DE60126048T2 - Mass spectrometer and mass spectrometric method - Google Patents

Abstract

A way of increasing the dynamic range of a mass spectrometer which incorporates a time to digital converter such as commonly used with a time of flight mass analyser 9 is disclosed. A z-lens 4 upstream of the analyser 9 can be switched between a high sensitivity mode wherein a beam of ions 2 passing therethrough is substantially focused on to the entrance slit 10 of the analyser 9, and a low sensitivity mode wherein the beam of ions 2 is defocused so that the diameter of the beam substantially exceeds that of the entrance slit 10 of the analyser 9. Obtaining data in the low sensitivity mode in combination with obtaining data in the high sensitivity mode enable an order of magnitude increase in the dynamic range to be obtained. <IMAGE>

Description

The The present invention relates to a mass spectrometer and a mass spectrometry method.

Various Types of mass spectrometers are known which include a mass analyzer which includes a time-to-digital converter ("TDC"), also known as an ion-arrival counter. Time-to-digital converter z. B. at time-of-flight mass analyzers used in which packages of ions with substantially the same kinetic energy ejiziert in a field-free drift region or pushed out become. In the drift region, ions move with different Mass-to-charge ratios in each ion packet at different speeds and therefore reach an ion detector at the output of the drift region is arranged, at different times. A measurement of Ion transit time therefore determines the mass-to-charge ratio of this special ion.

Currently is one of the most common used ion detectors in time-of-flight mass spectrometers Single ion counting detector wherein an ion impinging on a detection surface receives an electron pulse generated by means of, for example, an electron multiplier. The electron pulse is typically amplified by an amplifier and a resultant electrical signal is produced. The electrical signal coming from produced the amplifier is used to determine the transit time of the ion, which has acted upon the detector by means of a time-to-digital converter, which is started as soon as an ion packet enters the first time Drift region is accelerated to determine. The ion detector and an associated one Circuit are therefore able to detect a single ion, which impinges on the detector or acts on this.

however such ion detectors have a certain dead time after an ion impact during the meeting the detector can not react to another ion impact. A typical detector dead time may be on the order of 1 to 5 ns. If during the determination of a mass spectrum ions arrive during the detector dead time, these are not detected in the sequence and this will have a disturbing effect have the resulting mass spectra.

It It is known to use dead-time correction software to detect glitches in to correct the mass spectra. However, software correction techniques are only able to provide a limited degree of correction. Even after the application of dead-time correction software, ionic signals, that to more than one ion arrival on average per ejection event at a given mass charge value, a saturation of the ion detector and therefore give a nonlinear response and inaccurate mass determination.

This Problem becomes particularly with the gas chromatography and similar Mass spectrometry applications because of the narrow chromatographic peaks or spikes, which typically presents to the mass spectrometer be, which z. B. at the base can be two seconds wide, amplified.

Known Time of flight mass spectrometers therefore suffer from a limited dynamic range especially in certain special applications.

The US 5,300,774 discloses a time-of-flight mass spectrometer with an aperture that can be adjusted to set a trade-off between sensitivity and resolution.

It is therefore desirable an improved mass spectrometer and improved mass spectrometry methods specify.

According to one The first aspect of the present invention is a mass spectrometer according to claim 1 proposed.

The Mass spectrometers according to the invention provides an extended dynamic range of the detector. Especially Is it possible, between two or more ranges of sensitivity during one Recording to choose or switch. One area is set to one high sensitivity to show or to offer. A second area is set, at a sensitivity lower by a factor of up to 100 than the first area to work. Preferably, the sensitivity difference at least one factor between the first and second sensitivity modes x10, x20, x30, x40, x50, x60, x70, x80, x90 or x100.

exact Mass measurements can carried out by adding a single point-lock or point-lock mass used in both the high and the low sensitivity range is common.

