Preparation of (3-Aminopropyl)triethoxysilane-Modified Silica Particles with Tunable Isoelectric Point.

Silica particles modified with amino groups hold immense potential across diverse fields, owing to their distinctive properties. The widely adopted method of surface modification, utilizing (3-aminopropyl)triethoxysilane (APTES), facilitates the incorporation of amino-functional groups onto the silica surface, thereby creating sites for subsequent functionalization with other molecules. In this context, the ability to precisely tailor the surface properties of amino-functionalized silica particles is crucial for optimizing their performance in various applications. In this work, we systematically investigated the influence of the APTES concentration and water content on the density of amino groups grafted on the silica surface within an ethanol-water mixture. The rational control of hydrolysis and condensation of APTES enabled the precise regulation of the amino density on the silica surface, resulting in a notable shift in the isoelectric point from 2.9 to 9.2. Subsequently, we assembled amino-functionalized silica with different isoelectric points with gold nanoparticles to demonstrate their tunable ability as surface-enhanced Raman scattering (SERS) substrates. This controlled and tailored amino-functionalization process opens up new routes for fine-tuning the properties of silica particles, thereby expanding their utility across various applications in materials science, nanotechnology, and biomedicine.

Fabrication of Flexible Pyramid Array as SERS Substrate for Direct Sampling and Reproducible Detection.

Rapid extraction and analysis of target molecules from irregular surfaces are in high demand in the field of on-site analysis. Herein, a flexible platform used for surface-enhanced Raman scattering (SERS) based on an ordered polymer pyramid structure with half-imbedded silver nanoparticles (AgNPs) was prepared to address this issue. The fabrication includes the following steps: (1) creating inverted pyramid arrays in silicon substrate, (2) preparing a layer of AgNPs on the surface of the inverted pyramids, and (3) obtaining a substrate with an ordered polymer pyramids array with half-imbedded AgNPs by the molding method. This flexible substrate is capable of rapid extraction via a simple and convenient "paste and peel off" method. In addition, the substrate exhibits great repeatability and good sensitivity thanks to the uniformity and larger surface area of the ordered pyramids. The density of "hot spots" (local electromagnetic field with high intensity) is increased on the structured surface. Semi-imbedding silver particles in the polymer pyramids makes "hot spots" robust on the substrate. In addition, the preprepared silicon template with the inverted pyramids can be reused, which greatly reduces the production cost. With this substrate, we successfully analyzed thiram molecules on the epidermis of apples, cucumbers, and oranges, and the detection limits are 2.4, 3, and 3 ng/cm2, respectively. These results demonstrate the great potential of the substrate for in situ analysis, which can provide reference for the design of ideal SERS substrates.

Increasing hotspots density for high-sensitivity SERS detection by assembling array of Ag nanocubes.

Trace analysis has great promise in the fields of disease diagnosis and environment protection. Surface-enhanced Raman scattering (SERS) has wide range of utilization due to its reliable fingerprint detection. However, the sensitivity of SERS still needs to be enhanced. Raman scattering of target molecules around hotspots, the area with extremely strong electromagnetic field, can be highly amplified. Therefore, to increase the density of hotspots is one of the major approaches for enhancing the detection sensitivity of target molecules. In this paper, an ordered array of Ag nanocubes was assembled on a thiol modified silicon substrate as a SERS substrate, which provided high-density hotspots. The detection sensitivity is demonstrated by the limit of detection, which is down to 10-6 nM with Rhodamine 6G as probe molecule. The wide linear range (10-7-10-13 M) and low relative standard deviation (<6.48%) indicate the good reproducibility of the substrate. Furthermore, the substrate can be used for the detection of dye molecules in lake water. This method provides an approach for increasing hotspots of SERS substrate, which could be a promising method to achieve good reproducibility and high sensitivity.

Enhancing Detection Reproducibility of Surface-Enhanced Raman Scattering by Controlling Analytes under One Laser Spot.

