Raman Signal Enhancement Research Articles

Reusable SERS Platform of Femtosecond Laser Processed Substrate for Detection of Malachite Green

This study presents the development of highly efficient Surface-Enhanced Raman Scattering (SERS) substrates through femtosecond (fs) laser processing of crystalline silicon (Si), resulting in mountain-like microstructures. These microstructures, when decorated with gold nanoparticles (Au NPs), exhibit remarkable SERS performance due to the creation of concentrated hotspots. The enhanced Raman signals originate from the excitation of localized surface plasmon resonance (LSPR) of the Au NPs and the multi-scale rough morphology of the Si substrates. Finite-element method simulations confirm the electromagnetic field enhancement in narrow gaps, supporting the experimental observations. The fabricated substrates show high uniformity, oxidation resistance, long-term stability, and exceptional reproducibility, making them ideal for molecular detection, especially in food safety applications. A remarkable enhancement factor (EF) of 1010 is attained in the detection of Malachite Green (MG), boasting a limit of detection (LoD) as low as 10−14 M. This underscores the immense potential of this technique for achieving highly sensitive and dependable SERS-based sensing capabilities.

Zr-MOF-based substrate with inherent internal standards facilitates reliable SERS analysis of sulfonamide antibiotics

A multifunctional structure comprising gold nanoparticles immobilized within a zirconium-based metal-organic framework (AuNPs/Zr-MOF) was systematically designed. With the capabilities of analyte enrichment, Raman signal enhancement and internal standard calibration, the as-prepared AuNPs/Zr-MOF substrates demonstrate the outstanding SERS sensing performance toward the representative sulfonamide antibiotics (SAs), sulfadiazine, sulfamerazine, sulfamethazine and sulfaquinoxaline. For the first time, these four SAs are detected by SERS in real honey samples at levels of 2.8 ∼ 5.2 ng·g−1 within 10 min. The extensive π-bond conjugated system of Zr-MOF significantly enhances the concentration of SAs through π-π interactions. The entrapped SAs are adsorbed perpendicularly onto the surface of Au via coordinated interactions between Au and two oxygen atoms, or between Au and the terminal amino group. To achieve reliable quantitative analysis, the inherent vibration of the Zr-MOF structure was used as an internal standard label. Combined with a simple clean-up protocol, the established SERE sensing method is superior to conventional methods in terms of time, while achieving the impressive sensitivity. This study presents a robust SERS-based approach for the rapid detection and monitoring of multiple analytes.

Rapid detection of drugs in blood using “molecular hook” surface-enhanced Raman spectroscopy and artificial intelligence technology for clinical applications

Accurate detection of cardiovascular drugs in blood is complicated by interference from serum biomolecules. This study introduces a novel surface-enhanced Raman spectroscopy (SERS) platform incorporating “molecular hooks” to capture small drug molecules while excluding larger biomolecules selectively. The self-assembled nanoparticles with the A13 molecule enhance Raman signals by creating dense electromagnetic “hotspot” regions, achieving detection limits of 10 pg/mL for dobutamine hydrochloride and 10 ng/mL for milrinone-substantially below therapeutic thresholds. Artificial intelligence (AI) integration enables automated spectral analysis, allowing rapid and precise drug detection in clinical blood samples. This approach offers a transformative solution for real-time diagnostics, significantly advancing personalized treatment strategies in clinical settings.

Versatile self-assembled near-infrared SERS nanoprobes for multidrug-resistant bacterial infection-specific surveillance and therapy

