Droplet Microarrays – Readout by MALDI imaging

Cell-based assays in pharmaceutical research and development primarily rely on fluorescence-based and other label-dependent technologies for high-throughput screening and on morphometric microscopy readouts or transcriptional signatures for high-content screening. Superhydrophobic-hydrophilic droplet microarrays (DMA) and MALDI mass spectrometry (MS) have recently emerged as key technologies for miniaturized high-throughput cell assays and for label-free molecular high-content drug profiling, respectively.

Here, we integrate nanoliter-scale cell assays on DMAs with MALDI MS imaging approaches to a Droplet Microarray-Mass Spectrometry Imaging (DMA-MSI) platform. Using A549 lung cancer cells, we demonstrate concentration-response profiling of a pharmaceutical compound, the fatty acid synthase inhibitor GSK2194069. Direct cell culture on DMAs enables combination of microscopy and high speed and high molecular content analysis using MALDI MS imaging. Miniaturization of array spots down to 0.5 mm confining 40 nL droplets allows for MALDI imaging analysis of as few as 10 cells per spot. Partial automation ensures a fast sample preparation workflow.

Taken together, the integrated DMA-MSI platform that combines MALDI-MS imaging as label-free analytical technique, with superhydrophobic-hydrophilic  DMAs is a valuable complement for high throughput cell-based assays technologies.