{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/89267"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/89267","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Nanopores for detecting and sensing biological molecules","abstract":"In spite of significant advances in the detection, separation and counting of single biological molecules (DNA, proteins, aminoacids, etc.) with solid-state nanopores, atomically-resolved scanning and detection of these molecules remains a significant challenge. In most nanopore-based DNA sequencing and single molecule detection techniques, ionic current blockade and blockade duration are the primary signatures associated with reading and scanning. Although these techniques are good enough for single molecule detection, they are not sophisticated enough to analyze and detect single DNA bases, fine structures, homologues and mutagenesis. Aside from the detection difficulties, low signal to noise ratio (SNR), fast speed of translocation, and lack of a cross-check signal are the biggest challenges of current nanopore technology. In this study, we explored different nanopore architectures and materials to find solutions to these current challenges. Using extensive atomistic simulations, we showed that a single layer molybdenum Disulfide (MoS2) nanopore is attractive pore for single base DNA detection with high SNR and multi-level conductance. We introduced and simulated MscL (Mechano-Sensitive Channel of Large Conductance) as an alternative to traditional biological nanopores (Alpha-Hemolysin, MspA) since it provides a flexible nanopore with adaptability to DNA base types. Induced tension in MscL is shown to be different and distinguishable for each DNA base type. The speed of DNA translocation is also decreased by one order of magnitude in MscL, providing a better detection resolution compared to its counterpart, e.g. MspA. Next, we explored DNA origami-graphene hybrid nanopore for DNA detection. We found that the dwell time of each base type in the hybrid pore is different and distinguishable compared to pristine graphene nanopore. The specific interaction (hydrogen bonds) between the complimentary bases at the edge of the pore and the translocating DNA bases give rise to distinguishable dwell time for each DNA. In addition to DNA sequencing studies, we also investigated the recognition of natively folded proteins using graphene nanopore. We specifically focused on the detection of Immunoglobin G subclasses since the separation and the detection of different subclasses of IgG is the signature of many diseases. These four subclasses differ only in their hinge regions and are 95% homologues. We showed that the one atom thick graphene is highly capable of distinguishing between the subclasses by using ionic current and water flux signals.","abstract_html":"In spite of significant advances in the detection, separation and counting of single biological molecules (DNA, proteins, aminoacids, etc.) with solid-state nanopores, atomically-resolved scanning and detection of these molecules remains a significant challenge. In most nanopore-based DNA sequencing and single molecule detection techniques, ionic current blockade and blockade duration are the primary signatures associated with reading and scanning. Although these techniques are good enough for single molecule detection, they are not sophisticated enough to analyze and detect single DNA bases, fine structures, homologues and mutagenesis. Aside from the detection difficulties, low signal to noise ratio (SNR), fast speed of translocation, and lack of a cross-check signal are the biggest challenges of current nanopore technology. In this study, we explored different nanopore architectures and materials to find solutions to these current challenges. Using extensive atomistic simulations, we showed that a single layer molybdenum Disulfide (MoS2) nanopore is attractive pore for single base DNA detection with high SNR and multi-level conductance. We introduced and simulated MscL (Mechano-Sensitive Channel of Large Conductance) as an alternative to traditional biological nanopores (Alpha-Hemolysin, MspA) since it provides a flexible nanopore with adaptability to DNA base types. Induced tension in MscL is shown to be different and distinguishable for each DNA base type. The speed of DNA translocation is also decreased by one order of magnitude in MscL, providing a better detection resolution compared to its counterpart, e.g. MspA. Next, we explored DNA origami-graphene hybrid nanopore for DNA detection. We found that the dwell time of each base type in the hybrid pore is different and distinguishable compared to pristine graphene nanopore. The specific interaction (hydrogen bonds) between the complimentary bases at the edge of the pore and the translocating DNA bases give rise to distinguishable dwell time for each DNA. In addition to DNA sequencing studies, we also investigated the recognition of natively folded proteins using graphene nanopore. We specifically focused on the detection of Immunoglobin G subclasses since the separation and the detection of different subclasses of IgG is the signature of many diseases. These four subclasses differ only in their hinge regions and are 95% homologues. We showed that the one atom thick graphene is highly capable of distinguishing between the subclasses by using ionic current and water flux signals.","abstract_has_math":false,"creators":["Barati Farimani, Amir"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Mechanical Engineering","degree_department":null,"school":null,"contributors":["Aluru, Narayan R","Jakobsson, Eric","Tajkhorshid, Emad","Lyding, Joseph W"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-03-08T17:21:20Z","date_published":"2016-03-08T17:21:20Z","updated_at":"2026-07-22T22:26:32Z","subjects":["Nanopore","Deoxyribonucleic acid (DNA)","Detection","Protein","DNA origami","molybdenum Disulfide (MoS2)","Graphene"],"languages":["en"],"rights":["Copyright 2015 Amir Barati Farimani"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/89267","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Aluru, Narayan R","Jakobsson, Eric","Tajkhorshid, Emad","Lyding, Joseph W"]},{"key":"dc:creator","label":"Author","values":["Barati