1064 nm Dispersive Raman Micro-Spectroscopy and Optical Trapping of Pharmaceutical Aerosols

Research output: Contribution to journalArticle

Authors

  • Peter J Gallimore
  • Francis Pope
  • Andrew D Ward
  • Nick M Davidson
  • Markus Kalberer

Colleges, School and Institutes

External organisations

  • Central Laser Facility, Rutherford Appleton Laboratory, Harwell, Oxford, OX11 0QX, UK.

Abstract

Raman spectroscopy is a powerful tool for investigating chemical composition. Coupling Raman spectroscopy with optical microscopy (Raman micro-spectroscopy) and optical trapping (Raman Tweezers) allows microscopic length scales and hence femtolitre volumes to be probed. Raman micro-spectroscopy typically uses UV/visible excitation lasers, but many samples including organic molecules and complex tissue samples fluoresce strongly at these wavelengths. Here we report the development and application of dispersive Raman micro-spectroscopy designed around a near-infrared continuous wave 1064 nm excitation light source. We analyse micro-particles (1-5 μm diameter) composed of polystyrene latex and from three real-world pressurised metered dose inhalers (pMDIs) used in the treatment of asthma: salmeterol xinafoate (Serevent®), salbutamol sulfate (Salamol®), and ciclesonide (Alvesco®). For the first time, single particles are captured, optically levitated and analysed using the same 1064 nm laser, which permits a convenient non-destructive chemical analysis of the true aerosol phase. We show that particles exhibiting overwhelming fluorescence using a visible laser (514.5 nm) can be successfully analysed with 1064 nm excitation irrespective of sample composition and irradiation time. Spectra are acquired rapidly (1-5 min) with a wavelength resolution of 2 nm over a wide wavenumber range (500-3100 cm-1). This is despite the microscopic sample size and low Raman scattering efficiency at 1064 nm. Spectra of individual pMDI particles compare well to bulk samples and the Serevent pMDI delivers the thermodynamically preferred crystal form of salmeterol xinafoate. 1064 nm dispersive Raman micro-spectroscopy is a promising technique which could see diverse applications for samples where fluorescence-free characterisation is required with high spatial resolution.

Details

Original languageEnglish
JournalAnalytical Chemistry
Early online date29 Jun 2018
Publication statusE-pub ahead of print - 29 Jun 2018