ASMS 2026 Poster – Identification of hemoglobin (Hb) variants is of significant value in the clinical diagnosis of hemoglobinopathies. Conventional methods used to identify Hb variants in clinical laboratories can narrow down the range of candidates for a Hb variant sample but are unable to pinpoint the exact Hb variant. In this study, a semiconductor chip-based single-molecule protein sequencing (SMPS) technology was explored as a novel method to identify Hb variants. Two heterozygous Hb variant samples underwent SMPS analysis. Proteotypic peptides corresponding to Hb variants were successfully detected, enabling the identification of the samples as Hb Handsworth (Hb SMPS subunit G18R) and Hb G-Accra (Hb β-G-Accra subunit D73N). Independent liquid chromatography —high‑resolution mass spectrometry (LC‑HR‑MS) analysis confirmed the presence of both variants. This is the first demonstration of SMPS for direct identification of clinical hemoglobin variants.

Download Poster