A new molecular imprinted PEDOT glassy carbon electrode for carbamazepine detection.

An electrochemical sensor for the detection of carbamazepine was fabricated by the electropolymerization of PEDOT on glassy carbon electrodes. Molecular imprinted polymer sites were synthesized by cyclic voltammetry on the electrodes' surfaces providing high selectivity and sensitivity towards carbamazepine molecules. Scanning electron microscopy validated the formation of the polymer. Extraction of carbamazepine from the polymer was performed by immersion in acetonitrile and validated by ultraviolet-visible spectroscopy along with cyclic voltammetry experiments comparing pre- and post-template extraction data. Further cyclic voltammetry and square-wave voltammetry tests aided in characterizing the electrodes' response to carbamazepine concentration in PBS solution with [Fe(CN)6]3-/4- as a redox pair/mediator. The limits of detection and quantification were found to be 0.98 x 10-3 M and 2.97 x 10-3 M respectively. The biosensor was highly sensitive to carbamazepine molecules in comparison to non-imprinted electrodes, simple to construct and easy to operate.

A versatile wearable sEMG recording system for long-term epileptic seizure monitoring.

Surface electromyography (sEMG) can be used to detect motor epileptic seizures non-invasively. For clinical use, a compact-size, user-friendly, safe and accurate sEMG measurement system can be worn by epileptic patients to detect and characterize a seizure. Such devices must be small, wireless, power-efficient minimally invasive and robust to avoid movement artefacts, friction, and slipping of the electrode, which can compromise data integrity and/or generate false positives or false negatives. This paper presents a highly versatile device that can be worn in different locations on the body to capture sEMG signals in a freely moving user without movement artefact. The system can be safely worn on the body for several hours to capture sEMG from wet Ag/AgCl electrodes, while sEMG data is wirelessly transmitted to a host computer within a range of 20 m. We demonstrate the versatility of our sensor by recording sEMG from five different body locations in a freely moving volunteer. Then, simulated seizure data was captured while the device was placed on the extensor carpi ulnaris. We show that sEMG bursts were successfully recorded to characterize the seizure afterward. The presented sensor prototype is small (5 cm x 3.5 cm x 1 cm), lightweight (46 g), and has an autonomy of 12 hrs from a small 110-mAh battery.

Unsupervised Clustering of HRV Features Reveals Preictal Changes in Human Epilepsy.

Over a third of patients suffering from epilepsy continue to live with recurrent disabling seizures and would greatly benefit from personalized seizure forecasting. While electroencephalography (EEG) remains most popular for studying subject-specific epileptic precursors, dysfunctions of the autonomous nervous system, notably cardiac activity measured in heart rate variability (HRV), have also been associated with epileptic seizures. This work proposes an unsupervised clustering technique which aims to automatically identify preictal HRV changes in 9 patients who underwent simultaneous electrocardiography (ECG) and intracranial EEG presurgical monitoring at the University of Montreal Hospital Center. A 2-class k-means clustering combined with a quantitative preictal HRV change detection technique were adopted in a subject- and seizure-specific manner. Results indicate inter and intra-patient variability in preictal HRV changes (between 3.5 and 6.5 min before seizure onset) and a statistically significant negative correlation between the time of change in HRV state and the duration of seizures (p<0.05). The presented findings show promise for new avenues of research regarding multimodal seizure prediction and unsupervised preictal time assessment.Clinical Relevance- This study proposed an unsupervised technique for quantitatively identifying preictal HRV changes which can be eventually used to implement an ECG-based seizure forecasting algorithm.

A 110-nW in-channel sigma-delta converter for large-scale neural recording implants.

Advancement in wireless and microsystems technology have ushered in new devices that can directly interface with the central nervous system for stimulating and/or monitoring neural circuitry. In this paper, we present an ultra low-power sigma-delta analog-to-digital converter (ADC) intended for utilization into large-scale multi-channel neural recording implants. This proposed design, which provides a resolution of 9 bits using a one-bit oversampled ADC, presents several desirable features that allow for an in-channel ADC scheme, where one sigma-delta converter is provided for each channel, enabling development of scalable systems that can interface with different types of high-density neural microprobes. The proposed circuit, which have been fabricated in a TSMC 180-nm CMOS process, employs a first order noise shaping topology with a passive integrator and a low-supply voltage of 0.6 V to achieve ultra low-power consumption and small size. The proposed ADC clearly outperforms other designs with a power consumption as low as 110 nW for a precision of 9 bits (11-fJ per conversion), a silicon area of only 82 µm × 84 µm and one of the best reported figure of merit among recently published data converters utilized in similar applications.

Low-power adaptive spike detector based on a sigma-delta control loop.

