Mass resolution in time-of-flight mass spectrometers with reflectors

A method for the high resolution analysis of analyte ions in a time-of-flight mass spectrometer. The method consists of the generation of an intermediate time-focus plane for ions of a certain mass at a location between an ion source and an ion reflector, and then using the ion reflector to temporally focus the ions of equal mass and differing velocities which pass this plane at the same time onto a detector. For time-of-flight mass spectrometers with an ion selector, the ion selector is particularly favorable location for this intermediate plane with time focus; and with a collision cell for the collision fragmentation of the ions, the collision cell is a particularly favorable location.

The invention relates to high resolution analysis of ions with reflectron 
type time-of-flight mass spectrometers, whereby the ions are generated by 
laser desorption, particularly matrix-assisted laser desorption, from 
sample substances (analytes) on sample supports. In detail it relates to 
the process for improving mass resolution by the known method of delayed 
acceleration (sometimes called "delayed extraction", "time lag focusing", 
or "pulsed ion extraction") of the ions, and devices for the performance 
of this method. 
The invention consists of the generation of an intermediate time-focus 
plane for ions of a certain mass at a location between ion source and 
reflector, and then using the reflector to temporally focus the ions of 
equal mass and differing velocities which pass this plane at the same time 
onto the detector. For time-of-fight mass spectrometers with an ion 
selector, the ion selector is a particularly favorable location for this 
intermediate plane with time focus. For time-of-flight mass spectrometers 
with a collision cell for the collision fragmentation of the ions, the 
collision cell is a particularly favorable location. 
PRIOR ART 
The usual method of time-of-flight mass spectrometry with ionization of 
sample molecules (analytes) by laser-induced desorption from a sample 
support consists of subjecting the sample support to a constantly applied 
voltage of 5 to 30 kilovolts while facing a ground potential base 
electrode at a distance of about 10 to 20 millimeters. The ions, generated 
by a 1 to 20 nanosecond long laser light pulse, focused at the analyte 
layer on the sample support, leave the surface with a large spread of 
velocities. Particularly for the ionization method using matrix-assisted 
laser desorption, the spread of velocities can no longer be well focused, 
not even by a good reflector, which results in limitation of the mass 
resolution. 
For the ionization of large sample molecules using matrix-assisted laser 
desorption (MALDI), the large sample molecules are deposited on a sample 
support in a layer of minute crystals of low molecular matrix substance. A 
light pulse from a laser lasting only a few nanoseconds, which is focused 
onto the sample surface, vaporizes a small amount of matrix substance and 
causes a quasi-explosive process, whereby the sample molecules are 
embraced by the expanding vapor cloud. 
The vapor cloud expanding into the vacuum not only accelerates the 
molecules and ions of the matrix substance through its adiabatic 
expansion, but also the molecules and ions from the sample substance 
through viscous entrainment, which thereby receive higher kinetic energies 
than they would in conjunction with a thermal equilibrium. Even without an 
acceleration field, the ions attain average velocities of about 700 meters 
per second; the velocities are largely independent of the mass of the 
ions, but have a large velocity spread which extends from about 200 to 
2,000 meters per second. It can be assumed that the neutral molecules in 
the cloud also possess these velocities. 
During formation of the vapor cloud, a small portion of the molecules are 
ionized, and this includes the matrix molecules as well as the sample 
molecules. But during expansion of the vapor cloud, continuous ionization 
of the large molecules takes place due to further ion-molecule reactions, 
at the expense of the smaller matrix ions. 
The large velocity distribution and the time distribution of ion formation 
limit the mass resolution in linear as well as in energy-focusing, 
so-called reflectron type time-of-flight mass spectrometers. The 
resolution R of linear time-of-flight spectrometers is limited to values 
of about 600, even during application of high acceleration voltages which 
allow the spread of initial velocities to be reduced relative to the 
average velocity ultimately attained. 
But resolution is also limited in time-of-flight mass spectrometers with 
energy-focusing reflectors, because not all ions are formed at the same 
time and at the same potential in this process of continuing ionization. A 
spread of initial velocities alone could be focused out with the 
energy-focusing reflector. But ions are formed later in the expanding 
cloud through ion-molecule reactions, and these ions experience an initial 
potential which does not correspond to the surface of the sample support. 
