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Research neuronal signaling is the subject of a very large community, but progresses face a dense multi-scale dynamics involving signaling at the molecular, cellular and large neuronal network levels. Whereas the brain capabilities are most likely emerging from large neuronal networks, available electrophysiological methods limit our access to single cells and typically provides only a fragmented observation, on limited spatial/temporal scales. Therefore, broadening the spectrum of scales for observing neuronal signaling within large neuronal networks is a major challenge that can revolutionize our capability of studying the brain and its physio-pathological functions, as well as of deriving bio-inspired concepts to implement artificial system based on neuronal circuits. We propose the development of an innovative electro-plasmonic multifunctional platform that by combining different methodologies emerging from distant fields of Science and Technology will provide a radically new path for real time neurointerfacing at different scale levels: from the molecular scale to large neuronal networks.This is achieved by exploiting an innovative nanofabrication method able to realize 3D nanostructures which can work at the same time as plasmonic nanoantennas and as nanoelectrodes thus combining CMOS technology with spectroscopic investigations.

Intracellular and Extracellular Recording of Spontaneous Action Potentials in Mammalian Neurons and Cardiac Cells with 3D Plasmonic Nanoelectrodes

Via the combination of vertical nanoelectrodes with plasmonic optoporation, we demonstrate the ability to continuously record both extracellular and intracellular-like action potentials at each electrode site in spontaneously active mammalian neurons and HL-1 cardiac-derived cells. We demonstrate long-term and stable recordings with a very good signal-to-noise ratio. Additionally, plasmonic opto-poration does not perturb the spontaneous electrical activity; it permits continuous recording even during the poration process, and can regulate extracellular and intracellular contributions by means of partial cellular poration.

Plasmonic meta-electrodes allow intracellular recordings at network level on high-density CMOS-multi-electrode arrays

The ability to monitor electrogenic cells accurately plays a pivotal role in neuroscience, cardiology and cell biology. Despite pioneering research and long-lasting efforts, the existing methods for intracellular recording of action potentials on the large network scale suffer limitations that prevent their widespread use. Here, we introduce the concept of a meta-electrode, a planar porous electrode that mimics the optical and biological behaviour of three-dimensional plasmonic antennas but also preserves the ability to work as an electrode. Its synergistic combination with plasmonic optoacoustic poration allows commercial complementary metal–oxide semiconductor multi-electrode arrays to record intracellular action potentials in large cellular networks. We apply this approach to measure signals from human-induced pluripotent stem cell-derived cardiac cells, rodent primary cardiomyocytes and immortalized cell types and demonstrate the possibility of non-invasively testing a variety of relevant drugs. Due to its robustness and easiness of use, we expect the method will be rapidly adopted by the scientific community and by pharmaceutical companies.