Imaging without sputtering the matrix: how pre-treatment-free methods are lowering the barrier to entry for mass spectrometry imaging

Whether mass spectrometry imaging is user-friendly often depends not on how expensive the instrument is, but on ‘how much preparation is required before analysis’. Traditional imaging methods that require matrix spraying present a cumbersome pre-treatment hurdle; however, New Ceyuan’s MSI DPI and MSI LDPI both emphasise ‘no matrix spraying’ and ‘no matrix interference’, and are gradually lowering this barrier.

Traditional approach: first spray a layer of matrix

In matrix-assisted imaging, a uniform layer of small-molecule matrix must be sprayed onto the sample surface; the laser or energy then passes through the matrix to desorb and ionise the analytes. This process presents two challenges: firstly, ensuring uniform and optimised spraying is a technical challenge in itself; secondly, the matrix molecules themselves enter the mass spectrometer, causing background interference—particularly in the low-mass region of small molecules, where matrix peaks often ‘mask’ the desired signals.

Matrix-free approach: direct analysis

Xin Ceyuan’s two imaging sources take different approaches. The MSI DPI employs desorption electrospray coupled with photochemical secondary ionisation; it requires no matrix spraying, has low ion suppression effects, and allows complex samples to be analysed directly; The MSI LDPI utilises a combination of laser desorption and post-photochemical ionisation; similarly, it requires no matrix spraying, is free from matrix interference, and can detect compounds with a minimum charge-to-mass ratio as low as 70 (m/z), yielding exceptionally clean spectra in the low-mass region for small molecules.

What does levelling the playing field mean?

Firstly, there is the time factor. The elimination of pre-treatment removes the steps of spraying, optimisation and waiting, reducing sample preparation time from ‘at least half a day’ to ‘take and analyse immediately’—which is particularly crucial for high-throughput screening. Large batches of samples, such as traditional Chinese medicinal materials, blood, natural products and pharmaceuticals, can be processed much more quickly.

Secondly, there is information fidelity. Without matrix background, small molecules in the low-mass region are visible with greater clarity; as no chemical derivatisation or purification is required, the sample’s original spatial chemical information remains unaltered, resulting in a distribution that more closely reflects reality.

Thirdly, accessibility. The elimination of pre-treatment encourages more users outside the field of mass spectrometry to try imaging: quality control personnel in pharmaceutical companies, food inspectors and forensic investigators can obtain a reliable molecular spatial map without first having to become ‘spray experts’.

Viewed from an industrial perspective, ‘matrix-free’ imaging is, in fact, one of the key factors enabling imaging technology to transition from research to practical application. Only when a device requires no pre-treatment, is ready to use straight out of the box, and operates with long-term stability does it truly have the potential to move beyond research laboratories and into production lines and testing laboratories. Once the barriers to entry are lowered, the number of users will naturally increase.