A comparison of 2 micron inner diameter open tubular column liquid chromatography with pressure-driven isocratic, slip-flow, and electrochromatographic modes of operation: a theoretical study.

Modifications to the flow profile used in open tube capillary liquid chromatography (OT-CLC) include using slip-flow walls and using electroosmosis as a fluid pump as practiced in electrochromatography. These modifications are implemented experimentally by changing the capillary surface and solvent conditions which results in the change of boundary conditions at the capillary wall. In this paper we employ a theory-based study and compare the zone broadening of simple solutes using parabolic flow from a liquid pump, slip-flow from a highly hydrophobic inner surface with water eluent, and electroosmosis for the conditions of pure water and dilute salt utilizing 2 µm inner diameter OT capillaries.

Estimation of low-level components lost through chromatographic separations with finite detection limits.

The search for biomarkers allowing the assessment of disease by early diagnosis is facilitated by liquid chromatography. However, it is not clear how many components are lost due to being present in concentrations below the detection limit and/or being obscured by chromatographic peak overlap. First, we extend the study of missing components undertaken by Enke and Nagels, who employed the log-normal probability density function (pdf) for the distribution of signal intensities (and concentrations) of three mixtures.

Measuring porosities of chromatographic columns utilizing a mass-based total pore-blocking method: Superficially porous particles and pore-blocking critical pressure mechanism.

Experimentally determined total, interstitial and intraparticle porosity values are necessary to equate theory, simulation and experimental column performance. This paper reports a study of a mass-based technique for determining total, interstitial and intraparticle porosity measurements based on the total pore-blocking (TPB) method. Commercially available superficially porous particle (SPP) columns, in a variety of small-pore and wide-pore materials, with both hydrophobic and hydrophilic surfaces, are utilized as samples.

Column selection for comprehensive two-dimensional liquid chromatography using the hydrophobic subtraction model.

Two-dimensional (2D) liquid chromatography (2DLC) methods have grown in popularity due to their enhanced peak capacity that allows for resolving complex samples. Given the large number of commercially available column types, one of the major challenges in implementing 2DLC methods is the selection of suitable column pairs. Column selection is typically informed by chemical intuition with subsequent experimental optimization.

Simulation and theory of open-tube dispersion in short and long capillaries with slip boundaries and retention.

Using random walk techniques, high resolution simulations of zone shape are conducted in open capillary tubes for short and long tube conditions. Finite size solutes are used as tracers in this treatment. Slip flow boundary conditions and wall retention are utilized as needed.

Transport properties and size exclusion effects in wide-pore superficially porous particles.

The effects of hydrodynamic radius on the transport of solute molecules in packed beds of wide-pore superficially porous particles (SPP) are studied using pore-scale simulation. The free molecular diffusion rate varies with radius through the Stokes-Einstein relation. Lattice Boltzmann and Langevin methods are used to model fluid motion and the transport of an ensemble of solute molecules in the fluid, providing statistics on solute concentration, flux, molecule age and residence time, as a function of depth in the SPP.

Ellipsoidal particles for liquid chromatography: Fluid mechanics, efficiency and wall effects.

Ellipsoidal particles are investigated as packing media for liquid chromatography using high resolution fluid mechanics and Brownian dynamics simulations. The simulations are conducted with packed capillary columns, as well as beds with periodic boundary conditions (PBCs) to study transport in the absence of wall effects. The performance of ellipsoidal particles is evaluated over a range of aspect ratios.

Using molecular simulations to probe pore structures and polymer partitioning in size exclusion chromatography.

Molecular simulations have been extensively utilized to understand and predict the polymer partitioning in size-exclusion chromatography (SEC). However, idealized pore models (e.g.

Orthogonality measurements for multidimensional chromatography in three and higher dimensional separations.

