Three-dimensional (3D) tomography using electrons and x-rays has pushed and expanded our understanding of the micro- and nanoscale spatial organization of inorganic, organic, and biological materials. While a significant impact on the field of materials science has already been realized from tomography applications, new advanced methods are quickly expanding the versatility of this approach to better link structure, composition, and function of complex 3D assemblies across multiple scales. In this article, we highlight several frontiers where new developments in tomography are empowering new science across biology, chemistry, and physics. The five articles that appear in this issue of MRS Bulletin describe some of these latest developments in detail, including analytical electron tomography, atomic resolution electron tomography, advanced recording schemes in scanning transmission electron microscopy (STEM) tomography, cryo-STEM tomography of whole cells, and multiscale correlative tomography.

Over the last two decades, three-dimensional (3D) imaging by transmission electron microscopy or “electron tomography” has evolved into a powerful tool to investigate a variety of nanomaterials in different fields, such as life sciences, chemistry, solid-state physics, and materials science. Most of these results were obtained with nanometer-scale resolution, but different approaches have recently pushed the resolution to the atomic level. Such information is a prerequisite to understand the specific relationship between the atomic structure and the physicochemical properties of (nano)materials. We provide an overview of the latest progress in the field of atomic-resolution electron tomography. Different imaging and reconstruction approaches are presented, and state-of-the-art results are discussed. This article demonstrates the power and importance of electron tomography with atomic-scale resolution.

This article highlights recent advances in analytical electron tomography (AET), the three-dimensional (3D) extension of conventional nanoanalytical techniques, in which electron energy loss, x-ray spectroscopy, and electron diffraction are combined with tomographic acquisition and reconstruction. Examples from the literature illustrate how new 3D information, gleaned from AET, provides insights into not just morphology and composition, but also the electronic, chemical, and optical properties of materials at the nanoscale. We describe how the “multidimensional” nature of AET leads to “big data” sets, how these can be analyzed optimally, and how AET may develop further.

Three-dimensional (3D) scanning transmission electron microscopy (STEM) has become one of the primary tools for analytical characterization in materials science and also finds increasing use in the life sciences. A number of different recording schemes exist for the acquisition of 3D data using STEM, each capturing different spatial frequencies and, thus, different information about the shape of a specimen. In this article, we present and compare different sampling approaches based on images with both large and small depth of field. We highlight the latest contribution to 3D data acquisition, the combined tilt, and focal series. This recording scheme combines the advantages of tilt series-based tomography with 3D data acquisition using a focal series and is particularly beneficial for imaging specimens with a thickness of 1 µm or greater.

The electron microscope has made paramount contributions to understanding the structure of biological molecules, cells, and tissues. In general, the most faithful preservation of biological specimens and other soft-organic materials is achieved through cryogenic fixation. The embedding medium is the native aqueous environment itself, immobilized in vitrified form by rapid or pressurized cooling. Until recently, imaging of such vitrified thin specimens by electron cryo-microscopy has been nearly synonymous with wide-field transmission electron microscopy (TEM). Several new approaches have entered the cryo-microscopy field, including soft x-ray imaging, serial surface imaging using focused ion beam scanning electron microscopy, phase plates, and scanning TEM (STEM). In this article, we focus on the STEM method and its adaptation to biological cryo-microscopy. Cryogenic imaging of unstained specimens by STEM introduces specific challenges. Difficulties were long considered insurmountable, and the potential advantages were underappreciated. Future developments in experimental setup and detector technologies will allow for extension of the method to thicker specimens with improved resolution and analytic capabilities.

The intricate hierarchical microstructures typical of biological materials give rise to fascinating combinations of anisotropic mechanical properties that can surpass those of man-made materials. The linking together of three-dimensional (3D) imaging techniques has the potential to reveal these structures in unprecedented detail. However, a complete understanding can only be reached if the relationship between structure and mechanical properties can be elucidated. X-ray-computed tomography (CT) is uniquely placed to image such structures across a wide range of length scales. We review recent technical advances that are leading to improved contrast and spatial resolution. We highlight how time-lapse CT 3D studies can track the response of hierarchical microstructures to mechanical loading.

Thermogelling polymers belong to a class of stimuli-responsive hydrogels that undergo a macroscopic sol-to-gel transition in response to temperature. Much of the ongoing research in this field is focused on hydrogels for biomedical applications as an injectable sustained drug-release matrix or scaffolds for tissue regeneration. Despite robust developments in biodegradable thermogelling polymers in recent decades, the field still faces challenges in the optimization of materials properties. Thorough investigation must be performed to understand the effectiveness of drug delivery using hydrogel-forming polymer carriers. A highlighted case study on OncoGel, an experimental drug delivery depot formulation, sheds some light on the shortcomings of biodegradable thermogelling polymers as drug delivery systems. In this article, we highlight developments in biodegradable thermoresponsive polymers for biomedical applications over the past three years, with a focus on materials/technical challenges and the approaches used to resolve these problems.