Nanopore Fingerprinting of Neurodegenerative Proteins and Phosphoproteins within a Minute

作者：Kai-Li Xin, Linlin Zhang, Min Li, Shao-Chuang Liu, Han-Qing She, Yi-Lun Ying, Yi-Tao Long, Zheng‐Li Hu · 发表于：JACS Au · 年份：2026 · DOI：10.1021/jacsau.6c00115 · 被引用次数：2 · 研究领域：Nanopore and Nanochannel Transport Studies、Anodic Oxide Films and Nanostructures、Lipid Membrane Structure and Behavior

Reliable identification of proteins and their post-translationally modified variants remains a formidable analytical challenge due to charge heterogeneity, sequence similarity, and comparable molecular weights. In this study, we demonstrate distinctive nanopore current fingerprints for clear identification of neurodegenerative disease-associated Tau protein and its phosphorylated variants using an asymmetric-electrolyte sensing system composed of different salts. The asymmetric configuration facilitates simultaneous detection of positively, neutrally, and negatively charged peptide fragments, resulting in 3.2-16-fold higher capture frequencies and 2.1-5.3-fold longer event durations, thereby yielding information-rich fingerprints that enhance protein recognition. Protein profiling was achieved within 1 min through integration with a droplet nanopore platform, which reduces sample consumption to the nanogram level while increasing throughput to >1800 events per minute. This work advances the nanopore fingerprinting approach for rapid, high-throughput, and low-sample protein biomarker detection, offering strong potential for clinical proteomics and early disease diagnosis.