Farimani, Amir"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016-03-08T17:21:20Z","2018-03-09T10:15:34Z","2015-08-28","2015-12"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Mechanical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Nanopore","Deoxyribonucleic acid (DNA)","Detection","Protein","DNA origami","molybdenum Disulfide (MoS2)","Graphene"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2015 Amir Barati Farimani"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/89267"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["In spite of significant advances in the detection, separation and counting of single biological molecules (DNA, proteins, aminoacids, etc.) with solid-state nanopores, atomically-resolved scanning and detection of these molecules remains a significant challenge. In most nanopore-based DNA sequencing and single molecule detection techniques, ionic current blockade and blockade duration are the primary signatures associated with reading and scanning. Although these techniques are good enough for single molecule detection, they are not sophisticated enough to analyze and detect single DNA bases, fine structures, homologues and mutagenesis. Aside from the detection difficulties, low signal to noise ratio (SNR), fast speed of translocation, and lack of a cross-check signal are the biggest challenges of current nanopore technology. In this study, we explored different nanopore architectures and materials to find solutions to these current challenges. Using extensive atomistic simulations, we showed that a single layer molybdenum Disulfide (MoS2) nanopore is attractive pore for single base DNA detection with high SNR and multi-level conductance. We introduced and simulated MscL (Mechano-Sensitive Channel of Large Conductance) as an alternative to traditional biological nanopores (Alpha-Hemolysin, MspA) since it provides a flexible nanopore with adaptability to DNA base types. Induced tension in MscL is shown to be different and distinguishable for each DNA base type. The speed of DNA translocation is also decreased by one order of magnitude in MscL, providing a better detection resolution compared to its counterpart, e.g. MspA. Next, we explored DNA origami-graphene hybrid nanopore for DNA detection. We found that the dwell time of each base type in the hybrid pore is different and distinguishable compared to pristine graphene nanopore. The specific interaction (hydrogen bonds) between the complimentary bases at the edge of the pore and the translocating DNA bases give rise to distinguishable dwell time for each DNA. In addition to DNA sequencing studies, we also investigated the recognition of natively folded proteins using graphene nanopore. We specifically focused on the detection of Immunoglobin G subclasses since the separation and the detection of different subclasses of IgG is the signature of many diseases. These four subclasses differ only in their hinge regions and are 95% homologues. We showed that the one atom thick graphene is highly capable of distinguishing between the subclasses by using ionic current and water flux signals.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2017-12-01","The student, Amir Barati Farimani, accepted the attached license on 2015-08-27 at 15:51.","The student, Amir Barati Farimani, submitted this Dissertation for approval on 2015-08-27 at 16:21.","This Dissertation was approved for publication on 2015-08-28 at 15:12.","DSpace SAF Submission Ingestion Package generated from Vireo submission #8665 on 2016-03-08 at 11:04:53","Made available in DSpace on 2016-03-08T17:21:20Z (GMT). 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In most nanopore-based DNA sequencing and single molecule detection techniques, ionic current blockade and blockade duration are the primary signatures associated with reading and scanning. Although these techniques are good enough for single molecule detection, they are not sophisticated enough to analyze and detect single DNA bases, fine structures, homologues and mutagenesis. Aside from the detection difficulties, low signal to noise ratio (SNR), fast speed of translocation, and lack of a cross-check signal are the biggest challenges of current nanopore technology. In this study, we explored different nanopore architectures and materials to find solutions to these current challenges. Using extensive atomistic simulations, we showed that a single layer molybdenum Disulfide (MoS2) nanopore is attractive pore for single base DNA detection with high SNR and multi-level conductance. We introduced and simulated MscL (Mechano-Sensitive Channel of Large Conductance) as an alternative to traditional biological nanopores (Alpha-Hemolysin, MspA) since it provides a flexible nanopore with adaptability to DNA base types. Induced tension in MscL is shown to be different and distinguishable for each DNA base type. The speed of DNA translocation is also decreased by one order of magnitude in MscL, providing a better detection resolution compared to its counterpart, e.g. MspA. Next, we explored DNA origami-graphene hybrid nanopore for DNA detection. We found that the dwell time of each base type in the hybrid pore is different and distinguishable compared to pristine graphene nanopore. The specific interaction (hydrogen bonds) between the complimentary bases at the edge of the pore and the translocating DNA bases give rise to distinguishable dwell time for each DNA. In addition to DNA sequencing studies, we also investigated the recognition of natively folded proteins using graphene nanopore. We specifically focused on the detection of Immunoglobin G subclasses since the separation and the detection of different subclasses of IgG is the signature of many diseases. These four subclasses differ only in their hinge regions and are 95% homologues. We showed that the one atom thick graphene is highly capable of distinguishing between the subclasses by using ionic current and water flux signals.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2017-12-01","The student, Amir Barati Farimani, accepted the attached license on 2015-08-27 at 15:51.","The student, Amir Barati Farimani, submitted this Dissertation for approval on 2015-08-27 at 16:21.","This Dissertation was approved for publication on 2015-08-28 at 15:12.","DSpace SAF Submission Ingestion Package generated from Vireo submission #8665 on 2016-03-08 at 11:04:53","Made available in DSpace on 2016-03-08T17:21:20Z (GMT). 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