Company > 22 - December - 2016

Nano Imaging Using Tip Enhanced Raman Scattering (TERS)

In this issue:

Feature: Nano Imaging Using Tip Enhanced Raman Scattering (TERS)

Tip Enhanced Raman Scattering (TERS) is an imaging technique that brings Raman Spectroscopy to a nanoscale resolution. It combines the chemical sensitivity of surface-enhanced Raman spectroscopy (SERS) with high spatial resolution of scanning probe microscopy (SPM) which allows chemical imaging of surfaces at the nanometer length-scale.

The enhancement of Raman scattering occurs only at the point of a near atomically sharp pin, typically coated with gold. Over the last 15 years, the technique has been used to study scientific problems in biology, photovoltaics, catalysis, semiconductors, carbon nanotubes, graphene and single molecule detection.

TERS imaging requires a confocal microscope and a scanning probe microscope (SPM). The optical microscope is used to align the laser focal point with the tip coated with a SERS active metal. The three typical experimental configurations are bottom illumination, side illumination, and top illumination, depending on which direction the incident laser propagates towards the sample, with respect to the substrate.

TERS systems can be classified into three types according to the different feedback mechanisms used to keep the tip in contact with the surface: contact/tapping mode AFM, shear force and scanning tunneling microscope (STM). In the case of STM-TERS, the sample is moved rather than the tip so that the laser remains focused on the tip. The sample can be moved systematically to build up a series of tip enhanced Raman spectra from which a Raman map of the surface can be built allowing for surface heterogeneity to be assessed with up to 1.7 nm resolution.

Unlike electron spectroscopy and microscopy techniques that require vacuum for their operation, TERS can be used in ambient environment and it is well-suited for the investigation of samples in aqueous mediums. Because TERS is a label-free imaging technique, it can be used to study molecules directly in any biological sample in its native state. This makes TERS very popular among researchers in studying pathogens, lipid and cell membranes, nucleic acids, peptides and proteins.

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. TERS has been used to investigate a single RNA strand which revealed seven distinct Raman spectra, originating for 30-60 bases. This lead to a non-destructive sequencing procedure for DNA using TERS. 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. This can be particularly useful when the amount of sample is not enough for other existing methods as for example forensic and archaeological investigations. Lastly, protein studies enabled by TERS are highly useful in pharmacological studies.

With the recent progress in tip-yield, automation of instrumentation, and preparation of effective reference samples and standards, TERS can become a routine analytical technique with unique capability of chemical characterization at <50 nm spatial resolution. Laserglow Technologies offers many laser wavelengths which are well suited for exploring standard and enhanced TERS experiments. We welcome the opportunity to collaborate with researchers in this field.


1. "Tip-enhanced Raman spectroscopy: principles and applications", Kumar et al. 2014, EPJ Techniques and Instrumentation 2015 2:9 DOI: 10.1140/epjti/s40485-015-0019-5 Springer Open Published Paper

2. TERS application notes- Horiba Scientific: Application Notes

Research: Photothermal Therapy of Cancer Using Hybrid Nanoparticles

Laserglow's LRD-808 LabSpec series diode laser was recently used as an excitation source by researchers at Tianjin University in collaboration with King's College London, in a study that used hybrid nanoparticles as a photo-thermal agent in diagnosing and eradicating tumors.

Photo thermal therapy (PTT) using light-absorbing agents to convert near-infrared (NIR) light into heat to burn cancer cells is a promising approach for cancer treatment. However, for effective PTT treatment, it is crucial to identify the location and size of the tumors before therapy, to monitor the distribution of photo thermal agents during therapy and to evaluate effectiveness after therapy. Therefore, imaging-guided PTT is desired for cancer therapy and those photo thermal agents with dual imaging and therapeutic functions have attracted intensive research interest.

Photoacoustic (PA) imaging incorporates the good spectral selectivity of laser light and uses the detected acoustic signals to reconstruct the absorption distribution in tissue. NIR light-triggered PA and photo thermal theranostics are widely used in cancer treatment due to their ability to use NIR light absorbing agents to generate heat, leading to the thermal ablation of cancer cells. NIR-PA is also an excellent option for imaging tissues since their absorption / scattering is so low in the 650 nm to 950 nm range.

Designing a versatile photo thermal agent for the integration of precise diagnosis and effective photo thermal treatment of tumors is desirable but remains a great challenge. In this study, folic acid ligand conjugated lipid-coated polyaniline hybrid nanoparticles (FA-Lipid-PANI NPs) were successfully fabricated by the research team. The obtained hybrid FA-Lipid-PANI NPs with small size exhibited not only significant photoacoustic (PA) imaging signals, but also a remarkable photo thermal effect for tumor treatment. With PA imaging and photo thermal therapy (PTT), the tumor could be accurately positioned and thoroughly eradicated in vivo after intravenous injection of FA-Lipid-PANI NPs.

The researchers are confident that these multifunctional nanoparticles could play an important role in simultaneously facilitating imaging and PTT to achieve better therapeutic efficacy. Read the full paper at: PubMed Full Paper

News: Birds flying through laser light reveal faults in flight research

A new study has explored Particle Image Velocimetry (or PIV) to analyze how birds fly, with the aim of revealing faults in current flight research methods and suggest ways to improve performance and safety of aircrafts and drones.

As a graduate student working with Stanford mechanical engineer David Lentink, Eric Gutierrez- the lead author of this study, trained a tiny parrotlet named Obi in order to precisely measure the vortices it creates during flight. Their results, published in the Dec. 6 issue of Bioinformatics and Biomimetics, help explain the way animals generate enough lift to fly and could have implications for how flying robots and drones are designed. "The goal of our study was to compare very commonly used models in the literature to figure out how much lift a bird, or other flying animal, generates based off its wake," said Diana Chin, a graduate student in the Lentink lab and co-author of the study. They found that existing models are very unreliable, and a more precise method is needed to measure lift and interpret airflow.

For this experiment, Gutierrez, made parrotlet-sized goggles using lenses from human laser safety goggles, 3D-printed sockets and veterinary tape. The goggles also had reflective markers on the side so the researchers could track the bird's velocity. Then he trained Obi to wear the goggles and to fly from perch to perch.

Once trained, the bird flew through a laser sheet that illuminated nontoxic, micron-sized aerosol particles. As the bird flew through the seeded laser sheet, its wing motion disturbed the particles to generate a detailed record of the vortices created by the flight.

Those particles swirling off Obi's wingtips created the clearest picture to date of the wake left by a flying animal. Past measurements had been taken a few wingbeats behind the animal, and predicted that the animal-generated vortices remain relatively frozen over time, like airplane contrails before they dissipate. But the measurements in this work revealed that the bird's tip vortices break up in a sudden dramatic fashion.

"Many people look at the results in the animal flight literature for understanding how robotic wings could be designed better," said Lentink. "Now, we've shown that the equations that people have used are not as reliable as the community hoped they were. We need new studies, new methods to really inform this design process much more reliably." Read more at: full article