This mixture of distributions of start velocities, start locations and 
start times for the ions can only be compensated for very incompletely, 
even with the best reflectors. The resolution of reflectron type mass 
sectrometrers, operated with MALDI, is limited to about R.apprxeq.2000. To 
a lesser degree, this also applies to other types of ionization by 
desorption with laser light pulses. 
The fundamental principle for an increase in the mass resolving power under 
conditions of pure velocity spread of the ions has been known for more 
than 40 years already. The method has been published in the article 
W. C. Wiley and I. H. McLaren, "Time-of-Flight Mass Spectrometer with 
Improved Resolution", Rev. Scient. Instr. 26, 1150, 1955. 
It concerns a method called "time lag focusing" by the authors. More 
recently it has been examined under various names (for example "delayed 
extraction" or "pulsed ion extraction") in scientific articles relating to 
MALDI ionization. Recent publications such as 
R. S. Brown and J. J. Lennon, "Mass Resolution Improvement by Incorporation 
of Pulsed Ion Extraction in a Matrix-Assisted Laser Desorption/Ionization 
Linear Time-of-Flight Mass Spectrometer", Anal. Chem., 67, 1998, (1995) 
or 
R. M. Whittal and L. Li, "High-Resolution Matrix-Assisted Laser 
Desorption/Ionization in a Linear Time-of-Flight Mass Spectometers", Anal. 
Chem., 67, 1950, (1995) 
may be regarded as the state of the art in current technology for 
application with linear time-of-flight mass spectometers. Up to now, no 
articles in the literature have appeared with technical solutions on 
time-of-flight mass spectrometers with energy-focusing ion reflectors. 
The fundamental principle of this method is simple: the ions of the cloud 
are allowed to fly at first for a brief time in a drift region without any 
electrical acceleration. The faster ions thereby separate themselves 
farther from the sample support electrode than the slow ones, and from the 
velocity distribution of the ions, a location distribution results. Only 
then is the acceleration of the ions suddenly initiated through a 
homogeneous acceleration field, i.e. with a linearly declining 
acceleration potential. The faster ions then have a larger distance from 
the sample support electrode, consequently, at the onset of the 
acceleration, they find themselves at a somewhat reduced acceleration 
potential, which results in a somewhat lower ultimate velocity for the 
drift section in the time-of-flight spectrometer than the ions which were 
initially slower. With correct selection of the time lag for the start of 
acceleration the initially slower, but after acceleration faster ions 
catch up to the initially faster, but after acceleration slower ions, 
directly at the detector. Ions of equal mass are consequently focused, in 
first order, at the location of the detector with respect to their flight 
time. In this way a high mass resolution is attained in a linear 
time-of-flight mass spectrometer. 
As a result, it is no longer important whether the ions have already formed 
during the laser light pulse, or after this time in the expanding cloud 
through ion-molecule reactions, as long as this formation takes place 
within the time before the acceleration potential is switched on. Since 
the velocity of the molecules is virtually unchanged by the ion-molecule 
reactions, those ions which were initially released as fast neutral 
molecules are also focused by this method. 
This time-focusing plane for ions of equal mass, which is normally adjusted 
at the location of the detector, can wilfully be adjusted to any location 
in the time-of-flight spectrometer by a different selection of time lag 
and potential drop. 
For reasons of good temporal resolution, time-of-flight spectrometers are 
often operated at very high acceleration voltages of up to 30 kilovolts. 
The switching of such high voltages for extremely short times of only a 
few nanoseconds is still almost unattainable even today and is associated 
with high costs. The authors of the 1955 article have already shown 
however that the total acceleration voltage need not be switched. 
Switching of a partial voltage suffices but requires an intermediate 
electrode to be installed in the acceleration path. Only the area between 
the sample support electrode and intermediate electrode need initially be 
field-free and then switched over into an acceleration field after the 
delay. The authors of the two cited most recent publications also use 
intermediate electrodes. 
To switch on the acceleration field, so far it has always been the 
potential of the sample support electrode which has been switched, and 
this was also the case with the authors of the two recent articles. As 
will be realised, the switching range is dependent on the distance between 
the intermediate electrode, and the sample support because for the same 
acceleration field the voltage difference to be switched is the smaller, 
the smaller the electrode distance. 
