Biocompatible microchannel scaffold with microwires for recording regenerative peripheral nerve neural spikes

A new process for the fabrication of a microchannel scaffold with microwires for peripheral nerve applications is presented. This microchannel scaffold implemented between the ends of nerves, the axons of which regenerate through microchannel in scaffold and fixed microelectrodes. This device is entirely handcrafted using commercially available materials such as microwires, PDMS film, liquid PDMS, dental cement, and epoxy glue. This device was implemented in the a Lewis rat sciatic nerve to better analyze the electrical signals of regenerated axons. 64-electrode microchannel scaffolds were developed for both peripheral nerve interfacing and peripheral nerve regeneration. The microwires were used for recording electrode to capture neural signal from the regenerated peripheral nerves. To further differentiate the methodology, the new addition of a ribbon cable will facilitate the transmission of the electrical signals. A total of eight devices have been developed, the nerve regeneration were examined four weeks after device implantation

W:Ti flexible transversal electrode array for peripheral nerve stimulation: a feasibility study

The development of hardware for neural interfacing remains a technical challenge. We introduce a flexible, transversal intraneural tungsten:titanium electrode array for acute studies. We characterize the electrochemical properties of this new combination of tungsten and titanium using cyclic voltammetry and electrochemical impedance spectroscopy. With an in-vivo rodent study, we show that the stimulation of peripheral nerves with this electrode array is possible and that more than half of the electrode contacts can yield a stimulation selectivity index of 0.75 or higher at low stimulation currents. This feasibility study paves the way for the development of future cost-effective and easy-to-fabricate neural interfacing electrodes for acute settings, which ultimately can inform the development of technologies that enable bi-directional communication with the human nervous system

Printable microscale interfaces for long-term peripheral nerve mapping and precision control

The nascent field of bioelectronic medicine seeks to decode and modulate peripheral nervous system signals to obtain therapeutic control of targeted end organs and effectors. Current approaches rely heavily on electrode-based devices, but size scalability, material and microfabrication challenges, limited surgical accessibility, and the biomechanically dynamic implantation environment are significant impediments to developing and deploying advanced peripheral interfacing technologies. Here, we present a microscale implantable device – the nanoclip – for chronic interfacing with fine peripheral nerves in small animal models that begins to meet these constraints. We demonstrate the capability to make stable, high-resolution recordings of behaviorally-linked nerve activity over multi-week timescales. In addition, we show that multi-channel, current-steering-based stimulation can achieve a high degree of functionally-relevant modulatory specificity within the small scale of the device. These results highlight the potential of new microscale design and fabrication techniques for the realization of viable implantable devices for long-term peripheral interfacing.https://www.biorxiv.org/node/801468.fullFirst author draf

FLEXIBLE NEURAL INTERFACES FOR RECORDING AND STIMULATION OF PERIPHERAL AND VISCERAL NERVES

Ph.DDOCTOR OF PHILOSOPH

Implantable Transducers for Neurokinesiological Research and Neural Prostheses

The objective of this thesis was to develop a family of advanced electrical and mechanical interfaces to record activity of nerves and muscles during natural movements. These interfaces have applications in basic research and may eventually be refined for used in restoring voluntary control of movement in paralyzed persons. I) A muscle length gauge was designed that is based on piezoelectric crystals attached at the ends of a fluid filled extensible tubing. The in-vivo performance of these gauges was equal to previous length gauge designs. In addition, the ultrasound based design provided for the first time a direct muscle length calibration method. 2) An innovative nerve cuff closing technique was devised that does not reqmre suture closures. The new design uses interdigitated tubes to lock the opening and fix the lumen of a nerve cuff. The cuffs were tested in long-term mammalian implants and their performance matched or surpassed previous closure designs. The nerve cuff was further redesigned to include a more compliant cuff wall and wire electrodes. 3) Floating microelectrodes previously used for central nervous system recordings were adapted for chronic use in the peripheral nervous system. These electrodes proved disappointing in terms of signal quality and longevity. The reasons for failure are thought to be of both electrical and mechanical origin. 4) An innovative silicon micromachined peripheral single unit electrode was designed and tested. In the in-vivo tests, a limited number of recording sites successfully established short-term neural interfaces. However, the quality of the electrode performance, in terms of signal amplitude and ability to discriminate single unit potentials, was insufficient. 5) Using a finite difference model, a numerical simulation of static and dynamic electrical interactions between peripheral axons and microelectrode interfaces was derived. The model consisted of resistive and capacitive elements arranged in a 3-dimensional conductive universe (two spatial dimensions and time). Models of intrafascicular fine wire or silicon based electrodes were used to record simulated propagating action potentials. It was confirmed that electrode movement affected the recorded signal amplitude and that a dielectric layer on a silicon electrode accentuated the recorded potential field. A conducting back plane facing away from axon sources did not have a significant effect on the electrode recording properties. In conclusion, several novel implantable transducers were developed for use in neurokinesiological research. A numerical simulation of the axonal potentials recorded by intrafascicular electrodes helped interpret various shortcomings found in the in-vivo electrode performance. Although not attempted in the present thesis some of the developed technologies may have potential of transferring to clinical neural prostheses applications

