METHOD AND DEVICE FOR SPATIAL COMPRESSION AND ENHANCED MOBILITY RESOLUTION OF IONS

Description

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. Patent Application No. 15 / 157,217, filed May 17, 2016.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] This invention was made with Government support under Contract DE-AC0576RL01830 awarded by the U.S. Department of Energy. The Government has certain rights in the invention.TECHNICAL FIELD

[0003] This invention relates to ion spatial compression, accumulation, and increasing mobility resolution of ion separations. More specifically, this invention relates to compressing distributions of ions into narrower peaks or redistribution of ion peaks by applying an intermittent traveling wave, resulting in increased signal-to-noise ratio and peak resolution.BACKGROUND

[0004] In a traveling wave (TW) separation, ions of different mobilities separate based on their relative motion in a moving electric field, typically by the intermittent application of DC voltages. This TW profile moves in the intended direction of ion motion. The TW creates periodic highs and valleys, and the ions are trapped in valleys if the field moves very slowly relative to their mobilities. As the TW moves forward, depending on the speed of motion of the TW, the ions either stay within their valley or roll over the wave to fall back into the previous potential valley. The number of such rollovers is dependent on the ion mobility of the species and this leads to mobility based separation; species with lower mobilities roll over more often and take longer periods to traverse a given distance.

[0005] US patent application US2004 / 031920 discloses a mass spectrometer comprising an ion mobility separator. The ion mobility separator comprises a plurality of electrodes and a transient DC voltage or a transient DC voltage waveform are progressively applied to the electrodes so that ions having a certain ion mobility are separated from other ions having different ion mobilities.

[0006] US patent application US2012 / 032073 discloses a mass spectrometer adapted to exchange quickly hydrogen and deuterium in molecules for isotopic labelling. This labelling is performed on molecules retained in the potential wells of travelling waves.

[0007] Publication by Giles K. et al: "A method for direct measurement of ion mobilities using a travelling wave ion guide", International Journal of Mass Spectrometry 298 (2010) 10-16 teaches the use of an ion mobility-mass spectrometer in which travelling waves are implemented.

[0008] With conventional ion mobility separations, larger voltages are required as the separation distance is increased, as in traditional mobility separations that use constant drift fields. Thus, extremely long path length separations are not feasible. TW based separations can be used to avoid this limitation, however limitations still persist. The practical realization of the benefit of TW ion mobility separations is limited by considerations that include the peak broadening due to diffusion ion roll over in the traveling waves. This results in broad peaks for ion mobility separations when using very long path lengths, making detection difficult and signal-to-noise (S / N) low. Further, multi-pass / cyclical path ion mobility separations are similarly limited in their extent due to peak broadening and signal dilution at large number of passes. Indeed, for such devices one peak can expand by such effects to fill the entire path, and making the approach ineffective for even species of very similar mobility. The solution to this problem for TW separations would enable overcoming diffusional / peak broadening related issues and allow novel instrumentation providing very high ion mobility spectrometry (IMS) resolution.

[0009] A related challenge in such application is to increase the initial ion population significantly, so as to increase the S / N at the time of detection, but space charge effects limit the size of the ion population that can initially injected for IMS separations. Thus, while an ion trap is often used to accumulate ions for injection to IMS, a key limitation is the space charge capacity that limits the maximum number of charges, typically to about 10 6< or at most 10 7< . While the initial injection pulse can be made greater by extending it over a longer period, a longer injection pulse also makes peaks wider and is incompatible with the desired higher resolution. No solution to the problem has been evident, resulting in the need to often repeat the separation many times, and then sum or average the results, to improve the S / N.

