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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

14 Citaten (Scopus)
53 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Artikelnummer e202206227
Aantal pagina's7
TijdschriftAngewandte Chemie (International ed. in English)
Volume61
Nummer van het tijdschrift34
Vroegere onlinedatum27-jun.-2022
DOI's
StatusPublished - 22-aug.-2022

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