Thank you very much for the introduction. As James mentioned, I am at Gilead, where I’m part of the Protein Therapeutics group in Early R&D.

We have two high-throughput protein production workflows: one is a small-scale, plate-based workflow where we use the Dynamic Devices VVP to assist in transfections and purifications. The second is a tube-spin 50 mL bioreactor-based production workflow. Today, I’ll be discussing some of our recent efforts using Dynamic Devices MagLynx instruments to automate purifications from those bioreactors.

So, what do I mean by “50 mL bioreactors”? These are essentially 50 mL Falcon tubes with vented caps to allow gas exchange and a septum for easy addition of cells, reagents, or media—without the need to decap and recap the tubes.

In our tube-spin-based workflow, the goal is to produce a few milligrams of purified, QC’d protein for downstream assays—whether for binder characterization, biophysical profiling, or functional analyses.

To do this, we transfect in these bioreactors and allow them to express for approximately five days. Preparation for purification involves centrifuging to pellet the cells, followed by filtration to remove debris that might clog the ÄKTA purification system. For standard monoclonal antibodies or symmetric molecules, we typically use a two-step ÄKTA purification method: first, a protein A column, then a desalting column to transfer the product into formulation buffer.

When we scaled to 150 samples, this worked reasonably well. However, as we aimed to double throughput to 300 samples per week (we’re currently at 150), several pain points became apparent. Centrifugation and supernatant clarification are labor-intensive and consume significant resources. Someone must manually centrifuge, filter, label, and transfer samples before purification. Each sample in the two-step ÄKTA method takes about 25 minutes, totaling over two full days of run-time for 150 samples. Additionally, we process multiple Fc and isotype species, and not all are compatible with fast-flow columns, requiring separate workflows and more time. Scaling beyond 300 would require doubling both instruments and staff—a solution that quickly becomes unsustainable.

Fortunately, based on prior experience, I knew that magnetic bead-based purification could address these bottlenecks.

Magnetic bead-based purification has multiple advantages—it eliminates the need for cell removal, avoids clogging, and allows simultaneous processing. While sequential workflows exist, there’s no reason not to go parallel with the right equipment. Although we had one magnetic bead purification instrument, its throughput was limited to 40–60 samples per day and required manual intervention after elution. It also lacked full automation.

What we needed was a fully automated solution that could process up to 150 samples per day—ideally producing eluted protein directly into 96-well plates for easier handling and logistics.

At that time, through conferences and networking, we learned that Dynamic Devices was developing a new instrument called the MagLynx, specifically designed for high-throughput magnetic bead-based purification. We were fortunate to partner with them and test this alpha instrument for our bioreactor workflows.

The MagLynx uses a standard LM900 deck outfitted with multiple I-Mag Zs, labware holders, and pipetting tools. The deck includes custom-printed holders for our bioreactors—thanks to Scott, who iterated several 3D-printed versions to accommodate varying Falcon tube geometries.

The system includes an NCPA-compatible head for aspiration, sparging, and wash buffer dispensing, and a six-channel pipetting head capable of handling elution buffers and transferring eluates to 96-well plates. The I-Mag Zs raise the beads to the tube walls, clearing the bottom for media and cell aspiration, followed by wash buffer application through dedicated ports.

For our protein A purifications, we use PBS as the wash buffer. From experience, I knew not all magnetic beads behave equally—especially regarding incubation time required for complete binding.

To test this, we produced a large batch of antibody and compared standard ÄKTA purification to mag bead protocols with varying incubation times: 2, 4, and 24 hours. We observed a near-linear increase in recovery with longer incubation, with the 24-hour samples yielding about 70% more protein than ÄKTA—even after accounting for ÄKTA losses.

But yield alone isn’t enough—quality matters. We ran analytical SEC, SDS-PAGE, and endotoxin testing. The MagLynx-purified proteins had SEC profiles nearly identical to ÄKTA, and SDS-PAGE showed comparable purity, with only minimal contaminants. Endotoxin levels were manageable with weekly sodium hydroxide washes.

Another advantage: the magnetic beads we use are reusable, unlike single-use resin-filled tips. This not only improves cost-efficiency but also supports scalability.

Finally, because we work with diverse antibody formats—not just human IgG1 and IgG4—we tested MagLynx with various species and isotypes. We spiked pre-purified proteins into media with magnetic beads and ran them through the MagLynx workflow.