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Nanopore sensing offers a label\u2010free route to such resolution, but most implementations rely on fragmentation, probes, or functionalization, leaving intact isotypes inaccessible. Here, a nanopore\u2010based assay that directly discriminates full\u2010length IgG, monomeric IgA, and IgM under non\u2010denaturing conditions, resolving intrinsic molecular signatures in real time is presented. In a lithium chloride electrolyte, glass nanopipettes operate in an electroosmotic\u2010flow\u2013dominated regime where flow\u2010driven transport and nanoscale confinement produce distinct ionic fingerprints for each isotype. Affinity\u2010based signal modulation with protein G, which selectively binds the IgG Fc domain, further introduces a tunable contrast mechanism that sharpens IgG\u2010IgA separability while preserving native structure and binding functionality. Quantitative analysis demonstrates robust separation (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.0001) in binary and ternary mixtures with low misclassification. Evaluation in diluted human serum with a physiologically representative IgG:IgA:IgM ratio (7:2:1) shows that isotype\u2010specific fingerprints remain distinguishable in a serum\u2010derived background. The EOF\u2010governed assay establishes a scalable framework for direct, multiplexed immunoprofiling and extends label\u2010free nanopore analysis beyond antibodies toward broader proteomic targets.\n                  <\/jats:p>","DOI":"10.1002\/smtd.70758","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T08:22:43Z","timestamp":1780388563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Label\u2010Free Profiling of Immunoglobulin Isotypes Using Solid\u2010State Nanopores"],"prefix":"10.1002","volume":"10","author":[{"given":"Iris Baffour","family":"Ansah","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of California  Riverside California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California  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