(224a) Using Isopycnic Plots for Faster Method Development of Supercritical Fluid Chromatography Operations

Chromatography is a separation technique, which plays a critical role in bio-pharmaceutical, chiral and fine chemical industries. The main strength of this technique is its ability to separate almost any complex mixture with great precision. The problems, on the other hand, are its low productivity and usage of a significant volume of solvents, which threaten its future sustainability.

Supercritical fluid chromatography (SFC), which mainly uses supercritical carbon-dioxide as the solvent in chromatographic operations, is emerging as the more sustainable version of chromatographic processes. One of the main problems in a widespread use of SFC is its operational complexity and lack of physical understanding in designing competitive industrial processes. This hinders the industrial practitioners from developing or transferring effective operational methods for a particular separation.

The separation performance in SFC strongly depends on the solvent density, and to a lesser extent, on the temperature. This indicates that the effects of the operating conditions on chromatographic performances can be understood more clearly by following the changes in both the density and the temperature, rather than analyzing the operating variables i.e. the pressure and the temperature. In other words, SFC operations can be more clearly analyzed based on the iso-density or isopycnic plots, drawn on the pressure-temperature plane, rather than by the isobars and the isotherms alone.

The talk will demonstrate that guided by the solvent isopycnic lines on the pressure-temperature plane and by the position of the critical isotherm, one can develop effective separation methods quickly, without the help of detailed simulation studies. The talk will also discuss the issue of operating in the subcritical zone of carbon-dioxide, as done in several industrial separations, and will show that while operations in the subcritical zone may lead to more stable conditions, operations in the high pressure supercritical zone brings greater operational dividends along with the stability. Relative advantages and disadvantages of operating in different zones on the pressure-temperature diagram will be discussed and it will be demonstrated that although the most attractive operating conditions in SFC are in the low pressure supercritical region, where the viscosity is low and the diffusivity high, hence where separations could be faster, it is also more difficult to design SFC operations here. The talk will elucidate the physical reasons behind the operational difficulties in this region.