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Competing Interests: Competing interests: J.T.R. is a shareholder, director and employee of Motif Neurotech, Inc. S.L.N. is a director and employee of Forest Neurotech. T.D. is founder and director of Amber Therapeutics, non-exec chairman of Mint Neurotechnologies Ltd. and advisor for Cortec Neuro. N.V. is a shareholder, director and employee of Neurosoft Bioelectronics S.A., a Swiss company building BCIs. M.M.S. is an inventor on patents or patent applications related to neural decoding and stimulation. R.M.F. is a shareholder, director and employee of Kernel. A.L.O. is a scientific advisor for Meta Reality Labs. S.A.S. is a shareholder of Motif Neurotech, and has consulting agreements with Neuropace, Boston Scientific, Zimmer Biomet and Koh Young. A.F. is a shareholder, director and employee of Cognixion Corporation. M.R.A. is a shareholder, director and employee of Paradromics, Inc. C.J.R. is an inventor on intellectual property related to neurotechnology, and a shareholder and member of the scientific advisory board of Motif Neurotech, Inc. S.D.S. is an inventor on patents or patent applications related to BCIs and is an advisor to Sonera. T.G.C. is a shareholder and director of Mint Neurotechnologies, Ltd. M.S. is an inventor on patents or patent applications related to neural decoding and stimulation. C.X. is an inventor on intellectual property related to neurotechnology, and a shareholder of Neuralthread, Inc. J.P.D. is a shareholder and board member of Pathmaker Neurosystems, and an advisor to Neurable and to Beacon Biosignals. All other authors declare no competing interests.

Wireless communication technologies for bioelectronic implants enable remote monitoring for diagnosis and adaptive therapeutic intervention without the constraints of wired connections. However, wireless data uplink from millimeter-scale devices deep in the body struggles to achieve low power consumption while maintaining large misalignment tolerances. Here, we report a passive wireless backscatter communication system based on magnetoelectric transducers that consumes less than 0.3 pJ/bit and achieves less than 1E-6 bit error rate at a distance of 55 mm while tolerating a misalignment of 10 mm. Using this robust data uplink, we designed a wireless cardiac sensing node that can transmit electrocardiogram signals from the beating heart surface of a porcine model to a custom external transceiver using the magnetoelectric backscatter uplink. This reliable, near-zero-power communication method provides opportunities for next-generation bioelectronics to feature real-time physiological monitoring and closed-loop therapies while maintaining a small form factor and low power consumption., Competing Interests: Conflict of interest F.A., J.E.W., K.Y., and J.T.R. receive monetary and/or equity compensation from Motif Neurotech. The terms of these arrangements have been reviewed and approved by Rice University in accordance with their policies on conflict of interest in research.

Miniature bioelectronic implants promise revolutionary therapies for cardiovascular and neurological disorders. Wireless power transfer (WPT) is a significant method for miniaturization, eliminating the need for bulky batteries in devices. Despite successful demonstrations of millimetric battery free implants in animal models, the robustness and efficiency of WPT are known to degrade significantly under misalignment incurred by body movements, respiration, heart beating, and limited control of implant orientation during surgery. This article presents an omnidirectional WPT platform for millimetric bioelectronic implants, employing the emerging magnetoelectric (ME) WPT modality, and magnetic field steering technique based on multiple transmitter (TX) coils. To accurately sense the weak coupling in a miniature implant and adaptively control the multicoil TX array in a closed loop, we develop an active echo (AE) scheme using a tiny coil on the implant. Our prototype comprises a fully integrated 14.2 mm3 implantable stimulator embedding a custom low power system on chip (SoC) powered by an ME film, a TX with a custom three channel AE RX chip, and a multicoil TX array with mutual inductance cancellation. The AE RX achieves negative 161 dBm per Hz input referred noise with 64 dB gain tuning range to reliably sense the AE signal, and offers fast polarity detection for driver control. AE simultaneously enhances the robustness, efficiency, and charging range of ME WPT. Under 90 degree rotation from the ideal position, our omnidirectional WPT system achieves 6.8x higher power transfer efficiency (PTE) than a single coil baseline. The tracking error of AE negligibly degrades the PTE by less than 2 percent from using ideal control.

Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of endocisternal neural interfaces that approach brain and spinal cord targets through inner and outer spaces filled with cerebrospinal fluid. Thus, the interfaces gain access to the entire brain convexity, to deep brain structures within the ventricles and to the spinal cord from the spinal subarachnoid space. We combined an endocisternal neural interface with wireless miniature magnetoelectrically powered bioelectronics so that it can be freely navigated percutaneously from the spinal space to the cranial subarachnoid space, and from the cranial subarachnoid space to the ventricles. In sheep, we show recording and stimulation functions, as well as repositioning of the flexible electrodes and explantation of the interface after chronic implantation. Minimally invasive endocisternal bioelectronics may enable chronic and transient therapies, particularly for stroke rehabilitation and epilepsy monitoring., Competing Interests: Competing interests J.T.R., Sunil A. Sheth, Sameer A. Sheth and J.E.W. receive monetary or equity compensation from Motif Neurotech. Sameer A. Sheth has consulting agreements with Boston Scientific, Zimmer Biomet, Koh Young, Neuropace, Sensoria Therapeutics and Varian Medical. Sunil A. Sheth has consulting agreements with Viz.ai, Penumbra, Medtronic and Imperative Care, as well as grant funding from the McNair Foundation and the NIH. The terms of these agreements have been reviewed and approved by Rice University, UTHealth and Baylor College of Medicine in accordance with their policies on conflicts of interest in research. A.K.W. is a cofounder of Deinde and P.K. is an investor in Deinde. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

