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The implantable brain-computer interface has been widely used in recent years due to its great application potential and research value. Few neural implants have been designed to gather neural spikes, which require a higher sampling frequency than ECoG and LFPs. These systems are still constrained by low channel counts and their bulky size. Furthermore, wire connection is still used in many neural interfaces for further data analysis, facing challenges such as tissue infection, limited movement, and increased noise interference. To address the aforementioned problems, this paper presents a compact multi-channel wireless implantable brain-computer interface system that meets the requirements of spike signals collection and miniaturization. A WiFi module is utilized to transmit information between the system and terminal equipment to eliminate the tethering effects. A 128-channel signal acquisition module, consisting of two pieces of commercial digital electrophysiology amplifier chips, is designed to realize high channel counts for capturing spike events. The proposed system has successfully recorded the analog spike signals from a digital neural signal simulator.

This paper presents ultra-low power photoplethysmography (PPG) readout circuits. The proposed system architecture uses a current buffer between the photodiode (PD) and the transimpedance amplifier (TIA) to isolate the large parasitic capacitance of the PD leading to improves the power consumption of the TIA. A class AB topology is exploited at the output of the amplifier, which allows for increased drive capability without the use of auxiliary circuits. The maximum input current range of the TIA is 160 µA, so the large DC current of the input signal does not saturate the circuit. In the LED driver circuit, by varying the duty cycle of a pulse wave modulation (PWM) signal, the ON and OFF times of the circuits. The amplifier and LED driver are manufactured in the 130 nm TSMC CMOS process. The power consumption of the circuits with a duty cycle of 1% is 3.28 µW (at VDD = 1.2V).Clinical Relevance- Vital signs are becoming a very important research topic due to the recent prevalence of COVID-19 and other respiratory diseases. This research aims to develop and interface circuits to monitor vital signs including blood pressure, heart rate, and respiratory rate to study respiratory disease, drug safety, and efficacy.

This work presents the design, manufacture, test, and preliminary in-vivo assessment of the proof-of-concept of a miniaturized wireless platform for acquiring electroencephalography signals, where the input stage is a high-CMRR current-efficiency custom-made integrated neural preamplifier.Clinical relevance- Small, low-power consumption, wireless, wearable devices for chronically monitoring EEG recordings may contribute to the diagnosis of transient neurological events, the characterization and potential forecasting of epileptic seizures, and provide signals for controlling prosthetic and aid devices.

Aside from a clinical interest in electroencephalography (EEG) measurements of real-time data with a high temporal resolution, there is a demand for acquisition systems that are operable outside the laboratory environment. In this study, we designed a wearable and low-power EEG system for multichannel EEG acquisition beyond the lab doors. Around-the-ear cEEGrid electrodes are used to capture 8 biopotential channels which are amplified by low-power precision instrumentation amplifiers and passed on to an analog-to-digital converter (ADC). An ESP32 micro-controller captures the data from the ADC and stores it on an external SD card. The proposed system is compared to a state-of-the-art EEG acquisition system (BioSemi) to assess its diagnostic power for auditory brainstem responses (ABRs). The recordings with our portable system match, and even outperform, the baseline method's specifications. Our hardware opens up new avenues for fast sampling-rate auditory EEG recordings that can be used in hearing diagnostics, damage prevention and treatment follow up.

The MRI hybrid ablation system is an approach to use the MR (magnetic resonance) scanner's radiofrequency amplifier itself as power source for ablation. Hereby, an electrode is connected to the MR internal radiofrequency amplifier. An average RF power is provided through a train of short RF pulses, which is sufficient to thermally destroy tissue. However, ablation with too high power values can cause tissue carbonizations, thus impeding the ablation procedure. Therefore, monitoring of the energy and the power absorbed inside the tissue is necessary. For this purpose, a measurement system was designed to measure the energy applied to the tissue when using the concept of an MRI hybrid ablation system. The system consists of a dual-directional coupler, RF-to-RMS sensors, and a microcontroller. The gradient calculation of the measured energy curve provides information about the absorbed RF power in the tissue. Validation measurements of the system were performed and compared with measurements from the MR-internal power measurement system. The energy monitoring system was also tested in an ablation experiment with ex-vivo animal tissue using the MRI hybrid ablation system. The measurements showed that the applied RF power can be monitored in real-time. It has been shown that the mean RF power absorbed in the patient decreased during an ablation procedure due to an occurring impedance mismatch and tissue changes. In further work, the influence of the monitoring system on the quality of the MR images should be investigated. Clinical relevance- This paper demonstrates an energy monitoring system for an RF ablation system, which can be used inside an MR environment.

Corticokinematic coherence (CKC) is computed between limb kinematics and cortical activity (e.g. MEG, EEG), and it can be used to detect, quantify and localize the cortical processing of proprioceptive afference arising from the body. EEG-based studies on CKC have been limited to lab environments due to bulky, non-portable instrumentations. We recently proposed a wireless and miniaturized EEG acquisition system aimed at enabling EEG studies outside the laboratory. The purpose of this work is to compare the EEG-based CKC values obtained with this device with a conventional wired-EEG acquisition system to validate its use in the quantification of cortical proprioceptive processing. Eleven healthy right-handed participants were recruited (six males, four females, age range: 24-40 yr). A pneumatic-movement actuator was used to evoke right index-finger flexion-extension movement at 3 Hz for 4 min. The task was repeated both with the wireless-EEG and wired-EEG devices using the same 30-channel EEG cap preparation. CKC was computed between the EEG and finger acceleration. CKC peaked at the movement frequency and its harmonics, being statistically significant (p < 0.05) in 8-10 out of 11 participants. No statistically significant differences (p < 0.05) were found in CKC strength between wireless-EEG (range 0.03-0.22) and wired-EEG (0.02-0.33) systems, that showed a good agreement between the recording systems (3 Hz: r = 0.57, p = 0.071, 6 Hz: r = 0.82, p = 0.003). As expected, CKC peaked in sensors above the left primary sensorimotor cortex contralateral to the moved right index finger. As the wired-EEG device, the tested wireless-EEG system has proven feasible to quantify CKC, and thus can be used as a tool to study proprioception in the human neocortex. Thanks to its portability, the wireless-EEG used in this study has the potential to enable the examination of cortical proprioception in more naturalistic conditions outside the laboratory environment. Clinical Relevance-Our study will contribute to provide innovative technological foundations for future unobtrusive EEG recordings in naturalistic conditions to examine human sensorimotor system.

