Wearable High Voltage Compliant Current Stimulator for Restoring Sensory Feedback.

Transcutaneous Electrical Nerve Stimulation (TENS) is a promising technique for eliciting referred tactile sensations in patients with limb amputation. Although several studies show the validity of this technique, its application in daily life and away from laboratories is limited by the need for more portable instrumentation that guarantees the necessary voltage and current requirements for proper sensory stimulation. This study proposes a low-cost, wearable high-voltage compliant current stimulator with four independent channels based on Components-Off-The-Shelf (COTS). This microcontroller-based system implements a voltage-current converter controllable through a digital-to-analog converter that delivers up to 25 mA to load up to 3.6 kΩ. The high-voltage compliance enables the system to adapt to variations in electrode-skin impedance, allowing it to stimulate loads over 10 kΩ with currents of 5 mA. The system was realized on a four-layer PCB (115.9 mm × 61 mm, 52 g). The functionality of the device was tested on resistive loads and on an equivalent skin-like RC circuit. Moreover, the possibility of implementing an amplitude modulation was demonstrated.

Wearable System Based on Ultra-Thin Parylene C Tattoo Electrodes for EEG Recording.

In an increasingly interconnected world, where electronic devices permeate every aspect of our lives, wearable systems aimed at monitoring physiological signals are rapidly taking over the sport and fitness domain, as well as biomedical fields such as rehabilitation and prosthetics. With the intent of providing a novel approach to the field, in this paper we discuss the development of a wearable system for the acquisition of EEG signals based on a portable, low-power custom PCB specifically designed to be used in combination with non-conventional ultra-conformable and imperceptible Parylene-C tattoo electrodes. The proposed system has been tested in a standard rest-state experiment, and its performance in terms of discrimination of two different states has been compared to that of a commercial wearable device for EEG signal acquisition (i.e., the Muse headset), showing comparable results. This first preliminary validation demonstrates the possibility of conveniently employing ultra-conformable tattoo-electrodes integrated portable systems for the unobtrusive acquisition of brain activity.

Non-rectangular neurostimulation waveforms elicit varied sensation quality and perceptive fields on the hand.

Electrical stimulation of the nerves is known to elicit distinct sensations perceived in distal parts of the body. The stimulation is typically modulated in current with charge-balanced rectangular shapes that, although easily generated by stimulators available on the market, are not able to cover the entire range of somatosensory experiences from daily life. In this regard, we have investigated the effect of electrical neurostimulation with four non-rectangular waveforms in an experiment involving 11 healthy able-bodied subjects. Weiss curves were estimated and rheobase and chronaxie values were obtained showing increases in stimulation time required to elicit sensations for some waveforms. The localization of the sensations reported in the hand also appeared to differ between waveforms, although the total area did not vary significantly. Finally, the possibility of distinguishing different charge- and amplitude-matched stimuli was demonstrated through a two-alternative-forced-choice (2AFC) match-to-sample task, showing the ability of participants to successfully distinguish between waveforms with similar electrical characteristics but different shapes and charge transfer rates. This study provides evidence that, by using different waveforms to stimulate nerves, it is possible to affect not only the required charge to elicit sensations but also the sensation quality and its localization.

Systematic analysis of wavelet denoising methods for neural signal processing.

Objective.Among the different approaches for denoising neural signals, wavelet-based methods are widely used due to their ability to reduce in-band noise. All wavelet denoising algorithms have a common structure, but their effectiveness strongly depends on several implementation choices, including the mother wavelet, the decomposition level, the threshold definition, and the way it is applied (i.e. the thresholding). In this work, we investigated these factors to quantitatively assess their effects on neural signals in terms of noise reduction and morphology preservation, which are important when spike sorting is required downstream.Approach.Based on the spectral characteristics of the neural signal, according to the sampling rate of the signals, we considered two possible decomposition levels and identified the best-performing mother wavelet. Then, we compared different threshold estimation and thresholding methods and, for the best ones, we also evaluated their effect on clearing the approximation coefficients. The assessments were performed on synthetic signals that had been corrupted by different types of noise and on a murine peripheral nervous system dataset, both of which were sampled at about 16 kHz. The results were statistically analysed in terms of their Pearson's correlation coefficients, root-mean-square errors, and signal-to-noise ratios.Main results.As expected, the wavelet implementation choices greatly influenced the processing performance. Overall, the Haar wavelet with a five-level decomposition, hard thresholding method, and the threshold proposed by Hanet al(2007) achieved the best outcomes. Based on the adopted performance metrics, wavelet denoising with these parametrizations outperformed conventional 300-3000 Hz linear bandpass filtering.Significance.These results can be used to guide the reasoned and accurate selection of wavelet denoising implementation choices in the context of neural signal processing, particularly when spike-morphology preservation is required.