ConspectusThe coupling of magnetic and electric properties manifested in magnetoelectric (ME) materials has unlocked numerous possibilities for advancing technologies like energy harvesting, memory devices, and medical technologies. Due to this unique coupling, the magnetic properties of these materials can be tuned by an electric field; conversely, their electric polarization can be manipulated through a magnetic field.Over the past seven years, our lab work has focused on leveraging these materials to engineer implantable bioelectronics for various neuromodulation applications. One of the main challenges for bioelectronics is to design miniaturized solutions that can be delivered with minimally invasive procedures and yet can receive sufficient power to directly stimulate tissue or power electronics to perform functions like communication and sensing.Magnetoelectric coupling in ME materials is strongest when the driving field matches a mechanical resonant mode. However, miniaturized ME transducers typically have resonance frequencies >100 kHz, which is too high for direct neuromodulation as neurons only respond to low frequencies (typically <1 kHz). We discuss two approaches that have been proposed to overcome this frequency mismatch: operating off-resonance and rectification. The off-resonance approach is most common for magnetoelectric nanoparticles (MENPs) that typically have resonance frequencies in the gigahertz range. In vivo experiments on rat models have shown that MENPs could induce changes in neural activity upon excitation with <200 Hz magnetic fields. However, the neural response has latencies of several seconds due to the weak coupling in the off-resonance regime.To stimulate neural responses with millisecond precision, we developed methods to rectify the ME response so that we could drive the materials at their resonant frequency but still produce the slowly varying voltages needed for direct neural stimulation. The first version of the stimulator combined a ME transducer and analog electronics for rectification. To create even smaller solutions, we introduced the first magnetoelectric metamaterial (MNM) that exhibits self-rectification. Both designs have effectively induced neural modulation in rat models with less than 5 ms latency.Based on our experience with in vivo testing of the rectified ME stimulators, we found it challenging to deliver the precisely controlled therapy required for clinical applications, given the ME transducer's sensitivity to the external transmitter alignment. To overcome this challenge, we developed the ME-BIT (MagnetoElectric BioImplanT), a digitally programmable stimulator that receives wireless power and data through the ME link.We further expanded the utility of this technology to neuromodulation applications that require high stimulation thresholds by introducing the DOT (Digitally programmable Overbrain Therapeutic). The DOT has voltage compliance up to 14.5 V. We have demonstrated the efficacy of these designs through various in vivo studies for applications like peripheral nerve stimulation and epidural cortical stimulation.To further improve these systems to be adaptive and enable a network of coordinated devices, we developed a bidirectional communication system to transmit data to and from the implant. To enable even greater miniaturization, we developed a way to use the same ME transducer for wireless power and data communication by developing the first ME backscatter communication protocol.

Understanding how neural circuits are regenerated following injury is a fundamental question in neuroscience. Hydra is a powerful model for studying this process because it has a simple neural circuit structure, significant and reproducible regenerative abilities, and established methods for creating transgenics with cell-type-specific expression. While Hydra is a long-standing model for regeneration and development, little is known about how neural activity and behavior is restored following significant injury. In this study, we ask if regenerating neurons terminally differentiate prior to reforming functional neural circuits, or if neural circuits regenerate first and then guide the constituent naive cells toward their terminal fate. To address this question, we developed a dual-expression transgenic Hydra line that expresses a cell-type-specific red fluorescent protein (tdTomato) in ec5 peduncle neurons, and a calcium indicator (GCaMP7s) in all neurons. With this transgenic line, we can simultaneously record neural activity and track the reappearance of the terminally-differentiated ec5 neurons. Using SCAPE (Swept Confocally Aligned Planar Excitation) microscopy, we monitored both calcium activity and expression of tdTomato-positive neurons in 3D with single-cell resolution during regeneration of Hydra's aboral end. The synchronized neural activity associated with a regenerated neural circuit was observed approximately 4 to 8 hours after expression of tdTomato in ec5 neurons. These data suggest that regenerating ec5 neurons undergo terminal differentiation prior to re-establishing their functional role in the nervous system. The combination of dynamic imaging of neural activity and gene expression during regeneration make Hydra a powerful model system for understanding the key molecular and functional processes involved in neural regeneration following injury., (© 2024. The Author(s).)

Wireless minimally invasive bioelectronic implants enable a wide range of applications in healthcare, medicine, and scientific research. Magnetoelectric (ME) wireless power transfer (WPT) has emerged as a promising approach for powering miniature bio-implants because of its remarkable efficiency, safety limit, and misalignment tolerance. However, achieving low-power and high-quality uplink communication using ME remains a challenge. This paper presents a pulse-width modulated (PWM) ME backscatter uplink communication enabled by a switched-capacitor energy extraction (SCEE) technique. The SCEE rapidly extracts and dissipates the kinetic energy within the ME transducer during its ringdown period, enabling time-domain PWM in ME backscatter. Various circuit techniques are presented to realize SCEE with low power consumption. This paper also describes the high-order modeling of ME transducers to facilitate the design and analysis, which shows good matching with measurement. Our prototyping system includes a millimeter-scale ME implant with a fully integrated system-on-chip (SoC) and a portable transceiver for power transfer and bidirectional communication. SCEE is proven to induce >50% amplitude reduction within 2 ME cycles, leading to a PWM ME backscatter uplink with 17.73 kbps data rate and 0.9 pJ/bit efficiency. It also achieves 8.5 × 10 -5 bit-error-rate (BER) at a 5 cm distance, using a lightweight multi-layer-perception (MLP) decoding algorithm. Finally, the system demonstrates continuous wireless neural local-field potential (LFP) recording in an in vitro setup.

Networks of miniature bioelectronic implants would enable precise measurement and manipulation of the complex and distributed physiological systems in the body. For example, sensing and stimulation nodes throughout the heart, brain, or peripheral nervous system would more accurately track and treat disease or support prosthetic technologies with many degrees of freedom. A main challenge to creating this type of in-body bioelectronic network is the fact that wireless power and data transfer are often inefficient when communicating through biological tissues. This challenge is typically compounded as one increases the number of implants within the network. Here, we show that magnetoelectric wireless data and power transfer enable a network of millimeter-sized bioelectronic implants where the power transfer efficiency of the system improves as the number of implanted devices increases. Using this property, we demonstrate networks of wireless battery-free bioelectronics ranging from 1 to 6 implants where the wireless power transfer efficiency for the system increases from 0.2% to 1.3%, with each node in the network receiving 2.2 mW at a distance of 1 cm. We use this system for efficient and robust wireless data and power transfer to demonstrate proof-of-concept networks of miniature spinal cord stimulators and cardiac pacing devices in large animals. The scalability of this network architecture enabled by magnetoelectric wireless power transfer provides a platform for building wireless closed-loop networks of bioelectronic implants for next-generation electronic medicine., Competing Interests: Competing interests J.T.R., F.A., and J.E.W. receive monetary and/or equity compensation from Motif Neurotech. A.F. is a consultant for Medtronic, Inc. and Abbott, Inc. M.R. receives monetary and/or equity compensation from Maxwell Biomedical, Rhythio, XNHealth, consults for Ziopatch, and is the medical director for IRhythm. The terms of these arrangements have been reviewed and approved by Rice University, the Houston Methodist Research Institute, Baylor College of Medicine, and The Texas Heart Institute in accordance with their policies on conflict of interest in research. The other authors declare no competing interests.

