In situ multimodal transparent electrophysiological hydrogel for in vivo miniature two-photon neuroimaging and...

Hydrogels are widely used in nerve tissue repair and show good histocompatibility. There remain, however, challenges with hydrogels for applications related to neural signal recording, which requires a tissue-like biomechanical property, high optical transmission, and low impedance. Here, we describe a transparent hydrogel that is highly biocompatible and has a low Young's modulus (0.15 MPa). Additionally, it functions well as an implantable electrode, as it conformably adheres to brain tissue, results in minimal inflammation and has a low impedance of 150 Ω at 1 kHz. Its high transmittance, corresponding to 93.35% at a wavelength of 300 nm to 1100 nm, supports its application in two-photon imaging. Consistent with these properties, this flexible multimodal transparent electrophysiological hydrogel (MTEHy) electrode was able to record neuronal Ca²⁺ activity using miniature two-photon microscopy. It also used to monitor electrocorticogram (ECoG) activity in real time in freely moving mice. Moreover, its compatibility with magnetic resonance imaging (MRI), indicates that MTEHy is a new tool for studying activity in the cerebral cortex. STATEMENT OF SIGNIFICANCE: Future brain science research requires better-performing implantable electrodes to detect neuronal signaling in the brain. In this study, we developed a new hydrogel material, MTEHy-3, that shows high biocompatibility, high optical transmittance (93.35%) and a low Young's modulus (0.15 MPa). Using as high-biocompatible metal-free hydrogel electrode, MTEHy-3 can be implanted for a long time to study the cerebral cortex, and synchronously record the Ca²⁺ signaling activity of individual neurons and monitor electrocorticogram activity through ionic conduction in freely moving mice. At the same time, non-metallic MTEHy-3 is also suitable for magnetic resonance imaging. Thus MTEHy-3 provides one in situ multimodal tool to detect neuronal signaling with both high spatial resolution and high temporal resolution in the brain.