DE10361023A1 - Mass spectrometer separating on ion mobility basis, e.g. for decoding human genome, processes time of flight results, to reduce intensity or significance of ions with undesired charge state - Google Patents

Abstract

The instrument includes a time-of-flight mass analyzer and a processor. A first mass spectrum data set is produced, concerning time of flight of at least some ions of the first group through the flight region. This data is processed, such that the ion intensity or significance of ions with a first undesired charge state, is reduced relative to that of ions with a second differing and desired charge state. The ions are pulsed x times during introduction into the ion mobility spectrometer. To the first data set, a further set is added, formed by summing at least x sets of mass spectral data covering separate ion pulses of ions. At least some of the ions of at least n further groups of ions are analyzed using the flight time mass analyzer. These emerge from the ion mobility separator during at least n further time intervals. n or more further mass spectral data sets are produced, containing data corresponding with the flight time of at least some ions of the at least n further groups of ions passed through the flight region. When determining significance, examination of drift time is performed. An upstream section of electrodes with orifices is arranged in a vacuum section at 0.1-10 mbar. Electrodes in the upstream section of the ion mobility separator are supplied with a high frequency voltage at 0.1 - 3.0 MHz. Electrodes in a downstream section are similarly supplied. They are held under a pressure of 10 -> 3> - 10 -> 2>.

Description

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

With the decoding of the 20-30,000 genes representing the human genome form, has paid attention to the identification of the translated Gene products comprising the proteome, changed. Mass spectrometry has firmly as primary Technology to identify the proteins due to their unequaled Speed, sensitivity and specificity established. Strategies can either the analysis of the intact protein or more commonly the Digestion or digestion of a protein using a specific Proteases which run along predictable residues along the peptide backbone or -backbones adhered include. This represents smaller distances of peptide sequences available, which can be analyzed in a simpler manner by means of mass spectrometry are.

The mass spectrometry technique that provides the highest level of specificity and sensitivity is electrospray ionization ("ESI"), which interfaces with a tandem mass spectrometer, which involves the separation of the complex selection spectra. or digest mixture by microcapillary liquid chromatography with on-line mass spectral detection using automated acquisition modes, collecting conventional MS and MS / MS spectra in a data-dependent manner This information can be used directly to search databases for matching sequences This approach can be used to identify proteins that are present in low endogenous concentrations, but often the limiting factor for identifying the protein is not the quality of the MS / MS produced. MS spectrum s, but the first-time discovery of the multiply charged peptide precursor ion in the MS mode. This is due to the level of background chemical noise, which is largely simply charged, which can be generated by the ion source of a mass spectrometer. 1 Figure 12 shows a typical conventional mass spectrum and illustrates how doubly charged species can be obscured in a simply charged background. A method by which the chemical noise (mainly caused by singly charged ions) is reduced so that the mass spectrometer can more easily detect peptide-related ions would be highly advantageous for the study of protein digests. In the field of proteomics, the limiting factor in the identification of proteins is often not the inability to generate adequate fragmentation data (or "MS / MS") but the inability to recognize peptide precursor ions in the mass spectrum A large proportion of the peptide productions from a tryptic digest a mixture of proteins is multiply charged, and this fact can be used as a means of recognizing peptide productions, but at relatively low levels, these multiply charged peptide productions may be relatively or substantially discernible due to the presence of more intense, singly charged, chemical background ions.

One known method for favoring the detection of multiply charged species over singly charged species is the use of an electrospray ionization orthogonal acceleration time of flight mass analyzer ("ESI-oaTOF"). The orthogonal acceleration time of flight mass analyzer counts the arrival of ions using a time-to-digital converter ("TDC") having a discriminator threshold. The voltage pulse of a single ion must be high enough to trigger the discriminator and thus register the arrival of an ion. The voltage generating detector may be an electron multiplier or microchannel plate detector ("MCP") .These detectors are charge sensitive so that the signal magnitude they produce increases with increasing state of charge. "Discrimination to favor higher charge states may be increased the discriminator voltage level, lowering the detector gain or the Detektorgains, or a combination of these two measures can be accomplished. 2A shows a mass spectrum obtained with a normal detector gain, and 2 B shows a comparable mass spectrum obtained with a reduced detector gain. A major disadvantage in lowering the detector gain (or increasing the level of discriminators) is a decrease in sensitivity. As at the ordinate axis in 2a and 2 B As can be seen, the sensitivity is reduced by a factor of about 4 when a lower detector gain is used. Using this method, it is also impossible to select an individual charge state. Rather, the best that can be achieved is a reduction in the detection efficiencies of lower charge states with respect to higher charge states.

Another ionization technique that has recently been coupled with tandem mass spectrometers for biological mass spectrometry is matrix-assisted laser desorption ionization ("MALDI") When a MALDI ion source is used, high rates of singly charged matrix-related ions as well as chemical noise are generated, making it difficult to identify candidates for peptide ions.

It is therefore desirable an improved mass spectrometer and an improved mass spectrometry method to provide each one not some or all of the above described disadvantages of the prior art.

• (i) Erzeugung eines ersten Massenspektral-Datensatzes einschließlich Daten, die der Flugzeit wenigstens einiger der Ionen der ersten Gruppe von Ionen durch die Flugregion entsprechen; und
• (ii) Verarbeitung des ersten Massenspektral-Datensatzes zur Bildung eines ersten verarbeiteten Massenspektral-Datensatzes, bei dem bzw. wobei die Intensität oder Signifikanz von Ionen mit einem ersten unerwünschten Ladungszustand relativ zu Ionen mit einem zweiten, unterschiedlichen, gewünschten Ladungszustand reduziert ist.

According to a first aspect of the present invention, a mass spectrometer is provided with:
an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals;
a time-of-flight mass analyzer having a flight region, the time-of-flight mass analyzer configured to mass-analyze at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval; and
Processing means, which are designed for:

• (i) generating a first mass spectral data set including data corresponding to the time of flight of at least some of the ions of the first group of ions through the flight region; and
• (ii) processing the first mass spectral data set to form a first processed mass spectral data set, wherein the intensity or significance of ions having a first undesired charge state relative to ions having a second, different, desired charge state is reduced.

Preferably becomes the intensity attenuated by ions with a first, undesirable state of charge or reduced, preferably significantly reduced, whereas the intensity of ions with a second, desired Charge state preferably remains unaffected.

ions are preferably at least x times in the ion mobility separator pulsed, and wherein the first mass spectral data set is a composite Set of mass spectral data obtained by summing at least x sentences or sets of mass spectral data is obtained, wherein the x-sets of Mass spectral data on separate pulses or pulses of ions Respectively. The value x can be within the range 1 - 10, 10 - 20, 20 - 30, 30 - 40, 40 - 50, 50 - 60, 60 - 70, 70 - 80, 80 - 90, 90 - 100, 100 - 150 , 150-200, 200-250, 250-300, 300-350, 350-400, 400-450, 450-500 or> 500.

At least some of the ions of at least n other groups of ions which from the ion mobility separator while can emerge at least n further time intervals can in Mass analysis with the time-of-flight mass analyzer. The processing means preferably generate n further mass spectral data sets each contain data that the flight time of at least some the ions of the at least n further groups of ions through the Flight region correspond.

ions are preferably at least x times in the ion mobility parabola pulsed, and where the n other mass spectral data sets are compounded Sets of Mass spectral data are, each composed of Mass spectral data by summing at least x sets of Mass spectral data is obtained, where the x sets of mass spectral data refer to separate pulses of ions.

The Processing means preferably process the at least n others Mass spectral data sets for forming at least n further processed mass spectral data sets, wherein the intensity or significance of ions with a first, undesirable Charge state relative to ions with the second, desired Charge state is reduced.

The Processing means preferably process the first and / or n additional mass spectral data sets by reducing the intensity or Significance of ions with a time of flight that is less than one minimum flight time.

alternative can the processing means performs the first and / or n further mass spectral data sets Diminution of intensity or Significance of ions with a time of flight that is smaller or smaller as a minimum flight time and greater than a maximum flight time is, process.

According to one another embodiment, the Processing means the first and / or n further mass spectral data sets Reduction of intensity or significance of ions with a time of flight that is greater as a maximum flight time, process.

Of the Value n can be within the range 1 - 10, 10 - 20, 20 - 30, 30 - 40, 40 - 50, 50 - 60, 60 - 70, 70 - 80, 80 - 90, 90 - 100, 100 - 110, 110 - 120, 120 - 130, 130 - 140, 140 - 150, 150 - 160, 160 - 170, 170 - 180, 180 - 190, 190 - 200, 200 - 250, 250 - 300, 350 - 400, 400 - 450, 450-500 and> 500 lie.

Preferably is the minimum flight time and / or the maximum flight time at the Processing mass spectral data sets that be obtained from successive time intervals, progressively increased or diminished. The minimum flight time and / or the maximum flight time is preferably increased progressively or diminished in (i) a substantially continuous manner; (ii) a substantially stepped way; (iii) one essentially linear way; (iv) a substantially non-linear manner; or (v) a substantially exponential manner.

The Processing means preferably form using the first processed mass spectral data set a mass spectrum. The Processing agents preferably form a mass spectrum Use of at least n further processed mass spectral data sets.

• (i) Erzeugung eines ersten Ionenmobilitäts-Datensatzes einschließlich Daten, die einer Driftzeit von wenigstens einigen Ionen durch den Ionenmobilitätsseparator entsprechen; und
• (ii) Verarbeitung des ersten Ionenmobilitäts-Datensatzes zur Bildung eines ersten verarbeiteten Ionenmobilitäts-Datensatzes, wobei die Intensität oder Signifikanz von Ionen mit einem ersten unerwünschten Ladungszustand relativ zu Ionen mit einem zweiten, unterschiedlichen, gewünschten Ladungszustand reduziert wird.

In accordance with another aspect of the present invention, a mass spectrometer is provided with:
an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals;
a time-of-flight mass analyzer having a flight region, wherein the time-of-flight mass analyzer is adapted for mass analysis of at least some of the ions exiting the ion mobility parabola; and
Processing means which are set up for:

• (i) generating a first ion mobility data set including data corresponding to a drift time of at least some ions through the ion mobility separator; and
• (ii) processing the first ion mobility data set to form a first processed ion mobility data set, wherein the intensity or significance of ions having a first undesired charge state relative to ions having a second, different, desired state of charge is reduced.

Preferably is the first ion mobility record a composite set of ion mobility data obtained by summing a number of sentences of ion mobility data is obtained.

The Processing means preferably process the first one and / or a number of other ion mobility data sets by reducing the intensity or significance of ions having a drift time through the ion mobility separator, the greater than a maximum drift time is.

alternative the processing means preferably process the first one and / or a number of other ion mobility data sets by reducing the intensity or significance of ions with a drift time through the ion mobility separator, which is less than a minimum drift time and greater than a maximum drift time is.

According to one another embodiment the processing means process the first or the first and / or a number of other ion mobility data sets by reducing the Intensity or Significance of ions with a drift time through the ion mobility separator, which is less than a minimum drift time.

The minimal drift time and / or the maximum drift time is at the Processing of consecutive, consecutive or adjacent ones Sets of Ion mobility data progressively increased or diminished.

The minimum drift time and / or maximum drift time becomes progressive elevated or diminished in: (i) a substantially continuous manner; (ii) a substantially stepped way; (iii) one essentially linear way; (iv) a substantially non-linear manner; or (v) a substantially exponential manner.

The Processing means preferably form using the first processed ion mobility data set a mass spectrum. The processing means preferably form using a number of other processed ion mobility data sets Mass spectrum.

Of the first charge state preferably comprises singly charged ions. The second state of charge preferably comprises multiply charged ions, for example, doubly charged ions, triply charged ions, four times charged ions or ions with five or more charges.

According to one embodiment has the ion mobility separator a plurality of electrodes, each electrode having an opening which ions are transmitted or transmitted during use be a DC voltage gradient over at least a portion of the ion mobility separator is maintained and at least some of the electrodes with a AC or high frequency or RF voltage source connected are.

The ion mobility separator preferably has:
an upstream portion having a first number of electrodes with openings arranged in a vacuum chamber; and a downstream portion having a second plurality of orifices with openings formed in a further vacuum Chamber are arranged, wherein the vacuum chamber or vacuum chambers are separated or separated by a differential pumping opening.

At least some of the electrodes in the upstream section are preferably provided with an AC or RF voltage having a frequency within the range of 0.1-3.0 MHz, preferably 0.5-1.1 MHz, preferably about 780 kHz, applied. The upstream portion is preferably maintained at a pressure in the range of 0.1 - 10 mbar, preferably 1 mbar. At least some of the electrodes in the downstream section are preferably provided with an AC or RF voltage having a frequency in the range of 0.1-3.0 MHz, preferably 1.8-2.4 MHz, most preferably 2 , 1 MHz applied. The downstream portion is preferably maintained at a pressure in the range of 10 ^-3 to 10 ^-2 mbar. According to one embodiment, a first DC voltage gradient is maintained across at least a portion of the upstream portion and a second DC voltage gradient is maintained across at least a portion of the downstream portion, wherein the first DC voltage gradient is greater than the second DC voltage gradient. None of the stress gradients must necessarily be linear, with a stepped stress gradient being particularly preferred.

At least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% of the electrodes preferably have openings on, which are essentially the same size or the same area exhibit.

According to one further embodiment the ion mobility separator a segmented or subdivided set of rods, wherein a DC voltage gradient over at least a section of the ion mobility separator is maintained.

According to one further embodiment the ion mobility separator a drift tube together with one or more electrodes or electrodes to maintain an axial DC voltage gradient at least a portion of the drift tube.

According to one further embodiment the ion mobility separator a number of electrodes, wherein in use one or more transient DC voltages or one or more transient DC voltage waveforms be applied progressively to the electrodes, so that at least some ions with a first ion mobility or mobility of other ions separated with a second, different ion mobility become.

The one or more transient DC voltages or the one or a plurality of DC voltage waveforms are preferably such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% the ions with the first ion mobility along the ion mobility separator with a higher one Speed are moved as the ions with the second ion mobility.

According to one further embodiment the ion mobility separator a number of electrodes, wherein in use one or more transient DC voltages or one or more transient DC voltage waveforms be applied progressively to the electrodes so that ions in Be moved towards a region of the ion mobility separator, wherein at least one electrode has a potential, so that at least some ions with a first ion mobility the potential happen while at least some other ions with a second, different ion mobility the potential does not happen.

