•Inductively charged implantable telemetry device to interface peripheral nerves.•Capable of 256 channel recording and 15 channel ±4 mA electrical stimulation.•Recorded vagus nerve spikes in pigs and ...electromyograms from leg muscles in rat.•Stimulated pelvic nerves, changing bladder pressure in urinary incontinent dogs.
Peripheral nerve interfacing has many applications ranging from investigation of neural signals to therapeutic intervention for varied diseases. This need has driven technological advancements in the field of electrode arrays and wireless systems for in-vivo electrophysiological experiments. Hence we present our fully implantable, programmable miniaturized wireless stimulation and recording devices.
The method consists of technological advancements enabling implantable wireless recording up to 128 channels with a sampling rate of 50Khz and stimulation up to ±4 mA from 15 independent channels. The novelty of the technique consists of induction charging cages which enables freely moving small animals to undergo continuous electrophysiological and behavioral studies without any impediments. The biocompatible hermetic packaging technology for implantable capsules ensures stability for long-term chronic studies.
Electromyographs wirelessly recorded from leg muscles of a macaque and a rat using implantable technology are presented during different behavioral task studies. The device's simultaneous stimulation and recording capabilities are reported when interfaced with the vagus and pelvic nerves.
The wireless interfacing technology has a large number of recording and stimulating channels without compromising on the signal quality due to sampling rates or stimulating current output capabilities. The induction charging technology along with transceiver and software interface allows experiments on multiple animals to be carried out simultaneously.
This customizable technology using wireless power transmission, reduced battery size, and miniaturized electronics has paved way for a robust, fully implantable, hermetic neural interface system enabling the study of bioelectronic medical therapies.
To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to ...record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.
Neural stimulation is an important method used to activate or inhibit action potentials of the neuronal anatomical targets found in the brain, central nerve and peripheral nerve. The neural ...stimulator system produces biphasic pulses that deliver balanced charge into tissue from single or multichannel electrodes. The timing and amplitude of these biphasic pulses are precisely controlled by the neural stimulator software or imbedded algorithms. Amplitude mismatch between the anodic current and cathodic current of the biphasic pulse will cause permanently damage for the neural tissues. The main goal of our circuit and layout design is to implement a 16-channel biphasic current mode programmable neural stimulator with calibration to minimize the current mismatch caused by inherent complementary metal oxide semiconductor (CMOS) manufacturing processes.
This paper presents a 16-channel constant current mode neural stimulator chip. Each channel consists of a 7-bit controllable current DAC used as sink and source current driver. To reduce the LSB quantization error and the current mismatch, an automatic calibration circuit and flow diagram is presented in this paper. There are two modes of operation of the stimulator chip-namely, stimulation mode and calibration mode. The chip also includes a digital interface used to control the stimulator parameters and calibration levels specific for each individual channel.
This stimulator Application Specific Integrated Circuit (ASIC) is designed and fabricated in a 0.18 μm High-Voltage CMOS technology that allows for ±20 V power supply. The full-scale stimulation current was designed to be at 1 mA per channel. The output current was shown to be constant throughout the timing cycles over a wide range of electrode load impedances. The calibration circuit was also designed to reduce the effect of CMOS process variation of the P-channel metal oxide semiconductor (PMOS) and N-channel metal oxide semiconductor (NMOS) devices that will result in charge delivery to have less than 0.13% error.
A 16-channel integrated biphasic neural stimulator chip with calibration is presented in this paper. The stimulator circuit design was simulated and the chip layout was completed. The chip layout was verified using design rules check (DRC) and layout versus schematic (LVS) design check using computer aided design (CAD) software. The test results we presented show constant current stimulation with charge balance error within 0.13% least-significant-bit (LSB). This LSB error was consistent throughout a variety stimulation patterns and electrode load impedances.
In recent years optogenetics has rapidly become an essential technique in neuroscience. Its temporal and spatial specificity, combined with efficacy in manipulating neuronal activity, are especially ...useful in studying the behavior of awake behaving animals. Conventional optogenetics, however, requires the use of lasers and optic fibers, which can place considerable restrictions on behavior. Here we combined a wirelessly controlled interface and small implantable light-emitting diode (LED) that allows flexible and precise placement of light source to illuminate any brain area. We tested this wireless LED system in vivo, in transgenic mice expressing channelrhodopsin-2 in striatonigral neurons expressing D1-like dopamine receptors. In all mice tested, we were able to elicit movements reliably. The frequency of twitches induced by high power stimulation is proportional to the frequency of stimulation. At lower power, contraversive turning was observed. Moreover, the implanted LED remains effective over 50 days after surgery, demonstrating the long-term stability of the light source. Our results show that the wireless LED system can be used to manipulate neural activity chronically in behaving mice without impeding natural movements.
