PCA-assisted direct diagnosis of Aβ proteins for Alzheimer's disease using non-metallic SERS platform of graphitic carbon nitride@metal-organic framework.

Application of serum SERS technology based on thermally annealed silver nanoparticle composite substrate in breast cancer.

Heterostructures have emerged as promising contenders for surface-enhanced Raman scattering (SERS) applications. Nevertheless, the construction of a composite SERS substrate with well-matched energy levels persists as a challenge, primarily due to the restricted selection of SERS-active materials. In this study, we successfully synthesized a Ag nanoparticles (NPs)/ZnO nanorods (NRs)/GaN heterojunction featuring type II staggered energy bands, which provides an outstanding platform for efficient SERS detection. Moreover, considering that both ZnO and GaN are pyroelectric semiconductor materials, the pyroelectric potential generated at the ZnO and GaN heterojunctions improves energy level matching. This, in turn, promotes charge transfer within the composite structure and substantially enhances the chemical enhancement of SERS. Under the modulation of pyroelectricity, the SERS signal intensity of rhodamine 6G (R6G) increased by approximately 15-fold, and the detection limit decreased by at least 2 orders of magnitude. Additionally, the substrate exhibited the capability to detect pollutants, such as 20 nm nanoplastics and thiram, indicating its significant potential for environmental monitoring.

Preface to the special issue dedicated to Professor Richard P. Van Duyne (1945–2019)

Noble metal and semiconductor composite substrates possess high sensitivity, excellent stability, good biocompatibility, and selective enhancement, making them an important research direction in the field of surface-enhanced Raman scattering (SERS). Ta2O5, as a semiconductor material with high thermal stability, corrosion resistance, outstanding optical properties, and catalytic performance, has great potential in SERS research. This study aims to design and fabricate a composite SERS substrate based on Ta2O5 nanostructures, achieving optimal detection performance by combining the urchin-like structure of Ta2O5 with silver nanoparticles (Ag NPs). The urchin-like Ta2O5 nanostructures were prepared using a hydrothermal reaction method. The bandgap was modulated through structure design and the self-doping technique, the charge transfer efficiency and surface plasmon resonance effects were improved, thereby achieving better SERS performance. The composite substrate enables highly sensitive quantitative detection. This composite SERS substrate combines the electromagnetic enhancement mechanism (EM) and chemical enhancement mechanism (CM), achieving ultra-low detection limits of 10-13 M for R6G. Within the concentration range above 10-12 M, there is a good linear relationship between concentration and peak intensity, demonstrating excellent quantitative analysis capabilities. Furthermore, this composite SERS substrate is capable of precise detection of analytes such as crystal violet (CV) and methylene blue (MB), holding broad application prospects in areas such as food safety and environmental monitoring.

Three-dimensional urchin-like K2Ti8O17 / Ag NPs composite as a SERS substrate for detecting folic acid and thiram.

As a noninvasive and label-free optical technique, Raman spectroscopy offers significant advantages in studying the structure and properties of biomacromolecules, as well as real-time changes in cellular molecular structure. However, its practical applications are hindered by weak scattering responses, low signal intensity, and poor spectral uniformity, which affect the subsequent accuracy of spectral analysis. To address these issues, we report a novel surface-enhanced Raman scattering (SERS) substrate based on a pyramidal pitted silicon (PPSi) array structure adhered with Au-shell Ag-core nanospheres (Au@Ag NSs). By preparing a highly uniform PPSi array substrate with controllable size and arrangement, and constructing SERS-active Au@Ag NSs on this substrate, a three-dimensional (3D) composite SERS substrate is realized. The enhancement performance and spectral uniformity of 3D composite SERS substrate were examined using crystal violet (CV) and Rhodamine 6G (R6G) molecules, achieving a minimum detectable concentration of R6G at 10-9 M and the analytical enhancement factor (AEF) of 4.2 × 108. Moreover, SERS detection of biological samples with varying concentrations of Staphylococcus aureus demonstrated excellent biocompatibility of the SERS substrate and enabled quantitative analysis of bacterial concentration (R 2 = 99.7 %). Theoretical simulations using finite-difference time-domain (FDTD) analysis were conducted to examine the electromagnetic field distribution of the three-dimensional SERS composite substrate, confirming its local electric field enhancement effect. These experimental and theoretical results indicate that the Au@Ag NSs/PPSi substrate with a regulable pyramidal pitted array is a promising candidate for sensitive, label-free SERS detection in medical and biotechnological applications.

Surface-enhanced Raman spectroscopy for studying the interaction of N-propyl substituted imidazole compound with salmon sperm DNA.

