Graphene Oxide-Based Targeting of Extracellular Cathepsin D and Cathepsin L As A Novel Anti-Metastatic Enzyme Cancer Therapy

This is the final version. Available from the publisher via the DOI in this record.Overexpression and secretion of the enzymes cathepsin D (CathD) and cathepsin L (CathL) is associated with metastasis in several human cancers. As a superfamily, extracellularly, these proteins may act within the tumor microenvironment to drive cancer progression, proliferation, invasion and metastasis. Therefore, it is important to discover novel therapeutic treatment strategies to target CathD and CathL and potentially impede metastasis. Graphene oxide (GO) could form the basis of such a strategy by acting as an adsorbent for pro-metastatic enzymes. Here, we have conducted research into the potential of targeted anti-metastatic therapy using GO to adsorb these pro-tumorigenic enzymes. Binding of CathD/L to GO revealed that CathD/L were adsorbed onto the surface of GO through its cationic and hydrophilic residues. This work could provide a roadmap for the rational integration of CathD/L-targeting agents into clinical settings.Engineering and Physical Sciences Research Council (EPSRC)FORCE Cancer Charit

Transfer-free growth of graphene on SiO2 insulator substrate from sputtered carbon and nickel films

AbstractHere we demonstrate the growth of transfer-free graphene on SiO2 insulator substrates from sputtered carbon and metal layers with rapid thermal processing in the same evacuation. It was found that graphene always grows atop the stack and in close contact with the Ni. Raman spectra typical of high quality exfoliated monolayer graphene were obtained for samples under optimised conditions with monolayer surface coverage of up to 40% and overall graphene surface coverage of over 90%. Transfer-free graphene is produced on SiO2 substrates with the removal of Ni in acid when Ni thickness is below 100nm, which effectively eliminates the need to transfer graphene from metal to insulator substrates and paves the way to mass production of graphene directly on insulator substrates. The characteristics of Raman spectrum depend on the size of Ni grains, which in turn depend on the thickness of Ni, layer deposition sequence of the stack and RTP temperature. The mechanism of the transfer-free growth process was studied by AFM in combination with Raman. A model is proposed to depict the graphene growth process. Results also suggest a monolayer self-limiting growth for graphene on individual Ni grains

An empirical study of mesoscopic fluctuations in electron transport

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Interference and interaction of charge carriers in graphene

Electron transport at low temperatures in two-dimensional electron systems is governed by two quantum corrections to the conductivity: weak localisation and electron-electron interaction in the presence of disorder. We present the first experimental observation of these quantum corrections in graphene, a single layer of carbon atoms, over a temperature range 0.02 - 200 K. Due to the peculiar properties of graphene, weak localisation is sensitive not only to inelastic, phase-breaking scattering events, but also to elastic scattering mechanisms. The latter includes scattering within and between the two valleys (intra- and inter-valley scattering, respectively). These specifics make it possible, for example, to observe a transition from weak localisation to antilocalisation. Our work reveals a number of surprising features. First of all the transition occurs not only as the carrier density is varied, but also as the temperature is tuned. The latter has never been observed in any other system studied before. Second, due to weak electron-phonon interaction in graphene, quantum interference of electrons survives at very high temperatures, up to 200 K. For comparison, in other two-dimensional (2D) systems the weak localisation effect is only seen below 50 K. The electron-electron interaction correction is also affected by elastic scattering. In a two-valley system, there are two temperature regimes of the interaction correction that depend on the strength of inter-valley scattering. In both regimes the correction has its own expression. We show that because of the intra-valley scattering, a third regime is possible in graphene, where the expression for the correction takes a new form. The study of weak localisation demonstrates that the third regime is realised in our experiments. We use the new expression to determine the Fermiliquid parameter, which turns out to be smaller than in other 2D systems due to the chirality of charge carriers. At very low temperatures (below 100 mK) we observe a saturation of the electron dephasing length. We study different mechanisms that could be responsible for the saturation and discuss in detail one of them – spin-orbit interaction. We determine the spin coherence length from studies of weak localisation and the temperature dependence of the conductivity and found good agreement between the two types of experiments. We also show the way to tune the spin coherence length by an order of magnitude by controlling the level of disorder. However, experiment shows contradictions with theory both in values of the spin coherence length and the type of spin relaxation. We speculate about another spin-related mechanism, spin flip by vacancies, which to some extent could also explain our observations. We also present electron transport in graphene irradiated by gallium ions. Depending on the dosage of irradiation the behavior of electrons changes. Namely, electron localisation can be tuned from weak to strong. At low dosages we observe the weak localisation regime, where the mentioned quantum corrections to the conductivity dominate at low temperatures. We found the electron scattering between the valleys to be enhanced, attributing it to atomically sharp defects (kicked out carbon atoms) produced by ion irradiation. We also speculate that gallium ions can be embedded in the substrate or trapped between silica and graphene. We draw this conclusion after investigation of the spin-orbit interaction in irradiated samples. At high dosages electrons become strongly localised and their transport occurs via variable-range hopping.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Electronic transport and flicker noise in graphene structures

