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We describe the development, operation, and application of the 4D Camera-a 576 by 576 pixel active pixel sensor for scanning/transmission electron microscopy which operates at 87,000 Hz. The detector generates data at ∼480 Gbit/s which is captured by dedicated receiver computers with a parallelized software infrastructure that has been implemented to process the resulting 10-700 Gigabyte-sized raw datasets. The back illuminated detector provides the ability to detect single electron events at accelerating voltages from 30 to 300 kV. Through electron counting, the resulting sparse data sets are reduced in size by 10--300× compared to the raw data, and open-source sparsity-based processing algorithms offer rapid data analysis. The high frame rate allows for large and complex scanning diffraction experiments to be accomplished with typical scanning transmission electron microscopy scanning parameters.

The complexity of information processing in the brain requires the development of technologies that can provide spatial and temporal resolution by means of dense electrode arrays paired with high-channel-count signal acquisition electronics. In this work, we present an ultra-low noise modular 512-channel neural recording circuit that is scalable to up to 4096 simultaneously recording channels. The neural readout application-specific integrated circuit (ASIC) uses a dense 8.2 mm × 6.8 mm 2D layout to enable high-channel count, creating an ultra-light 350 mg flexible module. The module can be deployed on headstages for small animals like rodents and songbirds, and it can be integrated with a variety of electrode arrays. The chip was fabricated in a TSMC 0.18 µm 1.8 V CMOS technology and dissipates a total of 125 mW. Each DC-coupled channel features a gain and bandwidth programmable analog front-end along with 14 b analog-to-digital conversion at speeds up to 30 kS/s. Additionally, each front-end includes programmable electrode plating and electrode impedance measurement capability. We present both standalone and in vivo measurements results, demonstrating the readout of spikes and field potentials that are modulated by a sensory input.

In a scanning transmission electron microscope (STEM), producing a high-resolution image generally requires an electron beam focused to the smallest point possible. However, the magnetic lenses used to focus the beam are unavoidably imperfect, introducing aberrations that limit resolution. Modern STEMs overcome this by using hardware aberration correctors comprised of many multipole elements, but these devices are complex, expensive, and can be difficult to tune. We demonstrate a design for an electrostatic phase plate that can act as an aberration corrector. The corrector is comprised of annular segments, each of which is an independent two-terminal device that can apply a constant or ramped phase shift to a portion of the electron beam. We show the improvement in image resolution using an electrostatic corrector. Engineering criteria impose that much of the beam within the probe-forming aperture be blocked by support bars, leading to large probe tails for the corrected probe that sample the specimen beyond the central lobe. We also show how this device can be used to create other STEM beam profiles such as vortex beams and probes with a high degree of phase diversity, which improve information transfer in ptychographic reconstructions.

Direct X-ray detection in silicon has been transformative for scattering experiments in biology and materials science. While bump-bonded hybrid pixels have been attractive for hard X-ray detection, the challenge for single photon soft X-ray detection is sufficiently low noise. CCD structures on thick, high-resistivity silicon have been successfully used as sensors over the range of soft to hard X-rays at storage rings and FELs. The VeryFastCCD is a high frame rate, column-parallel CCD sensor with 48 μm pixels. Combined with 256-channel custom readout ASICs, frame rates of 5–10 kHz have been achieved with readout noise as low as 20 e and full-well capacity >4 × 105 e/pixel. Thin (10 nm and 100 nm) entrance window contact processes have also been developed which provide >85% quantum efficiency for 285 eV X-rays. Systems are currently being developed for several beamlines at the upgraded Advanced Light Source.

Resonant Inelastic X-ray Scattering (RIXS) is a powerful spectroscopic technique to study quantum properties of materials in the bulk. A novel variant of RIXS, called 2D RIXS, enables concurrent measurement of the scattered X-ray spectrum for a wide range of input energies, improving on the typically low throughput of 1D RIXS. In the soft X-ray domain, 2D RIXS demands an X-ray camera system with small pixels, large area, high quantum efficiency and low noise to limit the false detection rate in long duration exposures. We designed and implemented a 7.5 Megapixel back-illuminated CMOS detector with 5 μm pixels and high quantum efficiency in the 200–1,000 eV X-ray energy range for the QERLIN 2D RIXS spectrometer at the Advanced Light Source. The QERLIN beamline and detector are currently in commissioning. The camera noise from in-situ 3 s long dark exposures is 7e− or less and the leakage current is 6.5 × 10−3 e−/(pixel ∙ s). For individual 500 eV X-rays, the expected efficiency is greater than 75% and the false detection rate is ∼1 × 10−5 per pixel.

