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.