Microfluidic technologies enable replacement of time-consuming and complex steps of biochemical laboratory protocols with a tiny chip. Sample preparation (i.e., dilution or mixing of fluids) is one of the primary tasks of any bioprotocol. In real-life applications where several assays need to be executed for different diagnostic purposes, the same sample fluid is often required with different target concentration factors ( CF s). Although several multi-target dilution algorithms have been developed for digital microfluidic biochips, they are not efficient for implementation with continuous-flow-based microfluidic chips, which are preferred in the laboratories. In this article, we present a multi-target dilution algorithm ( MTDA ) for continuous-flow-based microfluidic biochips, which to the best of our knowledge is the first of its kind. We design a flow-based rotary mixer with a suitable number of segments depending on the target- CF profile, error tolerance, and optimization criteria. To schedule several intermediate fluid-mixing tasks, we develop a multi-target scheduling algorithm ( MTSA ) aiming to minimize the usage of storage units while producing dilutions with multiple CF s. Furthermore, we propose a storage architecture for efficiently loading (storing) of intermediate fluids from (to) the storage units.

With the evolution of the technology, digital microfluidic (DMF) biochips have become a vital part of biochemical research. Hence, it is required to consider the reliability of the different fluidic operations performed on a biochip. Sample preparation is an important process of any real-life bioprotocol implementation on a DMF biochip. In this process, sequence of mixing and dilution steps are determined to get the desired target concentrations. The mixers used for performing mix-split steps may incorporate some noise during mixing and can result in the erroneous concentrations of the reagents. Thus, the reliability analysis of the resultant target concentration is necessary and methods are required to be developed to reduce these concentration errors. In this paper, the error and reliability models are discussed to compare the reliabilities of the existing mixing algorithms. Simulation results show that for a given target ratio, reliability of common dilution operation sharing (Liuet al., ICCAD-2013) is higher. We also discuss the mixer assignment techniques and the heuristic approach is found to quickly provide the better order of mixer assignment in order to achieve highly reliable mixture after sample preparation.

Recent studies in algorithmic microfluidics have led to the development of several techniques for automated solution preparation using droplet-based digital microfluidic (DMF) biochips. A major challenge in this direction is to produce a mixture of several reactants with a desired ratio while optimizing reactant cost and preparation time. The sequence of mix-split operations that are to be performed on the droplets is usually represented as a mixing tree (or graph). In this article, we present an efficient mixing algorithm, namely, Mixing Tree with Common Subtrees ( MTCS ), for preparing single-target mixtures. MTCS attempts to best utilize intermediate droplets, which were otherwise wasted, and uses morphing based on permutation of leaf nodes to further reduce the graph size. The technique can be generalized to produce multitarget ratios, and we present another algorithm, namely, Multiple Target Ratios ( MTR ). Additionally, in order to enhance the output load, we also propose an algorithm for droplet streaming called Multitarget Multidemand ( MTMD ). Simulation results on a large set of target ratios show that MTCS can reduce the mean values of the total number of mix-split steps ( T ms ) and waste droplets ( W ) by 16% and 29% over Min-Mix (Thies et al. 2008) and by 22% and 34% over RMA (Roy et al. 2015), respectively. Experimental results also suggest that MTR can reduce the average values of T ms and W by 23% and 44% over the repeated version of Min-Mix , by 30% and 49% over the repeated version of RMA , and by 9% and 22% over the repeated-version of MTCS , respectively. It is observed that MTMD can reduce the mean values of T ms and W by 64% and 85%, respectively, over MTR . Thus, the proposed multitarget techniques MTR and MTMD provide efficient solutions to multidemand, multitarget mixture preparationon a DMF platform.

In recent years, digital microfluidic biochips are being dominantly used for implementing a wide range of biochemical laboratory protocols (bioprotocols) on hand-held devices. Accurate preparation of fluid-samples is a fundamental preprocessing step that is needed in many bioprotocols. Oftentimes, the number of reservoirs built on-chip may be far less than that of the reactant fluids to be mixed. Hence, during the execution of an assay, several fluids are to be unloaded from the reservoirs to make room for loading new fluids stored off-line. Such unload-wash-load steps (switching) may be required several times, and these steps, being manual, significantly impact assay-completion time. In this paper, we propose a new scheduling scheme namely Reservoir and Mixer constrained Scheduling (RMS) that can schedule a mixing tree obtained by a mixing algorithm, while minimizing the number of switching such that the total completion time can be minimized. Simulation results over a large number of target ratios show that given the mixing trees obtained by standard mixing algorithms such as MinMix/RMA/CoDOS, RMS reduces switching steps (on average by 40.3%/41.9%/33%) at the cost of increasing mixing time (by only 3.5%/6.2%/4.8%), compared to an existing scheduling scheme invoked with reservoir constraints.