{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:11:29Z","timestamp":1773864689430,"version":"3.50.1"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>The first sequencing of a complete genome was published forty years ago by the double Nobel Prize in Chemistry winner Frederick Sanger. That corresponded to the small sized genome of a bacteriophage, but since then there have been many complex organisms whose DNA have been sequenced. This was possible thanks to continuous advances in the fields of biochemistry and molecular genetics, but also in other areas such as nanotechnology and computing. Nowadays, sequencing sensors based on genetic material have little to do with those used by Sanger. The emergence of mass sequencing sensors, or new generation sequencing (NGS) meant a quantitative leap both in the volume of genetic material that was able to be sequenced in each trial, as well as in the time per run and its cost. One can envisage that incoming technologies, already known as fourth generation sequencing, will continue to cheapen the trials by increasing DNA reading lengths in each run. All of this would be impossible without sensors and detection systems becoming smaller and more precise. This article provides a comprehensive overview on sensors for DNA sequencing developed within the last 40 years.<\/jats:p>","DOI":"10.3390\/s17030588","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T11:53:52Z","timestamp":1489492432000},"page":"588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["DNA Sequencing Sensors: An Overview"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2785-0027","authenticated-orcid":false,"given":"Jose","family":"Garrido-Cardenas","sequence":"first","affiliation":[{"name":"Department of Biology and Geology, University of Almeria, 04120 Almeria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Garcia-Maroto","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Physics, University of Almeria, 04120 Almeria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5815-7858","authenticated-orcid":false,"given":"Jose","family":"Alvarez-Bermejo","sequence":"additional","affiliation":[{"name":"Department of Informatics, University of Almeria, 04120 Almeria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0085-030X","authenticated-orcid":false,"given":"Francisco","family":"Manzano-Agugliaro","sequence":"additional","affiliation":[{"name":"Department of Engineering, University of Almeria, 04120 Almeria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,14]]},"reference":[{"key":"ref_1","first-page":"137","article-title":"Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types Induction of Transformation by a Deoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III","volume":"79","author":"Avery","year":"1944","journal-title":"J. Exp. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/171737a0","article-title":"Molecular structure of nucleic acids","volume":"171","author":"Watson","year":"1953","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/265687a0","article-title":"Nucleotide sequence of bacteriophage phi X174 DNA","volume":"265","author":"Sanger","year":"1977","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"ref_5","first-page":"586","article-title":"Technology: Getting Moore from DNA sequencing","volume":"12","author":"Muers","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1002\/bies.200900181","article-title":"High-throughput DNA sequencing\u2014Concepts and limitations","volume":"32","author":"Kircher","year":"2010","journal-title":"BioEssays"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1126\/science.283.5409.1867","article-title":"Sequencing the Genome, Fast","volume":"283","author":"Mullikin","year":"1999","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.1093\/nar\/19.18.4955","article-title":"Multiwavelength fluorescence detection for DNA sequencing using capillary electrophoresis","volume":"19","author":"Karger","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/321674a0","article-title":"Fluorescence detection in automated DNA sequence analysis","volume":"321","author":"Smith","year":"1986","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1093\/nar\/22.11.2121","article-title":"Direct detection of nucleic acid hybridization on the surface of a charge coupled device","volume":"22","author":"Lamture","year":"1994","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nrg2626","article-title":"Sequencing technologies\u2014The next generation","volume":"11","author":"Metzker","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1146\/annurev-anchem-062012-092628","article-title":"Next-Generation Sequencing Platforms","volume":"6","author":"Mardis","year":"2013","journal-title":"Annu. Rev. Anal. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1242\/jeb.001370","article-title":"Advanced sequencing technologies and their wider impact in microbiology","volume":"210","author":"Hall","year":"2007","journal-title":"J. Exp. