The ultra-thin, minimally invasive surface electrode array NeuroWeb for probing neural activity.

Electrophysiological recording technologies can provide valuable insights into the functioning of the central and peripheral nervous systems. Surface electrode arrays made of soft materials or implantable multi-electrode arrays with high electrode density have been widely utilized as neural probes. However, neither of these probe types can simultaneously achieve minimal invasiveness and robust neural signal detection. Here, we present an ultra-thin, minimally invasive neural probe (the "NeuroWeb") consisting of hexagonal boron nitride and graphene, which leverages the strengths of both surface electrode array and implantable multi-electrode array. The NeuroWeb open lattice structure with a total thickness of 100 nm demonstrates high flexibility and strong adhesion, establishing a conformal and tight interface with the uneven mouse brain surface. In vivo electrophysiological recordings show that NeuroWeb detects stable single-unit activity of neurons with high signal-to-noise ratios. Furthermore, we investigate neural interactions between the somatosensory cortex and the cerebellum using transparent dual NeuroWebs and optical stimulation, and measure the times of neural signal transmission between the brain regions depending on the pathway. Therefore, NeuroWeb can be expected to pave the way for understanding complex brain networks with optical and electrophysiological mapping of the brain.

Stitching Flexible Electronics into the Brain.

Understanding complex neuronal networks requires monitoring long-term neuronal activity in various regions of the brain. Significant progress has been made in multisite implantations of well-designed probes, such as multisite implantation of Si-based and polymer-based probes. However, these multiprobe strategies are limited by the sizes and weights of interfaces to the multiple probes and the inability to track the activity of the same neurons and changes in neuronal activity over longer time periods. Here, a long single flexible probe that can be implanted by stitching into multiple regions of the mouse brain and subsequently transmit chronically stable neuronal signals from the multiple sites via a single low-mass interface is reported. The probe at four different sites is implemented using a glass capillary needle or two sites using an ultrathin metal needle. In vitro tests in brain-mimicking hydrogel show that multisite probe implantations achieve a high connection yield of >86%. In vivo histological images at each site of probes, implanted by stitching using either glass capillary or ultrathin metal insertion needles exhibit seamless tissue-probe interfaces with negligible chronic immune response. In addition, electrophysiology studies demonstrate the ability to track single neuron activities at every injection site with chronic stability over at least one month. Notably, the measured spike amplitudes and signal-to-noise ratios at different implantation sites show no statistically significant differences. Multisite stitching implantation of flexible electronics in the brain opens up new opportunities for both fundamental neuroscience research and electrotherapeutic applications.

All-Tissue-like Multifunctional Optoelectronic Mesh for Deep-Brain Modulation and Mapping.

The development of a multifunctional device that achieves optogenetic neuromodulation and extracellular neural mapping is crucial for understanding neural circuits and treating brain disorders. Although various devices have been explored for this purpose, it is challenging to develop biocompatible optogenetic devices that can seamlessly interface with the brain. Herein, we present a tissue-like optoelectronic mesh with a compact interface that enables not only high spatial and temporal resolutions of optical stimulation but also the sampling of optically evoked neural activities. An in vitro experiment in hydrogel showed efficient light propagation through a freestanding SU-8 waveguide that was integrated with flexible mesh electronics. Additionally, an in vivo implantation of the tissue-like optoelectronic mesh in the brain of a live transgenic mouse enabled the sampling of optically evoked neural signals. Therefore, this multifunctional device can aid the chronic modulation of neural circuits and behavior studies for developing biological and therapeutic applications.