Ion trap mass spectrometer with vacuum-external ion generation

The invention relates to an RF quadrupole ion trap mass spectrometer with ionization of the substance molecules outside the vacuum system. The invention consists of using only a single high-vacuum pump for generating the vacuum without any differential pump stages and generating the necessary pressure stages for operating the mass spectrometer by means of a sequence of openings with adjusted conductances. The necessarily very small inlet opening to the vacuum system is only able to transport very small quantities of ions of the analyzed substances in the gas stream. However, these quantities are adequate for operating the mass spectrometer because the ion trap used as mass spectrometer is capable of collecting and storing ions over relatively long periods of time.

The invention relates to an RF quadrupole ion trap mass spectrometer with 
ion of the substance molecules outside the vacuum system. 
The invention consists of using only a single high-vacuum pump for 
generating the vacuum without any differential pump stages and generating 
the necessary pressure stages for operating the mass spectrometer by means 
of a sequence of openings with adjusted conductances. The necessarily very 
small inlet opening to the vacuum system is only able to transport very 
small quantities of ions of the analyzed substances in the gas stream. 
However, these quantities are adequate for operating the mass spectrometer 
because the ion trap used as mass spectrometer is capable of collecting 
and storing ions over relatively long periods of time. 
PRIOR ART 
The generation of ions for mass spectrometric analysis within the vacuum 
system has the disadvantage that a large excess of substance molecules has 
to be introduced into the vacuum system because the yield of ions produced 
by in-vacuum ionization methods is generally very small. This entails the 
risk of contamination of the vacuum system by condensation of substance 
molecules on the walls. Therefore the trend is increasingly towards 
generating the ions outside the vacuum system of mass spectrometers and 
transporting them into the vacuum system by suitable methods. 
Such vacuum-external ion sources include, for example, electrospray 
ionization (ESI), with which substances of exceptionally high molecular 
weights can be ionized. Electrospraying is frequently coupled with modem 
separation methods, such as liquid chromatography or capillary 
electrophoresis. The generation of ions by ionization with inductively 
coupled plasma (ICP), which are needed for inorganic analysis, also 
belongs to this group of vacuum-external ion production. Finally, there is 
atmospheric pressure chemical ionization (APCI) with a primary ionization 
of the reactant gases by means of corona discharges or beta emitters with 
low energy of the emitted electrons. APCI is used, amongst other things, 
for the analysis of pollutants in the air and, in addition, is 
particularly suitable for coupling mass spectrometry with gas 
chromatography. Other types of vacuum-external ion sources, such as 
Grimm's hollow cathode glow discharges and others, are still being 
investigated and developed. 
According to prior customary practice, the ions from these ion sources are 
admitted into the vacuum of the mass spectrometer together with large 
quantities of ambient gas. For this purpose, small openings with diameters 
of approximately 30 to 300 micrometers, or 10 to 20 centimeter long 
capillaries with internal diameters of approximately 500 micrometers are 
used. The excess gas must be removed by means of differentially operating 
pump stages; in the case of commercially available mass spectrometers, two 
or even three differential high-vacuum pump stages are used with a 
corresponding number of pump-connected chambers in front of the main 
chamber of the mass spectrometer. Including the roughing stages, three to 
four (or even five) vacuum pumps are therefore used with one mass 
spectrometer. 
The successive vacuum chambers are only connected by very small openings 
and the ions must be passed through these small openings from chamber to 
chamber. The pressure in the first differential pump chamber of 
commercially available mass spectrometers is usually a few millibars, in 
the second differential pump chamber it is approximately 10.sup.-3 to 
10.sup.-4 millibar, if only two differential pump chambers are used, and a 
level of 10.sup.-6 to 10.sup.4 millibar is maintained in the main vacuum 
chamber. The mass spectrometer is located in the main vacuum chamber. The 
ions have to be passed through the differential pump chambers and the 
small openings between the chambers, during which process large ion losses 
occur. 
To transfer the ions through these chambers, RF multipole ion guides are 
often used, but these are only suitable at pressures below several 
10.sup.-2 millibars, as otherwise electrical discharges occur. The ion 
guides can therefore only be used in the second differential pump chamber 
or in the main vacuum chamber. They are used to advantage in a pressure 
range of some 10.sup.-3 millibars, since they then rapidly damp the radial 
oscillations and also the longitudinal movements of the ions, thereby 
providing good conditions for further transport of the ions and for 
analysis of the ions in the mass spectrometer. 
