A Soft, High-Density Neuroelectronic Array.

Techniques to study brain activities have evolved dramatically, yet tremendous challenges remain in acquiring high-throughput electrophysiological recordings minimally invasively. Here, we develop an integrated neuroelectronic array that is filamentary, high-density and flexible. Specifically, with a design of single-transistor multiplexing and current sensing, the total 256 neuroelectrodes achieve only a 2.3 × 0.3 mm2 area, unprecedentedly on a flexible substrate. A novel single-transistor multiplexing acquisition circuit further reduces noise from the electrodes, decreased the footprint of each pixel, and potentially increased the device lifetime. The filamentary neuroelectronic array also integrates with a rollable contact pad design, allowing the device to be injected through a syringe, enabling potential minimally invasive array delivery. Successful acute auditory experiments in rats validate the ability of the array to record neural signals with high tone decoding accuracy. Together, these results establish soft, high-density neuroelectronic arrays as promising devices for neuroscience research and clinical applications.

Flexible electronic/optoelectronic microsystems with scalable designs for chronic biointegration.

Flexible biocompatible electronic systems that leverage key materials and manufacturing techniques associated with the consumer electronics industry have potential for broad applications in biomedicine and biological research. This study reports scalable approaches to technologies of this type, where thin microscale device components integrate onto flexible polymer substrates in interconnected arrays to provide multimodal, high performance operational capabilities as intimately coupled biointerfaces. Specificially, the material options and engineering schemes summarized here serve as foundations for diverse, heterogeneously integrated systems. Scaled examples incorporate >32,000 silicon microdie and inorganic microscale light-emitting diodes derived from wafer sources distributed at variable pitch spacings and fill factors across large areas on polymer films, at full organ-scale dimensions such as human brain, over ∼150 cm2 In vitro studies and accelerated testing in simulated biofluids, together with theoretical simulations of underlying processes, yield quantitative insights into the key materials aspects. The results suggest an ability of these systems to operate in a biologically safe, stable fashion with projected lifetimes of several decades without leakage currents or reductions in performance. The versatility of these combined concepts suggests applicability to many classes of biointegrated semiconductor devices.

Cortical Decoding of Individual Finger Group Motions Using ReFIT Kalman Filter.

Objective: To date, many brain-machine interface (BMI) studies have developed decoding algorithms for neuroprostheses that provide users with precise control of upper arm reaches with some limited grasping capabilities. However, comparatively few have focused on quantifying the performance of precise finger control. Here we expand upon this work by investigating online control of individual finger groups. Approach: We have developed a novel training manipulandum for non-human primate (NHP) studies to isolate the movements of two specific finger groups: index and middle-ring-pinkie (MRP) fingers. We use this device in combination with the ReFIT (Recalibrated Feedback Intention-Trained) Kalman filter to decode the position of each finger group during a single degree of freedom task in two rhesus macaques with Utah arrays in motor cortex. The ReFIT Kalman filter uses a two-stage training approach that improves online control of upper arm tasks with substantial reductions in orbiting time, thus making it a logical first choice for precise finger control. Results: Both animals were able to reliably acquire fingertip targets with both index and MRP fingers, which they did in blocks of finger group specific trials. Decoding from motor signals online, the ReFIT Kalman filter reliably outperformed the standard Kalman filter, measured by bit rate, across all tested finger groups and movements by 31.0 and 35.2%. These decoders were robust when the manipulandum was removed during online control. While index finger movements and middle-ring-pinkie finger movements could be differentiated from each other with 81.7% accuracy across both subjects, the linear Kalman filter was not sufficient for decoding both finger groups together due to significant unwanted movement in the stationary finger, potentially due to co-contraction. Significance: To our knowledge, this is the first systematic and biomimetic separation of digits for continuous online decoding in a NHP as well as the first demonstration of the ReFIT Kalman filter improving the performance of precise finger decoding. These results suggest that novel nonlinear approaches, apparently not necessary for center out reaches or gross hand motions, may be necessary to achieve independent and precise control of individual fingers.

Conductively coupled flexible silicon electronic systems for chronic neural electrophysiology.

Materials and structures that enable long-term, intimate coupling of flexible electronic devices to biological systems are critically important to the development of advanced biomedical implants for biological research and for clinical medicine. By comparison with simple interfaces based on arrays of passive electrodes, the active electronics in such systems provide powerful and sometimes essential levels of functionality; they also demand long-lived, perfect biofluid barriers to prevent corrosive degradation of the active materials and electrical damage to the adjacent tissues. Recent reports describe strategies that enable relevant capabilities in flexible electronic systems, but only for capacitively coupled interfaces. Here, we introduce schemes that exploit patterns of highly doped silicon nanomembranes chemically bonded to thin, thermally grown layers of SiO2 as leakage-free, chronically stable, conductively coupled interfaces. The results can naturally support high-performance, flexible silicon electronic systems capable of amplified sensing and active matrix multiplexing in biopotential recording and in stimulation via Faradaic charge injection. Systematic in vitro studies highlight key considerations in the materials science and the electrical designs for high-fidelity, chronic operation. The results provide a versatile route to biointegrated forms of flexible electronics that can incorporate the most advanced silicon device technologies with broad applications in electrical interfaces to the brain and to other organ systems.

Quantitative simulation of extracellular single unit recording from the surface of cortex.

OBJECTIVE: Neural recording is important for a wide variety of clinical applications. Until recently, recording from the surface of the brain, even when using micro-electrocorticography (µECoG) arrays, was not thought to enable recording from individual neurons. Recent results suggest that when the surface electrode contact size is sufficiently small, it may be possible to record single neurons from the brain's surface. In this study, we use computational techniques to investigate the ability of surface electrodes to record the activity of single neurons. APPROACH: The computational model included the rat head, µECoG electrode, two existing multi-compartmental neuron models, and a novel multi-compartmental neuron model derived from patch clamp experiments in layer 1 of the cortex. MAIN RESULTS: Using these models, we reproduced single neuron recordings from µECoG arrays, and elucidated their possible source. The model resembles the experimental data when spikes originate from layer 1 neurons that are less than 60 µm from the cortical surface. We further used the model to explore the design space for surface electrodes. Although this model does not include biological or thermal noise, the results indicate the electrode contact area should be 100 µm2 or smaller to maintain a detectable waveform amplitude. Furthermore, the model shows the width of lateral insulation could be reduced, which may reduce scar formation, while retaining 95% of signal amplitude. SIGNIFICANCE: Overall, the model suggests single-unit surface recording is limited to neurons in layer 1 and further improvement in electrode design is needed.