Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease Diagnosis

Abstract Alzheimer's disease (AD) is a progressive neurological disorder that gradually impairs all cognitive functions. The diagnosis typically requires a combination of cognitive assessments, neuroimaging techniques, and biomarker analysis. In healthy neurons, Tau protein stabilizes microtubu...

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Main Authors: Alberto Sinibaldi, Francesco Chiavaioli, Agostino Occhicone, Norbert Danz, Peter Munzert, Francesco Baldini, Ambra Giannetti, Francesco Michelotti
Format: Article
Language:English
Published: Wiley-VCH 2025-05-01
Series:Advanced Sensor Research
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Online Access:https://doi.org/10.1002/adsr.202400164
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author Alberto Sinibaldi
Francesco Chiavaioli
Agostino Occhicone
Norbert Danz
Peter Munzert
Francesco Baldini
Ambra Giannetti
Francesco Michelotti
author_facet Alberto Sinibaldi
Francesco Chiavaioli
Agostino Occhicone
Norbert Danz
Peter Munzert
Francesco Baldini
Ambra Giannetti
Francesco Michelotti
author_sort Alberto Sinibaldi
collection DOAJ
description Abstract Alzheimer's disease (AD) is a progressive neurological disorder that gradually impairs all cognitive functions. The diagnosis typically requires a combination of cognitive assessments, neuroimaging techniques, and biomarker analysis. In healthy neurons, Tau protein stabilizes microtubules, which are vital for maintaining the structure and proper functioning of nerve cells. However, elevated levels of Tau in cerebrospinal or other body fluids can be related to the progression of Alzheimer's disease. This study introduces an optical technique that employs a dual label‐free and fluorescence operation mode to detect Tau protein in both standard running buffer and cerebrospinal fluid. This innovative method enables label‐free analysis of the bio‐conjugation process on biochips used for resolved fluorescence‐based Tau detection. This work successfully demonstrates Tau protein detection in both matrixes, achieving an outstanding limit of detection of 2.4 pM in cerebrospinal fluid. Moreover, the analysis of the dose‐response curve allows to estimate the dissociation constant (KD = 18 nM) for Tau interactions, yielding values that are in excellent agreement with existing literature using other techniques. These aspects highlight the added value of this technique, providing a valuable tool for investigating Alzheimer's‐related biomarkers, as demonstrated in this study with Tau protein.
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spelling doaj-art-ec00659b66594946a2fbcd6d9be428ba2025-08-20T02:14:22ZengWiley-VCHAdvanced Sensor Research2751-12192025-05-0145n/an/a10.1002/adsr.202400164Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease DiagnosisAlberto Sinibaldi0Francesco Chiavaioli1Agostino Occhicone2Norbert Danz3Peter Munzert4Francesco Baldini5Ambra Giannetti6Francesco Michelotti7Department of Basic and Applied Science for Engineering Sapienza University of Rome Via A. Scarpa 16 Rome 00161 ItalyInstitute of Applied Physics “Nello Carrara” (IFAC) National Research Council of Italy (CNR) Via Madonna del Piano 10 Sesto Fiorentino Firenze 50019 ItalyDepartment of Basic and Applied Science for Engineering Sapienza University of Rome Via A. Scarpa 16 Rome 00161 ItalyFraunhofer Institute for Applied Optics and Precision Engineering A.‐Einstein‐Str. 7 07745 Jena GermanyFraunhofer Institute for Applied Optics and Precision Engineering A.‐Einstein‐Str. 7 07745 Jena GermanyInstitute of Applied Physics “Nello Carrara” (IFAC) National Research Council of Italy (CNR) Via Madonna del Piano 10 Sesto Fiorentino Firenze 50019 ItalyInstitute of Applied Physics “Nello Carrara” (IFAC) National Research Council of Italy (CNR) Via Madonna del Piano 10 Sesto Fiorentino Firenze 50019 ItalyDepartment of Basic and Applied Science for Engineering Sapienza University of Rome Via A. Scarpa 16 Rome 00161 ItalyAbstract Alzheimer's disease (AD) is a progressive neurological disorder that gradually impairs all cognitive functions. The diagnosis typically requires a combination of cognitive assessments, neuroimaging techniques, and biomarker analysis. In healthy neurons, Tau protein stabilizes microtubules, which are vital for maintaining the structure and proper functioning of nerve cells. However, elevated levels of Tau in cerebrospinal or other body fluids can be related to the progression of Alzheimer's disease. This study introduces an optical technique that employs a dual label‐free and fluorescence operation mode to detect Tau protein in both standard running buffer and cerebrospinal fluid. This innovative method enables label‐free analysis of the bio‐conjugation process on biochips used for resolved fluorescence‐based Tau detection. This work successfully demonstrates Tau protein detection in both matrixes, achieving an outstanding limit of detection of 2.4 pM in cerebrospinal fluid. Moreover, the analysis of the dose‐response curve allows to estimate the dissociation constant (KD = 18 nM) for Tau interactions, yielding values that are in excellent agreement with existing literature using other techniques. These aspects highlight the added value of this technique, providing a valuable tool for investigating Alzheimer's‐related biomarkers, as demonstrated in this study with Tau protein.https://doi.org/10.1002/adsr.2024001641D photonic crystalsAlzheimer's diseasebiophotonic platformcerebrospinal fluidtau protein
spellingShingle Alberto Sinibaldi
Francesco Chiavaioli
Agostino Occhicone
Norbert Danz
Peter Munzert
Francesco Baldini
Ambra Giannetti
Francesco Michelotti
Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease Diagnosis
Advanced Sensor Research
1D photonic crystals
Alzheimer's disease
biophotonic platform
cerebrospinal fluid
tau protein
title Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease Diagnosis
title_full Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease Diagnosis
title_fullStr Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease Diagnosis
title_full_unstemmed Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease Diagnosis
title_short Picomolar Detection of Tau Protein Using 1D Photonic Crystal Biochips for Alzheimer's Disease Diagnosis
title_sort picomolar detection of tau protein using 1d photonic crystal biochips for alzheimer s disease diagnosis
topic 1D photonic crystals
Alzheimer's disease
biophotonic platform
cerebrospinal fluid
tau protein
url https://doi.org/10.1002/adsr.202400164
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