A Power-and-Area-Efficient Channel-Interleaved Neural Signal Processor for Wireless Brain-Computer Interfaces with Unsupervised Spike Sorting.

Next generation of wireless brain-computer-interface (BCI) devices require dedicated neural signal processors (NSPs) to extract key neurological information while operating within given power consumption and transmission bandwidth limits. Spike detection and clustering are important signal processing steps in neurological research and clinical applications. Computational-friendly spike detection and feature extraction algorithms are first systematically evaluated in this work. The nonlinear energy operator (NEO) and the first-and-second-derivative (FSDE) together with the 'perturbed' K-mean clustering achieve the highest accuracy performance. An NSP ASIC is implemented in a channel-interleaved architecture and the folding ratio of 16 leads to the minimum power-and-area product. As the result, the NSP consumes 2-µW power consumption and occupies 0.0057 mm2 for each channel in a 65-nm CMOS technology. The proposed system achieves the unsupervised spike classification accuracy of 92% and a data-rate reduction of 98.3%, showing the promise for realizing high-channel-count wireless BCIs.

Vagus nerve stimulation using a miniaturized wirelessly powered stimulator in pigs.

Neuromodulation of peripheral nerves has been clinically used for a wide range of indications. Wireless and batteryless stimulators offer important capabilities such as no need for reoperation, and extended life compared to their wired counterparts. However, there are challenging trade-offs between the device size and its operating range, which can limit their use. This study aimed to examine the functionality of newly designed wirelessly powered and controlled implants in vagus nerve stimulation for pigs. The implant used near field inductive coupling at 13.56 MHz industrial, scientific, and medical band to harvest power from an external coil. The circular implant had a diameter of 13 mm and weighed 483 mg with cuff electrodes. The efficiency of the inductive link and robustness to distance and misalignment were optimized. As a result, the specific absorption rate was orders of magnitude lower than the safety limit, and the stimulation can be performed using only 0.1 W of external power. For the first time, wireless and batteryless VNS with more than 5 cm operation range was demonstrated in pigs. A total of 84 vagus nerve stimulations (10 s each) have been performed in three adult pigs. In a quantitative comparison of the effectiveness of VNS devices, the efficiency of systems on reducing heart rate was similar in both conventional (75%) and wireless (78.5%) systems. The pulse width and frequency of the stimulation were swept on both systems, and the response for physiological markers was drawn. The results were easily reproducible, and methods used in this study can serve as a basis for future wirelessly powered implants.

A 13.56-MHz -25-dBm-Sensitivity Inductive Power Receiver System-on-a-Chip With a Self-Adaptive Successive Approximation Resonance Compensation Front-End for Ultra-Low-Power Medical Implants.

Battery-less and ultra-low-power implantable medical devices (IMDs) with minimal invasiveness are the latest therapeutic paradigm. This work presents a 13.56-MHz inductive power receiver system-on-a-chip with an input sensitivity of -25.4 dBm (2.88 µW) and an efficiency of 46.4% while driving a light load of 30 µW. In particular, a real-time resonance compensation scheme is proposed to mitigate resonance variations commonly seen in IMDs due to different dielectric environments, loading conditions, and fabrication mismatches, etc. The power-receiving front-end incorporates a 6-bit capacitor bank that is periodically adjusted according to a successive-approximation-resonance-tuning (SART) algorithm. The compensation range is as much as 24 pF and it converges within 12 clock cycles and causes negligible power consumption overhead. The harvested voltage from 1.7 V to 3.3 V is digitized on-chip and transmitted via an ultra-wideband impulse radio (IR-UWB) back-telemetry for closed-loop regulation. The IC is fabricated in 180-nm CMOS process with an overall current dissipation of 750 nA. At a separation distance of 2 cm, the end-to-end power transfer efficiency reaches 16.1% while driving the 30-µW load, which is immune to artificially induced resonance capacitor offsets. The proposed system can be applied to various battery-less IMDs with the potential improvement of the power transfer efficiency on orders of magnitude.