[0010] In IMS, achieving high resolution has been traditionally addressed by: 1) increasing the physical size of the IMS cell by building a long path length, 2) increasing the pressure, and 3) in a few cases, circulating ion packets in cyclic or multi-pass devices. Increasing the physical size of the IMS cell is hindered by the practicality of fabricating such systems and, in the case of constant field IMS, increasing the physical length requires a proportional increase of the drift voltage. The maximum drift voltage is limited by the electrical breakdown phenomena. Alternatively, the pressure of the buffer gas can be increased which is, however, accompanied by a significant loss of ions due to the poor ability to trap ions at high pressure over extended periods. Increasing the pressure also requires a proportional increase of the drift voltage in constant field IMS which, as mentioned above, is limited by the breakdown voltage. Finally, the path length can be increased by circulating ion packets multiple times in a cyclotron device in order to achieve high resolution. However, the number of passes that can be usefully applied is progressively limited by both the increasing separation between ions and the increased size of the peak, and ultimately as one peak fills the entire device. The length of the cyclic or multi-pass arrangement can be made greater to increase the range of mobilities that can be separated simultaneously, however such devices are cumbersome and difficult to fabricate. As such, there is a need for novel approaches to solve the aforementioned challenges.SUMMARY

[0011] The present invention is defined by independent claims 1 and 6 and is directed to methods and apparatuses for ion spatial compression and increasing resolution of ions in IMS, or increasing the S / N following other separations. In one embodiment of the present invention, an apparatus for peak ion compression is disclosed. The apparatus includes a device into which a substantially continuous beam of ions is introduced. The apparatus also includes an intermittent traveling wave applied to the device for compressing the ions into a narrower distribution of ion peaks. In one embodiment, the ion packets are compressed into the narrower distribution of peaks by varying a duty cycle of the intermittent traveling wave.

[0012] In one embodiment, the reduction in peak distribution widths occurs due to a substantial continuous incoming beam being merged into a single trap at the interface between a normal (non-intermittent) traveling wave and the intermittent traveling wave portions of the device.

[0013] In another embodiment, the present invention is used in multi-pass designs to trap and accumulate much larger ion populations and then spatial compression applied at different times during the separation, resulting in greatly increased S / N in conjunction with much greater IMS resolution.

[0014] In another embodiment of the present invention, a method of ion peak compression is disclosed. The method includes introducing a substantially continuous beam of ions into a device. The method also includes applying an intermittent traveling wave to the device for compressing the ions into narrower ion peaks.

[0015] In another embodiment of the present invention, an apparatus for ion peak compression is disclosed. The apparatus includes a device into which packets of ions are introduced. The apparatus further includes a first electric field for dispersing the ion packets temporally or spatially according to their mobilities. The apparatus also includes a second intermittent traveling wave for regrouping or merging the dispersed ion packets into a lesser number of trapping regions with narrower peaks. In one embodiment, the ion packets are merged into the narrower peak regions by varying a duty cycle of the intermittent traveling wave.

[0016] The first electric field may be a continuous traveling wave field formed according to the description provided in US Patent Application 62 / 238,291 filed 7 October 2015 entitled Method and Apparatus for Controlling Ions in a Gas Phase, the entirety of which is hereby incorporated by reference.

[0017] In one embodiment, the first electric field is applied to a first region of ion motion and the second intermittent traveling wave (or "stuttering" wave) is applied to a second region of ion motion. The direction of ion motion in the first electric field region can be orthogonally aligned or aligned in the same direction to the direction of ion motion in the second intermittent traveling wave region. Alternatively, the first electric field region and the second intermittent traveling wave region may be aligned at any angle between 0° - 359° relative to one another.

[0018] In one embodiment, the intermittent traveling wave merges ions from two or more trapping regions into one. In another embodiment, the intermittent traveling wave merges ions from four or more trapping regions into one.

[0019] In one embodiment, the intermittent traveling wave may be replaced with a non-intermittent traveling wave after a predetermined range of ion packets are regrouped or merged into the narrower peak regions and prior to detection.

