Direct Mass Spectrometry Analysis of Complex Mixtures by Nanoelectrospray with Simultaneous Atmospheric Pressure Chemical Ionization and Electrophoretic Separation Capabilities

Abstract

Accuracy and rapid analysis of complex microsamples are challenging tasks in translational research. Nano-electrospray ionization (nESI) is the method of choice for analyzing small sample volumes by mass spectrometry (MS) but this technique works well only for polar analytes. Herein we describe a versatile dual non-contact nESI/nAPCI (nano-atmospheric pressure chemical ionization) source that allows simultaneous detection of both polar and nonpolar analytes in microliter quantities of samples under ambient conditions and without pre-treatment. The same device can be activated to enable electrophoretic separation. The non-contact nESI/nAPCI MS platform was applied to analyze different samples, including high sensitive direct analysis of biofluids and the efficient detection of proteins in buffers with high concentration of nonvolatile salts. Excellent linearity, accuracy and limits of detection were achieved for compounds with different chemical properties in different matrices. The high sensitivity, universality, simplicity and ease of operation make this MS technique promising for use in clinical and forensic applications.

Nested-channel for on-demand alternation between electrospray ionization regimes

“…It is worth noting that the ion source alternate into the sub-channel regime solely due to the variation of liquid meniscus, while the plasma and electric field were kept constant. Separation caused by electric field changes 30,38 was not observed in the experiments of this work.…”

“…† The plasma source was 4–9 cm away from the ESI plume and did not produce APCI type ions. 30 Both regimes ionized compounds to the same types of typical ESI ions (Table S1 † ), suggesting that charged droplets play a major role in the sub-channel regime.…”

An integrated electrocatalytic nESI-MS platform for quantification of fatty acid isomers directly from untreated biofluids

“…The reactive nature of the current nESI MS platform utilizing the Ir electrode means that information on the original chemical content of the analyte solution can be lost. To address this issue, we employed the non-contact nESI method 34 recently developed in our laboratory to provide "native-state" mass spectra without oxidation. This nESI setup enables electrospray without physical contact between the reactive metal electrode and analyte solution.…”

“…As an application, we used the developed electrocatalytic nESI-MS platform to analyze FFAs in complex biouid. An established protocol exists to extract FFAs from biouid before MS analysis, 34,36 but we sought to develop a two-tiered integrated system where we not only perform in situ catalytic epoxidation, but also enable in-capillary liquid/liquid extraction prior to MS analysis. Therefore, we proposed the integrated experimental process illustrated in Fig.…”

A:Recent advances in ambient electrospray ionization technologies

“…This process is repeated until singularly charged analyte molecules are formed, which enter the MS [Amer et al, 2019]. This process is depicted in compounds without any sample pretreatment [Kulyk et al, 2019]. The method was successfully applied on bio-fluids and proteins in high buffer concentrations, proving the possible applications in clinical and forensic settings.…”