Understanding how internal states such as satiety are connected to animal behavior is a fundamental question in neuroscience. Hydra vulgaris, a freshwater cnidarian with only 12 neuronal cell types, serves as a tractable model system for studying state-dependent behaviors. We found that starved hydras consistently move towards light, while fed hydras do not. By modeling this behavior as a set of three sequences of head orientation, jump distance and jump rate, we demonstrate that the satiety state only affects the rate of the animal jumping to a new position, while the orientation and jump distance are unaffected. These findings yield insights into how internal states in a simple organism, Hydra, affect specific elements of a behavior, and offer general principles for studying the relationship between state-dependent behaviors and their underlying molecular mechanisms., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Summary: Copy number variation (CNV) and alteration (CNA) analysis is a crucial component in many genomic studies and its applications span from basic research to clinic diagnostics and personalized medicine. CNVpytor is a tool featuring a read depth-based caller and combined read depth and B-allele frequency (BAF) based 2D caller to find CNVs and CNAs. The tool stores processed intermediate data and CNV/CNA calls in a compact HDF5 file-pytor file. Here, we describe a new track in igv.js that utilizes pytor and whole genome variant files as input for on-the-fly read depth and BAF visualization, CNV/CNA calling and analysis. Embedding into HTML pages and Jupiter Notebooks enables convenient remote data access and visualization simplifying interpretation and analysis of omics data., Availability and Implementation: The CNVpytor track is integrated with igv.js and available at https://github.com/igvteam/igv.js. The documentation is available at https://github.com/igvteam/igv.js/wiki/cnvpytor. Usage can be tested in the IGV-Web app at https://igv.org/app and also on https://github.com/abyzovlab/CNVpytor., (© The Author(s) 2024. Published by Oxford University Press.)

Harnessing electronic excitations involving coherent coupling to bosonic modes is essential for the design and control of emergent phenomena in quantum materials. In situations where charge carriers induce a lattice distortion due to the electron-phonon interaction, the conducting states get "dressed", which leads to the formation of polaronic quasiparticles. The exploration of polaronic effects on low-energy excitations is in its infancy in two-dimensional materials. Here, we present the discovery of an interlayer plasmon polaron in heterostructures composed of graphene on top of single-layer WS 2 . By using micro-focused angle-resolved photoemission spectroscopy during in situ doping of the top graphene layer, we observe a strong quasiparticle peak accompanied by several carrier density-dependent shake-off replicas around the single-layer WS 2 conduction band minimum. Our results are explained by an effective many-body model in terms of a coupling between single-layer WS 2 conduction electrons and an interlayer plasmon mode. It is important to take into account the presence of such interlayer collective modes, as they have profound consequences for the electronic and optical properties of heterostructures that are routinely explored in many device architectures involving 2D transition metal dichalcogenides., (© 2024. The Author(s).)

Miniaturized neuromodulation systems could improve the safety and reduce the invasiveness of bioelectronic neuromodulation. However, as implantable bioelectronic devices are made smaller, it becomes difficult to store enough power for long-term operation in batteries. Here, we present a battery-free epidural cortical stimulator that is only 9 millimeters in width yet can safely receive enough wireless power using magnetoelectric antennas to deliver 14.5-volt stimulation bursts, which enables it to stimulate cortical activity on-demand through the dura. The device has digitally programmable stimulation output and centimeter-scale alignment tolerances when powered by an external transmitter. We demonstrate that this device has enough power and reliability for real-world operation by showing acute motor cortex activation in human patients and reliable chronic motor cortex activation for 30 days in a porcine model. This platform opens the possibility of simple surgical procedures for precise neuromodulation.

Histopathology plays a critical role in the diagnosis and surgical management of cancer. However, access to histopathology services, especially frozen section pathology during surgery, is limited in resource-constrained settings because preparing slides from resected tissue is time-consuming, labor-intensive, and requires expensive infrastructure. Here, we report a deep-learning-enabled microscope, named DeepDOF-SE, to rapidly scan intact tissue at cellular resolution without the need for physical sectioning. Three key features jointly make DeepDOF-SE practical. First, tissue specimens are stained directly with inexpensive vital fluorescent dyes and optically sectioned with ultra-violet excitation that localizes fluorescent emission to a thin surface layer. Second, a deep-learning algorithm extends the depth-of-field, allowing rapid acquisition of in-focus images from large areas of tissue even when the tissue surface is highly irregular. Finally, a semi-supervised generative adversarial network virtually stains DeepDOF-SE fluorescence images with hematoxylin-and-eosin appearance, facilitating image interpretation by pathologists without significant additional training. We developed the DeepDOF-SE platform using a data-driven approach and validated its performance by imaging surgical resections of suspected oral tumors. Our results show that DeepDOF-SE provides histological information of diagnostic importance, offering a rapid and affordable slide-free histology platform for intraoperative tumor margin assessment and in low-resource settings., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Mesoscopic calcium imaging enables studies of cell-type specific neural activity over large areas. A growing body of literature suggests that neural activity can be different when animals are free to move compared to when they are restrained. Unfortunately, existing systems for imaging calcium dynamics over large areas in non-human primates (NHPs) are table-top devices that require restraint of the animal's head. Here, we demonstrate an imaging device capable of imaging mesoscale calcium activity in a head-unrestrained male non-human primate. We successfully miniaturize our system by replacing lenses with an optical mask and computational algorithms. The resulting lensless microscope can fit comfortably on an NHP, allowing its head to move freely while imaging. We are able to measure orientation columns maps over a 20 mm 2 field-of-view in a head-unrestrained macaque. Our work establishes mesoscopic imaging using a lensless microscope as a powerful approach for studying neural activity under more naturalistic conditions., (© 2024. The Author(s).)

