Algorithms for Producing Linear Dilution Gradient with Digital Microfluidics

摘要

Digital microfluidic (DMF) biochips are now being extensively used toautomate several biochemical laboratory protocols such as clinical analysis,point-of-care diagnostics, and polymerase chain reaction (PCR). In manybiological assays, e.g., in bacterial susceptibility tests, samples andreagents are required in multiple concentration (or dilution) factors,satisfying certain "gradient" patterns such as linear, exponential, orparabolic. Dilution gradients are usually prepared with continuous-flowmicrofluidic devices; however, they suffer from inflexibility,non-programmability, and from large requirement of costly stock solutions. DMFbiochips, on the other hand, are shown to produce, more efficiently, a set ofrandom dilution factors. However, all existing algorithms fail to optimize thecost or performance when a certain gradient pattern is required. In this work,we present an algorithm to generate any arbitrary linear gradient, on-chip,with minimum wastage, while satisfying a required accuracy in the concentrationfactor. We present new theoretical results on the number of mix-splitoperations and waste computation, and prove an upper bound on the storagerequirement. The corresponding layout design of the biochip is also proposed.Simulation results on different linear gradients show a significant improvementin sample cost over three earlier algorithms used for the generation ofmultiple concentrations.