AFM-TERS provides nanoscale spatial resolution, which means that analysis of a single biological molecule is possible. This may allow a better understanding of biological systems and processes at the molecular level. Furthermore, it is possible to work in liquid conditions, which allows the study of biological samples in their native conditions.
Pathogens: Viruses and bacteria
AFM-TERS can also be used to monitor the interaction of pathogens with their hosts or antibiotics and guide the design of therapeutic drugs that specifically bind to the correct part of the infected cell.
- Neugebauer et al. : The first TERS spectrum from a bacterial surface. Doi: Visit site
- Cialla et al.: TERS investigation of a virus surface. Rapid identification and characterization of nanoscopic pathogens such as viruses. Doi: Visit site
- Wood et al.: TERS to probe hemozoin crystals in the digestive vacuole of a sectioned malaria parasite-infected single red-blood cell. Doi: Visit site
- Rusciano et al.: Bacillus subtilis spores were investigated giving important information about the component distribution of the spore ridges. Doi: Visit site
- Hermann et al.: TERS spectra obtained from different particles of the same virus strain show variations in relative peak intensities and positions of most spectral features observed. Doi: Visit site
- Zhe He et al.: TERS Imaging of Single-Stranded DNA with Single Base Resolution. DOI: Visit site
Amino Acids: proteins
The high spatial resolution and sensitivity of TERS can be exploited to investigate protein structures for pharmaceutical research. Furthermore, inherent complexity of investigating individual molecules calls for underpinning metrology to accurately analyse and interpret AFM and TERS spectra.
- Deckert-Gaudig et al.: TERS to provide information about the coordination sites of a peptide on a metal Surface. Doi: Visit site
- Blum et al.: compare the Raman spectra obtained by conventional Raman, SERS and TERS on a biological sample. Doi: Visit site
- Kurouski et al.: TERS investigation of insulin protofilaments and fibril polymorphs. Doi: Visit site
Nucleic Acids: RNA and DNA
DNA bases have characteristic Raman spectra, and with substantial increase in spatial resolution and sensitivity TERS can be used to identify individual bases of DNA.
- Bailo E et al.: TERS investigation of a single RNA strand, each base contributed an SNR to the near-field spectrum, indicating the single-base sensitivity of TERS. Doi: Visit site
- Lipiec et al.: Molecular characterisation of DNA double strand breaks (DSBs) with TERS. Doi: Visit site
- Najjar et al.: Combed double-stranded (DS) DNA immobilised on a glass surface using TERS. Doi: Visit site
- Treffer et al.: demonstrated that TERS was capable of resolving individual nucleobases of individual RNA and DNA molecules. Doi: Visit site
Cell membrane: Lipids
Lipids are the fundamental building blocks of biological cell membranes and mediate the interaction of a cell with its external environment such as drugs, pathogens and neighbouring cells involved in biological processes such as cell signalling. AFM-TERS provides label-free measurement of molecular distribution on a cell membrane at the nanoscale.
- Böhme et al.: Supported lipid bilayer and human cells. Visit site
- Opilik et al.: nanoscale chemical imaging of phase-separated lipid domains. Visit site
- Richter et al.: They demonstrated that using this powerful data processing methodology signals from both protein and lipid domains could be differentiated. This allowed for increasing the spatial resolution of these cell membrane components down to the nanometer scale. Visit site
Semiconductors and materials
Semiconductor devices are the foundation of modern electronics and information technology. The need to reduce its size on a micro and nano scale is due to the needs of miniaturization and integration. Therefore, the use of the AFM-TERS technique is necessary to determine the high-resolution topography and the detection of chemical information for the characterization of the fine structure and the quality control of high-performance devices.
Electronics and optoelectronics: 2D Materials
TERS can be used to investigate local structural heterogeneities in such inorganic 2D materials at the nanoscale, which is of great importance for potential device applications. The effect of doping from the metal-coating of the tip is likely to influence such measurements.
- Rahaman et al.: TERS of an ultrathin MoS2 flake on a nanostructured Au on silicon surface forming a two-dimensional (2D) crystal/plasmonic heterostructure. This tip-enhanced Raman spectroscopy study allows us to determine the built-in strain that arises when 2D materials interact with other nanostructures. DOI: Visit site
- A.G. Milekhin et al.: Our results will open the perspectives of optical diagnostics with nanometer resolution for many other 2D materials. With TERS technique it is observed a structural change of MoS2 from the 2H to the 1T phase. Due to the very good spatial resolution, it is able to spatially resolve those doping sites. doi: Visit site
- Park et al.: reported a hybrid nano-optomechanical approach combining TERS, TEPL, and atomic force local strain control to study the associated effects on the excitonic properties in monolayer WSe2 with a spatial resolution of ∼ 15 nm. Doi: Visit site
Carbon nanotubes (CNTs): 1D Materials
TERS has been used to both detect and gather information about the chemistry and the structure of CNTs. The discrimination of mixed CNT bundles of different diameters has been achieved by analyzing the distribution of Raman intensity of the ring-breathing modes in the obtained chemical images based on TERS spectra.
- Chan et al.: TERS is used for measuring chemical images with nanometre spatial resolution. The results demonstrate that TERS is a viable tool for the detection and localization of different SWCNTs and amorphous carbon in mixed SWCNTs based on the spectral differences in the radial breathing mode and the D bands. Doi: Visit site
- Chaunchaiyakul et al.: used TERS to determinate the relationship between the 2D and G band intensities and the number of walls of a multiwalled carbon nanotube, which enables spatial resolution of nanometer order. Visit site
The electrochemical interface is the place where the electron transfer, energy conversion and storage, and mass transfer occur. This is important for understanding the local electrochemical processes in the interface, which is highly significant to solar cells, electrocatalytic systems, energy storage devices, electrosynthesis, etc. To study these systems it is needed a in situ sensitive technique that can provide fingerprint molecular information at the nanometer resolution. TERS has the advantages of nanometer spatial resolution, single-molecule sensitivity, and rich vibrational information, is apparently a promising tool for the molecular level and nanoscale analysis of the electrochemical interfaces.
