LLNL inventors have developed a method and device for the high throughput screening of various chemical and biological entities using a novel combination of cell-free protein synthesis (in vitro transcription-translation), microencapsulation and optical interrogation (Figure below). This includes automated sample handling, microemulsions, microfluidics manipulation, machine vision, and fluorescent interrogation. This automated system can be used to partition analytes into thousands of independent microdroplet reactions that are tracked and optically interrogated for assay activity. Since timing of droplet generation and position are known, an n-dimensional pooling strategy can be performed to increase screening throughput over the traditional 1:1 assay method. An optical interrogation method such as fluorescence correlation spectroscopy (FCS) can provide highly quantitative information for each reaction in real time (e.g., affinity constant for novel antibodies), significantly increasing the precision and quality of data that informs future models and experiments. The approach outlined will enable the feedback loop from experimental evaluations to occur in about 3 days rather than 6 weeks, thereby enabling high quality antibody designs in weeks rather than months.