Temporal interference stimulation has been suggested as a method to reach deep targets during transcutaneous electrical stimulation. Despite its growing use in transcutaneous stimulation therapies, the mechanism of its operation is not fully understood. Recent efforts to fill that gap have focused on computational modelling, in vitro and in vivo experiments relying on physical observations - e.g., sensation or movement. This paper expands the current range of experimental methods by demonstrating in vivo extraneural recordings from the ulnar nerve of a pig while applying temporal interference stimulation at a location targeting a distal part of the nerve. The main aim of the experiment was to compare neural activation using sinusoidal stimulation (100 Hz, 2 kHz, 4 kHz) and temporal interference stimulation (2 kHz and 4 kHz). The recordings showed a significant increase in the magnitude of stimulation artefacts at higher frequencies. While those artefacts could be removed and provided an indication of the depth of modulation, they resulted in the saturation of the amplifiers, limiting the stimulation currents and amplifier gains used. The results of the 100 Hz sine wave stimulation showed clear neural activity correlated to the stimulation waveform. However, this was not observed with temporal interference stimulation. The results suggest that, despite its greater penetration, higher currents might be required to observe a neural response with temporal interference stimulation, and more complex artefact rejection techniques may be required to validate the method.

A capacitor transimpedance amplifier (CTIA) for wireless-powered wearable electrochemical sweat sensors is designed and tested. Correlative double sampling (CDS) technology is utilized to suppress offset voltage and noise. Dedicated low-power and low-voltage designs meet the requirements of wireless-powered wearable applications where the power supply is limited, and voltage is unstable. The proposed CDS-CTIA is fabricated in 0.18-µm complementary metal oxide semiconductor (CMOS) process, occupying an active area of 0.0285mm2. The measured low-frequency gain is 33.2MΩ/150.4dBΩ under a 1.8V supply voltage, with a total power consumption of 17.694µW (including 14.882µW static power and 2.812µW dynamic power). The input current ranges from -24nA to +19nA, and the input referred noise current is 7.76pArms in the 0.1-100 Hz frequency band. The proposed CDS-CTIA is capable of operating under a wide power supply ranging from 0.9V to 2.0V. In addition, its practicality is verified by measuring glucose concentration with an enzyme electrode.

This paper presents an ultra-low power mixed-signal neural data acquisition (MSN-DAQ) system that enables a novel low-power hybrid-domain neural decoding architecture for implantable brain-machine interfaces with high channel count. Implemented in 180nm CMOS technology, the 32-channel custom chip operates at 1V supply voltage and achieves excellent performance including 1.07µW/channel, 2.37/5.62 NEF/PEF and 88dB common-mode rejection ratio (CMRR) with significant back-end power-saving advantage compared to prior works. The fabricated prototype was further evaluated with in vivo human tests at bedside, and its performance closely follows that of a commercial recording system.

Electrochemical impedance spectroscopy (EIS) is a useful approach for modeling the equivalent circuit of biosensors such as field-effect transistor (FET)-based biosensors. During the process of sensor development, laboratory potentiostats are mainly used to realize the EIS. However, those devices are normally not applicable for real use-cases outside the laboratory, so miniaturized and optimized instrumentations are needed. Various integrated circuits (IC) are available that provide EIS, but these make developed systems highly dependent on semiconductor manufacturers, including component availability. In addition, these generally do not meet the instrumentation requirements for FET-based biosensors, thus external circuitry is necessary as well. In this work, an instrumentation is presented that performs EIS between 10 Hz and 100 kHz for FET-based biosensors. The instrumentation includes the generation of the excitation signal, the configuration of the semiconductor and the readout circuit. The readout circuit consists of a transimpedance amplifier with automatic gain adjustment, filter stages, a magnitude and a phase detection circuit. Since magnitude and phase are converted to a DC signal, digitization of the results is trivial without further signal processing steps, minimizing the computational load on the microcontroller. The transmission behavior of the magnitude and phase measurement circuits shows a high linearity for sinusoidal signals. Furthermore, the overall system was tested with resistors, whereby the magnitude measurement error (1.7%) and the phase shift error (1.6°) were determined within the working range of the instrumentation. The functionality of the instrumentation is demonstrated using pH-sensitive field-effect transistors (ISFET) in various solutions.Clinical relevance- Based on the electrochemical impedance spectroscopy of FET-based biosensors such as ImmunoFETs, new point-of-care testing (POCT) devices can be developed that e.g. quantitatively detect the concentration of biomarkers with very low detection limits in body fluids. The instrumentation presented in this work can be part of new generation of diagnostic tools featuring innovative sensor technologies.

Class-D half and full-bridge power amplifiers (PA) finds their usefulness in wireless power transfer (WPT) blocks for a biomedical implant. This brief presents a 13.56-MHz wireless power transfer system using an adaptive PA structure and digital control scheme for providing sufficient power during downlink data transfer. This scheme prevents efficiency degradation due to amplitude modulation. Simultaneously changing PA structure and operating frequency gives a higher degree of freedom for power modulation. The transmitter and receiver sides were designed in the 0.18-μm CMOS process using 1.8 V and 5 V devices.

