Subcellular-sized, ultraflexible electrodes form seamless integration with the living brain and afford chronically reliable recording.

Understanding brain functions at the circuit level requires time‐resolved simultaneous measurement of a large number of densely distributed neurons, which remains a great challenge for current neural technologies. In particular, penetrating neural electrodes allow for recording from individual neurons at high temporal resolution, but often have larger dimensions than the biological matrix, which induces significant damage to brain tissues and therefore precludes the high implant density that is necessary for mapping large neuronal populations with full coverage. Here, it is demonstrated that nanofabricated ultraflexible electrode arrays with cross‐sectional areas as small as sub‐10 µm² can overcome this physical limitation. In a mouse model, it is shown that these electrodes record action potentials with high signal‐to‐noise ratio; their dense arrays allow spatial oversampling; and their multiprobe implantation allows for interprobe spacing at 60 µm without eliciting chronic neuronal degeneration. These results present the possibility of minimizing tissue displacement by implanted ultraflexible electrodes for scalable, high‐density electrophysiological recording that is capable of complete neuronal circuitry mapping over chronic time scales.

Objective . Implanted microelectrodes provide a unique means to directly interface with the nervous system but have been limited by the lack of stable functionality. There is growing evidence suggesting that substantially reducing the mechanical rigidity of neural electrodes promotes tissue compatibility and improves their recording stability in both the short- and long-term. However, the miniaturized dimensions and ultraflexibility desired for mitigating tissue responses preclude the probe’s self-supported penetration into the brain tissue. Approach . Here we demonstrate the high-throughput implantation of multi-shank ultraflexible neural electrode arrays with surgical footprints as small as 200 µ m ² in a mouse model. This is achieved by using arrays of tungsten microwires as shuttle devices, and bio-dissolvable adhesive polyethylene glycol (PEG) to temporarily attach a shank onto each microwire. Main results . We show the ability to simultaneously deliver electrode arrays in designed patterns, to adjust the implantation locations of the shanks by need, to target different brain structures, and to control the surgical injury by reducing the microwire diameters to cellular scale. Significance . These results provide a facile implantation method to apply ultraflexible neural probes in scalable neural recording.

The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits, which provides a promising approach for the study of progressive neurophysiological phenomena. Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance. However, lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness. Herein, we report a hybrid probe (Silk-Optrode) consisting of a silk protein optical fiber and multiple flexible microelectrode arrays. The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals. Silk plays an important role due to its high transparency, excellent biocompatibility, and mechanical controllability. Through the hydration of the silk optical fiber, the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue. The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses, surpassing previous work of a similar type. Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions.