Patent Grant
11209393
Embodiments of the present disclosure relate to ion mobility separations and related ion manipulations. More specifically, the disclosed embodiments relate to performing ion manipulations including movement in moving ion trapping regions and ion mobility separations using a continuous, alternating current (AC) voltage waveform or, multiple continuous AC voltage waveforms, applied to one or more segmented electrodes.
Ion mobility spectrometry (IMS) is a technique for separating and identifying ions. IMS can be employed to separate structural isomers and resolve conformational features of macromolecules. IMS may also be employed to augment mass spectroscopy (MS) in a broad range of applications, including metabolomics, glycomics, and proteomics.
For example, when performing IMS, a sample containing different ions is injected into a first end of an enclosed cell containing a carrier gas, also referred to as a buffer gas. In the cell, the ions move from the first end of the cell to a second end of the cell under the influence of an applied electric field. The ions are subsequently detected at the second end of the cell as a current as a function of time. The sample ions achieve a maximum, constant velocity (i.e., a terminal velocity) arising from the net effects of acceleration due to the applied electric field and deceleration due to collisions with the buffer gas molecules. The terminal velocity of ion within the IMS cell is proportional to their respective mobilies, related to ion characteristics such as mass, size, shape, and charge. Ions that differ in one or more of these characteristics will exhibit different mobilities when moving through a given buffer gas under a given electric field and, therefore, different terminal velocities. As a result, each ion exhibits a characteristic time for travel from the first end of the cell to the second end of the cell. By measuring this characteristic travel time for ions within a sample, the ions may be identified.
There are a number of IMS formats used for chemical and biochemical analysis, including constant field drift tube ion mobility spectrometry (DT-IMS), high field asymmetric ion mobility spectrometry (FA-IMS), differential mobility analysis (DMA), and traveling wave ion mobility spectrometry (TW-IMS). These formats vary in the manner by which the electric field is applied to separate the ions within the IMS cell. Notably, however, conventional IMS devices are limited in their ability to separate ions (separation power) due to practical limitations on size and complexity of the electrode structures generating the electric fields that separate the ions.
Accordingly, there exists an ongoing need for improved systems and methods for ion mobility separation.
In an embodiment of the disclosure, an apparatus for ion manipulations is provided. The apparatus includes at least one surface, a first plurality of continuous electrodes, and a second plurality of segmented electrodes. The first plurality of continuous electrodes is coupled to the at least one surface and in electrical communication with a radiofrequency (RF) voltage source. An RF voltage applied to adjacent electrodes of the first plurality of electrodes by the RF voltage source is phase shifted on the adjacent electrodes of the first plurality of electrodes by approximately 180°. The second plurality of segmented electrodes is coupled to the at least one surface and arranged in longitudinal sets between or adjacent to the first plurality of electrodes. The second plurality of segmented electrodes is further in electrical communication with an alternating current (AC) voltage source. An AC voltage waveform applied to adjacent electrodes within a longitudinal set of the second plurality of segmented electrodes by the AC voltage source is phase shifted on the adjacent electrodes of the second plurality of electrodes by 1°-359°.
Embodiments of the apparatus may include one or more of the following, in any combination.
In an embodiment, the apparatus further includes a plurality of guard electrodes positioned on outer ends of the first and second plurality of electrodes on the at least one surface. The plurality of guard electrodes are in electrical communication with a DC voltage source. The plurality of guard electrodes generate electric fields that constrain ion motion towards the guard electrodes when receiving a constant DC voltage from the DC voltage source.
In an embodiment of the apparatus, the AC voltage waveform is a sine wave.
In an embodiment of the apparatus, the AC voltage waveform is the sum of more than one AC voltage waveform.
In an embodiment of the apparatus, the AC voltage waveform applied to adjacent electrodes within a longitudinal set of the second plurality of segmented electrodes is phase shifted on the adjacent electrodes of the second plurality of segmented electrodes in a repeating pattern.
In an embodiment of the apparatus, the AC voltage waveform applied to adjacent electrodes within a longitudinal set of the second plurality of segmented electrodes is phase shifted by approximately 45°, 90° or 120° on the adjacent electrodes of the second plurality of electrodes in a stepwise fashion.
In an embodiment of the apparatus, the at least one surface includes a single and non-planar surface.
In an embodiment of the apparatus, the single, non-planar surface is one of the following shapes: curved, cylindrical, a spiral, a funnel, hemispherical, or elliptical.
In an embodiment of the apparatus, the at least one surface includes two surfaces spaced apart from one another.
In an embodiment of the apparatus, the two surfaces are approximately parallel to one another.
In an embodiment of the apparatus, a frequency of the applied AC voltage waveform is selected from the range of 10 Hz-200 kHz, and a frequency of the applied RF voltage is selected from the range of 100 kHz-5 MHz.
In an embodiment of the apparatus, a frequency applied AC voltage waveform is selected from the range of 1 Hz to 1 kHz.
In an embodiment of the apparatus, a pressure range of the apparatus is from atmospheric pressure to 1 mtorr vacuum.
In another embodiment of the disclosure, an apparatus for ion manipulations is provided. The apparatus includes at least one surface and a plurality of segmented electrodes. The plurality of segmented electrodes is coupled to the at least one surface and arranged in one or more longitudinal sets. The plurality of segmented electrodes is further in electrical communication with an alternating current (AC) voltage source and a radiofrequency (RF) voltage source. An AC voltage waveform applied to adjacent electrodes within a longitudinal set of the plurality of electrodes by the AC voltage source is phase shifted by 1°-359°. An RF voltage applied to adjacent electrodes of the plurality of electrodes by the RF voltage source is phase shifted by approximately 180°.
Embodiments of the apparatus may include one or more of the following in any combination.
In an embodiment, the apparatus further includes a plurality of guard electrodes positioned on outer ends of the plurality of electrodes on the at least one surface. The plurality of guard electrodes are further in electrical communication with a DC voltage source. The plurality of guard electrodes generate electric fields that constrain ion motion towards the plurality of guard electrodes when receiving a constant DC voltage from the DC voltage source.
In an embodiment of the apparatus, the applied AC voltage waveform is a sine wave.
In an embodiment of the apparatus, the AC voltage waveform is the sum of more than one AC voltage waveform.
In an embodiment of the apparatus, the applied the AC voltage waveform is phase shifted on the adjacent electrodes of the plurality of electrodes in a repeating pattern.
In an embodiment of the apparatus, the applied AC voltage waveform is phase shifted by approximately 45°, 90°, 120°, or 180° on the adjacent electrodes of the plurality of electrodes in a stepwise fashion.
In an embodiment of the apparatus, the at least one surface includes a single and non-planar surface.
In an embodiment of the apparatus, the single, non-planar surface is one of the following shapes: curved, cylindrical, a spiral, a funnel, hemispherical, or elliptical.
In an embodiment of the apparatus, the at least one surface includes two surfaces spaced apart from one another.
In an embodiment of the apparatus, the two surfaces are approximately parallel to one another.
In an embodiment of the apparatus, a frequency of the applied AC voltage waveform is selected from the range of 1 kHz-200 kHz, and the RF voltage is selected from the range of 100 kHz-5 MHz.
In an embodiment of the apparatus, a pressure range of the apparatus is from atmospheric pressure to 1 mtorr vacuum.
In an additional embodiment of the disclosure, a method of ion manipulations is provided. The method includes providing at least one surface. The at least one surface includes a first plurality of continuous electrodes coupled to the at least one surface and in electrical communication with a radiofrequency (RF) voltage source. The at least one surface further includes a second plurality of segmented electrodes coupled to the at least one surface and arranged in longitudinal sets between or adjacent to the first plurality of electrodes. The second plurality of segmented electrodes is further in electrical communication with an alternating current (AC) voltage source. The method further includes applying, by the RF voltage source, an RF voltage to adjacent electrodes of the first plurality of electrodes, where the applied RF voltage is phase shifted on the adjacent electrodes of the first plurality of electrodes by approximately 180°. The method additional includes applying, by the AC voltage source, an AC voltage waveform within a longitudinal set of the second plurality of segmented electrodes, where the applied AC voltage waveform is phase shifted on the adjacent electrodes of the second plurality of electrodes by 1°-359°.
Embodiments of the method may include one or more of the following, in any combination.
In an embodiment, the method further includes positioning a plurality of guard electrodes on outer ends of the first and second plurality of electrodes on the at least one surface. The plurality of guard electrodes are further in electrical communication with a DC voltage source. The plurality of guard electrodes generate electric fields that constrain ion motion towards the guard electrodes when receiving a constant DC voltage from the DC voltage source.
In an embodiment of the method, the AC voltage waveform is a sine wave.
In an embodiment of the method, the AC voltage waveform is the sum of more than one AC voltage waveform.
In an embodiment of the method, the applied AC voltage waveform is phase shifted on the adjacent electrodes of the second plurality of segmented electrodes in a repeating pattern.
In an embodiment of the method, the applied AC voltage waveform is phase shifted by approximately 45°, 90°, or 120° on the adjacent electrodes of the second plurality of segmented electrodes in a stepwise fashion.
In an embodiment of the method, the at least one surface includes a single and non-planar surface.
In an embodiment of the method, the single, non-planar surface is one of the following shapes: curved, cylindrical, a spiral, a funnel, hemispherical, or elliptical.
In an embodiment of the method, the at least one surface includes two surfaces spaced apart from one another.
In an embodiment of the method, the two surfaces are approximately parallel to one another.
In an embodiment of the method, a frequency of the applied AC voltage waveform is selected from the range of 10 Hz-200 kHz, and a frequency of the RF voltage is selected from the range of 100 kHz-5 MHz.
In another embodiments of the disclosure, a method of ion manipulation is provided. The method includes providing at least one surface including a plurality of segmented electrodes coupled to the at least one surface and arranged in one or more longitudinal sets. The plurality of segmented electrodes are in electrical communication with an alternating current (AC) voltage source and a radiofrequency (RF) voltage source. The method further includes applying, by the AC voltage source, an AC voltage waveform to adjacent electrodes within a set of the plurality of segmented electrodes. The applied AC voltage waveform is phase shifted on the adjacent electrodes of the plurality of segmented electrodes by 1°-359°. The method also includes applying, by the RF voltage source, an RF voltage to adjacent electrodes of the plurality of segmented electrodes. The applied RF voltage is phase shifted on the adjacent electrodes of the plurality of segmented electrodes by approximately 180°.
Embodiments of the method may include one or more of the following, in any combination.
In an embodiment, the method further includes positioning a plurality of guard electrodes on outer ends of the plurality of segmented electrodes on the at least one surface. The plurality of guard electrodes is further in electrical communication with a DC voltage source. The plurality of guard electrodes generate electric fields that constrain ion motion towards the guard electrodes when receiving a constant DC voltage from the DC voltage source.
In an embodiment of the method, the AC voltage waveform is a sine wave.
In an embodiment of the method, the AC voltage waveform is the sum of more than one AC voltage waveform wave.
In an embodiment of the method, the applied AC voltage waveform is shifted on the adjacent electrodes of the plurality of segmented electrodes in phase in a repeating pattern.
In an embodiment of the method, the applied AC voltage waveform is phase shifted on the adjacent electrodes of the plurality of segmented electrodes by approximately 45°, 90°, or 120° in a stepwise fashion.
In an embodiment of the method, the at least one surface includes a single and non-planar surface.
In an embodiment of the method, the single, non-planar surface is one of the following shapes: curved, cylindrical, a spiral, a funnel, hemispherical, or elliptical.
In an embodiment of the method, the at least one surface includes two surfaces spaced apart from one another.
In an embodiment of the method, the two surfaces are approximately parallel to one another.
In an embodiment of the method, a frequency of the applied AC voltage waveform is selected from the range of 10 Hz-200 kHz, and a frequency of the applied RF voltage is selected within the range of 100 kHz-5 MHz.
In an embodiment, the electrodes may be arranged to cause ions to be trapped and accumulated in a region of an ion manipulation device, such as, but not limited to, the device described in U.S. Pat. No. 8,835,839, incorporated by reference in its entirety.
In an embodiment, the AC waveform can be adjusted to change, reduce, or eliminate a degree of ion heating by the AC traveling waveform compared to the transient application of DC voltages.
In an embodiment, the ion mobility separation can be stopped by increasing the amplitude of the AC waveform.
In one embodiment, the AC traveling waveform is stopped by changing the phase shift applied to adjacent AC electrodes to approximately zero or by reducing the AC frequency to approximately zero.
The following description includes embodiments of the present disclosure. These embodiments are not limited to these illustrated but also include a variety of modifications and embodiments thereto. Therefore, the present description should be seen as illustrative and not limiting. While the disclosed embodiments are susceptible of various modifications and alternative constructions, it should be understood, that there is no intention to limit the disclosure to the specific form discussed, but, on the contrary, the disclosure is to cover all modifications, alternative constructions, and equivalents falling within the spirit and scope of the disclosure as defined in the claims.
Embodiments of the present disclosure are directed to improved methods and apparatuses for separation of gas phase ions based on their mobilities employing continuous, alternating current (AC) waveforms or multiple continuous AC waveforms applied to one or more segmented electrodes. As discussed in detail below, these embodiments provide advantages over conventional ion mobility separation devices and methods, including reduced heating of ions, while providing comparable separation ability.
Conventional drift tube ion mobility separation (DT-IMS) employs a fixed voltage drop over the length of an IMS tube to provide a relatively weak, constant electric field under which ions move through the IMS tube. In this technique, ions are separated according to their relative mobilities when moving through a given buffer gas under a the applied electric field. The mobility is related to the collision cross-section of the ion with the inert buffer gas, the area around the ion in which the center of a buffer gas molecule must strike in order for a collision to occur. As discussed above, the collision cross-section is related to ion characteristics such as mass, size shape, and charge. In general, ions with a relatively larger collision cross-section possess lower mobility and vice versa. For example, an ion having a relatively low ion mobility (larger ion collision cross-section) will arrive at the detector at a later time as compared to an ion having a relatively larger ion mobility (smaller collision cross-section). Thus, by measuring the number of ion counts as a function of time, a spectrum of peaks and valleys is obtained. Comparing such spectra to spectra of known ions under the measurement conditions permits identification of the respective ions within a sample.
For any IMS measurements, it is desirable to adequately separate different ions so that they appear as distinct peaks IMS spectrum. That is to say, interpretation of IMS spectra becomes considerably more difficult when peaks due to different ions overlap. Thus, the ability of an IMS instrument to resolve closely spaced peaks is of significant interest.
