On-chip sample preparation for multiple targets using digital microfluidics
In many biochemical protocols, sample preparation is an extremely important step for mixing multiple reagents in a given ratio. Dilution of a biochemical sample/reagent is the special case of mixing or solution preparation where only two fluids (sample and buffer) are mixed at a certain ratio corresponding to the desired concentration factor. Many bioassays often require multiple concentration values of the same sample/reagent, and implementing them efficiently on a digital microfluidic biochip is a challenge. In this paper, we present an algorithmic solution for the problem of producing a set of different target droplets in a minimum number of mix-split steps, and satisfying a given upper bound in concentration error. Unlike prior methods, this approach does not require any intermediate storage. We represent the underlying search space using a binary de Brujin graph and show that a shortest mix-split sequence can be obtained by solving an asymmetric traveling salesman problem therein. Simulation results over a large data set reveal that the proposed technique outperforms existing methods in terms of the number of mix-split steps, waste droplets, and reactant usage. The method is applicable in general scenarios of either one mixer or more mixers on the chip. A digital microfluidic platform can be easily designed to implement such a technique for rapid on-chip sample preparation. © 2014 IEEE.
Mitra, D; Roy, S; Bhattacharjee, S; Chakrabarty, K; Bhattacharya, BB
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