GB2331837A - Preselection of externally generated ions for quadrupole ion traps - Google Patents
Preselection of externally generated ions for quadrupole ion traps Download PDFInfo
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- GB2331837A GB2331837A GB9825980A GB9825980A GB2331837A GB 2331837 A GB2331837 A GB 2331837A GB 9825980 A GB9825980 A GB 9825980A GB 9825980 A GB9825980 A GB 9825980A GB 2331837 A GB2331837 A GB 2331837A
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- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/004—Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn
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Abstract
An ion trap mass spectrometer has an RF ion guide system comprising rod-shaped electrodes, for transferring ions from an ion generator (1) outside the ion trap of the spectrometer to the ion trap (12,13,14). The ion guide system comprises a first multipole system (8) (e.g. an octopole) that is operated by RF with or without superimposed DC voltage for good ion capture, followed by a second multipole system (e.g. quadrupole) (10) which acts as a mass filter and is operated by RF voltage with superimposed DC voltage that is greater than that applied to the first multipole. Thus only the ions of a small mass range around that of the wanted ions are passed to the ion trap.
Description
1 2331837 Preselection of Externally -Genera ted ions for Quadrupole Ion
Traps This invention relates to the isolation of individual ion types for further analysis in an ion trap mass spectrometer, in which the ions are generated outside the trap and transportation of the ions to the ion trap by a RF ion guide system.
It is the strength of mass spectrometers with RF quadrupole ion traps according to Wolfgang Paul that they are capable of tandem mass spectrometry in a simple manner. They can isolate and fragment parent ions, and thus scan and produce daughter or even granddaughter ion spectra according to a principle that has become known as "tandem in time", and therefore no longer require two mass spectrometers as is required in the "tandem in space" principle.
In an analogue manner, tandem-in-time mass spectrometry can be performed in ICR (ion cyclotron resonance) ion trap mass soectrometers.
Therefore isolating of a single type of ions is a frequently performed task in an ion trap. Isolation is a process which leaves only a single type of ion in the ion trap which is for further analysis. All unwanted ion types are removed from the ion trap. The isolation of one ion type with a uniform massto-charge ratio corresponds to the task of the first mass spectrometer in the former "tandem in space"-method: the selection of parent ions.
This isolation of desired ion types in the ion trap generally proceeds as follows. First, all ions in a large m/e range are introduced into the ion trap and stored there. Then all unwanted ions are removed from the ion trap, primarily using the method of resonant ejection through an excitation AC voltage 2 across one pair of electrodes (the end cap electrodes in the case of quadrupole ion traps).
This method works satisfactorily with a h-gh yield of desired ions, however it is relatively time-consuming and requires a relatively high share of the cycle time for measurement of a daughter ion spectrum. An ion trap mass soectrometer, however, works all the more economically the lower the total time for a measurement cycle.
A device and a method has been described in US 5,179,278 (D.J. Douglas) by which externally generated ions can be introduced to a quadrupole ion trap by an ion guide, stored there temporarily and cleared of unwanted ions before their eventual storage in the trap. This method therefore appears to be a possible and appealing solution to the problem of isolation.
In the cited patent, an ion guide system is used as a -C feeding device, designed as multipole with rod-shaped electrodes, 2C i.e. as quadrupole, hexapole, octopole or higher multipole for the generation of a two-dimensional, longitudinally constant RF field. The multi-pole field is used, according to the patent claims, both for temporary storage of the ions during the time in which the ions are analyzed in the ion trap, as well as for preselection. The preselection process uses resonant ejection of ions from the multipole rod system through an AC voltage specially introduced to at least two electrode rods. This method permits removal of individual unwanted ion types by selection of the frequency of additional AC voltage.
RF ion guide systems with rod-shaped electrodes have become standard for such ion traPs that operate with vacuum-external generation of ions, such as using ESI (electrosprav ionization) or APCI (atmospheric pressure chemical ionization) However, 3c, these do not provide eLther the temporary storage or preselection. It is easy to dispense with the temporary storage 3 J if no preselection is applied, because it may, as described in the cited patent itself, enlarge the gain in ions by a factor of 2 in the most favourable case, though generally much less.