Recording and manipulating neuronal ensemble activity is a key requirement in advanced neuromodulatory and behavior studies. Devices capable of both recording and manipulating neuronal activity ...brain-computer interfaces (BCIs) should ideally operate un-tethered and allow chronic longitudinal manipulations in the freely moving animal. In this study, we designed a new intracortical BCI feasible of telemetric recording and stimulating local gray and white matter of visual neural circuit after irradiation exposure. To increase the translational reliance, we put forward a Göttingen minipig model. The animal was stereotactically irradiated at the level of the visual cortex upon defining the target by a fused cerebral MRI and CT scan. A fully implantable neural telemetry system consisting of a 64 channel intracortical multielectrode array, a telemetry capsule, and an inductive rechargeable battery was then implanted into the visual cortex to record and manipulate local field potentials, and multi-unit activity. We achieved a 3-month stability of the functionality of the un-tethered BCI in terms of telemetric radio-communication, inductive battery charging, and device biocompatibility for 3 months. Finally, we could reliably record the local signature of sub- and suprathreshold neuronal activity in the visual cortex with high bandwidth without complications. The ability to wireless induction charging combined with the entirely implantable design, the rather high recording bandwidth, and the ability to record and stimulate simultaneously put forward a wireless BCI capable of long-term un-tethered real-time communication for causal preclinical circuit-based closed-loop interventions.
We have developed, manufactured, and tested two analog CMOS integrated circuit "neurochips" for recording from arrays of densely packed neural electrodes. Device A is a 16-channel buffer consisting ...of parallel noninverting amplifiers with a gain of 2 V/V. Device B is a 16-channel two-stage analog signal processor with differential amplification and high-pass filtering. It features selectable gains of 250 and 500 V/V as well as reference channel selection. The resulting amplifiers on Device A had a mean gain of 1.99 V/V with an equivalent input noise of 10 /spl mu/V/sub rms/. Those on Device B had mean gains of 53.4 and 47.4 dB with a high-pass filter pole at 211 Hz and an equivalent input noise of 4.4 /spl mu/V/sub rms/. Both devices were tested in vivo with electrode arrays implanted in the somatosensory cortex.
A digital microfluidic biochip (DMB) is an attractive platform for automating laboratory procedures in microbiology. To overcome the problem of cross-contamination due to fouling of the electrode ...surface in traditional DMBs, a contactless liquid-handling biochip technology, referred to as acoustofluidics, has recently been proposed. A major challenge in operating this platform is the need for a control signal of frequency 24 MHz and voltage range <inline-formula><tex-math notation="LaTeX">\pm 10/\pm 20</tex-math></inline-formula> V to activate the IDT units in the biochip. In this paper, we present a hardware design that can efficiently activate/de-activated each IDT, and can fully automate an bio-protocol. We also present a fault-tolerant synthesis technique that allows us to automatically map biomolecular protocols to acoustofluidic biochips. We develop and experimentally validate a velocity model, and use it to guide co-optimization for operation scheduling, module placement, and droplet routing in the presence of IDT faults. Simulation results demonstrate the effectiveness of the proposed synthesis method. Our results are expected to open new research directions on design automation of digital acoustofluidic biochips.
This paper presents the design and test results of a fourth-order and sixth-order 14-bit 2.2-MS/s sigma-delta analog-to-digital converter (ADC). The analog modulator and digital decimator sections ...were implemented in a 0.35 /spl mu/m CMOS double-poly triple-level metal 3.3-V process. The design objective for these ADC's was to achieve 85 dB signal-to-noise distortion ratio (SNDR) with less than 200 mW power dissipation. Both modulators employ a cascade sigma-delta topology. The fourth-order modulator consists of two cascaded second-order stages which include 1-bit and 5-bit quantizers, respectively. The sixth-order modulator has a 2-2-2 cascade structure and 1-bit quantizer at the end of each stage. An oversampling ratio of 24 was selected to give the best SNDR and power consumption with realizable gain-matching requirements between the analog and digital sections.
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The continuous monitoring of electrical brain activity with implanted electrodes is essential for understanding the neural substrates of many physiological and pathological brain ...functions. Although this is done in some patients before undergoing surgical treatment, such recordings are extremely difficult in experimental animals, particularly in small rodents. The wires from the implanted electrodes restrain and interfere with the natural behavior of the animals. Consequently, it has been impossible to correlate truly normal behavior with neuronal activity. In addition, it would be ideal if brain activity could be monitored while animals live in a natural and enriched environment. Because of the complexity of such environments with natural hiding places and burrows, recordings of brain activity with wires attached to the animal's skull are impossible. Triangle BioSystems Inc. (TBSI) has overcome these challenges with the design of a miniature, multi‐channel wireless recording system with selectable gain and bandpass filtering. This will give rise to greatly expanded experimental capabilities, and serve as a platform for the development of clinical neural prosthetic devices to treat a variety of ailments including: Alzheimer's disease, epilepsy, and Parkinson's disease.
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