For instance, iodine based contrast is used extensively for contrast in X-ray (CT) imaging -either extrinsically intravenously injected or intrinsically (genetically encoded) cell-specific contrast with iodine transporters. Optical microscopy boasts a large palette of contrast tools, ranging from extrinsically applied dyes and stains (e.g., Gram, Eosin, Methylene Blue, Masson's Trichrome) to genetically encoded 'cloneable' contrast agents such a wide variety of fluorescent proteins. In electron microscopy of cells, where contrast depends on electron density (scaling with atomic number Z) intrinsic contrast is especially poor as the major elemental components (C, O, N, P) are very similar in electron density. Furthermore, all contrast tools in electron microscopy, both extrinsic metal stains and intrinsic cloneable approaches only function well in fixed cells. Lack of contrast tools represents a major limitation in imaging of cryogenically preserved frozenhydrated cells in EM.