Rational design of near-infrared fluorescent carbon nanotube biosensors with covalent DNA-anchors

Semiconducting single wall carbon nanotubes (SWCNTs) are versatile near infrared (NIR) fluorophores. They are non-covalently modified to create sensors that change their fluorescence when interacting with biomolecules. However, non-covalent chemistry has several limitations and prevents a consistent way to molecular recognition and reliable signal transduction. Here, we introduce a widely applicable covalent approach to create molecular sensors without impairing the fluorescence in the NIR (>1000 nm). For this purpose, we attach single-stranded DNA (ssDNA) via guanine quantum defects as anchors to the SWCNT surface. A connected sequence without guanines acts as flexible capture probe allowing hybridization with complementary nucleic acids. Hybridization modulates the SWCNT fluorescence and the magnitude increases with the length of the capture sequence (20 > 10 >> 6 bases). Incorporation of additional recognition units via this sequence enables a generic route to NIR fluorescent biosensors with improved stability. To demonstrate the potential, we design sensors for bacterial siderophores and the SARS CoV-2 spike protein. In summary, we introduce covalent guanine quantum defect chemistry as rational design concept for biosensors.