Raman Microimaging Using a Novel Multifiber-Based Device: A Feasibility Study on Pharmaceutical Tablets

Raman microimaging is a potential analytical technique in health field and presents many possible pharmaceutical applications. In this study, we tested a micrometer spatial resolution probe coupled to a portable Raman imager via an indexed multifiber bundle. At the level of the probe, the fibers were arranged in a circular geometry in order to fit to the pupil of an objective. The imaging potential of this Raman system was assessed on pharmaceutical-like pellets. We showed that this setup permits to record, nearly in real time, Raman images with a micrometer resolution. The collected images revealed a marked heterogeneity in chemicals distribution. Further investigations will be led on cells and biological tissues to evaluate the potential of this Raman imaging device for biomedical applications. 1. Introduction Raman microimaging is a promising analytical technique permitting to combine molecular and spatial information. Several studies have demonstrated that Raman analysis can bring valuable in situ information applicable as well in biological research [1, 2] as in pharmaceutical control [3]. Raman analyses require no staining, no solvent addition nor particular sample preparation, contrary to standard analytical methods. Experiments proved that Raman spectroscopy is an aspiring technique comparable to reference methods in quality control. It was proven that Raman approach is an accurate and precise method for active ingredient quantification when combined to data processing, even when the substance comprises less than 1% of the total mass of the tablet [4–6]. In addition, Raman measure is nondestructive and preserves the distribution of actives over the sample. Considering Raman spectral imaging, the most widely cited studies consist of point by point mapping of a defined surface by using a motorized plate. Recent works reported the use of line-scanning system exploiting the bi-dimensionality of charge coupled device (CCD) matrix detector [7]. In this technique, the exciting laser beam is used to illuminate a line on the sample along which several Raman spectra can be recorded simultaneously. The sample is subsequently displaced in small increments perpendicular to the direction of the laser line. Although these laboratory equipments present a good efficiency allowing rapid spectral image acquisition, they do not fully exploit the capability of multiplexing, that is, simultaneous collection of several spectra by one-shot reading of the CCD. However, Schulmerich et al. took advantage of this capability to collect transcutaneous in vivo Raman spectra