Ion fragmentation device

Abstract

The invention relates to the field of mass spectrometry and ion mobility spectrometry, and more particularly to the fragmentation of ions in collision cells. An ion fragmentation device is characterized in that it comprises an ion transport channel which has an inlet end and an outlet end and is delimited by surfaces on which are arranged radiofrequency and / or DC electrodes which generate a travelling wave field that guides ions toward the outlet end of the channel, wherein the middle part of the device is provided with electrodes that perform the function of fragmenting and thermalizing ions, said electrodes differing from the other electrodes on the rest of the device in terms of their power supply mode and / or geometry. The technical result of the invention consists in increased fragmentation efficiency, efficient ion transport through all of the component parts of CID cells, reduced ion loss in CID cells and greater analytical sensitivity, less blurring of ion packets over time, and a decrease in the pressure in adjacent chambers of the mass spectrometer, which permits the use of pumps with a lower pumping speed.

Description

[0001] ION FRAGMENTATION DEVICE

[0002] Field of technology to which the invention relates

[0003] The invention relates to the field of mass spectrometry and ion mobility spectrometry and, in particular, to ion fragmentation in collision cells.

[0004] State of the art

[0005] The invention relates to a method of ion fragmentation in collision cells - Collision Induced Dissociation (CID).

[0006] Fragmentation is the dissociation of molecular ions that are formed when molecules pass through a collision cell. When the kinetic energy of the precursor ion is high enough and collisions with the neutral gas are frequent enough, the internal energy of the precursor ion rapidly increases above the fragmentation threshold, causing bonds within the molecule to break and dissociate. The fragments of the molecule create a unique spectrum that carries information about the original structure of the parent molecular ion.

[0007] Tandem mass spectrometry is commonly used to determine the structure of molecules or to analyze mixtures using LID fragmentation. A typical setup for tandem mass spectrometry is two mass analyzers separated by a LID cell. In the collision cell, dissociation of the parent ion is achieved by collisions with neutral gas molecules, which leads to the accumulation of internal energy and bond cleavage. The parent ion is fragmented to form a series of product ions. The term product ion is used to denote any of the ionic products of collisions between the parent ions and gas molecules in the collision cell, including the parent ions themselves that have not undergone fragmentation. More specifically, they are also called fragment ions. The product ions (and the remaining precursor ions) from the collision cell are then transferred to a second mass analyzer, where they are scanned to obtain their mass spectrum.

[0008] Partial or complete structure of the precursor ion can be determined from fragmentation information. The kinetic energy of the parent ions determines the amount of energy that can be converted into internal energy, and the collision frequency determines the rate of conversion. Different values ​​of kinetic energy and neutral gas pressure in the collision cell give different patterns of precursor ion fragmentation. The main parameters of the SID that determine the quality of the analysis and the level of mass spectrometer characteristics are: fragmentation efficiency, the level of ion signal loss during the SID passage, the reproducibility of fragmentation conditions, and the rate of fragmentation cycles. A fragmentation cycle is understood as the entire chain of manipulations performed, including the fragmentation process itself, thermalization of product ions, and the release of the SID from the product ions of the previous fragmentation cycle.The latter process determines such a parameter as the level of cross-contamination for the subsequent fragmentation cycle (cross-talk effects). In addition, such a parameter of the SID as the level of gas load on the pumping system is important, which is determined by the gas pressure in the SID and the gas conductivity of the input and output diaphragms.

[0009] The technical problem of using LEDs is to ensure a high level of characteristics for the set of LED parameters listed above.

[0010] The most frequently used tandem mass spectrometers are axial LEDs based on the linear Paul trap in the form of gas-filled quadrupole, hexapole or octupole transport channels. Typically, the gas pressure inside them is maintained at a level of several mTorr to ensure a sufficient number of collisions and subsequent relaxation of the kinetic energy of ions; the length of such LEDs is usually 10-25 cm [Tanner, SD at. al., (2002). Reaction cells and collision cells for ICP-MS: a tutorial review. Spectrochimica Acta Part B: Atomic Spectroscopy, 57(9), 1361-1452.; US5847386 1997]. Without an axial field, LEDs of this type have a rather long fragmentation cycle.

