Coupling of ion mobility spectrometer with mass spectrometer

An ion carousel includes a first surface and a second surface adjacent to the first surface. The first and the second surfaces define an ion confinement volume. The second surface including a first inner array of electrodes arranged along a first path and configured to receive, at a first location on the first path, a first ion packet. The first inner array of electrodes are configured to generate a plurality of potential wells that include a first potential well and a second potential well. The first ion packet includes a first sub-packet of ions having a first mobility and a second sub-packet of ions having a second mobility, and the second ion packet includes a third sub-packet of ions having the first mobility and a fourth sub-packet of ions having the second mobility.

BACKGROUND

Ion mobility spectrometry (IMS) is a technique for separating and identifying ions in gaseous phase based on their mobilities. For example, IMS can be employed to separate structural isomers and macromolecules that have different mobilities. IMS relies on applying a constant or a time-varying electric field to a mixture of ions. An ion having a larger mobility (or smaller collision cross section [CCS]) moves faster under the influence of the electric field compared to an ion with a smaller mobility (or larger CCS). By applying the electric field over a separation distance (e.g., in a drift tube) of an IMS device, ions from an ion mixture can be spatially separated based on their mobility. Because ions with different mobilities arrive at the end of the drift tube at different times (temporal separation), and they can be identified based on the time of detection by a detector at the end of the drift tube. Resolution of the mobility separation can be varied by changing the separation distance.

Mass spectrometry (MS) is an analytical technique that can separate a mixture of chemical species based on their mass-to-charge ratio. MS involves ionizing the mixture of chemical species followed by acceleration of the ion mixture in the presence of electric and/or magnetic fields. In some mass spectrometers, ions having the same mass-to-charge ratio undergo the same deflection. Ions with different mass-to-charge ratios can undergo different deflections, and can be identified based on the spatial location of detection by a detector (e.g., electron multiplier).

IMS combined with MS can generate an IMS-MS spectrum that can be used in a broad range of applications, including metabolomics, glycomics, and proteomics. IMS-MS ion separation can be performed by coupling an ion mobility spectrometer with a mass spectrometer. For example, an ion mobility spectrometer can first separate the ions based on their mobility. Ions having different mobilities can arrive at the mass spectrometer at different times, and are then separated based on their mass-to-charge ratio. An example of an IM spectrometer is a structures for lossless ion manipulations (SLIM) device that can generate an IMS spectrum with minimal ion loss.

SUMMARY

In general, embodiments of the disclosure provide systems and corresponding methods for coupling of an ion mobility spectrometer with a mass spectrometer.

An ion carousel includes a first surface and a second surface adjacent to the first surface. The first and the second surfaces define an ion confinement volume. The second surface including a first inner array of electrodes arranged along a first path and configured to receive, at a first location on the first path, a first ion packet. The first inner array of electrodes are configured to generate a plurality of potential wells configured to travel along a first direction on the first path. The plurality of potential wells include a first potential well and a second potential well. The first ion packet includes a first sub-packet of ions having a first mobility and a second sub-packet of ions having a second mobility, and the second ion packet includes a third sub-packet of ions having the first mobility and a fourth sub-packet of ions having the second mobility. The first potential well is configured to receive the first sub-packet of ions and the third sub-packet of ions, and the second potential well is configured to receive the second sub-packet of ions and the fourth sub-packet of ions. The second surface further includes an output switch configured to selectively eject ions in one or more of the first potential well and the second potential well out of the ion carousel.

In one implementation, the output switch is proximal to a second location along the first path. The output switch is configured to generate a first ejection potential during a first ejection period. The first ejection potential is configured to drive ions out of the ion carousel at the second location. The output switch is further configured to generate a first confinement potential during a first confinement period. The first confinement potential is configured to prevent ions in the ion carousel from exiting the ion carousel at the second location. In another implementation, the output switch is configured to selectively transfer ions in the first potential well out of the ion carousel by synchronizing the first ejection period with a first time of arrival of the first potential well at the second location. In yet another implementation, the output switch is configured to generate a second ejection potential during a second ejection period. The second ejection potential is configured to drive ions out of the ion carousel at the second location.

In one implementation, the output switch is configured to selectively transfer ions in the second potential well out of the ion carousel by synchronizing the second ejection period with a second time of arrival of the second potential well at the second location. In another implementation, the output switch is configured to prevent ions in the second potential well from exiting the ion carousel by synchronizing the first confinement period with a second time of arrival of the second potential well at the second location. In yet another implementation, the first ion packet includes a fifth sub-packet of ions having a third mobility and the second ion packet includes a sixth sub-packet of ions having the third mobility. The plurality of potential wells include a third potential well configured to receive the fifth sub-packet and the sixth sub-packet.

In one implementation, the output switch is configured to selectively transfer ions in the third potential well out of the ion carousel by synchronizing the second ejection period with a third time of arrival of the third potential well at the second location. In another implementation, the first inner array of electrodes are configured to reverse the first direction of travel of the second potential well and direct the second potential well to the second location. In yet another implementation, the output switch is configured to selectively transfer ions in the second potential well out of the ion carousel by synchronizing a third ejection period with a fourth time of arrival of the second potential well at the second location. The output switch is configured to generate a third ejection potential during the third ejection period and the third ejection potential is configured to drive ions out of the second potential well at the second location.

In one implementation, the ion carousel further includes a controller. The controller includes a DC control circuit configured to apply the first ejection voltage and the first confinement voltage to the output switch during the first ejection period and the first confinement period, respectively. The controller is further configured to apply the second ejection voltage to the output switch during the second ejection period. In another implementation, the controller includes a master control circuit communicatively coupled to the first DC control circuit. The master control circuit is configured to determine one or more of the first ejection period, the first confinement period, and the second ejection period. The master control circuit is also configured to provide a first control signal to the DC control switch. The DC control switch is configured to generate one or more of the first ejection voltage during the first ejection period, first confinement voltage during the first confinement period, and the second ejection voltage during the second ejection period.

