A1 Refereed original research article in a scientific journal
Label-free electronic detection of peptide post-translational modification with functional enzyme-driven assay at the physical limit
Authors: Macchia, Eleonora; Björkström, Kim; Tewari, Amit; Eskonen, Ville; Luukkonen, Axel; Ghafari, Amir Mohammad; Sarcina, Lucia; Caputo, Mariapia; Tong-Ochoa, Natalia; Kopra, Kari; Pettersson, Fredrik; Gounani, Zahra; Torsi, Luisa; Härmä, Harri; Österbacka, Ronald
Publisher: Cell Press
Publication year: 2024
Journal: Cell Reports Physical Science
Journal name in source: Cell Reports Physical Science
Article number: 101874
Volume: 5
Issue: 8
ISSN: 2666-3864
eISSN: 2666-3864
DOI: https://doi.org/10.1016/j.xcrp.2024.101874
Web address : https://doi.org/10.1016/j.xcrp.2024.101874
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/387400193
High-performance, ultra-sensitive, and universal protein post-translational modification (PTM) and protein-protein interaction (PPI) technologies are eagerly pursued in the pharmaceutical industry and bioanalytical research. Novel PTM and PPI detection methods outperform traditional assays in scope and scalability, enabling the collection of information on multiple biochemical targets. Detecting peptides and proteins at the single-molecule level is done by utilizing nanosized transducing elements and assaying solutions at very high analyte concentrations, in the nanomolar range or higher. Here, a proof of principle of a biosensing platform for single-molecule PTM detection is demonstrated. This platform is based on the single molecule with a large transistor (SiMoT) technology, encompassing a millimeter-sized electrolyte-gated organic field-effect transistor, for label-free PTM detection with a zeptomolar limit of detection. Sensitivity is improved 106- to 1012-fold compared with mass-spectrometry and luminescence-based assay methods. A functional assay for detecting enzyme-driven peptide PTMs in the zeptomolar concentration range is demonstrated using multivariate data processing, opening the way for future applications to monitor PTMs.
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Funding information in the publication:
The following are all acknowledged for partial financial support: Academy of Finland projects 296225, 323433, 269973, 316881, 316883, 332106, 296093, and 270010; PON SISTEMA (MIUR); H2020, Electronic Smart Systems, SiMBiT (single-molecule bioelectronic smart system array for clinical testing) (grant agreement ID: 824946 ); Doctoral Network of Materials Research at Åbo Akademi University; NoOne (a binary sensor with a single-molecule digit to discriminate biofluids enclosing zero or at least one biomarker), ERC Stg2021 , GA: 101040383 ; I primi mille clinical trial con il Centro DIGITAL ASSAY, Centro di Innovazione Regionale Digital Assay, Presidente Prof. L. Torsi; Responsabile Scientifico UNIBA E. Macchia Regione PUGLIA Delibera Regionale n 702 del 08/11/2022 (CUP B93C22000840001 ); PMGB – Sviluppo di piattaforme meccatroniche, genomiche e bioinformatiche per l’oncologia di precisione and ARS01_01195 – PON RICERCA E INNOVAZIONE 2014–2020 projects; Italian network of excellence for advanced diagnosis (INNOVA), Ministero della Salute -code PNC-E3-2022-23683266 PNC-HLS-DA , CUP: C43C22001630001 ; Complementary National Plan PNC-I.1 research initiatives for innovative technologies and pathways in the health and welfare sector D.D. 931 of 06/06/2022; DARE (DigitAl lifelong pRevEntion initiative), code PNC0000002 , CUP: B53C22006420001 ; Åbo Akademi University CoE bioelectronic activation of cell functions; CSGI - Center for Colloid and Surface Science; Vilho, Yrjö, and Kalle Väisälä Foundation; and the Drug Research Doctoral Programme (University of Turku Graduate School).
