Properties, Processes and Applications
Currently (2017), over 10,000 academic papers about graphene, its properties and applications, are being published every year together with almost the same number of patent applications. This page describes the principles involved and some of the more common developments.
Source: AlexanderAlUS (Modified)
3D graphite consists of many layers of 2D graphene which are not molecularly bonded but instead held together by much weaker van der Waals bonding. Because of this weak bonding, the graphene layers easily slide over eachother which gives the graphite a soft and slippery feel and makes it suitable for use as a lubricant. Monolayer graphene sheets were first isolated by Geim and Novoselov in 2003 from the surface of a highly oriented pyrolytic graphite flake by a multiple-peeling process using common adhesive tape. This so-called mechanical exfoliation method leads to monolayer graphene with a highly crystalline structure and outstanding, unique physical properties.
See History - An unlikely beakthrough.
Graphene (G) is a two-dimensional allotrope of carbon consisting of a single, flat layer of carbon atoms just one atom thick bonded together in a hexagonal, honeycomb lattice with the appearance of "chicken wire" in which one atom forms the vertex of each hexagon. Carbon atoms have a total of 6 electrons; 2 in the inner shell and 4 in the outer, valence shell. Each carbon atom is bonded to three other carbon atoms with very strong covalent σ (sigma) bonds which are difficult to break, leaving one of the four electrons in each carbon atom's outer valence shell available for conduction and free to "wander" or to interact with other atoms or molecules. These highly mobile electrons are called π (pi) electrons or π orbitals (π and π*) are located above and below the graphene sheet. The pi orbitals overlap and help to enhance the carbon to carbon bonds in graphene. The electronic properties of graphene are dictated by the bonding of these π orbitals.
This 2D carbon graphene lattice is typically found in the form of platelets or flakes about 0.3 nanometres thick with the layer extending up to around 0.5 millimetres in the lateral dimension but is typically smaller than this.
This wonder nanomaterial has the following properties:
- 200 times stronger than steel, yet incredibly lightweight, due to the compact structure and the strong covalent bonding between the carbon atoms.
- Ultra-light yet immensely tough.
- Flexible and can be bent or folded.
- Can act as a perfect barrier due to its compact structure. Not even helium can pass through it.
- Transparent due to its infinitesimal thickness. Graphene absorbs only 2.3% of light transmitted through it so that it is almost invisible.
- The thinnest material known to exist.
- Chemically inert.
- Non toxic.
- Because the fourth electron, the pi (π) electron, from the carbon atom's valence shell is not naturally raised to a higher level there is no band gap associated with a separate conduction band.
- Electrically and thermally conductive with better conductivity than copper due to the highly mobile free pi (π) electrons.
- Since carbon is the Earth's fourth most common element, graphene is very inexpensive.
- Stretchable causing a change in sheet resistance. Can be stretched by as much as 20 per cent without inducing defects.
- It has also been observed by researchers at the Lawrence Berkeley National Laboratory and the University of Maryland that stretching a graphene sheet can alter its magnetic properties. This causes its pi (π) electrons to move in circles in the plane of the graphene sheet, as if a very strong magnetic field (up to 300 Tesla or 107 times the Earth's magnetic field) has been applied perpendicular to the sheet even when there was no actual external magnetic field. This could potentially enable control of the graphene's conductivity, optical and microwave properties. Currently, there is no other sustainable method for generating magnetic fields of this magnitude.
- The quantum Hall effect is another unusual behaviour which they observed in two-dimensional graphene systems subjected to low temperatures and strong magnetic fields. This is a quantum-mechanical version of the Hall effect, in which the Hall conductance σ undergoes quantum Hall transitions to take on quantised values and electrons fall into quantised energy levels.
- By means of doping or other processes (see below), graphene can be endowed with semiconducting properties including a tunable band gap.
- Using graphene oxide as a precursor, graphene derivatives with a wide range of physical and chemical properties customised for particular applications, can be produced. (see Functionalisation below).
The unique properties of this new wonder material opened up a multitude of potential new applications. The following examples are just a small sample of the many possibilities.
Graphene nanotechnology is still in its infancy and many of the manufacturing processes and applications may have only been demonstrated in the laboratory while others are be still in the development stage. The biomedical experiments in particular have mainly been carried out on lab samples in test tubes and Petri dishes (in vitro) and have not been fully tested on living persons (in vivo). It could be some time before graphene is ready to be used in safe, reliable, cost effective, high volume, practical products.
- Energy Harvesting and Storage
- Batteries - Graphene could dramatically increase the power and energy densities as well as the life span of traditional lithium ion batteries. Graphene used for the anodes in lithium ion batteries replaces both the traditional graphite electrode and also the anode's copper current carrier. Its high surface area to mass ratio and its high conductivity improve the battery's power handling, allowing higher currents and faster charge and discharge rates. Graphene's higher conductivity also improves the battery's Coulombic efficiency by reducing the Joule heating loss while its lower weight is a bonus which also improves the battery's energy density.
