Colloidal gold
Encyclopedia
Colloid
A colloid is a substance microscopically dispersed evenly throughout another substance.A colloidal system consists of two separate phases: a dispersed phase and a continuous phase . A colloidal system may be solid, liquid, or gaseous.Many familiar substances are colloids, as shown in the chart below...
) of sub-micrometre
Micrometre
A micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...
-sized particles of gold
Gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...
in a fluid — usually water. The liquid is usually either an intense red colour (for particles less than 100 nm
Nanometre
A nanometre is a unit of length in the metric system, equal to one billionth of a metre. The name combines the SI prefix nano- with the parent unit name metre .The nanometre is often used to express dimensions on the atomic scale: the diameter...
), or a dirty yellowish colour (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
Electronics
Electronics is the branch of science, engineering and technology that deals with electrical circuits involving active electrical components such as vacuum tubes, transistors, diodes and integrated circuits, and associated passive interconnection technologies...
, nanotechnology
Nanotechnology
Nanotechnology is the study of manipulating matter on an atomic and molecular scale. Generally, nanotechnology deals with developing materials, devices, or other structures possessing at least one dimension sized from 1 to 100 nanometres...
, and materials science.
Properties and applications of colloidal gold nanoparticles depends upon shape. For example, rodlike particles have both transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly.
History
Known since ancient times, the synthesis of colloidal gold was originally used as a method of staining glassStained glass
The term stained glass can refer to coloured glass as a material or to works produced from it. Throughout its thousand-year history, the term has been applied almost exclusively to the windows of churches and other significant buildings...
. Modern scientific evaluation of colloidal gold did not begin until Michael Faraday's
Michael Faraday
Michael Faraday, FRS was an English chemist and physicist who contributed to the fields of electromagnetism and electrochemistry....
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
Ancient Rome
Ancient Rome was a thriving civilization that grew on the Italian Peninsula as early as the 8th century BC. Located along the Mediterranean Sea and centered on the city of Rome, it expanded to one of the largest empires in the ancient world....
times to colour glass intense shades of yellow, red, or mauve, depending on the concentration of gold, and in Hindu Chemistry, for various potions. In the 16th century, the alchemist
Alchemy
Alchemy is an influential philosophical tradition whose early practitioners’ claims to profound powers were known from antiquity. The defining objectives of alchemy are varied; these include the creation of the fabled philosopher's stone possessing powers including the capability of turning base...
Paracelsus
Paracelsus
Paracelsus was a German-Swiss Renaissance physician, botanist, alchemist, astrologer, and general occultist....
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
John Herschel
Sir John Frederick William Herschel, 1st Baronet KH, FRS ,was an English mathematician, astronomer, chemist, and experimental photographer/inventor, who in some years also did valuable botanical work...
invented a photographic process called Chrysotype
Chrysotype
Chrysotype is a photographic process invented by John Herschel in 1842. Named from the Greek for "gold", it uses colloidal gold to record images on paper....
(from the Greek word for gold) that used colloidal gold to record images on paper. Paracelsus
Paracelsus
Paracelsus was a German-Swiss Renaissance physician, botanist, alchemist, astrologer, and general occultist....
' work is known to have inspired Michael Faraday
Michael Faraday
Michael Faraday, FRS was an English chemist and physicist who contributed to the fields of electromagnetism and electrochemistry....
to prepare the first pure sample of colloidal gold, which he called 'activated gold', in 1857. He used phosphorus
Phosphorus
Phosphorus is the chemical element that has the symbol P and atomic number 15. A multivalent nonmetal of the nitrogen group, phosphorus as a mineral is almost always present in its maximally oxidized state, as inorganic phosphate rocks...
to reduce a solution of gold chloride
Gold chloride
Gold chloride can refer to:* Gold chloride , AuCl* Gold chloride , AuCl2* Gold chloride , AuCl3* Chloroauric acid, HAuCl4...
.
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
Richard Adolf Zsigmondy
Richard Adolf Zsigmondy was an Austrian-Hungarian chemist and Nobel laureate for chemistry known for his research in colloids. The crater Zsigmondy on the Moon is named in his honour....
prepared the first colloidal gold in diluted solution. Apart from Zsigmondy, Theodor Svedberg
Theodor Svedberg
Theodor H. E. Svedberg was a Swedish chemist and Nobel laureate, active at Uppsala University. His work with colloids supported the theories of Brownian motion put forward by Einstein and the Polish geophysicist Marian Smoluchowski...
, who invented ultracentrifugation, and Gustav Mie
Gustav Mie
Gustav Adolf Feodor Wilhelm Ludwig Mie was a German physicist.-Biography:Mie was born in Rostock. From 1886 he studied mathematics and physics at the University of Rostock. In addition to his major subjects, he also attended lectures in chemistry, zoology, geology, mineralogy, astronomy as well as...
, who provided the theory for scattering and absorption by spherical particles, were also interested in understanding synthesis and properties of colloidal gold.
Synthesis
Generally, gold nanoparticles are produced in a liquid ("liquid chemical methods") by reduction of chloroauric acidChloroauric acid
Chloroauric acid is a inorganic compound with the formula HAuCl4. This pale yellow compound is a common precursor to gold in a variety of purposes. The term chloroauric acid is also sometimes used to describe other gold chlorides....
