{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:17:45Z","timestamp":1792462665679,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bioengineering"],"abstract":"<jats:p>Rapid, point-of-care detection of Escherichia coli O157:H7 remains an unmet clinical need, as culture and molecular methods are slow and poorly suited to decentralized or emergency settings. A label-free, monolithic aptasensor biochip was fabricated in a standard 65 nm CMOS process, featuring three aptamer-functionalized gold sensing pads with matched reference pads for differential readout. A 37-mer DNA aptamer targeting the E. coli O157:H7 lipopolysaccharide was immobilized via thiol\u2013gold self-assembled monolayer chemistry. Binding events were transduced into surface-potential shifts, amplified by an on-chip analog front-end (~100 V\/V gain, 101.5 \u00b5W), and evaluated using calibration standards, patient specimens, and hospital environmental samples, with fluorescence microscopy for validation. The sensor achieved 47.42 mV\/decade sensitivity across 1\u201310,000 CFU\/mL, an IUPAC detection limit near 3.74 CFU\/mL, and an empirical LOD of about 11 CFU\/mL, with outputs tracking bacterial load and ~5.7% matrix-related deviation. Hospital samples were detectable to 28 CFU\/mL. Because the patient-derived and hospital-acquired cohorts (n = 10 and n = 6, respectively) were assembled for pilot analytical and matrix-tolerance characterization rather than for diagnostic-accuracy determination, these results establish detectability and matrix robustness in real clinical and environmental specimens rather than clinical diagnostic sensitivity or specificity, which will require a larger, prospectively enrolled cohort in future work. Sensor kinetics followed Langmuir-type adsorption, saturating within 16\u201325 min for target pathogens versus slower responses for non-target strains. Selectivity tests against six bacterial species showed discrimination, with cross-reactivity decreasing from related E. coli pathotypes to Enterobacteriaceae to Gram-positive species. Inter-pad variability stayed below 1.5 mV, supporting this compact, low-power platform for scalable, enrichment-free point-of-care pathogen detection.<\/jats:p>","DOI":"10.3390\/bioengineering13080858","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Monolithic, Thiol-Functionalized Au-Based Bio-CMOS Aptasensor for Rapid, Label-Free Detection of Escherichia coli O157:H7 in Patient-Derived and Hospital-Acquired Specimens"],"prefix":"10.3390","volume":"13","author":[{"given":"Zahra","family":"Nejad Shahrokh Abadi","sequence":"first","affiliation":[{"name":"Countess of Chester Hospital Foundation NHS Trust, Chester CH2 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7256-6263","authenticated-orcid":false,"given":"M. H.","family":"Shahrokh Abadi","sequence":"additional","affiliation":[{"name":"Electrical and Computer Engineering Faculty, Hakim Sabzevari University, Sabzevar 9617976487, Iran"},{"name":"Living Materials Research Group, Hakim Sabzevari University, Sabzevar 9617976487, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Nejad Shahrokh Abadi","sequence":"additional","affiliation":[{"name":"Leipzig Center of Metabolism, Faculty of Medicine, Leipzig University, 04103 Leipzig, Germany"},{"name":"Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/fpd.2013.1704","article-title":"Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: A systematic review and knowledge synthesis","volume":"11","author":"Majowicz","year":"2014","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lake, R., Devleesschauwer, B., Majowicz, S., Robertson, L.J., Jakobsen, L.S., Agudo, A., Pires, S.M., Kirk, M.D., Walter, E.S., and Keddy, K.H. (2026). WHO estimates of the global, regional, and national burden of 42 foodborne infectious and chemical hazards, 2000\u20132021: An updated data synthesis. Lancet Glob. Health, 103994.","DOI":"10.1016\/j.langlo.2026.103994"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.3201\/eid2707.204638","article-title":"Shiga toxin-associated hemolytic uremic syndrome in adults, France, 2009\u20132017","volume":"27","author":"Travert","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kitagawa, H., Kojima, M., Tadera, K., Kogasaki, S., Omori, K., Nomura, T., Shigemoto, N., Hiyama, E., and Ohge, H. (2025). Clinical diagnostic performance of droplet digital PCR for pathogen detection in patients with Escherichia coli bloodstream infection: A prospective observational study. BMC Infect. Dis., 25.","DOI":"10.1186\/s12879-024-10396-y"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e19011","DOI":"10.7717\/peerj.19011","article-title":"Detection of O25B-ST131 clone and blaCTX-M-15 gene in Escherichia coli isolated from patients with COVID-19","volume":"13","author":"Anwar","year":"2025","journal-title":"PeerJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e16393","DOI":"10.7717\/peerj.16393","article-title":"A multicentre study to determine the in vitro efficacy of flomoxef against extended-spectrum beta-lactamase producing Escherichia coli in Malaysia","volume":"11","author":"Yap","year":"2023","journal-title":"PeerJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e12830","DOI":"10.7717\/peerj.12830","article-title":"A retrospective study on molecular epidemiology trends of carbapenem resistant Enterobacteriaceae in a teaching hospital in Malaysia","volume":"10","author":"Kong","year":"2022","journal-title":"PeerJ"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Abbas, N., Song, S., Chang, M.S., and Chun, M.S. (2023). Point-of-care diagnostic devices for detection of Escherichia coli O157:H7 using microfluidic systems: A focused review. Biosensors, 13.","DOI":"10.3390\/bios13070741"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1021\/acssensors.3c02339","article-title":"Rapid and ultrasensitive colorimetric biosensors for onsite detection of Escherichia coli O157:H7 in fluids","volume":"9","author":"Pan","year":"2024","journal-title":"ACS Sens."