When incorporated into the alternative, high capacity, silicon enhanced anodes which suffer from cyclic mechanical stress, the graphene acts as a structurally rigid network or scaffold which prevents the repetitive swelling of the silicon which causes deterioration of the anode thus enabling longer cycle life.
The use of graphene for the electrode current collectors also makes flexible batteries possible. They could be so flexible and light that they can be stitched into clothing.
- Supercapacitors - As with batteries, the use of graphene for the plates/electrodes improves the capacitor's energy density and its current handling capacity due to its high conductivity and high surface area to mass ratio.
- Graphene Semiconductors
Semiconductors are defined by their band gap: the energy required to excite an electron in the valence band, where it cannot conduct electricity, to jump the energy barrier into the conduction band, where it can.
The zero band gap of graphene enables its free electrons to move through the graphene with almost no resistance causing the it to behave like a metal. But without a band gap, there is no way of controlling the number of free electrons in the material, so there is no "off" state and no way to control its conductivity. Pure graphene alone, without a band gap, thus can not have semiconducting properties. It will always be in the "on" state.
See details of How it Works
A semiconductor's band gap needs to be large enough so that there is a clear contrast between a its "on" and "off" states, and so that it can process information without generating errors.
Creating a Band Gap
Research is going on at many establishments throughout the World to find a practical way of modifying the graphene crystal lattice so as to induce a band gap into its electron orbitals to enable graphene to be used in the manufacture of diodes and transistors. Methods being pursued include doping or alternatively, physical stress on, or disruption of, the crystal lattice. Working graphene based semiconducting materials have been produced by various methods on a laboratory scale, some of which can be tuned to different band gap levels of up to 6 eV. (Materials with band gaps greater than 4 eV are normally considered to be insulators.) Sample field effect transistors (FETs) have also been constructed using the modified graphene. Up to now (2017) however it has been difficult to achieve consistent repeatable results and none of these methods have been scaled up into practical production. The following are some example methods of creating a band gap in graphene material:
- Band gaps have been successfully induced into graphene by doping the lattice with nitrogen (N) and boron (B) to form carbon alloys. These two dopant elements were chosen because they are the closest in size to the carbon atom so as to minimise the structural disruption of the graphene crystal lattice when they are inserted into it, to replace some of the carbon atoms. Compared with carbon which has an atomic mass of 6 with 6 electrons, nitrogen with an atomic mass of 7 has 7 electrons and is comparatively electron rich and is thus a N type dopant. Boron on the other hand with an atomic mass of 5 is relatively electron deficient with only 5 electrons and is thus an P type dopant.
The band gap produced depends on the concentration of the dopants so that it is possible to tune the band gap for specific applications.
- Graphene fabricated by epitaxial growth on a silicon carbide (SiC) substrate has been shown to exhibit a band gap. The high temperature annealing process causes the decomposition of the crystalline SiC substrates with the desorption of the silicon from the surface leaving behind an epitaxial layer (or layers) of graphene. The first of these layers, normally called the buffer layer, forms a band gap greater than 0.5 eV, due to the distortion of the graphene lattice caused by the highly periodic way it bonds to the SiC substrate.
- Band gaps have also been produced in bi-layers graphene, two sheets of graphene lying one on top of the other. There is no band gap when the two layers are perfectly aligned in mirror like symmetry and the layers behave like a metal, but if the symmetry is disturbed then they behave like a semiconductor. Electrical fields introduce asymmetry into the bilayer structure yielding a band gap that can be selectively tuned.
- Cutting graphene sheets into small ribbons can also be used to create band gaps in the narrow strips due to structural disorders in the graphene lattice near the edge of the ribbon.
- Another method of creating a band gap is by adsorption of aromatic molecules by the graphene layer when the molecules are brought up to its surface. Accommodating the molecules creates distortions in the graphene lattice which in turn lead to the opening of a band gap.
- Similarly, the presence of ions on the surface of the graphene lattice can influence the valence electronic structure of the lattice resulting in a band gap.
- Graphene Semiconductor Applications
Graphene's excellent electron mobility together with its compact size make it ideal high-speed electronics applications.
High electron mobility and thermal conductivity enable faster field effect transistors (FETs) and integrated circuits with increased heat dissipation keeping them cool. Graphene's thin structure also allows smaller components and circuits with a corresponding increase in high frequency performance as well as the benefits of miniaturisation.