As is already apparent from this description, the differentially operating 
pump stages used up to now are disadvantageous. They make it more 
difficult to transfer the ions to the mass spectrometer, make operation of 
the mass spectrometer complex and require the use of several costly, large 
fore-pumps and high vacuum pumps. 
In the following pages the examination is restricted to mass spectrometers 
using quadrupole RF ion traps invented by Wolfgang Paul. These offer the 
advantage of extremely high sensitivity and the possibility of temporal 
tandem mass spectrometry (MS/MS or MS.sup.n) for scanning daughter ion 
spectra or granddaughter spectra of selected, fragmented parent ions. The 
main goal of this invention is the operation of a mass spectrometer with 
only a single high vacuum pump. The ion trap mass spectrometers, referred 
to below as "ion traps" for short, offer four decisive advantages for this 
purpose. Firstly, they function optimally when operated with a collision 
gas pressure between 10.sup.-4 and 10.sup.-2 millibar in their interior. 
This is helpful for operation with only a single high vacuum pump. 
Secondly, these mass spectrometers require only very small ion currents, 
since they are able to collect the ions over long periods of time, if 
necessary many minutes, and do allow the mass spectrometric analysis of 
the ions to wait up to time when the mass spectrometer has been filled 
with a sufficient number of ions. Thirdly, they use all of the ions 
collected, in contrast of most other types of mass spectrometers which 
operate as filters an throw away most of the ions. Finally, they are 
exceptionally fast in analysis operation, so that spectrum scanning takes 
only approximately 20 milliseconds. 
The ion traps essentially consist of a rotation-hyperbolically shaped ring 
electrode and two rotation hyperbolic end cap electrodes. Usually the ring 
electrode is supplied with the necessary RF voltage for generating the 
quadrupolar RF field, whilst the end cap electrodes are kept near to 
ground potential. The RF voltage is also frequently referred to as "drive 
voltage" of the ion trap. The ions are held and stored in quasi-harmonic 
retroactive force fields by the effect of the quadrupolar RF field. Their 
quasi-harmonic ("secular" ) oscillation can be damped by a collision gas, 
and the ions then collect in a cloud in the center of the ion trap. 
Well-formed ion traps can store ions for a very long time. If the ions do 
not decompose, they can remain stored for many hours without any losses. 
This makes it possible for ions to be collected over a period of many 
hundreds of milliseconds, or even many seconds or minutes, and only then 
examined by mass spectrometry. 
At the end cap electrodes an RF voltage can be applied, which has a lower 
frequency and a much smaller voltage compared to the driving voltage. With 
this "excitation RF voltage" the ions, whose secular oscillation in the 
axial direction of the ion trap conforms with the excitation frequency, 
can be resonantly excited to produce oscillations, and, if so wanted, they 
can be ejected from the ion trap through ion ejection holes in one of the 
end caps. The ions can then be measured as an ion current outside the ion 
trap using an ion detector. Since the secular oscillation of the ions is 
unambiguously dependent on their mass-to-charge ratio, mass spectra can be 
scanned with this method. Such a mass-selective ejection of ions can be 
improved in many different ways, for example by making use of non-linear 
resonances generated by the addition of higher multipole fields, or by 
superimposing additional quadrupole fields with other frequencies. 
Dipolar excitation of the ion oscillations can be used in the way already 
known for isolating individual ion types and for collisionally induced 
fragmentation. In this way it is possible to scan daughter spectra of 
selected parent ions. 
In general, the end cap electrodes are adjusted and fixed very precisely in 
relation to the ring electrode, usually using insulating spacers. If rings 
made of glass, ceramic or plastic are used for this purpose, ion traps are 
produced in the form of sealed chambers whose only connection with the 
surrounding vacuum is via the ion inlet holes and ion ejection holes. 
OBJECTION OF THE INVENTION 
The objective of the invention is to find a device with which ions from a 
vacuum-external ion source can be measured and analyzed with an ion trap 
mass spectrometer, without using more than one high vacuum pump for the 
mass spectrometer. It would be advantageous, though not necessary, to have 
temporary storage of the ions in the vacuum section of the mass 
spectrometer in order to also collect ions during the periods when the 
ions are being analyzed in the ion trap. 
