Secondary ion generator detector for time-of-flight mass...

Details Secondary ion generator detector for time-of-flight mass... Secondary ion generator detector for time-of-flight mass...

1998-09-22

2001-09-25

Berman, Jack (Department: 2881)

Radiant energy

With charged particle beam deflection or focussing

With detector

Reexamination Certificate

active

06294790

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates in general to an ion detector, and more particularly to an ion detector for selective and enhanced detection of large mass to charge ratio ions.
Ions having large mass to charge ratio (m/z) (ions greater than approximately 12,000 daltons) typically may be generated via several different ionization techniques, including but not limited to: Plasma Desorption/Ionization (PDI), Matrix-assisted Laser Desorption/Ionization (MALDI), Surface-enhanced Laser Desorption/Ionization (SELDI), and Electrospray Ionization (ESI). The large m/z values for these ions are such that they are beyond the m/z dynamic range for most simple magnetic sector, electrostatic analyzer, magnetic sector hybrid, and quadrapole filter analyzers. Consequently, the analysis of these ions is typically performed using ion-trap, fourier transform ion cyclotron resonance, and time-of-flight (TOF) mass spectrometers. Because of their simplicity and economy, when compared to the other previously mentioned devices, TOF systems are most frequently used of analyzing such large ions.
In time-of-flight methods of mass spectrometry, charged (ionized) molecules are produced in a vacuum and accelerated by an electric field produced by an ion-optic assembly into a free-flight tube or drift time. The velocity to which the molecules may be accelerated is proportional to the square root of the accelerating potential, the square root of the charge of the molecule, and inversely proportional to the square root of the mass of the molecule. The charged molecules travel, i.e., “drift” down the TOF tube to a detector.
FIG. 1
generally illustrates a laser desorption ionization time-of-flight mass spectrometer. Briefly, the system comprises ion optics
20
, which include a repeller
21
, an extractor
22
, and a ground plate
23
. A mass filter
24
may be included. A detector
25
completes the system. A crystallized layer of sample/matrix mixture
30
is applied to the surface of a probe
19
. The ion optics are then energized and a laser beam
31
is applied to sample mixture
30
to thereby release or desorb ions. Repeller
21
is held at a potential of, for example, 30 kV, extractor
22
is held at a potential of, for example, 15 kV, while groundplate
23
is held at ground potential. An electric field is set up due to the potential difference between repeller
21
, extractor
22
, and groundplate
23
, and thereby accelerates desorbed ions through the ion optics. Among the desorbed ions are matrix molecules and analyte molecules. Since the analyte molecules are the molecules of interest, mass filter
24
may be utilized to filter out the matrix molecules. Mass filter
24
typically comprises an entry plate and exit plate (not shown) and deflector. Finally, the ions reach detector
25
and the time-of-flight in traveling to the detector is utilized to calculate a mass to charge ratio. Since laser beam
31
passes through a beam splitter
27
such that a portion of laser beam
31
activates a trigger photo diode
32
, the time the process started is known.
A laser desorption/ionization time-of-flight mass spectrometer (LDIMS), as depicted in
FIG. 1
, could be used to perform MALDI or SELDI analysis.
For MALDI analysis, samples are prepared as solid-state co-crystals or thin films by mixing them with an energy absorbing compound or colloid (the matrix) in the liquid phase, and ultimately drying the solution to the solid state upon the surface of an inert probe. In SELDI analysis, the probe or sample presenting surface plays an active role in the ionization, purification, selection, characterization or modification of the applied sample. In some cases an energy absorbing molecule (EAM) is an integral component of the sample presenting surface. In other cases, an energy absorbing molecule is added after the SELDI surface has completed its required interaction with the sample. Regardless of EAM application strategy, the probe contents are allowed to dry to the solid state prior to introduction into the LDIMS.
The output of detector
25
is integrated at some duty cycle as a function of time with respect to the time of the irradiating laser pulse
31
as sensed by the trigger photo diode
32
. The molecular weight of an ion is then determined using the time-of-flight expression: m/z=A (Tf−To)
2
where: M/Z is the ions determined mass to charge ratio, Tf is the total flight time of the ion, To is the time interval that exists between the triggering of the timing device and acceleration of resultant ions and A is a constant that accounts for ion total kinetic energy and total flight distance. The values for A and To are empirically determined by comparing the experimental Tf flight number of well characterized analytes with their respective m/z. The determination of A and To calibrates the instrument and allows for more accurate m/z assignment.
During MALDI and SELDI analysis, a significant population of ions may be generated as a direct consequence of the use of matrix or EAM, respectively. These ions are transmitted down to the detector's conversion surface along with those ions created from the analytes of interest. In ESI analysis, a large number of ions are created from the solvents which make up the carrier solution. As was the case for SELDI and MALDI, these ions are also transmitted down to the detector's conversion surface. In all of these ionization techniques, it is not uncommon for these “unwanted ions” to be a major component of the entire ion current, far exceeding the number of analyte ions that are of interest. Since the ion transmission time period for a single LDIMS scan is rarely greater than 500 microseconds, detector electrons consumed during the conversion/gain process are usually not replaced during this rapid duty cycle. The result is charge depletion and field collapse to a level that seriously compromises detector gain.
In order to avoid field collapse and attendant gain reduction, presently used devices provide ways by which unwanted ions are prevented from striking the ion detector or ways by which detector gain voltage is rapidly switched on after the last unwanted ions strike the conversion surface. The former is accomplished by employing the additional set of ion optic elements that function as a mass gate or mass filter. The latter is accomplished through the use of high speed switching devices such as field effect transistors. Both of these methods add complexity and cost to TOFMS instruments. Because the gain rise time of a detector conversion surface is often several microseconds, the rapid switching technique does not allow for steep cut-off ranges, creating the possibility of inadequate gain during the initial phase of its duty cycle.
Ion detection in TOF mass spectrometry is typically achieved with the use of electro-emissive detectors such as electron multipliers (EMP) or microchannel plates (MCP). Both of these devices function by converting primary incident charged particles into a cascade of secondary, tertiary, quaternary, etc. electrons. The probability of secondary electrons being generated by the impact of a single incident charged particle can be taken to be the ion-to-electron conversion efficiency of this charged particle (or more simply, the conversion efficiency). The total electron yield for cascading events when compared to the total number of incident charged particles is typically described as the detector gain. Because generally the overall response time of MCPs is far superior to that of EMPs, MCPs are the preferred electro-emissive detector for enhancing m/z resolving power. However, EMPs function well for detecting ion populations of disbursed kinetic energies, where rapid response time and broad frequency band width are not necessary.
The conversion efficiency of large ions is known to be two to three orders of magnitude less than that of smaller ions. To compensate for this effect, secondary ion generators (SIG) have been used. Such a secondary ion generator is disclosed in U.S. Pat. Nos. 5,382,793,

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