Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers

The detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer’s disease. A biomarker’s low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is dire...

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Main Authors: Stefanus Renaldi Wijaya, Augusto Martins, Katie Morris, Steven D. Quinn, Thomas F. Krauss
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biosensors
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Online Access:https://www.mdpi.com/2079-6374/15/1/50
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author Stefanus Renaldi Wijaya
Augusto Martins
Katie Morris
Steven D. Quinn
Thomas F. Krauss
author_facet Stefanus Renaldi Wijaya
Augusto Martins
Katie Morris
Steven D. Quinn
Thomas F. Krauss
author_sort Stefanus Renaldi Wijaya
collection DOAJ
description The detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer’s disease. A biomarker’s low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is directly proportional to the mass bound on the sensor’s surface. To address this challenge, we used a resonant Young’s slit interferometer geometry and implemented several innovations, such as phase noise matching and optimisation of the fringe spacing, to maximise the signal-to-noise ratio. As a result, we achieved a limit of detection of 2.9 × 10<sup>−6</sup> refractive index units (RIU). We validated our sensor’s low molecular weight capability by demonstrating the detection of Aβ-42, a 4.5 kDa peptide indicative of Alzheimer’s disease, and reached the clinically relevant pg/mL regime. This system builds on the guided mode resonance modality we previously showed to be compatible with handheld operation using low-cost components. We expect this development will have far-reaching applications beyond Aβ-42 and become a workhorse tool for the label-free detection of low-molecular-weight biomarkers across a range of disease types.
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spelling doaj-art-0038b095b3f640b49def41790d088d662025-01-24T13:25:33ZengMDPI AGBiosensors2079-63742025-01-011515010.3390/bios15010050Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight BiomarkersStefanus Renaldi Wijaya0Augusto Martins1Katie Morris2Steven D. Quinn3Thomas F. Krauss4School of Physics, Engineering and Technology, University of York, York YO10 5DD, UKSchool of Physics, Engineering and Technology, University of York, York YO10 5DD, UKSchool of Physics, Engineering and Technology, University of York, York YO10 5DD, UKSchool of Physics, Engineering and Technology, University of York, York YO10 5DD, UKSchool of Physics, Engineering and Technology, University of York, York YO10 5DD, UKThe detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer’s disease. A biomarker’s low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is directly proportional to the mass bound on the sensor’s surface. To address this challenge, we used a resonant Young’s slit interferometer geometry and implemented several innovations, such as phase noise matching and optimisation of the fringe spacing, to maximise the signal-to-noise ratio. As a result, we achieved a limit of detection of 2.9 × 10<sup>−6</sup> refractive index units (RIU). We validated our sensor’s low molecular weight capability by demonstrating the detection of Aβ-42, a 4.5 kDa peptide indicative of Alzheimer’s disease, and reached the clinically relevant pg/mL regime. This system builds on the guided mode resonance modality we previously showed to be compatible with handheld operation using low-cost components. We expect this development will have far-reaching applications beyond Aβ-42 and become a workhorse tool for the label-free detection of low-molecular-weight biomarkers across a range of disease types.https://www.mdpi.com/2079-6374/15/1/50optical sensorsguided-mode resonanceYoung’s interferometerbiosensorslimit of detection
spellingShingle Stefanus Renaldi Wijaya
Augusto Martins
Katie Morris
Steven D. Quinn
Thomas F. Krauss
Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers
Biosensors
optical sensors
guided-mode resonance
Young’s interferometer
biosensors
limit of detection
title Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers
title_full Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers
title_fullStr Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers
title_full_unstemmed Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers
title_short Resonant Young’s Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers
title_sort resonant young s slit interferometer for sensitive detection of low molecular weight biomarkers
topic optical sensors
guided-mode resonance
Young’s interferometer
biosensors
limit of detection
url https://www.mdpi.com/2079-6374/15/1/50
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AT augustomartins resonantyoungsslitinterferometerforsensitivedetectionoflowmolecularweightbiomarkers
AT katiemorris resonantyoungsslitinterferometerforsensitivedetectionoflowmolecularweightbiomarkers
AT stevendquinn resonantyoungsslitinterferometerforsensitivedetectionoflowmolecularweightbiomarkers
AT thomasfkrauss resonantyoungsslitinterferometerforsensitivedetectionoflowmolecularweightbiomarkers