- Photovoltaic (PV) Cells
The conversion of light into electric currents and voltages is normally defined by the quantum effect of photons on semiconductor materials in which photons with energies corresponding to a particular light wavelength transfer their energy to electrons in the the material's valence band. This gives the valence electrons enough energy overcome the material's characteristic band gap and jump to its conduction band where they become current carriers creating electron-hole pairs. Semiconductors of a particular type have typically only one band gap which corresponds to the atoms which make up the semiconducting material. This means that semiconductors are normally sensitive to light from only a small region of the optical spectrum and the energy from light from the rest of the optical spectrum is dissipated as heat so that their conversion efficiency is consequently low.
Graphene Photovoltaic Cells
The structure of the graphene lattice with its free π electron orbitals provides the opportunity for additional energy transfer mechanisms including charge carrier multiplication and makes it suitable for the construction much higher efficiency PV cells.
- When light energy impinges on doped graphene based PV cells the photon energy associated with the band gap of the semiconducting graphene causes the creation of an electron-hole pair as noted above. But this is just the first step of a longer process. The excess energy from the light source, over and above the "band gap energy" consumed in releasing the original hole-pair, is not just dissipated as heat but can cause a secondary hole-pair to be released when collisions occur as the new electron-hole pair is scattered in the graphene lattice. The resulting two electron-hole pairs can create two more electrons which in turn generate four more causing an avalanche multiplication effect. The current generated depends on the level of doping.
Though initiated by a single absorbed photon, this carrier multiplication in the graphene enables a much greater energy conversion efficiency. Novel photovoltaic devices using graphene could harvest light energy across the entire solar spectrum with lower energy loss than current systems.
- Graphene's high optical transparency coupled with its high electrical conductivity make it an ideal material for PV electrodes since it allows the maximum solar energy to reach the active material while offering minimal resistance of the charge collector to the take off of the generated current.
- Graphene Oxide (GO)
In its natural state GO is used in membrane form in filtration applications, however it also finds important use as an intermediary product in the manufacturing of pure graphene (see Graphene Production below) as well as a precursor in the production of hundreds of chemically modified graphene derivatives.
- GO Properties
Graphene is noted for its ease of functionalisation and low costs. Thanks to its abundant oxygen-containing groups, the properties of graphene oxide can be modified in a variety of ways by changing its surface chemistry, either replacing its oxygen atoms with alternative atoms or molecules, or attaching molecules to the oxygen sites to create nanocomposite derivatives. Functionalisation is a fundamental chemical technique which has a decisive influence on the material's reactivity enabling new functions, features, capabilities, or properties to be added. This allows graphene be customised for particular applications such as biosensors, drug delivery, catalysts and semiconductors or to enhance the physical properties of composite materials.
By means of covalent and non-covalent bonding, unique properties of both G and GO can be combined with other molecules and nanomaterials such as metals, metal oxides, magnetic nanoparticles and quantum dots (very small semiconductor particles with unique properties), to enable a wide range of applications.
Bonding is also used to bind molecules such as enzymes to graphene supporting structures where they are immobilised. The graphene acts as a carrier in drug transport applications where the enzymes are used as catalysts in biochemical actions. The immobilisation means that the enzymes are less affected by the surrounding environment. They are thus more stable and do not mix freely with the surrounding chemicals so that their integrity and efficacy are preserved and they may be re-used.
- Covalent Bonding
With covalent functionalisation, the oxygen-containing functional groups on the surface of the GO lattice, or on the edges of the GO sheets, can be used as anchoring sites for covalent bonding with different molecules and nanoparticles which change its surface functionality enabling it to be used in diverse applications. Graphene is thus a possible starting material for immobilisation of a large number of substances including a wide range of metals, biomolecules, fluorescent molecules, drugs, and inorganic nanoparticles.
Covalent functionalisation however can compromise the structure of G lattices caused by accommodating the extra molecules resulting in defects and the degrading of the electronic properties of the lattice.
- Non-covalent Bonding
The non-covalent functionalisation of G and GO depends on the weaker van der Waals forces or electrostatic forces or the π–π interactions (also known as π stacking) between the graphene and the target molecules. It does not alter the structure and electronic properties of graphene lattice while it simultaneously introduces new chemical groups on the surface.
Non-covalent functionalisation can be used to enhance the graphene's dispersibility, biocompatibility, reactivity, binding capacity and sensing properties.
Bonding between G and organic molecules typically depends on van der Walls forces. Ionic bonds are not possible with pristine G since it has no oxygen atoms which could contribute to such interactions.
Ionic interactions and hydrogen bonding are however possible with GO derivatives because of the presence of oxygen groups on the surface and edges of the GO.
Non-covalent π–π bonds result from overlap of atomic orbitals that are in contact through two areas of overlap. Molecular π–π interactions also occur between cyclic atomic structures in the form of hexagonal rings, often called aromatic rings, which each have a free π electron.