Although in the preferred embodiment the sensitivity is changed by the actuation of a z-lens, other embodiments are also conceivable in which, in a more general arrangement, the ion optical system between the ion source and the mass analyzer is changed or altered so that ions passing therethrough happen, be focused / defocused, whereby the ion transmission efficiency is changed. It is possible to alter ion transmission efficiency by a number of methods, including (i) altering a y-focusing lens, which may be a single lens; (ii) changing a z-focusing lens, which may be a single lens; (iii) using a stigmatic focusing lens, preferably having a circular opening which focuses / defocuses an ion beam in both the y and z directions; and (iv) using a DC quadrupole lens which can focus / defocus in the y-direction and / or z-direction as desired.

The Using an z-focus is opposite to other types of change the ion transmission efficiency is preferred because it has been proven has that there is a change at the resolution, the Mass position and the spectral offset, which otherwise with seem to be linked to focusing / deflecting the ion beam in the y direction, minimized. However, in less preferred embodiments the ion beam in the y direction, either instead of the z direction or additionally changed to the z-direction become.

With the preferred embodiment may be an increase of at least one order of magnitude in the dynamic range be achieved. It has been shown that the dynamic range of about 3.25 orders of magnitude at about 4.25 orders of magnitude at a GC peak width (gas chromatography peak width) of about 1.5 seconds at half height can be extended.

The The ion source is preferably a continuous ion source. Further Preferably, the ion source is selected from the group comprising: (i) an electron impact ion source ("EI ion source"); (ii) a chemical ionization ion source ("CI ion source"); and (iii) a Field ionization ion source ("FI ion source"). All of these ion sources can work with you a gas chromatography source (GC source). alternative and especially when using a liquid chromatography source (LC source) can an electrospray ion source or an atmospheric pressure ion source with chemical Ionization ("APCI ion source") can be used.

preferably, The mass analyzer includes a time-to-digital converter.

preferably, the mass analyzer is selected from the group comprising: (i) a quadrupole mass analyzer; (ii) a magnetic sector mass analyzer; (iii) an ion trap mass analyzer; (iv) a Time of Flight mass analyzer, preferably an orthogonal acceleration time-of-flight mass analyzer.

The Mass spectrometer further comprises control means which arranged or can be set up, around the z-lens, or more generally the ion optics, alternating or otherwise regularly and to switch between at least the first and second modes. In this arrangement, two data streams are considered to be two discrete functions, which represent two discrete data sets, saved. Once the ratio the data with high sensitivity to the data with low sensitivity, the Data used to produce linear quantitative calibration curves over four orders of magnitude to reach. Furthermore, the system can be arranged so that exact mass data is extracted from each track can. Therefore, if a particular eluent produces a mass spectral peak, which is saturated in the high sensitivity record and therefore low Mass measurement accuracy shows, the same mass spectral peak can be unsaturated and the mass in the lane with lower sensitivity is correct be measured. By using a combination of both tracks, how they can elute a sample exact mass measurements via a wide range of sample concentration can be generated.

The relative residence times in the high and low mode sensitivity can be either the same or more time can be in the mode with higher sensitivity than in the mode with lower sensitivity.

Z. For example, relative time can be compared in a high-sensitivity mode is spent on a low-sensitivity mode, at least Be 50:50, 60:40, 70:30, 80:20 or 90:10. In other words, can at least 50%, 60%, 70%, 80% or 90% of the time in the mode with higher sensitivity compared be brought to the mode with lower sensitivity.

According to one embodiment of the present invention, the control means may be arranged to switch the z-lens, or more generally the ion optics, from the first mode to the second mode as the detector approaches or undergoes saturation and / or the saturation z-lens, or more generally the ion optics from the second mode to switch to the first mode, if a higher sensitivity is possible without the detector is substantially saturated in the first mode. In the preferred embodiment, low mass peaks may be ignored in determining whether or not the sensitivities should be switched, and in one embodiment, the control means only switches the sensitivity modes when masses peaks that fall into, saturate or approach saturation in a particular bulk charge region (eg, m / z ≥ 50 or 75 or 100). In addition / alternatively, ignoring saturation of low mass peaks and concentrating on mass peaks in one or more specific mass ranges (which are preferably predetermined, but need not necessarily be in less preferred embodiments), the control means may determine the sensitivity modes based on whether specific, preferably predetermined, mass peaks approximate or saturated, or if an improved mass spectrum including this particular mass peak could be obtained by switching to another sensitivity mode.

