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Colloidal gold is a suspension (or colloid) of sub-micrometre-sized particles of gold in a fluid – usually water. The liquid is usually either an intense red colour (for particles less than 100 nm), or blue/purple (for larger particles). Due to the unique optical, electronic, and molecular-recognition properties of gold nanoparticles, they are the subject of substantial research, with applications in a wide variety of areas, including electron microscopy, electronics, nanotechnology, and materials science.
Properties and applications of colloidal gold nanoparticles strongly depend upon their size and shape. For example, rodlike particles have both transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly.
Known since ancient times, the synthesis of colloidal gold was originally used as a method of staining glass. Modern scientific evaluation of colloidal gold did not begin until Michael Faraday's work of the 1850s. A so-called Elixir of Life, a potion made from gold, was discussed, if not actually manufactured, in ancient times. Colloidal gold has been used since Ancient Roman times to colour glass intense shades of red or mauve, depending on the concentration of gold, and in Hindu Chemistry, for various potions. In the 16th century, the alchemist Paracelsus claimed to have created a potion called Aurum Potabile (Latin: potable gold). In the 17th century the glass-colouring process was refined by Andreus Cassius and Johann Kunckel. In 1842, John Herschel invented a photographic process called Chrysotype (from the Greek word for gold) that used colloidal gold to record images on paper. Paracelsus' work is known to have inspired Michael Faraday to prepare the first pure sample of colloidal gold, which he called 'activated gold', in 1857. He used phosphorus to reduce a solution of gold chloride.
For a long time the composition of the Cassius ruby-gold was unclear. Several chemists suspected it to be a gold tin compound, due to its preparation. Faraday was the first to recognize that the color was due to the minute size of the gold particles. In 1898 Richard Adolf Zsigmondy prepared the first colloidal gold in diluted solution. Apart from Zsigmondy, Theodor Svedberg, who invented ultracentrifugation, and Gustav Mie, who provided the theory for scattering and absorption by spherical particles, were also interested in understanding synthesis and properties of colloidal gold.
Generally, gold nanoparticles are produced in a liquid ("liquid chemical methods") by reduction of chloroauric acid (H[AuCl4]). After dissolving H[AuCl4], the solution is rapidly stirred while a reducing agent is added. This causes Au3+ ions to be reduced to neutral gold atoms. As more and more of these gold atoms form, the solution becomes supersaturated, and gold gradually starts to precipitate in the form of sub-nanometer particles. The rest of the gold atoms that form stick to the existing particles, and, if the solution is stirred vigorously enough, the particles will be fairly uniform in size.
To prevent the particles from aggregating, some sort of stabilizing agent that sticks to the nanoparticle surface is usually added. Alternatively, gold colloids can be synthesised without stabilizers by laser ablation in liquids.
They can be functionalized with various organic ligands to create organic-inorganic hybrids with advanced functionality.
Turkevich method 
The method pioneered by J. Turkevich et al. in 1951  and refined by G. Frens in 1970s, is the simplest one available. Generally, it is used to produce modestly monodisperse spherical gold nanoparticles suspended in water of around 10–20 nm in diameter. Larger particles can be produced, but this comes at the cost of monodispersity and shape. It involves the reaction of small amounts of hot chlorauric acid with small amounts of sodium citrate solution. The colloidal gold will form because the citrate ions act as both a reducing agent, and a capping agent.
Recently, the evolution of the spherical gold nanoparticles in the Turkevich reaction has been elucidated. Interestingly, extensive networks of gold nanowires are formed as a transient intermediate. These gold nanowires are responsible for the dark appearance of the reaction solution before it turns ruby-red.
To produce larger particles, less sodium citrate should be added (possibly down to 0.05%, after which there simply would not be enough to reduce all the gold). The reduction in the amount of sodium citrate will reduce the amount of the citrate ions available for stabilizing the particles, and this will cause the small particles to aggregate into bigger ones (until the total surface area of all particles becomes small enough to be covered by the existing citrate ions).
Brust method 
This method was discovered by Brust and Schiffrin in early 1990s, and can be used to produce gold nanoparticles in organic liquids that are normally not miscible with water (like toluene). It involves the reaction of a chlorauric acid solution with tetraoctylammonium bromide (TOAB) solution in toluene and sodium borohydride as an anti-coagulant and a reducing agent, respectively.
It is important to note that TOAB does not bind to the gold nanoparticles particularly strongly, so the solution will aggregate gradually over the course of approximately two weeks. To prevent this, one can add a stronger binding agent, like a thiol (in particular, alkanethiols), which will bind to gold, producing a near-permanent solution. Alkanethiol protected gold nanoparticles can be precipitated and then redissolved. Some of the phase transfer agent may remain bound to the purified nanoparticles, this may affect physical properties such as solubility. In order to remove as much of this agent as possible the nanoparticles must be further purified by soxhlet extraction.
Perrault Method 
This approach, discovered by Perrault and Chan in 2009, uses hydroquinone to reduce HAuCl4 in an aqueous solution that contains gold nanoparticle seeds. This seed-based method of synthesis is similar to that used in photographic film development, in which silver grains within the film grow through addition of reduced silver onto their surface. Similarly, gold nanoparticles can act in conjunction with hydroquinone to catalyze reduction of ionic gold onto their surface. The presence of a stabilizer such as citrate results in controlled particle growth. Typically, the nanoparticle seeds are produced using the citrate method. The hydroquinone method complements that of Frens, as it extends the range of monodispersed spherical particle sizes that can be produced. Whereas the Frens method is ideal for particles of 12-20 nm, the hydroquinone method can produce particles of at least 30–250 nm.