Magnetoplethysmogram (MPG) is typically acquired by placing a giant magnetoresistance sensor (GMR)-magnet system in a blood vessel's (e.g., radial artery) vicinity. This brief analyzed multiple linearizing front ends for the GMR-magnet system. GMR based analog front end's (AFE) gain requirement is derived through COMSOL and MATLAB-based simulation considering the raw signal data. After that, we designed a fully differential difference amplifier (FDDA) in 0.18 µm, 1.8 V process using the SPICE environment for amplification of MPG signals. An automatic calibration method is used for compensating the GMR sensor's offset and lowering it to a few µV level during constant current excitation. This proposed GMR-magnet system is a stepping stone towards noninvasive arterial pulse waveform (APW) detection using the MPG principle, with or without direct skin contact. The DDA achieves open and closed-loop gain of 102 dB and 32 dB, phase margin of 62 ◦ , an IRN of 1.8µV, and a unity-gain frequency of 32kHz, resulting in a closed-loop bandwidth of 800 Hz while dissipating 1.2 µA from a 1.8-V supply.

Amplitude shift keying (ASK) data demodulation method has been widely used for simultaneous wireless data and power transfer in implantable medical devices (IMDs). Small amplitude modulation depth (MD) is usually preferred as it helps promote energy harvesting efficiency. This paper presents an ASK data demodulator that has good immunity to disturbances and can demodulate ultra-low MD ASK signal. A three-stage amplifying structure (3SAS) is proposed, in which the common-mode level of each amplifier is set between the high and low levels of its input signal envelope to prevent amplifier gain saturation and maximize the amplification of the envelope difference. Two envelope detectors (EDs) are used before and after the 3SAS respectively. The first one is to obtain a coarse envelope for 3SAS input and the second one is to further suppress the residual carrier interference and get a fine envelope. The proposed demodulator is implemented in 0.18-μm high-voltage Bipolar-CMOS-DMOS (BCD) technology. The detectable MD is measured as low as 0.034%, showing that the proposed demodulator can work smoothly and robustly in some extreme cases of simultaneous data and power transferring.Clinical Relevance- The ASK data demodulator proposed in this paper supports ultra-low modulation depth. This reduces the bit error rate of the data link and keeps a highly power conversion efficiency for wireless power and data transfer in implantable medical devices.

We present an extended-range near-field wireless data communication designed for high-resolution mapping of gastrointestinal bioelectrical activity. The system is composed of an implantable unit (IU), a wearable unit (WU) and a stationary unit (SU). The WU transfers power to the IU and recharges its battery through an inductive link, wirelessly; and over the same link, reads the 64-channel slow waves data encoded by a differential pulse position coding algorithm, which is modulated through a load shift-keying technique and sent by a back-telemetry circuit at the IU. To guarantee simultaneous WU-IU wireless power transfer and maximize the IU-WU data transfer rate, the duty cycle of the data stream is reduced to 6.25%. A newly designed 13.56 MHz high-power radio frequency power amplifier at the WU, extends the efficient range of IU-WU near-field data communication and power transfer. The retrieved data at the WU are either transmitted to the SU via a 2.4 GHz RF link for real-time monitoring or stored locally on a memory card. The measurements on the implemented system, demonstrate IU-WU data transfer rate of 125 kb/s, while the distance between the transmitter and receiver coils can reach up to 7 cm while maintaining the specific absorption rate below the guidelines.

The benefits of array coils in MRI and MRS are well known. A key component of essentially all array coils used today is the decoupling preamplifier. Unlike conventional 50 ohm low-noise preamps, decoupling preamps present a reactive impedance to the coil, which can be used to 'block' currents from being induced in the receive coil, reducing the impact of any electromagnetic coupling between array elements. While available from a number of vendors, a lower-cost solution would be advantageous. We investigate the use of conventional operational amplifiers as low-noise decoupling preamplifiers. In this paper the performance of the op-amp preamplifier is compared to conventional 50 Ω. The op-amp preamp design shows promise for use as a decoupling preamplifier with array coils.Clinical Relevance- This work could facilitate the development of array coils for spectroscopy and imaging.

In recent years, high-density surface electromyography (HD-sEMG) has shown promising advantages in many robotics applications. Using HD-sEMG can not only reduce the sensitivity of the sensor position on the muscle belly but can also facilitate the acquisition of more muscle activity information due to spatial sampling. As current commercial HD-EMG systems use stationary amplifiers, leading to bulky measurements and poor portability, the interest in developing an HD-EMG sensor has increased. However, the insufficient electrode density and complicated fabrication process are challenges to overcome. In this paper, we propose a flexible HD-EMG sensor with an on-board amplifier capable of a density level of 0.53 channel/cm 2 , higher than those in previous works. First, we investigated the effects of different sensor parameters (i.e., the electrode material, the inter-electrode distance (IED) and the size of the electrode) on the measured signal quality. Second, a low-cost, easily fabricated, easily customized HD-EMG fabrication method was proposed based on the selected sensor parameters with a signal-to-noise ratio (SNR) comparable to those of commercial sensors. Finally, we applied a muscle activation estimation algorithm to validate the feasibility of the designed HD-EMG sensor, showing higher estimation accuracy levels. The results here demonstrate that the designed HD-EMG sensor can be used as an effective human-machine interface for robotics applications.

In this paper, a power efficient, low-noise and high swing capacitively-coupled amplifier (CCA) for neural recording applications is proposed. The use of current splitting technique and current scaling technique in a current mirror operational transconductance amplifier (CM-OTA) has lead to a very good trade-off between power and noise. The presented architecture is simple, without cascode transistor while it has more than 80 dB open-loop gain without extra power consumption. As a result, the proposed structure has a better power efficiency factor (PEF) and output swing in comparison with previous reported architectures is increased to the 2Vov below the maximum supply voltage. In order to reduce flicker noise and achieve better trade-off between the power and noise, PMOS transistors with an optimum size have been utilized which operate in sub-threshold region. The amplifier is designed and simulated in a commercially available 0.18 μm CMOS technology. Monte Carlo simulations for process and mismatch have been carried out. The gain of the proposed amplifier is 39.22 dB in its bandwidth (3 Hz - 5 kHz). Total input-referred noise is 3.03 μVrms over 1 Hz - 10 kHz. The power consumption of the amplifier is 2.98 μW at supply voltage of 1.4 V. The noise efficiency factor (NEF) and PEF are 2.4 and 8.06, respectively. The output swing is about 1.16 V. It means the proposed amplifier can tolerate up to 13.2 mV peak-to-peak input signal while its total harmonic distortion (THD) is less than 1%.