IDEA OF THE INVENTION 
For all sensitive mass spectrometers, electron multipliers are used 
exclusively as detectors, and these detectors are the most 
pressure-critical devices of the whole spectrometer. It is therefore the 
basic idea of the invention to make the gas stream which guides the ions 
into the vacuum system so small that the high vacuum pump used is adequate 
for generating the necessary high vacuum in the region of the detector. 
For this purpose, the ion detector is best installed directly in front of 
the high vacuum pump. 
For modern secondary electron multipliers, a working pressure of 10.sup.-5 
millibar is sufficient, and for some multipliers even a still poorer 
vacuum of up to 10.sup.-4 millibar will do. If one uses a small 
turbomolecular pump with a suction capacity of only 70 liters per second, 
a gas inflow of 0.7 microliters per second, i.e. approx. 40 microliters 
(or cubic millimeters) per minute, can be tolerated for maintaining a 
vacuum pressure of 10.sup.-5 in front of the pump port. Such high vacuum 
pumps with suction capacities of 70 liters per second are supplied as 
standard by several companies. They are each equipped with a drag stage 
and can be operated with simple diaphragm fore-pumps. This combination 
provides a very economical and space-saving solution for vacuum generation 
for the small mass spectrometer. 
However, this high vacuum pump with 70 liters per second is only intended 
as particularly favorable example. For an ion getter pump with a suction 
capacity of 20 liters per second, an only slightly less favorable case can 
be constructed. Even with a tiny ion getter pump with only 2 liters per 
second, an interesting mass spectrometer for pollutant analysis can be 
designed. Nevertheless, in the following pages the mass spectrometer with 
the pump for 70 liters per second will be considered primarily. 
To be able to transport the largest possible number of ions in the small 
gas stream of 0.7 cubic millimeters per second, the gas velocity during 
inflow into the vacuum system must be made as high as possible. Only then 
will the space-charge limitations in the gas flow be small. So it is 
important to find an easy-to-handle and easy-to-manufacture inlet nozzle 
with favorable characteristics, with which the ions can be transferred 
into the vacuum. 
It is therefore a further basic idea of the invention to use commercially 
available capillaries for this inflow, which are, however, kept extremely 
short. 
As an example, a commercially available glass capillary with a diameter of 
10 micrometers, which is shortened to a length of one millimeter, 
generates a gas flow of 0.64 cubic millimeters of normal air into the 
vacuum. A gas velocity in the inlet area of the inlet capillary of approx. 
13 meters per second is generated, whilst on the vacuum side the velocity 
in the capillary is very much higher. If one assumes that (a) the ions fly 
into the inlet capillary at intervals of 2 micrometers, (b) approx. 10,000 
ions per filling are needed, and (c) the ion trap really traps only 5% of 
the ions introduced, the ion trap can be filled in 40 milliseconds under 
these conditions. The plasmas required for this purpose with a density of 
5,000,000 ions per cubic millimeter (corresponding to 10 attomol of 
ionized substance in 30 nanomol of air, or a concentration of 0.3 ppbm), 
can certainly be manufactured if the plasma contains positive and negative 
particles simultaneously. Since one needs only 20 milliseconds for the 
analysis, approximately 14 spectra per second can be scanned on the basis 
of these assumptions. 
If the space between the ions flying into the inlet area of the capillary 
is larger, e.g. only one ion every 10 micrometers, this is still 
sufficient for four to five spectra per second. 
Commercially available metal capillaries with very small capillary 
diameters can also be used in this way. 
However, the invention is not necessarily restricted to short capillaries. 
Very narrow orifice nozzles manufactured, for example, by electron-beam 
drilling or laser drilling can be used for this purpose. Short orifice 
nozzles have a still higher inflow velocity and can, when viewed 
superficially, guide more ions into the vacuum. However, this no longer 
applies if the Debye length of the ionized plasma that is to be guided 
into the vacuum is significantly smaller than the orifice diameter. 
Therefore, in all probability, there is an optimum ratio between diameter 
and length of the inlet opening, which must be determined experimentally. 
On the other hand, orifice nozzles are more liable to become blocked by 
minute dust particles. 
Since it is not yet known which shape of inlet nozzle provides optimum use 
of the ion inflow, the term "capillary inlet openings" used in the 
following pages is intended to also include fine orifice nozzles. 
