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Laser Desorption and Ionisation (LDI) and Matrix-Assisted Laser Desorption (MALDI): How lasers ‘illuminate’ macromolecules

2026-07-10 103

Laser desorption ionisation (LDI) is a technique that utilises the energy of a pulsed laser to desorb and ionise sample molecules from a surface. Matrix-Assisted Laser Desorption/Ionisation (MALDI) is the most commonly used form of LDI: a ‘matrix’ that strongly absorbs laser energy is mixed with the sample; the matrix absorbs the laser, causing the analyte to be desorbed and ionised along with it.

Basic Principles

MALDI involves three steps: mixing the sample with the matrix and depositing it onto a metal target; irradiating it with a pulsed laser to trigger the desorption and ablation of the sample and matrix; and, whilst the analytes are within the thermal plume generated by ablation, forming ions through protonation or deprotonation, which are then analysed by mass spectrometry. MALDI is a form of “soft ionisation”, producing few fragments from macromolecules such as proteins, DNA, peptides and lipids.

Key Facts

  • Commonly used lasers (source: Wikipedia “Matrix-assisted laser desorption/ionisation”): Ultraviolet lasers are the most common, including nitrogen lasers (337 nm) and Nd:YAG lasers (355 nm, 266 nm); infrared lasers (such as 2.94 μm Er:YAG) may also be used, offering gentler ionisation.

  • Differences between LDI and MALDI: LDI does not rely on an exogenous matrix, instead utilising the sample itself or simple absorption assistance; however, it is inefficient for macromolecules that do not absorb the laser wavelength and is prone to fragmentation. MALDI, on the other hand, relies on an exogenous matrix to absorb energy and form a co-crystal, thereby enabling the soft ionisation of macromolecules.

  • Applications: proteomics, peptide mass fingerprinting, analysis of lipids and oligonucleotides, microbial identification (MALDI-TOF typing), and MALDI imaging mass spectrometry (for imaging the spatial distribution of biomolecules).

  • Landmark publications: Karas M, Hillenkamp F. 1988: Laser desorption and ionisation of proteins exceeding 10,000 Da (Anal. Chem. 60:2299); Tanaka K. et al. 1988: Analysis of macromolecules with m/z up to 100,000 using laser ionisation (work related to the Nobel Prize, Rapid Commun. Mass Spectrom. 2:151).

Relation to Neo Source products

Neo Source INSTRUMENT’s MSI LDPI imaging ion source utilises laser desorption (LDI) as the primary desorption method, combined with post-laser photoionisation (PI), to achieve imaging resolution on the order of 2–3 μm.

References

  1. Wikipedia: Matrix-assisted laser desorption/ionisation. https://en.wikipedia.org/wiki/Matrix-assisted_laser_desorption_ionization

  2. Karas M, Hillenkamp F. Laser desorption ionisation of proteins with molecular masses exceeding 10,000 daltons. Analytical Chemistry. 1988;60(20):2299–2301.

  3. Hillenkamp F, Karas M, et al. Matrix-assisted laser desorption/ionisation mass spectrometry of biopolymers. Analytical Chemistry. 1991;63(24):1193A–1203A.