This paper presents a high-throughput screening platform using drop-based microfluidics that enables the rapid and efficient screening of large libraries of enzyme variants. The system uses picoliter-volume aqueous drops dispersed in oil as reaction vessels, allowing for the screening of up to 10^8 individual enzyme reactions in just 10 hours with a total reagent volume of less than 150 µL. This is significantly faster and more cost-effective than traditional robotic screening systems, which can process up to 100,000 assays per day but require much larger volumes of reagents and are limited in throughput. The platform was used to perform directed evolution on horseradish peroxidase (HRP), an enzyme already known for its high catalytic efficiency. The system was able to identify mutants of HRP with catalytic rates more than 10 times faster than the parent enzyme, approaching diffusion-limited efficiency. The high-throughput nature of the system allowed for the initial purifying selection of active mutants, reducing the library to a manageable size and enabling the identification of variants with significantly improved catalytic efficiency after subsequent rounds of mutagenesis and screening. The system's ability to screen large libraries of enzyme variants at high speed and low cost makes it a powerful tool for directed evolution and other biotechnological applications. The results demonstrate that the platform can significantly enhance the efficiency and effectiveness of screening processes, enabling the discovery of highly efficient enzymes and other biotechnological applications. The system's design allows for the compartmentalization of individual elements of the library in aqueous drops, enabling the independent probing of each member of the library. The platform's high throughput and low reagent volume make it a promising tool for future biotechnological applications.This paper presents a high-throughput screening platform using drop-based microfluidics that enables the rapid and efficient screening of large libraries of enzyme variants. The system uses picoliter-volume aqueous drops dispersed in oil as reaction vessels, allowing for the screening of up to 10^8 individual enzyme reactions in just 10 hours with a total reagent volume of less than 150 µL. This is significantly faster and more cost-effective than traditional robotic screening systems, which can process up to 100,000 assays per day but require much larger volumes of reagents and are limited in throughput. The platform was used to perform directed evolution on horseradish peroxidase (HRP), an enzyme already known for its high catalytic efficiency. The system was able to identify mutants of HRP with catalytic rates more than 10 times faster than the parent enzyme, approaching diffusion-limited efficiency. The high-throughput nature of the system allowed for the initial purifying selection of active mutants, reducing the library to a manageable size and enabling the identification of variants with significantly improved catalytic efficiency after subsequent rounds of mutagenesis and screening. The system's ability to screen large libraries of enzyme variants at high speed and low cost makes it a powerful tool for directed evolution and other biotechnological applications. The results demonstrate that the platform can significantly enhance the efficiency and effectiveness of screening processes, enabling the discovery of highly efficient enzymes and other biotechnological applications. The system's design allows for the compartmentalization of individual elements of the library in aqueous drops, enabling the independent probing of each member of the library. The platform's high throughput and low reagent volume make it a promising tool for future biotechnological applications.