isotope contrast
Two isotopes of an element are chemically the same atom — same number of protons and electrons, so the same bonds and the same shape — but different numbers of neutrons in the nucleus. To X-rays, which scatter off electrons, isotopes are completely indistinguishable. To neutrons, which scatter off the nucleus, they can look utterly different, because the neutron scattering length b jumps between isotopes. Isotope contrast is the technique of exploiting exactly this: you swap one isotope for another and, without changing the chemistry at all, you change how strongly that atom scatters neutrons. It is like being able to repaint one ingredient of a recipe a different colour while leaving its taste identical.
The champion example is hydrogen versus deuterium. Ordinary hydrogen has b about -3.7 fm (negative), while its heavier isotope deuterium has b about +6.7 fm (positive and larger). Because they even scatter with OPPOSITE sign, mixing them in the right proportion can make the average scattering of a region equal to zero, or match it to that of its surroundings. This is the trick of contrast matching, heavily used in small-angle neutron scattering of soft matter: dissolve a structure in a blend of light water (H2O) and heavy water (D2O) tuned so the solvent's average scattering length density exactly matches one component, making that component effectively 'invisible' and throwing the rest into sharp relief.
The same idea sharpens the study of structure more generally. By selectively labelling one type of atom or one molecule with a different isotope and taking two otherwise identical measurements, the difference between them isolates the contribution of just the labelled species — a way to peel one atom type out of a crowded structure or a disordered liquid. The honest limitations: isotope contrast is unique to neutrons and impossible with X-rays; and it depends on obtaining isotopically substituted samples, which for deuterated compounds can be expensive and for many elements is simply not practical.
To study a protein in solution, researchers dissolve it in a mix of about 40 percent D2O and 60 percent H2O so that the solvent's scattering matches the protein's — making the protein vanish — then dial the ratio the other way to make it stand out. Two measurements, same chemistry, and the isotope contrast alone isolates the shape of the molecule.
Blending H2O and D2O tunes the solvent's scattering to hide or reveal a component — contrast the chemistry cannot change.
Isotope contrast works only with neutrons; X-rays scatter off electrons, which are identical for two isotopes, so they cannot tell them apart. The price is needing isotopically labelled samples, which for deuteration and many elements is costly or impractical.