Faster Raman spectroscopy gives new views of molecular dynamics

30 Oct 2024

University of Tokyo increases measurement rate 100-fold for analysis of irreversible events.

Raman scattering spectroscopy has been widely adopted as an analytical technique, thanks to its ability to detect characteristic spectral fingerprints for individual molecules.

However, its measurement rate tends to be inherently slow, and although a number of Fourier transform and time-stretch methods have aimed to improve matters, rates have remained below 500 kilo-spectra per second, according to a project at the University of Tokyo.

This can be too low to keep up with the speed of changes in some chemical and physical reactions, commented the Tokyo team, which set out to improve the measurement rate by building a bespoke Raman system from scratch.

As published in Ultrafast Science, the team's proof-of-concept platform increased the measurement rate of Raman spectroscopy by 100-fold, opening up promise for "unprecedented measurements of sub-microsecond dynamics of irreversible phenomena and extremely high-throughput measurements."

"I had been contemplating this idea for over ten years without being able to start the project," said Takuro Ideguchi of Tokyo's Institute for Photon Science and Technology. "It was the new, optimal laser system we developed a few years ago that finally made progress possible."

The project combined its own two-color Yb:fiber mode-locked laser with a time-stretch detection scheme using a picosecond probe pulse. This combined platform has been termed time-stretch coherent Stokes Raman scattering (TS-CSRS) spectroscopy, combining broadband generation and time-stretch detection of the CSRS spectra.

Biomedical diagnostics and ultra-rapid processes

In trials using organic molecules covering the molecular fingerprint region from 200 to 1,200 cm⁻¹ the platform achieved a 50 megaspectra per second measurement rate, a 100-fold increase compared to the normal values.

Further improvements to the rate will be possible, noted the Tokyo team, since the repetition rate of the laser currently employed sets a practical limit. A laser with a higher repetition rate should increase the speed, at the expense of spectral bandwidth or resolution under the same detection bandwidth.

The project expects several applications to benefit from the increased speed of a TS-CSRS approach. Continuous measurement capability at around 20-nanoseconds temporal resolution can reveal ultra-rapid and irreversible complex phenomena such as dynamics of photoreactive proteins, noted the team in its paper. High-speed hyperspectral imaging is another promising direction.

TS-CSRS could also substantially improve the signal-to-noise ratio of the sampling operation, allowing it to measure a wide range of molecular species at a higher event rate comparable to fluorescence-based counterparts.

"We aim to apply our spectrometer to microscopy, enabling the capture of 2D or 3D images with Raman scattering spectra," said Takuro Ideguchi. "Additionally we envision its use in flow cytometry by combining this technology with microfluidics. These systems will enable high-throughput, label-free chemical imaging and spectroscopy of biomolecules in cells or tissues."