[0020] In another embodiment of the present invention, a method of ion peak compression is disclosed. The method includes introducing packets of ions into a device. The method further includes applying a first electric field for dispersing ion packets into multiple trapping regions. The method also includes applying a second intermittent traveling wave for regrouping or merging the dispersed ion packets into a lesser number of trapping regions with narrower peaks.BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 is a schematic diagram of an apparatus for ion peak compression including a normal traveling wave and a "stuttering" or intermittent traveling wave, in accordance with one embodiment of the present invention. Linear and other arrangements are also practical. Figures 2A-2C shows the results of spatial peak compression using the apparatus of Figure 1. Figure 2A is the initial distribution of the ion peak spread, and Figures 2B and 2C involving application of the intermittent traveling wave having a narrowing effect on the distribution of the ions. Figures 3A and 3B shows the spatial peak compression with no compression (Figure 3A) and with 2x compression after imposition of the intermittent traveling wave (Figure 3B). Figure 4A shows ion motion through a separation region orthogonally aligned to a compressor region of the apparatus, in accordance with one embodiment of the present invention. Figure 4B is a graph of frequency over time for a normal traveling wave applied to the separation region. Figure 4C is a graph of frequency over time for the intermittent traveling wave applied to the compressor region of the apparatus. Figure 5 is one variation of the separation and compressor regions, with the two regions aligned in the same or similar direction. Figure 6 is another variation of the separation and compressor regions, with the compressor region preceding the separation region. Figure 7 is another variation of the separation and compressor regions, which includes dynamically gating ions into either of the two regions. Figures 8A, 8B, and 8C are variations of the separation and compressor regions, with any combination of relative size and relative position of the two regions. Figures 9A and 9B show the arrival time distribution and intensities of a non-compressed ion packet (Figure 9A) and a compressed ion packet (Figure 9B). Figures 10A and 10B show the arrival time distribution and intensities of a non-compressed continuous ion beam (Figure 10A) and a compressed continuous ion beam (Figure 10B). Figure 11 illustrates change in duty cycle when the voltage is applied to one of the compressor electrodes of Figure 1 over time. Initially there is no compression, then the duty cycle changes to allow the compression, and then after a certain time the duty cycle is changed to a different duty cycle which may be similar or different to the initial duty cycle. Figure 12 is a simplified block diagram of an apparatus for increasing resolution in IMS. Figures 13A-13E show the different stages, some optional, for increasing resolution in IMS, including ion separation (Figure 13A), optional ion compression with reversing of the electric field direction (Figure 13B), ions moving back to a position prior to the separation stage (Figure 13C), optional ion compression (Figure 13D), and repeating, if considered necessary, ion separation until a desired resolution is obtained (Figure 13E). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] The following description includes preferred embodiments of the present invention. It will be clear from this description of the invention that the invention is not limited to these illustrated embodiments but that the invention also includes a variety of modifications and embodiments thereto. Therefore the present description should be seen as illustrative and not limiting. While the invention is susceptible of various modifications and alternative constructions, it should be understood, that there is no intention to limit the invention to the specific form disclosed, but, on the contrary, the invention is to cover all modifications, alternative constructions, and equivalents falling within the scope of the invention as defined in the claims.

[0023] Disclosed are methods, devices, and apparatuses for increasing signal-to-noise ratio in traveling wave ion mobility and other applications in which ions are separated based on their mobilities when an external force, e.g., a voltage field, is imposed on the ions, or separated by other means, including before ionization. The present invention includes the imposition of an intermittent or "stuttering" traveling wave that sorts, compresses, or regroups ions into fewer mobility 'bins', where bin is defined herein as one of the trapping regions between two waves. Signal intensity increases as a result of this binning of ions with the same or very similar mobilities. Any loss of resolution as a result of peak bunching can be regained by a short additional drift time after the sorting / regrouping / compressing step. This "rebinning" can simply be combining each two or more adjacent bins into one - i.e. giving a compression ratio of 2 or larger integer value, but other more complex rebinnings are feasible, and where the compression ratio varies or is programmed in a certain fashion, to e.g. apply greater compression as peaks get broader during a separation.

