Capillary-Based Instrument for the Simultaneous Measurement of Solution Viscosity and Solute Diffusion Coefficient at Pressures up to 2000 bar and Implications for Ultrahigh Pressure Liquid Chromatography

Abstract

An instrument based on the Poiseuille flow principle capable of measuring solution viscosities at high pressures has been modified to observe UV-absorbent analytes in order to allow for the simultaneous measurement of analyte diffusivity. A capillary time-of-flight (CTOF) instrument was used to measure the viscosity of acetonitrile-water mixtures in all decade volume percent increments and the corresponding diffusion coefficients of small aromatic molecules in these solvent mixtures from atmospheric pressure to 2000 bar (approximately 30,000 psi) at 25 degrees C. The instrument works by utilizing a relatively small pressure drop (<100 bar) across a fused-silica capillary which has both the inlet and outlet pressurized so that the average column pressure can be significantly elevated (up to 2000 bar). Measurements with this instrument agree with high-pressure viscosity data collected previously using a CTOF viscometer, as well as with literature values obtained with falling-body viscometers of the Bridgman design. It has been further determined that, for the small molecules included in this study, trends in solute diffusivity with respect to pressure follow the predictions of the Stokes-Einstein equation when the solvent viscosity is corrected as a function of pressure. Because the instrument described herein determines viscosity and diffusivity independently, the effect of pressure on analyte hydrodynamic radius can also be monitored. An analysis of ultrahigh pressure liquid chromatography (UHPLC) data was performed using the pressure-corrected diffusion coefficient of hydroquinone to demonstrate the effect of this phenomenon on the analysis of chromatographic performance.

Implementation of high slurry concentration and sonication to pack high-efficiency, meter-long capillary ultrahigh pressure liquid chromatography columns

“…Reduced plate height curves h = H / d p vs. v = u av d p / D m were calculated using the particles’ Sauter diameter ( d p = 2.02 μm) and D m , the pressure-dependent diffusion coefficient of an analyte in the bulk mobile phase [32]. High frequency noise was removed from the chromatograms using a digital frequency filter and low frequency baseline drift was eliminated by background subtraction.…”

1.1 μm Superficially porous particles for liquid chromatography

“…Reduced parameter plots for each column were generated in order to analyze chromatographic performance. The volume average particle size (1.2 m) and the pressure dependent diffusion coefficient for each analyte were used to determine the reduced parameters for each column [29,38].…”

Measurement and Modeling of Extra-Column Effects Due to Injection and Connections in Capillary Liquid Chromatography

“…The mobile phase used through all experiments was 50% acetonitrile in water (with 0.1% trifluoroacetic acid) and the test analyte was 4-methyl catechol (in the mobile phase). For calculations using the Taylor-Aris equation (Equation 6), the diffusion coefficient of 4-methyl catechol was set at 9.2 × 10 −6 cm 2 /s (using a previously measured experimental value [95]). For all four diameters, analyte variance was tested at flow rates of 0.…”

“…This method was utilized because there were no extra connecting unions or detection cells that could impact the broadening measurement. 4-methyl catechol was selected as the analyte of choice as its diffusion coefficient has been experimentally measured with the mobile phase and pressures used here [95] and it is detectable using the microelectrode. A Foley-Dorsey type EMG function (Equation 12) was used for peak fitting because it works well for tailing peaks (common when measuring ECBB effects) and because it allows for the separation of Gaussian-type ("sigma-type") and exponential decay ("tau-type") broadening.…”