Cross-Contamination Avoidance for Droplet Routing in Digital Microfluidic Biochips

Abstract

Abstract-Recent advances in droplet-based digital microfluidics have enabled biochip devices for DNA sequencing, immunoassays, clinical chemistry, and protein crystallization. Since crosscontamination between droplets of different biomolecules can lead to erroneous outcomes for bioassays, the avoidance of crosscontamination during droplet routing is a key design challenge for biochips. We propose a droplet-routing method that avoids cross-contamination in the optimization of droplet flow paths. The proposed approach targets disjoint droplet routes and minimizes the number of cells used for droplet routing. We also minimize the number of wash operations that must be used between successive routing steps that share unit cells in the microfluidic array. Two real-life biochemical applications are used to evaluate the proposed droplet-routing methods.

Droplet microfluidics for kinetic studies of viral fusion

“…34,35 In the experiments presented here, the pH of the chemical switch was typically set to a desired pH, followed by the collection of data from a train of droplets. After rigorous washing, the system was operated at a new desired pH.…”

An open-source compiler and PCB synthesis tool for digital microfluidic biochips

“…Many papers on DMFB routing have been published in recent years [7,12,19,21,22,32,35,64,71,81,83]; since assay operations (mixing, detection, etc.) are several orders of magnitude slower than droplet transport latencies, we have not prioritized a thorough implementation of all known droplet routing algorithms.…”

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“…At the intersection site of two droplet routes, a droplet that arrives at a later clock cycle can be contaminated by the residue left behind by another droplet that passed through at an earlier clock cycle. To avoid assay execution error, washing operations (i.e., wash-droplet routing) are introduced to clean the contamination left on the surface [22], [58], [60]. In Ref.…”

“…In Ref. [58], a disjoint route algorithm is applied to avoid the overlap between different routes, with insertions of washing operations between successive droplet routing subproblems. In Ref.…”