The unprecedented ability of plasmonic nanostructures to manage and to concentrate light at nanoscale level has driven their use to a wide range of applications. Essentially, this project relies on a synergic combination of advanced Nanofabrications, Plasmonics, Neuro-Electronics, and enhanced Spectroscopies to develop an electro-plasmonic multifunctional platform able to perform real-time neurointerfacing on a wide multi-scale spatial and temporal domain. This is achieved by 3D nanostructures able to work at the same time as plasmonic nanoantennas and as nanoelectrodes, and by integrating these structures on CMOS multi-electrode arrays (MEA) designed to manage multi-scale measurements from the molecular level up to network level on several thousand of measurement sites.
Research neuronal signaling, on both the artificial and biological side, is the subject of a very large community, but progresses remain slow and 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 networks of neuronal populations, available electrophysiological methods limit our access to single cells and typically provides only an averaged observation of neuronal signaling, fragmented to limited spatial and temporal scales. Thus, to investigate neuronal signaling with current technologies it is necessary to interpret experimental results performed with different techniques, e.g. patch-clamp, micro-electrode arrays or implantable probes, functional optical imaging, (real-time) PCR, etc.. Due to the richness of signaling pathways and variability characterizing each level, this effort appears constantly growing in its complexity. Therefore, broadening the spectrum of scales for observing neuronal signaling within large neuronal networks is a major scientific and technological challenge that can revolutionize our capability of studying and treating the brain and its physiological and pathological functions, as well as of deriving bio-inspired concepts to implement artificial system based on neuronal circuits.
Under this point of view we remark the importance of facing this challenge by accessing to the temporal and spatial scales where things happen, i.e. the molecular scale. At the present, the prime methodology for investigating neuronal circuit is based on the employment of MEA that do not access to information at the nanoscale level. Concurrently, Plasmonic and Raman Spectroscopy emerged for their capability of managing the electromagnetic field and molecular information at the nanoscale, respectively. The interest in Raman spectroscopy relies in its capability of providing a clear chemical and physical insight of the nano-environment under study: chemical structure, binding event, chemical and physical interactions, and local temperature, can be accurately measured. Even time resolved studies of vibrational spectra in chemical reactions were demonstrated on the femtosecond landscape. In view of that, we propose the development of an innovative electro-plasmonic platform that by combining different methodologies emerging from distant fields of Science and Technology will provide a radically new path for neurointerfacing at different scale levels. Namely, (see sketch in figure 1):
- The molecular scale: the employment of 3D plasmonic nanoantennas will give access to information at molecular level by means of enhanced spectroscopies with particular regard of time resolved Raman scattering.
- The single-neuron scale within neuronal networks: by both in-cell and extra-cell couplings with 3D nanostructures which work at the same time as plasmonic antennas and CMOS 3D nanoelectrodes.
- The scale of large neuronal networks: by CMOS high-density electrode arrays for spatially and temporally resolving neuronal signaling form thousands of measuring sites.
Figure 1. Investigation multi-scale access level: plasmonic nanoelectrode can provide information at molecular scale level by means of Raman spectroscopy, whereas CMOS array can access from single cell level to network level.
As we will show thereafter in detail, by employing a novel top-down approach (still not published) we are able to fabricate innovative kinds of 3D plasmonic nanoantennas made of noble metals and dielectrics. These 3D nanostructures are shorted by an uninterrupted metal layer that does not prevent their plasmonic functioning, thus allowing them to work as plasmonic nanoantennas and CMOS nanoelectrodes at the same time.
Neuronal signaling in brain circuits occurs at multiple scales ranging from molecules and cells to large neuronal assemblies. Both spatial and temporal scales span over several order of magnitudes. However, current sensing neurotechnologies are not designed for parallel access of signals at such broad scales. With the aim of combining nanoscale molecular sensing with electrical neural activity recordings within large neuronal assemblies, we have developed three-dimensional (3D) plasmonic nanoantennas integrated with multielectrode arrays (MEA).