The one or more transient DC voltages or the one or more transient DC voltage waveforms are preferable such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the ions with the first ion mobility pass the potential. The one or more transient DC voltage waveforms are preferably such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the ions with the second ion mobility the potential not happen. Preferably, the one or more transients DC voltages or the one or more transient DC voltage waveforms such that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the ions with the first ion mobility essentially in front of the ions with the second ion mobility from the ion mobility separator escape.

A Most of the ions with the first ion mobility preferably occur for a time t in front of a majority of the ions with the second ion mobility from the ion mobility separator where t is in a range <1 μs, 1-10 μs, 10-50 μs, 50-100 μs, 100-200 μs, 200-300 μs, 300-400 μs, 400-500 μs, 500-600 μs , 600 - 700 μs, 700 - 800 μs, 800 - 900 μs, 900 - 1,000 μs, 1.0 - 1, 1 ms, 1,1 - 1,2 ms, 1.2 - 1.3 ms, 1.3 - 1.4 ms, 1.4 - 1.5 ms, 1.5 - 1.6 ms, 1, 6 - 1.7 ms, 1.7 - 1.8 ms, 1.8 - 1.9 ms, 1.9 - 2.0 ms, 2, 0 - 2, 5 ms, 2.5 - 3.0 ms, 3.0 - 3.5 ms, 3.5 - 4.0 ms, 4,0 - 4,5 ms, 4,5 - 5, 0 ms, 5 - 10 ms, 10 - 15 ms, 15 - 20 ms, 20 - 25 ms or 25-30 ms falls.

According to a further embodiment, the ion mobility separator comprises a number of electrodes, wherein in use one or more transient DC voltages or one or more transient DC voltage waveforms are progressively applied to the electrodes such that: (i) ions are moved toward a region of the ion mobility separator, wherein at least one electrode has a first potential such that at least some ions having first and second different ion mobilities pass the first potential while other ions having a third, different ion mobility do not pass the first potential; and then (ii) moving ions with the first and second ion mobilities, respectively, toward a region of the ion mobility parabola, wherein at least one electrode has a second potential such that at least some ions with the first ion mobility pass through the second potential other ions with the second, different ion mobility do not pass the second potential.

The one or more transient DC voltages may be one potential hill or a potential barrier, a potential well, a combination from a potential hill or a potential barrier and a potential well, a number of potential hills or barriers, a number of potential sinks or a combination from a number of potential hills or barriers and generate a number of potential wells. The One or more transient DC voltage waveforms may be one repeating waveform, or a square wave.

The One or more transient DC voltage waveforms may be one Number of potential peaks or sinks, which by Intermediate regions are separated. Preferably is the DC voltage gradient in the intermediate regions of zero different, positive, negative, linear, not linear, or rising exponentially on or falls exponentially.

The Amplitude of the potential peaks or sinks can be substantially remain constant, progressively smaller or larger, or either linear or do not increase or decrease linearly.

One axial Gleichspannungsgradient can along at least one section the length of the ion mobility separator be maintained, the axial stress gradient with the time varies or may vary.

Of the ion mobility separator 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or> 30 segments, each segment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or> 30 electrodes and wherein the electrodes in a segment are substantially the same DC potential can be maintained.

A Number of segments can be at substantially the same DC potential being held. Each segment can be essentially the same DC potential are held as the subsequent y-th segment, where y = 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or> 30.

ions are preferably radially inside the ion mobility separator enclosed by an AC or an RF or RF electric field. Ions can Radially enclosed within the ion mobility separator in a pseudo-potential well radially be, or can axially along the ion mobility separator be moved by means of a real potential barrier or sink.

According to one less preferred embodiment can one or more DC or RF or RF voltage waveforms be applied to at least some of the electrodes, so that the ions along at least a portion of the length of the Ionenmobilitätsseparators packed become. The minimum, average or maximum transit or Transit time of the ions through the ion mobility separator may be smaller or be equal to 20 ms, 10 ms, 5 ms, 1 ms or 0.5 ms.

Of the ion mobility separator can be kept in use at a pressure that is off the group selected which comprises the following values: (i) greater than or equal to 0.0001 mbar; (Ii) bigger or equal to 0.0005 mbar; (ii) greater than or equal to 0.001 mbar; (iv) greater or equal to 0.005 mbar; (v) greater or equal to 0.01 mbar; (vi) greater or equal to 0.05 mbar; (vii) greater or equal to 0.1 mbar; (viii) greater or equal to 0.5 mbar; (ix) larger or equal to 1 mbar; (x) greater or equal to 5 mbar; (xi) greater or equal to 10 mbar.

Of the ion mobility separator can be kept in use at a pressure that is off the group selected which includes the following values: (i) less than or equal to 10 mbar; (ii) less than or equal to 5 mbar; (iii) less than or equal to 1 mbar; (iv) less than or equal to 0.5 mbar; (v) less than or equal to 0.1 mbar; (vi) less than or equal to 0.05 mbar; (vii) smaller or equal to 0.01 mbar; (viii) less than or equal to 0.005 mbar; (ix) smaller or equal to 0.001 mbar; (x) less than or equal to 0.0005 mbar; and (xi) is less than or equal to 0.0001 mbar.

The ion mobility separator can be maintained in use at a pressure that is selected from the group comprising the following values: (i) between 0.0001 and 10 mbar; (ii) between 0.0001 and 1 mbar; (iii) between 0.0001 and 0.1 mbar; (iv) between 0.0001 and 0.01 mbar; (v) between 0.0001 and 0.001 mbar; (vi) between 0.0001 mbar and 10 mbar; (vii) between 0.0001 and 1 mbar; (viii) between 0.001 and 0.1 mbar; (ix) between 0.001 and 0.01 mbar; (x) between 0.01 and 10 mbar; (xi) between 0, 01 and 1 mbar; (xii) between 0, 01 and 0, 1 mbar; (xiii) between 0.1 and 10 mbar; (xiv) between 0.1 and 1 mbar; and (xv) between 1 and 10 mbar.

Of the ion mobility separator can be kept in a pressure during use, so that a viscous drag on ions which is the ion mobility separator happen or go through.

The one or more transient DC voltages or the one or the plurality of transient DC voltage waveforms may be initially on be provided a first axial position, and then below at second and then third different axial positions along of the ion mobility separator to be provided.

The one or more transient DC voltages or the one or the multiple transient DC voltage waveforms may become from one end of the ion mobility separator move one end of the ion mobility separator so that at least some ions are forced along the ion mobility separator.

The one or more transient DC voltages or the one or the plurality of DC voltage waveforms may travel along the ion mobility separator moving at a speed of 10-250 m / s, 250-500 m / s, 500-750 m / s, 750-1000 m / s, 1000-1250 m / s, 1250-1500 m / s, 1500-1750 m / s, 1750-2000 m / s, 2000-2250 m / s, 2250-2500 m / s, 2500-2750 m / s, 2750-3000 m / s or> 3000 m / s.

Two or more transient DC voltages or two or more transient DC voltage waveforms can be simultaneously through the ion mobility separator go through or pass this.

According to one embodiment can be a continuous ion beam at the entrance of the ion mobility separator be received. Alternatively you can Ion packets are received at the entrance of the ion mobility separator.

Of the ion mobility separator can 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-110, 110-120, 120-130, 130 -140, 140-150 or more than 150 electrodes. At least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the ion mobility separator forming electrodes are preferably both with a DC voltage as well as an AC or RF or RF power supply connected. Axially adjacent electrodes of the ion mobility separator are preferably with alternating or RF or RF voltages with a phase difference of 180 ° applied.

The Mass spectrometer may be an electrospray ion source ("ESI"), an atmospheric pressure chemical ionization ion ("APCI") source, an atmospheric pressure photo ionization ion source ("APPI"), a matrix-assisted laser desorption ionization ion source ("MALDI"), a laser desorption ionization ion source ("LDI"), an inductive one coupled plasma ion source ("ICP"), an electron impact ion source ("EI"), a chemical Ionization ion source ("CI"), a fast atom bombardment ion source ("FAB"), a liquid secondary ion mass spectrometry ion source ("LSIMS"), a field ionization ion source ("FI") or a field desorption ion source ("FD").

According to one less preferred embodiment For example, the mass spectrometer may be a Fourier transform mass spectrometer or a Fourier transform ion cyclotron resonance mass spectrometer include. The ion source can be a continuous ion source or a pulsed ion source. The ion source can with a Gas chromatograph ("GC") or a liquid chromatograph ("LC") be coupled.

Of the Time of flight mass analyzer preferably has an injection or Injection electrode for injecting at least some ions in one direction substantially orthogonal or parallel with respect an axis, along the ions first in the time of flight mass analyzer enter, on.

A Ion trap upstream the time of day mass analyzer can store and periodically release ions into the time-of-flight mass analyzer be provided. In similar Way, an ion trap may preferably be upstream of the Ionenmobilitätsseparators for storing ions and periodically releasing ions into the ion mobility separator be provided.

A collision cell may be provided downstream of the ion mobility separator in which, in one mode of operation, at least some ions entering the collision cell are fragmented. A mass filter, preferably before a four also may be provided downstream of the ion mobility separator, and preferably upstream of the collision cell (if provided).

According to one less preferred embodiment can instead of a post or post-processing of a complete sentence mass spectral data selective uptake of mass spectral data be made from the outset.

According to another aspect of the invention, a mass spectrometer is provided with:
an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility parabola at different time intervals;
a time of flight mass analyzer having a flight region, the time of flight mass analyzer configured to mass analyze at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval; and
Processing means adapted to receive the flight time of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, the intensity or significance of ions having a flight time less than or less than a minimum flight time; is reduced.

According to another aspect of the invention, there is provided a mass spectrometer having the following features:
an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals;
a time of flight mass analyzer having a flight region, the time of flight mass analyzer configured to mass analyze at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval; and
Processing means adapted to receive the flight time of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, the intensity or significance of ions having a flight time less than a minimum flight time and greater than a maximum flight time Flight time is reduced.

According to another aspect of the present invention, there is provided a mass spectrometer having the following features:
an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals;
a time of flight mass analyzer having a flight region, the time of flight mass analyzer configured to mass analyze at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval; and
Processing means adapted to receive the flight time of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance of ions having a flight time greater than a maximum flight time is reduced.

According to another aspect of the present invention, there is provided a mass spectrometer having the following features:
an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals;
a time-of-flight mass analyzer having a flight region, the time-of-flight mass analyzer configured to mass-analyze at least some of the ions exiting the ion mobility separator; and
Processing means adapted to receive the drift time of at least some of the ions exiting the ion mobility separator to form a first ion mobility data set, wherein the intensity or significance of ions having a drift time through the ion mobility separator greater than one maximum drift time is reduced.

According to another aspect of the present invention, there is provided a mass spectrometer having the following features:
an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals;
a time of flight mass analyzer having a flight region, wherein the time of flight mass analyzer is adapted for mass analysis of at least some of the ions exiting the ion mobility separator; and
Processing means adapted to receive the drift time of at least some of the ions exiting the ion mobility separator to form a first ion mobility data set, the intensity or significance of the ions having a drift time through the ion mobility separator which is less than a minimum drift time and greater than a maximum drift time is reduced.

According to another aspect of the present invention, there is provided a mass spectrometer having the following features:
an ion mobility separator for the separation of ions entsprechned their ion mobility, so that ions over different time intervals from the Io exit from the mobility unit;
a time of flight mass analyzer having a flight region, wherein the time of flight mass analyzer is adapted for mass analysis of at least some of the ions exiting the ion mobility separator; and
Processing means adapted to receive the drift time of at least some of the ions exiting the ion mobility separator to form a first ion mobility data set, the intensity or significance of ions having a drift time through the ion mobility separator being less than a minimum drift time; is reduced.

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Separating ions according to their ion mobility in an ion mobility separator such that ions exit the ion mobility separator over different time intervals;
Mass analyzing at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval with a time of flight mass analyzer, the time of flight mass analyzer having a flight region;
Generating a first mass spectral data set including data corresponding to the time of flight of at least some of the ions of the first group of ions through the flight region; and
Processing the first mass spectral data set to form a first processed mass spectral data set, wherein the intensity or significance of ions having a first undesired charge state relative to ions having a second, different, desired state of charge is reduced.

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Separating ions according to their ion mobility in an ion mobility separator so that ions exit the ion mobility separator over different time intervals;
Passing at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval to a Time of Flight mass analyzer, the time of flight mass analyzer having a flight region; and
Recording the time of flight of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance of ions having a flight time that is less than a minimum flight time is reduced ,

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Separating ions according to their ion mobility in an ion mobility separator so that ions exit the ion mobility separator over different time intervals;
Passing at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval to a Time of Flight mass analyzer, the time of flight mass analyzer having a flight region; and
Recording the time of flight of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance of ions having a time of flight that is less than a minimum flight time and greater than a maximum flight time , is reduced or is.

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Separating ions according to their ion mobility in an ion mobility separator so that the ions exit the ion mobility separator over different time intervals;
Passing at least some of the ions of a first group of ions emerging from the ion mobility separator during a first time interval to a time of flight mass analyzer, the time of flight mass analyzer having a flight region; and
Recording the time of flight of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance of ions having a flight time greater than a maximum flight time is reduced ,

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Separating ions according to their ion mobility in an ion mobility separator such that ions exited the ion mobility separator over different time intervals;
Passing at least some of the ions exiting the ion mobility separator to a time of flight mass analyzer, the time of flight mass analyzer having a flight region; and
Recording the ion mobility of the ions of at least some of the ions to form a first ion mobility data set, wherein the intensity or significance of ions having a drift time the ion mobility separator is greater than a maximum drift time is reduced or is.

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Separating ions according to their ion mobility in an ion mobility separator so that ions exit the ion mobility separator over different time intervals;
Passing at least some of the ions exiting the ion mobility separator to a time of flight mass analyzer, the time of flight mass analyzer having a flight region; and
Recording the ion mobility of the ions of at least some of the ions to form a first ion mobility data set, wherein the intensity or significance of the ions having a drift time through the ion mobility separator that is less than a minimum drift time and greater than a maximum drift time; is reduced or is.

According to another aspect of the present invention, there is provided a method of mass spectrometry comprising the steps of:
Separating ions according to their ion mobility in an ion mobility separator such that ions exit the ion mobility separator over different time intervals;
Passing at least some of the ions exiting the ion mobility separator to a time of flight mass analyzer, the time of flight mass analyzer having a flight region; and
Recording the ion mobility of the ions of at least some of the ions to form a first ion mobility data set, wherein the intensity or significance of ions having a drift time through the ion mobility separator that is less than a minimum drift time is reduced.

According to one Another aspect of the present invention is a method for Mass spectrometry provided at the mass spectral data or ion mobility data and the data to exclude ions with an undesirable Charge state to be processed.

