An AC-Coupled Wideband Neural Recording Front-End With Sub-1 mm² × fJ/conv-step Efficiency and 0.97 NEF

This letter presents an energy-and-area-efficient ac-coupled front-end for the multichannel recording of wideband neural signals. The proposed unit conditions local field and action potentials using an inverter-based capacitively coupled low-noise amplifier, followed by a per-channel 10-b asynchronous SAR ADC. The adaptation of unit-length capacitors minimizes the ADC area and relaxes the amplifier gain so that small coupling capacitors can be integrated. The prototype in 65-nm CMOS achieves 4× smaller area and 3× higher energy–area efficiency compared to the state of the art with 164 μm×40μm footprint and 0.78 mm²× fJ/conv-step energy-area figure of merit. The measured 0.65- μW power consumption and 3.1 - μVrms input-referred noise within 1 Hz–10 kHz bandwidth correspond to a noise efficiency factor of 0.97

An AC-Coupled Wideband Neural Recording Front-End With Sub-1 mm² × fJ/conv-step Efficiency and 0.97 NEF

This letter presents an energy-and-area-efficient ac-coupled front-end for the multichannel recording of wideband neural signals. The proposed unit conditions local field and action potentials using an inverter-based capacitively coupled low-noise amplifier, followed by a per-channel 10-b asynchronous SAR ADC. The adaptation of unit-length capacitors minimizes the ADC area and relaxes the amplifier gain so that small coupling capacitors can be integrated. The prototype in 65-nm CMOS achieves 4× smaller area and 3× higher energy–area efficiency compared to the state of the art with 164 μm×40μm footprint and 0.78 mm²× fJ/conv-step energy-area figure of merit. The measured 0.65- μW power consumption and 3.1 - μVrms input-referred noise within 1 Hz–10 kHz bandwidth correspond to a noise efficiency factor of 0.97

Low-Noise Micro-Power Amplifiers for Biosignal Acquisition

There are many different types of biopotential signals, such as action potentials (APs), local field potentials (LFPs), electromyography (EMG), electrocardiogram (ECG), electroencephalogram (EEG), etc. Nerve action potentials play an important role for the analysis of human cognition, such as perception, memory, language, emotions, and motor control. EMGs provide vital information about the patients which allow clinicians to diagnose and treat many neuromuscular diseases, which could result in muscle paralysis, motor problems, etc. EEGs is critical in diagnosing epilepsy, sleep disorders, as well as brain tumors. Biopotential signals are very weak, which requires the biopotential amplifier to exhibit low input-referred noise. For example, EEGs have amplitudes from 1 μV [microvolt] to 100 μV [microvolt] with much of the energy in the sub-Hz [hertz] to 100 Hz [hertz] band. APs have amplitudes up to 500 μV [microvolt] with much of the energy in the 100 Hz [hertz] to 7 kHz [hertz] band. In wearable/implantable systems, the low-power operation of the biopotential amplifier is critical to avoid thermal damage to surrounding tissues, preserve long battery life, and enable wirelessly-delivered or harvested energy supply. For an ideal thermal-noise-limited amplifier, the amplifier power is inversely proportional to the input-referred noise of the amplifier. Therefore, there is a noise-power trade-off which must be well-balanced by the designers. In this work I propose novel amplifier topologies, which are able to significantly improve the noise-power efficiency by increasing the effective transconductance at a given current. In order to reject the DC offsets generated at the tissue-electrode interface, energy-efficient techniques are employed to create a low-frequency high-pass cutoff. The noise contribution of the high-pass cutoff circuitry is minimized by using power-efficient configurations, and optimizing the biasing and dimension of the devices. Sufficient common-mode rejection ratio (CMRR) and power supply rejection ratio (PSRR) are achieved to suppress common-mode interferences and power supply noises. Our design are fabricated in standard CMOS processes. The amplifiers’ performance are measured on the bench, and also demonstrated with biopotential recordings

A neural probe with up to 966 electrodes and up to 384 configurable channels in 0.13 μm SOI CMOS

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13-μm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 μm wide, 10 mm long, 20 μm thick), achieving a crosstalk of −64.4 dB. The probe base (5 × 9 mm2) implements dual-band recording and a 1

Wired, wireless and wearable bioinstrumentation for high-precision recording of bioelectrical signals in bidirectional neural interfaces