The vacuum-external generation of ions requires the introduction of ions into the vacuum system. A combination of inlet capillary, first differential pump stage, skimmer nozzle, second differential pump stage, and higher multipole ion guide system have proven effective for the capture of ions moving divergently apart from one another beyond the skimmer nozzle. In order that the capture of ions escaping at a moderately wide angle from the skimmer will have as high a yield as possible, a multipole system of a higher order, i.e. with many rods is used, for example, at least a hexapole system, if not an octopole system. These multipole rod systems have a more improved capture ability for a divergent ion bundle than a quadrupole system, due to better reflection of ions at the cylindrical rod grid.
In the initial part of the ion guide system, a considerable residual pressure still prevails on the order of magnitude of 0.1 to 10 Pascal, which effects a very rapid deceleration of the residual kinetic energy of the ions in an axial direction as well as transversely. The ions thus preferably collect along the axis of the ion guide system.
In principle, tandem mass spectrometry in ion traps can also function with several parent ions, which are simultaneously fragmented and analyzed. In practice however, the primary objective by far is to store only a single type of ions with uniform mass-to-charge ratio m/z in the ion trap in order to further analyze them using MS/MS after fragmentation into daughter ions.
Although the method of isolation of one ion type bv resonant ion ejection has been broadly established, it is disadvantageous for the removal of many unwanted ion types 4 because it takes too long. Many frequencies must be applied one after another, for example in the form of contiguous or even =terrupted frequency scans in order to remove all unwanT-ed ions. lt is also possible to apply corresponding frequency mixtures for the ejection of all unwanted ions at the same time, but in this method also, a long period of time with very small amplitudes of the frequency mixture is required if good results are to be achieved. Due to the necessary initial overfilling of the ion trap and the spacecharge problems which result, it is usually necessary in both cases to work in two stages. All these methods are time consuming, and therefore require a certain minimal time for storage.
There is no major difference with respect to these time considerations, whether the ions are ejected resonantly from the temporary storage of the ion guide system or from the ion trap itself. Isolation of the ions in the temporary store of the ion guide system is therefore no more advantageous than removal of unwanted ions from the ion trap itself, a method that has become very refined in the meantime and is available in all commercial instruments of this type.
In addition, preselection cannot be used without the temporary storage step. if the ion guide system is used for direct transfer of ions without temporary storage, the residence time of the ions in the ion guide is not sufficient for resonant ejection of unwanted ions. Additionally, only methods with frequency mixtures can be applied at all for a real-time method, since a frequency scan which can only eliminate one ion t pe at a y time cannot be considered for the ion beam passing through the ion guide only once.
The advantage of temporary storage of ions according to US 5,179,278 should however be precisely the fact that ions resulting in the period of the ion analysis in the ion trap, in addition to the ions formed in the filling period, can be stored. However, the need for temporary storage negates this advantage.
Since the ion trap must in any case be equipped with a method for isoLation, so that isolation c_f one -ion::ype from the daughter ion spectrum is possible in fur--ner steps of the MS/MS/MS process, additional equipment of the ion guide system with selectable generators for the frequency mixtures only increases the expense, but otherwise has no advantage. Consequently, this initially promising solution of ion preselection can only be associated with disadvantages. For this reason, it is not in use in any commercially available ion trap mass spectrometer.
It would therefore be desirable to provide a device such that storage of a single ion type in the ion trap can be performed much more quickly than by isolation methods in the ion trap itself or isolation by resonant ejection in an upstream temporary ion store. It should be presumed that the ions are generated externally from the ion trap and come out of an aperture in the form of a (possibly slightly divergent) ion beam, for example out of a skimmer or an ion source which is inside the vacuum but outside the ion trap and are transported in the normal manner through an ion guide system to the ion trap.