Author Correction: Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers.

About 30% of patients with impaired cardiac function have ventricular dyssynchrony and seek cardiac resynchronization therapy (CRT). In this study, we demonstrate synchronized biventricular (BiV) pacing in a leadless fashion by implementing miniaturized and wirelessly powered pacemakers. With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The power consumption of these pacemakers is reduced to µW-level by a novel integrated circuit design, which considerably extends the maximum operating distance. Leadless BiV pacing is demonstrated for the first time in both open-chest and closed-chest porcine settings. The clinical outcomes associated with different interventricular delays are verified through electrophysiologic and hemodynamic responses. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2-3 orders of magnitude lower than the safety regulation limit. This work serves as a basis for future wirelessly powered leadless pacemakers that address various cardiac resynchronization challenges.

A UHF/UWB Hybrid RFID Tag With a 51-m Energy-Harvesting Sensitivity for Remote Vital-Sign Monitoring.

A novel ultra-high frequency (UHF)/ultra-wideband (UWB) hybrid RFID tag is reported for object-specific remote vital-sign monitoring application. The tag achieves a record energy-harvesting sensitivity at UHF band by codesigning a meander dipole antenna and a passive rectifier. The especially high quality-factor makes the frontend sensitive to near-field motions such as heartbeats and respiration in a wearable setting. The custom CMOS IC of approximately 1-µW power consumption builds around a low-power UWB transmitter and converts variations of the supply voltage to the impulse repetition rate. The tag consisting of the IC and UHF/UWB antennas requires no other discrete components and features a size of 4.2 cm × 2.9 cm and a weight of 0.93 g. A long-distance experiment verifies that the tag can be wirelessly powered up at 51 meters from a 4-W equivalent-isotropic-radiation-power (EIRP) UHF transmitter. Remote vital-sign monitoring is validated on a human subject, in which the UHF power source is placed 2 meters away from the subject with a power emission of less than 20 dBm. This work proposes a first-of-its-kind remote vital-sign monitoring scheme based on a noncontact wearable tag. The design of the far-field energy-harvesting frontend with a record sensitivity serves as a reference for future works on battery-free remote sensors.

Stretchable Transparent Wireless Charging Coil Fabricated by Negative Transfer Printing.

Wearable electronics, such as smartwatches, VR (virtual reality)/AR (augmented reality) smartglasses, and E-textiles, are an emerging technology platform that is reshaping the way people interact with the surrounding world. However, the power source of these devices can be a critical issue, causing short operational/standby times and frequent charging. Here, a stretchable transparent wireless charging coil fabricated by negative adhesive transfer printing (NATP) is demonstrated. The stretchable transparent conductor is based on the silver nanowire (AgNW)-polyurethane acrylate (PUA) composite with high conductivity and robustness under harsh mechanical treatment. A 10.6 ohm/sq thin film has a transmittance of 84% and is still conductive under a mechanical deformation up to 60% tensile strain. A maximum power of 59 mW (power transfer efficiency ∼24%) is transferred wirelessly. A green-light-emitting diode (LED) was wirelessly powered to illustratively demonstrate the functionality of the system. This work provides an alternative power solution which is compatible with the soft and flexible components of wearable devices.

A 430-MHz Wirelessly Powered Implantable Pulse Generator With Intensity/Rate Control and Sub-1 µA Quiescent Current Consumption.

This work presents a miniaturized µW-level implantable pulse generator (IPG) inductively powered at 430 MHz. Notches are intentionally applied to the incident power, which are replicated to precisely control the timing of the output pulses. Fabricated in a 180-nm CMOS process, the concise circuitry occupies a pad-included footprint of 850 µm × 450 µm and achieves a quiescent current consumption of 950 nA. To reduce the form factor, 401-457 MHz MedRadio-band is utilized to realize the induction link. The finalized assembly achieves one of the smallest dimensions (4.6 mm × 7.0 mm) for near-field IPGs with the Rx coil size of 4.5 mm × 3.6 mm. Codesign of the rectifier and Rx coil accommodates the possible resonant frequency drifts in biological tissues. In the benchtop measurement, a 430-MHz Tx coil is demonstrated to operate the IPG at 4.5 and 4 cm proximities in the air and through water, respectively. An in vivo experiment has been performed, in which the IPG was implanted on the hindlimb muscle belly of an anesthetized rat with the connective tissue and skin sutured. The electrical stimuli induced the isolated ankle flexion at specific strengths and rates, and the experiment complies with the specific absorption rate regulations. This work shows the potential for applications requiring stringent form factors and high sensitivities.

