With the current growth and the increasing average age of the global population, we can expect an increase in the number of chronic aging-related pathologies, like neurodegenerative diseases or cancer. Early diagnosis could enable better medical care and improve the quality of life. Various pathologies are associated with misfolding or conformational changes in proteins, which alter their function or binding properties. Current methods cannot simultaneously detect and quantify analytes in different conformational states. With an increasing understanding of the role conformational variation plays in health and disease physiology, there is a growing demand for a sensitive conformational sensor capable of quantifying analytes in different states at low concentrations in biological fluids. Electrical detection by nanopores has proven sufficiently powerful to sense and quantify subtle conformational changes in proteins and peptides (Ratinho et al., Nat. Commun., 2025). I will present the work carried out by our laboratory on the identification of peptide biomarkers that differ by a single amino acid (depleted) (Greive et al., ACS Nano , 2024), chiral amino acid substitution ( RSC Chemical Science, 2025), or post-translational modification (Stierlen et al, ACS Central Science , 2023) involved in normal biological processes and many disabling pathologies. I will show the proof of concept for directly identifying a family of biomarkers in serum and discriminating biomarker enantiomers at the single-molecule level using a protein nanopore. Finally, I will discuss the possible role of peptide secondary structures in their electrical detection (Meyer et al., ACS Nano, 2025).
Ratinho et al. (Sun,) studied this question.
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