Automated liquid handling can achieve higher precision for low-volume dispensing than hand-held pipetting while increasing sample processing throughput and avoiding human error. Current commercial liquid-handling platforms range in cost from tens to hundreds of thousands of dollars, which can be prohibitive for smaller research groups. Home-built systems offer customized functionality but require significant technical knowledge and specialized parts. We reduced the burden of developing homebuilt systems by adapting the hardware and software of a low-cost open-source platform, the Opentrons OT-2. The modifications extend accurate pipetting for the OT-2 to the low nanoliter range, enabling sensitive sample preparation. We then augmented the capabilities of this platform by incorporating control of two-position valves and selector valves for autosampling applications. Our modified system is flexible and can be readily configured to meet the needs of novel LC applications. We demonstrated the system for both sub-microliter sample preparation and autosampling for nano-LC-MS applications. The software developed to control the modified system can be adapted to other custom liquid handling and separations platforms.
Axtell et al. (2026) studied this question.