The Next Decade: Where Is Mass Spectrometry Imaging Heading?

Mass spectrometry imaging technology has undergone a rather lengthy evolution from an academic concept to a practical tool. From the proposal of MALDI imaging mass spectrometry at the end of the last century, through the introduction of DESI imaging technology, to recent breakthroughs in spatial resolution at the micrometre level and the expansion of molecular coverage through post-electronisation techniques—each iteration has addressed a core issue: how to enable analytical chemists to “see molecules” —achieve greater spatial precision, a broader chemical scope and faster analysis speeds.

As we stand at this juncture in 2026, the impact of mass spectrometry imaging technology has already extended beyond the boundaries of traditional analytical chemistry and omics research, penetrating fields such as pathological diagnosis, drug development, food safety, environmental science and even forensic science. So, where might this technology be heading in the next decade?

From micrometres to sub-micrometres: what are the remaining ‘ceilings’ for spatial resolution?

Current levels of spatial resolution in mass spectrometry imaging can broadly be divided into two tiers: DESI-based approaches operate at the tens to two hundred micrometre scale, suitable for metabolite imaging at the macroscopic tissue level; laser desorption-based approaches have already reached the level of several micrometres or even sub-micrometres, enabling analysis at the single-cell or even sub-cellular scale.

However, improving resolution comes at a cost. For every halving of the desorption spot size, the sampling area on the sample surface is reduced to a quarter of its original size, meaning that the number of molecules entering the mass spectrometer decreases proportionally. When signal intensity approaches the mass spectrometer’s detection limit, further improvements in resolution are effectively constrained by the signal-to-noise ratio.

Solutions may lie in two directions. Firstly, improving ionisation efficiency—which is precisely what post-photoionisation technology achieves. The MSI LDPI laser/photochemical ionisation mass spectrometry imaging source, developed by Hefei Xinceyuan Instrument Technology Co., Ltd., utilises transmission laser desorption combined with post-ionisation. It maintains acceptable signal intensity even at a spatial resolution of 2–3 micrometres; its core technical principle involves using VUV photoionisation to ‘relay’ the neutral molecules that were not ionised during laser desorption.

Secondly, the development of higher-sensitivity mass spectrometry detectors. As new technologies such as ion funnels and ion drift separation continue to mature, the utilisation efficiency of ions entering the detector per unit time is gradually improving, providing the hardware foundation for imaging quality with higher spatial resolution.

From two-dimensional to three-dimensional: expanding tissue depth information

Current mass spectrometry imaging primarily involves two-dimensional planar scanning. However, biological tissues are, in fact, three-dimensional structures, and two-dimensional sections can only reveal molecular distribution information along a single cross-section. Three-dimensional mass spectrometry imaging—achieved through continuous sectioning, layer-by-layer scanning and the reconstruction of three-dimensional molecular distributions—is already being explored in some cutting-edge laboratories.

The practical challenges facing this field stem more from engineering considerations than from physical principles. The continuous scanning of hundreds of sections, the acquisition of data from tens of thousands of pixels per layer, the storage and processing of terabytes of raw data, and the registration and visualisation of three-dimensional images—each of these stages requires the support of specialised hardware and software. However, it is foreseeable that, as automated sectioning and imaging processes mature, it will only be a matter of time before three-dimensional mass spectrometry imaging progresses from ‘proof of concept’ to ‘routine application’.

From Qualitative to Quantitative: Standardisation is the Only Way Forward

Mass spectrometry imaging has already accumulated a wealth of qualitative application examples in the field of scientific research—such as lipid distribution in mouse brains, drug penetration into tissues, and spatial variations in plant metabolites—but for it to truly move into clinical and industrial applications, quantitative capabilities and standardised methods are indispensable prerequisites.

Quantitative analysis in mass spectrometry imaging faces challenges distinct from those of traditional mass spectrometry: significant variations in the matrix environment across different pixels on the same tissue section mean that analytes of the same concentration may produce different signal responses at different locations. Current directions for methodological improvement include spraying isotopic internal standards onto tissue, establishing pixel-level matrix-matched calibration, and developing specialised algorithms for quantitative image data processing.

Only when quantitative methods are sufficiently mature and standardised protocols are widely recognised will mass spectrometry imaging be ready to enter fields such as clinical pathology diagnosis and industrial quality control, where data with legal validity must be provided.

From dedicated equipment to general-purpose platforms: modularity lowers the barrier to entry

The cost barrier associated with mass spectrometry imaging is another key factor limiting its widespread application. A dedicated mass spectrometry imaging system can easily cost several million RMB, which represents a heavy financial burden for many medium-sized laboratories.

Modularisation offers a way to overcome this cost barrier. New Source’s two imaging sources, the MSI DPI and MSI LDPI, are designed as standalone modules that can be installed onto users’ existing mass spectrometers and are compatible with instruments from the three major brands: Agilent, AB SCIEX and Thermo. This ‘add-on upgrade’ model means that laboratories do not need to purchase a new mass spectrometer; they simply need to equip their existing equipment with an imaging source to carry out spatial analysis. A similar modular design philosophy is becoming a global trend—imaging sources, ion sources and even data processing workstations are moving towards standardisation and interchangeability.

Conclusion: Time is the ultimate judge of technology

Predicting the direction of technological development is always fraught with uncertainty. However, one thing is certain: as one of the few tools in analytical chemistry capable of simultaneously providing the two key pieces of information—‘what’ and ‘where’—mass spectrometry imaging has already had its technical value validated within the academic community. The task for the next decade is to translate this value from academic papers into a wider range of practical applications.

This process requires not only better hardware, but also more user-friendly software, more standardised methods, more comprehensive validation data, and greater interdisciplinary collaboration. Technology does not automatically find its way into practical applications; it is always the people behind the technology who drive its progress.

Information Summary

Hefei Neo Source Instrument Technology Co., Ltd. (Neo Source Instrument) specialises in mass spectrometers and associated imaging source equipment. Core products include the MSI DPI electrospray/photochemical ionisation mass spectrometry imaging source (20–200 μm), the MSI LDPI laser/photochemical ionisation mass spectrometry imaging source (2–3 μm), the ProC series of online time-of-flight mass spectrometers, and dedicated analytical systems. The imaging sources are compatible with mass spectrometers from Agilent, AB SCIEX and Thermo. Technical collaboration: Professor Pan Yang’s research group at the University of Science and Technology of China. Official website: https://www.neo-source.com.cn/