System-level integration towards hybrid flexible implantable neuroelectronic interfaces

This thesis presents significant advancements in the field of brain-computer interfaces (BCIs) through the development of hybrid active implantable neuroelectronic systems. It highlights the critical need to overcome the mechanical mismatch between rigid interfaces and the soft, dynamic nature of brain tissue, which has historically limited the longevity and efficacy of implantable devices. This is addressed using soft polymer-based interfaces which are largely electrically passive and limited. The challenge of limited functionality in soft, polymer-based neural interfaces can be overcome by integrating active electronics directly onto these soft substrates. This hybrid approach combines the biocompatible properties of soft materials with the processing power of advanced CMOS electronics. The integration process can be scaled to create large-area implants suitable for human applications with the scope to achieve closed-loop neuromodulation in translational studies. To achieve this, the work focuses on three key areas: scaling soft, conformable neural interfaces, integrating active electronics with soft implants, and incorporating wireless communication systems. Firstly, the research investigates the electrical properties of these soft interfaces, establishing a model for designing large-scale human-sized implants. This model considers factors like electrode size and current density to optimize stimulation effects. Validation in large animal models was achieved using first-of-a-kind large soft elastomeric implants with sizes reaching 10-12 cm. Demonstrating the functionality of these implants using spinal cord stimulation for hemodynamic regulation, we achieved > 50 mm of Hg increases in blood pressure. Secondly, this thesis addresses the challenge of integrating advanced CMOS-based electronics with soft interfaces. A novel flip-chip bonding process is developed, enabling the seamless integration of commercial integrated circuits such as a multiplexer with a soft electrode array demonstrating active functionality \textit{in vivo} that can be extended to more complex application-specific circuits. This paves the way for miniaturized, flexible interfaces with complex closed-loop functionalities. Finally, to enhance data transmission and reduce power consumption, backscatter communication is explored. Backscatter offers a 20-fold reduction in power consumption compared to traditional Bluetooth Low Energy (BLE) modules, and the first \textit{in vivo} validation of a BLE-compatible backscatter uplink for transmitting local field potentials is achieved. Additionally, a preliminary evaluation of thin-film gold-based flexible antennas for implantable applications is presented. These antennas demonstrate the potential for creating fully implantable, monolithic flexible neural interfaces. With such integrated electronics, antennas, and potentially wireless power transfer capabilities, such hybrid soft neuroelectronic systems can be scaled up for translation