Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector

Tatu Rojalin, Lauri Kurki, Timo Laaksonen, Tapani Viitala, Juha Kostamovaara, Keith C. Gordon, Leonardo Galvis, Sebastian Wachsmann-Hogiu, Clare J. Strachan, Marjo Yliperttula

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)761-774
Number of pages14
JournalAnalytical and Bioanalytical Chemistry
Volume408
Issue number3
DOIs
StatePublished - Jan 1 2016

Fingerprint

Avalanches
Avalanche diodes
Semiconductors
Raman Spectrum Analysis
Photons
Oxides
Raman spectroscopy
Raman scattering
Fluorescence
Metals
Detectors
Ranitidine
Pulsed lasers
Pharmaceutical Preparations
Lasers
Crystalline materials
Laser excitation
Excitation energy
Fluorescence spectroscopy
Caffeine

Keywords

  • CMOS SPAD
  • Fluorescence suppression
  • Pharmaceuticals
  • Process analytical technology (PAT)
  • Raman
  • Time resolved

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Medicine(all)

Cite this

Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector. / Rojalin, Tatu; Kurki, Lauri; Laaksonen, Timo; Viitala, Tapani; Kostamovaara, Juha; Gordon, Keith C.; Galvis, Leonardo; Wachsmann-Hogiu, Sebastian; Strachan, Clare J.; Yliperttula, Marjo.

In: Analytical and Bioanalytical Chemistry, Vol. 408, No. 3, 01.01.2016, p. 761-774.

Research output: Contribution to journalArticle

Rojalin, Tatu ; Kurki, Lauri ; Laaksonen, Timo ; Viitala, Tapani ; Kostamovaara, Juha ; Gordon, Keith C. ; Galvis, Leonardo ; Wachsmann-Hogiu, Sebastian ; Strachan, Clare J. ; Yliperttula, Marjo. / Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector. In: Analytical and Bioanalytical Chemistry. 2016 ; Vol. 408, No. 3. pp. 761-774.
@article{b1ee4fd8a9e54c3786b5785d172a977a,
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.",
keywords = "CMOS SPAD, Fluorescence suppression, Pharmaceuticals, Process analytical technology (PAT), Raman, Time resolved",
author = "Tatu Rojalin and Lauri Kurki and Timo Laaksonen and Tapani Viitala and Juha Kostamovaara and Gordon, {Keith C.} and Leonardo Galvis and Sebastian Wachsmann-Hogiu and Strachan, {Clare J.} and Marjo Yliperttula",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/s00216-015-9156-6",
language = "English (US)",
volume = "408",
pages = "761--774",
journal = "Fresenius Zeitschrift fur Analytische Chemie",
issn = "0016-1152",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Fluorescence-suppressed time-resolved Raman spectroscopy of pharmaceuticals using complementary metal-oxide semiconductor (CMOS) single-photon avalanche diode (SPAD) detector

AU - Rojalin, Tatu

AU - Kurki, Lauri

AU - Laaksonen, Timo

AU - Viitala, Tapani

AU - Kostamovaara, Juha

AU - Gordon, Keith C.

AU - Galvis, Leonardo

AU - Wachsmann-Hogiu, Sebastian

AU - Strachan, Clare J.

AU - Yliperttula, Marjo

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - CMOS SPAD

KW - Fluorescence suppression

KW - Pharmaceuticals

KW - Process analytical technology (PAT)

KW - Raman

KW - Time resolved

UR - http://www.scopus.com/inward/record.url?scp=84955186349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955186349&partnerID=8YFLogxK

U2 - 10.1007/s00216-015-9156-6

DO - 10.1007/s00216-015-9156-6

M3 - Article

VL - 408

SP - 761

EP - 774

JO - Fresenius Zeitschrift fur Analytische Chemie

JF - Fresenius Zeitschrift fur Analytische Chemie

SN - 0016-1152

IS - 3

ER -