Chronic Implantation of Multiple Flexible Polymer Electrode Arrays

Abstract

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of scientific and clinical development. The use of flexible polymer electrode arrays can support long-lasting recording, but the same mechanical properties that allow for longevity of recording make multiple insertions and integration into a chronic implant a challenge. Here is a methodology by which multiple polymer electrode arrays can be targeted to a relatively spatially unconstrained set of brain areas. The method utilizes thin-film polymer devices, selected for their biocompatibility and capability to achieve long-term and stable electrophysiologic recording interfaces. The resultant implant allows accurate and flexible targeting of anatomically distant regions, physical stability for months, and robustness to electrical noise. The methodology supports up to sixteen serially inserted devices across eight different anatomic targets. As previously demonstrated, the methodology is capable of recording from 1024 channels. Of these, the 512 channels in this demonstration used for single neuron recording yielded 375 single units distributed across six recording sites. Importantly, this method also can record single units for at least 160 days. This implantation strategy, including temporarily bracing each device with a retractable silicon insertion shuttle, involves tethering of devices at their target depths to a skull-adhered plastic base piece that is custom-designed for each set of recording targets, and stabilization/protection of the devices within a silicone-filled, custom-designed plastic case. Also covered is the preparation of devices for implantation, and design principles that should guide adaptation to different combinations of brain areas or array designs.

Figure 1:. Inserter components.

(A) Pieces 1 and 2 are temporarily fixed to each other with a removable screw and will later be docked onto the retraction micromanipulator piston (orange). (B) The array and insertion shuttle are adhered to piece 1 and the array connector is attached to piece 2 with double-sided tape. Piece 3 connects the retraction micromanipulator and pieces 1 and 2 to the insertion micromanipulator (green). The insertion micromanipulator is fixed to a stereotactic adapter for implant positioning. Pieces 1–3 are pictured in their relative sizes. Piece 4 is a stabilizing piece for proper alignment of the insertion shuttle.

Figure 2:. Assembly for array-shuttle alignment.

(A) Assembly of pieces 1, 2, and stabilizing piece in preparation of insertion shuttle attachment. (B) Pieces 1 and 2 held together with thumb screw.

Figure 3:. Alignment, attachment, and sterilization of array-shuttle.

(A) Proper orientation of insertion shuttle-electrode array device for application of glue on docking station of piece 1. Two-shank array-shuttle shown. (B) Polymer electrode array and insertion shuttle mounted on insertion piece, with temporary stabilizing piece for alignment. Two-shank array-shuttle shown. (C) Insertion device encased in plastic box for protection during sterilization.

Figure 4:. Skull prepared for implant.

Durectomies complete with skull screws, base acrylic layer, and base piece fixed to skull.

Figure 5:. Assembly of inserter.

(A) Mounting of piece 3 to micromanipulators. (B) Attachment of pieces 1 and 2 onto insertion apparatus. (C) Insertion pieces with mounted electrode array-insertion shuttle device. (D) Thumb screw holding piece 1 and 2 together removed.

Figure 6:. Array-shuttle insertion.

Array-shuttle is advanced into brain to target depth. Four-shank array-shuttle shown.

Figure 7:. Retraction of shuttle.

(A) Tethering of wings before retraction. Two-shank array and shuttle shown. (B) PEG dissolution and wing adhesion with shank feature (circled, blue) that allows for visual confirmation of successful decoupling of array and shuttle during retraction. (C) A successful array insertion after insertion shuttle has been retracted. (D) Base piece with silicone gel fills for a single two-shank array insertion. The low-viscosity silicone gel used has a blue tint.

Figure 8:. Multiple inserted arrays and rat after recovery from implantation.

(A) Hardware connectors in locations to not interfere with subsequent insertions. (B) A 1,024-channel, chronic polymer array implant. Reproduced with permission from Neuron [Supplemental Figure 1H].

Figure 9:. Single-unit yield and recording longevity.

(A) Number of putative single-unit clusters from 512 channels (of the 1,024-channel implant), stratified by quality metric thresholds. Automated curation using MountainSort (noise overlap 0.03, isolation 0.96, black box in upper right) resulted in the identification of 375 single units from the 512 channels. Reproduced with permission from Neuron [Figure 2A]. (B) Single-unit yields for polymer arrays per channel (left y-axis) or per 16-channel shank (right y-axis) over 160 days post-implantation (x-axis) in rats. Solid line is the mean cell yield across 8 shanks, dotted lines ± 1 SE. Individual time points per shank are shown as color-coded dots by region. Reproduced with permission from Neuron [Figure 3A].