Also known as colloidal gold, gold nanoparticles are small gold crystals that can range in size from a few nanometers (10-9 meters) to several hundred nm in diameter. While they have been around since Roman times, Michael Faraday was the first scientist to seriously experiment with them starting in the 1850s. They have recently become the focus of researchers interested in their electrical and optical properties.

Nanoparticles can come in different shapes and sizes, such as spheres or wires. Spherical particles are relatively easy to synthesize and have useful optical properties, which make them useful for medicine and cellular biology. Specifically, spherical gold particles reflect light depending on their size. The smallest particles are 2 – 3 nm in diameter and reflect dark red light, imparting a startling deep red color to solutions of particles. As the particle size increases the color shifts through orange to yellow, eventually becoming violet. Larger particles are much brighter: a 70 nm particle will reflect more than 1000 times as much light as a 15 nm particle.

These reflective properties make gold particles useful as contrast agents to help detect specific molecular targets. Traditional contrast agents in cellular biology are generally fluorescing proteins, but these degrade quickly when exposed to light and are not always appropriate for use on humans. Gold particles are more biocompatible and stable, and are much brighter, making it relatively easy to image individual molecules. Current medical research is focused on the early detection of cancer in soft tissues (cervix, mouth, throat) using a non-invasive technique involving gold nanoparticles.

Spherical gold particles can be easily manufactured by reducing a solution of HAuCl4, hydrogen tetrachloroaurate. The glassware used in this synthesis must be exceptionally clean; in order to remove all ions it is necessary to boil it in aqua regia, a potent mixture of nitric and hydrochloric acid, for several minutes. A solution of deionized ultra-filtered water containing ionized gold is then stirred and brought to a boil. Sodium citrate is then added and acts as a reducing agent to cause gold ions to aggregate into small particles. The amount of sodium citrate controls the size of the particles – more citrate makes smaller particles. Above 70 nm the particles become unstable and tend to aggregate, shifting their optical scattering into the violet range.

Solutions of particles can be easily modified by conjugating with antibodies targeted to the molecular target of choice. In cancer research the target is often a growth receptor such as epithelial growth factor receptor (EGFR). This molecule is found in much greater abundance in cancer cells, making it easy to differentiate between normal and cancer cells before other characteristics typical of cancer become apparent. A solution of gold-conjugated antibodies would be washed over the tissue of interest, and then a probe would shine light on the tissue and detect the level of reflectance. A high level of reflectance is indicative of cancerous tissue; algorithms analyze the data to make the determination between healthy and diseased tissue. Devices utilizing this technique are currently in clinical trials to determine their sensitivity and specificity.

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