Title TBD (Bioanalytics)

Slalom chromatography (SC) is a unique separation mode first reported in 1988 and largely abandoned for more than two decades due to limited mechanistic understanding, insufficient column technology, and a lack of compelling application spaces. With the explosive growth of cell and gene therapy, this once‑overlooked technique has been revitalized using bio‑inert, ultra‑high‑pressure liquid chromatography (UHPLC) columns and advanced instrumentation, enabling rapid, high‑resolution analysis of large nucleic acids ranging from 3 kbp to over 50 kbp.

This presentation revisits the reinvention of slalom chromatography, beginning with the fundamental research and development of a new commercial column—GT × Resolve™ Slalom Column (MaxPeak™ Premier, 2.5 μm, 4.6 × 300 mm). We elucidate the physical origins of SC separation, rooted in the slow coil‑to‑stretch transition experienced by large biopolymers such as dsDNA and dsRNA when subjected to combined extensional and shear flows within the confined interparticle domains of UHPLC columns. This mechanistically driven mode of separation unlocks selectivity that is fundamentally distinct from conventional size‑exclusion or ion‑pair chromatography.

The second part of the presentation highlights impactful applications across cell and gene therapy workflows. Case studies include plasmid purity assessment through the separation of supercoiled and open circular DNA, evaluation of plasmid linearization efficiency for in vitro transcription (IVT) processes, detailed dsRNA impurity profiling in mRNA samples, DNA restriction mapping, and preparation of highly purified DNA fractions for IVT processes and next generation sequencing. Performance is benchmarked against gel electrophoresis, demonstrating superior speed, resolution, and automation compatibility.