The current approach to improving TEM camera frame rates involves incremental advances in image sensor technology. While there are cameras on the market that offer high-frame-rate imaging, the price of those products is often prohibitive and sometimes greater than the cost of the microscopes they are installed on. Relativity

similar high frame rates to be achieved with existing scintil- lator/CCD TEM cameras, while it also can synchronize with newer high-end camera systems potentially enabling multi- kilohertz sustained frame rates. Key applications of Relativity ® include in situ electron microscopy, cryo electron microscopy, and scanning transmission electron microscopy diffraction. The advantages of high-frame-rate imaging for in situ electron microscopy are obvious, however an equally valuable aspect of Relativity ® is its ability to serve as the high-speed timing control system for triggering a variety of in situ sample holders and other TEM accessories.

® allows

Engineered Materials for Nanoscale Hyper-lensing

US Naval Research Laboratory and Vanderbilt University . Developers : Alexander J. Giles, Joshua Caldwell, and James Edgar

Hexagonal boron nitride (hBN) is a two-dimensional material, similar to graphene in that it consists of atomically thin, planar sheets that are vertically stacked upon each other. Using the imaging

response of hBN, earlier work showed that it was possible to resolve objects 32× smaller than the incident imaging wavelength. This achievement was based on the concept of hyperlensing, which is a label-free method for imaging nanoscale objects, of a size below the usual diffraction limit of light. The method requires highly anisotropic materials with permittivities that are opposite in sign along orthogonal axes. The current innovation is a method to drastically improve the material quality through isotopic enrichment, effectively making an isotopically pure material. This affords both tunability and ultra-high-resolution imaging capabilities that were previously unavailable. By controlling the atomic (isotopic) masses in hBN, we observed up to an eight-fold increase in the quality factor of the phonon resonances in this material. This provides several benefits, most importantly higher transmission throughput (lower absorption), but also almost an order of magnitude enhancement in the spatial resolution (~30 nm minimum imaged feature size). With further advances such as coupling with active elements like graphene and expansion of the image to the far-field, this method could provide the first label-free imaging of nano-sized objects using mid-infrared light. This method would also allow electrical control of the


depth of field. Further, by imaging with light that is tuned to or off the vibrational resonances of the specimen material, spectroscopic identification would also be possible. This technique does not require fluorescent labels, vacuum, or cryogenic environments and can be fitted on conventional light optical microscopes. Thus, the isotopi- cally pure material for the hyperlens creates tremendous opportunities in bioimaging since the capability of this system has improved image resolution from 300 nm to 30 nm. Contained within this length scale are viruses, phages, larger proteins, and cellular organelles. Perhaps most importantly, these features can be imaged at room temperature and atmospheric pressure. This innovation holds the promise of enabling the real-time imaging of biological processes.


Neurescence, Inc. Developer: Yasaman Soudagar

microscope system for observing neurons in several areas of the brain and spinal cord over extended periods of time. In operation the researcher tags particular types of neurons in regions of rodent brain and spinal cord with a protein called

Quartet™ is a miniature

GCaMP6 that changes its fluorescence level as it binds to calcium 2+ ions flowing in and out of the neurons. A patent-pending connector, containing lenses that employ gradient-index optics, is then surgically implanted at the tagged regions. After a 3-week recovery time for the rodent, a fiber optic probe is connected to each implanted lens. Under software control an LED is turned on, and the illumination level is adjusted for the amount of expression of fluorescence in the imaged regions. The camera is focused by manually turning the screw on the lens-side of the lens-fiber connector. The animal is then released into the experi- mental setup, and the system will begin saving images at 20 fps in continuous mode. At the end of the imaging session, the fiber optic probes are disconnected from the lenses. When the fiber probe is disconnected, the initial setting of the microscope focus remains the same, assuring that the same plane of neurons is imaged as days go by. Thus, observable changes that come from changes in the neuronal micro-circuitry, and not from focusing on a different plane of neurons, are recorded. Neuronal activity of particular neurons is processed and analyzed by selecting the imaged neurons via the software. The software saves the evidence of neuronal activity, time tags the amount of activity, and labels the particular neuron in a spreadsheet file. Quartet

multiple imaging regions anywhere in the brain, including • 2018 September

™ provides monitoring of neuronal activity in

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