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We report a miniaturized, minimally invasive high-density neural recording interface that occupies only a 1.53 mm2 footprint for hybrid integration of a flexible probe and a 256-channel integrated circuit chip. To achieve such a compact form factor, we developed a custom flip-chip bonding technique using anisotropic conductive film and analog circuit-under-pad in a tiny pitch of 75 m. To enhance signal-to-noise ratios, we applied a reference-replica topology that can provide the matched input impedance for signal and reference paths in low-noise aimpliers (LNAs). The analog front-end (AFE) consists of LNAs, buffers, programmable gain amplifiers, 10b ADCs, a reference generator, a digital controller, and serial-peripheral interfaces (SPIs). The AFE consumes 51.92 W from 1.2 V and 1.8 V supplies in an area of 0.0161 mm2 per channel, implemented in a 180 nm CMOS process. The AFE shows > 60 dB mid-band CMRR, 6.32 Vrms input-referred noise from 0.5 Hz to 10 kHz, and 48 M input impedance at 1 kHz. The fabricated AFE chip was directly flip-chip bonded with a 256-channel flexible polyimide neural probe and assembled in a tiny head-stage PCB. Full functionalities of the fabricated 256-channel interface were validated in both in vitro and in vivo experiments, demonstrating the presented hybrid neural recording interface is suitable for various neuroscience studies in the quest of large scale, miniaturized recording systems.

This paper presents an 8-channel energy-efficient analog front-end (AFE) for neural recording, with improvements in power supply rejection ratio (PSRR) and dynamic range. The input stage in the low noise amplifier (LNA) adopts low voltage supply (0.35 V) and current-reusing to achieve ultralow power. To maintain a high PSRR performance while using such a low-voltage supply, a replica-biasing scheme is proposed to generate a stable bias current for the input stage of the LNA despite large supply interference. By exploiting the signal characteristics in the tetrode recording, an averaged local field potential (A-LFP) servo loop is introduced to extend the dynamic range without consuming too much extra power and chip area. The A-LFP signal is generated by integrating the four-channel PGA outputs from the same tetrode. Furthermore, the outputs of the programmable gain amplifier (PGA) are level shifted to bias the input nodes of the amplifier through large pseudo resistors, thus increase the maximum output range without distortion under the low-voltage supply. The proof-of-concept prototype is fabricated in a 65 nm CMOS process. Each recording channel including an LNA and a PGA occupies 0.04 mm $^2$ and consumes 340 nW from the 0.35 V and 0.7 V supply. Each A-LFP servo loop, which is shared by four recording channels, occupies 0.04 mm $^2$ and consumes 190 nW. The maximum gain of the AFE is 54 dB, and the input-referred noise is 6.7 $\mu$ V over the passband from 0.5 Hz to 6.5 kHz. Measurement also shows that the 0.35 V replica-biasing input stage can tolerate a large interferer up to 200 mVpp with a PSRR of 74 dB, which has been improved to 110 dB with a silicon respin that shields critical wires in the layout.

Purpose In the spirit of overcoming the signal-to-noise limitations of active matrix, flat-panel imagers (AMFPIs) which employ array circuits based on a-Si:H thin-film transistors (TFTs), an empirical investigation of the noise properties of prototype active pixel arrays based on polycrystalline silicon (poly-Si) TFTs is reported. Like a-Si:H, poly-Si supports fabrication of large area, monolithic x-ray imaging arrays and offers good radiation damage resistance, while providing electron and hole mobility orders of magnitude higher. Compared to pixel circuits typically consisting of a single addressing switch in an AMFPI array, the pixel circuit of an active pixel array includes an amplifier that magnifies the imaging signal prior to readout by external acquisition electronics. Also, while readout erases signal stored in the pixels for AMFPI arrays, active pixel arrays allow multiple nondestructive readout, which can be used to reduce noise. The prototype arrays investigated in this paper were developed to explore the effect of variation in amplifier design on noise. Methods A pair of prototype arrays incorporating single-stage and two-stage poly-Si pixel amplifiers were examined. The arrays incorporate various amplifier designs in which dimensions of some of the three (or four) poly-Si TFTs per pixel circuit for the single-stage array, and some of the five poly-Si TFTs for the two-stage array, were varied. The arrays were operated using a recently developed electronic data acquisition system that allows variation of operational conditions such as voltages and timing of control signals. The arrays were operated in the absence of radiation in various correlated multiple sampling modes, with and without the injection of charge directly into the pixel circuits for measurements of in-pixel gain and pixel noise. Pixel noise, referred back to the input of the pixel amplifier, was compared to predictions generated by a sophisticated circuit simulation model. Results Across the various pixel circuit designs, the median in-pixel gain for the single-stage and two-stage arrays was measured to be ×9.3 and ×25, respectively. These gain levels were sufficient to reduce the contribution of external noise, defined as the electronic additive noise in the absence of noise contributions from circuitry in the pixel and referred back to the input of the pixel amplifier, to less than 340 e. As a result, median pixel noise results as low as ~695 e and 866 e, acquired using eight samples, were observed from the best-performing single-stage and two-stage designs, respectively. While the magnitude of pixel noise predicted by simulation was lower than the measured results, there was generally good agreement between simulation and measurement for the functional dependence of noise on operating voltages, timing, and sampling mode. Conclusions The single-stage and two-stage arrays examined in this study demonstrated pixel noise well below that typically demonstrated by AMFPIs. Through proper design, it should be possible to maintain the noise levels observed in this study irrespective of the size and pitch of an active pixel array. Further reduction in pixel noise may be possible through more optimized pixel circuit design, faster readout, or improvements in fabrication.

The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload. NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions.

