Tech Note

Solid-Phase DNA Synthesis Technology Allows Tight Control of Combinatorial Library Quality and Diversity

Combinatorial DNA libraries are essential to modern protein and metabolic engineering research. As modular sets of DNA sequences, they can be arranged and rearranged as needed to achieve novel or improved protein properties. Modern, high-throughput DNA synthesis technologies have lowered the cost and improved the throughput of library synthesis, making them more accessible to both academic and biotech scientists. The utility of combinatorial libraries for discovering desired protein variants, however, depends on library quality and complexity. 

In this article, we present the most commonly used approaches and technologies available for combinatorial library synthesis and explain their associated codon bias, amino acid distribution, error rate, yield, library diversity, and quality. We demonstrate that Twist Bioscience’s proprietary silicon-based solid-phase technology stands apart with its impressive ability to offer high throughput and low cost while enabling tight control of library quality and diversity.