[0011] As the analysis shows, the most effective way to increase the efficiency of the LED, its speed and reduce the loss of ions when passing the LED is to increase the pressure inside the LED. To ensure the required degree of ion cooling after fragmentation, at a reduced pressure in the LED, it is necessary to increase the length of the LED, which increases the times of ion exit from the LED and the blurring of the exit times. High-pressure LEDs provide a more stable fragmentation pattern compared to low-pressure LEDs.

[0012] High-pressure LEDs are known, for example, those disclosed in patent US6534764B1 Verenchikov, article 2006 N. P. Verenchikov. The patent describes a LED, where its characteristics are improved by shortening the LED and increasing the pressure in it. The LED includes an RF multipole for spatial confinement of the beam; the kinetic energy of ions introduced into the cell can be regulated by changing static voltages or by applying electrical pulses. The pressure in the LED is from 0.1 to 1 Torr, which improves ion cooling. The problem of increased gas load on the vacuum system is solved by creating additional pumping stages at the ends of the LED.

[0013] The disadvantages of known solutions are low fragmentation efficiency, increased gas load on the vacuum system, the need to focus the beam at the entrance to the cell with a counter-flow of gas, the need for an additional high-vacuum pump, which leads to a more complex device, an increased fragmentation cycle time due to an increase in the output of ions from the LED, which results from the absence of axial fields in the LED and the ion transport channel.

[0014] Disclosure of invention

[0015] The technical challenge is to create a collision cell for ion dissociation with an improved set of characteristics, such as operating speed, fragmentation efficiency, level of ion signal loss during the passage of the LED, reproducibility of fragmentation conditions, speed of fragmentation cycles, while there should be a low level of gas load on the pumping system of the mass spectrometer.

[0016] The technical result of the invention consists in increasing the efficiency of fragmentation, ensuring efficient transport of ions through all components of the LED, reducing ion losses in the LED and increasing the sensitivity of the analysis, reducing the blurring of ion packets over time, reducing the pressure in adjacent chambers of the mass spectrometer, allowing the use of pumps with a lower pumping speed.

[0017] The technical result is achieved due to the fact that the device for fragmenting ions contains an ion transfer channel having an input and output end, limited by surfaces on which radio frequency and / or DC electrodes are located, creating a traveling wave field directing ions to the output end of the channel, wherein in the middle part of the device there are electrodes providing the function of fragmentation and thermalization of ions, differing from other electrodes located on the rest of the device, in the power supply mode and / or geometry.

[0018] In addition, the surfaces limiting the ion transfer channel form a sealed channel or the channels have limited gas permeability, and the inlet and outlet channels are designed with the possibility of creating resistance to the gas flow passing through them.

[0019] In addition, the ion transport channel has a rectangular, round or oval cross-section.

[0020] In addition, the ion transfer channel has narrowing sections with the ability to create resistance to the gas flow and focus ions into narrow beams. In addition, the ion transfer channel is formed by two flat surfaces located opposite each other with radiofrequency electrodes and two flat opposite surfaces with DC electrodes.

[0021] In addition, the ion transport channel is formed by four flat surfaces with radiofrequency electrodes or alternating electrodes in the form of diaphragms along the channel.

[0022] In addition, the electrodes are made in the form of groups of two and / or three and / or four and / or five and / or more electrodes, to which the corresponding high-frequency power supply with a phase shift is supplied.

[0023] In addition, the electrodes located in the middle part of the device are made in the form of a separate group and are located along the length of the ion transfer channel.

[0024] In addition, the geometry of the electrodes located in the middle part of the device, which is primarily responsible for ion fragmentation, is made to repeat the geometry of the electrodes located in the rest of the device.

[0025] In addition, the electrodes have a repeating pattern along the length of the surface.

[0026] In addition, the electrodes have a pattern and scale that vary along the length of the surface.

[0027] In addition, the surfaces limiting the ion transport channel and the field-setting electrodes are manufactured using printed circuit board technologies.

[0028] Brief description of the drawings

[0029] Fig. 1. The main embodiment of the invention, a) view ZX, b) view YX;

[0030] Fig. 2. An embodiment where the volume of the LED chamber is formed by curved surfaces with electrodes;

[0031] Fig. 3. An embodiment where the volume of the LED chamber is formed by surfaces with electrodes.