Microelectrode arrays (MEAs) have been extensively used to measure extracellular spike activity from cultured neurons using multiple electrodes embedded in a planar glass substrate. This system has been implemented to investigate drug effects by detecting pharmacological perturbation reflected in spontaneous network activity. By configuring multiple wells in an MEA, a high-throughput electrophysiological assay has become available, speeding up drug tests. Despite its merits in acquiring massive amounts of electrophysiological data, the high cost and the bulky size of commercial multi-well MEA systems and most importantly its lack of customizability prevent potential users from fully implementing the system in drug experiments. In this work, we have developed a microelectrode array based drug testing platform by incorporating a custom-made compact 256-channel multi-well MEA in a standard microscope slide and commercial application-specific integrated circuit (ASIC) chip based recording system. We arranged 256 electrodes in 16 wells to maximize data collection from a single chip. The multi-well MEA in this work has a more compact design with reduced chip size compared to previously reported multi-well MEAs. Four synaptic modulators (NMDA, AMPA, bicuculline (BIC) and ATP) were applied to a multi-well MEA and neural spike activity was analyzed to study their neurophysiological effects on cultured neurons. Analyzing various neuropharmacological compounds has become much more accessible by utilizing commercially available digital amplifier chips and customizing a user-preferred analog-front-end interface design with additional benefits in reduced platform size and cost.

An 8-channel wearable wireless device for ambulatory surface EEG monitoring and analysis is presented. The entire multi-channel recording, quantization, and motion artifact removal circuitries are implemented on a 4-layer polyimide flexible substrate. The recording electrodes and active shielding are also integrated on the same substrate, yielding the smallest form factor compared to the state of the art. Thanks to the dry non-contact electrodes, the system is quickly mountable with minimal assistance required, making it an ideal ambulatory front- and temporal-lobe EEG monitoring device. The flexible main board is connected to a rechargeable battery on one end and to a 13 × 17 mm $^2$ rigid board on the other end. The mini rigid board hosts a low-power programmable FPGA and a BLE 5.0 transceiver, which add diagnostic capability and wireless connectivity features to the device, respectively. Design considerations for a wearable EEG monitoring and diagnostic device are discussed in details. The theory of the novel fully-analog method for motion artifact detection and removal is described and the detailed circuit implementation is presented. The device performance in terms of voltage gain (260 V/V), bandwidth (DC-300 Hz), motion artifact removal, and wireless communication throughput (up to 1 Mbps) is experimentally validated. The entire wearable solution with the battery weighs 9.2 grams.

Photoplethysmography (PPG) enables wearable vitals monitoring. Nevertheless, it is still limited by the few mA of the LEDs driving current. We present a PPG sensor integrating an array of dedicated pinned-photodiodes (PPD) with a full readout chain integrated in a 0.18 $\mu$ m CMOS Image Sensor (CIS) process. The sensor features a total input referred noise of 0.68 e-rms per PPD, independently of the input light, and achieves a 4.6 $\mu$ W total power consumption, including the 2 $\mu$ W LED power, at 1.38 bpm heart rate average error.

Monolithic integration of photoacoustic (PA) sensor with compact size, lightweight, and low power consumption is attractive to be implemented on wearable medical devices for in vivo blood metabolic sensing and imaging. This work presents a miniaturized chip-scale mixed-signal photoacoustic sensor system which can achieve coherent lock-in function to detect weak target PA signals noninvasively at in vivo scenarios of poor signal to noise ratio (SNR) and strong interferences. A low-noise amplifier (LNA), a 3rd order Butterworth low-pass filter (LPF), and a variable-gain amplifier (VGA) chain with 10 MHz cutoff frequency are implemented on-chip to attain a high-quality sensing performance with 50-dB dynamic range. A Gilbert-cell type multiplier is integrated on-chip to fulfill the coherent lock-in process on acquired PA signals in a closed-loop process with an embedded FPGA system. Fabricated in 65-nm CMOS technology, the prototype PA sensor system demonstrated 50 μV sensitivity. The functions of the chip-scale PA sensor system enhanced by coherent lock-in process were validated through the experiments on temperature monitoring and vessel imaging. The PA receiver chip occupies an area of 0.6 mm2 and consumes 20 mW at a 1.8-V supply.

Photothermal microscopy has enabled highly sensitive label-free imaging of absorbers, from metallic nanoparticles to chemical bonds. Photothermal signals are conventionally detected via modulation of excitation beam and demodulation of probe beam using lock-in amplifier. While convenient, the wealth of thermal dynamics is not revealed. Here, we present a lock-in free, mid-infrared photothermal dynamic imaging (PDI) system by MHz digitization and match filtering at harmonics of modulation frequency. Thermal-dynamic information is acquired at nanosecond resolution within single pulse excitation. Our method not only increases the imaging speed by two orders of magnitude but also obtains four-fold enhancement of signal-to-noise ratio over lock-in counterpart, enabling high-throughput metabolism analysis at single-cell level. Moreover, by harnessing the thermal decay difference between water and biomolecules, water background is effectively separated in mid-infrared PDI of living cells. This ability to nondestructively probe chemically specific photothermal dynamics offers a valuable tool to characterize biological and material specimens., Photothermal microscopy is limited for imaging of thermal dynamics. Here, the authors introduce a lock-in free, mid-infrared photothermal dynamic imaging system, which significantly increases SNR and imaging speed, and demonstrate metabolism analysis at single-cell level and background removal.

This paper presents an 8-channel array of low-noise (30.3 fA/Hz) current sensing front-ends with on-chip microelectrode electrochemical sensors. The analog front-end (AFE) consists of a 1st-order continuous-time delta-sigma (CT) modulator that achieves 123 fA sensitivity over a 10 Hz bandwidth and 139 dB cross-scale dynamic range with a 2-bit programmable current reference. A digital predictor and tri-level pulse width modulated (PWM) current-steering DAC realize the equivalent performance of a multi-bit in an area- and power-efficient manner. The AFE consumes 50.3 W and 0.11 mm2 per readout channel. The proposed platform was used to observe protein-ligand interactions in real-time using transient induced molecular electronic spectroscopy (TIMES), a label- and immobilization-free biosensing technique.

