Previous work has demonstrated the utility of desorption/ionization on silicon (DIOS) time-of-flight mass spectrometry (TOFMS) in drug molecule and peptide detection[1-7]. In this work, the utility of DIOS for small molecule detection is established using commercially available porous silicon (por Si)-based target plates for MS. Since the morphology and handling of the substrates can have dramatic effects on the MS characteristics, the development of consistent manufacturing methods and characterization protocols has been central to the production of reproducible target plates. Using sample substrates manufactured in-house, we show that 1) small molecules and protein digests were detected without matrix-related peaks, 2) por Si morphology was optimized for small molecule detection, 3) reproducible DIOS plates were produced, 4) although the target plates were shown to be sensitive to contamination, a consistent cleaning procedure was developed to remove contaminants, and 5) stability and shelf life were characterized as a function of surface derivatization. Dynamic range, sensitivity, quantitation, speed of analysis, solution composition, and automated deposition have also been evaluated and are described in related work[7-9]. Potential applications include high-throughput small molecule assays for drug discovery[10a] and high sensitivity (sub-femtomole) peptide identification for proteomics[10b].