Ultra-stable, tunable magnetic fields are desirable for a wide range of applications in medical imaging, electron microscopy, quantum science, and atomic physics. Superconducting magnets operated in persistent current mode, with device current flowing in a closed superconducting loop disconnected from a power source, are a common approach for applications with the most stringent requirements on temporal field stability. We present a method for active control of this persistent current by means of dynamic inductance change within the superconducting circuit. For a first realization of this general technique, we consider a variable superconducting inductor placed in series with the main magnet. The inductor acts as a dynamic flux storage device capable of transferring flux to or from the main magnet through inductance change. This allows for fine and fast adjustments of the persistent current without the use of thermal switches that limit the speed and accuracy of many present-day methods. With first experiments employing this technique, we demonstrate stabilization of a 1.95 T Nb-Ti round lens for electron microscopy against decay resulting from residual losses in the superconducting circuit, and more generally show flexibility for precise control over the magnitude and waveform of the persistent current.

Measuring electrical potentials in the extracellular space of the brain is a popular technique because it can detect action potentials from putative individual neurons. Electrophysiology is undergoing a transformation where the number of recording channels, and thus number of neurons detected, is growing at a dramatic rate. This rapid scaling is paving the way for both new discoveries and commercial applications; however, as the number of channels increases there will be an increasing need to make these systems more power efficient. One area ripe for optimization are the signal acquisition specifications needed to detect and sort action potentials (i.e., "spikes") to putative single neuron sources. In this work, we take existing recordings collected using Intan hardware and modify them in a way that corresponds to reduced recording performance. The accuracy of these degraded recordings to spike sort using MountainSort4 is evaluated by comparing against expert labels. We show that despite reducing signal specifications by a factor of 2 or more, spike sorting accuracy does not change substantially. Specifically, reducing both sample rate and bit depth from 30 kHz and 16 bits to 12 kHz and 12 bits resulted in a 3% drop in spike sorting accuracy. Our results suggest that current neural acquisition systems are over-specified. These results may inform the design of next generation neural acquisition systems enabling higher channel count systems.

The combination of electrophysiology and optogenetics enables the exploration of how the brain operates down to a single neuron and its network activity. Neural probes are in vivo invasive devices that integrate sensors and stimulation sites to record and manipulate neuronal activity with high spatiotemporal resolution. State-of-the-art probes are limited by tradeoffs involving their lateral dimension, number of sensors, and ability to access independent stimulation sites. Here, we realize a highly scalable probe that features three-dimensional integration of small-footprint arrays of sensors and nanophotonic circuits to scale the density of sensors per cross-section by one order of magnitude with respect to state-of-the-art devices. For the first time, we overcome the spatial limit of the nanophotonic circuit by coupling only one waveguide to numerous optical ring resonators as passive nanophotonic switches. With this strategy, we achieve accurate on-demand light localization while avoiding spatially demanding bundles of waveguides and demonstrate the feasibility with a proof-of-concept device and its scalability towards high-resolution and low-damage neural optoelectrodes.

The analysis of chemical states and morphology in nanomaterials is central to many areas of science. We address this need with an ultrahigh-resolution scanning transmission soft x-ray microscope. Our instrument provides multiple analysis tools in a compact assembly and can achieve few-nanometer spatial resolution and high chemical sensitivity via x-ray ptychography and conventional scanning microscopy. A novel scanning mechanism, coupled to advanced x-ray detectors, a high-brightness x-ray source, and high-performance computing for analysis provide a revolutionary step forward in terms of imaging speed and resolution. We present x-ray microscopy with 8-nm full-period spatial resolution and use this capability in conjunction with operando sample environments and cryogenic imaging, which are now routinely available. Our multimodal approach will find wide use across many fields of science and facilitate correlative analysis of materials with other types of probes.

Battery function is determined by the efficiency and reversibility of the electrochemical phase transformations at solid electrodes. The microscopic tools available to study the chemical states of matter with the required spatial resolution and chemical specificity are intrinsically limited when studying complex architectures by their reliance on two-dimensional projections of thick material. Here, we report the development of soft X-ray ptychographic tomography, which resolves chemical states in three dimensions at 11 nm spatial resolution. We study an ensemble of nano-plates of lithium iron phosphate extracted from a battery electrode at 50% state of charge. Using a set of nanoscale tomograms, we quantify the electrochemical state and resolve phase boundaries throughout the volume of individual nanoparticles. These observations reveal multiple reaction points, intra-particle heterogeneity, and size effects that highlight the importance of multi-dimensional analytical tools in providing novel insight to the design of the next generation of high-performance devices.

We demonstrate a method for obtaining increased spatial resolution and specificity in nanoscale chemical composition maps through the use of full refractive reference spectra in soft x-ray spectro-microscopy. Using soft x-ray ptychography, we measure both the absorption and refraction of x-rays through pristine reference materials as a function of photon energy and use these reference spectra as the basis for decomposing spatially resolved spectra from a heterogeneous sample, thereby quantifying the composition at high resolution. While conventional instruments are limited to absorption contrast, our novel refraction based method takes advantage of the strongly energy dependent scattering cross-section and can see nearly five-fold improved spatial resolution on resonance.

