Coated Blade Spray with a Barrier: Improving Negative Electrospray Ionization and Sample Preparation

Substrate-based electrospray ionization (ESI) techniques like paper, wooden tip, plastic tip, and metal-needle-based spray suffer from corona discharge, high background noise, and unstable spray in negative ionization mode, especially for the analysis of complex biological matrices, such as blood and urine. Coated blade spray coupled with mass spectrometry (CBS-MS) combines solid-phase microextraction's (SPME) efficient sample clean-up and enrichment and ambient MS's fast analysis and has proven to be an appealing alternative tool for the fast screening of target analytes in complex matrices. This paper documents the development of a new CBS blade design that features a barrier at the far end of the ESI tip. The findings of this work show that the addition of this simple barrier enabled the total RSD% to be reduced to less than 10% for sample preparation, ionization, and the MS detection of several drugs of abuse in negative mode, without compensation using internal standards. The improved stability of ESI in negative mode was investigated by observing the ESI process with a microscope camera and testing via CBS-MS. The new design was applied for the analysis of three drugs of abuse in urine, with the calibration curve correlation coefficient (R2 ≥ 0.9997) being calculated without the use of internal standards. The overall RSD% of the peak area for one compound in 42 samples was 6.9%, which highlights the method's incredible reproducibility compared to other ambient MS techniques for analyzing real samples. The CBS device with a barrier was also applied for the on-blade sampling of 14 drugs of abuse in 20 μL of plasma spot in positive ionization mode. The results of these tests yielded a calibration curve correlation coefficient of R2 ≥ 0.9883 and limits of quantification (LOQs) between 0.25 and 25 ng/mL. The obtained results provide guidance on CBS device design optimization and the effective automation of the protocol.