Organic molecules and polymers are typical of such rings and graphene has a similar ring structure. The free π electrons however would tend to repel eachother if the hexagonal rings were directly opposite and parallel to eachother (face to face) weakening the effect of the non-covalent π–π interaction between the aromatic rings and reducing the stability of the bond. The space between the atoms forming the peripheral of individual rings is however less negative than the space between the electrons of two layers directly opposite to eachother. If the rings are offset laterally from eachother by half the distance between adjacent peripheral atoms forming the ring so that the electrons are not directly opposite eachother, and instead fall within the slightly less negative spaces at either side of the opposite pairs of atoms, there will be a slight reduction in the repulsive force between the rings strengthening the effect of the non-covalent π–π interaction. It is not a covalent bond in the strict definition of the word since it does not involve the sharing of electrons, but rather involves electromagnetic interactions within or between molecules. Similar interactions exist if the rings are arranged in other configurations such as perpendicular to eachother in a T- shaped structure.
More generally an electron-rich π system such as graphene can interact with a metal, an anion, another molecule and even another π system. Non-covalent interactions involving π systems are fundamental to biological relationships including π stacking within the the double-ringed bases in RNA and DNA
An important advantage of non-covalent bonding is that for most applications the G or GO lattice is not disrupted, which means that important properties such as electrical conductivity, mechanical strength or solubility are not affected. For larger or extended systems, such as polymers containing repeating aromatic rings, the multiple π–π interactions between graphene derivatives and polymers can strongly bind the monolayers leading to highly homogeneous polymer composites with enhanced mechanical, electrical, and thermal properties.
On the other hand, in simpler systems, because of the weak binding interactions with the smaller molecules, the bonding is relatively easy to bring about and potential to release the bonded molecules from the lattice also exists. This latter advantage is useful in drug delivery systems.
See more about Bonding.
- Barriers (Graphene)
Graphene is thought to be completely impermeable to all gases and liquids. That makes it an extremely effective barrier film.
- Graphene coatings on food and pharmaceutical packaging can stop the transfer of water and oxygen keeping food and perishable goods fresher for longer.
- Graphene is both inert and hydrophobic and so can act as an anti corrosion barrier between oxygen and water diffusion. This could mean that it has the potential to be grown onto metal surfaces, such as car bodies, make them corrosion resistant.
- Similarly graphene sheets could create hydrophobic coating materials to build water repellent structures.
- Filters (Graphene Oxide)
Filtration applications use graphene oxide (GO) membranes instead of the impermeable graphene because the filter must allow some substances to pass through the membrane.
- Water Filtration, Gas Separation and Desalination
The ability to filter out small nanoparticles, organic molecules, and even large salts has already been demonstrated by graphene oxide membranes which have a larger pore size, however they were not able to sieve out common salts used in desalination technologies, which require smaller pore sizes. This is because graphene oxide membranes become slightly swollen when immersed in water, and while larger ions or molecules are blocked by the membrane, smaller salts flow through along with water.
Researchers at Manchester University recently (2017) discovered that by stacking layers of graphene oxide on top of each other in a film to form a membrane, the resulting inter-layer spaces between the GO flakes in multi-layer stacks can form capillaries or pores about one atom wide. These tiny capillaries just like graphene, were impermeable to a small, inert gas molecules such as helium, but surprisingly, they allowed water to freely move through the film by capillary action. Helium however was able to pass when dissolved in water in a process still not well understood.
Despite this, and somewhat contradictively, they have shown that the swelling of the graphene oxide can be prevented and the pore sizes precisely controlled so that they can be made small enough to sieve common salts out of salty water and make it safe to drink. The reason however given as to why the salt molecules don't get through the sieve is not that the pores are smaller. Instead they explain that when the common salts are dissolved in water, they always form a 'shell' of water molecules around the salt's molecules which increases their size. This allows the tiny capillaries of the graphene-oxide membranes to block the salt from flowing along with the water.
In all cases water molecules are able to permeate quickly through the graphene oxide membrane barrier and flow anomalously fast which these membranes is ideal for desalination applications.
Like many new discoveries, the potential use of graphene oxide for filtration applications has been demonstrated in the laboratory. For practical applications however, the size of the membranes needs to be scaled up from the 1 cm diameter used in the lab tests while at the same time they must be able to withstand the high pressures encountered in industrial applications.
- Mechanical Applications and Composite Materials
Graphene's many unique mechanical and electrical properties have been employed in the following applications.
- Aircraft Structures - Graphene-based composites can have high strength to weight ratios. Used in aircraft wings they could substantially decrease the weight permitting increased fuel efficiency and range. Similarly they could be used to reduce the weight of wind turbine blades.
- Graphene's electrical conductivity could also be exploited for de-icing the aircraft's working surfaces.
- Automotive components including structural parts and safer fuel tanks - Exploiting graphene's light weight, high strength and conductivity.