Characterizing the chemistry and magnetism of magnetotactic bacteria (MTB) is an important aspect of understanding the biomineralization mechanism and function of the chains of magnetosomes (Fe3O4 nanoparticles) found in such species. Images and X-ray absorption spectra (XAS) of magnetosomes extracted from, and magnetosomes in, whole Magnetovibrio blakemorei strain MV-1 cells have been recorded using soft X-ray ptychography at the Fe 2p edge. A spatial resolution of 7 nm is demonstrated. Precursor-like and immature magnetosome phases in a whole MV-1 cell were visualized, and their Fe 2p spectra were measured. Based on these results, a model for the pathway of magnetosome biomineralization for MV-1 is proposed. Fe 2p X-ray magnetic circular dichroism (XMCD) spectra have been derived from ptychography image sequences recorded using left and right circular polarization. The shape of the XAS and XMCD signals in the ptychographic absorption spectra of both sample types is identical to the shape and signals measured with conventional bright-field scanning transmission X-ray microscope. A weaker and inverted XMCD signal was observed in the ptychographic phase spectra of the extracted magnetosomes. The XMCD ptychographic phase spectrum of the intracellular magnetosomes differed from the ptychographic phase spectrum of the extracted magnetosomes. These results demonstrate that spectro-ptychography offers a superior means of characterizing the chemical and magnetic properties of MTB at the individual magnetosome level.

A high frame rate detector system is being developed to enable fast real-time data analysis of scanning diffraction experiments in scanning transmission electron microscopy (STEM). This is an end-to-end development that encompasses the data producing detector, data transportation, and real-time processing of data. The detector will consist of a central pixel sensor that is surrounded by annular silicon diodes. Both components of the detector system will synchronously capture data at almost 100 kHz frame rate, which produces an approximately 400 Gb/s data stream. Low-level preprocessing will be implemented in firmware before the data is streamed from the National Center for Electron Microscopy (NCEM) to the National Energy Research Scientific Computing Center (NERSC). Live data processing, before it lands on disk, will happen on the Cori supercomputer and aims to present scientists with prompt experimental feedback. This online analysis will provide rough information of the sample that can be utilized for sample alignment, sample monitoring and verification that the experiment is set up correctly. Only a compressed version of the relevant data is then selected for more in-depth processing.

Neuroscience is entering the era of `extreme data` with little experience and few plans for the associated volume, velocity, variety, and veracity challenges. This is a serious impediment for both the sharing of data across labs, as well as the utilization of modern and high-performance computing capabilities to enable data driven discovery. Here, we introduce BRAINformat, a novel file format and model for management and storage of neuroscience data. The BRAINformat library defines application-independent design concepts and modules that together create a general framework for standardization of scientific data. We describe the formal specification of scientific data standards, which facilitates sharing and verification of data and formats. We introduce the concept of Managed Objects, enabling semantic components of data formats to be specified as self-contained units, supporting modular and reusable design of data format components and file storage. The BRAINformat is built off of HDF5, enabling portable, scalable, and self-describing data storage. We introduce the novel concept of Relationship Attributes for modeling and use of semantic relationships between data objects, and discuss the annotation of data using dedicated data annotation modules provided by the BRAINformat library. Based on these concepts we implement dedicated, application-oriented modules and design a data standard for neuroscience data.The BRAINformat software library is open source, easy-to-use, and provides detailed user and developer documentation and is freely available at: https://bitbucket.org/oruebel/brainformat.

The performance of battery electrode materials is strongly affected by inefficiencies in utilization kinetics and cycle life as well as size effects. Observations of phase transformations in these materials with high chemical and spatial resolution can elucidate the relationship between chemical processes and mechanical degradation. Soft X-ray ptychographic microscopy combined with X-ray absorption spectroscopy and electron microscopy creates a powerful suite of tools that we use to assess the chemical and morphological changes in lithium iron phosphate (LiFePO4) micro- and nanocrystals that occur upon delithiation. All sizes of partly delithiated crystals were found to contain two phases with a complex correlation between crystallographic orientation and phase distribution. However, the lattice mismatch between LiFePO4 and FePO4 led to severe fracturing on microcrystals, whereas no mechanical damage was observed in nanoplates, indicating that mechanics are a principal driver in the outstanding electrode performance of LiFePO4 nanoparticles. These results demonstrate the importance of engineering the active electrode material in next generation electrical energy storage systems, which will achieve theoretical limits of energy density and extended stability. This work establishes soft X-ray ptychographic chemical imaging as an essential tool to build comprehensive relationships between mechanics and chemistry that guide this engineering design.

The fill pattern in proton synchrotrons usually features an empty gap, longer than the abort kicker raise time, for machine protection. This gap is referred to as the "abort gap" and any particles, which may accumulate in it due to injection errors and diffusion between RF buckets, would be lost inside the ring, rather than in the beam dump, during the kicker firing. In large proton rings, due to the high energies involved, it is vital to monitor the build up of charges in the abort gap with a high sensitivity. We present a study of an abort gap monitor based on a photomultiplier with a gated microchannel plate, which would allow for detecting low charge densities by monitoring the synchrotron radiation emitted. We show results of beam test experiments at the Advanced Light Source using a Hamamatsu 5916U MCP-PMT and compare them to the specifications for the Large Hadron Collider