The term "high" potential, or "high voltage" always refers, in this 
context, to a potential which repels the ions and therefore accelerates 
them towards the drift tube. It can be a positive potential if the ions 
are positive and the drift tube is on ground potential, or it may be a 
negative potential if the ions are negative. 
Because quick switching of the voltage is technically all the easier to 
manage and all the more cost-effective, the smaller the switchable 
voltage, it is advantageous to position the intermediate electrode as 
closely as possible in front of the sample support electrode. Nevertheless 
there is also a lower limit for this distance, since the fastest ions must 
always remain in the drift region during the delay. 
Since the fastest ions however only move at velocities of about 2,000 
meters per second, and the delay according to the literature may only 
amount to about 1 microsecond at a maximum, the maximum flight path of the 
fastest ions during the field-free time lag is only about 2 millimeters. 
In practice, the distance of about 2 to 4 millimeters is selected between 
the intermediate electrode and the sample support electrode. 
This intermediate electrode however then impairs access for the focused 
laser light beam. Since it is also desirable to be able to observe the 
sample during analysis via a microscope aided by a television camera, 
access for a light beam for illumination and a clear view of the sample 
are also impaired. On the other hand, the acceleration field must be very 
homogeneous to create an non-divergent ion beam for the flight through the 
flight tube. 
As prior art for this method, use of a large area, very transparent, meshed 
metal grid had therefore been introduced as an intermediate electrode, at 
a distance of about 3 millimeters from the sample support electrode. The 
meshed grid generates a very homogeneous acceleration field in front of 
the sample support electrode. The large area meshed grid allows the laser 
light pulse to also pass through this grid. Microscopic observation is 
also performed through this meshed grid. Both of the most recent cited 
articles use this type of meshed grids (see e.g. FIG. 1 in Brown and 
Lennon's article), for both the intermediate and the base electrodes. 
This arrangement nevertheless has disadvantages. The laser light pulse 
liberates electrons from the meshed grid, the acceleration of which leads 
to interfering ions via impact with the residual gas. Observation suffers 
from considerable impairment of contrast, which is not very high anyway 
during this type of sample observation, due to a "curtain effect". The 
meshed grid can indeed be manufactured with good transparency, but even 
then however retains a portion of the ions. With more than one grid, the 
losses increase exponentially with the number of grids. Even with highly 
transparent grids of 80% transparency, only 2/3 of the ions still remain 
with two grids. At the grid of the intermediate electrode secondary ions 
are liberated which are accelerated in the field between the intermediate 
electrode and the base electrode, causing background noise. Another result 
of the inhomogeneous fields inside the grid meshes is the small-angle 
scattering of the ions leading to diffuse expansion of the beam which can 
no longer be corrected by lenses. 
In a concurrent patent application ref. number BFA 32/95, a gridless 
optical device is suggested for this method, which uses open apertures for 
the intermediate electrode and base electrode, and corrects the divergence 
of the ion beam generated by this using a single lens within the drift 
region past the base electrode. Laser light and illumination can penetrate 
through further apertures adjacent to the ion beam aperture, and 
observation is also possible through another such aperture. At this point 
the descriptive text of the cited patent application should be included 
here in full. 
The purpose of striving for good mass resolution is not only to achieve 
good mass determination or attain statements regarding the presence of 
heteroatom characteristic of an isotope by way of the visibly resolved 
isotopic pattern. A good mass resolution always provides an improved 
signal-to-noise ratio at the same time. In this way the analytic method 
becomes more sensitive and smaller substance amounts can be analyzed. 
OBJECTIVE OF THE INVENTION 
A method and a device for implementation of the known method for improving 
the resolution of time-of-flight spectrometers by delayed acceleration of 
the ions created by laser desorption ion sources is to be found, which can 
also be used on time-of-flight mass spectrometers with energy-focusing 
reflectors, and which particularly allows the high resolution measurement 
of daughter ions decomposed due to metastability or ones randomly 
fragmented by collision gases. 
DESCRIPTION OF THE INVENTION 
In a time-of-flight mass spectrometer with reflector, it makes absolutely 
no sense to make the time focusing plane coincide with the detector plane 
by appropriately adjusting the delayed acceleration, as is common use in 
linear time-of-flight mass spectrometers. The reflector temporally 
disperses ions of the same mass but different velocity, and thus destroys 
the velocity focusing caused by the delayed acceleration method. 
