Field-Portable Nano-Imaging: A New Tool for On-Demand Microscopy

Abstract

Electron microscopy is widely regarded as a high-end laboratory science tool, where substantial resources are pooled to collect image data of exquisite quality. Electron microscopes (EM's) are uniquely able to produce detailed structural images that support discoveries from basic science to monitoring of industrial process. The strong scattering, large depth of focus, and unique blend of signals including elemental analysis are attractive in many applications. Being difficult to operate relative to many other common laboratory tools, EM's are traditionally housed in centers at universities and large research institutions where ample laboratory space, support staff, supplies, and skilled operators come together, or at industrial sites for organizations with research or quality control needs that justify the substantial cost. For those who do not have access to an on-site EM, many larger institutions and service centers accept samples sent in to be imaged, at great expense and often delay of weeks to months for complex analyses. The complexity, high cost, and significant maintenance associated with collecting EM image data has until now severely limited the fields in which EM can be realistically used [1]. This is exemplified in the number of EM instruments deployed (in the tens of thousands) to the number of deployed light microscopes (in the hundreds of millions) [2].A new, smaller, more reliable and user-friendly personal EM --the Mochii TM scanning electron microscope -has been developed by us at Voxa in Seattle, WA (Fig. 1). This low voltage microscope has features that bring accessible and on-demand EM imaging into fields and laboratories where EM was previously hindered by form factor, complexity, and cost. Among these features are small size and light weight (0.25m tall, light enough to carry in a suitcase); user-friendly native wireless tablet interface; multi-and distance-user capabilities (connection to unlimited client nodes), exceedingly low power consumption (by virtue of lowpower magnetic-electrostatic optics), and an integrated metal evaporator for easy sample preparation (only one pump-down cycle to image). We expect the cost to own and operate a Mochii TM microscope to be a fraction of the cost of typical EM's with similar imaging performance due to its low power consumption, simple design, and commoditized user-replaceable consumables.The improved tablet interface and reduced cost compared to existing benchtop systems significantly lowers the barrier of entry to EM imaging in fields where money, space, and/or operational expertise were limited. Learners and scientists in schools and community science centers can begin using EM imaging to explore scientific phenomena at below light-diffraction-limit resolutions for the first time (Fig. 2). We also expect that smaller research labs and new labs or startup companies can easily begin accessing image data without the enormous investment that would be required for a typical EM.Novel miniaturization features also open up access to EM imaging in scientif...

Multi-order Scaling of High-throughput Transmission Electron Microscopy

“…Coauthors at Voxa have previously reported on novel pipelined tools, collectively called Blade™, for increasing transmission electron microscopy (TEM) throughput to enable extremely large 3D volume reconstructions [3][4]. A centerpiece of the pipeline is the GridStage™ sample handling system that enables high-volume low latency delivery and imaging of serial sequential samples under vacuum into the electron microscope.…”

“…A centerpiece of the pipeline is the GridStage™ sample handling system that enables high-volume low latency delivery and imaging of serial sequential samples under vacuum into the electron microscope. Supporting capabilities within the Blade pipeline include a) post-staining to apply stains after sectioning (Strider™), b) conductive layer deposition to control charging and stabilize deposited films (Glow™, previously referred to as Pupa), and c) cassette-based vacuum sample storage (Pod™) [3]. These tools have been deployed at imaging centers focusing on neuroscience, including at the Allen Institute for Brain Science and at the Princeton Neuroscience Institute (PNI), acquiring datasets with detail down to the synaptic level (sub-10 nm) in extremely large volumes exceeding 1 mm 3 (Fig.…”