Detection of single amino acid differences in haemoglobin from blood samples using a nanopore

The real-time identification of protein biomarkers is under intense investigation for the development of point-of-care and portable devices. Here we use a PlyAB biological nanopore to detect a range of folded Haemoglobin (Hb) variants in blood samples. Blockades of HbA and sickle cell anaemia HbS, which differ by just one amino acid, and fetal HbF were distinguished with more than 97% accuracy on the basis of individual events. This nanopore approach is quick and straightforward. It can count and confirm the identity of Hb variants instantaneously directly from blood samples. Therefore, PlyAB nanopores are promising single-molecule nanoreactors for real-time folded protein analysis, and identification with immediate application in point-of-care Hb counting and sickle cell anaemia diagnosis.