Preferably the mass spectrometer also has a power supply, which is capable of the z-lens with DC voltage from -100 to +100 To supply volts. In one embodiment, the z-lens be a three-piece single lens in which the front and rear Electrode at substantially the same DC voltage, z. For positive ions about -40 V DC, be kept and a central electrode can be varied for positive Ions of about -100 V DC in the (focusing) mode with high sensitivity up to approximately +100 V DC in the (defocusing) mode with lower Sensitivity. For example, in the low sensitivity mode, a voltage may be present from -50 V DC, 0 V DC, 25 V DC, 50 V DC or 100 V DC can be applied to the central electrode.

Preferably the ion beam is diverged to have a profile or area which is essentially the profile or area of an entrance opening or aperture to the mass analyzer by at least a factor x2, x4, x10, x25, x50, x75 or x100, when the z lens transmits an ion beam passing through the z lens defocused.

Preferably in the first mode at least 85%, 90%, 95%, 96%, 97%, 98%, 99% or substantially 100% of the ions arranged or furnished or aligned to pass through the entrance opening.

Preferably be less than or equal to 15%, 10%, 5% in the second mode, 4%, 3%, 2% or 1% of the ions are arranged or set up, around the entrance opening to happen.

Preferably is the difference in sensitivity between the first and the second mode at least x10, x20, x30, x40, x50, x60, x70, x80, x90 or x100.

According to one second aspect of the present invention is a mass spectrometry method according to claim 20 proposed.

According to one embodiment is the ion-optical system arranged and set up, to operate in at least three different sensitivity modes. In further embodiments can four five, six, etc., to practically an infinite number of sensitivity modes be.

Various embodiments The present invention will now be purely exemplary and with With reference to the accompanying drawings, in which:

1 shows an array of y-focusing lenses and a z-lens upstream of a mass analyzer;

2 (a) and 2 B) Side views of a mass spectrometer according to a preferred embodiment show;

3 a plan view and a planar view of a mass spectrometer, which is connected to a gas chromatograph shows; and

4 shows experimental data showing the extended dynamic range achievable with the preferred embodiment.

A preferred embodiment of the present invention will be described below. 1 shows an ion source 1 , preferably an electron impact or chemical ionization ion source. An ion beam 2 coming from the ion source 1 is emitted, moving along an axis commonly referred to as the x-axis. The ions in the beam 2 are shown in a first y-direction as shown in the figure by the y-focusing and collimating lenses 3 focused. A z-lens 4 , preferably downstream of the y-lens 3 , is arranged to deflect or focus the ions in a second z-direction which is perpendicular to both the first y-direction and the x-axis. The z-lens 4 may comprise a number of electrodes, and in one embodiment may comprise a single lens in which the front and rear electrodes are maintained substantially at the same fixed DC voltage and the DC voltage applied to a central electrode can be varied to vary the DC voltage Degree of focusing / defocusing of an ion beam 2 that happens to change. A single lens can also be used for the y-lens 3 be used. At less preferred th arrangements can either be a z-lens 4 or a y-lens 3 (but not both) are provided.

The 2 (a) and 2 B) show side views of a mass spectrometer. In 2 (a) is shown that the ion beam 2 from an ion source 1 is emitted by the y-focusing and condensing lens 3 happens. The z-lens 4 , which works in a first mode (with higher sensitivity), focuses the beam 2 essentially within the acceptance area and the acceptance angle of an entrance slot 10 of the mass analyzer 9 , so that a significant proportion of the ions (ie a normal intensity) in the sequence in the analyzer 9 penetrates, which downstream of the entrance slot 10 is arranged.

2 B) shows the z-lens 4 operating in a second (lower sensitivity) mode, with the z-lens 4 being the ion beam 2 defocused, leaving the ion beam 2 a much larger diameter or area than the entrance slot 10 into the mass analyzer 9 Has. Accordingly, a much smaller portion of the ions (ie, a reduced intensity) in the sequence becomes the analyzer 9 in this mode of operation compared to the mode of operation in 2 (a) is shown to penetrate because a large percentage of the ions are outside the acceptance area and the acceptance angle of the entrance slit 10 will lie.