The rise of multidrug-resistant bacteria (MDRB) has made bacterial infection one of the biggest health threats, causing numerous antibiotics to fail. Real-time monitoring of bacterial disease treatment efficacy at the infection site is required. Herein, we report a versatile Raman tag 3,3′-diethylthiatricarbocyanine iodide (DTTC)-conjugated star-shaped Au-MoS2@hyaluronic acid (AMD@HA) nanocomposite as a surface-enhanced Raman scattering (SERS) nanoprobe for quick bacterial identification and in-situ eradication. Localized surface plasmon resonance (LSPR) from the hybrid metallic nanostructure makes AMD@HA highly responsive to the near-infrared laser, enabling it to demonstrate a photothermal (PTT) effect, increased SERS activity, and peroxidase-like catalytic reaction to release reactive oxygen species. The tail vein injection of AMD@HA nanoprobes is invasive, however SERS imaging for bacterial identification is non-invasive and sensitive, making it an efficient residual bacteria monitoring method. The detection limit for methicillin-resistant Staphylococcus aureus (MRSA) is as low as 102 CFU·mL-1, and the substrates allow for taking 120 s to acquire a Raman image of 1600 (40 × 40) pixels. In mouse models of MRSA-induced wound infection and skin abscess, the combination of AMD@HA-mediated PTT and catalytic therapy demonstrates a synergistic effect in promoting wound healing through rapid sterilization. This SERS-guided therapeutic approach exhibits little toxicity and does not cause considerable collateral damage, offering a highly promising intervention for treating diseases caused by MDRB. Statement of significanceThis research introduces a SERS nanoprobe, AMD@HA, for the rapid identification and eradication of multidrug-resistant bacteria (MDRB), a critical health threat. The nanoprobe leverages localized surface plasmon resonance for photothermal therapy and enhanced Raman signals, offering a sensitive, non-invasive diagnostic tool. With a low detection limit for MRSA and a synergistic therapeutic effect in mouse models, our approach holds significant promise for treating MDRB-driven infections with minimal toxicity, advancing the field of antimicrobial strategies.

Formation of Armored Silicon Nanowires Array via High-Repetition-Rate Femtosecond Laser Oxidation for Robust Surface-Enhanced Raman Scattering Detection.

Superhydrophobic nanostructures with dense hotspots and high concentration efficiency are of paramount importance for highly sensitive surface-enhanced Raman scattering (SERS) detection. However, their low mechanical strength makes them susceptible to damage from external interferences, leading to hotspot loss and superhydrophobicity failure. In this study, robust SERS detection is achieved using an armored superhydrophobic silicon nanowires array. A micro/nanocross-scale oxide mask is created through high-repetition-rate femtosecond laser oxidation to fabricate the armored nanowires array. The underlying mechanisms of the nanoparticle layer serving as a mask in deep reactive ion etching (DRIE) are analyzed to elucidate the formation of the silicon nanowires. The armored nanowires array SERS substrate exhibits a high contact angle of 158°, demonstrating exceptional analyte enrichment capability. Combined with the dense hotspots provided by the high aspect ratio nanostructures, the detection limit for Rhodamine 6G is 10-13 M, and the enhancement factor (EF) is 4.35 × 109. After undergoing various mechanical tests, the substrate maintains its superhydrophobicity along with a stable Raman signal enhancement, demonstrating its resistance to potential external interference in SERS detection. The sensitive detection of various analytes highlights the promising applications of the armored nanowires substrate in diverse SERS scenarios.

Silver nanoparticles modified with MoS2 and β-cyclodextrin as SERS substrate for rapid determination of cysteamine hydrochloride in meat products

An efficient Surface-enhanced Raman scattering (SERS) method for the detection of cysteamine hydrochloride (CSH) was developed by synthesizing a composite substrate comprising silver nanoparticles (AgNPs) functionalized with MoS2 and β-cyclodextrin (β-CD). The enhanced Raman signals of CSH by β-CD/MoS2/AgNPs substrate were the contribution of electromagnetic enhancement (EM) as well as chemical enhancement (CM), and the enhancement factor (EF) can reach up to 3.11 × 106 (peak at 633 cm−1). Various instrumental techniques were used to characterize the substrate, such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and ultraviolet visible (UV–vis). The binding of β-CD/MoS2/AgNPs and CSH was confirmed by UV–vis and Fourier transform infrared (FT-IR). The optimal experimental conditions were determined by single factor experiments as well as response surface model. The influences of different metal ions and analogous drugs on the detection of CSH were investigated. Under optimum conditions, a good linear correlation (R = 0.9997) was established for CSH in the range of 10.00–1000.00 nmol/L, and the limit of detection (LOD) was as low as 0.78 nmol/L (S/N = 3). The contents of CSH in meat samples were detected. The recovery was 96.6–103.1 %, and the relative standard deviation (RSD) of the measurement was 0.7–3.9 % (n = 7).

Development and Application of Surface-Enhanced Raman Scattering (SERS).

