Key technological breakthrough achieved in domestically produced mass spectrometry imaging sources: signal sensitivity improved by 1–3 orders of magnitude, breaking the reliance on imported equipment

Hefei Xinceyuan Instrument Technology Co., Ltd. recently announced that its independently developed MSI DPI electrospray/photochemical ionisation mass spectrometry imaging sources and MSI LDPI laser/photochemical ionisation mass spectrometry imaging sources have been commercialised and launched onto the market. Both mass spectrometry imaging ion sources are based on post-photoionisation technology, which recovers neutral molecules—over 99.9 per cent of which are typically wasted in conventional mass spectrometry imaging—as detectable ions. This enhances the overall metabolite signal intensity by 1–3 orders of magnitude, enabling fully polar, non-discriminatory molecular spatial imaging. The commercialisation of this technology marks a significant breakthrough in core technologies for domestically produced mass spectrometry imaging sources.

Technical bottleneck: the ‘one-thousandth dilemma’ of traditional mass spectrometry imaging ion sources

Mass spectrometry imaging technology, which obtains spatial distribution information of molecules by scanning the sample surface point by point, has been widely applied in fields such as pathological diagnosis, drug development and plant metabolism. However, traditional mass spectrometry imaging ion sources have long faced a fundamental bottleneck: extremely low ionisation efficiency.

Whether based on desorption electrospray ionisation (DESI) or laser desorption ionisation (LDI), the ionisation efficiency of imaging sources remains below one thousandth. This means that although over 99.9 per cent of the analytes are successfully desorbed from the tissue surface, they cannot be detected by the mass spectrometer because they fail to acquire a charge—resulting in a vast amount of molecular information being wasted during the ionisation stage.

Low ionisation efficiency gives rise to a cascade of problems. Highly polar molecules (such as choline and phosphocholine) are easily ionised, whilst weakly polar and non-polar molecules (such as cholesterol, triglycerides and steroid compounds) are virtually undetectable, resulting in severe ‘polarity bias’. At the same time, high-concentration components in complex biological samples produce an ion suppression effect, which suppresses the signals of low-concentration components, forcing researchers to carry out cumbersome sample preparation procedures.

A breakthrough in principle: Post-photoionisation recovers ‘invisible’ molecules

Building on the academic achievements of Professor Pan Yang’s research group at the University of Science and Technology of China, the R&D team at Hefei Xinceyuan has successfully commercialised post-photoionisation technology.

The core principle of post-photoionisation is straightforward: a vacuum ultraviolet (VUV) photochemical ionisation system (a Kr lamp emitting photons at 10.0 eV and 10.6 eV) is installed downstream of the conventional desorption-ionisation zone. When neutral molecules that have not undergone primary ionisation pass through the photoionisation zone, the VUV photons ionise them into secondary ions, which are subsequently detected by the mass spectrometer.

The energy of the VUV photons (10–10.6 eV) is sufficient to ionise the vast majority of organic compounds—whose ionisation energies typically range between 7 and 10 eV—whilst avoiding excessive fragmentation of the molecules, thereby preserving molecular weight integrity. As the ionisation process between photons and neutral molecules is independent of molecular polarity, non-polar and polar molecules are afforded equal opportunities for ionisation, thereby eliminating polarity discrimination.

Two products catering to different spatial resolution requirements

Based on post-photoionisation technology, Hefei Xinceyuan has launched two mass spectrometry imaging source products, each designed for different desorption methods and spatial resolution requirements.

The MSI DPI electrospray/photochemical ionisation mass spectrometry imaging source employs a dual-ionisation architecture combining DESI with photochemical secondary ionisation. DESI spray desorbs molecules from the tissue surface, whilst the post-photoionisation device performs secondary ionisation on neutral molecules. Spatial resolution ranges from 20 to 200 μm and can be adjusted as required. This product is compatible with the three major mass spectrometry brands: Agilent (MSI DPI-25A), AB SCIEX (MSI DPI-25S) and Thermo (MSI DPI-25T). By switching the photoionisation source, users can obtain imaging data in both DESI mode and DESI/PI mode on the same sample.