Another method for the experimental generation of gold particles is by sonolysis. In one such process based on ultrasound, the reaction of an aqueous solution of HAuCl4 with glucose, the reducing agents are hydroxyl radicals and sugar pyrolysis radicals (forming at the interfacial region between the collapsing cavities and the bulk water) and the morphology obtained is that of nanoribbons with width 30–50 nm and length of several micrometers. These ribbons are very flexible and can bend with angles larger than 90°. When glucose is replaced by cyclodextrin (a glucose oligomer) only spherical gold particles are obtained suggesting that glucose is essential in directing the morphology towards a ribbon.
Block Copolymer-mediated Method 
An economical, environmentally benign and fast synthesis methodology for gold nanoparticles using block copolymer has been developed by Sakai et al. . In this synthesis methodology, block copolymer plays the dual role of a reducing agent as well as a stabilizing agent. The formation of gold nanoparticles comprises three main steps: reduction of gold salt ion by block copolymers in the solution and formation of gold clusters, adsorption of block copolymers on gold clusters and further reduction of gold salt ions on the surfaces of these gold clusters for the growth of gold particles in steps, and finally its stabilization by block copolymers. But this method usually has a limited yield (nanoparticle concentration) which does not increase with the increase in the gold salt concentration. Recently, Ray et al. demonstrated that the presence of an additional reductant (trisodium citrate) in 1:1 molar ratio with gold salt enhances the yield by manyfold .
Electron Microscopy 
Colloidal gold and various derivatives have long been among the most widely-used labels for antigens in biological electron microscopy. Colloidal gold particles can be attached to many traditional biological probes such as antibodies, lectins, superantigens, glycans, nucleic acids, and receptors. Particles of different sizes are easily distinguishable in electron micrographs, allowing simultaneous multiple-labelling experiments.
Health and medical applications 
Chrysotherapy and chrysiasis 
Chrysotherapy (or aurotherapy), often self-administered allegedly by alchemists and snake oil vendors before modern medicine isolated effective compounds, relates to the intake of gold salts and or colloidal gold . Although colloidal gold has been successfully used as a therapy for rheumatoid arthritis in rats, one noticeable side-effect in humans to whom are administered gold based DMARDs is the coloring of the skin in shades of mauve to a purplish dark grey when exposed to sunlight, if the salts are taken on a regular basis over a long period of time . Excessive intake of gold salts and colloidal gold while undergoing chrysotherapy result – through complex redox processes – in the saturation by relatively stable gold compounds and colloidal gold of skin tissue and organs (as well as teeth and ocular tissue in extreme cases), a condition known as chrysiasis, similar to a certain extent to argyria which is related to silver salts and colloidal silver. Chrysiasis can ultimately lead to acute renal failure (such as tubular necrosis, nephrosis, glomerulitis ), severe heart conditions, hematologic complications (leukopenia, anemia): while some effects can be healed with moderate success, the pigmentation of the skin is considered permanent.
Experimental medication for Alzheimer's disease 
An in vitro experiment has shown that the combination of microwave radiation and colloidal gold can destroy the beta-amyloid fibrils and plaque which are associated with Alzheimer's disease. The possibilities for numerous similar radiative applications are also currently under exploration.
Drug carrier 
Gold nanoparticles are being investigated as carriers for drugs such as Paclitaxel. The administration of hydrophobic drugs require molecular encapsulation and it is found that nanosized particles are particularly efficient in evading the reticuloendothelial system.
Tumor detection 
In cancer research, colloidal gold can be used to target tumors and provide detection using SERS (Surface Enhanced Raman Spectroscopy) in vivo. These gold nanoparticles are surrounded with Raman reporters which provide light emission that is over 200 times brighter than quantum dots. It was found that the Raman reporters were stabilized when the nanoparticles were encapsulated with a thiol-modified polyethylene glycol coat. This allows for compatibility and circulation in vivo. To specifically target tumor cells, the pegylated gold particles are conjugated with an antibody (or an antibody fragment such as scFv), against e.g. Epidermal growth factor receptor, which is sometimes overexpressed in cells of certain cancer types. Using SERS, these pegylated gold nanoparticles can then detect the location of the tumor.
Photothermal agents 
Gold nanorods are being investigated as photothermal agents for in-vivo applications. Gold nanorods are rod shaped gold nanoparticles whose aspect ratios tune the surface plasmon resonance (SPR) band from the visible to near infrared wavelength. The total extinction of light at the SPR is made up of both absorption and scattering. For the smaller axial diameter nanorods (~10 nm), absorption dominates, whereas for the larger axial diameter nanorods (>35 nm), scattering can dominate. Consequently, for in-vivo applications, small diameter gold nanorods are being used as photothermal converters of near infrared light due to their high absorption cross sections. Since near infrared light transmits readily through human skin and tissue, these nanorods can be used as ablation components for cancer, and other targets. When coated with polymers, gold nanorods have been known to circulate in-vivo for greater than 15 hours half life. Apart from rod-like gold nanoparticles, also spherical colloidal gold nanoparticles are recently used as markers in combination with photothermal single particle microscopy.
Radiotherapy dose enhancer 
Following work by Hainfield et al. there has been considerable interest in the use of gold and other heavy-atom containing nanoparticles to enhance the dose delivered to tumors. Since the gold nanoparticles are taken up by the tumors more than the nearby healthy tissue, the dose is selectively enhanced. The biological effectiveness of this type of therapy seems to be due to the local deposition of the radiation dose near the nanoparticles. This mechanism is the same as occurs in heavy ion therapy.
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