A SERRS-based lateral flow assay for sensitive detection of mitochondrial DNA in endometriosis screening

Laura M Rey Gomez, Kazi Morshed Alom, Audrey Nadalini, Su Su Thae Hnit, Benjamin Clark, Nana Lyu, Rena Hirani, Sian Sloan‐Dennison, Stacey Laing, Cicely Rathmell, David Creasey, Dieter Bingemann, Jonathan Faircloth, Neil C. Shand, Duncan Graham, Karen Faulds, Yuling Wang
2026 · doi:10.17868/strath.00096086 · W7155416833
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A proof-of-concept lateral flow assay integrating surface-enhanced resonance Raman scattering with gold nanoparticles enables sensitive detection of mitochondrial DNA deletion mutations for endometriosis screening, achieving a significantly lower limit of detection than colorimetric methods.

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This study developed a surface-enhanced resonance Raman scattering lateral flow assay to detect mitochondrial DNA deletion mutations in plasma for endometriosis screening. The digital SERRS-based method achieved a limit of detection significantly lower than standard colorimetric PCR workflows, demonstrating high sensitivity for mutant DNA amidst wild-type background. Quantitative analysis using a handheld Raman reader indicated the potential for amplification-free, point-of-care diagnostics. This paper is centrally about endometriosis — specifically focusing on a novel biosensor technology aimed at reducing diagnostic delays by detecting cell-free mitochondrial DNA biomarkers in plasma.

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Abstract

Endometriosis (EMT) is an incurable and painful chronic illness that affects approximately 10% of people assigned female at birth worldwide. Currently, EMT takes on average 5–7 years to diagnose after histological confirmation with a tissue sample collected via laparoscopy. Therefore, there is a demand for developing new and powerful detection tools that can work in conjunction with imaging techniques to make EMT diagnosis more accessible and reduce diagnostic delays. This study proposes a proof-of-concept lateral flow assay (LFA) for the detection of an EMT biomarker based on mitochondrial DNA deletion mutations found in cell-free mitochondria in plasma. Surface-enhanced resonance Raman scattering (SERRS) was integrated with the LFA to increase sensitivity and allow quantitation using gold nanoparticles functionalised with the near-infrared fluorescent dye NIR 4f. The SERRS-LFA was compared to gel electrophoresis and colorimetry in a typical polymerase chain reaction (PCR) workflow. SERRS signals were analysed using confocal Raman microscopy in combination with digital SERRS. This digital SERRS-LFA demonstrated a limit of detection (LOD) of 5.6 × 102 input copies, about 109-fold lower than the reference colorimetric method. When mutant DNA was tested as abundance of background wild type DNA, an LOD of 0.35% was obtained, about 14-fold lower than the reference colorimetric method. Finally, quantitative analysis with a handheld Raman reader demonstrated the potential of bringing future amplification-free SERRS-based LFAs to point-of-care settings.
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A SERRS-based lateral flow assay for sensitive detection of mitochondrial DNA in endometriosis screening Rey Gomez, Laura M. and Alom, Kazi Morshed and Nadalini, Audrey and Hnit, Su Su Thae and Clark, Benjamin and Lyu, Nana and Hirani, Rena and Sloan-Dennison, Sian and Laing, Stacey and Rathmell, Cicely and Creasey, David and Bingemann, Dieter and Faircloth, Jonathan and Shand, Neil and Graham, Duncan and Faulds, Karen and Wang, Yuling (2026) A SERRS-based lateral flow assay for sensitive detection of mitochondrial DNA in endometriosis screening. ACS Sensors, 11 (3). 2707–2720. ISSN 2379-3694 (https://doi.org/10.1021/acssensors.5c04674) Preview | Text. Filename: Rey-Gomez-etal-ACSS-2026-A-SERRS-based-lateral-flow-assay-for-sensitive-detection-of-mitochondrial-DNA-in-endometriosis-screening.pdf Accepted Author Manuscript License: Download (5MB)| Preview | Abstract Endometriosis (EMT) is an incurable and painful chronic illness that affects approximately 10% of people assigned female at birth worldwide. Currently, EMT takes on average 5–7 years to diagnose after histological confirmation with a tissue sample collected via laparoscopy. Therefore, there is a demand for developing new and powerful detection tools that can work in conjunction with imaging techniques to make EMT diagnosis more accessible and reduce diagnostic delays. This study proposes a proof-of-concept lateral flow assay (LFA) for the detection of an EMT biomarker based on mitochondrial DNA deletion mutations found in cell-free mitochondria in plasma. Surface-enhanced resonance Raman scattering (SERRS) was integrated with the LFA to increase sensitivity and allow quantitation using gold nanoparticles functionalised with the near-infrared fluorescent dye NIR 4f. The SERRS-LFA was compared to gel electrophoresis and colorimetry in a typical polymerase chain reaction (PCR) workflow. SERRS signals were analysed using confocal Raman microscopy in combination with digital SERRS. This digital SERRS-LFA demonstrated a limit of detection (LOD) of 5.6 × 102 input copies, about 109-fold lower than the reference colorimetric method. When mutant DNA was tested as abundance of background wild type DNA, an LOD of 0.35% was obtained, about 14-fold lower than the reference colorimetric method. Finally, quantitative analysis with a handheld Raman reader demonstrated the potential of bringing future amplification-free SERRS-based LFAs to point-of-care settings. ORCID iDs Rey Gomez, Laura M., Alom, Kazi Morshed, Nadalini, Audrey, Hnit, Su Su Thae, Clark, Benjamin, Lyu, Nana, Hirani, Rena, Sloan-Dennison, Sian ORCID: https://orcid.org/0000-0003-2473-1425, Laing, Stacey ORCID: https://orcid.org/0000-0001-5781-349X, Rathmell, Cicely, Creasey, David, Bingemann, Dieter, Faircloth, Jonathan, Shand, Neil, Graham, Duncan ORCID: https://orcid.org/0000-0002-6079-2105, Faulds, Karen ORCID: https://orcid.org/0000-0002-5567-7399 and Wang, Yuling;- - Item type: Article ID code: 96086 Dates: DateEvent27 March 2026Published12 March 2026Published Online18 February 2026AcceptedSubjects: Science > Chemistry Department: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 23 Apr 2026 15:28 Last modified: 17 Jun 2026 00:26 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/96086

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