Chemically labeled nucleotides and oligonucleotides encode DNA for sensing with nanopores.

The labeling of nucleotides and oligonucleotides with reporter groups is an important tool in the sequence-specific sensing of DNA, as exemplified by fluorescence tags. Here we show that chemical tags can encode sequence information for electrical nanopore recordings. In nanopore recordings, individual DNA strands are electrophoretically driven through a nanoscale pore leading to detectable blockades of ionic current. The tags cause characteristic electrical signatures in the current blockades of translocating DNA strands and thereby encode sequence information. The viability of the strategy is demonstrated by discriminating between drug resistance-conferring point mutations. By being independent of pore engineering, the new approach can potentially enhance the sensing repertoire of durable solid-state nanopores for which alternative sensing strategies developed for protein pores are not easily accessible.