Surface-enhanced Raman scattering (SERS), as a sensitive analytical technique, is expected to be used for quantification of trace analytes. At the current stage, high detection reproducibility should be guaranteed for realizing quantification analysis of trace analytes. The main obstacle to achieving high detection reproducibility is the nonuniform distribution of analyte molecules on substrates, particularly, the "coffee-ring" effect introduced by the flow of solute to the pinning of the contact line. Herein, we report a method to tackle this problem by controlling the location of analytes through tuning the wettability of the SERS substrate. With the combination of silver-assisted chemical etching and photolithography, the ordered Si patterns grafted silver nanoparticles with tunable wettability were integrated into a SERS substrate. With this substrate, high detection reproducibility was achieved by confining all the analyte molecules on the area of active plasmonic hot-spots within one laser, and the quantitative analysis was realized with ultrahigh sensitivity. Furthermore, the substrate is applicable for high-throughput detection.

Laser desorption/ionization on nanostructured silicon: morphology matters.

The surface morphology of the silicon nanostructure plays a crucial role in the laser desorption/ionization (LDI) process. Understanding the correlation between the surface morphology and LDI performance is the foundation for creating silicon substrates with high LDI efficiency. Most of the present studies focus only on the structural parameters (such as porosity, depth, total surface area, dimension, etc.) of a single structure, but their effects on LDI efficiency vary with the types of silicon structures. Herein, two representative types of silicon nanostructures, porous silicon (PSi) and thorny silicon (TSi), were created to address this issue. The results indicate that the PSi substrate can generate a stronger heat effect and is beneficial to desorption; the TSi substrate can facilitate electron transfer and is favorable to ionization. Subsequently, the assertion was further confirmed by simultaneously detecting a dozen of standard samples and a real sample on both the TSi and PSi substrates, in which PSi can significantly enhance the detection signals of organic salts, whereas the TSi substrate can greatly increase the LDI efficiencies of neutral analytes. This finding provides a foundation for improving the LDI performance by tailoring silicon nanostructures, which is helpful for designing and creating substrates with high LDI performance.

Silver-nanoparticle-grafted silicon nanocones for reproducible Raman detection of trace contaminants in complex liquid environments.

Super-hydrophobic delivery (SHD) is an efficient approach to enrich trace analytes into hot spot regions for ultrasensitive surface-enhanced Raman scattering (SERS) detection. In this article, we propose an efficient and simple method to prepare a highly-uniform SHD-SERS platform of high performance in trace detection, named as "silver-nanoparticle-grafted silicon nanocones" (termed AgNPs/SiNC) platform. It is fabricated via droplet-confined electroless deposition on the super-hydrophobic SiNC array. The AgNPs/SiNC platform allows trace analytes enriched into hot spots formed by AgNPs, leading to an excellent reproducibility and sensitivity. The relative standard deviation (RSD) for detecting R6G (10-7 M) is down to 4.70% and the lowest detection concentration for R6G is 10-14 M. Moreover, various contaminants in complex liquid environments, such as, crystal violet (10-9 M) in lake water, melamine (10-7 M) in liquid milk and methyl parathion (10-7 M) in tap water, can be detected using the SERS platform. This result demonstrates the great potential of the AgNPs/SiNC platform in the fields of food safety and environmental monitoring.

Carbon nanoparticles derived from carbon soot as a matrix for SALDI-MS analysis.

Carbon nanoparticles (NPs) from the incomplete combustion of a candle were used as matrix for surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). The washed carbon soot NPs (WCS NPs, ~48 nm) exhibit higher laser desorption/ionization efficiency and less background compared with other common metal and carbon matrices. WCS NPs present good reproducibility and high sensitivity in analyzing a wide range of molecules in both positive and negative ionization mode in SALDI-MS. The detection limit of glucose is 1 pmol with WCS NPs as matrix. WCS NPs can be used to quantitatively determine urine glucose, visualize latent fingerprint and image it with SALDI-MS. The UV absorption of WCS NPs and MS spectra analyzed with WCS NPs matrix remain the same after 10 months storage, indicating the good stability of WCS NPs as matrix. Graphical abstractSchematic representation of carbon nanoparticles derived from carbon soot and its application as matrix in SALDI-MS.

Size-matching hierarchical micropillar arrays for detecting circulating tumor cells in breast cancer patients' whole blood.