The MSI LDPI laser/photochemical ionisation mass spectrometry imaging source employs a technical architecture combining transmission laser desorption (t-AP-LDI) with post-photochemical ionisation, representing a globally pioneering patented technology. A 355 nm laser is transmitted through the sample from the rear, achieving micron-scale ablation at the interface between the substrate and the sample, with a spatial resolution of 2–3 μm. The introduction of post-photoionisation compensates for the loss of sensitivity caused by reduced substance concentration per pixel in high-resolution imaging, thereby resolving the conflict between micrometre-level resolution and high sensitivity. This product requires no matrix coating, thereby avoiding the matrix background interference associated with MALDI technology, and can detect compounds with a charge-to-mass ratio as low as m/z 70.

Experimental validation: supported by multiple high-impact publications

The technical principles underlying these two mass spectrometry imaging ion source products have been validated through numerous academic studies, with the relevant findings published in renowned journals in the field of analytical chemistry.

In 2019, the DESI/PI mass spectrometry imaging method was published in *Analytical Chemistry* (91, 6616), where cholesterol and more than a dozen neutral GalCer lipids were spatially localised in mouse brain tissue for the first time—these non-polar molecules are completely invisible in conventional DESI.

In 2022, the results of optimisations to the DESI/PI method were published in *Analytical Chemistry* (94, 15108). In tea leaf imprint imaging, the theanine signal was enhanced by a factor of 14.5 and the caffeine signal by a factor of 61, whilst over a hundred new secondary metabolites—including amino acids, catechins and flavonoids—were detected.

In 2024, the t-AP-LDI/PI method was published as a cover article in *Analytical Chemistry* (96, 14). Subregions of mouse hippocampal tissue, such as the dentate gyrus, superior colliculus and hippocampal horns, were clearly resolved at a resolution of 4 μm, whilst the detection sensitivity for various metabolites—including histamine, adenosine, choline, cholesterol and glutamate—was improved by 2–3 orders of magnitude.

Furthermore, the DESI/PI mass spectrometry imaging source has been utilised in pathological studies of melanocytic nevi (*Talanta*, 2021, 231, 122380), spatial toxicity studies of tomato contaminants (*Environmental Science & Technology*, 2024, 58), and investigations into the causes of cinnabar spots on the traditional Chinese medicine Atractylodes macrocephala (*Molecular Horticulture*, 2025, 5:11).

Significance of domestic production: From core technology to product commercialisation

Currently, commercial mass spectrometry imaging sources on the international market are primarily reliant on imports and suffer from fundamental limitations such as polarity bias and ion suppression. The two mass spectrometry imaging sources launched by Hefei Xinceyuan—the MSI DPI and MSI LDPI—have been independently developed from core design to key components, thereby breaking through the technical barriers associated with imported mass spectrometry imaging ion sources.

The compatibility design of both products reduces system implementation costs for users. Laboratories already equipped with Agilent, AB SCIEX or Thermo mass spectrometers can acquire mass spectrometry imaging capabilities simply by retrofitting an MSI DPI or MSI LDPI imaging source, without the need to purchase a complete mass spectrometry imaging system. This ‘retrofit upgrade’ model significantly lowers the barrier to entry for mass spectrometry imaging technology.

Hefei Xinceyuan Instrument Technology Co., Ltd. has stated that the company will continue to advance the research, development and upgrading of mass spectrometry imaging and in-situ online mass spectrometry technologies, focusing on addressing the ‘bottleneck’ issues in domestically produced mass spectrometers, and utilising independently controlled core technologies to support the high-quality development of domestic scientific research and industry.

About Hefei Xinceyuan Instrument Technology Co., Ltd.

Hefei Xinceyuan Instrument Technology Co., Ltd. was established in 2026. Focusing on the field of mass spectrometers and ancillary equipment, the company integrates research and development, production, sales and technical services, and is committed to providing specialised, customised mass spectrometry testing solutions for various industries. 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.