Peripheral nerve interfaces (PNIs) are electrical systems designed to integrate with peripheral nerves in patients, such as following central nervous system (CNS) injuries to augment or replace CNS control and restore function. We review the literature for clinical trials and studies containing clinical outcome measures to explore the utility of human applications of PNIs. We discuss the various types of electrodes currently used for PNI systems and their functionalities and limitations. We discuss important design characteristics of PNI systems, including biocompatibility, resolution and specificity, efficacy, and longevity, to highlight their importance in the current and future development of PNIs. The clinical outcomes of PNI systems are also discussed. Finally, we review relevant PNI clinical trials that were conducted, up to the present date, to restore the sensory and motor function of upper or lower limbs in amputees, spinal cord injury patients, or intact individuals and describe their significant findings. This review highlights the current progress in the field of PNIs and serves as a foundation for future development and application of PNI systems., (Creative Commons Attribution license.)

The layered insulator hexagonal boron nitride (hBN) is a critical substrate that brings out the exceptional intrinsic properties of two-dimensional (2D) materials such as graphene and transition metal dichalcogenides (TMDs). In this work, the authors demonstrate how hBN slabs tuned to the correct thickness act as optical waveguides, enabling direct optical coupling of light emission from encapsulated layers into waveguide modes. Molybdenum selenide (MoSe 2 ) and tungsten selenide (WSe 2 ) are integrated within hBN-based waveguides and demonstrate direct coupling of photoluminescence emitted by in-plane and out-of-plane transition dipoles (bright and dark excitons) to slab waveguide modes. Fourier plane imaging of waveguided photoluminescence from MoSe 2 demonstrates that dry etched hBN edges are an effective out-coupler of waveguided light without the need for oil-immersion optics. Gated photoluminescence of WSe 2 demonstrates the ability of hBN waveguides to collect light emitted by out-of-plane dark excitons.Numerical simulations explore the parameters of dipole placement and slab thickness, elucidating the critical design parameters and serving as a guide for novel devices implementing hBN slab waveguides. The results provide a direct route for waveguide-based interrogation of layered materials, as well as a way to integrate layered materials into future photonic devices at arbitrary positions whilst maintaining their intrinsic properties., (© 2023 Wiley-VCH GmbH. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Two-dimensional (2D) films of conjugated porous organic polymers (C-POPs) can translate the rich in-plane functionalities of conjugated frameworks into diverse optical and electronic applications while addressing the processability issues of their crystalline analogs for adaptable device architectures. However, the lack of facile single-step synthetic routes to obtain large-area high-quality films of 2D-C-POPs has limited their application possibilities so far. Here, we report the synthesis of four mechanically robust imine-linked 2D-C-POP free-standing films using a single-step fast condensation route that is scalable and tunable. The rigid covalently bonded 2D structures of the C-POP films offer high stability for volatile gas sensing in harsh environments while simultaneously enhancing site accessibility for gas molecules due to mesoporosity by structural design. Structurally, all films were composed of exfoliable layers of 2D polymeric nanosheets (NSs) that displayed anisotropy from disordered stacking, evinced by out-of-plane birefringent properties. The tunable in-plane conjugation, different nitrogen centers, and porous structures allow the films to act as ultraresponsive colorimetric sensors for acid sensing via reversible imine bond protonation. All the films could detect hydrogen chloride (HCl) gas down to 0.05 ppm, far exceeding the Occupational Safety and Health Administration's permissible exposure limit of 5 ppm with fast response time and good recyclability. Computational insights elucidated the effect of conjugation and tertiary nitrogen in the structures on the sensitivity and response time of the films. Furthermore, we exploited the exfoliated large 2D NSs and anisotropic optoelectronic properties of the films to adapt them into micro-optical and triboelectric devices to demonstrate their real-time sensing capabilities.

Magnetoelectric materials convert magnetic fields into electric fields. These materials are often used in wireless electronic and biomedical applications. For example, magnetoelectrics could enable the remote stimulation of neural tissue, but the optimal resonance frequencies are typically too high to stimulate neural activity. Here we describe a self-rectifying magnetoelectric metamaterial for a precisely timed neural stimulation. This metamaterial relies on nonlinear charge transport across semiconductor layers that allow the material to generate a steady bias voltage in the presence of an alternating magnetic field. We generate arbitrary pulse sequences with time-averaged voltage biases in excess of 2 V. As a result, we can use magnetoelectric nonlinear metamaterials to wirelessly stimulate peripheral nerves to restore a sensory reflex in an anaesthetized rat model and restore signal propagation in a severed nerve with latencies of less than 5 ms. Overall, these results showing the rational design of magnetoelectric metamaterials support applications in advanced biotechnology and electronics., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative 'enhancer rewiring' events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA., (© 2023. The Author(s).)

Miniature wireless bioelectronic implants that can operate for extended periods of time can transform how we treat disorders by acting rapidly on precise nerves and organs in a way that drugs cannot. To reach this goal, materials and methods are needed to wirelessly transfer energy through the body or harvest energy from the body itself. We review some of the capabilities of emerging energy transfer methods to identify the performance envelope for existing technology and discover where opportunities lie to improve how much-and how efficiently-we can deliver energy to the tiny bioelectronic implants that can support emerging medical technologies.

To maximize the capabilities of minimally invasive implantable bioelectronic devices, we must deliver large amounts of power to small implants; however, as devices are made smaller, it becomes more difficult to transfer large amounts of power without a wired connection. Indeed, recent work has explored creative wireless power transfer (WPT) approaches to maximize power density [the amount of power transferred divided by receiver footprint area (length × width)]. Here, we analyzed a model for WPT using magnetoelectric (ME) materials that convert an alternating magnetic field into an alternating voltage. With this model, we identify the parameters that impact WPT efficiency and optimize the power density. We find that improvements in adhesion between the laminated ME layers, clamping, and selection of material thicknesses lead to a power density of 3.1 mW/mm 2 , which is over four times larger than previously reported for mm-sized wireless bioelectronic implants at a depth of 1 cm or more in tissue. This improved power density allows us to deliver 31 and 56 mW to 10 and 27-mm 2 ME receivers, respectively. This total power delivery is over five times larger than similarly sized bioelectronic devices powered by radiofrequency electromagnetic waves, inductive coupling, ultrasound, light, capacitive coupling, or previously reported magnetoelectrics. This increased power density opens the door to more power-intensive bioelectronic applications that have previously been inaccessible using mm-sized battery-free devices., Competing Interests: A.S. and J.T.R. own equity in and receive compensation from Motif Neurotech, Inc., (© 2023 Author(s).)