Circulating tumor cells (CTCs) are important markers for cancer diagnosis and treatment, but it is still a challenge to recognize and isolate CTCs because they are very rare in the blood. To selectively recognize CTCs and improve the capture efficiency, micro/nanostructured substrates have been fabricated for this application; however the size of CTCs is often ignored in designing and engineering micro/nanostructured substrates. Herein, a spiky polymer micropillar array is fabricated for capturing CTCs with high efficiency. The surface of the micropillar is cactus-like, and is composed of nanospikes. This hierarchical polymer array is designed according to the size of CTCs, which allows for more interactions of the CTCs with the array by setting the size of gaps among the micropillars to match with the CTCs. This polymer array is created by molding on an ordered silicon array, and then it is coated with an antiepithelial cell adhesion molecule antibody (anti-EpCAM). After co-culture with MCF-7 cells for 45 min, the capture efficiency of this array for CTCs is up to 91% ± 2%. Moreover, the anti-EpCAM modified polymer micropillar arrays present an excellent capacity to isolate CTCs from the whole blood samples of breast cancer patients. This study may provide a new concept for capturing target cells by designing and engineering micro/nanostructured substrates according to the size of target cells.

Confining analyte droplets on visible Si pillars for improving reproducibility and sensitivity of SALDI-TOF MS.

We present a universal method to efficiently improve reproducibility and sensitivity of surface-assisted laser desorption/ionization time of flight mass spectrometry (SALDI-TOF MS). In this method, the Si pillar array with unique surface wettability is used as substrate for ionizing analyte. The Si pillar is fabricated based on the combination of photolithography and metal-assisted chemical etching, which is of hydrophilic top and hydrophobic bottom and side wall. Based on the surface wettability of the Si pillar, a droplet of an aqueous analyte solution can be confined on the top of the Si pillar. After evaporation of solvent, an analyte deposition spot is formed on the top of Si pillar. The visible size of the Si pillar allows the sample spot to be easily found. Meanwhile, the diameter of the Si pillar is smaller than that of the laser, allowing the observation of all analyte molecules under one laser shot. Therefore, the reproducibility and sensitivity are highly improved with this method, which allows for the quantitative analysis. Furthermore, this method is applicable for different analytes dissolved in water, including amino acids, dye molecules, polypeptides, and polymers. The application of this substrate is demonstrated by analyzing real samples at low concentration. It should be a promising method for sensitive and reproducible detection for SALDI-TOF MS. Graphical abstract ᅟ.

A silver nanoislands on silica spheres platform: enriching trace amounts of analytes for ultrasensitive and reproducible SERS detection.

The performance of surface-enhanced Raman scattering (SERS) for detecting trace amounts of analytes depends highly on the enrichment of the diluted analytes into a small region that can be detected. A super-hydrophobic delivery (SHD) process is an excellent process to enrich even femtomolar analytes for SERS detection. However, it is still challenging to easily fabricate a low detection limit, high sensitivity and reproducible SHD-SERS substrate. In this article, we present a cost-effective and fewer-step method to fabricate a SHD-SERS substrate, named the "silver nanoislands on silica spheres" (SNOSS) platform. It is easily prepared via the thermal evaporation of silver onto a layer of super-hydrophobic paint, which contains single-scale surface-fluorinated silica spheres. The SNOSS platform performs reproducible detection, which brings the relative standard deviation down to 8.85% and 5.63% for detecting 10-8 M R6G in one spot and spot-to-spot set-ups, respectively. The coefficient of determination (R2) is 0.9773 for R6G. The SNOSS platform can be applied to the quantitative detection of analytes whose concentrations range from sub-micromolar to femtomolar levels.

Droplet-Confined Electroless Deposition of Silver Nanoparticles on Ordered Superhydrophobic Structures for High Uniform SERS Measurements.

Surface-enhanced Raman scattering spectroscopy (SERS) is a nondestructive testing technique. To increase reproducibility of the SERS measurement is the key issue for improving the performance of SERS. In this article, we demonstrate an efficient method to improve the reproducibility, using confined silver nanoparticles (AgNPs) as a substrate. The AgNPs are formed uniformly on the tops of the prepared nanopillars by droplet-confined electroless deposition on the hydrophobic Si nanopillar arrays. The AgNPs present an excellent reproducibility in Raman measurement; the relative standard deviation is down to 3.40%. There exists a great linear correlation between the concentration of Rhodamine 6G (R6G) and the Raman intensity in the log-log plot; R2 is 0.998, indicating that this SERS substrate can be applied for the quantitative SERS analysis. Meanwhile, the minimum detection concentration is down to 10-11 M on the hydrophobic substrate, with R6G as a probe molecule.