As was however already mentioned above, the plane of exact time-focusing 
for ions of equal mass can be adjusted as desired to any location along 
the flight path by the choice of time lag and acceleration field strength 
in front of the sample support electrode. 
It is therefore the basic idea of the invention to adjust this 
time-focusing plane to an arbitrary but fixed location between the ion 
source and the reflector by using delayed acceleration, and to set the 
reflector so that it consequently focuses the ions of equal mass which, in 
spite of differing velocities, pass this focusing plane at the same time, 
onto the detector. The reflector therefore views the focus plane as an 
intermediate (virtual) ion source which supplies ions of equal mass with 
the same start point (at exactly this plane) and the same start time but 
different start energies, and it can reflect these ions in such an 
excellent manner (to second order) that they again arrive on the detector 
at the same time in spite of differing start velocities. The conditions 
for creation of this intermediate (virtual) ion source can be easily set 
by the choice of delay (time lag) and potential drop (voltage difference) 
of the delayed acceleration. 
It is not disadvantageous that the ions of different masses already display 
a temporal mass dispersion when passing this focus plane. This mass 
dispersion becomes even larger due to the differing flight times for ions 
of differing masses up to the detector and generates the desired mass 
dispersion of the reflectron time-of-flight mass spectrometer. 
For this changed method of delayed acceleration for time-of-flight mass 
spectrometers with energy-focusing reflectors, the gridless ion source 
optical device can also be used to advantage, as is described in the 
concurrent patent application BFA 32/95 (U.S. patent application filed 
Apr. 4, 1996, having named inventors Armin Holle, Claus Koster and Jochen 
Franzen, and being identifiable by Bookstein & Kudirka, P.C. Attorney 
Docket No. B0004/7020.) 
This improvement of resolution for reflecting time-of-flight spectrometers 
is not however in itself of particular value, since the same results can 
be achieved by a longer linear time-of-flight spectrometer, which also has 
a greater mass dispersion due to its greater length, much more easily and 
without the complicated reflector. Only the additional spatial focusing of 
some types of reflectors may be additionally advantageous. 
However, it is a further basic idea of the invention to also use the same 
principle of focusing on ions decomposing due to metastability or on ions 
randomly fragmented in collision chambers. 
In time-of-flight mass spectrometers, ions are accelerated to have the same 
kinetic energy. The ion's mass is then measured by its velocity (via 
measured flight time and known flight length), which is, at constant 
energy, dependent on the mass only. In reflectron type spectrometers, a 
slight spread of initial kinetic energies can be fosused out by the 
energy-focusing reflector. 
During the generation of daughter ions by decay of parent ions, the 
velocity is kept, and mass and energy are reduced in the same proportion. 
The initial energy spread becomes a velocity spread. For daughter ions of 
a certain mass, the velocity spread again can be focused out by the 
energy-focusing (now: velocity-focusing) reflector. 
If a metastable ion decomposes en route between the ion source and 
reflector, its mass indeed changes but its velocity and direction 
undergoes virtually no change. If the reflector is now set so that it can 
reflect daughter ions of reduced mass with the same velocity, it enables a 
mass analysis of daughter ions. The electric field inside the reflector 
performs primarily an energy analysis, but because energy and mass of the 
newly formed daughter ions are proportionally reduced, a mass spectrum is 
taken with focusing of their differences in velocity. In this way a high 
mass resolution is attained during the detection of fragmentation products 
from metastable ions. The spectra of daughter ions from decomposing 
metastable parent ions can thereby be measured at high resolution. 
This principle of mass analysis for ion fragments of ions decomposing due 
to metastability has become known by the name "post source decay" (PSD). 
The method has now become wide-spread, although it only provides a low 
mass-resolving power. The improvement of mass resolving power described 
here can in particular provide the normally very noisy method with an 
improved signal-to-noise ratio. But also the mass determination of the 
fragment ions, which is especially important for amino acid sequence 
analysis of peptides and proteins, can be greatly improved. 
