Development of a paper-based diagnostic for influenza detection

Abstract

The development of novel paper-based diagnostic tests has surged in recent years, due to the suitability of these tests for use at the point of care. These emerging paper-based tests retain the low cost and ease of use of traditional lateral flow tests, while offering increased sophistication and capabilities that approach those of traditional microfluidic devices. Here, we report on the development of a novel paper-based test for the diagnosis of influenza, commonly known as the flu. Influenza is a ubiquitously occurring infection, affecting 5−20% of Americans and resulting in an average of 23,000 deaths in the U.S., and up to 500,000 deaths globally, each year. Despite its prevalence, the diagnosis of influenza remains unsatisfactory, especially at the point of care. In particular, lateral flow tests for influenza suffer from poor sensitivity and provide only limited information about the infecting flu virus. Point-of-care testing of influenza therefore stands to benefit substantially from improved technology. To this end, we have developed two different versions of a paper-based flu assay, both using computationally designed affinity proteins, or “binders,” that bind to the influenza hemagglutinin (HA) protein. One version of the assay utilizes an HA stem-region binder and the other an HA head-region binder. With these assays, we demonstrate the detection of clinically relevant concentrations of recombinant HA and intact influenza virus, as well as the translation of this paper-based system to a two-dimensional paper network (2DPN) folding card device.