This paper presents a resources-optimized digital action potential (AP) detector featuring an adaptive threshold based on a new Sigma-delta control loop. The proposed AP detector is optimized for utilizing low hardware resources, which makes it suitable for implementation on most popular low-power microcontrollers units (MCU). The adaptive threshold is calculated using a digital control loop based on a Sigma-delta modulator that precisely estimates the standard deviation of the amplitude of the neuronal signal. The detector was implemented on a popular low-power MCU and fully characterized experimentally using previously recorded neural signals with different signal-to-noise ratios. A comparison of the obtained results with other thresholding approaches shows that the proposed method can compete with high performance and highly resources demanding spike detection approaches while achieving up to 100% of true positive detection rate at high SNR, and up to 63% for an SNR as low as 0 dB, while necessitating an execution time as low as 11 µs with the MCU operating at 8 MHz.

Effect of early bladder stimulation on spinal shock: experimental approach.

The period of spinal shock which frequently follows spinal cord injury is associated with bladder areflexia and urinary retention. We studied the effect of early bladder electric stimulation on detrusor activity during the spinal shock phase in the dog. The animals had a spinal cord section at T10 vertebra, and their bladder management was assigned to one of the three following groups: intermittent catheterization, indwelling catheterization, and electric bladder stimulation. The parameters for evaluating each treatment included: blood chemistry, and radiographic and urodynamic tests. The most important finding was the early return of detrusor activity in the group of animals treated by early electric stimulation of the bladder.

Computerized transcutaneous control of a multichannel implantable urinary prosthesis.

In the present paper we describe a personal computer interface of a multichannel implantable urinary prosthesis. This system is composed of two main parts: the first one is internal and consists of an implant using a 4-microns CMOS gate array chip controlling a wide variety of waveforms via eight monopolar channels. The second, an external controller featuring a versatile software, a PCB card plugged in a portable microcomputer, and a radiofrequency-coupled technique. This device is used to transmit the power, the data and the synchronization clock to the implant by a simple binary signal modulating a 20 MHz carrier. We also report the features of implant encapsulation and electrode design and fabrication. In the experimental phase, we studied the effect of early electric stimulation of the bladder during the spinal shock phase in the dog. We present the operative techniques that enabled us to perform chronic electrostimulation of the sacral roots and discuss the results.

Implantable multiprogrammable microstimulator dedicated to bladder control.

An implantable multiprogrammable microstimulator that is intended to restore normal bladder functions (retention and incontinence) to spinal cord injured patients is presented. The implantable microstimulator circuitry is externally controlled and is powered by a single encoded radio frequency carrier and has four bipolar (eight monopolar) independently controlled channels. It offers a higher degree of reprogrammability and flexibility and can be used in any neuromuscular applications. The implant system is adaptable to the patient's needs and to future developments in stimulation algorithms, without changing the implant. Features of the microstimulator include its capabilities to generate a wide range of waveforms and to combine up to four different programmable frequencies in each wave train. By using a forward error detection and correction communication protocol, the reliability of the implant is increased. The chip has been designed for structural testability by means of a scan-based test approach and uses circuit techniques to reduce power consumption and ensure long-term stability.

Proposed new bladder volume monitoring device based on impedance measurement.

A new implantable bladder volume-monitoring device based on the impedance measurement of the detrusor muscle is described. The system is completely autonomous and forms a mixed-signal (analogue/digital) feedback loop with a neuro-stimulator to rectify bladder dysfunctions (incontinence and retention) through neuromuscular stimulation techniques. A programmable instrumentation amplifier and a signal processing block, to eliminate the artefacts caused by the patient's movements, have been designed and tested. The layout for the signal processing block has been realised in 0.8 micron BiCMOS technology.

Implantable measurement technique dedicated to the monitoring of electrode-nerve contact in bladder stimulators.

A fully integrated electrode-nerve contact monitoring circuit intended to increase safety and reliability in implantable bladder stimulators is described. The proposed integrated circuit converts a measurement of the impedance of two electrode-nerve contacts into frequency. The measurement is derived from a test current generated by the stimulation current source. The obtained results is the frequency of a square wave signal. This frequency is then converted into 8-bit data, which are serially transmitted to an external controller through an inductive link. The whole circuit can be set in idle model during stimulation, ensuring low energy consumption. It is fully testable, and an internal calibration technique makes it possible to reduce errors due to temperature and process variations. The total area of the proposed monitoring circuit is 0.1 mm2 when fabricated with a 0.35 micron technology, including a digitally controlled, current source. The design has been fabricated and successfully tested.

Implantable stimulation system dedicated for neural selective stimulation.