With complicated primary spectra showing many different ion types, the 
fragmented ions which have decomposed due to metastability can no longer 
be assigned to a certain parent ion type. Here, an ion selector helps 
which selects ions of equal velocity during their flight through the drift 
section. The ion selector is a fast switching element for the ion beam 
which deflects the unwanted ions and allows the selected ions to pass 
through. These ions consist of the parent ions and their metastable 
daughters which both have the same speed. There are different embodiments 
for this switching element, which is essentially a short pair of 
electrodes between which the ions must pass, and to which a laterally 
deflecting electric field can be applied very quickly. The ion selector 
must be located at a position where good separation of the ions of 
different masses through mass dispersion prevails, usually selecting for 
this a position somewhat midway between ion source and reflector. The mass 
resolving power (R) attained by velocity selection is moderate, amounting 
to only about 50 to 200 for very good ion selectors. The mass resolving 
power is limited by the fact that ions of the same mass do not pass the 
selector all at the same time due to the spread of velocities. In order to 
increase mass resolution, the intermediate time-focusing plane can be 
situated directly in the ion selector by delayed acceleration. 
As already noted, the ion selector chooses ions not actually according to 
mass, but rather to flight velocity. Since a daughter ion which has 
decomposed due to metastability has the same velocity as the parent ion 
from which it came, the ion selector also allows all fragmented ions of 
the selected ionic type to pass through as desired. In this way all the 
fragmented ions which decompose between the ion source and the reflector 
can be measured by an energy analysis by the reflector, resulting in a 
mass spectrum of the daughter ions. 
There are however particular advantages in measuring not only the 
independently decomposing, so-called metastable ions, but also the ions 
randomly fragmented in a collision cell through collisions with collision 
gas. During these collisions, particularly when using very effective heavy 
collision gases, notable changes in the velocity of the resulting 
fragmented ions can arise due to the principle of pulse reservation. If 
one however now locates the intermediate time-focusing plane by delayed 
acceleration exactly in the collision chamber, the initial and additional 
collision-induced spread of velocities can again be focused out in this 
way by the reflector. Fragmented ions which come from parent ions of the 
same mass and therefore leave the collision chamber at the same time, can 
be detected with high resolution, even if they suffer notable velocity 
changes due to heavy collision gases. 
When simultaneously using the ion selector and collision chamber, they 
should both be located as closely as possible to one another. Whether to 
locate the focusing plane by delayed acceleration in the ion selector or 
in the collision chamber is dependent upon problem definition of the 
analysis.

TICULARLY FAVORABLE EMBODIMENTS 
A particularly favorable embodiment is shown schematically in FIG. 1. The 
sample substance, together with the matrix substance, is applied in the 
form of a thin crystal layer onto the surface of metal Sample Support 
Electrode 1. The sample support electrode can be brought through a vacuum 
lock (not shown) into the vacuum of the mass spectrometer and contact is 
automatically made with a high voltage feeder (not shown). The sample 
support electrode can be moved in x-y direction using a moving device (not 
shown) parallel to its sample surface. In this way several sample 
assignments can be applied next to one another and analyzed one after 
another. 
The ion source consists of Sample Support Electrode 1, the Intermediate 
Electrode 2, the potential of which is switchable for this method, of Base 
Electrode 3, which is at the same potential as the flight tube, and of 
Single Lens 5. The flight tube (not shown) consists of Flight Path 8 of 
the time-of-flight spectrometer in front of Reflector 10, Flight Path 11 
after the ion Reflector 10, and Ion Detector 12. It is normally at ground 
potential. Einzel Lens 5, consisting of front electrode, terminating 
electrode, and center electrode, is attached at the start of the flight 
path directly behind Base Electrode 3. The front electrode and terminating 
electrode are both at the same potential as the flight tube, the center 
electrode at the same potential as the lens. 
At the beginning of the procedure, Sample Support Electrode 1 and 
Intermediate Electrode 2 are both at the high acceleration potential of 
about 30 kilovolts. Base Electrode 3 is at ground potential. The center 
electrode of the lens is at a previously optimized lens potential of about 
10 to 15 kilovolts. 
