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: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Biosensors |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6374/15/1/50 |
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| Summary: | 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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| ISSN: | 2079-6374 |