Polyimide-based Microelectrode Arrays Research Articles

Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation.

Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn2+. In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn2+ ions, so that the system can release Mn2+ ions rather than MnCl2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging invivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases.

Sustained elevation of activity of developing neurons grown on polyimide microelectrode arrays (MEA) in response to ultrasound exposure

High frequency ultrasound (HFUS) is an attractive modality for noninvasive clinical applications such as imaging, diagnostics and more recently for stimulation of the central nervous system. The aim of this study was to investigate the modulation in the electrical activity of developing neurons due to the application of HFUS using polyimide based microelectrode array (MEA) that is acoustically transparent in order to allow ultrasound waves to transmit through the substrate and reach the growing neural layer. High frequency tone bursts of ultrasound were applied to a monolayer of developing primary neurons grown on an acoustical transparent polyimide MEA. HFUS was applied to primary neuronal culture at two frequencies (4.4 and 96 MHz) with spatial peak-temporal average intensities of 100 and 10 mW/cm2. Exposures were found to increase the spike rate of neurons in culture up to 20-fold in some cases and induce silent or still developing neurons to fire at a maximum rate of up to three new units per recording microelectrode. Another new observation reported in this study is that the increase in spike rate was sustained for over 6 min post stimulation. Our results also suggest that mechanical and not thermal effects of ultrasound largely mediate the increase in electrical excitability without any discernible spatial pattern or preference across the monolayer for the US parameters used in this study. The accessibility of the disassociated neuronal cultures to stimulation, imaging and recording provides a useful model for investigating the exact mechanisms behind the effect of ultrasound on neuronal excitability.

Precaution for volume conduction in rodent cortical electroencephalography using high-density polyimide-based microelectrode arrays on the skull.

In humans, significant progress has been made to link spatial changes in electroencephalographic (EEG) spectral density, connectivity strength, and phase-amplitude modulation to neurological, physiological, and psychological correlates. In contrast, standard rodent EEG techniques employ only few electrodes, which results in poor spatial resolution. Recently, a technique was developed to overcome this limitation in mice. This technique was based on a polyimide-based microelectrode (PBM) array applied on the mouse skull, maintaining a significant number of electrodes with consistent contact, electrode impedance, and mechanical stability. The present study built on this technique by extending it to rats. Therefore, a similar PBM array, but adapted to rats, was designed and fabricated. In addition, this array was connected to a wireless EEG headstage, allowing recording in untethered, freely moving rats. The advantage of a high-density array relies on the assumption that the signal recorded from the different electrodes is generated from distinct sources, i.e., not volume-conducted. Therefore, the utility and validity of the array were evaluated by determining the level of synchrony between channels due to true synchrony or volume conduction during basal vigilance states and following a subanesthetic dose of ketamine. Although the PBM array allowed recording with high signal quality, under both drug and drug-free conditions, high synchronization existed due to volume conduction between the electrodes even in the higher spectral frequency range. Discrimination existed only between frontally and centrally/distally grouped electrode pairs. Therefore, caution should be used in interpreting spatial data obtained from high-density PBM arrays in rodents.

Massively-Parallel Neuromonitoring and Neurostimulation Rodent Headset With Nanotextured Flexible Microelectrodes

We present a compact wireless headset for simultaneous multi-site neuromonitoring and neurostimulation in the rodent brain. The system comprises flexible-shaft microelectrodes, neural amplifiers, neurostimulators, a digital time-division multiplexer (TDM), a micro-controller and a ZigBee wireless transceiver. The system is built by parallelizing up to four 0.35 μm CMOS integrated circuits (each having 256 neural amplifiers and 64 neurostimulators) to provide a total maximum of 1024 neural amplifiers and 256 neurostimulators. Each bipolar neural amplifier features 54 dB-72 dB adjustable gain, 1 Hz-5 kHz adjustable bandwidth with an input-referred noise of 7.99 μVrms and dissipates 12.9 μW. Each current-mode bipolar neurostimulator generates programmable arbitrary-waveform biphasic current in the range of 20-250 μA and dissipates 2.6 μW in the stand-by mode. Reconfigurability is provided by stacking a set of dedicated mini-PCBs that share a common signaling bus within as small as 22 × 30 × 15 mm³ volume. The system features flexible polyimide-based microelectrode array design that is not brittle and increases pad packing density. Pad nanotexturing by electrodeposition reduces the electrode-tissue interface impedance from an average of 2 MΩ to 30 kΩ at 100 Hz. The rodent headset and the microelectrode array have been experimentally validated in vivo in freely moving rats for two months. We demonstrate 92.8 percent seizure rate reduction by responsive neurostimulation in an acute epilepsy rat model.

