Ondax Low-Frequency / THz-Raman™
Resolution of Chiral Drug Cocrystals: Complementary Roles of NMR, Low-Frequency Raman and Vibrational Circular Dichroism
Věra Schrenková, Adam Sklenář, Martin Dračínský, Jan Rohlíček, Petr Bouř, Argyro Chatziadi and Jakub Kaminský
Talanta 2027 311, 130238
DOI: 10.1016/j.talanta.2026.130238
This study evaluates solid-state NMR, low-frequency Raman, infrared spectroscopy, and vibrational circular dichroism (VCD) for resolving chiral drug cocrystals. It highlights the complementary strengths of each method in screening, structural characterization, and chiral identification, supporting reliable pharmaceutical solid-form analysis, enantiomeric assessment, cocrystal development, quality control, formulation research, and applications.
Synchrotron X-ray powder diffraction validation of real-time in situ terahertz-Raman monitoring of resonant acoustic mixing cocrystallization
Cameron B. Lennox, Jogirdas Vainauskas, Joseph M. Marrett, Jean-Louis Do, Mihails Arhangelskis, Filip Topić, Michael Ferguson, Alexander Wahrhaftig-Lewis, Martin Etter, Andrew J. Morris, Tomislav Friščić and Tristan H. Borchers
Communications Chemistry 2026
DOI: 10.1038/s42004-026-02072-w
This study validates real-time, in situ THz-Raman monitoring of cocrystallization during resonant acoustic mixing using synchrotron X-ray powder diffraction (XRPD). The tandem approach qualitatively and quantitatively tracks crystal formation, phase evolution, and reaction progress, supporting faster, non-destructive pharmaceutical cocrystal screening, process understanding, mechanochemical development, solid-form control, industrial use.
Full vibrational spectroscopy for simultaneous mechanical, structural and chemical analysis
Morteza Behrouzitabar, Kārlis Bērziņš, Renzo Vanna, Victor Alcolea-Rodriguez, Ben J. Boyd, Laura D’Alfonso, Cristian Manzoni, Dario Polli, Giulio Cerullo and Giuseppe Antonacci
Nature Communications 2026 17, 5632
DOI: 10.1038/s41467-026-74558-z
This article presents full vibrational spectroscopy, an all-optical, label-free technique that simultaneously measures mechanical, structural and chemical properties by capturing Brillouin, ultra‑low‑frequency Raman and conventional Raman signals in one experiment. Demonstrated on pharmaceutical solids, it distinguishes polymorphs and microstructural differences, enabling advanced materials characterization, drug development, quality control and non‑destructive process monitoring.
Potential of Low-Frequency Raman Spectroscopy for Structural Screening of Lipid-Based Drug Delivery Systems for Poorly Water-Soluble Drugs
Ka̅rlis Be̅rziņš, Lasse S. Krog, and Ben J. Boyd
Molecular Pharmaceutics 2026 23 (6), 3287-3297
DOI: 10.1021/acs.molpharmaceut.5c01876
This study uses low-frequency THz-Raman spectroscopy, combined with SAXS, to monitor lipid mesophase transitions and nanostructure formation, enabling structure-sensitive screening of lipid-based carriers that enhance solubilization of poorly water-soluble drugs.
Low-Frequency Raman Spectroscopy: Opportunities in Solid-State Modeling and Analysis
Peter J. G. Remoto and Keith C. Gordon
ACS Applied Optical Materials 2026 4 (4), 1000-1029
DOI: 10.1021/acsaom.5c00643
Low-frequency THz-Raman spectroscopy is presented as a non-destructive probe of low-energy lattice vibrations, enabling advanced solid-state modeling, chemometric analysis, and DFT-supported interpretation across pharmaceuticals, materials, and geological systems, while outlining current challenges and future opportunities.
Characterizing Organic Gunshot Residues with Low-Frequency Raman and Terahertz Vibrational Spectroscopies
Salvatore Zarrella, Margaret P. Davis, Mary N. Boyden, and Timothy M. Korter
ACS Omega 2026 11 (5), 8209-8221
DOI: 10.1021/acsomega.5c10754
This work applies low-frequency THz-Raman and terahertz spectroscopy to distinguish structurally similar organic gunshot residues and their mixtures via unique lattice vibrational fingerprints, enabling sensitive, non-destructive forensic detection.