In the context of conventional DT-IMS, increasing the resolving power, a quantity characterizing the separation efficiency of the IMS, requires increasing the magnitude of the voltage drop (V) over the length (d) of the tube. As discussed above, in DT-IMS, the electric field (E) is held constant and given by E=V/d. Accordingly, it may be understood that increasing the resolving power (increasing V) requires an increase in the length of the drift tube, d, to maintain a constant electric field. Therefore practical constraints on the magnitude of the voltage drop and the tube length, amongst other considerations, limit the resolving power achieved in DT-IMS.
Turning to another conventional IMS technique, traveling wave ion mobility separation (TW-IMS), a traveling electric field waveform is employed to move ions through the IMS tube, in contrast to the constant electric field discussed above. The traveling waveform in this case is generated by application of a transient and repetitive direct current (DC) voltage profile on a series of electrodes along the length of the IMS tube. For example, as discussed in greater detail below with respect to the example of
In general, the variables affecting ion motion in TW-IMS are the amplitude of the traveling wave, the traveling wave velocity, and the operating pressure. The ability of an ion to keep up with the traveling wave in the presence of collisions with the buffer gas is a function of the ion's velocity (mobility). Depending on the ratio of the maximum ion velocity to the speed of the traveling wave, c, three modes of ion behavior are observed.
Notably, however, commercially available TW-IMS devices have limited separation ability due to practical limitations on the size and complexity of the electrode structures. This limited separation ability can be inadequate for many potential applications, a challenge that is general to IMS, particularly where high sensitivity is also desired. Furthermore, because the transient DC voltages in conventional TW-IMS are applied in an on-or-off basis, the magnitude of the resultant electric field at the front of the wave is relatively high, as compared to the magnitude of the electric field used in DT-IMS. The high electric field in TW-IMS leads to ions spending more time in high electric fields and further results in some increased extent of internal ‘heating’ of ions compared to drift tube arrangements. This heating can lead to undesired changes of conformation or shape of ions, as well as reduced precision in the determination of collision cross-sections for ions being separated.
To address these limitations, embodiments of the disclosure present development and characterization of a new traveling wave-based Structure for Lossless Ion Manipulations (SLIMS) for ion mobility separations that employs continuous, alternating current (AC) voltage waveforms (AC-SLIMS) to form the traveling wave, as opposed to the transient DC voltage waveforms of conventional TW-IMS.
As discussed in greater detail below, certain embodiments of the AC-SLIMS apparatus include a first plurality of continuous radiofrequency (RF) electrodes and a second plurality of segmented AC electrodes. The first plurality of RF electrodes are mounted to a surface and positioned generally parallel to one another. The second plurality of segmented AC electrodes are positioned laterally adjacent to the first plurality of RF electrodes (e.g., interposed between). Application of RF voltages to the first plurality of continuous electrodes generates electric fields that provide ion confinement. Application of a continuous, time-varying AC voltage to the second plurality of segmented electrodes forms an alternating current (AC) voltage waveform to create a TW that generates an electric field to provide longitudinal ion motion and separation. The AC voltage waveform may be applied in the form of a sine wave, a cosine wave, or a combinations of multiple sine and/or cosine waves.
As illustrated below in the Examples, the AC-SLIMS approach achieves comparable resolution to conventional TW-IMS. Furthermore, an unexpected feature of the AC-SLIMS embodiments is that ions appear to spend less time at higher electric fields. As a result, ions separated using the AC-SLIMS approach undergo fewer conformational changes from ion heating, as compared to conventional TW-IMS using transient application of DC voltage waveforms. Furthermore since conformation changes also change the ion collision cross-section, reducing the number of these changes using the AC-SLIMS approach enables more precise measurement of ion collision cross-sections.
The ability of the AC-SLIMS approach to provide more precise measurement of collision cross-section is highly beneficial. In one aspect, this precision facilitates ion measurements performed in one laboratory to be reproduced in another laboratory. In another aspect, this precision provides a greater degree of confidence in acquired measurements using the AC-SLIMS apparatus and methods. In a further aspect, this precision is important for detailed examination of ion structure, as it allows for reasonable determinations of what different structures may be present in a sample. In an additional aspect, as the collision cross-section may be used in other calculations as a physical constant, this precision lends itself to further precision in those other calculations as well.
The discussion will now turn to
For example, in certain embodiments, a pair of surfaces may be approximately parallel if a spacing between the pair of surfaces along their respective lengths deviates from a selected value by less than a pre-determined amount. The predetermined amount may be selected within the range from 0.001% to 10%.
In an embodiment, the at least one surface is a substrate formed from a material suitable for receiving one or more electrically conductive elements (e.g., electrodes) and/or forming electrical circuits thereon. For example, the at least one surface may be formed from any insulating material (e.g., a semiconductor, a ceramic, a polymer, etc.). In another example, the at least one surface may be formed by additive manufacturing process (e.g., 3-D printing).
In further examples, the at least one surface is a printed circuit board (PCB). PCBs may be formed from materials including, but not limited to, reinforced or unreinforced polymer resins. Example reinforcements may include, but are not limited to, continuous and discontinuous fibers (e.g., glass fibers). Example polymer resins may include, but are not limited to, epoxies.
In further embodiments, the dimensions of the at least one surface may be provided, as necessary, without limit. In certain embodiments, each of the dimensions of the at least one surface may be independently selected from the range of 3 cm-300 cm in length and 0.75 cm-76 cm in width.
The plurality of electrodes includes a first plurality of continuous electrodes 110 and 120 and a second plurality of 125 of segmented electrodes. A plurality of guard electrodes 130 are also positioned to the side of the first plurality of continuous electrodes 110 and 120. As discussed in greater detail below, the first plurality of continuous electrodes 110, 120 serve to confine the ions in the y-direction (e.g., vertically), while the guard electrodes 130 serve to confine the ions in the x-direction (e.g., in the width direction). The second plurality of segmented electrodes 125 form the TW that moves the ions in the z-direction (e.g., in the longitudinal direction) through the apparatus 100.
The discussion will continue with further reference to the first plurality of continuous electrodes 110, 120. As an initial matter, these electrodes may be interchangeably referred to herein as RF electrodes, first plurality of electrodes, or simply electrodes 110 and/or electrodes 120. Each of the first plurality of electrodes 110, 120 is generally elongated and continuous, extending along at least a portion of a length of the at least one surface (e.g., the z-direction). For example, as illustrated in
The dimensions of the first plurality of electrodes 110, 120, and their respective spacing to one another, may be independently selected to generate effective potentials that confine ions within the apparatus 100. In general, there is no maximum or minimum length or width of the first plurality of electrodes 110, 120. The length of the first plurality of electrodes 110, 120 is limited only by the desired dimensions of the at least one surface upon which they are secured. The width and lateral spacing of the first plurality of electrodes 110, 120 is generally desired to be as small as feasible to provide fine control of the confining electric field. In an example, the width of the first plurality of electrodes 110, 120 may be independently selected from the range of 0.05 mm to 5 mm (e.g., 0.5 mm). In a further example, the lateral spacing between adjacent electrodes of the first plurality of electrodes 110, 120 may be selected from the range of 0.04 mm-4 mm.
