From The Editor | June 12, 2024

3 Things You May Not Know About Raman Spectroscopy

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By John Oncea, Editor

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Raman2RNA, FSRS, and portable Raman devices are three recent Raman spectroscopy advancements. But what are they and how are they moving the needle?

Sir Chandrasekhara Venkata Raman was born November 7, 1888, in Tiruchirappalli, India, and died just over 84 years later in Bangalore, India. Raman is best known for his work in the field of light scattering highlighted by his 1928 discovery that a small portion of scattered light acquires other wavelengths than that of the original light.

Raman became the first Asian to be awarded a Nobel Prize in all fields of science in 1930 for this light-scattering discovery which was subsequently called Raman scattering. The spectroscopic technique most often used to determine vibrational modes of molecules – Raman spectroscopy – also was named after him and is commonly used in chemistry to provide a structural fingerprint by which molecules can be identified.

Raman spectroscopy has proved to be an important technology over the years but has historically damaged live proteins during optical measurements, leading to inconsistent results, according to SciTechDaily. But, after 50 years of frustration, researchers “from Texas A&M University and TEES have introduced a new approach called thermostable-Raman-interaction-profiling (TRIP), allowing low-concentration, low-dose screenings for protein-to-ligand interactions in relevant conditions, promising label-free, highly reproducible measurements, and potential applications in rapid and cost-effective drug, vaccine, and virus testing, and DNA analysis.”

Unlike traditional Raman spectroscopy TRIP provides highly reproducible results. It can detect protein-ligand interactions in real time, potentially shortening the timeline for drug and vaccine testing. Additionally, TRIP requires smaller sample sizes and lower protein concentrations, making it a cost-effective process for testing. This breakthrough has applications in rapid and cost-effective drugs, vaccines, virus testing, and DNA analysis.

TRIP is just one of several recent Raman spectroscopy breakthroughs. Here, we take a look at several other exciting advancements in recent years.

Portable Devices, New Techniques

Raman spectroscopy has seen exciting advancements in recent years, advancements that highlight the ongoing innovation that is continually opening new avenues for research and practical applications across various scientific disciplines. These advancements hold promise for improving medical diagnostics, drug development, clinical testing, and more. Here are some of the latest breakthroughs:

Portable Raman Devices: Electrical engineer Nili Persits has developed low-cost, portable Raman spectroscopy systems that allow instant chemical analysis, making Raman accessible for various applications like medical studies and manufacturing, according to MIT Technology Review.

Persits’ Raman device is a laser about the size and shape of a Wi-Fi router with just one probe and a cell phone-size photodetector attached. It is less sensitive and provides higher resolution than existing portable Raman systems, according to Persits. It also delivers results on par with those of bigger and pricier versions.

Whereas the bigger device is intended for large-scale operations such as chemical manufacturing facilities or wastewater monitoring, this one is suited for smaller uses such as medical studies, notes MIT.

Raman2RNA Technique: According to SciTechDaily, a groundbreaking development in Raman spectroscopy has been the creation of Raman2RNA, an algorithm that predicts the genomic profiles of live cells from their Raman images. This MIT-developed technique allows researchers to track cell differentiation and genomic changes over time without the need for invasive procedures and could eventually lead to diagnostic applications in medical fields.

“Using this technique, the researchers showed that they could monitor embryonic stem cells as they differentiated into several other cell types over several days,” writes SciTechDaily. “This technique could enable studies of long-term cellular processes such as cancer progression or embryonic development, and one day might be used for diagnostics for cancer and other diseases.”

Researchers intend to use this technique to analyze cell populations that evolve, such as aging cells and cancerous cells. Currently, they are conducting experiments with cells cultivated in a laboratory dish. However, in the future, they aspire to refine this method as a possible diagnostic tool for use in patients.

“One of the biggest advantages of Raman is that it’s a label-free method. It’s a long way off, but there is potential for the human translation, which could not be done using the existing invasive techniques for measuring genomic profiles,” says Jeon Woong Kang, an MIT research scientist who is also an author of the study.

Femtosecond Stimulated Raman Spectroscopy (FSRS): This is a powerful, ultrafast spectroscopic technique that utilizes three laser pulses:

  • An actinic pump pulse initiates the photochemical reaction of interest
  • A picosecond narrowband Raman pump pulse
  • A broadband femtosecond Stokes probe pulse

According to the National Library of Medicine, the temporal overlap of the Raman pump and Stokes probe pulses induces stimulated Raman scattering, amplifying the Stokes and anti-Stokes frequencies within the probe spectrum at positions corresponding to the vibrational transitions in the sample. This stimulated Raman gain provides high spectral resolution vibrational spectra free from a fluorescence background.

FSRS has found wide applications in studying ultrafast photochemical reactions, energy transfer processes, and biochemical dynamics by providing unprecedented insights into the structural evolution of molecular systems with combined high temporal and spectral resolution.

According to Nature, FSRS “has gained popularity since the early 2000s as an ultrafast pump-probe vibrational spectroscopy technique with the potential to circumvent the time and energy limitations imposed by the Heisenberg uncertainty principle.”

4 More Notes Of Interest – Rapid Fire Style

Following are a couple more Raman-related notes of interest in no particular order:

  1. Exciton Polaron Formation in 2D Perovskites: Researchers have established the room-temperature polaronic nature of excitons in two-dimensional Dion-Jacobson-type perovskites using Raman spectroscopy, providing insights into the interplay between electronic and lattice dynamics in these materials.
  2. Single-Molecule Counting with Colloid-Enhanced Single Molecule: A study in Nature demonstrates that surface-enhanced Raman spectroscopy with colloids can quantify a range of molecules down to femtomolar concentrations by single-molecule counting.
  3. Accurate Molecular Spectra Prediction with Deep Learning: A deep learning model called DetaNet can predict organic molecular spectra with quantum chemistry accuracy while improving computational efficiency, which is essential for substance discovery and structure identification, according to Nature.
  4. Tip-Induced Structural Variation at Single-Bond Limit: One more from Nature which notes researchers explored tip-molecule interactions and molecular motions like tilting and hopping at the single-chemical-bond limit using sub-nanometer-resolved tip-enhanced Raman spectroscopy.

The commercial market for Raman spectroscopy is expanding, driven by its applications in quality control, pharmaceuticals, and biomedical research. Techniques like Raman2RNA and SRS, as well as the development of portable systems, are enhancing the capabilities of Raman spectroscopy, making it a versatile tool for monitoring cellular processes and analyzing complex biological systems. ​