Compound nerve action potentials (CNAPs) were used as a metric to assess the stimulation performance of a novel high-density, transverse, intrafascicular electrode in rat models. We show characteristic CNAPs recorded from distally implanted cuff electrodes. Evaluation of the CNAPs as a function of stimulus current and calculation of recruitment plots were used to obtain a qualitative approximation of the neural interface’s placement and orientation inside the nerve. This method avoids elaborate surgeries required for the implantation of EMG electrodes and thus minimizes surgical complications and may accelerate the healing process of the implanted subject.

BACKGROUND:This paper describes a method to reversibly block nerve conduction through direct application of a 1 Hz sinusoidal current waveform delivered through a bipolar nerve cuff electrode. This low frequency alternating current (LFAC) waveform was previously shown to reversibly block the effects of vagal pulse stimulation evoked bradycardia in-vivo in the anaesthetised rat model (Mintch et al. 2019). The present work measured the effectiveness of LFAC block on larger caliber myelinated vagal afferent fibers in human sized nerve bundles projecting to changes in breathing rate mediated by the Hering-Breuer (HB) reflex in anaesthetized domestic swine (n=5).METHODS:Two bipolar cuff electrodes were implanted unilaterally to the left cervical vagus nerve, which was crushed caudal to the electrodes to eliminate cardiac effects. A tripolar recording cuff electrode was placed rostral to the bipolar stimulating electrodes on the same nerve to measure changes in the compound nerve action potentials (CNAP) elicited by the vagal pulse stimulation and conditioned by the LFAC waveform. Standard pulse stimulation was applied at a sufficient level to induce a reduction in breathing rate through the HB reflex. If unblocked, the HB reflex would cause breathing to slow down and potentially halt completely. Block was quantified by the ability of LFAC to reduce the effect of the HB reflex by monitoring the respiration rate during LFAC alone, LFAC and vagal stimulation, and vagal stimulation alone.RESULTS:LFAC achieved 87.2 ±8.8% block (n=5) at current levels of 1.1 ±0.3 mAp (current to peak), which was well within the water window of the working electrode. CNAP showed changes that directly correlated to the effectiveness of LFAC block, which manifested itself as the slowing and amplitude reduction of components of the CNAP.CONCLUSION:These novel findings suggest that LFAC is a potential alternative or complementary method to other electrical blocking techniques in clinical applications.

Activation of peripheral nervous system (PNS) fibres to produce variable tactile and proprioceptive sensations in advanced bidirectional prosthetic limbs relies on neural stimulators with high spatial selectivity, dynamic range and resolution. A multi-channel application-specific integrated circuit (ASIC) is developed for PNS fibre activation using a wide dynamic range (10 nA-5 mA), high-resolution (30 nA step, 100 ns pulse accuracy) current stimulator, dissipating 0.73-2.75 mW at 3 V. The ASIC also enables encoding of external pressure signals via an integrate-and-fire methodology. Electrophysiological data of compound nerve action potentials were recorded for a range of stimulus amplitudes and pulse widths. This data was used to benchmark the performance of the ASIC with a known neural stimulator.

The performance of upper-limb prostheses is currently limited by the relatively poor functionality of unintuitive control schemes. This paper proposes to extract, from multichannel electromyographic signals (EMG), motor neuron spike trains and project them into lower dimensional continuous signals, which are used as multichannel proportional inputs to control the prosthetic's actuators. These control signals are an estimation of the common synaptic input that the motor neurons receive. We use the simplest of metric learning approaches known as principal component analysis (PCA), as a linear unsupervised metric projection to extract the spectral information of high dimensional data into the subspace of the prosthetic hand degrees of freedom. We also investigate the importance of a rotation in the projection space that best aligns the PCA subspace with the space of degrees of freedom of the prosthetic hand, to attempt to approximate the sparseness properties of the motor axes (which are orthogonal), while no sparseness is enforced by PCA. Proof of concept for the feedforward path (open loop) is given by successful estimation of concurrent movements with up to three degrees of freedom. We also analyze and quantify the performance of the proposed decoding algorithm under implementation constraints and hardware limitations and propose a space-time subsampling strategy, to maximize projection fidelity, in each extracted source over time. The results confirm that the proposed decoding approach can directly project the motor neuron spike trains into kinematics for simultaneous and proportional prosthesis control that can be extended to multiple degrees of freedom. We show that the method is robust to reducing the training data in space (number of sources) and time, which makes it potentially suitable for clinical applications.