In this article, by choosing and optimizing suitable structure in each stage, we have designed a multi-purpose low noise chopper amplifier. The proposed neural chopper amplifier with high CMRR and PSRR is suitable for EEG, LFP and AP signals while it has a low NEF. In order to minimize the noise and increase the bandwidth, a single stage current reuse amplifier with pseudo-resistor common-mode feedback is chosen, while a simple fully differential amplifier is implemented at the second stage to provide high swing. A DC servo loop with an active RC integrator is designed to block the DC offset of electrodes and a positive feedback loop is used to increase the input impedance. Finally, an area and power-efficient ripple reduction technique and chopping spike filter are used in order to have a clear signal. The designed circuit is simulated in a commercially available 0.18 μm CMOS technology. 3.7 μA current is drawn from a ±0.6V supply. The total bandwidth is from 50 mHz to 10 kHz while the total inputreferred noise in this bandwidth is 2.9 μV rms and the mid-band gain is about 40 dB. The designed amplifier can tolerate up to 60 mV DC electrode offset and the amplifier's input impedance with positive feedback loop is 17 MΩ while the chopping frequency is 20 kHz. With the designed ripple reduction, there is just a negligible peak in the input-referred noise due to upmodulated noise at chopping frequency. In order to prove the performance of the designed circuit, 500 Monte Carlo analysis is done for process and mismatch. The mean value for CMRR and PSRR are 94 and 80 dB, respectively.

A surface electromyography (sEMG) detector, that not only removes stimulation artifacts entirely but also increases the recording time, has been developed in this paper. The sEMG detector consists of an sEMG detection circuit and a stimulation isolator. The sEMG detection circuit employs a stimulus isolate switch (SIS), a blanking (BLK) and non-linear feed-back (NFB) circuit to remove the artifacts and to increase the recording time. In the SIS, the connection between stimulator and stimulation electrodes, along with the stimulation electrodes and the ground are controlled by an opto-isolator, and the connection of instrument amplifier and the recording electrodes are controlled by CMOS-based switches. The mode switches of the BLK and the NFB circuit also employs CMOS-based switches. By an accurate timing adjustment, the voluntary EMG can be recorded during electrical stimulation. Two 6 able-bodied experiments have been performed to test the three anti-artifact sEMG detector: BLK, BLK&SIS, BLK&SIS&NFB. The results indicate that the BLK&SIS&NFB proposed in this work effectively removes stimulus artifacts and M-waves, and has a longer recording time compared with BLK and BLK&SIS circuits.

This paper summarizes our recent progress towards Gastric Seed which is an ultrasonically interrogated millimeter-sized implant for gastric electrical activity (also known as slow waves, SWs) recording. We present a proof-of-concept wireless system designed to collect, transmit, and store in vivo SW signals by integrating a prototype Gastric Seed chip, fabricated in a 0.35-μm 2P4M CMOS process, with a commercial-off-the-shelf (COTS) amplifier, 10-bit analog-to-digital converter (ADC), and pair of microcontrollers (MCU) as radio-frequency (RF) transceivers. The chip includes ultrasonic self-regulated power management and addressable pulse-based data transfer. Utilizing two pairs of millimeter-sized stacked power/data ultrasonic transducers spaced by 6 cm in a water tank, the chip achieved a regulated voltage of 2.5 V and a data rate of 16 kbps. The amplifier was configured to have a gain of 60 dB with a 3-dB bandwidth of 18 mHz to 500 mHz. The MCU's built-in 10-bit ADC and RF transceiver were used to digitize the SW signal and transmit the data to a computer. In vivo, SW was recorded wirelessly from the stomach of an anesthetized rat. The recorded SWs showed a frequency of 1.5 cycle-per-minute (cpm) and maximum and minimum amplitudes of 1.03 mV and 0.28 mV peak-to-peak, respectively.

This paper presents an integrated biopotential preamplifier architecture targeting applications that simultaneously require high common-mode rejection ratio (CMRR), low noise, high input common-mode range (ICMR), and current-efficiency (low Noise Efficiency Factor or NEF). A biopotential preamplifier, which performs well in line with the state-of-the-art of the field while providing enhanced ICMR and CMRR performance, was fabricated in a 0.5 μm CMOS process. Results from measurements show that the gain is 47 dB, the bandwidth ranges from 1 Hz to 7.7 kHz, the equivalent input noise is 1.8 μV rms , the CMRR is 100.5 dB, the ICMR is 1.7 V and the NEF is 3.2.

In order to effectively record from electrically active cells through microelectrode arrays a low-noise amplification and data acquisition system is required. Although commercially available, these systems can be expensive and lack the freedom to customise hardware and software. In this work we present a low-cost (US$21 for the first channel + US$11 for each additional channel), low-noise amplifier coupled with an analog to digital converter from National Instruments. The amplifier was designed to (i) operate between 0 and 5 V utilising a DC battery power supply, (ii) operate within a bandwidth of 10 kHz, (iii) remove DC voltage created at the electrode/electrolyte interface with a high-pass cut-off frequency of 0.7 Hz and (iv) have a gain of 2000. Strategies to reduce environment electromagnetic interference at the amplifier front end were employed and involved a customised neural interface board connected between the microelectrode array and amplifier. The constructed amplifier achieved an intrinsic noise amplitude of 0.8 μV rms , which facilitated high quality recordings as exemplified by in vitro recordings from primary hippocampal neurons.

