Easy and Versatile Synthesis of Bulk Quantities of Highly Enriched (13)C-Graphene Materials for Biological and Safety Applications

[Image: see text] The preparation of bulk quantities of (13)C-labeled graphene materials is relevant for basic investigations and for practical applications. In addition, (13)C-labeled graphene materials can be very useful in biological and environmental studies, as they may allow the detection of graphene or its derivatives in cells or organs. In this paper, we describe the synthesis of (13)C-labeled graphene materials (few-layer graphene, FLG, and graphene oxide, GO) on a tens of mg scale, starting from (13)C-labeled methane to afford carbon fibers, followed by liquid-phase exfoliation (FLG) or oxidation (GO). The materials have been characterized by several analytical and microscopic techniques, including Raman and nuclear magnetic resonance spectroscopies, thermogravimetric analysis, X-ray photoelectron spectroscopy, and X-ray powder diffraction. As a proof of concept, the distribution of the title compounds in cells has been investigated. In fact, the analysis of the (13)C/(12)C ratio with isotope ratio mass spectrometry (IRMS) allows the detection and quantification of very small amounts of material in cells or biological compartments with high selectivity, even when the material has been degraded. During the treatment of (13)C-labeled FLG with HepG2 cells, 4.1% of the applied dose was found in the mitochondrial fraction, while 4.9% ended up in the nuclear fraction. The rest of the dose did not enter into the cell and remained in the plasma membrane or in the culture media.