A multi-path integrate-and-fire circuit is proposed as a new method of providing prosthesis sensory feedback in an effort to improve the response to dynamic stimuli. The proposed integrate and fire (I&F) utilizes adjustable thresholds and offsets on each path to provide two degrees of freedom to correctly match afferent firing frequencies. The proposed I&F was designed in TSMC 65 nm and its functionality was confirmed through simulations and comparing the response to afferent firing patterns expected for three sets of excitations.

Within our internal FITEP technology platform (FITEP: Flexible Implantable Thin Electronic Package), a novel implantable packaging technology is under development in order to realize a very small, flexible, biomimetic package for electronic implants. This new platform enables a radical miniaturization of the final implanted device, which opens many new possibilities for the medical world, since it will be possible to insert electronic sensors in very small locations, such as arteries, nerves, glands,... The device encapsulation consists of a multilayer of biocompatible polymers and ultrathin ceramic diffusion barriers deposited using ALD techniques (ALD: atomic layer deposition) in order to fabricate a very thin and flexible but also highly hermetic device packaging. Concerning the selection of biocompatible polymers, polyimide can offer a profound mechanical support for the various device components, while Parylene with its excellent step coverage creates a highly conformal coating surrounding all components. Hermeticity can be realized by the use of ultrathin ceramic ALD layers such as Al2O3 and HfO2. An optimized ALD process will result in layers from very high quality with very good step coverage. As such, selected ALD layers of only a few tens of nm thick, can exhibit very low Water Vapor Transmission Rates (WVTR), making these ALD materials ideal as ultrathin diffusion barriers. The tested polyimide/ALD stack proved to be a very hermetic enclosure: copper patterns protected with the polyimide/ALD stack are still in perfect condition after more than 2 years of immersion in saline at 60 °C (test is still ongoing), while Cu patterns protected by the polyimide stack without ALD barriers showed first signs of damage already after 6 weeks exposure to saline. Platinum and gold are best suited for metallization of implanted electronics, but these noble metals do not adhere easily to polymers, hence dedicated measures to promote metal-polymer adhesion are essential. The FITEP platform is applied on a Si-probe for implantation in the peripheral nerves, consisting of a CMOS chip with recording and stimulation electrodes [Op de Beeck, M. 2017]. The chip is thinned down to 35um and packaged using polyimide and ALD multi-stacks, resulting in a 75um thin fully encapsulated chip, optimized to reduce the Foreign Body Reaction to obtain optimum electrode-nerve contact. Flexible interconnects are fabricated using gold and platinum sandwiched between polymers and ALD layers. For optimal charge injection, iridium oxide is used as electrode material. After this hermetic FITEP-based chip encapsulation, the CMOS chip is still fully functional, which was tested dry (in air) as well as during submersion in saline. First acute in vivo stimulation tests have shown good electrode stimulation capabilities. Mechanical bending tests on long 5um thick gold interconnects are performed, showing that even after up to 1.5 million bending cycles, no cracks occurred in the gold patterns (testing in air). Longer term immersion in saline and in-vivo testing showed some problems related to loss of adhesion and to galvanic effects of the metallization. These observations were leading to some improvements in the fabrication of the encapsulation. In a second packaging iteration of the CMOS chip, these improvements were realized and a new series of encapsulated devices is fabricated. First results are promising, showing improved metal adhesion. Longer term stability tests are on its way.