The use of multiple surface EMG electrodes (High-Density surface EMG - HD-sEMG) allows the extraction of anatomical and physiological information either at the muscle or at the motor unit level with applications in several fields ranging from clinical neurophysiology to the control of prosthetic devices. These applications need to acquire monopolar sEMG signals free from power line interference arising from the capacitive coupling between the subject, the acquisition system and the power line. The aim of this work is to provide a common mode analysis of the detection system used to collect monopolar sEMG signals, characterizing different configuration of the reference electrodes leading to different behaviors in terms of immunity to the power line interference. Based on the experimental results, a new impedance-controlled HD-sEMG signal amplifier is proposed and discussed.

This paper presents a portable and modular wireless multichannel sensor system for high-density surface electromyography (HD-sEMG) signals acquisition. Featuring low-power and high-quality off-the-shelf components such as the Intan Technologies RHD2132 digital electrophysiology interface chip, the current iteration of the proposed sensor system allows the recording of 32 surface electromyography (sEMG) channels, each at a sampling rate of 1 kHz, and a sample resolution of 16 bits. It features the RHD2132's typical input-referred noise of 2.4 μV rms , with <; 15% variation with amplifier bandwidth as specified by the manufacturer, and a total power consumption of 49.5 mW. Data is sent in real-time to a base station using a 2.4-GHz industrial, scientific and medical (ISM) wireless link. Along with the recording platform, the integrated sensor system includes a dry surface electrodes array prototype directly built on a printed circuit board. Intended for complex muscles activity patterns detection on the forearm, the flexible 32 surface electrodes array is designed to be placed flat or to fit a curved area like the forearm in a hand gestures recognition prosthetic system. In such applications, this device will offer improved prosthesis control scheme intuitiveness and ease-of-use. Among other core features of the system are its compact, light-weight and easy to install physical design. The complete system fits on a 2 by 6.5 cm 2 printed circuit board mounted on a 7.6 by 11.8 cm 2 electrodes array. HD-sEMG user forearm output data collected with the system is presented with a proposed frequency-time-space cross-domain preprocessing method for visualization of HD-EMG data and building training datasets.

We present a method for embedding integrated circuit chips in parylene neural probes where Anisotropic Conductive Film (ACF) electrically and physically connects the chip to the probe. Adequate insulation of the assembly is verified up to 150 h in vitro (testing ongoing). A custom-designed 8-to-1 multiplexing amplifier for neural application was fabricated in a 0.18 μm CMOS process. As a feasibility demonstration, the $830 \mu \mathrm {m}\times 1030 \mu \mathrm {m}$ die was connected to a parylene probe on a glass substrate. Preliminary results of the amplifier tests indicate similar performance in air and in phosphate buffered saline (PBS), and demonstrate around 200 V/V amplification of signals in saline.

This paper presents a low-noise transimpedance amplifier (TIA) employing chopper-stabilized technique for nanopore applications. The TIA, which is used as a headstage for the monitoring system, must achieve low-noise performance to accurately measure a minute ionic current signal generated from the nanopore. In this work, we analyze detailed input- referred noise current of the capacitive-feedback TIA and propose a core amplifier adopting the chopper-stabilized technique to effectively reduce flicker noise in a bandwidth of interest for nanopore applications. This proposed circuit schematic is designed by harnessing 0.35 $\mu \mathrm{m}$ CMOS process and is verified using elaborate simulation results.

Collecting EEG involves digitizing a very small signal across a vast potential dynamic range, particularly within real-world neuroimaging conditions, where noise can be especially prominent. Conventional methods require highresolution, power-hungry data acquisition systems (DAQs), creating limits on usable time before manual interaction is necessary for recharge. Here, we discuss continued work on an alternative DAQ approach capable of acquiring high resolution data with ultra-low power use by adjusting parameters of the analog front end (AFE) in real time to allow use of low-resolution ADCs. This work compares signal quality of a hardware implementation of our adaptive AFE DAQ to that of an industry standard DAQ. Results demonstrate successful reconstruction of signals in both clean and noisy EEG monitoring environments at low bit-depths while maintaining high correlation and low standard deviation of error. This suggests promise for a fully integrated implementation with substantially lower power consumption.

An innovative 3-stage miller compensted, cross-coupled load, based photodiode front end readout is designed for glucose monitoring. The Near Infrared Spectroscopy (NIRS) technique is used for the optical sensing of glucose non-invasively. The stable 3-stage open loop amplifier is designed for a gain of 68.3 dB, phase margin of 65°, GBW of 12.6 MHz and has a power consumption of 0.26 mW. The transimpedance amplifier achieves a gain of 84.46 dB, phase margin of 65°, has an input referred noise of 20.4 pAHz and consumes 0.55 mW of power from a 3.3 V supply using a 0.18 $\mu \mathrm{m}$ CMOS technology node.

Neuroblastoma cells are often used as a cell model to study Parkinson's disease, which causes reduced dopamine release in substantia nigra, the midbrain that controls movements. In this paper, we developed a 1024-ch monolithic CMOS sensor array that has the spatiotemporal resolution as well as low-noise performance to monitor single vesicle release of dopamine from neuroblastoma cells. The CMOS device integrates 1024 on-chip electrodes with an individual size of $15 \mu \mathrm{m}\times 15 \mu \mathrm{m}$ and 1024 transimpedance amplifiers for each electrode, which are each capable of measuring sub-pA current. Thus, this device can be used to study the detailed molecular dynamics of dopamine secretion at single vesicle resolution.

