Charles N. McEwen PhD

Charles N. McEwen PhD

Houghton Endowed Chairholder in Chemistry and Biochemistry

Professor of Chemistry


BS (The College of William and Mary)

MS (Atlanta University)

PhD (University of Virgina)

Research Interests

Development of new and improved techniques in mass spectrometry, including atmospheric pressure ionization (API) and matrix-assisted laser desorption/ionization (MALDI), as applied to drug discovery, metabolomics and small molecule analysis.

The immediate goal of the research program is to develop new ionization methods and integrate them into commercial atmospheric pressure (AP) ion sources making them capable of nearly universal ionization. We expect to develop an ion source that allows high throughput analysis and LC/MS of nonvolatile compounds such as peptides and carbohydrates as well as non-polar compounds such as pesticides and polynuclear aromatic hydrocarbons. These new methods will be applied not only to demonstrate their utility but to solve important biological and chemical problems.
See attachment one for a picture and attachment two for a schematic of an auto ASAP source capable of high throughput analysis and providing a new LC/MS method.
Scientific advances are often led by improvements in measurement techniques. Outstanding examples are the introduction of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) techniques which propelled mass spectrometry (MS) deeper into the arena of biological materials analysis and spawned the fields of ‘omics’ analysis (e.g. proteomics, metabolomics, and lipidomics). These ionization methods led to a paradigm shift in mass measurement and the awarding of the 2002 Nobel Prize in chemistry to the inventors. Prior to the development of ESI, almost all existing MS instruments involved vacuum ion sources. The capability of ESI to ionize polar and high-mass compounds from a liquid stream at atmospheric pressure resulted in the widespread use of liquid chromatography (LC) MS instruments using AP ionization. So complete has been the transformation that many laboratories no longer have traditional instrumentation with vacuum sources such as electron impact (EI) and chemical ionization (CI); methods that work well with low polarity vaporizable compounds.
API-MS instruments, however, were unable to analyze low polarity compounds with good sensitivity, and sometimes not at all. This problem becomes especially apparent when a sample that gives a major peak in LC by UV detection is not observed by MS. Even more daunting are examples where a compound is not detected and it is not known that the compound is present in the sample; an example being a drug contaminant. This shortcoming of API-MS instruments is the result of the failure of ESI and the complementary technique atmospheric pressure chemical ionization (APCI) to ionize with acceptable sensitivity many low polarity compounds. We have addressed this issue by developing GC/API-MS techniques as well as an atmospheric solids analysis probe (ASAP) MS method for the analysis of virtually all vaporizable compounds using commercial API-MS instruments. (1,5,6) The ASAP method is a fast direct method that can be used to rapidly analyze a variety of materials as shown for melamine (see attachment 3) which has been in the news because of adulteration of animal food and more recently baby formula. The ASAP method can be used to detect melamine down to low ppb levels in seconds on a high resolution mass spectrometer without sample cleanup or time consuming separation.
MALDI based MS instruments are also prevalent in biological and polymer laboratories and have the potential for high-throughput analyses. The problematic step has been sample preparation and we recently developed a method that overcomes this limitation for low-mass compounds.(3,4) We also developed a modified MALDI method that we refer to as matrix ionization laser desorption (MILD) for the analysis of compounds previously problematic by standard MALDI analysis methods.(2) These techniques need to be refined and automated and will be part of the future research discussed above.



Dr. McEwen holds a PhD from the University of Virginia.  The immediate goal of his research program is to develop new ionization methods and integrate them into commercial atmospheric pressure (AP) ion sources making them capable of nearly universal ionization.

Selected Scholarly Activity

Trimpin, S.; Inutan, E. D.; Herath, T. N.; McEwen, C. N., Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Method for Selectively Producing Either Singly or Multiply Charged Molecular Ions. Anal. Chem. 2010, 82, 11-15.
Trimpin, S.; Inutan, E.D.;Herath, T.N. and McEwen, C.N. Laserspray ionization - A New AP-MALDI Method for Producing Highly Charged Gas-Phase Ions of Peptides and Proteins Directly from Solid Solutions, Mol. and Cell. Proteomics, 2009, M900527-MCP200.
McEwen, C. N.; Larsen, B. S “Ionization Mechanisms Related to Negative Ion APPI, APCI, and DART” J. Of The American Soc. For Mass Spectrometry 2009, 20, 1518-1521.
Lloyd, J. A.; Harron, A. F; McEwen, C. N. "Combination Atmospheric Pressure Solids Analysis Probe and Desorption Electrospray Ionization Mass Spectrometry Ion Source", Anal. Chem., 2009, 81, 9158-9162.
Trimpin, S.; Wijerathne, K.; McEwen, C. N. “Rapid methods of polymer and polymer additives identification: Multi-sample solvent-free MALDI, pyrolysis at atmospheric pressure, and atmospheric solids analysis probe mass spectrometry” Analytica Chimica Acta 2009, 654, 20-25.
Ionkin, A. S.; Marshall, W. J.; Fish, B. M.; Schiffhauer, M. F.; Davidson, F. and McEwen, C. N. “Highly Unsaturated Phosphorus Compounds: Generation and Reactions on Both Multiple Bonds of Vinyl Phosphaalkyne" Organometallics, 2009, 28 , 2410-
McEwen, CN, GC/MS on an LC/MS instrument using atmospheric pressure photoionization, Int J Mass Spectrom, 259, 57-64, 2007.
Trimpin S, Clemmer DE, McEwen CN, Charge-remote fragmentation of lithiated fatty acids on a TOF-TOF instrument using matrix-ionization, J Am Soc Mass Spectrom, 18, 1967-1972, 2007.
Trimpin S, Weidner SM, Falkenhagen J, McEwen, CN, Fractionation and solvent-free MALDI-MS analysis of polymers using liquid adsorption chromatography at critical conditions in combination with a multisample on-target homogenization/transfer sample preparation method, Anal Chem, 79, 7565-7570, 2007.
Trimpin S, McEwen CN, Multisample preparation methods for the solvent-free MALDI-MS analysis of synthetic polymers, J Am Soc Mass Spectrom, 18, 377-381, 2007.
McEwen CN, McKay RG, Larsen BS, Analysis of solids, liquids, and biological tissues using solids probe introduction at atmospheric pressure on commercial LC/MS instruments ,Anal Chem, 77, 7826-7831, 2005.
McEwen CN, McKay RG , A combination atmospheric pressure LC/MS : GC/MS ion source: Advantages of dual AP-LC/MS : GC/MS instrumentation, J Am Soc Mass Spectrom, 16, 1730-1738, 2005.
Clements A, Johnston MV, Larsen BS, McEwen CN, Fluorescence-based peptide labeling and fractionation strategies for analysis of cysteine-containing peptides , Anal Chem, 77, 4495-4502, 2005.
Fagan PJ, Krusic PJ, McEwen CN, Production of perfluoroalkylated nanospheres from buckminsterfullerenes, Science, 262, 404-407, 1993.
McEwen CN, McKay RG, Larsen BS, C-60 as a radical sponge, J Am Chem Soc, 114, 4412-4414, 1992.
McEwen CN, Rudat MA, Radical trapping in a mass spectrometer ion source,1 , J Am Chem Soc, 103, 4343-4349, 1981.

Contact Information

Office location: Griffith Hall Room 325
Mailing address: Box 48
University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495
Office Phone: 215.596.8552

c [dot] mcewen [at] usciences [dot] edu