CMOS microelectronics design has evolved tremendously during the last two decades. The evolution of CMOS devices to short channel designs where the feature size is below 1000 nm brings a great deal of uncertainty in the way the microelectronics design cycle is completed. After the conceptual idea, developing a thinking model to understand the operation of the device requires a good “ballpark” evaluation of transistor sizes, decision making, and assumptions to fulfill the specifications. This design process has iterations to meet specifications that exceed in number of the available degrees of freedom to maneuver the design. Once the thinking model is developed, the simulation validation follows to test if the design has a good possibility of delivering a successful prototype. If the simulation provides a good match between specifications and results, then the layout is developed. This paper shows a useful open science strategy, using the Excel software, to develop CMOS microelectronics hand calculations to verify a design, before performing the computer simulation and layout of CMOS analog integrated circuits. The full methodology is described to develop designs of passive components, as well as CMOS amplifiers. The methods are used in teaching CMOS microelectronics to students of electronic engineering with industrial partner participation. This paper describes an exhaustive example of a low-voltage operational transconductance amplifier (OTA) design which is used to design an instrumentation amplifier. Finally, a test is performed using this instrumentation amplifier to implement a front-end signal conditioning device for CMOS-MEMS biomedical applications.

Medical ultrasound has become a crucial part ofmodern society and continues to play a vital role in the diagnosis and treatment of illnesses. Over the past decades, the development of medical ultrasound has seen extraordinary progress as a result of the tremendous research advances in microelectronics, transducer technology and signal processing algorithms. However, medical ultrasound still faces many challenges including power efficient driving of transducers, low-noise recording of ultrasoundechoes, effective beamforming in a non-linear, high-attenuation medium (human tissues) and reduced overall form factor. This paper provides a comprehensive review of the design of integrated circuits for medical ultrasound applications. The most important and ubiquitous modules in a medical ultrasound system are addressed, i) transducer driving circuit, ii) low-noise amplifier, iii) beamforming circuit and iv) analog-digital converter. Within each ultrasound module, some representative research highlights are described followed by a comparison of the state-of-the-art. Thispaper concludes with a discussion and recommendations for future research directions.

This paper presents a reconfigurable electrocardiogram (ECG) analog front-end (AFE) exploiting bio-signals' inherent low activity and quasi-periodicity to reduce power consumption. This is realized by an agile, on-the-fly dynamic noise-power trade-off performed over specific cardiac cycle regions guided by a least mean squares (LMS)-based adaptive predictor leading to ~2.5 data-dependent power savings. Implemented in 65 nm CMOS, the AFE has tunable performance exhibiting an input-referred noise ranging from 1.90 2.91 VRMS while consuming 307 769 nW from a 0.8 V supply. A comprehensive system performance verification was performed using ECG records from standard databases to establish the feasibility of the proposed predictor-based approach for power savings without compromising the systems anomaly detection capability or ability to extract pristine ECG features.

In 1938, Walker Bleakney and John A. Hipple first described the cycloidal mass analyzer as the only mass analyzer configuration capable of "perfect" ion focusing. Why has their geometry been largely neglected for many years and how might it earn a respectable place in the world of modern chemical analysis? This Perspective explores the properties of the cycloidal mass analyzer and identifies the lack of suitable ion array detectors as a significant reason why cycloidal mass analyzers are not widely used. The recent development of capacitive transimpedance amplifier array detectors can enable several techniques using cycloidal mass analyzers including spatially coded apertures and single particle mass analysis with a "virtual-slit", helping the cycloidal mass analyzer earn a respectable place in chemical analysis.

Air flow measurements provide significant information required for understanding the characteristics of insect movement. This study proposes a four-channel low-noise readout integrated circuit (IC) in order to measure air flow (air velocity), which can be beneficial to insect biomimetic robot systems that have been studied recently. Instrumentation amplifiers (IAs) with low-noise characteristics in readout ICs are essential because the air flow of an insect’s movement, which is electrically converted using a microelectromechanical systems (MEMS) sensor, generally produces a small signal. The fundamental architecture employed in the readout IC is a three op amp IA, and it accomplishes low-noise characteristics by chopping. Moreover, the readout IC has a four-channel input structure and implements an automatic offset calibration loop (AOCL) for input offset correction. The AOCL based on the binary search logic adjusts the output offset by controlling the input voltage bias generated by the R-2R digital-to-analog converter (DAC). The electrically converted air flow signal is amplified using a three op amp IA, which is passed through a low-pass filter (LPF) for ripple rejection that is generated by chopping, and converted to a digital code by a 12-bit successive approximation register (SAR) analog-to-digital converter (ADC). Furthermore, the readout IC contains a low-dropout (LDO) regulator that enables the supply voltage to drive digital circuits, and a serial peripheral interface (SPI) for digital communication. The readout IC is designed with a 0.18 μm CMOS process and the current consumption is 1.886 mA at 3.3 V supply voltage. The IC has an active area of 6.78 mm2 and input-referred noise (IRN) characteristics of 95.4 nV/√Hz at 1 Hz.

This paper presents a remote 16 Ch × 200 GHz dense wavelength division multiplexing (DWDM)-passive optical fiber sensor (OFS) network. We particularly investigate the remote water-level monitoring capability of the OFS network based on an optical power measurement that features simplicity and a fast processing speed. The OFS network utilizes a seeded amplified spontaneous emission (ASE) light that is spectrum-sliced and distributed by an arrayed waveguide grating (AWG) towards multiple sensing units (SU), where each SU is installed at a different height in the water pool. Then, each SU reflects either of the two different optical powers according to the medium (air vs. water) back to the monitoring station. Therefore, the total received optical power at the monitoring station linearly changes according to the water level. We can simply recognize the water level by utilizing the optical power meter (OPM) at the monitoring station rather than the optical spectrum analyzer (OSA), which is bulky and expensive and requires a relatively long processing time. Consequently, we can reduce the system complexity, processing time, and cost (both installation and maintenance). However, the OPM-based OFS network requires a new methodology to derive the water level from the measured optical power. Thus, we come up with the reference-to-power ratio (RPR) analysis, which can be used for the maximum distance analysis as well as water level recognition. Based on the new reception architecture supported by the new post-processing scheme, the OFS network can distinguish 17 different water levels of the SFP at the monitoring station, which is &gt, 40 km away from the SFP, without using any active devices (such as optical amplifiers) at the remote places.

