Habibollahi, Maryam; (2024) Implantable Active Microchannel Electrodes for Highly Selective Control of the Peripheral Nerves. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Bioelectronic medicines have given rise to a new class of therapies that address chronic diseases outside the reach of pharmacological solutions. Neuromodulation of the peripheral nerves, such as vagus nerve stimulation (VNS), has been an accepted therapy for treating a number of neurological, inflammatory and cardiac disorders that traditional medicine falls short of, such as refractory epilepsy and depression, rheumatoid arthritis, diabetes, and heart failure. The benefits of VNS on the post-operation symptoms of heart transplant recipients have recently sparked an interest in using this method to provide a viable solution for improving the patient's quality of life. Typically, a bidirectional neural interface is implemented to electrically stimulate the nerve while collecting valuable data from the neural fibres to help understand the treatment efficacy and optimise its performance. Achieving this task requires a highly selective neural interface, capable of chronic biocompatibility, isolation of the electrode-tissue interface sites, as well as high-performance, isolated electronic circuits to carry out concurrent, efficacious electrical stimulation and neural recording with minimum crosstalk. Of the various types of neural interface systems developed, promising results have been shown for the regenerative neural interfaces, which support injured peripheral nerve fibres to grow through their geometry. In particular, the microchannel neural electrodes have shown a high degree of selectivity and isolation across channels. However, challenges in the development of high-density implants due to passive interconnects have limited the spatial selectivity of regenerative electrodes. Although solutions with active interfaces capable of multiplexing numerous electrode sites on an integrated circuit have been proposed to address the challenges in contact density, additional functionalities are necessary to record high-quality biopotentials in parallel with electrical stimulation. This thesis investigates active peripheral nerve interfaces and proposes regenerative electrodes for recipients of heart transplants. The active microchannel neural interface (MNI) presented is capable of the simultaneous operation of multiple channels for high-voltage stimulation and detection of neural spikes with a sufficiently large signal-to-noise ratio via in-situ amplification. First, a passive interface system was developed and characterised in vitro, describing the fabrication method, tools and processes that were employed to manufacture a biocompatible, miniaturised electrode. To achieve greater selectivity and superior performance in electrical stimulation and neural recording, a bidirectional application-specific integrated circuit (ASIC) was fabricated in 180 nm CMOS technology and combined with the passive electrode structure, forming an active interface. Analog and mixed signal circuit design strategies such as blanking and pole shifting were implemented in parallel with automatic artifact detection to address the challenges in recording action potentials that range from tens to hundreds of uV concurrently with applying stimulus pulses several orders of magnitude larger, resulting in a 41 dB artifact attenuation ratio during concurrent operation. High-voltage integration techniques enabled a 45-V compliance voltage for stimulus pulses ranging up to 124 uA. Meanwhile, low-voltage and low-noise design architectures were implemented to achieve a low-power analog front end that consumes less than 5 uW, with in input-referred noise of 2.74 uVrms, approximately 10% of the minimum expected input signal amplitude. Methods of ASIC post-processing and device integration were optimised to develop a miniaturised, long-lasting active MNI system by achieving gold-coated electrode surfaces and a 78% reduction in the ASIC thickness, coated in a protective, biocompatible polymeric layer. Finally, a comparative analysis of the passive and active systems was carried out, supporting superior performance in peripheral nerve modulation.

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