Pareto-optimality study into the comparison of the separation potential of comprehensive two-dimensional liquid chromatography in the column and spatial modes

The expected performance of spatial (“flat-bed”) two-dimensional liquid chromatography (xLC × xLC) has been calculated using the Pareto-optimality strategy. This approach allowed different objectives (total peak capacity, total analysis time, and total dilution) to be considered simultaneously and to establish optimal parameters (pressure drop, particle size, bed length, and initial spot size). The performance of spatial two-dimensional chromatographic systems was compared with that of conventional on-line, real-time two-dimensional column-liquid-chromatography systems (tLC × tLC). The potential gain in peak capacity and/or analysis time of the spatial configuration was confirmed. By restricting the spatial parameters to realistic chromatographic conditions (limiting the stress, as counterbalance for the pressure drop through the sorbent bed, to 2500 kg) it was found that xLC × xLC is attractive for very fast analysis of complex samples, rather than for extremely efficient separations. For example, a peak capacity of 780 may be achieved in only 2.7 min using a 100 × 100 mm sorbent bed of a quality currently encountered thin-layer chromatography. Furthermore, if beds can be packed as efficiently as contemporary columns, the predicted peak capacity increases to around 1000, corresponding to a peak-production rate of about 6.3 peaks/s. Possibilities to boost the performance of xLC × xLC further are briefly discussed. Unless we can overcome the severe stress requirements of high-performance xLC × xLC, conventional tLC × tLC may be more amenable to very complex separations, thanks to the very high peak capacities. However, tLC × tLC separations will require long analysis times (e.g. 10,000 peaks in 37 h, corresponding to 0.075 peaks/s at a pressure drop of 40 MPa). The best trade-off between total peak capacity, total analysis time, and total dilution under restricted (realistic) conditions was obtained using high pressures, small chromatographic beds, small particles, and relatively large sample spots.

► Spatial two-dimensional liquid chromatography was optimized.
► Pareto-optimality studies were performed with two and three objectives.
► Spatial and time-based (column) comprehensive two-dimensional LC were compared.
► Spatial LC × LC is attractive for very fast analysis of relatively complex samples.
► Peak capacities exceeding 1000 can be achieved within a few minutes.