Why is Time-of-Flight Mass Spectrometry (TOFMS) considered a more ideal detector relative to Quadrupole Mass Spectrometry (QMS)?

Time-of-Flight Mass Spectrometry (TOFMS) has inherent performance advantages over Quadrupole Mass Spectrometry (QMS). TOFMS captures instantaneous full-spectrum information, significantly enhancing the instrument's analysis speed and sensitivity, ensuring no critical information is lost and allowing retrospective analysis. This capability makes it easier to identify unknown analytes and resolve measurement results. Moreover, TOFMS's ultra-high mass resolution and high accuracy are particularly beneficial for the accurate identification of unknown species in complex matrices, as detailed in the following text.

Quadrupole Mass Analyzer

A Quadrupole Mass Analyzer, in simple terms, is an "ion filter": at any given moment, only ions with specific m/Q values can pass through the quadrupole rods and be detected by the rear-end detector. In the second step, a partial or complete mass spectrum is obtained by selecting or sequentially scanning mass-to-charge ratios.

Figure 1 is a simple animated diagram of the quadrupole principle: an RF (radiofrequency) electric field focuses ions on the axis of the quadrupole rods; an overlaid DC (direct current) electric field is used to destabilize the stable flight trajectory of ions and eject them from the quadrupole rods. By adjusting the intensities of these two electric fields, only ions within a small m/Q range can maintain a stable flight trajectory and pass through the quadrupole rods smoothly. Other ions outside this m/Q range are destabilized and lost (filtered out). Then, by scanning specific or each ion's mass-to-charge ratio across the entire m/Q range, a partial or complete mass spectrum can be recorded.

The voltage output of the electronic device that generates the RF field has a physical upper limit, which in turn limits the upper range of mass-to-charge ratios that the quadrupole can measure.

Figure 1. Animated Diagram of the Quadrupole Principle

Time-of-Flight Mass Analyzer

A TOF analyzer separates ions based on their different flight times through a specific region (often called a flight tube), where ions are accelerated and then fly at constant velocity through the field-free flight tube to the detector. The entire process is akin to a race: ions are accelerated at the starting point (race start), then they fly at constant speed through the field-free flight tube (race process), and finally they reach the detector (finish line). The time from the starting point of the flight tube to when ions "hit" the detector, known as the flight time, is recorded by a high-speed detector.

Intuitively, heavier molecules should "fly" slower than lighter ones, meaning they take longer to reach the detector. Therefore, under the assumption of equal charge states, ions with smaller m/Q ratios will pass through the TOF region faster and reach the detector sooner. The instrument measures the flight time of each ion from the starting acceleration region to the detector at high speed and then converts it into a mass spectrum: mass-to-charge ratio (m/Q) and signal intensity.

Figure 2. Animated Diagram of the Time-of-Flight Mass Spectrometry Principle

The animation in the above figure lasts for a few seconds. In TOFWERK instruments, the actual ion flight speeds are much faster: ions fly tens of thousands of times per second, with flight times ranging from 10 to 100 microseconds. Typically, we do not need data acquisition rates as high as tens of thousands of times per second, so the data is often accumulated into spectra at intervals such as every 0.1 seconds (10 Hz) or longer.

For example, when the TOF operates at a data acquisition rate of 20,000 times per second, data from every 2000 flight events can be accumulated into one spectrum, resulting in an instrument response of 10 spectra per second.

Modern TOF instruments employ sophisticated electronic and mechanical designs to enhance mass resolution, including components like electrostatic field reflectors. Moreover, there are many steps in the system design and consideration from the ion "collision" detector to the display of the mass spectrum on the instrument screen.

TOFMS Fast "Panorama" Measurements

Unlike quadrupole mass analyzers, which record only single m/Q ions in each measurement, time-of-flight mass spectrometry continuously records the signal intensity of all m/Q ions. TOF simultaneously detects all ion characteristics, which inherently provides advantages over QMS ion monitoring (SIM) and full-spectrum scanning.

