The project was completed on May 31st, 2024. All scientific, management, dissemination, communication and exploitation activities were successfully completed. A summary of the main results is provided below:
1) New Nanowire Array technologies: we developed a new in-vitro platform for neuron-on-a-chip interfacing through nanowires. We performed extensive studies of various materials of the PtSi layer, including the surface oxidation for a proper integration of the coating layers. We also fabricated a 60-channel NWA and established the procedure for electrical characterization of such a system in recording (impedance) and stimulation. We developed a low temperature NWA process compatible with an integration on CMOS circuit and performed a first line of nano-electrode arrays that were integrated on CMOS.
2) New biophysical model of Alzheimer’s disease: we developed the AlzModel software, a detailed, multiscale, neuronal network model that reproduces key deficits of Alzheimer’s disease such as impaired synaptic plasticity/rigidity, decreased NMDA currents, dendritic atrophy etc.
3) The Synaptor: we developed a computational model of the Synaptor, which served as the interface between the nanoelectrodes and the neurons that were cultured on the surface of the chip. The Synaptor was developed and validated with electrophysiological data from rat hippocampus neuronal cultures on nanowire array prototypes and on the high-density planar multi-electrode array provided by our industrial partner.
4) The integrated NEUREKA system: we established a controllable hybrid system, whereby a hardware chip device (multi- or nanowire electrode array) is interfaced with the AlzModel and used to control the activity of cultured neurons on the surface of the array. Software pipelines were also developed to ensure a seamless exchange of data between the AlzModel and the chip in a bidirectional manner. The integrated NEUREKA system was implemented using two different platforms: the 60-channel nanowire array and the high density multielectrode array MaxOne.
5) Testing of the NEUREKA platform: we tested the ability of the AlzModel to successfully drive disease-related states on both chip platforms, using rat and hiPSC cultures. To do so, we developed a software package for automatic detection and functional characterization of subcellular axonal physiological signals, across hundreds of neurons within a neuronal network. We also established protocols for stable and reproducible culturing of human iPSC-derived glutamatergic neurons and human astrocytes.
4) Drug testing pilot: we tested the ability of the NEUREKA platform to serve as a drug screening device using both rat and hiPSC cultures. Abeta homogenate was used to induce the Alzheimer’s phenotype on cultured neurons and the effectiveness of known drugs (memantine and valproic acid) on the activity and connectivity properties of cultured neurons, when driven by the AlzModel, was assessed. Our results suggest that NEUREKA has the potential to serve as a reliable drug screening device.
Exploitation activities:
The nanoelectrode technology, implemented on various substrates (including CMOS chips), has been granted a patent in France (CNRS-LAAS), with several international extensions still pending. CNRS is actively promoting the transfer of this technology to an industrial environment for commercialization and wider application.
A second patent for the AlzModel as an integrated system for drug screening is being drafted (FORTH-UNIPD). Efforts are made to secure funding to further develop both of the technologies into marketable products (e.g. through EIC Transition applications).
