Radiant energy – Ionic separation or analysis – Ion beam pulsing means with detector synchronizing means
Reexamination Certificate
2002-07-10
2004-07-20
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
Ion beam pulsing means with detector synchronizing means
C250S286000, C250S281000, C250S282000, C250S42300F
Reexamination Certificate
active
06765199
ABSTRACT:
BACKGROUND OF THE INVENTION
Time-of-flight mass spectrometry (TOFMS) is an analytical process that determines the mass-to-charge ratio (m/z) of an ion by measuring the time it takes a given ion to travel a fixed distance after being accelerated to a constant final velocity. There are two fundamental types of time-of-flight mass spectrometers: those that accelerate ions to a constant final momentum and those that accelerate ions to a constant final energy. Because of various fundamental performance parameters, constant energy TOF systems are preferred.
A previously known constant kinetic energy TOF mass spectrometer is shown in FIG.
1
A. Ions are created in a region typically referred to as the ion source. Two ions with masses M
1
and M
2
have been created as shown in
FIG. 1A. A
uniform electrostatic field created by the potential difference between repeller lens
10
and ground aperture
11
accelerates ions M
1
and M
2
through a distance s. After acceleration, ions pass through ground aperture
11
and enter an ion drift region where they travel a distance x at a constant final velocity prior to striking ion detector
12
.
The time-of-flight of the ions can be measured to calculate their mass-to-charge ratio values. For example, referring to
FIG. 1A
, within the ion optic assembly, accelerating electrical field (E) is taken to be the potential difference (V) between the two lens elements (
10
and
11
) as applied over acceleration distance s, (E=V/s). Equation (1) defines the final velocity (v) for ion M
1
with charge z. The final velocity of ion M
2
is determined in a similar manner.
v
=
(
2
s
E
z
M
1
)
1
/
2
(
1
)
Inverting equation (1) and integrating with respect to distance s yields equation (2), which describes the time spent by ion M
1
in the acceleration region (t
s
)
t
s
=
(
M
1
2
Esz
)
1
/
2
(
2
s
)
(
2
)
The total time-of-flight for ion M
1
(t
1
) is then derived by adding t
s
to the time spent during flight along distance x (the ion drift region). Time t
s
equals the product of the length of free flight distance x with 1/v, as shown in Equation (3).
t
t
=
(
M
1
2
Esz
)
1
2
(
2
s
+
x
)
2
(
3
)
Rearranging equation (3) in terms of M
1
/z yields equation (4)
M
1
z
=
2
t
t
2
Es
(
2
s
+
x
)
2
(
4
)
For all TOFMS systems, E, s, and x are intentionally held constant during analysis, thus equation (4) can be reduced to equation (5).
M
1
z
=
k
t
t
2
(
5
)
Equations (1)-(5) simplify the TOFMS process by assuming that all ions are created at the same time, within the same location, and have no initial velocity prior to acceleration. Routinely, this is not the case and in many instances, variations in formation time, original location, and initial velocity (also referred to as initial energy) are often demonstrated for various ions of a given m/z population. Such variation ultimately limits the mass resolving power of the instrument. Mass resolving power is typically defined as the ability to determine subtle differences in m/z.
For a TOFMS system, mass resolving power R is mathematically defined by equation (6), where dm and dt are the respective full mass or full temporal width of a measured signal at its half magnitude.
R
=
m
dm
=
T
2
d
t
(
6
)
Ultimately, factors that limit mass resolving power are dictated by the ionization means, geometry of the ionization source, geometry and stability of the TOF mass spectrometer, as well as the nature of the sample itself. Various strategies have been adapted to improve mass resolving power in time-of-flight mass spectrometry.
Another example of a TOF mass spectrometer is shown in FIG.
1
B. The TOF mass spectrometer shown in
FIG. 1B
is an orthogonal extraction device. In the device, ions are generated from ion source
20
and directed to repeller lens
22
via RF ion guide
21
. A uniform electrostatic field created between repeller lens
22
, extractor lenses
29
, and ground apertures
28
accelerate ions. After acceleration, ions pass through ground apertures
28
and enter an ion drift region along path
35
where they travel through reflectron
27
. Reflectron
27
functions to narrow ion energy spread, and then it redirects the ions to detector
26
.
The output signal of ion detector
26
can be an analog signal, which is then converted to a digital signal. The analog-to-digital conversion may be accomplished, for example, using a time-interval recording device, such as a time-to-digital converter (TDC). For instance, detector
26
outputs a signal to high speed time-to-digital converter (TDC)
24
when an ion impacts its detecting surface. TDC
24
converts analog signals from detector
26
to digital information suitable for software processing at stage
25
. TDC
24
records a single impulse when the detector
26
output signal exceeds a predetermined threshold. HV pulser
23
indicates to TDC
24
the start of an ion detection cycle when the repeller lens
22
starts to accelerate the ions.
Previously known systems have employed means for providing gain in the output signal of detector
26
prior to digitization. Such gain has been provided by primary ion to secondary product or primary ion to secondary electron conversion prior to striking an electromissive detector surface. Primary ions are converted to secondary products through the mechanisms of surface induced dissociation, generating ion and neutral fragments, and/or fast ion bombardment of solid surfaces, creating sputtered products. Primary ions can also be converted to secondary electrons by directing them to strike a metal of low work potential, ultimately releasing low energy electrons. These secondary products are then directed to strike an electromissive device, creating an amplification cascade provided by the generation of secondary, tertiary, quaternary, etc. electrons.
The probability of producing an output signal from the detector
26
decreases with increasing time-of-flight (and also increasing m/z values). As shown in
FIG. 2
as ion m/z increases, the ion-to-electron conversion probability decreases.
Ions are more likely to be detected by a detector if they have high velocities. Ions with high m/z values have greater mass and have lower velocities than ions with low m/z values. Consequently, ions with high m/z values have a lower probability of generating secondary charged particles such as electrons in the detector and have a lower probability of being detected by the detector than ions with low m/z values. For example,
FIG. 2
depicts the ion to electron conversion probability for ions of various mass-to-charge ratio values (m/z) at two different kinetic energy levels: 50 KeV (line
30
) and 25 KeV (line
31
). As shown in
FIG. 2
, the ions with higher kinetic energy (line
30
) are more likely to produce electrons than ions with low kinetic energy (line
31
).
Also, ions are less likely to arrive at the detector if they remain in flight for longer periods of time. Ions with high m/z values have a higher mass and take a longer time to arrive at the detector than ions with low m/z values. Because ions with high m/z values remain in flight longer than ions with low m/z values, there is an increased chance that the ions may not arrive at the detector. Accordingly, the probability of transporting ions to the detector decreases as the m/z value of an ion increases. The decreased probability often results in shorter peaks in the mass spectrum signal at high m/z values than would be the case if all ions had the same chance of reaching the detector.
Furthermore, in TOF mass spectra, empirical data indicate that peaks tend to widen with increasing with time-of-flight values (and m/z values). A number of factors can contribute to increasing peak widths including differences in the initial velocity of the ions of a given m/z value, differences in the initial spatial distributions of the ions, slight differences in the chemical composition of the analytes, etc. As ions are in flight for longer periods of tim
Gavin Edward
Rich William E.
Youngquist Michael G.
Ciphergen Biosystems Inc.
Lee John R.
Souw Bernard
Townsend and Townsend / and Crew LLP
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