It should be noted that the embodiment of
Each of the electrodes of first plurality of electrodes 110, 120 is additionally in electrical communication with an RF voltage source (not shown). In use, RF voltages are applied to laterally adjacent ones of the first set of electrodes 110 and 120, approximately 180° out of phase with respect to each other. That is, an RF voltage applied to the plurality of first electrodes 110 is 180° out of phase with an RF voltage applied to the plurality of first electrodes 120, as one example. Thus, the charge on laterally adjacent ones of the first plurality of electrodes 110 and 120 at any given time is of opposite polarity, indicated in
An example of ion behavior within electric fields generated by application of RF voltages to the first set of electrodes 110 and 120 is illustrated in
Assume, for example, first and second positive ions 400, 402 positioned between the two surfaces, with the first positive ion 400 positioned approximately in the middle of the two surfaces and the second positive ion (solid outline) positioned near an electrode 110. In general, the magnitude of the voltage applied to the first plurality of electrodes 110, 120 is such that the resultant electrical fields only influence the motion of the ions when the distance between the ion and the electrode is less than two electrode widths. This creates a “neutral zone” (dot-dot-dash lines) between the surfaces where the first positive ion experiences approximately no net attraction or repulsion due to the electric fields generated by the first plurality of electrodes 110, 120. In contrast, the second positive ion, which is close to positively charged electrode 110, experiences a repulsive force urging the second positive ion towards the neutral zone (e.g., upwards in
With further reference to
Subsequently, as time further advances, the polarity of the first plurality of electrodes 110, 120 reverses again, returning to the state of
For a given charge, the RF frequency and amplitude are selected from their respective ranges based upon the mass of the ions and the pressure of the buffer gas. Relatively higher frequencies and higher amplitudes are selected for relatively light ions (i.e., faster moving ions) and lower frequencies and lower amplitudes selected within this range for relatively heavy ions (i.e., slower moving ions). Relatively higher voltages are employed for higher pressures. The electric field generated by the RF electrodes in this manner may be represented by an effective electric field, Eeff, RF, as illustrated in
With further reference to
In use, a constant DC voltage is applied to each of the plurality of guard electrodes 130 to further confine ions in the x-direction (e.g., laterally, orthogonal to the direction of longitudinal motion of the ions). The polarity of the DC voltage is selected to be the same as that of the ions, generating an electric field, EDC that repels the ions, as illustrated in
The discussion will now turn to the second plurality of electrodes 125 with further reference to
It may be understood, however, that other configurations of the second plurality of electrodes are also contemplated. For example, a set of the second plurality of electrodes may be positioned laterally adjacent to the guard electrodes, and thus not necessarily be interposed between laterally adjacent ones of the first plurality of electrodes. In other embodiments, the length of respective ones of the second plurality of electrodes may be independently varied. Further alternative configurations of the second plurality of electrodes are discussed in greater detail with respect to
Each of the segmented electrodes of the second plurality of electrodes 125 is further in electrical communication with an AC voltage source (not shown). With further reference to
For example, as illustrated in
Subsequently, the AC voltage waveform is applied in a repeating and stepwise manner to the plurality of second electrodes that follow electrodes 141-148. For example, with further reference to
At a given time, an ion within the apparatus 100 is generally located at the lowest energy position, which depends upon the ion velocity to keep up with the traveling wave motion. For example, assume this lowest energy position lies at or near to the position of the segmented electrode having the lowest magnitude of the AC voltage waveform (i.e., electrode segment 146 having a phase shift of 270°). When the maximum ion velocity is approximately equal to the speed of the traveling wave, c≈1, ions can move with the wave much of the time, but are also occasionally passed over by waves. Ions of lower velocity or mobility tend to fall behind more often than those of higher velocity or mobility, and ion separation is achieved. Thus, under the conditions of c≈1, translation of the AC voltage waveform in the z-direction forms a traveling wave that urges the ion to move so as to stay within the lowest energy position.
In an embodiment, the frequency of the AC voltage waveform may be selected from the range between 10 Hz-200 kHz (e.g., 1 kHz-200 kHz) and the amplitude of the AC voltage waveform may be selected from the range between 1 V to 200 V. For example, in one embodiment, the frequency of the AC voltage waveform can be selected from the range of 1 Hz-1 kHz. In further embodiments, the pressure of the carrier gas is selected from the range of atmospheric pressure to 1 mtorr vacuum. For a given charge, the frequency and amplitude of the AC voltage waveform are selected from their respective ranges based upon one or more of pressure of the buffer gas, dimensions of the segmented electrodes of the second plurality of electrodes 125, and the mass to charge ratio of the ions.
The embodiment of
In the example of
In additional embodiments, the number of segmented electrodes of the second plurality of electrodes may be different than that illustrated in
Turning now to
Still referring to
Each of the plurality of segmented electrodes 250 is in electrical communication with an AC voltage source and an RF voltage source (not shown). With further reference to
For example, an AC voltage waveform exhibiting a 45° phase and a separate RF voltage are each applied to electrode segment 251; an AC voltage waveform exhibiting a 90° phase and an RF voltage, 180° out-of-phase from the RF voltage applied to the electrode segment 251, are each applied to the electrode segment 252; an AC voltage waveform exhibiting a 135° phase and an RF voltage, 180° out-of-phase from the RF voltage applied to the electrode segment 252, are each applied to the electrode segment 253; an AC voltage waveform exhibiting a 180° phase and an RF voltage, 180° out-of-phase from the RF voltage applied to the electrode segment 253, are each applied to the electrode segment 254; an AC voltage waveform exhibiting a 225° phase and an RF voltage, 180° out-of-phase from the RF voltage applied to the electrode segment 254, are each applied to the electrode segment 255; an AC voltage waveform exhibiting a 270° phase and an RF voltage, 180° out-of-phase from the RF voltage applied to the electrode segment 255, are each applied to the electrode segment 256; an AC voltage waveform exhibiting a 315° phase and an RF voltage, 180° out-of-phase from the RF voltage applied to the electrode segment 256, are each applied to electrode segment 257; and an AC voltage waveform exhibiting a 360° phase and a RF voltage, 180° out-of-phase from the RF voltage applied to electrode segment 257, are each applied to electrode segment 258.
Continuing on the segmented electrodes in
In an embodiment, the frequency of the RF voltage may be selected from the range between 100 kHz-5 MHz and the amplitude of the RF voltage may be selected from the range between 10 V to 500 V. In further embodiments, the frequency of the AC waveform may be selected from the range between 10 Hz-200 kHz and the amplitude of the AC waveform may be selected from the range between 1 V to 200 V.
With further reference to
The example above employs a constant phase shift of 45° between the AC voltage waveform applied to longitudinally adjacent ones of the plurality of segmented electrodes 250 (i.e., 360° divided by the number of electrodes over which the AC waveform is spread). However, in further embodiments, the traveling AC voltage waveform may adopt other phase shifts, selected from the range of 0°-359°, without limit. For example, in one alternative embodiment, the phase shift may be 90° or 120°. In other alternative embodiments, the phase shift between at least one pair of longitudinally adjacent segmented electrodes may be different. In further alternative embodiments, AC voltage waveform may exhibit at least one discontinuity (i.e., the sum of phase shifts between the electrodes over which the AC voltage waveform is spread does not sum to 360°).
