Amino acid (AA) substitutions are directly correlated with specific pathologies such as Alzheimer's disease, making their rapid screening and detection critical to treatment and scientific study. A proof-of-concept implementation of the label-free and noninvasive Raman spectroscopy technique for the detection of AA substitutions in primary peptide fragments is demonstrated. By encoding the Raman “fingerprint” of individual AAs into binary formats called optical identification tags (OITs), a library of identifiers is created, which can then be used for detecting mutations. When the recorded Raman signal is enhanced by using surface-enhanced Raman scattering substrate, the mutation screening strategy can detect a single point missense mutation in an 11-AA peptide fragment of amyloid beta Aβ(25–35) and a frameshift mutation in a 42-AA fragment Aβ(1–42) down to picomolar concentrations. The combination of high sensitivity and simple operation makes the use of OITs a promising approach for high-throughput automated screening.
Bibliographical noteKAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This work was supported by King Abdullah University of Science and Technology (KAUST). The authors gratefully acknowledge useful conversations with Dr. Emily Ringe. The authors also acknowledge Dr. Jeremy A. Bau for proofreading the manuscript. They also thank Ivan Gromicho, a scientific illustrator at KAUST, for creating Figure 1 and ToC image.