Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity

dc.citation.articleNumbere2112812119en_US
dc.citation.issueNumber5en_US
dc.citation.journalTitleProceedings of the National Academy of Sciencesen_US
dc.citation.volumeNumber119en_US
dc.contributor.authorFuller, Carl W.en_US
dc.contributor.authorPadayatti, Pius S.en_US
dc.contributor.authorAbderrahim, Hadien_US
dc.contributor.authorAdamiak, Lisaen_US
dc.contributor.authorAlagar, Nolanen_US
dc.contributor.authorAnanthapadmanabhan, Nagarajen_US
dc.contributor.authorBaek, Jihyeen_US
dc.contributor.authorChinni, Saraten_US
dc.contributor.authorChoi, Chulminen_US
dc.contributor.authorDelaney, Kevin J.en_US
dc.contributor.authorDubielzig, Richen_US
dc.contributor.authorFrkanec, Julieen_US
dc.contributor.authorGarcia, Chrisen_US
dc.contributor.authorGardner, Calvinen_US
dc.contributor.authorGebhardt, Danielen_US
dc.contributor.authorGeiser, Timen_US
dc.contributor.authorGutierrez, Zachariahen_US
dc.contributor.authorHall, Drew A.en_US
dc.contributor.authorHodges, Andrew P.en_US
dc.contributor.authorHou, Guangyuanen_US
dc.contributor.authorJain, Sonalen_US
dc.contributor.authorJones, Teresaen_US
dc.contributor.authorLobaton, Raymonden_US
dc.contributor.authorMajzik, Zsolten_US
dc.contributor.authorMarte, Allenen_US
dc.contributor.authorMohan, Prateeken_US
dc.contributor.authorMola, Paulen_US
dc.contributor.authorMudondo, Paulen_US
dc.contributor.authorMullinix, Jamesen_US
dc.contributor.authorNguyen, Thuanen_US
dc.contributor.authorOllinger, Fredericken_US
dc.contributor.authorOrr, Sarahen_US
dc.contributor.authorOuyang, Yuxuanen_US
dc.contributor.authorPan, Paulen_US
dc.contributor.authorPark, Namseoken_US
dc.contributor.authorPorras, Daviden_US
dc.contributor.authorPrabhu, Keshaven_US
dc.contributor.authorReese, Cassandraen_US
dc.contributor.authorRuel, Traversen_US
dc.contributor.authorSauerbrey, Trevoren_US
dc.contributor.authorSawyer, Jaymie R.en_US
dc.contributor.authorSinha, Premen_US
dc.contributor.authorTu, Jackyen_US
dc.contributor.authorVenkatesh, A. G.en_US
dc.contributor.authorVijayKumar, Sushmithaen_US
dc.contributor.authorZheng, Leen_US
dc.contributor.authorJin, Sunghoen_US
dc.contributor.authorTour, James M.en_US
dc.contributor.authorChurch, George M.en_US
dc.contributor.authorMola, Paul W.en_US
dc.contributor.authorMerriman, Barryen_US
dc.date.accessioned2022-03-24T13:31:45Zen_US
dc.date.available2022-03-24T13:31:45Zen_US
dc.date.issued2022en_US
dc.description.abstractFor nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.en_US
dc.identifier.citationFuller, Carl W., Padayatti, Pius S., Abderrahim, Hadi, et al.. "Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity." <i>Proceedings of the National Academy of Sciences,</i> 119, no. 5 (2022) National Academy of Sciences: https://doi.org/10.1073/pnas.2112812119.en_US
dc.identifier.digitalpnas-2112812119en_US
dc.identifier.doihttps://doi.org/10.1073/pnas.2112812119en_US
dc.identifier.urihttps://hdl.handle.net/1911/112054en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsThis open access article is distributed under Creative Commons AttributionNonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleMolecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activityen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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