In the emerging research field of bioelectronic medicine, it has been indicated that neuromodulation of the vagus nerve (VN) has the potential to treat various conditions such as epilepsy, depression, and autoimmune diseases. In order to reduce side effects, as well as to increase the effectiveness of the delivered therapy, sub-fascicle stimulation specificity is required. In the electrical domain, increasing spatial selectivity can only be achieved using invasive and potentially damaging approaches like compressive forces or nerve penetration. To avoid these invasive methods while obtaining a high spatial selectivity, a 2-mm diameter extraneural cuff-shaped proof-of-concept design with integrated lead zirconate titanate (PZT) based ultrasound (US) transducers is proposed in this article. For the development of the proposed concept, wafer-level microfabrication techniques are employed. Moreover, acoustic measurements are performed on the device, in order to characterize the ultrasonic beam profiles of the integrated PZT-based US transducers. A focal spot size of around 200× 200 μ m is measured for the proposed cuff. Moreover, the curvature of the device leads to constructive interference of the US waves originating from multiple PZT-based US transducers, which in turn leads to an increase of 45% in focal pressure compared to the focal pressure of a single PZT-based US transducer. Integrating PZT-based US transducers in an extraneural cuff-shaped design has the potential to achieve high-precision US neuromodulation of the VN without requiring intraneural implantation.

@en

This work presents the design and simulation of a PVT-robust x16 gain dynamic open-loop inverter-based Gm-ratio residue-amplifier for high-speed SAR-assisted pipeline ADCs. The amplifier is designed in a 28 nm standard bulk CMOS process with a regulated 0.9 V power supply and simulated across a -20°C to 85°C temperature range. It achieves a power dissipation of 1.67 mW at 1.3 GHz, corresponding to a power-speed ratio of 1.28 mW/GHz, with less than ±5% gain variation throughout all temperature corners in typical conditions.

@en

Piezoelectric Micromachined Ultrasonic Transducers (PMUT) and Capacitive Micromachined Ultrasonic Transducers (CMUT) have seen great developments in recent years, both in terms of performance and scope of applications within the biomedical ultrasound domain. This paper presents a review of the state-of-the-art of PMUT and CMUT technologies, focusing on their principle of operation, microfabrication techniques and use in different biomedical imaging and therapeutic applications. The advantages and drawbacks of PMUT and CMUT technologies in comparison with conventional bulk transducers are highlighted, the trade-offs among PMUTs and CMUTs are discussed, and their relevance in the current landscape of medical diagnostics and therapeutic uses is outlined, thus providing a clear overview of these promising technologies for the present and the next generation biomedical ultrasound applications.@en

Ultrasound (US) neuromodulation and ultrasonic power transfer to implanted devices demand novel ultrasound transmitters capable of steering focused ultrasound waves in 3D with high spatial resolution and US pressure, while having a miniaturized form factor. Meeting these requirements needs a 2D array of ultrasound transducers directly integrated with a high-frequency 2D phased-array ASIC. However, this imposes severe challenges on the design of the ASIC. In order to avoid the generation of grating lobes, the elements in the 2D phased-array should have a pitch of half of the ultrasound wavelength, which, as frequency increases, highly reduces the area available for the design of high-voltage beamforming channels. This article addresses these challenges by presenting the system-level optimization and implementation of a high-frequency 2D phased-array ASIC. The system-level study focuses on the optimization of the US transmitter toward high-frequency operation while minimizing power consumption. This study resulted in the implementation of two ASICs in TSMC 180 nm BCD technology: firstly, an individual beamforming channel was designed to demonstrate the tradeoffs between frequency, driving voltage, and beamforming capabilities. Finally, a 12-MHz pitch matched 12 × 12 phased-array ASIC working at 20-V amplitude and 3-bit phasing was designed and experimentally validated, to demonstrate high-frequency phased-array operation. The measurement results verify the phasing functionality of the ASIC with a maximum DNL of 0.35 LSB. The CMOS chip consumes 130 mW and 26.6 mW average power during the continuous pulsing and delivering 200-pulse bursts with a PRF of 1 kHz, respectively.

