Enhancing High-Throughput Experimentation Liquid-Handling Capabilities via Strategic Hardware Development of the Mantis Liquid Handler

Liquid dispensing technologies that enhance experimental efficiency and deliver high accuracy across multiple volume ranges are critically important in high-throughput experimentation (HTE) workflows for reaction exploration and optimization. The Mantis liquid handler stands out as a compact, highly modular system featuring a wide array of input options and near plug-and-play functionality with carousels, all while employing positive displacement dispensing technology for precise liquid delivery that is largely independent of liquid properties. However, the system was originally designed to handle aqueous-based biological media at low volumes (1–5 μL/dispense), limiting its applications in nonaqueous chemistry. Herein, we report a hardware development effort from a cross-industry collaboration aimed at enhancing Mantis’ capabilities to handle organic solvents and chemical reagents, even at larger deliverable volumes (up to 50 μL/dispense). Various chemistry examples are provided to demonstrate the implementation of newly developed chip designs, which allow the acquisition of accurate, reproducible, and robust data, enabling more efficient workflows for new reaction discovery, reaction optimization, and data set production. Most importantly, by implementing the Mantis liquid handler from the outset, an increase of 77% in HTE execution efficiency relative to a manual workflow incorporating traditional liquid handling operations was achieved in an amide coupling demonstration.