Adam Fitchett, Jason D. Fabbri, Yaoxing Hu, Justin Cange, Karolina Kozeniauskaite, Kenneth Shepard, David S. Holder, and Kirill Aristovich, “Imaging Circuit Activity in the Rat Brain with Fast Neural EIT and Depth Arrays,” 2023 11th International IEEE/EMBS Conference on Neural Engineering (NER), Baltimore, MD, USA, 2023, pp. 1-4.
Abstract
Few techniques are specialized for neuroscience at the “mesoscopic” level of neural circuits. Fast neural electrical impedance tomography (fnEIT) is a novel imaging technique that offers affordability, portability, and high spatial (∼100 μm) and temporal (~1 ms) resolution. fnEIT with depth arrays offers the opportunity to study the dynamics of circuits in the brains of animal models. However, current depth array geometries are not optimized for this imaging modality. They feature small, closely packed electrodes with high impedance that do not provide sufficient SNR for high resolution EIT image reconstruction. They also have a highly limited range. It is necessary to develop depth arrays suitable for fnEIT and evaluate their performance in a representative setting for circuit neuroscience. In this study, we optimized the geometry of depth arrays for fnEIT, and then investigated the prospects of imaging thalamocortical circuit activity in the rat brain. Optimization was consistent with the hypothesis that small, closely spaced electrodes were not suitable for fnEIT. In vivo experiments with the optimized geometry then showed that fnEIT can image thalamocortical circuit activity at a high enough resolution to see the activity propagating from specific thalamic nuclei to specific regions of the somatosensory cortex. This bodes well for fnEIT’s potential as a technique for circuit neuroscience.
Sukjin S. Jang, Sarah Dubnik, Jason Hon, Björn Hellenkamp, David G. Lynall, Kenneth L. Shepard, Colin Nuckolls and Ruben L. Gonzalez, Jr. Characterizing the Conformational Free-Energy Landscape of RNA Stem-Loops Using Single-Molecule Field-Effect Transistors. December 22, 2022 J. Am. Chem. Soc. 2023, 145, 1, 402–412
Abstract
We have developed and used single-molecule field-effect transistors (smFETs) to characterize the conformational free-energy landscape of RNA stem-loops. Stem-loops are one of the most common RNA structural motifs and serve as building blocks for the formation of complex RNA structures. Given their prevalence and integral role in RNA folding, the kinetics of stem-loop (un)folding has been extensively characterized using both experimental and computational approaches. Interestingly, these studies have reported vastly disparate timescales of (un)folding, which has been interpreted as evidence that (un)folding of even simple stem-loops occurs on a highly rugged conformational energy landscape. Because smFETs do not rely on fluorophore reporters of conformation or mechanical (un)folding forces, they provide a unique approach that has allowed us to directly monitor tens of thousands of (un)folding events of individual stem-loops at a 200 μs time resolution. Our results show that under our experimental conditions, stem-loops (un)fold over a 1–200 ms timescale during which they transition between ensembles of unfolded and folded conformations, the latter of which is composed of at least two sub-populations. The 1–200 ms timescale of (un)folding we observe here indicates that smFETs report on complete (un)folding trajectories in which unfolded conformations of the RNA spend long periods of time wandering the free-energy landscape before sampling one of several misfolded conformations or the natively folded conformation. Our findings highlight the extremely rugged landscape on which even the simplest RNA structural elements fold and demonstrate that smFETs are a unique and powerful approach for characterizing the conformational free-energy of RNA.
Sabina Hillebrandt, Hang, Adriaan J. Taal, Henry Overhauser,Kenneth L. Shepard, and Malte C. Gathe High-Density Integration of Ultrabright OLEDs on a Miniaturized Needle-Shaped CMOS Backplane. Advanced Materials, July 20, 2023
Abstract
Direct deposition of organic light-emitting diodes (OLEDs) on silicon-based complementary metal–oxide–semiconductor (CMOS) chips has enabled self-emissive microdisplays with high resolution and fill-factor. Emerging applications of OLEDs in augmented and virtual reality (AR/VR) displays and in biomedical applications, e.g., as brain implants for cell-specific light delivery in optogenetics, require light intensities orders of magnitude above those found in traditional displays. Further requirements often include a microscopic device footprint, a specific shape and ultrastable passivation, e.g., to ensure biocompatibility and minimal invasiveness of OLED-based implants. In this work, up to 1024 ultrabright, microscopic OLEDs are deposited directly on needle-shaped CMOS chips. Transmission electron microscopy and energy-dispersive X-ray spectroscopy are performed on the foundry-provided aluminum contact pads of the CMOS chips to guide a systematic optimization of the contacts. Plasma treatment and implementation of silver interlayers lead to ohmic contact conditions and thus facilitate direct vacuum deposition of orange- and blue-emitting OLED stacks leading to micrometer-sized pixels on the chips. The electronics in each needle allow each pixel to switch individually. The OLED pixels generate a mean optical power density of 0.25 mW mm−2, corresponding to >40 000 cd m−2, well above the requirement for daylight AR applications and optogenetic single-unit activation in the brain.
Nanyu Zeng, Taesung Jung, Mohit Sharma, Guy Eichler, Jason Fabbri, R. James Cotton, Eleonora Spinazzi, Brett Youngerman, Luca Carloni and Kenneth L. Shepard A Wireless, Mechanically Flexible, 25μμm-Thick, 65,536-Channel Subdural Surface Recording and Stimulating Microelectrode Array with Integrated Antennas. 2023 IEEE Symposium on VLSI Technology and Circuits (VLSI Technology and Circuits).
Abstract
Adriaan J. Taal, Ilke Uguz, , Sabina Hillebrandt, Chang-Ki Moon, Victoria Andino-Pavlovsky, Jaebin Choi, Changmin Keum, Karl Deisseroth, Malte C. Gather& Kenneth L. Shepard Optogenetic stimulation probes with single-neuron resolution based on organic LEDs monolithically integrated on CMOS. Nature Electronics, August 12, 2023.
Abstract
The use of optogenetic stimulation to evoke neuronal activity in targeted neural populations—enabled by opsins with fast kinetics, high sensitivity and cell-type and subcellular specificity—is a powerful tool in neuroscience. However, to interface with the opsins, deep-brain light delivery systems are required that match the scale of the spatial and temporal control offered by the molecular actuators. Here we show that organic light-emitting diodes can be combined with complementary metal–oxide–semiconductor technology to create bright, actively multiplexed emissive elements. We create implantable shanks in which 1,024 individually addressable organic light-emitting diode pixels with a 24.5 µm pitch are integrated with active complementary metal–oxide–semiconductor drive and control circuitry. This integration is enabled by controlled electrode conditioning, monolithic deposition of the organic light-emitting diodes and optimized thin-film encapsulation. The resulting probes can be used to access brain regions as deep as 5 mm and selectively activate individual neurons with millisecond-level precision in mice.
Elena Poggio, Francesca Vallese, Andreas J. W. Hartel, Travis J. Morgenstern, Scott A. Kanner, Oliver Rauh, Flavia Giamogante, Lucia Barazzuol, Kenneth L. Shepard, Henry M. Colecraft, Oliver Biggs Clarke, Marisa Brini and Tito Calì Perturbation of the host cell Ca2+ homeostasis and ER- mitochondria contact sites by the SARS-CoV-2 structural proteins E and M. Cell Death and Disease, April 29, 2023.
Abstract
Coronavirus disease (COVID-19) is a contagious respiratory disease caused by the SARS-CoV-2 virus. The clinical phenotypes are variable, ranging from spontaneous recovery to serious illness and death. On March 2020, a global COVID-19 pandemic was declared by the World Health Organization (WHO). As of February 2023, almost 670 million cases and 6,8 million deaths have been confirmed worldwide. Coronaviruses, including SARS-CoV-2, contain a single-stranded RNA genome enclosed in a viral capsid consisting of four structural proteins: the nucleocapsid (N) protein, in the ribonucleoprotein core, the spike (S) protein, the envelope (E) protein, and the membrane (M) protein, embedded in the surface envelope. In particular, the E protein is a poorly characterized viroporin with high identity amongst all the β-coronaviruses (SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-OC43) and a low mutation rate. Here, we focused our attention on the study of SARS-CoV-2 E and M proteins, and we found a general perturbation of the host cell calcium (Ca2+) homeostasis and a selective rearrangement of the interorganelle contact sites. In vitro and in vivo biochemical analyses revealed that the binding of specific nanobodies to soluble regions of SARS-CoV-2 E protein reversed the observed phenotypes, suggesting that the E protein might be an important therapeutic candidate not only for vaccine development, but also for the clinical management of COVID designing drug regimens that, so far, are very limited.
Thierry Tambe, Jeff Zhang, Coleman Hooper, Tianyu Jia, Paul N. Whatmough, Joseph Zuckerman, Maico Cassel Dos Santos, Erik Jens Loscalzo, Davide Giri, Kenneth Shepard, Luca Carloni, Alexander Rush, David Brooks1, Gu-Yeon Wei1 22.9 A 12nm 18.1TFLOPs/W Sparse Transformer Processor with Entropy-Based Early Exit, Mixed-Precision Predication and Fine-Grained Power Management. March 23, 2023, IEEE International Solid- State Circuits Conference (ISSCC).
Abstract
Large language models have substantially advanced nuance and context understanding in natural language processing (NLP), further fueling the growth of intelligent conversational interfaces and virtual assistants. However, their hefty computational and memory demands make them potentially expensive to deploy on cloudless edge platforms with strict latency and energy requirements. For example, an inference pass using the state-of-the-art BERT-base model must serially traverse through 12 computationally intensive transformer layers, each layer containing 12 parallel attention heads whose outputs concatenate to drive a large feed-forward network [1]. To reduce computation latency, several algorithmic optimizations have been proposed, e.g., a recent algorithm dynamically matches linguistic complexity with model sizes via entropy-based early exit [2]. Deploying such transformer models on edge platforms requires careful co-design and optimizations from algorithms to circuits, where energy consumption is a key design consideration.
Jake Rabinowitz, Andreas J. W. Hartel, Hannah Dayton, Jason D. Fabbri, Jeanyoung Jo, Lars E. P. Dietrich, and Kenneth L. Shepard Charge Mapping of Pseudomonas aeruginosa Using a Hopping Mode Scanning Ion Conductance Microscopy Technique. Anal. Chem., March 15, 2023.
Abstract
Scanning ion conductance microscopy (SICM) is a topographic imaging technique capable of probing biological samples in electrolyte conditions. SICM enhancements have enabled surface charge detection based on voltage-dependent signals. Here, we show how the hopping mode SICM method (HP-SICM) can be used for rapid and minimally invasive surface charge mapping. We validate our method usingPseudomonas aeruginosaPA14 (PA) cells and observe a surface charge density of σPA = −2.0 ± 0.45 mC/m2 that is homogeneous within the ∼80 nm lateral scan resolution. This biological surface charge is detected from at least 1.7 μm above the membrane (395× the Debye length), and the long-range charge detection is attributed to electroosmotic amplification. We show that imaging with a nanobubble-plugged probe reduces perturbation of the underlying sample. We extend the technique to PA biofilms and observe a charge density exceeding −20 mC/m2. We use a solid-state calibration to quantify surface charge density and show that HP-SICM cannot be quantitatively described by a steady-state finite element model. This work contributes to the body of scanning probe methods that can uniquely contribute to microbiology and cellular biology.
Neil L. Harrison , Geoffrey W. Abbott , Martina Gentzsch , Andrei Aleksandrov, Anna Moroni , Gerhard Thiel, Stephen Grant , Colin G. Nichols, Henry A. Lester, Andreas Hartel, Kenneth Shepard, David Cabrera Garcia & Masayuki Yazawa How many SARS-CoV-2 “viroporins” are really ion channels? 25 August 2022, Communications Biology
Maico Cassel dos Santos1, Tianyu Jia, Martin Cochet, Karthik Swaminathan, Joseph Zuckerman, Paolo Mantovani, Davide Giri, Jeff Jun Zhang, Erik Jens Loscalzo, Gabriele Tombesi, Kevin Tien, Nandhini Chandramoorthy, John-David Wellman, David Brooks, Gu-Yeon Wei, Kenneth Shepard, Luca P. Carloni, and Pradip Bose Columbia University, Harvard University, IBM Research A Scalable Methodology for Agile Chip Development with Open-Source Hardware Components. 22 March 2023, IEEE/ACM International Conference On Computer Aided Design (ICCAD).
Abstract
We present a scalable methodology for the agile physical design of tile-based heterogeneous system-on-chip (SoC) architectures that simplifies the reuse and integration of open-source hardware components. The methodology leverages the regularity of the on-chip communication infrastructure, which is based on a multi-plane network-on-chip (NoC), and the modularity of socket interfaces, which connect the tiles to the NoC. Each socket also provides its tile with a set of platform services, including independent clocking and voltage control. As a result, the physical design of each tile can be decoupled from its location in the top-level floorplan of the SoC and the overall SoC design can benefit from a hierarchical timing-closure flow, design reuse and, if necessary, fast respin. With the proposed methodology we completed two SoC tapeouts of increasing complexity, which illustrate its capabilities and the resulting gains in terms of design productivity.
D. Lynall and K. L. Shepard Single-molecule field-effect transistors: carbon nanotube devices for temporally encoded biosensing.2022, International Electron Devices Meeting (IEDM).
Abstract
Observation of biomolecular interactions at the single-molecule level reveals kinetic information crucial for understanding biophysical processes and provide the basis for a new class of molecular diagnostics based on time-domain analysis of molecular interactions. Point-functionalized carbon nanotubes, otherwise known as single-molecule field-effect transistors (smFETs), have shown significant advantage over fluorescence-based approaches for such single-molecule applications due to their high measurement bandwidths, virtually unlimited observation times, low cost, and capabilities for integration with CMOS in large arrays. Here, we demonstrate the capabilities of single-molecule field-effect transistors to measure DNA hybridization kinetics and to selectively detect small molecules through conformational changes of a single-stranded DNA aptamer. In both cases, kinetics can also be modified electrostatically by changes in the bias between the smFET and the surrounding electrolyte.
Sajjad Moazeni, Kevin Renehan, Eric H. Pollmann, and Kenneth L. Shepard, An Integrated-Circuit Node for High-Spatiotemporal Resolution Time-Domain Near Infrared Diffuse Optical Tomography Imaging Arrays, IEEE Journal of Solid-State Circuits (Early Access), 2022.
Abstract
Next-generation brain–computer interfaces (BCIs) for healthy individuals are expected to largely rely on noninvasive functional imaging methods to record cortex-wide neural activity because of the risk associated with surgically implanted devices. In this work, we present a fully integrated 1.8 × 1.8 mm single chip that can be arrayed on a wearable patch to perform noninvasive, functional brain imaging over large cortical areas. This chip node contains two bonded vertical-cavity surfaceemitting lasers (VCSELs), an 8 × 8 single-photon avalanche diode (SPAD) array with event-driven time-to-digital converters (TDCs) per row, and a digital back-end for on-chip histogramming and time-gating. We achieved 70-ps resolution for time-of-flight (ToF) imaging at the record-high 100-MHz laser repetition rate with 80-mW total power. We showed that time-gating improves the imaging contrast by as much as 36% using a brain-skull phantom. The fully integrated and compact node presented here is the key enabler for future high-spatiotemporal-resolution timedomain diffuse optical tomography (TD-DOT) imaging arrays.
Index Terms—Diffuse optical tomography (DOT), noninvasive brain imaging, time-of-flight (ToF) imager, wearable patch.
Eric H Pollmann, Yatin Gilhotra, Heyu Yin, Kenneth L Shepard, Fully Implantable 192× 256 SPAD Sensor with Global-Shutter and Micro-LEDs for Bidirectional Subdural Optical Brain-Computer Interfaces, ESSCIRC 2022-IEEE 48th European Solid State Circuits Conference (ESSCIRC), pp. 205-208
Abstract
We demonstrate a fully implantable optoelectronic neural interface device featuring an array of single-photon avalanche photodiode (SPAD) detectors with a global shutter and monolithically integrated with an array of flip-chip bonded microLEDs (µLED) for fluorescence excitation and optogenetic stimulation. The device is integrated with optical filters and a lensless computation mask to create a 200-μm-thick implantable device. To enable the global shutter, an area-efficient 10b roll-over counter is used in-pixel. With a phase unwrapping algorithm, these counters can be used in a “modulo” fashion providing high dynamic range extension. Our SPAD sensor architecture achieves a better noise ∙ power figure-of-merit (FoM) than comparable photodiode image sensors.
Keywords—optoelectronic implants, single photon avalanche diodes, optogenetics, heterogeneous co-integration, brain computer interfaces.