Upstream of the Flight region may be provided an ion trap. This ion trap is separated from an ion trap, which is preferably upstream of the ion trap Ionenmobilitätsseparators can be provided. The ion trap may preferably be periodic Save and release ions, making a pulsed (as opposed to admitted to a continuous) ion source or otherwise is introduced into the flight region. The injection electrode is for Injection of ions for a predetermined period of time, After the first ion from the ion trap upstream of the Drift region have been released, arranged or trained. The Time is set so that only ions with a desired Mass-to-charge ratio or a mass-to-charge ratio within a desired Area substantially through the injection electrode in an orthogonal Direction be injected and then forwarded.

ions in an ion mobility separator (also called ion mobility spectrometer can be designated) are preferably an electric field exposed in the presence of a buffer gas, so that different Ion species will assume different rates as they the ion mobility separator happen. The speed of the ion mobility separator Passing ions will depend on their mobility, the in turn depends on the mass-to-charge ratio of the respective ion. ions with a relatively high ion mobility become a relatively high Speed compared to ions with a relatively low ion mobility accept. Accordingly, are relatively heavy, simply loaded Ions lower ion mobilities (and therefore lower speeds) than lighter, single charged Accept ions.

According to one more preferred embodiment can the ion mobility separator a number of electrodes with openings, through which ions transmit or transmit in use be, have. A constant axial electric field gradient may be along at least a portion of the length of the ion mobility separator be maintained.

According to one another embodiment, a or more transient DC voltages or one or more DC voltage waveforms on the Ionmobilitätsseparator forming or extensive electrodes are applied so that ions with a certain ion mobility preferably entrained along the ion mobility separator be taken while other ions longer will need to emerge from the ion mobility separator. The ion mobility seperator can ion both radially and axially within the ion mobility separator trap so that ions with a desired ion mobility from the Ion mobility separator ejected be while all other ions effectively within the ion mobility separator be captured.

A time-of-flight mass analyzer becomes live downstream of the ion mobility separator for analyzing the ions exiting the ion mobility separator. The time-of-flight mass analyzer may have either an axial or an orthogonal acceleration time-of-flight mass analyzer. Time-of-flight mass analyzes are parallel analyzers that detect and analyze ions of all mobilities and states of charge.

Various embodiments The present invention will be described purely by way of example and under Reference to the attached Drawing, described.

1 shows a conventional mass spectrum;

2A shows a conventional mass spectrum obtained with a normal detector gain and a normal detector gain, and 2 B shows a comparable mass spectrometer, which was obtained by reducing the detector gain.

3A shows the known relationship between the time of flight in a Time of Flight mass analyzer as a function of the drift time in an ion mobility separator for various singly and doubly charged ions, and 3B shows an experimentally obtained relationship between the mass-to-charge ratio of a sample of ions and their drift time through an ion mobility separator;

4 illustrates the general principle of producing a mass spectrum in which singly charged ions have been effectively excluded according to an embodiment of the present invention;

5 Fig. 12 shows the general principle of selecting mass spectral data relating to ions with a particular charge state according to an embodiment of the present invention;

6A FIG. 12 is a schematic illustration of a basic embodiment of the present invention having an ion mobility separator upstream of an orthogonal acceleration time-of-flight mass analyzer; and FIG 6B Figure 4 shows how the pusher electrode of the Time of Flight mass analyzer is preferably energized multiple times before a new pulse of ions is introduced into the ion mobility separator;

7A shows an ion mobility separator according to an embodiment, 7B shows the various DC voltages that can be applied to the ion mobility separator and other components, and 7C Figure 4 shows how the DC voltage applied to an ion gate upstream of the ion mobility separator can be varied as a function of time to release ions into the ion mobility separator;

8th Figure 4 shows how mass spectral data can be processed so that ions of desired charge state (s) can be used to provide a composite mass spectrum that effectively excludes ions with an undesirable charge state;

9 shows an ion mobility separator according to another embodiment in an initial equilibrium state prior to application of one or more transient DC voltages to the electrodes forming the ion mobility separator;

10 shows a transient DC pulse generated at one end of the ion mobility separator;

11 shows the transient DC pulse that carries ions of relatively high mobility in the direction of an exit of the ion mobility separator;

12 shows ions of relatively high mobility just prior to their ejection from the ion mobility separator;

13 shows the original stage of a bandpass mode of an ion mobility separator;

14 shows ions with relatively high and moderate ion mobilities which have been entrained in a separate region of the ion mobility separator and thus have been effectively isolated from relatively low mobility ions;

15 Figure 4 shows how ions with a relatively high ion mobility can be entrained from the separate region, leaving ions of intermediate ion mobility in the separate region;

16 Figure 4 shows a conventional mass spectrum of a mixture of singly charged leucine-enkephalin and doubly charged gramicidin S-ions;

17 Figure 4 shows a mass spectrum obtained in accordance with a preferred embodiment of the present invention, in which the mass spectral data which is completely contained in the mass spectral data shown in FIG 16 have been processed, so that singly charged leucine enkephalin ions essentially in the resulting masses spekrum are absent;

18 shows an ion mobility spectrum for leucine enkephalin and gramicidin S ions;

19 shows a schematic diagram of a mass spectrometer according to a preferred embodiment;

20 shows a stacked-ring ion mobility separator; and

21 Figure 12 shows the axial potential along a portion of a preferred ion mobility separator showing the slight nonuniformity of the gradient due to the grouping of rings in groups of four electrodes, all of which are held in a group at substantially the same DC potential.

Various embodiments of the present invention will now be described. 3A Figure 11 shows the known relationship of time-of-flight through a flight time region of a Time of Flight mass analyzer as a function of drift time through an ion mobility separator for various single and double or double charged ions.

An experimentally obtained relationship between the mass-to-charge ratio of the ions and their drift time by an ion mobility separator is shown in FIG 3B shown. It becomes clear that singly charged [M + H] ⁺ ions lie on a different characteristic line, curve or within a different characteristic band relative to the doubly charged [M + 2H] ²⁺ ions, ie doubly charged ions have one shorter drift time through the ion mobility separator compared to singly charged ions with the same mass to charge ratio. Since the time of flight of an ion by a time-of-flight mass analyzer is related to the mass-to-charge ratio of the ion, the y-axis may be considered substantially equivalent to the mass-to-charge ratio of the ions. Accordingly, it is off 3B more clearly, singly charged ions having a given mass-to-charge ratio have lower ion mobility, ie, longer drift time through an ion mobility separator than doubly charged ions of substantially the same mass-to-charge ratio. This relationship may be represented by an experimentally derived polynomial expression or by other relationships (eg, exponential).

4 Figure 4 shows how mass spectral data can be processed such that mass spectral data relating to ions of a particular charge state can be effectively selected to be used from the resulting mass spectrum, whereas data relating to ions having an undesirable charge state , can be effectively rejected (or at least reduced) and thus not used to form the resulting mass spectrum. The known data according to 3A and the experimentally derived data according to 3B may be interpreted as meaning that all ions having the same state of charge as within a particular region or band of a 2D graph of mass-to-charge ratio versus drift time may be viewed through an ion mobility separator. In 4 For example, singly and doubly charged ions are shown as falling within an intermediate intermediate region, with very few ions of interest to be found. Triple and quadruple charged ions, etc. are not shown for the sake of simplicity of illustration only. The large area under the scan line may be considered as representing simply charged ions, and the other area above the scan line may be considered as representing twice charged ions.

Looking at the 4 It can be seen that at about 4 ms after ions have first entered or been allowed to enter the drift region of the ion mobility separator, ions of various different mass-to-charge ratios can exit the ion mobility separator. These ions that exit and have a mass to charge ratio in the range of 1 to 790 are most likely to be singly charged ions, whereas those that exit at a mass to charge ratio in the range of 1070 to 1800 are most likely to be charged twice Ions are. Very few, if any, ions will exit at that time and have a mass to charge ratio of between 790 and 1070 (which corresponds to the intermediate region of the graph). Therefore, when the mass spectral data obtained is post-processed so that mass spectral data obtained at that particular time is manipulated so that only data relating to ions with a mass-to-charge ratio greater than 790 It can be seen that simply charged ions are effectively excludable from the resulting composite mass spectrum. Advantageously, the mass spectrum will only refer to doubly charged ions (and ions with a higher charge state). This is particularly advantageous in that it allows, for example, simply loaded background reason can be effectively excluded from the mass spectrum, and thus the signal-to-noise ratio of, for example, multiply charged analyte ions within a background of singly charged ions can be significantly improved. Improvements in the signal-to-noise ratio on the order of about 100 have been observed experimentally.

When the mass spectral data is post-processed such that the minimum mass-to-charge ratio of the mass spectral data that is retained (ie, used to use the resulting mass spectrum) is the "scan line" in accordance with FIG 4 it will be seen that only mass spectral data related to multiply charged ions are used essentially to form the composite mass spectrum.

According to others embodiments can track the lower predetermined mass-to-charge ratio for twice charged ions become. The cutoff mass to charge ratio can also for at least part of a processing cycle within the intermediate region, which separates the regions with singly and doubly charged ions, lie. The minimum cut-to-mass-to-charge ratio, the is applied to the mass spectral data, can also be in a predetermined or random manner between one upper threshold of the singly charged ion region, the intermediate region and the lower threshold of the dual charged ion region. It will be understood that, in accordance with less preferred embodiments the minimum mass-to-charge ratio for less may fall a portion of the processing cycle within the region, comprising the ions labeled as either single or double charged is seen. Under such circumstances, ions of a potential undesirable State of charge continues to occur in the resulting mass spectrum, however, the intensity and significance of such ions will nevertheless be diminished.

According to one preferred embodiment the minimum cut-to-mass-charge ratio, which is based on the Mass spectral data for filtering mass spectral data, which is on ions with an unwanted Charge state, from the resulting mass spectrum, varies evenly and preferably as a function of ion drift time through the ion mobility separator elevated. Alternatively, the minimum cut-to-mass-charge ratio, preferably, may be the obtained mass spectral data is applied in a stepped one As a function of ion drift time through the ion mobility separator elevated become.

5 shows how the principle of formation of a mass spectrum, which refers to doubly charged ions, as described with reference to 4 can be extended, so that ions with a specific state of charge or specific charge states can be represented in the resulting mass spectrum, excluding ions with other charge states. 5 shows how the mass spectral data can be post-processed so that ions of a specific charge state (in this case, triply charged ions) are preferentially selected before ions of any other charge state. The mass spectral data obtained at time T after ions are first introduced or introduced into the ion mobility separator may be post-processed such that mass spectral data relating to ions having a mass to charge ratio greater than (>) P and less than (<) Q is obtained , wherein P is preferably at the upper threshold of the region containing doubly charged ions, and Q is preferably at the lower threshold of the region containing four times charged ions. After the mass spectral data obtained at a time T has been processed, the lower and upper mass-to-charge ratio cutoff values P, Q may then be preferably increased so that for the mass spectral data obtained at a later time T ' , the lower mass-to-charge ratio cutoff value applied to the mass spectral data has been increased from P to P ', and the upper mass to charge ratio cutoff value applied to the mass spectral data has changed from Q to Q. 'has been increased. As with the referring to 4 In the illustrated embodiment, the lower and upper mass-to-charge ratio cutoff values applied to the mass spectral data do not necessarily follow the lower and / or upper threshold of any particular charge state region, and according to the other embodiments, the lower and upper cutoff values be applied to the mass spectral data, are known to be found in one or more known intermediate regions and / or one or more of the bands in the ions with a certain state of charge. For example, in one embodiment, the lower and upper mass-to-charge ratio cutoff values applied to the mass spectral data may easily follow the thresholds of the regions comprising twice, three, four times, and so on charged ions. According to further embodiments, mass spectral data that may be refer to two, three, four or more charge states, preferably before any other charge states are selected (eg, dual and triple charged ions may be transmitted). Embodiments are also conceivable in which non-adjacent charge states (eg, doubly and quadruply charged ions) are selected for presentation in a resulting mass spectrum, but not ions of any other charge state.

6A shows a basic embodiment of the present invention. In one embodiment, a continuous ion source, such as an electrospray ion source, generates an ion beam 3 , Ions are then preferably in an ion trap 4 upstream of an ion mobility separator or spectrometer 1 captured. The ions may then be applied, for example, by applying an extraction voltage to an ion gate 7 at the exit of the ion trap 4 and upstream of the ion mobility separator 1 is arranged to be pulsed out of the ion trap or impulsively excreted. 6B shows the relationship between the pulsed inputs of ions into the ion mobility separator 1 and then mass analyzing the ions. This will be described in further detail below.

The ion trap 4 may for example have a quadruple set of rods, for example, has a length of about 75 mm. According to a further embodiment, the ion trap 4 however, comprise an ion tunnel ion trap having a plurality of apertured electrodes. The openings are preferably all of the same size. In other embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the electrodes have openings that are substantially the same size. The ion tunnel ion trap may preferably have about 50 electrodes. Adjacent electrodes of the ion trap 4 are preferably connected to opposite or opposite phases of an AC or RF power supply so that ions in use radially within the ion trap 4 are captured or limited.

The on the Ionengate or Ionengatter 7 or another voltage applied, which effectively captures the ions in an ion trapping region upstream of the ion mobility separator, may drop for a short period of time, causing ions to escape from the ion trap 4 in a substantially pulsatile manner into the ion mobility separator 1 be ejected.

In less preferred embodiments, a pulsed ion source, such as a matrix assisted laser desorption ionization ion source ("MALDI") or a laser desorption ionization source ("LDI") may be used in place of a continuous ion source. If a pulsed ion source is used, the ion trap can 4 and the ion gate can be omitted.

The ion mobility separator 7 is a device that causes ions to be temporarily separated while passing through the ion mobility separator 1 pass through or pass through their ion mobility. A number of different forms of ion mobility separators 1 can be used.

According to one embodiment, the ion mobility separator 1 a drift tube (not shown) having a number of guard rings distributed within the drift tube. The monitoring rings can be interconnected by resistors of the same size or values and connected to a DC voltage source. A linear DC voltage gradient can be generated along the length of the drift tube. The monitoring rings are not connected to an AC or RF or RF voltage source.

According to a further, more preferred embodiment, the ion mobility separator 1 a plurality of ring electrodes, ring-like electrodes or plate electrodes, or more generally electrodes having openings formed therein through which ions are transmitted in use. The openings are preferably the same size and are preferably circular. In other embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the electrodes are formed with openings having substantially the same size or area.