In additional embodiments, the number of the plurality of segmented electrodes 250 may be different than that illustrated in
The AC voltage waveforms applied to the plurality of electrodes of the apparatus of
With reference to
A first plurality of curved electrodes 310 and 320 are laterally spaced from one another and in electrical communication with an RF voltage source (not shown) In operation, opposite phase RF voltages is are applied to laterally adjacent ones of the first plurality of electrodes 310 and 320 to confine the ions within the y-direction. The dimensions and positioning of the curved electrodes 310, 320, as well as the manner of applying the RF voltages, may be provided as discussed above with respect to the first plurality of electrodes 110, 120 of
Electrodes 330 are curved guard electrodes, laterally spaced from one another and adjacent the outermost ones of the curved electrodes 310, 320, and 325. For example, as illustrated in
A second plurality of curved electrodes 325 are segmented and interposed between respective ones of the first plurality of curved electrodes 310, 320. The second plurality of curved electrodes are further in electrical communication with an AC voltage source (not shown). A given set of electrodes of the second plurality of curved electrodes 325 may be positioned between a given pair of the first plurality of curved electrodes 310, 320. In operation, a continuous AC voltage waveform is applied to a second plurality of curved electrodes 325, where the AC voltage waveform is phase shifted on longitudinally adjacent electrodes within a given set of the second plurality of curved electrodes to move the ions through the length of the apparatus 300 (i.e., in the z-direction). The dimensions and positioning of the second plurality of curved electrodes 325, as well as the manner of applying the continuous AC voltages, may be provided as discussed above with respect to the second plurality of electrodes 120 of
Alternative embodiments of electrode configurations coupled to the at least one surface are illustrated in
In alternative embodiments, the positions of the first plurality of continuous electrodes 110, 120 and the second plurality of segmented electrodes 125 in the electrode configurations of
It may be understood that, in further alternative embodiments, the respective orientations of the first and second segments 600E-1, 600E-2 may be varied. For example, the first segment 600E-1 need not be perpendicular to the second segment 600E-2 but may adopt a non-90° angle.
Notably, however, a mechanism of transporting ions between levels is necessary to insert and remove ions from the respective levels. Accordingly, an opening 604 (e.g., a square or circular opening) is formed each of the opposing parallel surfaces of levels 602a, 602b. The opening 604 is positioned so as to intersect second plurality of segmented electrodes 125 (e.g.,
Embodiments of electrodes within each electrode array 610 are illustrated in
Embodiments of elevators 606 having different stacking arrangements of electrode arrays 610 are illustrated in
In an alternative embodiment, the apparatus 100 includes an elevator 620, as illustrated in
In a further alternative embodiment, illustrated in
It may be understood that embodiments of each of the multi-level apparatus illustrated in embodiments of
Simulations were performed to explore the performance of embodiments of the AC-SLIMS approach discussed above for ion separation using flat and curved surfaces. Corresponding simulations are further performed for conventional TW-IMS using transient DC voltages for comparison. The following examples further serve to illustrate embodiments and aspects of the present disclosure and are not meant to be construed as limiting the scope thereof.
(i) AC-SLIMS Simulation Parameters
The schematic module shown in
The module is operated at a pressure of 4 Torr utilizing nitrogen as the buffer gas. Singly charged ions with a mass to charge ratio (m/z) of 622 and 922 are used for the simulations. RF voltages are applied to the six RF electrodes 110 and 120, 180° out-of-phase for adjacent electrodes on each surface to create the pseudopotentials to confine the ions and inhibit ion loss to the two PCBs.
AC voltage waveforms, sine waves in this simulation, are further applied to the first eight segmented electrodes 141, 142, 143, 144, 145, 146, 147, and 148 and the second set of eight segmented electrodes 151, 152, 153, 154, 155, 156, 157 and 158, positioned between the RF electrodes 110, 120.
A 45° phase shift of the AC voltage waveform is further employed to each adjacent electrode segments 141, 142, 143, 144, 145, 146, 147, and 148. The AC waveforms applied to longitudinally adjacent electrode segments 141, 142, 143, 144, 145, 146, 147, and 148 are shifted in phase in a repeating pattern. That is, the phases of the applied AC voltage waveform are shifted by 45°, 90°, 135°, 180°, 225°, 270°, 315°, and 360°, respectively, on the segmented electrodes 141, 142, 143, 144, 145, 146, 147, and 148 in a stepwise fashion so as to move and separate the ions in the direction of the increasing phase shift.
Subsequently, the AC voltage waveforms are further applied in a repeating and stepwise manner to the AC electrodes 151, 152, 153, 154, 155, 156, 157, and 158. The phases of the applied AC voltage waveform are shifted by 45°, 90°, 135°, 180°, 225°, 270°, 315°, and 360°, respectively, on the segmented electrodes 151, 152, 153, 154, 155, 156, 157, and 158 in a stepwise fashion so as to move and separate the ions in the direction of the increasing phase shift.
For additional arrays of segmented electrodes, the phase of the AC voltage waveform applied to those additional electrode arrays would repeat in a stepwise fashion so as to move and separate the ions in the direction of the increasing phase shift.
(ii) DC-TW Simulation Parameters
The schematic module 700 shown in
The module 700 is fabricated using PCBs and included of a pair of parallel PCBs (30.5 cm long×7.6 cm wide) spaced by a gap of 4.75 mm. The module used 5 arrays of DC electrodes 725, separated from adjacent arrays of RF electrodes 610 and 120 by 0.13 mm. The dimensions of the DC electrodes 725 were 1.98 mm in length and 0.43 mm in width. Guard electrodes 730 were 0.508 mm wide. The dimensions of the RF electrodes 710 and 720 were each 0.43 mm in width.
The module is operated at a pressure of 4 Torr utilizing nitrogen as the buffer gas. Singly charged ions with mass to charge (m/z) of 622 and 922 are used for the simulations.
RF voltages, are applied to the six RF electrodes 710 and 720, 180° out-of-phase for adjacent RF electrodes on each surface to create the pseudopotentials to confine the ions and inhibit ion loss to the two PCBs. The transient DC voltage waveform is applied to a series of adjacent segmented DC electrodes 725. For example, as illustrated in
(iii) Comparison of Arrival Time Distribution
(iv) Comparison of Resolution
Notably, embodiments of the SLIMS AC approach disclosed herein achieve nearly identical resolution as compared to the conventional, transient DC waveform approach.
(iv) Comparison of Electric Field Exposure
The data of
(i) AC-SLIMS Simulation Parameters
The schematic module shown in
The module is fabricated using PCBs and included a single PCB (15 cm long×0.5 cm wide). The module uses 2 sets of AC electrodes 325, separated from adjacent RF electrodes 310 and 320 by 0.3 mm. The dimensions of the AC electrodes 125 are 2 mm in length and 0.4 mm in width. Guard electrodes 130 are each 1 mm wide. The dimensions of the RF electrodes 110 and 120 are each 1 mm in width. The radius of curvature of the electrodes is 3.6 mm.
The module is operated at a pressure of 4 Torr utilizing nitrogen as the buffer gas. Singly charged ions with a mass to charge ratio (m/z) of 622 and 922 were used for the simulations.
RF voltages are applied to the three RF electrodes 310 and 320, 180° out-of-phase for adjacent electrodes to create the pseudopotentials to confine the ions and inhibit ion loss to the PCB. The RF voltage is 300 Vp-p in amplitude and 1 MHz in frequency.