Tianyu Jia, Paolo Mantovani, Maico Cassel Dos Santos, Davide Giri, Joseph Zuckerman, Erik Jens Loscalzo, Martin Cochet, Karthik Swaminathan, Gabriele Tombesi, Jeff Jun Zhang, Nandhini Chandramoorthy, John-David Wellman, Kevin Tien, Luca Carloni, Kenneth Shepard, David Brooks, Gu-Yeon Wei, Pradip Bose, A 12nm Agile-Designed SoC for Swarm-Based Perception with Heterogeneous IP Blocks, a Reconfigurable Memory Hierarchy, and an 800MHz Multi-Plane NoC, ESSCIRC 2022-IEEE 48th European Solid State Circuits Conference (ESSCIRC), pp. 269-272
Abstract
This paper presents an agile-designed domainspecific SoC in 12nm CMOS for the emerging application domain of swarm-based perception. Featuring a heterogeneous tile-based architecture, the SoC was designed with an agile methodology using open-source processors and accelerators, interconnected by a multi-plane NoC. A reconfigurable memory hierarchy and a CSGALS clocking scheme allow the SoC to run at a variety of performance/power operating points. Compared to a high-end FPGA, the presented SoC achieves 7× performance and 62× efficiency gains for the target application domain.
llke Uguz and Kenneth L. Shepard, “Spatially controlled, bipolar, cortical stimulation with high-capacitance, mechanically flexible subdural surface microelectrode arrays“, 19 Oct 2022, Science Advances, volume 8, Issue 42
Abstract
Jeffrey Elloian, Jakub Jadwiszczak, Volkan Arslan, Jeffrey D. Sherman, David O. Kessler & Kenneth L. Shepard, “Flexible ultrasound transceiver array for non‑invasive surface‑conformable imaging enabled by geometric phase correction“, Scientific Reports volume 12, Article number: 16184 (2022)
Abstract
Ultrasound imaging provides the means for non-invasive real-time diagnostics of the internal structure of soft tissue in living organisms. However, the majority of commercially available ultrasonic transducers have rigid interfaces which cannot conform to highly-curved surfaces. These geometric limitations can introduce a signal-quenching air gap for certain topographies, rendering accurate imaging difficult or impractical. Here, we demonstrate a 256-element flexible two-dimensional (2D) ultrasound piezoelectric transducer array with geometric phase correction. We show surface-conformable real-time B-mode imaging, down to an extreme radius of curvature of 1.5 cm, while maintaining desirable performance metrics such as high signal-to-noise ratio (SNR) and minimal elemental cross-talk at all stages of bending. We benchmark the array capabilities by resolving reflectors buried at known locations in a medical-grade tissue phantom, and demonstrate how phase correction can improve image reconstruction on curved surfaces. With the current array design, we achieve an axial resolution of ≈ 2 mm at clinically-relevant depths in tissue, while operating the array at 1.4 MHz with a bandwidth of ≈ 41%. We use our prototype to image the surface of the human humerus at different positions along the arm, demonstrating proof-of-concept applicability for real-time diagnostics using phase-corrected flexible ultrasound probes.
Yihan Zhang, Prashant Muthuraman, Victoria Andino-Pavlovsky, Ilke Uguz, Jeffrey Elloian & Kenneth L. Shepard, “Augmented ultrasonography with implanted CMOS electronic motes,” Nature Communications volume 13, Article number: 3521 (2022)
Abstract
Modern clinical practice benefits significantly from imaging technologies and much effort is directed toward making this imaging more informative through the addition of contrast agents or reporters. Here, we report the design of a battery-less integrated circuit mote acting as an electronic reporter during medical ultrasound imaging. When implanted within the field-of-view of a brightness-mode (B-mode) ultrasound imager, this mote transmits information from its location through backscattered acoustic energy which is captured within the ultrasound image itself. We prototype and characterize the operation of such motes in vitro and in vivo. Performing with a static power consumption of less than 57 pW, the motes operate at duty cycles for receiving acoustic energy as low as 50 ppm. Motes within the same field-of-view during imaging have demonstrated signal-to-noise ratios of more than 19.1 dB at depths of up to 40 mm in lossy phantom. Physiological information acquired through such motes, which is beyond what is measurable with endogenous ultrasound backscatter and which is biogeographically located within an image, has the potential to provide an augmented ultrasonography.”
Cheng Tan, Derek Y. H. Ho, Lei Wang, Jia I. A. Li, Indra Yudhistira, Daniel A. Rhodes, Takashi Taniguchi, Kenji Watanabe, Kenneth Shepard, Paul L. McEuen, Cory R. Dean, Shaffique Adam, James Hone, “Dissipation-enabled hydrodynamic conductivity in a tunable bandgap semiconductor,” SCIENCE ADVANCES • 15 Apr 2022 • Vol 8, Issue 15
Abstract
Electronic transport in the regime where carrier-carrier collisions are the dominant scattering mechanism has taken on new relevance with the advent of ultraclean two-dimensional materials. Here, we present a combined theoretical and experimental study of ambipolar hydrodynamic transport in bilayer graphene demonstrating that the conductivity is given by the sum of two Drude-like terms that describe relative motion between electrons and holes, and the collective motion of the electron-hole plasma. As predicted, the measured conductivity of gapless, charge-neutral bilayer graphene is sample- and temperature-independent over a wide range. Away from neutrality, the electron-hole conductivity collapses to a single curve, and a set of just four fitting parameters provides quantitative agreement between theory and experiment at all densities, temperatures, and gaps measured. This work validates recent theories for dissipation-enabled hydrodynamic conductivity and creates a link between semiconductor physics and the emerging field of viscous electronics.
Adriaan J. Taal, Changhyuk Lee, Jaebin Choi, Björn Hellenkamp, and Kenneth L. Shepard, “Toward implantable devices for angle-sensitive, lens-less, multifluorescent, single-photon lifetime imaging in the brain using Fabry–Perot and absorptive color filters,” Light: Science & Applications volume 11, Article number: 24 (2022)
Abstract
Implantable image sensors have the potential to revolutionize neuroscience. Due to their small form factor requirements; however, conventional filters and optics cannot be implemented. These limitations obstruct high-resolution imaging of large neural densities. Recent advances in angle-sensitive image sensors and single-photon avalanche diodes have provided a path toward ultrathin lens-less fluorescence imaging, enabling plenoptic sensing by extending sensing capabilities to include photon arrival time and incident angle, thereby providing the opportunity for separability of fluorescence point sources within the context of light-field microscopy (LFM). However, the addition of spectral sensitivity to angle-sensitive LFM reduces imager resolution because each wavelength requires a separate pixel subset. Here, we present a 1024-pixel, 50 µm thick implantable shank-based neural imager with color-filter-grating-based angle-sensitive pixels. This angular-spectral sensitive front end combines a metal–insulator–metal (MIM) Fabry–Perot color filter and diffractive optics to produce the measurement of orthogonal light-field information from two distinct colors within a single photodetector. The result is the ability to add independent color sensing to LFM while doubling the effective pixel density. The implantable imager combines angular-spectral and temporal information to demix and localize multispectral fluorescent targets. In this initial prototype, this is demonstrated with 45 μm diameter fluorescently labeled beads in scattering medium. Fluorescent lifetime imaging is exploited to further aid source separation, in addition to detecting pH through lifetime changes in fluorescent dyes. While these initial fluorescent targets are considerably brighter than fluorescently labeled neurons, further improvements will allow the application of these techniques to in-vivo multifluorescent structural and functional neural imaging.
Hyungsik Kim, Young Duck Kim, Tong Wu, Qingrui Cao, Irving P. Herman, James Hone, Jing Guo, Kenneth L. Shepard, “Electroluminescence of atoms in a graphene nanogap,” SCIENCE ADVANCES • 21 Jan 2022 • Vol 8, Issue 3
Abstract
Here, we report light emission from single atoms bridging a graphene nanogap that emit bright visible light based on fluorescence of ionized atoms. Oxygen atoms in the gap shows a peak emission wavelength of 569 nm with a full width at half maximum (FWHM) of 208 nm. The energy states produced by these ionized oxygen atoms bridging carbon atoms in the gap also produce a large negative differential resistance (NDR) in the transport across the gap with the highest peak-to-valley current ratio (PVR = 45) and highest peak current density (~90 kA/cm2) ever reported in a solid-state tunneling device. While tunneling transport has been previously observed in graphene nanogaps, the bridging of ionized oxygen observed here shows a low excess current, leading to the observed PVR. On the basis of the highly reproducible light emission and NDR from these structures, we demonstrate a 65,536-pixel light-emitting nanogap array.
Jakub Jadwiszczak, Jeffrey Sherman, David Lynall, Yang Liu, Boyan Penkov, Erik Young, Rachael Keneipp, Marija Drndić, James C. Hone, and Kenneth L. Shepard, “Mixed-Dimensional 1D/2D van der Waals Heterojunction Diodes and Transistors in the Atomic Limit,” ACS Nano 2022 16 (1), 1639-1648
Abstract
Inverting a semiconducting channel is the basis of all field-effect transistors. In silicon-based metal-oxidesemiconductor field-effect transistors (MOSFETs), a gate dielectric mediates this inversion. Access to inversion layers may be granted by interfacing ultrathin low-dimensional semiconductors in heterojunctions to advance device downscaling. Here we demonstrate that monolayer molybdenum disulfide (MoS2) can directly invert a single-walled semiconducting carbon nanotube (SWCNT) transistor channel without the need for a gate dielectric. We fabricate and study this atomically thin one-dimensional/two-dimensional (1D/2D) van der Waals heterojunction and employ it as the gate of a 1D heterojunction field-effect transistor (1D-HFET) channel. Gate control is based on modulating the conductance through the channel by forming a lateral p−n junction within the CNT itself. In addition, we observe a region of operation exhibiting a negative static resistance after significant gate tunneling current passes through the junction. Technology computer- aided design (TCAD) simulations confirm the role of minority carrier drift-diffusion in enabling this behavior. The resulting van der Waals transistor architecture thus has the dual characteristics of both field-effect and tunneling transistors, and it advances the downscaling of heterostructures beyond the limits of dangling bonds and epitaxial constraints faced by III−V semiconductors.
Sajjad Moazeni, Eric H. Pollmann, Vivek Boominathan, Filipe A. Cardoso, Jacob T. Robinson, Ashok Veeraraghavan and Kenneth L. Shepard, “A Mechanically Flexible, Implantable Neural Interface for Computational Imaging and Optogenetic Stimulation over 5.4 x 5.4mm2 FoV“, IEEE Transactions on Biomedical Circuits and Systems (Early Access)
Abstract
Emerging optical functional imaging and optogenetics are among the most promising approaches in neuroscience to study neuronal circuits. Combining both methods into a single implantable device enables all-optical neural interrogation with immediate applications in freely-behaving animal studies. In this paper, we demonstrate such a device capable of optical neural recording and stimulation over large cortical areas. This implantable surface device exploits lens-less computational imaging and a novel packaging scheme to achieve an ultra-thin (250μm-thick), mechanically flexible form factor. The core of this device is a custom-designed CMOS integrated circuit containing a 160 x 160 array of time-gated single-photon avalanche photodiodes (SPAD) for low-light intensity imaging and an interspersed array of dual-color (blue and green) flip-chip bonded micro-LED (μLED) as light sources. We achieved 60μm lateral imaging resolution and 0.2mm3 volumetric precision for optogenetics over a 5.4 x 5.4mm2 field of view (FoV). The device achieves a 125-fps frame-rate and consumes 40mW of total power.
Tiago Costa, Chen Shi, Kevin Tien, Jeffrey Elloian, Filipe A. Cardoso and Kenneth L. Shepard, “An Integrated 2D Ultrasound Phased Array Transmitter in CMOS with Pixel Pitch-Matched Beamforming,” IEEE Transactions on Biomedical Circuits and Systems, 2021 (Early Access)
Abstract
Emerging non-imaging ultrasound applications, such as ultrasonic wireless power delivery to implantable devices and ultrasound neuromodulation, require wearable form factors, millisecond-range pulse durations and focal spot diameters approaching 100 m with electronic control of its three-dimensional location. None of these are compatible with typical handheld linear array ultrasound imaging probes. In this work, we present a 4 mm x 5 mm 2D ultrasound phased array transmitter with integrated piezoelectric ultrasound transducers on complementary metal-oxide-semiconductor (CMOS) integrated circuits, featuring pixel-level pitch-matched transmit beamforming circuits which support arbitrary pulse duration. Our direct integration method enabled up to 10 MHz ultrasound arrays in a patch form-factor, leading to focal spot diameter of ~200 m, while pixel pitch-matched beamforming allowed for precise three-dimensional positioning of the ultrasound focal spot. Our device has the potential to provide a high-spatial resolution and wearable interface to both powering of highly-miniaturized implantable devices and ultrasound neuromodulation.
Chen Shi, Victoria Andino-Pavlovsky, Stephen A. Lee, Tiago Costa, Jeffrey Elloian, Elisa E. Konofagou, and Kenneth L. Shepard, “Application of a sub-0.1-mm3 implantable mote for in vivo real-time wireless temperature sensing,” Science Advances 7, No. 19 (2021)
Abstract
There has been increasing interest in wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. Here, we present such an implant that uses a conventional ultrasound imager for wireless powering and data communication and acts as a probe for real-time temperature sensing, including the monitoring of body temperature and temperature changes resulting from therapeutic application of ultrasound. The sub–0.1-mm3, sub–1-nW device, referred to as a mote, achieves aggressive miniaturization through the monolithic integration of a custom low-power temperature sensor chip with a microscale piezoelectric transducer fabricated on top of the chip. The small displaced volume of these motes allows them to be implanted or injected using minimally invasive techniques with improved biocompatibility. We demonstrate their sensing functionality in vivo for an ultrasound neurostimulation procedure in mice. Our motes have the potential to be adapted to the distributed and localized sensing of other clinically relevant physiological parameters.
Adriaan Taal, Jake Rabinowitz, and K. L. Shepard, “mr-EBL: ultra-high sensitivity negative-tone electron beam resist for highly selective silicon etching and large-scale direct patterning of permanent structures,” Nanotechnology 32 (2021) 245302
Abstract
“Electron beam lithography (EBL) is the state-of-the-art technique for rapid prototyping of nanometer-scale devices. Even so, processing speeds remain limited for the highest resolution patterning. Here, we establish Mr-EBL as the highest throughput negative tone electron-beamsensitive resist. The 10 μC cm−2 dose requirement enables fabricating a 100 mm2 photonic diffraction grating in a ten minute EBL process. Optimized processing conditions achieve a critical resolution of 75 nm with 3× faster write speeds than SU-8 and 1–2 orders of magnitude faster write speeds than maN-2400 and hydrogen silsesquioxane. Notably, these conditions significantly differ from the manufacturers’ recommendations for the recently commercialized Mr-EBL resist. We demonstrate Mr-EBL to be a robust negative etch mask by etching silicon trenches with aspect ratios of 10 and near-vertical sidewalls. Furthermore, our optimized processing conditions are suitable to direct patterning on integrated circuits or delicate nanofabrication stacks, in contrast to other negative tone EBL resists. In conclusion, Mr-EBL is a highly attractive EBL resist for rapid prototyping in nanophotonics, MEMS, and fluidics.”
Sajjad Moazeni, Eric H. Pollmann, Vivek Boominathan, Filipe A.Cardoso,Jacob T. Robinson, Ashok Veeraraghavan, Kenneth L. Shepard, A Mechanically Flexible Implantable Neural Interface for Computational Imaging and Optogenetic Stimulation over 5.4×5.4mm2 FoV, International Solid-State Circuits Conference, 2021
Sajjad Moazeni, Kevin Renehan, Eric Pollmann, Kenneth Shepard, Integrated-Circuit Node for Time-Domain Near-infrared Diffuse Optical Tomography Imaging Arrays with On-chip Histogramming and Integrated VCSELs, IEEE Custom Integrated Circuits Conference (CICC), 2021
Rabinowitz, Jake, Elizabeth Whittier, Zheng Liu, Krishna Jayant, Joachim Frank, Kenneth Shepard. “Nanobubble-controlled nanofluidic transport.” Science Advances 6, no. 46 (2020).
Abstract
Nanofluidic platforms offering tunable material transport are applicable in biosensing, chemical detection, and filtration. Prior studies have achieved selective and controllable ion transport through electrical, optical, or chemical gating of complex nanostructures. Here, we mechanically control nanofluidic transport using nanobubbles. When plugging nanochannels, nanobubbles rectify and occasionally enhance ionic currents in a geometry-dependent manner. These conductance effects arise from nanobubbles inducing surface-governed ion transport through interfacial electrolyte films residing between nanobubble surfaces and nanopipette walls. The nanobubbles investigated here are mechanically generated, made metastable by surface pinning, and verified with cryogenic transmission electron microscopy. Our findings are relevant to nanofluidic device engineering, three-phase interface properties, and nanopipette-based applications.
