Radiant energy – Ionic separation or analysis – Ion beam pulsing means with detector synchronizing means
Reexamination Certificate
2000-05-11
2003-07-01
Lee, John R. (Department: 2881)
Radiant energy
Ionic separation or analysis
Ion beam pulsing means with detector synchronizing means
C250S281000
Reexamination Certificate
active
06586728
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a software filter for use with time-of-flight mass spectrometry, and more particularly, to a variable width digital filter for use with time-of-flight mass spectrometry.
2. Description of the Prior Art
With reference to
FIG. 1
, time-of-flight mass analyzers or spectrometers consist of a source/extraction region
10
, a drift region
11
and a detector
12
. In the source region, an electrical field (E=V/s) accelerates the ions to a constant energy. The drift region is field free and ions cross the drift region with velocities that are inversely proportional to the square root of their respective masses. Thus, lighter ions have higher velocities and arrive at the detector sooner than heavier ions.
In the ideal situation where ions are formed at a single point in the source region, ions are accelerated to the same final kinetic energy:
1
2
mv
2
=
e
V
and cross the drift regions with velocities:
v
=
[
2
e
V
m
]
1
/
2
and flight times:
t
=
[
m
2
e
V
]
1
/
2
These relationships depend upon the square root of the ions' masses.
In a mass spectrometer, the mass resolution is defined as m/&Dgr;m. In a time-of-flight mass spectrometer in which ions are accelerated to constant energy:
m
Δ
m
=
t
2
Δ
t
In time-of-flight mass spectrometers, it is not unusual to see a wide mass range being scanned at any given time. Ions with molecular weights between 100 and several thousand Da, ions ranging from 3,000 to about 20,000 Da, as well as all ions greater than 20,000 Da, are typically simultaneously studied in such techniques as Surface Enhanced Laser Desorption Ionization SELDI and Matrix Assisted Laser Desorption Ionization (MALDI).
The fundamental physical processes involved in the previously mentioned processes are such that signals created by heavy ion populations are generally composed of lower frequency components than their light ion counter parts. For signals created by light ion populations, broad detection bandwidths are required to accurately sample these fast transients allowing for enhanced resolution mass measurement. Signals from heavier ion populations typically do not possess significant high frequency components and thus may be sampled at significantly lower bandwidth frequencies. Table 1 lists theoretical major frequency components and estimates peak widths and mass resolutions of various ion signal populations along with their estimated times of flight and molecular weights as generated by a SELDI or MALDI time-of-flight mass spectrometer with one-meter drift region and 25 keV total energy.
TABLE 1
Ion
Ion Flight
Peak Width
Molecular
Time
Major Component
At Half
Mass
Weight (m/z)
(uSec)
Frequency (MHZ)
Height (uSec)
Resolution
500
10.2
740
0.0010
5000
1,000
14.4
500
0.0016
4500
2,000
20.4
250
0.0034
3000
5,000
32.2
70
0.0134
1200
15,000
55.8
19
0.0254
1100
40,000
91.1
2
0.3037
150
150,000
176.3
.290
1.7600
50
250,000
227.6
.130
3.8000
30
500,000
321.9
.063
8.0500
20
Thus, by reviewing Table 1, it can be seen that the peak width at half height and mass resolution of a given ion population can be correlated to ion flight time for a given ion total kinetic energy and a given free flight distance. Most time-of-flight mass spectrometers incorporate a fixed drift region distance. Furthermore, these devices also operate using either a fixed level or precisely selectable levels of ion acceleration, thus allowing qualified approximations of ion total kinetic energy. Under such conditions, it would be possible to predict the signal frequency requirements for a variety of ion populations based upon their time of detection.
The wider a peak width is, the more ions of different “sizes” may be contained within the particular ion population that is being detected. Hence, it is desirable to accurately display peak widths.
Just as in other forms of spectroscopy, time-of-flight mass spectrometry has several sources of signal noise. Such signal noise may increase peak widths. Typical noise sources such as sampling noise (alaising), Johnson noise, and flicker noise contribute to the total system noise. However, sensible engineering approaches will often reduce these noise sources to insignificant levels. Often, the most frequently encountered noise in time-of-flight mass spectrometry measurements is high frequency noise created by the detection apparatus. The combined use of secondary ions/electron generation schemes with high gain electroemissive detection surfaces frequently introduce high frequency noise that is the direct result of spurious background gas ionization, thermal or low energy photon noise (dark current noise), as well as higher energy photon or other particle-induced noise. Thus, when considering the above factors regarding ion signal component frequencies and time-of-flight mass spectrometry noise characteristics, it is evident that a fixed width filter is not a desirable solution for addressing noise problems. A filter in which the bandwidth may be varied over time range of the time-of-flight spectrum may better optimize the tradeoffs between increasing the signal to noise ratio while having the least negative effect on the mass resolution.
SUMMARY OF THE INVENTION
A method of detecting mass to charge ratio of ions in accordance with the present invention includes producing charged ions in a vacuum, accelerating the charged ions with an electric field into a free flight tube, and detecting the charged ions at a detector associated with the free flight tube. With a control system, a bandwidth for filtering a signal produced by the detector is selected. The signal produced by the detector is then filtered with a variable width digital filter based upon the selected bandwidth.
In accordance with one aspect of the present invention, the bandwidth for filtering the signal is selected from a look-up table within the control system based upon the mass to charge ratio of an ion of interest.
In accordance with a further aspect of the present invention, the method of detecting mass to charge ratio of ions further includes determining a peak bandwidth within the signal and filtering the signal produced by the detector with the variable width digital filter based upon the determined peak bandwidth.
Accordingly, the present invention provides a system and method, especially well suited for time-of-flight mass spectrometry wherein the width of a digital filter of varied over the mass spectrum to optimize the signal to noise improvement throughout the mass range. This is done without significantly compromising the mass resolution.
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patent: 4733073 (1988-03-01), Becker et al.
patent: 4945234 (1990-07-01), Goodman et al.
patent: 5168158 (1992-12-01), McComas et al.
patent: 5187365 (1993-02-01), Kelley
patent: 5594243 (1997-01-01), Weinberger et al.
patent: 5703358 (1997-12-01), Hoekman et al.
patent: 5770857 (1998-06-01), Fuerstenau et al.
patent: 5905258 (1999-05-01), Clemmer et al.
William H. Press et al, “Numerical Recipes in C”The Art of Scientific Computing Second Edition, 1992 (pp. 651-654).
Braginsky Leonid
Gavin Edward J.
Ciphergen Biosystems Inc.
Lee John R.
Quash Anthony
Townsend and Townsend / and Crew LLP
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