Intercellular calcium waves (ICW) are complex signalling phenomena that control many essential biological activities, including smooth muscle contraction, vesicle secretion, gene expression and changes in neuronal excitability. Accordingly, the remote stimulation of ICW could result in versatile biomodulation and therapeutic strategies. Here we demonstrate that light-activated molecular machines (MM)-molecules that perform mechanical work on the molecular scale-can remotely stimulate ICW. MM consist of a polycyclic rotor and stator that rotate around a central alkene when activated with visible light. Live-cell calcium-tracking and pharmacological experiments reveal that MM-induced ICW are driven by the activation of inositol-triphosphate-mediated signalling pathways by unidirectional, fast-rotating MM. Our data suggest that MM-induced ICW can control muscle contraction in vitro in cardiomyocytes and animal behaviour in vivo in Hydra vulgaris. This work demonstrates a strategy for directly controlling cell signalling and downstream biological function using molecular-scale devices., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Hydrogels are 3D scaffolds used as alternatives to in vivo models for disease modeling and delivery of cells and drugs. Existing hydrogel classifications include synthetic, recombinant, chemically defined, plant- or animal-based, and tissue-derived matrices. There is a need for materials that can support both human tissue modeling and clinically relevant applications requiring stiffness tunability. Human-derived hydrogels are not only clinically relevant, but they also minimize the use of animal models for pre-clinical studies. This study aims to characterize XGel, a new human-derived hydrogel as an alternative to current murine-derived and synthetic recombinant hydrogels that features unique physiochemical, biochemical, and biological properties that support adipocyte and bone differentiation. Rheology studies determine the viscosity, stiffness, and gelation features of XGel. Quantitative studies for quality control support consistency in the protein content between lots. Proteomics studies reveal that XGel is predominantly composed of extracellular matrix proteins, including fibrillin, collagens I-VI, and fibronectin. Electron microscopy of the hydrogel provides phenotypic characteristics in terms of porosity and fiber size. The hydrogel demonstrates biocompatibility as a coating material and as a 3D scaffold for the growth of multiple cell types. The results provide insight into the biological compatibility of this human-derived hydrogel for tissue engineering., (© 2023 Wiley-VCH GmbH.)

Traditional miniaturized fluorescence microscopes are critical tools for modern biology. Invariably, they struggle to simultaneously image with a high spatial resolution and a large field of view (FOV). Lensless microscopes offer a solution to this limitation. However, real-time visualization of samples is not possible with lensless imaging, as image reconstruction can take minutes to complete. This poses a challenge for usability, as real-time visualization is a crucial feature that assists users in identifying and locating the imaging target. The issue is particularly pronounced in lensless microscopes that operate at close imaging distances. Imaging at close distances requires shift-varying deconvolution to account for the variation of the point spread function (PSF) across the FOV. Here, we present a lensless microscope that achieves real-time image reconstruction by eliminating the use of an iterative reconstruction algorithm. The neural network-based reconstruction method we show here, achieves more than 10000 times increase in reconstruction speed compared to iterative reconstruction. The increased reconstruction speed allows us to visualize the results of our lensless microscope at more than 25 frames per second (fps), while achieving better than 7 µm resolution over a FOV of 10 mm 2 . This ability to reconstruct and visualize samples in real-time empowers a more user-friendly interaction with lensless microscopes. The users are able to use these microscopes much like they currently do with conventional microscopes., Competing Interests: The authors declare no conflicts of interest., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Here, we present FusionInspector for in silico characterization and interpretation of candidate fusion transcripts from RNA sequencing (RNA-seq) and exploration of their sequence and expression characteristics. We applied FusionInspector to thousands of tumor and normal transcriptomes and identified statistical and experimental features enriched among biologically impactful fusions. Through clustering and machine learning, we identified large collections of fusions potentially relevant to tumor and normal biological processes. We show that biologically relevant fusions are enriched for relatively high expression of the fusion transcript, imbalanced fusion allelic ratios, and canonical splicing patterns, and are deficient in sequence microhomologies between partner genes. We demonstrate that FusionInspector accurately validates fusion transcripts in silico and helps characterize numerous understudied fusions in tumor and normal tissue samples. FusionInspector is freely available as open source for screening, characterization, and visualization of candidate fusions via RNA-seq, and facilitates transparent explanation and interpretation of machine-learning predictions and their experimental sources., Competing Interests: A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was a scientific advisory board member of Thermo Fisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov until July 31, 2020. From August 1, 2020, A.R. has been an employee of Genentech. M.G. is a current employee and stockholder at Monte Rosa Therapeutics., (© 2023 The Authors.)

Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial ZFTA-fusion associated and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment. Although molecular mechanisms underlying these diseases have recently been uncovered, they remain difficult to target and innovative therapeutic approaches are urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C), complemented with CTCF and H3K27ac ChIP-seq, as well as gene expression and DNA methylation analysis in primary and relapsed ependymoma tumors, to identify chromosomal conformations and regulatory mechanisms associated with aberrant gene expression. In particular, we observe the formation of new topologically associating domains ('neo-TADs') caused by structural variants, group-specific 3D chromatin loops, and the replacement of CTCF insulators by DNA hyper-methylation. Through inhibition experiments, we validate that genes implicated by these 3D genome conformations are essential for the survival of patient-derived ependymoma models in a group-specific manner. Thus, this study extends our ability to reveal tumor-dependency genes by 3D genome conformations even in tumors that lack targetable genetic alterations., (© 2023. The Author(s).)

Engineering the transition metal dichalcogenide (TMD)-metal interface is critical for the development of two-dimensional semiconductor devices. By directly probing the electronic structures of WS 2 -Au and WSe 2 -Au interfaces with high spatial resolution, we delineate nanoscale heterogeneities in the composite systems that give rise to local Schottky barrier height modulations. Photoelectron spectroscopy reveals large variations (>100 meV) in TMD work function and binding energies for the occupied electronic states. Characterization of the composite systems with electron backscatter diffraction and scanning tunneling microscopy leads us to attribute these heterogeneities to differing crystallite orientations in the Au contact, suggesting an inherent role of the metal microstructure in contact formation. We then leverage our understanding to develop straightforward Au processing techniques to form TMD-Au interfaces with reduced heterogeneity. Our findings illustrate the sensitivity of TMDs' electronic properties to metal contact microstructure and the viability of tuning the interface through contact engineering.