Significance We introduce a multiplex-then-amplify (MTA) scheme that requires only one amplifier per multiplexer, significantly reducing the number of components in multichannel acquisition systems while enabling arbitrary waveform stimulation independently on all channels. Based on this scheme, we developed a fully implantable, miniaturized, responsive embedded system that can acquire neural oscillations and action potentials using conformable conducting polymer-based electrodes as well as perform real-time onboard processing, low-latency arbitrary waveform stimulation, and local data storage. MTA devices enabled development of a protocol for suppression of pathologic coupling within an epileptic network. These devices will allow application of targeted high-spatiotemporal resolution responsive neurostimulation approaches to a variety of brain functions, broadening our ability to chronically modify neural networks in health and disease., Responsive neurostimulation is increasingly required to probe neural circuit function and treat neuropsychiatric disorders. We introduce a multiplex-then-amplify (MTA) scheme that, in contrast to current approaches (which necessitate an equal number of amplifiers as number of channels), only requires one amplifier per multiplexer, significantly reducing the number of components and the size of electronics in multichannel acquisition systems. It also enables simultaneous stimulation of arbitrary waveforms on multiple independent channels. We validated the function of MTA by developing a fully implantable, responsive embedded system that merges the ability to acquire individual neural action potentials using conformable conducting polymer-based electrodes with real-time onboard processing, low-latency arbitrary waveform stimulation, and local data storage within a miniaturized physical footprint. We verified established responsive neurostimulation protocols and developed a network intervention to suppress pathological coupling between the hippocampus and cortex during interictal epileptiform discharges. The MTA design enables effective, self-contained, chronic neural network manipulation with translational relevance to the treatment of neuropsychiatric disease.

Recent technological advances have led to a rapid increase in alternative listening devices to conventional hearing aids. The aim was to systematically review the existing evidence to assess the effectiveness of alternative listening devices in adults with mild and moderate hearing loss. A systematic search strategy of the scientific literature was employed, reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) checklist. Eleven studies met eligibility for inclusion: two studies evaluated personal sound amplification products, and nine studies assessed remote microphone systems (frequency modulation, Bluetooth, wireless). The evidence in this review suggests that alternative listening devices improve behavioural measures of speech intelligibility relative to unaided and/or aided conditions. Evidence for whether alternative listening devices improve self-reported outcomes is inconsistent. The evidence was judged to be of poor to good quality and subject to bias due to limitations in study design. Our overall recommendation is that high-quality evidence (i.e. randomised controlled trials) is required to demonstrate the effectiveness of alternative listening devices. Such evidence is not currently available and is necessary to guide healthcare commissioners and policymakers when considering new service delivery models for adults with hearing loss. Review registration: Prospective Register of Systematic Reviews (PROSPERO), CRD42015029582.

Structures, kinetics, and chemical reactivities at interfaces and surfaces are key to understanding many of the fundamental scientific problems related to chemical, material, biological, and physical systems. These steady-state and dynamical properties at interfaces and surfaces require even-order techniques with time-resolution and spectral-resolution. Here, we develop fourth-order interface-/surface-specific two-dimensional electronic spectroscopy, including both two-dimensional electronic sum frequency generation (2D-ESFG) spectroscopy and two-dimensional electronic second harmonic generation (2D-ESHG) spectroscopy, for structural and dynamics studies of interfaces and surfaces. The 2D-ESFG and 2D-ESHG techniques were based on a unique laser source of broadband short-wave IR from 1200 nm to 2200 nm from a home-built optical parametric amplifier. With the broadband short-wave IR source, surface spectra cover most of the visible light region from 480 nm to 760 nm. A translating wedge-based identical pulses encoding system (TWINs) was introduced to generate a phase-locked pulse pair for coherent excitation in the 2D-ESFG and 2D-ESHG. As an example, we demonstrated surface dark states and their interactions of the surface states at p-type GaAs (001) surfaces with the 2D-ESFG and 2D-ESHG techniques. These newly developed time-resolved and interface-/surface-specific 2D spectroscopies would bring new information for structure and dynamics at interfaces and surfaces in the fields of the environment, materials, catalysis, and biology.

Size and absolute concentration of suspensions of nanoparticles are important information for the study and development of new materials and products in different industrial applications spanning from biotechnology and pharmaceutics to food preparation and conservation. Laser Transmission Spectroscopy (LTS) is the only methodology able to measure nanoparticle size and concentration by performing a single measurement. In this paper we report on a new variable gain calibration procedure for LTS-based instruments allowing to decrease of an order of magnitude the experimental indetermination of the particle size respect to the conventional LTS based on the double ratio technique. The variable gain calibration procedure makes use of a specifically designed tunable-gain, dual-channel, dual-phase Lock-In Amplifier (LIA) whose input voltage signals are those ones generated by two Si photodiodes that measure the laser beam intensities passing through the sample containing the nanoparticles and a reference optical path. The LTS variable gain calibration procedure has been validated by firstly using a suspension of NIST standard polystyrene nanoparticles even 36 hours after the calibration procedure was accomplished. The paper reports in detail the LIA implementation describing the design methodologies and the electronic circuits. As a case example of the characterization of biological nanostructures, we demonstrate that a single LTS measurement allowed to determine size density distribution of a population of extracellular vesicles extracted from orange juice (25 nm in size) with the presence of their aggregates having a size of 340 nm and a concentration smaller than 3 orders of magnitude.

There is a growing interest to improve the quality of life of blind people. An implanted intracortical prosthesis could be the last resort in many cases of visual impairment. Technology at this moment is at a stage that implementation is at sight. Making the data communication to and from the implanted electrodes wireless is beneficial to avoid infection and to ease mobility. Here, we focus on the stimulation side, or downlink, for which we propose a low-power non-coherent digital demodulator on the implanted receiver. The experimentally demonstrated downlink is on a scaled-down version at a 1 MHz carrier frequency showing a data rate of 125 kbps. This provides proof of principle for the system with a 12 MHz carrier frequency and a data rate of 4 Mbps, which consumes under 1 mW at the receiver side in integrated circuit (IC) simulation. Due to its digital architecture, the system is easily adjustable to an ISM frequency band with its power consumption scaling linearly with the carrier frequency. The tested system uses off-the-shelf coils, which gave sufficient bandwidth, while staying within safe SAR limits. The digital receiver achieved a reduction in power consumption by skipping clock cycles of redundant bits. The system shows a promising pathway to a low-power wireless-enabled visual prosthesis.