In this work, the development of an active high-density transverse intrafascicular micro-electrode (hd-TIME) probe to interface with the peripheral nervous system is presented. The TIME approach is combined with an active probe chip, resulting in improved selectivity and excellent signal-to-noise ratio. The integrated multiplexing capabilities reduce the number of external electrical connections and facilitate the positioning of the probe during implantation, as the most interesting electrodes of the electrode array can be selected after implantation. The probe chip is packaged using thin-film manufacturing techniques to allow for a minimally invasive electronic package. Special attention is paid to the miniaturization, the mechanical flexibility and the hermetic encapsulation of the device. A customized probe chip was designed and packaged using a flexible, implantable thin electronic package (FITEP) process platform. The platform is specifically developed for making slim, ultra-compliant, implantable complementary metal-oxide-semiconductor based electronic devices. Multilayer stacks of polyimide films and HfO2/Al2O3/HfO2 layers deposited via atomic layer deposition act as bidirectional diffusion barriers and are key to the hermetic encapsulation. Their efficacy was demonstrated both by water vapor transmission rate tests and accelerated immersion tests in phosphate buffered saline at 60 degrees C. Using the hd-TIME probe, an innovative implantation method is developed to prevent the fascicles from moving away when the epineurium is pierced. In addition, by transversally implanting the hd-TIME probe in the proximal sciatic nerve of a rat, selective activation within the nerve was demonstrated. The FITEP process platform can be applied to a broader range of integrated circuits and can be considered as an enabler for other biomedical applications.

Scaling down autonomous robotic systems introduces numerous challenges in mechanical design, electrical/sensor subsystems, and autonomous control. One particularly daunting task is the design of the power system, since this will ultimately limit all microrobot or micro-UAV's operations. Power sources like lithium polymer batteries possess sufficient power density for basic mobility (walking, fixed wing flight, flapping/hovering), but improved power sources are needed that offer increased energy density in order to extend mission lifetimes - preferably pushing from minutes to multiple hours or days. Additionally, the source power must be efficiently converted and distributed to the various microrobot subsystems. Each system may require a different voltage, current, and duty cycle. This paper will review some of the power-specific challenges related to developing small, mobile autonomous systems.

Contemporary electronic systems often contain power circuits to support the unique power conversion or conditioning needs of each of the various subsystems. Each of these power circuits is generally implemented with discrete passive and active electronic components soldered next to the load devices on the printed circuit board. As greater levels of functionality are demanded within diminishing size and weight allowances, power management solutions will increasingly demand highly miniaturized power converters that are more tightly integrated into single-package solutions or even directly integrated onto the points of source and load. Experimental converters have demonstrated great potential in switching at very high frequencies (100+ MHz) to reduce the size of the requisite passive storage elements (inductors, transformers, and capacitors) to values that may be suitable for in-package or on-chip integration. However, integrating the passives into the same package as the active switching and control circuitry remains a significant fabrication challenge due to material incompatibility and inadequate performance of the passives.This paper discusses progress towards a fully integrated power converter module with a focus on microfabrication processes for both passive component development and wafer-level packaging. The passive components have been optimized for high performance at hundreds of MHz through the use of thick copper traces, intricate three-dimensional winding patterns. The capability of detaching the passives from the fabrication wafer produces a passives substrate that can serve directly as a routing platform for full integration of all components into a single-package solution.

Bi-directional interfaces for peripheral nerve stimulation and recording aim to improve control and acceptance of sensorized prosthetic limbs. The implantable multimodal peripheral recording and stimulation system (IMPRESS) is an intraneural interface technology supporting a high-density transverse intrafascicular multichannel electrode (hd-TIME). Herein we report on in vivo selectivity studies using a passive hd-TIME, and computational modeling towards optimal stimulation parameters for fiber recruitment.

While high-speed single-ended signaling maximizes pin and wire utilization within on- and off-chip serial links, problems associated with conventional signaling methods result in energy inefficiencies. Ground-referenced signaling (GRS) solves many of the problems of single-ended signaling systems and can be adapted for signaling across RC-dominated channels and LC transmission lines. The combination of GRS and clock forwarding enables simple but efficient signaling across on-chip communication fabrics, off-chip organic packages, and off-package printed circuit boards. Various methodologies compatible with GRS are presented in this paper, including design considerations and various circuit architectures. Experimental results for multiple generations of GRS-based serial links are presented, which includes a 16Gb/s 170fJ/b/mm on-chip link, a 20Gb/s 0.58pJ/b link across an organic package, and a 25Gb/s 1.17pJ/b link signaling over a printed-circuit board.

