The effect of Raman scattering is a result of inelastic light scattering processes, which lead to the emission of scattered light with a different frequency associated with molecular vibrations of the identified molecule. Spontaneous Raman scattering is usually weak, resulting in complexities with the separation of weak inelastically scattered light and intense Rayleigh scattering. These limitations have led to the development of various techniques for enhancing Raman scattering, including resonance Raman spectroscopy (RRS) and nonlinear Raman spectroscopy (coherent anti-Stokes Raman spectroscopy and stimulated Raman spectroscopy). Furthermore, the discovery of the phenomenon of enhanced Raman scattering near metallic nanostructures gave impetus to the development of the surface-enhanced Raman spectroscopy (SERS) as well as its combination with resonance Raman spectroscopy and nonlinear Raman spectroscopic techniques. The combination of nonlinear and resonant optical effects with metal substrates or nanoparticles can be used to increase speed, spatial resolution, and signal amplification in Raman spectroscopy, making these techniques promising for the analysis and characterization of biological samples.
Analyte | SERS Substrate/Receptor Molecule | Assay | SERS Nanotag | LOD | Sample | Features | Year, Ref. |
---|---|---|---|---|---|---|---|
Gp51 antigen of bovine leukemia virus | Magnetic gold nanoparticles (AuNPs)/the native (anti-gp51) and fragmented anti-gp51 antibody (Ab) | Homogenous SERS-based sandwich immunoassay | Gold nanorods modified with 5-thio-nitrobenzoic acid (DTNB) and specific anti-gp51 Ab | 0.95 μg/mL | Milk | Oriented and random Ab immobilization, application of two kinds of nanoparticles | 2013, [13][175] |
Escherichia coli (E. coli) | Gold-coated magnetic spherical nanoparticles/polyclonal antibody (pAb) | Homogenous SERS-based sandwich immunoassay | Rod shaped AuNPs modified with DTNB, avidin, and biotin-labeled Ab | 8 cfu/mL | Real water samples | Two kinds of AuNPs | 2011, [14][153] |
E. coli and Staphylococcus aureus (S. aureus) | Magnetic beads (400 nm)/anti-E. coli2, anti-S. aureus2 monoclonal antibody (mAb) | Homogenous SERS-based sandwich immunoassay | Poly-l-lysine-coated triple-bond-coded AuNPs modified with 4-cyanobenzenethiol (MBN) | 10 and 25 cfu/mL | Bottled water and milk | Simultaneous detection with “hot spot” effect resulting in a significant enhancement of the Raman signal at 2105 and 2227 cm−1 | 2020, [15][152] |
Human immunoglobulin (hIgG) | 100 nm thick gold film evaporated on microscope slide or silicon wafer/goat anti-human IgG Ab | SERS immunoassay of human immunoglobulin | 60 nm gold nanoparticles modified with 4-nitrobenzenethiol (4-NBT) and anti-human IgG Ab | 3 pM on silicon and 28 pM on gold | Standard solution | Comparison of Si wafer and tradition gold surface | 2020, [16][154] |
Human IgG, prostate-specific antigen (PSA) | 2D arrays of Au (42 nm-core)@Ag (4.5 nm-shell) NPs on ITO substrate/polyclonal anti H-IgG, PSA mAb | Heterogenous SERS-based sandwich immunoassay | SH-PEG-COOH-coated AuNPs modified with 4-mercaptobenzoic acid (MBA) and anti H-IgG or PSA mAb | 0.3 pg/mL (10 fM) for PSA and 0.05 pg/mL (0.3 fM) for H-IgG | Standard solution | Comparison of the size of AuNPs in SERS nanotag (26, 53, 110 nm) | 2017, [17][155] |
Escherichia coli (E. coli) | Spherical gold coated magnetic nanoparticles/pAb | Homogenous SERS-based sandwich immunoassay | Gold nanorods labeled with alkaline phosphatase (ALP) enzyme and also modified with 5-bromo-4-chloro-3-indolyl phosphate (BCIP) and E. coli Ab |
10 cfu mL−1 | Standard solution | ALP activity; BCIP was hydrolyzed to SERS-active product; 5-bromo-4-chloro-3-indole (BCI) | 2018, [3][166] |
IgM and IgG to SARS-CoV-2 | No SERS substrate/mouse anti-human IgM and IgG capture Abs | SERS-based LFIA | Gap-enhanced Raman nanotags (GERTs) with 4-nitrobenzenethiol (4-NBT) between core and shell, modified with COVID-19 recombinant antigens (CN97) | 1 ng/mL (IgM), 0.1 ng/mL (IgG) | Standard solution | Simultaneous determination of IgM and IgG | 2021, [18][176] |