The ion trap must only be filled with ions during the filling period. In 
the analysis phase of the ions, e.g. during the spectrum scanning phase, 
filling must not take place. However, it is difficult to ensure that ion 
transport in front of or in the capillary nozzle is restricted to the 
filling period of the ion trap. It is far easier to allow ion transport 
into the vacuum to take place continuously and to switch the ion beam only 
where and when the ions enter the ion trap. For this purpose a switching 
element is required which can hinder the ions at the inlet of the ion trap 
in spite of the high velocity which keeps the ions in the outflowing gas. 
It is therefore a further basic idea of the invention to store the ions 
temporarily in the vacuum, but before they enter the ion trap, and when so 
doing to thermalize them and only introduce them into the ion trap during 
the filling period. Intermediate storage is achieved simply with an RF ion 
guide in which the ions can easily be stored by means of ion reflectors 
installed on both sides. In the ion guide, ions are thermalized when the 
ion guide is in an area of favorable pressure between 10.sup.-2 and 
10.sup.-3 millibar. Thermalization increases the trapping likelihood in 
the ion trap, and makes entry into the ion trap more easily switchable. 
Filling the trap with ions from the ion guide can be achieved by raising 
the mid-potential of the RF ion guide above the potential of the end cap 
of the quadrupole ion trap for the duration of the filling period, so that 
the ions can flow off into the quadrupole ion trap. However, the ion trap 
can also be filled, without changing the mid-potential of the RF voltage 
of the ion guide, by means of a switchable drawing lens located between 
ion guide and ion trap. 
Filling from the ion guide takes approximately 20 milliseconds. Together 
with a further 20 milliseconds analysis time, this gives a scanning rate 
of 25 spectra per second. This high scanning rate naturally presupposes a 
sufficiently high ion density outside the vacuum so that sufficient ions 
for a spectrum scan can be introduced into the ion guide in 40 
milliseconds and stored, as already discussed above. 
Such a high scanning rate for the spectra is, however, often unnecessary. 
Even for ionization methods which deliver lower ion densities, such a 
low-cost mass spectrometer is quite useful. 
For scanning daughter ion spectra, approximately 80 milliseconds are 
needed, which produces approximately 10 daughter ion spectra per second. 
Here the collecting time of the ions in the ion guide is longer. This can 
be used favorably for overfilling the ion trap before isolating the parent 
ions, which produces daughter ion spectra with a significantly better 
signal-to-noise ratio. 
Furthermore, collection of ions in the ion guide can be used to separate 
out undesirable ions below a threshold for the mass-to-charge ratio, for 
example the reactant gas ions of an APCI ionization. For this purpose the 
ion guide is operated with an RF voltage in such a way that these ions are 
not stored stably and therefore escape from the ion guide. 
For operating the ion guide and ion trap, vacuum pressures far above the 
operating pressure of the secondary electron multiplier are necessary. 
Therefore, pressure stages must be introduced which achieve the optimum 
operating pressures. Favorable collision gas pressures in the ion trap and 
ion guide are between 10.sup.-4 and 10.sup.-2 millibar. If air is used as 
the collision gas, the optimum collision gas pressure in the ion trap is 
between 4.times.10.sup.-4 and 8.times.10.sup.-4 millibar, and in the 
antechamber with the ion guide it is approx. 5.times.10.sup.-3 millibar. 
This pressure of 5.times.10.sup.-3 millibar can be maintained by a single 
ion entrance hole in the ion trap end cap with 1.4 millimeter diameter. 
With 7 holes of 1,4 millimeter diameter as ion exit holes, a pressure of 
6.times.10.sup.-4 millibar is maintained inside the ion trap, under the 
above flow conditions of 0.7 microliters per second. If helium is used by 
the optimum pressures should be higher by approximately a factor of 6. It 
is therefore a further basic idea of the invention to design the ion traps 
as sealed chambers, to guide the gas stream from the capillary inlet 
opening to the pump entirely through the ion trap, and to design the 
dimensions of the ion inlet opening (if present) and the ion ejection 
opening(s) such that optimum pressure conditions are created.

