Study of spray ionization mechanisms and development of paper spray sampling ionization for direct analysis of biological samples

He Wang, Purdue University

Abstract

Mass spectrometry (MS) is a powerful tool for the analysis of biological samples. Different types of chemicals, such as therapeutic drugs, proteins, peptides, oligonucleotides, can be identified with high specificity and high sensitivity in a high-throughput manner. Sampling and ionization, the physical processes of converting the sample molecules into ions, is a key step for analyzing biological samples using mass spectrometry. The production of non-volatile intact ions using soft ionization techniques has significantly widened the scope of applying mass spectrometry in biological studies. Spray ionization is one of the most favorable soft ionization methods for biological sample analysis especially for biological macromolecules. However, conventional spray ionization methods suffer from the matrix effects. Salts and other contaminants in the samples can strongly inhibit the ionization efficiency of the targeting molecules, and sample extraction and separation are usually required before ionization and mass analysis are performed. The goal of the research is to develop and study new spray ionization methods to obtain the intact analyte ions from complex biological matrices without any sample preparation. Two problems need to be solved to achieve the goal: how to get intact ions with little fragmentations and how to overcome the matrix effects. Even though spray ionization techniques are generally regarded as soft ionization methods with little fragmentations produced, recently, a surprising phenomenon was found that under specific conditions, significant backbone fragmentation could be observed during nanoESI of peptides. Thus, it is interesting and helpful to study what factors are important to decide whether intact ions or fragmented ions will be produced during spray ionization. At the meantime, the conventional spray ionization methods are vulnerable to the matrix effects. Porous materials such as paper are proposed to be effective substrates for direct sampling and ionization of biological samples. By selecting the proper porous substrates and solvents, the extraction of targeting molecules is expected to be enhanced and the matrix effect could be reduced. Due to the simple setup and good sensitivity, the new ionization method, named as paper spray ionization, which could obtain the intact analyte ions directly from complex biological matrices, offers a great opportunity for point-of-care (POC) testing of biological samples using MS.

Degree

Ph.D.

Advisors

Ouyang, Purdue University.

Subject Area

Analytical chemistry|Biomedical engineering

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