A BIOCOMPATIBLE GLASS-ENCAPSULATED TRIAXIAL FORCE SENSOR FOR IMPLANTABLE TACTILE SENSING APPLICATIONS.

This paper reports a microfabricated triaxial capacitive force sensor. The sensor is fully encapsulated with inert and biocompatible glass (fused silica) material. The sensor comprises two glass plates, on which four capacitors are located. The sensor is intended for subdermal implantation in fingertips and palms and providing tactile sensing capabilities for patients with paralyzed hands. Additional electronic components, such as passives and IC chips, can also be integrated with the sensor in a hermetic glass package to achieve an implantable tactile sensing system. Through attachment to a human palm, the sensor has been shown to respond appropriately to typical hand actions, such as squeezing or picking up a bottle.

An implantable, wireless, battery-free system for tactile pressure sensing.

The sense of touch is critical to dexterous use of the hands and thus an essential component of efforts to restore hand function after amputation or paralysis. Prosthetic systems have addressed this goal with wearable tactile sensors. However, such wearable sensors are suboptimal for neuroprosthetic systems designed to reanimate a patient's own paralyzed hand. Here, we developed an implantable tactile sensing system intended for subdermal placement. The system is composed of a microfabricated capacitive pressure sensor, a custom integrated circuit supporting wireless powering and data transmission, and a laser-fused hermetic silica package. The miniature device was validated through simulations, benchtop assessment, and testing in a primate hand. The sensor implanted in the fingertip accurately measured applied skin forces with a resolution of 4.3 mN. The output from this novel sensor could be encoded in the brain with microstimulation to provide tactile feedback. More broadly, the materials, system design, and fabrication approach establish new foundational capabilities for various applications of implantable sensing systems.

An implantable wireless tactile sensing system.

The sense of touch is critical to dexterous use of the hands and thus an essential component to efforts to restore hand function after amputation or paralysis. Prosthetic systems have focused on wearable tactile sensors. But wearable sensors are suboptimal for neuroprosthetic systems designed to reanimate a patient's own paralyzed hand. Here, we developed an implantable tactile sensing system intended for subdermal placement. The system is composed of a microfabricated capacitive force sensor, a custom integrated circuit supporting wireless powering and data transmission, and a laser-fused hermetic silica package. The miniature device was validated through simulations, benchtop testing, and ex vivo testing in a primate hand. The sensor implanted in the fingertip accurately measured skin forces with a resolution of 4.3 mN. The output from this novel sensor could be encoded in the brain with microstimulation to provide tactile feedback. More broadly, the materials, system design, and fabrication approach establish new foundational capabilities for various applications of implantable sensing systems.

A 10.8 µW Neural Signal Recorder and Processor With Unsupervised Analog Classifier for Spike Sorting.

Implantable brain machine interfaces for treatment of neurological disorders require on-chip, real-time signal processing of action potentials (spikes). In this work, we present the first spike sorting SoC with integrated neural recording front-end and analog unsupervised classifier. The event-driven, low power spike sorter features a novel hardware-optimized, K-means based algorithm that effectively eliminates duplicate clusters and is implemented using a novel clockless and ADC-less analog architecture. The 1.4 mm2 chip is fabricated in a 180-nm CMOS SOI process. The analog front-end achieves a 3.3 µVrms noise floor over the spike bandwidth (400 - 5000 Hz) and consumes 6.42 µW from a 1.5 V supply. The analog spike sorter consumes 4.35 µW and achieves 93.2% classification accuracy on a widely used synthetic test dataset. In addition, higher than 93% agreement between the chip classification result and that of a standard spike sorting software is observed using pre-recorded real neural signals. Simulations of the implemented spike sorter show robust performance under process-voltage-temperature variations.

Learning active sensing strategies using a sensory brain-machine interface.

Diverse organisms, from insects to humans, actively seek out sensory information that best informs goal-directed actions. Efficient active sensing requires congruity between sensor properties and motor strategies, as typically honed through evolution. However, it has been difficult to study whether active sensing strategies are also modified with experience. Here, we used a sensory brain-machine interface paradigm, permitting both free behavior and experimental manipulation of sensory feedback, to study learning of active sensing strategies. Rats performed a searching task in a water maze in which the only task-relevant sensory feedback was provided by intracortical microstimulation (ICMS) encoding egocentric bearing to the hidden goal location. The rats learned to use the artificial goal direction sense to find the platform with the same proficiency as natural vision. Manipulation of the acuity of the ICMS feedback revealed distinct search strategy adaptations. Using an optimization model, the different strategies were found to minimize the effort required to extract the most salient task-relevant information. The results demonstrate that animals can adjust motor strategies to match novel sensor properties for efficient goal-directed behavior.