EZClust: A Robust Machine Learning-Based Powder X-Ray Diffraction and Raman Cluster Analysis Model for Efficient High-Throughput Crystallization Polymorph Screening
Zhiwei Yin, Victor W. Rosso, Frederick Roberts, Ariel Furman, Jason M. Stevens, Taylor Watts, Cameron Cook, Anisha Patel, and Jun Qiu
Organic Process Research & Development 2026 30 (2), 372-383
DOI: 10.1021/acs.oprd.5c00382
EZClust applies machine learning to cluster high-throughput crystallization datasets using PXRD and Raman spectroscopy, improving polymorph screening speed and robustness versus commercial tools through shape-based distance metrics and streamlined preprocessing.
Implementation-focused evaluation of transmission low-frequency Raman spectroscopy parameters for non-destructive quality control of solid dosage forms
Reo Kasahara, Motoki Inoue and Toshiro Fukami
RSC Pharm 2026 3, 441-448
DOI: 10.1039/D5PM00214A
This paper evaluates transmission low-frequency THz-Raman spectroscopy parameters for non-destructive detection and quantification of trace crystallinity in amorphous tablets, providing practical guidelines for implementing TLRS in routine solid-dosage quality control.
Quantification of drug contents in molded tablets via transmission low-frequency Raman spectroscopy
Motoki Inoue, Tatsuya Akiyamab and Toshiro Fukami
Analyst 2025 12 (150), 2574-2579
DOI: 10.1039/D5AN00079C
This paper uses transmission low-frequency THz-Raman spectroscopy as a fast, non-destructive method to quantify active pharmaceutical ingredients in molded orally disintegrating tablets, enabling real-time quality control during wet tableting.
Terahertz-Raman spectroscopy for in situ benchtop monitoring of changes to extended, supramolecular structure in milling mechanochemistry
Tristan H. Borchers, Filip Topic, Mihails Arhangelskis, Michael Ferguson, Cameron B. Lennox, Patrick A. Julien, Tomislav Friscic
Chem 2025 11 (2)
DOI: 10.1016/j.chempr.2024.09.018
This paper demonstrates benchtop THz-Raman spectroscopy for real-time, in situ monitoring of mechanochemical milling, tracking crystalline intermediates, polymorphs, cocrystals, and halogen-bond changes via low-frequency lattice vibrations without needing synchrotron X-rays.
In-Situ Monitoring of Dissolution and Crystallization Processes of Carbamazepine Using Low-Frequency Raman Spectroscopy and Multivariate Analysis
Takayuki Kudo, Haruka Uchida, Mana Yamato, Ryo Ohashi, Vasanthi Palanisamy and Toshiro Fukami
Chemical and Pharmaceutical Bulletin 2025 73 (1), 58-62
DOI: 10.1248/cpb.c24-00745
This study uses low-frequency THz-Raman spectroscopy with multivariate analysis to in-situ monitor dissolution and crystallization of carbamazepine, resolving polymorph-specific lattice vibrations in real time and enabling quantitative process control for pharmaceutical manufacturing.
Calibration free approaches for rapid polymorph discrimination via low frequency (THz) Raman spectroscopy
Magdalene W. S. Chong, Martin R. Ward, Catriona McFarlan, Andrew J. Parrott, Paul Dallin, John Andrews, Iain D. H. Oswald and Alison Nordon
Chem. Communication 2025 61 (5): 925–928
DOI: 10.1039/d4cc05591h
This Chemical Communications article presents calibration-free approaches for rapid polymorph discrimination via low-frequency (THz) Raman spectroscopy in solid pharmaceuticals. By exploiting lattice phonon bands in the 10–400 cm⁻¹ region, the method distinguishes polymorphs of active pharmaceutical ingredients and excipients without reference standards, enabling fast, non‑destructive polymorph screening, solid‑form control, process analytical technology (PAT) deployment, and robust pharmaceutical quality assurance.
