
Slalom chromatography speeds mRNA QC—separating plasmid forms and spotting dsRNA impurities in minutes with higher sensitivity than gels or ELISA.

Dr. Fabrice G. Gritti earned his Ph.D. in Chemistry and Physics of Condensed Matter from the University of Bordeaux I in 2001. After serving as a research scientist at the University of Tennessee through 2014, he joined Waters Corporation (Millford, USA) in 2015, where he is now a Distinguished Research Scientist advancing chromatographic separation science. He has authored over 300 peer‑reviewed publications and delivered more than 95 keynote lectures worldwide. His honors include the Csaba Horvath Memorial Award (2023) and the A.J.P. Martin Medal (2024).

Slalom chromatography speeds mRNA QC—separating plasmid forms and spotting dsRNA impurities in minutes with higher sensitivity than gels or ELISA.

Part 1 of this two-part article series reviews the history of slalom chromatography (SC), the rationale for its recent revival, and the updated mechanistic framework of this technique. Rooted in the fundamental physical properties of deoxyribonucleic acid/ribonucleic acid (DNA/RNA) biopolymers and laminar flow dynamics in packed chromatographic beds, SC is highlighted for its most promising applications in cell and gene therapy. Recent two-year experimental investigations have revealed that SC operates through an out‑of‑equilibrium mechanism, coupling the entropic elasticity of double‑stranded deoxyribonucleic acid/ribonucleic acid (dsDNA/RNA) with the extension and shear forces generated within the interparticle spaces of ultrahigh-pressure liquid chromatography (UHPLC) columns. In contrast to gel permeation chromatography (GPC) or hydrodynamic chromatography (HDC), SC functions at high speed and uniquely elutes smaller dsDNA fragments first, followed by progressively larger ones. Unlike agarose gel electrophoresis (AGE), SC achieves separations of large DNAs in less than three minutes, with nearly twice the resolution power of typical AGE. These findings paved the way for the recent design of a new SC column intended for use in cell and gene therapy as an alternative to standard AGE. Further applications of this new SC column within cell and gene therapy workflows will be discussed in Part 2.

A harmonization of all conventional hold-up volume methods was successfully applied to RPLC, HILIC, AEX, and RP-AEX mixed-mode chromatography, regardless of the mobile phase.

An UHPLC–MS research prototype instrument was built to improve the resolution power and the usability of conventional LC–MS hyphenated instruments for routine analyses in pharmaceutical applications.

With a new prototype, we explore how to improve the resolution power and usability of LC–MS instruments for routine analysis in pharmaceutical applications.

A gradient twin-column recycling liquid chromatography (GTCRLC) process has been developed and applied for the isolation of a single polycyclic aromatic hydrocarbon (PAH), chrysene, present in a complex PAH mixture.

We investigate a phenomenon observed by many practitioners of reversed- phase LC: a dramatic loss in retention volume or time after the column flow is stopped and resumed when using highly aqueous mobile phases with certain columns.

LCGC North America
At the 43rd International Symposium on Capillary Chromatography (ISCC 2019) in Fort Worth, Texas, a panel addressed the current challenges and potential future directions in capillary liquid chromatography. How can their vision be achieved?

LCGC Europe
The “State-of-the-Art in Capillary Liquid Chromatography” panel discussion at the 43rd International Symposium on Capillary Chromatography (ISCC 2019) in Fort Worth, Texas, USA, was a thoughtful dialogue on current challenges and potential future directions in the field. The session included a general overview of the current state of the field, key drawbacks preventing widespread use of capillary liquid chromatography (LC) columns, and how these challenges might be overcome. In this article, we highlight some of the common themes that were discussed as part of this panel.

Special Issues
This article demonstrates how a user-friendly vacuum-jacketed column (VJC) has been designed without the need of a large internal diameter vacuum chamber and low- and high-vacuum pumps.

Special Issues
The design of a user-friendly vacuum-jacketed column (VJC) is described for improved LC–MS performance, which does not require a large vacuum chamber with multiple vacuum pumps. Using this configuration, the experimental peak capacities measured for a 2.1 mm × 100 mm column packed with sub-2-μm particles and placed in the VJC-MS probe are doubled with respect to standard LC–MS systems.

Special Issues
Thermal effects in UHPLC and low-density SFC cause peak broadening and distortion. A solution to this problem is to thermally insulate the chromatographic column. Vacuum-jacketed column technology has been developed as a new approach to insulate the column in a practical way.

LCGC North America
Despite the theoretical promise of reduced plate heights (h) < 1, most modern UHPLC columns can only deliver plate heights in the range from 1.4 to 2.5. However, improved packing procedures, a better understanding of the colloidal properties of particle suspensions, and the study of the rheological behavior of packed beds and the final bed structure should lead us to practical solutions that can double the column efficiencies.

LCGC Europe
In this extended special feature to celebrate the 30th anniversary edition of LCGC Europe, leading figures from the separation science community explore contemporary trends in separation science and identify possible future developments. We asked key opinion leaders in the field to discuss the current state of the art in liquid chromatography column technology, gas chromatography, sample preparation, and liquid chromatography instruments. They also describe the latest practical developments in supercritical fluid chromatography, 3D printing, capillary electrophoresis, data handling, comprehensive two‑dimensional liquid chromatography, and multidimensional gas chromatography.

LCGC North America
When Professor Georges Guiochon passed away last October, at the age of 83, the separation science community mourned the loss of one of the great pioneers of the field.

LCGC North America
This article reports on the physical phenomena that control column efficiency and on experimental protocols designed to accurately measure their contributions to band broadening of analytes during their passage from the injection to the detection device. The results of these protocols are analyzed, allowing for the accurate determination of the complete mass transfer mechanism in different separation modes and providing solutions and future directions to further improve the efficiency of liquid chromatography columns.

LCGC Europe
Professor Georges Guiochon spoke to Fabrice Gritti about his pioneering contributions to the field of separation science.

LCGC North America
Detailed study results challenge common beliefs about the mechanisms behind the excellent performance of core–shell particles.

Published: April 6th 2026 | Updated: April 7th 2026

July 1st 2022

Published: April 6th 2026 | Updated: April 7th 2026