@en

Electrical stimulation is proven to be an effective way of neuromodulation in bioelectronic medicine (e.g. cochlear implants, deep brain stimulators, etc.), delivering localized treatment by the means of electrical pulses. To increase the stimulation efficiency and neural-type selectivity, there is an increasing interest to employ non-rectangular stimulation waveforms [1-4]. Even though delivering and storing digital data at the stimulator provides the highest flexibility for generating stimulation waveforms, state-of-the-art approaches suffer either from poor resolution or the requirement of high data bandwidth for wirelessly powered implants [2]. Using Analog waveform generators is an alternative approach at the cost of extra implementation complexity for each type of waveform [3]. To fulfill the same goals as employing arbitrary waveforms for stimulation, we propose to shape the typical rectangular waveform using a programmable first-order low-pass filter, mimicking the natural filtering characteristic of the neural membrane. Using bio-realistic modeling, we show that such a pre-filtered waveform requires less or equal energy for the activation of neurons when compared with other energy-efficient waveforms (e.g. Gaussian). Notably, this comes at the low cost of only one extra programmable parameter (i.e., the filter’s corner frequency), on top of the typical duration and amplitude parameters. The basic concept of this work is driven by the fact that the natural low-pass characteristic of the neuron’s membrane limits the energy transfer efficiency from the stimulator to the cell. Thus, it is proposed to pre-filter the high-frequency components of the stimulus [4]. The method is validated for a Hodgkin-Huxley (HH) axon-cable model using NEURON v8.0 software. The required activation energy is simulated for rectangular, Gaussian, half-sine, triangular, ramp-up, and ramp-down waveforms, all with pulse durations of 10-1000µs, and low-pass filtered with cut-off frequencies of 0.5-50kHz. Simulations show a 51.5% reduction in the required activation energy for the shortest rectangular pulse (i.e., 10-μs pulse width) after filtering at 5kHz. It is also shown that the minimum required activation energy can be decreased by 11.04%, 9.49%, 8.28%, 1.81%, 0.17%, and 0% when an appropriate pre-filter is applied to the rectangular, ramp-down, ramp-up, half-sine, triangular, and Gaussian waveforms, respectively. Finally, a perspective usage of this method to improve the selectivity of electrical stimulation is drawn. @en

Developing neuroprosthetic bioelectronic devices requires wirelessly-powered implantable stimulator systems with hundreds to thousands of output channels. Power efficiency optimization is crucial for scaling up the number of output channels. Current-mode electrical stimulation is favored for safety but is power-inefficient in conventional designs, particularly in multichannel stimulators. An adaptive voltage supply can improve power efficiency, but implementing channel-specific voltage supplies in large-scale systems is challenging. Conventional power management suffers from losses and low efficiency due to multiple conversion stages. This work proposes a multichannel current-mode stimulator with a parallel, adaptive ac/dc power management strategy using single-stage phase-controlled converters to prevent cascaded losses. This allows for generating channel-specific supply voltages within a small area for high power efficiency and high-density electrical stimulation. The proposed circuit was designed and simulated using TSMC 180 nm technology and demonstrates an improvement in the power efficiency of up to 45% with respect to a conventional power-management strategy using a fixed supply voltage.@en

Emerging ultrasound (US) biomedical applications, from battery-powered US imaging to US neuromodulation, demand wearable form factor and power-efficient US transmitters. Fulfilling these specifications demands a high-frequency and power-efficient 2D US phased-array transmitter directly integrated with the ASIC. In such systems, pulsers are the most power-hungry block owing to delivering high-voltage pulses to the US transducers. This paper presents a power-efficient high-voltage pulser to drive a 2D phased-array of piezoelectric transducers. The proposed pulser employs two storage capacitors per channel to save the charge of the US transducer and reuse it in the next phase. Moreover, utilizing a stack of two low-voltage CMOS transistors enables delivering 15-MHz pulses with an amplitude of 10 V to the piezoelectric transducers. The proposed pulser is designed and simulated in 180 nm CMOS technology. The simulation results demonstrate that the proposed pulser reduces the power consumption by 40.9% compared to the conventional class D pulser.@en