Morphological Neural Computation Restores Discrimination of Naturalistic Textures in Trans-radial Amputees.

Humans rely on their sense of touch to interact with the environment. Thus, restoring lost tactile sensory capabilities in amputees would advance their quality of life. In particular, texture discrimination is an important component for the interaction with the environment, but its restoration in amputees has been so far limited to simplified gratings. Here we show that naturalistic textures can be discriminated by trans-radial amputees using intraneural peripheral stimulation and tactile sensors located close to the outer layer of the artificial skin. These sensors exploit the morphological neural computation (MNC) approach, i.e., the embodiment of neural computational functions into the physical structure of the device, encoding normal and shear stress to guarantee a faithful neural temporal representation of stimulus spatial structure. Two trans-radial amputees successfully discriminated naturalistic textures via the MNC-based tactile feedback. The results also allowed to shed light on the relevance of spike temporal encoding in the mechanisms used to discriminate naturalistic textures. Our findings pave the way to the development of more natural bionic limbs.

Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback.

OBJECTIVE: Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated. METHODS: To this aim, we performed a 6-month clinical study with 3 transradial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks. RESULTS: All subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state. INTERPRETATION: The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings. ANN NEUROL 2019;85:137-154.

Electronic Detection of DNA Hybridization by Coupling Organic Field-Effect Transistor-Based Sensors and Hairpin-Shaped Probes.

In this paper, the electronic transduction of DNA hybridization is presented by coupling organic charge-modulated field-effect transistors (OCMFETs) and hairpin-shaped probes. These probes have shown interesting properties in terms of sensitivity and selectivity in other kinds of assays, in the form of molecular beacons (MBs). Their integration with organic-transistor based sensors, never explored before, paves the way to a new class of low-cost, easy-to-use, and portable genetic sensors with enhanced performances. Thanks to the peculiar characteristics of the employed sensor, measurements can be performed at relatively high ionic strengths, thus optimizing the probes' functionality without affecting the detection ability of the device. A complete electrical characterization of the sensor is reported, including calibration with different target concentrations in the measurement environment and selectivity evaluation. In particular, DNA hybridization detection for target concentration as low as 100 pM is demonstrated.

A 64-channels neural interface for biopotentials recording and PNS stimulation.

A biomedical interface that combines into a single and compact device the recording of biopotentials and the electrical stimulation of neural fibres is presented. It is intended for enabling the control over a robotic hand and for restoring the sensory feedback in amputees by directly interfacing the peripheral nervous system (PNS) in closed-loop. A modular system consisting in one or more independent 16-channels bidirectional units was conceived. Each module is based on three 0.35µm bulk-CMOS integrated circuits (ICs): a recording unit, a High-Voltage (HV) stimulator and a HV booster. A tunable bandwidth (10Hz-8kHz) allows the recording IC to acquire both electroneurographyc (ENG) and electromiographyc (EMG) signals with a programmable gain up to 43.5dB. The signals are then converted into a digital domain by means of a ΣΔ converter. Due to the typical high impedance at the electrode-tissue interface, a programmable HV booster that increases the stimulation voltage up to 19V was designed. It is directly controlled by the stimulation module that generates current-based pulses with a programmable amplitude and pulse-width. The whole system was validated by means of in-vivo experiments in rats.

