Electrochemically actuated microelectrodes for minimally invasive peripheral nerve interfaces.

Electrode arrays that interface with peripheral nerves are used in the diagnosis and treatment of neurological disorders; however, they require complex placement surgeries that carry a high risk of nerve injury. Here we leverage recent advances in soft robotic actuators and flexible electronics to develop highly conformable nerve cuffs that combine electrochemically driven conducting-polymer-based soft actuators with low-impedance microelectrodes. Driven with applied voltages as small as a few hundreds of millivolts, these cuffs allow active grasping or wrapping around delicate nerves. We validate this technology using in vivo rat models, showing that the cuffs form and maintain a self-closing and reliable bioelectronic interface with the sciatic nerve of rats without the use of surgical sutures or glues. This seamless integration of soft electrochemical actuators with neurotechnology offers a path towards minimally invasive intraoperative monitoring of nerve activity and high-quality bioelectronic interfaces.

Electrophysiological In Vitro Study of Long-Range Signal Transmission by Astrocytic Networks.

Astrocytes are diverse brain cells that form large networks communicating via gap junctions and chemical transmitters. Despite recent advances, the functions of astrocytic networks in information processing in the brain are not fully understood. In culture, brain slices, and in vivo, astrocytes, and neurons grow in tight association, making it challenging to establish whether signals that spread within astrocytic networks communicate with neuronal groups at distant sites, or whether astrocytes solely respond to their local environments. A multi-electrode array (MEA)-based device called AstroMEA is designed to separate neuronal and astrocytic networks, thus allowing to study the transfer of chemical and/or electrical signals transmitted via astrocytic networks capable of changing neuronal electrical behavior. AstroMEA demonstrates that cortical astrocytic networks can induce a significant upregulation in the firing frequency of neurons in response to a theta-burst charge-balanced biphasic current stimulation (5 pulses of 100 Hz × 10 with 200 ms intervals, 2 s total duration) of a separate neuronal-astrocytic group in the absence of direct neuronal contact. This result corroborates the view of astrocytic networks as a parallel mechanism of signal transmission in the brain that is separate from the neuronal connectome. Translationally, it highlights the importance of astrocytic network protection as a treatment target.

Self-organization of random copolymers to nanopatterns by localized e-beam dosing.

Strategic electron beam (e-beam) irradiation on the surface of an ultrathin (<100 nm) film of polystyrene-poly(methyl methacrylate) (PS-PMMA) random copolymer followed by solvent annealing stimulates a special variety of dewetting, leading to large-area hierarchical nanoscale patterns. For this purpose, initially, a negative (positive) tone of resist PS (PMMA) under weak e-beam exposure is exploited to produce an array of sites composed of cross-linked PS (chain-scissioned PMMA). Subsequently, annealing with the help of a developer solvent engenders dewetted patterns in the exposed zones where PMMA blocks are confined by the blocks of cross-linked PS. The e-beam dosage was systematically varied from 180µC cm-2to 10 000µC cm-2to explore the tone reversal behavior of PMMA on the dewetted patterns. Remarkably, at relatively higher e-beam dosing, both PMMA and PS blocks act as negative tones in the exposed zone. In contrast, the chain scission of PMMA in the periphery of the exposed regions due to scattered secondary electrons caused confined dewetting upon solvent annealing. Such occurrences eventually lead to pattern miniaturization an order of magnitude greater than with conventional thermal or solvent vapor annealed dewetting. Selective removal of PMMA blocks of RCP using a suitable solvent provided an additional 50% reduction in the size of the dewetted features.

Microelectrode Arrays for Simultaneous Electrophysiology and Advanced Optical Microscopy.

Advanced optical imaging techniques address important biological questions in neuroscience, where structures such as synapses are below the resolution limit of a conventional microscope. At the same time, microelectrode arrays (MEAs) are indispensable in understanding the language of neurons. Here, the authors show transparent MEAs capable of recording action potentials from neurons and compatible with advanced microscopy. The electrodes are made of the conducting polymer poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) and are patterned by optical lithography, ensuring scalable fabrication with good control over device parameters. A thickness of 380 nm ensures low enough impedance and >75% transparency throughout the visible part of the spectrum making them suitable for artefact-free recording in the presence of laser illumination. Using primary neuronal cells, the arrays record single units from multiple nearby sources with a signal-to-noise ratio of 7.7 (17.7 dB). Additionally, it is possible to perform calcium (Ca2+) imaging, a measure of neuronal activity, using the novel transparent electrodes. Different biomarkers are imaged through the electrodes using conventional and super-resolution microscopy (SRM), showing no qualitative differences compared to glass substrates. These transparent MEAs pave the way for harnessing the synergy between the superior temporal resolution of electrophysiology and the selectivity and high spatial resolution of optical imaging.

Microdroplet based disposable sensor patch for detection of α-amylase in human blood serum.

Concentration of α-amylase in human serum is a key indicator of various pancreatic ailments and an affordable point-of-care detection of this biomarker can benefit millions suffering from these diseases. In view of this situation, we report the development of a flexible patch-sensor, which simply requires a microdroplet of aqueous starch-FeSO4 solution to detect α-amylase in serum. The detection is achieved through the generation of mixing vortices (~12 rpm) inside the droplet with the help of an imposed thermal gradient. Such vortices due to Marangoni and natural convections are found to be strongest at an optimal temperature difference of ~18 °C - 23 °C across the droplet which in turn facilitate mixing and promote the specific starch-amylase enzymatic reaction. Subsequently, the large (~80%) variation in the electrical resistance across the droplet is correlated to detect the level of the α-amylase in the analyte. Importantly, the sensor can detect even in the limits of 15-110 units/liter. Further, the sensitivity of flexible sensors is ~8.6% higher than the non-flexible one. Interestingly, the sensitivity of the proposed sensor has been nearly three-times than the previously reported optical ones. The results of patch-sensor match very closely with the standard path-lab tests while detecting unknown level of amylase in serum. The prototype has shown significant potential to translate into an affordable device for the real-time detection and easy prognosis of pancreatic disorders.

Reusable nano-BG-FET for point-of-care estimation of ammonia and urea in human urine.

A back-gate-field-effect-transistor (BG-FET) has been developed to selectively detect ammonia and urea. The BG-FET was prepared on a p-type Si substrate with an n-type channel of CdS-TiO2 nanocomposite and poly-methyl methacrylate film as dielectric layer. The reusability of the sensor was ensured by putting it as a cover to a chamber where samples were detected. The BG-FET showed an increase in drain current with the increase in ammonia release from chamber because higher numbers of charge carriers were created when ammonia adsorped on CdS-TiO2 nanostructures. Control experiments suggested that the variation in current-to-voltage response of BG-FET could also be calibrated to measure the activity of a host of other hazardous gases. The lowest concentration of ammonia detected was ∼0.85 ppm with a response time of 30 s at a gate voltage of 0.5 V or less, which were superior than available field effect transistors ammonia sensors. Addition of urease in urine liberated ammonia equivalent to urea content in urine, which could be detected by the proposed BGFET. The urea-urease enzyme catalysis reaction made the sensor specific in detecting the biomarker. The accuracy, sensitivity, and reusability of the device was found to be suitable to develop a point-of-care testing device for ammonia and urea detection.