Recent developments in flow modeling and fluid control for paper-based microfluidic biosensors

Over the last 10 years, researchers have shown that paper is a promising substrate for affordable biosensors. The field of paper-microfluidics has evolved rapidly in that time, with simple colorimetric assays giving way to more complex electrochemical devices that can handle multiple samples at a given time. As paper devices become more complex, the ability to precisely control different fluids simultaneously becomes a challenge. Specifically, automated flow control is a necessary attribute to make paper-based devices more useable in resource-limited settings. Flow control strategies on paper are typically developed experimentally through trial-and-error, with little focus on theory. This is because flow behavior in paper is not well understood and sometimes difficult to predict precisely. Additionally, popular theoretical models are too simplistic, making them unsuitable for complex device designs and application conditions. A better understanding of flow theory would allow devices conceived straight from theoretical models. This could save time and resources by reducing experimental work. In this review, we provide an overview of different theoretical models used to characterize imbibition in paper substrates and document the latest flow control strategies that have been applied to automated fluid control on paper. Additionally, we look at current efforts to commercialize paper-based devices along with challenges facing this industry.