In one implementation, ions in the first potential well, the second potential well and the third potential well are transferred to a first ion manipulation device at the second location. A first end of the first ion manipulation device is coupled to the ion carousel and a second end of the first ion manipulation device is coupled to a mass spectrometer (or an ion detector). In another implementation, the ion carousel further includes a second array of electrodes comprising a first electrode and a second electrode. The first inner array of electrodes is located between the first electrode and the second electrode. In yet another implementation, the first electrode and the second electrode are configured to receive one or more RF voltages and generate a pseudopotential configured to inhibit ions in the ion confinement volume from approaching the second surface.

An ion carousel includes a first surface and a second surface adjacent to the first surface. The first and the second surfaces define an ion confinement volume. The second surface includes a first inner array of electrodes arranged along a first path and configured to receive, at a first location on the first path, a first ion packet including a first sub-packet of ions having a first mobility. The first inner array of electrodes are configured to generate a first potential well configured to receive the first sub-packet, generate a second potential well configured to receive the second sub-packet after the first sub-packet is received, and generate a third potential well configured to receive the third sub-packet after the second sub-packet is received. The first, the second and the third potential wells are configured to travel along a first direction on the first path. The second surface further includes an output switch proximal to a second location along the first path. The output switch is configured to generate, during a first ejection period, a first ejection potential configured to eject ions in the first potential well. The output switch is also configured to generate, during a first confinement period after the first ejection period, a first confinement potential configured to prevent ions in the second potential well from exiting the ion carousel. The output switch is further configured to generate, during a second ejection period after the first confinement period, a second ejection potential configured to eject ions in the third potential well.

In one implementation, the output switch is configured to transfer ions in the first potential well out of the ion carousel by synchronizing the first ejection period with a first time of arrival of the first potential well at the second location. In another implementation, the output switch is configured to prevent ions in the second potential well from exiting the ion carousel by synchronizing the first confinement period with a second time of arrival of the second potential well at the second location. In yet another implementation, the output switch is configured to transfer ions in the third potential well out of the ion carousel by synchronizing the second ejection period with a third time of arrival of the third potential well at the second location.

In one implementation, the first inner array of electrodes are configured to reverse the first direction of travel of the second potential well and direct the second potential well to the second location. In another implementation, the output switch is configured to selectively transfer ions in the second potential well out of the ion carousel by synchronizing a third ejection period with a fourth time of arrival of the second potential well at the second location.

In one implementation, an ion carousel can include a first planar surface, a second planar surface, and a first inner array of electrodes arranged along a first path and coupled to the first and the second planar surfaces. The first inner array of electrodes are configured to receive a first ion packet and a second ion packet temporally separated from the first ion packet by a separation time. The first inner array of electrodes are configured to generate a plurality of potential wells configured to travel along the first path. The plurality of potential wells includes a first potential well and a second potential well. The first ion packet includes a first sub-packet of ions having a first mobility and a second sub-packet of ions having a second mobility, and the second ion packet includes a third sub-packet of ions having the first mobility and a fourth sub-packet of ions having the second mobility. The first potential well is configured to receive the first sub-packet of ions and the third sub-packet of ions, and the second potential well is configured to receive the second sub-packet of ions and the fourth sub-packet of ions. The accumulation device can also include an output switch coupled to the inner array of electrodes, and configured to eject ions in the first potential well and the second potential well out of the ion carousel.

In one implementation, the output switch includes a plurality of electrodes coupled to the first planar surface and second planar surface. The plurality of electrodes are configured to receive an ejection voltage and generate an ejection potential. The ejection potential is configured to drive ions in the first potential well to a mass spectrometer system during a first ejection period. The ejection potential is configured to drive ions in the second potential well to the mass spectrometer system during a second ejection period.

In another implementation, the plurality of electrodes of the output switch is configured to receive a confinement voltage and generate a confinement potential. The confinement potential is configured to prevent ions in the plurality of potential wells from entering the mass spectrometer system during a mass spectrometer scanning period of an ejected ion packet.

In one implementation, the mass spectrometer system includes a first ion manipulation device coupled to the output switch, and a mass spectrometer coupled to the ion manipulation device. The first ion manipulation device is configured to guide ions in the first potential well and ions in the second potential well to the mass spectrometer.

In one implementation, the first ion manipulation device includes a second inner array of electrodes coupled to the first and second planar surfaces, and arranged along a second path. The second inner array of electrodes are configured to receive a second RF voltage generating a second pseudopotential, and receive a third DC voltage generating a third DC potential. The generated second pseudopotential inhibits ions in the first and second potential well from approaching the first and the second planar surfaces. The third DC voltage is configured to guide ions in the first and second potential well along the second path. In another implementation, the second path is directed towards the mass spectrometer.

In one implementation, the first ion packet includes a fifth sub-packet of ions having a third mobility and the second ion packet includes a sixth sub-packet of ions having the third mobility. The plurality of potential wells include a third potential well configured to receive the fifth sub-packet and the sixth sub-packet. In another implementation, the output switch is configured to eject ions in the third potential well during the first ejection period. In yet another implementation, the first path is a closed loop.

In one implementation, the plurality of potential wells are configured to traverse a length of the closed loop in a surfing time. The surfing time is substantially similar to the separation time. In another implementation, the first inner array of electrodes are segmented along the first path. In yet another implementation, the first inner array of electrodes are configured to receive a first RF voltage generating a pseudopotential that inhibits ions from approaching either of the first planar surface and the second planar surfaces. The first inner array of electrodes are configured to receive a first DC voltage generating the plurality of potential wells.

