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In recent years, there has been a revived appreciation for the importance of spatial context and morphological phenotypes for both understanding disease progression and guiding treatment decisions. Compared with conventional 2D histopathology, which is the current gold standard of medical diagnostics, nondestructive 3D pathology offers researchers and clinicians the ability to visualize orders of magnitude more tissue within their natural volumetric context. This has been enabled by rapid advances in tissue-preparation methods, high-throughput 3D microscopy instrumentation, and computational tools for processing these massive feature-rich data sets. Here, we provide a brief overview of many of these technical advances along with remaining challenges to be overcome. We also speculate on the future of 3D pathology as applied in translational investigations, preclinical drug development, and clinical decision-support assays.

 

An end-to-end pipeline for deep learning–assisted computational 3D histology analysis of whole prostate biopsies shows that nondestructive 3D pathology has the potential to enable superior prognostic stratification of patients with prostate cancer.

 

Micro-electromagnetic actuators have been used in many fields and industries for systems such as microftuidic systems, positioning stages, and robotic manipulators. Small-scale electromagnetic actuators are able to provide rapid motion with high positioning accuracy. The actuator presented in this paper utilizes a displacement amplification mechanism to increase the maximum stroke length that can be achieved. The dynamics of this actuator are nonlinear due to the dependence of the applied force on gap distance between the coils and the amplification mechanism. This nonlinearity causes the performance of PID control to vary with respect to the displacement of the actuator. The control method proposed in this paper to limit the overshoot resulting from nonlinearity uses a combination of PID control and robust input shapers. Using robust input shapers to account for parameter variation across the workspace, the combined controller eliminates the overshoot while maintaining short settling times. Simulations are presented to demonstrate the performance of the proposed method. 

Through the efforts of many groups, a wide range of fluorescent protein reporters and sensors based on green fluorescent protein and its relatives have been engineered in recent years. Here we explore the incorporation of sensing modalities into de novo designed fluorescence-activating proteins, called mini-fluorescence-activating proteins (mFAPs), that bind and stabilize the fluorescentcis-planar state of the fluorogenic compound DFHBI. We show through further design that the fluorescence intensity and specificity of mFAPs for different chromophores can be tuned, and the fluorescence made sensitive to pH and Ca²⁺for real-time fluorescence reporting. Bipartite split mFAPs enable real-time monitoring of protein–protein association and (unlike widely used split GFP reporter systems) are fully reversible, allowing direct readout of association and dissociation events. The relative ease with which sensing modalities can be incorporated and advantages in smaller size and photostability make de novo designed fluorescence-activating proteins attractive candidates for optical sensor engineering.