Graphene transistors for interfacing with cells: towards a deeper understanding of liquid gating and sensitivity

Abstract

This work is focused on the fabrication and analysis of graphene-based, solution-gated field effect transistor arrays (GFETs) on a large scale for bioelectronic measurements. The GFETs fabricated on different substrates, with a variety of gate geometries (width/length) of the graphene channel, reveal a linear relation between the transconductance and the width/length ratio. The area normalised electrolyte-gated transconductance is in the range of 1–2 mS·V−1·□ and does not strongly depend on the substrate. Influence of the ionic strength on the transistor performance is also investigated. Double contacts are found to decrease the effective resistance and the transfer length, but do not improve the transconductance. An electrochemical annealing/cleaning effect is investigated and proposed to originate from the out-of-plane gate leakage current. The devices are used as a proof-of-concept for bioelectronic sensors, recording external potentials from both: ex vivo heart tissue and in vitro cardiomyocyte-like HL-1 cells. The recordings show distinguishable action potentials with a signal to noise ratio over 14 from ex vivo tissue and over 6 from the cardiac-like cell line in vitro. Furthermore, in vitro neuronal signals are recorded by the graphene transistors with distinguishable bursting for the first time.

Ultrasensitive Field‐Effect Biosensors Enabled by the Unique Electronic Properties of Graphene

“…Therefore it might not always be fair to make such comparisons with different samples . For example, performing high quality biosensing (e.g., extracellular) measurements reproducibly require identical or nearly identical devices …”

“…During the fabrication of a GFET for liquid‐gate operation, a passivation is required in order to prevent any contact between the metal lines and the electrolyte as well as to define the active gate area . Technologically this means additional layer of chemically stable resist, such as polyimide or epoxy . In a typical example, a biocompatible, two‐component epoxy were applied after wire bonding for sealing the metallic electrodes against the liquid‐gate voltage V ref applied via the Ag/AgCl reference electrode, to prevent any possible leakage current in electrolyte environment .…”

“…We note here that owing to the unique frequency dependent dielectric properties of the water solution, electrolyte gating is capable of tuning the conductance of GFETs without shunting the propagating radio frequency (RF) signal . For life science application, a new passivation type has been recently introduced and argued to provide a better interface between the GFETs and neuronal cells . This “feedline follower” passivation covers only the area over the metallic feedlines, thus helping to prevent membrane bending as the neuron cell approaches the graphene and grows consistently on it.…”

“…For comparison, the typical area normalized transconductance of an electrolyte‐gated GFET is reported in the range of 1–2 mS V −1 . Figure c–e depicts a typical GFET biosensing measurement.…”

Dielectrophoresis assisted rapid, selective and single cell detection of antibiotic resistant bacteria with G-FETs

“…These mobilities are consistent with reported values for CVD graphene on SiO2 substrates. 18,30 Bacterial detection using G-FETs with bare graphene.…”