1 research outputs found
Fast Nanoliter-Scale Cell Assays Using Droplet MicroarrayâMass Spectrometry Imaging
In pharmaceutical research and development, cellâbased assays are primarily used with readout that rely on fluorescenceâbased and other labelâdependent techniques for analysis of different cellular processes. Superhydrophobicâhydrophilic droplet microarrays (DMA) and matrixâassisted laser desorption/ionization (MALDI) mass spectrometry (MS) have recently emerged as key technologies for miniaturized highâthroughput cell assays and for labelâfree molecular highâcontent drug profiling, respectively. Here, nanoliterâscale cell assays are integrated on DMAs with MALDIâMS imaging (MALDIâMSI) approaches to a droplet microarrayâmass spectrometry imaging (DMAâMSI) platform. Using A549 lung cancer cells, concentrationâresponse profiling of a pharmaceutical compound, the fatty acid synthase inhibitor GSK2194069, are demonstrated. Direct cell culture on DMAs enables combination of microscopy and high speed, high molecular content analysis using MALDIâMSI. Miniaturization of array spots down to 0.5 mm confining 40 nL droplets allows for MALDI imaging analysis of as few as ten cells per spot. Partial automation ensures a fast sample preparation workflow. Taken together, the integrated DMAâMSI platform that combines MALDIâMSI, as a labelâfree analytical readout, with the miniaturized droplet microarray platform is a valuable complement to high throughput cellâbased assays technologies