Combinatorial chemistry (organic synthesis of libraries)
The first reports of rapid, automated synthesis of diverse organic molecules appeared in late 1960s and early 1970s. Solid-phase-synthesis approach introduced in 1963 led to development of polypeptide synthesis machines, which allowed rapid and automatic synthesis of polypeptides with diverse amino acid sequences. However, in these machines, a single - peptide sequence was created in a single vessel.

Use of beads and split pool method.
The above parallel synthesis is limited by the number of containers (or fixed supports) used to localize the products. Therefore, solid support was modified into submillimeter polymer beads, which will remain separated permitting spatial localization of reactions and permitting synthesis of millions of potential new molecules.
The diversity was increased further by using split-pool procedure, which involves splitting (division) of beads into groups, each group subjected to a separate addition step followed by pooling all the groups again after each step of reaction. Several cycles of splitting and pooling are used to enhance diversity.
Although each bead had a single type of molecules, the identification of this molecule was difficult with a small quantity of 200pmol of molecule on each bead. Therefore, during I 990s, methods were developed to encode (tag) individual beads uniquely to identify the molecules on individual beads.