In one implementation, the RF voltage received by a first inner electrode of the first inner array of electrodes is phase shifted from the RF voltage received by a second inner electrode of the first inner array of electrodes. The first inner electrode and the second inner electrode are adjacently located. In another implementation, the accumulation device further includes an outer array of electrodes coupled to the first and the second planar surfaces. The outer array of electrodes are configured receive a second DC voltage generating a potential configured to confine ions over the first inner array of electrodes in a lateral direction. The lateral direction is transverse to the first path.

In one implementation, the outer array of electrodes include a first outer array of electrodes and a second outer array of electrodes. The first outer array of electrodes are positioned on a first side of the first inner array of electrodes, and the second outer array of electrodes are positioned on a second side of the first inner array of electrodes. In another implementation, the closed path is one of a rectangle and a circle. In another implementation, the ion carousel further includes an input switch configured to direct the first ion packet and the second ion packet to the first inner array of electrodes during an accumulation period.

In one implementation, a method includes injecting a first ion packet into an ion carousel. The first ion packet includes a first sub-packet of ions having a first mobility and a second sub-packet of ions having a second mobility. The method also includes injecting a second ion packet into the ion carousel. The second ion packet includes a third sub-packet of ions having the first mobility and a fourth sub-packet of ions having the second mobility. The second ion packet separated from the first ion packet by a separation time. The method also includes applying a DC voltage and/or a traveling AC voltage to an inner array of electrodes of the ion carousel to generate a plurality of potential wells includes a first potential well and a second potential well, the inner array of electrodes are arranged along the first path. The first potential well and the second potential well are configured to travel along the first path. The first sub-packet of ions and the third sub-packet of ions are injected in the first potential well, and the second sub-packet of ions and the fourth sub-packet of ions are injected in the second potential well.

In another implementation, the method includes applying an ejection voltage to an output switch to generate an ejection potential. The output switch can be coupled to the inner array of electrodes. The ejection potential is configured to drive ions in the first potential well to a mass spectrometer system during a first ejection period. The ejection potential is configured to drive ions in the second potential well to the mass spectrometer system during a second ejection period. In yet another implementation, the method further includes applying a confinement voltage to the output switch to generate a confinement potential, wherein the confinement potential is configured to prevent ions in the plurality of potential wells from entering the mass spectrometer system during a mass spectrometer scanning period of an ejected ion packet.

DETAILED DESCRIPTION

Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the structure, function, manufacture, and use of the systems, devices, and methods disclosed herein.

Coupling of ion mobility spectrometry with mass spectrometry (IMS-MS coupling) can allow for separation of ions based on both ion mobility and mass-to-charge ratio. Separating ions based on both their mobility and mass-to-charge ratio can allow for characterization of complex biological mixture. IMS-MS coupling can produce an IMS-MS spectrum. The IMS-MS spectrum can be represented by a two-dimensional plot where a first axis represents separation based on mobility and a second axis represents separation based on mass-to-charge ratio. IM spectrometers, such as structures for lossless ion manipulations (SLIM), can have short scan times (e.g., scan times in the order of milliseconds). In other words, a SLIM device can perform ion mobility separation of an ion mixture (e.g., from an ionization source) and generate an ion packet in a short time (e.g., milliseconds). The ion packet can include multiple ion sub-packets having ions of different mobilities that are temporally separated. For example, the separation between adjacent ion sub-packets can be in the millisecond regime. Mass spectrometers, on the other hand, can have long scan times. For example, quadrupole mass spectrometers can take several milliseconds to separate ions based on their mass-to-charge ratio.

Mismatch between the scan times of SLIM devices and mass spectrometers can affect the resolution of ion separation of IMS-MS device. For example, a mass spectrometer, having a scan time greater than the temporal separation between adjacent ion sub-packets, may not be able to resolve the mass-to-charge spectrum of the adjacent ion sub-packets. Mass spectrometers, such as time-of-flight (TOF) spectrometers, can have shorter scan times (e.g., in the microsecond regime). However, TOF spectrometers may need to repeat measurements on several ion packets from the SLIM device. For example, this may be needed so that mass and ion mobility spectra of multiple ion packets are added (referred to as “co-adding”) to achieve acceptable signal-to-noise ratio. However, addition of mass and ion mobility spectra need to be carefully synchronized. For example, it can be desirable that mass spectrum of ion sub-packets that have similar mobilities are added. This can be challenging, for example, when mass spectra of large numbers of ion sub-packets that arrive at the TOF spectrometer at different times need to be added. Additionally, adding mass spectrum of multiple ion sub-packet can require a digitizer in the TOF that can increase the cost and the complexity of the TOF and can decrease the efficiency of the TOF.

Therefore, it can be desirable to develop systems and methods of coupling SLIM devices with mass spectrometers that have different scan rates. Subject matter described in this application provides for an ion carousel that can act as a liaison between a SLIM device and a mass spectrometer. The ion carousel can receive ion packets from an input SLIM device and place ion sub-packets having similar mobility in a given potential well. The ion carousel can selectively eject ions of similar mobility into the mass spectrometer. Further, temporal separation between ejection of ions of different mobility can be determined based on the scan rate of the mass spectrometer. This can prevent over-lapping of mass spectra of different mobilities. Additionally, addition of multiple ion packets in the accumulation device prior to ejection to the mass spectrometer can obviate the need for adding mass spectra for improved signal-to-noise ratio.

FIG. 1is a schematic illustration of an exemplary coupled SLIM-device-mass-spectrometer (SLIM-MS)100. The coupled SLIM-MS100includes an ionization source102that can generate ions (e.g., ions having varying mobility and mass-to-charge-ratios) and inject the ions into an input SLIM device104. This can be done at multiple time instances (e.g., periodically). During an ion separation event, the input SLIM device104can receive the ions from the ionization source102and generate an ion packet in which the ions are separated (e.g., temporally and spatially) into multiple ion sub-packets based on their mobility. In some implementations, an ion funnel trap can be used to generate ion packets.