Closed-loop optogenetic stimulation (CLOS) involves real-time neural data collection and analysis, feedback control, and optical neuromodulation. Despite emergence of the CLOS devices, methods for validating such devices in-vitro are limited. This paper presents a CLOS device and introduces an in-vitro setup for validating CLOS devices. The CLOS device consists of an electrode, a neural detector, a control algorithm, and an optogenetic stimulator. The in-vitro setup consists of saline solution, a neural signal emitter, a photodiode and its amplifier, and a closed-loop simulation program. Synthetic neural signals are delivered to the CLOS device, and based on the sensed optical stimulations from the light source, the properties of the delivered neural signals are changed. Experiments are conducted to evaluate the closed-loop operation of the CLOS device, and verify the capability of the in-vitro setup to for validating the CLOS devices. The in-vitro setup enables refinement of CLOS devices before arduous in-vivo trials.

A low power Programmable Analog Front End (PAFE) for biopotential measurements is presented in this paper. The PAFE circuit processes electrocardiogram (ECG), electromyography (EMG) and electroencephalogram (EEG) signals with higher accuracy. It consists mainly of improved transconductance programmable gain instrumentational amplifier (PGIA), programmable high pass filter (PHPF), and second order low pass filter (SLPF). A 15-bit programmable 5-stage successive approximation analog-to-digital converter (SAR-ADC) is implemented for improving the performance, whose power consumption is reduced due to multiple stages and by OTA/Comparator sharing technique between the stages. The power consumption is further reduced by operating the analog portion of PAFE on 0.5V supply voltage and digital portion on 0.3V supply voltage generated internally through a voltage regulator. The proposed low power PAFE has been fabricated in 180nm standard CMOS process. The performance parameters of PAFE in 15-bit mode are found to be, gain of 31-70 dB, input referred noise of 1.15 μVrms, CMRR of 110 dB, PSRR of 104 dB, and signal-to-noise distortion ratio (SNDR) of 83.5dB. The power consumption of the design is 1.1 μW @ 0.5 V supply voltage and it occupies a core silicon area of 1.2 mm 2 .

This paper presents a flexible organic thin-film transistor (OTFT) amplifier for bio-signal monitoring and presents the chip component assembly process. Using a conductive adhesive and a chip mounter, the chip components are mounted on a flexible film substrate, which has OTFT circuits. This study first investigates the assembly technique reliability for chip components on the flexible substrate. This study also specifically examines heart pulse wave monitoring conducted using the proposed flexible amplifier circuit and a flexible piezoelectric film. We connected the amplifier to a bluetooth device for a wearable device demonstration.

This paper describes an integrated multichannel neural recording analog front end (AFE) with a novel area-efficient driven right leg (DRL) circuit to improve the system common mode rejection ratio (CMRR). The proposed AFE consists of an AC-coupled low-noise programmable-gain amplifier, an area-efficient DRL block and a 10-bit SAR ADC. Compared to conventional DRL circuit, the proposed capacitor-less DRL design achieves 90% chip area reduction with enhanced CMRR performance, making it ideal for multichannel biomedical recording applications. The AFE circuit has been designed in a standard 0.18-μm CMOS process. Post-layout simulation results show that the AFE provides two gain settings of 54dB/60dB while consuming 1 μA per channel under a supply voltage of 1 V. The input-referred noise of the AFE integrated from 1 Hz to 10k Hz is only 4 μVrms and the CMRR is 110 dB.

This paper presents a low-power analog front-end (AFE) photoplethysmography (PPG) sensor fabricated in 0.35 μm CMOS process. The AFE amplifies the weak photocurrent from the photodiode (PD) and converts it to a strong voltage at the output. In order to decrease the power consumption, the circuits are designed in subthreshold region; so the total biasing current of the AFE is 10 μ A. Since the large input DC photocurrent is a big issue for the PPG sensing circuit, we apply a DC photocurrent rejection technique by adding a DC current-cancellation loop to reject the large DC photocurrent up to 10 μA. In addition, a pseudo resistor is used to reduce the high-pass corner frequency below 0.5 Hz and Gm-C filter is adapted to reject the out-of-band noise higher than 16 Hz. For the whole sensor, the amplifier chain can achieve a total gain of 140 dBμ and an input integrated noise current of 68.87 pA rms up to 16 Hz.

Advances in minimally-invasive, distributed biological interface nodes enable possibilities for networks of sensors and actuators to connect the brain with external devices. The recent development of the neural dust sensor mote has shown that utilizing ultrasound backscatter communication enables untethered sub-mm neural recording devices. These implanted sensor motes require a wearable external ultrasound interrogation device to enable in-vivo, freely-behaving neural interface experiments. However, minimizing the complexity and size of the implanted sensors shifts the power and processing burden to the external interrogator. In this paper, we present an ultrasound backscatter interrogator that supports real-time backscatter processing in a rodent-wearable, completely wireless device. We demonstrate a generic digital encoding scheme which is intended for transmitting neural information. The system integrates a front-end ultrasonic interface ASIC with off-the-shelf components to enable a highly compact ultrasound interrogation device intended for rodent neural interface experiments but applicable to other model systems.

The initial amplification stage is a critical element of a neural signal acquisition system, and the design of low-noise, low-power amplifiers has received a great deal of attention in recent publications. In this paper we discuss practical considerations for the design of amplifiers intended for neural interfaces. Noise is a major issue due to the low amplitude of neural signals. Practical system deployments also require adequate rejection of common-mode interference, such as that due to line power noise or muscle artifacts, and supply noise. This paper attempts to provide some guideance for system and circuit designers and point out opportunities for potential future exploration.

We here demonstrate multi-chip heterogeneous integration of microfabricated extracellular recording electrodes with neural amplifiers, highlighting a path to scaling electrode channel counts without the need for more complex monolithic integration. We characterize the noise and impedance performance of the heterogeneously integrated neural recording electrodes, and analyze the design parameters that enable the low-voltage neural input signals to co-exist with the high-frequency and high-voltage digital outputs on the same silicon substrate. This heterogeneous integration approach can enable future scaling efforts for microfabricated neural probes, and provides a design path for modular, fast, and independent scaling innovations in recording electrodes and neural amplifiers.

