The graphene family has captured the interest and the imagination of an increasing number of scientists working in different fields, ranging from composites to flexible electronics. In the area of biomedical applications, graphene is especially involved in drug delivery, biosensing and tissue engineering, with strong contributions to the whole nanomedicine area. Besides the interesting results obtained so far and the evident success, there are still many problems to solve, on the way to the manufacturing of biomedical devices, including the lack of standardization in the production of the graphene family members. Control of lateral size, aggregation state (single vs. few layers) and oxidation state (unmodified graphene vs. oxidized graphenes) is essential for the translation of this material into clinical assays. In this Tutorial Review we critically describe the latest developments of the graphene family materials into the biomedical field. We analyze graphene-based devices starting from graphene synthetic strategies, functionalization and processibility protocols up to the final in vitro and in vivo applications. We also address the toxicological impact and the limitations in translating graphene materials into advanced clinical tools. Finally, new trends and guidelines for future developments are presented.

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Promises, facts and challenges for graphene in biomedical applications

Functional graphene nanomaterials (FGNs) are fast emerging materials with extremely unique physical and chemical properties and physiological ability to interfere and/or interact with bioorganisms; as a result, FGNs present manifold possibilities for diverse biological applications. Beyond their use in drug/gene delivery, phototherapy, and bioimaging, recent studies have revealed that FGNs can significantly promote interfacial biointeractions, in particular, with proteins, mammalian cells/stem cells, and microbials. FGNs can adsorb and concentrate nutrition factors including proteins from physiological media. This accelerates the formation of extracellular matrix, which eventually promotes cell colonization by providing a more beneficial microenvironment for cell adhesion and growth. Furthermore, FGNs can also interact with cocultured cells by physical or chemical stimulation, which significantly mediate their cellular signaling and biological performance. In this review, we elucidate FGNs–bioorganism int...

Functional Graphene Nanomaterials Based Architectures: Biointeractions, Fabrications, and Emerging Biological Applications

Graphene research and their outputs: Status and prospect

Application of graphene-based flexible antennas in consumer electronic devices

Neural interfaces are becoming a powerful toolkit for clinical interventions requiring stimulation and/or recording of the electrical activity of the nervous system. Active implantable devices offer a promising approach for the treatment of various diseases affecting the central or peripheral nervous systems by electrically stimulating different neuronal structures. All currently used neural interface devices are designed to perform a single function: either record activity or electrically stimulate tissue. Because of their electrical and electrochemical performance and their suitability for integration into flexible devices, graphene-based materials constitute a versatile platform that could help address many of the current challenges in neural interface design. Here, how graphene and other 2D materials possess an array of properties that can enable enhanced functional capabilities for neural interfaces is illustrated. It is emphasized that the technological challenges are similar for all alternative types of materials used in the engineering of neural interface devices, each offering a unique set of advantages and limitations. Graphene and 2D materials can indeed play a commanding role in the efforts toward wider clinical adoption of bioelectronics and electroceuticals.

Graphene in the Design and Engineering of Next-Generation Neural Interfaces

Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor's transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

/pdf/flexible-graphene-transistors-for-recording-cell-action-2vwc56oqap.pdf

Flexible graphene transistors for recording cell action potentials

Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfils important key requirements for for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor's transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

/pdf/flexible-graphene-transistors-for-recording-cell-action-2d9k5jzn8s.pdf

Abstract The chemical processing of low‐dimensional carbon nanostructures is crucial for their integration in future devices. Here we apply a new methodology in atomically precise engineering by combining multistep solution synthesis of N‐doped molecular graphene nanoribbons (GNRs) with mass‐selected ultra‐high vacuum electrospray controlled ion beam deposition on surfaces and real‐space visualisation by scanning tunnelling microscopy. We demonstrate how this method yields solely a controllable amount of single, otherwise unsublimable, GNRs of 2.9 nm length on a planar Ag(111) surface. This methodology allows for further processing by employing on‐surface synthesis protocols and exploiting the reactivity of the substrate. Following multiple chemical transformations, the GNRs provide reactive building blocks to form extended, metal–organic coordination polymers.

/pdf/depositing-molecular-graphene-nanoribbons-on-ag-111-by-2s98qrnv.pdf

Depositing Molecular Graphene Nanoribbons on Ag(111) by Electrospray Controlled Ion Beam Deposition: Self‐Assembly and On‐Surface Transformations

A combination of X-ray photoelectron spectroscopy (XPS), temperature-programmed XPS (TP-XPS), temperature-programmed desorption (TPD) measurements, and complementary scanning tunneling microscopy (STM) was employed to shed light on the complex thermal evolution of Bisphenol A and diethylstilbestrol on Cu(111) and provides clear evidence for hydroxy-directed on-surface polymerization, originating from ortho C–H bond activation. Both these technologically highly relevant molecules follow a common pattern of sequential chemical transformations, as highlighted by TPD and XPS results, eventually yielding disordered networks of branched polymers, which are observed by STM. The presented findings via an original methodological approach contribute to the store of knowledge in surface-supported, covalent coupling reactions, stressing the impact of directing group, role of the chosen substrate, and nature of the selected molecules.

Karolina Stoiber

Papers

Flexible graphene transistors for recording cell action potentials

Flexible graphene transistors for recording cell action potentials

Depositing Molecular Graphene Nanoribbons on Ag(111) by Electrospray Controlled Ion Beam Deposition: Self‐Assembly and On‐Surface Transformations

Bisphenol A and Diethylstilbestrol on Cu(111): On-Surface Polymerization Initiated by Hydroxy-Directed Ortho C–H Bond Activation