Sensing ion channel in neuron networks with graphene field effect transistors

Abstract

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 (mm2). 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.

Recording Spikes Activity in Cultured Hippocampal Neurons Using Flexible or Transparent Graphene Transistors

“…For SiO2 substrates, we have used both Pd and Ti/Pt/Au (for comparison with the sapphire, and the glass or PID substrates, respectively). The contact resistance is qualitatively estimated by measuring the two-point resistance of G-FETs with different widths, being around R C = 0.3 k Ω, per contact, while the square resistance R □ of the graphene sheet is about R □ = 0.65 ± 0.05 k Ω / □ (Veliev et al, 2017 ). Finally, the metallic contact leads are insulated using biocompatible polymers, either polyimide (Fujifilm, photosensitive PID) or the negative photoresist SU8-2000, and are annealed during 2 h at 200°C in N2 atmosphere, and 30 min at 150°C, respectively.…”

“…Since the past few years, graphene field effect transistors (G-FETs) have been able to provide versatile detectors that enabled to sense low pH change (Ohno et al, 2009 ) DNA translocation (Xu et al, 2017 ) cancer cells (Feng et al, 2011 ), or bacteria (Mannoor et al, 2012 ). Also, G-FETs were able to detect single spike evoked in electrogenic cells line, such as, cardiomyocytes (Cohen-Karni et al, 2010 ) or HEK/PC12 cells (Hess et al, 2011b ) and more recently ion channel activity (Veliev et al, 2017 ) and slow potential waves resulting from synchronous activity of a large population of neurons have been recorded by electrocorticograms performed on living rats (Blaschke et al, 2017 ). Compared to previous results, one has to note that neurons are much smaller, fragile, and less accessible.…”

Nano-scale transistors for interfacing with brain: design criteria, progress and prospect

“…In addition. In 2018, Velive F. et al used graphene based FETs in the detection of ion activity in the channel when exposed to cultured hippocampal neuron networks [99]. Graphene is grown using chemical vapor depsition and resulted in stable measured ion currents in FETs with different channel sizes [100][101][102][103][104][105][106][107].…”

“…(C) Global conductance due to one grain boundary estimated from the conductance of the grapheme FET without the grain boundary (black curve) and with a single grain boundary (red curve). Reprinted with permission from[99].…”

Ion-Selective Carbon Nanotube Field-Effect Transistors for Monitoring Drug Effects on Nicotinic Acetylcholine Receptor Activation in Live Cells

“…On the other hand, field-effect transistor (FET) biosensors have been utilized for monitoring the activities of versatile biomolecules, exhibiting some advantages such as a rather straightforward operation and label-free detection [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Recently, FET-based biosensors have been studied as a tool to measure the electrical activities of live cells [ 29 , 30 , 31 , 32 , 33 , 34 ]. However, previous FET-based ion sensors often suffer from rather low sensitivity and can be used to monitor ion channel activities only in close proximity of individual cells.…”