Molecular Detection Using Mass Spectrometry
Biological fluids are enormously complex in molecular composition, and their analysis has become a central challenge in biology and medicine. Mass spectrometry (MS) is a method of analysis in which molecules are converted to gas phase ions and manipulated by electric and/or magnetic fields in a low pressure environment. We can measure the ion's mass-to-charge ratio, or isolate an ion of a given mass-to-charge ratio, induce it to fragment, and then measure the mass-to-charge ratio of the fragments, a process called MS/MS. Such measurements identify the molecule. Our laboratory has developed computer models and accumulated biomedical analyses data concerning a new type of ion optical device that has significant potential to address both research and clinical problems in biomarker development. The device would operate on a complex population of trapped ions to deduce structure from a hierarchy of ion selection and dissociation steps using multiple mass spectrometry (MSn). Mixtures would be analyzed without chromatographic separation using low-flow static electrospray (nanospray) giving optimal ionization efficiency (sensitivity), reducing costs, and simplifying operation. Technical properties of the ion selection physics allow for relatively low-amplitude radio frequency trapping fields and relatively low precision in electrode machining compared with existing MS instruments, thereby also reducing costs. The device would operate as a molecular detector in which a database of MSn fragmentation patterns would be used to quantify these molecular components in very complex biological samples at high sensitivity and at high dynamic range.