A bio-potential recorder working under 0.8 V supply voltage with a tunable low-pass filter is proposed in this paper. The prototype is implemented in TSMC 180 nm CMOS technology, featuring a power consumption of 2.27 $\mu$ W, while preserving a high tolerance of power-line interference (PLI) up to 600 m $V_{pp}$ , a common-mode rejection ratio (CMRR) of higher than 100 dB, a THD of −65.5 dB, and a noise density of 50 nV/ $\sqrt{Hz}$ by employing four new techniques, including 1) low noise chopper modulator, 2) feedback loop based common-mode cancellation loop (CMCL), 3) offset cancellation loop (OCL) with PMOS backgate control scheme, and 4) a very-lower transconductance (VLT) operational transconductance amplifier (OTA) using in the DC-servo-loop (DSL). The measured mid-band gain is 43.3 dB with a high-pass cut-off frequency of 1.2 Hz. The low-pass cut-off frequency can be configured from 650 Hz to 7.5 kHz. The measured input-referred integrated noise is 1.2 uVrms in the frequency band of 1-650 Hz and 4.1 uVrms in the 1 Hz–7.5 kHz frequency band, respectively, leading to a power efficiency factor (PEF) of 7.49 and 7.59.

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/cm2, 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.

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.

Significance: Optical coherence tomography (OCT) has been widely used in clinical studies. However, the image quality of OCT decreases with increasing imaging depth since the light is rapidly attenuated in biological tissues. Aim: We present a compensation approach to preserve weak high-frequency signals from deep structures and compress the dynamic range of the detected signal for superior analog-to-digital conversion and image display capability. Approach: A homemade frequency gain compensation amplifier is designed and fabricated to amplify the electrical signal from a balanced photodetector and compensate for the signal attenuation in swept-source OCT (SSOCT). Results: It is demonstrated in imaging various objects that this cost-efficient technique effectively enhances the contrast of the deep tissue image. Conclusions: A frequency gain compensation amplifier is designed and used to compress the dynamic range of the electrical signal detected by the photodetector of an SSOCT system, which enables weak signals from deep structures to be acquired by the ADC and displayed with enhanced local contrast.

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%. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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.

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.

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.

This article presents a high energy efficiency, high-integrated, and low-power on–off keying transceiver for a 2.4 GHz industrial scientific medical band. The proposed receiver includes an input matching network, a low-noise amplifier, a novel single-to-differential envelope detector, a level shifter, cascaded baseband amplifiers, and a hysteresis comparator. The proposed transmitter includes a bias-stimulating circuit, a current-reused self-mixing voltage controlled oscillator, and a quadruple-transconductance power amplifier. Numerous proposed techniques implemented in the mentioned circuits improve the energy per bit and power efficiency. Therefore, the proposed receiver for short-distanced propagation can achieve a sensitivity of −46 dBm with a carrier frequency of 2.45 GHz and a high data rate of 2 Mbps. The proposed transmitter achieves an output power of −17 dBm with a high data rate of 20 Mbps. This work is fabricated in a TSMC 0.18 μm CMOS process and consumes 160 μW and 0.6 mW in the receiver and transmitter, respectively, from a 1.2 V supply voltage. The energy per bit of 80 pJ/bit in the receiver part and the figure of merit of 9 in the transmitter part are better than those of existing state-of-the-art transceivers.

High-frequency oscillations (HFO) are promising EEG biomarkers of epileptogenicity. While the evidence supporting their significance derives mainly from invasive recordings, recent studies have extended these observations to HFO recorded in the widely accessible scalp EEG. Here, we investigated whether scalp HFO in drug-resistant focal epilepsy correspond to epilepsy severity and how they are affected by surgical therapy. In eleven children with drug-resistant focal epilepsy that underwent epilepsy surgery, we prospectively recorded pre- and postsurgical scalp EEG with a custom-made low-noise amplifier (LNA). In four of these children, we also recorded intraoperative electrocorticography (ECoG). To detect clinically relevant HFO, we applied a previously validated automated detector. Scalp HFO rates showed a significant positive correlation with seizure frequency (R

Objective. When developing approaches for automatic preprocessing of electroencephalogram (EEG) signals in non-isolated demanding environment such as intensive care unit (ICU) or even outdoor environment, one of the major concerns is varying nature of characteristics of different artifacts in time, frequency and spatial domains, which in turn causes a simple approach to be not enough for reliable artifact removal. Considering this, current study aims to use correlation-driven mapping to improve artifact detection performance. Approach. A framework is proposed here for mapping signals from multichannel space (regardless of the number of EEG channels) into two-dimensional RGB space, in which the correlation of all EEG channels is simultaneously taken into account, and a deep convolutional neural network (CNN) model can then learn specific patterns in generated 2D representation related to specific artifact. Main results. The method with a classification accuracy of 92.30% (AUC = 0.96) in a leave-three-subjects-out cross-validation procedure was evaluated using data including 2310 EEG sequences contaminated by artifacts and 2285 artifact-free EEG sequences collected with BrainStatus self-adhesive electrode and wireless amplifier from 15 intensive care patients. For further assessment, several scenarios were also tested including performance variation of proposed method under different segment lengths, different numbers of isoline and different numbers of channel. The results showed outperformance of CNN fed by correlation coefficients data over both spectrogram-based CNN and EEGNet on the same dataset. Significance. This study showed the feasibility of utilizing correlation image of EEG channels coupled with deep learning as a promising tool for dimensionality reduction, channels fusion and capturing various artifacts patterns in temporal-spatial domains. A simplified version of proposed approach was also shown to be feasible in real-time application with latency of 0.0181 s for making real-time decision.