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.molcel.2015.05.004","article-title":"High-Throughput Sequencing Technologies","volume":"58","author":"Reuter","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nrg.2016.49","article-title":"Coming of age: Ten years of next-generation sequencing technologies","volume":"17","author":"Goodwin","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.tig.2014.07.001","article-title":"Ten years of next-generation sequencing technology","volume":"30","author":"Auger","year":"2014","journal-title":"Trends Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"i420","DOI":"10.1093\/bioinformatics\/btq365","article-title":"Characteristics of 454 pyrosequencing data enabling realistic simulation with flowsim","volume":"26","author":"Balzer","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0003-2697(88)90041-3","article-title":"A new method of sequencing DNA","volume":"174","author":"Hyman","year":"1988","journal-title":"Anal. Biochem."},{"key":"ref_19","first-page":"65","article-title":"Pyrosequencing-Principles and Applications","volume":"2","author":"Chowdhury","year":"2012","journal-title":"Int. J. Life Sci. Pharma Res."},{"key":"ref_20","unstructured":"Marsh, S. (2007). Pyrosequencing Protocols, Springer."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1006\/abio.2001.5494","article-title":"Long-read pyrosequencing using pure 2\u2032-deoxyadenosine-5\u2032-O\u2032-(1-thiotriphosphate) Sp-isomer","volume":"301","author":"Gharizadeh","year":"2002","journal-title":"Anal. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1101\/gr.076463.108","article-title":"A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning","volume":"18","author":"Valouev","year":"2008","journal-title":"Genome Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/bib\/bbq015","article-title":"A survey of sequence alignment algorithms for next-generation sequencing","volume":"11","author":"Li","year":"2010","journal-title":"Brief. Bioinform."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1093\/bioinformatics\/btq151","article-title":"Correction of sequencing errors in a mixed set of reads","volume":"26","author":"Salmela","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rumble, S.M., Lacroute, P., Dalca, A.V., Fiume, M., Sidow, A., and Brudno, M. (2009). SHRiMP: Accurate mapping of short color-space reads. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000386"},{"key":"ref_26","first-page":"78","article-title":"Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays","volume":"1469","author":"Drmanac","year":"2009","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1146\/annurev-biochem-060410-094158","article-title":"Toward the Single-Hour High-Quality Genome","volume":"81","author":"Lundeberg","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev-genom-082908-145957","article-title":"Applications of new sequencing technologies for transcriptome analysis","volume":"10","author":"Morozova","year":"2009","journal-title":"Annu Rev Genom. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.gde.2006.10.009","article-title":"Whole-genome re-sequencing","volume":"16","author":"Bentley","year":"2006","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nature07517","article-title":"Accurate whole human genome sequencing using reversible terminator chemistry","volume":"456","author":"Bentley","year":"2008","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1034\/j.1600-0854.2001.21104.x","article-title":"Total internal reflection fluorescence microscopy in cell biology","volume":"2","author":"Axelrod","year":"2001","journal-title":"Traffic"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13351","DOI":"10.1364\/OE.19.013351","article-title":"Total internal reflection STED microscopy","volume":"19","author":"Gould","year":"2011","journal-title":"Opt. Express"},{"key":"ref_33","first-page":"107","article-title":"Next Generation: Sequencing & Applications Four Generations of Sequencing\u2014Is it Ready for the Clinic Yet?","volume":"1","author":"Srinivasan","year":"2014","journal-title":"Next Gener. Seq. Appl."},{"key":"ref_34","first-page":"A11","article-title":"From sample to insight: Bringing NGS into clinical routine","volume":"28","author":"Hermitte","year":"2013","journal-title":"Drug Metab. Drug Interact."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1002\/elps.201200424","article-title":"Progress in Ion Torrent semiconductor chip based sequencing","volume":"33","author":"Merriman","year":"2012","journal-title":"Electrophoresis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1109\/ACCESS.2015.2410256","article-title":"From Sensors to Systems: CMOS-Integrated Electrochemical Biosensors","volume":"3","author":"Singh","year":"2015","journal-title":"IEEE Access"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, H., Liu, X., Li, L., Mu, X., Geron, R., and Mason, A.J. (2016). CMOS Electrochemical Instrumentation for Biosensor Microsystems: A Review. Sensors, 17.","DOI":"10.3390\/s17010074"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/nature10242","article-title":"An integrated semiconductor device enabling non-optical genome sequencing","volume":"475","author":"Rothberg","year":"2011","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.bbadis.2014.06.015","article-title":"Next generation sequencing technology: Advances and applications","volume":"1842","author":"Buermans","year":"2014","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1049\/el.2011.3231","article-title":"Piet Bergveld\u201440 years of ISFET technology: From neuronal sensing to DNA sequencing","volume":"47","author":"Toumazou","year":"2011","journal-title":"Electron. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0168-1656(03)00023-3","article-title":"Single-molecule PCR using water-in-oil emulsion","volume":"102","author":"Nakano","year":"2003","journal-title":"J. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lee, H., Gurtowski, J., Yoo, S., Nattestad, M., Marcus, S., Goodwin, S., McCombie, W.R., and Schatz, M. (2016). Third-generation sequencing and the future of genomics. bioRxiv.","DOI":"10.1101\/048603"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Quail, M., Smith, M.E., Coupland, P., Otto, T.D., Harris, S.R., Connor, T.R., Bertoni, A., Swerdlow, H.P., Gu, Y., and Rothberg, J. (2012). A tale of three next generation sequencing platforms: Comparison of Ion torrent, pacific biosciences and illumina MiSeq sequencers. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-341"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"365","DOI":"10.2144\/000113962","article-title":"Direct sequencing of small genomes on the pacific biosciences RS without library preparation","volume":"53","author":"Coupland","year":"2012","journal-title":"Biotechniques"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1126\/science.1162986","article-title":"Real-time DNA sequencing from single polymerase molecules","volume":"323","author":"Eid","year":"2009","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1126\/science.1079700","article-title":"Zero-mode waveguides for single-molecule analysis at high concentrations","volume":"299","author":"Levene","year":"2003","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1364\/OL.33.001026","article-title":"Parallel confocal detection of single molecules in real time","volume":"33","author":"Lundquist","year":"2008","journal-title":"Opt. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/nbt.1495","article-title":"The potential and challenges of nanopore sequencing","volume":"26","author":"Branton","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3389\/fgene.2014.00449","article-title":"The evolution of nanopore sequencing","volume":"5","author":"Wang","year":"2015","journal-title":"Front. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3418","DOI":"10.1002\/elps.201200272","article-title":"Recent advances in nanopore sequencing","volume":"33","author":"Maitra","year":"2012","journal-title":"Electrophoresis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18611","DOI":"10.3390\/s141018611","article-title":"Ion-channel genosensor for the detection of specific DNA sequences derived from plum pox virus in plant extracts","volume":"14","author":"Malecka","year":"2014","journal-title":"Sensors"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nbt0412-295","article-title":"Oxford Nanopore announcement sets sequencing sector abuzz","volume":"30","author":"Eisenstein","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/1755-0998.12324","article-title":"A first look at the Oxford Nanopore MinION sequencer","volume":"14","author":"Mikheyev","year":"2014","journal-title":"Mol. Ecol. Resour."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nnano.2009.12","article-title":"Continuous base identification for single-molecule nanopore DNA sequencing","volume":"4","author":"Clarke","year":"2009","journal-title":"Nat. Nanotechnol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nbt.3423","article-title":"Three decades of nanopore sequencing","volume":"34","author":"Deamer","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1166\/jnn.2013.7756","article-title":"Advances in Nanopore Sequencing Technology","volume":"13","author":"Yang","year":"2013","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/nbt873","article-title":"Electrochemical DNA sensors","volume":"21","author":"Drummond","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_58","unstructured":"Lobo-Casta\u00f1\u00f3n, M.J. (2016). Analytical and Bioanalytical Chemistry, Springer."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16292","DOI":"10.3390\/s131216292","article-title":"Aptamer-based analysis: A promising alternative for food safety control","volume":"13","year":"2013","journal-title":"Sensors"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/elan.200900571","article-title":"Graphene based electrochemical sensors and biosensors: A review","volume":"22","author":"Shao","year":"2010","journal-title":"Electroanalysis"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S0165-9936(04)00102-5","article-title":"Electrochemical sensors based on molecularly imprinted polymers","volume":"23","year":"2004","journal-title":"Trends Anal. Chem."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/17\/3\/588\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:30:23Z","timestamp":1760207423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/17\/3\/588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,14]]},"references-count":61,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["s17030588"],"URL":"https:\/\/doi.org\/10.3390\/s17030588","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,14]]}}}