3 shows a plan view of a preferred embodiment. A removable ion source 1 is together with a gas chromatography interface or reentry tube 7 shown, which with a gas chromatography furnace 6 communicates. A sealant inlet is typically present but not shown. An ion beam 2 from the ion source 1 is emitted passes through the lens stack and the bundle plates 3 . 4 , which is a switchable z-lens 4 exhibit. The z-focusing lens 4 is arranged in a field-free region of the optics and connected to a fast-switching power supply, which can apply a DC voltage of -100 to +100 V. For positive ions, a DC voltage of -100 V becomes an ion beam 2 that passes through, focus and a more positive tension, eg. B. up to +100 V DC, becomes an ion beam 2 which passes through, essentially defocusing and thereby reducing the intensity of the ions entering the analyzer 9 penetrate, reduce.

Initially, the system can be set to a full (high) sensitivity. The voltage on the z-focus lens may then be varied, preferably manually, until the desired lower sensitivity is achieved. In one arrangement, the recording then results in rapidly switching the z-lens power supply between two (or more) predetermined voltages to repeatedly switch between the high sensitivity mode of operation and the low sensitivity mode of operation. High sensitivity and low sensitivity spectra can be stored as separate functions for post-processing. In the preferred embodiment, the z-lens switches 4 only between the higher sensitivity mode and the lower sensitivity mode by (and vice versa) if either the detector 13 saturated in one mode or the sensitivity can be increased in another mode without saturation.

Downstream of the ion optics or ion optics 3 . 4 is an automatic pneumatic isolation valve 8th arranged. The ion beam 2 by the ion optics 3 . 4 happened, then passes through an entrance slot or opening 10 into the analyzer 9 , Ion packets are then placed in the drift region of the preferred orthogonal acceleration time-of-flight mass analyzer 9 through a pressure plate 11 injected. Ion packets are then preferably reflected by a reflectron. The ions contained in a package are temporarily separated in the drift region and then separated from the detector 13 detected, which preferably contains a time-to-digital converter in its connected circuit.

4 Figure 12 shows experimental data showing that the dynamic range is from about 3.25 orders of magnitude to about 4.25 orders of magnitude (for a GC peak width of 1.5 seconds at half height) using a combination of the data from both the high sensitivity data set as well as from the low sensitivity record. In this particular case, the system has been set to provide a ratio of approximately 80: 1 between the high sensitivity record and the low sensitivity record. The experiment allowed equal acquisition time for both sets of data by alternating between the two sensitivity ranges between the spectra.

Standard solutions in In a concentration range from 10 pg to 100 ng HCB (hexachlorobenzene) were over the Gas chromatograph injected. The peak area response (equivalent to the ion number or count) for the recovered ion chromatogram of a mass-to-charge ratio of 283.8102 was plotted against the concentration. The results from the records with low sensitivity were multiplied by a factor of x80 before application to normalize them to the record with high sensitivity.

Claims (20)

