Toward the nanoscale chemical and physical probing of milk-derived extracellular vesicles using Raman and tip-enhanced Raman spectroscopy.

Tip-enhanced Raman spectroscopy (TERS) is an advanced technique to perform local chemical analysis of the surface of a sample through the improvement of the sensitivity and the spatial resolution of Raman spectroscopy by plasmonic enhancement of the electromagnetic signal in correspondence with the nanometer-sized tip of an atomic force microscope (AFM). In this work, TERS is demonstrated to represent an innovative and powerful approach for studying extracellular vesicles, in particular bovine milk-derived extracellular vesicles (mEVs), which are nanostructures with considerable potential in drug delivery and therapeutic applications. Raman spectroscopy has been used to analyze mEVs at the micrometric and sub-micrometric scales to obtain a detailed Raman spectrum in order to identify the 'signature' of mEVs in terms of their characteristic molecular vibrations and, therefore, their chemical compositions. With the ability to improve lateral resolution, TERS has been used to study individual mEVs, demonstrating the possibility of investigating a single mEV selected on the surface of the sample and, moreover, analyzing specific locations on the selected mEV with nanometer lateral resolution. TERS potentially allows one to reveal local differences in the composition of mEVs providing new insights into their structure. Also, thanks to the intrinsic properties of TERS to acquire the signal from only the first few nanometers of the surface, chemical investigation of the lipid membrane in correspondence with the various locations of the selected mEV could be performed by analyzing the peaks of the Raman shift in the relevant range of the spectrum (2800-3000 cm-1). Despite being limited to mEVs, this work demonstrates the potential of TERS in the analysis of extracellular vesicles.

Strained Silicon Technology: Non-Destructive High-Lateral-Resolution Characterization Through Tip-Enhanced Raman Spectroscopy.

The semiconductor industry is undergoing a transformative phase, marked by the relentless drive for miniaturization and a constant demand for higher performance and energy efficiency. However, the reduction of metal-oxide-semiconductor field-effect transistor sizes for advanced technology nodes below 10 nm presents several challenges. In response, strained silicon technology has emerged as a key player, exploiting strain induction in the silicon crystal lattice to improve device performance. At the same time, there has been a growing need for characterization techniques that allow in-line monitoring of sample conditions during semiconductor manufacturing, as an alternative to traditional methods such as transmission electron microscopy or high-resolution X-ray diffraction, which have several limitations in terms of measurement time and sample destructiveness. This paper explores the application of advanced spectroscopic characterization techniques, in particular µ-Raman spectroscopy and tip-enhanced Raman spectroscopy (TERS), to meet the evolving needs of the semiconductor industry for quality control and failure analysis, increasingly requiring faster and non-destructive characterization techniques. µ-Raman provides insight into strain values and distributions of strained layers with different thicknesses and germanium concentrations, but its lateral resolution is constrained by the Abbe diffraction limit. TERS, on the other hand, emerges as a powerful non-destructive technique capable of overcoming diffraction limits by exploiting the combination of an atomic force microscope with a Raman spectrometer. This breakthrough makes it possible to estimate the chemical composition and induced strain in the lattice by evaluating the Raman peak position shifts in strained and unstrained silicon layers, providing crucial insights for nanoscale strain control. In particular, this paper focuses on the TERS characterization of Si0.7Ge0.3 epitaxial layers grown on a silicon-on-insulator device, demonstrating the effectiveness of this technique and the high lateral resolution that can be achieved.