A Low-Cost Multi-Electrode Array System for the Simultaneous Acquisition of Electrophysiological Signal and Cellular Morphology

This study aimed to develop a low-cost multichannel neural recording system and multi-electrode array (MEA)chip for a number of research laboratories. Because these elaborate systems may be cost-prohibitive for manylaboratories, the simple fabrication of the MEA chip and the construction of the low-cost recording systemwith cellular image acquisition is presented in this study. The MEA chip is a polyimide-based microelectrodearray with 60 electrodes (5 m thick, 30 m in radius and with 200 m spacing) and is based on the semi-conductor process and advanced microelectro-mechanical system (MEMS) technology. The three-dimensional(3D) structure of the electrodes is fabricated by electroplating, which produces rough textures that increasedthe effective surface area. The

Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording

An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode–tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 µm thick and with a diameter of 16 µm). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode–electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (ΣSSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models.

Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain

The design and testing of a new microelectrode array, the NCTU (National Chiao Tung University) probe, was presented. Evaluation results showed it has good biocompatibility, high signal-to-noise ratio ( SNR: the root mean square of background noise to the average peak-to-peak amplitude of spikes) during chronic neural recordings, and high reusability for electrolytic lesions. The probe was a flexible, polyimide-based microelectrode array with a long shaft (14.9 mm in length) and 16 electrodes (5 μm-thick and 16 μm in radius); its performance in chronic in vivo recordings was examined in rodents. To improve the precision of implantation, a metallic, impact-resistant layer was sandwiched between the polyimide layers to strengthen the probe. The three-dimensional (3D) structure of electrodes fabricated by electroplating produced rough textures that increased the effective surface area. The in vitro impedance of electrodes on the NCTU probe was 2.4 ± 0.52 MΩ at 1 kHz. In addition, post-surgical neural recordings of implanted NCTU probes were conducted for up to 40 days in awake, normally behaving rats. The electrodes on the NCTU probe functioned well and had a high SNR (range: 4–5) with reliable in vivo impedance (<0.7 MΩ). The electrodes were also robust enough to functionally record events, even after the anodal current (30 μA, 10 s) was repeatedly applied for 60 times. With good biocompatibility, high and stable SNR for chronic recording, and high tolerance for electrolytic lesion, the NCTU probe would serve as a useful device in future neuroscience research.

Fabrication and testing of polyimide-based microelectrode arrays for cortical mapping of evoked potentials

Modern microfabrication techniques make it possible to develop microelectrode arrays that may be utilized not only in neurophysiological research but also in the clinic, e.g. in neurosurgery and as elements of neural prostheses. The aim of this study was to test whether a flexible microelectrode array is suitable for recording cortical surface field potentials in rats. Polyimide-based microelectrode arrays were fabricated by utilizing microfabrication techniques e.g. photolithography and magnetron sputter deposition. The present microelectrode array consists of eight platinum microelectrodes (round-shaped, Ø: 200 μm), transmission lines and connector pads sandwiched between two thin layers of biocompatible polyimide. The microelectrode arrays were electrochemically characterized by impedance spectroscopy in physiological saline solution and successfully tested in vivo by conducting acute and chronic measurements of evoked potentials on the surface of rat cortex. The arrays proved excellent flexibility and mechanical strength during handling and implantation onto the surface of cortex. The excellent electrochemical characteristics and stable in vivo recordings with high spatiotemporal resolution highlight the potential of these arrays. The fabrication protocol described here allows implementation of several other neural interfaces with different layouts, material selections or target areas either for recording or stimulation purposes.

Evoked cortical potentials after electrical stimulation of the inner retina in rabbits

Electrical stimulation of the retina using implantable devices may be one possible approach in the treatment of blindness causing progressive degeneration of the outer retina. Stimulation of ganglion cells or fibers could be achieved by epiretinal positioning of a microelectrode array as one component of a retinal prosthesis. Experiments were performed in rabbits to determine whether it is possible to elicit cortical responses with current pulses delivered via an epiretinal placed microelectrode array. Polyimide-based microelectrode arrays with platinum electrodes and silicon-based TiN electrode arrays were implanted and placed onto the retinal surface of healthy pigmented rabbits after vitrectomy. The devices were temporarily fixated under PFCL and connected to constant current sources delivering bi- or monophasic current pulses. Cortical evoked potentials were recorded using subcutaneously implanted EEG electrodes over the visual cortex. The surgical procedures for implantation and fixation could be performed without serious complications. The electrode array could be placed in the area of the visual streak. Cortical potentials could be recorded after pulse train stimulation either with biphasic or with monophasic pulses. At threshold, pulses of 10 microA/phase and 100 micros/phase were necessary for detection of an electrically evoked cortical potential (EEP). Charge delivery at threshold varied between 0.1 and 0.3 nC/phase and charge densities varied between 1 and 12 microC/cm2. The EEP amplitude increased with increasing stimulus strength. The cortical response could be completely blocked with a retrobulbar injection of 4 ml lidocaine 2%. Constant current pulses delivered via Retina Stimulator devices equipped either with platinum electrodes or with TiN electrodes placed onto the inner retinal surface were able to elicit cortical potentials in the rabbit visual system. At threshold the charge delivery seems to be in a safe range.