Further studies on the signal enhancement effect in laser diode thermal desorption‐triple quadrupole mass spectrometry using microwell surface coatings

The laser diode thermal desorption (LDTD) ionization source allows ultrafast and sensitive analysis of small molecules by mass spectrometry. Signal enhancement in LDTD has been observed when coating the surface of sample microwells with a solution of ethylenediaminetetraacetic acid (EDTA) or nitrilotriacetic acid. Here we present a quantitative analysis of signal enhancement using solutions of diverse commercial proteins (lysozyme, immunoglobulin G, albumin, and fibrinogen) as coatings. Results showed that compounds with polar chemical functions such as carboxylic acid, sulfonyl, and nitro had signal enhancement factors, in most cases higher than 10, when using any of the tested proteins as coating agent. Analysis of variance revealed that immunoglobulin G and fibrinogen gave the best results. However, the signal enhancement factors obtained with these proteins were not superior to those observed with EDTA. To explain the signal enhancement effect of proteins, analysis by scanning electron microscopy of dried samples on the microwell sample plates was carried out. Images showed that salicylic acid, one of the compounds with the highest observed signal enhancement, formed a thick layer when applied directly on the uncoated surface, but it formed small crystals (