Moreaux, Laurent C., Dimitri Yatsenko, Wesley D. Sacher, Jaebin Choi, Changhyuk Lee, Nicole J. Kubat, R. James Cotton, Edward S. Boyden, Michael Z. Lin, Lin Tian, Andreas S. Tolias, Joyce K.S. Poon, Kenneth L. Shepard, and Michael L. Roukes, “Integrated Neurophotonics: Toward Dense Volumetric Interrogation of Brain Circuit Activity—at Depth and in Real Time” Neuron 108, pages 66-92(2020)
Abstract
We propose a new paradigm for dense functional imaging of brain activity to surmount the limitations of present methodologies. We term this approach ‘‘integrated neurophotonics’’; it combines recent advances in microchip-based integrated photonic and electronic circuitry with those from optogenetics. This approach has the potential to enable lens-less functional imaging from within the brain itself to achieve dense, largescale stimulation and recording of brain activity with cellular resolution at arbitrary depths. We perform a computational study of several prototype 3D architectures for implantable probe-array modules that are designed to provide fast and dense single-cell resolution (e.g., within a 1-mm3 volume of mouse cortex comprising -100,000 neurons). We describe progress toward realizing integrated neurophotonic imaging modules, which can be produced en masse with current semiconductor foundry protocols for chip manufacturing. Implantation of multiple modules can cover extended brain regions.
Sherman, Jeffrey D., Jeffrey Elloian, Jakub Jadwiszczak, and Kenneth L. Shepard, “On the Temperature Dependence of the Piezoelectric Response of Prepoled Poly(vinylidene fluoride) Films” ACS Applied Polymer Materials (2020)
Abstract
There is growing interest in integrating piezoelectric materials with complementary metal-oxide-semiconductor (CMOS) technology to enable expanded applications. A promising material for ultrasound transducer applications is poly(vinylidene fluoride) (PVDF), a piezoelectric polymer. One of the challenges with PVDF is that its piezoelectric properties can deteriorate when exposed to temperatures in excess of 70 °C for extended periods of
time during fabrication. Here, we report on the effects of both shortening annealing times and providing this heating nonuniformly, as is characteristic of some processing conditions, on the piezoelectric coefficient (d33) of PVDF films for various thicknesses. In this case, no degradation in the d33 was observed at temperatures below 100 °C for anneal times of under 1 min when this heating is applied through one side of the film, making PVDF compatible with many bonding and photolithographic processing steps required for CMOS integration. More surprisingly, for one-sided heating to temperatures between 90 and 110 °C, we observed a transient enhancement of the d33 by nearly 40% that lasted for several hours after these anneals. We attribute this effect to induced strain in these films.
Jaebin Choi, Adriaan J. Taal, William L. Meng, Eric H. Pollmann, John W. Stanton, Changhyuk Lee, Sajjad Moazeni, Laurent C. Moreaux, Michael L. Roukes, and Kenneth L. Shepard, “Fully Integrated Time-Gated 3D Fluorescence Imager for Deep Neural Imaging,” IEEE Transactions on Biomedical Circuits and Systems 14, no. 4, pages 636-645 (2020).
Abstract
This paper reports an implantable 3D imager for time-gated fluorescence imaging in the deep brain. Fluorescence excitation is provided by dual ns-pulsed blue micro-light-emitting diodes (μLED), and fluorescence emission is collected by an 8-by64 single-photon avalanche diode (SPAD) array, together packaged to a width of 420 μm to allow deep insertion through a cannula. Each SPAD is masked by a repeating pattern of Talbot gratings that give each pixel a different angular sensitivity, allowing three-dimensional image reconstruction to a resolution of ~20 μm. The integrated imager is able to monitor fluorescent targets across a field of view of 1000 μm by 600 μm by 500 μm at arbitrary tissue depths.
William Cole Cornell, Yihan Zhang, Anastasia Bendebury, Andreas J.W. Hartel, Kenneth L. Shepard, Lars E.P. Dietrich. “Phenazine oxidation by a distal electrode modulates biofilm morphogenesis.” Biofilm 2 (2020) 100025.
Abstract
Microbes living in biofilms, dense assemblages of cells, experience limitation for resources such as oxygen when cellular consumption outpaces diffusion. The pathogenic bacterium Pseudomonas aeruginosa has strategies for coping with hypoxia that support cellular redox balancing in biofilms; these include (1) increasing access to oxygen by forming wrinkles in the biofilm surface and (2) electrochemically reducing endogenous compounds called phenazines, which can shuttle electrons to oxidants available at a distance. Phenazine-mediated extra-cellular electron transfer (EET) has been shown to support survival for P. aeruginosa cells in anoxic liquid cultures, but the physiological relevance of EET over a distance for P. aeruginosa biofilms has remained unconfirmed. Here, we use a custom-built electrochemistry setup to show that phenazine-mediated electron transfer at a distance inhibits wrinkle formation in P. aeruginosa biofilms. This result demonstrates that phenazine-dependent EET to a distal oxidant affects biofilm morphogenesis.
Chia-Han Chiang, Sang Min Won, Amy L. Orsborn, Ki Jun Yu, Michael Trumpis, Brinnae Bent, Charles Wang, Yeguang Xue, Seunghwan Min, Virginia Woods, Chunxiu Yu, Bong Hoon Kim, Sung Bong Kim, Rizwan Huq, Jinghua Li, Kyung Jin Seo, Flavia Vitale, Andrew Richardson, Hui Fang, Yonggang Huang, Kenneth Shepard, Bijan Pesaran, John A. Rogers, Jonathan Viventi. “Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates.” Science translational medicine 12, no. 538 (2020).
Abstract
Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called “Neural Matrix,” that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.
Thimot, Jordan, Kukjoo Kim, Chen Shi, and Kenneth L. Shepard. “A 27-Mbps, 0.08-mm3 CMOS Transceiver with Simultaneous Near-field Power Transmission and Data Telemetry for Implantable Systems.” In 2020 IEEE Custom Integrated Circuits Conference (CICC), pp. 1-4. IEEE, 2020.
Abstract
This paper describes an inductively powered 27-Mbps, 0.08-mm3 CMOS transceiver with integrated RF receivercoils for simultaneous two-way, near-field data telemetry andpower transmission for implantable systems. A four-coil inductivelink operates at a 27-MHz carrier for power and a 700-MHzcarrier for data telemetry with the antennae taking an area of only2 mm by 2 mm. Amplitude-shift-keying (ASK) modulation is usedfor data downlink at 6.6 kbps and load-shift keying (LSK)backscattering is used for data uplink at 27 Mbps. The transceiverconsumes 2.7 mW and can power a load consuming up to anadditional 1.5 mW. Implemented in a 0.18-um silicon-on-insulator(SOI) technology, post-processing steps are used to decrease chipthickness to approximately 15um, making the chip flexible with atissue-like form factor and removing the effects of the substrate oncoil performance. Power harvesting circuitry, including passiverectifier, voltage regulator, RF limiter, ASK and LSK modulator,clock generator, and digital controller are positioned adjacent tothe coils and limited to an area of 0.5 mm by 2mm. Completetransceiver functionality of the system has been achieved withoverall power transfer efficiency (PTE) of 1.04% through 1 mm oftissue phantom between reader and implant.
Y. Zhang, F. Cadoso, and K. L. Shepard, A 0.72 nW, 1 Sample/s Fully Integrated pH Sensor with 65.8 LSB/pH Sensitivity, Proceedings of the Symposium on VLSI Circuits, 2020.
Abstract
This paper presents a 0.85 mm 2 fully integrated pH sensor IC utilizing an ion sensitive field effect transistor (ISFET) and reference field effect transistor (REFET) pair in which the native foundry passivation layer is used as an ion sensitive layer. The pH sensor has 10 bit resolution with 65.8 LSB/pH sensitivity, while consuming only 0.72 nW at 1 sample/s, improving an overall figure of merit (FoM) that accounts for power, sampling frequency, and sensitivity by > 4000×.
Shi, Chen, Tiago Costa, Jeffrey Elloian, Yihan Zhang, and Kenneth Shepard. “A 0.065-mm3 Monolithically-integrated Ultrasonic Wireless Sensing Mote for Real-time Physiological Temperature Monitoring.” IEEE Transactions on Biomedical Circuits and Systems (2020).
Abstract
Accurate monitoring of physiological temperature is important for many biomedical applications, including monitoring of core body temperature, detecting tissue pathologies, and evaluating surgical procedures involving thermal treatment such as hyperthermia therapy and tissue ablation. Many of these applications can benefit from replacing external temperature probes with injectable wireless devices. Here we present such a device for real-time in vivo temperature monitoring that relies on “chip-as-system” integration. With an on-chip piezoelectric transducer and measuring only 380 μm ×× 300 μm × 570 μm, the 0.065-mm3 monolithic device, in the form of a mote, harvests ultrasound energy for power and transmits temperature data through acoustic backscattering. Containing a low-power temperature sensor implemented with a subthreshold oscillator and consuming 0.813 nW at 37 °C, the mote achieves line sensitivity of 0.088 °C/V, temperature error of +0.22/-0.28 °C, and a resolution of 0.0078 °C rms. A long-term measurement with the mote reveals an Allan deviation floor of <138.6 ppm, indicating the feasibility of using the mote for continuous physiological temperature monitoring.
Elloian, Jeffrey, Jeffrey Sherman, Tiago Costa, Chen Shi, and Kenneth Shepard. “Ablation of piezoelectric polyvinylidene fluoride with a 193 nm excimer laser.” Journal of Vacuum Science & Technology A: Vacuum, Surfaces, and Films 38, no. 3 (2020): 033202.
Abstract
The unique flexible and piezoelectric properties of polyvinylidene fluoride (PVDF) films would allow for new appli-cations for integrated bioelectronic devices. The use of these films has been precluded by the difficulty in machiningit into small, discrete features without damaging the properties of the material. The etching of piezoelectric PVDF bymeans of a 193 nm excimer laser is explored and characterized. Etch rates are shown for common laser fluence values,along with images of the quality of the cuts to provide the reader with an understanding of the compromise betweenetch rate and edge roughness.
Jake Rabinowitz, Charishma Cohen, and K. L. Shepard, An Electrically Actuated, Carbon-Nanotube-Based Biomimetic Ion Pump, Nano Letters, DOI: 10.1021/acs.nanolett.9b04552
Abstract
Single-walled carbon nanotubes (SWCNTs) are well-established transporters of electronic current, electrolyte, and ions. Inthis work, we demonstrate an electrically actuated biomimetic ionpump by combining these electronic and nanofluidic transportcapabilities within an individual SWCNT device. Ion pumping isdriven by a solid-state electronic input, as Coulomb drag couplingtransduces electrical energy from solid-state charge along the SWCNTshell to electrolyte inside the SWCNT core. Short-circuit ioniccurrents, measured without an electrolyte potential difference, exceed 1 nA and scale larger with increasing ion concentrationsthrough 1 M, demonstrating applicability under physiological (∼140 mM) and saltwater (∼600 mM) conditions. The interlayercoupling allows ionic currents to be tuned with the source−drain potential difference and electronic currents to be tuned withthe electrolyte potential difference. This combined electronic−nanofluidic SWCNT device presents intriguing applications as abiomimetic ion pump or component of an artificial membrane.
Jaebin Choi, Adriaan J. Taal, Eric H. Pollmann, William Meng, Sajjad Moazeni, Laurent C. Moreaux, Michael L. Roukes, Kenneth L. Shepard. Fully Integrated Time-Gated 3D Fluorescence Imager for Deep Neural Imaging. IEEE Biomedical Circuits and Systems Conference, October 18, 2019.
Abstract
This paper reports an implantable 3D imager for time-gated fluorescence imaging in the deep brain. Fluorescence excitation is provided by dual ns-pulsed blue micro-light-emitting diodes (μLED), and fluorescence emission is collected by an 8-by-64 single-photon avalanche diode (SPAD) array, together packaged to a width of 420 μm to allow deep insertion through a cannula. Each SPAD is masked by a repeating pattern of Talbot gratings that give each pixel a different angular sensitivity, allowing three-dimensional image reconstruction to a resolution of ~20μm. The integrated imager is able to monitor fluorescent targets across a field of view of 1000 μm by 600 μm by 500 μm at arbitrary tissue depths.
Jaebin Choi, Adriaan J. Taal, Eric H. Pollmann, Changhyuk Lee, Kukjoo Kim, Laurent C. Moreaux, Michael L. Roukes, Kenneth L. Shepard. A 512-Pixel, 51-kHz-Frame-Rate, Dual-Shank, Lens-Less, Filter-Less Single-Photon Avalanche Diode CMOS Neural Imaging Probe. IEEE Journal of Solid-State Circuits, volume 54, pages 2957-2968, November, 2019 DOI:10.1109/JSSC.2019.2941529
Abstract
We present an implantable single-photon shank-based imager, monolithically integrated onto a single CMOSIC. The imager comprises of 512 single-photon avalanchediodes distributed along two shanks, with a 6-bit depth in-pixelmemory and an on-chip digital-to-time converter. To scale downthe system to a minimally invasive form factor, we substituteoptical filtering and focusing elements with a time-gated,angle-sensitive detection system. The imager computationallyreconstructs the position of fluorescent sources within a 3-Dvolume of 3.4 mm×600μm×400μm.
David Kleinfeld, Lan Luan, Partha P.Mitra, Jacob T.Robinson, Rahul Sarpeshkar Kenneth Shepard, ChongXie, Timothy D.Harris. Can One Concurrently Record Electrical Spikes from Every Neuron in a Mammalian Brain?. Neuron, 5 September 2019, DOI: 10.1016/j.neuron.2019.08.011
Abstract
Physical limits do not preclude simultaneous recordings of all spikes in neocortex
Future electrodes need nontraditional materials and fabrication procedures
Challenges for dense recording include heat dissipation from interface electronics
Chen-Chi Chien, Siddharth Shekar, David J. Niedzwiecki, Kenneth L. Shepard and Marija Drndić.
“Single-Stranded DNA Translocation Recordings through Solid-State Nanopores on Glass Chips at 10 MHz Measurement Bandwidth“. ACS Nano, 26 August, 2019, DOI: 10.1021/acsnano.9b04626
Jacob T. Robinson, Eric Pohlmeyer, Malte C. Gather, Caleb Kemere, John E. Kitching,George G. Malliaras, Adam Marblestone, Kenneth L. Shepard, Thomas Stieglitz, Chong Xie “Developing Next-generation Brain Sensing Technologies – A Review“, IEEE Sensors Journal, 25 July 2019, DOI:10.1109/JSEN.2019.2931159
Abstract
Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients.
Siddharth Shekar, Krishna Jayant, M Angeles Rabadan, Raju Tomer, Rafael Yuste and Kenneth L. Shepard “A miniaturized multi-clamp CMOS amplifier for intracellular neural recording” Nature Electronics volume 2, pages343–350 (2019)
Abstract
Intracellular electrophysiology is a foundational method in neuroscience and uses electrolyte-filled glass electrodes and bench-top amplifiers to measure and control transmembrane voltages and currents. Commercial amplifiers perform such recordings with high signal-to-noise ratios but are often expensive, bulky and not easily scalable to many channels due to reliance on board-level integration of discrete components. Here, we present a monolithic complementary metal–oxide–semiconductor multi-clamp amplifier integrated circuit capable of recording both voltages and currents with performance exceeding that of commercial benchtop instrumentation. Miniaturization enables high-bandwidth current mirroring, facilitating the synthesis of large-valued active resistors with lower noise than their passive equivalents. This enables the realization of compensation mod-ules that can account for a wide range of electrode impedances. We validate the amplifier’s operation electrically, in primary neuronal cultures, and in acute slices, using both high-impedance sharp and patch electrodes. This work provides a solution for low-cost, high-performance and scalable multi-clamp amplifiers.
Jake Rabinowitz, Martin A. Edwards, Elizabeth Whittier, Krishna Jayant and Kenneth L. Shepard. “Nanoscale Fluid Vortices and Nonlinear Electroosmotic Flow Drive Ion Current Rectification in the Presence of Concentration Gradients“, J. Phys. Chem. A 2019.
Abstract
Ion current rectification (ICR) is a transport phenomenon inwhich an electrolyte conducts unequal currents at equal and opposite voltages.Here, we show that nanoscalefluid vortices and nonlinear electroosmoticflow(EOF) drive ICR in the presence of concentration gradients. The same EOFcan yield negative differential resistance (NDR), in which current decreaseswith increasing voltage. Afinite element model quantitatively reproducesexperimental ICR and NDR recorded across glass nanopipettes underconcentration gradients. The model demonstrates that spatial variations ofelectrical double layer properties induce the nanoscale vortices and nonlinearEOF. Experiments are performed in conditions directly related to scanningprobe imaging and show that quantitative understanding of nanoscale transport under concentration gradients requiresaccounting for EOF. This characterization of nanopipette transport physics will benefit diverse experimentation, pushing theresolution limits of chemical and biophysical recordings.