Mass spectrometer comprising: an ion source ( 1 ); a lens ( 4 ) downstream of the ion source ( 1 ), the lens ( 4 ) in a first operating mode with relatively high sensitivity an ion beam ( 2 ) and the lens ( 4 ) in a second operating mode with relatively low sensitivity an ion beam ( 2 ) defocused; and a mass analyzer ( 9 ) downstream of the lens ( 4 ), wherein the mass analyzer ( 9 ) an ion detector ( 13 ) having; and characterized by control means arranged around the lens ( 4 from the first mode of relatively high sensitivity into the second mode of relatively low sensitivity, to the determination that certain mass peaks in a mass spectrum are becoming saturated or approaching saturation, and / or mass peaks within a given mass range are becoming saturated in a mass spectrum approach saturation, switch over. Mass spectrometer according to claim 1, wherein the lens ( 4 ) comprises a y-focusing lens. Mass spectrometer according to claim 1 or 2, wherein the lens ( 4 ) comprises a z-focusing lens. Mass spectrometer according to claim 2 or 3, wherein the lens ( 4 ) comprises a single lens having front, middle and rear electrodes, wherein the front and rear electrodes are maintained at substantially the same DC voltage during use and the center electrode is maintained at a different voltage than the front and rear electrodes. A mass spectrometer according to claim 4, wherein the front and rear electrode when used for positive ions between -30 and -50V dc be held and the middle electrode of a voltage in the first mode with high sensitivity from ≤ -80V DC to a voltage ≥ 0V DC in the second mode with low sensitivity is switchable. A mass spectrometer according to any one of the preceding claims, further comprising a power supply capable of supporting the lens ( 4 ) with a voltage of -100 to + 100V DC supply. Mass spectrometer according to claim 1, wherein the lens ( 4 ) is selected from the group consisting of: (i) a stigmatic focusing lens; and (ii) a DC quadrupole lens. Mass spectrometer according to one of the preceding claims, in which an ion beam ( 2 ) is diverged in the second low sensitivity mode to have a profile substantially over the profile or area of an entrance aperture (10). 10 ) to the mass analyzer ( 9 ) goes out. A mass spectrometer according to any one of the preceding claims, wherein in the first high sensitivity mode at least 85%, 90%, 95%, 96%, 97%, 98%, 99% or substantially 100% of the ions in an ion beam ( 2 ) to pass through an entrance opening ( 10 ) to the mass analyzer ( 9 ) to happen. A mass spectrometer as claimed in any preceding claim, wherein in the second low sensitivity mode, less than or equal to 15%, 10%, 5%, 4%, 3%, 2% or 1% of the ions in an ion beam ( 2 ) to pass through an entrance opening ( 10 ) to the mass analyzer ( 9 ) to happen. Mass spectrometer according to one of the preceding claims, wherein the difference in sensitivity between the first mode with high sensitivity and the second low sensitivity mode at least a factor x10, x20, x30, x40, x50, x60, x70, x80, x90 or x100. Mass spectrometer according to one of the preceding claims, wherein the ion source ( 1 ) is a continuous ion source. Mass spectrometer according to claim 12, wherein the ion source ( 1 ) is selected from the group consisting of: (i) an electron impact ion source ("EI ion source"); (ii) a chemical ionization ion source ("CI ion source"); and (iii) a field ionization ion source ("FI ion source"). Mass spectrometer according to claim 13, wherein the ion source ( 1 ) is connected to a gas chromatograph. Mass spectrometer according to claim 12, wherein the ion source ( 1 ) is selected from the group consisting of: (i) an electrospray ion source; and (ii) an atmospheric pressure chemical ionization ("APCI") source. Mass spectrometer according to claim 15, in which the ion source ( 1 ) is connected to a liquid chromatograph. Mass spectrometer according to one of the preceding claims, in which the mass analyzer ( 9 ) has a time-to-digital converter. Mass spectrometer according to one of the preceding claims, in which the mass analyzer ( 9 ) is selected from the group consisting of: (i) a quadrupole mass analyzer; (ii) a magnetic sector mass analyzer; (iii) an ion trap mass analyzer; (iv) a Time of Flight mass analyzer; and (v) an orthogonal acceleration time-of-flight mass analyzer. Mass spectrometer according to one of the preceding claims, wherein the special mass range includes a region of mass-to-charge ratio ("m / z") is selected from the group consisting of: (i) m / z ≥ 40; (ii) m / z ≥ 50; (Iii) m / z ≥ 60; (iv) m / z ≥ 70; (v) m / z ≥ 80; (vi) m / z ≥90; (vii) m / z ≥100; and (viii) m / z ≥ 110. Mass spectrometry method comprising the steps of: providing an ion source ( 1 ); Providing a lens ( 4 ) downstream of the ion source ( 1 ), the lens ( 4 ) focused in a first operating mode with relatively high sensitivity an ion beam and the lens ( 4 ) in an operating mode of relatively low sensitivity substantially defocusses an ion beam; and providing a mass analyzer ( 9 ) downstream of the lens ( 4 ), wherein the mass analyzer ( 9 ) an ion detector ( 13 ) having; and characterized by setting up, the lens ( 4 ) switch from the first high sensitivity mode to the second low sensitivity mode on the determination that certain mass peaks in a mass spectrum saturate or approach saturation and / or mass peaks within a given mass range in a mass spectrum are saturated or saturated to approach a saturation.