Data Compression Versus Signal Fidelity Tradeoff in Wired-OR Analog-to-Digital Compressive Arrays for Neural Recording.

Future high-density and high channel count neural interfaces that enable simultaneous recording of tens of thousands of neurons will provide a gateway to study, restore and augment neural functions. However, building such technology within the bit-rate limit and power budget of a fully implantable device is challenging. The wired-OR compressive readout architecture addresses the data deluge challenge of a high channel count neural interface using lossy compression at the analog-to-digital interface. In this article, we assess the suitability of wired-OR for several steps that are important for neuroengineering, including spike detection, spike assignment and waveform estimation. For various wiring configurations of wired-OR and assumptions about the quality of the underlying signal, we characterize the trade-off between compression ratio and task-specific signal fidelity metrics. Using data from 18 large-scale microelectrode array recordings in macaque retina ex vivo, we find that for an event SNR of 7-10, wired-OR correctly detects and assigns at least 80% of the spikes with at least 50× compression. The wired-OR approach also robustly encodes action potential waveform information, enabling downstream processing such as cell-type classification. Finally, we show that by applying an LZ77-based lossless compressor (gzip) to the output of the wired-OR architecture, 1000× compression can be achieved over the baseline recordings.

Tailoring electrode surface charge to achieve discrimination and quantification of chemically similar small molecules with electrochemical aptamers.

Electrochemical biosensors based on structure-switching aptamers offer many advantages because they can operate directly in complex samples and offer the potential to integrate with miniaturized electronics. Unfortunately, these biosensors often suffer from cross-reactivity problems when measuring a target in samples containing other chemically similar molecules, such as precursors or metabolites. While some progress has been made in selecting highly specific aptamers, the discovery of these reagents remains slow and costly. In this work, we demonstrate a novel strategy to distinguish molecules with miniscule difference in chemical composition (such as a single hydroxyl group) - with cross reactive aptamer probes - by tuning the charge state of the surface on which the aptamer probes are immobilized. As an exemplar, we show that our strategy can distinguish between DOX and many structurally similar analytes, including its primary metabolite doxorubicinol (DOXol). We then demonstrate the ability to accurately quantify mixtures of these two molecules based on their differential response to sensors with different surface-charge properties. We believe this methodology is general and can be extended to a broad range of applications.

Accelerated Electron Transfer in Nanostructured Electrodes Improves the Sensitivity of Electrochemical Biosensors.

Electrochemical biosensors hold the exciting potential to integrate molecular detection with signal processing and wireless communication in a miniaturized, low-cost system. However, as electrochemical biosensors are miniaturized to the micrometer scale, their signal-to-noise ratio degrades and reduces their utility for molecular diagnostics. Studies have reported that nanostructured electrodes can improve electrochemical biosensor signals, but since the underlying mechanism remains poorly understood, it remains difficult to fully exploit this phenomenon to improve biosensor performance. In this work, electrochemical aptamer biosensors on nanoporous electrode are optimized to achieve improved sensitivity by tuning pore size, probe density, and electrochemical measurement parameters. Further, a novel mechanism in which electron transfer is physically accelerated within nanostructured electrodes due to reduced charge screening, resulting in enhanced sensitivity is proposed and experimentally validated. In concert with the increased surface areas achieved with this platform, this newly identified effect can yield an up to 24-fold increase in signal level and nearly fourfold lower limit of detection relative to planar electrodes with the same footprint. Importantly, this strategy can be generalized to virtually any electrochemical aptamer sensor, enabling sensitive detection in applications where miniaturization is a necessity, and should likewise prove broadly applicable for improving electrochemical biosensor performance in general.

Going beyond the Debye Length: Overcoming Charge Screening Limitations in Next-Generation Bioelectronic Sensors.

Electronic biosensors are a natural fit for field-deployable diagnostic devices because they can be miniaturized, mass produced, and integrated with circuitry. Unfortunately, progress in the development of such platforms has been hindered by the fact that mobile ions present in biological samples screen charges from the target molecule, greatly reducing sensor sensitivity. Under physiological conditions, the thickness of the resulting electric double layer is less than 1 nm, and it has generally been assumed that electronic detection beyond this distance is virtually impossible. However, a few recently described sensor design strategies seem to defy this conventional wisdom, exploiting the physics of electrical double layers in ways that traditional models do not capture. In the first strategy, charge screening is decreased by constraining the space in which double layers can form. The second strategy uses external stimuli to prevent double layers from reaching equilibrium, thereby effectively reducing charge screening. In this Perspective, we describe these relatively new concepts and offer theoretical insights into mechanisms that may enable electronic biosensing beyond the Debye length. If these concepts can be further developed and translated into practical electronic biosensors, we foresee exciting opportunities for the next generation of diagnostic technologies.

Power-saving design opportunities for wireless intracortical brain-computer interfaces.

