Flexible and three-dimensional CMOS-compatible intracerebral neural probes

Abstract: This thesis presents advanced fabrication and assembly technologies for intracerebral neural probes with highly-dense electrode arrangements for neural ensemble recording realized using microelectromechanical systems (MEMS) technology. The work first describes the realization of a novel hybrid neural probe that combines mechanical flexibility with complementary metal oxide semiconductor (CMOS) circuits integrated in the probe tip. The related chapters encompass the component fabrication, chip-level probe assembly using flip-chip bonding, heterogeneous wafer-level integration and probe implantation in brain models. The second aspect of this thesis is the extension of planar neural probes with one- (1D-) or two-dimensional (2D) electrode arrangements into three-dimensional (3D) electrode arrays in a compact, customizable and accurate manner. Finally, the in vivo application of the 3D electrode arrays in a chronic setup is demonstrated.
The CMOS-based, flexible, hybrid neural probe combines flexible, 12.9 μm-thick polyimide cables with 50 µm-thick, silicon-based probe tips that feature a width and length of as little as 100 µm and 3.1 mm, respectively. Using dissolvable polyethylene glycol coatings and silicon-based insertion shuttles for temporary probe stiffening, the minute probe tips can be deeply implanted at speeds as low as 2 µm/s. The probe concept then enables multiplexing of 72 electrodes located on the probe tip to a reduced number of analog signal lines in the polyimide cable, which allows for optimization of the electrode position and unties the channel count of the probe from its geometrical proportions. Furthermore, compared to a rigid, conventional silicon-based neural probe, the approach lowers the volume of the probe shank by a factor of around 4 and its stiffness by roughly three orders of magnitude.
As an alternative to the sequential chip-level assembly of the hybrid probe, a heterogenous wafer-level integration process is described. The process transfers a set of silicon chips from a densely patterned host substrate into a carrier wafer that is equipped with a sacrificial shellac membrane. By embedding the chips in the membrane during processing, chips of arbitrary thickness and shape can be interconnected with highly flexible interconnects of only a few micrometers in thickness. The process is demonstrated with the parallel fabrication of 14 hybrid devices per process run. The devices are composed of 50 µm-thick silicon-based chips interconnected by 10 µm-thick, flexible parylene-C cables. Steps between the planarizing shellac layer and the chips of only 0.63 ± 0.12 µm and a position accuracy of the chips with respect to their target position of around 10 µm enable via and line widths in the cable of 5 and 10 µm, respectively, and contact pads on the chips of around 55 µm in width.
The extension of planar probes into 3D electrode arrays is realized with two variants of a modular stacking technology. Using a silicon component equipped with several alignment features, which is referred to as the stacking module, planar probes of different size and configuration are accurately combined into more complex systems. The proposed stacking modules also define the pitch between individual stacked probes and are realized exemplarily in this work in variants that create values for the probe pitch between 200 and 350 µm (and integer multiples of these values). The specific stacking approach proposed here achieves this design freedom without any modification of the applied fabrication tools, which is usually required in other approaches and would entail additional cost and time for prototype fabrication. It is further demonstrated that the proposed assembly concepts and methods result in accurately defined 3D electrode arrays that meet the expected pitch and an orthogonal orientation with an accuracy of 2 µm and 0.1°, respectively.
Finally, the proposed probe technology was applied for in vivo neural recordings in non-human primates primarily for the study of the pre-supplementary motor area F6. Additional data were collected for the validation of the chronic recording performance of the stacked neural probes. The probes provided single-unit activity on more than 55% of their 64 channels, and operated stably during the validation phase of 42 days, in which the spiking activity of at least 35% of the units remained stable and their functional properties were reproducible. Furthermore, the well-aligned systems created only minor damage to the cortical tissue, as evidenced by Nissl-stained tissue sections

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2022

Classification and Topics

• Keyword: Neuronales Netz ; Nervennetz ; Hirnfunktion ; Modell ; Gehirn-Computer-Schnittstelle ; Mikrosystemtechnik ; MEMS ; Bio-MEMS ; Neuroprothese ; Elektrodenarray ; Sonde ; Gehirn-Computer-Schnittstelle ; Implantat

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: Barz, Falk
• Contributor: Paul, Oliver ; Paul, Oliver ; Lacour, Stéphanie ; Albert-Ludwigs-Universität Freiburg. Fakultät für Angewandte Wissenschaften ; Albert-Ludwigs-Universität Freiburg. Institut für Mikrosystemtechnik ; Albert-Ludwigs-Universität Freiburg. Professur für Materialien der Mikrosystemtechnik

Further information

• DOI: 10.6094/UNIFR/236225
• URN: urn:nbn:de:bsz:25-freidok-2362254
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:47 PM CET