Current Research Projects

My educational background covers biology and chemistry, with a current (since 2000) focus on separation science. The active projects in my laboratory are all ultimately focused on the development of Multi-Dimensional Liquid Chromatography, and described below. Because of the complexity of multi-dimensional methods, and the number of experimental variables involved, some of our projects (e.g., Selectivity in RPLC, and Optimization of LC Performance) necessarily play a supporting role in achieving our overall goals. Links to our work are embedded throughout these descriptions; here are links to my full CV, and publication and presentations lists.

Multi-dimensional Liquid Chromatography

My interest in multi-dimensional chromatography (MDLC) was initiated when I was a graduate student, with Prof. Peter Carr at the University of Minnesota. From the start I have been intrigued and motivated by: 1) the potential of MDLC to extend the capabilities of HPLC to handle more complicated samples (e.g., blood, urine, plant extracts) then has been possible with conventional one-dimensional methods; 2) the challenge of building and optimizing MDLC instrumentation and methodologies to extend the state-of-the-art. While working with Prof. Carr I developed and studied Fast, Comprehensive Two-Dimensional HPLC (LC x LC). In this work we implemented the principles of High Temperature Liquid Chromatography, and studied the limitations to fast gradient elution reversed-phase HPLC, in dramatically improve the speed of second dimension separations, and thus the overall productivity of LC x LC.

More recent work in my laboratory at Gustavus Adolphus College has focused more on the uses of 2D and 3DLC for targeted analysis, as opposed to comprehensive analyses (LC x LC). We have demonstrated (see Simpkins et al., 2009) highly targeted heartcutting 3DLC (h3DLC) for accurate, quantitative analysis of trace components of river water and urine, for example. The selectivity that is achieveable in this type of setup is so extraordinary that less selective detectors (e.g, UV/Vis absorption spectroscopy) that those normally used for this kind of work can be used without sacrificing quantitative accuracy. Recognizing that the h3DLC approach is rather limited in terms of the number of target compounds that can be analyzed in a reasonable time, our most recent work has focused on the development of a completely new methodology we refer to as Selective Comprehensive Two-Dimensional HPLC (sLC x LC). We assert that this approach combines the best of the more extreme but complementary heartcutting and comprehensive modes of separation, and provides the opporunity to achieve very high selectivity for up to tens of compounds in a single analysis, and in a reasonable time.

 Selectivity in Liquid Chromatography

One of the most important variables in 2DLC is the choice of separation modes in the first and second dimension separations. Early in my career I spent several years studying zirconia-based phases, which offer significant differences in selectivity compared to other more common phases (e.g., bonded silica-based phases). I have been and continue to be very interested in the properties of carbon-based phases, which are exhibit radically different selectivity compared to all other known phases for reversed-phase HPLC (RPLC). Currently we are studying the characteristics of carbon-modified silica phases that offer some exciting advantages over existing carbon-based phases.

Most recently my laboratory has taken on responsibility for maintenance and further development of the Hydrophobic Substraction Model (HSM) of reversed-phase selectivity originally developed by Lloyd Snyder, John Dolan, and Peter Carr. This project, which started about a decade ago, and has been very successful due in large part to broad involvement by column manufacturers, has aimed to characterize all RPLC columns using a five-parameter linear model that is based on intuitive solute-stationary phase interactions. As of June, 2012, about 560 columns have been characterized, and the data resulting from these characterizations are freely available at the website of the United States Pharmacopoeia. Please contact me if you are interested in having your columns characterized and listed in the database, or are interested in the project in other ways.

Optimization of Performance in HPLC

Given the continuously changing landscape of HPLC particle and column technology, and the fact that very different conditions are usually used in the two dimensions of 2DLC systems, we are also inherently interested in the principles of performance optimization in HPLC. In the last five years or so, we have seen a transformation in the HPLC column market, with multiple vendors now offering sub-two-micron fully porous particles, in addition to multiple offerings of superficially porous particles. During the same time period, we have seen a tranformation in HPLC instrumentation, exemplified by the departure from the long-standing 6,000 psi pressure limit to instruments with 15 to 20,000 psi limits from several vendors at this time. Along with this change in pressure capability have come improvements in the extra-column dispersion and gradient delay volume characteristics of the instruments, which are particularly important when using many of the new particle technologies. We have done both theoretical (see Carr et al., 2009; Carr et al., 2010) and experimental work (see Wang et al., 2010) in this area, and continue to study new materials and components in this context.