A schematic example of such an ion mobility separator is shown in FIG 7A shown. The ion mobility separator 1 can be a number of electrodes 1a . 1b which are arranged either in a single vacuum chamber, or, as in 7A shown in two adjacent vacuum chambers, which are separated by a differential pumping Ap Ap. In one embodiment, the portion of the ion mobility separator 1a in an upstream vacuum chamber have a length of, for example, about 100 mm, and the portion of the ion mobility separator 1b in a downstream vacuum chamber may have a length of, for example, about 85 mm. The ion trap 4 , the ion gate 7 and the upstream section 1a of the ion mobility comparator is 1 may be provided in the same vacuum chamber, which is preferably maintained at a pressure in the range 0.1 to 10 mbar during use. According to less preferred embodiments, the vacuum chamber covering the upstream portion 1a includes, be maintained at a pressure greater than 10 mbar to a pressure at or in the vicinity of the atmospheric pressure. Further, according to less preferred embodiments, the vacuum chamber may alternatively be maintained at a pressure below 0.1 mbar.

The ion trap 4 _Forming or comprehensive electrodes can be maintained at a DC voltage V _rf1 . The ion gate 7 can normally be kept at a higher DC voltage V _trap than V _rf1 , but that on the ion gate 7 applied voltage may be periodically lowered to a voltage V _extract , which is preferably less than V _rf1 , causing ions from the ion trap 4 and into the ion mobility separator 1 be admitted.

Adjacent electrodes that are part of the ion trap 4 are preferably connected to opposite phases of a first dc or rf voltage supply to drive the ions radially within the ion trap 4 withhold. The first DC or RF power supply preferably has a frequency within the range 0.1 to 3.0 MHz, preferably 0.5 to 1.1 MHz, more preferably 780 kHz.

Alternating electrodes covering the upstream section 1a of the ion mobility separator are preferably capacitively coupled to the opposite phases of a first DC or RF power supply.

The ion trap 4 forming or encompassing electrodes that cover the upstream section 1a of the ion mobility separator forming electrons and the differential pump aperture Ap1, which is the upstream section 1a from the upstream section 1b of the ion mobility separator 1 disconnects or separated, are preferably connected to one another via resistors with a DC voltage supply, which in one embodiment comprises a 400 V supply. The resistors that connect the electrodes to each other, the upstream section 1a of the ion mobility separator 1 can have substantially the same values or size, in which case an axial Gleichspannungsgradient is obtained, as in 7B is shown. The DC voltage gradient is shown to be linear, for simplicity of illustration only, but may be at least partially stepped in practice. An applied AC voltage or RF voltage is superimposed on the DC voltage and serves for radial confinement within the ion mobility separator. The DC voltage V _trap or V _extract , which is on the Io n gate 7 is applied, floats preferably on the DC power supply. The first AC or RF power supply is preferably isolated from the DC power supply by means of a capacitor.

In a similar manner, alternate electrodes are the downstream portion 1b of the ion mobility separator 1 preferably capacitively coupled to the opposite phases of a second AC or RF power supply. The second AC or HF voltage supply preferably has a frequency in the range 0.1 to 3.0 MHz, preferably 1.8 to 2.4 MHz, more preferably 2.1 MHz. In a similar way to the upstream area 1a becomes a substantially linear or stepped axial DC voltage gradient along the length of the downstream section 1b of the ion mobility separator 1 maintained. As with the upstream section 1a The applied AC voltage or RF voltage is superimposed on the DC voltage and serves to radially restrict the ions within the ion mobility separator 1 , The DC voltage gradient, which is above the upstream section 1a is preferably not equal to the DC voltage gradient that is above the downstream portion 1b is maintained. In a preferred embodiment, the DC voltage gradient is above the upstream portion 1a is maintained larger than the DC voltage gradient across the downstream section 1b is maintained.

The pressure in the vacuum chamber that cut the downstream section 1b is preferably in the range of 10 ^-3 to 10 ^-2 mbar. According to less preferred embodiments, the pressure may be greater than 10 ^-2 mbar, and could be similar to the pressure in the vacuum chamber covering the upstream portion 1a includes, be. It is believed that the greatest temporal or temporal separation of ions in the upstream section 1a due to the higher background gas pressure occurs. If the pressure is too low, the ions do not carry out enough collisions with gas molecules for a significant time separation of the ions.

The size of the opening in the ion gate 7 is preferably of a similar size or has substantially the same inner diameter or the same inner size as the differential pumping Ap1 opening. Downstream of the Io nenmobilitätsseparators may be provided a further differential pumping Ap2. The openings of the electrodes containing the ion mobility separator 1 preferably all have the same size. In other embodiments, at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% of the electrodes have openings that are substantially the same size.

In a further embodiment, the ion mobility separator 1 have an ion tunnel consisting of a number of segments. In one embodiment, 15 segments may be provided. Each segment may have two electrodes with openings that are nested or overlapped with two other electrodes that also have openings. All four electrodes in a segment can be maintained at substantially the same DC voltage, but adjacent electrodes are preferably connected to opposite phases of the same AC voltage or RF supply. The DC and AC / RF power supplies are isolated from each other. Preferably, at least 90% of all electrodes are the ion mobility separator consisting of a number of segments 1 form, formed with openings which have substantially similar or equal sizes.

Typical drift times due to the ion mobility separator 1 can be on the order of a few ms. After all generated ions the ion mobility separator 1 a new ion pulse or ion pulse can be introduced into the ion mobility separator, which marks the beginning of a new operating cycle. Many cycles (for example, 200 or more) can be performed in a single trial run (which may take, for example, 1 second).

A collision or gas cell and / or a quadruple mass filter (in 6A not shown) may preferably be downstream of the ion mobility separator 1 and upstream of the transfer lens 5 be provided. Ions can be designed to be sufficiently energetic when they enter the collision cell so that they collide with gas molecules present in the gas cell and fragment into daughter ions. Subsequent mass analysis of the daughter ions yields valuable mass spectral information regarding the parent ions and parent ions, respectively. The ions may also be designed to enter the gas or collision cell in a different operating mode with substantially less energy, where they may not fragment significantly in this case. For example, the energy of the ions entering the collision cell may be controlled by adjusting the level of the voltage gradient experienced by the ions prior to their entry into the collision cell. Since the voltage gradient can be switched almost instantaneously, the collision cell can also effectively be switched between a relatively high fragmentation mode and a relatively low fragmentation mode.

A transfer lens 5 may be provided downstream of the ion mobility separator to guide ions through another differential pumping port and into an analyzer chamber with a time of flight mass analyzer. The mass analyzer is preferably an orthogonal acceleration-time-of-flight mass analyzer 2 with a slider and / or puller electrode 6 for injecting ions into an orthogonal flying region. A reflectron is preferably for reflecting ions traveling through the orthogonal flight region back to an ion detector 8th intended. As is known in the art, at least some of the ions in an ion packet entering an orthogonal acceleration Time of Flight mass analyzer will be accelerated orthogonally into the orthogonal flight region. Ions are temporarily separated in the orthogonal flight region in a manner that depends on their mass-to-charge ratio. Ions with a smaller mass-to-charge ratio will travel faster in the flight region, and the ion detector 8th reach ions with a higher mass-to-charge ratio. The time taken for an ion to pass through the flight region and to reach the ion detector 8th may be used to accurately determine the mass-to-charge ratio of the ion in question. The intensity of the detected ions and their mass-to-charge ratios can be used to produce a mass spectrum.

In a less preferred embodiment, the time of flight mass analyzer may comprise an axial time of flight mass analyzer. Ions can be pulsed or pulsed into the axial time-of-flight region. To pulse ions into an axial flight region, a second ion trap and optionally a second ion gate may be provided upstream of the axial flight region. From the ion mobility separator 1 received ions can be trapped in the second ion trap. Packages of ions may then preferably be periodically released from the second ion trap, for example by reducing the DC voltage applied to the second ion gate, in a manner similar to ions from the first ion gate 7 into the ion mobility separator 1 can be let out. However, in other embodiments, the second ion trap may capture and release ions without the need for a special second ion gate.

The second ion trap may include an ion tunnel ion trap which a number of electrodes with openings formed therein having. The electrodes can in the form of rings or in other ring-shaped or rectangular form Be formed plates. Preferably at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the electrodes, the second Forming ion traps, openings which are essentially the same size or the same area exhibit. Adjacent electrodes are preferably opposed Connected to phases of an AC or RF power supply, such that ions are retained radially within the second ion trap become. A particular advantage of an ion tunnel ion trap lies founded in that the DC voltage applied to each electrode is individual can be controlled. This allows the Generating more diverse different axial DC voltage profiles along the length of Ion tunnel ion trap. According to one preferred embodiment becomes a V-shaped DC potential profile in one mode of operation with an upstream Section with a negative DC voltage gradient and a downstream Provided with a positive DC gradient, such that (positive) ions move towards the center of the ion trap be captured. When the positive DC voltage gradient is along of the downstream Section of the ion trap is maintained and then to a zero gradient or more preferably converted to a negative gradient becomes (positively charged) ions as an ion pulse accelerated out of the ion trap. In this particular embodiment If a partially provided second ion gate then superfluous or become redundant.

According to others embodiments The second ion trap can be a 3D quadruple ion trap with one central donut-shaped Have electrode together with two end cap electrons. According to one another embodiment For example, the second ion trap may have a hexapole ion guide. This embodiment However, it is less preferred because there is no axial DC voltage gradient to urge Ions from the hexapole ion guide is available. For this reason, an ion tunnel ion trap particularly preferred.

The second ion trap can serve both as an ion trap and as a collision cell. The ion tunnel ion trap / collision cell may have a number of segments (eg, 15 segments), each segment having four electrodes that are interleaved with another four electrodes. All eight electrodes in a segment can be maintained at the same DC voltage, but adjacent electrodes are preferably supplied with opposite phases of an AC or RF or RF power supply. A collision gas, preferably nitrogen or argon, may be added to the collision cell, preferably at a pressure in the range of 10 ^-3 to 10 ^-2 mbar. Ions can be trapped and / or fragmented in the ion trap / collision cell by appropriately adjusting the DC voltages applied to the electrode and the energy given to the ions as they enter the ion trap / collision cell.

According to a preferred embodiment, the upstream ion trap 4 and the ion mobility separator 1 an ion tunnel, ie a number of electrodes, each electrode having an aperture therein through which the ions are transmitted in use. The electrodes, which are the ion trap 4 and / or the ion mobility separator 1 Preferably, they are substantially apertures of the same size, and may comprise a substantially square or rectangular plate electrode or a ring electrode or a circular electrode. The openings are preferably circular. According to various embodiments, the ion traps 4 and / or the ion mobility separator 1 at least 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 electrodes, of which at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% openings may have, which have substantially the same size or the same area.

Embodiments of the invention are also conceivable in which the DC profile along the length of the Ionenmobilitätsseparators 1 and / or the ion trap 4 and / or the collision cell is not strictly linear, but has a stepped profile.

ions 3 from, for example, an electrospray ion source are preferably in the ion trap 4 or any other ion capture device and are then periodically pulsed into the ion mobility separator. How out 3B As can be seen, the typical drift time of the ions through an ion mobility separator is on the order of a few ms. During this period, the orthogonal acceleration electrode becomes 6 the time of day mass analyzer 2 energized several times. For example, ions that are in the ion mobility separator 1 be pulsed, up to 10 ms to pass through the ion mobility separator 1 to drift. From the ion mobility separator 1 leaking ions become the pusher electrode 6 the time of flight mass analyzer further transmitted or transmitted, which energeti with a repetition rate of, for example, 50 microseconds can be siert. According to further embodiments, the repetition rate may be less than 10 μs, 10 to 20 μs, 20 to 30 μs, 30 to 40 μs, 40 to 50 μs, 50 to 60 μs, 60 to 70 μs, 70 to 80 μs, 80 to 90 μs. 90 to 100 microseconds or greater 100 microseconds. Accordingly, the slide electrode 6 For example, 200 times per pulse of ions are energized in the ion mobility separator. The mass spectral data from the 200 or such number-executing mass analyzes may then be processed, and a composite mass spectrum may be generated from the processed mass spectral data. After all ions through the ion mobility separator 1 may be a new pulse of ions from the ion trap 4 into the ion mobility separator 4 be left out so that the process can start again. For example, during a period of 1 second, ions can travel 100X into the ion mobility separator 1 pulsed, with 200 sets of mass spectral data per pulse of ions in the ion mobility separator 1 to be obtained. Accordingly, 20,000 sets of mass spectral data can be obtained during a one-second trial run.

The time that an ion passes through the ion mobility separator 1 , to exit from this and to arrive at the gate electrode 6 of the time-of-flight mass spectrometer 2 needed, will depend on the mobility of the ion. Larger mobility ions will require a shorter time to travel through the ion mobility separator than ions with relatively lower ion mobility 1 pass.

6B shows the temporal relationship between ions entering the ion mobility separator 1 be pulsed, and the Energetisierung or Energiebeaufschlagung the slide electrode 6 , For simplicity of illustration are merely 6 Slider pulses per gate pulse or pulse shown. However, as discussed above, typically the slider electron may be 100 to 200 times per pulse of ions into the ion mobility separator 1 be energized. The ions attached to the ion detector 8th the time of day mass analyzer 2 arrive from the pusher pulse p1, have a higher mobility than the ions arriving from subsequent pusher pulses p2, etc. at the ion detector. That of the pusher pulse Pn at the ion detector 8th incoming ions will then have a higher mobility than the ions arriving from the pusher pulse Pn + 1 at the ion detector. Ions arriving at the ion detector from a pusher pulse Pn will produce a set of mass spectral data corresponding to ions corresponding to a specific ion mobility associated with the pusher pulse Pn.

The summation of all mass spectral data from all shifter pulses occurring during a single gate pulse period (ie, the time between subsequent pulses of ions into the ion mobility separator 1 ) in a conventional manner gives an integrated or assembled mass spectrum comprising all ions independent of their mass-to-charge ratio ion mobility, and therefore of the state of charge.

The mass spectral data obtained on the basis of a particular slider pulse Pn can be expressed as a vertical section through the graph or the plot according to FIG 3D Tn are considered to be the time delay from the gate pulse (ie release of the ions into the ion mobility separator ( 1 )) to the pusher pulse Pn (ie, energization of the electrode 6 ) is defined.

According to a less preferred embodiment, the acquisition by the Time of Flight mass analyzer for a given pusher pulse Pn may be configured so that only mass spectral data related to ions arriving after a certain cut-off time of flight arrives , acquired, stored or otherwise recorded. For example, this clipping time-of-flight may be between the two-way and three-way loaded bands as shown in FIG 3B are shown lie. Therefore, the resulting mass spectrum would then contain only doubly charged ions (or ions of higher charge or order). Overall, the mass spectral data would be processed on the flight or taken in advance only in a predetermined manner. Such an approach would reduce the amount of mass spectral data to be processed, but is less flexible than the preferred embodiment, which acquires complete data sets and subsequently reprocesses these data.

