Development, Characterization, and Application of Paper Spray Ionization

Abstract

Paper spray is developed as a direct sampling ionization method for mass spectrometric analysis of complex mixtures. Ions of analyte are generated by applying a high voltage to a paper triangle wetted with a small volume (<10 microL) of solution. Samples can be preloaded onto the paper, added with the wetting solution, or transferred from surfaces using the paper as a wipe. It is demonstrated that paper spray is applicable to the analysis of a wide variety of compounds, including small organic compounds, peptides, and proteins. Procedures are developed for analysis of dried biofluid spots and applied to therapeutic drug monitoring with whole blood samples and to illicit drug detection in raw urine samples. Limits of detection of 50 ng/mL (or 20 pg absolute) are achieved for atenolol in bovine blood. The combination of sample collection from surfaces and paper spray ionization also enables fast chemical screening at high sensitivity, for example 100 pg of heroin distributed on a surface and agrochemicals on fruit peels are detectable. Online derivatization with a preloaded reagent is demonstrated for analysis of cholesterol in human serum. The combination of paper spray with miniature mass spectrometers offers a powerful impetus to wide application of mass spectrometry in nonlaboratory environments.

Rapid measurement of tacrolimus in whole blood by paper spray-tandem mass spectrometry (PS-MS/MS)

“…Paper spray (PS) is a direct technique that generates gas phase analyte ions directly from dried blood spots (DBS) or other fluids without the need for complex sample pretreatment and chromatography (6,7). Sample extraction and ionization are all performed in automated fashion by the PS ion source directly from a paper substrate stored within a single-use cartridge ( Figure 1).…”

“…An appropriate solvent is applied to the rear of the paper so that it flows through the dried blood spot sample by capillary action. As the solvent wicks through the sample, soluble components are extracted into the solvent, leaving behind the bulk of proteins and lipids [6]. A high voltage (3-5 kV) is applied to the moist paper, and an electrospray is induced at the sharp tip of the triangular shaped paper in the cartridge, which is held stationary in front of the inlet to the MS. As solvent evaporates, gas phase ions of the analyte molecules are generated which can then be detected by MS. PS-MS/MS has been successfully used for quantitative analysis of xenobiotics (8)(9)(10)) and endogenous compounds (11) from whole blood.…”

Biogenic aldehyde determination by reactive paper spray ionization mass spectrometry

“…Ambient ionization [6][7][8][9][10][11][12][13][14] is a relatively recent approach to MS analysis which avoids chromatography and is characterized by the absence of any requirement for sample preparation. Paper spray ionization [15][16][17][18][19][20] is a particularly simple ambient ionization technique which can be employed to study reactions and identify intermediates as well as to measure trace constituents of complex mixtures. Like other spray ionization methods, paper spray is least successful for non-polar or weakly polar compounds.…”

Characterization and application of droplet spray ionization for real‐time reaction monitoring

“…[12] Additionally, novel ionization sources with readily simplicity, rapid establishment and low cost are continuously progressing, such as wooden tip electrospray [13] , aluminum foil [14] and bamboo pen nib spray. [15] However, they have such drawbacks as the unwanted contamination to the sample loaded on a substrate and the un-reusability of the source.Recently, droplet spray ionization (DSI), [16] a modified version based on replacing the paper substrate [17] with a microscope cover glass, was developed by our laboratory. It is achieved by using a corner of a microscope cover glass to load a sample solution and launch a charged droplet spray.…”

“…Recently, droplet spray ionization (DSI), [16] a modified version based on replacing the paper substrate [17] with a microscope cover glass, was developed by our laboratory. It is achieved by using a corner of a microscope cover glass to load a sample solution and launch a charged droplet spray.…”