Furthermore, by measuring diffraction intensity with a numerical aperture significantly higher than that of X-ray lenses, ptychography can reach spatial resolution far beyond those of conventional X-ray microscopy. The overlap between views can then be used as a strong constraint in phase retrieval algorithms 30, leading to a unique, robust reconstruction of the complex exit wave of the object and the illumination function 27, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42. During such a 2D scan, diffraction patterns are recorded from overlapping fields of view with a pre-defined trajectory. In ptychography, an extended sample is observed by illuminating with a coherent wave via a 2D raster scan. Since the first experimental demonstration in 1999 5, various CDI methods have been developed 25 and a particularly powerful approach for imaging extended objects such as whole cells is ptychographic CDI (also known as ptychography) 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42. One method ideally suited to probe individual nanoparticles inside cells is coherent diffractive imaging (CDI) since it can image thick specimens with high resolution and contrast 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24. The ability to localize individual nanoparticles within cells is critical as it allows interactions between the nanoparticles and their target cells to be characterized, informing of the biological effects imparted by the nanoparticles. The ability to precisely localize individual fluorescent nanoparticles within mammalian cells will expand our understanding of the structure/function relationships for functionalized nanoparticles.įunctionalized nanoparticles are used in a broad array of nanomedicine applications for their utility as labels and drug delivery systems 1, 2, 3, 4. Our correlative microscopy results confirmed a subset of particles to be fully internalized, and high-contrast ptychographic images showed two oxidation states of individual nanoparticles with a resolution of ~16.5 nm. These fluorescent core-shell nanoparticles act as landmarks and offer clarity in a cellular context. By tuning the X-ray energy to the Fe L-edge, we demonstrated sensitive detection of nanoparticles composed of a 22 nm magnetic Fe 3O 4 core encased by a 25-nm-thick fluorescent silica (SiO 2) shell. We identified cellular features of interest by fluorescence microscopy, followed by scanning transmission X-ray tomography to localize the particles in 3D, and ptychographic coherent diffractive imaging of the fine features in the region at high resolution. Using a chemically-fixed HeLa cell labeled with fluorescent core-shell nanoparticles as a model system, we implemented a graphene-oxide layer as a substrate to significantly reduce background scattering. Here, we report a proof-of-principle experiment for imaging individual functionalized nanoparticles within a mammalian cell by correlative microscopy. The Fe3O4/SiO 2 (Ir) nanocomposite demonstrates its versatility in various applications: the magnetic core provides the capability for magnetic resonance imaging and the great enhancement of the spinorbit coupling in the iridium complex makes it well suited for phosphorescent labeling and simultaneous singlet oxygen generation to induce apoptosis.Precise localization of nanoparticles within a cell is crucial to the understanding of cell-particle interactions and has broad applications in nanomedicine. The Fe3O4/SiO 2 (Ir) nanocomposite demonstrates its versatility in various applications: the magnetic core provides the capability for magnetic resonance imaging and the great enhancement of the spinorbit coupling in the iridium complex makes it well suited for phosphorescent labeling and simultaneous singlet oxygen generation to induce apoptosis.ĪB - Highly uniform Fe3O4/SiO2 core/shell nanoparticles functionalized by phosphorescent iridium complexes (Ir) have been strategically designed and synthesized. N2 - Highly uniform Fe3O4/SiO2 core/shell nanoparticles functionalized by phosphorescent iridium complexes (Ir) have been strategically designed and synthesized.
T2 - A facile three-in-one system in magnetic resonance imaging, luminescence imaging, and photodynamic therapy T1 - Iridium-complex-functionalized Fe3O4/SiO2 core/shell nanoparticles
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