Ambient Ionization Mass Spectrometry Today and Tomorrow: Embracing Challenges and Opportunities

Abstract

Ambient ionization mass spectrometry (AIMS) has grown into a group of emerging analytical techniques that allow rapid, real-time, high-throughput, in situ, and in vivo analysis in many scientific fields including biomedicine, pharmaceuticals, and forensic sciences. While dozens of AIMS techniques have been introduced over the past two decades, their broad commercial and industrial use is still restricted by multiple challenges. In this Perspective, we discuss the most relevant technical challenges facing AIMS, i.e., reproducibility, quantitative ability, molecular coverage, sensitivity, and data complexity, and scientists' recent attempts to overcome these hurdles. Furthermore, we present future directions of AIMS from our perspective, including the necessity that efforts should be made to unravel blind biomolecules in routine analysis, the construction of a data depository for AIMS users, the full automation of pipelines for prospect integration in a robotic laboratory, the movement toward on-site tests, and the expansion of outreach to motivate government officials in policymaking. We anticipate that, with progress in these critical but immature areas, AIMS technology will keep evolving to become a more robust and user-friendly set of technologies and, consequently, be translated into everyday life practice.

Mass Spectrometry Analysis of Intact Proteins from Crude Samples

“…The screening of surfaces, as exemplified by the ambient ionization methods, is foreseen to be translated into benchtop analytical devices for on-site tests, such as intraoperative tumor margin assessment and environmental, forensics, and defense applications. 27 Moreover, given the promising results of MALDI and ambient MS methods, these methods are expected to be highly beneficial for the rapid identification of microorganisms, analysis of biofluids, and diagnostic studies. 26 Thus, a critical aspect in the coming years will be to keep evolving these approaches into a robust and user-friendly set of technologies.…”

Applications of direct analysis in real time mass spectrometry in food analysis: A review

“…DESI and DART are complementary techniques in terms of analyte polarity and mass range due to the differences in ionization processes. In DESI, electrospray droplets are employed for the ionization of analyte molecules, whereas in DART a gas‐phase plasma is used 8 . Due to the obviation of chromatographic separation and any solvents, DART‐MS is very well suited for the rapid and high‐throughput analysis of food samples in various applications.…”

Electrospray ionization rapid screening sans liquid chromatography column: A sensitive method for detection and quantification of chemicals in animal tissues and urine

“…2,11,12 However, ambient ionization methods have limitations, including (i) an inability to provide accurate quantitative data equivalent to LC/ESI-MS, (ii) a tendency to return false-positive and/or false-negative results, (iii) poor autosampling platforms relative to LC/MS, (iv) increased costs associated with technique-specific ionization sources, and (v) uncontained ionization of samples, which could lead to hazardous chemical exposures. 2,7,[13][14][15] Given the accurate quantitative ability of ESI-MS, but the ability of ambient techniques to reliably detect analytes in highly complex matrices, we hypothesized that ESI-MS could be used for rapid screening applications without prior LC separation of target analytes. To test this hypothesis, we investigated the detection and quantitation of several animal health compounds incurred into kidney, liver, lung, muscle and urine from cows, pigs and/or sheep using ESI-MS without prior chromatographic separation.…”

“…As a result, ambient ionization methods reduce the labor, cost and time of analysis 9,10 and are ideal for rapid screening (RS) or other qualitative or semi‐quantitative applications 2,11,12 . However, ambient ionization methods have limitations, including (i) an inability to provide accurate quantitative data equivalent to LC/ESI‐MS, (ii) a tendency to return false‐positive and/or false‐negative results, (iii) poor autosampling platforms relative to LC/MS, (iv) increased costs associated with technique‐specific ionization sources, and (v) uncontained ionization of samples, which could lead to hazardous chemical exposures 2,7,13–15 . Given the accurate quantitative ability of ESI‐MS, but the ability of ambient techniques to reliably detect analytes in highly complex matrices, we hypothesized that ESI‐MS could be used for rapid screening applications without prior LC separation of target analytes.…”