Low-frequency Raman spectroscopy

Significance of the Topic

Low-frequency Raman spectroscopy extends conventional Raman analysis into the spectral region below 200 cm⁻¹, revealing lattice vibrations, hydrogen bonding and collective modes that are invisible in the fingerprint region. Access to these modes enables deeper insights into biomolecular conformations, polymorphism, phase behavior and materials structure, which are critical for pharmaceutical development, quality control and advanced material research.

Objectives and Study Overview

This application note demonstrates how the i-Raman Plus 785S spectrometer combined with the BAC102 low-frequency probe can record Raman signals down to 65 cm⁻¹. The study aims to illustrate its utility in:

• Amino acid characterization
• Polymorph detection in pharmaceuticals
• Monitoring phase transitions in materials

Methodology and Instrumentation

Samples were analyzed at room temperature using a 785 nm laser with up to 300 mW power. Integration times ranged from 0.1 s to 10 s depending on sample and application. The i-Raman Plus 785S features CleanLaze® excitation and a TE-cooled CCD detector for low noise. The BAC102 E-grade fiber-optic probe supports cutoff at 65 cm⁻¹ and enables non-contact sampling.

• Key Instrument Parameters: 785 nm laser, 0.2 nm linewidth, 300 mW output, 4.5 cm⁻¹ spectral resolution
• Probe: BAC102 E-grade, 65 cm⁻¹ cutoff, 105 µm excitation fiber, quartz window

Key Results and Discussion

• Amino Acid Analysis: Low-frequency bands below 200 cm⁻¹ were resolved in L-asparagine, providing information on intermolecular interactions and conformational flexibility.
• Polymorph Detection: α-D-glucose and its monohydrate form produced distinct peaks in the 65–200 cm⁻¹ region, enabling clear differentiation of pseudo-polymorphs crucial for API performance.
• Phase Transition Monitoring: Real-time heating of sulfur showed peak broadening and shift at 83.6 cm⁻¹, indicating the α- to λ-form transition during melting, while fingerprint bands remained unchanged.

Benefits and Practical Applications

Low-frequency Raman analysis enhances detection sensitivity for subtle structural differences. This capability supports:

• Protein and biomolecule conformation studies
• Pharmaceutical polymorph screening and quality control
• Real-time monitoring of crystallization and melting processes
• Characterization of semiconductors, nanotubes, minerals and pigments

Future Trends and Opportunities

Advances in probe design and laser stability will push low-frequency detection below 50 cm⁻¹, while integration with multivariate analysis software will automate fingerprint and low-frequency interpretation. Emerging applications include in situ monitoring of complex formulations, phase transitions under extreme conditions and nanoscale materials research.

Conclusion

The i-Raman Plus 785S paired with the BAC102 probe offers a cost-effective, high-resolution method for low-frequency Raman spectroscopy down to 65 cm⁻¹. It delivers valuable structural information for academic and industrial laboratories engaged in pharmaceuticals, biomolecular research and advanced materials characterization.

References

1. Teixeira AMR, Freire PTC, Moreno AJ, et al. High-Pressure Raman Study of L-Alanine Crystal. Solid State Commun. 2000;116(7):405–409.
2. Larkin PJ, Dabros M, Sarsfield B, et al. Polymorph Characterization of Active Pharmaceutical Ingredients Using Low-Frequency Raman Spectroscopy. Appl Spectrosc. 2014;68(7):758–776.
3. Golichenko BO, Naseka VM, Strelchuk VV, et al. Raman Study of L-Asparagine and L-Glutamine Molecules Adsorbed on Aluminum Films in a Wide Frequency Range. Semicond Phys Quantum Electron Optoelectron. 2017;20(3):297–304.
4. Smith E, Dent G. Modern Raman Spectroscopy: A Practical Approach. 2nd ed. John Wiley & Sons; 2019.
5. Pelletier MJ. Analytical Applications of Raman Spectroscopy. Blackwell Science; 1999.