Poster Z16 - Bioinspired electronics for brain-machine interface

Introduction: Bioelectronic devices have been very important both as fundamental research tools and as therapeutic avenues for treating brain disorders and injuries. I will talk about how I drew inspiration from biological systems and art forms to design and develop a series of bio-inspired and art-inspired bioelectronics with distinctive biomedical applications. I have introduced bioinspired neuron-like electronics, a biomimetic brain-machine interface designed such that the key building blocks mimic the subcellular structural features and mechanical properties of neurons. I have developed multifunctional vasculature-like electronic scaffolds that guide and longitudinally track neural migration following brain injury. Moreover, we devised flexible kirigami-inspired electronics that transition from a 2D pattern to a 3D basket-like configuration to enable long-term integration and interrogation of human brain organoids and assembloids. Our studies advance bioelectronics in fundamental studies and therapeutic applications, encompassing neural probes for brain-machine interface, electronic scaffolds for brain repair, and platforms for detecting human genetic diseases and tracking human neural development.

Materials and

Methods: The key fabrication steps are as follows: (1) A Ni sacrificial layer was evaporated onto a Si wafer. (2) The Si wafer was cleaned with oxygen plasma immediately before being spin coated with LOR 3A and baked at 180 °C for 3 min. Positive photoresist was spin coated on the Si wafer and baked at 115 °C for 3 min. The positive photoresist was patterned by PL with a mask aligner and developed. (3) Electron-beam evaporation sequentially deposited Ti and Au, followed by a lift-off step for the Au input/output pads. (4) Negative photoresist SU-8 2000.5 was diluted in cyclopentanone, spin coated on the Si wafer, prebaked sequentially at 65 °C for 1 min and 95 °C for 3 min and patterned by PL. The Si wafer was postbaked sequentially at 65 °C for 1 min and 95 °C for 3 min after PL exposure. (5) The negative photoresist was developed for 2 min, rinsed with isopropanol, dried and hard baked at 180 °C for 1 h. (6) Negative photoresist SU-8 2000.5 was mixed with Lissamine rhodamine B ethylenediamine to afford stable fluorescence labeling. PL was performed by repeating steps 4 and 5 to pattern the bottom SU-8 layer. (7) Steps 2 and 3 were repeated for PL patterning of the interconnect layer. (8) Step 6 was repeated for PL patterning of the top SU-8 layer as the insulating layer of the interconnect lines. The Si wafer was hard baked at 195 °C for 1.5 h.

Results, Conclusions, and Discussions: We developed KiriE, a kirigami-inspired electrophysiology platform, that is flexible, fully suspended in liquid and deformable in 3D. Live-cell imaging, immunohistochemistry and single-cell transcriptomics suggested that KiriE integration does not perturb the morphology or cell composition of organoids. KiriE can chronically record from intact neural organoids over several months and can detect electrophysiological phenotypes associated with disease. Furthermore, KiriE can be used to monitor the circuit connectivity in assembloids in vitro.
The KiriE platform has several advantages compared to prior technologies. First, the 3D basket-like geometry of KiriE is designed for stable integration with intact neural organoids in suspension without the need for insertion, slicing or contacting the substrate. This strategy helps preserve the self-organization of 3D cultures with minimal perturbation. Second, the multimodal culture platform enables long-term medium perfusion and in situ assays, including longitudinal morphology monitoring, live-cell imaging, electrophysiology and optogenetic and pharmacological modulation, without the need to transfer across setups that could perturb development or induce cellular stress. Finally, KiriE detects disease-associated electrophysiological phenotypes and network connectivity in assembloids integrated in situ, which could be applicable to other multicellular systems such as cardiac organoids and cortico–spinal–muscle assembloids. There are a number of limitations of the KiriE platform. For instance, simulating and optimizing the mechanical behavior of KiriE is computationally intensive, thus posing a potential challenge to design more complex geometric patterns. Furthermore, the process of fabricating and assembling KiriE devices requires advanced expertise. Future developments of this platform could incorporate pH, oxygen and neurotransmitter sensors, or micro-LEDs, for localized optogenetic activation. It is also conceivable to design KiriE into complex 3D geometries, such as interconnected baskets, for probing neural transmission in linear or loop assembloids.

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