title: Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector.
abstract: In this work, we utilize a short-wavelength, 532-nm picosecond pulsed laser coupled with a time-gated complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector to acquire Raman spectra of several drugs of interest. With this approach, we are able to reveal previously unseen Raman features and suppress the fluorescence background of these drugs. Compared to traditional Raman setups, the present time-resolved technique has two major improvements. First, it is possible to overcome the strong fluorescence background that usually interferes with the much weaker Raman spectra. Second, using the high photon energy excitation light source, we are able to generate a stronger Raman signal compared to traditional instruments. In addition, observations in the time domain can be performed, thus enabling new capabilities in the field of Raman and fluorescence spectroscopy. With this system, we demonstrate for the first time the possibility of recording fluorescence-suppressed Raman spectra of solid, amorphous and crystalline, and non-photoluminescent and photoluminescent drugs such as caffeine, ranitidine hydrochloride, and indomethacin (amorphous and crystalline forms). The raw data acquired by utilizing only the picosecond pulsed laser and a CMOS SPAD detector could be used for identifying the compounds directly without any data processing. Moreover, to validate the accuracy of this time-resolved technique, we present density functional theory (DFT) calculations for a widely used gastric acid inhibitor, ranitidine hydrochloride. The obtained time-resolved Raman peaks were identified based on the calculations and existing literature. Raman spectra using non-time-resolved setups with continuous-wave 785- and 532-nm excitation lasers were used as reference data. Overall, this demonstration of time-resolved Raman and fluorescence measurements with a CMOS SPAD detector shows promise in diverse areas, including fundamental chemical research, the pharmaceutical setting, process analytical technology (PAT), and the life sciences.
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland. tatu.rojalin@helsinki.fi.|Department of Pathology and Laboratory Medicine, and Center for Biophotonics, University of California Davis, 2700 Stockton Blvd, Sacramento, CA, 95817, USA. tatu.rojalin@helsinki.fi.
authors.forename: Tatu
authors.initials: T
authors.lastname: Rojalin
authors.affiliation: Faculty of Information Technology and Electrical Engineering, Department of Electrical Engineering, University of Oulu, P.O. Box 4500, 90014, Oulu, Finland.
authors.forename: Lauri
authors.initials: L
authors.lastname: Kurki
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Laaksonen
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland.
authors.forename: Tapani
authors.initials: T
authors.lastname: Viitala
authors.affiliation: Faculty of Information Technology and Electrical Engineering, Department of Electrical Engineering, University of Oulu, P.O. Box 4500, 90014, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Kostamovaara
authors.affiliation: Department of Chemistry, MacDiarmid Institute for Advanced Materials and Nanotechnology, University of Otago, Union Place West, Dunedin, 9054, New Zealand.
authors.forename: Keith C
authors.initials: KC
authors.lastname: Gordon
authors.affiliation: School of Chemical Technology, Department of Forest Products Technology, Aalto University, P.O. Box 16300, 00076, Helsinki, Finland.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Galvis
authors.affiliation: Department of Pathology and Laboratory Medicine, and Center for Biophotonics, University of California Davis, 2700 Stockton Blvd, Sacramento, CA, 95817, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wachsmann-Hogiu
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Viikinkaari 9, 00014, Helsinki, Finland. clare.strachan@helsinki.fi.
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Strachan
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, P.O. Box 56, 00014, Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
mesh_terms: D005453:Fluorescence; D008670:Metals / Q000737:chemistry; D010087:Oxides / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013059:Spectrum Analysis, Raman / Q000295:instrumentation / Q000379:methods*
chemical_list: D008670:Metals; D010087:Oxides; D004364:Pharmaceutical Preparations
keywords: CMOS SPAD; Fluorescence suppression; Pharmaceuticals; Process analytical technology (PAT); Raman; Time resolved