Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable.

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Microelectrode array recordings of neuronal activity present significant opportunities for studying the brain with single-cell and spike-time precision. However, challenges in device manufacturing constrain dense multisite recordings to two spatial dimensions, whereas access to the three-dimensional (3D) structure of many brain regions appears to remain a challenge. To overcome this limitation, we present two novel recording modalities of silicon-based devices aimed at establishing 3D functionality. First, we fabricated a dual-side electrode array by patterning recording sites on both the front and back of an implantable microstructure. We found that the majority of single-unit spikes could not be simultaneously detected from both sides, suggesting that in addition to providing higher spatial resolution measurements than that of single-side devices, dual-side arrays also lead to increased recording yield. Second, we obtained recordings along three principal directions with a multilayer array and demonstrated 3D spike source localization within the enclosed measurement space. The large-scale integration of such dual-side and multilayer arrays is expected to provide massively parallel recording capabilities in the brain.

A method for fabricating planar implantable microelectrode arrays was demonstrated using a process that relied on ultra-thin silicon substrates, which ranged in thickness from 25 to 50 μm. The challenge of handling these fragile materials was met via a temporary substrate support mechanism. In order to compensate for putative electrical shielding of extracellular neuronal fields, separately addressable electrode arrays were defined on each side of the silicon device. Deep reactive ion etching was employed to create sharp implantable shafts with lengths of up to 5 mm. The devices were flip-chip bonded onto printed circuit boards (PCBs) by means of an anisotropic conductive adhesive film. This scalable assembly technique enabled three-dimensional (3D) integration through formation of stacks of multiple silicon and PCB layers. Simulations and measurements of microelectrode noise appear to suggest that low impedance surfaces, which could be formed by electrodeposition of gold or other materials, are required to ensure an optimal signal-to-noise ratio as well a low level of interchannel crosstalk.