Direct Detection Of Neuronal Activity Using Organic Photodetectors

Calcium- and voltage-sensitive indicators allow for the optical monitoring of neuronal activity at both cellular and population levels. However, conventional approaches for the optical detection of electrical activity in an intact brain typically involve a trade-off between tissue depth and resolution. Cameras of high temporal and spatial resolution can detect activity with single-cell resolution, but are restricted to more superficial structures such as the neocortex and require elaborate optical setups. In contrast, optical fibers can collect fluorescent neural activity from deeper brain areas, but with low spatial resolution. Here, we present a new class of high-resolution, light-sensing devices that are capable of detecting ultralow changes in fluorescent neuronal activity without the need for an optical setup. We show that organic photodetectors (OPDs) based on rubrene and fullerene feature a photovoltage responsivity of 2 V m(2) W-1 and that can directly detect changes in fluorescent neuronal activity as low as 2.3 nW cm(-2). Primary cortical neurons were loaded with the fluorescent calcium indicator Cal-520, and neuronal activity was evoked with brief pulses of electrical field stimulation. During simultaneous sCMOS camera acquisition, the OPD was observed to reliably detect electrically evoked fluorescent activity with high fidelity and signal-to-noise ratio. The device also detected time-locked spontaneous fluorescent transients, demonstrating sufficient sensitivity for the detection of physiological events. Our results pave the way for a new class of subdermally implanted stereotactic sensors, representing a capacity for minimally invasive, high-resolution in vivo recordings, which are especially suited to record neuronal populations in behaving animals.