A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease Studies

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is marked by the abnormal production of amyloid-beta (A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></m...

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Main Authors: Margarida O. Correia, Paulo Sousa, Raquel O. Rodrigues, Graça Minas
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Applied Sciences
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Online Access:https://www.mdpi.com/2076-3417/15/7/3837
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author Margarida O. Correia
Paulo Sousa
Raquel O. Rodrigues
Graça Minas
author_facet Margarida O. Correia
Paulo Sousa
Raquel O. Rodrigues
Graça Minas
author_sort Margarida O. Correia
collection DOAJ
description Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is marked by the abnormal production of amyloid-beta (A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula>) fibrils, a key biomarker for diagnosis and illness monitoring. Advanced microfluidic devices, such as brain-on-a-chip (BoC), are innovative preclinical tools with the potential to revolutionize AD early diagnosis and treatment. However, existing BoCs face limitations, including challenges in biosensing integration, limited sensitivity, and automation. In this study, we demonstrate the feasibility of integrating fluorescence-based detection of A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> fibrils within microfluidic platforms, improving efficiency and precision in biomarker analysis, while also reducing sample volume requirements, with potential application in BoC. The fluorescent probe CRANAD-2, known for its in vivo specificity and strong fluorescence response to A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> fibrils, was first characterized in a macroscale system to establish baseline performance. These results were used to guide subsequence microfluidic experiments, reducing sample volume while maintaining analytical reliability. The study revealed consistent fluorescence responses and a strong linear relationship between A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> concentration and fluorescence intensity in both setups. This proof-of-concept study shows, for the first time, the potential of integrating optical biosensing into microfluidic devices for A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> detection, offering a new technological tool for advancing AD studies.
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spelling doaj-art-620070ee17c0404384861cf2db256f322025-08-20T02:15:55ZengMDPI AGApplied Sciences2076-34172025-03-01157383710.3390/app15073837A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease StudiesMargarida O. Correia0Paulo Sousa1Raquel O. Rodrigues2Graça Minas3Center for MicroElectromechanical Systems (CMEMS-UMinho), University of Minho, Campus de Azurém, 4800-058 Guimarães, PortugalCenter for MicroElectromechanical Systems (CMEMS-UMinho), University of Minho, Campus de Azurém, 4800-058 Guimarães, PortugalCenter for MicroElectromechanical Systems (CMEMS-UMinho), University of Minho, Campus de Azurém, 4800-058 Guimarães, PortugalCenter for MicroElectromechanical Systems (CMEMS-UMinho), University of Minho, Campus de Azurém, 4800-058 Guimarães, PortugalAlzheimer’s disease (AD), a progressive neurodegenerative disorder, is marked by the abnormal production of amyloid-beta (A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula>) fibrils, a key biomarker for diagnosis and illness monitoring. Advanced microfluidic devices, such as brain-on-a-chip (BoC), are innovative preclinical tools with the potential to revolutionize AD early diagnosis and treatment. However, existing BoCs face limitations, including challenges in biosensing integration, limited sensitivity, and automation. In this study, we demonstrate the feasibility of integrating fluorescence-based detection of A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> fibrils within microfluidic platforms, improving efficiency and precision in biomarker analysis, while also reducing sample volume requirements, with potential application in BoC. The fluorescent probe CRANAD-2, known for its in vivo specificity and strong fluorescence response to A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> fibrils, was first characterized in a macroscale system to establish baseline performance. These results were used to guide subsequence microfluidic experiments, reducing sample volume while maintaining analytical reliability. The study revealed consistent fluorescence responses and a strong linear relationship between A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> concentration and fluorescence intensity in both setups. This proof-of-concept study shows, for the first time, the potential of integrating optical biosensing into microfluidic devices for A<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>β</mi></semantics></math></inline-formula> detection, offering a new technological tool for advancing AD studies.https://www.mdpi.com/2076-3417/15/7/3837Alzheimer’s diseaseamyloid-betaCRANAD-2 fluorophorefluorescence spectroscopybiomarker quantificationmicrofluidic systems
spellingShingle Margarida O. Correia
Paulo Sousa
Raquel O. Rodrigues
Graça Minas
A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease Studies
Applied Sciences
Alzheimer’s disease
amyloid-beta
CRANAD-2 fluorophore
fluorescence spectroscopy
biomarker quantification
microfluidic systems
title A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease Studies
title_full A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease Studies
title_fullStr A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease Studies
title_full_unstemmed A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease Studies
title_short A Proof-of-Concept Study Aiming for the Integration of an Optical Biosensor in Advanced Microfluidic Devices for Alzheimer’s Disease Studies
title_sort proof of concept study aiming for the integration of an optical biosensor in advanced microfluidic devices for alzheimer s disease studies
topic Alzheimer’s disease
amyloid-beta
CRANAD-2 fluorophore
fluorescence spectroscopy
biomarker quantification
microfluidic systems
url https://www.mdpi.com/2076-3417/15/7/3837
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