[0032] Implementation of the invention

[0033] The present invention proposes a device for the LED, which allows increasing the pressure in the LED, reducing the gas flow from the LED, which will lead to a decrease in the pressure in the chamber of the mass spectrometer and / or will allow using pumps with a lower pumping speed. At the same time, the proposed LED provides a high operating speed.

[0034] The claimed device for fragmenting ions comprises an ion transport channel having an input and output end, limited by surfaces on which radio frequency and / or DC electrodes are located, creating a traveling wave field directing ions to the output end of the channel, wherein in the middle part of the device there are electrodes providing the function of fragmentation and thermalization of ions, differing from other electrodes located on the rest of the device in the power supply mode and / or geometry.

[0035] To explain one of the preferred embodiments of the invention, let us refer to Fig. 1. The collision cell includes ... and its operation occurs as follows. The parent ions come from the preceding stage of the mass spectrometer MS1 and enter the ion fragmentation device (1) (IFD). The preceding stage of the mass spectrometer can be, for example, a differential pumping interface, a mobility spectrometer or a first-stage mass analyzer of the mass spectrometer. In preferred embodiments of the invention, the ion fragmentation device (IFD) includes the following main elements: an input channel (2), an output channel (3) and the IFD cell itself (4). At the input of the IFD, the parent ions come to the ion channel (7), which is formed by the electrode system (8). Inside the volume of the electrode system of the device, a field holding the ions near the axis is formed by applying a combination of RF and DS voltages to the electrodes, which form a traveling wave field.A field of this type allows not only to retain ions inside the ion-transport channel, but also to move them along this channel towards the exit. The groups of electrodes (8, 9, 10) form a pseudopotential field directing ions from the surfaces of the electrodes to the axis of the channels. In one of the variants, DC voltage is applied to the groups of electrodes (12), directing ions to the axis of the channels, which prevents ion losses. Ions are directed along the channel (7) to the ion-transport channel (5) of the LED cell (4), which is formed by the electrode system (9).

[0036] Fragmentation of parent ions in the LED cell (4) occurs due to their collision with molecules or atoms of neutral gas. Ions are accelerated to energies exceeding the binding energy, enter the molecular flow, undergo collisions and are fragmented. Fragmentation of molecular ions occurs as a result of their collision with gas molecules, and various mechanisms of this process are possible. The simplest mechanism assumes that the energy of a single collision is greater than the energy of intramolecular bonds, and the disintegration of the molecule into fragments occurs already in a single collision. Such a process occurs if molecular ions enter the fragmentation cell with sufficiently high energy. Fragmentation can also occur as a result of the accumulation of internal energy of the ionized molecule as a result of multiple collisions with neutral gas.The internal energy has time to distribute itself over many bonds within the molecule, and the most probable dissociation occurs at the site of the weakest bond. This mechanism continues to repeat itself with fragment ions. This mechanism mainly corresponds to high-pressure collision cells. In this case, the dissociation pattern is more reproducible in comparison with dissociation resulting from a single collision.

[0037] Fragmented ions lose energy due to collisions with gas and, together with this, move to the LED output (4) due to the traveling wave field, which also focuses the ions on the channel output (5) and then enter the output channel (3), which is formed by the electrode system (10). Then, due to the traveling wave field, the ions move to the channel output (3) and enter the next stage of the MA_2 mass spectrometer for subsequent analysis.

[0038] The required pressure level to ensure fragmentation in the LED cell (4) is maintained by feeding gas through the capillary (6). The pressure in the LED cell can be from 10 -4 mbar to 1..10 mbar. Preferred value - 0.01..0.1 mbar.

[0039] One of the solutions that allows achieving the technical result is to increase the lengths of the channels (2 and 3), through which ions are transported to the next stage, when the channel length is five or more times, i.e. significantly greater than its characteristic size in the cross-section. Firstly, with an increase in the channel length, it is possible to significantly increase the input aperture of the UFI. Secondly, this solution limits the gas flow into the surrounding chambers of the mass spectrometer or into the next separation stage. In the preferred embodiments of the invention, a rectangular channel cross-section was chosen, since the effect of the volume charge is reduced compared to a round channel of a similar cross-section, flat surfaces are easy to implement and convenient for placing the electrode system, which creates a transporting and focusing field.

