Industry Insights into Mass Spectrometry Imaging: Post-Photoionisation Technology is Reshaping the Detection Logic of Molecular Spatial Analysis

Since its inception, mass spectrometry imaging has been at the forefront of molecular spatial analysis. From MALDI to DESI, and from ambient-pressure imaging to vacuum imaging, each technological iteration has pushed the boundaries of our ability to “see where molecules are”. However, a long-overlooked fundamental issue persists: the efficiency of traditional ionisation methods is less than one-thousandth, meaning that over 99.9 per cent of molecular information is lost during the ionisation process.

The emergence of post-electron ionisation technology is fundamentally changing this situation. Hefei Xinceyuan Instrument Technology Co., Ltd. has launched two mass spectrometry imaging sources, the MSI DPI and MSI LDPI, commercialising this technology that originated in the laboratories of the University of Science and Technology of China and introducing a new detection logic to the mass spectrometry imaging industry.

Industry Status: Polarity Discrimination Limits Application Depth

In the current mass spectrometry imaging market, DESI (Desorption Electrospray Ionisation) and MALDI (Matrix-Assisted Laser Desorption/Ionisation) are the two mainstream ionisation methods, corresponding to different mass spectrometry imaging ion source products.

The advantage of DESI mass spectrometry imaging ion sources lies in their ability to operate at atmospheric pressure without the need for matrix spraying; however, they are limited by the polarity dependence inherent in the electrospray mechanism—highly polar molecules are easily ionised and detected, whilst weakly polar and non-polar molecules remain virtually undetectable. This ‘polarity bias’ results in mass spectrometry imaging data being systematically skewed towards polar components, leading to the omission of a large number of important non-polar molecules (such as cholesterol, triglycerides and steroid compounds).

Although MALDI mass spectrometry imaging ion sources offer a broader coverage range, they require matrix spraying; matrix molecules generate significant background signals in the low-mass range (m/z < 500), severely interfering with the detection of small-molecule metabolites. Furthermore, the uniformity of matrix spraying affects imaging reproducibility, and the sample preparation process is complex.

Both technologies also face a common efficiency bottleneck: ionisation efficiency is less than one thousandth. This means that, regardless of the desorption method used, over 99.9 per cent of the analytes desorb from the tissue surface as neutral molecules and dissipate, failing to enter the mass spectrometer for detection.

The industry requires a technical solution capable of simultaneously addressing the three issues of polarity discrimination, matrix interference and low ionisation efficiency.

Technical variable: Post-photodissociation alters the ionisation logic

The core logic of post-photodissociation technology is to add a step of photochemical secondary ionisation following conventional ionisation.

The operating principle of conventional mass spectrometry imaging is “detect what is ionised” — the mass spectrometer detects only as much signal as the number of ions produced by primary ionisation; an efficiency of 1/1000 implies a corresponding 1/1000 reduction in information.

Post-photoionisation changes this operating principle to “detect what is desorbed” — provided a molecule is successfully desorbed from the tissue surface, regardless of whether primary ionisation was successful, the VUV photons in the post-photoionisation unit will provide it with a second opportunity for ionisation. The energy of VUV photons (10–10.6 eV, Kr lamp) covers the ionisation energy range of the vast majority of organic compounds (7–10 eV), and does not exhibit selectivity based on molecular polarity; non-polar and polar molecules thus have an equal chance of ionisation.

The implications of this shift in logic are systemic:

Polarity discrimination is eliminated—non-polar molecules go from being ‘invisible’ to ‘visible’. Sensitivity increases by 1–3 orders of magnitude—neutral molecules that were previously wasted are recovered as detectable ions. The ion suppression effect is reduced—photons directly ionise neutral molecules, independent of charge competition. The trade-off between resolution and sensitivity is resolved—a reduction in substance concentration per pixel during high-resolution imaging no longer results in a loss of sensitivity.

Product variants: Two mass spectrometry imaging sources covering the full range of spatial scales

Hefei Xinceyuan has commercialised post-photoionisation technology into two mass spectrometry imaging ion sources, each corresponding to different desorption methods and spatial resolutions.

The MSI DPI electrospray/photochemical ionisation mass spectrometry imaging source utilises a DESI+ photochemical secondary ionisation architecture, with a spatial resolution of 20–200 μm. This mass spectrometry imaging source is compatible with the three major mass spectrometry brands—Agilent, AB SCIEX and Thermo—allowing laboratories with existing mass spectrometers to build a mass spectrometry imaging system simply by retrofitting the instrument. The product has been validated through imaging of various samples, including mouse brain tissue, tea leaves, sage, ginkgo, Atractylodes macrocephala and tomatoes; the relevant findings have been published in journals such as *Analytical Chemistry*, *Talanta*, *Environmental Science & Technology* and *Molecular Horticulture*.