Bulk piezoelectric ultrasound transducers on integrated circuits offer unique properties for therapeutic applications of ultrasound neuromodulation. However, current implementations of such transducers are not optimized for the high transmit efficiency required to stimulate neurons. This is mainly due to the challenge of implementing a metal layer on top of the piezoelectric film using microfabrication techniques. Here, we propose a micromachined capping structure providing an electrical connection on top of the piezoelectric film with minimal acoustic losses. The structure can potentially be used as a common ground connection in phased-array ultrasound transducers.@en

Responsive neuromodulation is increasingly being used to treat patients with neuropsychiatric diseases. Yet, inefficient bridges between traditional and new materials and technological innovations impede advancements in neurostimulation tools. Signaling in the brain is accomplished predominantly by ion flux rather than the movement of electrons. However, the status quo for the acquisition of neural signals is using materials, such as noble metals, that can only interact with electrons. As a result, ions accumulate at the biotic/abiotic interface, creating a double-layer capacitance that increases impedance and negatively impacts the efficiency of neural interrogation. Alternative materials, such as conducting polymers, allow ion penetration in the matrix, creating a volumetric capacitor (two orders of magnitude larger than an area-dependent capacitor) that lowers the impedance and increases the spatiotemporal resolution of the recording/stimulation. On the other hand, the increased development and integration capabilities of CMOS-based back-end electronics have enabled the creation of increasingly powerful and energy-efficient microchips. These include stimulation and recording systems-on-a-chip (SoCs) with up to tens of thousands of channels, fully integrated circuitry for stimulation, signal conditioning, digitation, wireless power and data telemetry, and on-chip signal processing. Here, we aim to compile information on the best component for each building block and try to strengthen the vision that bridges the gap among various materials and technologies in an effort to advance neurostimulation tools and promote a solution-centric way of considering their complex problems.@en

Deep brain stimulation is currently the only technique used in the clinical setting to modulate the neural activity of deep brain nuclei. Recently, low-intensity transcranial focused ultrasound (LIFU) has been shown to reversibly modulate brain activity through a transcranial pathway. Transcranial LIFU requires a low-frequency ultrasound of around 0.5 MHz due to skull attenuation, thus providing poor axial and lateral resolution. This paper proposes a new conceptual device that would use a stent to place a high-frequency ultrasound array within the brain vasculature to achieve high axial and lateral spatial resolution. The first part of this work identified the most commonly treated deep brain nuclei and examined the human brain vasculature for stent placement. Next, a finite element analysis was carried out using a piezoelectric array that follows the blood vessels curvature, and its ability to focus ultrasound waves in clinically relevant brain nuclei was evaluated. The analytical solution provided promising results for deep brain stimulation via a stent with ultrasound transducers for high spatial resolution neuromodulation.@en

New non-imaging ultrasound applications, such as ultrasound stimulation and ultrasonic power transfer, need sub-millimeter volumetric spatial resolution, electronically control of the focal spot location, high ultrasound intensity, and a tiny form factor. Satisfying these requirements demands a high-frequency phased array ultrasound transducer. On the other hand, the pitch size in a phased array must be half of the sound wavelength to avoid grating lobes in the ultrasound beam profile. In other words, higher frequency results in a smaller available area to implement a high-voltage electronics beamforming channel. While prior efforts have reached a maximum frequency of 8.3 MHz, this work utilizes a low area high-voltage level shifter coupled with optimum phase wrapping to present two 15 MHz and 12 MHz pixel-level pitch-matched beamforming channels that deliver 20 V and 36 V to the ultrasound transducer load, respectively. Furthermore, the phase of the output is programmable with 3-bits resolution that allows fine control of focal spot location. The proposed beamforming channels have been implemented in 0.18-µm BCD technology and consume 960 µA and 1.23 mA from 20 V and 36 V power supplies, respectively.@en

