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).

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).

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.

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

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

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

Most neuromodulation approaches rely on extracellular electrical stimulation with penetrating electrodes at the cost of cortical damage. Surface electrodes, in contrast, are much less invasive but are challenged by the lack of proximity to axonal processes, leading to poor resolution. Here, we demonstrate that high-density (40-μm pitch), high-capacitance (>1 nF), single neuronal resolution PEDOT:PSS electrodes can be programmed to shape the charge injection front selectively at depths approaching 300 micrometers with a lateral resolution better than 100 micrometers. These electrodes, patterned on thin-film parylene substrate, can be subdurally implanted and adhere to the pial surface in chronic settings. By leveraging surface arrays that are optically transparent with PEDOT:PSS local interconnects and integrated with depth electrodes, we are able to combine surface stimulation and recording with calcium imaging and depth recording to demonstrate these spatial limits of bidirectional communication with pyramidal neurons in mouse visual cortex both laterally and at depth from the surface.

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)

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)

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

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)

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

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

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.