Ions are ubiquitous biological regulators playing a key role for vital processes in animals and plants. The combined detection of ion concentration and real-time monitoring of small variations with respect to the resting conditions is a multiscale functionality providing important information on health states. This multiscale functionality is still an open challenge for current ion sensing approaches. Here we show multiscale real-time and high-sensitivity ion detection with complementary organic electrochemical transistors amplifiers. The ion-sensing amplifier integrates in the same device both selective ion-to-electron transduction and local signal amplification demonstrating a sensitivity larger than 2300 mV V−1 dec−1, which overcomes the fundamental limit. It provides both ion detection over a range of five orders of magnitude and real-time monitoring of variations two orders of magnitude lower than the detected concentration, viz. multiscale ion detection. The approach is generally applicable to several transistor technologies and opens opportunities for multifunctional enhanced bioelectronics., Though organic electrochemical transistor (OECT)-based ion sensors are attractive for highly sensitive ion detection and monitoring, its limited sensitivity hinders its practical applicability. Here, the authors report real-time, high sensitivity ion detection with complementary OECT amplifiers.

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. © 2020 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.

A multi-channel biopotential recording analog front-end (AFE) with a fully integrated area-efficient driven-right-leg (DRL) circuit is presented in this paper. The proposed AFE includes 10 channels of low-noise capacitive coupled instrumentation amplifier (CCIA), one shared 10-bit SAR ADC and a fully integrated DRL to enhance the system-level common-mode rejection ratio (CMRR). The proposed DRL circuit senses the common-mode at the CCIA output so that the AFE gain is reused as the DRL loop gain. Therefore, area efficient unit-gain buffer with small averaging capacitors can be used in DRL circuit to reduce the circuit area significantly. The proposed AFE has been implemented in a standard 0.18-μm CMOS process. The DRL circuit achieved more than 85% chip area reduction compared to the state-of-art on-chip DRL circuits and maximum 60 dB enhancement to system-level CMRR. Measurement results show high/low AFE gain of 60 dB/54 dB respectively with 1 μA/channel current consumption under 1.0 V power supply. The measured AFE input-referred noise in 1 Hz - 10k Hz range is 4.2 μVrms and the maximum system-level CMRR is 110 dB. Agency for Science, Technology and Research (A*STAR) This work was supported by A∗STAR (Agency for Science, Technology and Research) BMRC (Biomedical Research Council), Singapore, under Grant IAF311022. This paper was recommended by Associate Editor Y. Zheng. (Corresponding author: Yuan Gao.)

We present an image sensor incorporating angle-selective gratings for resolution enhancement in contact imaging applications. Optical structures designed in the CMOS metal layers above each photodiode form the angle-selective gratings that limit the sensor angle of view to $\pm$ 18 $^{\circ }$ , rejecting background light and deblurring the image. The imager is based on a high-gain capacitive transimpedance amplifier pixel using a custom 11fF MOM capacitor, achieving $\text{8.2}\;\text{V s}^{-1} \text{pW}^{-1}$ sensitivity. The pixel includes a leakage current minimization circuit to remove signal-dependent reset switch leakage and the corresponding dark current is $\text{14}\;\text{aA}/{\mu }\text{m}{^2}$ . The resulting 4.7 mm by 2.25 mm sensor (80 by 36 pixels) is designed specifically for intraoperative cancer imaging in order to solve the pervasive challenge of identifying microscopic residual cancer foci in vivo , where they can be removed. We demonstrate imaging and detection of foci containing less than 200 cancer cells labeled with fluorescent biomarkers in 50 ms with signal-to-noise ratios greater than 15 dB and the detection of microscopic residual tumor in mice models. The absence of large optical elements enables extreme miniaturization, allowing manipulation within a small, morphologically complex, tumor cavity.

This paper presents the design of a low-power discrete-time signal-folding amplifier intended for use in place of programmable-gain amplifiers (PGA) in electrocardiogram (ECG) acquisition systems. The amplifier provides a fixed high gain while preventing output signal saturation even with rail-to-rail inputs, thanks to the proposed discrete-time signal folding technique; the fixed gain eliminates the need of gain-control circuitry while the high gain helps relax the resolution requirement of the analog-to-digital converter (ADC) that follows, thus resulting in lower power consumption and design complexity for the ADC. Fabricated in a standard 0.18- $\mu$ m CMOS process, the amplifier occupies an active area of 0.254 $\mathrm{mm}^2$ and consumes 2.64 $\mu$ W from a 1.2-V supply voltage. While amplifying a rail-to-rail input (2.4 $V_\mathrm{pp}$ differential) with a gain of 17.8 V/V, the amplifier achieves a signal-to-noise-plus-distortion ratio (SNDR) of 71 dB, thus making it very attractive for high-fidelity ECG recording amid large input interferences.

© 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting /republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works This paper presents a 1.2 V 36 µW reconfigurable analog front-end (R-AFE) as a general-purpose low-cost IC for multiple-mode biomedical signals acquisition. The R-AFE efficiently reuses a reconfigurable preamplifier, a current generator (CG), and a mixed signal processing unit, having an area of 1.1 mm2 per R-AFE while supporting five acquisition modes to record different forms of cardiovascular and respiratory signals. The R-AFE can interface with voltage-, current-, impedance-, and light-sensors and hence can measure electrocardiography (ECG), bio-impedance (BioZ), photoplethysmogram (PPG), galvanic skin response (GSR), and general-purpose analog signals. Thanks to the chopper preamplifier and the low-noise CG utilizing dynamic element matching, the R-AFE mitigates 1/f noise from both the preamplifier and the CG for improved measurement sensitivity. The IC achieves competitive performance compared to the state-of-the-art dedicated readout ICs of ECG, BioZ, GSR, and PPG, but with approximately 1.4×-5.3× smaller chip area per channel.

Magnetic biosensing is an emerging technique for ultra-sensitive point-of-care (PoC) biomolecular detection. However, the large baseline-to-signal ratio and sensor-to-sensor mismatch in magnetoresistive (MR) biosensors severely complicates the design of the analog front-end (AFE) due to the high dynamic range (DR) required. The proposed AFE addresses these issues through new architectural and circuit level techniques including fast settling duty-cycle resistors (DCRs) to reduce readout time and a high frequency interference rejection (HFIR) sampling technique embedded in the ADC to relax the DR requirement. The AFE achieves an input-referred noise of 46.4 nT/√Hz, an input-referred baseline of less than 0.235 mT, and a readout time of 11 ms while consuming just 1.39 mW. Implemented in a 0.18 μm CMOS process, this work has state-of-the-art performance with 22.7× faster readout time, >7.8× lower baseline, and 2.3× lower power than previously reported MR sensor AFEs.

