Fast Nanoliter-Scale Cell Assays Using Droplet Microarray-Mass Spectrometry Imaging.

In pharmaceutical research and development, cell-based assays are primarily used with readout that rely on fluorescence-based and other label-dependent techniques for analysis of different cellular processes. Superhydrophobic-hydrophilic droplet microarrays (DMA) and matrix-assisted laser desorption/ionization (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, nanoliter-scale cell assays are integrated on DMAs with MALDI-MS imaging (MALDI-MSI) approaches to a droplet microarray-mass spectrometry imaging (DMA-MSI) platform. Using A549 lung cancer cells, concentration-response 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 MALDI-MSI. 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 DMA-MSI platform that combines MALDI-MSI, as a label-free analytical readout, with the miniaturized droplet microarray platform is a valuable complement to high throughput cell-based assays technologies.

Droplet Sorting and Manipulation on Patterned Two-Phase Slippery Lubricant-Infused Surface.

Slippery lubricant-infused surfaces are composite materials consisting of a solid matrix permanently infused by a lubricant. Such surfaces have proved to be highly repellent to various liquids immiscible with the lubricant. Depending on the underlying surface chemistry, different lubricants can be used, including perfluorinated or alkylated oils. Here, we construct patterned slippery surfaces that consist of virtual channels permanently impregnated with an organic oil and surrounded by areas permanently impregnated with a perfluorinated oil. We demonstrate that water droplets preferentially occupy the organic-oil-lubricated virtual channels. Based on a simple model, we evaluate the forces acting on droplets crossing over to the regions impregnated with perfluorinated oil and show that the cloaking of the droplets plays an important role. We study the actuation of droplets in virtual oil-in-oil channels based on gravity and magnetic fields. Finally, we construct a variety of organic-oil-lubricated channel architectures permitting droplet sorting according to size. We believe that this novel approach for the formation of virtual all-liquid surface-tension-confined channels based on lubricant-infused surfaces, channel networks, or patterns will advance the field of droplet-based microfluidics. The approach presented can be potentially useful for applications in biotechnology, diagnostics, or analytical chemistry.