The first article relating to continuous flow peptide synthesis was published in 1986, but due to technical limitations, it was not until the early 2010's when more academic groups started using continuous flow for the rapid synthesis of peptides. The advantages of continuous flow over traditional batch methods is the ability to heat reagents with good temperature control, allowing the speed of reaction kinetics while minimising side reactions. cycles times vary from 30 seconds, up to 6 minutes, depending on reaction conditions and excess of reagent.
Thanks to inline analytics, such as UV/Vis spectroscopy and the use of Variable Bed Flow reactor (VBFR) that monitor the resin volume, on-resin aggregation can be identified and coupling efficiency can be evaluated.