Nanoparticle-based drugs are rapidly evolving to treat different conditions and have considerable potential. A new system based on the combination of electrical impedance tomography (EIT) imaging and a power amplifier with a RF coil has been developed to study the effect of gold nanoparticles (AuNPs) when excited in the MHz frequency range. We show that samples including AuNPs have a temperature increase of 1&ndash, 1.5 &deg, C due to the presence of RF excitation at 13.56 MHz which provides a higher rate of change for solutions without AuNPs. They also show more than a 50% increase in conductivity in difference imaging as the result of this excitation. The change for samples without AuNPs is 40%.

Due to the large number of individuals with Unilateral Hearing Loss (UHL) and the recommendation to use hearing assistive devices, studies are required to define possibilities of intervention for this population. Objective: To evaluate the performance of the Remote Microphone System (RMS) in children with UHL. Methodology: Prospective clinical study with a convenience sample. Eleven children (mean age of 9.2 years) with severe and profound sensorineural UHL, hearing aid users and enrolled in regular schools participated in the study. They were evaluated using the Hearing in Noise Test (HINT), the Classroom Participation Questionnaire (CPQ), and the Sustained Auditory Attention Ability Test (SAAAT) with RMS. Results: HINT results were analyzed using variance to three criteria of repeated measures, which revealed differences between intervention, position, and time factors and significant interaction between these three factors. The comparative analysis of the results from CPQ showed significant differences in the statistical t-test (p=

Heart-sound auscultation is a rapid and fundamental technique used for examining the cardiovascular system. The main components of heart sounds are the first and second heart sounds. Discriminating these heart sounds under the presence of additional heart sounds and murmurs will be difficult. To recognize these signals efficiently, this study proposes a monitoring system with phonocardiogram and electrocardiogram. This system has two key points. The first is chip implementation, including capacitor coupled amplifier, transimpedance amplifier, high-pass sigma–delta modulator, and digital signal processing block. The chip in the system is fabricated in 0.18 μm standard complementary metal–oxide–semiconductor process. The second is a software application on smartphones for heart-related physiological signal recording, display, and identification. A wavelet-based QRS complex detection algorithm verified by MIT/BIH Arrhythmia Database is also proposed. The overall measured positive prediction, sensitivity, and error rate of the proposed algorithm are 99.90%, 99.82%, and 0.28%, respectively. During auscultation, doctors may refer to these physiological signals displayed on the smartphone and simultaneously listen to the heart sounds to diagnose the potential heart disease. By taking advantage of signal visualization and keeping the original diagnosis procedure, the uncertainty existing in heart sounds can be eliminated, and the training period to acquire auscultation skills can be reduced.

Dry contact electrode-based EEG acquisition is one of the easiest ways to obtain neural information from the human brain, providing many advantages such as rapid installation, and enhanced wearability. However, high contact impedance due to insufficient electrical coupling at the electrode-scalp interface still remains a critical issue. In this paper, a two-wired active dry electrode system is proposed by combining finger-shaped spring-loaded probes and active buffer circuits. The shrinkable probes and bootstrap topology-based buffer circuitry provide reliable electrical coupling with an uneven and hairy scalp and effective input impedance conversion along with low input capacitance. Through analysis of the equivalent circuit model, the proposed electrode was carefully designed by employing off-the-shelf discrete components and a low-noise zero-drift amplifier. Several electrical evaluations such as noise spectral density measurements and input capacitance estimation were performed together with simple experiments for alpha rhythm detection. The experimental results showed that the proposed electrode is capable of clear detection for the alpha rhythm activation, with excellent electrical characteristics such as low-noise of 1.131 &mu, VRMS and 32.3% reduction of input capacitance.

We propose an upgraded version of our previously designed open-source lipid bilayer amplifier. This improved amplifier is now suitable both for the use in introductory courses in biophysics and neurosciences at the undergraduate level and for scientific research. Similar to its predecessor, the OpenPicoAmp-100k is designed using the common lithographic printed circuit board fabrication process and off-the-shelf electronic components. It consists of the high-speed headstage, followed by voltage-gain amplifier with built-in 6-order Bessel filter. The amplifier has a bandwidth of 100 kHz in the presence of 100-pF input membrane capacitance and is capable of measuring ion channel current with amplitudes from sub-pA and up to ± 4 nA. At the full bandwidth and with a 1 GΩ transimpedance gain, the amplifier shows 12 pArms noise with an open input and 112 pArms noise in the presence of 100-pF input capacitance, while at the 5-kHz bandwidth (typical in single-channel experiments), noise amounts to 0.45 pArms and 2.11 pArms, respectively. Using an optocoupler circuit producing TTL-controlled current impulses and using 50% threshold analysis, we show that at full bandwidth, the amplifier has deadtimes of 3.5 μs and 5 μs at signal-to-noise ratios (SNR) of 9 and 1.7, respectively. Near 100% of true current impulses longer than 5 μs and 6.6 μs are detected at these two respective SNRs, while false event detection rate remains acceptably low. The wide bandwidth of the amplifier was confirmed in bilayer experiments with alamethicin, for which open ion channel current events shorter that 10 μs could be resolved.

OBJECTIVE: This research assessed the reduction of peak levels, equivalent energy and sound power of firearm suppressors. DESIGN: The first study evaluated the effect of firearm suppressors at several positions around the firearm for four firearms. The second study assessed the reduction of sound power with a 3-meter hemispherical array of microphones for two firearms. RESULTS: The suppressors reduced exposures at the ear between 17- and 24-dB peak sound pressure level and reduced the 8-hour equivalent A-weighted energy between 9 and 21 dB depending upon the firearm and ammunition. Noise reductions observed for the instructor’s position about a meter behind the shooter were between 20- and 28-dB peak sound pressure and between 11 and 26 dB L(Aeq,8h). Firearm suppressors reduced the measured sound power levels between 2 and 23 dB. Sound power reductions were greater for the low-velocity ammunition than for the same weapons fired with high-velocity ammunition due to the effect of N-waves produced by a supersonic projectile. CONCLUSIONS: Whereas firearms suppressors are an effective engineering control to reduce firearm noise exposures, firearm users should always wear hearing protection whenever using weapons. The cumulative exposures of suppressed firearms can still present a significant hearing risk.

