The global increase in population aging has led to a rise in neurodegenerative diseases (NDs), posing significant challenges to public health. Developing selective and specific biomarkers for early diagnosis and drug development is crucial addressing the growing burden of NDs. In this context, the RNA-binding protein TDP-43 has emerged as a promising biomarker for amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and TDP-43-associated proteinopathies. However, existing detection methods suffer from limitations such as cost, complexity, and operator dependence. Here, we present a novel electrochemical biosensor integrated into a lab-on-chip (LoC) platform to detect TDP-43. The sensor utilizes electrosynthesized polypyrrole derivatives with carboxylic groups for transducer functionalization, enabling targeted immobilization of TDP-43 antibodies. Differential pulsed voltammetry (DPV) is used for the indirect detection and quantification of TDP-43. The chip exhibits rapid response, good reproducibility, a linear detection range, and sensitivity from 0.01 ng/mL to 25 ng/mL of TDP-43 protein concentration with a LOD = 10 pg/mL. Furthermore, successful TDP-43 detection in complex matrices like serum of ALS patients and healthy individuals demonstrates its potential as a point-of-care diagnostic device. This electrochemical biosensor integrated into a chip offers good sensitivity, rapid response, and robust performance, providing a promising avenue for advancing neurodegenerative disease diagnostics and therapeutic development.

Advancing amyotrophic lateral sclerosis disease diagnosis: A lab-on-chip electrochemical immunosensor for ultra-sensitive TDP-43 protein detection and monitoring in serum patients’

Turco, Antonio
Co-primo
;
Primiceri, Elisabetta
Co-primo
;
Chiriacò, Maria Serena;Ferrara, Francesco;Maruccio, Giuseppe
Co-ultimo
2024

Abstract

The global increase in population aging has led to a rise in neurodegenerative diseases (NDs), posing significant challenges to public health. Developing selective and specific biomarkers for early diagnosis and drug development is crucial addressing the growing burden of NDs. In this context, the RNA-binding protein TDP-43 has emerged as a promising biomarker for amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and TDP-43-associated proteinopathies. However, existing detection methods suffer from limitations such as cost, complexity, and operator dependence. Here, we present a novel electrochemical biosensor integrated into a lab-on-chip (LoC) platform to detect TDP-43. The sensor utilizes electrosynthesized polypyrrole derivatives with carboxylic groups for transducer functionalization, enabling targeted immobilization of TDP-43 antibodies. Differential pulsed voltammetry (DPV) is used for the indirect detection and quantification of TDP-43. The chip exhibits rapid response, good reproducibility, a linear detection range, and sensitivity from 0.01 ng/mL to 25 ng/mL of TDP-43 protein concentration with a LOD = 10 pg/mL. Furthermore, successful TDP-43 detection in complex matrices like serum of ALS patients and healthy individuals demonstrates its potential as a point-of-care diagnostic device. This electrochemical biosensor integrated into a chip offers good sensitivity, rapid response, and robust performance, providing a promising avenue for advancing neurodegenerative disease diagnostics and therapeutic development.
2024
Istituto di Nanotecnologia - NANOTEC - Sede Lecce
Biosensor
Electropolymerization
Immunosensor
Neurodegenerative diseases
TDP-43
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/510729
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