The input SLIM device104can inject the ion packet into an ion carousel106during an accumulation period. For example, ion sub-packets with different mobilities can arrive at the ion carousel106at different times. The ion carousel106can generate a pseudopotential that can inhibit ions from approaching a surface of the ion carousel106and a traveling waveform that includes potential wells (e.g., by application of one or more of an RF and/or AC and/or DC voltage on electrodes in the ion carousel). The traveling waveform can be configured to move in the ion carousel such that ion sub-packets from different ion packets that have similar mobility (e.g., mobility in a given mobility range) are injected into one or more predetermined potential wells. The potential wells can prevent diffusion of ions from one potential well to the adjacent potential well. This can prevent mixing of ions of different mobilities in the ion carousel106.

During an ejection period, ions trapped in one or more potential wells of the waveform in the ion carousel106are ejected into an output SLIM device108. Ions can be ejected based on their mobility at different times. For example, ions having a desirable range of mobility that are trapped in one or more potential wells (e.g., adjacent potential wells) can be released into the output SLIM device108. The output SLIM device108can guide the released ions to the mass spectrometer110that can detect the mass spectrum. The release time interval between successive ion ejections into the output SLIM device108can be determined based on the scan rate of the mass spectrometer110. For example, the release time interval can be chosen to be longer than the time taken by the mass spectrometer to measure a mass spectrum. This can prevent overlap between mass spectra of successive ion ejections.

The controller150can control the operation of ionization source102, input SLIM device104, ion carousel106, output SLIM device108and the mass spectrometer110. The controller150can control the ion separation event (e.g., accumulation time, rate of injection of ions into the input SLIM device104by the ionization source102, operation of the input SLIM device104, and the like). The controller150can also control the characteristics and motion of potential waveform in the ion carousel106. For example, controller150can synchronize the arrival time of an ion sub-packet (from the ion separation event) with the trajectory of a potential well designated to receive the ion sub-packet in the ion carousel106. The controller150can also control the ejection of ions trapped in the potential wells of the waveform in the ion carousel106. For example, the controller150can control an output switch in the ion carousel that can be activated to a confinement state to confine ions in the ion carousel106. The output switch can be activated to an ejection state to eject ions trapped in the potential waveform in ion carousel106to output SLIM device108. The controller150can also determine the time duration of the ejection state (e.g., based on desired ion mobility resolution of the IMS-MS spectrum). Furthermore, the controller can determine the delay time between successive ion ejections. The controller150can determine the delay time based on, for example, scan rate of the mass spectrometer110, mass of the ions, charge of the ions, and the like. The controller150can include multiple controller modules that are distributed over the coupled SLIM-device-mass-spectrometer (SLIM-MS)100.

The controller150can include multiple power supply modules (e.g., current/voltage supply circuits) that generate various voltage (or current) signals that drive the electrodes in the coupled SLIM-MS100. For example, the controller150can include RF control circuits that generate RF voltage signals, traveling wave control circuits that generate traveling wave voltage signals, DC control circuits that generate DC voltage signals, etc. The RF voltage signals, traveling wave voltage signals, DC voltage signal can be applied to electrodes in the input SLIM device104, ion carousel106, output SLIM device108, and the various input/output switches. The controller150can also include a master control circuit that can control the operation of the RF/traveling wave/DC control circuits. For example, the master control circuit can control the amplitude and/or phase of voltage (or current) signals generated by the RF/traveling wave/DC control circuits to achieve a desirable operation of the coupled SLIM-MS100.

In some implementations, one or more components of the coupled SLIM-MS100(e.g., input SLIM device104, ion carousel106, output SLIM device108etc.) can generate traveling potential waveforms (e.g., resulting from potentials generated by multiple electrodes in the component(s) of the coupled SLIM-MS100). The potential waveform can travel at a predetermined velocity based on, for example, frequency of voltage signals applied to the electrodes. In some implementations, the speed of the potential waveform can determine whether a mobility-based separation occurs or not. For example, speed of a potential waveform in the ion carousel106can be set to a value below the speed associated with ions having the lowest mobility. This can prevent ion mobility separation, and the traveling waveform can be used to transport ions (e.g., in separate potential wells). Additionally or alternately, speed of a potential waveform in the input SLIM device104(or output SLIM device108) can be set to a higher value than the aforementioned example. This can result in mobility-based separation (e.g., in input SLIM device104).

In some implementations, the traveling potential waveform can be spatially periodic and the spatial periodicity can depend on the phase differences between the voltage signals applied to adjacent electrode pairs. In some implementations, the phase differences can determine the direction of propagation of the potential waveform. The master control circuit can control the frequency and/or phase of voltage outputs of RF/traveling wave control circuits such that the traveling potential waveform has a desirable (e.g., predetermined) spatial periodicity and/or speed.

In some implementations, the controller150can be communicatively coupled to a computing device160. For example, the computing device160can provide operating parameters of the coupled SLIM-MS100via a control signal to the master control circuit. In some implementations, a user can provide the computing device160(e.g., via a user interface) with the operating parameters. Based on the operating parameters received via the control signal, the master control circuit can control the operation of the RF/AC/DC control circuits which in turn can determine the operation of the coupled SLIM-MS100. In some implementations, RF/AC/DC control circuits can be physically distributed over the coupled SLIM-MS100. For example, one or more of the RF/AC/DC control circuits can be located on the coupled SLIM-MS100. The controller150can receive power from a power source170(e.g., DC power source that provides a DC voltage to the controller150). The various RF/AC/DC control circuits can operate based on the power from the power source170.

