Fully integrated silicon probes for high-density recording of neural activity

Abstract

Summary Paragraph Sensory, motor, and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures1,2. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution but from only a few dozen neurons per shank. Optical Ca2+ imaging3–5 offers more coverage but lacks the temporal resolution to reliably distinguish individual spikes and does not measure local field potentials. To date, no technology compatible with unrestrained animals has combined high spatiotemporal resolution with large volume coverage. To satisfy this need, we designed, fabricated, and tested a new silicon probe called Neuropixels. Each probe has 384 recording channels that can programmably address 960 CMOS processing-compatible low-impedance TiN6 sites that tile a single 10 mm long, 70x20 µm cross section shank. The 6x9 mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed, and digitized on the base, allowing noise-free digital data transmission directly from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were simultaneously recorded from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed recording large populations of neurons from multiple brain structures in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens the path to record brain-wide neural activity during behavior.

Tissue-like Neural Probes for Understanding and Modulating the Brain

“…54 Due to the technical challenges of in vivo intracellular patch clamp that is only applicable to acute recordings in anesthetized animals, 55,56 most intracerebral electrophysiology studies employ single-neuron level extracellular monitoring of neuronal activity with a focus on improving chronic stability 33 and increasing the throughput of simultaneously measured neurons. 7,32 …”

“…31 The external region with I/O pads is injected onto a thin polymer film that allows direct ‘by-hand’ insertion and clamping of the I/O pads into a ZIF connector pre-mounted on a printed circuit board (PCB, Figure 3B). The PCB is fixed onto the animal’s skull as a compact and low mass interface (1.3 g and 0.65 g, with and without the detachable amplifier connected, respectively, 32 compared to at least 3 g for Michigan array silicon probes 7,57 ) for removable attachment of measurement electronics during chronic recording from awake restrained or free-moving animals (Figure 3C). In addition to facilitating adoption of the mesh electronics by nonexpert laboratories, the plug-and-play interface has also enabled implementation of sterilization protocols necessary for human surgical environments.…”

“…1 In comparison, silicon microelectrode arrays have overall probe sizes that are always >4 times larger than a single neuron, 6,7 although subcellular-sized recording electrodes with high density and multiplexity can be achieved by top-down fabrication processes. 8 On the other hand, microwire-based brain probes become significantly larger than neuron somata with increasing channel number, 9 despite subcellular feature size for single-channel carbon electrodes.…”

Towards high-density recording of brain-wide neural activity

“…They found that probes based on TiN performed as well as those made of conventional materials when implanted in animals for 8 weeks. What's more, sites made of TiN are compatible with the CMOS processing, ensuring scalable fabrication of the Neuropixels probes at low cost [6].…”

“…To meet this challenge, Jun and colleagues [6] have developed a silicon based probe called Neuropixels containing 960 sites on a single shank, which can simultaneously record the activity of more than 200 individual neurons. What's more, the length of the recording shank as long as 10 mm enables recording from multiple brain regions simultaneously, and even the deepest structures of a mouse brain can be accessed.…”