Conspectus
Mass spectrometry
(MS) is one of the most widely used technologies
in the chemical sciences. With applications spanning the monitoring
of reaction products, the identification of disease biomarkers, and
the measurement of thermodynamic parameters and aspects of structural
biology, MS is well established as a universal analytical tool applicable
to small compounds as well as large molecular complexes. Regardless
of the application, the generation of gas-phase ions from neutral
compounds is a key step in any MS experiment. However, this ionization
step was for many years limited to high-energy approaches that required
gas-phase analytes and thus it was restricted to volatile samples.
Over the last few decades, new methodologies have been developed to
address this limitation and facilitate ionization of biological molecules.
Electrospray ionization (ESI) is the most broadly used of these methods,
as it facilitates the ionization of intact polar compounds from solution.
Twenty years ago, our group reported a new ionization method that
uses a charged solvent spray to impact a surface, generating ions
from objects rather than just solutions and doing so directly in the ambient environment with no vacuum
requirements and little to no sample preparation. This method was
termed desorption electrospray ionization (DESI), and it initiated
a new field that would come to be known as ambient mass spectrometry.
The simplicity and wide applicability of the DESI technologyand
the tens of ambient ionization methods developed subsequentlyrevolutionized
the MS analysis of complex materials for their organic components,
especially for in situ applications.
This Account
describes the history of DESI, starting with the development
of the technique from early electrosonic spray ionization (ESSI) experimental
observations as well as the studies leading to the understanding of
its mechanism as a “droplet pick-up” phenomenon involving
sequential events (i.e., thin film formation, solid–liquid
extraction, secondary droplet generation, and ESI-like ionization
from these droplets). We also overview the developments and applications
of the technology that have been demonstrated by our group during
the last two decades. In particular, we describe (i) the use of DESI
for tissue imaging, one of its more significant applications to date,
and its extension to intraoperative clinical diagnosis; (ii) the integration
of the technology with portable instrumentation for in situ analysis, especially when coupled with tandem mass spectrometry
(MS/MS); (iii) the use of DESI microdroplets as microvessels to accelerate
organic reactions by orders of magnitude compared to those in bulk
solution; and (iv) the combination of all these capabilities for automated
high-throughput experiments aimed at accelerating drug discovery.