Advancing neural interfaces: a framework for the fabrication and characterization of freestanding micro-nanodevices

Freestanding micro-nanodevices stand out as excellent candidates for the next generation of neural interfaces. Their wireless nature, coupled with their subcellular dimensions, promises to enable minimally invasive neuromodulation with high spatial resolution within three-dimensional tissues. Nevertheless, their practical implementation is hindered by technical challenges. Specifically, fabricating and harvesting freestanding devices with subcellular sizes proves exceedingly difficult, and characterizing their functionality in a representative freestanding configuration presents an even greater challenge. In this work, we present a comprehensive framework for fabricating, collecting, and characterizing freestanding micro-nanodevices to advance progress in neural interfaces. We developed three distinct micro-nanofabrication methods tailored for manufacturing freestanding micro-nanodevices with varying characteristics. These methods include a very large-scale integration process for manufacturing and manipulating freestanding microdevices (2-200 µm) with high throughput, a cell-friendly approach utilizing only biocompatible materials and solvents for rapid microdevice production, and a protocol for fabricating and handling freestanding devices with even smaller size scale (200 nm to 3 µm). We subsequently devised an effective approach to rapidly characterize the electrical modulation capabilities of freestanding micro-nanodevices in a cell-like environment, employing artificial bilayer lipid membranes. We showcased this method by studying the variation of bilayer lipid membrane transmembrane potential in response to a light stimulus when sprinkled with organic semiconductor devices. Ultimately, we established an analytical model of the characterization system to translate experimental findings made with bilayer lipid membrane into single cells. By overcoming the technical limitations hindering the fabrication, manipulation, and characterization of freestanding micro-nanodevices, we hope that our research efforts will contribute to accelerating progress in the development of next-generation neural interfaces and unlock the full potential of neuromodulation technologies in fundamental and clinical research.