PlyAB Nanopores Detect Single Amino Acid Differences in Folded Haemoglobin from Blood

Gang Huang, Aderik Voorspoels, Roderick Corstiaan Abraham Versloot, Nieck Jordy Van Der Heide, Enrico Carlon, Kherim Willems, Giovanni Maglia*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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The real-time identification of protein biomarkers is crucial for the development of point-of-care and portable devices. Here, we use a PlyAB biological nanopore to detect haemoglobin (Hb) variants. Adult HbA and sickle cell anaemia HbS, which differ by just one amino acid, were distinguished in a mixture with more than 97 % accuracy based on individual blockades. Foetal Hb, which shows a larger sequence variation, was distinguished with near 100 % accuracy. Continuum and Brownian dynamics simulations revealed that Hb occupies two energy minima, one near the inner constriction and one at the trans entry of the nanopore. Thermal fluctuations, the charge of the protein, and the external bias influence the dynamics of Hb within the nanopore, which in turn generates the unique ionic current signal in the Hb variants. Finally, Hb was counted from blood samples, demonstrating that direct discrimination and quantification of Hb from blood using nanopores, is feasible.

Original languageEnglish
Article number e202206227
Number of pages7
JournalAngewandte Chemie (International ed. in English)
Issue number34
Early online date27-Jun-2022
Publication statusPublished - 22-Aug-2022

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