Implantable interfaces for neuromodulation is necessary to advance fundamental neuroscience research, develop new treatments for neurological disorders, and create efficient breakthrough neuroprosthetics. However, modern implants based on multi-electrode arrays suffer from low spatial resolution, high invasiveness with complicated implantable procedures, the need for a chronic opening for connecting wires, and substantial foreign body reaction, eventually leading to device failure. On the other hand, various groups have developed nanoparticles-based transducers that can wirelessly modulate neurons with high precision when actuated with external stimuli. Nevertheless, nanoparticles hold several disadvantages due to their small size (resulting in neurotoxicity, migration, aggregation, etc.), restricted fabrication procedures, and limited design or integration opportunities. Hence, minimally invasive and non-genetic technology that can enable wireless neuromodulation with high spatio-temporal resolution and stable interface remains an unmet goal till date. Therefore, we propose to develop an innovative thin-film-based structure able to wirelessly influence the neuronal membrane to induce or inhibit action potential propagation along a specific path of connected neurons. These devices will be designed and produced with subcellular dimensions to be injected into the neural tissue, diffuse, and wrap around axons and dendrites (creating conformable and stable neural interface); hence, they are named nanoCUFFs. The nanoCUFFs will be composed of two types of polymers: i) an azobenzene polymer for photo-induced reconfiguration of thin films rolled into microtubes, accommodating single axons; and ii) a semiconducting polymer for transduction of light pulses into stimuli for neuronal opto-modulation. Polymers allow creating soft, biocompatible, and conformable structures for a minimal mismatch and maximal coupling with the biological tissue. Once the nanoCUFFs are produced and characterized, we will verify their wrapping capabilities around axons and dendrites, neuromodulation efficiencies as well as ability to influence distinct selected subpopulations of neurons (using micro-patterned light) in neural cultures. The ability to engineer the nanoCUFFs’ material composition and photo-induced effects on a thin-film platform favors the future integration of nanoelectronics components for additional functionalities. For instance, multiplexing and sensing devices could be developed for smart closed-loop neuromodulation. This technology can simultaneously achieve ultra-low invasiveness, high-spatio-temporal precision, selectivity and stable junction with cells and thus, is highly promising for not only fundamental neuroscience but also novel therapeutics.

Neuromodulation through brain-machine interfaces such as neural implants is essential to study the functions of our brain and to develop treatments for neurological disorders. Our goal is to develop a novel minimally-invasive and optoelectronic interface to wirelessly modulate the activity of neurons with subcellular resolution, overcoming the major limitations of current implantable technologies. This interface will be constructed as an ultra-small and thin polymeric film that will conform to the neuronal membrane and establish an exceptional symbiosis with the cell, pioneering a novel concept of brain-machine interface for advances in treatment of brain diseases and elucidating neurological questions like learning and plasticity.