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Mathematical ratio used in analysis of radioactive materials
An isotopic signature (also isotopic fingerprint) is a ratio of non radiogenic 'stable isotopes', stable radiogenic isotopes, or unstable radioactive isotopes of particular elements in an investigated material. The ratios of isotopes in a sample material are measured by isotope ratio mass spectrometry against an isotopic reference material. This process is called isotope analysis.

The atomic mass of different isotopes affect their chemical kinetic behavior, leading to natural isotope separation processes.

Nitrogen 15, or 15N, is often used in agricultural and medical research, for example in the Meselson–Stahl experiment to establish the nature of DNA replication. An extension of this research resulted in development of DNA based stable isotope probing, which allows examination of links between metabolic function and taxonomic identity of microorganisms in the environment, without the need for culture isolation. Proteins can be isotopically labelled by cultivating them in a medium containing 15N as the only source of nitrogen, e. g., in quantitative proteomics such as SILAC. Nitrogen 15 is extensively used to trace mineral nitrogen compounds (particularly fertilizers) in the environment. When combined with the use of other isotopic labels, 15N is also a very important tracer for describing the fate of nitrogenous organic pollutants. Nitrogen 15 tracing is an important method used in biogeochemistry. The ratio of stable nitrogen isotopes, 15N/14N or δ15N, tends to increase with trophic level, such that herbivores have higher nitrogen isotope values than plants, and carnivores have higher nitrogen isotope values than herbivores. Depending on the tissue being examined, there tends to be an increase of 3 4 parts per thousand with each increase in trophic level. The tissues and hair of vegans therefore contain significantly lower δ15N than the bodies of people who eat mostly meat. Similarly, a terrestrial diet produces a different signature than a marine based diet. Isotopic analysis of hair is an important source of information for archaeologists, providing clues about the ancient diets and differing cultural attitudes to food sources. A number of other environmental and physiological factors can influence the nitrogen isotopic composition at the base of the food web (i. e. in plants) or at the level of individual animals. For example, in arid regions, the nitrogen cycle tends to be more 'open' and prone to the loss of 14N, increasing δ15N in soils and plants. This leads to relatively high δ15N values in plants and animals in hot and arid ecosystems relative to cooler and moister ecosystems. Furthermore, elevated δ15N have been linked to the preferential excretion of 14N and reutilization of already enriched 15N tissues in the body under prolonged water stress conditions or insufficient protein intake. δ15N also provides a diagnostic tool in planetary science as the ratio exhibited in atmospheres and surface materials "is closely tied to the conditions under which materials form".

Lead consists of four stable isotopes: 204Pb, 206Pb, 207Pb, and 208Pb. Local variations in uranium/thorium/lead content cause a wide location specific variation of isotopic ratios for lead from different localities. Lead emitted to the atmosphere by industrial processes has an isotopic composition different from lead in minerals. Combustion of gasoline with tetraethyllead additive led to formation of ubiquitous micrometer sized lead rich particulates in car exhaust smoke; especially in urban areas the man made lead particles are much more common than natural ones. The differences in isotopic content in particles found in objects can be used for approximate geolocation of the object's origin. Measurement of carbon isotopic ratios can be used for detection of adulteration of honey. Addition of sugars originated from corn or sugar cane (C4 plants) skews the isotopic ratio of sugars present in honey, but does not influence the isotopic ratio of proteins; in an unadulterated honey the carbon isotopic ratios of sugars and proteins should match. As low as 7% level of addition can be detected. Nuclear explosions form 10Be by a reaction of fast neutrons with 13C in the carbon dioxide in air. This is one of the historical indicators of past activity at nuclear test sites.

Isotopic fingerprints are used to study the origin of materials in the Solar System. Oxygen isotopic ratios, which may be measured very precisely, yield a unique and distinct signature for each Solar System body. Different oxygen isotopic signatures can indicate the origin of material ejected into space. The Moon's titanium isotope ratio (50Ti/47Ti) appears close to the Earth's (within 4 ppm). In 2013, a study was released that indicated water in lunar magma was 'indistinguishable' from carbonaceous chondrites and nearly the same as Earth's, based on the composition of water isotopes.

Isotope biogeochemistry has been used to investigate the timeline surrounding life and its earliest iterations on Earth. Isotopic fingerprints typical of life, preserved in sediments, have been used to suggest, but do not necessarily prove, that life was already in existence on Earth by 3.85 billion years ago. Sulfur isotope evidence has also been used to corroborate the timing of the Great Oxidation Event, during which the Earth's atmosphere experienced a measurable rise in oxygen (to about 9% of modern values) for the first time about 2.3 2.4 billion years ago. Mass independent sulfur isotope fractionations are found to be widespread in the geologic record before about 2.45 billion years ago, and these isotopic signatures have since ceded to mass dependent fractionation, providing strong evidence that the atmosphere shifted from anoxic to oxygenated at that threshold. Modern sulfate reducing bacteria are known to favorably reduce lighter 32S instead of 34S, and the presence of these microorganisms can measurably alter the sulfur isotope composition of the ocean. the absence of sulfur isotope fractionations in sulfide minerals suggests the absence of these bacterial processes or the absence of freely available sulfate. Some have used this knowledge of microbial sulfur fractionation to suggest that minerals (namely pyrite) with large sulfur isotope fractionations relative to the inferred seawater composition may be evidence of life. This claim is not clear cut, however, and is sometimes contested using geologic evidence from the ~3.49 Ga sulfide minerals found in the Dresser Formation of Western Australia, which are found to have δ34S values as negative as 22‰. Because it has not been proven that the sulfide and barite minerals formed in the absence of major hydrothermal input, it is not conclusive evidence of life or of the microbial sulfate reduction pathway in the Archean.