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As opposed to traditional membrane\u2010based nanopores, the DNP\u2010ToF reader uses two sub\u201010\u00a0nm pores placed in series and are made from plastic to allow securing the resistive pulse sensing (RPS) independent ToF variable as well as the traditional RPS variables. The device enables on\u2010chip proteolytic digestion with downstream identification of peptide fragments. Using amyloid\u2010\u03b2 (A\u03b2) as a model system, we demonstrate efficient digestion under nanoscale confinement consistent with a reaction\u2010limited regime and convection\u2010dominated transport. The device achieved robust event detection with &gt;95% successful pairing of dual nanopore RPS signals enabling extraction of five key features (\u0394I\n                    <jats:sub>1<\/jats:sub>\n                    \/I\n                    <jats:sub>0<\/jats:sub>\n                    , \u0394I\n                    <jats:sub>2<\/jats:sub>\n                    \/I\n                    <jats:sub>0<\/jats:sub>\n                    , t\n                    <jats:sub>D1<\/jats:sub>\n                    , t\n                    <jats:sub>D2<\/jats:sub>\n                    , and ToF) from individual peptide events. Machine learning provided high\u2010confidence peptide identification with a random forest (RF) classifier achieving 100% accuracy and a cross\u2010validated accuracy of 99.6%\u00a0\u00b1\u00a00.9%. Digestion efficiency was tunable through occupancy\u2010controlled conditions with RF\u2010assigned intact A\u03b2 events decreasing from \u223c9.5% at 1\u00a0nM to \u223c0.33% at 100 pM. These results establish a scalable, high\u2010sensitivity platform for integrated single molecule analysis to secure proteomic data from mass\u2010limited samples.\n                  <\/jats:p>","DOI":"10.1002\/smtd.71044","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:13:24Z","timestamp":1789550004000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptide Fingerprinting of Single Protein Molecules Using In\u2010Plane Nanopore Sensors Integrated to an Extended Immobilized Nanoscale Enzymatic Reactor (eINER)"],"prefix":"10.1002","author":[{"given":"Suresh","family":"Shivanka","sequence":"first","affiliation":[{"name":"Department of Chemistry The University of Kansas  Lawrence KS USA"},{"name":"Center of BioModular Multiscale Systems for Precision Medicine  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2330-0407","authenticated-orcid":false,"given":"Randy F. Espinal","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Kansas  Lawrence KS USA"},{"name":"Center of BioModular Multiscale Systems for Precision Medicine  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximillian","family":"Chibuike","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Kansas  Lawrence KS USA"},{"name":"Center of BioModular Multiscale Systems for Precision Medicine  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4284-7041","authenticated-orcid":false,"given":"Pramodi","family":"Vithanage","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Kansas  Lawrence KS USA"},{"name":"Center of BioModular Multiscale Systems for Precision Medicine  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indu A.","family":"Chandrasoma","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Kansas  Lawrence KS USA"},{"name":"Center of BioModular Multiscale Systems for Precision Medicine  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pubudu","family":"Premarathne","sequence":"additional","affiliation":[{"name":"Department of Chemistry The University of Kansas  Lawrence KS USA"},{"name":"Center of BioModular Multiscale Systems for Precision Medicine  USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Verber","sequence":"additional","affiliation":[{"name":"Center of BioModular Multiscale Systems for Precision Medicine  USA"},{"name":"University of North Carolina  Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-7058","authenticated-orcid":false,"given":"Steven 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