As one of the key fields that require strong (laser) irradiation in nature, MS imaging techniques, such as matrix assisted laser desorption/ionization (MALDI) MS, can help to visualise the spatial distribution of molecules without purification, extraction, separation, or labelling of bio-samples, which are important in early stage disease diagnosis and forensic applications.1, 2 Despite the substantial progress, the application of MALDI MS towards small molecules is limited because the matrices (normally small organo molecules like α-cyano-4-hydroxycinnamic acid, CHCA) introduce significant background signals during laser ablation in the low molecular weight range (< 1000 Da). In addition, the large and irregular sizes of the matrix crystals (> 10 µm) and sweet-spot effects limit the imaging spatial resolution and detection efficiency.3, 4 To date, overcoming the low sensitivity of MS based imaging towards small molecules and the preparation of stable functional materials under irradiation represent the key challenges to the field.
To address the above challenges, matrix-free MS techniques have been developed.3-14 Secondary ion MS (SIMS) was one of the first matrix-free approaches used to detect and image molecules from biological samples using a high-energy primary ion beam to desorb and generate secondary ions from a surface.15, 16 For matrix free MS imaging applications, an ideal substrate should have the following attributes: (1) stable with minimum matrix interference; (2) able to provide sufficient surface area and desirable interaction with analyte molecules; (3) electric conductive with high electron mobility and efficient in laser absorbance for desorption/ionization; and (4) homogeneous in surface for reproducibility and faithful replication of imaging.3, 4, 17