Work in our research group focuses on three broad areas: 1) research on the mechanism and applications of the matrix-assisted laser desorption/ionization (MALDI) technique; 2) development of improved time-of-flight mass spectrometer (TOFMS) instrumentation; and 3) use of chemometrics, particularly correlation analysis techniques, to aid in the automated interpretation of mass spectral information.

Matrix-Assisted Laser Desorption/Ionization Analysis

Many groups around the world are using the MALDI technique to determine the molecular weight and structure of biological materials such as proteins, peptides, oligonucleotides, as well as the molecular weight distribution of synthetic polymers. Work in our group has focused on several important areas: detailed investigation of the sample preparation process, mechanistic studies of the molecular desorption and ionization events (two distinct processes), the development of quantitative sample analysis strategies, and application of the technique to the analysis of synthetic polymer materials.

​

In the MALDI experiment the analyte of interest is mixed with a 1000 to 10,000 fold excess of a light absorbing organic matrix material. Successful matrices include 3,5-dimethoxy-4-hydroxy cinnamic acid (sinapinic acid), 2,5-dihydroxybenzoic acid (DHB), and alpha-cyano-4-hydroxycinnamic acid (CHCA). A solution containing the matrix and analyte is dried to a crystalline solid and then illuminated with a short pulse of ultraviolet laser light. Depending upon the sample identity and intensity of the laser pulse, various amounts of positive ions, negative ions, and neutral molecules are released from the surface. One major study in our laboratory involves investigation of the requirement of "matrix isolation" of the large analyte molecules during the crystallization step, including the effect of solvent, sample application method (i.e. air drying, drying under vacuum or heat, electrospraying), and addition of matrix modifiers on the distribution of analyte material in the crystal. Spectroscopic studies of the photodecomposition of the matrix molecules, and determination of the fragments present and their velocity distribution in the plume give information about the desorption event. Studies of the ions observed under various experimental conditions, particularly when ionization "additives" are employed, yields information about the ionization process. Our studies of the basic mechanisms of the MALDI process have enabled us to extend the applicability of the technique to sample chemistries spanning the range from highly non-polar materials (perfluoropolyethers, polydimethylsiloxanes) to moderately polar materials (polyethylene glycols, polyvinylalcohols). We are also making progress in the MALDI analysis of unique co-polymer materials with interesting surfactant properties.

​

TOFMS Instrument Development

The time-of-flight mass spectrometer (TOFMS) has several attractive characteristics, including an unlimited mass range and the ability to acquire a complete mass spectrum from each ionization event. In our work, ion optical modeling (used to calculate ion trajectories) and ion temporal peak shape calculations (based on Monte Carlo techniques) are employed to design instruments with improved sensitivity, mass resolution, or both. We have designed and constructed a pulsed electron-impact ion source as well as a novel scintillator based detector that shows improved sensitivity over conventional tandem microchannel plate based detectors for high mass ions. Further, by changing the experimental conditions (e.g., the position of ionization, time of ionization, initial velocity of the desorbed molecule, etc.) for the Monte Carlo simulations, we have gained some insight into the mechanism of the matrix-assisted laser desorption/ionization (MALDI) process.

​

Chemometrics

Coupling of a mass spectrometer with one of a variety of sample separation methods (such as gas chromatography, high performance liquid chromatography or capillary zone electrophoresis) is extremely attractive. One problem with this approach, however, is the fact that copious amounts of data are produced during the chromatographic run. Correlation analysis techniques (from information theory) are being explored to both enhance the qualitative and quantitative information present in the collected mass spectrum, and also to aid the analyst by automating the spectral interpretation process. A new and particularly promising area of work is a combination of correlation analysis with a genetric algorithm for the analysis of product ion spectra obtained from combined LC/MS/MS runs of compounds of both pharmaceutical and environmental interest.

​

Collaborative Projects

A long-standing collaboration involves Dr. Nick Cernansky and Dr. David Miller in the Department of Mechanical Engineering and Mechanics at Drexel University. The work generally involves the development of laser diagnostic methods for use in combustion chemistry research. Laser and associated analysis equipment in the combustion research laboratory, located in the Hess Building, have been used in laser induced fluorescence, degenerate four-wave mixing, cavity ring-down laser absorption spectroscopy, and most recently cavity-enhanced magneto-optic rotation spectroscopy.

​