2, CNR, Genova, , Italy
3, University of Cagliari, Cagliari, , Italy
Micro-Electrode-Arrays (MEAs) based systems coupled to neuronal populations constitute a well-established experimental in vitro and in vivo neuro-electronic platforms to study fundamental mechanisms of brain (dys)functions and brain interfaces. 2D neuronal networks coupled to electronic devices have been widely used as a model for understanding basic neurophysiological mechanisms, for in vitro neuropharmacology and as neurotoxicity assays. Upon use of co-culturing techniques and genetic manipulation, these 2D models have been also used to investigate neural diseases via electrophysiological and optical (e.g., optogenetics) means. However, the inherent limitations of existing (in vitro and in vivo) animal models pushed the development of alternative in vitro models, able to better replicate the complex structure and function of a tissue-organ system.
Here we present an array of Organic Charge Modulated FETs (OCMFETs) called MOAs (Micro OCMFET Arrays) coupled with excitable cells for electrophysiological and metabolic monitoring. The neuro-electronic interface is validated with in vitro neuronal networks towards the development of brain-on-a-chip model systems and to understand limits of applicability in in vivo conditions. The microsystem has been fabricated on highly flexible and compliant plastic films, in order to allow the developed system to be employed for in vivo applications such as electrocorticography (ECoG) or intra-cortical brain interfaces.
The developed microtransducer arrays showed optimal biocompatibility, no need for an external reference electrode, good signal-to-noise ratio and good stability. The same OCMFET is able to measure metabolic activity (i.e., through local pH variations; quasi-static measurements) and electrophysiological activity (i.e., through induced charge variations onto the sensing area by ions displacement across the plasma membrane). Moreover, the transduction principle is addressed and compared with the sensing capabilities of microtransducers fabricated with standard MEA and CMOS technologies. Finally, engineered 3D networks, to be coupled to MOA microsystems, are presented together with future applications for the development of disposable and low-cost brain-on-a-chips (i.e., precision-personalized medicine). Comparisons with standard MEA and CMOS technologies and possible applications for in vivo neuro-electronic interfaces are presented and discussed.