A robust robotic high-throughput antibody purification platform.

Area of Science:

• Biotechnology
• Protein Chemistry
• Pharmaceutical Development

Background:

• Monoclonal antibodies (mAbs) are a rapidly growing segment of the drug market, necessitating efficient methods for lead candidate selection.
• High-throughput production and purification of antibodies are crucial for reducing lead times in drug development.
• Transient gene expression (TGE) systems, like Expi293F™, enable high recombinant mAb titers, facilitating downstream processing.

Purpose of the Study:

• To describe a novel automated platform for purifying recombinant mAbs expressed using TGE.
• To establish a high-throughput process for antibody purification directly from cell-free culture supernatant.
• To enable rapid screening and development of antibody-based therapeutics.

Main Methods:

• Development of a robotic purification platform using a Perkin Elmer JANUS-VariSpan automated liquid handling instrument (ALH) with a plate shuttle.
• Implementation of a 2-step purification process: Protein A chromatography followed by desalting/size exclusion chromatography.
• Utilized micro columns (RoboColumns) for miniaturized and automated chromatography.

Main Results:

• The platform enables automated 2-step purification of several hundred mAbs per week.
• Achieved high recovery rates of >90% for purified mAbs.
• Obtained yields of up to 2mg of purified mAb from 4mL of cell-free culture supernatant at sub-milligram levels.

Conclusions:

• The described robotic platform offers an efficient and scalable solution for high-throughput purification of recombinant mAbs.
• This automated method accelerates the selection and development process for antibody therapeutics.
• The platform is well-suited for purifying antibodies produced by TGE systems, supporting rapid drug discovery efforts.