DC voltages are applied to the curved guard electrodes to contrain lateral ion motion (in the x-direction). The DC voltage amplitude is 30 V.
An AC voltage waveform is a sinusoid applied over a repeating sequence of eight AC electrodes 325 to move and separate the ions in the longitudinal direction. The applied AC voltage waveform has an amplitude of 30 V and a frequency of 20 KHz. A 45° phase shift of the AC voltage waveform is applied to longitudinally adjacent AC electrodes 325.
(ii) DC-TW Simulation Parameters
The module is fabricated using a single PCB (15 cm long×0.5 cm wide). The module uses 2 outer DC electrodes 1210, 2 inner DC electrodes 1230, and 2 pairs of RF electrodes 1220, 1225, of opposite phase, RF+ and RF−. Each inner DC electrode 1230 is positioned between an adjacent pair of inner DC electrodes 1220 and 1225. The dimensions of the RF electrodes 1220, 1222 are 76 mm in length and 1 mm in width. Outer DC electrodes 1210 are 2 mm in length and 0.4 mm in width. Inner DC electrodes 1230 are 2 mm in length and 0.4 mm in width. The radius of curvature of the electrodes is 3.5 mm.
The DC voltages applied to the outer DC electrodes 1210 is the same. The voltage applied to inner RF electrodes 1220 is out of phase with its neighboring inner electrode 1225. Fields generated by the potentials applied to the electrodes 1210, 1220, 1225 provide ion confinement. The DC voltage applied to the inner array electrodes 1230 is a time dependent DC field or waveform for moving and separating ions positioned within the module 1200.
The combination of RF and DC fields applied to the electrodes 1210, 1220, 1225, 1230 create, in combination with the shape of the curved surface 1205, confining and driving fields that move ions through the module 1200. Lateral confinement is achievable by a combination of electric fields applied to the outer electrodes 1210 as well as the curvature of the surface 1205. Further details regarding the module 1200 may be found in U.S. patent application Ser. No. 14/851,935, incorporated by reference in its entirety.
The module 1200 is operated at a pressure of 4 Torr utilizing nitrogen as the buffer gas. Singly charged ions with a mass to charge ratio (m/z) of 622 and 922 are used for the simulations.
Comparing
While a number of embodiments of the present disclosure 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 disclosure in its broader aspects. The appended claims, therefore, are intended to cover all such changes and modifications as they fall within the true spirit and scope of the disclosure.
This is a continuation of U.S. National Stage application Ser. No. 15/774,837, titled METHOD AND APPARATUS FOR ION MOBILITY SEPARATIONS UTILIZING ALTERNATING CURRENT WAVEFORMS, filed May 9, 2018, which application is a 371 of International Application No. PCT/US2016/047070, titled METHOD AND APPARATUS FOR ION MOBILITY SEPARATIONS UTILIZING ALTERNATING CURRENT WAVEFORMS, filed Aug. 15, 2016, which was published in English under PCT Article 21(2), which in turn claims priority to the benefit of U.S. Provisional Application Ser. No. 62/238,291, filed Oct. 7, 2015, titled “METHOD AND APPARATUS FOR CONTROLLING IONS IN A GAS PHASE,” all of which are hereby incorporated by reference in their entireties.
This invention was made with Government support under Contract DE-AC0576RL01830 awarded by the U.S. Department of Energy and Grant Number GM103493 awarded by the National Institutes of Health. The Government has certain rights in the invention.
| Number | Name | Date | Kind |
|---|---|---|---|
| 3202995 | Schultz | Aug 1965 | A |
| 3617908 | Greber | Nov 1971 | A |
| 4777363 | Eiceman et al. | Oct 1988 | A |
| 5206506 | Kirchner | Apr 1993 | A |
| 5572035 | Franzen | Nov 1996 | A |
| 5818055 | Franzen | Oct 1998 | A |
| 5834771 | Yoon et al. | Nov 1998 | A |
| 6107628 | Smith et al. | Aug 2000 | A |
| 6322703 | Taniguchi et al. | Nov 2001 | B1 |
| 6417511 | Russ, IV | Jul 2002 | B1 |
| 6727495 | Li | Apr 2004 | B2 |
| 6744043 | Loboda | Jun 2004 | B2 |
| 6835928 | Bateman | Dec 2004 | B2 |
| 6891157 | Bateman et al. | May 2005 | B2 |
| 6960760 | Bateman et al. | Nov 2005 | B2 |
| 7071467 | Bateman | Jul 2006 | B2 |
| 7095013 | Bateman et al. | Aug 2006 | B2 |
| 7151255 | Weiss et al. | Dec 2006 | B2 |
| 7157698 | Makarov et al. | Jan 2007 | B2 |
| 7180078 | Pau et al. | Feb 2007 | B2 |
| 7365317 | Whitehouse et al. | Apr 2008 | B2 |
| 7391021 | Stoermer et al. | Jun 2008 | B2 |
| 7405401 | Hoyes | Jul 2008 | B2 |
| 7548818 | Kieser | Jun 2009 | B2 |
| 7786435 | Whitehouse et al. | Aug 2010 | B2 |
| 7838826 | Park | Nov 2010 | B1 |
| 7872228 | Kim et al. | Jan 2011 | B1 |
| 7888635 | Belov et al. | Feb 2011 | B2 |
| 7928375 | Mangan et al. | Apr 2011 | B1 |
| 8003934 | Hieke | Aug 2011 | B2 |
| 8049169 | Satake et al. | Nov 2011 | B2 |
| 8222597 | Kim et al. | Jul 2012 | B2 |
| 8299443 | Shvartsburg et al. | Oct 2012 | B1 |
| 8319180 | Nikolaev et al. | Nov 2012 | B2 |
| 8373120 | Verentchikov | Feb 2013 | B2 |
| 8389933 | Hoyes | Mar 2013 | B2 |
| 8410429 | Franzen et al. | Apr 2013 | B2 |
| 8581181 | Giles | Nov 2013 | B2 |
| 8658969 | Nishiguchi | Feb 2014 | B2 |
| 8698075 | Kurulugama et al. | Apr 2014 | B2 |
| 8716660 | Green et al. | May 2014 | B2 |
| 8809769 | Park | Aug 2014 | B2 |
| 8835839 | Anderson | Sep 2014 | B1 |
| 8841608 | Shvartsburg et al. | Sep 2014 | B2 |
| 8901490 | Chen et al. | Dec 2014 | B1 |
| 8907272 | Wouters et al. | Dec 2014 | B1 |
| 8907273 | Chen et al. | Dec 2014 | B1 |
| 8969800 | Tolmachev et al. | Mar 2015 | B1 |
| 9063086 | Garimella et al. | Jun 2015 | B1 |
| 9165693 | Urbanus et al. | Oct 2015 | B2 |
| 9536721 | Berdnikov et al. | Jan 2017 | B2 |
| 9704701 | Ibrahim et al. | Jul 2017 | B2 |