A Multi-site Heart Pacing Study Using Wirelessly Powered Leadless Pacemakers.

In this work, we report an energy-efficient switched capacitor based millimeter-scale pacemaker (5 mm ×7.5 mm) and a multi-receiver wireless energy transfer system operating at around 200 MHz, and use them in a proof-of-concept multi-site heart pacing study. Two pacemakers were placed on two beating Langendorff rodent heart models separately. By utilizing a single transmitter positioned 20-30 cm away, both Langendorff hearts captured the stimuli simultaneously and were electromechanically coupled. This study provides an insight for future energy-efficient and distributed cardiac pacemakers that can offer cardiac resynchronization therapies.

Leadless multisite pacing: A feasibility study using wireless power transfer based on Langendorff rodent heart models.

INTRODUCTION: Fifteen to thirty percent of patients with impaired cardiac function have ventricular dyssynchrony and warrant cardiac resynchronization therapy (CRT). While leadless pacemakers eliminate lead-related complications, their current form factor is limited to single-chamber pacing. In this study, we demonstrate the feasibility of multisite, simultaneous pacing using miniaturized pacing nodes powered through wireless power transfer (WPT). METHODS: A wireless energy transfer system was developed based on resonant coupling at approximately 200 MHz to power multiple pacing nodes. The pacing node comprises circuitry to efficiently convert the harvested energy to output stimuli. To validate the use of these pacing nodes, ex vivo studies were carried out on Langendorff rodent heart models (n = 4). To mimic biventricular pacing, two beating Langendorff rodent heart models, kept 10 cm apart, were paced using two distinct pacing nodes, each attached on the ventricular epicardial surface of a given heart. RESULTS: All ex vivo Langendorff heart models were successfully paced with a simple coil antenna at 2 to 3 cm from the pacing node. The coil was operated at 198 MHz and 0.3 W. Subsequently, simultaneous pacing of two Langendorff heart models 30 cm apart using an output power of 5 W was reliably demonstrated. CONCLUSION: WPT provides a feasible option for multisite, wireless cardiac pacing. While the current system remains limited in design, it offers support and a conceptual framework for future iterations and eventual clinical utility.

An Energy-Efficient Wirelessly Powered Millimeter-Scale Neurostimulator Implant Based on Systematic Codesign of an Inductive Loop Antenna and a Custom Rectifier.

In this work, a switched-capacitor-based stimulator circuit that enables efficient energy harvesting for neurostimulation applications is presented, followed by the discussion on the optimization of the inductive coupling front-end through a codesign approach. The stimulator salvages input energy and stores it in a storage capacitor, and, when the voltage reaches a threshold, releases the energy as an output stimulus. The dynamics of the circuit are automatically enabled by a positive feedback, eliminating any stimulation control circuit blocks. The IC is fabricated in a 180 nm CMOS process and achieves a quiescent current consumption of 1.8 µA. The inductive coupling front-end is optimized as a loaded resonator, in which the input impedance of the custom rectifier directly loads the inductive loop antenna. The loaded quality factor and the rectifier's efficiency determine the reception sensitivity of the stimulator, while a balance should be achieved for the robustness of the system against dielectric medium variations by increasing the reception bandwidth. The finalized stimulator adopts a 4.9 mm × 4.9 mm inductive loop antenna and achieves an overall assembly dimension of 5 mm × 7.5 mm. Operating at the resonant frequency of 198 MHz, the stimulator works at a 14 cm distance from the transmitter in the air. An animal experiment was performed, in which a fully implanted stimulator excited the sciatic nerve of a rat that consequently triggered the movement of the limb.

Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays.

Recent advances in optical technologies such as multi-photon microscopy and optogenetics have revolutionized our ability to record and manipulate neuronal activity. Combining optical techniques with electrical recordings is of critical importance to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity. However, integration of optical modalities with electrical recordings is challenging due to generation of light-induced artifacts. Here we report a transparent graphene microelectrode technology that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. We achieve fabrication of crack- and residue-free graphene electrode surfaces yielding high optical transmittance for 2-photon imaging down to ~ 1 mm below the cortical surface. Transparent graphene microelectrode technology offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.

Deep-submicron Graphene Field-Effect Transistors with State-of-Art fmax.

In order to conquer the short-channel effects that limit conventional ultra-scale semiconductor devices, two-dimensional materials, as an option of ultimate thin channels, receive wide attention. Graphene, in particular, bears great expectations because of its supreme carrier mobility and saturation velocity. However, its main disadvantage, the lack of bandgap, has not been satisfactorily solved. As a result, maximum oscillation frequency (fmax) which indicates transistors' power amplification ability has been disappointing. Here, we present submicron field-effect transistors with specially designed low-resistance gate and excellent source/drain contact, and therefore significantly improved fmax. The fabrication was assisted by the advanced 8-inch CMOS back-end-of-line technology. A 200-nm-gate-length GFET achieves fT/fmax = 35.4/50 GHz. All GFET samples with gate lengths ranging from 200 nm to 400 nm possess fmax 31-41% higher than fT, closely resembling Si n-channel MOSFETs at comparable technology nodes. These results re-strengthen the promise of graphene field-effect transistors in next generation semiconductor electronics.

Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing.

Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial.

Graphene Distributed Amplifiers: Generating Desirable Gain for Graphene Field-Effect Transistors.

Ever since its discovery, graphene bears great expectations in high frequency electronics due to its irreplaceably high carrier mobility. However, it has long been blamed for the weakness in generating gains, which seriously limits its pace of development. Distributed amplification, on the other hand, has successfully been used in conventional semiconductors to increase the amplifiers' gain-bandwidth product. In this paper, distributed amplification is first applied to graphene. Transmission lines phase-synchronize paralleled graphene field-effect transistors (GFETs), combining the gain of each stage in an additive manner. Simulations were based on fabricated GFETs whose fT ranged from 8.5 GHz to 10.5 GHz and fmax from 12 GHz to 14 GHz. A simulated four-stage graphene distributed amplifier achieved up to 4 dB gain and 3.5 GHz bandwidth, which could be realized with future IC processes. A PCB level graphene distributed amplifier was fabricated as a proof of circuit concept.

Double-Balanced Graphene Integrated Mixer with Outstanding Linearity.

A monolithic double-balanced graphene mixer integrated circuit (IC) has been successfully designed and fabricated. The IC adopted the cross-coupled resistive mixer topology, integrating four 500 nm-gate-length graphene field-effect transistors (GFETs), four on-chip inductors, and four on-chip capacitors. Passive-first-active-last fabrication flow was developed on 200 mm CMOS wafers. CMOS back-end-of-line processes were utilized to realize most fabrication steps followed by GFET-customized processes. Test results show excellent output spectrum purity with suppressed radio frequency (RF) and local oscillation (LO) signals feedthroughs, and third-order input intercept (IIP3) reaches as high as 21 dBm. The results are compared with a fabricated single-GEFT mixer, which generates IIP3 of 16.5 dBm. Stand-alone 500 nm-gate-length GFETs feature cutoff frequency 22 GHz and maximum oscillation frequency 20.7 GHz RF performance. The double-balanced mixer IC operated with off-chip baluns realizing a print-circuit-board level electronic system. It demonstrates graphene's potential to compete with other semiconductor technologies in RF front-end applications.