Towards ideal modulators for LC×LC

Two-dimensional liquid chromatography (LC×LC) is a separation technique that both industry and academia look towards when complex non-volatile samples need to be analysed. As both hardware and software continues to develop in this field, the number of LC×LC applications will only grow. Most of this thesis covers modulation strategies and concepts for LC×LC and the aim is to contribute knowledge to the field of LC×LC modulation. This is achieved by examining the limitations of LC×LC without advanced modulation and by introducing the concept of in-column focusing that could lead to an ideal modulator, the criteria for which are described. Proof-of-concept experiments for ICF as a trapping technique are presented. A computational model, designed to reveal the intricacies of ICF, predicts how the method would perform under circumstances typically encountered in LC×LC modulation and a prototype is presented that can perform the necessary operations to carry out ICF in a timeframe compatible with LC×LC modulation. An LC×LC separation of an industrial sample containing long poly(acrylic acid) chains and short maltodextrin hybrid grafts, as well as excess reagents, salts, and other additives is presented. Finally the thesis results as well as the current (and likely future) research efforts in the field of comprehensive two-dimensional liquid chromatography are discussed.