The objective is to solve the problem of transforming intact complex molecules of bio-medical interest into ions in vacuo ready for mass analysis. Methods now in use often require elaborate sample preparation and usually cause substantial, even catastrophic, decomposition. The present approach consists in electrospraying a solution of species to be analyzed into a bath gas such as nitrogen. The resulting gaseous dispersion of ions is expanded into vacuum as a small supersonic free jet of the kind widely used as molecular beam sources. The ions can then be analyzed by any common method of mass spectrometry. So far positive and/or negative ion mass spectra have been obtained for a variety of """"""""difficult"""""""" species including: amino acids, peptides, nucleic acids, sugars, vitamins and antibiotics. The spectra are clean with only two kinds of peaks: (1) cations or anions from the solution and (2) un-ionized solute species associated with a solute ion. The virtually complete absence of fragment peaks greatly simplifies interpretation of the spectra even though ions are sometimes solvated. Solute species peaks have been easily resolved with nanograms of solute in milligrams of solution. Indications are that further large increases of at least 103 in sensitivity should be achievable. We have recently resolved peaks containing as little as 10 pg of gramacidin-s. To develop this approach into a useful art will require elucidation of the electrospray process, an understanding of the role of solution chemistry in ion formation, and optimization of the ion optics along with the gas dynamic parameters. About two to three years of research will be needed to provide a firm foundation of knowledge and experience that will make possible the design and operation of useful ion sources. It should then be possible to carry out difficult analyses for those who might need them and to help others build and operate similar systems. In addition, it will be desirable to develop techniques for adapting this source to tandem mass spectrometry in order to take full advantage of its abilities. It seems likely that the proposed work will lead to an effective LC-MS interface, will substantially enhance MS-MS techniques and will open many avenues of progress in those aspects of research and clinical medicine that depend upon detailed, accurate and rapid analysis of materials comprising complex organic molecules.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Metallobiochemistry Study Section (BMT)
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Yale University
Schools of Arts and Sciences
New Haven
United States
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