EP0613171B1 - Mass spectrometer for mass discrimination according to the time of flight - Google Patents

Description

The invention relates to a mass spectrometer with time-dependent mass separation with a micro-channel plate detector arrangement and with deflection electrodes which are subjected to time-variable deflection voltages, in which all ions fly straight ahead at a deflection potential of zero volts and by measuring their respective flight times can be detected.

Mass spectrometers are known which work with magnetic and / or electrical deflection elements and which separate an ion current as a function of mass and charge, so that a mass spectrum is produced.

High-resolution devices are e.g. double-focusing magnetic sector instruments with a resolution of more than 150,000 and ion cyclotron resonance mass spectrometers with a resolution of well over 1 million. Very heavy ions of a few 100,000 mass units are inaccessible to these devices because they can no longer be deflected or their cyclotron frequency can be determined too imprecisely.

Another type of mass spectrometer is the time-of-flight mass spectrometer, in which defined ion packets on their flight path are separated into isobaric ion packets which hit one detector in succession due to different speeds. With state-of-the-art data processing and time measurement, the time-of-flight mass spectrometers, which have been known for over 50 years, win in recent years in the detection of very high masses, although they are known to have a significantly poorer resolution.

In time-of-flight mass spectrometers, the time of flight is not proportional to the ion mass, but proportional to its root. Towards higher masses, the difference in flight time per mass unit becomes increasingly smaller. The flight times of the masses 100 and 101 differ by 0.5%, that of the masses 1000 and 1001 by 0.05%, etc. Flight distances of 1 to 2 m or more are common in these spectrometers. In order to record the flight time differences of the respective masses, enormous demands are made on the memory and processor capacity of the data system, which has its limits, however.

Very heavy ions of a few 100,000 mass units can be detected with time-of-flight mass spectrometers, but in the known systems they have an inaccuracy of +/- a few 100 mass units. For a resolution in individual dimensions, e.g. If the substance's isotope pattern could be recognized, the known time-of-flight mass spectrometry has so far not been able to do so in the high mass range.

In addition, in the very high mass range, it can happen that in the case of masses immediately following one another, only the first one generates a signal and the subsequent one is not detected because it arrives within the regeneration time of the detector.

Time-of-flight mass spectrometers with deflection electrodes are also known, in which, however, the deflection voltages do not cause the generation of a mass spectrum. For example, R.J. COTTER et al. (ANALYTICAL CHEMISTRY Vol. 64, No. 21, November 1, 1992, Columbus (US) pages 1027-1039: "Time-of-flight Mass Spectometry for the Structural Analysis of Biological Molecules") by applying a constant voltage to the deflection electrodes (cf. Fig. 7a page 1034) that with an orthogonal FAB ion source, the velocity component of all ions is compensated perpendicular to the mass spectrometer flight direction in order to direct the ions on mass-independent paths to the channel plate detector.

By applying the constant deflection voltage in a pulsed manner, certain mass ranges, which should not be analyzed by mass spectrometry, even become eliminated. However, the mass is determined exclusively by measuring the flight time of the ions (equation 4 page 1028 or equation 5 page 1029).

Time-of-flight mass spectrometers are also known for mass and energy analysis by means of position-sensitive time-of-flight measurement ("Rev.Sci. Instrum." 61 (1990), S 3134 - 3136). According to FIG. 1, page 3134, the ion masses are determined solely by measuring their flight times. Only the energy distribution of the ions can be additionally determined by measuring the local offset of the ions along the detector plane.

The object of the invention is to provide a mass spectrometer which works with time-dependent mass separation and causes a mass-dependent splitting of the different particles into different orbits in accordance with their mass to charge ratio.

This object is achieved according to the invention in that an ion packet from time-of-flight mass spectrometry flies past one or more deflection electrodes on its flight path, which are subject to time-varying deflection voltages which rise and / or fall according to a continuous time function and which can be set between two variable limit values with freely selectable gradients are, whereby the ion packets that fly past one another in time according to their mass-to-charge ratio are deflected to different extents, so that a spatially resolved mass spectrum can be registered which, in addition to and regardless of the temporally resolved mass spectrum, determines the mass on the basis of the locally different occurrence of the Allows ions at the detector level.

These training features ensure that masses arriving at a detector in time do not arrive at the same location, but are deflected to different extents depending on their mass and generate a spatially resolved mass spectrum.

The invention thus has the advantage that the time-of-flight differences, which become smaller and smaller with increasing mass, are meaningless for the mass determination because the mass determination takes place in another way, namely by determining the differently strong deflection of the ions. Another advantage is that the mass resolution with increasing mass gets better because the mass window detectable on the detector depends exclusively on the value of the voltage gradient, but not on the mass range examined.

The invention is shown in more detail in FIG. The mass spectrometer consists of a mass spectrometer housing 1, which has a length of approximately 300 mm. An ion source 7 and a channel plate 2 as a detector are arranged in this housing. Between the ion source 7 and the channel plate 2, two deflection electrodes 3 and 4 are calculated after a distance from the ion source 7 100 mm perpendicular to the flight direction of the ions. Shield electrodes 5 and 6 are also provided, which serve as diaphragms and to limit the electric field of the deflection electrodes.

