Systems and methods for acquiring full resolution ion mobility data and performing multi-analyte target data acquisition

Abstract

A system for acquiring full resolution ion mobility data includes an ion mobility separation device that receives ions, guides a portion of the ions, and separates the guided ions based on mobility. An ion detector receives the ions, detects ions having a predetermined mass-to-charge ratio during a time period, and generates a response signal. A data acquisition system receives the signal from the detector and generates a time-dependent ion signal representing the intensity of the signal at different arrival time periods during the time period. A system for performing multi-analyte target data acquisition includes an ion mobility separation device that receives a stream of ions, guides a portion of the ions, and separates the ions based on mobility. The ion detector receives ions and switches from detecting a first mass-to-charge ratio during a first arrival time of a first scan to detecting a second mass-to-charge ratio during a second arrival time.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 066,852, filed August 18, 2020, the entire disclosure of which is expressly incorporated herein by reference.

[0002] The present disclosure relates generally to the fields of ion mobility spectrometry (IMS) and mass spectrometry (MS). More particularly, the present disclosure relates to systems and methods for acquiring full resolution ion mobility data with a low acquisition rate filtered mass spectrometer achieved through the use of a high bandwidth acquisition system and performing multi-analyte target data acquisition by switching between mass-to-charge ratio detection and multi-scan analysis. [Background technology]

[0003] IMS is a technique for separating and identifying ions in the gas phase based on their mobility. For example, IMS can be used to separate structural isomers and macromolecules with different mobilities. IMS relies on applying a constant or time-varying electric field to a mixture of ions in a static or dynamic background gas. Ions with higher mobilities (or smaller collision cross sections [CCS]) move faster under the influence of the electric field compared to ions with lower mobilities (or larger CCS). By applying an electric field across a separation distance (e.g., within a drift tube) in an IMS device, ions from an ion mixture can be separated in time or space based on their mobility. Ions with different mobilities arrive at the end of the drift tube at different times (temporal separation), and these ions can be identified based on their detection time by a detector at the end of the drift tube. The resolution of mobility separation can be altered by varying the separation distance.

[0004] 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 accelerating the ion mixture in the presence of an electric and / or magnetic field. In some mass spectrometers, ions with the same mass-to-charge ratio receive the same deflection or time-dependent response. Ions with different mass-to-charge ratios may receive different deflection or time-dependent responses, and these ions can be distinguished based on their spatial or temporal detection location by a detector (e.g., an electron multiplier).

[0005] Combining IMS and MS can produce IMS-MS spectra, which can be used in a wide range of applications, including metabolomics, glycobiology, and proteomics. IMS-MS ion separation can be performed by coupling an ion mobility spectrometer to a mass spectrometer. For example, the ion mobility spectrometer can first separate ions based on their mobility. Ions with different mobilities can arrive at the mass spectrometer at different times and are then separated based on their mass-to-charge ratio. One example of an IM spectrometer is a lossless ion manipulation (SLIM) device, which can generate IMS spectra with minimal ion loss. SLIM devices can use traveling wave separation as one technique to separate ions of different mobilities.

[0006] A typical mass spectrometry acquisition system, such as a triple quadrupole (QQQ) mass spectrometer, operates in pulse-counting mode, where the detector is set to detect ions of a specific mass-to-charge ratio over a set pause time and sum the number of detected ions. Each set pause time is represented by a single number corresponding to the number of ions that arrive at the detector during that pause time. That is, the number of ions received during the pause time is summed regardless of when during the pause time the ions arrive at the detector. This ultimately reduces the detector signal to a single number. In addition, different analytes, for example, ions with the same mass-to-charge ratio but different mobilities, are summed rather than being distinguished and recorded separately, resulting in incomplete data.

[0007] Furthermore, samples analyzed by mass spectrometry systems can contain multiple ions or analytes with different mass-to-charge ratios. However, detectors that target a single mass-to-charge ratio or fragmentation transition only record ion mobility data for that single mass-to-charge ratio and therefore do not record data for other analytes. That is, such systems do not simultaneously monitor multiple targets. Furthermore, such systems generally cannot detect multiple analytes or ions with different mass-to-charge ratios but similar mobilities from a sample because the detector is configured to detect one specific mass-to-charge ratio. Summary of the Invention [Problem to be solved by the invention]

[0008] Therefore, there is a need for additional systems and methods for acquiring full resolution ion mobility data and performing multi-analyte targeted IMS-MS data acquisition. [Means for solving the problem]

[0009] The present disclosure relates to systems and methods for acquiring full resolution ion mobility data and performing multi-analyte target data acquisition using a filtering mass spectrometer.

[0010] According to an embodiment of the present disclosure, an exemplary system for acquiring full-resolution ion mobility data includes an ion mobility separation device, an ion detector, a data acquisition system, and a controller in communication with the ion mobility separation device, the ion detector, and the data acquisition system. The ion mobility separation device is configured to receive a stream of ions and direct at least a portion of the stream of ions through the ion mobility separation device to separate ions in the portion based on ion mobility. The ion detector is configured to receive the portion of the stream of ions from the ion mobility separation device, detect ions having a predetermined mass-to-charge ratio during a first time period, and generate one or more signals in response to detecting ions having the predetermined mass-to-charge ratio. The data acquisition system is configured to receive the one or more signals from the ion detector and generate time-dependent ion signals based on the signals received from the ion detector, the time-dependent ion signals representing the intensities of the one or more signals at a plurality of different arrival time periods during the first time period.