Significance: Imaging through scattering media is critical in many biomedical imaging applications, such as breast tumor detection and functional neuroimaging. Time-of-flight diffuse optical tomography (ToF-DOT) is one of the most promising methods for high-resolution imaging through scattering media. ToF-DOT and many traditional DOT methods require an image reconstruction algorithm. Unfortunately, this algorithm often requires long computational runtimes and may produce lower quality reconstructions in the presence of model mismatch or improper hyperparameter tuning., Aim: We used a data-driven unrolled network as our ToF-DOT inverse solver. The unrolled network is faster than traditional inverse solvers and achieves higher reconstruction quality by accounting for model mismatch., Approach: Our model "Unrolled-DOT" uses the learned iterative shrinkage thresholding algorithm. In addition, we incorporate a refinement U-Net and Visual Geometry Group (VGG) perceptual loss to further increase the reconstruction quality. We trained and tested our model on simulated and real-world data and benchmarked against physics-based and learning-based inverse solvers., Results: In experiments on real-world data, Unrolled-DOT outperformed learning-based algorithms and achieved over 10× reduction in runtime and mean-squared error, compared to traditional physics-based solvers., Conclusion: We demonstrated a learning-based ToF-DOT inverse solver that achieves state-of-the-art performance in speed and reconstruction quality, which can aid in future applications for noninvasive biomedical imaging., (© 2023 The Authors.)

Summary: igv.js is an embeddable JavaScript implementation of the Integrative Genomics Viewer (IGV). It can be easily dropped into any web page with a single line of code and has no external dependencies. The viewer runs completely in the web browser, with no backend server and no data pre-processing required., Availability and Implementation: The igv.js JavaScript component can be installed from NPM at https://www.npmjs.com/package/igv. The source code is available at https://github.com/igvteam/igv.js under the MIT open-source license. IGV-Web, the end-user application built around igv.js, is available at https://igv.org/app. The source code is available at https://github.com/igvteam/igv-webapp under the MIT open-source license., Supplementary Information: Supplementary information is available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)

While heterostructures are ubiquitous tools enabling new physics and device functionalities, the palette of available materials has never been richer. Combinations of two emerging material classes, two-dimensional materials and topological materials, are particularly promising because of the wide range of possible permutations that are easily accessible. Individually, both graphene and Pb 1-x Sn x Te (PST) are widely investigated for spintronic applications because graphene's high carrier mobility and PST's topologically protected surface states are attractive platforms for spin transport. Here, we combine monolayer graphene with PST and demonstrate a hybrid system with properties enhanced relative to the constituent parts. Using magnetotransport measurements, we find carrier mobilities up to 20 000 cm 2 /(V s) and a magnetoresistance approaching 100%, greater than either material prior to stacking. We also establish that there are two distinct transport channels and determine a lower bound on the spin relaxation time of 4.5 ps. The results can be explained using the polar catastrophe model, whereby a high mobility interface state results from a reconfiguration of charge due to a polar/nonpolar interface interaction. Our results suggest that proximity induced interface states with hybrid properties can be added to the still growing list of behaviors in these materials.

Real-time in vivo detection of biomarkers, particularly nitric oxide (NO), is of utmost importance for critical healthcare monitoring, therapeutic dosing, and fundamental understanding of NO's role in regulating many physiological processes. However, detection of NO in a biological medium is challenging due to its short lifetime and low concentration. Here, we demonstrate for the first time that photonic microring resonators (MRRs) can provide real-time, direct, and in vivo detection of NO in a mouse wound model. The MRR encodes the NO concentration information into its transfer function in the form of a resonance wavelength shift. We show that these functionalized MRRs, fabricated using complementary metal oxide semiconductor (CMOS) compatible processes, can achieve sensitive detection of NO (sub-μM) with excellent specificity and no apparent performance degradation for more than 24 h of operation in biological medium. With alternative functionalizations, this compact lab-on-chip optical sensing platform could support real-time in vivo detection of myriad of biochemical species.

Precisely timed activation of genetically targeted cells is a powerful tool for the study of neural circuits and control of cell-based therapies. Magnetic control of cell activity, or 'magnetogenetics', using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and freely behaving animal studies. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents precise temporal modulation of neural activity. Moreover, magnetogenetics has yet to achieve in vivo multiplexed stimulation of different groups of neurons. Here we produce subsecond behavioural responses in Drosophila melanogaster by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A). Furthermore, by tuning magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we achieve subsecond, multichannel stimulation. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation possible only by magnetic control., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Scientists around the globe are joining the race to achieve engineering feats to read, write, modulate, and interface with the human brain in a broadening continuum of invasive to non-invasive ways. The expansive implications of neurotechnology for our conception of health, mind, decision-making, and behavior has raised social and ethical considerations that are inextricable from neurotechnological progress. We propose "socio-technical" challenges as a framing to integrate neuroethics into the engineering process. Intentionally aligning societal and engineering goals within this framework offers a way to maximize the positive impact of next-generation neurotechnologies on society., Competing Interests: Declaration of interests K.S.R. offers consultation for nonprofits, policy institutions, NGOs, and neurotechnology companies. A.E. leads all Sevo-related work at CMU and Precision Neuroscopics and offers paid talks related to this technology. R.W.P. receives royalties on patents for her AI-related and wearables inventions owned by MIT and is a co-founder and shareholder of Empatica, Inc., where she serves as Chairman of the Board and consults part-time as Chief Scientist. She is also a shareholder at Smart Eye AB, which acquired Affectiva, a company she co-founded. At MIT, her lab’s research receives funding from the NIH via Massachusetts General Hospital Depression Research Clinic and from a consortium of over fifty companies listed at https://www.media.mit.edu/posts/member-companies. She receives speaker fees through Stern Strategy. These relationships present no conflict of interest at the time of this paper submission., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We introduce cytoNet, a cloud-based tool to characterize cell populations from microscopy images. cytoNet quantifies spatial topology and functional relationships in cell communities using principles of network science. Capturing multicellular dynamics through graph features, cytoNet also evaluates the effect of cell-cell interactions on individual cell phenotypes. We demonstrate cytoNet's capabilities in four case studies: 1) characterizing the temporal dynamics of neural progenitor cell communities during neural differentiation, 2) identifying communities of pain-sensing neurons in vivo, 3) capturing the effect of cell community on endothelial cell morphology, and 4) investigating the effect of laminin α4 on perivascular niches in adipose tissue. The analytical framework introduced here can be used to study the dynamics of complex cell communities in a quantitative manner, leading to a deeper understanding of environmental effects on cellular behavior. The versatile, cloud-based format of cytoNet makes the image analysis framework accessible to researchers across domains., Competing Interests: The authors have declared that no competing interests exist. Author David T Ryan was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via a digitally programmable 1 mm × 0.8 mm system-on-a-chip. Implantation of the device directly on top of the sciatic nerve in rats and near a femoral artery in pigs (with a stimulation lead introduced into a blood vessel through a catheter) allowed for wireless stimulation of the animals' sciatic and femoral nerves. Minimally invasive magnetoelectric implants may allow for the stimulation of nerves without the need for open surgery or the implantation of battery-powered pulse generators., (© 2022. The Author(s).)