A functional electrical stimulation system is presented, which is dedicated for the selective neural stimulation of the bladder. The proposed system is composed of an internal stimulator (implant) and an external controller. The system is used to produce low-pressure voiding of the bladder in spinal cord injured patients. The implant is powered and operated by the external controller via radio-frequency electromagnetic coupling. All stimulation parameters are chosen externally using the controller and are sent to the implant, which produces the desired stimuli. These stimuli are applied directly to the S2 nerve which is linked to the sphincter and bladder muscles. A high-frequency signal is used to inhibit the contraction of the sphincter muscle, and low-frequency pulses stimulate the bladder muscle (the detrusor). Dedicated computer software is used by the physician to select the optimal parameters for each patient and to activate the implant through a parallel port interface with built-in transmitter. The parameters are then transferred to a hand-held controller which is used by the technical staff and by the patients themselves. Acute studies have been performed to validate the selective stimulation strategy, and chronic experimentation is currently underway in dogs.

Nerve cuff electrode with shape memory alloy armature: design and fabrication.

In this paper, a new nerve cuff electrode with shape memory alloy armature is presented. The proposed electrode is dedicated either to peripheral nerve stimulation or recording and its manufacturing does not require any expensive or complex technique. Shape Memory Alloy (SMA) armature ensures the complete and firm closing of the electrode, so that the complexity of the installation procedure is considerably reduced. A preliminary analysis of the electrode mechanical behavior prior, during and after installation has been done through numerical simulations and in vitro testing. It was proved theoretically and experimentally that the SMA electrode closes completely with an appropriate few second delay after its installation. No external fixation such as sutures is needed to secure permanent electrode-nerve contact. Furthermore, theoretical analysis has shown that the design of SMA electrode can be adapted for safe close-fitting installation, thanks to the device partial opening in case of nerve swelling.

A new bladder stimulator--hand-held controller and miniaturized implant: preliminary results in dogs.

A new urinary-tract stimulator that is intended to restore normal bladder function to patients who have spinal-cord injuries is described. The system is composed of two principal parts. The first, which is external, consists of a hand-held device based on an inductive-coupling technique. This controller incorporates all the circuitry necessary to transmit data transdermally. The second, a fully programmable implantable device, includes a complementary metal oxide semiconductor gate-array integrated circuit controlling eight monopolar (or four bipolar) stimulation channels. To protect the tissues and the device, three different biocompatible polymers encapsulate the implant. In the experimental phase, the authors investigated the effect of early electrical stimulation of the bladder during the spinal-shock phase in paraplegic dogs. In addition, using the stimulator, they localized the parameters of stimulation that give the best results in terms of effective bladder pressure and voiding a high volume of urine.

Towards a wireless optical stimulation system for long term in-vivo experiments.

This paper presents our recent progresses towards the development of a wirelessly powered head mountable optical stimulator for enabling long-term optogenetic experiments with small freely moving transgenic models. The proposed system includes a wireless power transmission chamber with uniform power distribution in 3D and a wireless head mountable optical stimulator prototype with power recovery. The wireless power link, which includes the inductive chamber and power recovery circuits, is robust against subject movements in all directions, and against angular misalignment. Such link provides uniform power distribution without the need for a closed-loop control system, and can localize the transmitted power towards the receiver, without using additional detection and control circuitry compared to other systems. Additionally, the chamber is equipped with a camera for capturing the animal motion and behavior after applying optical stimulation patterns. A low-power microcontroller unit is embedded with the stimulator prototype to generate arbitrary light stimulation patterns. Measurement results show that the inductive chamber can continuously deliver 70 mW to the stimulator prototype with a power efficiency of 59%.

Multicoil resonance-based parallel array for smart wireless power delivery.

This paper presents a novel resonance-based multicoil structure as a smart power surface to wirelessly power up apparatus like mobile, animal headstage, implanted devices, etc. The proposed powering system is based on a 4-coil resonance-based inductive link, the resonance coil of which is formed by an array of several paralleled coils as a smart power transmitter. The power transmitter employs simple circuit connections and includes only one power driver circuit per multicoil resonance-based array, which enables higher power transfer efficiency and power delivery to the load. The power transmitted by the driver circuit is proportional to the load seen by the individual coil in the array. Thus, the transmitted power scales with respect to the load of the electric/electronic system to power up, and does not divide equally over every parallel coils that form the array. Instead, only the loaded coils of the parallel array transmit significant part of total transmitted power to the receiver. Such adaptive behavior enables superior power, size and cost efficiency then other solutions since it does not need to use complex detection circuitry to find the location of the load. The performance of the proposed structure is verified by measurement results. Natural load detection and covering 4 times bigger area than conventional topologies with a power transfer efficiency of 55% are the novelties of presented paper.

A transcutaneous power transfer interface based on a multicoil inductive link.