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Discriminating Model Microcalcifications Immersed and Under Varying Depths of Wax Using Deep Low-Frequency Raman Spectroscopy
Mitchell C. Chalmers, Teemu Tomberg, Keith C. Gordon and Sara J. Fraser-Miller
Applied Spectroscopy Practica 2024 2 (4)
DOI: 10.1177/27551857241302079
This work uses deep low-frequency THz-Raman spectroscopy to classify model breast microcalcifications (amorphous/crystalline CaOx and HA) buried under wax, showing the low-frequency region significantly improves discrimination versus mid-frequency spectra for clinically relevant depths.
Surface-Enhanced, Low-Frequency Raman Spectroscopy: A Sensitive Screening Tool for Structural Characterization of Pharmaceuticals
Ka̅rlis Be̅rziņš and Ben J. Boyd
Analytical Chemistry 2024 96 (43), 17100-17108
DOI: 10.1021/acs.analchem.4c01977
This study uses surface-enhanced low-frequency THz-Raman spectroscopy to sensitively distinguish paracetamol polymorphs and probe template-assisted crystallization, enabling small-scale, multicomponent structural screening for pharmaceutical solids without changing standard SERS setups.
Applications of multi-parameter sensing in pharmaceutical, agriculture and mineral industries using THz spectroscopy and Low-Wavenumber Raman spectroscopy
Khushboo Singh, Naini Bajaj, Mayuri Kashyap, Aparajita Bandyopadhyay and Amartya Sengupta
Optics & Laser Technology 2024 177, 111020
DOI: 10.1016/j.optlastec.2024.111020
THz and low-wavenumber Raman (THz-Raman) spectroscopy are showcased in this review as powerful, non-destructive tools for multi-parameter sensing, enabling simultaneous structural, compositional and polymorphic analysis across pharmaceutical quality control, agriculture (crops and soils) and mineral identification, thereby improving precision, efficiency and sustainability in these industries.
In Situ Imaging of Subcutaneous Drug Delivery Systems Using Microspatially Offset Low-Frequency Raman Spectroscopy
Ka̅rlis Be̅rziņš, Grzegorz S. Czyrski, Anas Aljabbari, Andrea Heinz, and Ben J. Boyd
Analytical Chemistry 2024 96 (16), 6408-6416
DOI: 10.1021/acs.analchem.4c00488
This proof-of-concept uses microspatially offset low-frequency THz-Raman spectroscopy to noninvasively image subcutaneous implants through skin, tracking implant erosion and caffeine solid-state changes in situ for potential point-of-care monitoring of drug delivery systems.
Old Polymorph, New Technique: Assessing Ritonavir Crystallinity Using Low-Frequency Raman Spectroscopy
Manolya K. Hatipoglu, Yeakub Zaker, Daniel R. Willett, Nirzari Gupta, Jason D. Rodriguez, Suhas Patankar, Peter Capella, and Huzeyfe Yilmaz
Analytical Chemistry 2023 95 (41), 15325-15332
DOI: 10.1021/acs.analchem.3c02781
This study demonstrates how low-frequency THz-Raman spectroscopy can rapidly and non-destructively quantify ritonavir polymorphs in commercial tablets, delivering XRPD-comparable sensitivity while drastically cutting analysis time and sample preparation for crystallinity and stability monitoring.
In Situ Monitoring of Drug Precipitation from Digesting Lipid Formulations Using Low-Frequency Raman Scattering Spectroscopy
Salim, Malinda, Sara J. Fraser-Miller, Kārlis Bērziņš, Joshua J. Sutton, Keith C. Gordon, and Ben J. Boyd
Pharmaceutics 2023 15 (7), 1968
DOI: 10.3390/pharmaceutics15071968
Low-frequency THz-Raman spectroscopy is applied in situ to monitor crystalline precipitation of fenofibrate from digesting lipid formulations, providing an accessible, structure-sensitive alternative to SAXS for tracking precipitation kinetics in lipid-based drug delivery systems.
