Abstract: Methods of synthesizing oligonucleotides with high coupling efficiency (>99.5%) are provided. Methods for purification of synthetic oligonucleotides are also provided. Instrumentation configurations for oligonucleotide synthesis are also provided. Methods of designing and synthesizing polynucleotides are also provided. Polynucleotide design is optimized for subsequent assembly from shorter oligonucleotides. Modifications of phosphoramidite chemistry to improve the subsequent assembly of polynucleotides are provided. The design process also incorporates codon biases into polynucleotides that favor expression in defined hosts. Design and assembly methods are also provided for the efficient synthesis of sets of polynucleotide variants. Software to automate the design and assembly process is also provided.

Abstract: The invention provides improved chemical synthesizers and methods for their use. In one exemplary embodiment, a chemical synthesizer system has a reaction vessel block having a plurality of reaction vessels which are adapted to hold solid supports. A wash plate is removably attachable to a top end of the reaction vessel block. The wash plate has a plurality of fluid delivery orifices which are aligned with the reaction vessels when the wash plate is attached to the top end of the reaction vessel block. In this way, fluids may be supplied to each of the reaction vessels through the orifices. The system can include a vortex mixer that is held stationary by evacuation a cavity formed between the mixer base and a gasket.

Abstract: The invention provides systems, devices and methods for synthesizing various chemicals onto solid supports, cleaving the synthesized compounds and preparing samples for analysis. In one exemplary embodiment, the invention provides a device comprising a housing which defines an enclosure. A plate having a plurality of wells is received into the enclosure. Each of the wells has a bottom end and at least some of the wells have a hole in the bottom end. A pressure source is in fluid communication with the holes in the bottom ends of the wells. In this manner, a fluid may be maintained within the wells by application of pressure from the pressure source.

Abstract: The invention provides a method for synthesizing various chemicals onto solid supports, cleaving the synthesized compounds and preparing samples for analysis. In one exemplary embodiment, the invention provides a device comprising a housing which defines an enclosure. A plate having a plurality of wells is received into the enclosure. Each of the wells has a bottom end and at least some of the wells have a hole in the bottom end. A pressure source is in fluid communication with the holes in the bottom ends of the wells. In this manner, a fluid may be maintained within the wells by application of pressure from the pressure source.

Abstract: The invention provides systems, devices and methods for synthesizing various chemicals onto solid supports, cleaving the synthesized compounds and preparing samples for analysis. In one exemplary embodiment, the invention provides a device comprising a housing which defines an enclosure. A plate having a plurality of wells is received into the enclosure. Each of the wells has a bottom end and at least some of the wells have a hole in the bottom end. A pressure source is in fluid communication with the holes in the bottom ends of the wells. In this manner, a fluid may be maintained within the wells by application of pressure from the pressure source.