FIG. 2is a top-down cross-sectional view of an exemplary ion carousel206coupled with an input SLIM device204and an output SLIM device208. The ion carousel206is configured to receive ions from an input SLIM device204and eject ions into an output SLIM device208for detection by a mass spectrometer. As shown inFIG. 2, ion carousel206, input SLIM device204and output SLIM device208include arrays of electrodes that receive a voltage signal from a voltage source, and generate a potential that can manipulate the ions. For example, the potential generated by electrodes in the input SLIM device204can perform ion mobility separation on a gas mixture from an ionization source (e.g., ionization source102), and guide an ion packet resulting from the mobility separation to the ion carousel206along an input path220. The electrodes in the ion carousel206can generate a potential waveform that can be configured to travel along a closed path222. The traveling potential wells can trap the ions from the input SLIM device204, and transport them along the closed path222. Output SLIM device208can direct ions ejected from the ion carousel206to the mass spectrometer along an output path224.

The ion carousel206can include an input switch212and an output switch214. The input switch212can regulate the injection of ions from the input SLIM device204into the ion carousel206. The input switch212can include multiple electrodes that can receive a voltage signal (e.g., from a DC control circuit in the controller150) and generate an input switching potential (switched-on state) that can prevent ions packets in the input SLIM device204from entering the ion carousel206. During an accumulation period, the input switch212can allow ion packets from the input SLIM device204to enter the ion carousel206(switched-off state). In one implementation, the input switch can generate a second input switching potential that can push the ion packet into the ion carousel206.

The output switch214can regulate the ejection of ions from the ion carousel206to the output SLIM device208. The output switch214can include multiple electrodes that can receive a voltage signal (e.g., from a DC control circuit in the controller150) and generate an output switching potential (confinement state of output switch214) that can prevent ions packets in the ion carousel206from entering the output SLIM device208. During an ejection period, the output switch214can direct ions trapped in potential wells of the ion carousel into the output SLIM device208to enter the mass spectrometer (ejection state of the output switch214). The output switch can generate a second output switching potential that can push ions trapped in potential wells into the output SLIM device208.

Each of the ion carousel206, input SLIM device204, output SLIM device208, input switch212and output switch214include a second surface (e.g., parallel to the x-y plane) displaced from the surface illustrated inFIG. 2along the z-direction. Movement of ions (e.g., from input SLIM device204to ion carousel206, from ion carousel206to the output SLIM device208) is confined between the two surfaces. In some implementations, ion carousel206, input SLIM device204, output SLIM device208, input switch212and output switch214can include multiple pairs of surfaces.

FIG. 3Ais an illustration of a cross-section of an exemplary electrode arrangement300located on a first surface or a second surface (e.g., parallel to the x-y plane and displaced from the surface illustrated inFIG. 3Aalong the z-direction). Various components of the coupled SLIM-MS200(e.g., surface of ion carousel206, input SLIM device204, output SLIM device208, etc.) can include the electrode arrangement300. The electrode arrangement300includes an inner array of electrodes302coupled to both the first and/or second surfaces, and arranged along a longitudinal axis306. The inner array of electrodes302are configured to receive an RF voltage and generate a pseudopotential that inhibits ions from approaching the first (or second) surface. The RF voltage applied to adjacent electrodes of the inner array of electrodes can be phase shifted (e.g., by 45 degrees, 90 degrees, 135 degrees, 180 degrees, etc.) The pseudopotential can confine the ions in the z-direction between the first and the second surfaces. The inner array of electrodes302can receive a DC voltage and generate a traveling DC or AC along the x-axis (longitudinal axis306) potential that can separate ions based on their mobility. For example, electrode arrangement300can receive a mixture of ions (e.g., from an ionization source at a first end316) and produce an ion packet with ions separated based on mobility (e.g., at a second end318). The electrode arrangement300also includes outer electrodes304and305that can receive a second DC voltage and generate a confinement potential along the y-axis (lateral direction). The confinement potential can prevent ions over the inner array of electrodes302from escaping in the lateral direction.

The application of the first DC voltage, the second DC voltage and the RF voltage can be controlled by a controller (e.g., controller150). For example, the aforementioned voltages can be produced by one or more voltage sources. The controller can also control the operating parameters of these voltage sources (e.g., amplitude of the voltages, frequency of the RF voltage, traveling speed of the first DC voltage, and the like).

FIG. 3Bis an illustration of a cross-section of another exemplary electrode arrangement350. Various components of the coupled SLIM-MS200(e.g., surface of ion carousel206, input SLIM device204, output SLIM device208, etc.) can include the electrode arrangement350. The electrode arrangement350can be a travelling wave (TW) SLIM device and can include a first outer array of electrodes310(also referred to as guard electrodes310) and a second outer array of electrodes315(also referred to as guard electrodes315) that can receive a DC voltage. The outer array of electrodes310and315can generate a DC potential that can confine the electrodes along the lateral direction308. The electrode arrangement350can include a first inner array of electrodes330, positioned between an adjacent pair of second inner array of RF electrodes320(RF−) and325(RF+).

The first inner array of electrodes330can include multiple electrodes that are segmented/arranged along (or parallel to) the propagation axis. The first inner array of electrodes330can receive a second voltage signal and generate a drive potential (or traveling potential waveform) that can drive ions along the longitudinal axis306. The drive potential can include one or more of a sinusoidal waveform, a rectangular waveform, a sawtooth waveform, a biased sinusoidal waveform, and the like. The drive potential can lead to separation of ions based on their mobility as they move along the longitudinal axis306. If the speed of the drive potential is less than the speed associated with ions having the lowest mobility, the drive potential can transport the ions without ion mobility separation.

In some implementations, adjacent electrodes of the first inner array of electrodes can receive AC voltages that are phase shifted. An RF voltage waveform can be applied to the second inner array of RF electrodes320and325. The RF voltage waveforms applied to the array of electrodes320can be out of phase (e.g., 180 degrees) with the RF voltage waveforms applied to the adjacent inner array of electrodes325. The second inner array of electrodes can generate a pseudopotential when applied with the RF voltage waveforms. The pseudopotential can repel ions away from the electrode arrangement350.