The simple and compact optics of lensless microscopes and the associated computational algorithms allow for large fields of view and the refocusing of the captured images. However, existing lensless techniques cannot accurately reconstruct the typical low-contrast images of optically dense biological tissue. Here we show that lensless imaging of tissue in vivo can be achieved via an optical phase mask designed to create a point spread function consisting of high-contrast contours with a broad spectrum of spatial frequencies. We built a prototype lensless microscope incorporating the 'contour' phase mask and used it to image calcium dynamics in the cortex of live mice (over a field of view of about 16 mm 2 ) and in freely moving Hydra vulgaris, as well as microvasculature in the oral mucosa of volunteers. The low cost, small form factor and computational refocusing capability of in vivo lensless microscopy may open it up to clinical uses, especially for imaging difficult-to-reach areas of the body., (© 2022. The Author(s).)

Objective. We present a combination of a power electronics system and magnetic nanoparticles that enable frequency-multiplexed magnetothermal-neurostimulation with rapid channel switching between three independent channels spanning a wide frequency range. Approach. The electronics system generates alternating magnetic field spanning 50 kHz to 5 MHz in the same coil by combining silicon (Si) and gallium-nitride (GaN) transistors to resolve the high spread of coil impedance and current required throughout the wide bandwidth. The system drives a liquid-cooled field coil via capacitor banks, forming three series resonance channels which are multiplexed using high-voltage contactors. We characterized the system by the output channels' frequencies, field strength, and switching time, as well as the system's overall operation stability. Using different frequency-amplitude combinations of the magnetic field to target specific magnetic nanoparticles with different coercivity, we demonstrate actuation of iron oxide nanoparticles in all three channels, including a novel nanoparticle composition responding to magnetic fields in the megahertz range. Main results. The system achieved the desired target field strengths for three frequency channels, with switching speed between channels on the order of milliseconds. Specific absorption rate measurements and infrared thermal imaging performed with three types of magnetic nanoparticles demonstrated selective heating and validated the system's intended use. Significance. The system uses a hybrid of Si and GaN transistors in bridge configuration instead of conventional amplifier circuit concepts to drive the magnetic field coil and contactors for fast switching between different capacitor banks. Series-resonance circuits ensure a high output quality while keeping the system efficient. This approach could significantly improve the speed and flexibility of frequency-multiplexed nanoparticle actuation, such as magnetogenetic neurostimulation, and thus provide the technical means for selective stimulation below the magnetic field's fundamental spatial focality limits., (© 2022 IOP Publishing Ltd.)

This paper presents a hardware platform including stimulating implants wirelessly powered and controlled by a shared transmitter for coordinated leadless multisite stimulation. The adopted novel single-transmitter, multiple-implant structure can flexibly deploy stimuli, improve system efficiency, easily scale stimulating channel quantity and relieve efforts in device synchronization. In the proposed system, a wireless link leveraging magnetoelectric effects is co-designed with a robust and efficient system-on-chip to enable reliable operation and individual programming of every implant. Each implant integrates a 0.8-mm 2 chip, a 6-mm 2 magnetoelectric film, and an energy storage capacitor within a 6.2-mm 3 size. Magnetoelectric power transfer is capable of safely transmitting milliwatt power to devices placed several centimeters away from the transmitter coil, maintaining good efficiency with size constraints and tolerating 60-degree, 1.5-cm misalignment in angular and lateral movement. The SoC robustly operates with 2-V source amplitude variations that spans a 40-mm transmitter-implant distance change, realizes individual addressability through physical unclonable function IDs, and achieves 90% efficiency for 1.5-to-3.5-V stimulation with fully programmable stimulation parameters.

Lensless imaging provides opportunities to design imaging systems free from the constraints imposed by traditional camera architectures. Thanks to advances in imaging hardware, fabrication techniques, and new algorithms, researchers have recently developed lensless imaging systems that are extremely compact, lightweight or able to image higher-dimensional quantities. Here we review these recent advances and describe the design principles and their effects that one should consider when developing and using lensless imaging systems.