Andreas J.W. Hartel, siddharth Shekar, Peijie Ong, Indra Schroeder, Gerhard Thiel, Kenneth L. Shepard. High bandwidth approaches in nanopore and ion channel recordings – A tutorial review. Analytica Chimica Acta. January 5, 2019, DOI: 10.1016/j.aca.201901.034
Abstract
Transport processes through ion-channel proteins, protein pores, or solid-state nanopores are tradi-tionally recorded with commercial patch-clamp amplifiers. The bandwidth of these systems is typicallylimited to 10 kHz by signal-to-noise-ratio (SNR) considerations associated with these measurementplatforms. At high bandwidth, the input-referred current noise in these systems dominates, determinedby the input-referred voltage noise of the transimpedance amplifier applied across the capacitance at theinput of the amplifier. This capacitance arises from several sources: the parasitic capacitance of theamplifier itself; the capacitance of the lipid bilayer harboring the ion channel protein (or the membraneused to form the solid-state nanopore); and the capacitance from the interconnections between theelectronics and the membrane. Here, we review state-of-the-art applications of high-bandwidthconductance recordings of both ion channels and solid-state nanopores. These approaches involvetightly integrating measurement electronics fabricated in complementary metal-oxide semiconductors(CMOS) technology with lipid bilayer or solid-state membranes. SNR improvements associated with thistight integration push the limits of measurement bandwidths, in some cases in excess of 10 MHz. Recentcase studies demonstrate the utility of these approaches for DNA sequencing and ion-channel recordings.In the latter case, studies with extended bandwidth have shown the potential for providing new insightsinto structure-function relations of these ion-channel proteins as the temporal resolutions of functionalrecordings matches time scales achievable with state-of-the-art molecular dynamics simulations.
Yihan Zhang and K. L. Shepard, “A 0.6-mm2 powering and data telemetry system compatible with ultrasound b-mode imaging for freely moving biomedical sensor systems,” Custom Integrated Circuits Conference, 2019
Abstract
A 0.6 mm2 integrated circuit, fabricated in a 180 nm process, is designed to operate within the field of view of an ultrasound B-mode imager, allowing data to be received from ultra-small-form-factor devices that can be localized, powered, and configured as multiple freely moving ingestible or implantable systems. Power is harvested from ultrasound pulses emitted by the imaging transducer array and a bi-directional data link is established that is synchronized to the frame rate of the imager. The chip consumes 57 pW of power and supports data rates of 25 bit/s for uplink and 50 bit/s for downlink for an imager operating at 50 frames per second. Fully packaged within 11 mm3 with a piezoelectric transducer, the chip enables tissue implants as deep as 71 mm. Real-time localizations of devices is possible within the field of view of the imager at 0.8-mm accuracy. An on-chip instruction set allows for software configuration and a smooth transition to a more power-intensive mode of operation using focused ultrasound pulses after localization, with 280 nW power delivery verified using 0.5% duty cycle ultrasound.
Tiago Costa, Chen Shi, Kevin Tien, and K. L. Shepard, “A CMOS 2D transmit beamformer with integrated PZT ultrasound transducers for neuromodulation,” Custom Integrated Circuits Conference, 2019
Abstract
While the mechanisms are not yet completely understood, ultrasound-based neuromodulation has been emerging as a noninvasive modality for interfacing to both the central and peripheral nervous systems, due to its high penetration depth and good spatial resolution. Commercially available ultrasound transducers for neuromodulation applications are typically single-element focused transducers with a bulky form factor and off-the-shelf electronics for drive. Changing the focal position requires mechanical movement of the transducer itself. High-density ultrasound phased arrays allow for electronic focusing. Here, we present a CMOS 2D beamformer with integrated lead zirconate titanate (PZT) ultrasound transducers for neuromodulation of the peripheral nerves. The proposed prototype can achieve a maximum focal pressure of approximately 100 kPa with a 5 V supply at 0.5 cm depth without including an acoustic matching layer.
Changhyuk Lee, Adriaan J. Taal, Jaebin Choi, Kukjoo Kim, Kevin Tien, Laurent Moreaux, Michael L. Roukes, Kenneth L. Shepard. A 512-Pixel 3kHz-Frame-Rate Dual-Shank Lensless Filterless Single-Photon-Avalanche-Diode CMOS Neural Imaging Probe. IEEE International Solid-State Circuits Conference February 19, 2019.
Siddharth Shekar, Chen-Chi Chien, Andreas Hartel, Peijie Ong, Oliver B Clarke, Andrew Marks, Marija Drndic, and Kenneth L Shepard. Wavelet Denoising of High-Bandwidth Nanopore and Ion-Channel Signals. Nano Letters January 2, 2019, DOI: 10.1021/acs.nanolett8b04388.
Abstract
Recent work has pushed the noise-limitedbandwidths of solid-state nanopore conductance recordings tomore than 5 MHz and of ion channel conductance recordingsto more than 500 kHz through the use of integratedcomplementary metal-oxide-semiconductor (CMOS) inte-grated circuits. Despite the spectral spread of the pulse-likesignals that characterize these recordings when a sinusoidalbasis is employed, Besselfilters are commonly used to denoisethese signals to acceptable signal-to-noise ratios (SNRs) at thecost of losing many of the faster temporal features. Here, wereport improvements to the SNR that can be achieved usingwavelet denoising instead of Besselfiltering. When combinedwith state-of-the-art high-bandwidth CMOS recording in-strumentation, we can reduce baseline noise levels by over a factor of 4 compared to a 2.5 MHz Besselfilter while retainingtransient properties in the signal comparable to thisfilter bandwidth. Similarly, for ion-channel recordings, we achieve atemporal response better than a 100 kHz Besselfilter with a noise level comparable to that achievable with a 25 kHz Besselfilter. Improvements in SNR can be used to achieve robust statistical analyses of these recordings, which may provide importantinsights into nanopore translocation dynamics and mechanisms of ion-channel function.
Krishna Jayant, Michael Wenzel, Yuki Bando, Jorndan P Hamm, Nicola Mandriota, Jake H Rabinowitz, Ilan Jen-La Plante, Jonathan S Owen, Ozgur Sahin, Kenneth L Shepard, and Rafael Yuste. Flexible Nanopipettes for Minimally Invasive Intracellular Electrophysiology In Vivo. Cell Reports January 2, 2019, DOI: doi.org/10.1016/celrep.2018.12.019.
Abstract
Intracellular recordingsin vivoremains the best tech-nique to link single-neuron electrical properties tonetwork function. Yet existing methods are limitedin accuracy, throughput, and duration, primarily viawashout, membrane damage, and movement-induced failure. Here, we introduce flexible quartznanopipettes (inner diameters of 10–25 nm andspring constant of ~0.08 N/m) as nanoscale analogsof traditional glass microelectrodes. Nanopipettesenable stable intracellular recordings (seal resis-tances of 500 to ~800 MΩ,5 to ~10 cells/nanopip-ette, and duration of ~1 hr) in anaesthetized andawake head-restrained mice, exhibit minimal diffu-sional flux, and facilitate precise recording and stim-ulation. When combined with quantum-dot labelsand microprisms, nanopipettes enable two-photontargeted electrophysiology from both somata anddendrites, and even paired recordings from neigh-boring neurons, while permitting simultaneous popu-lation imaging across cortical layers. We demon-strate the versatility of this method by recordingfrom parvalbumin-positive (Pv) interneurons whileimaging seizure propagation, and we find that Pv de-polarization block coincides with epileptic spread.Flexible nanopipettes present a simple method toprocure stable intracellular recordingsin vivo.
Yuhao Zhang, Min Sun, Josh Perozek, Zhihong Liu, Ahmad Zubair, Daniel Piedra, Nadim Chowdhury, Xiang Gao, Kenneth Shepard, and Tomás Palacios. Large Area 1.2 kV GaN Vertical Power FinFETs with a Record Switching Figure-of-Merit. IEEE Electron Device Letters DOI 10.1109/LED.2018.2880306 November 9, 2018
Hyungsik Kim, Gwan-Hyoung Lee, James Hone, and Kenneth L. Shepard. Ambipolar Memristive Phenomenon in Large-Scale, Few-Layered αMoO3 Recrystallized Films. Advanced Material Interfaces 2018 DOI: 10.1002/admi.201801591
C. Shi, T. Costa, J. Elloiain, and K. L. Shepard, “Monolithic integration of micron-scale piezoelectric materials with CMOS for biomedical applications,” IEDM 2018.
Young Duck Kim, Yuanda Gao, Ren-Jye Shiue, Lei Wang , Ozgur Burak Aslan, Myung-Ho Bae, Hyungsik Kim, Dongjea Seo, Heon-Jin Choi, Suk Hyun Kim, Andrei Nemilentsau, Tony Low, Cheng Tan, Dmitri K. Efetov, Takashi Taniguchi, Kenji Watanabe, Kenneth L. Shepard, Tony F. Heinz, Dirk Englund, and James Hone. Ultrafast Graphene Light Emitters. Nano Letters DOI: 10.1021/acs.nanolett.7b04324,Publication Date (Web): January 16, 2018.
Abstract
Ultrafast electrically driven nanoscale light sources are critical components in nanophotonics. Compound semiconductor-based light sources for the nanophotonic platforms have been extensively investigated over the past decades. However, monolithic ultrafast light sources with a small footprint remain a challenge. Here, we demonstrate electrically driven ultrafast graphene light emitters that achieve light pulse generation with up to 10 GHz bandwidth across a broad spectral range from the visible to the near-infrared. The fast response results from ultrafast charge-carrier dynamics in graphene and weak electron-acoustic phonon-mediated coupling between the electronic and lattice degrees of freedom. We also find that encapsulating graphene with hexagonal boron nitride (hBN) layers strongly modifies the emission spectrum by changing the local optical density of states, thus providing up to 460% enhancement compared to the gray-body thermal radiation for a broad peak centered at 720 nm. Furthermore, the hBN encapsulation layers permit stable and bright visible thermal radiation with electronic temperatures up to 2000 K under ambient conditions as well as efficient ultrafast electronic cooling via near-field coupling to hybrid polaritonic modes under electrical excitation. These high-speed graphene light emitters provide a promising path for on-chip light sources for optical communications and other optoelectronic applications.
Yoonhee Lee, Scott M. Trocchia, Steven B. Warren, Erik F. Young, Sefi Vernick, and Kenneth L. Shepard, “Electrically Controllable Single-Point Covalent Functionalization of Spin-Cast Carbon-Nanotube Field-Effect Transistor Arrays“. ACS Nano Publication Date: September 27, 2018, DOI: 10.1021/acsnano.8b03073.
Abstract
Single-point-functionalized carbon-nanotube field-effect transistors (CNTFETs) have been used to sense conformational changes and binding events in protein and nucleic acid structures from intrinsic molecular charge. The key to utilizing these devices as single-molecule sensors is the ability to attach a single probe molecule to an individual device. In contrast, with noncovalent attachment approaches such as those based on van der Waals interactions, covalent attachment approaches generally deliver higher stability but have traditionally been more difficult to control, resulting in low yield. Here, we present a single-point-functionalization method for CNTFET arrays based on electrochemical control of a diazonium reaction to create sp3 defects, combined with a scalable spin-casting method for fabricating large arrays of devices on arbitrary substrates. Attachment of probe DNA to the functionalized device enables single-molecule detection of DNA hybridization with complementary target, verifying the single-point functionalization. Overall, this method enables single-point defect generation with 80% yield.
Daniel A. Fleischer, Siddharth Shekar, Shanshan Dai, Ryan M. Field, Jenifer Lary, Jacob K. Rosenstein and Kenneth L. Shepard. CMOS-Integrated Low-Noise Junction Field-Effect Transistors for Bioelectronic Applications. IEEE Electron Device Letters Date of Publication: 06 June 2018, DOI: 10.1109/LED.2018.2844545.
Abstract
In this work, we present a CMOS-integrated lownoise junction field-effect transistor (JFET) developed in a standard 0.18 μm CMOS process. These JFETs reduce inputreferred flicker noise power by more than a factor of 10 when compared to equally sized n-channel MOS devices by eliminating oxide interfaces in contact with the channel. We show that this improvement in device performance translates into a factor-of-10 reduction in the input-referred noise of integrated CMOS operational amplifiers when JFET devices are used at the input, significant for many applications in bioelectronics.
Andreas J. W. Hartel, Peijie Ong, Indra Schroeder, M. Hunter Giese, Siddharth Shekar, Oliver B. Clarke, Ran Zalk, Andrew R. Marks, Wayne A. Hendrickson and Kenneth L. Shepard. Single-channel recordings of RyR1 at microsecond resolution in CMOS-suspended membranes. PNAS February 20, 2018. 115 (8) E1789-E1798, DOI:10.1073/pnas.1712313115.
Abstract
Single-channel recordings are widely used to explore functional properties of ion channels. Typically, such recordings are performed at bandwidths of less than 10 kHz because of signal-to-noise considerations, limiting the temporal resolution available for studying fast gating dynamics to greater than 100 µs. Here we present experimental methods that directly integrate suspended lipid bilayers with high-bandwidth, low-noise transimpedance amplifiers based on complementary metal-oxide-semiconductor (CMOS) integrated circuits (IC) technology to achieve bandwidths in excess of 500 kHz and microsecond temporal resolution. We use this CMOS-integrated bilayer system to study the type 1 ryanodine receptor (RyR1), a Ca2+-activated intracellular Ca2+-release channel located on the sarcoplasmic reticulum. We are able to distinguish multiple closed states not evident with lower bandwidth recordings, suggesting the presence of an additional Ca2+ binding site, distinct from the site responsible for activation. An extended beta distribution analysis of our high-bandwidth data can be used to infer closed state flicker events as fast as 35 ns. These events are in the range of single-file ion translocations.
Y. Zhang, M. Sun, D. Piedra, J. Hu, Z. Liu, Y. Lin, X. Gao, K. Shepard, and T. Palacios. 1200 V GaN Vertical Fin Power Field-Effect Transistors. Proceedings of the International Electron Devices Meeting, 2016.
Abstract
We demonstrate record performance in a novel normally-off GaN vertical transistor with submicron finshaped channels. This vertical fin transistor only needs nGaN layers, with no requirement for epitaxial regrowth or pGaN layers. A specific on-resistance of 0.2 mΩ·cm2 and a breakdown voltage over 1200 V have been demonstrated with extremely high ON current (over 25 kA/cm2) and low OFF current at 1200 V (below 10-4 A/cm2), rendering an excellent Baliga’s figure of merit up to 7.2 GW/cm2. A threshold voltage of 1 V was achieved and was stable up to 150 oC.Large devices with high current up to 10 A and breakdown voltage over 800 V were also demonstrated. These results show the great potential of GaN vertical fin transistors for high-current and high-voltage power applications.
David Tsai, Rafael Yuste, and Kenneth L. Shepard. Statistically Reconstructed Multiplexing for Very Dense, High-Channel-Count Acquisition Systems. IEEE Transactions on Biomedical Circuits and Systems, 12(1), 13-23.
Abstract
Multiplexing is an important strategy in multichannel acquisition systems. The per-channel antialiasing filters needed in the traditional multiplexing architecture limit its scalability for applications requiring high channel density, high channel count, and low noise. A particularly challenging example is multielectrode arrays for recording from neural systems. We show that conventional approaches must tradeoff recording density and noise performance, at a scale far from the ideal goal of one-to-one mapping between neurons and sensors. We present a multiplexing architecture without per-channel antialiasing filters. The sparsely sampled data are recovered through a compressed sensing strategy, involving statistical reconstruction and removal of the undersampled thermal noise. In doing so, we replace large analog components with digital signal processing blocks, which are much more amenable to scaled CMOS implementation. The resulting statistically reconstructed multiplexing architecture recovers input signals at significantly improved signal-to-noise ratios when compared to conventional multiplexing with antialiasing filters at the same per-channel area. We implement the new architecture in a 65 536-channel neural recording system and show that it is able to recover signals with performance comparable to conventional high-performance, single-channel systems, despite a more than four-orders-of-magnitude increase in channel density.
Oliver Rauh, Ulf-Peter Hansen, Sebastian Mach1, Andreas J.W. Hartel, Kenneth L. Shepard, Gerhard Thiel and Indra Schroeder. Extended beta distributions open the access to fast gating in bilayer experiments—assigning the voltage-dependent gating to the selectivity filter. FEBS Letters. DOI: 10.1002/1873-3468.12898. Volume 591, Issue 23, December 2017, Pages 3850–3860.
Abstract
Lipid bilayers provide many benefits for ion channel recordings, such as control of membrane composition and transport molecules. However, they suffer from high membrane capacitance limiting the bandwidth and impeding analysis of fast gating. This can be overcome by fitting the deviations of the open-channel noise from the baseline noise by extended beta distributions. We demonstrate this analysis step-by-step by applying it to the example of viral K+ channels (Kcv), from the choice of the gating model through the fitting process, validation of the results, and what kinds of results can be obtained. These voltage sensor-less channels show profoundly voltage-dependent gating with dwell times in the closed state of about 50 μs. Mutations assign it to the selectivity filter.