Fundamental insights into the function of the neural circuits often follows from the advances in methodologies and tools for neuroscience. Electrode- and optical- based stimulation methods have been used widely for neuro-modulation with high resolution. However, they are suffering from inherent invasive surgical procedure. Ultrasound has been proved as a promising technology for neuro-stimulation in a non-invasive manner. However, no portable ultrasound system has been developed particularly for neuro-stimulation. The utilities used currently are assembled by traditional functional generator, power amplifier, and general transducer, therefore, resulting in lack of flexibility. This paper presents a portable system to achieve ultrasonic neuro-stimulation to satisfy various studies. The system incorporated a high voltage waveform generator and a matching circuit that were optimized for neuro-stimulation. A new switching mode power amplifier was designed and fabricated. The noise generated by the power amplifier was reduced (about 30 dB), and the size and weight were smaller in contrast with commercial equipment. In addition, a miniaturized ultrasound transducer was fabricated using Pb(Mg1/3Nb2/3)O3-PbTiO3(PMN-PT) 1–3 composite single crystal for the improved ultrasonic performance. The spatial peak temporal average pressure was higher than 250 kPa in the range of 0.5–5 MHz. In vitro and in vivo studies were conducted to show the performance of the system.

The development of giant magnetoresistive (GMR) sensors has demonstrated significant advantages in nanomedicine, particularly for ultrasensitive point-of-care diagnostics. To this end, the detection system is required to be compact, portable, and low power consuming at the same time that a maximum signal to noise ratio is maintained. This paper reports a CMOS front-end with integrated magnetoresistive sensors for biomolecular recognition detection applications. Based on the characterization of the GMR sensor's signal and noise, CMOS building blocks (i.e., current source, multiplexers, and preamplifier) were designed targeting a negligible noise when compared with the GMR sensor's noise and a low power consumption. The CMOS front-end was fabricated using AMS $\mathrm{{\text{0.35}}\;\mu{\text{m}}}$ technology and the magnetoresistive sensors were post-fabricated on top of the CMOS chip with high yield ( ${\text{97.9}}\%$ ). Due to its low circuit noise (16 $\mathrm{{\text{nV}}/\sqrt{{\text{Hz}}}}$ ) and overall equivalent magnetic noise ( $\mathrm{{\text{11.5}}\;{\text{nT}}/\sqrt{{\text{Hz}}}}$ ), the full system was able to detect 250 nm magnetic nanoparticles with a circuit imposed signal-to-noise ratio degradation of only $-$ 1.4 dB. Furthermore, the low power consumption (6.5 mW) and small dimensions ( $\mathrm{{\text{7.59: mm}}^{2}}$ ) of the presented solution guarantees the portability of the detection system allowing its usage at the point-of-care.

Objective: Conventional brain-computer interfaces (BCIs) are often expensive, complex to operate, and lack portability, which confines their use to laboratory settings. Portable, inexpensive BCIs can mitigate these problems, but it remains unclear whether their low-cost design compromises their performance. Therefore, we developed a portable, low-cost BCI and compared its performance to that of a conventional BCI. Methods: The BCI was assembled by integrating a custom electroencephalogram (EEG) amplifier with an open-source microcontroller and a touchscreen. The function of the amplifier was first validated against a commercial bioamplifier, followed by a head-to-head comparison between the custom BCI (using four EEG channels) and a conventional 32-channel BCI. Specifically, five able-bodied subjects were cued to alternate between hand opening/closing and remaining motionless while the BCI decoded their movement state in real time and provided visual feedback through a light emitting diode. Subjects repeated the above task for a total of 10 trials, and were unaware of which system was being used. The performance in each trial was defined as the temporal correlation between the cues and the decoded states. Results: The EEG data simultaneously acquired with the custom and commercial amplifiers were visually similar and highly correlated ( $\rho$ = 0.79). The decoding performances of the custom and conventional BCIs averaged across trials and subjects were 0.70 $\pm$ 0.12 and 0.68 $\pm$ 0.10, respectively, and were not significantly different. Conclusion: The performance of our portable, low-cost BCI is comparable to that of the conventional BCIs. Significance: Platforms, such as the one developed here, are suitable for BCI applications outside of a laboratory.

Inductive sensor-based measurement techniques are useful for a wide range of biomedical applications. However, optimizing the noise performance of these sensors is challenging at broadband frequencies, owing to the frequency-dependent reactance of the sensor. In this work, we describe the fundamental limits of noise performance and bandwidth for these sensors in combination with a low-noise amplifier. We also present three equivalent methods of noise matching to inductive sensors using transformer-like network topologies. Finally, we apply these techniques to improve the noise performance in magnetic particle imaging, a new molecular imaging modality with excellent detection sensitivity. Using a custom noise-matched amplifier, we experimentally demonstrate an 11-fold improvement in noise performance in a small animal magnetic particle imaging scanner.

This paper presents a multielement annular ring ultrasound transducer formed by individual high-frequency PMUTs (17.5 MHz in air and 8.7 MHz in liquid) intended for high-precision axial focalization and high-performance ultrasound imaging. The prototype has five independent multielement rings fabricated by a monolithic process over CMOS, allowing for a very compact and robust design. Crosstalk between rings is under 56 dB, which guarantees an efficient beam focusing on a range between 1.4 mm and 67 µm. The presented PMUT-on-CMOS annular array with an overall diameter down to 669 µm achieves an output pressure in liquid of 4.84 kPa/V/mm2 at 1.5 mm away from the array when the five channels are excited together, which is the largest reported for PMUTs. Pulse-echo experiments towards high-resolution imaging are demonstrated using the central ring as a receiver. With an equivalent diameter of 149 µm, this central ring provides high receiving sensitivity, 441.6 nV/Pa, higher than that of commercial hydrophones with equivalent size. A 1D ultrasound image using two channels is demonstrated, with maximum received signals of 7 mVpp when a nonintegrated amplifier is used, demonstrating the ultrasound imaging capabilities.