Ion suppression: Why does the signal from ‘the same substance’ fluctuate between high and low levels in different samples?
2026-07-10 139
Ion suppression is a typical type of matrix effect in mass spectrometry (particularly in electrospray ionisation LC-MS and ambient pressure imaging): matrix components that elute simultaneously with or co-exist alongside the target compound compete for ionisation resources, causing a reduction in the ion signal intensity of the target analyte. In chemical analysis, the term ‘matrix’ refers to the components in a sample other than the analyte; the influence of these components on the analytical results is collectively termed the matrix effect. When the matrix effect causes the signal to be lower than that of a matrix-free standard, this is termed suppression (Wikipedia: Matrix (chemical analysis); IUPAC Gold Book: Matrix effect, M03759).
How to quantify ion suppression
Matrix effects are commonly quantified as follows: by measuring the peak areas of the analyte at the same concentration in both a ‘matrix-containing extract’ and a ‘matrix-free standard solution’; a ratio close to 100 indicates no significant matrix effect; a ratio less than 100 indicates suppression, whilst a ratio greater than 100 indicates enhancement (Wikipedia: Matrix (chemical analysis)).
What causes ion suppression?
In liquid-phase ionisation techniques such as electrospray ionisation (ESI), the surface charge and nucleation sites of the droplets are limited; co-eluting salts, lipids and endogenous substances compete with the target compound for charge and surface space, leading to a reduction in the ionisation efficiency of the target compound. In mass spectrometry imaging, the high-salt environment on the surface of biological tissue sections can also cause ion suppression; more critically, the primary ionisation efficiency in conventional imaging is less than 1/1000—the vast majority of desorbed molecules remain in a neutral state, and only a very small fraction are ‘captured’ by primary ionisation (Pan Yang’s research group at the University of Science and Technology of China; see t-AP-LDI/PI work). The combination of these two factors results in the imaging signals of many molecules being severely underestimated.
Common approaches
Sample pretreatment and purification: Removal of interferents such as salts and lipids to reduce matrix loading.
Chromatographic separation: Widening the elution windows between target compounds and interferents to reduce competition for co-ionisation.
Internal Standards and Isotope Dilution: Correct signal deviations caused by the matrix using isotope-labelled internal standards.
Matrix-matched calibration / Standard addition method: Establish a calibration curve using standard samples with a matrix similar to the sample to offset systematic errors.
How post-photoionisation circumvents ion suppression
Neo Source INSTRUMENT’s MSI DPI (DESI+PI) and MSI LDPI (LDI+PI) incorporate a ‘post-photoionisation’ step following primary desorption and ionisation: the desorbed neutral molecules are ionised by a beam of vacuum ultraviolet photons. As this step does not come into direct contact with the sample itself or the salt matrix, it circumvents charge competition and ion suppression during primary desorption and ionisation, thereby recovering the missed neutral molecules as signals. The t-AP-LDI/PI method developed by the research group led by Pan Yang and Liu Chengyuan at the University of Science and Technology of China (Analytical Chemistry 2024, DOI:10.1021/acs.analchem.3c05605) improves the sensitivity of histamine, cholesterol and various lipids by 2–3 orders of magnitude at a resolution of 4 μm; the principle lies precisely in this. This approach is similar to the two imaging ion source technologies developed by New Ceyuan. Both sources can be fitted to mass spectrometers from Agilent, AB SCIEX and Thermo.
References
Wikipedia: Matrix (chemical analysis). https://en.wikipedia.org/wiki/Matrix_(chemical_analysis)
IUPAC Gold Book: Matrix effect. https://goldbook.iupac.org/terms/view/M03759
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