David Tsai, Daniel Sawyer, Adrian Bradd, Rafael Yuste & Kenneth L. Shepard. A very large-scale microelectrode array for cellular- resolution electrophysiology. Nature Communications 8, Article number: 1802 (2017) | DOI: 10.1038/s41467-017-02009-x
Abstract
In traditional electrophysiology, spatially inefficient electronics and the need for tissue-toelectrode proximity defy non-invasive interfaces at scales of more than a thousand low noise, simultaneously recording channels. Using compressed sensing concepts and silicon complementary metal-oxide-semiconductors (CMOS), we demonstrate a platform with 65,536 simultaneously recording and stimulating electrodes in which the per-electrode electronics consume an area of 25.5 μm by 25.5 μm. Application of this platform to mouse retinal studies is achieved with a high-performance processing pipeline with a 1 GB/s data rate. The platform records from 65,536 electrodes concurrently with a ~10 µV r.m.s. noise;senses spikes from more than 34,000 electrodes when recording across the entire retina; automatically sorts and classifies greater than 1700 neurons following visual stimulation; and stimulates individual neurons using any number of the 65,536 electrodes while observing spikes over the entire retina. The approaches developed here are applicable to other electrophysiological systems and electrode configurations.
Sefi Vernick, Scott M. Trocchia, Steven B. Warren, Erik F. Young, Delphine Bouilly, Ruben L. Gonzalez, Colin Nuckolls & Kenneth L. Shepard. Electrostatic melting in a single-molecule field-effect transistor with applications in genomic identification. Nature Communications 8, Article number: 15450 (2017) | DOI: 10.1038/ncomms15450.
Abstract
The study of biomolecular interactions at the single-molecule level holds great potential for both basic science and biotechnology applications. Single-molecule studies often rely on fluorescence-based reporting, with signal levels limited by photon emission from single optical reporters. The point-functionalized carbon nanotube transistor, known as the single-molecule field-effect transistor, is a bioelectronics alternative based on intrinsic molecular charge that offers significantly higher signal levels for detection. Such devices are effective for characterizing DNA hybridization kinetics and thermodynamics and enabling emerging applications in genomic identification. In this work, we show that hybridization kinetics can be directly controlled by electrostatic bias applied between the device and the surrounding electrolyte. We perform the first single-molecule experiments demonstrating the use of electrostatics to control molecular binding. Using bias as a proxy for temperature, we demonstrate the feasibility of detecting various concentrations of 20-nt target sequences from the Ebolavirus nucleoprotein gene in a constant-temperature environment
Ko-Tao Lee, Can Bayram, Daniel Piedra, Edmund Sprogis, Hariklia Deligianni, Balakrishnan Krishnan, George Papasouliotis, Ajit Paranjpe, Eyal Aklimi, Ken Shepard, Tomás Palacios, and Devendra Sadana. GaN Devices on a 200 mm Si Platform Targeting Heterogeneous Integration. IEEE Electron Device Letters (Volume: 38, Issue: 8, Aug. 2017 ).
Abstract
GaN-based high electron mobility transistors (HEMTs) were fabricated on 200-mm silicon-oninsulator (SOI) substrates possessing multiple crystal orientations. These SOI substrates have the Si (100)-SiO2- Si (111) structure, which allows Si (111) to be exposed below the buried oxide to enable GaN epitaxial growth adjacent to Si (100). The current collapse in GaN HEMTs of < 150 × 150 µm2 patterns is 2%–6%, which is remarkably lower than the devices on blanket materials. We believe that stress relaxation resulting from substrate patterning contributes to the reduction of current collapse. By creating small GaN patterns on a larger diameter Si wafer, co-integration of GaN with Si technology may be possible.
Hassan M. Edrees, Aida R. Colón-Berrios, Daniel de Godoy Peixoto, Kenneth L. Shepard, Peter R. Kinget, and Ioannis Kymissis. Monolithically Integrated CMOS-SMR Oscillator in 65 nm CMOS Using Custom MPW Die-Level Fabrication Process, Journal of Microelectromechanical Systems. Journal of Microelectromechanical Systems ( Volume: 26, Issue: 4, Aug. 2017 )
Abstract
Hasti Amiri, Kenneth L. Shepard, Colin Nuckolls, and Raúl Hernández Sánchez Single-Walled Carbon Nanotubes: Mimics of Biological Ion Channels. Nano Lett., 2017, 17 (2), pp 1204–1211, DOI: 10.1021/acs.nanolett.6b04967.
Abstract
Here we report on the ion conductance through individual, small diameter single-walled carbon nanotubes. We find that they are mimics of ion channels found in natural systems. We explore the factors governing the ion selectivity and permeation through single-walled carbon nanotubes by considering an electrostatic mechanism built around a simplified version of the Gouy−Chapman theory. We find that the single-walled carbon nanotubes preferentially transported cations and that the cation permeability is size-dependent. The ionic conductance increases as the absolute hydration enthalpy decreases for monovalent cations with similar solid-state radii, hydrated radii, and bulk mobility. Charge screening experiments using either the addition of cationic or anionic polymers, divalent metal cations, or changes in pH reveal the enormous impact of the negatively charged carboxylates at the entrance of the single-walled carbon nanotubes. These observations were modeled in the low-to-medium concentration range (0.1−2.0 M) by an electrostatic mechanism that mimics the behavior observed in many biological ion channel-forming proteins. Moreover, multi-ion conduction in the high concentration range (>2.0 M) further reinforces the similarity between single-walled carbon nanotubes and protein ion channels.
Eyal Aklimi, Student Member, IEEE, Daniel Piedra, Student Member, IEEE, Kevin Tien, Student Member, IEEE, Tomás Palacios, Member, IEEE, and Kenneth L. Shepard, Fellow, IEEE Hybrid CMOS/GaN 40-MHz Maximum 20-V Input DC–DC Multiphase Buck Converter. IEEE Journal of Solid-State Circuits, Volume: 52, Issue: 6, June 2017.
Abstract
This paper presents a 40-MHz hybrid CMOS/GaN integrated multiphase dc–dc switched-inductor buck converter with a maximum 20-V input voltage. The half-bridge switches are realized using lateral AlGaN/GaN HEMTs, while the drivers and other circuitry are implemented in standard 180-nm CMOS. The interface between the CMOS and GaN dice is achieved through face-to-face bonding, reducing inductive parasitics for the connection to less than 15 pH. A capacitively coupled level shifter provides the gate drive for the high-side GaN switch using 5-V CMOS devices. The converter demonstrates 76% efficiency for 8:1 V conversion and over 60% efficiency for conversion ratios up to 16:1.
Jordan Thimot and Kenneth L. Shepard. Wirelessly powered implants. Nature Biomedical Engineering 1, Article number: 0051 (2017), DOI:10.1038/s41551-017-005.
Abstract
Phased-array antennas that conform to body surfaces efficiently transfer electromagnetic energy to miniaturized semiconductor devices implanted in pigs.
Mantovani P, Cota EG, Tien K, Pilato C, Di Guglielmo G, Shepard K, Carloni LP. An FPGA-based infrastructure for fine-grained DVFS analysis in high-performance embedded systems. InProceedings of the 53rd Annual Design Automation Conference 2016 Jun 5 (pp. 1-6).
Abstract
Emerging technologies provide SoCs with fine-grained DVFS capabilities both in space (number of domains) and time (transients in the order of tens of nanoseconds). Analyzing these systems requires cycle-accurate accounting of rapidly-changing dynamics and complex interactions among accelerators, interconnect, memory, and OS. We present an FPGA-based infrastructure that facilitates such analyses for high-performance embedded systems. We show how our infrastructure can be used to first generate SoCs with looselycoupled accelerators, and then perform design-space exploration considering several DVFS policies under full-system workload scenarios, sweeping spatial and temporal domain granularity.
Hao Wu, Michael Lekas, Ryan Davies, Kenneth L. Shepard Fellow, IEEE, and Noah Sturcken. Integrated Transformers With Magnetic Thin Films IEEE Transactions on Magnetics, Vol. 52, No. 7, July 2016
Abstract
This paper presents the design and electrical performance of transformers with magnetic thin films for on-chip power conversion and isolation. The inductance of the devices is greatly enhanced by the use of a high-permeability magnetic material as a solenoid core, resulting in an inductance density of 108 nH/mm2. The total thickness of the transformer structures is 3. By laminating the magnetic core, losses are well controlled leading to a peak quality factor (Q) of 16 at 40 MHz.
Krishna Jayant, Jan J. Hirtz, Ilan Jen-La Plante, David M. Tsai, Wieteke D. A. M. De Boer, Alexa Semonche, Darcy S. Peterka, Jonathan S. Owen, Ozgur Sahin, Kenneth L. Shepard and Rafael Yuste. Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes Nature Nanotechnology, published online DOI: 10.1038/NNANO.2016.268
Abstract
Dendritic spines are the primary site of excitatory synaptic input onto neurons, and are biochemically isolated from the parent dendritic shaft by their thin neck. However, due to the lack of direct electrical recordings from spines, the influence that the neck resistance has on synaptic transmission, and the extent to which spines compartmentalize voltage, specifically excitatory postsynaptic potentials, albeit critical, remains controversial. Here, we use quantum-dot-coated nanopipette electrodes (tip diameters ∼15–30 nm) to establish the first intracellular recordings from targeted spine heads under two-photon visualization. Using simultaneous somato-spine electrical recordings, we find that back propagating action potentials fully invade spines, that excitatory postsynaptic potentials are large in the spine head (mean 26 mV) but are strongly attenuated at the soma (0.5–1 mV) and that the estimated neck resistance (mean 420 MΩ) is large enough to generate significant voltage compartmentalization. Nanopipettes can thus be used to electrically probe biological nanostructures.
Siddharth Shekar, David J. Niedzwiecki, Chen-Chi Chien, Peijie Ong, Daniel A. Fleischer, Jianxun Lin, Jacob K. Rosenstein, Marija Drndić, Kenneth L. Shepard. Measurement of DNA Translocation Dynamics in a Solid-State Nanopore at 100 ns Temporal Resolution NanoLetters DOI: 10.1021/acs.nanolett.6b01661
Abstract
Despite the potential for nanopores to be a platform for high-bandwidth study of single-molecule systems, ionic current measurements through nanopores have been limited in their temporal resolution by noise arising from poorly optimized measurement electronics and large parasitic capacitances in the nanopore membranes. Here, we present a complementary metal-oxide-semiconductor (CMOS) nanopore (CNP) amplifier capable of low noise recordings at an unprecedented 10 MHz bandwidth. When integrated with state-of-the-art solid-state nanopores in silicon nitride membranes, we achieve an SNR of greater than 10 for ssDNA translocations at a measurement bandwidth of 5 MHz, which represents the fastest ion current recordings through nanopores reported to date. We observe transient features in ssDNA translocation events that are as short as 200 ns, which are hidden even at bandwidths as high as 1 MHz. These features offer further insights into the translocation kinetics of molecules entering and exiting the pore. This platform highlights the advantages of high-bandwidth translocation measurements made possible by integrating nanopores and custom-designed electronics.
Delphine Bouilly, Jason Hon, Nathan S. Daly, Scott Trocchia, Sefi Vernick, Jaeeun Yu, Steven Warren, Ying Wu, Ruben L. Gonzalez, Jr., Kenneth L. Shepard, and Colin Nuckolls Single-Molecule Reaction Chemistry in Patterned Nanowells NanoLetters DOI: 10.1021/acs.nanolett.6b01657
Abstract
A new approach to synthetic chemistry is performed in ultraminiaturized, nanofabricated reaction chambers. Using lithographically defined nanowells, we achieve single-point covalent chemistry on hundreds of individual carbon nanotube transistors, providing robust statistics and unprecedented spatial resolution in adduct position. Each device acts as a sensor to detect, in real-time and through quantized changes in conductance, single-point functionalization of the nanotube as well as consecutive chemical reactions, molecular interactions, and molecular conformational changes occurring on the resulting single-molecule probe. In particular, we use a set of sequential bioconjugation reactions to tether a single-strand of DNA to the device and record its repeated, reversible folding into a G-quadruplex structure. The stable covalent tether allows us to measure the same molecule in different solutions, revealing the characteristic increased stability of the G-quadruplex structure in the presence of potassium ions (K+) versus sodium ions (Na+). Nanowell-confined reaction chemistry on carbon nanotube devices offers a versatile method to isolate and monitor individual molecules during successive chemical reactions over an extended period of time.
Tarun Chari, Rebeca Ribeiro-Palau, Cory R. Dean, and Kenneth Shepard Resistivity of Rotated Graphite−Graphene Contacts NanoLetters DOI: 10.1021/acs.nanolett.6b01657
Abstract
Robust electrical contact of bulk conductors to two-dimensional (2D) material, such as graphene, is critical to the use of these 2D materials in practical electronic devices. Typical metallic contacts to graphene, whether edge or areal, yield a resistivity of no better than 100 Ω μm but are typically >10 kΩ μm. In this Letter, we employ single-crystal graphite for the bulk contact to graphene instead of conventional metals. The graphite contacts exhibit a transfer length up to four-times longer than in conventional metallic contacts. Furthermore, we are able to drive the contact resistivity to as little as 6.6 Ω μm2 by tuning the relative orientation of the graphite and graphene crystals. We find that the contact resistivity exhibits a 60° periodicity corresponding to crystal symmetry with additional sharp decreases around 22° and 39°, which are among the commensurate angles of twisted bilayer graphene.
Hassan Sakhtah, Leslie Koyama, Yihan Zhang, Diana K. Moralesa, Blanche L. Fields, Alexa Price-Whelan, Deborah A. Hogan, Kenneth Shepard, and Lars E. P. Dietricha The Pseudomonas aeruginosa efflux pump MexGHIOpmD transports a natural phenazine that controls gene expression and biofilm development PNAS, Early Edition, June 6, 2016.
Abstract
Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHIOpmD in the opportunistic pathogen Pseudomonas aeruginosa. Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHIOpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We also show that 5-Me-PCA is sufficient to fully induce MexGHI-OpmD expression and that it is required for wild-type colony biofilm morphogenesis. These physiological effects are consistent with the high redox potential of 5-Me-PCA, which distinguishes it from other well-studied P. aeruginosa phenazines. Our observations highlight the importance of this compound, which was previously overlooked due to the challenges associated with its detection, in the context of P. aeruginosa gene expression and multicellular behavior. This study constitutes a unique demonstration of efflux-based selfresistance, controlled by a simple circuit, in a Gram-negative pathogen.
S. B. Warren, S. Vernick, E. Romano, and K. L. Shepard Complementary Metal-Oxide-Semiconductor Integrated Carbon Nanotube Arrays: Toward Wide-Bandwidth Single-Molecule Sensing Systems Nano Letters DOI: 10.1021/acs.nanolett.6b00319
Abstract
There is strong interest in realizing genomic molecular diagnostic platforms that are label-free, electronic, and single-molecule. One attractive transducer for such efforts is the single-molecule field-effect transistor (smFET), capable of detecting a single electronic charge and realized with a point-functionalized exposed-gate one-dimensional carbon nanotube field-effect device. In this work, smFETs are integrated directly onto a custom complementary metaloxide-semiconductor chip, which results in an array of up to 6000 devices delivering a measurement bandwidth of 1 MHz. In a first exploitation of these high-bandwidth measurement capabilities, point functionalization through electrochemical oxidation of the devices is observed with microsecond temporal resolution, which reveals complex reaction pathways with resolvable scattering signatures. High-rate random telegraph noise is detected in certain oxidized devices, further illustrating the measurement capabilities of the platform.
D. L. Bellin, H. Sakhtah, Y. Zhang, A. Price-Whelan, L. E.P. Dietrich & K. L. Shepard Electrochemical camera chip for simultaneous imaging of multiple metabolites in biofilms. Nat. Commun. 7:10535 doi: 10.1038/ncomms10535 (2016).
Abstract
Monitoring spatial distribution of metabolites in multicellular structures can enhance understanding of the biochemical processes and regulation involved in cellular community development. Here we report on an electrochemical camera chip capable of simultaneous spatial imaging of multiple redox-active phenazine metabolites produced by Pseudomonas aeruginosa PA14 colony biofilms. The chip features an 8mm8mm array of 1,824 electrodes multiplexed to 38 parallel output channels. Using this chip, we demonstrate potential-sweepbased electrochemical imaging of whole-biofilms at measurement rates in excess of 0.2 s per electrode. Analysis of mutants with various capacities for phenazine production reveals distribution of phenazine-1-carboxylic acid (PCA) throughout the colony, with 5-methylphenazine-1-carboxylic acid (5-MCA) and pyocyanin (PYO) localized to the colony edge. Anaerobic growth on nitrate confirms the O2-dependence of PYO production and indicates an effect of O2 availability on 5-MCA synthesis. This integrated-circuit-based technique promises wide applicability in detecting redox-active species from diverse biological samples.
J. M. Roseman, J. Lin, S. Ramakrishnan, J. Rosenstein, and K. L. Shepard, Hybrid integrated biological–solid-state system powered with adenosine triphosphate. Nat. Commun. 6:10070 doi: 10.1038/ncomms10070 (2015).
