Development of a particle-settling tolerant transmission Raman scheme for analysis of suspension samples

We have demonstrated a simple and effective strategy, the so-called axial illumination scheme, that is able to obtain representative Raman spectra of suspension samples with minimal influence from internal particle settling. In a partially settled suspension sample, since particle concentrations at given points throughout the sample differ, the acquisition of Raman spectra representative of the entire sample composition is critically important for accurate quantitative analysis. The proposed scheme used axially irradiated laser radiation in the same or opposite direction of settling, thus allowing laser photons to migrate through the settling-induced particle-density gradient formed in the suspension and to widely interact with particles regardless of their settled locations. Therefore, transmitted Raman signals gathered opposite to the illumination could be more representative of the overall suspension composition even with partial settling. In this study, the performance of axial illumination schemes (TB (Top-to-Bottom) and BT (Bottom-to-Top) illumination) was evaluated for the determination of the aceclofenac (a non-steroidal anti-inflammatory drug) concentration in suspensions. Although the spectral features exhibited minute variations during settling, settling did not significantly degrade the accuracy of the concentration determination, thereby indicating effective acquisition of settling-tolerant Raman spectra. In addition, the characteristics of photon migration in a partially settled suspension sample were studied using a simulation based on Monte-Carlo method.