[0011] In some embodiments, the data acquisition system may be a high-bandwidth data acquisition system, hi such embodiments, the high-bandwidth data acquisition system may be an analog-to-digital converter and may have at least 8-bit resolution, and the one or more signals produced by the ion detector may be analog signals.

[0012] In some other embodiments, the data acquisition system can be configured to separate the first time period into a plurality of sub-time periods, separately sum the received one or more signals for each of the plurality of sub-time periods, and generate a time-dependent ion signal based on the sum and the plurality of sub-time periods. In such embodiments, the data acquisition system can have a bandwidth greater than 1 kHz.

[0013] In yet another aspect, the ion mobility separation device can be configured to generate a traveling drive potential configured to guide ions through the ion mobility separation device and separate the ions based on ion mobility. In another aspect, the ion mobility separation device can include an accumulation region and an ion mobility separation path. The accumulation region can be configured to accumulate ions into one or more ion packets and pulse the one or more ion packets into the ion mobility separation path.

[0014] According to an embodiment of the present disclosure, an exemplary method for acquiring full-resolution ion mobility data is provided. The method includes introducing a flow of ions into an ion mobility separation device. The method further includes directing, by the ion mobility separation device, at least a portion of the flow of ions through the ion mobility separation device to an ion detector. The method additionally includes separating, by the ion mobility separation device, the ions in the portion based on ion mobility. The method also includes receiving, by the ion detector, ions having a predetermined mass-to-charge ratio during a first time period. The method further includes generating, by the ion detector, one or more signals in response to detecting the ions having the predetermined mass-to-charge ratio, and receiving, by a data acquisition system, the one or more signals from the ion detector. The method also includes generating, by the data acquisition system, a time-dependent ion signal based on the one or more signals received from the ion detector, the time-dependent ion signal representing the intensity of the one or more signals at a plurality of different arrival time periods during the first time period.

[0015] In some aspects, the method includes a controller in communication with the ion mobility separation device, the ion detector, and the data acquisition system.

[0016] In some embodiments, the data acquisition system may be a high-bandwidth data acquisition system, hi such embodiments, the high-bandwidth data acquisition system may be an analog-to-digital converter and may have at least 8-bit resolution, and the one or more signals produced by the ion detector may be analog signals.

[0017] In another aspect, the method can include separating, by a data acquisition system, the first time period into a plurality of sub-time periods, separately summing the received one or more signals for each of the plurality of sub-time periods, and generating a time-dependent ion signal based on the sum and the plurality of sub-time periods. In such an aspect, the data acquisition system can have a bandwidth greater than 1 kHz.

[0018] In some other aspects, the method may include generating, by the ion mobility separation device, a travel driving potential that guides ions through the ion mobility separation device and separates the ions based on ion mobility.

[0019] In yet another aspect, an ion mobility separation device can include an accumulation region and an ion mobility separation path. The accumulation region can be configured to accumulate ions into one or more ion packets and pulse the one or more ion packets into the ion mobility separation path.

[0020] According to an embodiment of the present disclosure, an exemplary system for performing multi-analyte target data acquisition includes an ion mobility separation device, an ion detector, and a controller in communication with the ion mobility separation device and the ion detector. The ion mobility separation device is configured to receive a stream of ions, direct at least a first portion of the stream of ions through the ion mobility separation device, and separate ions in the first portion based on ion mobility. The ion detector is configured to receive the first portion of the stream of ions from the ion mobility separation device and perform a first scan of the received ions, the first scan including detecting first ions having a first mass-to-charge ratio during a first arrival time and detecting second ions having a second mass-to-charge ratio during a second arrival time. The ion detector switches from detecting the first mass-to-charge ratio during the first arrival time of the first scan to detecting the second mass-to-charge ratio during the second arrival time of the first scan.

[0021] In some embodiments, the ion mobility separation device can be configured to direct a second portion of the stream of ions through the ion mobility separation device and separate the ions in the second portion based on ion mobility. In such embodiments, the ion detector can be configured to receive the second portion of the stream of ions from the ion mobility device and perform a second scan of the received ions, the second scan including detecting third ions having a third mass-to-charge ratio during the first arrival time. The ion detector can switch from detecting one of the first and second mass-to-charge ratios to detecting the third mass-to-charge ratio.

[0022] In other embodiments, the data detected during the first scan and the data detected during the second scan can be combined to form a multi-analyte data plot.

[0023] In still other aspects, the system can include a computing device that stores a data set, the data set including data regarding ions in a first portion of the ion stream and a second portion of the ion stream. In these aspects, the computing device can be configured to determine, based on the data set, a first ion to detect during a first scan, a second ion to detect during the first scan, and a third ion to detect during a second scan. The data can include one or more of arrival time and mass-to-charge ratio. The computing device can be configured to group the ions into a first, second, and third scan based on the data.

[0024] In a further aspect, the ion mobility separation device can include an accumulation region and an ion mobility separation path. The accumulation region can be configured to accumulate ions into one or more ion packets and pulse the one or more ion packets into the ion mobility separation path. In such an aspect, a first scan can be performed on a first packet of the one or more ion packets, and a second scan can be performed on a second packet of the one or more ion packets.

[0025] In other aspects, the ion mobility separation device can be configured to generate a travel driving potential configured to guide ions through the ion mobility separation device and separate the ions based on ion mobility.

