Development of a Porous Silicon Product for Small Molecule Mass Spectrometry
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Development of a Porous Silicon Product for Small Molecule Mass Spectrometry Grace Credo1, Hillary Hewitson2, Christopher Benevides2 and Edouard S. P. Bouvier1 1
Advanced Separations Technology Group (R&D Engineering) and 2Life Sciences R&D, Waters Corporation, Milford, Massachusetts, 01757, U.S.A.
ABSTRACT 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[7]. 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]. INTRODUCTION In drug discovery and development efforts, synthesized molecules from medicinal chemists in a pharmaceutical company are usually screened by an internal analytical chemistry group. These analytes are typically < 1000 amu and are small compared to polymers. Sample cycle time is a key figure-of-merit because each individual compound can generate hundreds of samples to analyze. Currently the industry standard in high-throughput pharmaceutical analysis is liquid chromatography-mass spectrometry (LC/MS). However, another option is to use a matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) instrument which is known to have a relatively short sampling time compared to LC. In MALDI, samples are ionized by a pulsed laser and detected in gas phase. In LC, solution components are separated in liquid phase and subject to longer analysis times due to limitations on speed of sample flow. Fast MALDI analyses can be conducted with cycle times of 10 sec while fast LC/MS analyses are around 300 sec (5 min). In addition, LC often requires significant time for chromatography optimization and method development. MALDI TOFs exhibit high sensitivity and analyte solutions can be easily sampled with minimal sample preparation. However, there are several well-known problems with the use of MALDI mat
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