Automated 96-well protein purification-to-screening platform

Overview

This automated 96-well platform addresses a major bottleneck in early protein discovery: the repetitive manual processing required between protein expression and functional screening. The system automates recombinant protein purification from clarified lysates and prepares assay-ready samples for downstream biochemical or binding assays, enabling parallel comparison of multiple constructs and purification conditions in a single run.

The platform combines liquid-handling automation with magnetic affinity resin to perform capture, separation, washing, elution, and sample normalization in 96-well format—eliminating the need for packed columns or centrifugation. This makes it well suited to plate-based automation and consistent, high-throughput processing of many samples and conditions. The workflow is designed to accommodate multiple affinity chemistries and variable purification conditions, with commercially available automation and affinity reagents reducing technical risk.

Technical specifications

Key features:

• Automated magnetic IMAC purification (expandable to additional affinity chemistries) using an Opentrons liquid handling platform
• Hands-free binding, separation, washing, elution, fraction tracking, and sample normalization from clarified lysates
• Retention of unbound, wash, and elution fractions for QC, SDS-PAGE, or functional assays
• Automated fraction tracking and condition optimization to compare constructs and purification parameters
• Direct handoff to downstream biochemical or binding assays, enabling a walk-away workflow from lysate to assay-ready samples
• Benchmarkable against manual purification for recovery, purity, reproducibility, retained activity, and hands-on time

Planned validation: The workflow will first be configured and programmed on an existing liquid handling platform, using IMAC capture of recombinant proteins. Bead handling, binding, washing, elution, fraction recovery, and sample normalization will be optimized across representative proteins and purification conditions. The workflow will then be expanded to parallel comparison of multiple constructs and purification conditions, and integrated with automated preparation for downstream QC and functional assays.

Technology readiness level

The platform is in the early development and validation stage. Initial configuration and programming of the 96-well magnetic affinity purification workflow is planned, with optimization across representative proteins and purification conditions. Performance will be benchmarked against manual purification to establish recovery, reproducibility, retained activity, and time savings. Following optimization, the workflow will be expanded to parallel construct comparison and integrated with downstream assay preparation. Deliverables will include validated automation protocols, operating parameters, performance data, and a scalable workflow for broader protein discovery applications. Representative proteins and screening readouts can be incorporated to demonstrate performance in a relevant discovery workflow.