EDC (or EDAC; 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) is the most popular carbodiimide used for conjugating biological substances containing carboxylates and amines. In fact, it may also be the most frequently used crosslinking agent of all. Its application in particle and surface conjugation procedures along with NHS (N-hydroxysulfosuccinimide) or sulfo-NHS is nearly universal (Chapter 14) and this fact makes it the most common bioconjugation reagent in use today. EDC is water soluble, which allows for its direct addition to a reaction without prior organic solvent dissolution. Both the reagent itself and the isourea formed as the byproduct of the crosslinking reaction are water soluble and may be removed easily by dialysis or gel filtration (Sheehan et al., 1961, 1965). The reagent is, however, labile in the presence of water, especially in acidic solutions.