The electrode arrangement350can include guard electrodes310and315that are positioned adjacent to the outer most of the first/second plurality of electrodes. For example, the guard electrodes310and315can be located at the edges of the electrode arrangement300along the lateral direction. The guard electrodes310and315can receive a voltage signal (e.g., DC voltage signal from a DC control circuit) and generate a guard potential that can confine ions in the ion channels between the guard electrodes along the lateral direction308.

The first inner array of electrodes, first inner array of RF electrodes, and the guard electrodes can be connected to one or more voltage control circuits (e.g., voltage control circuits in the controller150). In some implementations, electrodes320and325can receive radio frequency (RF) signals that are phase shifted with respect to each other. In some implementations, the master control circuit can control the operation of two RF control circuits to generate two RF voltage signals that are phase shifted from one another (e.g., by 0 degrees, 15 degrees, 30 degrees, 45 degrees, 60 degrees, 75 degrees, 90 degrees, 105 degrees, 120 degrees, 135 degrees, 150 degrees, 165 degrees, 180 degrees, etc.).

FIG. 4is an illustration of a cross-section of a top-down view of an exemplary ion carousel206located on a first surface. The ion carousel206includes a second surface (e.g., parallel to the x-y plane) displaced from the surface illustrated inFIG. 4along the z-direction. The ion carousel206includes an inner array of electrodes402, a first outer electrode404and a second outer electrode406coupled to the first surface and the second surface. The inner array of electrodes402are configured to receive an RF voltage and generate a pseudopotential that inhibits ions from approaching the two surfaces of the ion carousel206. The RF voltage applied to adjacent electrodes of the inner array of electrodes can be phase shifted (e.g., by 45 degrees, 90 degrees, 135 degrees, 180 degrees, etc.) The pseudopotential can confine the ions in the z-direction between the two surfaces of the ion carousel206.

The inner array of electrodes402can receive a first DC voltage waveform and generate a potential waveform420having multiple potential wells that can travel along the closed path222. The closed path222can be rectangular, circular, and the like. The potential waveform420can be generated due application of a multiple DC and/or AC voltages on the segmented electrodes (e.g., segmented along the closed path222) of the inner array of electrodes402. The potential waveform420can be characterized by operational parameters, for example, a depth, width and travel speed of the potential wells of the potential waveform420. The potential waveform420can receive and trap ions from the input SLIM device (e.g., electrode arrangement300, electrode arrangement350, and the like) and move them along the closed path222(e.g., based on the motion of the potential waveform420). The outer electrodes404and406can receive a second DC voltage and generate a confinement potential along a lateral direction (e.g., orthogonal to the closed path222). The confinement potential can prevent ions over the inner array of electrodes402from escaping in lateral direction.

The input switch212and output switch214can include multiple electrodes coupled to the first and the second surface. Electrodes of the input switch can receive a voltage signal and generate an input switching potential (switched-on state) that can prevent ions packets in the input SLIM device from entering the ion carousel206. During an accumulation period, the input switch212can allow ion packets from the input SLIM device to enter the ion carousel206(switched-off state) and be trapped in one or more potential wells of the potential waveform420.

By synchronizing the motion of the potential waveform420(e.g., portion of the potential wells) with the time of arrival of an ion packet from input SLIM device204, ions in the ion packet can be placed in different potential wells of the potential waveform420. For example, the ion packets emerging from the input SLIM device may have undergone mobility based separation in the input SLIM. As a result, ion sub-packets that include ions with different mobility ranges can arrive the ion carousel206at different times. The temporal separation of ion packet into ion sub-packets based on mobilities, can facilitate trapping of the various ion sub-packet into different potential wells of the potential waveform420.

In some implementations, the inner array of electrodes402can include the first inner array of electrodes330and adjacent pair of second inner array of electrodes320and325. As described in reference toFIG. 3B, the first inner array of electrodes330can receive an AC voltage waveform and can generate a potential waveform (e.g., potential waveform420) that has multiple potential wells that can travel along the closed path222. The pair of second inner array of electrodes320and325can receive RF voltages (e.g. RF voltage applied to electrodes320can be phase shifted from the RF voltage applied to electrodes325) and generate a pseudopotential. The pseudopotential can inhibit ions form approaching the first and the second surfaces.

FIG. 5is a schematic illustration of an exemplary mobility-based accumulation of ions in a waveform520traveling in the ion carousel206. Ion packet510which is produced by the input SLIM device204can enter the ion carousel206during an accumulation period (input switch212in the switched-off state). The ion packet510includes ion sub-packets512,514and516that include ions with different ranges of mobility. For example, ion sub-packet512enters the ion carousel206at time T1; ion sub-packet514enters the ion carousel at time T2; and ion sub-packet516enters the ion carousel at time T3. The ion sub-packet512has higher mobility than ion sub-packet514which has higher mobility than ion sub-packet516. In other words, ion sub-packet512arrives before the ion sub-packet514which arrives before the ion sub-packet516(T1<T2<T3). At time T1, the potential well522can be positioned adjacent to the input switch212and can receive the ion sub-packet512. At time T2, the potential waveform520has traveled along the closed path222such that the potential well524is positioned adjacent to the input switch212, and can receive the ion sub-packet514. At time T3, the potential waveform520has traveled further along the closed path222such that the potential well526can be positioned adjacent to the input switch212, and can receive the ion sub-packet516.

The input SLIM device204can perform multiple ion separation events successively and generate multiple ion packets that are separated in time (e.g., time of arrival at the ion carousel206). For example, the input SLIM device204can generate a second ion packet530that can be temporally separated from the ion packet510by a separation time (T_sep). The ion mobility profile of the two ion packets can be similar (e.g., when the operating parameters of the input SLIM device204does not change substantially between the two ion separation events). The second ion packet can include ion sub-packets532,534and536that have ion mobility ranges similar to that of ion sub-packets512,514and516, respectively.