The sample is then irradiated by a brief laser pulse of about 3 nanoseconds 
length from Laser 7. The laser light pulse is deflected by Tilted Mirror 4 
onto Concave Mirror 6, and Concave Mirror 6 focuses the light pulse onto 
the sample surface on Sample Support Electrode 1. Cost-efficient nitrogen 
lasers have proven to be particularly suitable, delivering light at a 
wavelength of 337 nanometers. Relatively weak light pulses with a total 
energy of about 50 microjoules with a focus diameters of roughly 150 
mikrometers show good results. 
As has already been described above, a small amount of matrix and sample 
substance vaporizes, forming a cloud which explosively expands 
adiabatically into the surrounding vacuum. Some ions from the sample 
analyte substance form during the vaporization process, others form later 
in the cloud due to ion-molecule reactions with the ions from the matrix. 
Acceleration of all the molecules in the field-free region is essentially 
generated by the adiabatic expansion of the cloud which mainly consists of 
molecules from the matrix substance. The heavier molecules and ions from 
the sample substance are accelerated within the exploding cloud due to 
viscous entrainment, and therefore all the molecules and ions have about 
the same velocity distribution, ranging from about 200 to 2,000 meters per 
second, and reaching a maximum at about 700 meters per seconds. The cloud 
plasma is first neutral, since positive as well as negative ions, as well 
as some electrons, are present. Since the electrons quickly escape from 
the plasma, a slightly ambipolar acceleration of fringe ions takes place 
in the fringe areas which the escaping electrons generate between 
themselves and the remaining plasma. This effect is however minimal. 
The process of the adiabatic expansion of the cloud lasts only about 30 to 
100 nanoseconds, depending on the density of the cloud. After this time, 
all contact between the molecules is lost due to the thinning of the 
cloud, and further acceleration no longer takes place. The velocity 
distribution is thereby frozen and there are no more ion-molecule 
reactions. 
After a selectable time lag, the potential of the intermediate electrode is 
switched down to a new, selectable potential. We use a potential supply 
which can be switched with a delay of 100 to 300 nanoseconds at a 
potential range of up to 8 kilovolts with a switching speed of 8 
nanoseconds for the potential. Favorable values for raising the resolution 
are about 140 nanoseconds for time lag and 8 kilovolts for switching 
range. 
Until the acceleration is switched on, the fastest ions have flown further 
away from the sample support than the slow ones. They are therefore at a 
lower potential when acceleration is switched on, and no longer receive 
full acceleration from the high voltage. This effect leads, as already 
stated above, to a temporal focusing of ions of equal mass in one focus 
plane, the position of which can be adjusted by choice of time lag and 
acceleration field. For a time-of-flight mass spectrometer without 
reflector operation, the position of this focus plane is adjusted exactly 
to the ion detector; in this way, all ions of equal mass arrive there 
through the cloud at the same time, in spite of different initial 
velocities, and mass resolution is increased. 
If the reflector is used, the position of the focus plane must then, 
according to the invention, be adjusted to a location between the ion 
source and ion reflector, therefore for example at Position 9 on FIG. 1. 
This location then forms, for Reflector 10, a kind of virtual ion source, 
which releases ions of the same mass at exactly the same time although the 
ions do have a velocity spread. Reflector 10 must therefore now be 
adjusted in such a way using a certain ratio of deacceleration field and 
reflection field, that it velocity-focuses the ions from this virtual ion 
source with time-focus onto Detector 12. 
If certain types of ions decompose during the flight path between ion 
source and ion reflector into daughter ions and neutral fragments, the 
daughter ions have the same gross velocity (and same velocity spread) as 
the parent ions from which they came. The daughter ions however have a 
lower mass and therefore at the same velocity a lower kinetic energy. 
Since the ion reflector can be used as an energy analyzer, it can be 
implemented for measurement of energies and therefore of masses of the 
daughter ions. This principle of mass analysis for ion fragments of ions 
decomposing due to metastability is widely known by the name "post source 
decay" (PSD). The method has now become widespread. 
The principle of the virtual ion source with time-focused ions of one mass 
also applies to the daughter ions. These too have strict time-focusing in 
the focus plane. Even such ions which decompose after flying through this 
focus plane have virtual focusing in this plane, i.e. they appear to have 
flown away from the focus plane at the same time. The previously small 
mass resolving power of the PSD method is therefore greatly increased by 
this invention, as a result of which mass determination of the fragmented 
ions, which is particularly important for the amino acid sequence analysis 
of peptides and proteins, is greatly improved. In addition, the method has 
suffered up to now from very strong background noise in the spectra. The 
improvement in the mass resolving power mentioned here now provides the 
method with a highly improved signal-to-noise ratio. Both 
improvements--mass resolution and signal-to-noise ratio--open up new 
application areas for this method. 