Recovering neural responses from electrode recordings is fundamental for understanding the dynamics of neural networks. This effort is often obscured by stimulus artifacts in the recordings, which result from stimuli injected into the electrode-tissue interface. Stimulus artifacts, which can be orders of magnitude larger than the neural responses of interest, can mask short-latency evoked responses. Furthermore, simultaneous neural stimulation and recording on the same electrode generates artifacts with larger amplitudes compared to a separate electrode setup, which inevitably overwhelm the amplifier operation and cause unrecoverable neural signal loss. This paper proposes an end-to-end system combining hardware and software techniques for actively cancelling stimulus artifacts, avoiding amplifier saturation, and recovering neural responses during current-controlled in-vivo neural stimulation and recording. The proposed system is tested in-vitro under various stimulation settings by stimulating and recording on the same electrode with a superimposed pre-recorded neural signal. Experimental results show that neural responses can be recovered with minimal distortion even during stimulus artifacts that are several orders greater in magnitude.

This paper covers the design aspects of a new multi-channel electrode for the acquisition of surface electromyography signals from a selected muscle. The new multi-channel electrode has 11 pins where the monopolar signals produced will be configured in a software either as Linear array or Laplacian configuration. The design specification of the pre-amplifier ideally was to have a voltage gain of 500 with bandpass filtering of 5 Hz-1 kHz. The final design of the pre-amplifier circuit using an INA 118 instrumentation amplifier was built and tested to give values for voltage gain of 484 with bandpass filtering of 6.8 Hz-1.02 kHz. The software configuration that gives clearer and more defined signals in terms of motor unit action potentials for future signal processing is the Laplacian rather than Linear array.

This paper presents the operation of a dual-mode wideband CMOS analog front-end (AFE) for electrical impedance spectroscopy. The chip combines two current-readout (CR) channels and four voltage-readout (VR) channels suitable for both bipolar and tetrapolar EIS analysis. The chip addresses the need for flexible readout units for real-time simultaneous single-cell and large scale tissue/organ analysis. Postlayout simulations show that the VR channel is capable of wideband operation up to 12 MHz with noise floor as low as 16.4 nV/Hz1/2. A 2-bit control allows to select between a high-frequency low-gain channel and a bandwidth-limited high-gain channel. Each VR channel occupies an area of 0.48 mm2. The CR channel is capable of 80 dB of dynamic range, by converting currents between 1 nA to 10μA, while achieving a noise floor of 1.4 pA/Hz1/2. An automatic gain control (AGC) unit can be enabled in order maintain the sensor signal within the ADC dynamic range. Each CR channel occupies an area of 0.21 mm2. The chip consumes between 290 μA and 690 μA per channel and operates from a 1.8 V supply. The chip will be part of a fully flexible and configurable dual-mode EIS systems for impedance sensors and bioimpedance analysis.

The need of continuous real-time monitoring device for in-vivo drug level detection has been widely articulated lately. Such monitoring could guide drug posology and timing of intake, detect low or high drug levels, in order to take adequate measures, and give clinicians a valuable window into patients' health and their response to therapeutics. This paper presents a novel implantable bio-sensor based on impedance measurement capable of continuously monitoring various antiepileptic drug levels. This portable point-of-care microsystem replaces large and stationary conventional macrosystems, and is a one of a kind system designed with an array of electrodes to monitor various anti-epileptic drugs rather than one drug. The micro-system consists of (i) the front-end circuit including an inductive coil to receive energy from an external base station, and to exchange data with the latter; (ii) the power management block; (iii) the readout and control block; and (iv) the biosensor array. The electrical circuitry was designed using the 0.18-um CMOS process technology intended to be miniature and consume ultra-low power.

This paper presents the system design of a highly-scalable system-on-a-chip (SoC) to wirelessly and chronically detect the mechanisms underlying gastric dysrhythmias. The proposed wireless implantable gastric-wave recording (WIGR) SoC records gastric slow-wave and spike activities from 256 sites, and establishes transcutaneous data communication with an external reader while being inductively powered. The SoC is highly scalable by employing a modular architecture for the analog front-end (AFE), a near-field pulse-delay modulation (PDM) data transmitter (Tx) that its data rate is proportional to the power carrier frequency (fp), and an adaptive power management equipped with automatic-resonance tuning (ART) that dynamically compensates for environmental and fp variations of the implant power coil. The simulation and measurement results for individual blocks have been presented.

This paper presents the preliminary design and simulation of a flexible and programmable analog front-end (AFE) circuit with current and voltage readout capabilities for electric impedance spectroscopy (EIS). The AFE is part of a fully integrated multifrequency EIS platform. The current readout comprises of a transimpedance stage and an automatic gain control (AGC) unit designed to accommodate impedance changes larger than 3 order of magnitude. The AGC is based on a dynamic peak detector that tracks changes in the input current over time and regulates the gain of a programmable gain amplifier in order to optimise the signal-to-noise ratio. The system works up to 1 MHz. The voltage readout consists of a 2 stages of fully differential current-feedback instrumentation amplifier which provide 100 dB of CMRR and a programmable gain up to 20 V/V per stage with a bandwidth in excess of 10MHz.

Next generation implantable medical devices will have the potential to provide more precise and effective therapies through adaptive closed-loop controllers that combine sensing and stimulation across larger numbers of electrode channels. A major challenge in the design of such devices is balancing increased functionality and channel counts with the miniaturization required for implantation within small anatomical spaces. Customized therapies will require adaptive systems capable of tuning which channels are sensed and stimulated to overcome variability in patient-specific needs, surgical placement of electrodes, and chronic physiological responses. In order to address these challenges, we have designed a miniaturized implantable fully-reconfigurable front-end system that is integrated into the distal end of an 8-wire lead, enabling up to 64 electrodes to be dynamically configured for sensing and stimulation. Full reconfigurability is enabled by two custom 32×2 cross-point switch (CPS) matrix ASICs which can route any electrode to either an amplifier with reprogrammable bandwidth and integrated ADC or to one of two independent stimulation channels that can be driven through the lead. The 8-wire circuit includes a digital interface for robust communication as well as a charge-balanced powering scheme for enhanced safety. The system is encased in a hermetic package designed to fit within a 14 mm bur-hole in the skull for neuromodulation of the brain, but could easily be adapted to enhance therapies across a broad spectrum of applications.

