2. Laser desorption/ionization (LDI)-based methods. These techniques employ laser beams at specific wavelengths to irradiate the sample surface, desorbing and ionizing specific molecules. Although laser technology emerged in 1960 with Maiman's invention, the potential of LDI for MS was only realized in the 1980s, as early LDI methods could ionize only molecules absorbing specific laser wavelengths . Key LDI approaches include matrix-assisted laser desorption/ionization (MALDI-MS) and matrix-free LDI. MALDI, a soft ionization method, significantly enhances the ionization efficiency of large biomolecules, such as proteins and polymers . In a MALDI experiment, an organic matrix compound with strong UV absorption assists in laser absorption, enabling efficient energy transfer to the analytes. Ionization occurs through the interactions between the analyte and ionized matrix molecules, but the high vacuum environment required to prevent atmospheric interference may lead to molecular delocalization and other sample alterations. Additionally, matrix compounds often interfere with detection of lowmolecular-weight compounds (<1000 m/z), complicating studies on small molecules like metabolites and drug compounds . To minimize interference with matrix molecules, alternative MS techniques, such as matrix-free laser desorption/ionization MS (LDI-MS) and label-assisted laser desorption/ionization MS (LALDI-MS) , have been developed. These methods are particularly useful for analyzing relatively large cells, including plant and algae cells . In LALDI-MS, specific functional groups (e.g., fluorophores or polyaromatic structures) are used to label target molecules (e.g., peptides) to enable their desorption and ionization when exposed to soft lasers operating at visible wavelengths. While some LDI-based methods are described as matrix-free, it is often challenging to completely avoid the use of assistive molecules (e.g., 1,5-Diaminonaphthalene) when studying biological samples. This is largely due to the complexity of biomolecules, which often demand varied levels of desorption and ionization energy . While these vacuum-based SCMS methods minimize interference from experimental contaminants, allowing for enhanced detection sensitivity and high throughput analysis, they requires nontrivial sample preparation as well as precludes the analysis of live cells due to the extensive pretreatments involved .