[0026] According to an embodiment of the present disclosure, an exemplary method for multi-analyte target data acquisition is provided. The method includes introducing a flow of ions into an ion mobility separation device, directing at least a first portion of the flow of ions through the ion mobility separation device to an ion detector, and separating the ions in the first portion based on ion mobility using the ion mobility separation device. The method also includes receiving the first portion of the flow of ions using the ion detector and performing a first scan of the received ions using the ion detector, the first scan including detecting first ions having a first mass-to-charge ratio during a first arrival time and detecting second ions having a second mass-to-charge ratio during a second arrival time. The ion detector switches from detecting the first mass-to-charge ratio during the first arrival time of the first scan to detecting the second mass-to-charge ratio during the second arrival time of the first scan.

[0027] In some embodiments, the method can include directing, by an ion mobility separation device, a second portion of the stream of ions through the ion mobility separation device to an ion detector and separating, by the ion mobility separation device, the ions in the second portion based on ion mobility. Such embodiments can also include receiving, by the ion detector, the second portion of the stream of ions and performing a second scan of the received ions, the second scan including detecting third ions having a third mass-to-charge ratio during the first arrival time. The ion detector can switch from detecting one of the first and second mass-to-charge ratios to detecting the third mass-to-charge ratio.

[0028] In some embodiments, the method can include combining the data detected during the first scan and the data detected during the second scan to form a multi-analyte data plot.

[0029] In some other aspects, the method can include storing, by a computing device, a data set, the data set including data regarding ions in a first portion of the ion stream and a second portion of the ion stream. Such methods can include determining, by the computing device, a first ion to detect during the first scan, a second ion to detect during the first scan, and a third ion to detect during the second scan based on the data set. In some of these methods, the data can include one or more of arrival time and mass-to-charge ratio.

[0030] In some other embodiments, the method may include grouping, by the computing device, the ions into first, second, and third scans based on the data.

[0031] In yet another aspect, the ion mobility separation device can include an accumulation region and an ion mobility separation path. The accumulation region can be configured to accumulate ions into one or more ion packets and pulse the one or more ion packets into the ion mobility separation path. In such an aspect, a first scan can be performed on a first packet of the one or more ion packets, and a second scan can be performed on a second packet of the one or more ion packets.

[0032] In some aspects, the ion mobility separation device can be configured to generate a travel driving potential configured to guide ions through the ion mobility separation device and separate the ions based on ion mobility.

[0033] Other configurations will become apparent from consideration of the following detailed description in conjunction with the accompanying drawings, which, however, are designed for purposes of illustration only and not as a definition of the limits of the invention.

[0034] The above features of the present disclosure will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings. [Brief explanation of the drawings]