The efficacy of wireless intracortical brain-computer interfaces (iBCIs) is limited in part by the number of recording channels, which is constrained by the power budget of the implantable system. Designing wireless iBCIs that provide the high-quality recordings of today's wired neural interfaces may lead to inadvertent over-design at the expense of power consumption and scalability. Here, we report analyses of neural signals collected from experimental iBCI measurements in rhesus macaques and from a clinical-trial participant with implanted 96-channel Utah multielectrode arrays to understand the trade-offs between signal quality and decoder performance. Moreover, we propose an efficient hardware design for clinically viable iBCIs, and suggest that the circuit design parameters of current recording iBCIs can be relaxed considerably without loss of performance. The proposed design may allow for an order-of-magnitude power savings and lead to clinically viable iBCIs with a higher channel count.

A Data-Compressive Wired-OR Readout for Massively Parallel Neural Recording.

Neural interfaces of the future will be used to help restore lost sensory, motor, and other capabilities. However, realizing this futuristic promise requires a major leap forward in how electronic devices interface with the nervous system. Next generation neural interfaces must support parallel recording from tens of thousands of electrodes within the form factor and power budget of a fully implanted device, posing a number of significant engineering challenges. In this paper, we exploit sparsity and diversity of neural signals to achieve simultaneous data compression and channel multiplexing for neural recordings. The architecture uses wired-OR interactions within an array of single-slope A/D converters to obtain massively parallel digitization of neural action potentials. The achieved compression is lossy but effective at retaining the critical samples belonging to action potentials, enabling efficient spike sorting and cell type identification. Simulation results of the architecture using data obtained from primate retina ex-vivo with a 512-channel electrode array show average compression rates up to  âˆ¼ 40× while missing less than 5% of cells. In principle, the techniques presented here could be used to design interfaces to other parts of the nervous system.

Multi-scale ordering in highly stretchable polymer semiconducting films.

Stretchable semiconducting polymers have been developed as a key component to enable skin-like wearable electronics, but their electrical performance must be improved to enable more advanced functionalities. Here, we report a solution processing approach that can achieve multi-scale ordering and alignment of conjugated polymers in stretchable semiconductors to substantially improve their charge carrier mobility. Using solution shearing with a patterned microtrench coating blade, macroscale alignment of conjugated-polymer nanostructures was achieved along the charge transport direction. In conjunction, the nanoscale spatial confinement aligns chain conformation and promotes short-range π-π ordering, substantially reducing the energetic barrier for charge carrier transport. As a result, the mobilities of stretchable conjugated-polymer films have been enhanced up to threefold and maintained under a strain up to 100%. This method may also serve as the basis for large-area manufacturing of stretchable semiconducting films, as demonstrated by the roll-to-roll coating of metre-scale films.

Skin electronics from scalable fabrication of an intrinsically stretchable transistor array.

Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human-machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable-like human skin-would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current-voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.

Investigating Limiting Factors in Stretchable All-Carbon Transistors for Reliable Stretchable Electronics.

Stretchable form factors enable electronic devices to conform to irregular 3D structures, including soft and moving entities. Intrinsically stretchable devices have potential advantages of high surface coverage of active devices, improved durability, and reduced processing costs. This work describes intrinsically stretchable transistors composed of single-walled carbon nanotube (SWNT) electrodes and semiconductors and a dielectric that consists of a nonpolar elastomer. The use of a nonpolar elastomer dielectric enabled hysteresis-free device characteristics. Compared to devices on SiO2 dielectrics, stretchable devices with nonpolar dielectrics showed lower mobility in ambient conditions because of the absence of doping from water. The effect of a SWNT band gap on device characteristics was investigated by using different SWNT sources as the semiconductor. Large-band-gap SWNTs exhibited trap-limited behavior caused by the low capacitance of the dielectric. In contrast, high-current devices based on SWNTs with smaller band gaps were more limited by contact resistance. Of the tested SWNT sources, SWNTs with a maximum diameter of 1.5 nm performed the best, with a mobility of 15.4 cm2/Vs and an on/off ratio >103 for stretchable transistors. Large-band-gap devices showed increased sensitivity to strain because of a pronounced dependence on the dielectric thickness, whereas contact-limited devices showed substantially less strain dependence.

A highly stretchable, transparent, and conductive polymer.

Previous breakthroughs in stretchable electronics stem from strain engineering and nanocomposite approaches. Routes toward intrinsically stretchable molecular materials remain scarce but, if successful, will enable simpler fabrication processes, such as direct printing and coating, mechanically robust devices, and more intimate contact with objects. We report a highly stretchable conducting polymer, realized with a range of enhancers that serve a dual function: (i) they change morphology and (ii) they act as conductivity-enhancing dopants in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). The polymer films exhibit conductivities comparable to the best reported values for PEDOT:PSS, with over 3100 S/cm under 0% strain and over 4100 S/cm under 100% strain-among the highest for reported stretchable conductors. It is highly durable under cyclic loading, with the conductivity maintained at 3600 S/cm even after 1000 cycles to 100% strain. The conductivity remained above 100 S/cm under 600% strain, with a fracture strain of 800%, which is superior to even the best silver nanowire- or carbon nanotube-based stretchable conductor films. The combination of excellent electrical and mechanical properties allowed it to serve as interconnects for field-effect transistor arrays with a device density that is five times higher than typical lithographically patterned wavy interconnects.