A simple paper-based surface enhanced Raman scattering (SERS) platform and magnetic separation for cancer screening

The research reported in this thesis focuses on the fundamental science and engineering required for the fabrication and optimization of nanoparticles functionalized paper as Surface Enhanced Raman Scattering (SERS) bio-diagnostics platform. It addresses the current Sensitivity, Selectivity, Simplicity and Strength (4S) limitations of bioactive paper. The research vision is to develop a nanoparticles treated paper as a generic diagnostic platform to identify and quantify low concentrations of a specific (bio)analyte in aqueous solutions. The product concept is a “dipstick sensor” based on functionalized gold nanoparticle treated paper (AuNP paper) for SERS detection. Such AuNP paper test would allow the direct, rapid and easy detection of (bio)analyte molecules at very low concentrations (below the nanomolar range), making it suitable for biomedical analysis, such as in cancer detection. It also eliminates the tedious preparation of multiple reactants and washing steps involved in current technology such as the Enzyme-Linked Immunosorbent Assay (ELISA) based bioactive paper. Three parallel research length scales are investigated: nano, micro and macro. This involves quantifying the distribution and adsorption state of nanoparticles on paper (nanoscale). The effects of gold nanoparticles (AuNPs) concentration and 3-dimensional (3D) distribution profile on their adsorption and aggregation states on paper were explored. The surface coverage of AuNPs on paper scaled linearly with their concentration profile in solutions. The SERS performances of the AuNPs-treated papers were evaluated with a model Raman molecule, 4-aminothiophenol (4-ATP), and their SERS intensities increased linearly with the density of AuNPs on paper. The role of z-distribution of AuNPs within the bulk of paper was highlighted; their three-dimensional (3D) architecture was able to quench the background noise through interlayer plasmon coupling, thus amplifying the SERS signal. The retention and aggregation state of nanoparticles on paper was controlled to drastically optimize the SERS performance (microscale). Paper substrates were pre-treated with a series of cationic polyacrylamide (CPAM) solutions to control the AuNPs adsorption and aggregation state on paper. The CPAM pre-treated paper produced a more uniform distribution of AuNPs compared to untreated paper. CPAM chains which adsorbed on paper in a high loops and tails conformation promotes efficient bridging of AuNPs to achieve higher surface coverage and aggregation of AuNPs on paper. This configuration is favored by CPAM solutions of higher concentration, charge density and molecular weight. A simple approach to form and visualize polyelectrolyte-nanoparticles chaplet like structures on paper was developed by using negatively-charged gold nanoparticles (AuNPs) to decorate polymer chain of CPAM. AuNP chaplets were adsorbed in an opposite direction to the cellulose fibers and along the length of the CPAM molecules which were draped over the fibers. The effects of CPAM polymer concentration, charge density and molecular weight on the dimension of AuNP chaplets were quantified. Assembling nanometer-scale components (AuNPs) into micrometer-scale arrays (chaplets) on a porous paper substrate can be a promising strategy for low-cost nanoelectronics applications The SERS properties of nanoparticles functionalized paper were quantified and optimized (macroscale). The effect of CPAM concentration, charge density and molecular weight on the aggregation and surface coverage of AuNPs on paper and ultimately the SERS signal of 4-ATP was quantified. The optimized AuNPs-CPAM paper showed a higher sensitivity and Raman enhancement factor (EF), which was almost an order of magnitude higher than the untreated AuNPs paper. The effect of CPAM dissolution kinetic on the SERS reproducibility was also quantified. SERS reproducibility of AuNPs on CPAM pre-treated paper both increase with dissolution time of CPAM, as the heterogeneity of AuNP distribution and aggregate size decreases; increasing CPAM charge density accentuated this tendency. After the SERS efficiency towards the detection of model Raman molecule (4-ATP) was proven, AuNPs paper was upgraded by functionalizing the AuNPs with biotin/streptavidin assemblies for the detection of antibody-antigen binding. The modification of antibody local structure due to the interaction with antigen was detected. Evidence of antigen binding was elucidated from the SERS spectra, confirming the presence of antigen. Reproducible spectra features were observed for the functionalized AuNP papers which were exposed to different concentration of antigen; their intensity increased as a function of antigen concentration. By conducting these studies and merging these three length scales of research, a novel strategy to engineer AuNPs functionalized paper as a low-cost and generic SERS platform for bio-diagnostic applications was developed.