Hippocampal gamma-slow oscillation coupling in macaques during sedation and sleep.

Behavioral and neurophysiological evidence suggests that the slow (≤1 Hz) oscillation (SO) during sleep plays a role in consolidating hippocampal (HIPP)-dependent memories. The effects of the SO on HIPP activity have been studied in rodents and cats both during natural sleep and during anesthetic administration titrated to mimic sleep-like slow rhythms. In this study, we sought to document these effects in primates. First, HIPP field potentials were recorded during ketamine-dexmedetomidine sedation and during natural sleep in three rhesus macaques. Sedation produced regionally-specific slow and gamma (∼40 Hz) oscillations with strong coupling between the SO phase and gamma amplitude. These same features were seen in slow-wave sleep (SWS), but the coupling was weaker and the coupled gamma oscillation had a higher frequency (∼70 Hz) during SWS. Second, electrical stimuli were delivered to HIPP afferents in the parahippocampal gyrus (PHG) during sedation to assess the effects of sleep-like SO on excitability. Gamma bursts after the peak of SO cycles corresponded to periods of increased gain of monosynaptic connections between the PHG and HIPP. However, the two PHG-HIPP connectivity gains during sedation were both substantially lower than when the animal was awake. We conclude that the SO is correlated with rhythmic excitation and inhibition of the PHG-HIPP network, modulating connectivity and gamma generators intrinsic to this network. Ketamine-dexmedetomidine sedation produces a similar effect, but with a decreased contribution of the PHG to HIPP activity and gamma generation.

Design of a Closed-Loop, Bidirectional Brain Machine Interface System With Energy Efficient Neural Feature Extraction and PID Control.

This paper presents a bidirectional brain machine interface (BMI) microsystem designed for closed-loop neuroscience research, especially experiments in freely behaving animals. The system-on-chip (SoC) consists of 16-channel neural recording front-ends, neural feature extraction units, 16-channel programmable neural stimulator back-ends, in-channel programmable closed-loop controllers, global analog-digital converters (ADC), and peripheral circuits. The proposed neural feature extraction units includes 1) an ultra low-power neural energy extraction unit enabling a 64-step natural logarithmic domain frequency tuning, and 2) a current-mode action potential (AP) detection unit with time-amplitude window discriminator. A programmable proportional-integral-derivative (PID) controller has been integrated in each channel enabling a various of closed-loop operations. The implemented ADCs include a 10-bit voltage-mode successive approximation register (SAR) ADC for the digitization of the neural feature outputs and/or local field potential (LFP) outputs, and an 8-bit current-mode SAR ADC for the digitization of the action potential outputs. The multi-mode stimulator can be programmed to perform monopolar or bipolar, symmetrical or asymmetrical charge balanced stimulation with a maximum current of 4 mA in an arbitrary channel configuration. The chip has been fabricated in 0.18 µ m CMOS technology, occupying a silicon area of 3.7 mm 2. The chip dissipates 56 µW/ch on average. General purpose low-power microcontroller with Bluetooth module are integrated in the system to provide wireless link and SoC configuration. Methods, circuit techniques and system topology proposed in this work can be used in a wide range of relevant neurophysiology research, especially closed-loop BMI experiments.

A Fully Integrated Wireless Compressed Sensing Neural Signal Acquisition System for Chronic Recording and Brain Machine Interface.