The invention provides an ion trap mass spectrometer having an RF ion guide system comprising rod-shaped electrodes, for transferring ions from an ion generator outside the ion trap of the spectrometer to the ion trap, wherein the ion guide system comprises a first section for capturing ions from the ion source and a second section, wherein the first section is a multipole ion guide, and the second section is a quadrupole mass filter, and the apparatus includes means for supplying to the second section an RF voltage having superimposed DC voltage means for without a lower than for preselection of ions of a small m/z range,, and supplying to the first section an RF voltage, either superimposed DC voltage, or with a DC voltage which is that applied to the second section.
6 In accordance with one aspect of the invention, a part of the ion guide system functions as an ion-filtering mass spectrometer. For this in-itial, ion-isolating step in tandem mass spectrometry, the prnc-ple of "tandern in space" -s used.
For this however, only a quadrupole filter mass spectrometer is suitable. Hexapole and octopole systems could also function in principle as mass filters, if they were operated with an additional DC voltage; however, they have such a poor mass resolution and they especially separate so slowly that they cannot be used advantageously for the present purposes.
Since fine isolation of the ions can be done relatively quickly and with a good yield in the ion trap itself, the preselective mass spectrometer certainly only requires average mass resolution of several atomic mass units. Such a system need not have the precision in amplitude and ratio of the superimposed quadrupolar RF and DC fields, as is necessary for a stand-alone quadrupole mass spectrometer. Therefore, this quadrupole filter can be a quite an inexpensive, simple system, both in its mechanical embodiment as well as in its electronic drive circuit and power supply.
However, the quadrupole ion filter is not well suited for capturing the ions at its entrance, since it has a very poor acceptance for divergent ions in an ion beam. What is necessary 4s something that operates only with RF voltage, without the superimposed DC voltage that makes acceptance so poor. In addition, hexapole or octopole systems are far more suitable here than a quadrupolar ion guide system, since they possess a far better reflection at the cylindrical grid of rods for a divergent ion beam. Accordingly, in a further aspect of the invention a multipole system without superimposed DC voltage is used at the fron-: end of the ion guide system, such a system has good ion 3 5 capture properties, and is preferably a multipole system of relatively high order, preferably an octopole system. This multiple rod system forms the capturing part of the ion guide 7 system, and the part handling in particular the damping of the f the ions in the case of their vacuum-external kinetic energy o. generation. However, in the next step of the ion guide system, according to the invention, a transition must be made to a quadrupole filter with superimposed DC voltage; this quadrupole filter system is designed as a simple, statically working mass filter which handles the isolation of ions of the wanted ion type.
A preferred embodiment of the invention is illustrated in Figure 1.
In Figure 1, an electrospray ion source (1) with a spray capillary (2) generates ions that are introduced together with a great deal of ambient gas to the input capillary (3) and to the first stage (4) of a differential pressure system. The ions entering through the skimmer (5) of the partition (6) into the second chamber (7) of the differential pump unit are captured and decelerated by the octopole ion guide system (8). The ions near the axis pass through an aperture in the partition (9) into the quadrupole ion filter (10), which is mounted in the chamber (11) and segregates unwanted ions. The isolated, wanted ions pass through an aperture in the end cap electrode (12) into the ion trap, surrounded by the ring electrode (13) and closed off by the second end cap electrode (14). The chambers of the differential pump system are evacuated by pump nozzles (15, 16, 17).
