Table 2.

Components of SERS tags with some examples [7, 12, 13, 15, 17, 42, 63, 76–82]

SERS nanotag components Function	Type	Examples	Linking mode	Advantages	Disadvantages	Features to consider
Plasmonic nanoparticle Plasmonic activity Metal Size Shape	Au, Ag 20–200 Spheres, rods, stars	–	–	• Signal generation due to LSPR • Facile synthesis by bottom-up strategies	• Lack of standardised protocols • Lack of control over NP dispersity	• LSPR band location • Number of hotspots per particle • Synthesis: easy, reproducibility and scalable
Number of NPs		Monomer vs cluster
RR molecule Provide characteristic spectral signature for sensitive and indirect identification of the selected target	Dyes:nitrogen-containing cationic dye Sulphur-containing dye	Crystal Violet Rhodamine B/6G Nile blue Cyanine, CV, Malachite green	Electrostatic interaction N-Au(Ag) interaction S–Au(Ag) interaction	• Plentiful fingerprint information • Commercially-available • Larger Raman scattering cross section for dyes	• Emission in fingerprint region (400–1800 cm−1) • Spectral overlapping susceptibility in multiplexing assays • Fluorescence for dyes • Smaller Raman scattering cross section for thiol-small aromatic molecules	• Raman scattering cross section • Surface-seeking groups • Metal affinity • Ability to form SAM • Water solubility • Reactivity • Simplicity and low-cost
	Thiol-small aromatic molecules	Thiophenol,aminohexanethiol, naphthalene dithiol, mercaptobenzoicacid, 1,4-biphenyldithiol	S–Au(Ag) interaction
	Triple bond-containing RRs	4-Ethynylbenzenethiol derivatives 4- Mercaptobenzonitrile Metal carbonyl compounds	$C\equiv C$ $C\equiv N$ $C\equiv O$	• Emission in silent region (1800–2800 cm−1) • Single narrow band • High encoding capability • Interference-free	• Early-stage development • Not commercially-available: self-design and synthesis requirement
Protective shell Maintain the RR near the NP, stabilise the NPs and provide surface groups for bioconjugation	Hydrophilic short spacers Biomolecules Polymers Silica	Ethylene glycol Bovine serum albumin PEG Tetraethoxyorthosilicate (TEOS)	Electrostatic Interaction Covalent bond S–Au(Ag) interaction	• Improves colloidal stability • Terminal functional groups for bioconjugation • Core physical and chemical protection • Avoids loss of RR	• Increases SERS tag • Time-consuming • Labour-intensive	• Coating synthesis • Non-specific adsorption • Toxicity • Functional-end groups • Colloidal stability
Bioconjugation Molecular recognition of the target	Proteins: enzymes and antibodies Aptamers Small molecules	via COOH, NH2, SH click-chemistry	Covalent or non-covalent	• Specificity towards the target analyte	• Variable accordingly with chosen analyte	• Target-specificity ligand • Water solubility • Bioconjugation reproducibility • Price