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Here, a series of circular DNAs with discrete ssDNA fractions (0%, 33%, 66%, and 100%) was constructed and systematically interrogated for their voltage-dependent translocation through solid-state nanopores. Under fixed bias, ionic current blockade increases linearly with ss content, whereas dwell time scales exponentially with ss proportion. Notably, two voltage-dependent regimes emerge across a critical ss fraction threshold: constructs with high ss content (66% and 100%) exhibit dwell time decaying exponentially with voltage (t \u223c e\u2212v\/v0), consistent with entropy-limited uncoiling governed by entropic barriers; conversely, low-ss constructs (0% and 33%) show nearly voltage-invariant translocation, dominated by barrier-free electrophoretic drift due to rigid ds backbones and minimal entanglement. Weibull analysis of event charge deficit distributions confirms this kinetic transition, and ECD values correlate exponentially with ss fraction at all tested voltages, an effect attributed to enhanced excluded-volume crowding at the nanopore orifice by flexible ss segments, switching the driving force from entropic restriction to macromolecular crowding. Collectively, these results elucidate the interplay of hybrid ss\/ds architecture and applied field on circular DNA transport, establishing a quantitative physical framework for semiflexible biopolymer transport under nanoconfinement and informing the design of nanopore sensors targeting topologically complex nucleic acids.<\/jats:p>","DOI":"10.1021\/acsami.6c11554","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T03:02:01Z","timestamp":1788490921000},"page":"48799-48812","source":"Crossref","is-referenced-by-count":0,"title":["The Translocation of Circular DNA with Variable Single\/Double Strand Ratios through Solid-State Nanopores: Transition from Entropic Barriers to Crowding-Dominated Kinetics"],"prefix":"10.1021","volume":"18","author":[{"given":"Jiayi","family":"Liu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P.R. China, 330052"]},{"name":"Huankui Academy, Nanchang University , , ,","place":["Nanchang, Jiangxi, P.R. China, 330031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P.R. China, 330052"]},{"name":"Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P.R. China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5279-1392","authenticated-orcid":true,"given":"Hongwen","family":"Wu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P.R. China, 330052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyou","family":"Xiao","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqian","family":"Hu","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Deng","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichuang","family":"Gao","sequence":"additional","affiliation":[{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330103"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Huang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P.R. China, 330052"]},{"name":"The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3991-6329","authenticated-orcid":true,"given":"Derong","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P.R. China, 330052"]},{"name":"Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330103"]},{"name":"Jiangxi Medical College, Nanchang University , , , ,","place":["Nanchang, Jiangxi, P. R. China, 330031"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"issue":"7082","key":"2026092321454478300_cit1","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/nature04586","article-title":"Folding DNA to create nanoscale shapes and patterns","volume":"440","author":"Rothemund","year":"2006","journal-title":"Nature"},{"issue":"9","key":"2026092321454478300_cit2","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1021\/nl803189k","article-title":"Translocation of RecA-coated double-stranded DNA through solid-state nanopores","volume":"9","author":"Smeets","year":"2009","journal-title":"Nano Lett."},{"issue":"8","key":"2026092321454478300_cit3","doi-asserted-by":"publisher","first-page":"2953","DOI":"10.1021\/nl901370w","article-title":"Distinguishing single- and double-stranded nucleic acid molecules using solid-state nanopores","volume":"9","author":"Skinner","year":"2009","journal-title":"Nano Lett."},{"issue":"44","key":"2026092321454478300_cit4","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202507736","article-title":"Solid-State Nanopore Single-Molecule Capture: Advances and Challenges","volume":"21","author":"He","year":"2025","journal-title":"Small"},{"issue":"1","key":"2026092321454478300_cit5","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03762-8","article-title":"Nanopore-based sensing for biomarker detection: from fundamental principles to translational diagnostics","volume":"23","author":"Shrikrishna","year":"2025","journal-title":"J. Nano biotechnol."},{"issue":"11","key":"2026092321454478300_cit6","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/nnano.2010.202","article-title":"Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors","volume":"5","author":"Wanunu","year":"2010","journal-title":"Nat. Nanotechnol."},{"key":"2026092321454478300_cit7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2025.103417","article-title":"Single-molecule resolution of macromolecules with nanopore devices","volume":"338","author":"Ren","year":"2025","journal-title":"Adv. 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Rev. Lett."},{"issue":"7","key":"2026092321454478300_cit20","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1021\/nl100997s","article-title":"Detecting DNA folding with nanocapillaries","volume":"10","author":"Steinbock","year":"2010","journal-title":"Nano Lett."},{"issue":"5","key":"2026092321454478300_cit21","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.71.051903","article-title":"Translocation of double-strand DNA through a silicon oxide nanopore","volume":"71","author":"Storm","year":"2005","journal-title":"Phys. Rev. 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Visualized Exp."},{"issue":"18","key":"2026092321454478300_cit27","doi-asserted-by":"publisher","first-page":"7359","DOI":"10.1093\/nar\/17.18.7359","article-title":"Pulse time and agarose concentration affect the electrophoretic mobility of cccDNA during PFGE and FIGE [corrected]","volume":"17","author":"Sobral","year":"1989","journal-title":"Nucleic Acids Res."},{"issue":"11","key":"2026092321454478300_cit28","doi-asserted-by":"publisher","first-page":"4359","DOI":"10.1093\/nar\/17.11.4359","article-title":"Pulsed-field gel electrophoresis of circular DNA","volume":"17","author":"Simske","year":"1989","journal-title":"Nucleic Acids Res."},{"issue":"4","key":"2026092321454478300_cit29","doi-asserted-by":"publisher","first-page":"e24","DOI":"10.1093\/nar\/gku1255","article-title":"Electrophoretic mobility of supercoiled, catenated and knotted DNA molecules","volume":"43","author":"Cebri\u00e1n","year":"2015","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"2026092321454478300_cit30","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/0301-4622(78)80008-8","article-title":"Isolation and physical studies of the intact supercoiled, the open circular and the linear forms of ColE1-plasmid DNA","volume":"8","author":"Voordouw","year":"1978","journal-title":"Biophys. 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