The present invention provides improved automated systems and methods for synthesis of biopolymers including DNA and RNA. The automated systems and methods represent a number of improvements over existing systems for multiplex synthesis of biopolymers in a combinatorial fashion.

The invention is directed to systems, apparatus and kits for automated synthesis of a plurality of polynucleotides in an array of reaction chambers using a template-free polymerase. In some embodiments, adaptive elements and processes are provided to monitor and control disruption of the synthesis process and fluid movement by enzyme aggregation.

An automated material reaction system includes a material storage, which stores store at least one material, a dispensing module, which dispenses, to a reaction container, the at least one material stored in the material storage, a reaction module, which causes a reaction of the at least one material dispensed to the reaction container, a purification module, which extracts a target product from a product produced by the reaction module and purifies the target product, and a transport device, which transports the target product to the dispensing module such that the target product is used as a reactant.

The invention is directed to systems, apparatus and kits for automated synthesis of a plurality of polynucleotides in an array of reaction chambers using a template-free polymerase. In some embodiments, adaptive elements and processes are provided to monitor and control disruption of the synthesis process and fluid movement by enzyme aggregation.

The invention is directed to methods and apparatus for parallel enzymatic synthesis of polynucleotides in an array of reaction chambers using a template-free polymerase that has sequence-dependent coupling efficiencies. Whenever sequences causing low efficiency coupling occur at a 3 end of a growing chain of a polynucleotide being synthesized, one or more additional coupling cycles without de-protection steps are inserted into synthesis plans to provide additional time for completing the coupling reaction at that position of the polynucleotide.