Integrated SPPS on continuous-flow radial microfluidic chip.

Abstract

A novel integrated continuous-flow microfluidic system was designed and fabricated for solid phase peptide synthesis (SPPS) using conventional reactants. The microfluidic system was composed of a glass-based radial reaction chip, a diffluent chip, amino acid feeding reservoirs and continuous-flow reagent pathways. A tri-row cofferdam-fence structure was designed for solid phase supports trapping. Highly cross-linked, porous and high-loading 4-(hydroxymethyl)phenoxymethyl polystyrene (HMP) beads were prepared for microfluidic SPPS. The transfer losses, hazardous handling and time-consuming processes in traditional peptide cleavage steps were avoided by being replaced with the on-chip cleavage treatment. Six peptides from an antibody affinity peptide library against β-endorphin with different lengths and sequences were obtained simultaneously on the constructed continuous-flow microfluidic system within a short time. This microfluidic system is automatic, integrated, effective, low-cost, recyclable and environment-friendly for not only SPPS but also other solid phase chemical syntheses.