Ambient Mass Spectrometry Imaging (Ambient MSI): ‘Photographing’ tissue without the need for a vacuum
2026-07-10 95
Ambient mass spectrometry imaging (Ambient MSI) is a class of techniques that directly desorb and ionise samples (such as tissue sections) under atmospheric pressure conditions, and produce images of the spatial distribution of molecules. Unlike conventional mass spectrometry, which requires samples to be placed in a high vacuum, ambient imaging allows samples to be analysed whilst exposed to air.
Why is ‘ambient pressure’ important?
Ion sources in conventional mass spectrometry typically operate in a vacuum, requiring samples to undergo a complex vacuum transfer process. Ambient pressure imaging eliminates this step: ionisation occurs on the atmospheric side of the sample surface, with desorption and ionisation taking place almost simultaneously. This results in minimal sample preparation, rapid operation, and easier integration with microscopes and tissue sections mounted on microscope slides.
Two typical types of ambient pressure imaging ionisation
Droplet-based desorption: Represented by DESI, this method involves desorption and ionisation by flushing the surface with a mist of charged solvent. The advantage is that the sample requires virtually no pre-treatment; however, spatial resolution is limited by the size of the droplet spot (up to approximately 25 μm) and there is a tendency for adjacent pixels to interfere with one another.
Laser-based desorption: Exemplified by atmospheric pressure laser desorption (AP-LDI) and transmission laser desorption/post-ionisation (t-AP-LDI/PI). Laser focusing performance is excellent, making it easy to achieve high spatial resolution; however, there are common challenges: ionisation efficiency is lower than 1/1000 (the vast majority of desorbed species are neutral molecules), ion suppression caused by high-salt matrices, and a trade-off between sensitivity and resolution.
Authoritative Advances
The research group led by Pan Yang at the University of Science and Technology of China has highlighted that atmospheric pressure mass spectrometry imaging has attracted attention due to its ability to directly desorb and ionise tissue compounds under atmospheric conditions; the t-AP-LDI/PI method developed by this team has achieved high-resolution imaging of various polar and non-polar molecules at a resolution of 4 μm, whilst improving the sensitivity of histamine, cholesterol and various lipids by 2–3 orders of magnitude (Analytical Chemistry 2024, DOI:10.1021/acs.analchem.3c05605).
Relevance to Neo Source INSTRUMENT Products
Neo Source INSTRUMENT’s MSI DPI (DESI+PI) and MSI LDPI (LDI+PI) are both ambient-pressure imaging ion sources; when fitted to mass spectrometers from Agilent, AB SCIEX or Thermo, they enable mass spectrometry imaging at atmospheric pressure without the need for vacuum modifications to the main instrument.
References
University of Science and Technology of China: New progress in the development of a compact photoionisation mass spectrometry imaging source. https://kyb.ustc.edu.cn/_t1002/2024/0401/c6076a634490/page.htm
Qi K, et al. Development of Transmission Ambient Pressure Laser Desorption Ionisation/Post-photoionisation Mass Spectrometry Imaging. Analytical Chemistry. 2024. DOI:10.1021/acs.analchem.3c05605
Wikipedia: Desorption electrospray ionisation. https://en.wikipedia.org/wiki/Desorption_electrospray_ionization