The desired cutoff flight time value, which is preferably applied to the mass spectral data or less preferably to the initial acquisition of the data, may vary from the pusher pulse Pn to the pusher pulse Pn + 1, and may be, for example, as described in U.S. Pat 8th followed by the solid arrow follow. If the time-of-flight clipping does not follow the solid arrow in 8th following, the summation of all mass spectra from all the slider pulses in a single gate period would result in a resulting integrated spectrum comprising only multiply charged ions, ie singly charged ions would be effectively filtered out.

It will be understood that the characteristic band of ion drift times through the ion mobility separator 1 against the ion flight time through the flight region of the time-of-flight mass analyzer for triply charged ions to the left of the characteristic band for doubly charged ions, as in 8th as already stated with reference to 5 was discussed. The characteristic ionic drift time band of a ion versus the ionic charge ion flight time (n + 1) is similarly at lower drift times than the characteristic band for the state of charge n. By using combinations of ion mobility-dependent upper and lower time-of-flight cutoffs, which vary, preferably increase with the drift time, it is possible to select ions with a certain state of charge or a combination of states of charge. An upper time-of-flight cut-off value used in conjunction with a lower time-of-flight cut-off value allows a bandpass mode to filter the mass spectral data and select certain charge states. It is possible to define multiple bandpasses, and thus to select any desired combination of charge states.

According to the preferred embodiment, all ions entering the Time of Flight mass analyzer become 2 for a given pulse Pn, then detected and recorded. However, software is preferably used to selectively disregard ions having flight times below a minimum flight time, such as by the in-flight time 8th shown scan or scan line for a given pulse or thrust event Pn shown. The summation of the processed mass spectral data results in an integrated or assembled mass spectrum that includes only doubly charged ions (or higher order ions). This software approach also permits the generation of multiple bandpasses, whereby, as already mentioned, any combination of charge states can be selected.

According to another embodiment, mass spectral data related to multi-pulses may be grouped together, and a time-of-flight cut-off value for a group of pulses may be defined. Accordingly, the clipping time-of-flight applied to the mass spectral data would increase in steps (eg, according to the dashed line in FIG 8th ). This approach would also result in an improvement in the filtering out of unwanted charge states from the final mass.

9 shows another preferred form of ion mobility separator 1 that has a number of electrodes 12 each having an opening through which ions are transmitted in use. Adjacent electrodes 12 are preferably connected to opposite Pha sen of an AC or RF power supply. The ion mobility separator 1 is preferably maintained at a pressure such that ions that traverse its length make numerous collisions with gas molecules. The ion mobility separator 1 In one embodiment, it may receive ions generated by an electrospray or MALDI ion source. One or more end plates or electrodes 13a . 13b of the ion mobility separator 1 can be at a slightly positive voltage relative to the other electrodes 12 so that ions once entered the ion mobility separator effectively within the ion mobility separator 1 be captured, and thus can not overcome the potential barrier at one or both ends. After a certain period of time, a state of equilibrium within the Ionenmobilitässeparators 1 can be achieved so that ions of all masses and mobilities substantially along the length of the ion mobility separator 1 , as in 9 shown are equally distributed.

As in 10 In one embodiment, the voltage pulse Vg may be applied to an electrode adjacent to one of the end plates 13a be applied, so that some ions through the applied voltage pulse or Vg along the Ionenmobilitässeparators 1 be pushed or moved. The local field variation is given by U drift = KE (x), where V _{drift is} the rate of release of an ion, K is the mobility of the ion and E (x) is the electric field caused by the applied voltage. The electric field resulting from the applied voltage decreases rapidly within some electrode spacings to a negligible value.

The voltage pulse Vg is then preferably switched quickly to the next adjacent electrode. An ion which had enough time, at least one electrode spacing along the ion mobility separator 1 to drift will therefore experience the same force, and will once again move in the direction in which the voltage pulse Vg moves. However, ions with lower ion mobility may not have had the time to drift far enough to notice the influence of the voltage when it is switched to the adjacent electrode. Accordingly, these lower mobility ions effectively become affected by the migrating chip voltage pulse Vg or the voltage waveforms left behind.

The voltage pulse Vb preferably moves from electrode to electrode along the ion mobility separator, carrying with it the ions having sufficiently high ion mobility. As in the 11 and 12 shown, the ion mobility separator 1 Therefore, in one embodiment, they serve as high-pass ion mobility filters such that ions with ion mobilities greater than a certain value are preferably from the ion mobility separator 1 while ions with lower ion mobilities remain trapped substantially within the ion mobility separator. 12 At the end, ions show a voltage sweep coming out of the ion mobility particle 1 be ejected.

The sweep time T _{sweep of} the ion mobility separator 1 can then be reduced to select a slightly lower (intermediate) ion mobility, so that ions with intermediate ion mobility then successively from the ion mobility separator 1 can be ejected. By gradually further reducing the wobble, a complete mobility scan or full mobility scan can be established until the ion mobility separator 1 is essentially emptied of ions.

According to one another operating mode, the amplitude of the voltage pulse Vg be progressively increased with each sweep or sweep, resulting in ions with progressively decreasing ion mobilities collected in the same way become. Considering From the above equation, it will be understood that by doubling the Tension the speed of an ion is doubled.

The resolution of the ion mobility separator 1 is determined in part by the sweep time T _sweep or the voltage increment. The smaller the step (ie, reducing the sweep time or increasing the amplitude of the voltage pulse) between the adjacent wobbles, the greater the resolution of the ion mobility separator 1 ,

The operating mode described above may build up a mobility spectrum by a series of further high-pass steps. However, isolation of a particular range of ion mobilities, ie bandpass operation, can also be achieved by using a two-stage device. As in 13 As shown, ions having ion mobility greater than a certain value may pass along a portion of the ion mobility separator 1 be established by a voltage pulse Vg the ion mobility separator 1 happens. The ions from a first region 14 move towards an electrode 16 that are at a certain potential 17 is held, allowing ions with a minimum ion mobility, through the electrode 16 in a second region 15 which is preferably substantially empty of ions. As in 14 As soon as some ions enter the second region 15 have been deflected, the migrating voltage pulse Vg be reversed so that some ions from the second region 15 past the same (or another) electrode, which is preferably at a lower potential 17 ' is held back to the first region 14 can be distracted or entrained. The reverse sweep may be faster and / or have a higher voltage than the forward sweep, such that, as in FIG 15 shown ions having ion mobilities within a desired intermediate region in the second region 15 can be retained, with ions of higher and lower ion mobility in the first region 14 be located.

wobei mod X die räumliche Streuung aufgrund von Diffusion, L die Länge des Driftrohres und V der angewendete axiale Spannungsabfall ist.The resolution of the ion mobility separator 1 has been modeled taking into account the effect of ion diffusion. Diffusion effects are known to decrease the resolution of a drift tube ion mobility separator, and the relationship between the drift tube length and the applied axial voltage drop is given by:

where mod X is the spatial diffusion due to diffusion, L is the length of the drift tube, and V is the applied axial voltage drop.

To increase the resolving power of a drift tube mobility spectrometer, longer drift tubes and higher voltages can be used. An advantage of the preferred ion mobility separator 1 However, it is that the required voltage can be relatively low, for example 10 V at a pressure of 2 mbar. Furthermore, the low (10V) voltage must only be applied to a single electrode at any one time. The preferred ion mobility separator 1 can therefore achieve ion mobility separation using a low voltage source, whereas a conventional drift tube type mobility separator would require 1000V to achieve comparable ion mobility separation.

Further improvements in resolution can be achieved by repeated wobbling or distraction the ions can be achieved backwards and forwards by the same volume. This has the effect of increasing the effective length of the ion mobility separator 1 without increasing its actual physical dimensions. A compact ion mobility separator is thus provided. As can be seen, allows a larger number of passes through the ion mobility separator 1 a greater or better isolation of the desired species or type of ions.

Ions can be extinguished from the swept volume after passage of the migrating voltage by passing on the electrodes 12 applied AC voltage or RF voltage to be switched OFF and OFF, and thus the ions from this section of the ion mobility separator 1 can diffuse. After a desired number of passes through the same volume, the ions may be released from the ion mobility separator for subsequent mass analysis.

The ion mobility separator 1 Advantageously, according to the preferred embodiment, duty cycles approaching 100 may be accomplished by ejecting only ions having a desired ion mobility while storing the other ions for further analysis. This is in contrast to a field asymmetric ion mobility separator (FAIMS), which is a scanning device wherein ions that are not transmitted are lost on the walls of the device.

An embodiment is conceivable in which a quadruple mass filter downstream of a preferred ion mobility separator 1 is provided, and is set to a discrete mass-to-charge ratio transmission window so as to correspond to the desired mobility range expelled by the preferred ion mobility separator. This means that the desired ions in the quadruple mass filter are stable throughout the device. The equivalent of a scanning experiment can therefore be performed in a stepped manner without loss of duty cycle, as unejected ions still pass through the ion mobility separator 1 get saved.

In addition to embodiments in which a single transient DC potential or pulse Vg is along the length of the ion mobility separator 1 according to other embodiments, a traveling DC voltage having a repeating waveform may be used to separate ions according to their ion mobilities. The amplitude and velocity of the one or more DC voltage waveforms may be arranged so that ions do not ride on a single voltage pulse along the drift region, but instead roll over the top of successive pulses, thereby obtaining a series of small bursts , resulting in a total drift in the wave direction. The transit time of an ion through the ion mobility separator 1 will therefore depend on its ionic mobility.

According to this embodiment can be a traveling wave ion guide be used to provide the drift region. The ion guide can either a stack of plates or a segmented multi-stake set include. An ion trapping region upstream of the drift region may be combined with a Ion lattice may be provided to periodically bundle ions from the ion trap to pulse into the drift region or to introduce pulsating.

A traveling DC voltage waveform may include periodic pulses or pulses of constant amplitude and velocity. A reverse DC voltage gradient may be superimposed on the traveling DC voltage waveform so that the field between pulses for moving ions back to the upstream ion gate or the entrance of the ion mobility separator 1 acts. Such a DC voltage waveform may include the separation characteristics of the ion mobility separator 1 and can be used to avoid that ions with an ion mobility smaller than a certain value migrate with the traveling DC voltage wave and exit from the ion mobility separator.

According to a further embodiment, the DC potential waveform may be such that the magnitude of the voltage pulses along the drift region decrease with increasing potential due to an axial DC voltage gradient. Such a waveform may also favor separation. Further, the DC voltage waveform may be such that ions having a particular ion mobility may find equilibrium points along the length of the drift region where the movement caused by the traveling DC voltage wave is in opposition to the reverse axial DC voltage gradient. Therefore, ions of different mobility can have different equilibrium points along the length of the ion mobility separator 1 find or have. A static mobility separation can thus be generated and ions of similar mobility collected in specific regions. These ions can be transmitted in a bandpass mode. The operating mode using such a voltage waveform does not necessarily require an ion gate because it can work with a continuous ion beam. Furthermore, the DC axial field may be constant or variable with the position. This can be done by applying potentials to the electrodes forming the ion guide, these potentials increasing linearly or non-linearly. Alternatively, the amplitude of the traveling DC voltage may decrease linearly or non-linearly as it passes from the input to the output of the ion mobility separator 1 progresses. The DC axial field and the amplitude of the traveling wave may change with position. In accordance with a particular embodiment, the DC axial field may continuously increase from the input to the output of the ion mobility separator while the amplitude of the traveling DC voltage wave remains substantially constant.

Of the DC or DC-axial voltage gradient, the amplitude the wandering wave and the speed of the wandering DC wave can also change with time. Therefore, you can Ions of different mobility first spatial along the length the ion guide be separated and can then along the ion mobility separator be moved to one end or the other. It can thus causes ions with increasing or decreasing order their mobility the ion mobility separator escape.

Ions that have been separated from each other according to their ion mobility may go to the exit of the ion mobility separator 1 be moved by either the DC potential gradient decreases or the amplitude of the traveling DC voltage wave is increased. These ions can also be reduced by reducing the velocity of the traveling DC voltage wave or by reducing the gas pressure to the output of the ion mobility separator 1 to be moved. Movement of the ions can also be achieved by changing a combination of these controls. According to one embodiment, ions in the order of their ion mobility may be induced, the ion mobility separator 1 leave, starting with ions of the highest mobility.

According to another embodiment, the separated ions may be caused to move to the input of the ion mobility separator either by increasing the DC potential gradient and / or by decreasing the amplitude of the traveling DC voltage wave and / or by increasing the velocity of the DC voltage wave and / or increasing the gas pressure. According to this embodiment, it is possible to arrange ions over the area that is initially the entrance of the ion mobility separator 1 was to be emitted in the order of their mobility starting with ions of lowest ion mobility.

According to one embodiment can the pulse amplitude, the wave velocity, the pressure and the axial gradient during the operation to improve the separation can be varied.

One reverse axial stress gradient can improve separation by constant or recurrent return of the ions, which not transmitted or moved by the migrating DC voltage are to be used to the entrance of the separation region.

According to one embodiment, ions may first be collected in an ion tunnel ion trap consisting of a stack of 90 ring electrodes, each only 5 mm thick and spaced at 1.0 mm apart. The central opening of each ring may have a diameter of 5.0 mm, and the total length of the ion tunnel ion trap may be 134 mm. A 2.1 MHz RF voltage can be applied between adjacent rings to radially confine the ion beam within the ion trap. Ions can be retained by increasing the DC potential at each end of the ion trap by about 5V in the ion tunnel ion trap. The pressure in the ion tunnel ion trap can be about 10 ^-3 mbar.

Ions may be generated continuously using an electrospray ion source and may be directed continuously into the ion tunnel ion trap. The DC potential at the output end of the ion trap may then be periodically reduced to allow ions to exit the ion trap. Ions may be repeatedly collected and stored, for example, for 11 ms, and then released, for example, over a period of 26 ns. The ion trapping ions can then be accelerated over a 3V potential difference, and then optionally carried out by a quadruple-rod ion guide. The quadruple rod set ion guide can be operated in one mode so that only one RF voltage is applied to the rods so that it acts as an ion guide rather than as a mass filter. The quadruple rod-set ion guide ions can be transformed into an ion mobility separator 1 according to the preferred embodiment.