[0035] [Figure 1] 1 is a schematic diagram of an exemplary ion mobility separation system of the present disclosure; [Figure 2] FIG. 2 is a schematic diagram of the example IMS device of FIG. 1. [Figure 3] FIG. 2 is an exemplary timing diagram of the ion mobility separation system of FIG. 1. [Figure 4A] 1 is a graph of mass-to-charge ratio (m / z) versus collision cross section (CCS) demonstrating targeted single m / z ion mobility data collection. [Figure 4B] 1 is a graph of mass-to-charge ratio versus ion mobility demonstrating multi-analyte targeted IMS-MS data acquisition. [Figure 5] 1 is a graph of mass to charge ratio versus arrival time showing the activation times at which a detector detects ions of three different mass to charge ratios at three different arrival times. [Figure 6A] 1 is a graph of mass-to-charge ratio versus arrival time showing the activation times for a detector to detect ions of three different mass-to-charge ratios, two of which have the same arrival time. [Figure 6B] 6B is a first portion of the graph of FIG. 6A showing a first scan of the detector. [Figure 6C] 6B is a second portion of the graph of FIG. 6A showing a second scan of the detector. [Figure 7] 1 is a graph of mass-to-charge ratio versus arrival time for an exemplary glycan mixture. [Figure 8A] FIG. 8 is a detailed view of a first portion of the graph of FIG. 7 showing data in more detail for the arrival time range of 150 ms to 400 ms, including peak widths and groupings of data with gaps of less than 3 ms between peak widths. [Figure 8B]FIG. 8 is a detailed view of the second portion of the graph of FIG. 7 showing in more detail the data for the arrival time range of 625 ms to 975 ms, including peak widths and groupings of data with gaps of less than 3 ms between peak widths. [Figure 9A] FIG. 8 is a detailed view of a first portion of the graph of FIG. 7 showing data for the arrival time range of 160 ms to 260 ms in more detail and identifying data acquired by the first scan of the detector. [Figure 9B] FIG. 8 is a detailed view of a second portion of the graph of FIG. 7 showing data for the arrival time range of 260 ms to 400 ms in more detail and identifying data acquired by the first scan of the detector. [Figure 9C] FIG. 8 is a detailed view of the third portion of the graph of FIG. 7 showing data for the arrival time range of 625 ms to 975 ms in more detail and identifying data acquired by the first scan of the detector. [Figure 10A] FIG. 8 is a detailed view of a first portion of the graph of FIG. 7 showing data for the arrival time range of 160 ms to 260 ms in more detail and identifying data acquired by a second scan of the detector. [Figure 10B] FIG. 8 is a detailed view of a second portion of the graph of FIG. 7 showing data for the arrival time range of 260 ms to 400 ms in more detail and identifying data acquired by a second scan of the detector. [Figure 10C] FIG. 8 is a detailed view of the third portion of the graph of FIG. 7 showing data for the arrival time range of 625 ms to 975 ms in more detail and identifying data acquired by a second scan of the detector. [Figure 11A] FIG. 8 is a detailed view of a first portion of the graph of FIG. 7 showing data for the arrival time range of 160 ms to 260 ms in more detail and identifying data acquired by the third scan of the detector. [Figure 11B] FIG. 8 is a detailed view of the second portion of the graph of FIG. 7 showing data for the arrival time range of 260 ms to 400 ms in more detail and identifying data acquired by the third scan of the detector. [Figure 11C]FIG. 8 is a detailed view of the third portion of the graph of FIG. 7 showing data for the arrival time range of 625 ms to 975 ms in more detail and identifying data acquired by the third scan of the detector. [Figure 12A] FIG. 8 is a detailed view of a first portion of the graph of FIG. 7 showing data for the arrival time range of 160 ms to 260 ms in more detail and identifying data acquired by the fourth scan of the detector. [Figure 12B] FIG. 8 is a detailed view of the second portion of the graph of FIG. 7 showing data for the arrival time range of 260 ms to 400 ms in more detail and identifying data acquired by the fourth scan of the detector. [Figure 12C] FIG. 8 is a detailed view of the third portion of the graph of FIG. 7 showing data for the arrival time range of 625 ms to 975 ms in more detail and identifying data acquired by the fourth scan of the detector. [Figure 13A] 10A-10C, 11A-11C, and 12A-12C. A detailed view of a first portion of the graph of FIG. 7 showing data for the arrival time range of 160 ms to 260 ms in more detail and identifying data acquired by the first, second, third, and fourth scans of the detector shown in FIGS. 9A-9C, 10A-10C, 11A-11C, and 12A-12C. [Figure 13B] 10A-10C, 11A-11C, and 12A-12C. This is a detailed view of a second portion of the graph of FIG. 7, showing data for the arrival time range of 260 ms to 400 ms in more detail and identifying data acquired by the first, second, third, and fourth scans of the detector shown in FIGS. 9A-9C, 10A-10C, 11A-11C, and 12A-12C. [Figure 13C] 11A-11C, and 12A-12C. FIG. 12C is a detailed view of the third portion of the graph of FIG. 7, showing data for the arrival time range of 625 ms to 975 ms in more detail and identifying data acquired by the first, second, third, and fourth scans of the detector shown in FIGS. 9A-9C, 10A-10C, 11A-11C, and 12A-12C. DETAILED DESCRIPTION OF THE INVENTION

[0036] The present disclosure relates to systems and methods for filtering ions, as described in detail below in connection with FIGS. 1-13C.

[0037] Ions can be separated based on their mobility via ion mobility spectrometry (IMS). Mobility separation can be achieved, for example, by applying one or more potential waveforms (e.g., traveling potential waveforms, direct current (DC) gradients, or both) to a group of ions. As an example, IMS-based mobility separation can be achieved by a structure for lossless ion manipulation (SLIM) that can systematically apply traveling and / or DC potential waveforms to a group of ions, such as the devices disclosed and described in U.S. Pat. No. 8,835,839, entitled "Method and Apparatus for Ion Mobility Separations Utilizing Alternating Current Waveforms," ​​and U.S. Pat. No. 10,317,364, entitled "Ion Manipulation Device," both of which are incorporated herein by reference in their entireties. This results in a continuous stream of ions separated in time or space based on their mobility.

[0038] 1 is a schematic diagram of an exemplary ion mobility separation (IMS) system 100 according to the present disclosure. The IMS system 100 includes an ionization source 102, an IMS device 104, a detector 106 (e.g., a mass spectrometer such as a triple quadrupole (QQQ) mass spectrometer, or any other filtering mass spectrometer / analyzer), a high-bandwidth data acquisition system 108, a vacuum system 110, a controller 112, a computing device 114, and a power supply 116. The ionization source 102 generates ions (e.g., ions having varying mobilities and mass-to-charge ratios) and injects the ions into the IMS device 104. The IMS device 104 may be configured and operate in accordance with the SLIM devices disclosed and described in U.S. Patent Nos. 8,835,839 and 10,317,364. In particular, the IMS device 104 may be configured to transmit ions, accumulate ions, store ions, and / or separate ions, depending on the desired function and waveforms applied. In this regard, the IMS device 104 may be used to select ions having one or more predetermined mobility ranges and direct the selected group (or groups) of ions to a detector 106, for example a mass spectrometer such as a triple quadrupole (QQQ) mass spectrometer, which may be in communication with or include a high-bandwidth data acquisition system 108. The high-bandwidth data acquisition system 108 may be an analog or digital system configured to receive, monitor, and acquire the time-dependent ion signal of the detector 106 and generate a full-resolution ion mobility data signal, as discussed in more detail below.

[0039] It should be understood that the IMS device 104 does not have to be a SLIM device, but can be any IMS device that operates via temporal separation such that ions having different mass-to-charge ratios arrive at the detector 106 at different times.