In this study, we developed a simple surface-enhanced Raman Scattering (SERS) composite substrate, composed of an all-metal metasurface and on-surface random distributing silver nanoparticles (AgNPs), to enhance the performance of SERS sensing. The metasurface is made up of gold (Au) nanopillars array on aluminum (Al), it can localize the electromagnetic field energy with a resonant absorption peak near the 630 nm wavelength, which contributes to the SERS performance of AgNPs deposited into the structure. The composite substrate can significantly improve the sensing performance, and the SERS Enhancement Factor (EF) reaches 2.81 × 106. The substrate also has good stability and reproducibility. The research is based on the combination of Localized Surface Plasmon Resonance (LSPR) and SERS effects, providing a method and idea for improving the sensitivity of SERS detection, and achieving the trace detection of Rhodamine 6G (R6G) and Thiram at 10−10 M, respectively.

Aptamers are small oligonucleotides selected in vitro for their strong and specific binding to target analytes, increasingly serving as alternatives to antibodies in bioanalysis. Surface Enhanced Raman Scattering (SERS) is particularly noted for its high sensitivity and selectivity, providing a greatly amplified vibrational spectrum of the analyte compared to traditional Raman spectroscopy [1]. Combining aptamers with SERS transducers offers valuable tools for selective measurements. However, challenges such as nonspecific adsorption (NSA) and overlapping spectral contributions in complex samples can impede sensitivity and specificity. To improve detection with SERS aptasensors, simple approaches, that use widely available, low-cost substrates and reagents have a high chance to be adopted by the biosensor community.We hereby investigated several strategies for maximizing the specific to nonspecific signal ratio in the direct detection of two proteins, lysozyme and matrix metalloproteinase 9 (MMP9), in buffer and serum. The study explored the limits that can be reached for the direct, aptamer-based detection of these proteins by using simple SERS substrates (screen-printed electrodes) and common blocking agents (bovine serum albumin, various thiols). In addition, it was studied the effect of applying an electrical potential of ± 0.2 V on the detection performance of the aptasensor.Lysozyme (14 kDa, isoelectric point pI = 11) is a non-specific marker of inflammation [2]. Its detection was investigated with two DNA aptamer sequences [3,4] and was facilitated by the adenine bases in the aptamer, which provided an intense band at 724 cm-1 in the SERS spectrum. In the case of MMP9 (a cancer biomarker of 92 kDa), the aptamer immobilized on the SERS substrate has not provided bands with similar intensity (the aptamer contains only two adenine groups). A labeled aptamer was used instead, which was modified at the 3’ end with Cyanine 3 (Cy3), a fluorescent dye with a known Raman spectrum.Various screen-printed electrodes were tested as SERS substrates, including roughened Au electrodes, electrodes with electrodeposited gold nanoparticles (AuNP), or modified with AgNP by drop-casting. The best substrates were selected based on tests with 4-mercaptobenzoic acid (MBA), lysozyme aptamer, and Cy3-labeled, MMP 9 aptamer. For the selected electrodes, the intensity of specific Raman bands was correlated with the substrate morphology, investigated by Scanning Electron Microscopy and with the electrochemical characteristics measured by voltammetry.To evaluate the resistance to NSA, the various substrates, coated with antifouling layers, were incubated with protein and serum samples and the SERS spectra before and after incubation with foulants were compared. Differential pulse voltammetry measurements were also performed to confirm fouling. It was found that while backfilling with thiols such as 11-mercaptoundecanol protected the aptamer-functionalized substrates against NSA [5], the intensity of the relevant bands in the SERS spectrum decreased significantly, dramatically affecting the sensitivity of detection. Application of a negative potential (-0.2V vs. Ag/AgCl) promoted the NSA of the positively charged lysozyme, while a positive potential (+0.2 V vs. Ag/AgCl) discouraged NSA but also decreased the specific signal.Blocking the surface with BSA significantly reduced the NSA from protein and serum samples. However, the changes in the SERS spectrum upon testing MMP9 samples were minimal and observed mainly at concentrations of 1 µg/mL and higher. A better solution was to add BSA to the samples. In this case, 0.02 µg/mL MMP9 was successfully detected, and a limit test for MMP9 can be envisaged as a potential screening for cancer. Interpretation of SERS spectra of aptasensors and control electrodes by principal component analysis enabled the identification of the spectral bands that were most relevant for the specific aptamer-MMP9 binding and that can be used for quantitative detection.Overall, adding BSA to the sample, interpreting data by chemometric methods, and applying an electric field are some of the tools available to surpass some of the limitations of SERS aptasensors induced by NSA and fast dissociating aptamers. References Han, X.X., Rodriguez, R.S., Haynes, C.L. et al.Surface-enhanced Raman spectroscopy. Nat Rev Methods Primers 1, 87 (2021).Banciu M, Numan N, Vasilescu A. Optical biosensing of lysozyme. J Mol Structure 1250 (15) (2022), 131639.Cox, J.C.; Ellington, A.D. Automated selection of anti-protein aptamers. Med. Chem., 9 (2001), 2525–2531.Tran, D.T.; Janssen, K.P.; Pollet, J.; Lammertyn, E.; Anne, J.; Van Schepdael, A.; Lammertyn, J. Selection and characterization of DNA aptamers for egg white lysozyme. Molecules 15 (2010), 1127–1140Titoiu, A. M., Porumb, R., Fanjul-Bolado, P., Epure, P., Zamfir, M., Vasilescu, A. Detection of allergenic lysozyme during winemaking with an electrochemical aptasensor, Electroanalysis 31 (11) (2019), 2262-2273.

