Volatile Relay Biosensing and Mobile Phone Imaging for Detection of Influenza Virus

ABSTRACT Detection of volatile organic compounds for diagnostic purposes is highly promising but is equipment‐heavy. Herein, we redefine the use of volatiles in biosensing and demonstrate a point‐of‐care detection of influenza virus using a mobile phone camera. The key to this opportunity is the enzymatic amplification of a volatile chemical signal into the readily imaged luminescence output. To this end, we developed a non‐volatile substrate, which is converted into a volatile product by the virus. This product becomes airborne and leaves the test solution, re‐enters the adjacent assay volume, and therein activates an enzymatic reporter cascade. The latter affords strong signal amplification and production of light sufficient for detection by a mobile phone camera. One strong benefit of this assay is that physically separating the test and the reporter chemistries overcomes matrix incompatibilities that confound single‐volume assays. Using this method, we could distinguish influenza from other respiratory viruses using readily available laboratory plasticware and a mobile phone camera. Furthermore, the assay showed promise in detecting influenza in patient‐derived samples.