MALDI-MS techniques for high throughput drug screening are not as popular as the ESI-MS techniques. This is due in part to the facts that the m/z values of small drug molecules often overlap with the chemical noise of the MALDI matrix and that small drug molecules often fragment or rearrange, unlike peptides or oligonucleotides. In the near future, these disadvantages may be reduced dramatically with the use of porous silicon chips as MALDI targets [48-50] since no matrix is required, or with sol-gel derived polymeric matrixes which produce nearly no chemical background noise . In addition, these laser desorption/ionization mass spectrometric methods, respectively referred to as DIOS and SGALDI, may produce molecular ions without any significant fragmentation and may even be more sensitive than traditional MALDI methods (see Chapter 8). The future prospects for these technologies become even more promising when GPC methods are coupled with the recently demonstrated microfluidic compact disc (CD) technology (Gyros System; Gyros AB, Uppsala, Sweden) for MALDI sample preparation [52, 53]. The design of the Gyros system is a natural for GPC spin column applications because when the CD is spun it behaves as a centrifuge to produce the spin column eluate. A significant breakthrough for drug screening will be made when the microfluidic CD technology is developed in the GPC spin column mode coupled to ESI-MS as well as MALDI-MS in the IR and UV laser modes.
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