The emergence of nanoelectronics applied to neural interfaces has started few decades ago, and aims to provide new tools for replacing or restoring disabled functions of the nervous systems as well as further understanding the evolution of such complex organization. As the same time, graphene and other 2D materials have offered new possibilities for integrating micro and nano-devices on flexible, transparent, and biocompatible substrates, promising for bio and neuro-electronics. In addition to many bio-suitable features of graphene interface, such as chemical inertness and anti-corrosive properties, its optical transparency enables multimodal approach of neuronal based systems, the electrical layer being compatible with additional microfluidics and optical manipulation ports. The convergence of these fields will provide a next generation of neural interfaces for the reliable detection of single spike and record with high fidelity activity patterns of neural networks. Here, we report on the fabrication of graphene field effect transistors (G-FETs) on various substrates (silicon, sapphire, glass coverslips and polyimide), exhibiting high sensitivity (4mS/V) and low noise level (10-22 A²/Hz). We demonstrate the in-vitro detection of the spontaneous activity of hippocampal neurons in-situ-grown on top of the graphene sensors during several weeks in a microfluidic chamber. These results provide an advance towards the realization of biocompatible devices for reliable and high spatio-temporal sensing of neuronal activity for both in-vitro and in-vivo applications.

Graphene, the atomically-thin honeycomb carbon lattice, is a highly conducting 2D material whose exposed electronic structure offers an ideal platform for chemical and biological sensing. Its biocompatible, flexible and chemically inert nature associated with the lack of dangling bonds, offers novel perspectives for direct interfacing with biological molecules. Combined with its exceptional electronic and optical properties, this promotes graphene as a unique platform for bioelectronics. Among the successful bio-integrations of graphene, the detection of action potentials in numerous electrogenic cells including neurons has paved the road for the high spatio-temporal and wide-field mapping of neuronal activity. Ultimate resolution of sensing ion channel activity can be achieved with neural interfaces, and it was shown that macroscale electrodes can record extracellular current of individual ion channels in model systems, by charging the quantum capacitance of large graphene monolayer (mm ² ). Here, we show the field effect detection of ion channel activity within neuron networks, cultured during several weeks above graphene transistor arrays. Dependences upon drugs, reference potential gating and device geometry confirm the field effect detection of individual ion channel and suggest a significant contribution of grain boundaries, which provide highly sensitive nanoscale-sized sensing sites. Our theoretical analysis and simulations demonstrate that the ion gating of a single grain boundary in liquid affects the electronic transmission of the whole transistor channel, resulting in significant conductance variations. Monitoring the ion channels activity is of great interest as most of neurodegenerative diseases relied on channelopathies, which rely on ion channel abnormal activity. Thus, such highly sensitive and biocompatible neuro-electronics which open the way to FET detection at the sub-cell precision should be useful for a wide range of fundamental and applied research areas, including brain-on-chip, pharmacology, and in vivo monitoring or diagnosis.

Dual-light emitting Yb³⁺,Er³⁺-codoped α-La(IO₃)₃ nanocrystals, known to exhibit both second harmonic signal and photoluminescence (PL), are evaluated as optical nanoprobes and thermal sensors using both conventional microscopes and a more sophisticated micro-PL setup. When loaded in cortical and hippocampal neurons for a few hours at a concentration of 0.01 mg/mL, a visible PL signal arising from the nanocrystals can be clearly detected using an epifluorescent conventional microscope, enabling to localize the nanocrystals along the stained neurons and to record PL variation with temperature of 0.5% K⁻¹. No signal of cytotoxicity, associated with the presence of nanocrystals, is observed during the few hours of the experiment. Alternatively, a micro-PL setup can be used to discriminate the different PL lines. From ratiometric PL measurements, a relative thermal sensitivity of 1.2% K⁻¹ was measured.