Combining surface-sensitive microscopies for analysis of biological tissues after neural device implantation

In order to address the complexity of chemical analysis of biological systems, time-of-flight secondary ion mass spectrometry (ToF-SIMS), x-ray photoelectron spectroscopy (XPS), and x-ray photoemission electron microscopy (XPEEM) were used for combined surface imaging of a biological tissue formed around a surface neural device after implantation on a nonhuman primate brain. Results show patterns on biological tissue based on extracellular matrix (ECM) and phospholipid membrane (PM) molecular fragments, which were contrasted through principal component analysis of ToF-SIMS negative spectrum. This chemical differentiation may indicate severe inflammation on tissue with an early case of necrosis. Quantification of the elemental composition and the chemical bonding states on both ECM-rich and PM-rich features was possible through XPS analysis from survey and high-resolution spectra, respectively. Variable amounts of carbon (68%-80.5%), nitrogen (10%-2.4%), and oxygen (20.8%-16.5%) were detected on the surface of the biological tissue. Chlorine, phosphorous sodium, and sulfur were also identified in lower extends. Besides that, analysis of the C 1s high-resolution spectra for the same two regions (ECM and PM ones) showed that a compromise between C-C (41.8 at. %) and C-N/C-O (35.6 at. %) amounts may indicate a strong presence of amino acids and proteoglycans on the ECM fragment-rich region, while the great amount of C-C (70.1 at. %) on the PM fragment-rich region is attributed to the large chains of fatty acids connected to phospholipid molecules. The micrometer-scale imaging of these chemical states on tissue was accomplished through XPEEM analysis. The C-C presence was found uniformly distributed across the entire analyzed area, while C-N/C-O and C=O were in two distinct regions. The combination of ToF-SIMS, XPS, and XPEEM is shown here as a powerful, noninvasive approach to map out elemental and chemical properties of biological tissues, i.e., identification of chemically distinct regions, followed by quantification of the surface chemical composition in each distinct region.