In this thesis the properties of graphene are studied via the various aspects of the quantum transport: doping of the graphene surface with organic molecules, flicker noise and transport in the quantum Hall regime. First, it was shown that certain molecules (toluene, aniline and water), which possess such common properties as non zero dipole moment and ability to undergo the electrochemical reaction, have a peculiar doping effect on graphene. The effect of toluene doping was studied in detail and is explained by the electrochemical reaction, which takes place in the vicinity of the graphene and results in a gate voltage dependent doping. Second, the flicker noise in graphene and its relation to the scattering mechanisms were studied. The flicker noise as a function of the carrier concentration was demonstrated to be sensitive to the scattering potential determining the resistance of the graphene. Therefore, as it was suggested, the flicker noise can be used as a tool for determining the dominant scattering mechanism in graphene, although it was found that the resistance and noise can originate from different scattering potentials. Also, the flicker noise spectrum was shown to decompose into individual lorentzians at low temperatures (below ∼ 25 K), where the fluctuations of the resistance is supposedly coming from the random jumps of electrons between the conductive channel in the graphene flake and the nearby impurity states. Third, the transport properties of the bilayer/trilayer graphene structure were studied at different temperatures and different magnetic fields including the quantum Hall regime. Bilayer and trilayer parts of the sample revealed the signatures of the quantum Hall effect predicted theoretically. The transport through the interface between bilayer and trilayer parts was also investigated. Signatures of the interface resistance were seen, although the observed behaviour is not explained. Under high magnetic fields the properties of the interface longitudinal resistance were described qualitatively by the classic transport equations.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Non-equilibrium phenomena in graphene

Graphene has displayed much promise as an electrical conductor and as a optical material. To date there is a large body of literature dedicated to the equilibrium properties of graphene. In this thesis the properties of graphene out of equilibrium are probed. Through combined optical and transport measurements the behaviour of hot electrons are probed at temperatures over five orders of magnitude from 50mK to 2000K. This wide range of temperatures allows access to the behaviour of quantum corrections at the lowest temperatures to the highest energy phonon modes. From ultrafast femtosecond laser pulses to steady state heating from an electric field the cooling of hot electron populations through coupling to various phonon modes in the graphene and the substrate are explored. Additionally the effect of an electric field on the weak localisation correction to the conductivity was separated from heating effects using applied magnetic fields combined with careful modelling of the heat transport properties of the graphene. Finally the desorption dynamics of oxygen bound to the surface are shown using a combination of transport and two pulse correlation technique using an ultrafast laser. Surprisingly the cooling of hot carriers in graphene at low energies shows substrate surface phonons as an important cooling mechanism, highlighting the importance of substrate choice in future graphene devices. In contrast at the very highest energy scales accessed only by photoexcitation the cooling is shown not to be influenced by the presence of a substrate, but out-of-plane phonon modes increase cooling of the hot optical phonons.EThOS - Electronic Theses Online ServiceEPSRCGBUnited Kingdo