Several new instruments have been designed using a recently developed theoretical approach for optimizing the performance of each of the major elements of a time-of-flight (TOF) mass spectrometer. The major emphasis in the design and construction of these instrument is on biological applications employing Matrix Assisted Laser Desorption/Ionization (MALDI), but other applications of laser desorption have also been explored. The optimized elements include one and two-stage MALDI ion sources, two-stage ion mirrors, both gridded and gridless, timed-ion selectors, ion focusing and deflecting elements, pulsed and static ion accelerators, ion fragmentors, and ion detectors. Prototype instruments were constructed to allow performance of each of these elements to be evaluated and compared with theoretical predictions. In these prototypes an ion detector may be temporarily placed at any of the critical points in the ion flight path for thorough evaluation of ion beam properties and functionality of critical components.
Instruments developed and evaluated include a high-performance linear MALDI-TOF, a high resolution reflector MALDI-TOF with 200,000 resolving power, a MALDI-TOF-TOF instrument with high resolution precursor selection and multiplexed MS-MS operation, and a LD-TOF for measurement of sub-part-per-trillion levels of rare isotopes including 14C and 41Ca.
The designs of these instruments are specifically focused on providing the performance and features needed for particular measurements. Emphasis is on simplicity, reliability, and minimum cost consistent with high performance. A modular approach is employed where many of the major components are common to all systems. Common components include the sample plate handling system with motion control, 5 kHz laser and HV pulsers, laser optics and controls, vacuum system, digitizer and computer, and several electronics modules. All HV supplies, delay times, laser rate and fluence, digitizer and delay times, vacuum system including sample plate loading and sample motion are computer controlled, using new hardware and software designed and developed specifically for these instruments.
Recent results demonstrating the performance of these instruments for selected biological applications are summarized. These include LC-MS and MS-MS for analysis of proteins and lipids, and high-speed MS and MS-MS for imaging of tissue sections. Preliminary results on measurements of isotope ratios for C and Ca in biological samples are also discussed. |
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