A statistical approach to optimizing paper spray mass spectrometry parameters

Abstract

Rationale Paper spray mass spectrometry (PS‐MS) was used to analyze and quantify ampicillin, a hydrophilic compound and frequently utilized antibiotic. Hydrophilic molecules are difficult to analyze via PS‐MS due to their strong binding affinity to paper substrates and low ionization efficiency, among other reasons. Methods Solvent and paper parameters were optimized to increase the extraction of ampicillin from the paper substrate. After optimizing these key parameters, a Resolution IV 1/16 fractional factorial design with two center points was employed to screen eight different design parameters simultaneously. Results Pore size, sample volume, and solvent volume were the most significant factors affecting average peak area under the curve (AUC) and the signal‐to‐blank (S/B) ratio for the 1 μg/mL ampicillin calibrant. After optimizing the key parameters, a linear calibration curve with a range of 0.2 μg/mL to 100 μg/mL was generated (R2 = 0.98) and the limit of detection (LOD) and lower limit of quantification (LLOQ) were calculated to be 0.07 μg/mL and 0.25 μg/mL, respectively. Conclusions The statistical optimization procedure undertaken here increased the mass spectral signal intensity by more than a factor of 40. This statistical method of screening followed by optimization experiments proved faster and more efficient, and produced more drastic improvements than typical one‐factor‐at‐a‐time experiments.

Combining Mass Spectrometry of Picoliter Samples with a Multicompartment Electrodynamic Trap for Probing the Chemistry of Droplet Arrays

“…Papers were cut into triangular substrates with rounded lower corners using a universal laser cutter to create substrates with a base of 8 mm and height of 10 mm, leading to a spray tip angle of ∼45°. Other geometries and substrates were tested; however, a rigorous evaluation is not presented here, as other works have characterized the impact of the spray tip angle and substrates on PS-MS performance. − Paper substrates were mounted in a stainless steel alligator clip, and a voltage of −3 to −5 kV was applied to the solvent-soaked substrate. The solvent (either HPLC grade methanol or a methanol–chloroform mixture) was continuously supplied to the underside of the substrate with a PEEK delivery tube connected to a syringe pump operating at 20–30 μL min –1 .…”

Recent advances in on-site mass spectrometry analysis for clinical applications

“…This technology has advanced rapidly in the last decade and presented a huge implication on transferring MS technology to non-expert users, such as nurses and physicians for clinical and POC disease diagnosis. For instance, towards rapid quantitative analysis, a series of direct sampling methods have been developed [ [16] , [17] , [18] ], including paper spray (PS) [ 19 , 20 ], extraction spray [ 21 ], and slug flow microextraction [ 22 ]. For instance, paper spray has shown a good performance in analysis of therapeutic drug monitoring, especially for those in whole bloods [ 23 ], dry blood spots [ 24 ], and urines [ 25 ].…”

Build, Share and Remix: 3D Printing for Speeding Up the Innovation Cycles in Ambient Ionisation Mass Spectrometry (AIMS)

“…Although several commercial platforms are available, PSI is actively investigated by academic groups which build their own prototypes. The critical parameters for PSI systems are the geometry, the tip, the type of paper, and the used solvent system [66]. Off-the-shelf PSI cartridges provide paper support and reservoirs for ensuring a continuous solvent flow [67].…”