Time-of-flight (TOF) mass spectrometry (MS) works by imparting equal energies to all fragments. Since smaller particles thereby travel faster, their masses are determined by how quickly they travel from the source to the detector.
TOF provides exquisite mass accuracy and resolution at very high dynamic range and response linearity within a spectrum. These qualities, says Alessandro Baldi, Ph.D., business manager for MS at PerkinElmer (Waltham, MA), allow analysts to focus on very specific mass ranges and eliminate signals outside that window. “That’s why TOF shines for target characterization.” TOF’s other great benefit for this application is fast spectrum acquisition, up to 50 per second. Vendors will often couple instruments with software packages that supply results at a glance, which makes TOF a method of choice for rapid, routine screening for the presence or absence of particular masses in many samples.
Today’s instruments, particularly MS/MS TOF mass spectrometers, are routinely used in proteomics, protein discovery, lipids, metabolomics, and drug and drug metabolite identification. Pharmaceutical companies, in particular, use these instruments to quantify and positively identify known and unknown compounds.
Another relevant TOF workflow is the identification of unknown compounds in drug metabolism assays, drugs-of-abuse testing, foods and beverages, or environmental samples. Because of its highly discriminatory mass detection, TOF can distinguish, based on isotope ratios, whether a pharmaceutical was manufactured at an approved facility or by counterfeiters.
Accurate determination of isotope distributions also enables TOF instruments to distinguish between two compounds of equal molecular weight, providing unequivocal identification.
Ionization of MS samples is critical, since the instruments detect only ions. Numerous ionization techniques exist for solid and liquid samples prepared manually or obtained from the back end of a chromatograph. Most require exposing the sample to high temperature, radiation, or a stream of high-velocity gas. Direct analysis in real time (DART) directly ionizes samples, with no preparation, at atmospheric pressure and under gentle conditions. DART is suitable for the direct analysis of pharmaceuticals, chemicals, and even samples of dried blood, with no sample prep.
Diab Elmashni, senior marketing manager for LC and LC/ MS at Thermo Fisher Scientific (San Jose, CA), also notes that the current “big trend” in MS is more routine analysis.
Instruments have become easier to use in response. Specialists accustomed to room-size spectrometers of 20 years ago would marvel at how MS is now employed as a detector for liquid and gas chromatography. A related capability is the rapid expansion of MS targets from smallish organic molecules to macromolecules.
The greatest strides in usability, says Mr. Elmashni, have been in software design. Software opens a mass spectrometer’s full range of features to expert users while simplifying protocols for routine users through various levels of permissions. These allow the lab director or high-end operator to tweak the instrument as needed, or to write methods, while simplifying the interface for technicians through a nonalterable interface.
Similarly, software templates have simplified the process of running samples and analyzing data by taking over routine tasks such as data entry and report generation.
Recently Released TOF Mass Spectrometers
- Features capability to perform high-definition mass spectrometry (HDMS), a cost-effective technique for screening samples at trace levels
- Offers full-scan sensitivity at typical GC-quad SIM levels
- Lets users screen for both known and unknown compounds at much lower levels with a high degree of definition and clarity
- Features fast acquisition rates, up to 1,000 spectra/s over the entire mass range
- Features a wide linear dynamic range (105)
- Generates constant ion abundance ratios across the chromatographic peak
- Supports several MS libraries, such as the NIST mass spectral library
- Features proprietary Folded Flight Path™ (FFP™) technology to provide full-range mass spectra at speeds of up to 200 spectra per second
- Provides resolutions of up to 50,000 with high-performance mass accuracy
- KADAS® (Kinetic Algorithmic Data Acquisition System) provides high-integrity output under the most demanding acquisition conditions available
- Features UPLC®/MS and QuanTof™ technology for exact mass quantitative and qualitative performance
- UPLC/MS is a method of data acquisition that catalogs complex
- samples in a single analysis
- Can be upgraded to MS-MS capability using the same hardware