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An ultracentrifuge is a mechanical device that separates substances of different densities in a fluid by spinning them very fast. The spinning creates a force, which can be hundreds of thousands greater than the normal force of gravity, which acts on the particles in the sample fluid. Particles of differing densities will be propelled through the fluid at differing speeds.

The first successful centrifuge was invented in 1883 by Swedish engineer Carl de Laval. It was used to separate cream from milk. That design operated at a much lower speed than an ultracentrifuge; attaining the extremely high rotation of the sample holder (tens of thousands revolutions per minute) was a more difficult technical obstacle. The first ultracentrifuge design appeared forty years later, through the efforst of another Swede, chemist Theodor Svedberg.

All centrifuges use centrifugal force, the force directed outward from a something spinning in a circle, to separate particles. You can feel the effects of centrifugal force when you swing a rope with a weight tied to one end above your head. The faster you swing the rope, the more centrifugal force you create on the weight. A washing machine operating during the spin cycle represents a centrifuge. It spins water out of wet clothes using centrifugal force, albeit a force far less powerful than those created by an ultracentrifuge.

In an ultracentrifuge, samples are placed in a container holding closed, narrow tubes like test tubes. It spins them so fast that the centrifugal forces created can be more than one-half million times greater than the force of gravity. The tubes are suspended horizontally while they are spinning and heavier, denser particles, or those with high specific gravity, travel farther in the outstretched tubes than lighter, less dense particles or those with lower specific gravity. (Specific gravity is the mass of a substance divided by the mass of an equal volume of distilled water at 4° F [-16° C]. It is a way to compare objects based on how much mass they have packed into the space they occupy.) One common use of ultracentrifuges is to separate mixtures of different sized molecules. They are also used to separate and determine the relative sizes and densities of microscopic particles such as parts of cells. Ultracentrifuges are so powerful, for example, that they can separate two groups of molecules that differ only by having different types of nitrogen in their structures, nitrogen-14 versus nitrogen-15. Nitrogen-15 differs from nitrogen-14 by having one more neutron in its atomic nucleus.