Implantable Nanoscale Neural Probe for Single-Neuron Intracellular Electrophysiological Analysis in Vivo

This paper reports an implantable nanoscale neural probe (INNP) developed through a layer-by-layer deposition process based on MEMS manufacturing technology and a precision machining technique based on atmospheric microplasma jet, marking the first successful application of solid-state sensing methods for in vivo intracellular electrophysiological analysis. The exposed tip lengths of INNPs are precisely controlled to as low as$\sim 40$nm, with diameters of$\sim 100 \text{nm}$. Electrochemical stability, biocompatibility and minimal invasiveness of INNP during acute implantation were validated. Significant recordings of in vivo intracellular action potentials and ion currents were acquired: The amplitude and half-width of action potential spikes were$\sim 8.31 \text{mV}$and$\sim 1.11 \text{ms}$respectively, with the amplitude of superimposed action potential spikes reaching up to$\sim 70 \text{mV}$, while the amplitudes for fast electrical synaptic currents and postsynaptic currents (PSCs) ranged from tens of pA to several nA, with halfwidths of$\sim 0.10 \text{ms}$and$\sim 2.24 \text{ms}$respectively. Notably, pain stimuli resulted in a significant increase in amplitudes of negative spikes of PSCs along with a significant decrease in half-widths, and triggered an evident generation of positive spikes. This work represents a significant breakthrough in the development of next-generation nanoscale implantable brain-computer interface (BCI) devices aimed at single-neuron intracellular analysis.