- Automotive and Bicycle Tyres
- Graphene is also currently being developed as a potential replacement for Kevlar in protective clothing.
- Sporting Goods - Graphene composites are used to enhance the performance of bicycles, tennis racquets, skis and fishing rods. Graphene based coatings could also reduce the surface friction and increase the durability of skis.
- Protection Against Corrosion - By combining graphene with paint or other coatings, an impermeable, waterproof barrier can be formed to protect metals against corrosion and rust.
- Weatherproofing - The same technique could also by applied to brick and stone to weatherproof buildings.
- Electrically conductive adhesives and plastics.
- Lubricants - Graphene and graphene loaded composites make very effective friction free surfaces.
- Catalysts - Nitrogen doped graphene has been shown to be an effective replacement for the very expensive platinum catalyst used in proton exchange membrane fuel cells (PEMFCs) making fuel cells more cost effective.
- The non-covalent functionalisation of G/GO with magnetic nanoparticles (mainly iron oxides) provides an easy way to create a magnetically and electrically controllable system. Displacement of the magnet can cause an electrical current in the graphene lattice or alternatively the application of an electric current can cause the magnet to move. This makes possible very small motion sensors, actuators and switches for use in biomedicine or environmental applications.
- Graphene Sensors
Graphene is versatile low cost nanomaterial with a unique set of properties which make it ideal for use in physical, chemical and electrochemical sensors.
Every atom in in the graphene sheet is exposed to its environment on both sides of the sheet giving it the maximum exposure to sense changes in its surroundings. Coupled with its superlative low electrical noise performance, graphene sensors thus have exceptional sensitivity. This allows the detection of individual events on a molecular level by micrometre-sized sensors which can detect just one molecule of a potentially dangerous substance. Similarly graphene can be used to construct local probes sensitive to external changes such as magnetic fields or mechanical strain.
Graphene's low band gap and corresponding high electrical conductivity give rise to highly mobile free electrons which enable it to produce ultra-fast results while its high surface to mass ratio, its physical strength, stability and minimal thickness make possible tiny, robust, and inobtrusive sensors.
Graphene-based nanoelectronic devices have the potential of for use in a wide variety of physical and chemical sensors including: light sensors, strain gauges and pressure sensors, gas detectors, PH sensors, environmental contamination sensors and in DNA analysis where they are used for for detecting nucleobases and nucleotides. In biomedical applications they are small and inobtrusive enough to be dispersed throughout the body. Some examples follow:
- Mechanical Sensors
The strain gauge is the fundamental sensing element in many different types of sensors including stress, strain, pressure and torque.
- Sensors based on conductance/resistance change as the output are the easiest to build, test, and calibrate since there is a linear relationship between the strain applied to the graphene by stretching and its electrical resistivity.
- Strain Gauges are fabricated by bonding graphene to a suitable substrate. In a multi-layer graphene network the strain response mainly depends on the contact resistance between adjacent sheets.
- Gas Sensors
Because of its high sensitivity, graphene is an ideal material for building highly sensitive gas detectors since even the smallest quantity of a gas will get caught in its lattice, changing its electrical properties.
Micrometre-size graphene sensors are capable of detecting individual events when a gas molecule attaches to or detaches from graphene’s surface. The adsorbed molecules change the local current carrier concentration in graphene by one electron, changing its work function which in turn leads to step changes in its resistance. By incorporating the graphene sensor into the body of a field effect transistor (FET), where it doubles as the FET's gate electrode, the change in the input condition results in a major change in the current flow through the FET. This signal can be monitored and analysed to identify tell-tale characteristics which can identify the molecule.
When the gas molecule separates from the graphene, the graphene returns to its original state. Because the sensor does not rely on chemical reactions, it is both faster and more sensitive than existing technologies. Some examples follow:
- Common Gas Detection - In practice the above device has been shown to detect concentrations of nitrogen dioxide (NO2) and ammonia (NH3) of less than tens of parts per billion (ppb).
- Breath Testing - Future applications include the detection of gas components in breath, which can potentially identify possible lifestyle diseases.
- Defence - Highly sensitive graphene based sensors could be tuned to detect chemical warfare agents such as poison gases and low level vapours such as ammonia often associated with some explosives.
- Food Decay - Sealed packaging which has been coated with graphene has the ability to detect atmospheric changes caused by decaying food.
Larger scale or bulk gas detection is easier to implement and is achieved by means of loading the G lattice with metal oxide nanocomposites. Each metal oxide has a unique characteristic reaction to a particular gas or gases which will change the resistivity of the doped G lattice. Oxidising and reducing gases have different reactions which can lead to carrier (electron) generation or carrier annihilation on the sensing layer. This results in a change of resistance of the detection device and hence its current which can be monitored to provide the sensing signal.
- Chemical Sensors
Just like the gas sensors described above, chemical sensors typically use nanocomposite reagents with characteristic reactions to detect the presence of, and distinguish between, different materials including biomedical samples.
- pH Sensors - Sensors to measure alkalinity or acidity have been constructed from small pieces of graphene with two platinum contact electrodes. The resistance of the graphene sheet decreases linearly with increasing pH values in the surrounding environment in the range from 4 (acid) to 10 (alkali), 7 being neutral. The sensitivity is about 2kΩ/pH level.
(NOTE: The pH scale is logarithmic so that each whole pH value below 7 is ten times more acidic than the next higher pH value and for pH values above 7 each level is ten times more alkaline than the next lower whole value.)
- Optical Sensors
GO has interesting optical properties: It can fluoresce over a wide range of wavelengths and also effectively quench the fluorescence of other fluorescent dyes called fluorophores. These characteristics give GO the potential as a useful fluorescence label for optical imaging.
- Fluorescence is a property some molecules have which means they absorb a burst of light of one colour and emit light of a different colour. It occurs when a high energy photon (from the UV or blue end of the visible spectrum) is absorbed by the molecule and excites an electron from its ground state into a higher energy vibrational state in the conduction band.
When the excitation is removed the electron drops back to its ground state releasing its absorbed energy in the form of a lower energy photon of light since some of the electron's energy is lost as vibrational energy during the transfer. The light from a lower energy photon will consequently have a lower frequency or longer wave length than the original incident light and hence it's colour will be offset towards the IR or red end of the spectrum.
Different molecules exhibit different excitation and emission profiles.
- Fluorophores are molecules such as dyes and many aromatic modules which can fluoresce and thus emit light.
Most biological matter is fluorescent. Examples include the three aromatic amino acids and proteins containing them, as well as nucleic acids and nucleotides found in DNA and RNA.
- Chlorophores are acceptor molecules which absorb light at a specific frequency thus imparting colour to the molecule.
- Fluorescence resonance energy transfer (FRET) is the process by which an optical excitation in one fluorophore transfers energy non-radiatively to another fluorophore either overlapping it or in its very close vicinity. The energy intensity is distance dependent and works on a molecular scale making it one of the few tools capable of measuring nanometer scale distances.
- Quenching is the loss of fluorescence signal due to very short-range interactions between the fluorophore and the local molecular environment, including other fluorophores. It is a FRET effect.
In general, quenching occurs without any permanent change in the molecules, that is, without a photochemical reaction.
Optical Applications Including Bioimaging
Graphene and graphene-like nanomaterials can be tailored to form either fluorescent emitters or efficient fluorescence quenchers, making them powerful platforms for building optical biosensors which can sensitively detect various targets including ions, small biomolecules, proteins, DNA and RNA. Detection is based on spectral shift and intensity of the emitted light.
Changes in fluorescence can be monitored in the lab using a microscope. In vivo probes for monitoring living cells have been made using photodiode light detectors.
- GO can be used as a quenching material in a FRET sensor in which the excitation of an individual molecule transfers non-radiatively to the GO, or vice versa, depending on wether the GO or the molecule was illuminated. The proximity of the quenching material makes the fluorescence disappear from the other emitting fluorophore. The material under test can be identified from its characteristic emission.
- Because the intensity of the quenching effect changes rapidly with distance over a very short range, the FRET probe can measure distances and monitor interactions between domains in a single protein or between proteins.
- Biosensors to detect metal ions may contain a single fluorescent protein bonded to a graphene substrate that senses the presence or concentration of a given ion in a sample. When the metal ion is present, the sample fluoresces. When the ion is absent, the sample does not fluoresce
- Biomedical Applications
Many applications are just at the beginning stage and still have a long way to go. Before any large scale deployment, or even small scale experiments, of graphene's medical applications can take place there must be a full understanding its biocompatibility and potential risks and it must undergo numerous safety, clinical and regulatory trials which will take a very long time.
Graphene based materials are non toxic and demonstrate excellent electrochemical and optical properties, as well as the capability to adsorb a variety of aromatic biomolecules through a π–π stacking interaction and/or electrostatic interaction, which make them ideal materials for constructing biosensors and loading drugs. The following are some examples:
Graphene's unique features and excellent electrochemical properties as described in the section on gas sensors above also make it a good candidate for the development of fast, efficient and highly sensitive bioelectric sensory devices. In addition, its π–π stacking reaction which allows the direct electron transfer between the electrode surface and enzymes and other biomolecules can be used, among other things, for the detection of a range of analytes such as glucose, cholesterol, haemoglobin, glutamate (a chemical that nerve cells use to send signals to other cells) DNA, RNA and more.
