Objective.Optical fiber devices constitute significant tools for the modulation and interrogation of neuronal circuitry in the mid and deep brain regions. The illuminated brain area during neuromodulation has a direct impact on the spatio-temporal properties of the brain activity and depends solely on the material and geometrical characteristics of the optical fibers. In the present work, we developed two different flexible polymer optical fibers (POFs) with integrated microfluidic channels (MFCs) and an ultra-high numerical aperture (UHNA) for enlarging the illumination angle to achieve efficient neuromodulation. Approach. Three distinct thermoplastic polymers: polysulfone (PSU), polycarbonate (PC), and fluorinated ethylene propylene (FEP) were used to fabricate two step-index UHNA POF neural devices using a scalable thermal drawing process. The POFs were characterized in terms of their illumination map as well as their fluid delivery capability in phantom and adult rat brain slices. Main results. A 100-fold reduced bending stiffness of the proposed fiber devices compared to their commercially available counterparts has been found. The integrated MFCs can controllably deliver dye (trypan blue) on-demand over a wide range of injection rates spanning from 10 nL/min to 1000 nL/min. Compared with commercial silica fibers, the proposed UHNA POFs exhibited an increased illumination area by 17% and 21% under 470 and 650 nm wavelength, respectively. In addition, a fluorescent light recording experiment has been conducted to demonstrate the ability of our UHNA POFs to be used as optical waveguides in fiber photometry. Significance. Our results overcome the current technological limitations of fiber implants that have limited illumination area and we suggest that soft neural fiber devices can be developed using different custom designs for illumination, collection, and photometry applications. We anticipate our work to pave the way towards the development of next-generation functional optical fibers for neuroscience.

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Controlling neuronal activity using implantable neural interfaces constitutes an important tool to understand and develop novel strategies against brain diseases. Infrared neurostimulation is a promising alternative to optogenetics for controlling the neuronal circuitry with high spatial resolution. However, bi-directional interfaces capable of simultaneously delivering infrared light and recording electrical signals from the brain with minimal inflammation have not yet been reported. Here, we have developed a soft fibre-based device using high-performance polymers which are >100-fold softer than conventional silica glass used in standard optical fibres. The developed implant is capable of stimulating the brain activity in localized cortical domains by delivering laser pulses in the 2 μm spectral region while recording electrophysiological signals. Action and local field potentials were recorded in vivo from the motor cortex and hippocampus in acute and chronic settings, respectively. Immunohistochemical analysis of the brain tissue indicated insignificant inflammatory response to the infrared pulses while the signal-to-noise ratio of recordings still remained high. Our neural interface constitutes a step forward in expanding infrared neurostimulation as a versatile approach for fundamental research and clinically translatable therapies.

Controlling neuronal activity with high spatial resolution using multifunctional and minimally invasive neural interfaces constitutes an important step towards developments in neuroscience and novel treatments for brain diseases. While infrared neuromodulation is an emerging technology for controlling the neuronal circuitry, it lacks soft implantable monolithic interfaces capable of simultaneously delivering light and recording electrical signals from the brain while being mechanically brain-compatible. Here, we have developed a soft fibre-based device based on high-performance thermoplastics which are >100-fold softer than silica glass. The presented fibre-implant is capable of safely neuromodulating the brain activity in localized cortical domains by delivering infrared laser pulses in the 2 μm spectral region while recording electrophysiological signals. Action and local field potentials were recorded in vivo in adult rats while immunohistochemical analysis of the tissue indicated limited microglia and monocytes response introduced by the fibre and the infrared pulses. We expect our devices to further enhance infrared neuromodulation as a versatile approach for fundamental research and clinically translatable therapeutic interventions.