[0040] In one exemplary configuration, the IMS device 104 can include one or more surfaces (e.g., a printed circuit board surface) on which multiple electrodes can be disposed. The electrodes can receive a voltage signal, voltage waveform, and / or current waveform (e.g., a DC voltage or current, an RF voltage or current, or an AC voltage or current, or a superposition thereof) to generate a potential (e.g., a potential gradient) to confine, accumulate, or guide ions within the IMS device 104, thereby accumulating and separating ions based on their mobility. The voltage signal applied to the electrodes can be a sinusoidal waveform (e.g., an AC voltage waveform), a rectangular waveform, a DC square waveform, a sawtooth waveform, a biased sinusoidal waveform, a pulsed voltage or current waveform (which can be periodic without polarity reversal), etc., and the amplitude of the signal provided to the electrodes can be determined based on the applied voltage waveform. The electrodes of the IMS device 104 can be individually coupled to different traveling-wave control circuits, such as an AC control circuit, a DC (square wave) control circuit, a pulsed current control circuit, etc., that generate voltage signals that are phase-shifted relative to one another. Alternatively, the controller 112 can be a single traveling-wave control circuit that can generate voltage signals that can be applied simultaneously to all electrodes of the IMS device 104. It should be understood that the voltage or current waveforms can take various forms, such as square, triangular, rectangular, sawtooth, etc., and can be periodic, non-periodic, etc. For example, the controller 112 can be a traveling-wave control circuit that can include one or more DC (square wave) control circuits that generate DC voltage signals and an AC control circuit that generates sinusoidal signals.

[0041] The vacuum system 110 can be in fluid communication with the IMS device 104 and can regulate the gas pressure within the IMS device 104. Specifically, the vacuum system 110 can provide nitrogen to the IMS device 104 while maintaining a consistent pressure within the IMS device 104.

[0042] The controller 112 can receive power from a power supply 116, which can be, for example, a DC power supply providing a DC voltage to the controller 112, and can communicate with and control the operation of the ionization source 102, the IMS device 104, the detector 106, the high-bandwidth data acquisition system 108, and the vacuum system 110. For example, the controller 112 can control the rate of ion injection into the IMS device 104 by the ionization source 102, the target mobility of the IMS device 104, and the detection of ions by the detector 106. The controller 112 can also control the characteristics and dynamics of the potential waveforms generated by the IMS device 104 for ion transmission, accumulation, storage, and / or separation (e.g., by applying RF / AC / DC potentials to electrodes of the IMS device 104). In addition, the controller 112 can receive full-resolution ion mobility data signals generated by the high-bandwidth data acquisition system 108.

[0043] The controller 112 can control the characteristics of the potential waveform (e.g., amplitude, shape, frequency, etc.) by varying the characteristics of the applied RF / AC / DC potential (or current). In this regard, the controller 112 can vary the characteristics of the potential waveform for different regions of the IMS device 104, e.g., different groupings of electrodes, to collect / accumulate and later separate ions. This can be done to remove undesired ions (e.g., ions with non-target mobilities), increase mobility peak resolution, increase signal-to-noise ratios, and provide sharp separation around target mobilities.

[0044] In some implementations, the controller 112 can be communicatively coupled to a computing device 114. For example, the computing device 114 can provide operational parameters of the IMS system 100 to the master control circuitry via control signals. In some implementations, a user can provide the operational parameters to the computing device 114 (e.g., via a user interface). Based on the operational parameters received via the control signals, the master control circuitry can control the operation of the RF / AC / DC control circuits, and the RF / AC / DC control circuits can determine the operation of the coupled IMS devices 104. In some implementations, the RF / AC / DC control circuits can be physically distributed throughout the IMS system 100. For example, one or more of the RF / AC / DC control circuits can be located within the IMS system 100, and the various RF / AC / DC control circuits can operate based on power from the power source 116.

[0045] The detector 106 may be a filter-based detector that can be configured to detect ions of a single mass-to-charge ratio at a time, rather than detecting all ions at once. For example, the detector 106 may be a mass spectrometer, such as a triple quadrupole (QQQ) mass spectrometer. Thus, the detector 106 may rely on the IMS device 104 to separate ions in time, such that ions of different mass-to-charge ratios arrive at the detector 106 at different times.

[0046] 2 is a schematic diagram of the exemplary IMS device 104 of FIG. 1. The IMS device 104 may include an inlet channel 118, an accumulation region 120, a gate 122, and an ion mobility separation channel 124. The ion source 102 provides ions to the inlet channel 118 through interface ion optics 126, which focus the ions provided by the ion source 102. The interface ion optics 126 may be ion optics known in the art, such as an ion funnel, a quadrupole ion guide, a rectangular ion funnel, traveling wave ion optics, etc. The inlet channel 118 transmits ions to the accumulation region 120, for example, via a traveling wave.

[0047] Ions are accumulated in the accumulation region 120 and held therein by a gate 122, which may generate a high DC potential that prevents the ions from exiting the accumulation region 120, e.g., a DC potential greater than the voltage bias applied to the accumulation region 120. Ions may be accumulated in the accumulation region 120 for a predetermined time, at which point the DC potential applied to the gate 122 is lowered, thus releasing the accumulated ions into the ion mobility separation path 124. This procedure may be performed as many times as necessary so that multiple ion packets may be pulsed by the accumulation region 120 into the ion mobility separation path 124 for ion mobility separation. The ions pulsed into the ion mobility separation path 124 are separated based on mobility, e.g., in time, as they are forced through the ion mobility separation path 124, e.g., via traveling waves applied to and generated by electrodes of the ion mobility separation path 124. The ion mobility separation path 124 may be, for example, 13 meters long to adequately separate ions based on mobility. The ion mobility separation path 124 transmits ions through an ion guide 128 to the detector 106, which may be configured to detect ions of a single mass-to-charge ratio during a specific or fixed time period, e.g., a dwell time. The detector 106 integrates the number of pulses occurring during the dwell time, which represents the number of ions having the desired mass-to-charge ratio that reach the detector 106 during the dwell time. Thus, the system 100 filters ions based on both mobility and mass-to-charge ratio.