Since the discovery of the phenomenon of surface-enhanced Raman scattering (SERS), it has gradually become an important tool for the analysis of material compositions and structures. The applications of SERS have been expanded from the fields of environmental and materials science to biomedicine due to the extremely high sensitivity and non-destructiveness of SERS-based analytical technology that even allows single-molecule detection. This article provides a comprehensive overview of the surface-enhanced Raman scattering (SERS) phenomenon. The content is divided into several main sections: basic principles and the significance of Raman spectroscopy; historical advancements and technological progress in SERS; and various practical applications across different fields. We also discuss how electromagnetic fields contribute to the SERS effect, the role of chemical interactions in enhancing Raman signals, a modeling and computational approaches to understand and predict SERS effects.

Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo.

Raman spectroscopy using surface-enhanced Raman scattering (SERS) nanoprobes represents an ultrasensitive and high-precision technique for in vivo imaging. Clinical translation of SERS nanoprobes has been hampered by biosafety concerns about the metal substrates used to enhance Raman signals. We report a set of small molecules with bis-thienyl-substituted benzobisthiadiazole structures that enhance Raman signal through self-stacking rather than external substrates. In our technique, called stacking-induced charge transfer-enhanced Raman scattering (SICTERS), the self-stacked small molecules form an ordered spatial arrangement that enables three-dimensional charge transfer between neighboring molecules. The Raman scattering cross-section of SICTERS nanoprobes is 1350 times higher than that of conventional SERS gold nanoprobes of similar particle size. SICTERS outperforms SERS in terms of in vivo imaging sensitivity, resolution and depth. SICTERS is capable of noninvasive Raman imaging of blood and lymphatic vasculatures, which has not been achieved by SERS. SICTERS represents an alternative technique to enhance Raman scattering for guiding the design of ultrasensitive substrate-free Raman imaging probes.

Small molecules self-organized in an orderly manner to enhance Raman signals.

Small molecules self-organized in an orderly manner to enhance Raman signals.

Raman enhancement via double optical resonances in all-dielectric photonic crystal slabs

All-dielectric photonic structures are an important class of substrates in surface-enhanced Raman spectroscopy (SERS), utilizing optical resonant modes to significantly enhance the electromagnetic field and amplify the Raman signals. In this study, we demonstrate the double-resonance approach to realize significant Raman enhancement using all-dielectric photonic crystal (PhC) slab. The double-resonance condition is satisfied by designing optical resonant modes in photonic bands to match frequencies of both excitation laser and Raman signals. By the fabricated PhC slab, the significant enhancement for the Raman signal of silicon is demonstrated. The enhanced Raman signals exhibit a uniform distribution on the PhC slab. The method of Raman enhancement via double optical resonances can advance the field of all-dielectric SERS and holds potential for future SERS applications.

Synergistic SERS enhancement of NiCo-LDHs microurchins and silver nanoparticles for ultra-sensitive and reusable detection of thiabendazole

Two-dimensional layered semiconductor materials as a distinctive class of materials are comprehensively explored for widespread applications due to narrow bandgap, controllable morphology, and tunable metal cation composition. Herein, we constructed a sensing platform of surface enhanced Raman spectroscopy (SERS) by combination of nickel‑cobalt layered double hydroxide (NiCo-LDH) microurchins and plasmonic silver nanoparticles (Ag NPs) for fungicide detection of thiabendazole (TBZ). The NiCo-LDHs/Ag-NPs microcomposites consist of NiCo-LDHs microurchins having a large number of nanoneedles deposited with photoreduced Ag NPs. The SERS platform with NiCo-LDHs/Ag-NPs shows an excellent SERS performance for TBZ detection, including an ultra-low detection limit of 1.49 × 10−11 M, a sublime enhancement factor of 1.71 × 109, high uniformity, good reproducibility, and long-term storage stability. The ultrahigh SERS activity of NiCo-LDH/Ag-NPs can be attributed to strong electromagnetic enhancement in the nanoscale gaps between Ag NPs, massive charge transfer through large-area NiCo-LDH/Ag-NPs interfaces, and the synergistic action of electromagnetic and charge transfer mechanisms. Besides, the unique morphology of NiCo-LDHs/Ag-NPs microcomposite provides a broad surface area for adsorption of TBZ molecules for further Raman signal enhancement. The practicability of the proposed SERS platform is confirmed by detecting TBZ in the real samples of apple juice and river water. The exceptional self-cleaning capability of the NiCo-LDHs/Ag-NPs microcomposite with an retention rate of 81.97 % even after the fifth degradation cycle underscores its impressive sustainable reusability and cost-effectiveness. The findings in this work lay the foundation for the development of high-performance SERS platforms to ensure food safety and environmental protection.