This study proposes a novel pseudo resistor structure with a tunable DC bias voltage for biomedical front-end amplifiers (FEAs). In the proposed FEA, the high-pass filter composed of differential difference amplifier and a pseudo resistor is implemented. The FEA is manufactured by using a standard TSMC 0.35 μm CMOS process. In this study, three types FEAs included three different pseudo resistor are simulated, fabricated and measured for comparison and electrocorticography (ECoG) measurement, and all the results show the proposed pseudo resistor is superior to other two types in bandwidth. In chip implementation, the lower and upper cutoff frequencies of the high-pass filter with the proposed pseudo resistor are 0.15 Hz and 4.98 KHz, respectively. It also demonstrates lower total harmonic distortion performance of -58 dB at 1 kHz and higher stability with wide supply range (1.8 V and 3.3 V) and control voltage range (0.9 V and 1.65 V) than others. Moreover, the FEA with the proposed pseudo successfully recorded spike-and-wave discharges of ECoG signal in in vivo experiment on rat with pentylenetetrazol-induced seizures.

An implanted neural stimulator with closed loop control requires electrodes for stimulation pulses and recording neuron activity. Our system features arrays of 64 electrodes. Each electrode can be addressed through a cross bar switch, to enable it to be used for stimulation or recording. This electrode switch, a bank of low noise amplifiers with an integrated analog to digital converter, power conditioning electronics, and a communications and control gate array are co-located with the electrode array in a 14 millimeter diameter satellite package that is designed to be flush mounted in a skull burr hole. Our system features five satellite packages connected to a central hub processor-controller via ten conductor cables that terminate in a custom designed, miniaturized connector. The connector incorporates features of high reliability, military grade devices and utilizes three distinct seals to isolate the contacts from fluid permeation. The hub system is comprised of a connector header, hermetic electronics package, and rechargeable battery pack, which are mounted on and electrically interconnected by a flexible circuit board. The assembly is over molded with a compliant silicone rubber. The electronics package contains two antennas, a large coil, used for recharging the battery and a high bandwidth antenna that is used to download data and update software. The package is assembled from two machined alumina pieces, a flat base with brazed in, electrical feed through pins and a rectangular cover with rounded corners. Titanium seal rings are brazed onto these two pieces so that they can be sealed by laser welding. A third system antenna is incorporated in the flexible circuit board. It is used to communicate with an externally worn control package, which monitors the health of the system and allows both the user and clinician to control or modify various system function parameters.

We developed an EEG- and audio-based sleep sensing and enhancing system, called iSleep (interactive Sleep enhancement apparatus). The system adopts a closed-loop approach which optimizes the audio recording selection based on user's sleep status detected through our online EEG computing algorithm. The iSleep prototype comprises two major parts: 1) a sleeping mask integrated with a single channel EEG electrode and amplifier, a pair of stereo earphones and a microcontroller with wireless circuit for control and data streaming; 2) a mobile app to receive EEG signals for online sleep monitoring and audio playback control. In this study we attempt to validate our hypothesis that appropriate audio stimulation in relation to brain state can induce faster onset of sleep and improve the quality of a nap. We conduct experiments on 28 healthy subjects, each undergoing two nap sessions - one with a quiet background and one with our audio-stimulation. We compare the time-to-sleep in both sessions between two groups of subjects, e.g., fast and slow sleep onset groups. The p-value obtained from Wilcoxon Signed Rank Test is 1.22e-04 for slow onset group, which demonstrates that iSleep can significantly reduce the time-to-sleep for people with difficulty in falling sleep.

This paper presents an AC-coupled instrumentation amplifier for electroneurogram (ENG) activity recording. For this design, we evaluate gain and noise requirements based on interference sources (electrodes, power line, EMG). The circuit has been implemented in a commercially-available 0.35μm CMOS technology with total power consumption 460μW. The amplifier achieves CMRR 107 dB and integrated input referred noise 940 nV. The gain is 63 dB and the bandwidth is 0.5 Hz- 13 kHz. The chosen topology enables to minimise on-chip capacitance (only 27 pF), with a total chip area of 0.4mm2.

This article presents a low-noise readout front-end suitable for Electroencephalogram (EEG) acquisition. The chip includes 8-channel fully-differential instrumentation amplifiers, utilizing chopper stabilization technique for reducing the flicker noise, each amplifier with a small Gm-C low-pass filter, a programmable gain amplifier, and a 10-bit successive approximation register (SAR) ADC with a detect logic for DAC switching. The chip is fabricated with the TSMC 90nm CMOS process. The low-noise readout front-end has simulated frequency response from 0.57 Hz to 213 Hz, programmable gain from 54.4 dB to 87.6 dB, integrated input-referred noise of 0.358 μVrms within EEG bandwidth, a noise efficiency factor (NEF) of 2.43, and a power efficiency factor (PEF) of 2.95. The overall system consumes 32.08 μW under 0.5-V supply.

In this paper, the wireless data and power transfer for a novel optogenetic visual cortex implant system was demonstrated by using pork tissue mimic in-vitro at the ISM 2.4 GHz and 13.5 MHz frequency band respectively. The observed data rate was 120 kbps with no loss in data for up to a thickness of 35 mm in both water & pork. To increase the power level of the implant a Class E power amplifier is separately designed and simulated for the transmitter end and has an output power of around 223 mW with an efficiency of 81.83%. The transferred power at the receiver was measured to be 66.80 mW for the pork tissue medium considering a distance of 5 mm between the transmitter and the receiver coils, with a coupling coefficient of ~0.8. This serves the power requirement of the visual cortex implant.