TY  - THES
AU  - Jung, Marie
TI  - 3D neural implants for in vivo applications
VL  - 300
PB  - RWTH Aachen University
VL  - Dissertation
CY  - Jülich
M1  - FZJ-2025-03984
SN  - 978-3-95806-852-0
T2  - Schriften des Forschungszentrums Jülich Reihe Schlüsseltechnologien / Key Technologies
SP  - xvi, 215
PY  - 2025
N1  - Dissertation, RWTH Aachen University, 2025
AB  - 3D microelectrode arrays (MEAs) have become increasingly prominent in the field of brainmachine interfaces (BMI), particularly in the context of studying electrophysiological activity. The interaction between these arrays and neural tissue is influenced not only by the  electrochemical characteristics of the electrodes, but also by the mechanical and spatial characteristics of the recording platform. While 2D MEA are constrained in their capacity to capture the complexity of neural cell networks, conventional 3D platforms continue to necessitate enhancement with regard to resolution and tissue integration. Thus, the objective of this project was to increase the number of penetrating shanks on a 3D MEA thereby increasing the number of electrodes. Flexible polymers were selected as the primary material in order to minimize insertion damage and foreign body reactions (FBR). Two approaches to create a 3D structure out of a 2D design were followed: The electrodes were either printed on a flexible substrate (PiRi) or cut out to obtain kirigami structures (KiRi). The first approach utilizes a highly customizable 3D printing process in combination with template-assisted electrodeposition to fabricate up to 400 μm high 3D microelectrodes on a flexible substrate. The latter approach employs a matched-die forming process, enabling the fabrication of up to 512 electrodes distributed across 128 shanks within a single, flexible device, with shank heights reaching up to 1 mm. In order to test the implants in in vivo applications, it is necessary to take into consideration the characteristics of the design and the surgical methods to be employed. Thus, the objective of the research was to demonstrate the implantation feasibility, biocompatibility, long-term stability, and safety of the fabricated implants by performing a number of electrical and mechanical characterizations of the probes. The advantages inherent in both approaches are evident in the extent and flexibility of customization. This extends to the electrode count and configuration, allowing for the employment of the approaches in a number of different neural applications, such as the retina or the cortex. Healthy and degenerated retinas of rats were used to validate 3D-printed and kirigami electrodes demonstrating how electrophysiological activity differs throughout the 3D space of the retina. In Royal College of Surgeons (RCS) rats, characteristic pathological activity in the form of oscillations was identified and investigated. Following intraretinal insertions, cell stainings were conducted to evaluate the insertion impact, which was found to be low for both implants. Furthermore, in preparation for acute in vivo retinal applications, surgical approaches for 3D retinal implants were conducted in a cadaveric setting, including open-sky surgery as well as pars-plana implantation. Moreover, the KiRis and PiRis were optimized for use in cortical applications. In human brain slices, epileptic seizures were induced by treating them with modified artificial cerebrospinal fluid (aCSF) (high potassium and low magnesium). 3D recordings revealed seizure-like activity in distinct local networks at different time points. Furthermore, kirigami intraneural implants (KiRi)s and 3D printed intraneural implants (PiRi)s were implanted in the cortex of living mice in acute and short-term chronic settings, allowing the capture of spiking activity in the somatosensory cortex upon whisker stimulation and foot-pinches, and of typical local field potentials (LFP)s in the visual cortex upon visual stimuli, respectively. In summary, the present study examines the development, characterization and validation of two novel approaches to the fabrication of 3D flexible penetrating neural implants, PiRi and KiRi. As proven with the in vitro and in vivo studies, these tools offer enhanced capabilities for analyzing neural disorders and disease models where high spatial resolution is required.
LB  - PUB:(DE-HGF)3 ; PUB:(DE-HGF)11
DO  - DOI:10.34734/FZJ-2025-03984
UR  - https://juser.fz-juelich.de/record/1046903
ER  -