Silicon Probes Record Neural Activity From Brain Organoid

Written by Justin Kinney, LeafLabs, Member of Technical staff

 

Of all the organs in the human body, perhaps the most difficult to study is the brain, owing to its dazzling complexity and its isolation from the rest of the body afforded by the protective skull and blood-brain barrier. So imagine if a miniature copy of a brain could be grown in a dish from stem cells in the body. With such a technology, the possibilities seem endless for understanding brain diseases and for developing therapeutics quickly.

Now, in a recently accepted paper in Nature titled Cell Diversity and Network Dynamics in Photosensitive Human Brain Organoids, the lab of Paola Arlotta, at Harvard, and collaborators take another bold step toward making brain organoids a reality. The breakthrough was a new protocol for how to coax stem cells to divide, differentiate, and grow into a 3D brain. The discovery of this protocol allowed the Arlotta lab to grow the most mature and fully developed brain organoids to-date. Given the enhanced maturity of the organoids, the logical next step was to investigate whether neurons in the organoids were spontaneously active and organized in networks. To do so, it was desirable to record, with sub-millisecond precision, the electrical activity of individual neurons in the organoids. The sparsity of neurons in the organoids, however, presented a challenge.

Close-packed recording sites on a silicon shank, for spatially oversampled neural recording. SEM of the tip of a recording shank with two columns of 100 rows each. The close-packed recording sites of 9 × 9 μm have a pitch of 11 μm, and are visible as the light squares. The shank itself has a width of ∼50 μm in the region shown, and is 15-μm thick

Close-packed recording sites on a silicon shank, for spatially oversampled neural recording. SEM of the tip of a recording shank with two columns of 100 rows each. The close-packed recording sites of 9 × 9 μm have a pitch of 11 μm, and are visible as the light squares. The shank itself has a width of ∼50 μm in the region shown, and is 15-μm thick

A brain organoid is a miniature brain at an early stage of development, when active neurons are relatively few in number and sparsely distributed in the tissue. Accordingly, to increase the success of recording from these neurons, the Arlotta lab reached out to LeafLabs and the Boyden Lab at MIT to employ novel silicon probes with close-packed sites that provide dense recording of tissue continuously along the length of the probe. The complete coverage afforded by the probe allowed more neurons to be recorded per organoid and the close-packing eased spike sorting to allow single-unit recording.

Stay tuned for the full article in Nature. Once it is available we'll make sure to share!