(1079-D) A scalable liquid handling platform for high-throughput manipulation of live cell-based assays

Abstract: Performing high-throughput live cell-based assays with a broad range of liquid types remains a significant challenge for most research labs. We have developed a compact and portable fluidic platform termed surface patterned omniphobic tiles (SPOTs) for manipulating and metering reagents with a wide range of surface tensions. Our platform advances discontinuous dewetting approaches and microdroplet arrays to precisely mix and meter volumes ranging from less than 10 nanoliters to over 10 microliters with lower error than micropipettes. The scalability inherent to the platform enables rapid parallel manipulation of hundreds to thousands of droplets in custom configurations and is also easily adaptable to standard 96 or 384 well formats. We showcase the versatility of the SPOTs platform for life science applications through two distinct cell-based assays. In our first demonstration, we use the platform to perform high-throughput screening of pairwise antibiotic combinations to inhibit the growth of Escherichia coli. We performed 600 experiments containing five antibiotics with replicates against E. coli using only seven pipet tips. Utilizing dark-field time lapse microscopy we established repeatable growth curves and identified drug interactions that enhance or restrict the efficacy of these combinations. In our second demonstration, we use the platform as a volume metering and transfer device to 96 well plates to perform antibiotic susceptibility testing (AST) on 12 methicillin-resistant Staphylococcus pseudintermedius (MRSP) samples. We performed over 1,000 experiments using less than a box of pipet tips while reusing each SPOTs plate 12 times and found a near perfect agreement when comparing the results to the clinical AST findings. Our platform’s adaptability enabled us to establish a higher resolution of minimum inhibitory concentrations and for custom, clinically-relevant antibiotic panels for MRSP. We are currently working towards highlighting the platform’s capability to support the growth of adherent and non-adherent eukaryotic cells. Leveraging the ease of using small volumes, we tested a wide range of treatment assays for these distinct cell type while greatly reducing reagent cost compared to a typical well plate assay. Collectively, these cell-based assays establish the SPOTs platform as a versatile and cost-effective tool for facilitating high-throughput screening in any lab space.