Multimodal Gold Nanostars as SERS Tags for Optically-Driven Doxorubicin Release Study in Cancer Cells

Surface Enhanced Raman Scattering (SERS) active gold nanostars represent an opportunity in the field of bioimaging and drug delivery. The combination of gold surface chemical versatility with the possibility to tune the optical properties changing the nanoparticles shape constitutes a multimodal approach for the investigation of the behavior of these carriers inside living cells. In this work, SERS active star-shaped nanoparticles were functionalized with doxorubicin molecules and covered with immuno-mimetic thiolated polyethylene glycol (PEG). Doxorubicin-conjugate gold nanoparticles show an intense Raman enhancement, a good stability in physiological conditions, and a low cytotoxicity. The strong adsorption of the anticancer drug doxorubicin in close contact with the gold nanostars surface enables their use as SERS tag imaging probes in vivo. Upon laser irradiation of the nanoparticles, a strong SERS signal is generated by the doxorubicin molecules close to the nanostars surface, enabling the localization of the nanoparticles inside the cells. After long time irradiation, the SERS signal drops, indicating the thermally driven delivery of the drug inside the cell. Therefore, the combination of SERS and laser scanning confocal microscopy is a powerful technique for the real-time analysis of drug release in living cells.

Facile Detection and Quantification of Acetamiprid Using a Portable Raman Spectrometer Combined with Self-Assembled Gold Nanoparticle Array

Rapid and facile determination of pesticides is critically important in food and environmental monitoring. This study developed a self-assembled gold nanoparticle array based SERS method for highly specific and sensitive detection of acetamiprid, a neonicotinoid pesticide that used to be difficult in SERS analysis due to its low affinity with SERS substrates. SERS detection and quantification of acetamiprid was conducted with self-assembled gold nanoparticle arrays at the interface of chloroform and water as the enhancing substrate. Since targets dissolved in chloroform (organic phase) also have access to the hot-spots of Au NP array, the developed method exhibited good sensitivity and specificity for acetamiprid determination. Under the optimal conditions, SERS intensities at Raman shifts of 631 cm−1 and 1109 cm−1 displayed a good linear relationship with the logarithm concentration of acetamiprid in the range of 5.0 × 10−7 to 1.0 × 10−4 mol/L (0.11335 ppm to 22.67 ppm), with correlation coefficients of 0.97972 and 0.97552, respectively. The calculated LOD and LOQ of this method were 1.19 × 10−7 mol/L (0.265 ppb) and 2.63 × 10−7 mol/L (0.586 ppb), respectively, using SERS signal at 631 cm−1, and 2.95 × 10−7 mol/L (0.657 ppb) and 3.86 × 10−7 mol/L (0.860 ppb) using SERS signal at 1109 cm−1, respectively. Furthermore, the developed SERS method was successfully applied in determining acetamiprid on the surface of apple and spinach. This method offers an exciting opportunity for rapid detection of acetamiprid and other organic pesticides considering its advantages of simple preparation process, good specificity and sensitivity, and short detection time (within 1 h).

Stabile SERS Encoded Silver Silica Nanocomposites for Industrial Labeling – the Case of COVID-19 Diagnosis

Biosensors, especially those with a SERS readout, are required for an early and precise healthcare diagnosis. Unreproducible SERS platforms hampers the clinical translation of SERS. Here we report a synthetic procedure to obtain stabile, reproducible and robust highly-SERS performing nanocomposites for labelling. We control the NPs agglomeration and codification which results in an increased number of hot spots, thus exhibiting reproducible and superior Raman enhancement. We studied fundamental aspects affecting the plasmonic thiol bond resulting in pH exhibiting a determining role. We validated their biosensing performance by designing a SERS-based sandwich immunoassay against COVID-19. The limits of detection for the recombinant SARS-CoV-2 protein is below 0.01 ng/μL. We offered herein one nanostructure with robust and homogeneous SERS signal which can be potentially applied for biodiagnosis.

“Coffee Ring” Effect of Ag Colloidal Nanoparticles Dried on Glass: Impact to Surface-Enhanced Raman Scattering (SERS)

It is well known that spontaneous drying of some fluid droplets on certain solid surfaces forms a “coffee ring” pattern. In this paper, we studied “coffee ring” formation for two kinds of Ag colloidal nanoparticles (borohydride-reduced (b.-r.) and hydroxylamine-reduced (h.-r.)) and its impact on surface-enhanced Raman scattering (SERS). Optical and scanning electron microscopies were used to observe the morphology of the dried rings as well. We used 5,10,15,20-tetrakis(1-methyl-4-pyridyl)porphyrin (TMPyP) as a testing SERS molecular probe. The results showed that the structure of the edge rings of dried drops of Ag colloid/TMPyP systems was different for b.-r. and h.-r. nanoparticles. The inherent limitation of our approach is inhomogeneity in particle and “hot spots” distribution, SERS signal fluctuation, and consequently low spectral reproducibility. However, in the case of h.-r. nanoparticles, it formed a structure with highly enhancing sites (“hot spots”) providing enormous SERS signal of TMPyP. Higher sensitivity and the possibility of spectral mapping over the dried pattern are advantages in comparison with the measurements from colloidal suspension. Although our approach is not reliable for quantitative analytical SERS applications, it can serve as a simple, cheap, and fast prescan method, which can be easily implemented for preliminary SERS analysis.