Microfluidics and Neural Interfaces Development for the Safe Direct Current Stimulator

Safety of commercial neural implants fundamentally limits its working to the use of charge-balanced, biphasic pulses to interact with target neurons using metal electrodes. Short biphasic pulses are used to avoid toxic electrochemical reactions at the electrode-tissue interfaces. Biphasic pulses are effective at exciting neurons, but quite limited in inhibiting their activity. In contrast, direct current can both excite and inhibit neurons, however it leads to the formation of harmful, Faradaic reactions at the metal electrode/tissue interface. To address this challenge of safety over chronic use, we are developing the Safe Direct Current Stimulator (SDCS) technology, that generates an ionic direct current (iDC) from a biphasic input signal using a network of microfluidic channels and mechanical valves. This rectified iDC is applied to the target neural tissue through an ionically conductive neural interface. A key enabler towards transforming the SDCS concept from a benchtop design to an implantable neural prosthesis is the design of a miniature valve. Several valve architectures and actuation mechanism were studied for the development of the microfluidics in SDCS technology, before settling on the plunger-membrane microvalve design. This thesis characterizes a miniature polydimethylsiloxane (PDMS) based elastomeric normally closed (NC) mechanical valve actuated using a shape-memory alloy (SMA) wire through distinct tests and examines its current capability for iDC delivery. The analysis of the test outputs confirmed the feasibility of using this design for rectifying the charge-balanced alternating current (AC) into iDC. As metal electrodes are unsuitable for delivering iDC to the neural tissue safely, an ionic conductive neural lead is built. These gel-based, PDMS electrodes should be designed within the acceptable pressure limits that a nerve can handle safely. Preliminary experiments were conducted to verify the design and conductivity of the lead. While the results suggest that the lead design maintains the pressure below the maximum limit, its high impedance raises concerns. Although this thesis forms a basis for development of the SDCS device, further experimentation and progress is required for a reliable, safe, chronic, and fully functional device

Development of a novel intracortical electrode for chronic neural recordings

PhD ThesisMicromotion, attributable to the modulus mismatch between the brain and electrode materials, is a fundamental phenomenon contributing to electrode failure for invasive Brain-Machine Interfaces. Spike recording quality from conventional chronic electrode designs deteriorates over the weeks/months post-implantation, in terms of signal amplitude and single unit stability, due to glial cell activation by sustained mechanical trauma. Conventional electrode designs consist of a rigid straight shaft and sharp tip, which can augment mechanical trauma sustained due to micromotion. The sinusoidal probe has been fabricated to reduce micromotion related mechanical trauma. The electrode is microfabricated from flexible materials and has design measures such as a sinusoidal shaft, spheroid tip and a 3D polyimide ball anchor to restrict electrode movement relative to the surrounding brain tissue, thus theoretically minimising micromotion. The electrode was compared to standard microwire electrodes and was shown to have more stable chronic recordings in terms of SNR and LFP power. A longer chronic recording period was achieved with the sinusoidal probe for the first generation. Quantitative histology detecting microglia and astrocytes showed reduced neuronal tissue damage especially for the tip region between 6-24 months chronic indwelling period for the sinusoidal probe. This may be linked to the more stable chronic recordings. This is the first demonstration that electrode designs wholly incorporating micromotion- reducing measures may decrease the magnitude of gliosis, with possible chronic recording longevity enhancement

Conformable transistors for bioelectronics

The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy. However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature. In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit. Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant

Using primary afferent neural activity for predicting limb kinematics in cat

Kinematic state feedback is important for neuroprostheses to generate stable and adaptive movements of an extremity. State information, represented in the firing rates of populations of primary afferent neurons, can be recorded at the level of the dorsal root ganglia (DRG). Previous work in cats showed the feasibility of using DRG recordings to predict the kinematic state of the hind limb using reverse regression. Although accurate decoding results were attained, these methods did not make efficient use of the information embedded in the firing rates of the neural population. This dissertation proposes new methods for decoding limb kinematics from primary afferent firing rates. We present decoding results based on state-space modeling, and show that it is a more principled and more efficient method for decoding the firing rates in an ensemble of primary afferent neurons. In particular, we show that we can extract confounded information from neurons that respond to multiple kinematic parameters, and that including velocity components in the firing rate models significantly increases the accuracy of the decoded trajectory. This thesis further explores the feasibility of decoding primary afferent firing rates in the presence of stimulation artifact generated during functional electrical stimulation. We show that kinematic information extracted from the firing rates of primary afferent neurons can be used in a 'real-time' application as a feedback for control of FES in a neuroprostheses. It provides methods for decoding primary afferent neurons and sets a foundation for further development of closed loop FES control of paralyzed extremities. Although a complete closed loop neuroprosthesis for natural behavior seems far away, the premise of this work argues that an interface at the dorsal root ganglia should be considered as a viable option