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The (1;19)(q23;p13) translocation is a primary chromosomal abnormality present in 3\u201312% of ALL cases. The current study aims to develop a label-free innovative nanodevice for the ultrasensitive diagnosis of the TCF3-PBX1 chimeric oncogene, featuring simplified operation and rapid analysis using minimal sample volumes, which positions it as a superior alternative for clinical diagnostics and early leukemia identification. The biosensor system was engineered on a nanostructured platform composed of polypyrrole (PPy) and a novel chemically functionalized hybrid nanocomposite of platinum nanospheres and titanium dioxide nanoparticles (TiO2@Pt). Single-stranded oligonucleotide sequences were chemically immobilized on the nanoengineered transducer to enable biospecific detection. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), ultraviolet-visible spectroscopy (UV-Vis), and atomic force microscopy (AFM) were used to characterize each stage of the biotechnological device fabrication process. The analytical properties of the sensing tool were explored using recombinant plasmids containing the TCF3-PBX1 oncogenic sequence and clinical specimens from pediatric patients with B-cell ALL. After exposing the molecular monitoring system to the genetic target, significant variations were observed in the voltammetric oxidation current (\u2206I = 33.08% \u00b1 0.28 to 124.91% \u00b1 17.08) and in the resistance to charge transfer (\u0394RCT = 19.73% \u00b1 0.96 to 83.51% \u00b1 0.84). Data analysis revealed high reproducibility, with a relative standard deviation of 3.66%, a response range from 3.58 aM to 357.67 fM, a detection limit of 19.31 aM, and a limit of quantification of 64.39 aM. Therefore, a novel nanosensor for multiparametric electrochemical screening of the TCF3-PBX1 chimeric oncogene was described for the first time, potentially improving the quality of life for leukemic patients.<\/jats:p>","DOI":"10.3390\/s25175313","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T08:19:32Z","timestamp":1756282772000},"page":"5313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Attomolar-Level Biosensor Based on Polypyrrole and TiO2@Pt Nanocomposite for Electrochemical Detection of TCF3-PBX1 Oncogene in Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"25","author":[{"given":"Saulo Henrique","family":"Silva","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Inova\u00e7\u00e3o Terap\u00eautica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"Laborat\u00f3rio de Biodispositivos Nanoestruturados, Departamento de Bioqu\u00edmica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"OX-NANO Tecnologia, Porto Digital, Recife 50030-140, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Yasmim Pereira dos Santos","family":"Avelino","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Inova\u00e7\u00e3o Terap\u00eautica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"Laborat\u00f3rio de Biodispositivos Nanoestruturados, Departamento de Bioqu\u00edmica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"OX-NANO Tecnologia, Porto Digital, Recife 50030-140, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-1794","authenticated-orcid":false,"given":"Norma","family":"Lucena-Silva","sequence":"additional","affiliation":[{"name":"Instituto Aggeu Magalh\u00e3es, Funda\u00e7\u00e3o Oswaldo Cruz (Fiocruz), Recife 50670-420, PE, Brazil"},{"name":"Laborat\u00f3rio de Biologia Molecular, Departamento de Oncologia Pedi\u00e1trica, Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife 50070-550, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhamid","family":"Errachid","sequence":"additional","affiliation":[{"name":"Institut des Sciences Analytiques (ISA), Universit\u00e9 Claude Bernard Lyon 1, 5 rue de la Doua, 69100 Lyon, Villeurbane, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Danielly Lima","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Inova\u00e7\u00e3o Terap\u00eautica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"Laborat\u00f3rio de Biodispositivos Nanoestruturados, Departamento de Bioqu\u00edmica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"OX-NANO Tecnologia, Porto Digital, Recife 50030-140, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3271-2817","authenticated-orcid":false,"given":"C\u00e9sar Augusto Souza","family":"de Andrade","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Inova\u00e7\u00e3o Terap\u00eautica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"Laborat\u00f3rio de Biodispositivos Nanoestruturados, Departamento de Bioqu\u00edmica, Universidade Federal de Pernambuco, Recife 50670-901, PE, Brazil"},{"name":"OX-NANO Tecnologia, Porto Digital, Recife 50030-140, PE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1002\/cncr.34741","article-title":"Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study","volume":"129","author":"Zhang","year":"2023","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.3892\/or.2016.4948","article-title":"Regulation of the miRNA expression by TEL\/AML1, BCR\/ABL, MLL\/AF4 and TCF3\/PBX1 oncoproteins in acute lymphoblastic leukemia","volume":"36","year":"2016","journal-title":"Oncol. 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