The ion mobility separator 1 may be from a similar ion tunneling system tion, as used for the initial collection and storage of ions emitted by the ion source. The ion mobility separator 1 For example, it may consist of a stack of 122 ring electrodes each 0.5 mm thick and having a spacing of 1.0 mm. The central opening within each ring may have a diameter of 5.0 mm and the total length of the ring rod may be 182 mm. A 2.4 MHz RF voltage may be applied between adjacent rings to radially confine the ions within the ion mobility separator 1 be applied. The pressure in the ion mobility separator 1 may be about 2 × 10 ^-2 mbar. A migratory DC wave can be applied to the ion mobility separator 1 can be applied and can consist of a regular periodic pulse of constant amplitude and speed.

The traveling DC voltage wave can be generated by applying a DC voltage to a single ring electrode and each subsequent ring electrode offset by 9 rings along the ring rod. Therefore, a wavelength λ of the DC voltage waveform may consist of an electrode having a raised DC potential followed by 8 electrodes of a lower potential (reference potential). Thus, the wavelength λ may be equal to the length of 9 electrodes or 13.5 mm, and the total ion mobility separator may be approximately equivalent to 13.5 λ. The traveling DC voltage wave can be generated by applying approximately 0.65V to each ring electrode for 5ns before moving the applied voltage to the next (adjacent) ring electrode. Thus, the wave period or cycle time t according to this embodiment is 45 ns. This may be uniform along the length of the ion mobility separator 1 be repeated. Thus, in accordance with one embodiment, the DC shaft speed may be equal to 300 m / s.

At the exit of the ion mobility separator 1 For example, the ions can pass through another quadruple set of rods. This additional quadruple set of rods may be operated in an RF mode or a DC mode (ie mass filtering mode) and may be arranged to transmit only ions of a particular mass-to-charge ratio.

When a mixture of gramizidine-S (molar weight or molecular weight 1142 daltons) and leucine-enkephalin (molecular weight 555 daltons) is continuously introduced into an electrospray ion source, singly charged protonated leucine-enkephalin ions (mass / charge or m / z 556) and doubly charged protonated gramizidine S ions (m / z 572) and in the upstream ion trap 4 saved. These ions can then be released periodically and their transit times through the ion mobility separator 1 be measured. The transit time of gramizidine S ions through the ion mobility separator 1 for example, 2.2 ms from release from the Stromabgasionenfalle 4 For example, while the transit time of leucine Enkephlain ions is about 3.1 ms from release from the upstream ion source 4 be. Similarly, the transit time of Gramizidine-S through the ion mobility separator 1 about 940 ns less than that for leucine enkephalin ions. This despite the fact that the mass-to-charge ratio of gramizidine-S (572) is slightly larger than that of leucine-enkephalin (556), and although the gramizidine-S molecule (molecular weight 1142 daltons) is larger than the leucine Enkephalin molecule (molecular weight 555 daltons) is. Nevertheless, the shorter transit time for gramizidine-S can be expected because gramizidine S ions are doubly charged and due to the electric field of the traveling wave experience the double force experienced by singly charged leucine enkephalin ions.

Although doubly charged gramizidine S ions experience twice the force, they will not experience twice the viscous drag because the cross-sectional area of gramizidine S ions is not twice that of leucine enkephalin ions. It can be assumed that the relative cross-sectional areas are in a ratio of about (1,144 / 556) ^2/3 , ie about 1.6. Therefore, gramizidine S ions are more mobile than leucine enkephalin ions in the presence of the same electric field and high gas pressure. Therefore, gramizidine S ions are more affected by the traveling DC waveform than leucine enkephalin ions. As a result, the transit time for gramizidine S ions through the ion mobility separator is smaller than that for leucine enkephalin ions.

16 Figure 3 shows a conventional mass spectrum of singly and doubly charged ions from a mixture of 0.1 ng / μl leucine enkephalin and 0.1 ng / μl gramizidine S.

17 shows a mass spectrum obtained according to the preferred embodiment, wherein the mass spectral data used to generate the in 16 according to the preferred embodiment of the invention are processed, so that ions with a time of flight which is less than a minimum cut-off value (which as a function of the drift time by the ion mobility separator 1 varied), rejected or otherwise diminished, with the result that singly charged leucine-enkephalin ions are essentially absent in the resulting mass spectrum. It is from a comparison of 16 and 17 clearly that according to the preferred embodiment, the signal-to-noise ratio has been significantly improved by a factor of about 100 ×. When singly charged ions are considered to be noise, embodiments of the present invention may be envisioned where the signal-to-noise ratio of mass peaks due to doubly or multiply charged analyte ions is at least a factor x 2, x 3, x 4, x 5, X 10, x 20, x 30, x 40, x 50, x 60, x 70, x 80, x 90, x 100, x 110, x 120, x 130, x 140, x 150, x 160, x 170 , × 180, × 190, or × 200 is improved.

According to one embodiment, 100 ion pulses are injected into the ion mobility separator at 10 ms intervals over a period of 1 second 1 Approved. Each ion pulse results in 200 sets of mass spectral data, as the repetition rate between successive energizations of the gate electrode 6 56 μs was. Corresponding sets of mass spectral data resulting from each ion pulse into the ion mobility separator may then be summed to produce 200 composite sets of mass spectral data.

18 shows superimposed ion mobility spectra for leucine enkephalin and gramizidine S, and shows that these two ions, which have a similar mass to charge ratio, can be resolved using ion mobility separator 1.

The in the 16 to 18 mass spectra and ion mobility spectra were measured using an ion mobility separator 1 with a number of ring electrodes and a constant axial DC voltage gradient as described above.

In a particularly preferred embodiment, a Q-Tof Ultima (RTM) API hybrid quadrupole orthogonal time-of-flight mass spectrometer (Micromass, United Kingdom) has been modified to implement the preferred embodiment. A schematic representation of the mass spectrometer is shown in FIG 19 with the modifications to the standard instrument replacing an RF-only ion guide in the first transfer region 20 through an ion trap 4 , an ion gate 7 and an ion mobility particle 1 and modifying the RF-only (or RF) ion guide in the second transfer region 21 to allow generation of an axial stress gradient, for example by providing a stacked ring ion guide.

The ion trap 4 , the ion mobility separator 1 and the ion guide used in the mass spectrometer according to 19 are used, preferably have a stacked ring electrode geometry as shown in FIG 20 is shown, wherein adjacent electrodes with AC voltages or RF voltages are supplied with a phase difference of 180 °. The ring electrodes are preferably 0.5 mm thick and preferably spaced 1.5 mm from center to center so that they have a nominal spacing of 1 mm and have an ion transmission opening with a diameter of 5.0 mm.

The ion trap 4 may have an RF only ion storage region, which is preferably 75 mm long. The ion mobility separator 1 according to one embodiment is 152 mm long, and has the same DC voltages or voltages as the ion trap 4 however, is preferably additionally axially segmented to facilitate the generation of an axial electric field. The electrodes of the ion mobility separator 1 can be grouped into groups of 4 electrodes per segment, with one common DC voltage applied to a segment. The groups of 4 electrodes are preferably interconnected by means of a resistor string, and the applied DC voltages or RF voltages may be capacitively coupled to each in-phase electrode. By applying different voltages at each end of the resistor string, an axial DC electric field can be generated. The generated field may also not be axially uniform, and may for example have a slightly stepped profile similar to that in FIG 21 . shown Between the ion trap 4 and the ion mobility separator 1 is a gate electrode 7 provided to allow a pulsed provision of ions for mobility separation. The gate electrode 7 preferably has an opening of 2 mm, preferably no AC voltage and RF voltage on the gate electrode 7 applied or given. The gate voltage may be with respect to the voltage applied to the ion trap 4 is held at +10 volts to facilitate trapping of the negatively charged ions. This voltage can then over a short period of time (for example, about 200 microseconds) to that of the ion trap 4 (or lower) are decreased, so that ions in the ion mobility separator 1 be released. The gate pulses may be generated using a LeCroyLn120 arbitrary waveform generator. The ion trap 4 and the ion mobility separator 1 For example, they can be operated at a pressure of about 2.5 mbar. The applied RF voltage may have a frequency of 0.8 MHz and the peak-to-peak voltage may correspond be adjusted to the respective masses of interest. The ion mobility separator 1 can be operated with a potential difference of 200 volts, resulting in an average field of 13.2 volts / cm.

The stacking ring ion guide 21 located downstream of the ion mobility separator 1 according to the embodiment is 30.5 mm long and can be axially segmented to allow the application of a DC axial field to reduce the transit time of the ion packets generated by the mobility separation. The stacking ring ion guide 21 can be maintained at a pressure of about 10 ^-3 mbar. The ion guide 21 may be applied with an RF voltage of a frequency of 1.9 MHz and a peak-to-peak voltage adjusted according to the mass range of interest. The potential difference over the ion guide 21 can, for example 2 Volts, resulting in an average axial field of 0.66 volts / cm. A quadruple or quadrupole mass filter 22 and a collision cell 23 can be downstream of the ion mobility separator 1 and the ion guide 21 as in 19 may be provided to perform MS / MS experiments.

Ions preferably flow continuously from the ion source, preferably an electrospray ion source 24 , into the ion trap 4 , and are then applied by applying a DC voltage to the ion gate at the exit from the ion trap 4 prevented. The gate voltage may then be pulsed to remove the ions from the ion mobility separator 1 release, wherein the ions separate according to their ion mobility. After excitation of the ion mobility separator 1 the ions pass through a transfer lens 5 before using the time of flight analyzer 2 to pass mass analysis.

To determine the arrival time of the mobility-separated ion packets in the time-of-flight analyzer 2 For example, a modified MassLynx (RTM) control and data acquisition system can be used. The acquisition of time-of-flight data may be due to the voltage pulse applied to the ion gate 7 for releasing ions into the ion mobility separator 1 is applied. The following approximately 200 orthogonal acceleration pulses applied to the injection electrode 6 the time of day mass analyzer 2 can be applied (or thrusts thereof) can then be recorded as individual mass spectra. The individual mass spectra from all nth push-out events can then be combined to form a number of composite mass spectra. At 200 push-out events per ion pulse into the ion mobility separator 1 200 composite mass spectra are generated.

The duration of the individual mobility acquisitions depends on the mass range of interest to be acquired, and, as a consequence, on the slider pulse repetition time. For example, if a mass range of 1,250. As needed, this corresponds to a slider repetition time of 50 μs, and the entire mobility experiment would be recorded over a period of 10 ms (200 x 50 μs). The use of fixed 200 shift events per mobility spectrum includes all expected ion drift times through the ion mobility separator 1 , The mobility spectrum can be summed over 5 s and then repeated for another 5 s, etc. until the acquisition or data acquisition is stopped.

Embodiments are conceivable in which the AC voltage or HF voltage with which the electrode or the electrodes of the ion mobility separator 1 and / or the ion trap 4 are applied, not sinusoidal, which may take the form of a square wave, for example.

The has been described above mainly in terms of the processing (or selective uptake) of mass spectral data and the effective filtering of ions with a time of flight (or a mass-charge ratio), the outside a desired one Range is described as a function of drift time. There are but also embodiments conceivable in which the data is in the form of ion mobility data can be present which are then processed (or selectively recorded) to be effective Ions with drift times (or ion mobilities) outside a desired one Range lie, filter out.

Even though the present invention with reference to preferred embodiments has been described, it should be understood that the skilled person numerous changes in terms of Execute form and detail can, without departing from the scope of the invention as set forth in the appended claims is to leave.

Claims (109)