Particularly favourable embodiments Figure 1 shows a favourable embodiment of the invention. In the system shown, vacuum-externally generated ions are zransported through a capillary (3) together with a great flow of filtered air (or nitrogen) into the first stage (4) of a differential pump system. Air or nitrogen are preferably dry and warmed. in the first stage (4), a large portion of the neutral gas flowing in through the capillary (3) is deflected by the skimmer (5), while the ions are attracted chiefly to the skimmer (5) by a slight 8 voltage between the capillary end and skimmer. The ions passing 1:hrough the hole in the skimmer into:he second pump stage (IN are captured and transmitted on the other side of the skimmer in accordance with the invention by an octopole ion guide (8) without a superimposed DC field. At the same time, the velocity of the ions principally attained in the input capillary (3) through gas entrainment, is decelerated to thermal velocities by the high residual gas pressure in the octopole system (8) of about 1 Pascal after a very short path of 2 cm - 4 cm. Due to the retroactive forces of the pseudopotential in the octopole field (8), the ions collect at this point in the center of the octopole system (8) and flow, driven on by the incoming neutral gas, close to the axis toward the end of the octopole system (8). Here, in a favourable embodiment, is the wall (9) to the third stage of the pump system, with a hole through which the ions close to the axis can pass into the next chamber (11). In the next chamber (11) they enter directly behind the hole into the quadrupole filter (10) according to a further part of the invention, the axial potential of which is somewhat lower for the ions than the axis potential of the preceding octopole. Due to this slight potential shift and through the axially aligned arrangement, conditions for the acceptance of kinetically slow ions into the quadrupole filter are relatively favourable. By setting the RF and DC voltage, the unwanted ions are driven towards the quadrupole rods and thus removed. According to the invention, only the wanted -ons (and possibly some ions with similar m/z) are transmitted in this way to the ion trap (12, 13, 14), where they are introduced and captured by the usual means.
As described, it is favourable to keep the mid potential of the quadrupole mass filter somewhat lower than the mid potential of the octopole field. In this way, acceptance of the quadrupole filter for the ions of the octopole field is increased. Additionally, a backflow of ions reflected from the end cap
3 S electrode (12) of the ion trap into the octopole field is prevented.
9 The ion guide system is normally very slender. The octopole system usually has an inside diameter of about 3 to 5 m:7.. The quadrupole filter system must also be very slender, so as to be able to focus the ions well. upon the entrance hoLe of the ion trap with 1.5 to 2 mm diameter. The inside diameter of the quadrupole system should therefore be equal to that of the octopole system. The aperture in the wall (9) between the two sections of the ion guide system should be about 1.5 to 2 mm.
A quadrupole system with only 3 to 5 mm inside diameter requires high precision, even if only average mass resolution is to be achieved. Therefore, for a preferable embodiment, finely polished and hardened steel needles of about 1.5 mm - 4 mm diameter are used, which are glued into precisely ground grooves on ceramic rings (or, in another embodiment, soldered). Gluing proceeds in a holder around a precision ground form core, which very precisely defines the interior of the ion filter. Minimal evaporation products from the adhesive, which could cause a constant background spectrum for a mass spectrometer with vacuum internal ion generation, are of no importance for vacuum-external ion generation. The hardened steel needles are very dimensionally stable, thus there is no danger of bending. It is thus possible to achieve a form and position precision of 10 micrometers relatively simply and inexpensively, which results in a resolution of about 10 atomic mass units at a mass of 3,000 u. If the filter is operated at a resolution of only about 30 mass units, which can be adjusted by the DC voltage, good transmission provided for the selected ions.
The electric drive of the quadrupole mass filter may also be quite simple. No high precision drive is required for this, such as is used for quadrupole mass spectrometers. The constancy of the RF and DC voltages need not be more than about 5 x 10-4, in contrast to a minimum requirement of about 2 x 10-5 for commercial quadrupole mass spectrometers. The RF and DC voltages can be selected separately through two inexpensive digital-toanalog converters with a dynamic range of just 12 bits. The dynamic performance can be reduced, and the set duration for the v'tages can be a few milliseconds. I o Ln this way only a very low power is required from the voltage generators. Selection of the Z =equency and level of the voltages is dependent upon the mass range of the ion trap. The DC voltage can be 6 times lower than the RF voltage.
In most cases of isolation for larger ions, an isolation window of 30 mass units is fully sufficient to separate out an isotope group of ions of uniform composition from their surroundings. Postisolation in the ion trap is then no longer necessary if the ions of the entire group are to be fragmented and their daughter ion spectrum measured. This is the case for standard operation.
If on the other hand a single ion type with uniform nominal weight is to be isolated from the isotope group, postcleaning is necessary. This can be achieved easily using the available methods of the ion trap mass spectrometer. This postcleaning, for example using resonant ejection of the now only few remaining unwanted ion masses, normally takes only little time, so that the goal of saving time is maintained for the most part.