Exploring the Solid-State Landscape of Carbamazepine during Dehydration: A Low Frequency Raman Spectroscopy Perspective
Remoto, Peter III J. G., Kārlis Bērziņš, Sara J. Fraser-Miller, Timothy M. Korter, Thomas Rades, Jukka Rantanen, and Keith C. Gordon
Pharmaceutics 2023 15 (5), 1526
DOI: 10.3390/pharmaceutics15051526
This study uses low-frequency THz-Raman spectroscopy to track carbamazepine dihydrate dehydration, sensitively resolving transient polymorphs and solid-state pathways that are less visible in mid-frequency Raman, highlighting its value for pharmaceutical process monitoring and control.
Nondestructive Spatial Dehydration Analysis of Crystalline Hydrates in Pharmaceutical Solid Dosage Forms Using Spatially Offset Low-Frequency Raman Spectroscopy
Ka̅rlis Be̅rziņš, Peter III J. G. Remoto, Sara J. Fraser-Miller, and Keith C. Gordon
Crystal Growth & Design 2022 22 (5), 2946-2953
DOI: 10.1021/acs.cgd.1c01401
This study uses spatially offset low-frequency THz-Raman spectroscopy to non-destructively map dehydration of citric acid monohydrate inside tablets, revealing spatial dehydration kinetics and phonon-mode changes in pharmaceutical solid dosage forms.
Identification of Enantiomers Using Low-Frequency Raman Spectroscopy
Vinayaka Harshothama Damle, Hagit Aviv, and Yaakov R. Tischler
Analytical Chemistry 2022 94 (7), 3188-3193
DOI: 10.1021/acs.analchem.1c04710
Low-frequency THz-Raman spectroscopy with polarization control is used to differentiate solid-state enantiomers by exploiting subtle intensity changes in low-energy lattice vibrations, enabling a non-destructive, calibration-based route to assign molecular chirality.
Terahertz Raman scattering as a probe for electron–phonon coupling, disorder and correlation length in molecular materials
Tommaso Salzillo, Aldo Brillante and Alberto Girlandoe
J. Mater. Chem. C 2021 9 (33), 10677-10688
DOI: 10.1039/D1TC01698A
THz-Raman spectroscopy is used here to probe electron–phonon coupling, static and dynamic disorder, and correlation length in organic molecular materials, enabling insights into low-dimensional charge-transfer crystals and pentacene thin films beyond conventional X-ray diffraction and standard vibrational methods.
Solid-State Analysis of Alpha-Cyclodextrin Inclusion Complexes Using Low-Frequency Raman Spectroscopy
Motoki Inoue, Hiroshi Hisada, Kazuhiko Takatori, Tatsuo Koide, Toshiro Fukami, Anjan Roy, and James Carriere
Analytical Chemistry 2021 93 (2), 704-708
DOI: 10.1021/acs.analchem.0c03854
This work applies low-frequency THz-Raman spectroscopy to rapidly and non-destructively distinguish alpha-cyclodextrin crystalline inclusion complexes via their lattice vibrational signatures, overcoming limitations of conventional Raman for solid-state analysis.
Terahertz Raman Spectroscopy of Ligand-Protected Au8 Clusters
Kato, Masaru and Shichibu, Yukatsu and Ogura, Kazuya and Iwasaki, Mitsuhiro and Sugiuchi, Mizuho and Konishi, Katsuaki and Yagi, Ichizo
The Journal of Physical Chemistry Letters 2020 11 (19), 7996-8001
DOI: 10.1021/acs.jpclett.0c02227
This work applies low-frequency THz-Raman spectroscopy to rapidly and non-destructively distinguish alpha-cyclodextrin crystalline inclusion complexes via their lattice vibrational signatures, overcoming limitations of conventional Raman for solid-state analysis.
Low-wavenumber Raman spectral database of pharmaceutical excipients
Kārlis Bērziņš, Ruth E. Sales, Jonathan E. Barnsley, Greg Walker, Sara J. Fraser-Miller and Keith C. Gordon
Vibrational Spectroscopy 2020 107, 103021
DOI: 10.1016/j.vibspec.2020.103021
This study builds a low-wavenumber THz-Raman spectral database for 75 widely used pharmaceutical excipients, enabling solid-state characterization, polymorph identification, counterfeit detection, and process monitoring in drug products using THz-Raman spectroscopy.