Orthogonality metrics (OMs) for three and higher dimensional separations are proposed as extensions of previously developed OMs, which were used to evaluate the zone utilization of two-dimensional (2D) separations. These OMs include correlation coefficients, dimensionality, information theory metrics and convex-hull metrics. In a number of these cases, lower dimensional subspace metrics exist and can be readily calculated.

Superficially porous particles with 1000Å pores for large biomolecule high performance liquid chromatography and polymer size exclusion chromatography.

To facilitate mass transport and column efficiency, solutes must have free access to particle pores to facilitate interactions with the stationary phase. To ensure this feature, particles should be used for HPLC separations which have pores sufficiently large to accommodate the solute without restricted diffusion. This paper describes the design and properties of superficially porous (also called Fused-Core, core shell or porous shell) particles with very large (1000Å) pores specifically developed for separating very large biomolecules and polymers.

Size exclusion chromatography with superficially porous particles.

A comparison is made using size-exclusion chromatography (SEC) of synthetic polymers between fully porous particles (FPPs) and superficially porous particles (SPPs) with similar particle diameters, pore sizes and equal flow rates. Polystyrene molecular weight standards with a mobile phase of tetrahydrofuran are utilized for all measurements conducted with standard HPLC equipment. Although it is traditionally thought that larger pore volume is thermodynamically advantageous in SEC for better separations, SPPs have kinetic advantages and these will be shown to compensate for the loss in pore volume compared to FPPs.

Orthogonal separations: Comparison of orthogonality metrics by statistical analysis.

Twenty orthogonality metrics (OMs) derived from convex hull, information theory, fractal dimension, correlation coefficients, nearest neighbor distances and bin-density techniques were calculated from a diverse group of 47 experimental two-dimensional (2D) chromatograms. These chromatograms comprise two datasets; one dataset is a collection of 2D chromatograms from Peter Carr's laboratory at the University of Minnesota, and the other dataset is based on pairs of one-dimensional chromatograms previously published by Martin Gilar and coworkers (Waters Corp.).

Molecular simulation studies of reversed-phase liquid chromatography.

Over the past 20 years, molecular simulation methods have been applied to the modeling of reversed-phase liquid chromatography (RPLC). The purpose of these simulations was to provide a molecular-level understanding of: (i) the structure and dynamics of the bonded phase and its interface with the mobile phase, (ii) the interactions of analytes with the bonded phase, and (iii) the retention mechanism for different analytes. However, the investigation of chromatographic systems poses significant challenges for simulations with respect to the accuracy of the molecular mechanics force fields and the efficiency of the sampling algorithms.

Comparison of orthogonality estimation methods for the two-dimensional separations of peptides.

In two-dimensional chromatography, the orthogonality of separation is important for achieving high peak capacity. In this paper, a number of different metrics are compared as measures of orthogonality. Six peptide elution data sets acquired on different stationary phases are plotted against reversed phase retention data and examined as two-dimensional chromatographic pairs.

Modeling of dispersion in a polymeric chromatographic monolith.

Dispersion in a commercial polymeric monolith was simulated on a sample geometry obtained by direct imaging using high-resolution electron microscopy. A parallelized random walk algorithm, implemented using a velocity field obtained previously by the lattice-Boltzmann method, was used to model mass transfer. Both point particles and probes of finite size were studied.

A molecular simulation study of the effects of stationary phase and solute chain length in reversed-phase liquid chromatography.

The effects of stationary phase and solute chain length are probed by carrying out Monte Carlo simulations of dimethyl triacontyl (C₃₀), dimethyl octadecyl (C₁₈), dimethyl octyl (C₈), and trimethyl (C₁) silane grafted, and bare silica stationary phases in contact with a water/methanol mobile phase and by examining the retention of solutes from 1 to 14 carbons in length. Fairly small differences in structure are observed when comparing the C₃₀, C₁₈, C₈ systems and the retention mechanism of nonpolar alkane solutes shows contribution from both partitioning and adsorption on all three of these stationary phases. Unlike in the other systems, the mobile phase solvent is highly structured at its interface with the C₁ and bare silica phases, the former being enriched in methanol and the latter in water.