Mass spectrometer having an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals; a time-of-flight mass analyzer having a flight region, the time-of-flight mass analyzer being configured det is for mass analyzing at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval; and processing means configured to: (i) generate a first mass spectral data set comprising data corresponding to the time of flight of at least some of the ions of the first group of ions through the flight region; and (ii) processing the first mass spectral data set to form a first processed mass spectral data set, wherein the intensity or significance of ions having a first undesired charge state relative to ions having a second, different, desired state of charge is reduced. A mass spectrometer according to claim 1, wherein ions x times into the ion mobility separator pulsed or pulsed introduced, and wherein the first Mass spectral data is a composite set of mass spectral data obtained by Sum up at least x sets or sets of mass spectral data, where the x sets of mass spectral data refer to separate ion pulses or pulses of ions. Mass spectrometer according to one of claims 1 or 2, wherein at least some of the ions of at least n others Groups of ions from the ion mobility separator during at least n further time intervals, when used with the Time of flight mass analyzer mass analyzed. A mass spectrometer according to claim 3, wherein the processing means preferably generate n further mass spectral data sets, each of which data contain the time of flight of at least some of the ions of the at least n further groups of ions through the flight region correspond. A mass spectrometer according to claim 4, wherein ions preferably at least x times into the ion mobility separator are pulsed, and where the n other mass spectral data sets are compounded Sets of Mass spectral data are, each composed of Mass spectral data by summing at least x sets of Mass spectral data is obtained, where the x sets of mass spectral data refer to separate pulses of ions. Mass spectrometer according to one of claims 4 or 5, wherein the processing means form the at least n other mass spectral data sets process at least n further processed mass spectral data sets, to form at least n further processed mass spectral data sets, being the intensity or significance of ions with a first, undesirable Charge state relative to ions with the second, desired Charge state is reduced. Mass spectrometer according to one of the preceding claims, wherein the processing means perform the first and / or n further mass spectral data sets Reduction or damping the intensity or significance of ions with a time of flight that is less than a minimum flight time, process. Mass spectrometer according to one of claims 1 to 6, wherein the processing means the first and / or n more Mass spectral data sets by Reduction of intensity or significance of ions with a time of flight that is less than one minimum flight time and greater than a maximum flight time is process. Mass spectrometer according to one of claims 1 to 6, wherein the processing means the first and / or n more Mass spectral data sets by Reduction of intensity or significance of ions with a time of flight that is greater as a maximum flight time is process. Mass spectrometer according to one of claims 7, 8 or 9 where n is selected from the group that includes the following Values includes: (i) 1-10; (ii) 10-20; (iii) 20-30; (iv) 30-40; (v) 40-50; (Vi) 50-60; (vii) 60-70; (viii) 70-80; (ix) 80-90; (x) 90-100; (xi) 100-110; (xii) 110-120; (xiii) 120-130; (xiv) 130-140; (Xv) 140-150; (xvi) 150-160; (xvii) 160-170; (xviii) 170-180; (xix) 180-190; (xx) 190-200; (xxi) 200-250; (xxii) 250-300; (xxiii) 350-400; (xxiv) 400-450; (xxv) 450-500; and (xxvi)> 500. Mass spectrometer according to one of claims 7 to 10, where the minimum flight time and / or the maximum flight time in the processing of mass spectral data sets in successive Time intervals have been or will be, progressively extended or shortened becomes. A mass spectrometer according to claim 11, wherein said minimum flight time and / or the maximum flight time is progressively extended or shortened is in (i) a substantially continuous manner; (ii) one in a substantially stepped manner; (iii) a substantially linear one Wise; (iv) a substantially non-linear manner; or (v) a substantially exponential manner. Mass spectrometer according to one of the preceding claims, wherein the processing agents use a mass spectrum of the first processed mass spectral data set. A mass spectrometer according to claim 13, wherein said Processing means a mass spectrum using at least n generate further processed mass spectral data sets. Mass spectrometer with an ion mobility separator for separating ions according to their ion mobility, so that Ions over different or different time intervals from the ion mobility separator escape; a time-of-flight mass analyzer with a flight region, wherein the time of flight mass analyzer for mass analysis at least some of the ions exiting the ion mobility separator are formed; and Processing means which are set up for: (I) Generation of a first ion mobility data set including data that of a drift time of at least some ions through the ion mobility separator correspond; and (ii) processing a first ion mobility data set to form a first processed ion mobility data set, wherein or at which the intensity or significance of ions with a first unwanted one Charge state relative to ions with a second, different, desired Charge state is reduced. A mass spectrometer according to claim 15, wherein said first ion mobility record a composite set of ion mobility data obtained by summing a number of sentences of ion mobility data is received. Mass spectrometer according to one of claims 15 or 16, wherein the processing means the first and / or a number of other ion mobility data sets Reduction of intensity or significance of ions with a drift time through the ion mobility separator, the bigger than one maximum drift time is process. Mass spectrometer according to one of claims 15 or 16, wherein the processing means the first and / or a number of further ion mobility data sets by reduction the intensity or significance of ions with a drift time through the ion mobility separator, which is less than a minimum drift time and greater than a maximum drift time is, process. Mass spectrometer according to one of claims 15 or 16, wherein the processing means the first and / or a number of other ion mobility data sets Reduction of intensity or significance of ions with a drift time through the ion mobility separator, which is less than a minimum drift time, process. Mass spectrometer according to one of Claims 17, 18 or 19, where the minimum drift time and / or the maximum Drift time in processing consecutive, consecutive or adjacent sentences of ion mobility data progressively increased or diminished. The mass spectrometer of claim 20, wherein said minimal drift time and / or the maximum drift time is increased progressively or is reduced in (i) a substantially continuous manner; (ii) a substantially stepped way; (iii) one essentially linear way; (iv) a substantially non-linear manner; or (v) a substantially exponential manner. Mass spectrometer according to one of claims 15 to 21, wherein the processing means using the first processed ion mobility data set form a mass spectrum. A mass spectrometer according to claim 22, wherein said Processing means using a number of other processed Ion mobility data sets Form mass spectrum. Mass spectrometer according to one of the preceding claims, wherein the first charge state has simply charged ions or includes. Mass spectrometer according to one of the preceding claims, wherein the second charge state comprises multiply charged ions. Mass spectrometer according to one of the preceding claims, wherein the state of charge is selected is from the group consisting of (i) doubly charged ions; (ii) triplicate charged ions; (iii) four times charged ions; (iv) five- or multiply charged ions; (v) two and three times charged ions; (vi) ions having three or more charges; and (vii) four or four ions includes more charges. Mass spectrometer according to one of the preceding claims, wherein the ion mobility separator having a number of electrodes, each electrode having an opening, through which ions transmit or transmit in use be a DC voltage gradient over at least a portion of the ion mobility separator is maintained and at least some of the electrodes with an AC or high frequency or RF voltage source are connected. An ion mobility separator according to claim 27, wherein. the ion mobility separator comprises: an upstream portion having a first number of electrodes with openings arranged in a vacuum chamber; and a downstream section with a two th number of electrodes having openings which are arranged in a further vacuum chamber, wherein the vacuum chamber or vacuum chambers are separated by a differential pumping opening or separated. The mass spectrometer of claim 28, wherein some of the electrodes in the upstream section when used with an AC or RF or RF voltage be applied with a frequency in the range of 0.1 to 3.0 MHz. Mass spectrometer according to one of claims 28 or 29, where the upstream Section when used to a pressure in the range of 0.1 is kept to 10 mbar. Mass spectrometer according to one of claims 28, 29 or 30, at least some of the electrodes in the downstream section when used with an AC voltage or a HF or RF voltage applied at a frequency in the range of 0.1 to 3.0 MHz become. A mass spectrometer according to any one of claims 28 to 31, wherein the downstream portion is maintained in use at a pressure in the range of 10 ^-3 to 10 ^-2 mbar. Mass spectrometer according to one of claims 28 to 32, wherein a first DC voltage gradient over at least a portion of the upstream Section and a second DC voltage gradient over at least a section of the downstream Section is maintained in use, wherein the first DC voltage gradient greater than the second DC voltage gradient is. Mass spectrometer according to one of claims 27 to 33, where at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% the electrodes openings have substantially the same size or the same area exhibit. Mass spectrometer according to one of claims 1 to 26, in which the ion mobility separator a segmented or subdivided set of rods, wherein a DC voltage gradient over at least a section of the ion mobility separator is maintained. Mass spectrometer according to one of claims 1 to 26, in which the ion mobility separator a drift tube together with one or more electrodes to maintain an axial DC voltage gradient along at least one Section of the drift tube has. Mass spectrometer according to one of claims 1 to 26, in which the ion mobility separator a number of electrodes, wherein in use a or more transient DC voltages or one or more DC voltage waveforms applied progressively to the electrodes be so that at least some ions with a first ion mobility of others Separated ions with a second, different ion mobility become. A mass spectrometer according to claim 37, wherein said one or more transient DC voltages or the one or a plurality of transient DC voltage waveforms are formed such that at least 10%, 20%, 30%, 90%, 50%, 60%, 70%, 80%, 90% or 95% of the ions with the first ion mobility along the ion mobility separator with a higher one Speed are moved as the ions with the second ion mobility. Mass spectrometer according to one of claims 1 to 26, in which the ion mobility separator a number of electrodes, wherein in use a or more transient DC voltages or one or more transient DC voltage waveforms progressively onto the electrodes are applied so that ions move towards a region of the ion mobility separator be at least one electrode has a potential, such that at least some ions with a first ion mobility have the potential happen while at least some other ions with a second, different ion mobility the potential will not happen. A mass spectrometer according to claim 39, wherein said one or more transient DC voltages or the one or the plurality of DC transient voltage waveforms are formed such that at least 10% 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the ions with the first ion mobility the potential happen. A mass spectrometer according to claim 39 or 40, wherein the one or more transient DC voltages or the one or more DC voltage waveforms are configured that at least 10% 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the ions with the second ion mobility do not pass the potential. The mass spectrometer of any one of claims 37 to 41, wherein the one or more transient DC voltages or the one or more transient DC voltage waveforms are configured to have at least 10% 20%, 30%, 40%, 50%, 60%, 70 %, 80%, 90%, or 95% of the ions with the first ion mobility substantially equal to the ions with the second ion mobility from the ion mobility separator th. Mass spectrometer according to one of claims 37 to 42, in which a majority of the ions having the first ion mobility time t in front of a majority of the ions with the second ion mobility from the Ionenmobiliätsseparator exit, where t falls within an area selected from the group, which comprises: (i) <1 μs; (ii) 1-10 μs; (Iii) 10-50 μs; (iv) 50-100 μs; (v) 100-200 μs; (vi) 200-300 μs; (vii) 300-400 μs; (Viii) 400-500 μs; (ix) 500-600 μs; (x) 600-700 μs; (xi) 700-800 μs; (Xii) 800-900 μs; (xiii) 900-1000 μs; (Xiv) 1.0-1.1 ms (xv) 1.1-1.2 ms; (xvi) 1,2-1,3 ms; (xvii) 1.3-1.4 ms; (xviii) 1.4-1.5 ms; (xix) 1.5-1.6 ms; (xx) 1.6-1.7 ms; (xxi) 1.7-1.8 ms; (xxii) 1.8-1.9 ms; (xxiii) 1.9-2.0 ms; (xxiv) 2.0-2.5 ms; (xxv) 2.5-3.0 ms; (xxvi) 3.0-3.5 ms; (xxvii) 3.5-4.0 ms; (xxviii) 4.0-4.5 ms; (xxix) 4.5-5.0 ms; (xxx) 5-10 ms; (xxxi) 10-15 ms; (xxxii) 15-20 ms; (xxxiii) 20-25 ms; and (xxxiv) 25-30 ms. Mass spectrometer according to one of claims 1 to 26, in which the ion mobility separator having a number of electrodes, wherein in use a or more transient DC voltages or one or more transient DC voltage waveforms progressively onto the electrodes applied or applied so that (i) ions in the direction a region of the ion mobility separator be moved, wherein or in the at least one electrode, a first Has potential, so that at least some ions with first and second different ion mobilities pass the first potential while other ions with a third, different ion mobility the first potential not happen; and then (ii) ions having the first and second Ionic mobilities in the direction a region of the ion mobility separar be moved, wherein or in the at least one electrode, a second Potential, so that at least some ions with the first Ion mobility that second potential happen while other ions with the second, different ion mobility the second Potential does not happen. Mass spectrometer according to one of claims 37 to 44, wherein the one or more transient DC voltages (i) a potential hill or a potential barrier; (ii) a potential well; (iii) a Combination of a potential hill or a potential barrier and a potential well; (iv) one Number of potential hills or -barriers; (v) a number of potential wells or (vi) one Combination of a number of potential mounds or barriers and one Create number of potential wells. Mass spectrometer according to one of claims 37 to 45, wherein the one or more transient DC voltage waveforms (i) a repeating waveform; or (ii) a square wave include. Mass spectrometer according to one of claims 37 to 46, wherein the one or more transient DC voltage waveforms Number of potential peaks or sinks created by intermediate regions are separated from each other. A mass spectrometer according to claim 47, wherein said DC voltage gradient in the intermediate regions (i) different from zero, (ii) positive, (iii) negative, (iv) linear, (v) nonlinear, or (vi) exponentially increasing, or (vii) exponentially declining is trained. Mass spectrometer according to one of claims 47 or 48, in which the amplitude of the potential peaks or sinks (i) remains substantially constant, (ii) progressively larger or becomes smaller, or (iii) increases or decreases linearly or nonlinearly. Mass spectrometer according to one of claims 37 to 49, wherein in use an axial DC voltage gradient along at least a portion of the length of the ion mobility separator is maintained, wherein the axial voltage gradient with the Time varies. Mass spectrometer according to one of claims 37 to 50, where the ion mobility separator 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or> 30 segments, each segment 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or> 30 electrodes, and wherein the Electrodes in a segment substantially at the same DC potential being held. A mass spectrometer according to claim 51, wherein a Number of segments at substantially the same DC potential is held. Mass spectrometer according to one of claims 51 or 52, wherein each segment in use substantially on the same DC potential as the subsequent y-th Segment is held, where y = 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or> 30. A mass spectrometer according to any one of claims 37 to 53, wherein ions in use radially within the ion mobility separator by means of an AC field or RF or RF electric field are included. Mass spectrometer according to one of claims 37 to 54, in which ions in use within the ion mobility separator are radially enclosed in a pseudopotential well, and axially along the ion mobility separator by means of a real potential barrier or sink are moved. Mass spectrometer according to one of claims 37 to 55, where, in use, one or more dc voltage or RF voltage waveforms on at least some of the Electrodes are applied so that the ions along at least a section of the length of the Ionenmobilitätsseparators packed become. Mass spectrometer according to one of the preceding claims, wherein the minimum, average or maximum transit time or Transit time of ions through the ion mobility separator is selected from the group which comprises: (i) shorter or equal to 20 ms, (ii) shorter or equal to 10 ms, (iii) shorter or equal to 5 ms, (iv) shorter or 1 ms, and (vi) shorter or equal to 0.5 ms. Mass spectrometer according to one of the preceding claims, wherein the ion mobility separator held in use at a pressure that is from the group selected is, which comprises: (i) larger or equal to 0.0001 mbar; (ii) greater than or equal to 0.0005 mbar; (ii) greater or equal to 0.001 mbar; (iv) greater or equal to 0.005 mbar; (v) greater or equal to 0.01 mbar; (vi) greater or equal to 0.05 mbar; (vii) greater or equal to 0.1 mbar; (viii) greater than or equal to 0.5 mbar; (ix) larger or equal to 1 mbar; (x) greater or equal to 5 mbar; (xi) greater or equal to 10 mbar. Mass spectrometer according to one of the preceding claims, wherein the ion mobility separator held in use at a pressure that is from the group selected which comprises: (i) less than or equal to 10 mbar; (ii) smaller or equal to 5 mbar; (iii) less than or equal to 1 mbar; (iv) less or equal to 0.5 mbar; (v) less than or equal to 0.1 mbar; (vi) smaller or equal to 0.05 mbar; (vii) less than or equal to 0.01 mbar; (Viii) less than or equal to 0.005 mbar; (ix) less than or equal to 0.001 mbar; (x) less than or equal to 0.0005 mbar; and (xi) less than or equal to 0.0001 mbar. Mass spectrometer according to one of the preceding claims, wherein the ion mobility separator held in use at a pressure that is from the group selected which