It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Furthermore, electrical stimulation of specific target brain regions has been shown to alleviate symptoms of neurological disorders, such as Parkinson’s disease, essential tremor, dystonia, epilepsy etc. In recent years, the traditional practice of continuously stimulating the brain using static stimulation parameters has shifted to the use of disease biomarkers to determine the intensity and timing of stimulation. The main motivation behind closed-loop stimulation is minimization of treatment side effects by providing only the necessary stimulation required within a certain period of time, as determined from a guiding biomarker. Hence, it is clear that high-quality recording of local field potentials (LFPs) or electrocorticographic (ECoG) signals during deep brain stimulation (DBS) is necessary to investigate the instantaneous brain response to stimulation, minimize time delays for closed-loop neurostimulation and maximise the available neural data. To our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording ECoG signals, which are of particular importance in closed-loop DBS and epilepsy DBS. In addition, existing recording systems lack the ability to provide artefact-free high-frequency (> 100 Hz) LFP recordings during DBS in real time primarily because of the contamination of the neural signals of interest by the stimulation artefacts. To address the problem of limited mobility often encountered by patients in the clinic and to provide a wide variety of high-precision sensor data to a closed-loop neurostimulation platform, a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless multi-instrument (55 × 80 mm2) was designed and developed. The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5 – 500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile tool to be utilized in a wide range of applications and environments. Moreover, in order to offer the capability of sensing and stimulating via the same electrode, novel real-time artefact suppression methods that could be used in bidirectional (recording and stimulation) system architectures are proposed and validated. More specifically, a novel, low-noise and versatile analog front-end (AFE), which uses a high-order (8th) analog Chebyshev notch filter to suppress the artefacts originating from the stimulation frequency, is presented. After defining the system requirements for concurrent LFP recording and DBS artefact suppression, the performance of the realised AFE is assessed by conducting both in vitro and in vivo experiments using unipolar and bipolar DBS (monophasic pulses, amplitude ranging from 3 to 6 V peak-to-peak, frequency 140 Hz and pulse width 100 µs). Under both in vitro and in vivo experimental conditions, the proposed AFE provided real-time, low-noise and artefact-free LFP recordings (in the frequency range 0.5 – 250 Hz) during stimulation. Finally, a family of tunable hardware filter designs and a novel method for real-time artefact suppression that enables wide-bandwidth biosignal recordings during stimulation are also presented. This work paves the way for the development of miniaturized research tools for closed-loop neuromodulation that use a wide variety of bioelectrical signals as control signals.Open Acces

Noise Efficient Integrated Amplifier Designs for Biomedical Applications

The recording of neural signals with small monolithically integrated amplifiers is of high interest in research as well as in commercial applications, where it is common to acquire 100 or more channels in parallel. This paper reviews the recent developments in low-noise biomedical amplifier design based on CMOS technology, including lateral bipolar devices. Seven major circuit topology categories are identified and analyzed on a per-channel basis in terms of their noise-efficiency factor (NEF), input-referred absolute noise, current consumption, and area. A historical trend towards lower NEF is observed whilst absolute noise power and current consumption exhibit a widespread over more than five orders of magnitude. The performance of lateral bipolar transistors as amplifier input devices is examined by transistor-level simulations and measurements from five different prototype designs fabricated in 180 nm and 350 nm CMOS technology. The lowest measured noise floor is 9.9 nV/√Hz with a 10 µA bias current, which results in a NEF of 1.2

A 129NW Neural Amplifier and Gm-C Filter for EEG Using gm/ID Methodology

This Thesis presents a low-power analog front-end amplifier and Gm-C filter for biomedical sensing applications, specifically for Electroencephalogram (EEG) use. The proposed neural amplifier uses a supply voltage of 1.8V, it has a mid-band gain of 40.75dB, and consumes a total current of 71.82nA, for a total dissipated power of 129.276nW. Also presented is the design of a 3rd order Butterworth Low Pass Gm-C Filter which makes use of 14.7nS transconductors; the proposed filter has a pass band suitable for EEG recording use (1-100Hz). The amplifier and filter utilize current sources without bias resistances which provide 56nA and (1.154nA x 5) respectively. The proposed neural amplifier occupies a chip area of 0.275mm2 in a 0.3μm TSMC process. Simulation of the schematic and extracted chip layout is presented, along with a comparison of similar published works. Finally, a projected power consumption calculation for a multichannel system based on this system is offered

Advances in Microelectronics for Implantable Medical Devices

Implantable medical devices provide therapy to treat numerous health conditions as well as monitoring and diagnosis. Over the years, the development of these devices has seen remarkable progress thanks to tremendous advances in microelectronics, electrode technology, packaging and signal processing techniques. Many of today’s implantable devices use wireless technology to supply power and provide communication. There are many challenges when creating an implantable device. Issues such as reliable and fast bidirectional data communication, efficient power delivery to the implantable circuits, low noise and low power for the recording part of the system, and delivery of safe stimulation to avoid tissue and electrode damage are some of the challenges faced by the microelectronics circuit designer. This paper provides a review of advances in microelectronics over the last decade or so for implantable medical devices and systems. The focus is on neural recording and stimulation circuits suitable for fabrication in modern silicon process technologies and biotelemetry methods for power and data transfer, with particular emphasis on methods employing radio frequency inductive coupling. The paper concludes by highlighting some of the issues that will drive future research in the field