Advanced bionic prosthetics that can restore both the motor functionality and sensory perception of an amputee, require high-resolution recording and stimulation interfaces targeting the peripheral nervous system (PNS). To provide high nerve fiber selectivity, we propose a low-noise (3.67 mu Vrms), low-power (2.24mW) and high-density CMOS microelectrode probe for intra-neural implantation. The probe is composed of two ICs, encapsulated in a biocompatible and hermetic package, each featuring 64 recording and 16 stimulation electrodes. A backend IC digitizes the recorded signals at 31.25kS/s and provides spike detection.

A fully synthesizable analog-like loop filter for a Low-Dropout regulator using only digital standard cells is proposed. To accommodate this, various blocks such as comparator, time-to-digital converter and charge-pumps are developed using only standard cells. The fabricated prototype in 0.13μm process occupying 0.0875mm 2 provides 15mA current with minimum quiescent current of 140μA and load transient response of less than 600ns.

To realize optimal recording and stimulation of peripheral nerve cells, a CMOS chip is made with a multitude of electrodes which can be individually addressed in order to select after implantation the 16 best positioned electrodes. Since the Foreign Body Reaction should be minimal for optimum electrode-nerve contact, the CMOS chip is thinned down to 35um and fully packaged resulting in a 75um thin encapsulated chip. The chip is embedded in a biocompatible stack consisting of polymers and inorganic diffusion barriers deposited using atomic layer deposition (ALD). A biocompatible metallization is realized using gold and platinum sandwiched between polymers and ALD layers for flexible interconnects, and iridium oxide (IrOx) is selected as electrode material for optimal charge injection during stimulation. After this dedicated packaging based on the FITEP technology platform (Flexible Implantable Thin Electronic Package), the CMOS chip is still fully functional, which was tested dry (in air) as well as during submersion in saline. The form factor of the packaged chip is optimized for intra-fascicular implantation with minimum tissue damage. First acute in vivo stimulation tests proved that the stimulation capabilities of the IrOx electrodes are very good.

This paper presents a 50 nW wirelessly powered implant for the noninvasive monitoring of a bioartificial pancreas postimplantation in nuclear magnetic resonance (NMR) animal studies. The proposed implant increases NMR signal sensitivity across a 190-470 MHz frequency range in both 4.7 and 11.1 T magnetic fields through the use of a wirelessly programmable resonator. An integrated split capacitive array provides 51.8 pF tuning range and 52 fF resolution while maintaining resonant Q and reducing parasitic contributions. The implant supports forward data telemetry at 5-250 kbit/s using an envelope detector front-end and a 2.4 MHz oversampling clock/data recovery (CDR) receiver. An integrated logic-controlled RF-DC converter and strongly coupled resonant wireless link provide sustained reliable energy transfer during NMR acquisition. NMR signal isolation from the wireless power transmissions is achieved through frequency allocation and orthogonally embedded coil design that provides increased mechanical strength for incorporating device components. Experimental results in tissue-equivalent gel phantoms and small animal studies show an increase in acquired signal-to-noise ratio (SNR) by 141% (7.7 dB) and 83% (5.3 dB) within 4.7 and 11.1 T magnetic field strengths, respectively, with an approximate 100% (6 dB) increase in SNR within the region of interest (ROI) at higher image resolutions.

