Neuro-flakes: Direct Voltage Imaging of Neural Activity with Atomically-thin Optoelectronic Materials Recording electrical activity of neural populations with high resolution is essential to investigate neural circuits and cognitive functions. Although electrophysiology remains to be a widespread tool in neuroscience, it lacks practical scalability and chronic stability needed to tackle large-scale information processing in the brain. Penetrating electrodes are highly destructive to the neural tissue when inserted in large numbers across multiple areas and number of channels that can be simultaneously recorded are limited to a few hundreds, even with the most advanced probes. On the other hand, optical technologies such as calcium imaging are capable of recording neural activity from large populations. However, calcium transients are slow and also not a direct representation of output information of neurons. They are a secondary marker of some electrical and nonelectrical changes in neurons leading to significant discrepancies between electrically recorded action potentials and calcium transients. Direct measurement of electric potentials at multiple spatial scales is crucial to investigate information integration, distribution and processing in the brain. Here, we propose a unique and innovative voltage imaging technology, Neuro-flakes, for all-optical large-scale monitoring of electrical activity of neuron populations. Neuro-flakes will combine three key innovations: (i) 3-atom thick MoS2 nanosheets will provide quantum confinement-based excitonic photoluminescence for direct voltage sensing of neural activity across multiple spatial scales, (ii) Planar and injectable Neuro-flakes will serve as a nontoxic, nongenetic, and photostable alternative to genetically encoded voltage indicators (GEVIs) with a potential for human applications in the future, and (iii) MoS2 has a radiative lifetime on the order of several picoseconds, potentially enabling optical detection of neural activity with extraordinary temporal resolution. Neuro-flakes will combine the advantages of electrophysiology with the convenience of optical imaging, without the invasiveness of or the need for electrical wires, to directly probe voltages generated by single neurons and neuronal microcircuits at multiple spatial and temporal scales.

Proposed voltage imaging technology could enable high resolution mapping of network dysfunctions causing neurological disorders and can open up exciting avenues to develop therapeutic approaches based on neuromodulation. Neural circuit dysfunctions are the cause of most neurological diseases, including epilepsy, Parkinson’s disease, dystonia, depression and schizophrenia. That could greatly impact the outcome for many of the one billion people affected by neurological disorders worldwide.