(H[AuCl4]), although more advanced and precise methods do exist. After dissolving H[AuCl4], the solution is rapidly stirred while a reducing agent
Reducing agent
A reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
is added. This causes Au3+ ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s to be reduced to neutral gold atom
Atom
The atom is a basic unit of matter that consists of a dense central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...
s. 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. They can be functionalized with various organic ligands to create organic-inorganic hybrids with advanced functionality. It can also be synthesised by laser ablation
Laser ablation
Laser ablation is the process of removing material from a solid surface by irradiating it with a laser beam. At low laser flux, the material is heated by the absorbed laser energy and evaporates or sublimates. At high laser flux, the material is typically converted to a plasma...
.
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 monodisperseMonodisperse
A collection of objects are called monodisperse, or monosized, if they have the same size and shape when discussing particles, and the same mass when discussing polymers...
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
Sodium citrate
Trisodium citrate has the chemical formula of Na3C6H5O7. It is sometimes referred to simply as sodium citrate, though sodium citrate can refer to any of the three sodium salts of citric acid. It possesses a saline, mildly tart flavor. For this reason, citrates of certain alkaline and alkaline earth...
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 tolueneToluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
). It involves the reaction of a chlorauric acid solution with tetraoctylammonium bromide
Tetraoctylammonium bromide
Tetraoctylammonium bromide is a quaternary ammonium compound with the chemical formula: [CH37]4N Br. It is generally used as a phase transfer catalyst between an aqueous solution and an organic solution....
(TOAB) solution in toluene
Toluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
and sodium borohydride
Sodium borohydride
Sodium borohydride, also known as sodium tetrahydridoborate, is an inorganic compound with the formula NaBH4. This white solid, usually encountered as a powder, is a versatile reducing agent that finds wide application in chemistry, both in the laboratory and on a technical scale. Large amounts are...
as an anti-coagulant and a reducing agent, respectively.
Here, the gold nanoparticles will be around 5–6 nm. NaBH4 is the reducing agent, and TOAB is both the phase transfer catalyst
Phase transfer catalyst
In chemistry, a phase transfer catalyst or PTC is a catalyst that facilitates the migration of a reactant from one phase into another phase where reaction occurs. Phase transfer catalysis is a special form of heterogeneous catalysis. Ionic reactants are often soluble in an aqueous phase but...
and the stabilizing agent.
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
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
(in particular, alkanethiols), which will bind to gold covalently, 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
Solubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
. 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.
Sonolysis
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 glucoseGlucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, the reducing agent
Reducing agent
A reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
s are hydroxyl radicals and sugar pyrolysis
Pyrolysis
Pyrolysis is a thermochemical decomposition of organic material at elevated temperatures without the participation of oxygen. It involves the simultaneous change of chemical composition and physical phase, and is irreversible...
radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
(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
Cyclodextrin
Cyclodextrins are a family of compounds made up of sugar molecules bound together in a ring ....
(a glucose oligomer) only spherical gold particles are obtained suggesting that glucose is essential in directing the morphology towards a ribbon.
Electron Microscopy
Colloidal gold and various derivatives have long been among the most widely-used contrast agents for biological electron microscopy. Colloidal gold particles can be attached to many traditional biological probes such as antibodiesAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, lectin
Lectin
Lectins are sugar-binding proteins that are highly specific for their sugar moieties. They play a role in biological recognition phenomena involving cells and proteins. For example, some viruses use lectins to attach themselves to the cells of the host organism during infection...
s, superantigen
Superantigen
Superantigens are a class of antigens which cause non-specific activation of T-cells resulting in oligoclonal T cell activation and massive cytokine release...
s, glycans, nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
s, and receptors. Particles of different sizes are easily distinguishable in electron micrographs, allowing simultaneous multiple-labelling experiments.
Health and medical applications
Colloidal gold has been successfully used as a therapy for rheumatoid arthritisRheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
in rats. In a related study, the implantation of gold beads near arthritic hip joints in dogs has been found to relieve pain.
An in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
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
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. 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 PaclitaxelPaclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
. The administration of hydrophobic drugs require molecular encapsulation
Molecular encapsulation
Molecular encapsulation in supramolecular chemistry is the confinement of a guest molecule inside the cavity of a supramolecular host molecule...
and it is found that nanosized particles are particularly efficient in evading the reticuloendothelial system
Reticuloendothelial system
"Reticuloendothelial system" is an older term for the mononuclear phagocyte system. The mononuclear phagocyte system consists primarily of monocytes and macrophages. The spleen is the largest unit of the mononuclear phagocyte system. The monocyte is formed in the bone marrow and transported by the...
.
Tumor detection
In cancer research, colloidal gold can be used to target tumors and provide detection using SERS (Surface Enhanced Raman SpectroscopySurface Enhanced Raman Spectroscopy
Surface enhanced Raman spectroscopy or surface enhanced Raman scattering is a surface-sensitive technique that enhances Raman scattering by molecules adsorbed on rough metal surfaces...
) 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
Polyethylene glycol
Polyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
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
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
, which is sometimes overexpressed in cells of certain cancer types. Using SERS, these pegylated gold nanoparticles can then detect the location of the tumor.