Covalent Organic Framework-Structured Raman Probes for Ultrasensitive In Vivo Bioimaging.

Organic Raman probes, including polymers and small molecules, have attracted great attention in biomedical imaging owing to their excellent biocompatibility. However, the development of organic Raman probes is usually hindered by a mismatch between their absorption spectra and wavelength-fixed excitation, which makes it difficult to achieve resonance excitation necessary to obtain strong Raman signals. Herein, we introduce a covalent organic framework (COF) into the fine absorption spectrum regulation of organic Raman probes, resulting in their significant Raman signal enhancement. In representative examples, a polymer poly(diketopyrrolopyrrole-p-phenylenediamine) (DPP-PD) and a small molecule azobenzene are transformed into the corresponding COF-structured Raman probes. Their absorption peaks show an accurate match of less than 5 nm with the NIR excitation. As such, the COF-structured Raman probes acquire highly sensitive bioimaging capabilities compared to their precursors with negligible signals. By further mechanism studies, we discover that the crystallinity and size of COFs directly affect the π-conjugation degree of Raman probes, thus changing their bandgaps and absorption spectra. Our study offers a universal and flexible method for improving the signal performance of organic Raman probes without changing their structural units, making it more convenient to obtain the highly sensitive organic Raman probes for in vivo bioimaging.

Wavelength-swept spontaneous Raman spectroscopy system improves fiber-based collection efficiency for whole brain tissue classification.

Raman spectroscopy is a valuable technique for tissue identification, but its conventional implementation is hindered by low efficiency due to scattering. Addressing this limitation, we are further developing the wavelength-swept Raman spectroscopy approach. We aim to enhance Raman signal detection by employing a laser capable of sweeping over a wide wavelength range to sequentially excite tissue with different wavelengths, paired with a photodetector featuring a fixed narrow-bandpass filter for collecting the Raman signal at a specific wavelength. We experimentally validate our technique using a fiber-based swept-source Raman spectroscopy setup. In addition, simulations are conducted to assess the efficacy of our approach in comparison with conventional spectrometer-based Raman spectroscopy. Our simulations reveal that the wavelength-swept configuration leads to a significantly stronger signal compared with conventional spectrometer-based Raman spectroscopy. Experimentally, our setup demonstrates an improvement of at least 200× in photon detection compared with the spectrometer-based setup. Furthermore, data acquired from different regions of a fixed monkey brain using our technique achieves 99% accuracy in classification via -nearest neighbor analysis. Our study showcases the potential of wavelength-swept Raman spectroscopy for tissue identification, particularly in highly scattering media, such as the brain. The developed technique offers enhanced signal detection capabilities, paving the way for future in vivo applications in tissue characterization.

Influence of One-Dimensional Photonic Crystal on Raman Signal Enhancement: A Detailed Experimental Study

The enhancement of Raman signals using photonic crystal structures has been the subject of numerous experimental and theoretical studies, leading to a variety of issues and inconsistencies. This paper presents a comprehensive experimental investigation into the impact of alignment between the laser excitation wavelength and the specific position of the photonic band gap on signal enhancement in Raman spectroscopy. By employing one-dimensional (1D) porous silicon photonic crystals, a systematic analysis across a large number of spectra was conducted. The study focused on examining the signal enhancement of both the Raman ∼520 cm–1 silicon band, representing the constituent material of photonic crystal, and the most prominent Raman bands of crystal violet, used as a probe molecule. The probe molecules were both infiltrated into and adsorbed on top of the photonic crystal structure. The obtained experimental results for the contribution of 1D photonic crystals to Raman signal enhancement are much smaller compared to most predictions. The Raman signal of silicon and the signal from the probe molecule are enhanced ≤2.5 times when the laser excitation aligns with the edge of the photonic band gap, strictly defined as the position at the very bottom of the reflectance peak. The results have been discussed within the context of theoretical explanations.

