| Summary: | Two-dimensional nanostructures (2DNS) attract tremendous interest and have emerged as potential materials for a variety of applications, including biomolecule sensing, due to their high surface-to-volume ratio, tuneable optical and electronic properties. Advancements in the engineering of 2DNS and associated technologies have opened up new opportunities. Surface-enhanced Raman scattering (SERS) is a rapid, highly sensitive, non-destructive analytical technique with exceptional signal amplification potential. Several structurally and chemically engineered 2DNS with added advantages (e.g., π–π* interaction), over plasmonic SERS substrates, have been developed specifically towards biomolecule sensing in a complex matrix, such as biological fluids. This review focuses on the recent developments of 2DNS-SERS substrates for biomolecule sensor applications. The recent advancements in engineered 2DNS, particularly for SERS substrates, have been systematically surveyed. In SERS substrates, 2DNS are used as either a standalone signal enhancer or as support for the dispersion of plasmonic nanostructures. The current challenges and future opportunities in this synergetic combination have also been discussed. Given the prospects in the design and preparation of newer 2DNS, this review can give a critical view on the current status, challenges and opportunities to extrapolate their applications in biomolecule detection.
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