Kinetic plot method for the optimal column and instrument design for high speed chiral SFC applications

The present study presents a kinetic plot method that allows to explore various different parameters (column length and i.d., particle size, extra-column dispersion, flow rate) contributing to the speed of high-throughput SFC separations. As a representative example, the method has been applied to a set of experimental van Deemter data, averaged over 4 state-of-the-art chiral SFC columns (3 mm i.d., L = 5 and 10 cm and packed with 1.6 and 3 µm fully-porous particles) and 2 analytes. High throughput screening typically requires only a few 1000's of theoretical plates and it has been found that the upper limit on the available flow rate is the main impediment to produce such low plate numbers at the ultimate speed, i.e., at the kinetic performance limit of the particles. The flow rate is in most state-of-the-art instruments limited to a value around 4-5 mL/min, while 3 mm i.d. columns packed with 2 µm particles would respectively need pump flow rates around 15, 25 or 35 mL/min to respectively reach the kinetic performance limit for a N = 5000, 2000 and 1000 theoretical plate separation (assumed trans-column pressure-drop ΔP_col,max = 300 bar). With flow rates limited to F_max= 4 mL/min, the analysis time is a factor of 2.6, 4.2 and 5.7 for N = 5000, 2000 and 1000 respectively higher than if this limitation could be lifted. It has also been found that, the better packed the column, the higher the required flow rate to operate at the kinetic performance limit. Other instrument changes, such as a doubling of the column pressure-drop or a strong reduction of the instrument's extra-column band broadening also have a positive impact but to a lesser extent than would be obtained by increasing the maximal pump flow rate.