After the ions in the ion sub-packets512,514and516have been received and trapped in the potential wells522,524and526, respectively, the potential waveform520can travel along the closed path222and return back to the input switch212. If time taken by the potential wells522,524and526to complete a full revolution around the closed path222is similar (e.g., equal) to a temporal separation T_sep between ion packet510and the successive ion packet530, potential wells522,524and526can receive the ion sub-packet532,534and536, respectively. In some implementations, the potential wells522,524and526to complete a several revolutions around the closed path222during the temporal separation T_sep. In some implementations, the potential wells522,524and526can oscillate (e.g., along the x-direction) and capture the ion sub-packets532,534and536, respectively. This process can be repeated so that ions having similar mobility are trapped in the same potential well of the potential waveform520. The process of ion accumulation can be substantially lossless. For example, all ions received by the ion carousel206from the input SLIM device204can be ejected to the output SLIM device208.

FIG. 6is a schematic illustration of another exemplary mobility-based accumulation of ions in a potential waveform620traveling in the ion carousel206. Ion packet610which is produced by the input SLIM device204can enter the ion carousel206during an accumulation period (period when input switch212is in the switched-off state). The ion packet610includes ion sub-packets612,614and616that include ions with different mobility ranges. The ion sub-packets can enter the ion carousel at different times. For example, ion sub-packets612,614and616arrive successively, and are trapped in triangular potential wells622,624and626, respectively. The potential wells622,624and626can travel along (surf) the closed path222to return to the input switch212. By setting the time of travel (surfing time) of the potential wells622,624and626around the closed path222similar (e.g., equal) to the temporal separation T_sep between ion packet610and the successive ion packet630, potential wells622,624and626can receive the ion sub-packet632,634and636, respectively. This can allow for trapping of ions with similar mobilities in separate potential wells. For example, ion sub-packets612and632are trapped in potential well622; ion sub-packets614and634are trapped in potential well624; and ion sub-packets616and636are trapped in potential well626.

In some implementations, potential waveforms420,520and620can include one or more of a square waveform, a sinusoidal waveform, a triangular waveform, a ramp with a positive gradient, a ramp with a negative gradient, and the like. Potential waveforms420,520and620can be generated by application of a DC and/or an AC voltage waveforms to inner array of electrodes402(e.g., inner array of electrodes including the electrode arrangements300and/or350).

Returning toFIG. 4, the output switch214can regulate the ejection of ions trapped in the potential wells (e.g., potential wells522-526,622-626, etc.) to the output SLIM device208. The output switch214can include multiple electrodes coupled to the first and the second surface. The electrodes of the output switch214can receive a voltage signal, and generate an output switching potential (confinement state) that can prevent ions in the ion carousel206(e.g., ions trapped in potential wells of potential waveforms420,520,620etc.) from entering the output SLIM device208. For example, the voltage signal applied to the electrodes of the output switch214can be similar to the voltage signal applied to the first outer electrode404. This can prevent ions in the ion carousel206from entering the output SLIM device208.

During an ejection period, the output switch214can direct ions trapped in potential wells of the ion carousel206into the output SLIM device208(ejection state). The output switch214can generate a second output switching potential that can push ions trapped in the ion carousel206into the output SLIM device208. For example, the potential difference between the switching potential (e.g., AC and/or DC potential) applied to output switch214and the potential (e.g., AC and/or DC potential) applied to electrodes416of the inner array of electrodes can result in an electric field that can push the ions along the output path224towards the output SLIM device208. Additionally or alternately, a barrier potential can be applied to electrodes418of the inner array of electrodes which can prevent ions trapped in the potential wells from moving away from the output switch214(e.g., along the closed path222). A second output switch218can control the exit of ions/ion packets from the output SLIM device208along the output path224(e.g., to a mass spectrometer). For example, the second output switch218can receive a DC and/or an AC voltage that can generate a barrier potential which can prevent ions in the output SLIM device208from exiting to the mass spectrometer. The barrier potential can be periodically generated which can determine the periodicity of ion packets ejected into the mass spectrometer.

FIG. 7is a schematic illustration of an exemplary mobility-based ejection of ions in waveform720from ion carousel206to the output SLIM device208. During a first ejection period (T1_eject) ions trapped in potential wells722-725are ejected into the output SLIM device208. During a second ejection period (T2_eject) ions trapped in potential wells726-728are ejected into the output SLIM device208. This can be done, for example, by applying an output switching potential to the output switch214and/or applying a barrier potential to the electrodes418for a time period T1_eject. During T1_eject, potential wells722-725can approach the output switch214, and the output switching potential can drive ions trapped in the potential wells722-725into the output SLIM device208. During T2_eject, potential wells726-728can approach the output switch214, and the output switching potential can drive ions trapped in the potential wells726-728into the output SLIM device208.

The ejection time periods T1_eject and T2_eject can be separated by a delay time. The delay time can be determined (e.g., by controller150) based on the scan time of the mass spectrometer710. For example, properties of ions trapped in the waveform720(e.g., mass of the ions, charge of the ions, etc.) and/or operational parameters of the mass spectrometer710can determine the time needed by the mass spectrometer710to detect mass spectra (scan time) of ions trapped in the waveform720(e.g., ions in potential wells722-725, ions in potential wells726-728, etc.). The delay time can be set to a value greater than the scan time. This can prevent overlap of mass spectra of ions released at time T1_eject and T2_eject.