[0024] Figure 1 is a schematic diagram of an apparatus for ion mobility separations, in accordance with one embodiment of the present invention. As ions are introduced into the apparatus or device, a traveling wave electric field is applied for separating the ion packets temporally or spatially according to their mobilities. As such, the ions are dispersed or spread out over multiple traveling traps or bins. When this "normal" or continuously moving traveling wave is interfaced with a second region where a "stuttering" or intermittent traveling wave - where the moving traveling wave stops intermittently - the ions which are spread out over the multiple trapping bins of the normal traveling wave get repopulated into a lesser number of trapping regions with narrower peaks. Thus, the ions that were dispersed over a long path of many traveling traps are sorted into a different, narrower distribution involving a smaller number of bins.

[0025] The extent of such repopulation is dependent on the duty cycle of the intermittent traveling wave, i.e. the relative time for which the traveling wave stops and moves. After a chosen or predetermined range of ion mobility peaks are so repopulated, the intermittent traveling wave can be replaced with a normal traveling wave. This can occur prior to detection

[0026] A higher signal-to-noise ratio is achieved as a result of the regrouping of ions with similar mobilities into narrower mobility bins or traps. By interfacing the two electric fields - the normal traveling wave and the intermittent traveling wave - repeatedly, say, in a multiple pass type of separation, a larger number of cycles will be enabled. By appropriately choosing the frequency and order of such peak bunching, practically infinite peak resolution may be feasible.

[0027] Figures 2A-2C shows the results of spatial peak compression using the apparatus of Figure 1. Figure 2A is the initial distribution or peak of the ions spread over 48 electrodes in this example. The full width half maximum (FWHM) for the initial distribution was approximately 16 mm.

[0028] Figures 2B and 2C show the narrowing effect on the distribution of the ions when the intermittent traveling wave is applied. In Figure 2B, ions in two bins are merged into one, and the FWHM is reduced to approximately 9 mm. Figure 2C shows the effect of merging 4 bins of ions into one. The FWHM in Figure 2C is decreased further to approximately 6.3 mm, leading to an increase in signal-to-noise ratio.

[0029] Figures 3A and 3B shows the spatial peak compression with no compression (Figure 3A) and with 2x compression after imposition of the intermittent traveling wave (Figure 3B), for two ions with different mobilities - K 0 = 1.17 cm 2< / V.s and K 0 = 1.00 cm 2< / V.s.

[0030] Figure 4A shows ion motion through a separation region orthogonally aligned to a compressor region of the apparatus, in accordance with one embodiment of the present invention. The normal traveling wave region, referred to as the separation region, has a constant traveling wave frequency as shown in the graph of Figure 4B and is, in this example, vertically oriented and orthogonal to the intermittent traveling wave region. The intermittent traveling wave region, referred to as the compressor region, has an intermittently non-zero traveling wave frequency as shown in the graph of Figure 4C and is, in this example, horizontally oriented. The arrow indicates the ion trajectory path

[0031] Figure 5 is one variation of the separation and compressor regions of Figure 4A, with the two regions aligned in the same or similar direction. The effect on signal-to-noise and resolution when the regions are aligned in the same direction is similar to the orthogonal orientation of Figure 4A.

[0032] Figure 6 is another variation of the separation and compressor regions of Figure 4A and Figure 5, with the compressor region preceding the separation region. The configuration of Figure 6 may be useful, for example, when ion trapping or separating prior to ion compression is not necessary; the compressor is used as an injection device for subsequent separation.

[0033] Figure 7 is another variation of the separation and compressor regions for devices that include dynamically gating ions into either of the two regions, namely the separation and compressor regions.

[0034] Figures 8A, 8B, and 8C are variations of the separation and compressor regions, with any combination of relative size and relative position of the two regions. Figure 8A shows a compressor region followed by a separation region, and then a repeat of the same pattern. Figures 8B and 8C show the regions configured with or in orbital motion.

