Surface-enhanced Raman spectroscopy(SERS) is a spectroscopic technique that leverages the electromagnetic enhancement of Raman scattering signals. Based on the inelastic scattering of light, Raman spectroscopy provides a unique molecular fingerprint for different substances. However, the inherent weakness of Raman signals posed a limitation to its sensitivity. SERS overcomes this limitation by using nanostructured surfaces to amplify the Raman signal, enabling the detection of trace amounts of analytes.
SERS has been a game-changing method with far-reaching effects in many different scientific fields. Aluminum and noble metals are used as SERS substrates, demonstrating the method's adaptability to various research requirements and financial limitations. SERS has several clinical uses that highlight its potential to transform medical diagnostics and enhance patient outcomes. These uses include the detection of infectious diseases, cancer diagnosis, and therapy monitoring.
Fig 1 The schematic of SERS detection. The Raman scattering of the analyte, enhanced by the substrate, is detected by the detector. (Lin DY, et al., 2023)
Aluminum has emerged as a fascinating substrate for SERS applications due to its unique properties. The plasmonic characteristics of aluminum nanoparticles contribute significantly to the enhancement of Raman signals. The interaction between incident light and the surface plasmons of aluminum generates intense electromagnetic fields, boosting the Raman scattering cross-section of nearby molecules.
One key advantage of aluminum-based SERS substrates is their cost-effectiveness compared to noble metals. The affordability of aluminum makes SERS more accessible for a broader range of applications, from academic research to industrial quality control processes. Additionally, the ease of fabrication and functionalization of aluminum substrates adds to their attractiveness in SERS studies.
While aluminum has proven to be an economical choice for SERS substrates, noble metals like platinum (Pt) and palladium (Pd) have also gained prominence. These metals exhibit strong plasmonic properties, making them excellent candidates for enhancing Raman signals. The localized surface plasmon resonance (LSPR) of noble metals plays a crucial role in amplifying the electromagnetic field around the substrate, resulting in remarkable SERS enhancements.
Table 1 The average SERS performance of Si, Pt, Pd, Al, Cu-based substrates and conventional pure Ag, Au substrates. (Sultangaziyev A, et al., 2022)
Substrate | Average EF (Min; Max) | Average LOD, M (Min; Max) | ||
---|---|---|---|---|
Arithmetic | Geometric | Arithmetic | Geometric | |
Si without metals | 1.11×107 | 2.55×105 | 2.53×10−5 | 4.85×10−9 |
(500;4× 107) | (500; 4×107) | (10−12;10−4) | (10−12;10−4) | |
Si with metals | 1.59×1013 | 1.44×107 | 5.05×10−8 | 1.57×10−11 |
(33; 1015) | (33; 1015) | (10−18;2×10−6) | (10−18;2×10−6) | |
Overall Si | 1.48×1013 | 1.10×107 | 1.79×10−6 | 2.30×10−11 |
(33; 1015) | (33; 1015) | (10−18;10−4) | (10−18;10−4) | |
Pt | 3.94×108 | 1.23×105 | 6.67×10−6 | 2.71×10−10 |
(33; 4.7×109) | (33; 4.7×109) | (10−15;2×10−5) | (10−15;2×10−5) | |
Pd | 1.04×108 | 1.38×105 | 1.02×10−6 | 4.57×10−9 |
(102; 1.9×109) | (100; 1.9×109) | (10−11; 10−5) | (10−11;10−5) | |
Overall Pt/Pd | 1.97×108 | 1.39×105 | 2.15×10−6 | 2.86×10−9 |
(33; 1.9×109) | (33; 1.9×109) | (10−11; 10−5) | (10−11;10−5) | |
Pure Al | 3.4×105 | 1.27×105 | 1.03×10−6 | 5.85×10−7 |
(5×103; 106) | (5×103; 106) | (10−7; 2×10−6) | (10−7; 2×10−6) | |
Al + Au (R6G analyte) | 8.1×106 | 7×10−10 | 3.16×10−10 | |
(only one EF) | (10−10; 10−9) | (10−10; 10−9) | ||
Al + Ag (R6G analyte) | 5.39×107 | 3.13×107 | 2.50×10−7 | 1.78×10−11 |
(107; 9.77×107) | (107; 9.77×107) | (10−15; 10−6) | (10−15; 10−6) | |
Pure Cu | 7.36×106 | 1.25×106 | 4.46×10−7 | 7.2×10−8 |
(104; 4.70×107) | (104; 4.70×107) | (10−9; 10−6) | (10−9; 10−6) | |
Cu + Au | 2.52×105 | 7.81×104 | 3.33×10−4 | 10−7 |
(1.2×103; 5.0×105) | (1.2×103; 5.0×105) | (10−10; 10−3) | (10−10; 10−3) | |
Cu + Ag | 6.97×1010 | 1.76×107 | 5.01×10−9 | 5.3×10−12 |
(1.19×105; 4.88×1011) | (1.19×105; 4.88×1011) | (10−21; 3.30×10−8) | (10−21; 3.30×10−8) | |
Other metals (Zn, Ti, Fe, Co, Mo, Cr, Hf + Au, Ag) | 6.85×107 | 6.14×107 | 2.96×10−7 | 4.43×10−8 |
(2.70×107; 9.40×107) | (2.70×107; 9.40×107) | (10−12; 2.0×10−6) | (10−12; 1.0) | |
Au | 3.91×108 | 7.54×107 | 2.17×10−9 | 2.64×10−11 |
(2×106, 109) | (2×106, 109) | (10−13,10−7) | (10−13,10−7) | |
Ag | 5.07×107 | 1.35×107 | 4.07×10−8 | 3.36×10−10 |
(9×105,2× 108) | (9×105,2× 108) | 10−14;10−7 | 10−14;10−7 | |
Overall Au/Ag | 6.40×108 | 6.44×107 | 9.87×10−9 | 1.04×10−11 |
(9×105, 6× 109) | (9×105,6× 109) | (10−16;10−7) | (10−16;10−7) |
Pt/Pd-based SERS substrates offer distinct advantages, including high stability and biocompatibility. These characteristics make them suitable for various applications, particularly in the field of biomedical research. The ability to tailor the size and shape of noble metal nanoparticles further enhances their performance as SERS substrates, allowing researchers to fine-tune the sensitivity of the technique based on specific experimental requirements.
One notable application of SERS in clinical settings is its use in cancer diagnostics. The ability to detect specific biomarkers associated with various types of cancer at early stages provides a promising avenue for improving cancer diagnosis and treatment. SERS-based assays have demonstrated exceptional sensitivity in detecting biomolecules such as nucleic acids, proteins, and metabolites, offering a rapid and reliable method for cancer screening.
In addition to cancer diagnostics, SERS has found applications in infectious disease detection. The rapid identification of pathogens, including bacteria and viruses, is essential for timely and effective intervention. SERS enables the detection of specific molecular signatures associated with pathogens, allowing for quick and accurate diagnosis.
Furthermore, SERS has been employed in monitoring therapeutic drug levels in patients. The ability to quantitatively measure drug concentrations in real-time provides valuable information for optimizing drug dosages and ensuring the efficacy of treatments. This application holds great promise in personalized medicine, where treatments can be tailored to individual patient responses.
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