(211c) Towards Preparative Chromatographic Classification of Polydisperse Products

The quality of polydisperse products like polymers or nanoparticles depends strongly on their size distribution, that is, their molar weight distribution (MWD) or particle size distribution (PSD). The narrower a product’s size distribution, the higher its value, since the more defined are its properties like light absorption and emission, color brilliance, catalytic activity, behavior in biological systems, etc.

At lab-scale, quite defined MWDs and PSDs are attainable by synthesis. However, scale-up to industrial conditions generally leads to broader distributions, necessitating a subsequent classification. The challenge is that, for corresponding products, suitable industrial separation technologies are rare. Most promising for such task is preparative chromatography due to its unpreceded resolution power and proven scalability. Currently, a large collaborative research project funded by the German Science Foundation (CRC 1411 - “Design of Particulate Products” [1]) is devoted to this problem.

Here we present experimental and model-based developments of chromatographic classification for complementary model systems. The first is the reversed-phase separation of molar-weight distributed polyethylene glycols (PEGs). Based on detailed analytical-scale investigations, a computationally efficient process model is established that includes rigorous thermodynamic treatment of retention depending on the most relevant parameters, namely, degree of polymerization, temperature, and mobile phase composition. The model allows highly accurate prediction of chromatograms over a wide range of conditions [2]. After validation, it was applied successfully for designing semi-preparative chromatographic processes to isolate highly pure single PEG homologs of different molecular sizes. Second, the applicability to the separation of nanoparticles and the specific challenges related to this are discussed using selected examples.

Based on the insights, advanced chromatographic operating concepts like column combinations, recycle schemes or multi-column processes are presented and evaluated. The results are of general relevance for developing powerful separations capable of obtaining well-defined products from polydisperse mixtures.

[1] For details https://www.crc1411.research.fau.eu

[2] Supper, Heller, Söllner, Sainio, Kaspereit, Processes, 2022 (subm.)