Organic Solar Cells
In polymer blending photovoltaic solar cells, the photophysical processes occur on a nano scale. Component morphology analysis determines the efficiency and charge transport to the electrodes. TERS has been used successfully for nanoscale chemical mapping of components in photovoltaic polymer blends.
- Wang et al.: demonstrated this by TERS imaging of domains in P3HT:PCBM films for solar-cells at optical resolution of 9 nm. By these measurements, the authors related to the electron transfer from P3HT to PCBM. Visit site
- Zhang et al.: TERS measurements require an inert environment such as nitrogen or argon. TERS spectra from these samples need a reliable fitting procedure is required to accurately deconvolute the Raman and PL bands in order to measure their intensities. Visit site
Energy stores: Li-ion batteries
Raman images allow details and degradation of the cathode. Combination of AFM images allow the chemical properties of the cathode to be correlated with its topography.
- Nanda et al.: Employ TERS to study model amorphous silicon (a-Si) thin film anodes galvanostatically cycled for different numbers. For the 1× cycled a-Si, TERS shows good correlation between solid electrolyte interphase (SEI) topography and chemical mapping. DOI: Visit site
The capability to chemically and spatially resolve the chemical heterogeneity of the surface makes TERS a highly promising technique to obtain the information from such a complex interfacial region regarding the solid surface, the molecular layer and their interaction.
TERS has been successfully applied to the study of polymer-blends revealing numerous novel insights.
- Yeo et al. Nanoscale probing of the surface composition of a polystyrene-polyisoprene (PS-PI) blend film with AFM-TERS. The authors identified PI and PS at the surface and sub-surface, respectively and discovered the presence of sub-surface nanopores in the PS film; these results couldn’t be obtained using other characterisation technique. doi: Visit site
- Xue et al. reported the first high-resolution TERS image of a PMMA: SAN polymer blend. Visit site
TERS provides highly localized chemical sensitivity, making them ideal for studying chemical reactions, including processes on catalytic surfaces.
- Hartman et al.: Catalyst structures, adsorbates, and reaction intermediates can be observed in low quantities at hot spots where electromagnetic fields are the strongest, providing ample opportunities to elucidate reaction mechanisms. DOI: Visit site
- Harvey et al: The development and use of SERS and TERS to study heterogeneous catalytic reactions, and the exciting possibilities that may now be within reach thanks to the latest technical developments. This will be illustrated with showcase examples from photo- and electrocatalysis. Visit site
From the perspective of pharmaceutical analysis, TERS has enabled rapid non-invasive volumetric analysis with high spatial resolution of pharmaceutical formulations that could lead to many important applications in pharmaceutical settings, such as imaging and quantitative analysis of pharmaceutical tablets and capsules in processes and quality control.
- Cowcher et al.: TERS can be used to distinguish successfully between glycosylated and nonglycosylated proteins from the measurements of just a few molecules within a monolayer. Visit site
- Shashkov et al.: AFM images of tablets provide information about sample topography, grain structure, orientation, and grain boundaries. Raman maps provide distribution of chemical components without the need for complex sample preparation. In this study, the distribution of Aspirin and Paracetamol components within the ANADIN tablet was studied with high spatial resolution and free of any artifacts due to sample roughness. NTEGRA Spectra: Pharmaceutical Application. Visit site
Petroleum and cement: geochemistry
The AFM technique is another way to analyze asphaltene aggregates on a micro and nanometric scale, heterogeneity and surface force. Furthermore, Enhanced Surface Raman Spectroscopy (SERS) provides an additional method to detect low concentrations of asphaltenes and thus oil. The combination of both techniques would represent an advance in the simultaneous morphological and chemical characterization of the oil.
This methodology that delivers a clear image of the analyzed areas together with a reliable and univocal mineralogical characterization of the sample down to nanoscale. Other analytical methods are not able to provide unambiguous mineralogical data, since they are chemical methods using a spot size often larger than the mineral of interest although the imaging is detailed enough, or the imaging is in a too low resolution and does not allow knowing which mineral has been analyzed.
- Borromeo et al.: The final aim is to apply a methodology that delivers a clear image of the analyzed areas together with a reliable and univocal mineralogical characterization of the sample down to nanoscale. Other analytical methods are not able to provide unambiguous mineralogical data, since they are chemical methods using a spot size often larger than the mineral of interest although the imaging is detailed enough, or the imaging is in a too low resolution and does not allow knowing which mineral has been analyzed. Visit site
There is a wide range of applications of Raman spectroscopy for the study of cementitious materials. Studies ranging from structural determinations of pure phases, through hydration studies in situ, to the characterization of aged pastes and identification of degradation products. A major problem with these studies is improving Raman signal collection in real-time studies. The TERS technique could be applied to this type of samples to obtain in situ images of heterogeneous samples, most of them as pastes, to investigate the spatial relationship between the different phases, in addition to improving the signal of the raman spectrum.
- Assessment of the influence of additives in concrete by the Raman spectroscopy method. The Raman spectrum of C-S-H with silica zol is identical to the spectrum of hydrated cement. Visit site
- Raman spectroscopy of cementitious materials. DOI: Visit site
- Confocal Raman microscopy as a non-destructive tool to study microstructure of hydrating cementitious materials. Visit site
- Functionalization of Hydroxyapatite Ceramics: Raman Mapping Investigation of Silanization. Visit site