[0040] In preferred embodiments of the invention, the surfaces limiting the ion transport channels (7, 5 and 3) form sealed channels or the channels have limited gas permeability, and the channels (2, 3) are designed with the possibility of creating resistance to the gas flow passing through them.

[0041] The amount of gas flow from the LED to the mass spectrometer chamber is determined by the pressure in the LED and the aperture of the limiting diaphragms. Increasing the apertures leads to an increase in ion transmission, but at the same time the gas flow to the MS increases.

[0042] The conductivity of the diaphragm in the molecular flow regime is determined by the area of ​​the aperture. For a circular opening:

[0043] U hnl mn / — 91- with mijrnt where diaphragms.

[0044] Conductivity of a rectangular channel of length L:

[0045] 2 2

[0046] 308 -a -Ь

[0047] Uab_mol= -

[0048] L-(a + b), где а и- the lengths of the sides of a rectangular cross-section. For example, if we compare the conductivity of a long channel 1_=100 mm with a cross-section of 1x2.5 mm with the conductivity of a diaphragm, which will have a similar aperture area equal to 2.5 mm 2 , then the flow through such a diaphragm will be approximately 10 times higher.

[0049] The length of the channels (2 and 3) is selected to provide the required vacuum level in the mass spectrometer chamber, at the selected pumping speed and channel aperture size and in accordance with the task being solved. The length of the channels can be 10..200 mm or more. For example, for two channels 1_=100 mm, cross-section 2x4 mm, pressure Pcid=0.01 mbar to provide pressure in the surrounding chambers at the level of P=2x10' 6 mbar, pumps with a total pumping speed of ~400 l / s are required.

[0050] The length of the LED cell is selected in accordance with the desired thermalization of ions before the LED cell outlet at the selected pressure level in it. For example, as the simulation shows, for Pcid=0.01 mbar, 3 cm is enough for the M / z 200 ion to lose energy from 20 eV to <1 eV. Considering that the thermalization of ions will continue in the outlet channel, the length of the LED cell can be further reduced.

[0051] One of the solutions that allows achieving the technical result is the use of a traveling wave field for ion transport along the channels (2 and 3) and in the SID cell (4). Due to this, effective transport is carried out. This will avoid mixing of ion packets separated in time from different components of the sample. Their separation can be achieved at the previous separating stages of the MA_1 mass spectrometer, such as gas chromatography (GC), liquid chromatography (LC), ion mobility spectrometry (IMS). The declared UFI should provide minimal times of blurring of ion packets arriving at the input at a level of 100-200 μs and lower. Accordingly, the time cycle of the entire fragmentation device is reduced.

[0052] Alternatively, the electrode group (12) may not be used in the device, in which case the field preventing ion losses is formed entirely by means of radio frequency electrodes.

[0053] The LED also preferably comprises means for creating alternating or high-frequency voltages, arranged and adapted to supply two or more phase-shifted alternating or high-frequency voltages to the electrodes.

[0054] In preferred embodiments, individual electrodes from the plurality of radio frequency electrodes (8, 9, 10) have a rectangular shape and are separated by an insulator, have a periodically repeating pattern consisting of groups of 2, 3, 4, 5 and more electrodes. The most preferred embodiment is when the array of the plurality of radio frequency electrodes is divided into groups of 4 electrodes in order to set the traveling wave field. The size of the electrodes and the distance between them can be varied based on the requirements for the electric field for different ion transport conditions. In typical examples, when the ion transport device operates at pressures from 0.00001 to 100 Torr, the gap between the electrodes is from 0.05 to 1 mm, including more than 1 mm, the width of an individual electrode can be from 0.05 to 1 mm, including more than 1 mm.

[0055] The length of the electrodes for groups (8 and 9) in the Y direction is determined by the required channel cross-section, which is selected in accordance with the calculated gas load on the pumps. In preferred variants, it can be 1-10 mm.

