Large array of GFETs for extracellular communication with neuronal cells

Graphene has already shown its high ability for biosensing. Solution-gated graphene field effect transistors, which showed very high sensitivity in electrolytes [1], have another biologically important application: recording neuronal activity. Such devices exhibit very high signal-to-noise ratio for extracellular measurements [2]. The aim of this work is to optimize and scale both fabrication procedure and measurement system. When working with biological samples, there is a need in a large number of devices. High density of the devices is also preferable. Therefore we fabricate the devices on 4’’ wafer, resulting in 50 chips, 11*11mm each. Each chip consequently embodies an array of 32 graphene FETs (see fig.1). The active area of the chip is around 2 mm2 while each GFET’s channel differs between 5 and 20 um with altered configurations. Such devices, when used with the already developed multichannel measurements system make possible simultaneous measurement and stimulation of all 32 transistors in a time-scale. This makes possible to measure not just discrete spikes, but even propagation of the action potential through the neuronal network

How to image cell adhesion on soft polymers?

Here, we present a method to investigate cell adhesion on soft, non-conducting polymers that are implant candidate materials. Neuronal cells were grown on two elastomers (polydimethylsiloxane (PDMS) and Ecoflex®) and prepared for electron microscopy. The samples were treated with osmium tetroxide (OsO4) and uranylacetate (UrAc). Best results can be achieved when the polymers were coated with a thin iridium layer before the cell culture. This was done to emphasize the usage of soft polymers as supports for implant electrodes. A good contrast and the adhesion of the cells on soft polymers could be visualized

Wafer-scale fabrication of graphene-based field effect transistor arrays for extracellular measurements

The work is focused on the fabrication and analysis of graphene-based, solution-gated field effect transistor arrays (GFET arrays) in a large scale. The GFETs show extremely high electrolyte-gated transconductance promising exceptional biosensing capability. Signal-to-noise ratio (SNR) of the GFETs is analysed for different graphene areas. In the future we will apply these GFETs for extracellular recordings from neuronal and cardiac cells

Wafer-scale fabrication of graphene field effect transistors for neuronal interfacing

There are plenty of invasive methods for studying a neuronal network’s activities [1]. Of course, the invasiveness of the processes makes them undesired. In recent years, there has been vast research in the field of non-invasive neuronal interfacing and extracellular neuronal recordings [2]. Different methods (passive – MEAs and active – FETs) and different materials (carbon, silicon, PEDOT:PSS) have been used for the purpose.Graphene’s excellent electrical, mechanical and biological properties make it a perfect candidate for such a role. Firstly, liquid-gated graphene field effect transistors (GFETs, see fig. 1) show very high transconductance, and therefore sensitivity [3]. Secondly, graphene is a very stable and biocompatible material (fig.2). Thirdly, flexibility and bendability of graphene make it the most promising material for future bio-implantable devices [3].Therefore we established our 4-inch wafer fabrication process based on CVD-grown graphene (fig. 3a). Each fabricated wafer results in 52 biocompatible chips (fig. 3b). Each chip comprises 32 GFETs (fig. 3c). The size of graphene active area is varied in order to study the noise of the system. Each chip is measured on a multi-channel measurement system, which allows us to measure all the GFETs simultaneously. Thus, it is possible to measure not just single action potentials of the electrogenic cells, but even propagation of the potential through the network

Graphene Multielectrode Arrays as a Versatile Tool for Extracellular Measurements552

Graphene multielectrode arrays (GMEAs) presented in this work are used for cardio and neuronal extracellular recordings. The advantages of the graphene as a part of the multielectrode arrays are numerous: from a general flexibility and biocompatibility to the unique electronic properties of graphene. The devices used for extensive in vitro studies of a cardiac-like cell line and cortical neuronal networks show excellent ability to extracellularly detect action potentials with signal to noise ratios in the range of 45 ± 22 for HL-1 cells and 48 ± 26 for spontaneous bursting/spiking neuronal activity. Complex neuronal bursting activity patterns as well as a variety of characteristic shapes of HL-1 action potentials are recorded with the GMEAs. This paper illustrates that the potential applications of the GMEAs in biological and medical research are still numerous and diverse

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

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

Versatile Flexible Graphene Multielectrode Arrays

Graphene is a promising material possessing features relevant to bioelectronics applications. Graphene microelectrodes (GMEAs), which are fabricated in a dense array on a flexible polyimide substrate, were investigated in this work for their performance via electrical impedance spectroscopy. Biocompatibility and suitability of the GMEAs for extracellular recordings were tested by measuring electrical activities from acute heart tissue and cardiac muscle cells. The recordings show encouraging signal-to-noise ratios of 65 ± 15 for heart tissue recordings and 20 ± 10 for HL-1 cells. Considering the low noise and excellent robustness of the devices, the sensor arrays are suitable for diverse and biologically relevant applications