Application of low-wavenumber Raman spectroscopy to the analysis of human teeth
Kārlis Bērziņš, Joshua J. Sutton, Carolina Loch, Deanna Beckett, Benjamin J. wheeler, Bernadette K. Drummond, Sara J. Fraser-Miller and Keith C. Gordon
Journal of Raman Spectroscopy 2019 50 (10), 1375-1387
DOI: 10.1002/jrs.5648
This Journal of Raman Spectroscopy article demonstrates low‑wavenumber Raman spectroscopy as a non‑destructive tool for analysing human teeth, specifically enamel and dentin mineralization. By probing lattice vibrational modes below ~400 cm⁻¹, the method distinguishes normal and abnormal mineralization patterns, revealing crystallinity and structural changes relevant to caries, developmental defects and dental pathology. The study highlights low‑frequency Raman as a sensitive technique for tooth structure analysis, early diagnosis, biomineralization research and dental materials characterization.
Wavelength Stabilized Lasers
Volume Holographic Grating Wavelength Stabilized Laser Diodes
Gregory J. Steckman, Wenhai Liu, Ren Platz, Dominic Schroeder, Christophe Moser and Frank Havermeyer
IEEE Journal of Selected Topics in Quantum Electronics 2007 13 (3), 672-678
DOI: 10.1109/JSTQE.2007.896060
This paper reviews how volume holographic gratings enable temperature-stable, narrow-linewidth laser diodes, which are crucial as pump and probe sources for precise THz-Raman spectroscopy measurements in advanced photonics and sensing applications.
VBG
Compact single mode tunable laser using a digital micromirror device
Frank Havermeyer, Lawrence Ho and Christophe Moser
Optics Express 2011 19 (15), 14642-14652
DOI: 10.1364/OE.19.014642
Multiplexed volume holographic gratings (VBGs) are used as the compact external-cavity wavelength-selective element, splitting the spectrum into multiple Bragg-matched beams mapped onto a DLP micromirror array to achieve fast, discrete, single-mode multi-wavelength tuning for Continuous Wave THz generation and 3D metrology.
Ultra-narrow-band tunable laserline notch filter
C. Moser and F. Havermeyer
Applied Physics B 2009 95, 597-601
DOI: 10.1007/s00340-009-3447-6
This work demonstrates an ultra-narrow-band angularly tunable laser line notch filter based on multiple slanted reflective volume Bragg gratings (VBGs) bonded in glass, achieving OD≈5.7, sub-nanometer bandwidth, and high transmission for advanced Raman spectroscopy and laser rejection applications.
Development of stable, narrow spectral line-width, fiber delivered laser source for spin exchange optical pumping
Bo Liu, Xin Tong, Chenyang Jiang, Daniel R. Brown and Lee Robertson
Applied Optics 2015 54 (17), 5420-5424
DOI: 10.1364/AO.54.005420
This paper demonstrates a fiber-delivered laser source for spin exchange optical pumping that uses an external cavity with an off‑the‑shelf volume Bragg grating (VBG) to achieve a narrowed spectral linewidth, high side‑mode suppression, and excellent long‑term wavelength stability at high output power.
Phase stable OCT with a 1050 nm tunable VCSEL and photonic integrated circuit
Bart Johnson, Carlos Melendez, Ryan Niemeier, David Blasing, Tim Ford, Taran Huffman, Ajay Srinivasan, Thien-An Nguyen, Tina Trimble, and Peter Whitney
Optics Express 2025 33 (3), 6017-6028
DOI: 10.1364/OE.551295
This work presents a phase-stable 1050 nm swept-source OCT system in which a volume Bragg grating (VBG) inside a temperature-stabilized butterfly package provides an ultra-stable optical trigger, suppressing VCSEL sweep jitter and enabling precise, turnkey phase-sensitive imaging with a photonic integrated circuit interferometer.
