Drug and cell microencapsulation is a promising field for therapeutic applications. These microcapsules can be composed of different layers each of them ensuring a particular function (enhance mechanical stability, minimize fibrosis, reduce permeability, trigger the drug release). Before administration, it is important to be able to characterize the structure and composition of the capsule in 3-D, in particular the presence of contamination that could be harmful to a patient. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) has the potential to provide detailed insight into the 3D chemical composition and has already been used to analyze similar capsules [1]. Here we study alginate microcapsules with and without a surface coating.

The alginate hydrogel microcapsules are stable in solution. TOF-SIMS analysis is made under vacuum which may affect the shape and spatial distribution of elements within the microcapsules. Here we image two types of dried beads, prepared using supercritical CO₂ drying. This sample preparation method conserves the microbead structure before imaging although an extra solvent is needed which may introduce unwanted contamination.

ToF-SIMS is used to image the alginate microcapsules, using extraction delay to reduce topography effects and to identify surface contamination. To obtain information about the interior of the microcapsule both in-situ FIB milling and argon cluster sputtering are shown to be effective. Argon cluster sputtering is particularly well adapted for depth profiling of the surface coating.

Acknowledgements: This work was supported by the French "Recherches Technologiques de Base" Program and was performed on the Nano Characterization Platform (PFNC) of the CEA Grenoble.

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References:

1. A. M. Belu, et al.,Anal. Chem., 72, 5625, (2000).

3D SIMS imaging is a rapidly growing field in biological and pharmaceutical sciences owing to the technique’s ability to map metabolites and drug compound distributions in tissue and cells. In this context, the ability to correlate chemical images with histological features observed by optical microscopy is essential for studying diseased tissue, as well as, for DMPK studies. In this report, 3D laser confocal and optical microscopy techniques are combined with SIMS imaging to analyze biological materials. Image correlation was used to co-register ion images and optical images in order to elucidate morphological features on the macroscopic and microscopic scale.

The 3-dimensional chemical images obtained with SIMS are often distorted by topographical effects and variations in erosion rates. Here, the 3D laser confocal images will be used to correct these distortion effects and produce accurate 3D chemical renderings of cells and tissues. In this study, sectioned lung tissue was used as a model system. The porous tissue provided an extreme topographical challenge for 3D SIMS imaging reconstruction and vasculature in the tissue added to the complexity of the system by introducing heterogeneous cell types and structures. Confocal images of the tissue acquired as a function of depth and integrated to measure the thickness of the tissue section. The same area was subsequently subjected to SIMS depth profiling and the z-scale was corrected and re-scaled using the confocal data.

3D topographical imaging capacities of the LEXT microscope was also used to analyse sputter craters in biological tissues. As a proof-of-concept experiment, the volume of sputter craters was used to calculate secondary ion yields and sputter rates for an argon cluster beam in the range 2 < E/n < 10.