comprises: (i) between 0.0001 and 10 mbar; (ii) between 0.0001 and 1 mbar; (iii) between 0.0001 and 0.1 mbar; (iv) between 0.0001 and 0.01 mbar; (v) between 0.0001 and 0.001 mbar; (vi) between 0.0001 mbar and 10 mbar; (vii) between 0.0001 and 1 mbar; (Viii) between 0.001 and 0.1 mbar; (ix) between 0.001 and 0.01 mbar; (x) between 0, 01 and 10 mbar; (xi) between 0, 01 and 1 mbar; (xii) between 0.01 and 0.1 mbar; (xiii) between 0.1 and 10 mbar; (Xiv) between 0.1 and 1 mbar; and (xv) between 1 and 10 mbar. Mass spectrometer according to one of the preceding claims, wherein the ion mobility separator held in use at a pressure, allowing a more viscous Train is exerted on ions, the the ion mobility separator happen. Mass spectrometer according to one of claims 37 to 61, in which the one or more transients in use DC voltages or the one or more transient DC voltage waveforms first are provided at a first axial position, and then subsequently at second and then third different axial positions along the ion mobility separator to be provided. Mass spectrometer according to one of claims 37 to 62, wherein the one or more DC voltages or the one or more transient DC voltage waveforms differs from one end of the ion mobility separator move to another end of the ion mobility separator, so that at least some ions are forced along the ion mobility separator. Mass spectrometer according to one of claims 37 to 63, wherein the one or more DC voltages or the one or more transient DC voltage waveforms along of the ion mobility separator move at a speed that is selected from the group which comprises: (i) 10-250 m / s; (ii) 250-500 m / s; (iii) 500-750 m / s; (iv) 750-1000 m / s; (v) 1000-1250 m / s; (vi) 1250-1500 m / s; (vii) 1500-1750 m / s; (viii) 1750-2000 m / s; (ix) 2000-2250 m / s; (x) 2250-2500 m / s; (xi) 2500-2750 m / s; (xii) 2750-3000 m / s; and (xiii)> 3000 m / s. Mass spectrometer according to one of claims 37 to 64, in which two or more transient DC voltages or two or several transient DC voltage waveforms simultaneously through the ion mobility separator pass through or pass this. Mass spectrometer according to one of the preceding claims, wherein when in use, a continuous ion beam in use at an entrance of the ion mobility separator Will be received Mass spectrometer according to one of claims 1 to 65, in which when using packets of ions at an input of the ion mobility separator be received. Mass spectrometer according to one of the preceding claims, wherein the ion mobility separator consists of (i) 10-20 electrodes; (ii) 20-30 electrodes; (iii) 30-40 electrodes; (iv) 40-50 electrodes; (v) 50-60 electrodes; (vi) 60-70 electrodes; (vii) 70-80 electrodes; (viii) 80-90 electrodes; (ix) 90-100 electrodes; (x) 100-110 electrodes; (xi) 110-120 electrodes; (xii) 120-130 electrodes; (xiii) 130-140 electrodes; (xiv) 140-150 electrodes; or (xv) more than 150 electrodes. Mass spectrometer according to one of the preceding claims, wherein at least 10%, 20%, 30%, 40%, 50%, 60%; 70%, 80%, 90%, or 95% of the electrodes that make up the ion mobility separator both with a DC voltage as well as an AC voltage or RF or RF power supply are connected. Mass spectrometer according to one of the preceding claims, wherein the axially adjacent electrodes of the Ionenmobiliätsseparator with AC voltages or RF or RF voltages with a phase difference of 180 ° C be supplied or acted upon. A mass spectrometer according to any one of the preceding claims, further with an ion source selected from the group comprising: (i) electrospray or electrospray ion source ("ESI"), (ii) an atmospheric pressure chemical ionization ion source ("APCI"), (iii) an atmospheric pressure photo ionization ion source ("APPI"), (iv) a matrix assisted laser desorption ionization ion source ("MALDI"), (v) a laser desorption ionization ion source ("LDI"), (vi) an inductive coupled plasma ion source ("ICP"), (vii) an electron impact ion source ("EI"), (viii) a chemical Ionization ion source ("CI"), (ix) a fast atom bombardment ion source ("FAB"), (x) a liquid secondary ion mass spectrometry ion source ("LSIMS"), (xi) a field ionization ion source ("FI") or (xii) one Field desorption ion source ("FD"). A mass spectrometer according to any one of the preceding claims, further with a continuous ion source. Mass spectrometer according to one of the preceding claims 1 to 71, further comprising a pulsed ion source. Mass spectrometer according to one of claims 71, 72, or 73, in which the ion source with a gas chromatograph ("GC") or a liquid chromatograph ("LC") is coupled. Mass spectrometer according to one of the preceding claims, wherein the time of flight mass analyzer an injection or injection electrode for the Injecting at least some ions in one direction substantially orthogonal or parallel with respect an axis, along the ions first in the time of flight mass analyzer occur, has. The mass spectrometer of claim 75, further comprising an ion trap upstream of the time-of-flight mass analyzer for storage and periodic release ions into the time-of-flight mass analyzer. A mass spectrometer according to any one of the preceding claims, further with an ion trap for storing and periodically releasing Ions into the ion mobility separator. A mass spectrometer according to any one of the preceding claims, further with a collision cell, wherein in an operating mode at least some ions that enter the collision cell are fragmented. A mass spectrometer according to any one of the preceding claims, further with a mass filter downstream of the ion mobility separator. Mass spectrometer with: an ion mobility separator for separating ions according to their ion mobility, so that Ions over different or different time intervals from the ion mobility separator escape; a time-of-flight mass analyzer with a flight region, wherein the time-of-flight mass analyzer for mass analysis at least some of the ions of a first group of ions coming from the ion mobility separator while emerge from a first time interval is formed; and Processing means, for recording the time of flight of some of the ions of the first group of ions through the flight region to form a first mass spectral data set are formed, wherein or at which the intensity or Signi ficance of ions with a time of flight that is less than a minimum flight time is reduced. Mass spectrometer comprising: an ion mobility separator for separating ions according to their ion mobility so that ions exit the ion mobility separator over different time intervals; A time of flight mass analyzer having a flight region, wherein the time of flight mass analyzer is for mass analysis of at least some of the ions of a first group of ions derived from the ion mobility eigkeitsseparator exit during a first time interval is formed; and processing means adapted to receive the flight time of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance of ions having a flight time less than a minimum flight time and greater than a maximum flight time is reduced. Mass spectrometer with: an ion mobility separator to separate ions according to their ion mobility, so that Ions over different or different time intervals from the Ionenmobiliätsseparator escape; a time-of-flight mass analyzer with a flight region, wherein the time of flight mass analyzer for mass analysis of at least some the ions of a first group of ions coming from the ion mobility separator while emerge from a first time interval is formed; and Processing means, for recording the time of flight of some of the ions of the first group of ions through the flight region to form a first mass spectral data set are formed, wherein or in which the intensity or significance ions with a time of flight that is greater than a maximum time of flight, is reduced. Mass spectrometer with: an ion mobility separator for separating ions according to their ion mobility, so that Ions over different or different time intervals from the ion mobility separator escape; a time-of-flight mass analyzer with a flight region, wherein the time of flight mass analyzer for mass analysis at least some of the ions of a first group of ions coming from the ion mobility separator while emerge from a first time interval is formed; and Processing means, to record the drift time of some of the ions coming out of the ion mobility separator emerge, formed to form a first mass spectral data set where the intensity or significance of ions with a drift time through the ion mobility separator greater than a maximum drift time is reduced. Mass spectrometer with: an ion mobility separator for separating ions according to their ion mobility, so that Ions over different or different time intervals from the ion mobility separator escape; a time-of-flight mass analyzer with a flight region, wherein the time of flight mass analyzer for mass analysis at least some of the ions exiting the ion mobility separator are formed; and Processing agents used to record the drift time of at least some of the ions coming from the ion mobility separator emerge, formed to form a first ion mobility data set where the intensity or significance of ions with a drift time through the ion mobility separator that is less than a minimum drift time and greater than a maximum drift time is reduced. Mass spectrometer with: an ion mobility separator for separating ions according to their ion mobility, so that Ions over different or different time intervals from the ion mobility separator escape; a time-of-flight mass analyzer with a flight region, wherein the time of flight mass analyzer for mass analysis at least some of the ions exiting the ion mobility separator are formed; and Processing means for recording the drift time at least Some of the ions that emerge from the ion mobility separator to Forming a first ion mobility record formed where the intensity or significance of ions with a drift time through the ion mobility separator that is less than a minimum drift time is reduced. Method for mass spectrometry with the following steps: Separation of ions according to their ion mobility in one ion mobility separator, so that ions over different or different time intervals from the ion mobility separator escape; Mass analyzing at least some of the ions of one first group of ions coming from the ion mobility separator while a first time interval, with a Time of Flight mass analyzer, wherein the time of flight mass analyzer comprises a flight region; generation a first mass spectral dataset including data, the time of flight of at least some of the ions of the first group correspond to ions through the flight region; and processing of the first mass spectral data set to form a first processed one Mass spectral dataset, where or in which the intensity or significance of ions with a first unwanted Charge state relative to ions with a second, different, desired La Dungszustand is reduced or is. The method of claim 86, wherein ions are pulsed into the ion mobility separator at least x times, and wherein the first mass spectral data set is a composite set of mass spectral data obtained by summing at least x sets of mass spectral data, the x sets of mass spectral data yourself refer to separate pulses of ions. The method of any of claims 86 or 87, further comprising the step of mass analyzing at least some of the ions at least n further groups of ions coming from the ion mobility separator while emerge at least n further time intervals, by means of the time-of-flight mass analyzer. The method of claim 88, further comprising the step generating at least n further mass spectral data sets which Each data includes the flight time of at least some of the Ions of the at least n further groups of ions through the fly region correspond. The method of claim 89, wherein ions are at least x times in the ion mobility separator be pulsed, and where n other mass spectral data sets are compounded Mass spectral data sets are, each composed mass spectral dataset through Summing at least x mass spectral data sets is obtained, wherein the x mass spectral data sets refer to separate ion pulses or ion pulses. The method of any one of claims 89 or 90, further comprising at least n other mass spectral data sets for formation at least n further processed mass spectral data sets are processed, wherein the intensity or significance of ions with the first unwanted state of charge relative to ions with the second, desired Charge state is reduced. A method according to any of claims 86 to 91, wherein the Step of processing the first and / or n further mass spectral data sets Reduction of intensity or significance of ions with a time of flight that is less than one minimum flight time is included. A method according to any of claims 86 to 91, wherein the Step of processing the first and / or n further mass spectral data sets Reduction of intensity or significance of ions with a time of flight that is less than one minimum flight time and greater than a maximum flight time is included. A method according to any of claims 86 to 91, wherein the Step of processing the first and / or n further mass spectral data sets Reduction of intensity or significance of ions with a time of flight greater than a maximum flight time is included. A method according to any of claims 92, 93 or 94, wherein n selected from the group which comprises: (i) 1-10; (ii) 10-20; (iii) 20-30; (iv) 30-40; (V) 40-50; (vi) 50-60; (vii) 60-70; (viii) 70-80; (ix) 80-90; (x) 90-100; (xi) 100-110; (xii) 110-120; (xiii) 120-130; (xiv) 130-140; (xv) 140-150; (xvi) 150-160; (Xvii) 160-170; (xviii) 170-180; (xix) 180-190; (xx) 190-200; (xxi) 200-250; (xxii) 250-300; (xxiii) 350-400; (xxiv) 400-450; (xxv) 450-500; and (xxvi)> 500. A method according to any one of claims 92 to 95, wherein the minimum time of flight and / or the maximum time of flight during processing the mass spectral data sets, obtained in successive time intervals, progressive elevated or humiliated. The method of claim 96, wherein the minimum Flight time and / or the maximum flight time progressively increased or is reduced in (i) a substantially continuous manner, (ii) a substantially stepped manner, (iii) one substantially linear manner, (iv) a substantially non-linear manner or (v) a substantially exponential manner. A method according to any one of claims 86 to 97, wherein the Formation of a mass spectrum the formation of a mass spectrum below Use of the first processed mass spectral data set includes. The method of claim 98, further comprising a mass spectrum generated using at least n further processed mass spectral data sets becomes. A method according to any one of claims 86 to 99, wherein the first charge state comprises simply charged ions. A method according to any one of claims 86 to 100, wherein the second charge state comprises multiply charged ions. A method according to any one of claims 86 to 101, wherein the second charge state is selected from the group comprising: (i) two times charged ions; (ii) triply charged ions; (iii) four times charged ions; (iv) ions with five or more charges, (v) doubly and triply charged ions, (vi) Ions with three or more charges and (vii) ions with four or more more charges. A method of mass spectrometry comprising the steps of: separating ions according to their ion mobility in an ion mobility separator such that ions exit the ion mobility separator over different time intervals; Passing at least some of the ions of a first group of ions exiting the ion mobility separator during a first time interval to a time of flight mass analyzer, the time of flight mass analyzer having a flight region; and recording the flight time of some of the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance of ions with a flight time that is less than a minimum flight time is reduced or is. Method for mass spectrometry with the following steps: Separation of ions according to their ion mobility in one ion mobility separator, so that ions over different or different time intervals from the ion mobility separator escape; Passing or passing at least some of the ions a first group of ions during a first time interval from the ion mobility separator leak, to a time-of-flight mass analyzer, wherein the time-of-flight mass analyzer has a flight region; and Recording the flight time of some the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance of ions with a time of flight that is less than a minimum Flight time and is greater as a maximum flight time, is reduced or is. Method for mass spectrometry with the following steps: Separation of ions according to their ion mobility in one ion mobility separator, so that ions over different or different time intervals from the ion mobility separator escape; Passing or passing at least some of the ions a first group of ions during a first time interval from the ion mobility separator leak, to a time-of-flight mass analyzer, wherein the time-of-flight mass analyzer has a flight region; and Recording the flight time of some the ions of the first group of ions through the flight region to form a first mass spectral data set, wherein the intensity or significance ions with a time of flight that is greater than a maximum time of flight, is reduced or is. Method for mass spectrometry with the following steps: Separation of ions according to their ion mobility in one ion mobility separator, so that ions over different or different time intervals from the ion mobility separator escape; Transfer or passage of at least some of the ions, those from the ion mobility separator leak, to a time-of-flight mass analyzer, wherein the time-of-flight mass analyzer has a flight region; and Recording the ion mobility of the ions at least some of the ions to form a first ion mobility data set, wherein or at which the intensity or significance of ions with a drift time through the ion mobility separator, the bigger than a maximum drift time is, is reduced or is. Method for mass spectrometry with the following steps: Separation of ions according to their ion mobility in one ion mobility separator, so that ions over different or different time intervals from the ion mobility separator escape; Transfer or passage of at least some of the ions, those from the ion mobility separator leak, to a time-of-flight mass analyzer, wherein the time-of-flight mass analyzer has a flight region; and Recording the ion mobility of the ions at least some of the ions to form a first ion mobility data set, wherein or at which the intensity or significance of ions with a drift time through the ion mobility separator, which is less than a minimum drift time and greater than a maximum drift time, is reduced or is. Method for mass spectrometry with the following steps: Separation of ions according to their ion mobility in one ion mobility separator, so that ions over different or different time intervals from the ion mobility separator escape; Transfer or passage of at least some of the ions, those from the ion mobility separator leak, to a time-of-flight mass analyzer, wherein the time-of-flight mass analyzer has a flight region; and Recording the ion mobility of the ions at least some of the ions to form a first ion mobility data set, wherein or at which the intensity or significance of ions with a drift time through the ion mobility separator, which is less than a minimum drift time, is reduced. Mass spectrometry method using mass spectral data or ion mobility data be, and the data for excluding ions with an undesirable Charge state to be processed.