[0035] Figures 9A and 9B show the arrival time distribution and intensities of a non-compressed ion packet (Figure 9A) and a compressed ion packet (Figure 9B).

[0036] Figures 10A and 10B show the arrival time distribution and intensities of a non-compressed continuous mode ion beam (Figure 10A) and a compressed continuous mode ion beam (Figure 10B).

[0037] Figure 11 illustrates change in duty cycle when the voltage is applied to one of the compressor electrodes of Figure 1 over time. Initially there is no compression, then the duty cycle changes to allow the compression, and then after a certain time the duty cycle is changed to a different duty cycle which may be similar or different to the initial duty cycle.

[0038] Figure 12 is a simplified block diagram of an apparatus for increasing resolution in IMS, not included in the present invention. The apparatus includes an optional ion compressor coupled to an IMS separation device which is further coupled to another optional ion compressor.

[0039] Figures 13A-13E show the different stages, some optional, for increasing resolution in IMS, not included inof the present invention. In Figure 13A, pulsed ions are introduced into an IMS device where they are then separated according to their mobilities by applying a constant or variable electric field to the device. Next, in Figure 13B, an optional ion compressor narrows or compresses the ions, and the electric field is reversed. Reversing the electric field causes the ions to move back to a position prior to the separation stage, as shown in Figure 13C. Another optional ion compression stage is shown in Figure 13D. No IMS separation occurs between Figures 13B-13D. The process may be repeated, as shown in Figure 13E, until a desired resolution is obtained.

[0040] While a number of embodiments of the present invention have been shown and described, it will be apparent to those skilled in the art that many changes and modifications may be made without departing from the invention in its broader aspects. The appended claims, therefore, are intended to cover all such changes and modifications as they fall within the scope of the invention.

Claims

1. An apparatus for spatial ion peak compression comprising: a first region configured to receive ions means to apply a first electric field to the first region, the first electric field comprising a first traveling wave configured to disperse the ions into a plurality of ion packets based on mobility of the ions; and a second region separate from the first region and configured to receive the plurality of ion packets; means to apply a second electric field to form a second traveling wave for regrouping or merging the dispersed ion packets into a lesser number of trapping regions with narrower peaks; characterized in that the second traveling wave has an intermittently non-zero frequency.

2. The apparatus of Claim 1 wherein the first electric field is a traveling wave.

3. The apparatus of Claim 1 wherein the direction of ion motion in the first region is orthogonally aligned to the direction of ion motion in the second region.

4. The apparatus of Claim 1 wherein the direction of ion motion in the first region is aligned in the same direction to the direction of ion motion in the second region.

5. The apparatus of Claim 1 wherein the first region and the second region are aligned at any angle between 0°-359° relative to one another.

6. A method of spatial ion peak compression comprising: introducing ions into a device having a first region and a second region separate from the first region; applying a first electric field comprising a first traveling wave to the first region dispersing the ions into a plurality of ion packets based on mobility of the ions; and applying a second electric field to the second region to form a second traveling wave for regrouping or merging the dispersed ion packets into a lesser number of trapping regions with narrower peaks; characterized in that the second traveling wave has an intermittently non-zero frequency.

7. The method of Claim 6 wherein the first electric field is a traveling wave.

8. The method of Claim 6 wherein the direction of ion motion in the first region is orthogonally aligned to the direction of ion motion in the second region.

9. The method of Claim 6 wherein the direction of ion motion in the first region is aligned in the same direction to the direction of ion motion in the second region.

10. The method of Claim 6 wherein the first region and the second region are aligned at any angle between 0°-359° relative to one another.

11. The method of Claim 6 wherein the intermittent traveling wave merges ions from two or more trapping regions into one, or from four or more trapping regions into one.

12. The method of Claim 6 wherein the intermittent traveling wave is replaced with a non-intermittent traveling wave after a predetermined range of ion packets are regrouped or merged prior to detection.

13. The method of Claim 6 wherein the merged ion packet is temporally narrower than the two or more adjacent ion packets.