Time-of-flight mass spectrometry
To compensate for the spread of this average velocity and to improve mass resolution, it was proposed to delay the extraction of ions from the ion source toward the flight tube by a few hundred nanoseconds to a few microseconds with respect to the start of short (typically, a few nanosecond) laser pulse.
Delayed extraction generally refers to the operation mode of vacuum ion sources when the onset of the electric field responsible for acceleration (extraction) of the ions into the flight tube is delayed by some short time (200–500 ns) with respect to the ionization (or desorption/ionization) event.
Conversely, those ions with greater forward momentum start to be accelerated at lower potential since they are closer to the extraction plate.
The more energetic ions penetrate deeper into the reflectron, and take a slightly longer path to the detector.
A point of simultaneous arrival of ions of the same mass-to-charge ratio but with different energies is often referred as time-of-flight focus.
An additional advantage to the re-TOF arrangement is that twice the flight path is achieved in a given length of the TOF instrument.
[10] Continuous ion sources (most commonly electrospray ionization, ESI) are generally interfaced to the TOF mass analyzer by "orthogonal extraction" in which ions introduced into the TOF mass analyzer are accelerated along the axis perpendicular to their initial direction of motion.
Before entering the orthogonal acceleration region or the pulser, the ions produced in continuous (ESI) or pulsed (MALDI) sources are focused (cooled) into a beam of 1–2 mm diameter by collisions with a residual gas in RF multipole guides.
A system of electrostatic lenses mounted in high-vacuum region before the pulser makes the beam parallel to minimize its divergence in the direction of acceleration.
Some designs include precursor signal quenchers as a part of second TOF-MS to reduce the instant current load on the ion detector.
[22][23] Both quadrupoles can operate in RF mode only to allow all ions to pass through to the mass analyzer with minimal fragmentation.
Since the ion pulser transfers the same kinetic energy to all molecules, the flight time is dictated by the mass of the analyte.
QToF is capable of measuring mass to the 4th decimal place and is frequently used for pharmaceutical and toxicological analysis as a screening method for drug analogues.
Time-to-digital converters register the arrival of a single ion at discrete time "bins"; a combination of threshold triggering and constant fraction discriminator (CFD) discriminates between electronic noise and ion arrival events.
The TDC is a counting detector – it can be extremely fast (down to a few picosecond resolution), but its dynamic range is limited due to its inability to properly count the events when more than one ion simultaneously (i.e., within the TDC dead time) hit the detector.
To obtain peaks with statistically acceptable intensities, ion counting is accompanied by summing of hundreds of individual mass spectra (so-called hystograming).
Commercial orthogonal acceleration TOF mass analyzers typically operate at 5–20 kHz repetition rates.
Modern ultra-fast 10 GSample/sec analog-to-digital converters digitize the pulsed ion current from the MCP detector at discrete time intervals (100 picoseconds).
Modern 8-bit or 10-bit 10 GHz ADC has much higher dynamic range than the TDC, which allows its usage in MALDI-TOF instruments with its high peak currents.
[27] An early time-of-flight mass spectrometer, named the Velocitron, was reported by A. E. Cameron and D. F. Eggers Jr, working at the Y-12 National Security Complex, in 1948.
The idea had been proposed two years earlier, in 1946, by W. E. Stephens of the University of Pennsylvania in a Friday afternoon session of a meeting, at the Massachusetts Institute of Technology, of the American Physical Society.