The application of nanomaterials in ocular drug delivery is mainly concentrated in nano-controlled release systems. Due to the unique properties of nanomaterials, the use of nanomaterials to carry drugs for treating eye diseases has great advantages compared with traditional drug delivery methods. The nano-formulation of the drug has higher bioavailability and lower side effects. Therefore, the nano-controlled release system has a good application prospect in ophthalmology. In this paper, Fe2O3 magnetic nanoparticles were first prepared by co-deposition, and then the nanoparticles were clad with silica to prepare Fe2O3 @SiO2 core-shell nanostructures. Secondly, an ordered array surface-enhanced Raman scattering (SERS) active substrate was formed on the surface of the porous layer of porous anode aluminium oxide (PAA) and the barrier layer using vacuum electron beam evaporation technology using PAA films as templates. Then, the shell thickness of Fe2O3@SiO2 and the number of coated magnetic particles were controlled by controlling the dosage of ethyl orthosilicate, and a layer of SERS active gold nanoshells was grown after further adsorption of gold seeds to prepare a composite SERS active substrate. Enhanced performance magnetic nanomaterial Fe2O3@SiO2@PAA @Au. Finally, the SERS spectrum and fluorescence quenching characteristics of ocular cells adsorbed on the substrate were detected and analysed. The results show that the magnetic nanomaterial Fe2O3@SiO2@PAA @Au with enhanced performance of SERS active substrate has a good enhancement effect on the Raman scattering signal of eye cells, and to a certain extent, it can eliminate the interference of the fluorescent background. Moreover, the ordered array of SERS active substrates not only has a high SERS enhancement ability and ability to quench fluorescence, but also does not have interference peaks of oxalate impurities remaining in the PAA film, which can obtain more detailed information of the Raman scattering spectrum of eye cells to achieve eye care.

PCA-WRKNN-assisted label-free SERS serum analysis platform enabling non-invasive diagnosis of Alzheimer’s disease

Fabrication of SERS composite substrates using Ag nanotriangles-modified SiO2 photonic crystal and the application of malachite green detection

Rapid and reliable detection of antimicrobial-resistant (AMR) bacteria is critical in combatting the growing threat of multi-drug resistance. Among all the available detection techniques, surface-enhanced Raman scattering (SERS) has emerged as a powerful tool for detecting a vast range of molecules and microorganisms, with significant potential for identifying bacterial strains. However, current studies using SERS predominantly utilize a drop-cast method, where a bacterial sample is dried with the SERS substrate to produce SERS spectra of bacteria. While effective, this method is time-consuming and less consistent. In this study, we propose a liquid-based SERS method for the rapid identification and differentiation of bacteria strains. Using gold nanoparticles (AuNPs) as the SERS substrate, we focus on detecting and distinguishing Escherichia coli and Pseudomonas aeruginosa in aqueous samples. Our study investigates multiple variables including nanoparticle size (30, 50, and 80 nm), surface charge/capping agent (negative and positive), and analyte suspension media (water and 0.9% NaCl). We found that fresh bacteria samples in 0.9% NaCl mixed with citrate coated AuNPs with the size of 50 nm yielded optimal parameters for bacteria detection. Comparing drop-cast and liquid methods for SERS detection, we determined that the liquid method provided clearer and more consistent SERS spectra, facilitating effective analysis using Principal Component Analysis (PCA). Our method reliably differentiated E. coli bacterial strains and identified molecular features responsible for their differentiation. Overall, this manuscript presents a reproducible, straightforward, and efficient approach for bacteria detection and differentiation using SERS, contributing to strategies aimed at combating the spread of antibiotic-resistant bacteria.