The MSI LDPI laser/photochemical ionisation mass spectrometry imaging source employs a transmission-type laser desorption combined with post-photochemical ionisation architecture, offering a spatial resolution of 2–3 μm; this is a globally pioneering patented technology. This mass spectrometry imaging source requires no matrix spraying and is free from matrix background interference, capable of detecting compounds with a charge-to-mass ratio as low as m/z 70. In 4 μm resolution imaging of mouse hippocampal tissue, subregions such as the dentate gyrus, the arm of the superior colliculus and the hippocampal horn were clearly distinguishable. The findings of this technology were published as a cover article in *Analytical Chemistry* (2024, 96, 14).

Both products share the core technology of post-photoionisation; the difference lies in the “ the method of “first desorption” — electrospray offers broad coverage but limited precision, whilst laser desorption provides extremely high precision but a small desorption yield per cycle. The introduction of post-photoionisation effectively addresses the sensitivity issues caused by the low desorption yield of laser desorption, ensuring that micrometre-level resolution and high sensitivity are no longer mutually exclusive.

Market factors: Compatibility design lowers the barrier to adoption

The procurement cost of mass spectrometry imagers has long been a key factor limiting the widespread adoption of the technology. A complete imported mass spectrometry imaging system is prohibitively expensive; whilst many research laboratories and testing organisations have a need for mass spectrometry analysis, budget constraints prevent them from acquiring imaging capabilities.

The compatibility design of the MSI DPI offers an alternative approach. There is a considerable number of laboratories in China equipped with Agilent, AB SCIEX or Thermo mass spectrometers. By simply installing the MSI DPI imaging source, these laboratories can enable their existing mass spectrometers to perform mass spectrometry imaging—upgrading from a ‘mass spectrometer’ to a ‘mass spectrometry imager’—at a cost representing only a fraction of that required to purchase a complete imaging system.

This “add-on upgrade” model may alter the competitive landscape of the mass spectrometry imaging source market. Under the traditional model, users are required to purchase both the mass spectrometer and the imaging source simultaneously, resulting in significant overall investment and lengthy decision-making cycles. The MSI DPI add-on model lowers the decision-making threshold from “purchasing a complete system” to “installing a single component”, which is expected to accelerate the adoption of mass spectrometry imaging technology in more laboratories.

Application Variables: Expansion from Research to Industrial Testing Scenarios

The application scenarios for post-photoionisation mass spectrometry imaging sources are expanding from research laboratories to industrial testing.

In the field of traditional Chinese medicine, DESI/PI mass spectrometry imagers have revealed the chemical causes of cinnabar spots on Atractylodes macrocephala, providing spatial molecular evidence for the quality assessment and authenticity verification of traditional Chinese medicinal materials. In the field of environmental toxicology, mass spectrometry imagers have found that the concentration of pollutants at the margins of plant leaves is 2.3 times higher than in the central regions, revealing the spatial heterogeneity of plants’ responses to pollution. In the field of forensic science, mass spectrometry imaging ion sources can not only visualise the morphological characteristics of fingerprints but also detect chemical components such as cholesterol and squalene within them, thereby elevating fingerprints from ‘shape evidence’ to ‘chemical evidence’.

In the field of pathological diagnosis, the MSI LDPI mass spectrometry imager analysed the metabolic heterogeneity of melanoma tissue at a resolution of 2–3 μm; the differences in the spatial distribution of metabolites between tumour regions and normal tissue showed a high degree of correlation with H&E histological sectioning. This application highlights the potential value of mass spectrometry imagers in clinical molecular pathological diagnosis.

Hefei Xinceyuan stated that the company will continue to advance the validation and implementation of mass spectrometry imaging sources across a wider range of application scenarios, collaborating with research teams and testing institutions across various fields to drive the transformation of mass spectrometry imaging technology from a research tool to an industrial testing tool.

Industry Outlook

The impact of post-photoionisation technology on the mass spectrometry imaging industry is gradually becoming apparent. From a technical perspective, it resolves three core issues that have long constrained the application of mass spectrometry imaging: polarity discrimination, low ionisation efficiency and ion suppression; from a product perspective, compatibility design has lowered the barrier to adoption, whilst domestic, independently controlled production has reduced procurement and maintenance costs; from an application perspective, the ability to detect all polarities and the significant increase in sensitivity have expanded the scope of mass spectrometry imaging applications in fields such as traditional Chinese medicine, environmental toxicology, forensic science and pathological diagnosis.

As market promotion and application validation of the two mass spectrometry imaging ion source products—MSI DPI and MSI LDPI—continue to deepen, post-photoionisation technology is expected to become the next-generation technical standard in the field of mass spectrometry imaging sources, propelling the domestic mass spectrometry imaging instrument industry into a new stage of development.

About Hefei Xinceyuan Instrument Technology Co., Ltd.

Hefei Xinceyuan Instrument Technology Co., Ltd. was established in 2026 and specialises in the field of mass spectrometers and associated equipment, integrating research and development, production, sales and technical services. With independent control over core technologies as the foundation of its development, the company has established a comprehensive R&D and production system covering the entire supply chain, from core components to complete instruments. Its main products include the ProC series of online time-of-flight mass spectrometers, professional mass spectrometry analysis systems, and MSI DPI/LDPI mass spectrometry imaging sources.