Flexible ultrasound has emerged as the basis for wearable devices in healthcare. In this work, a flexible 1D phased transducer array has been proposed. This transducer array includes piezoelectric sensors underneath the transducer array, which detect its local curvature at different locations, corresponding to the positions of each piezoelectric sensor. Using FEA a simulation study was created, resulting in a deformed transducer array in which the number of curves and the number of sensors are varied. The piezoelectric sensors detect the local curvature resulting in a displacement map along the array. The sensing error of these sensors is calculated by taking the difference between the detected curvature from the sensors and the actual curvature the PCB was subjected to during the simulations. The results of these simulations show that, an increase of sensors results in a noticeable decrease in sensing error up to 9 sensors. Increasing the number of sensors after that point decreases the sensing error to a negligible value. The curvature information gathered from the piezoelectric sensors was then used to allow for the generation of focused ultrasound beams. To enable this, ultrasound beamforming algorithms were augmented to include curvature correction. These simulations showed that, despite a slight decrease in beam pressure of a curved transducer array compared to an uncurved array, the sensors can effectively detect and compensate for curvature in ultrasound transducer arrays.

@en

Power efficiency in electrical stimulator circuits is crucial for developing large-scale multichannel applications like bidirectional brain-computer interfaces and neuroprosthetic devices. Many state-of-the-art papers have suggested that some non-rectangular pulse shapes are more energy-efficient for exciting neural excitation than the conventional rectangular shape. However, additional losses in the stimulator circuit, which arise from employing such pulses, were not considered. In this work, we analyze the total energy efficiency of a stimulation system featuring non-rectangular stimuli, taking into account the losses in the stimulator circuit. To this end, activation current thresholds for different pulse shapes and durations in cortical neurons are modeled, and the energy required to generate the pulses from a constant voltage supply is calculated. The proposed calculation reveals an energy increase of 14%–51% for non-rectangular pulses compared to the conventional rectangular stimuli, instead of the decrease claimed in previous literature. This result indicates that a rectangular stimulation pulse is more power-efficient than the tested alternative shapes in large-scale multichannel electrical stimulation systems.@en

2D phased array ultrasonic transducers realized through the combination of bulk piezoelectric ceramics and complementary metal-oxide-semiconductor (CMOS) integrated circuits (IC) are enabling a new range of wearable ultrasound therapeutic applications. Traditional therapeutic ultrasound transducers have an air backing layer to maximize transmitted acoustic intensity. Yet, the pairing of piezoelectric transducers and silicon substrates commonly used in CMOS is still poorly understood. We integrated lead zirconate titanate (PZT) film on silicon membranes of various thicknesses to understand the im-pact of the silicon backing on the performance of bulk piezoe-lectric ultrasound transducers. The transducers with thinner sil-icon membranes exhibited higher acoustic intensity (up to 1.95 times while taking into account frequency shift), which is con-sistent with the simulation in finite element modeling. Transduc-ers with silicon substrate also demonstrated a consistent shift to a higher resonance frequency.

@en

This work proposes a guideline for designing more energy-efficient electrical stimulators by analyzing the frequency spectrum of the stimuli. It is shown that the natural low-pass characteristic of the neuron’s membrane limits the energy transfer efficiency from the stimulator to the cell. Thus, to improve the transfer efficiency, it is proposed to pre-filter the high-frequency components of the stimulus. The method is validated for a Hodgkin-Huxley (HH) axon cable model using NEURON v8.0 software. To this end, the required activation energy is simulated for rectangular pulses with durations between 10 µs and 5 ms, which are low-pass filtered with cut-off frequencies of 0.5-50 kHz. Simulations show a 51.5% reduction in the required activation energy for the shortest pulse width (i.e., 10 µs) after filtering at 5 kHz. It is also shown that the minimum required activation energy can be decreased by 11.04% when an appropriate pre-filter is applied. Finally, we draw a perspective for future use of this method to improve the selectivity of electrical stimulation.@en