Abstract
There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na+/K+ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2×106mm-2) are able to sustain a short-circuit current of 32.6 pAmm-2 and an open-circuit voltage of 78mV, providing for a maximum power transfer of 1.27pWmm-2 from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.
Michael Lekas, Sunwoo Lee, Wujoon Cha, James Hone, Member, IEEE, and Kenneth Shepard, Fellow, IEEE Noise Modeling of Graphene Resonant Channel Transistors, IEEE Transactions on Electron Devices (advanced on-line)
Abstract
In this paper, we present a compact model for graphene resonant channel transistors (G-RCTs) that uses extracted electrical and mechanical parameters to provide an accurate simulation of dc, RF, noise, and frequency-tuning characteristics of the device. The model is validated with measurements on fabricated G-RCTs, which include what we believe to be the first noise measurements conducted on any resonant transistor. The noise model, which considers both electrical and mechanical sources, is used to demonstrate the fundamental differences in the noise behavior of active and passive resonator technologies, and to show how optimization of device parameters can be used to improve the noise performance of RCTs.
Michael Lekas, Sunwoo Lee, Wujoon Cha, James Hone, and Kenneth Shepard Third-order intermodulation distortion in graphene resonant channel transistors, Applied Physics Letters 106, 073504 (2015); doi: 10.1063/1.4913462
Abstract
Third-order intermodulation distortion (IM3) is an important metric for electromechanical resonators used in radio frequency signal processing applications since it characterizes the nonlinearity of the device, and the amount of in-band interference it generates when subject to unwanted, out-of-band signals. In this letter, we measure and model IM3 in a strain-engineered graphene mechanical resonator operated as a graphene resonant channel transistor (G-RCT). The device analyzed in this work has a voltage third-order intercept point (VIIP3) of 69.5 dBm V at a gate-to-source DC bias (Vgs) of 2.5 V, which drops to 52.1 dBm V at Vgs=4.5V when driven with two out-of-band input tones spaced 5 and 10MHz from the resonant frequency. The decrease in the VIIP3 with Vgs coincides with an increase in the transmission response (S21) of the device, illustrating a trade-off between transduction efficiency and linearity. In addition, we find that conventional micro-electro-mechanical systems theory for IM3 calculation does not accurately describe our measurement data. To resolve this discrepancy, we develop a model for IM3 in G-RCTs that takes into account all of the output current terms present in the embedded transistor structure, as well as an effective Duffing parameter (αeff).
Matthew L. Johnston, Erik F. Young, Kenneth L. Shepard Whole-blood immunoassay for γH2AX as a radiation biodosimetry assay with minimal sample preparation, J Radiation and Environmental Biophysics (2015); doi: 10.1007/s00411-015-0595-4
Abstract
The current state of the art in high-throughput minimally invasive radiation biodosimetry involves the collection of samples in the field and analysis at a centralized facility. We have developed a simple biological immunoassay for radiation exposure that could extend this analysis out of the laboratory into the field. Such a forward placed assay would facilitate triage of a potentially exposed population. The phosphorylation and localization of the histone H2AX at double-stranded DNA breaks has already been proven to be an adequate surrogate assay for reporting DNA damage proportional to radiation dose. Here, we develop an assay for phosphorylated H2AX directed against minimally processed sample lysates. We conduct preliminary verification of H2AX phosphorylation using irradiated mouse embryo fibroblast cultures. Additional dosimetry is performed using human blood samples irradiated ex vivo. The assay reports H2AX phosphorylation in human blood samples in response to ionizing radiation over a range of 0–5 Gy in a linear fashion, without requiring filtering, enrichment, or purification of the blood sample.
Kevin J. Emmett, Jacob K. Rosenstein, Jan-Willem van de Meent, Ken L. Shepard, Chris H. Wiggins Statistical Inference for Nanopore Sequencing with a Biased Random Walk Model , Biophysical Journal Volume 108, Issue 8, p1852–1855, 21 April 2015
Abstract
Nanopore sequencing promises long read-lengths and single-molecule resolution, but the stochastic motion of the DNA molecule inside the pore is, as of this writing, a barrier to high accuracy reads. We develop a method of statistical inference that explicitly accounts for this error, and demonstrate that high accuracy (>99%) sequence inference is feasible even under highly diffusive motion by using a hidden Markov model to jointly analyze multiple stochastic reads. Using this model, we place bounds on achievable inference accuracy under a range of experimental parameters.
Kevin Tien, Noah Sturcken, Naigang Wang, Jae-woong Nah, Bing Dang, Eugene O’Sullivan, Paul Andry, Michele Petracca, Luca P. Carloni, William Gallagher, Kenneth Shepard “An 82%-Efficient Multiphase Voltage-Regulator 3D Interposer with On-Chip Magnetic Inductors,” VLSI Circuits Digest of Technical Papers, 2015 Symposium on, vol., no., pp.1,2, 16-19 June 2015.
Abstract
This paper presents a three-dimensional (3D) fully integrated high-speed multiphase voltage regulator. A complete switched-inductor regulator is integrated with a four-plane NoC in a two-high chip stack combining integrated magnetics, through-silicon vias (TSVs), and 45-nm SOI CMOS devices. Quasi-V2 hysteretic control is implemented over eight injection-locked fixed-frequency phases to achieve fast response, steady-state regulation, and fixed switching frequency. Peak efficiency of 82% for conversion from 1.66 V to 0.83 V is observed at a 150 MHz per-phase switching frequency. This is the first demonstration of high-speed voltage regulation using on-chip magnetic-core inductors in a 3D stack and achieves sub-μs dynamic supply voltage scaling for high-density embedded processing applications.
Jaebin Choi, Eyal Aklimi, Chen Shi, David Tsai, Harish Krishnaswamy, Member, IEEE, and Kenneth L. Shepard, Fellow, IEEE “Matching the Power, Voltage, and Size of Biological Systems: A nW-Scale, 0.023-mm3 Pulsed 33-GHz Radio Transmitter Operating From a 5 kT/q-Supply Voltage,” IEEE Transactions on Circuits and Systems Vol. 62, No. 8. August 2015
Abstract
This paper explores the extent to which a solid-state transmitter can be miniaturized, while still using RF for wireless information transfer and working with power densities and operating voltages comparable to what could be harvested from a living system. A 3.1 nJ/bit pulsed millimeter-wave transmitter, 300µm by 300µm by 250µm in size, designed in 32-nm SOI CMOS, operates on an electric potential of 130 mV and 3.1 nW of dc power. Farfield data transmission at 33 GHz is achieved by supply-switching an LC-oscillator with a duty cycle of 10-6. The time interval between pulses carries information on the amount of power harvested by the radio, supporting a data rate of 1 bps. The inductor of the oscillator also acts as an electrically small (λ/30) on-chip antenna, which, combined with millimeter-wave operation, enables the extremely small form factor.
D Tsai, E John, T Chari, R Yuste, K L Shepard, “High–channel–count, high–density micro- electrode array for closed–loop investigation of neuronal networks,” Proceedings of the 37th Annual International Conference of the IEEE EMBS, 2015
Abstract
We present a system for large-scale electrophysiological recording and stimulation of neural tissue with a planar topology. The recording system has 65,536 electrodes arranged in a 256 x 256 grid, with 25.5 µm pitch, and covering an area approximately 42.6 mm2 . The recording chain has 8.66 µV rms input-referred noise over a 100 ~ 10k Hz bandwidth while providing up to 66 dB of voltage gain. When recording from all electrodes in the array, it is capable of 10- kHz sampling per electrode. All electrodes can also perform patterned electrical microstimulation. The system produces ~ 1 GB/s of data when recording from the full array. To handle, store, and perform nearly real-time analyses of this large data stream, we developed a framework based around Xilinx FPGAs, Intel x86 CPUs and the NVIDIA Streaming Multiprocessors to interface with the electrode array.
Noah Sturcken, Ryan Davies, Hao Wu, Michael Lekas, Maurizio Arienzo, Kenneth Shepard, K.W. Cheng, C.C. Chen, Y.S. Su, C.Y. Tsai, K.D. Wu, J.Y. Wu, Y.C. Wang, K.C. Liu, C.C. Hsu, C.L. Chang, W.C. Hua, Alex Kalnitsky, “Magnetic Thin-Film Inductors for Monolithic Integration with CMOS,” Proceedings of the International Electron Device Meeting 2015
Abstract
This paper presents the fabrication, design and electrical performance of magnetic thin-film inductors for monolithic integration with CMOS for DC-DC power conversion. Magnetic core inductors were fabricated using conventional CMOS processes to achieve peak inductance density of 290nH/mm2 , quality factor 15 at 150MHz, current density exceeding 11A/mm2 and coupling coefficient of 0.89 for coupled inductors.
Chari, T.; Meric, I.; Dean, C.; Shepard, K., Properties of Self-Aligned Short-Channel Graphene Field-Effect Transistors Based on Boron-Nitride-Dielectric Encapsulation and Edge Contacts Electron Devices, IEEE Transactions on Year: 2015 (early access)
Abstract
We present the characterization of ballistic graphene field-effect transistors (GFETs) with an effective oxide thickness of 3.5 nm. Graphene channels are fully encapsulated within hexagonal boron nitride, and self-aligned contacts are formed to the edge of the single-layer graphene. Devices of channel lengths (LG) down to 67 nm are fabricated, and a virtual-source transport model is used to model the resulting current–voltage characteristics. The mobility and sourceinjection velocity as a function of LG yields a mean-free-path, ballistic velocity, and effective mobility of 850 nm, 9.3×107 cm/s, and 13 700 cm2/Vs, respectively, which are among the highest velocities and mobilities reported for GFETs. Despite these bestin- class attributes, these devices achieve transconductance (gm) and output conductance (gds) of only 600 and 300 μS/μm, respectively, due to the fundamental limitations of graphene’s quantum capacitance and zero-bandgap. gm values, which are less than those of comparable ballistic silicon devices, benefit from the high ballistic velocity in graphene but are degraded by an effective gate capacitance reduced by the quantum capacitance. The gds values, which limit the effective power gain achievable in these devices, are significantly worse than comparable silicon devices due to the properties of the zero-bandgap graphene channel.
Nicholas Petrone, Tarun Chari, Inanc Meric, Lei Wang, Kenneth L. Shepard, and James Hone, Flexible Graphene Field-Effect Transistors Encapsulated in Hexagonal Boron Nitride, ACS Nano, 2015, 9 (9), pp 8953–8959.
Abstract
Flexible graphene field-effect transistors (GFETs) are fabricated with graphene channels fully encapsulated in hexagonal boron nitride (hBN) implementing a self-aligned fabrication scheme. Flexible GFETs fabricated with channel lengths of 2 μm demonstrate exceptional room-temperature carrier mobility (μFE = 10 000 cm2 V-1 s-1), strong current saturation characteristics (peak output resistance, r0 = 2000 Ω), and high mechanical flexibility (strain limits of 1%). These values of μFE and r0 are unprecedented in flexible GFETs. Flexible radio frequency FETs (RF-FETs) with channel lengths of 375 nm demonstrate μFE = 2200 cm2 V-1 s-1 and r0 = 132.5 Ω. Unitycurrent gain frequencies, fT, and unitypower gain frequencies, fmax, reach 12.0 and 10.6 GHz, respectively. The corresponding ratio of cutoff frequencies approaches unity (fmax/fT = 0.9), a record value for flexible GFETs. Intrinsic fT and fmax are 29.7 and 15.7 GHz, respectively. The outstanding electronic characteristics are attributed to the improved dielectric environment provided by full hBN encapsulation of the graphene channel in conjunction with an optimized, self-aligned device structure. These results establish hBN as a mechanically robust dielectric that can yield enhanced electronic characteristics to a diverse array of graphene-based flexible electronics.
Jacob K. Rosenstein, Serge G. Lemay, Kenneth L. Shepard. Single-molecule bioelectronics, WIREs. 22 December 2014. DOI: 10.1002/wnan.1323
Abstract
Experimental techniques that interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. In this study, we review several technologies that can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms.
Adrian Balan, Bartholomeus Machielse, David Niedzwiecki, Jianxun Lin, Peijie Ong, Rebecca Engelke, Kenneth L. Shepard, and Marija Drndić. Improving Signal-to-Noise Performance for DNA Translocation in Solid-State Nanopores at MHz Bandwidths, Nano Lett., 2014, 14 (12), pp 7215–7220. DOI:
Abstract
DNA sequencing using solid-state nanopores is, in part, impeded by the relatively high noise and low bandwidth of the current state-of-the-art translocation measurements. In this Letter, we measure the ion current noise through sub 10 nm thick Si3N4 nanopores at bandwidths up to 1 MHz. At these bandwidths, the input-referred current noise is dominated by the amplifier’s voltage noise acting across the total capacitance at the amplifier input. By reducing the nanopore chip capacitance to the 1–5 pF range by adding thick insulating layers to the chip surface, we are able to transition to a regime in which input-referred current noise (∼117–150 pArms at 1 MHz in 1 M KCl solution) is dominated by the effects of the input capacitance of the amplifier itself. The signal-to-noise ratios (SNRs) reported here range from 15 to 20 at 1 MHz for dsDNA translocations through nanopores with diameters from 4 to 8 nm with applied voltages from 200 to 800 mV. Further advances in bandwidth and SNR will require new amplifier designs that reduce both input capacitance and input-referred amplifier noise.
Nicholas Petrone, Inanc Merici, Tarun Chari, Kenneth L. Shepard, and James Hone. Graphene Field-Effect Transistors for Radio-Frequency Flexible Electronics, Journal of the Electron Devices Society, 3:21. DOI: 10.1109/JEDS.2014.2363789
Abstract
Flexible radio-frequency (RF) electronics require materials which possess both exceptional electronic properties and high-strain limits. While flexible graphene field-effect transistors (GFETs) have demonstrated significantly higher strain limits than FETs fabricated from thin films of Si and III-V semiconductors, to date RF performance has been comparatively worse, limited to the low GHz frequency range. However, flexible GFETs have only been fabricated with modestly scaled channel lengths. In this paper, we fabricate GFETs on flexible substrates with short channel lengths of 260 nm. These devices demonstrate extrinsic unity-power-gain frequencies, fmax, up to 7.6 GHz and strain limits of 2%, representing strain limits an order of magnitude higher than the flexible technology with next highest reported fmax.
Bellin, Daniel L.; Warren, Steven B.; Rosenstein, Jacob K.; Shepard, Kenneth L. Interfacing CMOS electronics to biological systems: from single molecules to cellular communities, Biomedical Circuits and Systems Conference (BioCAS), 2014 IEEE
Abstract
Direct electronic interfaces between biological systems and solid-state devices offer considerable advantages over traditional optical interfaces by reducing system costs and affording increased signal levels. Integrating sensor transduction onto a complementary metal-oxide-semiconductor (CMOS) chip provides further advantages by enabling reduction of parasitics and improved sensor density. We present two sensing platforms that demonstrate the range of capabilities of CMOS-based bioelectronics. The first platform electrochemically images signaling molecules in multicellular communities, while the second focuses on single-molecule, high-bandwidth sensing using carbon nanotube field-effect transistors.
Jaebin Choi, Eyal Aklimi, Jared Roseman, David Tsai, Harish Krishnaswamy, Kenneth L. Shepard Matching the power density and potentials of biological systems: a 3.1-nW, 130-mV, 0.023-mm3 pulsed 33-GHz radio transmitter in 32-nm SOI CMOS, Custom Integrated Circuits Conference, 2014
Abstract
A 3.1 nJ/bit pulsed millimeter-wave transmitter, 300μm by 300μm by 250μm in size, designed in 32-nm SOI CMOS, operates on an electric potential of 130mV and 3.1nW of dc power. These achieved power levels and potentials are comparable to those present across cellular and intracellular membranes. Far-field data transmission at 33 GHz is achieved by supply-switching an LC-oscillator with a duty cycle of 10-6. The time interval between pulses carries information on the amount of power harvested by the radio, supporting a data rate of ~1bps. The inductor of the oscillator also acts as an electrically small (~λ/30) on-chip antenna, enabling the extremely small form factor.
Haig Norian, Ryan M. Field, Ioannis Kymissis and Kenneth L. Shepard An integrated CMOS quantitative-polymerase-chain-reaction lab-on-chip for point-of-care diagnostics, Lab Chip, 2014, Advance Article.
Abstract
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R.M. Field, S. Realov, and K.L. Shepard A 100-fps, Time-Correlated Single-Photon-Counting-Based Fluorescence-Lifetime Imager in 130-nm CMOS, IEEE Journal of Solid-State Circuite, vol.49, no.4 (2014) advanced online version.
Abstract
A fully-integrated single-photon avalanche diode (SPAD) and time-to-digital converter (TDC) array for high-speed fluorescence lifetime imaging microscopy (FLIM) in standard 130-nm CMOS is presented. This imager is comprised of an array of 64-by-64 SPADs each with an independent TDC for performing time-correlated single-photon counting (TCSPC) at each pixel. The TDCs use a delay-locked-loop-based architecture and achieve a 62.5-ps resolution with up to a 64-ns range. A data-compression datapath is designed to transfer TDC data to off-chip buffers, which can support a data rate of up to 42 Gbps. These features, combined with a system implementation that leverages a x4 PCIe-cabled interface, allow for demonstrated FLIM imaging rates at up to 100 frames per second.