Ion packets emitted by the ion source 7 with an energy of e.g. Accelerated 1000 eV to the channel plate 2, experience a respective directional deflection when passing between the deflection electrodes 3 and 4, which depends on the potentials present at the electrodes 3 and 4 at the moment when the ions between the deflection electrodes 3 and 4 fly through. Are the potentials symmetrical e.g. zero on both deflection electrodes 3 and 4, so all ions fly straight ahead. Are they statically asymmetrical, e.g. -150 V at electrode 3 and +150 V at electrode 4, it is known that all ions are deflected to the same extent regardless of their mass.

If the deflection potential of one of the deflection electrodes, e.g. electrode 3, is gradually changed as a function of time, or both electrode potentials are asymmetrically e.g. changed by voltage values with different signs, different ions are deflected to different extents, depending on their flight time, i.e. the ions which pass through the deflection electrodes 3 and 4 at a later time are deflected differently than the ions which have flown through at an earlier time. The differential changes in the electrode potentials must correspond to the ion flight times of the respective masses. Due to the adapted change in the potentials of the electrodes 3 and 4, ion packets arriving one after the other experience different deflections and hit the channel plate 2 at different locations.

mit:

U(t) =

Ablenkelektrodenspannung als Funktion der Zeit

U_dyn =

dynamischer Spannungsanteil

U_stat =

statischer Spannungsanteil

A time function that has proven to be particularly advantageous and according to which the deflecting electrode potentials can be varied is composed of a dynamic and a static part according to the equation: $${\text{U (t) = U}}_{\text{dyn}}{\text{- U}}_{\text{stat}}$$

With:

U (t) =

Deflection electrode voltage as a function of time

U _dyn =

dynamic voltage component

U _stat =

static voltage component

mit:

t =

Zeit, gemessen vom Start des Ionenpakets

t_delay =

wählbare Verzögerungszeit

U_deflect =

Ablenkspannungsgradient

The invention can advantageously be developed further by varying the dynamic component with the square of the time. In addition, the dynamic voltage component during ion flight time can be offset according to the equation: $${\text{U}}_{\text{dyn}}{\text{= (t}}^{\text{2nd}}{\text{- t}}_{\text{delay}}{\text{) x U}}_{\text{deflect}}$$

With:

t =

Time measured from the start of the ion packet

t _delay =

selectable delay time

U _deflect =

Deflection voltage gradient

If Equation 2 is used in Equation 1, the result is: $${\text{U (t) = (t}}^{\text{2nd}}{\text{- t}}_{\text{delay}}{\text{) x U}}_{\text{deflect}}{\text{- U}}_{\text{stat}}$$

A flight time-dependent mass deflection is achieved if a voltage which is time-dependent according to equation 3 is applied to one of the deflection electrodes 3 or 4. A comparatively greater deflection is obtained if the electrodes 3 and 4 have potentials of different signs, for example the voltage -U (t) on electrode 3 and the voltage + U (t) on electrode 4.

bezeichnet mit:

M(t) =

Ionenmasse in Abhängigkeit von der Flugzeit

U =

Beschleunigungsspannung und

c =

eine Gerätekonstante.

The following relationship is known from time-of-flight mass spectrometry: $${\text{t}}^{\text{2nd}}\text{= cx M (t) / U as}$$

labeled with:

M (t) =

Ion mass depending on the flight time

U =

Acceleration voltage and

c =

a device constant.

Substituting equation 4 into equation 3 and solving for M results in: $${\text{M (t) = ((U (t) + U}}_{\text{stat}}{\text{) / U}}_{\text{deflect}}{\text{+ t}}_{\text{delay}}\text{) x U / c}$$

mit:

M_g =

geradeaus fliegende, nicht abgelenkte Masse.

With U (t) = 0, both deflection electrodes 3 and 4 are dead. Equation 5 is simplified as follows for the undeflected mass flowing between deflection electrodes 3 and 4 at this time: $${\text{M}}_{\text{G}}{\text{= (U}}_{\text{stat}}{\text{/ U}}_{\text{deflect}}{\text{+ t}}_{\text{delay}}\text{) x U / c}$$

With:

M _g =

straight, undeflected mass.

