Abstract

Miniaturization and
parallelization of combinatorial organic synthesis is important to accelerate
the process of drug discovery, while reducing the consumption of reagents and
solvents. Here we present the droplet microarray (DMA) as a miniaturized
platform for on-chip solid phase combinatorial library synthesis and subsequent
cell screening via microscopic readout. DMA is based on a nanoporous polymer
coating on a glass slide, which was modified via photolithography to yield arrays
of hydrophilic spots surrounded by a superhydrophobic background. Distinct nanoliter-sized droplets are stabilized on this surface and serve as microvessels. The polymer acts as support for nanomolar solid phase synthesis, while a photocleavable linker enables
the release of the synthesized compounds into the droplets which can contain live
cells. The light induced
cleavage showed high flexibility in screening conditions by spatial, temporal
and quantitative control. Synthetic success can be analyzed via stamping of the array to a MALDI substrate and subsequent MALDI-TOF mass spectrometry.