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

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.