- Diagnostic Sensors
These sensors are based upon graphene's large surface area and the fact that molecules that are sensitive to particular diseases can attach to the carbon atoms in graphene. For example, researchers have found that graphene, strands of DNA, and fluorescent molecules can be combined to diagnose diseases. A sensor is formed by attaching fluorescent molecules to single strand DNA and then attaching the DNA to graphene. When an identical single strand DNA combines with the strand on the graphene a double strand DNA if formed that floats off from the graphene, increasing the fluorescence level. This method results in a sensor that can detect the same DNA for a particular disease in a sample.
- Biological Agents
G and GO can be functionalised with anti bacterial and other drugs.
- Experiments have shown that Staphylococcus and E. coli cells can not survive on a graphene films on Cu and Ge substrates because the graphene's free electrons interfere with the the morphology and membrane integrity of the cells thus killing the cells.
This experiment could be a two edged sword in the development of engineered graphene based biological agents in that graphene is normally non-toxic to humans but it has been shown to be toxic to bacteria in certain circumstances. This is a warning sign that will demand extensive safety approval testing before new developments can be released.
- Drug Delivery Systems
G and GO have several advantages over other nanomaterials used as carriers for drug delivery. Their ultrahigh surface area and single atom thick lattice with every atom exposed on its surface coupled with its π–π bonding capability make it possible to load large numbers of drug molecules on to both sides the lattice carrier. The minute size of graphene systems also allows carrier to penetrate basic biological structures disrupting their abnormal functions hence making them potential drug delivery carriers for anti-cancer drugs. Multiple layers can also be used to increase the nanoparticle's carrying capacity. The dispersal properties of multi-layer carriers can also be tuned by combining hydrophobic G layers with hydrophilic GO layers.
- It has been demonstrated that the aromatic anti cancer drug doxorubicin (DOX) can be attached to GO nanoparticles for delivery to target cancer cells by simple physisoption which does not affect the electronic structure of the GO. This non-covalent bonding depends on of π–π stacking.
- Similar transport methods are used for other drugs.
How drugs get to their targets
Drugs can not be delivered directly to an infected or damaged organ or body part as if it had an address unless they are injected directly into the target. Drugs taken orally instead are absorbed into the blood stream, along with oxygen and a host of other nutrients, and circulated to all parts of the body. Though some of the drug may be destroyed in its passage through the acidic chemical mix in the stomach, the environment is not as harsh as might be imagined.
The digestive process is very complex and involves the breaking down of food into a wide range of nutrients which are all absorbed into the blood stream and dispersed throughout the body where they are used for energy, growth, and cell repair. Various digestive juices including enzymes which catalyse the process are used to break down large molecules into smaller molecules which can be absorbed into the blood stream. The explanation below is limited to the aspects associated with the three major digestive organs, the stomach, the small intestine and the liver, which may influence the transport of drugs through the digestive tract.
With drugs, as in normal digestion, the stomach is the first major organ involved in the digestive process. It does not however cause complete chemical breakdown of its contents but converts them into chyme, a fluid mix of digestive juices and food categories such as proteins, fats, carbohydrates, fibre, together with the drug dose, which is passed on to the small intestine. The small intestine continues the digestive process using more digestive juices including alkaline bile secreted by the liver and bacteria to further break down the nutrients from the chyme. The resulting nutrients are absorbed through the intestine wall into the blood stream and passed on, together with the ingested drugs, to the liver leaving the waste products to be excreted via the large intestine.
The liver has multiple functions. Apart from the production of bile, it processes the blood coming from the small intestine containing the nutrients just absorbed and further breaks down the nutrients in the blood into forms suitable for absorbtion by the various organs and tissues of the body. It also purifies this blood of many impurities before passing it back into the blood stream completing this part of the digestive process.
Drugs taken orally are designed to survive the challenging environments of the acidic stomach and the alkaline intestine and liver as they make their way into the blood stream though up to 50% may be lost or destroyed in the process.
In the blood stream the drug is designed to react only to the specific set of chemicals which typify the source of the infection or the damaged tissue. Such precise action is not always possible and the drug may cause unwanted side effects elsewhere in the body. The drug dose is calculated to stay in the blood stream long enough to cure the problem, which may be up to a few days, and only enough of the drug to cure the problem is consumed. The amount actually used could be anything from 5% to 50% of the drugs which have entered the bloodstream. The balance is excreted.
The doctor's prescribed drug dose obviously takes into account the total expected losses incurred in the digestive system. Ultimately, the amount of the drug actually reaching and reacting with the target could be as low as 2% of the ingested dose.
- Tissue Engineering
Graphene's biocompatibility, its large surface area, excellent mechanical properties, and ease of functionalisation make it a unique material for bone tissue and stem cell research. GO substrates allow cell adhesion and proliferation, and have been shown to be capable of increasing the differentiation of stem cells into osteogenic lineage.