| 9812311 | Anderson et al. | Nov 2017 | B2 |
| 9939409 | Ibrahim et al. | Apr 2018 | B2 |
| 9966244 | Anderson et al. | May 2018 | B2 |
| 10139366 | Atamanchuk et al. | Nov 2018 | B2 |
| 10317364 | Garimella | Jun 2019 | B2 |
| 20010035498 | Li | Nov 2001 | A1 |
| 20020074492 | Taniguchi | Jun 2002 | A1 |
| 20020185606 | Smith et al. | Dec 2002 | A1 |
| 20030132379 | Li | Jul 2003 | A1 |
| 20030222213 | Taniguchi | Dec 2003 | A1 |
| 20040026611 | Bateman et al. | Feb 2004 | A1 |
| 20040051038 | Taniguchi | Mar 2004 | A1 |
| 20040089803 | Foley | May 2004 | A1 |
| 20040195503 | Kim et al. | Oct 2004 | A1 |
| 20040222369 | Makarov et al. | Nov 2004 | A1 |
| 20040225649 | Yeo et al. | Nov 2004 | A1 |
| 20040251411 | Bateman et al. | Dec 2004 | A1 |
| 20050040327 | Lee et al. | Feb 2005 | A1 |
| 20050109930 | Hill, Jr. et al. | May 2005 | A1 |
| 20050163183 | Shackleton et al. | Jul 2005 | A1 |
| 20050258364 | Whitehouse | Nov 2005 | A1 |
| 20060076484 | Brown et al. | Apr 2006 | A1 |
| 20060219896 | Hashimoto et al. | Oct 2006 | A1 |
| 20070034810 | Hoyes | Feb 2007 | A1 |
| 20070138384 | Keiser | Jun 2007 | A1 |
| 20070162232 | Patterson et al. | Jul 2007 | A1 |
| 20080073515 | Schoen | Mar 2008 | A1 |
| 20090173880 | Bateman et al. | Jul 2009 | A1 |
| 20090206250 | Wollnik | Aug 2009 | A1 |
| 20090294655 | Ding et al. | Dec 2009 | A1 |
| 20090294662 | Belov et al. | Dec 2009 | A1 |
| 20090302209 | Green et al. | Dec 2009 | A1 |
| 20090321655 | Marakov et al. | Dec 2009 | A1 |
| 20100032561 | Giles et al. | Feb 2010 | A1 |
| 20100038532 | Makarov et al. | Feb 2010 | A1 |
| 20100294923 | Kenny et al. | Nov 2010 | A1 |
| 20110049357 | Giles | Mar 2011 | A1 |
| 20110127417 | Ibrahim et al. | Jun 2011 | A1 |
| 20110192969 | Verentchikov | Aug 2011 | A1 |
| 20130009050 | Park | Jan 2013 | A1 |
| 20130099110 | Hoyes et al. | Apr 2013 | A1 |
| 20130175441 | Zanon et al. | Jul 2013 | A1 |
| 20130313421 | Taniguchi | Nov 2013 | A1 |
| 20140061457 | Berdnikov et al. | Mar 2014 | A1 |
| 20140124663 | Green et al. | May 2014 | A1 |
| 20140145076 | Park | May 2014 | A1 |
| 20140217278 | Green | Aug 2014 | A1 |
| 20140264014 | Ibrahim et al. | Sep 2014 | A1 |
| 20140299766 | Anderson et al. | Oct 2014 | A1 |
| 20140361163 | Taniguchi et al. | Dec 2014 | A1 |
| 20140367564 | Green et al. | Dec 2014 | A1 |
| 20150028200 | Green et al. | Jan 2015 | A1 |
| 20150206731 | Zhang et al. | Jul 2015 | A1 |
| 20150340220 | Hock et al. | Nov 2015 | A1 |
| 20150364309 | Welkie | Dec 2015 | A1 |
| 20150364313 | Zhang et al. | Dec 2015 | A1 |
| 20160027604 | Cho et al. | Jan 2016 | A1 |
| 20160047728 | Wilson | Feb 2016 | A1 |
| 20160049287 | Ding et al. | Feb 2016 | A1 |
| 20160071714 | Zhang et al. | Mar 2016 | A1 |
| 20160071715 | Anderson et al. | Mar 2016 | A1 |
| 20160175856 | Paschkewitz | Jun 2016 | A1 |
| 20160181080 | Williams | Jun 2016 | A1 |
| 20160189947 | Zhou et al. | Jun 2016 | A1 |
| 20160211129 | Gardner | Jul 2016 | A1 |
| 20170047212 | Kenny | Feb 2017 | A1 |
| 20170076931 | Ibrahim et al. | Mar 2017 | A1 |
| 20170125229 | Giles et al. | May 2017 | A1 |
| 20170200596 | Makarov et al. | Jul 2017 | A1 |
| 20180061621 | Anderson et al. | Mar 2018 | A1 |
| 20180068839 | Ibrahim et al. | Mar 2018 | A1 |
| 20180254178 | Ibrahim et al. | Sep 2018 | A1 |
| 20180350582 | Giles et al. | Dec 2018 | A1 |
| 20190004011 | Garimella et al. | Jan 2019 | A1 |
| 20190057852 | Ibrahim et al. | Feb 2019 | A1 |
| 20190066993 | Ramsey et al. | Feb 2019 | A1 |
| 20190103261 | Ibrahim et al. | Apr 2019 | A1 |
| 20190108990 | Prabhakaran et al. | Apr 2019 | A1 |
| 20190189393 | Ibrahim et al. | Jun 2019 | A1 |
| Number | Date | Country |
|---|---|---|
| 2014251354 | Nov 2017 | AU |
| 2016320584 | Apr 2018 | AU |
| 2016335524 | May 2018 | AU |
| 2908936 | Oct 2014 | CA |
| 2997910 | Mar 2017 | CA |
| 3000341 | Apr 2017 | CA |
| 1361922 | Jul 2002 | CN |
| 101126738 | Feb 2008 | CN |
| 102163531 | Aug 2011 | CN |
| 102945786 | Feb 2013 | CN |
| 105264637 | Sep 2017 | CN |
| 107507751 | Dec 2017 | CN |
| 108352288 | Jul 2018 | CN |
| 112013004733 | Jun 2015 | DE |
| 1566828 | Aug 2005 | EP |
| 1825495 | Aug 2007 | EP |
| 2065917 | Jun 2009 | EP |
| 2913839 | Sep 2015 | EP |
| 2984675 | Feb 2016 | EP |
| 3347913 | Jul 2018 | EP |
| 3359960 | Aug 2018 | EP |
| 2440970 | Feb 2008 | GB |
| 2506362 | Apr 2014 | GB |
| 2002015699 | Jan 2002 | JP |
| 2002015699 | Jan 2002 | JP |
| 2003514349 | Apr 2003 | JP |
| 2004-520685 | Jul 2004 | JP |
| 2006294582 | Oct 2006 | JP |
| 2009532822 | Sep 2009 | JP |
| 2009535759 | Oct 2009 | JP |
| 2009537070 | Oct 2009 | JP |
| 2011529623 | Dec 2011 | JP |
| 2012503286 | Feb 2012 | JP |
| 2012528437 | Nov 2012 | JP |
| 2014049196 | Mar 2014 | JP |
| 2014509743 | Apr 2014 | JP |
| 2014509772 | Apr 2014 | JP |
| 2016514896 | May 2016 | JP |
| 2018528427 | Sep 2018 | JP |
| 11201508277X | Nov 2015 | SG |
| WO0135441 | May 2001 | WO |
| WO 2006064274 | Jun 2006 | WO |
| WO 2007133469 | Nov 2007 | WO |
| WO 2010014077 | Feb 2010 | WO |
| WO 2010032015 | Mar 2010 | WO |
| WO 2011089419 | Jul 2011 | WO |
| WO 2012116765 | Sep 2012 | WO |
| WO2012123729 | Sep 2012 | WO |
| WO2012123730 | Sep 2012 | WO |
| WO 2013018529 | Feb 2013 | WO |
| WO 2014048837 | Apr 2014 | WO |
| WO 2014168660 | Oct 2014 | WO |
| WO 2015056872 | Apr 2015 | WO |
| WO 2015097462 | Jul 2015 | WO |
| WO-2015097462 | Jul 2015 | WO |
| WO 2016069104 | May 2016 | WO |
| WO2017044159 | Mar 2017 | WO |
| WO 2017062102 | Apr 2017 | WO |
| Entry |
|---|
| English translation of the first Chinese office action from corresponding Chinese Patent Application No. 201710799275.X, dated Nov. 2, 2018, 12 pages. |
| First Office Action mailed in Japanese Application No. 2018-216132, dated Aug. 21, 2019, 4 pages; with English translation, 4 pages. |
