAD, 2012) [13] and IDMA, for a single target CF. Finally, an architectural layout of a DMF biochip that supports the proposed scheme is designed. (C) 2014 Elsevier B.V. All rights reserved.