Analysis of Biological Samples Using Paper Spray Mass Spectrometry: An Investigation of Impacts by the Substrates, Solvents and Elution Methods

Abstract

Paper spray has been developed as a fast sampling ionization method for direct analysis of raw biological and chemical samples using mass spectrometry (MS). Quantitation of therapeutic drugs in blood samples at high accuracy has also been achieved using paper spray MS without traditional sample preparation or chromatographic separation. The paper spray ionization is a process integrated with a fast extraction of the analyte from the raw sample by a solvent, the transport of the extracted analytes on the paper, and a spray ionization at the tip of the paper substrate with a high voltage applied. In this study, the influence on the analytical performance by the solvent-substrate systems and the selection of the elution methods was investigated. The protein hemoglobin could be observed from fresh blood samples on silanized paper or from dried blood spots on silica-coated paper. The on-paper separation of the chemicals during the paper spray was characterized through the analysis of a mixture of the methyl violet 2B and methylene blue. The mode of applying the spray solvent was found to have a significant impact on the separation. The results in this study led to a better understanding of the analyte elution, on-paper separation, as well as the ionization processes of the paper spray. This study also help to establish a guideline for optimizing the analytical performance of paper spray for direct analysis of target analytes using mass spectrometry.

Analysis of Biofluids by Paper Spray MS: Advances and Challenges

“…As such, there has been interest in developing paper spray MS methods for the detection of biomolecules in a variety of matrices. In studies involving wet or dried blood spots the heme [6] group and the protein hemoglobin have been identified [26]. Peptides such as bradykinin 2-9 [12] or angiotensin I [1] have been analyzed from neat solvents.…”

Ionization Suppression and Recovery in Direct Biofluid Analysis Using Paper Spray Mass Spectrometry

“…After the solvent has wicked to the tip of the paper (typically within seconds), electrospray ionization is induced at the sharp tip of the wet paper via the application of a high voltage. Analytes are typically detected immediately, although separation effects have been reported in some cases [35,36]. Analyte signal can last for several minutes, allowing multiple analytes to be analyzed by MS n .…”

Clinical Application of Ambient Ionization Mass Spectrometry

“…e effects of paper geometry, structure and materials have also been extensively investigated to improve the PSI-MS performance. 66,[68][69][70][71][72][73][74][75] It is relatively di cult for direct AIMS methods to obtain accurate quantitative analysis. is is usually carried out by spiking a known quantity of isotopically labeled standard.…”

“…An investigation of the impacts to PSI-MS performance by the substrates, solvents and elution methods were reported by Ren et al 72) A higher voltage (±3.5 kV) is usually applied to PSI-MS. Espy et al have particularly focused on the voltage applied for spraying and the correct positioning of the paper tip in front of the inlet of the MS spectrometer. 78) In addition, the angle of the paper tip also plays a key role in the generation of the spray.…”