Retention mechanism for polycyclic aromatic hydrocarbons in reversed-phase liquid chromatography with monomeric stationary phases.

Reversed-phase liquid chromatography (RPLC) is the foremost technique for the separation of analytes that have very similar chemical functionalities, but differ only in their molecular shape. This ability is crucial in the analysis of various mixtures with environmental and biological importance including polycyclic aromatic hydrocarbons (PAHs) and steroids. A large amount of effort has been devoted to studying this phenomenon experimentally, but a detailed molecular-level description remains lacking.

The statistical overlap theory of chromatography using power law (fractal) statistics.

The chromatographic dimensionality was recently proposed as a measure of retention time spacing based on a power law (fractal) distribution. Using this model, a statistical overlap theory (SOT) for chromatographic peaks is developed that estimates the number of peak maxima as a function of the chromatographic dimension, saturation and scale. Power law models exhibit a threshold region whereby below a critical saturation value no loss of peak maxima due to peak fusion occurs as saturation increases.

Molecular simulations of retention in chromatographic systems: use of biased Monte Carlo techniques to access multiple time and length scales.

The use of configurational-bias Monte Carlo simulations in the Gibbs ensemble allows for the sampling of phenomena that occur on vastly different time and length scales. In this review, applications of this simulation approach to probe retention in gas and reversed-phase liquid chromatographic systems are discussed. These simulations provide an unprecedented view of the retention processes at the molecular-level and show excellent agreement with experimental retention data.

Modeling of flow in a polymeric chromatographic monolith.

The flow behavior of a commercial polymeric monolith was investigated by direct numerical simulations employing the lattice-Boltzmann (LB) methodology. An explicit structural representation of the monolith was obtained by serial sectioning of a portion of the monolith and imaging by scanning electron microscopy. After image processing, the three-dimensional structure of a sample block with dimensions of 17.

Mobile phase effects in reversed-phase liquid chromatography: a comparison of acetonitrile/water and methanol/water solvents as studied by molecular simulation.

Molecular simulations of water/acetonitrile and water/methanol mobile phases in contact with a C(18) stationary phase were carried out to examine the molecular-level effects of mobile phase composition on structure and retention in reversed-phase liquid chromatography. The simulations indicate that increases in the fraction of organic modifier increase the amount of solvent penetration into the stationary phase and that this intercalated solvent increases chain alignment. This effect is slightly more apparent for acetonitrile containing solvents.

The dimensionality of chromatographic separations.

The box-counting or capacity dimension algorithm, known from the fractal mathematics literature, is used to measure the dimensionality D of chromatographic separation techniques for any number of dimensions. It is shown that D has limit properties that match Giddings' sample dimensionality s. D values are shown to be sensitive to the uniformity of peak spacing.

The effects of chain length, embedded polar groups, pressure, and pore shape on structure and retention in reversed-phase liquid chromatography: molecular-level insights from Monte Carlo simulations.

Particle-based simulations using the configurational-bias and Gibbs ensemble Monte Carlo techniques are carried out to probe the effects of various chromatographic parameters on bonded-phase chain conformation, solvent penetration, and retention in reversed-phase liquid chromatography (RPLC). Specifically, we investigate the effects due to the length of the bonded-phase chains (C(18), C(8), and C(1)), the inclusion of embedded polar groups (amide and ether) near the base of the bonded-phase chains, the column pressure (1, 400, and 1000 atm), and the pore shape (planar slit pore versus cylindrical pore with a 60A diameter). These simulations utilize a bonded-phase coverage of 2.

Influence of bonded-phase coverage in reversed-phase liquid chromatography via molecular simulation I. Effects on chain conformation and interfacial properties.

Particle-based Monte Carlo simulations were employed to examine the effects of bonding density on molecular structure in reversed-phase liquid chromatography. Octadecylsilane stationary phases with five different bonding densities (1.6, 2.