With complicated primary spectra showing many different ion types the 
fragmented ions which have decomposed due to metastability can no longer 
be assigned to a certain parent ion type. Here, an ion selector helps 
which selects ions of equal velocity during their flight through the drift 
section. FIG. 2 shows a mass spectrometer with such an Ion Selector 13. 
Ion Selector 13 is a fast switching element for the ion beam which 
deflects the unwanted ions and allows the selected ions to pass through. 
It has usually the form of a short electrode plate pair between which the 
ions must pass and to which a laterally deflecting electric field can be 
applied very quickly. The masses of the ions must be separated here as 
well as possible, so that the ion selector already sees a good separation 
of ions of different masses. Usually the center position between the ion 
source and reflector is selected here. The focusing-plane generated by the 
delayed acceleration is best located exactly in the ion selector as is 
shown in FIG. 2. 
As already noted, the ion selector selects ions not actually according to 
their mass, but rather according to their flight velocity. Since a 
daughter ion which has decomposed due to metastability has the same 
velocity as the parent ion from which it came, the ion selector allows all 
fragment ions of the selected ion types to pass through as desired. 
Therefore all fragmented ions, which are formed between the ion source and 
reflector through decomposition of parent ions, are measured by energy 
analysis of the reflector as a mass spectrum, irrespective of whether the 
decay takes place in front of or behind the selector. 
There are particular advantages, however, if one not only measures the 
independently decomposing ions, but also the ions decomposinng in 
Collision Cell 14, as shown in FIG. 3, randomly fragmented through 
collisions with the molecules of a collision gas. Collision Cell 14 is 
differentially pumped by Pump 15, the collision gas supplied by Feeder 16. 
During collisions of ions flying through with the molecules of the 
collision gas, notable changes in the velocity of the resulting fragmented 
ions can arise due to the principle of pulse reservation, particularly if 
heavy collision gas molecules are used. If however Time-Focusing Plane 9 
is now situated by delayed acceleration exactly in Collision Chamber 14, 
the initial and additional collision-induced spread of velocities can be 
focused out again by the reflector. Fragmented ions which come from parent 
ions of equal mass, which therefore leave the collision chamber at the 
same time, can be detected with high resolution even if they suffer 
notable velocity changes due to heavy collision gases. Collision chambers 
are used to particular advantage in conjunction with ion selectors. 
Collision chambers need not be continuously filled with collision gas. It 
is sufficient if the collision chamber is filled with short gas bursts. 
The example given here of a time-of-flight mass spectrometer and of a 
method for this invention can naturally be varied in many ways. The 
specialist in the development of mass spectrometers, especially in the 
development of desorption ion sources, can easily implement these 
variations. 
For example, the collision chamber can be replaced by a simple gas nozzle 
which faces a high vacuum pump. This simple arrangement is equivalent to 
that of a complex collision chamber, but costs only a fraction. The nozzle 
can have gas fed through it continuously, but it is even better to operate 
it in pulses using a switching valve. The ion reflector, which is 
illustrated in the schematics of FIGS. 1 to 3 as a grid reflector, can be 
replaced favorably by a gridless reflector which even may have additional 
spatial focusing properties. The ion selector can be designed as a fanned 
switching element These changes are not to be described further here, 
since they are known to the specialist from publications and patents. 
FIGS. 4 to 6 show measurements of mass spectra using MALDI methods, which 
were scanned with an increase of mass resolution through delayed 
acceleration of the ions after a laser light pulse. In FIGS. 4 and 5, 
primary spectra are shown which normally only depict undecomposed ions. 
With bovine insulin (FIG. 4), the fragmented ions, which resulted from a 
splitting off of water, are however already visible at the same time as 
the molecule ions. In FIG. 6, a partial spectrum of fragmented ions from 
angiotensin is shown. This spectrum shows a resolution of isotopic lines 
which would not be visible without an improvement of the resolution by 
delayed application of acceleration and the special position of the focus 
plane according to this invention.