Quadrupole analyzers require a certain dwell time for scanning each ion (typically 0.1 seconds or more), which may result in longer times to complete full-spectrum scans, slower measurement speeds, and loss of significant information. For instance, Figure 3 (left) shows the results of a single exhalation measurement of 241 different VOC compounds using Vocus 2R PTR-TOF at a 4 Hz acquisition rate. In this simple experiment, all 241 VOCs were qualitatively and quantitatively measured. If a quadrupole mass analyzer were used to measure the same number of ions, assuming a single ion dwell time of 0.25 seconds, it would take at least one minute to complete the measurement. This means that when the volunteer finishes exhaling, the quadrupole full-spectrum scan is still ongoing (Figure 3, right).

Figure 3. Time series of various species in a single exhalation starting approximately 1.5 seconds.

In quadrupole mass spectrometry, the greater the number of ions scanned, the greater the impact on the instrument's sensitivity. During the dwell time of a single ion in quadrupole mass spectrometry, all other ions are discarded, which directly affects the overall sensitivity of the instrument. Consider measuring a calibration gas bottle for ten seconds: a quadrupole and a TOFMS spectrometer each measure ions corresponding to ten mass-to-charge ratios. In quadrupole mass spectrometry, the signal accumulation time for each mass-to-charge ratio does not exceed 1 second, while in TOFMS, the signal accumulation time for each m/Q is 10 seconds. Clearly, TOFMS accumulates more signal for each ion, thus having higher sensitivity relative to quadrupole mass spectrometry in a 10-second timeframe.

TOFMS Ensures Instantaneous Full Spectrum to Avoid Missing Vital Information

To improve measurement rates, a quadrupole can measure only a small number of specific ions (also known as selected ion monitoring, SIM). It is important to note that ions not included in the specific ion list may contain important information. For example, Figure 4 shows the mass spectrum of GC effluents measured at a rate of 5 spectra per second using a Tofwerk EI-TOF. To fully capture individual chromatographic peaks, quadrupole operators typically select no more than three ions for SIM. In contrast, the EI spectrum contained more than 200 ions in the largest chromatographic peak in the figure. Using full-spectrum data containing more than 200 ions offers significantly higher accuracy in peak identification against NIST library standard spectra compared to the few ions provided by quadrupole mass spectrometry.

Additionally, operators using SIM must be absolutely certain they are not interested in any other VOCs besides the target substances. This is particularly crucial for non-target analysis, which is extremely difficult because the exact composition of the sample is unknown. By measuring all ions at all times and storing full spectrum data, measurements become "future-proof": if research or new applications indicate a new molecule worth noting, analysts can revisit previously collected TOF data for retrospective analysis of these "new" species.

Figure 4. GC Gas Chromatography Effluents and Corresponding Chromatographic Peaks Measured by EI-TOF

High mass resolution is a necessary condition for accurately identifying unknown ions.

The resolving power of quadrupole mass analyzers is limited by the machining precision of the quadrupole rods and the performance of electronic components. Quadrupole analyzers typically operate at unit mass resolution. Even the most advanced quadrupole analyzers on the market today achieve a resolution of R=M/dM (FWHM)=3000-4000 Th/Th, often at the cost of significantly reducing instrument sensitivity. Figure 5 provides a detailed comparison between the unit mass resolution PTR quadrupole spectrum and the Vocus S PTR-TOF spectrum, which achieves a resolution of R=5000 Th/Th.

Figure 5. Comparison of Proton Transfer Reaction Quadrupole Mass Spectrometry (QMS) and Time-of-Flight (TOF) Spectra.

Conclusion

In conclusion, the advantages of Time-of-Flight Mass Spectrometry (TOFMS) over quadrupole analyzers are evident. It offers faster measurement speeds per sample and avoids "mass spectral skew" effects. TOFMS demonstrates better sensitivity than quadrupole analyzers for the same mass range. By recording full-spectrum data at all times, it ensures that no potentially important information is missed or lost. Finally, TOFMS's high mass resolution enables the identification of isobaric compounds and precise determination of elemental composition.