Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre ( n = 66) and 4 months later ( n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant ( p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales.
| Original language | English |
|---|---|
| Pages (from-to) | 5113-5120 |
| Number of pages | 8 |
| Journal | Analyst |
| Volume | 147 |
| Issue number | 22 |
| Early online date | 12 Oct 2022 |
| DOIs | |
| Publication status | E-pub ahead of print - 12 Oct 2022 |
Bibliographical note
Funding Information:The work was supported by Motor Neurone Disease Association (AMBRoSIA 972-797) and the NIHR Sheffield Biomedical Research Centre (IS-BRC-1215-20017). P. J. S. is supported as a National Institute for Health Research (NIHR) Senior Investigator (NF-SI-0617–10077). For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising. The authors gratefully acknowledge the patients who so enthusiastically participated in this study.
Publisher Copyright:
© 2022 The Royal Society of Chemistry.
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