A tetrafluorophenol acrylamide monomer unit was synthesised, co-polymerised and grafted onto a glass slide to form individual gel spots. As a proof of principle study, a small library of amides was rapidly synthesised within these gel spots using ‘catch-and-release’ chemistry, including the biologically interesting quorum sensing acyl-homoserine lactones. The tetrafluorophenol acrylamide gel provides an efficient platform to synthesise and screen small molecules for biological activity.The development of tetrafluorophenol acrylamide 3D gels as an effective platform for the synthesis of small molecules has been achieved. Furthermore, this offers the potential to synthesise and screen compounds for biological activity on the same slide.