| First Office Action mailed in Japanese Application No. 2018-226767, dated Aug. 20, 2019, 2 pages: with English translation, 1 page. |
| Office Action corresponding to European Application No. 16754384.2, dated Sep. 11, 2019, 4 pages. |
| CN App No. 201680069722.X filed Aug. 15, 2016 (same application as PCT/U82016/047070 published as WO2017062102 on Apr. 13, 2017), Battelle Memorial Institute. |
| JP Application No. 2018-518405 filed Aug. 15, 2016 (same application as PCT/U82016/047070 published as WO2017062102 on Apr. 13, 2017), Battelle Memorial Institute. |
| SG 11201801852Q filed May 2, 2016 (Same application as PCT/US2016/030455, published as WO 2017/044159 on Mar. 16, 2017), Battelle Memorial Institute. |
| SG 11201802494Q filed Aug. 15, 2016 (same application as PCT/US2016/047070 published as WO2017062102 on Apr. 13, 2017), Battelle Memorial Institute. |
| Hamid, Ahmed M. et al., “Characterization of Travelling Wave Ion Mobility Separations in Structures for Lossless Ion Manipulations,” Analytical Chemistry, 87(22):11301-11308 (Nov. 2015). |
| International Search Report and Written Opinion for PCT/US2016/047070 (dated Nov. 7, 2016). |
| Tolmachev, Aleksey V. et al., “Characterization of Ion Dynamics in Structures for Lossless Ion Manipulations,” Analytical Chemistry, 86(18):9162-9168 (Sep. 2014). |
| English translation of the first Chinese office action from corresponding Chinese patent application No. 201480032436.7, dated Oct. 14, 2016, 5 pages. |
| English translation of the search report from corresponding Chinese patent application No. 201480032436.7, dated Sep. 29, 2016, 2 pages. |
| European Search Report for European Patent Application No. 14782685.3, dated Oct. 25, 2016. |
| Examination Report No. 1 for related Australian Application No. 2016320584, dated Jun. 27, 2018, 3 pages. |
| First Office Action for related Canadian Application No. 2,997,910, dated May 4, 2018, 4 pages. |
| International Search Report and Written Opinion issued in related International Application No. PCT/US2016/030455, dated Jul. 25, 2016, 19 pages. |
| International Search Report and Written Opinion for related International Application No. PCT/US2014/011291, dated Jun. 6, 2014, 2 pages. |
| Search Report from corresponding Singapore patent application No. 11201508277X, dated Mar. 6, 2016, 7 pages. |
| Examination Report No. 2 for related Australian Application No. 2016320584, dated Sep. 3, 2018, 2 pages. |
| Examination Report No. 1 for related Australian Application No. 2016335524, dated May 15, 2018, 4 pages. |
| First Office Action for related Canadian Application No. 3,000,341, dated Jul. 30, 2018, 5 pages. |
| First Office Action for Chinese Application No. 201680065673.2, dated Sep. 30, 2018, 6 pages (English translation not yet available). |
| Written Opinion from the Intellectual Property Office of Singapore for related Application No. 11201802494Q, dated Aug. 21, 2018, 8 pages. |
| Chen, et al., “Mobility-Selected Ion Trapping and Enrichment Using Structures for Lossless Ion Manipulations”, Analytical Chemistry, Jan. 2016, 88, pp. 1728-1733. |
| Deng et al., “Serpentine Ultralong Path with Extended Routing (SUPER) High Resolution Traveling Wave Ion Mobility-MS using Structures for Lossles Ion Manipulations”, Analytical Chemistry, Mar. 2017, 89, pp. 4628-4634. |
| International Search Report and Written Opinion for related International Application No. PCT/US2018/041607, dated Sep. 20, 2018, 18 pp. |
| Webb et al., “Mobility-Resolved Ion Selection in Uniform Drift Field Ion Mobility Spectrometry/Mass Spectrometry: Dynamic Switching in Structures for Lossless Ion Manipulations,” Analytical Chemistry, Oct. 2014, 86, 9632-9637. |
| Wojcik et al., “Lipid and Glycolipid Isomer Analyses Using Uitra-High Resolution Ion Mobility Spectrometry Separations”, International Jouranl of Molecular Sciences, Jan. 2017, 18, 12 pp. |
| First Office Action for related Japanese Application No. 2018-513012, dated Aug. 2, 2018, 2 pages; with English translation, 2 pages. |
| First Office Action for related Chinese Application No. 201680065673.2, dated Sep. 30, 2018, 6 pages. |
| Written Opinion from the Intellectual Property Office of Singapore for related Application No. 11201801852Q, dated Nov. 22, 2018, 9 pages. |
| International Search Report and Written Opinion for related International Application No. PCT/US2018/046752, dated Dec. 4, 2018, 12 pp. |
| Office Action for European Application No. 14782685.3, dated Jan. 20, 2020. |
| Office Action for European Application No. 16724997.8, dated Jan. 8, 2020. |
| Office Action for U.S. Appl. No. 16/032,651, dated Jan. 10, 2020. |
| Search Report and Written Opinion from Singapore Patent Application No. 10201906362T, dated Oct. 9, 2019, 11 pages. |
| Office Action for U.S. Appl. No. 16/194,161, dated Oct. 23, 2019. |
| Office Action for Chinese Application No. 201680069722.X, dated Aug. 5, 2020 (w/English translation). |
| Examination Report No. 1 for Australian Application No. 2019203114, dated Jun. 22, 2020, 4 pages. |
| Examination Report No. 2 for Australian Application No. 2019203114, dated Oct. 28, 2020, 4 pages. |
| European Search Report and Written Opinion for European Patent Application No. 20207432.4, dated Mar. 17, 2021. |
| Notice of Acceptance for Australian Application No. 2019203114, dated Mar. 18, 2021. |
| Notification of Grant for Chinese Application No. 201680069722.X, dated Mar. 12, 2021. |
| Number | Date | Country | |
|---|---|---|---|
| 20190369050 A1 | Dec 2019 | US |
| Number | Date | Country | |
|---|---|---|---|
| 62238291 | Oct 2015 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 15774837 | US | |
| Child | 16404472 | US |
