News|Videos|September 30, 2026

The Return of Perfusion Chromatography

Perfusion chromatography offers improved separation of oligonucleotide biotherapeutics at ultra-high velocities.

At ISC 2026, LCGC International spoke to Daniel Meston from Agilent Technologies about his presentation “Perfusion Chromatography Enables Highly Efficient Separation of Oligonucleotide Biotherapeutics at Ultra-high Velocities”,1which explored the principles, development, and re-investigation of the attributes ofperfusion chromatography. The concept of perfusion chromatography, which was originally developed in the late 1980s for biomolecule separation, involves actively assisting analyte movement through particles rather than relying solely on diffusion. The interview highlights its potential to improve analytical throughput by enabling very high linear velocities without substantial loss of chromatographic performance. This attribute is particularly relevant for oligonucleotides, which typically require slow flow rates due to their limited diffusion. Effective perfusion requires columns with sufficiently large pore sizes, with approximately 2000–4000 Å identified as a suitable range, according to Meston. However, he emphasized that operating at high linear velocities introduces increased back pressure and, consequently, column dimensions, particle size, and temperature must be carefully considered to balance analytical speed, efficiency, and system pressure.

Meston answered the following questions:

  • What is perfusion chromatography, why is it being re-evaluated for applications in modern biotherapeutics, particularly for oligonucleotides?
  • What potential benefits can it offer the analyst for oligonucleotide analysis?
  • How does perfusion improve the efficiency during the separation?"
  • What type of columns can perform perfusion chromatography?
  • What are the trade-offs for working at very high linear velocities?

Reference

  1. Meston D. Perfusion Chromatography Enables Highly Efficient Separation of Oligonucleotide Biotherapeutics at Ultra-high Velocities. Presented at ISC 2026, in Prague, Czech Republic. https://www.czech-in.org/cmPortalv15/Searchable/isc26/config/normal#!sessionschedule(accessed 2026-09-18).

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