Spherification uses a reaction between alginate and calcium to form a gel membrane around a liquid. Direct and reverse methods place the reacting ingredients on different sides of the droplet or bath. It is used for small pearls and larger liquid-centered spheres.
Acidity, calcium already present in the liquid, concentrations and timing affect the result. Follow a tested culinary formula using food-grade ingredients. It is different from simply setting a liquid throughout with gelatin.
Reference: Further reading.