D.L. Bellin, H. Sakhtah, J.K. Rosenstein, P.M. Levine, J. Thimot, K. Emmet, L.E.P. Dietrich, and K.L. Shepard Integrated circuit-based electrochemical sensor for spatially resolved detection of redox-active metabolites in biofilms, Nature Communications 5:3256 (2014) doi:10.1038/ncomms4256
Abstract
Despite advances in monitoring spatiotemporal expression patterns of genes and proteins with fluorescent probes, direct detection of metabolites and small molecules remains challenging. A technique for spatially resolved detection of small molecules would benefit the study of redox-active metabolites that are produced by microbial biofilms and can affect their development. Here we present an integrated circuit-based electrochemical sensing platform featuring an array of working electrodes and parallel potentiostat channels. ‘Images’ over a 3.250.9mm2 area can be captured with a diffusion-limited spatial resolution of 750 μm. We demonstrate that square wave voltammetry can be used to detect, identify and quantify (for concentrations as low as 2.6 μm) four distinct redox-active metabolites called phenazines. We characterize phenazine production in both wild-type and mutant Pseudomonas aeruginosa PA14 colony biofilms, and find correlations with fluorescent reporter imaging of phenazine biosynthetic gene expression.
Rakheja, S.; Han Wang; Palacios, T.; Meric, I.; Shepard, K.; Antoniadis, D., “A unified charge-current compact model for ambipolar operation in quasi-ballistic graphene transistors: Experimental verification and circuit-analysis demonstration,” Electron Devices Meeting (IEDM), 2013 IEEE International , vol., no., pp.5.5.1,5.5.4, 9-11 Dec. 2013
Abstract
This paper presents a compact virtual source (VS) model to describe carrier transport valid in both unipolar and ambipolar transport regimes in quasi-ballistic graphene fieldeffect transistors (GFETs). The model formulation allows for an easy extension to bi-layer graphene transistors, where a bandgap can be opened. The model also includes descriptions of intrinsic terminal charges/capacitances obtained selfconsistently with the transport formulation. The charge model extends from drift-diffusive transport regime to ballistic transport regime, where gradual-channel approximation (GCA) fails. The model is calibrated exhaustively against DC and S-parameter measurements of GFETs. To demonstrate the model capability for circuit-level simulations, the Verilog-A implementation of the model is used to simulate the dynamic response of frequency doubling circuits with GFETs operating in the ambipolar regime.
A. P. Alivisatos, A. M. Andrews, E. S. Boyden, M. Chun, G. M. Church, K. Deisseroth, J. P. Donoghue, S. E. Fraser, J. Lippincott-Schwartz, L. L. Looger, S. Masmanidis, P. L. McEuen, A. V. Nurmikko, H. Park, D. S. Peterka, C. Reid, M. L. Roukes, A. Scherer, M. Schnitzer, T. J. Sejnowski, K. L. Shepard, D. Tsao, G. Turrigiano, P. S. Weiss, C. Xu, R. Yuste, and X. Zhuang. Nanotools for neuroscience and brain activity mapping. ACS Nano, 7: 1850-1866 (2013).
Abstract
Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function.
Michael Lekas, Sunwoo Lee, Changyao Chen, Wu-Joon Cha, Karthik Ayyagari, James Hone, Kenneth Shepard, Stress-enhanced chemical vapor deposited graphene NEMS RF resonators. IEEE 543-546 (2013). European Frequency and Time Forum & International Frequency Control Symposium (EFTF/IFC), 2013 Joint
Abstract
In this work we present room-temperature measurements of graphene nanoelectromechanical resonators (GN-ERs) demonstrating quality factors (Qs) greater than 200 at resonance. A nominal resonant frequency (fo) of 200 MHz is attained by applying strain to the suspended graphene using an SU-8 polymer clamp. Additionally, the device fo can be tuned by more than 5% by application of a DC gate bias on the order of 5V. Chemical vapor deposited (CVD) graphene is used to demonstrate the scalability of the process.
C. Chen, S. Lee, V.V. Deshpande, G-H. Lee, M. Lekas, K. Shepard & J. Hone, Graphene mechanical oscillators with tunable frequency, Nature Nanotechnology 8, 923–927 (2013) doi:10.1038/nnano.2013.232
Abstract
Oscillators, which produce continuous periodic signals from direct current power, are central to modern communications systems, with versatile applications including timing references and frequency modulators. However, conventional oscillators typically consist of macroscopic mechanical resonators such as quartz crystals, which require excessive off-chip space. Here, we report oscillators built on micrometre-size, atomically thin graphene nanomechanical resonators, whose frequencies can be electrostatically tuned by as much as 14%. Self-sustaining mechanical motion is generated and transduced at room temperature in these oscillators using simple electrical circuitry. The prototype graphene voltage-controlled oscillators exhibit frequency stability and a modulation bandwidth sufficient for the modulation of radiofrequency carrier signals. As a demonstration, we use a graphene oscillator as the active element for frequency-modulated signal generation and achieve efficient audio signal transmission.
J. K. Rosenstein, K. L. Shepard, Temporal resolution of nanopore sensor recordings, Conf. Proc. IEEE Emg. Med. Biol. Soc. (2013): 4110-4113.
Abstract
Here we discuss the limits to temporal resolution in nanopore sensor recordings, which arise from considerations of both small-signal frequency response and accumulated noise power. Nanopore sensors have strong similarities to patch-clamp ion channel recordings, except that the magnitudes of many physical parameters are substantially different. We will present examples from our recent work developing high-speed nanopore sensing platforms, in which we physically integrated nanopores with custom low-noise complementary metal-oxide-semiconductor (CMOS) circuitry. Close physical proximity of the sensor and amplifier electronics can reduce parasitic capacitances, improving both the signal-to-noise ratio and the effective temporal resolution of the recordings.
L. Wang, I. Meric, P.Y. Huang, Q. Gao, Y. Gao, H. Tran, T. Taniguchi, K. Watanabe, L.M. Campos, D.A. Muller, J. Guo, P. Kim, J. Hone, K.L. Shepard, C.R. Dean, “One-Dimensional Electrical Contact to a Two-Dimensional Material” Science 342, 614 (2013) doi: 10.1126/science.1244358.
Abstract
Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the 1D edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.
Xuetao Gan, Ren-Jye Shiue, Yuanda Gao, Inanc Meric, Tony F. Heinz, Kenneth Shepard, James Hone, Solomon Assefa & Dirk Englund, “Chip-integrated ultrafast graphene photodetector with high responsivity” Nature Photonics (2013) doi:10.1038/nphoton.2013.253
R. M. Field and K. L. Shepard, “A 100-fps Fluorescence Lifetime Imager in Standard 0.13-μm CMOS,” Symposium on VLSI Circuits, 2013.
Abstract
A wide-field fluorescence lifetime imager capable of up to 100 frames per second (fps) is presented. The imager consists of a64-by-64 array of low-noise single photon avalanche diodes (SPADs) in a standard 0.13-micron CMOS process, 4096 time-to- digital converters, and an application specific data path to enable continuous image acquisition at a total output data rate of 42 Gbps. These features combine to enable new lifetime-based diagnostic imaging.
Ryan P. Davies, ChengCheng, Noah Sturcken, William E. Bailey, and Kenneth L. Shepard, “Coupled Inductors With Crossed Anisotropy CoZrTz/SiO2Multilayer Cores,” IEEE Transactions On Magnetics, Vol. 49, No. 7, July 2013
Abstract
Four-turn coupled (flux-closed) inductor structures have been fabricated and tested for use in high-power-density integrated voltage regulator (IVR) applications. Our solenoid-like structure is comprised of a laminated magnetic core of four rungs surrounded by four Cu windings creating four coupled inductors. The magnetic core is made of laminations of ultra-high-vacuum-sputtered [5 nm Ta/200 nm Co91.5Zr4.0Ta4.5 (CZT)/7 nm SiO2 ] repeated 20 times. Individual CZT layers are deposited under a magnetic bias to induce uniaxial anisotropy. The quad-coupled inductor shows a frequency response with a measured self-inductance of 7.4 nH for one inductor sustained up to 100 MHz and roll-off to half this low-frequency value at ~450MHz. This inductance is more than 65X higher than what would be calculated from an air-core inductor of equivalent geometry.
I. Meric, N. Petrone, J. Hone, K. L. Shepard “Flexible graphene field-effect transistors for microwave electronics,” International Microwave Symposium, 2013
Abstract
The high-frequency characteristics of graphene field-effect transistors (GFETs) has received significant interest due the very high carrier velocities in graphene. In addition to excellent electronic performance, graphene possesses exceptional mechanical properties such as high flexibility and strength. Here, we demonstrate the potential of flexible-GFETs and show that the combination of electrical and mechanical advantages of graphene result in gigahertz-frequency operation at strain values up to 2%. These devices represent the only reported technology to achieve gigahertz-frequency power gain at strain levels above 0.5%.
I. Meric, C.R. Dean, N. Petrone, L. Wang, J. Hone, P. Kim, and K.L. Shepard, “Graphene Field-Effect Transistors Based on Boron–Nitride Dielectrics,” Proceedings of the IEEE, Vol. 101, No. 7., July 2013
Abstract
Two-dimensional atomic sheets of graphene represent a new class of nanoscale materials with potential applications in electronics. However, exploiting the intrinsic characteristics of graphene devices has been problematic due to impurities and disorder in the surrounding dielectric and graphene/dielectric interfaces. Recent advancements in fabricating graphene heterostructures by alternately layering graphene with crystalline hexagonal boron nitride (hBN), its insulating isomorph, have led to an order of magnitude improvement in graphene device quality. Here, recent developments in graphene devices utilizing boron–nitride dielectrics are reviewed. Field-effect transistor (FET) characteristics of these systems at high bias are examined. Additionally, existing challenges in material synthesis and fabrication and the potential of graphene/BN heterostructures for novel electronic applications are discussed.
H. Norian, I. Kymissis, and K. L. Shepard. “Integrated CMOS Quantitative Polymerase Chain Reaction Lab-on-Chip.” IEEE Symposium on VLSI Circuits, June 2013.
Abstract
An integrated lab-on-chip capable of performing quantitative polymerase chain reaction (qPCR) is demonstrated in a high-voltage 0.35-μm CMOS process operating at a 3.3 V supply. PCR thermal cycling can be performed by physically moving droplets between three distinct temperature zones on the surface of chip or by thermal cycling a droplet in place. Droplet actuation is enabled by electrowetting-on-dielectric transport at 90 V. On-chip temperature regulation to 0.15°C is performed with on-chip resistive heaters and temperature sensors. PCR cycles are monitored by measuring the fluorescence signal of an intercalator dye using integrated single photon avalanche diodes (SPADs). Results are demonstrated for the recognition of DNA extracts from Staphylococcus aureus (S. aureus) at a detection limit of a few copies per nL target volume.
C. R. Dean, L. Wang, P. Maher, C. Forsythe, F. Ghahari, Y. Gao, J. Katoch, M. Ishigami, P. Moon, M. Koshino, T. Taniguchi, K.Watanabe, K. L. Shepard, J.Hone & P. Kim, “Hofstadter’s butterfly and the fractal quantum Hall effect in moiré superlattices,” Nature, 2013.
Abstract
Electrons moving through a spatially periodic lattice potential develop a quantized energy spectrum consisting of discrete Bloch bands. In two dimensions, electrons moving through a magnetic field also develop a quantized energy spectrum, consisting of highly degenerate Landau energy levels. When subject to both a magnetic field and a periodic electrostatic potential, two-dimensional systems of electrons exhibit a self-similar recursive energy spectrum1.Known as Hofstadter’s butterfly, this complex spectrum results from an interplay between the characteristic lengths associated with the two quantizing fields, and is one of the first quantum fractals discovered in physics. In the decades since its prediction, experimental attempts to study this effect have been limited by difficulties in reconciling the two length scales. Typical atomic lattices (with periodicities of less than one nanometre) require unfeasibly large magnetic fields to reach the commensurability condition, and in artificially engineered structures (with periodicities greater than about 100 nanometres) the corresponding fields are too small to overcome disorder completely. Herewe demonstrate thatmoire´ superlattices arising in bilayer graphene coupled to hexagonal boron nitride provide a periodicmodulationwith ideal length scales of the order of ten nanometres, enabling unprecedented experimental access to the fractal spectrum. We confirm that quantum Hall features associated with the fractal gaps are described by two integer topological quantum numbers, and report evidence of their recursive structure. Observation of a Hofstadter spectrum in bilayer graphene means that it is possible to investigate emergent behaviour within a fractal energy landscape in a system with tunable internal degrees of freedom.
K. Venta, G. Shemer, M. Puster, J. A. Rodriguez-Manzo, A. Balan, J. K. Rosenstein, K. L. Shepard, and M. Drndic, “Differentiation of short, single-stranded DNA homopolymers in solid-state nanopores,” ACS Nano, Advanced On-Line Publication (April 26, 2013)
Abstract
In the last two decades, new techniques that monitor ionic current modulations as single molecules pass through a nanoscale pore have enabled numerous single-molecule studies. While biological nanopores have recently shown the ability to resolve single nucleotides within individual DNA molecules, similar developments with solid-state nanopores have lagged, due to challenges both in fabricating stable nanopores of similar dimensions as biological nanopores and in achieving sufficiently low-noise and high-bandwidth recordings. Here we show that small silicon nitride nanopores (0.8- to 2-nm diameter in 5- to 8-nm-thick membranes) can resolve differences between ionic current signals produced by short (30 base) ssDNA homopolymers (poly(dA), poly(dC), poly(dT)), when combined with measurement electronics that allow a signal-to-noise ratio of better than 10 to be achieved at 1-MHz bandwidth. While identifying intramolecular DNA sequences with silicon nitride nanopores will require further improvements in nanopore sensitivity and noise levels, homopolymer differentiation represents an important milestone in the development of solid-state nanopores.
J. K. Rosenstein, S. Ramakrishnan, J. Roseman, and K. L. Shepard, “Single ion channel recordings with CMOS-anchored lipid membranes,” Nano Letters, Advanced On Line publication (May 1, 2013)
Abstract
We present single-ion-channel recordings performed with biomimetic lipid membranes which are directly attached to the surface of a complementary metal−oxide−semiconductor (CMOS) preamplifier chip. With this system we resolve single-channel currents from several types of bacterial ion channels, including fluctuations of a single alamethicin channel at a bandwidth of 1 MHz which represent the fastest single-ion-channel recordings reported to date. The platform is also used for high-resolution α-hemolysin nanopore recordings. These results illustrate the high signal fidelity, fine temporal resolution, small geometry, and multiplexed integration which can be achieved by leveraging integrated semiconductor platforms for advanced ion channel interfaces.
S. Realov and K. L. Shepard, “Analysis of random telegraph noise in 45-nm CMOS using on-chip characterization system,” IEEE Transactions on Electron Devices 60, pp. 1716-1722 (May, 2013)
Abstract
An on-chip variability characterization system implemented in a 45-nm CMOS process is used for direct time-domain measurements of random telegraph noise (RTN) in small-area devices. A procedure for automated extraction of RTN parameters from large volumes of measured data is developed. Statistics for number of traps, NT, and single-trap amplitudes, ΔVth, are studied across device polarity, bias, and gate area. A Poisson distribution is used to model NT and a log-normal distribution is used to model ΔVth. The scaling of the two statistics across gate dimensions is discussed; the expected value of NT is shown to scale with (L −ΔL)−1, whereas the expected value of ΔVth is shown to scale with W−1(L −ΔL)−0.5. The two statistics are combined in a compact RTN probabilistic model representing the statistics of the overall ΔVth fluctuations because of RTN. This model is demonstrated to give accurate predictions of the tails of the measured RTN distributions at the 95th percentile level, which scale with W−1(L −ΔL)−1.5. A comparison between nMOS and pMOS devices shows that pMOS devices exhibit both a higher average number of traps and a larger average single-trap ΔVth amplitude, leading to a comparatively larger overall impact of RTN.
C. Cheng, R. Davies, N. Sturcken, K. Shepard, and W. E. Bailey, “Optimization of ultra-soft CoZrTa/SiO2/CoZrTa trilayer elements for integrated inductor structures,” Journal of Applied Physics 113, 17A343 (2013).
Abstract
We show the optimization of magnetic properties of ferromagnetic (FM)/SiO2/FM trilayer structures as potential candidates for the magnetic core in toroidal integrated inductors, with FM materials Co91.5Zr4.0Ta4.5 (CZT) and Ni80Fe20 (Py). In the single-layer parent films, we found a monotonic reduction of easy-axis coercivity (Hc down to 0.17 Oe in CZT, 0.4Oe in Py) with increasing dc magnetron sputtering voltage. In the trilayer rectangular structures, with induced easy-axis in the short lateral dimension, we found proof of dipolar coupling between the two FM layers from BH loop measurements in the CZT system, showing linear response with minimal hysteresis loss when the external field is applied in the long axis. Py elements did not show this optimized property. Further investigation of domain configurations using scanning transmission x-ray microscopy suggests an insufficient induced anisotropy in Py compared with the shape anisotropy to realize the antiparallel-coupled state.