A completely integrated 3.3 V to 10 Vpk-pk bidirectional switched-capacitor ladder converter is presented for driving the piezo actuators of a 2 mm wing micro-robotic flying insect. The 0.1-10 MHz converter, fabricated in 1.2 V/3.3 V triple-well 0.13 μm CMOS, operates as a switched-mode amplifier with 0-3.3 V waveforms at the input and a constant 3× step-up while exhibiting symmetric drive strength for positive and negative load currents. A feedforward switching scheme that effectively bootstraps gate-drive signals for the power switches of the ladder converter has been implemented to enable output waveforms above both the supply and device voltage rating, between 0 V and ~10 V. Nonoverlapping clock signals float with the dc-500 Hz arbitrary input waveform, or a 2× scaled replica, while keeping all transistors within safe operating conditions. A voltage compliant sub-circuit, the Nested-Bootstrapped Switch (NBS) cell, is introduced as a building block for the creation of the gate-drive signals. On-chip MIM capacitors and 3.3 V I/O MOS switches for the ladder converter were sized based on a charge-multiplier representation of the converter and the output impedance concept. Experiments show actuation of a 2 mm wing prototype, an effective 5 nF peak load, and efficiency of 77% at 800 μW and 80% at 32 μW.

A flexible aluminum-silver oxide microbattery activated by a liquid electrolyte for on-demand operation is presented. Four different electrolytes are tested: 1) aqueous sodium hydroxide; 2) blood; 3) urine; and 4) saliva. To start the operation of the microbattery 8 μL of the target electrolyte is pipetted onto the surface of the microbattery. The microbattery is fabricated on a polyimide substrate using conventional microfabrication techniques. The proposed microbatteries have an interdigitated electrode geometry and a minimum footprint area of 12 mm 2 . Seven different batteries designs having different electrode width and spacing have been fabricated and characterized. The experimental results show energy densities up to 26.6 μW h cm-2μm -1 , maximum voltage output of 1.75 V, maximum current output of 0.55 mA, maximum capacity of 7.17 μAh, and maximum operating time of 75 min.

Low-power and low-voltage oscillators are critical for many autonomous systems. Ultra low-power and low-voltage operation can enable these systems to remain functional under extreme supply conditions while consuming very little energy. Stable operation under these conditions and over a wide temperature range can be very challenging. This paper 1 presents the design of a relaxation oscillator that operates under 0.5V and consumes less than a 100nW and is thus suitable for many autonomous applications. Despite of the low supply voltage, simulation results shows a relaxation oscillator with a frequency stability better than ±2.5% from -55°C to 125°C.

Frequency and time domain models are developed for backplane (BP), printed circuit board (PCB), and silicon interposer (SI) links using six-port transfer matrices (ABCD matrices) for bumps, vias and connectors, and coupled multiconductor transmission lines for traces. The six-port transfer matrix approach enables easy computation of the transfer function, as well as near-end and far-end crosstalk. The intersymbol interference is accounted for by computing the pulse response for the worst case bit pattern. Furthermore, the models developed here are used to optimize the data-rate and trace width for each of the links, so that the aggregate bandwidth obtained per joule of energy supplied to the link is maximized. The modeling and optimization approach developed here serves as a good platform to compare the air-gap interconnects against BP, PCB, and SI interconnects on lossy dielectrics. It is shown that air-gap interconnects can provide an aggregate bandwidth improvement of 3x-4x for BP links at a comparable energy per bit, and a 5x-9x improvement in aggregate bandwidth of PCB links at the expense of 20% higher energy per bit. For SI links, airgap interconnects are shown to provide a 2x-3x improvement in aggregate bandwidth and a 1x-1.5x improvement in energy per bit.

This paper summarizes work towards creating mm-scale power converters using high-frequency CMOS as well as MEMS and micro-machined passives. Reducing the converter size is largely motivated by creating power supplies for micro-robotic platforms (with millimeter and milligram scales) without negatively impacting robotic system functionality. MEMS power passives are first presented where thin-film piezoelectric transformers and resonators are shown as an electromechanical approach to achieve ultra-miniature passives at the chip scale. Piezoelectric transformers fabricated with thin-film lead zirconate titanate (PZT) on silicon are measured and show ~60% efficiencies with 240 and 75 Ω loads. These transformers have resonant frequencies ranging between 14 and 20 MHz. Work towards creating transmission lines fabricated with air-core inductors and ferroelectric capacitors is also presented. Finally, a fullyintegrated bi-directional converter in CMOS is shown driving mm-scale robotic wings made with PZT. The converter’s maximum efficiency is 77% at ~800μW load with 9V output and demonstrates <3x voltage boost in 0.13-μm triple-well CMOS.