The invention naturally encloses other embodiments. Thus the ions need not be generated outside the vacuum system, but rather can be generated in any type of ion source even within the vacuum system, but outside the ion trap, and sent to the ion trap via an ion guide system.
Particularly desirable here are ion sources which are based on CI ionization, a chemical ionization of analysis ions by reactant gas ions in a buffer gas at about 100 Pascal pressure. This type of ion source principally generates molecule ions (more precisely: so-called pseudomolecular ions, which result from the attachment of a proton, and are therefore one atomic mass unit heavier than the analyte molecule). In this way only molecular 11 ions result principally from substance mixtures, and a mixture analysis is therefore also possib-'e without separation by means of chromatography or electrophoresis. The molecular ions may then be further analyzed advantageously using MSIMS or MS/MS/MS. Here 5 too, the ions flow together with the buffer gas as a divergent Jon beam out of a small aperture of the ion source. They must therefore be captured according to similar principles, like the ions which fly through the aperture of the skimmer in the case of vacuum-external generation. The buffer gas flow helps to damp the 10 kinetic energies of the ions.
Other vacuum-external ion sources may also be used, for example APCI (atmospheric pressure chemical ionization) or a vacuum-external air-MALDI (matrix-assisted laser desorption and ionization through APCI).
End pieces of the quadrupole filter without DC voltage can also be used (so-called Brubaker ramps), which generate a better acceptance of the quadrupole filter for introduced ions.
To increase the acceptance of ions for the quadrupole filter, a quadrupole prefilter with reduced DC voltage can also be interconnected. Here, a majority of the ions are already filtered out in this prefilter, though the range of mass-tocharge ratios which passes through is nevertheless much greater than in the terminal quadrupole mass filter.
The basic pattern of sections for the ion guide system can also be varied in other ways, for example by a three-part system, whereby the third section is designed as a temporary store for the selected ions, which are isolated in the second section through selective quadrupole filtration. In this system, the advantage of temporary storage would be restored.
12 -Iaims 2.
6.
An 'on trap mass spectrometer having an RF ion guide system comprising rod-shaped electrodes, for transferring ions from an ion generator outside the ion trap of the spectrometer to the ion trap, wherein the ion guide system comprises a first section for capturing ions from the ion source and a second section, wherein the first section is a multipole ion guide, and the second section is a quadrupole mass filter, and the apparatus includes means for supplying to the second section an RF voltage having superimposed DC voltage for preselection of ions of a small m/z range,, and means for supplying to -the first section an RF voltage, either without a superimposed DC voltage, or with a DC voltage which is lower than that applied to the second section.
Claims (1)
- An ion trap mass spectrometer as claimed in Claim 1, wherein the firstsection is in a differential pump stage at relatively high pressure, so as to decelerate ions of higher velocities in the ion beam to thermal velocities.3. An ion trap mass spectrometer as claimed in Claim 2, wherein the relatively high pressure of the differential pump stage for the first section is from 0.1 to 10 Pascal.4. An ion trap mass spectrometer as claimed in any one of the preceding claims, wherein the first partial system is a multipole system with at least three rod pairs.An ion trap mass spectrometer as claimed in any one of the preceding claims, wherein the first section is operated at a lower DC voltage than is the second section.A ion trap mass spectrometer as claimed in any one of the preceding claims, wherein the mid potentials along the axis of the sections for the captured ions are lower toward the ion trap.7. An ion trap mass spectrometer as claimed in any one of the lter preceding claims, wherein the quadrupole mass fi 13 comprises four round rods which are glued or soldered into electr 4 cally