- An obvious application is as a reinforcing agent in bone tissue applications.
- It is also anticipated that graphene scaffolds could play a role in tissue engineering and regenerative medicine. Researchers at Singapore's National University populated a graphene scaffold with stem cells and discovered that, not only did the cells survive, they divided, proliferated, and morphed into neuron-like cells.
Several methods are currently used to produce graphene including exfoliation, chemical vapour deposition (CVD), and epitaxial growth.
Exfoliation is the separation of the 2D graphene layers from 3D graphite. The original method of accomplishing this was by means of adhesive tape pulling graphene layers from the surface of the graphite. Since then several variations of this mechanical method have been developed including shearing with a single crystal diamond wedge.
A more promising method of exfoliation is by chemical means. This process involves the oxidation of graphite using strong oxidising agents to create graphite oxide. This modifies the graphite structure expanding the layer separation while at the same time making the material hydrophilic. This means that the layers can be dissolved and dispersed in water. Sonification, the application of sound waves, then separates the dissolved layers of graphite oxide into a small number of mono-layers of now called graphene oxide (GO). The final stage is the chemical reduction of the graphene oxide to form flakes of graphene. Work continues to refine the oxidation and reduction processes improve the quality and increase the size of the flakes.
- Chemical Vapour Deposition (CVD)
The process of chemical vapour deposition of hydrocarbons over a metal catalyst is well known and has been used for many years to produce various carbon materials such as carbon fibres and filaments. It is also used extensively in the semiconductor industry to produce thin films.
The first stage of the CVD process is pyrolysis, the high temperature decomposition of the precursor organic material, in this case methane, to form carbon, followed by the formation of the carbon structure of graphene using the disassociated carbon atoms. Precise control of the chemical reaction rate and the temperature are critical and metal catalysts used to achieve this.
To produce graphene, an intermediate metal substrate such as copper or nickel foil is put into a furnace and heated in a vacuum to around 1000° Celsius. Methane and Hydrogen at ambient temperature are then introduced into the furnace's reaction chamber. The hydrogen acts as a catalyst in the reaction between the surface of the metal substrate and the methane which decomposes, depositing its carbon atoms on the surface of the metal through chemical adsorption, crystallising into a contiguous graphene layer. The furnace is quickly cooled to prevent further carbon from building up on the deposited graphene layer turning it into bulk graphite.
By introducing suitable gas plasmas during the deposition process it is possible to produce n-doped and p-doped graphene directly.
The area of the graphene layer produced by this method is much larger than the individual flakes produced by exfoliation techniques.
To remove the graphene from the intermediate substrate, a polymer is coated onto the graphene to act as a carrier and the metal foil is removed from the carrier by etching, leaving the graphene attached to the polymer. This graphene layer with its polymer carrier can then be positioned on the substrate intended for its planned application such as a solar cell. The polymer can then be removed by dissolving it in a solvent leaving the graphene layer on the desired substrate.
Graphene samples with areas of several square centimetres and excellent electrical and optical properties have been fabricated using chemical vapour deposition and successfully used in the manufacture of FETs.
- Epitaxial Growth
Epitaxial deposition is a process used in the manufacture of transistors. It was originally developed for growing a new crystal layer of one material on the crystal face of another so that the two materials have the same crystallographic orientation as the substrate. Several methods are used depending on the materials concerned and the functions of the product.
The production of graphene using this technique is relatively simple. It is based on the high temperature annealing of silicon carbide SiC at over 1000° Celsius in a low pressure atmosphere of around 10−6 torr. This causes the sublimation (the phase transition directly from a solid to the gas phase without passing through the intermediate liquid phase) of the more active silicon atoms followed by their desorption as a vapour from the surface of the substrate leaving a carbon-rich surface behind. The high process temperature also ensures the ordered structure of the carbon left behind in the form of an epitaxial graphene layer on the surface of the SiC. In other words, the silicon is evaporated from the surface of the SiC, allowing the upper carbon atoms to reposition in the next lower layer.
This method has several advantages
- It is relatively simple.
- It enables large areas of graphene with uniform thickness to be produced, dependent on the size and surface of the SiC wafer.
- SiC wafers are commercially available from the semiconductor industry.
- Transfer of the graphene layer to another substrate is not necessary for many applications since many electronic devices are fabricated directly on SiC substrates.
- With the appropriate conditions it is possible to grow n-doped or p-doped graphene directly by this process.
While all of the above methods have been used to produce graphene in lab scale and small scale production it will be some time before the methods can be scaled up for commercial and industrial applications.
Great progress has been made in the last 13 years but applications are still limited by the maximum flake size available, contamination and lattice defects all contributing to low low yields and high costs.
With the worldwide effort being applied to this technology these problems are not insurmountable. They did it with transistors and semiconductors in the 1950s and 1960s.