Reliable, multi-channel neural recording is critical to the neuroscience research and clinical treatment. However, most hardware development of fully integrated, multi-channel wireless neural recorders to-date, is still in the proof-of-concept stage. To be ready for practical use, the trade-offs between performance, power consumption, device size, robustness, and compatibility need to be carefully taken into account. This paper presents an optimized wireless compressed sensing neural signal recording system. The system takes advantages of both custom integrated circuits and universal compatible wireless solutions. The proposed system includes an implantable wireless system-on-chip (SoC) and an external wireless relay. The SoC integrates 16-channel low-noise neural amplifiers, programmable filters and gain stages, a SAR ADC, a real-time compressed sensing module, and a near field wireless power and data transmission link. The external relay integrates a 32 bit low-power microcontroller with Bluetooth 4.0 wireless module, a programming interface, and an inductive charging unit. The SoC achieves high signal recording quality with minimized power consumption, while reducing the risk of infection from through-skin connectors. The external relay maximizes the compatibility and programmability. The proposed compressed sensing module is highly configurable, featuring a SNDR of 9.78 dB with a compression ratio of 8×. The SoC has been fabricated in a 180 nm standard CMOS technology, occupying 2.1 mm × 0.6 mm silicon area. A pre-implantable system has been assembled to demonstrate the proposed paradigm. The developed system has been successfully used for long-term wireless neural recording in freely behaving rhesus monkey.

The effects of acute cortical somatosensory deafferentation on grip force control.

Grip force control involves mechanisms to adjust to unpredictable and predictable changes in loads during manual manipulation. Somatosensory feedback is critical not just to reactive, feedback control but also to updating the internal representations needed for proactive, feedforward control. The role of primary somatosensory cortex (S1) in these control strategies is not well established. Here we investigated grip force control in a rare case of acute central deafferentation following resection of S1. The subject had complete loss of somatosensation in the right arm without any deficit in muscle strength or reflexes. In the first task, the subject was asked to maintain a constant grip force with and without visual feedback. The subject was able to attain the target force with visual feedback but not maintain that force for more than a few seconds after visual feedback was removed. In the second task, the subject was asked to grip and move an instrumented object. The induced acceleration-dependent loads were countered by adjustments in grip force. Both amplitude and timing of the grip force modulation were not affected by deafferentation. The dissociation of these effects demonstrates the differential contribution of S1 to the mechanisms of grip force control.

Somatosensory encoding with cuneate nucleus microstimulation: Detection of artificial stimuli.

The sense of touch and proprioception are critical to movement control. After spinal cord injury, these senses may be restored with direct, electrical microstimulation of the brain as part of a complete sensorimotor neuroprosthesis. The present study was designed to test, in part, the hypothesis that the cuneate nucleus (CN) of the brainstem is a suitable site to encode somatosensory information. Two rhesus macaques were implanted with microelectrode arrays providing chronic access to the CN. The monkeys were trained on an active touch oddity task to detect vibrotactile stimuli. When the vibrotactile stimuli were replaced with electrical stimuli delivered to the CN, initial detection probabilities were near chance. Detection performance improved over time, reaching a plateau after about 10 daily sessions. At plateau performance, the monkeys exhibited detection probabilities that were 68-80% higher than the chance probability. Finally, detection probability was quantified as a function of stimulus amplitude. The resulting psychometric curve showed a detection threshold of 45 µA for 100-Hz stimulus trains. These behavioral data are the first to show that artificial CN activation is sufficient for perception. The results are consistent with our hypothesis and motivate future tests of the CN as a somatosensory encoding site.

The PennBMBI: Design of a General Purpose Wireless Brain-Machine-Brain Interface System.

In this paper, a general purpose wireless Brain-Machine-Brain Interface (BMBI) system is presented. The system integrates four battery-powered wireless devices for the implementation of a closed-loop sensorimotor neural interface, including a neural signal analyzer, a neural stimulator, a body-area sensor node and a graphic user interface implemented on the PC end. The neural signal analyzer features a four channel analog front-end with configurable bandpass filter, gain stage, digitization resolution, and sampling rate. The target frequency band is configurable from EEG to single unit activity. A noise floor of 4.69 µVrms is achieved over a bandwidth from 0.05 Hz to 6 kHz. Digital filtering, neural feature extraction, spike detection, sensing-stimulating modulation, and compressed sensing measurement are realized in a central processing unit integrated in the analyzer. A flash memory card is also integrated in the analyzer. A 2-channel neural stimulator with a compliance voltage up to ± 12 V is included. The stimulator is capable of delivering unipolar or bipolar, charge-balanced current pulses with programmable pulse shape, amplitude, width, pulse train frequency and latency. A multi-functional sensor node, including an accelerometer, a temperature sensor, a flexiforce sensor and a general sensor extension port has been designed. A computer interface is designed to monitor, control and configure all aforementioned devices via a wireless link, according to a custom designed communication protocol. Wireless closed-loop operation between the sensory devices, neural stimulator, and neural signal analyzer can be configured. The proposed system was designed to link two sites in the brain, bridging the brain and external hardware, as well as creating new sensory and motor pathways for clinical practice. Bench test and in vivo experiments are performed to verify the functions and performances of the system.