Au nanodisks-based 2D photonic crystals fabricated by single-beam laser interference lithography: A simple and reliable alternative for highly efficient large-scale SERS molecular sensors

Noble metal-based Photonic Crystals (PCs) have emerged as outstanding candidates for precise light management, projecting applications in strategic areas for society like high-sensitivity and fast molecular (inorganic/organic/bio) sensing by Surface-Enhanced Raman Spectroscopy (SERS). In this work, we report an exhaustive study on the potential of large-scale (active area >1 [cm2]) Au nanodisks-based 2D PCs fabricated by single-beam Laser Interference Lithography (LIL) for high-performance SERS molecular sensing. This technique was used to fabricate periodic nanoarrays (period of 470 [nm]) of Au nanodisks with thicknesses from 50 up to 125 [nm]. The period was chosen following Finite-Difference Time-Domain (FDTD) simulations that suggested the best electric-near field enhancement for this condition. Confocal Raman microscopy and Methylene Blue (MB) as active Raman marker, were used to assess the samples' performance for molecular sensing. SERS studies have shown that the nanodisks' thickness can be a considerable size parameter for the Raman signal amplification, observing higher signal enhancements for higher thicknesses. The observed thickness effects on the Raman signal enhancement were consistent with FDTD simulations, which predicted higher electric-near field amplifications for higher thickness within the red/near-infrared range. Results show that our PCs enable to measure the characteristic Raman footprint of the analyte with good spectral resolution using relatively low powers (0.04–1 [mW]) and short acquisition times (1–30 [s]), considering an MB surface mass density as low as 2.6 [ng/cm2]. SERS enhancement factors as high as 2 x 107 were achieved for PCs with the highest thickness, representing a competitive performance concerning typically reported values (104–107) for current noble metal-based PCs technologies and a new record concerning PCs fabricated by LIL (104–105). This research demonstrates the high competitivity of these simple Au nanodisks-based 2D PCs, fabricated using an efficient large-scale and low-cost lithography technique, for fast, high spectral resolution and highly reproducible SERS-based molecular sensing.

Effects of valence changes of iodine on perovskite (CH3NH3PbI3) Raman

In recent years, organic–inorganic hybrid perovskite materials have garnered extensive attention from scholars. Given its high absorption coefficient, carrier mobility, and diffusion length, it is widely studied for applications in various optoelectronic devices, such as solar cells, photodetectors, field-effect transistors, and light emitting diodes. Among them, the interfacial charge transfer process is a key factor influencing the performance of devices using perovskite materials. The charge transfer (CT) at the interface is typically detected via Raman spectroscopy. There are three types of related CT processes, namely, the interfacial ground state charge transfer, the photoinduced charge transfer resonance, and the electronic excitation resonance within the molecule itself. Among these factors, electronic excitation resonance manifests as an exciton resonance within the perovskite structure, providing energy for nearby charge transfer, thereby promoting charge transfer and enhancing Raman signals. Therefore, enhancing exciton resonance within the perovskite structure plays a crucial role in optoelectronic devices. This paper aimed to study the mechanism of oxygen plasma passivation of interstitial iodine defects and its enhancement effect on the Raman of perovskite substrates. Typically, interstitial iodine defects induce electron–hole recombination. In the process of oxygen plasma treatment, interstitial iodine is converted into pentavalent iodine, which can effectively fill related defects, inhibit electron–hole recombination, and prolong exciton lifetime, thereby promoting charge transfer and enhancing Raman intensity.

Charge-transfer-driven ultrasensitive SERS sensing in a two-dimensional titanium carbonitride MXene.

Two-dimensional (2D) MXenes stand out as promising platforms for surface-enhanced Raman scattering (SERS) sensing owing to their metallic feature, various compositions, high surface area, compatibility with functionalization, and ease of fabrication. In this work, we report a high-performance 2D titanium carbonitride (Ti3CN) MXene SERS substrate. We reveal that the abundant electronic density of states near the Fermi level of Ti3CN MXene boosts the efficiency of photo-induced charge transfer at the interface of Ti3CN/molecule, resulting in significant Raman enhancement. The SERS sensitivity of Ti3CN MXene is further promoted through a 2D morphology regulation and molecular enrichment strategies. Moreover, prohibited drugs are detectable on this substrate, presenting the potential of trace-amount analysis on Ti3CN MXene. This work provides a deep insight of the SERS mechanisms of Ti3CN MXene and broadens the practical application of transition metal carbonitride MXene SERS substrates.