Highly stretchable polymer semiconductor films through the nanoconfinement effect.

Soft and conformable wearable electronics require stretchable semiconductors, but existing ones typically sacrifice charge transport mobility to achieve stretchability. We explore a concept based on the nanoconfinement of polymers to substantially improve the stretchability of polymer semiconductors, without affecting charge transport mobility. The increased polymer chain dynamics under nanoconfinement significantly reduces the modulus of the conjugated polymer and largely delays the onset of crack formation under strain. As a result, our fabricated semiconducting film can be stretched up to 100% strain without affecting mobility, retaining values comparable to that of amorphous silicon. The fully stretchable transistors exhibit high biaxial stretchability with minimal change in on current even when poked with a sharp object. We demonstrate a skinlike finger-wearable driver for a light-emitting diode.

A Pixel Pitch-Matched Ultrasound Receiver for 3-D Photoacoustic Imaging With Integrated Delta-Sigma Beamformer in 28-nm UTBB FD-SOI.

This paper presents a pixel pitch-matched readout chip for 3-D photoacoustic (PA) imaging, featuring a dedicated signal conditioning and delta-sigma modulation integrated within a pixel area of 250 µm by 250 µm. The proof-of-concept receiver was implemented in an STMicroelectronics's 28-nm Fully Depleted Silicon On Insulator technology, and interfaces to a 4 × 4 subarray of capacitive micromachined ultrasound transducers (CMUTs). The front-end signal conditioning in each pixel employs a coarse/fine gain tuning architecture to fulfill the 90-dB dynamic range requirement of the application. The employed delta-sigma beamforming architecture obviates the need for area-consuming Nyquist ADCs and thereby enables an efficient in-pixel A/D conversion. The per-pixel switched-capacitor ΔΣ modulator leverages slewing-dominated and area-optimized inverter-based amplifiers. It occupies only 1/4th of the pixel, and its area compares favorably with state-of-the-art designs that offer the same SNR and bandwidth. The modulator's measured peak signal-to-noise-and-distortion ratio is 59.9 dB for a 10-MHz input bandwidth, and it consumes 6.65 mW from a 1-V supply. The overall subarray beamforming approach improves the area per channel by 7.4 times and the single-channel SNR by 8 dB compared to prior art with similar delay resolution and power dissipation. The functionality of the designed chip was evaluated within a PA imaging experiment, employing a flip-chip bonded 2-D CMUT array.

A freely-moving monkey treadmill model.

OBJECTIVE: Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. APPROACH: We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. MAIN RESULTS: Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. SIGNIFICANCE: Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful translation of BMIs to people with paralysis.

A 256 pixel magnetoresistive biosensor microarray in 0.18µm CMOS.

Magnetic nanotechnologies have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors coupled with magnetic nanotags (MNTs) possess great promise as ultra-sensitive biosensors for diagnostics. We report an integrated sensor interface for an array of 256 GMR SV biosensors designed in 0.18 µm CMOS. Arranged like an imager, each of the 16 column level readout channels contains an analog front- end and a compact ΣΔ modulator (0.054 mm2) with 84 dB of dynamic range and an input referred noise of 49 nT/√Hz. Performance is demonstrated through detection of an ovarian cancer biomarker, secretory leukocyte peptidase inhibitor (SLPI), spiked at concentrations as low as 10 fM. This system is designed as a replacement for optical protein microarrays while also providing real-time kinetics monitoring.

Controlling electric dipoles in nanodielectrics and its applications for enabling air-stable n-channel organic transistors.

We present a new method to manipulate the channel charge density of field-effect transistors using dipole-generating self-assembled monolayers (SAMs) with different anchor groups. Our approach maintains an ideal interface between the dipole layers and the semiconductor while changing the built-in electric potential by 0.41-0.50 V. This potential difference can be used to change effectively the electrical properties of nanoelectronic devices. We further demonstrate the application of the SAM dipoles to enable air-stable operation of n-channel organic transistors.

Portable Biomarker Detection with Magnetic Nanotags.

This paper presents a hand-held, portable biosensor platform for quantitative biomarker measurement. By combining magnetic nanoparticle (MNP) tags with giant magnetoresistive (GMR) spin-valve sensors, the hand-held platform achieves highly sensitive (picomolar) and specific biomarker detection in less than 20 minutes. The rapid analysis and potential low cost make this technology ideal for point-of-care (POC) diagnostics. Furthermore, this platform is able to detect multiple biomarkers simultaneously in a single assay, creating a promising diagnostic tool for a vast number of applications.

Matrix-insensitive protein assays push the limits of biosensors in medicine.

Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse clinical samples (for example, serum, urine, cell lysates or saliva) with high sensitivity and large linear dynamic range. A major limitation confounding other technologies is signal distortion that occurs in various matrices due to heterogeneity in ionic strength, pH, temperature and autofluorescence. Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our magnetic nanosensor technology can be directly applied to a variety of settings such as molecular biology, clinical diagnostics and biodefense.