This determines the mass that lies in the middle of the spectrum shown. For a mass deflected by the amount + y, equation 5 is obtained as: $${\text{M (t}}_{\text{+ y}}{\text{) = ((U (t}}_{\text{+ y}}{\text{) + U}}_{\text{stat}}{\text{) / U}}_{\text{deflect}}{\text{+ t}}_{\text{delay}}\text{) x U / c}$$

For a mass deflected by the amount -y, equation 5 is obtained as: $${\text{M (t}}_{\text{-y}}{\text{) = ((U (t}}_{\text{-y}}{\text{) + U}}_{\text{stat}}{\text{) / U}}_{\text{deflect}}{\text{+ t}}_{\text{delay) x U / c}}$$

mit

M_window =

Massenfenster M(t_+y) - M(t_-y)

Since the voltages U (t) for the masses deflected upwards and downwards by the amounts + y and -y are equal in magnitude but differ in sign, one subtracts equations 7 and 8 for the Mass windows from M (t _{+ y} ) to M (t _-y ) _hitting the detector: $${\text{M}}_{\text{window}}{\text{x U}}_{\text{deflect}}\text{= constant}$$

With

M _window =

Mass window M (t _{+ y} ) - M (t _-y )

The fundamental equation 9 states that the mass window, which can be detected on the detector, is independent of the mass of the detected ions in such a device. If the detectable mass window remains the same during the transition from small to high masses, this represents a zoom effect towards high masses with increasing resolution towards higher masses. This is a valuable advantage in comparison to the known time-of-flight differences, which decrease with higher mass.

To counteract energy blurring of the ion sources, an energy filter, which is customary in mass spectrometry, can be provided in FIGS. 1 and 2 perpendicular to the fanned ion current. Such an energy filter, which is arranged between the ion source 7 and the deflection electrodes 3 and 4, ensures that only homoenergetic ions pass through the aperture 5. If, on the other hand, the energy filter is arranged between the deflection electrodes 3 and 4 on the one hand and the channel plate 2 on the other hand, there is a signal expansion perpendicular to the fanned ion current with additional information about the energy distribution of the ion source without the mass resolution being significantly disturbed thereby.

FIG. 2 shows a fragmentation device 8 which is known in principle and which, for the purpose of MS / MS fragment ion analysis, can be introduced into the trajectory of the ions separated according to their mass-to-charge ratio in such a way that only ions of a desired mass make up the fragmentation device 8 can happen. Furthermore, separation electrodes 9 and 10 are provided, which locally separate all ions which leave the fragmentation device 8 according to their mass-to-charge ratio, specifically both the daughter ions formed by fragment ion and unfragmented mother ions.

Several units of fragmentation devices 8 and separation electrodes 9, 10 arranged one after the other in the flight path are provided for the examination of consecutive fragmentations by means of MS / MS / MS ... analyzes.

Claims (12)

1. Mass spectrometer with transit time-dependent mass separation, comprising a channel plate in the form of a plurality of individual detectors disposed in the detector plane, as well as deflecting electrodes which deflecting voltages variable in terms of time are applied to, wherein when the deflecting potential is switched off all ions follow a straight flight path,
   characterized in that deflecting voltages increasing and/or decreasing with a continuous time function are applied to said deflecting electrodes (3, 4), which voltages are adjustable with optionally selectable gradients between two variable limit values so that the ions are deflectable in correspondence with their mass-to-charge ratio to different flight paths and permit a determination of the mass on the basis of their locally different impingement on said channel plate (2).
2. Mass spectrometer according to Claim 1, characterized in that said deflecting voltages at said electrodes (3, 4) are composed by a static and a dynamic fraction.
3. Mass spectrometer according to Claim 2, characterized in that said deflecting voltages variable in terms of time satisfy the equation $${\text{U}}_{\text{(t)}}{\text{= (t}}^{\text{2}}{\text{- t}}_{\text{delay}}{\text{) x U}}_{\text{deflect}}{\text{- U}}_{\text{stat}}\text{.}$$

   
4. Mass spectrometer according to Claims 1 to 3, characterized in that several deflecting electrodes (3, 4) are disposed in the flight path.
5. Mass spectrometer according to Claim 4, characterized in that said potentials variable in terms of time and of different signs are applied to said deflecting electrodes (3, 4).
6. Mass spectrometer according to Claims 1 to 4, characterized in that said dynamic fraction of said deflecting voltages is proportional to time.
7. Mass spectrometer according to Claims 1 to 5, characterized in that the dynamic fraction of said deflecting voltages commences with a delay.
8. Mass spectrometer according to Claims 1 to 5, characterized in that the mass located in the centre of the imaged spectrum is defined by the equation $${\text{M}}_{\text{g}}{\text{= (U}}_{\text{stat}}{\text{/U}}_{\text{deflect}}{\text{+ t}}_{\text{delay}}\text{) X U/c}$$

   
9. Mass spectrometer according to any of the remaining Claims, characterized in that an energy filter is provided in a direction orthogonal on the sense of the diverged ion beam.
10. Mass spectrometer according to Claim 1, characterized in that the local resolution of the mass window impinging on said channel plate is defined by the equation $${\text{M}}_{\text{window}}{\text{x U}}_{\text{deflect}}\text{= constant,}$$

    

    independently of the mass range to be resolved.
11. Mass spectrometer according to any of Claims 1 to 10, characterized in that fragmenting means (8) and separating electrodes (9, 10) are disposed in said flight path.
12. Mass spectrometer according to Claim 11, characterized in that several units of fragmenting means (8) and separating electrodes (9, 10) are disposed in said flight path.

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