[0048] It should be understood that the ion mobility separation path 124 may be constructed and configured in accordance with the SLIM devices shown and described in U.S. Patent Nos. 8,835,839 and 10,317,364. In particular, the ion mobility separation path 124 may include first and second parallel surfaces including a plurality of electrodes configured to receive electrical signals from the controller 112 to maintain ions on the path, transmit ions along the path, and separate ions based on mobility. However, it should also be understood that the ion mobility separation path 124 may alternatively be constructed and configured in accordance with other IMS devices known in the art that perform temporal separation of ions.

[0049] 3 is an exemplary timing diagram of the ion mobility system 100 of FIGS. 1 and 2. A first timing signal 130 represents the state of the gate 122, with a high state 130a indicating that the gate 122 is receiving or generating a high DC potential, thereby preventing ions from leaving the accumulation region 120 and entering the ion mobility separation path 124, and a low state 130b indicating that the gate 122 is receiving or generating a low DC potential, thereby allowing ions to leave the accumulation region 120 and enter the ion mobility separation path 124. A first time period t1 corresponds to the time when the first timing signal 130 is in the high state 130a and represents the fill time or collection time for the accumulation region 120 during which ions are collected and accumulated within the accumulation region 120 by the gate 122. That is, the first time period t1 represents the time period during which ions are being accumulated by the accumulation region 120. The second time period t2 represents the time during which the gate 122 allows ions to exit the storage region 120 and enter the ion mobility separation path 124, e.g., the time during which the gate 122 is in the low state 130b, which is called the release time, e.g., the time period during which the storage region 120 releases ions into the ion mobility separation path 124.

[0050] The second timing signal 132 represents the state of the detector 106, with a low signal 132a indicating that the detector 106 is not operational and a high signal 132b indicating that the detector 106 is operational and detecting ions reaching the detector 106 and having a desired mass-to-charge ratio, e.g., the mass-to-charge ratio that the detector 106 is configured to detect. The third time period t3 represents the ion arrival time, i.e., the time it takes for an ion to cross the ion mobility separation path 124 and reach the detector 106. The fourth time period t4 represents the time the detector 106 is operational and counting pulses / ions, which is generally referred to as the dwell time. A typical dwell time for a QQQ mass spectrometer can be, for example, 1 to 1,000 ms.

[0051] In a standard detector operating in "pulse counting" mode, the number of pulses occurring at the detector during a pause is summed, representing the number of ions with the correct arrival time and mass-to-charge ratio that arrived at the detector. However, when operating in the above-described "pulse counting" mode, the detector does not monitor or acquire time-dependent ion signals; instead, it sums all ions detected during the pause, regardless of their unique arrival times within the pause. This methodology ignores the possibility that ions with different arrival times may be present and summed together during the same pause, which may occur in the case of isomers, which are compounds with the same mass-to-charge ratio but different sizes and / or shapes, and which may have slightly different arrival times. Additionally, this methodology does not provide the location and shape of the actual ion mobility peak, thereby reducing the amount of information available from the signal generated by the detector.

[0052] The above is illustrated by the exemplary full-resolution ion mobility data graph 134 shown in FIG. 3, which is an exemplary graph of signal intensity versus arrival time distribution at the detector 106 during a fourth time period t4, e.g., a dwell time of the detector 106. As can be seen in graph 134, the full-resolution ion mobility data graph has three distinct ion mobility peaks 136a-c, indicating the presence of multiple isomers within the same dwell time window. This is for an IMS device implemented to separate ions based on mobility, e.g., temporal separation, such as the IMS device 104 shown and described in connection with FIG. 2. The ion mobility separation path 124 of such an IMS device has a length of 13 m and can separate ions based on mobility, thus forming ion mobility peaks with widths of approximately 3-10 ms, depending on the separation parameters. Notably, because the ion mobility peaks have widths much smaller than the dwell times, the detector 106 can acquire multiple ion mobility peaks within a single dwell time.

[0053] Rather than simply summing the detector 106 pulses over the pause time, the high-bandwidth data acquisition system 108 monitors and acquires the time-dependent ion signal to detect the location and shape of the actual ion mobility peak. This is achieved by implementing a high-bandwidth data acquisition system with the detector 106 to integrate the ion count over shorter time periods within a longer pause time. For example, the detector 106 can acquire data, e.g., detect ions, during the pause time, and the high-bandwidth data acquisition system 108 can divide the pause time into fewer time periods, sum the ion count for each of those time periods, and generate a profile based on the ion count for each time period within the pause time. For a system generating a 3 ms-wide ion mobility peak and targeting 10 points at the peak, the high-bandwidth data acquisition system 108 would require a bandwidth greater than about 1 kHz or an integration step size of about 300 μs. That is, for example, if the detector 106 has a 3 ms dwell time, the high-bandwidth data acquisition system 108 divides the 3 ms dwell time into ten 300 μs time periods and sums the pulses detected by the detector 106 for each of those 300 μs time periods to obtain ten separate data points representing the total ion mobility peak. The high-bandwidth data acquisition system 108 can then form a profile from the ten separate data points. Alternatively, the high-bandwidth data acquisition system 108 can receive and record the raw output / signal of the detector 106. For example, the ion mobility peak can be viewed on an oscilloscope that receives the raw output of the detector 106, and the high-bandwidth data acquisition system 108 can be a device that mimics the function of an oscilloscope or records oscilloscope data. Furthermore, the high-bandwidth data acquisition system 108 can be an analog-to-digital converter (ADC) with 8-bit or greater resolution that receives an analog signal from the detector 106 and directly records the analog signal.

