Chemical peptide synthesis is essential for a large range of applications. Advances in the synthesis protocols have increased greatly, but less automated devices have been developed or implemented as commercial instrument, especially devices that provide high-throughput and small-scale peptide assemblies for applications which need thousands kinds of peptides but very small in quantities, for example, proteomic research and drug screening.

We present an automated instrument for high-throughput peptide synthesis by solid phase peptide synthesis (SPPS), which applies continuous-flow method and works in assembly-line manner. Customized small-scale reactors are held in a turntable and one reaction cycle in each reactor is performed after the reactor passed through the assembly line for one time. Pneumatic valves are involved to provide pressure pulses, which ensure multiple synthesis reactions carry on as a continuous-flow process simultaneously. Solvent-resistant membranes prevent resin from leaking out while allow reagents flow through. Reagents are loaded with high accuracy solvent-resistant diaphragm pumps and three-dimensional loading arm.

The average purity more than 90% for the crude peptide products was characterized by HPLC data. The average yield is more than 80.0%, which was calculated by further RP-HPLC purification and substituting the peak area value into the standard linear equation. Each step of the assembly line was performed in only 15-25 seconds and the total line includes 128 steps. Therefore, one reaction cycle could accomplish in half to one hour and 128 products in the milligram scale could obtain in several hours, which were significantly reduced the synthesis time as compared to conventional reactors and commercial instruments. It is very suitable for applications such as “omics” research. In the near future, the instrument may be adapted to a range of chemical synthesis applications, including the production of biomolecules, such as peptoids, nucleic acids and polysaccharides.