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1007\/s00216-021-03377-6","article-title":"Emerging point-of-care biosensors for rapid diagnosis of COVID-19: Current progress, challenges, and future prospects","volume":"413","author":"Rasmi","year":"2021","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e15566","DOI":"10.7717\/peerj.15566","article-title":"Electrochemical biosensors in healthcare services: Bibliometric analysis and recent developments","volume":"11","author":"Yunus","year":"2023","journal-title":"PeerJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1021\/acssensors.9b02600","article-title":"Gold nanobones enhanced ultrasensitive surface-enhanced Raman scattering aptasensor for detecting Escherichia coli O157:H7","volume":"5","author":"Zhou","year":"2020","journal-title":"ACS Sens."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119984","DOI":"10.1016\/j.cca.2024.119984","article-title":"Electrochemical and optical biosensors for the detection of E. coli","volume":"565","author":"Roudsari","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wu, W., Zhang, J., Zheng, M., Zhong, Y., Yang, J., Wu, W., Ye, W., Wen, J., Wang, Q., and Lu, J. (2012). An aptamer-based biosensor for colorimetric detection of Escherichia coli O157:H7. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048999"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1038\/s41598-025-32516-7","article-title":"An aptamer-functionalized AuNPs\/rGO nanocomposite biosensor for ultrasensitive detection of foodborne pathogen E. coli O157:H7","volume":"16","author":"Izadi","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of RNA molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e21304","DOI":"10.7717\/peerj.21304","article-title":"Frontiers in aptamer-based diagnostics and therapeutics for zoonotic diseases","volume":"14","author":"Wong","year":"2026","journal-title":"PeerJ"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"L\u00e9guillier, V., Heddi, B., and Vidic, J. (2024). Recent advances in aptamer-based biosensors for bacterial detection. Biosensors, 14.","DOI":"10.20944\/preprints202402.0276.v1"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"McConnell, E.M., Nguyen, J., and Li, Y. (2020). Aptamer-based biosensors for environmental monitoring. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.00434"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Saad, M., and Faucher, S.P. (2021). Aptamers and aptamer-coupled biosensors to detect water-borne pathogens. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.643797"},{"key":"ref_22","first-page":"100394","article-title":"Advances in field effect transistor based electronic devices integrated with CMOS technology for biosensing","volume":"11","author":"Rai","year":"2024","journal-title":"Sens. Bio-Sens. Res."},{"key":"ref_23","first-page":"100025","article-title":"Extended-gate field-effect transistor chemo- and biosensors: State of the art and perspectives","volume":"3","author":"Baraban","year":"2023","journal-title":"Next Nanotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nikkhoo, N., Cumby, N., Gulak, P.G., and Maxwell, K.L. (2016). Rapid bacterial detection via an all-electronic CMOS biosensor. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162438"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ryazantsev, D., Shustinskiy, M., Sheshil, A., Titov, A., Grudtsov, V., Vechorko, V., Kitiashvili, I., Puchnin, K., Kuznetsov, A., and Komarova, N. (2024). A portable readout system for biomarker detection with aptamer-modified CMOS ISFET array. Sensors, 24.","DOI":"10.3390\/s24103008"},{"key":"ref_26","first-page":"3855","article-title":"Functionalization of an extended-gate field-effect transistor (EGFET) for bacteria detection","volume":"12","author":"Neumann","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pullano, S.A., Tasneem, N.T., Mahbub, I., Shamsir, S., Greco, M., Islam, S.K., and Fiorillo, A.S. (2019). Deep submicron EGFET based on transistor association technique for chemical sensing. Sensors, 19.","DOI":"10.3390\/s19051063"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s00604-022-05533-w","article-title":"Aptasensors for the detection of infectious pathogens: Design strategies and point-of-care testing","volume":"189","author":"Chen","year":"2022","journal-title":"Microchim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1109\/TBCAS.2023.3315671","article-title":"A highly integrated lab-on-a-CMOS platform for real-time monitoring of E. coli growth kinetics","volume":"18","author":"Duan","year":"2024","journal-title":"IEEE Trans. Biomed. Circuits Syst."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1109\/TLA.2021.9423850","article-title":"Self-calibrated readout frontend for capacitive biosensors","volume":"19","year":"2021","journal-title":"IEEE Lat. Am. Trans."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lav\u00edn, \u00c1., Vicente, J.D., Holgado, M., Laguna, M.F., Casquel, R., Santamar\u00eda, B., Maigler, M.V., Hern\u00e1ndez, A.L., and Ram\u00edrez, Y. (2018). On the determination of uncertainty and limit of detection in label-free biosensors. Sensors, 18.","DOI":"10.3390\/s18072038"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bios.2018.04.034","article-title":"Rapid, highly sensitive detection of Gram-negative bacteria with lipopolysaccharide based disposable aptasensor","volume":"112","author":"Zhang","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1063\/1.3160202","article-title":"Potassium ion-selective field-effect transistor device response in mixed-ion solutions","volume":"1136","author":"Abdullah","year":"2009","journal-title":"AIP Conf. Proc."}],"container-title":["Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/8\/858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:34:24Z","timestamp":1785170064000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2306-5354\/13\/8\/858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["bioengineering13080858"],"URL":"https:\/\/doi.org\/10.3390\/bioengineering13080858","relation":{},"ISSN":["2306-5354"],"issn-type":[{"value":"2306-5354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]}}}