As the therapeutic landscape shifts toward more complex biologics—like single-chain variable fragments (scFvs) and multispecific antibodies (msAbs)—the need for scalable, high-throughput purification systems becomes more urgent. A recent study by researchers at Numab Therapeutics (Switzerland) and Cytiva (Sweden), published in the Journal of Chromatography A, introduces a novel automated platform that may redefine early-stage antibody candidate screening.

Why Multispecific Antibodies Matter

Multispecific antibodies (msAbs) are engineered to bind two or more targets simultaneously, opening doors to highly tailored therapies for complex diseases such as cancer and autoimmune disorders. Built from a modular combination of Fab, scFv, Fc, or even VHH (nanobody) units, msAbs are increasingly popular in biopharma pipelines for their specificity and functional versatility.

But their development isn't easy. Screening hundreds of these constructs demands not just clever molecular design, but also rapid, scalable purification workflows to assess stability, binding behavior, and developability before moving into lead optimization.

Overcoming Traditional Limitations

Existing high-throughput purification platforms often rely on:

• Plate-based formats or tip columns, which are limited in scale,

• Customized robotic systems, which are expensive and inaccessible for many biotech labs and academic groups.

Moreover, traditional workflows often fail to deliver the monomeric purity required for extended biophysical characterization, a key step in understanding therapeutic viability.

The Innovation: A Modular Automated Purification Platform

The researchers developed a modular, automated purification platform using Cytiva's ÄKTA chromatography system—enhanced with membrane affinity chromatography and multi-column schemes.

Key features include:

• Autosampler integration for continuous operation, including overnight runs,

• Use of 1-, 2-, and 3-column configurations for flexible workflow design,

• Protein A membrane adsorbers, which significantly reduced cycle times without sacrificing yield or purity,
  

• Automated size-exclusion chromatography (SEC) for final polishing and monomer enrichment.
  

What It Can Do

• Up to 51 scFvs purified per day with monomeric purities exceeding 90%

• Up to 22 msAbs purified daily

• 15+ samples polished via SEC daily using the automated system

This level of throughput and reproducibility makes the platform especially powerful for early drug discovery, where candidate ranking and developability screening must happen quickly and at scale.

Implications for Antibody and Nanobody Development

For companies working with VHH antibodies, scFvs, or bispecific constructs, this platform offers a compelling blueprint for integrating automation, speed, and scalability into discovery pipelines. At AlpalifeBio, where we support clients in VHH discovery and screening, we recognize how crucial rapid purification and characterization are for moving candidates toward the clinic.

As more biotech innovators adopt similar modular strategies, we anticipate a broader shift toward automated, flexible purification workflows—especially in labs where time and resource efficiency are critical.

Learn More

If you're exploring high-throughput discovery using nanobodies or fragment-based therapeutics, AlpalifeBio can support your screening, purification, and downstream validation strategies. Reach out to discuss custom solutions designed for speed and precision.

Source: www.chromatographyonline.com