An optogenetic headstage for optical stimulation and neural recording in life science applications

L'optogénétique est une nouvelle méthode de contrôle de l’activité neuronale dans laquelle la lumière est employée pour activer ou arrêter certains neurones. Dans le cadre de ce travail, un dispositif permettant l’acquisition de signaux neuronaux et conduisant à une stimulation optogénétique de façon multicanale et temps-réel a été conçu. Cet outil est muni de deux canaux de stimulation optogénétique et de deux canaux de lecture des signaux neuronaux. La source de lumière est une DEL qui peut consommer jusqu’à 150 milliampères. Les signaux neuronaux acquis sont transmis à un ordinateur par une radio. Les dimensions sont d’environ 20×20×15 mm3 et le poids est de moins de 7 grammes, rendant l’appareil utile pour les expériences sur les petits animaux libres. Selon nos connaissances actuelles, le résultat de ce projet constitue le premier appareil de recherche optogénétique sans-fil, compact offrant la capture de signaux cérébraux et la stimulation optique simultanée.Optogenetics is a new method for controlling the neural activity where light is used to activate or silence, with high spatial and temporal resolution, genetically light-sensitized neurons. In optogenetics, a light source such as a LED, targets light-sensitized neurons. In this work, a light-weight wireless animal optogenetic headstage has been designed that allows multi-channel simultaneous real-time optical stimulation and neural recording. This system has two optogenetic stimulation channels and two electrophysiological reading channels. The optogenetic stimulation channels benefit from high-power LEDs (sinking 150 milliamps) with flexible stimulation patterns and the recorded neural data is wirelessly sent to a computer. The dimensions of the headstage are almost 20×20×15 mm3 and it weighs less than 7 grams. This headstage is suitable for tests on small freely-moving rodents. To the best of our knowledge, this is the first reported fully wireless headstage to offer simultaneous multichannel optical stimulation along with multichannel neural recording capability

Ultra-low power mixed-signal frontend for wearable EEGs

Electronics circuits are ubiquitous in daily life, aided by advancements in the chip design industry, leading to miniaturised solutions for typical day to day problems. One of the critical healthcare areas helped by this advancement in technology is electroencephalography (EEG). EEG is a non-invasive method of tracking a person's brain waves, and a crucial tool in several healthcare contexts, including epilepsy and sleep disorders. Current ambulatory EEG systems still suffer from limitations that affect their usability. Furthermore, many patients admitted to emergency departments (ED) for a neurological disorder like altered mental status or seizures, would remain undiagnosed hours to days after admission, which leads to an elevated rate of death compared to other conditions. Conducting a thorough EEG monitoring in early-stage could prevent further damage to the brain and avoid high mortality. But lack of portability and ease of access results in a long wait time for the prescribed patients. All real signals are analogue in nature, including brainwaves sensed by EEG systems. For converting the EEG signal into digital for further processing, a truly wearable EEG has to have an analogue mixed-signal front-end (AFE). This research aims to define the specifications for building a custom AFE for the EEG recording and use that to review the suitability of the architectures available in the literature. Another critical task is to provide new architectures that can meet the developed specifications for EEG monitoring and can be used in epilepsy diagnosis, sleep monitoring, drowsiness detection and depression study. The thesis starts with a preview on EEG technology and available methods of brainwaves recording. It further expands to design requirements for the AFE, with a discussion about critical issues that need resolving. Three new continuous-time capacitive feedback chopped amplifier designs are proposed. A novel calibration loop for setting the accurate value for a pseudo-resistor, which is a crucial block in the proposed topology, is also discussed. This pseudoresistor calibration loop achieved the resistor variation of under 8.25%. The thesis also presents a new design of a curvature corrected bandgap, as well as a novel DDA based fourth-order Sallen-Key filter. A modified sensor frontend architecture is then proposed, along with a detailed analysis of its implementation. Measurement results of the AFE are finally presented. The AFE consumed a total power of 3.2A (including ADC, amplifier, filter, and current generation circuitry) with the overall integrated input-referred noise of 0.87V-rms in the frequency band of 0.5-50Hz. Measurement results confirmed that only the proposed AFE achieved all defined specifications for the wearable EEG system with the smallest power consumption than state-of-art architectures that meet few but not all specifications. The AFE also achieved a CMRR of 131.62dB, which is higher than any studied architectures.Open Acces