Multimodal spatiotemporal phenotyping of human retinal organoid development.

Organoids generated from human pluripotent stem cells provide experimental systems to study development and disease, but quantitative measurements across different spatial scales and molecular modalities are lacking. In this study, we generated multiplexed protein maps over a retinal organoid time course and primary adult human retinal tissue. We developed a toolkit to visualize progenitor and neuron location, the spatial arrangements of extracellular and subcellular components and global patterning in each organoid and primary tissue. In addition, we generated a single-cell transcriptome and chromatin accessibility timecourse dataset and inferred a gene regulatory network underlying organoid development. We integrated genomic data with spatially segmented nuclei into a multimodal atlas to explore organoid patterning and retinal ganglion cell (RGC) spatial neighborhoods, highlighting pathways involved in RGC cell death and showing that mosaic genetic perturbations in retinal organoids provide insight into cell fate regulation.

Charge Dynamics Electron Microscopy: Nanoscale Imaging of Femtosecond Plasma Dynamics.

Understanding and actively controlling the spatiotemporal dynamics of nonequilibrium electron clouds is fundamental for the design of light and electron sources, high-power electronic devices, and plasma-based applications. However, electron clouds evolve in a complex collective fashion on the nanometer and femtosecond scales, producing electromagnetic screening that renders them inaccessible to existing optical probes. Here, we solve the long-standing challenge of characterizing the evolution of electron clouds generated upon irradiation of metallic structures using an ultrafast transmission electron microscope to record the charged plasma dynamics. Our approach to charge dynamics electron microscopy (CDEM) is based on the simultaneous detection of electron-beam acceleration and broadening with nanometer/femtosecond resolution. By combining experimental results with comprehensive microscopic theory, we provide a deep understanding of this highly out-of-equilibrium regime, including previously inaccessible intricate microscopic mechanisms of electron emission, screening by the metal, and collective cloud dynamics. Beyond the present specific demonstration, the here-introduced CDEM technique grants us access to a wide range of nonequilibrium electrodynamic phenomena involving the ultrafast evolution of bound and free charges on the nanoscale.

Emergent Low-Symmetry Phases and Large Property Enhancements in Ferroelectric KNbO3 Bulk Crystals.

The design of new or enhanced functionality in materials is traditionally viewed as requiring the discovery of new chemical compositions through synthesis. Large property enhancements may however also be hidden within already well-known materials, when their structural symmetry is deviated from equilibrium through a small local strain or field. Here, the discovery of enhanced material properties associated with a new metastable phase of monoclinic symmetry within bulk KNbO3 is reported. This phase is found to coexist with the nominal orthorhombic phase at room temperature, and is both induced by and stabilized with local strains generated by a network of ferroelectric domain walls. While the local microstructural shear strain involved is only ≈0.017%, the concurrent symmetry reduction results in an optical second harmonic generation response that is over 550% higher at room temperature. Moreover, the meandering walls of the low-symmetry domains also exhibit enhanced electrical conductivity on the order of 1 S m-1 . This discovery reveals a potential new route to local engineering of significant property enhancements and conductivity through symmetry lowering in ferroelectric crystals.

Imaging and controlling plasmonic interference fields at buried interfaces.

Capturing and controlling plasmons at buried interfaces with nanometre and femtosecond resolution has yet to be achieved and is critical for next generation plasmonic devices. Here we use light to excite plasmonic interference patterns at a buried metal-dielectric interface in a nanostructured thin film. Plasmons are launched from a photoexcited array of nanocavities and their propagation is followed via photon-induced near-field electron microscopy (PINEM). The resulting movie directly captures the plasmon dynamics, allowing quantification of their group velocity at ∼0.3 times the speed of light, consistent with our theoretical predictions. Furthermore, we show that the light polarization and nanocavity design can be tailored to shape transient plasmonic gratings at the nanoscale. This work, demonstrating dynamical imaging with PINEM, paves the way for the femtosecond and nanometre visualization and control of plasmonic fields in advanced heterostructures based on novel two-dimensional materials such as graphene, MoS2, and ultrathin metal films.

Thermotropic phase boundaries in classic ferroelectrics.

High-performance piezoelectrics are lead-based solid solutions that exhibit a so-called morphotropic phase boundary, which separates two competing phases as a function of chemical composition; as a consequence, an intermediate low-symmetry phase with a strong piezoelectric effect arises. In search for environmentally sustainable lead-free alternatives that exhibit analogous characteristics, we use a network of competing domains to create similar conditions across thermal inter-ferroelectric transitions in simple, lead-free ferroelectrics such as BaTiO3 and KNbO3. Here we report the experimental observation of thermotropic phase boundaries in these classic ferroelectrics, through direct imaging of low-symmetry intermediate phases that exhibit large enhancements in the existing nonlinear optical and piezoelectric property coefficients. Furthermore, the symmetry lowering in these phases allows for new property coefficients that exceed all the existing coefficients in both parent phases. Discovering the thermotropic nature of thermal phase transitions in simple ferroelectrics thus presents unique opportunities for the design of 'green' high-performance materials.