[0054] As previously mentioned, the high bandwidth data acquisition system 108 may be a separate component or may be integrated into any one of the detector 106 , the controller 112 , or the computing device 114 .

[0055] By monitoring and acquiring the time-dependent ion signal, rather than the integrated number of ions contained within the entire dwell time window, the actual ion mobility peak position and shape can be detected and analyzed. Additionally, if multiple isomers are present within the same dwell time window, the system can distinguish and record the different isomers, rather than grouping them together.

[0056] Additionally, as previously mentioned, the detector 106 is configured to detect ions of a particular mass-to-charge ratio, and all other ions, e.g., ions having different mass-to-charge ratios, are not detected by the detector 106. Thus, when the detector 106 is configured to detect a single mass-to-charge ratio over a long period of time, the detector 106 records an entire mobility profile 168 for the mass-to-charge ratio detected over that period of time, as shown in Figure 4A, which is a graph of mass-to-charge ratio (m / z) versus collision cross section (CCS) demonstrating targeted single-ion mobility data collection.

[0057] However, when multiple analytes are present, it may be desirable to detect different mass-to-charge ratios across the ion mobility range, as shown in FIG. 4B, which is a graph of mass-to-charge ratio versus ion mobility demonstrating multi-analyte targeted IMS-MS data acquisition. As can be seen in FIG. 4B, mobility profiles 170a-g for each of the analytes having different mass-to-charge ratios are detected and graphed by the detector 106. Generally, to perform multi-analyte targeted IMS-MS data acquisition, the mass-to-charge ratios and ion mobilities for the analytes being detected must be known, and at specific time periods, e.g., ion arrival times, the detector 106 is switched to detect the mass-to-charge ratio of ions known to arrive at the detector 106 at that time. The detector 106 can be switched multiple times to detect multiple different mass-to-charge ratios at different arrival times, allowing for the detection of multiple different ions within a single ion mobility separation.

[0058] To accomplish the above, the computing device 114 can determine the arrival time for each unique ion based on known ion mobility values, known mass-to-charge ratios, and details / attributes / configuration of the IMS device 104, such as separation path length, applied signal, separation time, on-substrate accumulation time, etc. For example, the computing device 114 can have a stored table containing a list of ions, their mass-to-charge ratios, their mobilities / CCSs, and the calculated arrival times for each ion. The controller 112 can then step the detector 106 through this table, configuring it to detect the appropriate mass-to-charge ratios at the appropriate arrival times and ensuring that data is recorded for the table. This can be done multiple times, for example, across multiple mobility separations, to complete the entire 2D plot and further refine the data. Thus, the system 100 synchronizes ion mobility and mass spectrometry data.

[0059] This technique can be implemented to detect ions having different mass-to-charge ratios, as shown in FIG. 5, which is a graph of mass-to-charge ratio versus arrival time illustrating the activation times of a detector 106 for detecting ions of three different mass-to-charge ratios at three different arrival times. As can be seen in FIG. 5, the detector 106 is activated for a first detection time period 172a to detect a first mass-to-charge ratio, a second detection time period 172b to detect a second mass-to-charge ratio, and a third detection time period 172c to detect a third mass-to-charge ratio. Additionally, the detection time periods 172a-c are spaced far enough apart that the detector 106 (e.g., a mass spectrometer) has sufficient time to switch from detecting one mass-to-charge ratio to detecting the next. For example, it may take 3 ms for the detector 106 to switch from detecting a first mass-to-charge ratio to detecting a second, different mass-to-charge ratio. Therefore, if the ion arrival times are too close to each other, the detector 106 will not switch in time. Thus, the detector 106 is able to detect multiple different ions within a single ion mobility separation.

[0060] However, for some ion mobility separations, two different ions may have different mass-to-charge ratios but similar mobilities, and therefore arrive at the detector 106 close to one another. In such cases, the detector 106 may detect only one of the mass-to-charge ratios during the arrival time of both ions, and therefore the ions with the undetected mass-to-charge ratio are discarded and the other mass-to-charge ratio is graphed. This is shown, for example, in Figure 6A, which is a graph of mass-to-charge ratio versus arrival time showing the activation time at which the detector 106 detects ions of three different mass-to-charge ratios, two of which have the same arrival time.