This paper presents a transcutaneous power transfer link based on a multicoil structure. Multicoil inductive links using 4-coil or 3-coil topologies have shown significant improvement over conventional 2-coil structures for transferring power transcutaneously across larger distances and with higher efficiency. However, such performance comes at the cost of additional inductors and capacitor in the system, which is not convenient in implantable applications. This paper presents a transcutaneous power transfer interface that takes advantage on a 3-coils inductive topology to achieve wide separation distances and high power transfer efficiency without increasing the size of the implanted device compared to a conventional 2-coil structure. In the proposed link, a middle coil is placed outside the body to act as a repeater between an external transmitting coil and an implanted receiving coil. The proposed structure allows optimizing the link parameters after implantation by changing the characteristics of the repeater coil. Simulation with a multilayer model of the biological tissues and measured results are presented for the proposed link.

Exponential current pulse generation for efficient very high-impedance multisite stimulation.

We describe in this paper an intracortical current-pulse generator for high-impedance microstimulation. This dual-chip system features a stimuli generator and a high-voltage electrode driver. The stimuli generator produces flexible rising exponential pulses in addition to standard rectangular stimuli. This novel stimulation waveform is expected to provide superior energy efficiency for action potential triggering while releasing less toxic reduced ions in the cortical tissues. The proposed fully integrated electrode driver is used as the output stage where high-voltage supplies are generated on-chip to significantly increase the voltage compliance for stimulation through high-impedance electrode-tissue interfaces. The stimuli generator has been implemented in 0.18-µm CMOS technology while a 0.8-µm CMOS/DMOS process has been used to integrate the high-voltage output stage. Experimental results show that the rectangular pulses cover a range of 1.6 to 167.2 µA with a DNL and an INL of 0.098 and 0.163 least-significant bit, respectively. The maximal dynamic range of the generated exponential reaches 34.36 dB at full scale within an error of ± 0.5 dB while all of its parameters (amplitude, duration, and time constant) are independently programmable over wide ranges. This chip consumes a maximum of 88.3 µ W in the exponential mode. High-voltage supplies of 8.95 and -8.46 V are generated by the output stage, boosting the voltage swing up to 13.6 V for a load as high as 100 kΩ.

Integrated high-voltage inductive power and data-recovery front end dedicated to implantable devices.

In near-field electromagnetic links, the inductive voltage is usually much larger than the compliance of low-voltage integrated-circuit (IC) technologies used for the implementation of implantable devices. Thus most integrated power-recovery approaches limit the induced signal to low voltages with inefficient shunt regulation or voltage clipping. In this paper, we propose using high-voltage (HV) complementary metal-oxide semiconductor technology to fully integrate the inductive power and data-recovery front end while adopting a step-down approach where the inductive voltage is left free up to 20 or 50 V. The advantage is that excessive inductive power will translate to an additional charge that can be stored in a capacitor, instead of shunting to ground excessive current with voltage limiters. We report the design of two consecutive HV custom ICs-IC1 and IC2-fabricated in DALSA semiconductor C08G and C08E technologies, respectively, with a total silicon area (including pads) of 4 and 9 mm(2), respectively. Both ICs include HV rectification and regulation; however, IC2 includes two enhanced rectifier designs, a voltage-doubler, and a bridge rectifier, as well as data recovery. Postlayout simulations show that both IC2 rectifiers achieve more than 90% power efficiency at a 1-mA load and provide enough room for 12-V regulation at a 3-mA load and a maximum-available inductive power of 50 mW only. Successful measurement results show that HV regulators provide a stable 3.3- to 12-V supply from an unregulated input up to 50 or 20 V for IC1 and IC2, respectively, with performance that matches simulation results.

A novel low-power-implantable epileptic seizure-onset detector.

A novel implantable low-power integrated circuit is proposed for real-time epileptic seizure detection. The presented chip is part of an epilepsy prosthesis device that triggers focal treatment to disrupt seizure progression. The proposed chip integrates a front-end preamplifier, voltage-level detectors, digital demodulators, and a high-frequency detector. The preamplifier uses a new chopper stabilizer topology that reduces instrumentation low-frequency and ripple noises by modulating the signal in the analog domain and demodulating it in the digital domain. Moreover, each voltage-level detector consists of an ultra-low-power comparator with an adjustable threshold voltage. The digitally integrated high-frequency detector is tunable to recognize the high-frequency activities for the unique detection of seizure patterns specific to each patient. The digitally controlled circuits perform accurate seizure detection. A mathematical model of the proposed seizure detection algorithm was validated in Matlab and circuits were implemented in a 2 mm(2) chip using the CMOS 0.18- µm process. The proposed detector was tested by using intracerebral electroencephalography (icEEG) recordings from seven patients with drug-resistant epilepsy. The seizure signals were assessed by the proposed detector and the average seizure detection delay was 13.5 s, well before the onset of clinical manifestations. The measured total power consumption of the detector is 51 µW.