isolated holding rings.8. An ion trap mass spectrometer as c-a-,med in any one of the preceding claims, wherein the said sections have about the same inside diameter.9. An ion trap mass spectrometer as claimed 4n Claim 9, wherein the inside diameter of the sections is from 3 mm to 5 mm.10. An ion trap mass spectrometer as claimed in any one of the preceding claims, wherein the said two sections are separated by a partition with an aperture.11. An ion trap mass spectrometer substantially as herein before described with reference to and as illustrated by the accompanying drawing.12. A method of operating a mass spectrometer, which method comprises providing an ion trap mass spectrometer having means for generating ions outside the ion trap with an RF ion guide system comprising rod-shaped electrodes, and having at least a first section and a second section, which method comprises applying to the second section an RF voltage with a superimposed DC voltage for the preselection of ions of a small m/z range, and applying to the first section an RF voltage for capturing ions from the ions source, either without a superimposed DC voltage, or with a DC voltage which is lower than that applied to the second section.13. A method as claimed in Claim 12, wherein the ion trap mass spectrometer is a mass spectrometer as claimed in any one of Claims 2 to 10.3C 14. A method of operating an ion trap mass spectrometer, substantially as herein before described with reference to and as illustrated by the accompanying drawing.15. 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(1) 0 41 0 t)'t 41 0 F a 0) Q) U) 0 4 - H (0 91. -11 v) Q ' (f) (f) f-- (f) 0 W W 0 m.0 (1) 4J 0 0 5 ---4 41 o 4 0 -4 -0 ---4 0 f 0 41 ---4 A 4-4 0 '1 A 41.14 ---A(f) (f) 5 ---1 0) '(J -1 ---4:5 Q) U) ---1 ---4 4 4 J 4.4 -4 (L) W 4 ro -4 (U f,' 4 T5:i 1-4 m 0 :1 0:j -H 44 -11 W 4 4 0:1 ---1 0 ---4 (1) ---1 4-4 0 C:: -1 0 ---1 0 f-' ---4 T5 > 4-, -Q 4-J U) 44 l: 0: 4-4 U 0 4-4 4 0 41 KC U xl, ot () (I 1 r OD m C) 1 C\i 4 r-l ---4 1-4 C\J T) Ln C) in C) tn -1 (\i (\i (1) rn 23. An ion trap mass spectrometer as claimed in Claim 22, wherein the inside diame-:er of the partial systems lies within a range between 3 mm and ion guide mm.24. An ion trap mass spectrometer as claimed in one of Claims 15 to 23, wherein two of the partial systems are separated by a partition with an aperture.
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DE1997152778 DE19752778C2 (en) | 1997-11-28 | 1997-11-28 | Ion trap mass spectrometer with multipolar high-frequency ion guidance system |
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GB9825980D0 GB9825980D0 (en) | 1999-01-20 |
GB2331837A true GB2331837A (en) | 1999-06-02 |
GB2331837B GB2331837B (en) | 2002-05-15 |
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GB2502155A (en) * | 2012-05-18 | 2013-11-20 | Fasmatech Science And Technology Sa | Controlling ions using descending order multipole electric fields |
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DE19930894B4 (en) | 1999-07-05 | 2007-02-08 | Bruker Daltonik Gmbh | Method for controlling the number of ions in ion cyclotron resonance mass spectrometers |
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1997
- 1997-11-28 DE DE1997152778 patent/DE19752778C2/en not_active Expired - Fee Related
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1998
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GB2301704A (en) * | 1995-06-02 | 1996-12-11 | Bruker Franzen Analytik Gmbh | Introducing ions into a high-vacuum chamber, e.g. of a mass spectrometer |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2502155A (en) * | 2012-05-18 | 2013-11-20 | Fasmatech Science And Technology Sa | Controlling ions using descending order multipole electric fields |
US9123517B2 (en) | 2012-05-18 | 2015-09-01 | Fasmatech Science And Technology Sa | Ion guide with different order multipolar field order distributions across like segments |
GB2502155B (en) * | 2012-05-18 | 2020-05-27 | Fasmatech Science And Tech Sa | Apparatus and method for controlling ions |
Also Published As
Publication number | Publication date |
---|---|
GB9825980D0 (en) | 1999-01-20 |
GB2331837B (en) | 2002-05-15 |
DE19752778A1 (en) | 1999-06-10 |
DE19752778C2 (en) | 2002-03-14 |
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