As described before, IMS-MS coupling (e.g., coupling between ion carousel206and mass spectrometer710) can generate an IMS-MS spectrum that describes a two-dimensional separation of ions based on ion mobility and mass-to-charge ratio. The ion mobility resolution can be determined based on mobility separation between adjacent ion mobility peaks. For example, ion mobility resolution of the ion carousel206can be determined based on ion mobility separation between ion packets in adjacent potential wells. The mass spectrum of the ejected ions (generated by the mass spectrometer710) represents ions having the aforementioned mobility range.

The mobility range of ions ejected during an ejection period can be varied by changing the duration of the ejection period. For example, increasing the duration of ejection period (e.g., T1_eject, T2_eject, etc.) can increase the mobility range of ejected ions and decreases the ion mobility resolution and vice versa. In some implementations, the mobility range of ions ejected during an ejection period can be varied by changing the mobility range of ions trapped in one or more potential wells (e.g., potential wells722-728). The mobility range of ions in a potential well can be determined by the mobility based ion separation event achieved in the input SLIM device204. Increasing the mobility separation of an ion packet in the input SLIM device204(e.g., by increasing the length of 204, etc.) can decrease the mobility range of ions trapped in the potential wells of the waveform (e.g.,520,620,720, etc.) in the ion carousel206.

In some implementations, desirable mobility resolution can be achieved by varying one or more of shape, speed, and height of potential waveform420,520and/or620generated by inner array of electrodes402. Changing the amplitude and/or frequency of the RF voltage applied to the inner array of electrodes402can vary the transmission efficiency of ions through the ion carousel206, vary the transmission of ions of various mass to charge (m/z) ratios.

The application of the first DC voltage, the second DC voltage and the RF voltage can be controlled by a controller (e.g., controller150). For example, the controller can vary the height and width of the potential wells. The controller can also control the travel speed (e.g., along the closed path222) of the potential wells. For example, the controller can vary the speed (e.g., increase or decrease the speed) of the potential wells; generate a static potential well, etc.

In some implementations, ions from the ion carousel (e.g., ion carousel206) can be selectively ejected to the output SLIM device (e.g., output SLIM device208) based on their mobility. In some implementations, ion mobility and mass-to-charge ratio of an ion can be correlated. For example, the ion mobility (e.g., indicative of structure of the ion) of ions can depend on their mass-to-charge ratios (e.g., quantified to be around 15%). In exemplary targeted analysis, mobility range in which an ion of a given mass-to-charge ratio will appear may be known a priori. After mobility-based separation of ions in the first input SLIM, mass-to-charge ratios of ions can be mapped to the various potential wells in the ion carousel. As a result, ions of a given mass-to-charge ratio (or a range of mass-to-charge ratios) can be selectively transferred to the mass spectrometer (via the output SLIM device) by selectively releasing ions from the corresponding potential wells. This can improve the performance of mass spectrometer (e.g., reduce time required to perform mass spectroscopy measurement).

In some implementations, the time of release of ions from the various potential wells in the ion carousel to the output SLIM device can be resorted (e.g., resorted based on their mobility, mass-to-charge ratio).FIGS. 8A-8Eillustrate exemplary resorting of time of release of ions in various potential wells.FIG. 8Aillustrates exemplary separation of ions based on their mobility by the input SLIM device804. As a result of this separation, ion packet816arrives at the ion carousel806, followed by ion packet814which in turn is followed by ion packet812(ion mobility of816> ion mobility of814> ion mobility of812).FIG. 8Billustrates the ion packets812-816trapped in different potential wells (not shown) traveling in the ion carousel806.FIG. 8Cillustrates the ejection of ion packet816. Ion packet816is the first ion packet to arrive at the intersection of ion carousel806and the output SLIM808, and is ejected from the ion carousel806to the output SLIM808. In some implementations, generation of an ejection potential by an output switch (during a first ejection period) can be synchronized with the time of arrival of the ion packet816at the intersection).

FIG. 8Dillustrates the ejection of ion packet812. Ion packet814arrives at the intersection after the ion packet816and continues to travel along the ion carousel806instead of being ejected to the output SLIM808. In some implementations, generation of a confinement potential by the output switch (during a first confinement period) can be synchronized with the time of arrival of the ion packet814at the intersection). Ion packet812arrives at the intersection after the ion packet814, and is ejected from the ion carousel806to the output SLIM808. In some implementations, generation of an ejection potential by the output switch (during a second ejection period) can be synchronized with the time of arrival of the ion packet812at the intersection). Following the ejection of ion packet812, the direction of travel of ion packet814can be reversed. The ion packet814can once again arrive at the intersection and is ejected from the ion carousel806to the output SLIM808. In some implementations, generation of an ejection potential by the output switch (during a third ejection period) can be synchronized with the second time of arrival of the ion packet814at the intersection).

FIG. 9Aillustrates the time of arrival of ion packets812-816at the ion carousel806from the input SLIM device804. As discussed above, the time of arrival of ion packet816is before the time of arrival of the ion packet814which is before the time of arrival of the ion packet816.FIG. 9Billustrates the ejection of ion packets812-816(e.g., which is related to the order in which the ion packets are scanned) from the ion carousel806to the input SLIM device804. As discussed above, ion packet816is ejected (and scanned by the mass spectrometer) followed by ion packet812which is followed by ion packet814.

Other embodiments are within the scope and spirit of the disclosed subject matter. One or more examples of these embodiments are illustrated in the accompanying drawings. Those skilled in the art will understand that the systems, devices, and methods specifically described herein and illustrated in the accompanying drawings are non-limiting exemplary embodiments and that the scope of the present disclosure is defined solely by the claims. The features illustrated or described in connection with one exemplary embodiment may be combined with the features of other embodiments. Such modifications and variations are intended to be included within the scope of the present disclosure. Further, in the present disclosure, like-named components of the embodiments generally have similar features, and thus within a particular embodiment each feature of each like-named component is not necessarily fully elaborated upon.