Toward Mail-in-Sensors for SARS-CoV-2 Detection: Interfacing Gel Switch Resonators with Cell-Free Toehold Switches br

The COVID-19 pandemic has emphasized the importance of widespreadtesting to control the spread of infectious diseases. The rapid development, scale-up, anddeployment of viral and antibody detection methods since the beginning of the pandemichave greatly increased testing capacity. Desirable attributes of detection methods are lowproduct costs, self-administered protocols, and the ability to be mailed in sealed envelopes forthe safe analysis and subsequent logging to public health databases. Herein, such a platform isdemonstrated with a screen-printed, inductor-capacitor (LC) resonator as a transducer anda toehold switch coupled with cell-free expression as the biological selective recognitionelement. In the presence of the N-gene from SARS-CoV-2, the toehold switch relaxes,protease enzyme is expressed, and it degrades a gelatin switch that ultimately shifts theresonant frequency of the planar resonant sensor. The gelatin switch resonator (GSR) can beanalyzed through a sealed envelope allowing for assessment without the need for carefulsample handling with personal protective equipment or the need for workup with otherreagents. The toehold switch used in this sensor demonstrated selectivity to SARS-CoV-2 virus over three seasonal coronavirusesand SARS-CoV-1, with a limit of detection of 100 copies/mu L. The functionality of the platform and assessment in a sealed envelopewith an automated scanner is shown with overnight shipment, and further improvements are discussed to increase signal stability andfurther simplify user protocols toward a mail-in platform