Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo

Abstract

Brain function depends on simultaneous electrical, chemical and mechanical signaling at the cellular level. This multiplicity has confounded efforts to simultaneously measure or modulate these diverse signals in vivo. Here we present fiber probes that allow for simultaneous optical stimulation, neural recording and drug delivery in behaving mice with high resolution. These fibers are fabricated from polymers by means of a thermal drawing process that allows for the integration of multiple materials and interrogation modalities into neural probes. Mechanical, electrical, optical and microfluidic measurements revealed high flexibility and functionality of the probes under bending deformation. Long-term in vivo recordings, optogenetic stimulation, drug perturbation and analysis of tissue response confirmed that our probes can form stable brain-machine interfaces for at least 2 months. We expect that our multifunctional fibers will permit more detailed manipulation and analysis of neural circuits deep in the brain of behaving animals than achievable before.

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

“…8% of a rigid microwire showed reduced accumulation of astrocytes (ca. 50%) around probes compared with microwires 1 and 2 wk postimplantation (20). However, accumulations of astrocytes and microglia have still been observed around the fiber probe surfaces, presumably due to the bending stiffness mismatch with soft neural tissue.…”

“…Recent studies have investigated the potential advantages of reducing mechanical stiffness (19)(20)(21), feature sizes (22), as well as density of the material used for fabrication of probes (15) in terms of reduced gliosis. For example, polymer fiber-based neural probes with bending stiffness values ca.…”

Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems

“…These systems are of interest because they can conform to the surfaces of biological systems in ways that enable important capabilities of relevance to both biomedical research and clinical practice. Examples include devices for continuous monitoring of health status through the skin (1)(2)(3)(4)(5)(6)(7)(8)(9), optical stimulation of targeted neural circuits in the brain (10)(11)(12)(13), and electrophysiological mapping on the epicardial surface (14)(15)(16)(17). These platforms are unique because their lightweight construction, thin geometry, and low bending stiffness allow high-quality, minimally invasive interfaces to soft, dynamic biological tissues, in a manner that cannot be replicated with conventional wafer-based forms of electronics.…”

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

“…For example, wireless stimulation and readouts of head-restrained, freely moving mice is now possible for interrogation and monitoring of neural activity during motor behavior [137,163]. Furthermore, light delivery options have been expanded into devices such as an optrode system for laser excitation and multielectrode recording [164,165], and a multifunctional fiber system for simultaneous optical, electrical, and chemical interrogation [166]. If a 2-photon microscopy set-up is used to record calcium signals, additional readouts important for stroke recovery are now possible, such as imaging of blood flow and synaptic structures [167].…”