Mass spectrometry imaging (MSI) has become a powerful
tool in diverse
fields, such as chemistry, physics, materials, and life science. Although
such research is getting more prevalent, it is limited by high-resolution
(HR) instrumental development. Recently, unceasing efforts have been
made toward taking spatial resolution from the microscale to nanoscale,
especially for near-field based techniques. These emerging and unique
features behind high-resolution mass spectrometry imaging (HR-MSI)
provide new possibilities in various aspects of biological researches.
Since many technological advances provided a forefront for HR-MSI,
compelling challenges including sensitivity, specificity, multimodal
imaging, data acquisition, and processing follow undoubtedly. Gratifyingly,
with attempts and experiences in the infancy, the emerging techniques
move toward much more mature to deal with underlying conundrums in
the future. Not only confined to commercial instruments, this perspective
highlights recent innovations covering all emerging HR-MSI (with spatial
resolution below 5 μm) techniques. Besides, vital limitations
and handicaps at this stage are presented while corresponding schemes
are proposed. This perspective also gives the authors’ personal
outlooks of developments and applications for HR-MSI in coming years.