Synthetic materials and devices that interact with light, ultrasound, or magnetic fields can be used to modulate neural activity with high spatial and temporal precision; however, these approaches often lack the ability to target genetically defined cell types and signaling pathways. Genetically encoded proteins can be expressed to modify the host tissue and provide cellular and molecular specificity, but compared to synthetic materials, these proteins often interact weakly with externally applied energy sources. Synthetic materials can respond to optical, acoustic, and magnetic stimuli to focus, convert, and amplify forms of energy to ones that are more accessible to engineered cells and proteins. By combining the devices, synthetic materials, and genetically encoded proteins or cells, researchers can gain the ability to interface with the nervous system with improved spatiotemporal, cell-type and molecular precision. Here we review recent advances in these 'biohybrid' approaches that use optical, acoustic, and magnetic energy sources., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

There is an intensive effort to control the nature of attractive interactions between ultrathin semiconductors and metals and to understand its impact on the electronic properties at the junction. Here, we present a photoelectron spectroscopy study on the interface between WS 2 films and gold, with a focus on the occupied electronic states near the Brillouin zone center (i.e., the Γ point). To delineate the spectra of WS 2 supported on crystalline Au from the suspended WS 2 , we employ a microscopy approach and a tailored sample structure, in which the WS 2 /Au junction forms a semi-epitaxial relationship and is adjacent to suspended WS 2 regions. The photoelectron spectra, as a function of WS 2 thickness, display the expected splitting of the highest occupied states at the Γ point. In multilayer WS 2 , we discovered variations in the electronic states that spatially align with the crystalline grains of underlying Au. Corroborated by density functional theory calculations, we attribute the electronic structure variations to stacking variations within the WS 2 films. We propose that strong interactions exerted by Au grains cause slippage of the interfacing WS 2 layer with respect to the rest of the WS 2 film. Our findings illustrate that the electronic properties of transition metal dichalcogenides, and more generally 2D layered materials, are physically altered by the interactions with the interfacing materials, in addition to the electron screening and defects that have been widely considered.

Traditionally, recording from and stimulating the brain with high spatial and temporal resolution required invasive means. However, recently, the technical capabilities of less invasive and non-invasive neuro-interfacing technology have been dramatically improving, and laboratories and funders aim to further improve these capabilities. These technologies can facilitate functions such as multi-person communication, mood regulation and memory recall. We consider a potential future where the less invasive technology is in high demand. Will this demand match that the current-day demand for a smartphone? Here, we draw upon existing research to project which particular neuroethics issues may arise in this potential future and what preparatory steps may be taken to address these issues., Competing Interests: DE was employed by Neurosensory, Inc. and Braincheck. KG was employed by Kilpatrick Townsend and Stockton LLP. AB was employed by The Substrate Group. KT was employed by Palo Alto Research Center (PARC), A Xerox Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gaudry, Ayaz, Bedows, Celnik, Eagleman, Grover, Illes, Rao, Robinson, Thyagarajan and The Working Group on Brain-Interfacing Devices in 2040.)

Fabricating inorganic materials with designed three-dimensional nanostructures is an exciting yet challenging area of research and industrial application. Here, we develop an approach to 3D print high-quality nanostructures of silica with sub-200 nm resolution and with the flexible capability of rare-earth element doping. The printed SiO 2 can be either amorphous glass or polycrystalline cristobalite controlled by the sintering process. The 3D-printed nanostructures demonstrate attractive optical properties. For instance, the fabricated micro-toroid optical resonators can reach quality factors (Q) of over 10 4 . Moreover, and importantly for optical applications, doping and codoping of rare-earth salts such as Er 3+ , Tm 3+ , Yb 3+ , Eu 3+ and Nd 3+ can be directly implemented in the printed SiO 2 structures, showing strong photoluminescence at the desired wavelengths. This technique shows the potential for building integrated microphotonics with silica via 3D printing., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective. Electrical measurement of the activity of individual neurons is a primary goal for many invasive neural electrodes. Making these 'single unit' measurements requires that we fabricate electrodes small enough so that only a few neurons contribute to the signal, but not so small that the impedance of the electrode creates overwhelming noise or signal attenuation. Thus, neuroelectrode design often must strike a balance between electrode size and electrode impedance, where the impedance is often assumed to scale linearly with electrode area. Approach and main results . Here we study how impedance scales with neural electrode area and find that the 1 kHz impedance of Pt electrodes (but not Au electrodes) transitions from scaling with area ( r -2 ) to scaling with perimeter ( r -1 ) when the electrode radius falls below 10 µ m. This effect can be explained by the transition from planar to spherical diffusion behavior previously reported for electrochemical microelectrodes. Significance. These results provide important intuition for designing small, single unit recording electrodes. Specifically, for materials where the impedance is dominated by a pseudo-capacitance that is associated with a diffusion limited process, the total impedance will scale with perimeter rather than area when the electrode size becomes comparable with the diffusion layer thickness. For Pt electrodes this transition occurs around 10 µ m radius electrodes. At even lower frequencies (1 Hz) impedance approaches a constant. This transition to r -1 scaling implies that electrodes with a pseudo-capacitance can be made smaller than one might expect before thermal noise or voltage division limits the ability to acquire high-quality single-unit recordings., (Creative Commons Attribution license.)

Progress in implanted bioelectronic technology offers the opportunity to develop more effective tools for personalized electronic medicine. While there are numerous clinical and pre-clinical applications for these devices, power delivery to these systems can be challenging. Wireless battery-free devices offer advantages such as a smaller and lighter device footprint and reduced failures and infections by eliminating lead wires. However, with the development of wireless technologies, there are fundamental tradeoffs between five essential factors: power, miniaturization, depth, alignment tolerance, and transmitter distance, while still allowing devices to work within safety limits. These tradeoffs mean that multiple forms of wireless power transfer are necessary for different devices to best meet the needs for a given biological target. Here six different types of wireless power transfer technologies used in bioelectronic implants-inductive coupling, radio frequency, mid-field, ultrasound, magnetoelectrics, and light-are reviewed in context of the five tradeoffs listed above. This core group of wireless power modalities is then used to suggest possible future bioelectronic technologies and their biological applications., (© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Hydra vulgaris is an emerging model organism for neuroscience due to its small size, transparency, genetic tractability, and regenerative nervous system; however, fundamental properties of its sensorimotor behaviors remain unknown. Here, we use microfluidic devices combined with fluorescent calcium imaging and surgical resectioning to study how the diffuse nervous system coordinates Hydra 's mechanosensory response. Mechanical stimuli cause animals to contract, and we find this response relies on at least two distinct networks of neurons in the oral and aboral regions of the animal. Different activity patterns arise in these networks depending on whether the animal is contracting spontaneously or contracting in response to mechanical stimulation. Together, these findings improve our understanding of how Hydra 's diffuse nervous system coordinates sensorimotor behaviors. These insights help reveal how sensory information is processed in an animal with a diffuse, radially symmetric neural architecture unlike the dense, bilaterally symmetric nervous systems found in most model organisms., Competing Interests: KB, AP, CJ, JR No competing interests declared, (© 2021, Badhiwala et al.)