Imec designs and fabricates world-first miniature neural probe for simultaneous recording of multiple brain regions at neuronal resolution

Imec, the world-leading research and innovation hub in nano-electronics and digital technologies, has designed and fabricated a breakthrough neural probe for the parallel recording of hundreds of neural signals. The Neuropixels probe was developed for an international consortium consisting of Howard Hughes Medical Institute (HHMI), the Allen Institute for Brain Science, the Gatsby Charitable Foundation and Wellcome, with funding of $5.5 million.Scientists at HHMI’s Janelia Research Campus, the Allen Institute and University College London (UCL) worked together with engineers at nanotechnology company imec to build and test the probes that were designed and fabricated on imec’s advanced silicon platform, demonstrating its ability to create ultraprecise tools which are being recognized as a new gold standard in neuroscience research. The results were published in an edition of Nature this month and will also be presented at the Annual Meeting of the Society for Neuroscience in Washington, D.C., Nov. 11-15, 2017.

Current techniques to map the activity of brain cells either lacked spatial or temporal resolution. Previous generations of neural probes can only record activity of a few dozen neurons, while optical imaging lacks in speed to distinguish individual spikes of activity. Imec’s Neuropixels probe solves both issues and enables precise real-time recording of the activity of hundreds of individual neurons. In addition, because of the length of the shank on which the sensors are placed, it is possible to record neural activity across different brain regions. This capability is essential to study the coordinated action of brain regions, and provides a better method of understanding the brain, and ultimately, for diagnostic and prosthetic tools to tackle human brain diseases.

The new probe has 960 sensors, each measuring 12×12µm, tiled on a superthin (20µm) shank that is 1cm long and 70µm wide. The shank is fabricated together with a 9x6mm base on a single chip. The sensor density allows it to record isolated spiking activity from hundreds of single neurons in parallel. The recorded signals are sent through 384 recording channels to the base where they are filtered, amplified and digitized to provide researchers with noise-free digital data.

The Neuropixels probe is an exceptional demonstration of what imec’s technology platform is capable of,” stated Silke Musa, Program Manager at imec. “Imec’s expertise in analog design, deep silicon etch, biocompatible electrode fabrication and proprietary SOI processes makes us one of the few research and development institutions worldwide that is able to manufacture probes like these.”

2014 Nobel Laureate John O’Keefe of the Sainsbury Wellcome Centre at University College London and lead PI on the Wellcome and Gatsby Charitable Foundation grants said he was eager for British involvement in the project right from the beginning. “It was clear to me that if these probes worked they would take our ability to relate single cell activity and behavior to a new level. And they would be particularly useful in cortical areas related to spatial memory such as the hippocampus and entorhinal cortex. In the past, we have had to put several implants with multiple tetrodes into these brain regions to collect enough data to do network analysis, to see how the cells interacted to form spatial representations, or to do decoding analysis where we try to figure out the animal’s position from the cell activity. Now we can place one Neuropixels probe along the length of the entorhinal cortex and record from twice as many grid cells as we could before, or record simultaneously from place cells in the CA1 and CA3 regions of the hippocampus, opening up a whole new level of analysis.”

“Neuropixels is the result of a unique partnership of world leading neuroscientists, generous and forward looking charities, HHMI, Allen, Gatsby, and Wellcome, and the state of the art design and fabrication capability of imec engineers,” said Timothy Harris, senior fellow at Janelia, leader of the Neuropixels collaboration. “Together I believe we have created a device that will change the thinking and practice of brain research in mammals. Paradigm shift is an overused expression, but I believe we are already seeing that shift, motivated by the astonishing data created with the first Neuropixels prototypes. Without imec engineering and vision, private funding generosity, and insight from scientists, we would not have made this advance. Together we have changed the game.”

“The way that the Neuropixels probe was designed and fabricated and how it is already transforming neuroscience, points to the relevancy and promise of a new model in which private research foundations with deep expertise, fund the design and fabrication of breakthrough tools which can then advance fundamental research,” added Barun Dutta, Chief Scientist at imec. “This project could not have succeeded without the contribution of all four funding partners, HHMI, The Gatsby Charitable Foundation, the Allen Institute and Wellcome. We’re proud to see that there are already more than 400 prototype probes being tested at research centers worldwide, a testament to the success of this new model. We expect to see more of these collaborations in the near future, which will enable other breakthrough tools that can advance human knowledge and medical research.”