TY - JOUR
T1 - PlyAB Nanopores Detect Single Amino Acid Differences in Folded Haemoglobin from Blood
AU - Huang, Gang
AU - Voorspoels, Aderik
AU - Versloot, Roderick Corstiaan Abraham
AU - Van Der Heide, Nieck Jordy
AU - Carlon, Enrico
AU - Willems, Kherim
AU - Maglia, Giovanni
N1 - © 2022 Wiley-VCH GmbH.
PY - 2022/8/22
Y1 - 2022/8/22
N2 - 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.
AB - 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.
U2 - 10.1002/anie.202206227
DO - 10.1002/anie.202206227
M3 - Article
C2 - 35759385
SN - 1433-7851
VL - 61
JO - Angewandte Chemie (International ed. in English)
JF - Angewandte Chemie (International ed. in English)
IS - 34
M1 - e202206227
ER -