TICULARLY FAVORABLE EMBODIMENTS 
The particularly favorable embodiment which is described here and shown in 
FIG. 1 operates according to the invention with a vacuum-external ion 
source 1 and an RF quadrupole ion trap consisting of two end cap 
electrodes 6 and 8 and a ring electrode 7, which takes the form of a mass 
spectrometer and has only a single high vacuum pump 13, according to the 
invention. A "turbo-drag" pump with 70 liters per second suction capacity 
and 65 millimeter flange diameter may be used, for which a fore-vacuum of 
approx. 20 millibars is sufficient. The latter can be operated at very low 
cost by means of a four stage diaphragm fore-pump which weighs less than 
800 grams. As a special feature, the mass spectrometer contains an ion 
guide 5, which serves to thermalize and temporarily store the ions which 
have been entrained and accelerated in the gas stream of the capillary 
inlet opening 3. The inlet capillary dimensions for the optimum flow of 
0.7 microliters per second, and the optimum aperture diameters for the 
inlet and exit holes in the ion trap end caps are given above. 
This mass spectrometer can be used for many purposes, for example as a very 
low-cost mass spectrometric detector for gas chromatography with the 
ability to confirm doubtful identifications by scanning daughter ion 
spectra of selected parent ions with the aid of various methods which are 
well known from the literature. 
Using electrospray methods for ionization, this mass spectroscopic detector 
can also be utilized for liquid chromatography or electrophoresis. 
Quadrupole systems, hexapole systems or systems with an even larger number 
of poles can be used as RF ion guide 5. Pentapole systems are also 
possible, whose operation requires a five-pole rotational RF voltage, as 
described in patent application BFA 20/95. Systems with a larger uneven 
number of rotational poles can also be used. 
By changing the potential on the axis or at the center of the ion guide 5 
in relation to the potentials of the wall pf the vacuum chamber 4 of end 
cap 6, the ion guide 5 can be used to store ions of a single polarity, 
i.e. either positive or negative ions. The potential on the axis is 
identical to the zero potential of the RF voltage on the RF ion guide. The 
stored ions constantly run back and forth in the ion guide 5. Since they 
attain a speed of approx. 500 to 1,000 meters per second in the adiabatic 
acceleration phase of gas expansion, they initially run through the length 
of the ion guide several times per millisecond. Their radial oscillation 
in the ion guide depends on the angle of injection. 
Another extreme of a favorable embodiment consists of a tiny mass 
spectrometer which works with a very small ion trap with a ring radius of 
only 0.5 centimeters and is evacuated by a tiny ion getter pump with a 
diameter of 2 centimeters and a suction capacity of 2 liters per second. 
The complete spectrometer--without the electronics--is only 2.5 
centimeters in diameter and 15 centimeters long. The ions are admitted 
direct into the ion trap via a capillary 6 micrometers in diameter and 4 
millimeters long. This gas inlet produces a particularly good trapping 
efficiency of approx. 25% of the ions. At the multiplier there is a 
pressure of 10.sup.-5 millibar. The 7 exit holes in the end cap should 
have diameters of 0.5 millimeter each, resulting in an ion trap pressure 
of 3.times.10.sup.-4 millibar. In the input area of the capillary the gas 
velocity is approx. 1 meter per second. With an ion spacing of 10 
micrometers and an optimum filing rate for the ion trap of 5,000 ions, 4 
spectra per second can be scanned in favorable cases. Ionization is 
produced by means of a .sup.63 Ni beta emitter.in a dustfree room in front 
of the inlet capillary. This beta emitter is connected to the outside air 
via a very thin silicone membrane, keeping the dust out. Pollution vapors 
penetrate the silicone membrane into the dust-free room. The ion feed can 
be interrupted by means of a tiny mechanical closure of the capillary 
inlet, e.g. by pneumatically moving the above-mentioned silicone membrane. 
This allows an extremely small mass spectrometer to be constructed for 
continuous air monitoring. Even if the scanning rate of 4 mass spectra per 
second cannot be achieved and, for example, a spectrum is only scanned 
every 10 seconds, such a mass spectrometer would still be of great 
interest. 
This mass spectrometer is also capable of scanning daughter ion spectra. 
This is achieved in a particularly easy manner as follows. By means of a 
partial scan, only those ions with masses below that of the selected 
parent ions are removed and then these parent ions are fragmented into 
daughter ions. The latter are scanned as the spectrum. In this way it is 
even possible to examine several different parent ion types with 
increasing masses in sequence without needing to refill the ion trap. This 
possibility of identifying substances in mixtures means that the apparatus 
can also be used for monitoring purposes without chromatographic 
separation, even if several components in a single mixture have to be 
analyzed.