Owens Research Group

Research Description

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

Matrix-Assisted Laser Desorption/Ionization TOFMS Analysis

  Many groups around the world are using the MALD/I 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 MALD/I 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, and trans-3-indole acrylic acid. 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 MALD/I 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 MALD/I 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 (MALD/I) process.

Chemometrics

Coupling of the time-of-flight 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 application of the technique for the analysis of daughter ion spectra obtained from combined LC/MS/MS runs of compounds of pharmaceutical 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.

Current Research Group Members

Dr. Rick Hock, Visiting Research Scientist

Mr. William Erb, Ph.D. student

Ms. Fang Li, part-time Ph.D. candidate

Ms. April Holcomb, Ph.D. candidate

Ms. Runbo Li, part-time Ph.D. student

Mr. Andrew Mahan, part-time Ph.D. candidate

Mr. James Rieben, Ph.D. candidate

 

Past Research Group Members

Dr. Kes Balasanmugam, (IBF, Inc., Wayne, NJ), Instructor Post-Doctoral Associate, B.S. University of Sri Lanka, Ph.D. University of Pittsburgh.

Dr. Richard King, (Merck Research Laboratories, West Point, PA), B.S. Syracuse University, Ph.D. Drexel University, "Laser Desorption/Laser Ionizatin Time-of-Flight Mass Spectrometry Instrument Design and Investigation of the Desorption and Ionization Mechanisms of Matrix-Assisted Laser Desorption/Ionization", July 1994.

Dr. Alex (Shang-Jih) Tsay (Mobil Research), Ph.D. Drexel University, "Developing and Using Degenerate Four-Wave Mixing Techniques as a Diagnostic Tool in Discharge and Combustion Research", March 1996.

Dr. Russell Hensel, (Johnson & Johnson, Inc., Raritan, NJ), B.S. West Chester University, Ph.D. Drexel University, "The Quantitative Aspects of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry", December 1996.

Dr. Yansan (Henry) Xiong, (Applications Scientist, MicroMass, Inc., Acton, MA, post-doctoral associate, University of Illinois at Chicago), B.S. Chemical Engineering, Central South University of Technology, People's Republic of China, Ph.D. Drexel University, "Mechanistic Investigation of the Cationization Process of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry", May 1997.

Dr. Robert Goldschmidt, (Scientist, US Dept of Agriculture, BHNRC FCL, Beltsville, MD, National Research Council Postdoctoral Fellow, National Institute of Standards and Technology, Gaithersburg, MD), B.A. University of Pennsylvania, Ph.D. Drexel University, "Some Quantitative Aspects of the Analysis of Synthetic Polymers by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry", July 1998.

Dr. Cynthia Chavez-Eng, (Merck Research Labs, West Point, PA), Ph.D. Drexel University, "Quantitative Aspects of Matrix-Assisted Laser Desorption/Ionization using Electrospray Deposition", March 2002.

Dr. Andrew Hoteling, (Eastman Kodak Company, Rochester, NY), Ph.D. Drexel University, "MALDI TOF PSD and CID: Understanding Precision, Resolution and Mass Accuracy and MALDI TOFMS: Investigation of Discrimination Issues Related to Solubility", June 2004.

Dr. David Lenhert, (National Research Council Postdoctoral Fellow, National Institute of Standards and Technology, Gaithersburg, MD), Ph.D. Drexel University, Department of Mechanical Engineering & Mechanics, December 2004.

 

Ms. Jennifer Zheng, (Rhone-Poulenc Rorer, Inc., Collegeville, PA), Master's candidate, B.A. Earlham College, M.S. Drexel University, 6/91.

Mrs. Laura Mulderig (nee Major), (MicroMass, Inc., Acton, MA), B.A. Johns Hopkins University, M.S. Drexel University, 6/93.

Ms. Laura El Musa, B.A. Catholic University of Puerto Rico, M.S. Drexel University, 6/92.

Mr. JoonBae Lee, M.S. Drexel University, 6/95.

Ms. Limin Zhu, (Merck Research Laboratories, West Point, PA), M.S. Drexel University, 6/98.

Ms. Sun (Cindy) Tong, (Mutual Pharmaceutical, Philadelphia, PA), M.S. Drexel University, 3/99.

Ms. Theresa Huh, M.S. Drexel University, 6/00.

Ms. Guangji Shi, M.S. Drexel University, 9/01.

Mr. Edward Palmer, part-time Ph.D. candidate.

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Last modified August 10, 2005

Copyright © 2001-2005 by Kevin G. Owens, All Rights Reserved.

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