[0056] The power supply to the electrodes (8, 9, 10) can be varied based on the electric field requirements for different ion transport conditions. In a preferred embodiment, the power supply to the electrodes is applied in such a way that a traveling wave field is created above the surface of the electrodes, when a field with alternating potential maxima and minima is created that move along the surface above the electrodes. In order to form a traveling wave electric field, a time-varying voltage with a phase shift relative to the adjacent group of electrodes is applied to alternating groups of electrodes. In each group, starting from the first to the last electrode in the direction of ion movement, the phase of the voltage on the adjacent electrodes is shifted in such a way that “peaks” and “troughs” of potential are formed that move along the surface. In the classical case, the phase shift value is selected as 360 / n, where n is the number of electrodes in the group.So in one group the first electrode is held at the first voltage value, the second electrode - at the second, and so on. At the first moment of time t1 the first voltage is applied to the first electrodes of all groups, the second voltage - to the second electrodes of all groups, and so on, respectively. At the second moment of time t2 the first voltage is applied to the second electrodes in each group, the second voltage - to the third electrodes in each group, and so on. Thus the pushing field above the electrodes "steps" creating a traveling wave that makes the ions move in the selected direction.

[0057] Depending on the ratio of the ion velocity to the “travelling wave” velocity, two types of ion motion are possible. If the ions have very high mobility, they move with the wave. In this case, the ion velocity is equal to the “travelling wave” velocity. If the ion is carried along by the potential wave, “slipping” along the “crests”, this leads to the ion velocity being lower than the wave velocity. In this case, the ions will move in the wave field with different velocities along the channel depending on their mobilities. Ions with higher mobility will move with the wave for a significant part of the time, while ions with lower mobility will “skip” the wave crests more often. The more ions “skip” the peaks, the slower they move through the device.

[0058] To ensure the device operating mode in which minimal blurring of ion packets occurs, it is preferable to select a power supply mode in which their synchronous movement in the traveling wave field occurs.

[0059] The preferred options for the power supply modes of the ion transport channel electrodes (8 and 10) are as follows. The amplitude and frequency of the RF voltages supplying the electrodes depend on the characteristic size of the electrodes, the pressure in the channel, the type of neutral gas, the step between them, and the set of M / z with CCS of the ions passing through the channel. For example, for the selected characteristic size of the electrodes following each other with a step of 1 mm, for ions with M / z=200 V, the amplitude of the voltage that sets the traveling wave field can be 2..70 V, with a characteristic frequency of 0.5-8 MHz, the signal is shifted by 90° for adjacent electrodes to provide a traveling wave field, but is not limited to this range.

[0060] In one embodiment, the supply voltages to the groups of electrodes may be a sum of voltages changing with different frequencies and with different sets of phases and amplitudes. In one preferred embodiment, the power is supplied as follows. An antiphase signal with a higher frequency, for example 0.2...10 MHz or more, with an amplitude of 2-100 V is supplied to the adjacent electrodes. This high-frequency voltage creates an ion-holding field inside the channel. To create a traveling wave field, a signal with a frequency that is preferably 1.2...20 or more times lower relative to the first and with a phase shift relative to the adjacent electrodes in the group, which is distributed among the aforementioned groups of electrodes, is superimposed on this signal. The signal is supplied to the adjacent electrodes with a phase shift that corresponds to the selected number of electrodes in the group. For example, if there are 4 electrodes in the group, the phase shift will be 90°. The amplitude of the second signal is preferably 0.02...20 V.

[0061] Preferred variants of the power supply modes of the LED electrodes (9) to ensure the retention of ions within the transport channel and their movement along the axis are similar to the modes described above. To ensure the fragmentation of ions, the electrodes are powered in such a way that a potential difference is formed between the average potential on the channel axis (2) and the potential on the LED cell axis (4), which accelerates the ions in the LED and ensures fragmentation with a characteristic energy proportional to this potential difference. This difference can preferably be 5-20 V, but can be less or more than the specified range, in accordance with the task being solved by the device. The supply voltage can be a sinusoidal signal, have a rectangular, triangular, sawtooth or other signal shapes. The term "radio frequency RF electrodes" 11 does not limit the power supply mode of the electrodes to RF voltage only.