Most academic and commercial tri-dimensional (3D) parasitic resistance extraction EDA/CAD tools rely on finite element methods (FEM) and are mainly suited to digital circuitry. In analog and mixed-signal (AMS) circuits, such as power converters and radio-frequency analog front-ends, the layout structures used for the metal interconnections become much more diversified and complex. This paper proposes an EDA/CAD tool, based on an innovative methodology for 3D parasitic resistance extraction, leveraged by image processing techniques and algorithms. Some practical examples are shown to demonstrate the attractiveness of the proposed tool. Moreover, since our tool efficiently works in the domains of 2D image processing, if an extensive database of layouts is provided and enough training is carried out, advanced deep-learning techniques can be straightforwardly employed, speeding up parasitic resistance extraction in highly complex AMS layouts.@en

There has been increasing interest in wireless, miniaturized implantable medical devices for in vivo and in situ physiological monitoring. Here, we present such an implant that uses a conventional ultrasound imager for wireless powering and data communication and acts as a probe for real-time temperature sensing, including the monitoring of body temperature and temperature changes resulting from therapeutic application of ultrasound. The sub-0.1-mm³, sub-1-nW device, referred to as a mote, achieves aggressive miniaturization through the monolithic integration of a custom low-power temperature sensor chip with a microscale piezoelectric transducer fabricated on top of the chip. The small displaced volume of these motes allows them to be implanted or injected using minimally invasive techniques with improved biocompatibility. We demonstrate their sensing functionality in vivo for an ultrasound neurostimulation procedure in mice. Our motes have the potential to be adapted to the distributed and localized sensing of other clinically relevant physiological parameters.

@en

Emerging non-imaging ultrasound applications, such as ultrasonic wireless power delivery to implantable devices and ultrasound neuromodulation, require wearable form factors, millisecond-range pulse durations and focal spot diameters approaching 100 μm with electronic control of its three-dimensional location. None of these are compatible with typical handheld linear array ultrasound imaging probes. In this work, we present a 4 mm × 5 mm 2D ultrasound phased array transmitter with integrated piezoelectric ultrasound transducers on complementary metal-oxide-semiconductor (CMOS) integrated circuits, featuring pixel-level pitch-matched transmit beamforming circuits which support arbitrary pulse duration. Our direct integration method enabled up to 10 MHz ultrasound arrays in a patch form-factor, leading to focal spot diameter of ∼200 μm, while pixel pitch-matched beamforming allowed for precise three-dimensional positioning of the ultrasound focal spot. Our device has the potential to provide a high-spatial resolution and wearable interface to both powering of highly-miniaturized implantable devices and ultrasound neuromodulation.

@en

The total economic cost of neurological disorders exceeds £100 billion per annum in the United Kingdom alone, yet pharmaceutical companies continue to cut investments due to failed clinical studies and risk [1]. These challenges motivate an alternative to solely pharmacological treatments. The emerging field of bioelectronics suggests a novel alternative to pharmaceutical intervention that uses electronic hardware to directly stimulate the nervous system with physiologically inspired electrical signals [2]. Given the processing capability of electronics and precise targeting of electrodes, the potential advantages of bioelectronics include specificity in the time, method, and location of treatment, with the ability to iteratively refine and update therapy algorithms in software [3]. A primary disadvantage of the current systems is invasiveness due to surgical implantation of the device. © 2009-2012 IEEE.@en

Accurate monitoring of physiological temperature is important for many biomedical applications, including monitoring of core body temperature, detecting tissue pathologies, and evaluating surgical procedures involving thermal treatment such as hyperthermia therapy and tissue ablation. Many of these applications can benefit from replacing external temperature probes with injectable wireless devices. Here we present such a device for real-time in vivo temperature monitoring that relies on 'chip-as-system' integration. With an on-chip piezoelectric transducer and measuring only 380 μm × 300 μm × 570 μm, the 0.065-mm ³ monolithic device, in the form of a mote, harvests ultrasound energy for power and transmits temperature data through acoustic backscattering. Containing a low-power temperature sensor implemented with a subthreshold oscillator and consuming 0.813 nW at 37 °C, the mote achieves line sensitivity of 0.088 °C/V, temperature error of +0.22/-0.28 °C, and a resolution of 0.0078 °C rms. A long-term measurement with the mote reveals an Allan deviation floor of <138.6 ppm, indicating the feasibility of using the mote for continuous physiological temperature monitoring.

@en