Research topics

The research in the Separation Science Group is driven by the overwhelming complexity experienced in especially natural but also in synthetic mixtures. Chromatography or electrophoresis is essential for qualitative and quantitative analysis of organic and inorganic molecules. After 100 year of development much open question remain and novel challenges continuously appear as users in all fields of chemistry and well beyond are confronted with new problems which can often only be addressed providing effective separation can be achieved. As progress is made new physical barriers are encountered which need be overcome. Research projects in the separation science group can roughly be grouped in two research types:

  1. The development of novel column chemistry, sample preparation or system technology to overcome contemporary limitations of chromatography, electrophoresis or organic mass spectrometry. This typically requires synthetic chemistry of organic, inorganic or polymeric nature.
  2. High- end implementation of state-of-the-art instrumentation to address problems in quantitative or qualitative analysis of organic molecules in complex mixtures in a targeted or untargeted way.

The current research projects are demonstrated below.

For bachelor students we have several available interesting Master dissertation topics.

Use of biopartitioning chromatography as a high throughput surrogate measure for brain penetration

The ability to permeate across the blood-brain barrier (BBB) is essential for drugs acting on the central nervous system (CNS). Biopartitioning chromatography can be used as an in vitro system to model the biopartitioning process of drugs when there are no active processes. The technique uses micellar mobile phases at physiological conditions and reversed phase columns to determine retention times (retention factors). The retention factor of a drug, which is influenced by the adsorption of surfactant monolayer to the stationary phase and by micelles present in the mobile phase, gives an indication of the drug penetration across a membrane.

The target of this project is to obtain an in vitro biopartitioning chromatography experiment that can correlate the retention factors with measured BBB penetration as good as possible.

Application of comprehensive two-dimensional HPLC in separation of copolymers

Knowledge of the exact composition and purity of advanced copolymers is of utmost importance given their influence on the final physical properties. The development of analytical techniques to examine these impurities is therefore crucial with respect of large industrial productions. A comprehensive two-dimensional HPLC separation technique with a slow size exclusion (SEC) separation in the first dimension and a fast reversed phase liquid chromatography (RPLC) separation in the second dimension was therefore developed and will be further elaborated to improve and optimise it's overall peak capacity. Separation methods for a range of different copolymer types will be developed as an asset for the polymer chemist.

New strategy for fast chiral screening by high-performance liquid chromatography coupled with multivariate curve resolution-alternating least squares

A strategy aimed at developing rapid chiral screening technology was proposed in this paper with compressed screening time by mixing samples and screening the mixture of racemates. The data matrix of the mixture obtained by diode array detector or mass spectrometry was deconvoluted into resolved chromatograms and spectra by the multivariate curve resolution - alternating least squares algorithm. The individual racemate was then identified by the resolved spectra and its enantioselectivity was evaluated by the resolved chromatograms. Two example experiments were carried out to verify the feasibility of the strategy.
A mixture consisting 5 racemates was successfully screened on Chiralcel OD column in one fifth of the conventional analysis time. Another mixture made by 10 racemates gained nine tenth of the original screening time on three CSPs with an prediction accuracy above 90%.


Selectivity optimization with commercial coupled columns by gradient stationary phase optimized selectivity liquid chromatography

The gradient SOSLC protocol is successfully extended to coupled columns of 4 different stationary phases. Fast and full baseline separations of the mixture composed of 12 compounds of phenones, benzoic acids and benzoates are demonstrated within analysis time of 15 minutes under both isocratic and linear gradient conditions. Although the extra column void volume is increased by the use of tubings, the average relative deviation of prediction on selectivity factor results less than 2% and the maximum relative deviations are below 5%. These results indicate that the proposed gradient SOSLC protocol on coupled columns can also bring us robust and promising solution for separation of a given mixture.

The benefits of extending the gradient SOSLC to coupled column chromatography include wider commercial availability of stationary phases / columns, full use of the present columns in the lab, more selection of column coupler and flexible applications.

Evaluation and optimization of Capillary ElectroChromatography as a high-efficient separation technique.

Capillary Electrochromatography (CEC) is theoretically a highly efficient technique but is not yet implemented in the industry as a standard separation technique.
This research is focused on the development of a neutral comparison tool for CEC capillaries in terms of speed and efficiency. The tool will be further used to address the problems in this electrodriven separation technique and to compare capillaries packed with the newest packing materials (sub-um, mixed mode, fused-core particles...) and new packing methods.