[0062] In one of the variants, the LED can be made with an increase in volume in the LED region, where fragmentation and thermalization of ions occurs (see Fig. 2). Such a variant is easily implemented and, at the same time, in this volume the pressure will have a more constant value than in a narrow channel, if gas enters there. But the creation of a special chamber of the LED cell with an increased volume is not of fundamental nature for this invention.

[0063] In one embodiment, the LED cell can be made without widening the gap between the electrodes (see Fig. 3). This embodiment is the simplest to implement.

[0064] The channel formed by the surfaces with high-frequency electrodes (8,9,10) can narrow towards the outlet in order to further reduce the overall conductivity of the channel and limit the flow of gas passing into the next stage.

[0065] In one embodiment, the scale of the repeating pattern may vary along the length of the surfaces forming the channel. For example, at the input of the LED cell (4) of the device, the scale of the pattern may be approximately 1.2-5 or more times larger than the scale of the pattern at the output of the ion-focusing device.

[0066] In one of the variants, the channels (7, 5 and 3) can be separated from each other by diaphragms, which create an additional focusing field, can additionally limit the gas flow passing through the channels. Also, the diaphragms can be located at the input of the channel (2) and at the output of the channel (3). characterized in that the channel, which is formed by the surfaces with electrodes, is hermetic or has limited gas permeability and is made with the possibility of creating resistance to the gas flow passing through the channel.

[0067] In one embodiment, the surfaces defining the ion transport channel and the field-setting electrodes are manufactured using printed circuit board technologies.

[0068] In addition, the claimed device has additional advantages:

[0069] • Ion-focusing devices such as ion funnels, ion carpets, and focusing lenses can be used at the entrance of ion-transport channels.

[0070] • Channel electrodes and LED cells can be located on the same surface, without being divided into chambers using diaphragms.

[0071] • Fragmentation occurs in a small volume, fragment ions are quickly thermalized. It is easy to create an extracting field along the axis.

[0072] • The ejection field can be pulsed.

Claims

CLAUSE OF THE INVENTION 1. A device for fragmenting ions characterized in that it contains an ion transport channel having an input and output end, limited by surfaces on which radio frequency and / or DC electrodes are located, creating a traveling wave field directing ions to the output end of the channel, wherein in the middle part of the device there are electrodes providing the function of fragmentation and thermalization of ions, differing from other electrodes located on the rest of the device in the power supply mode and / or geometry.

2. A device for fragmenting ions according to claim 1, characterized in that the surfaces limiting the ion transfer channel form a sealed channel or the channels have limited gas permeability, and the input and output channels are designed with the possibility of creating resistance to the gas flow passing through them.

3. A device for fragmenting ions according to claim 1, characterized in that the ion transfer channel has a rectangular, round or oval shape in cross-section.

4. A device for fragmenting ions according to claim 1, characterized in that the ion transfer channel has narrowing sections with the possibility of creating resistance to the gas flow and focusing the ions into narrow beams.

5. A device for fragmenting ions according to claim 1, characterized in that the ion transfer channel is formed by two flat surfaces located opposite each other with radio frequency electrodes and two flat opposite surfaces with DC electrodes.

6. A device for fragmenting ions according to claim 1, characterized in that the ion transfer channel is formed by four flat surfaces with radio frequency electrodes or electrodes in the form of diaphragms alternating along the channel.

7. A device for fragmenting ions according to claim 1, characterized in that the electrodes are made in the form of groups of two and / or three and / or four and / or five and / or more electrodes, to which the corresponding RF power supply with a phase shift is supplied.

8. A device for fragmenting ions according to claim 1, characterized in that the electrodes located in the middle part of the device are made in the form of a separate group and are located along the length of the ion transfer channel.

9. A device for fragmenting ions according to claim 1, characterized in that the geometry of the electrodes located in the middle part of the device, primarily responsible for fragmenting ions, is made to repeat the geometry of the electrodes located in the rest of the device.

10. A device for fragmenting ions according to claim 1, characterized in that the electrodes have a repeating pattern along the length of the surface.

11. The device for fragmenting ions according to claim 1, characterized in that the electrodes have a pattern and scale that vary along the length of the surface.

12. The device for fragmenting ions according to claim 1, characterized in that the surfaces that limit the channel for transporting ions and the field-setting electrodes are manufactured using printed circuit board technologies.

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