An integrated interface for peripheral neural system recording and stimulation: system design, electrical tests and in-vivo results.

The prototype of an electronic bi-directional interface between the Peripheral Nervous System (PNS) and a neuro-controlled hand prosthesis is presented. The system is composed of 2 integrated circuits: a standard CMOS device for neural recording and a HVCMOS device for neural stimulation. The integrated circuits have been realized in 2 different 0.35µ m CMOS processes available from ams. The complete system incorporates 8 channels each including the analog front-end, the A/D conversion, based on a sigma delta architecture and a programmable stimulation module implemented as a 5-bit current DAC; two voltage boosters supply the output stimulation stage with a programmable voltage scalable up to 17V. Successful in-vivo experiments with rats having a TIME electrode implanted in the sciatic nerve were carried out, showing the capability of recording neural signals in the tens of microvolts, with a global noise of 7µ V r m s , and to selectively elicit the tibial and plantar muscles using different active sites of the electrode.

Investigation on the hermeticity of an implantable package with 32 feedthroughs for neural prosthetic applications.

This paper presents an implantable package aimed at hosting a bidirectional neural interface for neural prosthetic applications. The package has been conceived to minimize the invasivity for the patient, for this reason a cylindrical container with an outer diameter of 7 mm and a length of 21 mm has been designed. The package, realized in alumina (Al2O3), presents 32 hermetic feedthroughs located at the top and bottom base of the cylinder. The hermetic housing has been assembled using a low-temperature soldering method based on a previous platinum/gold (Pt/Au) metallization of the ceramic parts. The package's hermeticity has been successfully proved by means of in-vitro tests, exhibiting an increase in the inner relative humidity of 20 %RH over 75 days of observation.

Organic FET-based DNA hybridization sensor with sub-picomolar sensitivity.

In this paper, a novel approach for DNA hybridization detection by means of organic field-effect transistors-based biosensors (bioFETs) is proposed. The reported device, namely Organic Charge-Modulated FET (OCMFET), is conceived for overcoming the main limitations of bioFETs, related to design, materials and measurement conditions. In particular, record performances in terms of sensitivity and selectivity will be reported. Moreover, as innovative features among bioFETs, the detection ability of the OCMFET at relatively high ionic strengths will be carefully discussed, unravelling the interactions between the bioreceptors characteristics at the nano-scale and the device polarization.

Charge sensing by organic charge-modulated field effect transistors: application to the detection of bio-related effects.

The ability of field effect transistors (FETs) to detect charge variations on the gate may be exploited for realizing chemo- and bio-sensors. In this paper, we focus our attention on a particular kind of field effect device, named organic charge modulated FETs, whose features can be optimized for charge detection in liquid solutions. The results of the measurement of different bio-related effects are shown. In particular, DNA hybridization and pH detection in liquid media are proposed. Finally, preliminary considerations about the applicability of these devices to the detection of the electrical activity of cells are also provided. The device has considerable potential for being employed as a reliable, high sensitivity, low cost technology for sensing signals derived from living systems.

Active devices based on organic semiconductors for wearable applications.

Plastic electronics is an enabling technology for obtaining active (transistor based) electronic circuits on flexible and/or nonplanar surfaces. For these reasons, it appears as a perfect candidate to promote future developments of wearable electronics toward the concept of fabrics and garments made by functional (in this case, active electronic) yarns. In this paper, a panoramic view of recent achievements and future perspectives is given.

Producing smart sensing films by means of organic field effect transistors.

We have fabricated the first example of totally flexible field effect device for chemical detection based on an organic field effect transistor (OFET) made by pentacene films grown on flexible plastic structures. The ion sensitivity is achieved by employing a thin Mylar foil as gate dielectric. A sensitivity of the device to the pH of the electrolyte solution has been observed A similar structure can be used also for detecting mechanical deformations on flexible surfaces. Thanks to the flexibility of the substrate and the low cost of the employed technology, these devices open the way for the production of flexible chemical and strain gauge sensors that can be employed in a variety of innovative applications such as wearable electronics, e-textiles, new man-machine interfaces.