Modification of a SERS-active Ag surface to promote adsorption of charged analytes: effect of Cu2+ ions

This work studies the impact of the electrostatic interaction between analyte molecules and silver nanoparticles (Ag NPs) on the intensity of surface-enhanced Raman scattering (SERS). For this, we fabricated nanostructured plasmonic films by immobilization of Ag NPs on glass plates and functionalized them by a set of differently charged hydrophilic thiols (sodium 2-mercaptoethyl sulfonate, mercaptopropionic acid, 2-mercaptoethanol, 2-(dimethylamino)ethanethiol hydrochloride, and thiocholine) to vary the surface charge of the SERS substrate. We used two oppositely charged porphyrins, cationic copper(II) tetrakis(4-N-methylpyridyl) porphine (CuTMpyP4) and anionic copper(II) 5,10,15,20-tetrakis(4-sulfonatophenyl)porphine (CuTSPP4), with equal charge value and similar structure as model analytes to probe the SERS signal. Our results indicate that the SERS spectrum intensity strongly, up to complete signal disappearance, correlates with the surface charge of the substrate, which tends to be negative. Using the data obtained and our model SERS system, we analyzed the modification of the Ag surface by different reagents (lithium chloride, polyethylenimine, polyhexamethylene guanidine, and multicharged metal ions). Finally, all those surface modifications were tested using a negatively charged oligonucleotide labeled with Black Hole Quencher dye. Only the addition of copper ions into the analyte solution yielded a good SERS signal. Considering the strong interaction of copper ions with the oligonucleotide molecules, we suppose that inversion of the analyte charge played a key role in this case, instead of a change of charge of the substrate surface. Changing the charge of analytes could be a promising way to get clear SERS spectra of negatively charged molecules on Ag SERS-active supports.

Modification of Ag SERS-active surface to promote charged analytes adsorption

This work aims at the impact of the electrostatic interaction between analyte molecules and silver nanoparticles (Ag NPs) on the surface enhanced Raman scattering (SERS) performance. For this, we fabricated nanostructured plasmonic films by immobilization of Ag NPs on glass plates and functionalized them by a set of differently charged hydrophilic thiols (sodium 2-mercaptoethyl sulfonate, mercaptopropionic acid, 2-mercaptoethanol, 2-(dimethylamino) ethanethiol hydrochloride and thiocholine) to vary the surface charge of the SERS-substrate. We used two oppositely charged porphyrins, cationic Cu(II)-tetrakis(4-N-methylpyridyl) porphine (CuTMpyP4) and anionic Cu(II)-5,10,15,20-tetrakis(4-sulphonatophenyl) porphine (CuTSPP4), with equal charge value and similar structure as model analytes to probe SERS signal. Our results indicate that the SERS spectrum intensity strongly, up to complete signal disappearance, correlates with the substrate’s surface charge that tends to be negative. Using the data obtained and our model SERS-system, we analyzed modification of Ag surface by different reagents (lithium chloride, polyethyleneimine, polyhexamethylene guanidine and multicharged metal ions). Finally, all those surface modifications were tested using a negatively charged oligonucleotide labeled with Black Hole Quencher (BHQ1) dye. Only addition of copper ions into the analyte solution allowed to get a good SERS signal. Considering strong interaction of copper ions with the DNA molecule, we suppose that the analyte charge inversion played the key role in that case, instead of the recharging of the substrate surface. Analyte recharging could be a promising way to get intensive SERS spectra of negatively charged molecules on Ag SERS-active supports.

Using Si/MoS2 Core-Shell Nanopillar Arrays Enhances SERS Signal

Two-dimensional layered material Molybdenum disulfide (MoS2) exhibits a flat surface without dangling bonds and is expected to be a suitable surface-enhanced Raman scattering (SERS) substrate for the detection of organic molecules. However, further fabrication of nanostructures for enhancement of SERS is necessary because of the low detection efficiency of MoS2. In this paper, period-distribution Si/MoS2 core/shell nanopillar (NP) arrays were fabricated for SERS. The MoS2 thin films were formed on the surface of Si NPs by sulfurizing the MoO3 thin films coated on the Si NP arrays. Scanning electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy were performed to characterize Si/MoS2 core-shell nanostructure. In comparison with a bare Si substrate and MoS2 thin film, the use of Si/MoS2 core-shell NP arrays as SERS substrates enhances the intensity of each SERS signal peak for Rhodamine 6G (R6G) molecules, and especially exhibits about 75-fold and 7-fold enhancements in the 1361 cm−1 peak signal, respectively. We suggest that the Si/MoS2 core-shell NP arrays with larger area could absorb more R6G molecules and provide larger interfaces between MoS2 and R6G molecules, leading to higher opportunity of charge transfer process and exciton transitions. Therefore, the Si/MoS2 core/shell NP arrays could effectively enhance SERS signal and serve as excellent SERS substrates in biomedical detection.