Label-free electronic detection of peptide post-translational modification with functional enzyme-driven assay at the physical limit

Eleonora Macchia, Kim Björkström, Amit Tewari, Ville Eskonen, Axel Luukkonen, Amir Mohammad Ghafari, Lucia Sarcina, Mariapia Caputo, Natalia Tong-Ochoa, Kari Kopra, Fredrik Pettersson, Zahra Gounani, Luisa Torsi*, Harri Härmä*, Ronald Österbacka*

*Korresponderande författare för detta arbete

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

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.

OriginalspråkEngelska
Artikelnummer101874
TidskriftCell Reports Physical Science
DOI
StatusAccepterad/under tryckning - 2024
MoE-publikationstypA1 Tidskriftsartikel-refererad

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