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Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures. 

Impedance-based protein detection sensors for point-of-care diagnostics require quantitative specificity, as well as rapid or real-time operation. Furthermore, microfabrication of these sensors can lead to the formation of factors suitable for in vivo operation. Herein, we present microfabricated needle-shaped microwell impedance sensors for rapid-sample-to-answer, label-free detection of cytokines, and other biomarkers. The microneedle form factor allows sensors to be utilized in transcutaneous or transvascular sensing applications. In vitro, experimental characterization confirmed sensor specificity and sensitivity to multiple proteins of interest. Mechanical characterization demonstrated sufficient microneedle robustness for transcutaneous insertion, as well as preserved sensor function postinsertion. We further utilized these sensors to carry out real-time in vivo quantification of human interleukin 8 (hIL8) concentration levels in the blood of transgenic mice that endogenously express hIL8. To assess sensor functionality, hIL8 concentration levels in serum samples from the same mice were quantified by ELISA. Excellent agreement between real-time in vivo sensor readings in blood and subsequent ELISA serum assays was observed over multiple transgenic mice expressing hIL8 concentrations from 62 pg/mL to 539 ng/mL.

 

Cell engineering, soft robotics, and wearable electronics often desire soft materials that are easy to deform, self‐heal readily, and can relax stress rapidly. Hydrogels, a type of hydrophilic networks, are such kind of materials that can be made responsive to environmental stimuli. However, conventional hydrogels often suffer from poor stretchability and repairability. Here, hydrogels consisting of boronic ester dynamic covalent bonds in a double network of poly(vinyl alcohol)/boric acid and chitosan are synthesized, which demonstrate extreme stretchability (up to 310 times the original length), instant self‐healing (within 5 s), and reusability and inherent adhesion. Their instant stress relaxation stems from a low activation energy of the boronic ester bond exchange (≤20 kJ mol⁻¹) and contributes to the extreme stretchability and self‐healing behaviors. Various water‐dispersible additives can be readily incorporated in the hydrogels via hand kneading for potential applications such as soft electronics, bio‐signal sensing, and soft artificial joints.

 

Neurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

 

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called “Neural Matrix,” that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.