Tilted pillars on wrinkled elastomers as a reversibly tunable optical window.

We demonstrate the design and fabrication of tilted micropillar arrays on wrinkled elastomeric poly(dimethylsiloxane) as a reversibly switchable optical window. Upon re-stretching the as-prepared (opaque) film to the original pre-strain, the grating color is restored and ∼ 30% transmittance is recovered. Further stretching beyond the pre-strain makes the film more transparent. This process is fully reversible and repeatable for many cycles.

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo.

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

Flexible organic electronics for use in neural sensing.

Recent research in brain-machine interfaces and devices to treat neurological disease indicate that important network activity exists at temporal and spatial scales beyond the resolution of existing implantable devices. High density, active electrode arrays hold great promise in enabling high-resolution interface with the brain to access and influence this network activity. Integrating flexible electronic devices directly at the neural interface can enable thousands of multiplexed electrodes to be connected using many fewer wires. Active electrode arrays have been demonstrated using flexible, inorganic silicon transistors. However, these approaches may be limited in their ability to be cost-effectively scaled to large array sizes (8 × 8 cm). Here we show amplifiers built using flexible organic transistors with sufficient performance for neural signal recording. We also demonstrate a pathway for a fully integrated, amplified and multiplexed electrode array built from these devices.

Dual-tier thin film polymer polarization imaging sensor.

Traditional imaging systems capture and replicate the imaged environment in terms of color and intensity. One important property of light, which the human eye is blind to and is ignored by traditional imaging systems, is polarization. In this paper we present a novel, low power imaging sensor capable of recording the optical properties of partially linearly polarized light in real-time. The imaging sensor combines polymer polarization filters with a CMOS image sensor in order to compute the first three Stokes parameters at the focal plane. The imaging array contains 100 x 100 pixels and consumes 48 mW at 30 fps.

1.05-GHz CMOS oscillator based on lateral- field-excited piezoelectric AlN contour- mode MEMS resonators.

This paper reports on the first demonstration of a 1.05-GHz microelectromechanical (MEMS) oscillator based on lateral-field-excited (LFE) piezoelectric AlN contourmode resonators. The oscillator shows a phase noise level of -81 dBc/Hz at 1-kHz offset frequency and a phase noise floor of -146 dBc/Hz, which satisfies the global system for mobile communications (GSM) requirements for ultra-high frequency (UHF) local oscillators (LO). The circuit was fabricated in the AMI semiconductor (AMIS) 0.5-microm complementary metaloxide- semiconductor (CMOS) process, with the oscillator core consuming only 3.5 mW DC power. The device overall performance has the best figure-of-merit (FoM) when compared with other gigahertz oscillators that are based on film bulk acoustic resonator (FBAR), surface acoustic wave (SAW), and CMOS on-chip inductor and capacitor (CMOS LC) technologies. A simple 2-mask process was used to fabricate the LFE AlN resonators operating between 843 MHz and 1.64 GHz with simultaneously high Q (up to 2,200) and kt 2 (up to 1.2%). This process further relaxes manufacturing tolerances and improves yield. All these advantages make these devices suitable for post-CMOS integrated on-chip direct gigahertz frequency synthesis in reconfigurable multiband wireless communications.

Fabrication of a dual-tier thin film micropolarization array.

A thin film polarization filter has been patterned and etched using reactive ion etching (RIE) in order to create 8 by 8 microns square periodic structures. The micropolarization filters retain the original extinction ratios of the unpatterned thin film. The measured extinction ratios on the micropolarization filters are approximately 1000 in the blue and green visible spectrum and approximately 100 in the red spectrum. Various gas combinations for RIE have been explored in order to determine the right concentration mix of CF(4) and O(2) that gives optimum etching rate, in terms of speed and under-etching. Theoretical explanation for the optimum etching rate has also been presented. In addition, anisotropic etching with 1 microm under cutting of a 10 microm thick film has been achieved. Experimental results for the patterned structures under polarized light are presented. The array of micropolarizers will be deposited on top of a custom made CMOS imaging sensor in order to compute the first three Stokes parameters in real time.