Modular Integration of Hydrogel Neural Interfaces

Anthony Tabet, Marc Joseph Antonini, Atharva Sahasrabudhe, Jimin Park, Dekel Rosenfeld, Florian Koehler, Hyunwoo Yuk, Samuel Hanson, Jordan Stinson, Melissa Stok, Xuanhe Zhao, Chun Wang, Polina Anikeeva

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Thermal drawing has been recently leveraged to yield multifunctional, fiber-based neural probes at near kilometer length scales. Despite its promise, the widespread adoption of this approach has been impeded by (1) material compatibility requirements and (2) labor-intensive interfacing of functional features to external hardware. Furthermore, in multifunctional fibers, significant volume is occupied by passive polymer cladding that so far has only served structural or electrical insulation purposes. In this article, we report a rapid, robust, and modular approach to creating multifunctional fiber-based neural interfaces using a solvent evaporation or entrapment-driven (SEED) integration process. This process brings together electrical, optical, and microfluidic modalities all encased within a copolymer comprised of water-soluble poly(ethylene glycol) tethered to water-insoluble poly(urethane) (PU-PEG). We employ these devices for simultaneous optogenetics and electrophysiology and demonstrate that multifunctional neural probes can be used to deliver cellular cargo with high viability. Upon exposure to water, PU-PEG cladding spontaneously forms a hydrogel, which in addition to enabling integration of modalities, can harbor small molecules and nanomaterials that can be released into local tissue following implantation. We also synthesized a custom nanodroplet forming block polymer and demonstrated that embedding such materials within the hydrogel cladding of our probes enables delivery of hydrophobic small molecules in vitro and in vivo. Our approach widens the chemical toolbox and expands the capabilities of multifunctional neural interfaces.

Original languageEnglish (US)
Pages (from-to)1516-1523
Number of pages8
JournalACS Central Science
Issue number9
StatePublished - Sep 22 2021

Bibliographical note

Funding Information:
A.T. thanks the National Science Foundation Graduate Research Fellowship and the Paul and Daisy Soros Fellowship for funding support. A.T. thanks Prof. K. Dane Wittrup for continuous mentorship throughout this project. A.T. also thanks thesis committee members Prof. Isaac Chiu, Prof. Kwanghun Chung, and Prof. Sean Lawler for thoughtful discussions and valuable feedback. The authors additionally thank Dr. Ameya Kirtane for support with DLS measurements, Dr. Andres Canales for assistance in constructing the integration tower, Georgios Varnavides for assistance with image processing, and Prof. James Frank for fruitful conversations on hydrophobic small molecules. This work was supported in part by the National Institute of Neurological Disorders and Stroke (R01-NS115025-01A1, P.A.), National Science Foundation (NSF) Center for Materials Science and Engineering (DMR-1419807, P.A.), NSF Center for Neurotechnology (EEC-1028725, P.A.), and the McGovern Institute for Brain Research at MIT (P.A.).

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