Polymer composite membranes as SERS substrate materials: Recyclable and highly stable

Surface-enhanced Raman spectroscopy (SERS), as an emerging molecular-level detection technology, has attracted considerable research attention, especially in the context of substrate materials exhibiting Raman enhancement effects. Membrane materials, owing to their commendable uniformity, stability, and ease of modification, hold a pivotal position in the landscape of SERS substrate materials. However, existing SERS substrates based on membrane materials have limited adaptability to a spectrum of extreme environments, including but not limited to high or low pH, elevated salinity, and corrosive solutions. Additionally, SERS substrate materials are synonymous with “waste” and “high investment” because of their inherent disposable nature. This study introduces a pioneering approach, presenting a polymer composite membrane founded on epoxy resin, cellulose paper, and nanometal particles as a novel SERS substrate material. Given the outstanding stability of epoxy resin, the substrate material exhibits normal functionality in environments ranging from −80 ℃ to 100 ℃, with pH levels spanning 1 to 13, and in highly acidic solutions (concentration ≤3 %) and highly alkaline solutions (concentration ≤0.1 M). Moreover, the cleanability inherent in the polymer composite membrane renders the substrate material recyclable. Experimental findings reveal that even after six repeated uses, the substrate material sustains a stable Raman signal enhancement effect. The integration of recyclability and heightened stability makes this SERS substrate material a promising candidate for real-time monitoring and batch testing in chemical production processes or other complex environments.

Thiol-functionalized mesoporous silica-embedded AuNPs with highly sensitive substrates for surface-enhanced Raman scattering detection

Surface-enhanced Raman spectroscopy (SERS) provides a fast, simple, and label-free approach that can directly detect various analytes attached to SERS substrates and provide qualitative and quantitative information based on the SERS spectra of the analyte. The signal enhancement provided by noble metal particles allows us to achieve high sensitivity and good stability even at low concentrations in water quality testing. Over the past decade, SERS has become increasingly popular in the detection field, highlighting its significant application potential. However, the signal enhancement of single AuNPs is inferior to that of AgNPs, but we can achieve an overall enhancement by uniformly arranging multiple AuNPs. The hot-spot effect, which is crucial for Raman signal enhancement, occurs only when NMNPs are within a specific distance. However, when noble metal particles come into contact with each other, the enhancement effect of the hot spot disappears. Therefore, in this study, AuNPs@MPS-SH substrates with surface-enhanced Raman scattering (SERS) activity were successfully synthesized by immobilizing AuNPs on thiol-functionalized mesoporous silica (MPS-SH). MPS nanospheres with tailored pore size and surface-bound -SH groups were synthesized for the controlled embedding of Au nanoparticles (AuNPs). By adjusting the ratio of reactants, uniform AuNP dispersion and strong MPS-AuNP interactions were achieved. This optimized structure creates localized surface plasmon resonance (LSPR) hotspots, significantly enhancing the surface-enhanced Raman scattering (SERS) effect for ultrasensitive analyte detection. Transmission electron microscopy (TEM) revealed that the average diameter of MPS nanoparticles is 260 nm, with a pore size of 8 nm. Optimal Raman enhancement was achieved at an AuNPs concentration of 2.6 × 1018 particles/mL. The lowest detection limit concentration for Rhodamine 6G was below 10−6 M, while for uremic toxin (urea) it was below 10−3 M. The ability to directly detect low concentrations by mixing with the analyte demonstrates the ultra-high sensitivity and label-free detection potential of this study in the fields of water quality and disease detection.

Two-dimensional tellurium nanosheet: A novel sensitive and stable surface-enhanced Raman scattering substrate

Two-dimensional (2D) materials with merits such as low cost, high chemical inertness and tunable electronic structure have become favorable candidates for next generation of surface-enhanced Raman scattering (SERS) platforms. However, the SERS sensitivity of 2D materials still needs to be improved and the large-scale synthesis methods should be developed to meet the requirements of practical applications. In this work, we explored performances of a brand-new SERS substrate made of 2D Te nanosheets (NSs), which exhibited thickness-dependent SERS properties, with thinner nanosheets yielding stronger SERS intensity. Under optimized conditions, the limits of detection (LODs) reached the order of 10−9 M combining with SERS enhancement factors (EFs) as high as 105 for copper phthalocyanine (CuPc) and methylene blue (MB). This impressive SERS performance could be attributed to the strong interaction and photoinduced charge transfer (PICT) processes between 2D Te NSs and molecules. Benefiting from the appropriate positions of valence band (VB) and conduction band (CB), the 2D Te NSs showed significant Raman enhancement for various molecules. Furthermore, the 2D Te NSs exhibited good air-stability for up to ∼2 months. These outstanding performances establish 2D Te NSs as a favorable SERS detection material with enormous potential in practical applications.