Integrated Array Tomography for High Throughput Electron Microscopy

Abstract

Volume electron microscopy (EM) is now increasingly looked to for answering complex biological questions, thanks in large part to revolutionary developments in instrumentation and sample preparation techniques. However, due to the slow nature of electron-probe-based scanning techniques, throughput has long remained the primary obstacle in pushing to larger areas at high resolution. An undesirable trade-off is therefore commonly made between imaging resolution, volume, and time. A recent approach that attempts to circumvent this trade-off involves selective imaging of the specimen in multiple iterations at increasing levels of magnification. Between iterations, the EM dataset is reconstructed and inspected to locate sites for higher magnification imaging in the next iteration [1]. While this approach can outpace indiscriminate scanning of the entire volume, overall throughput is limited by the overhead involved in reconstructing and evaluating the intermediate datasets.