IgM and IgG to SARS-CoV-2 | No SERS substrate/anti-human IgM and anti-human IgG Abs | SERS-based LFIA | Ag shell on SiO2 core (SiO2@Ag) 5,5-dithiobis-(2-nitrobenzoic acid) modified with dual layers of DTNB and SARS-CoV-2 spike (S) protein | 1.28 × 107-fold dilution by the IUPAC standard method, which is 800 times lower than that of the visualization results | Clinical serum samples (n = 68) | Simultaneous determination of IgM and IgG | 2021, [19][177] |
Ferritin (FER) | Hydrophilic AgNPs onto the specific area of the hydrophobic polydimethylsiloxane (PDMS)–hydrophilic/hydrophobic Ag/PDMS/anti-FER Ab | SERS-based LFIA | Raspberry-like AuNPs modified with 4-MBA and anti-FER Ab | 0.41 pg/mL | Standard solution | Combination of SERS substrate and SERS nanotag in LFIA format | 2020, [20][178] |
Carcinoembryonic antigen (CEA) | Hydrophilic AgNPs with polymethylmethacrylate (PMMA)/anti-CEA Ab | SERS-based LFIA | Flower-shaped Ag nanoplates modified with crystal violet and anti-CEA Ab | 4.92 pg/mL | Standard solution | Combination of SERS substrate and SERS nanotag in LFIA format | 2021, [21][156] |
α-Fetoprotein (AFP) | Few layers of MoS2 nanosheets exfoliated by NaK alloys/capture mAb | SERS-based sandwich immunoassay | Au@AgNCs and R6G–mAb complex | 0.03 pg/mL | Human blood serum samples | The sandwich immunocomplex “capture probe/target/SERS tag” was deposited on a silicon wafer and decorated with silver-coated gold nanocubes to increase the density of “hot spots” on the surface of the immunosensor | 2021, [22][110] |
Human immunoglobulin (hIgG) | AuNP array (AuA)-coated solid substrate/rabbit anti-human IgG Ab | SERS-based sandwich immunoassay | AuNPs modified with 4-aminothiophenol (4-ATP) and rabbit anti-human IgG Ab | 0.1 μg mL−1 | Human serum samples | The combination of a SERS substrate based on AuNP array with SERS nanotag resulted in sensitive detection | 2021, [23][109] |
Pancreatic cancer marker MUC4 | Immobilization of gold nanoflowers onto thiol-functionalized silicon wafer/Anti-MUC4 Ab | SERS-based sandwich immunoassay | Gold nanoflowers modified with 4-mercaptobenzoic acid and anti-MUC4 Ab | 0.1 ng mL−1 | Standard solution | Raman mapping was applied for a large substrate area to decrease a “spot-to-spot” variation of SERS signal | 2020, [24][179] |
IgG/PSA | No SERS substrate/anti-rabbit IgG/anti-PSA Ab | Homogeneous enzyme-amplified SERS immunoassay | AuNP-assembled silica NPs (SiO2@Au-RLC@Ag) with Ag shell modified with 4-aminothiophenol (4-ATP) Polyclonal alkaline phosphatase (AP)-conjugated goat anti-rabbit IgG or AP-streptavidin-biotin-conjugated anti-PSA Ab were used as a tracer Ab to produce ascorbic acid for reduction of Ag+ to Ag |
0.09 ng/mL for IgG and 0.006 ng/mL for PSA | Human serum samples | Enzyme-induced Ag growth on the surface of SERS nanotag to produce the amplification of the SERS signal | 2020, [25][180] |
Carcinoembryonic antigen (CEA) | Silver shell magnetic nanoparticles Fe3O4@Ag MNPs/anti-CEA monoclonal antibody | SERRS-based sandwich immunoassay | Silver-coated gold nanorods (Au@AgNRs) modified with diethylthiatricarbocyanineiodide (DTTC), coated with mPEG-SH and conjugated with anti-CEA antibodies | 4.75 fg/mL | Human serum samples | Au@AgNRs were in resonance with the resonant Raman dye DTTC at 785 nm excitation laser | 2016, [26][181] |
Mannose-capped lipoarabinomannan (ManLAM) | Resonance Raman-enhanced adlayer of cyanine 5 on a smooth gold surface/polyclonal rabbit antibody for Mycobacterium tuberculosis | SERRS-based sandwich immunoassay | AuNPs modified with 5,5′-dithiobis (succinimidyl-2-nitrobenzoate; DSNB) and MAb to ManLAM | 1.1 ng/mL | Human serum samples | Cy5 modified gold substrates were characterized; the SERRS performance was compared with SERS and revealed a ≈9.3 gain in sensitivity of immunoassay | 2019, [27][182] |