S. Realov and K. L. Shepard, “On-Chip Combined C-V/I-V Characterization System in 45-nm CMOS Technology,” IEEE Journal of Solid-State Circuits, Vol. 48, No. 3, March 2013.
Abstract
An on-chip system for combined capacitance-voltage (C-V) and current-voltage (I-V) characterization of a large integrated transistor array implemented in a 45-nm bulk CMOS process is presented. On-chip I-V characterization is implemented using a four-point Kelvin measurement technique with 12-bit sub-10 nA current measurement resolution, 10-bit sub-1 mV voltage measurement resolution, and sampling speeds on the order of 100 kHz. C-V characterization is performed using a novel leakage- and parasitics-insensitive charge-based capacitance measurement (CBCM) technique with atto-Farad resolution. The on-chip system is employed in studying both random and systematic sources of quasi-static device variability. For the first time, combined C-V/I-V characterization of circuit-representative devices is demonstrated and used to extract variations in the underlying physical characteristics of the device, including line-edge-roughness (LER) parameters and systematic device length variations across the die.
N. Petrone, I. Meric, J. Hone, and K. L. Shepard, “Graphene Field-Effect Transistors with Gigahertz-Frequency Power Gain on Flexible Substrates,” Nano Letters, 12 (1), pp. 121-125. 2013.
Abstract
The development of flexible electronics operating at radiofrequencies (RF) requires materials that combine excellent electronic performance and the ability to withstand high levels of strain. In this work, we fabricate graphene field-effect transistors (GFETs) on flexible substrates from graphene grown by chemical vapor deposition (CVD). Our devices demonstrate unity-current-gain frequencies, f T, and unity-power-gain frequencies, f max, up to 10.7 GHz and 3.7 GHz, respectively, with strain limits of 1.75%. These devices represent the only reported technology to achieve gigahertz-frequency power gain at strain levels above 0.5%. As such, they demonstrate the potential of CVD graphene to enable a broad range of flexible electronic technologies which require both high flexibility and RF operation.
Sturcken, N.; O’Sullivan, E. J.; Wang, N.; Herget, P.; Webb, B. C.; Romankiw, L. T.; Petracca, M.; Davies, R.; Fontana, R. E.; Decad, G. M.; Kymissis, I.; Peterchev, A. V.; Carloni, L. P.; Gallagher, W. J.; Shepard, K. L. , A 2.5D Integrated Voltage Regulator Using Coupled-Magnetic-Core Inductors on Silicon Interposer, IEEE Journal of Solid-State Circuits, January, 2013
Abstract
An integrated voltage regulator (IVR) is presented that uses custom fabricated thin-film magnetic power inductors. The inductors are fabricated on a silicon interposer and integrated with a multi-phase buck converter IC by 2.5D chip stacking. Several inductor design variations have been fabricated and tested. The best performance has been achieved with a set of eight coupled inductors that each occupies 0.245 mm2 and provides 12.5 nH with 270 mΩ DC. With early inductor prototypes, the IVR efficiency for a 1.8 V:1.0 V conversion ratio peaks at 71% with FEOL current density of 10.8 A/mm2 and inductor current density of 1.53 A/mm2 . At maximum load current, 69% conversion efficiency and 1.8 V:1.2 V conversion ratio the FEOL current density reaches 22.6 A/mm2 and inductor current density reaches 3.21 A/mm2 .
K. L. Shepard, T. Ito, and A. J. Griffith, “Extractin energy from the inner ear,” Nature Biotechnology 30, 1204-1205 (2012)
N. Sturcken, M. Petracca, S. Warren, P. Mantovani, L. P. Carloni, A. V. Peterchev, and K. L. Shepard, “A Switched-Inductor Integrated Voltage Regulator With Nonlinear Feedback and Network-on-Chip Load in 45 nm SOI,” IEEE Journal of Solid-State Circuits, Vol. 48, No. 8, August 2012.
Abstract
A four-phase integrated buck converter in 45 nm silicon-on-insulator (SOI) technology is presented. The controller uses unlatched pulse-width modulation (PWM) with nonlinear gain to provide both stable small-signal dynamics and fast response (700 ps) to large input and output transients. This fast control approach reduces the required output capacitance by 5 in comparison to a conventional, latched PWM controller at a similar operating point. The converter switches package-integrated air-core inductors at 80 MHz and delivers 1 A/mm at 83% efficiency and 0.66 conversion ratio. A network-on-chip (NoC) serves as a realistic digital load along with a programmable current source capable of generating load current steps with slew rate of 1 A/100 ps for characterization of the control scheme.
N. Petrone, C. R. Dean, I. Meric, A. M. van der Zande, P. Y. Huang, L. Wang, D. Muller, K. L. Shepard, and J. Hone, “Chemical Vapor Deposition-Derived Graphene with Electrical Performance of Exfoliated Graphene,” Nano Letters, doi.org/10.1021/nl204481s
Abstract
While chemical vapor deposition (CVD) promises a scalable method to produce large-area graphene, CVD-grown graphene has heretofore exhibited inferior electronic properties in comparison with exfoliated samples. Here we test the electrical transport properties of CVD-grown graphene in which two important sources of disorder, namely grain boundaries and processing-induced contamination, are substantially reduced. We grow CVD graphene with grain sizes up to 250 μm to abate grain boundaries, and we transfer graphene utilizing a novel, dry-transfer method to minimize chemical contamination. We fabricate devices on both silicon dioxide and hexagonal boron nitride (h-BN) dielectrics to probe the effects of substrate-induced disorder. On both substrate types, the large-grain CVD graphene samples are comparable in quality to the best reported exfoliated samples, as determined by low-temperature electrical transport and magnetotransport measurements. Small-grain samples exhibit much greater variation in quality and inferior performance by multiple measures, even in samples exhibiting high field-effect mobility. These results confirm the possibility of achieving high-performance graphene devices based on a scalable synthesis process.
N. Wang, E. J. O’Sullivan, P. Herget, B. Rajendran, L. E. Krupp, L. T. Romankiw, B. C. Webb, R. Fontana, E. A. Duch, E. A. Joseph, S. L. Brown, X. Hu, G. M. Decad, N. Sturcken, K. L. Shepard, and W. J. Gallagher, “Integrated on-chip inductors with electroplated magnetic yokes” (invited), J. Appl. Phys. 111, 07E732 (2012), DOI:10.1063/1.3679458
Abstract
Thin-film ferromagnetic inductors show great potential as the energy storage element for integrated circuits containing on-chip power management. In order to achieve the high energy storage required for power management, on-chip inductors require relatively thick magnetic yoke materials (several microns or more), which can be readily deposited by electroplating through a photoresist mask as demonstrated in this paper, the yoke material of choice being Ni45Fe55, whose properties of relatively high moment and electrical resistivity make it an attractive model yoke material for inductors. Inductors were designed with a variety of yoke geometries, and included both single-turn and multi-turn coil designs, which were fabricated on 200mm silicon wafers in a CMOS back-end-of-line (BEOL) facility. Each inductor consisted of electroplated copper coils enclosed by the electroplated Ni45Fe55 yokes; aspects of the fabrication of the inductors are discussed. Magnetic properties of the electroplated yoke materials are described, including high frequency permeability measurements. The inductance of 2-turn coil inductors, for example, was enhanced up to about 6 times over the air core equivalent, with an inductance density of 130 nH/mm2 being achieved. The resistance of these non-laminated inductors was relatively large at high frequency due to magnetic and eddy current losses but is expected to improve as the yoke material/structure is further optimized, making electroplated yoke-containing inductors attractive for dc-dc power converters.
J. K. Rosenstein, M. Wanunu, C. A. Merchant, M. Drndic, and K. L. Shepard, “Integrated nanopore sensing platform with sub-microsecond temporal resolution,” doi:10.1038/nmeth.1932, March 18, 2012.
Abstract
Nanopore sensors have attracted considerable interest for high-throughput sensing of individual nucleic acids and proteins without the need for chemical labels or complex optics. A prevailing problem in nanopore applications is that the transport kinetics of single biomolecules are often faster than the measurement time resolution. Methods to slow down biomolecular transport can be troublesome and are at odds with the natural goal of high-throughput sensing. Here we introduce a low-noise measurement platform that integrates a complementary metal-oxide semiconductor (CMOS) preamplifier with solid-state nanopores in thin silicon nitride membranes. With this platform we achieved a signal-to-noise ratio exceeding five at a bandwidth of 1MHz, which to our knowledge is the highest bandwidth nanopore recording to date. We demonstrate transient signals as brief as 1μs from short DNA molecules as well as current signatures during molecular passage events that shed light on submolecular DNA configurations in small nanopores.
M. L. Johnston, H. Edrees, I. Kymissis, and K. L. Shepard, “Integrated VOC Vapor Sensing on FBAR-CMOS Array,” The 25th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2012), pp. 846-849, 2012.
Abstract
This paper reports first results of volatile organic compound (VOC) detection on a monolithically integrated film bulk acoustic resonator (FBAR) array on a silicon integrated circuit substrate. The combined sensor platform uses thin polymer layers as gas absorbers for individual FBAR functionalization, and frequency shifts are measured on-chip in response to changing VOC concentration. Integrating sensors, drive, and read- out functionality on a single CMOS die enables a robust, multiplex sensor platform and obviates external measurement equipment.
N. Sturcken, E. O’Sullivan, N. Wang, P. Herget, B. Webb, L. Romankiw, M. Petracca, R. Davies, R. Fontana, G. Decad, I. Kymissis, A. Peterchev, L. Carloni, W. Gallagher, and K. L. Shepard, “A 2.5D Integrated Voltage Regulator Using Coupled- Magnetic-Core Inductors on Silicon Interposer Delivering 10.8A/mm2” Proceedings to the International Solid-State Circuits Conference (ISSCC), 2012.
Abstract
Energy consumption is a dominant constraint on the performance of modern microprocessors and systems-on-chip. Dynamic voltage and frequency scaling (DVFS) is a promising technique for performing “on-the-fly” energy-performance optimization in the presence of workload variability. Effective implementation of DVFS requires voltage regulators that can provide many independent power supplies and can transition power supply levels on nanosecond timescales, which is not possible with modern board-level voltage regulator modules (VRMs) [1]. Switched-inductor integrated voltage regulators (IVRs) can enable effective implementation of DVFS, eliminating the need for separate VRMs and reducing power distribution network (PDN) impedance requirements by performing dc-dc conversion close to the load while supporting high peak current densities [2-3]. The primary obstacle facing development of IVRs is integration of suitable power inductors. This work presents an early prototype switched-inductor IVR using 2.5D chip stacking for inductor integration.
N. Sturcken, R. Davies, C. Cheng, W. E. Bailey and K. L. Shepard “Design of Coupled Power Inductors with Crossed Anisotropy Magnetic Core for Integrated Power Conversion” Proceedings to the Applied Power Electronics Conference (APEC), 2012.
Abstract
Design and partial microfabrication of a coupled power inductor is presented for use in high power-density integrated voltage regulators (IVR). The proposed inductor uses many laminations of uniaxial, high-permeability magnetic material where the orientation of anisotropy between successive laminations is rotated to provide an effectively isotropic core. The high permeability core allows for an inductance density of 200nH/mm2, while coupling between phases prevents magnetic saturation and allows a current density as high as 11A/mm2 according to quasi-static finite-element-analysis (FEA) simulations. The coupling factor, inductance and resistance of the device are optimized for operation in a four-phase integrated buck converter switching at 100MHz.
C. Cheng, N. Sturcken, K. Shepard, W. E. Bailey, “Vector control of induced magnetic anisotropy using an in situ quadrupole electromagnet in ultrahigh vacuum sputtering, Review of Scientific Instruments,” 2012, pp. 063903 – 063903-4
J. Chae, S. Jung, A. F. Young, C. R. Dean, L. Wang, Y. Gao, K. Watanabe, T. Taniguchi, J. Hone, K. L. Shepard, P. Kim, N. B. Zhitenev, and J. A. Stroscio, “Renormalization of the Graphene Dispersion Velocity Determined from Scanning Tunneling Spectroscopy,” Phys. Rev. Lett. 109, 116802 (2012)
Abstract
In graphene, as in most metals, electron-electron interactions renormalize the properties of electrons but leave them behaving like noninteracting quasiparticles. Many measurements probe the renormalized properties of electrons right at the Fermi energy. Uniquely for graphene, the accessibility of the electrons at the surface offers the opportunity to use scanned probe techniques to examine the effect of interactions at energies away from the Fermi energy, over a broad range of densities, and on a local scale. Using scanning tunneling spectroscopy, we show that electron interactions leave the graphene energy dispersion linear as a function of excitation energy for energies within 200 meV of the Fermi energy. However, the measured dispersion velocity depends on density and increases strongly as the density approaches zero near the charge neutrality point, revealing a squeezing of the Dirac cone due to interactions.
C. Dean, A .F. Young, L. Wang, I. Meric, G.-H. Lee, K. Watanabe, T. Taniguchi, K. Shepard, P. Kim, J. Hone, “Graphene Based Heterostructures,” Solid State Communications 152, 1275-1282 (2012)
Abstract
The two dimensional charge carriers in monolayer and bilayer graphene are described by massless and massive chiral Dirac Hamiltonians, respectively. These two-dimensional materials are predicted to exhibit a wide range of behavior, etc. However, graphene devices on a typical three-dimensional insulating substrates such as SiO2 are highly disordered, exhibiting characteristics that are far inferior to the expected intrinsic properties of graphene. We have developed a novel technique for substrate engineering of graphene devices using layered dielectric materials to build graphene based vertical heterostructures. We employ hBN, an insulating isomorph of graphite, as a substrate and gate dielectric for graphen eelectronics. In this review, we describe the fabrication and characterization of high-quality exfoliated mono-and bilayer graphene devices on single-crystal hBN substrates, using a mechanical transfer process. Graphene devices on hBN substrates have mobilities and carrier in homogeneities that are almost an order of magnitude better than devices on SiO2. We use the enhanced mobility of electrons in hBN supported graphene to investigate the effects of electronic interactions. We find that interactions drive spontaneous breaking of the emergent SU(4) symmetry of the graphene Landau levels, leading to a variety of non-trivial integer and fractional quantum Hall states. The ability to assemble crystalline layered materials in a controlled way permits the fabrication of graphene devices on other promising dielectrics and allows for the realization of more complex grapheme heterostructures.
A. F. Young, C. R. Dean, I. Meric, S. Sorgenfrei, H. Ren, K. Watanabe, T. Taniguchi, J. Hone, K. L. Shepard, and P. Kim, “Electronic compressibility of gapped bilayer graphene,” Phys. Rev. B 85, 235458 (2012)
Abstract
We report on a capacitance study of dual gated bilayer graphene. The measured capacitance allows us to probe the electronic compressibility as a function of carrier density, temperature, and applied perpendicular electrical displacement D. As a band gap is induced with increasing D, the compressibility minimum at charge neutrality becomes deeper but remains finite, suggesting the presence of localized states within the energy gap. Temperature dependent capacitance measurements show that compressibility is sensitive to the intrinsic band gap. For large displacements, an additional peak appears in the compressibility as a function of density, corresponding to the presence of a one-dimensional van Hove singularity (vHs) at the band edge arising from the quartic bilayer graphene band structure. ForD > 0, the additional peak is observed only for electrons, while forD < 0 the peak appears only for holes. This asymmetry can be understood in terms of the finite interlayer separation and may be useful as a direct probe of the layer polarization.
A. F. Young, C. R. Dean, L. Wang, H. Ren, P. Cadden-Zimansky, K. Watanabe, T. Taniguchi, J. Hone, K. L. Shepard, and P. Kim, “Spin and valley quantum Hall ferromagnetism in graphene,” Nature Physics, 8, 553-556 (2012)
Abstract
Electronic systems with multiple degenerate degrees of freedom can support a rich variety of broken symmetry states. In a graphene Landau level (LL), strong Coulomb interactions and the fourfold spin–valley degeneracy lead to an approximate SU(4) isospin symmetry. At partial filling, exchange interactions can break this symmetry, manifesting as further Hall plateaus outside the normal integer sequence. Here we report the observation of a number of these quantum Hall isospin ferromagnetic (QHIFM) states, which we classify according to their real spin structure using tilted field magnetotransport. The large activation gaps confirm the Coulomb origin of all the broken symmetry states, but the order depends strongly on LL index. In the high-energy LLs the Zeeman effect is the dominant aligning field, leading to real spin ferromagnets hosting skyrmionic excitations at half filling, whereas in the ‘relativistic’ zero LL lattice scale interactions drive the system to a spin unpolarized state.