[0061] As can be seen in FIG. 6A, the detector 106 is activated for a first detection time period 174a to detect a first mass-to-charge ratio, a second detection time period 174b to detect a second mass-to-charge ratio, and a third detection time period 174c to detect a third mass-to-charge ratio. However, because the first and second detection time periods 174a, 174b overlap, the detector 106 cannot detect both corresponding mass-to-charge ratios during the same scan, e.g., for the same ion mobility separation. Therefore, to detect all of the desired ions, the mass-to-charge ratios are separated into two separate groups and detected in two separate scans. For example, the detector may perform a first scan detecting over the first and third time periods 174a, 174c, as shown in FIG. 6B, and a second scan detecting over the second time period 174b, as shown in FIG. 6C. Notably, the second time period 174b is scanned separately from the first time period 174a due to the overlapping arrival times. For example, as shown in Figure 6A, the data plots of the first and second scans can be combined to form a total data plot. It should be understood that the controller 112 or computing device 114 can separate the mass-to-charge ratio data into as many scans as necessary to obtain a total scan.

[0062] FIG. 7 is a graph of mass-to-charge ratio versus arrival time for the sample glycan data provided in Table A.

[0063] [Table 1]

[0064] 8A and 8B are detailed views of the first and second portions of the graphs in FIG. 7, respectively, showing in more detail the data, including peak widths and groupings for data with gaps of less than 3 ms between peak widths. In particular, the peak widths for each ion, e.g., twice the full width at half maximum (FWHM), are shown in FIGS. 8A and 8B. The detector 106 is maintained at a mass-to-charge ratio for detecting the desired ions for the entire peak width before switching to a different mass-to-charge ratio. That is, the detector 106 detects ions of a first desired mass-to-charge ratio for a first period of time, and then switches to detecting ions of a second mass-to-charge ratio for a second period of time. Additionally, for the detector 106 to switch in time to detecting a second, different mass-to-charge ratio, there must be a time between the peak widths of the first ion and the peak widths of the second ion that is greater than the minimum switching time period, e.g., greater than 3 ms. For example, this is shown in exemplary inset 176 of Figure 8A, which shows a first signal profile 178a for a first ion having a first mass-to-charge ratio m / z-1 separated from a second signal profile 178b for a second ion having a second mass-to-charge ratio m / z-2 by a switching time period 180. The switching time period 180 can be determined based on the capabilities of the detector 106 being utilized and can be, for example, 3 ms. However, it should be understood that the time period for the detector 106 to detect each mass-to-charge ratio can be based on other factors rather than on peak width, or can be a set time period.

[0065] 8A and 8B include multiple groupings 182a-h, shown as dashed boxes, each grouping a plurality of ions that have a switching time period 180 shorter than the respective peak width or predetermined detection window. In many cases, this indicates that not all of the ions in groupings 182a-h can be detected in a single scan, and therefore one or more of the ions in each of groupings 182a-h should be detected in a different scan. However, in some cases, ions that have a switching time period shorter than 180 can also be detected in the same scan. For example, two ions in the first grouping 182a and two ions in the seventh grouping 182g can be detected in the same scan because they have the same mass-to-charge ratio despite having different mobilities and therefore arrival times. Therefore, the detector 106 does not need to switch to detect different mass-to-charge ratios. Additionally, while temporally adjacent ions within a single grouping 182a-h may have insufficient switching time periods 180 between peak widths, such ions may have sufficient switching time periods 180 between peak widths of other ions within the same grouping 182a-h, allowing these ions to be detected in the same scan.

[0066] To ensure that all desired ions are scanned, the computing device 114 analyzes known data, such as the information in Table A, and groups the ions into the minimum number of groups so that all ions in the same group can be detected in the same scan. For example, as shown in Figures 9A-9C, 10A-10C, 11A-11C, 12A-12C, and 13A-13C, the ions in Table A can be grouped into four separate groups, each requiring its own scan.

[0067] 9A-9C are detailed views of the graphs of FIG. 7 identifying data acquired by a first scan of detector 106 within a first dashed box 184. FIG. 9A is a first portion of the graph of FIG. 7 showing data for an arrival time range of 160 ms to 260 ms, FIG. 9B is a second portion of the graph of FIG. 7 showing data for an arrival time range of 260 ms to 400 ms, and FIG. 9C is a third portion of the graph of FIG. 7 showing data for an arrival time range of 625 ms to 975 ms. As can be seen in FIGS. 9A-9C, all of the ions within first dashed box 184 have arrival times between peak widths that are greater than the required switching time period 180.

[0068] 10A-10C are detailed views of the graphs of FIG. 7 identifying data acquired by a second scan of detector 106 within a second dashed box 186. FIG. 10A is a first portion of the graph of FIG. 7 showing data for an arrival time range of 160 ms to 260 ms, FIG. 10B is a second portion of the graph of FIG. 7 showing data for an arrival time range of 260 ms to 400 ms, and FIG. 10C is a third portion of the graph of FIG. 7 showing data for an arrival time range of 625 ms to 975 ms. As can be seen in FIGS. 10A-10C, all of the ions within second dashed box 186 have arrival times between peak widths that are greater than the required switching time period 180.

[0069] 11A-11C are detailed views of the graphs of FIG. 7 that identify data acquired by the third scan of detector 106 within a third dashed-line box 188. FIG. 11A is a first portion of the graph of FIG. 7 showing data for the arrival time range of 160 ms to 260 ms, FIG. 11B is a second portion of the graph of FIG. 7 showing data for the arrival time range of 260 ms to 400 ms, and FIG. 11C is a third portion of the graph of FIG. 7 showing data for the arrival time range of 625 ms to 975 ms. As can be seen in FIGS. 11A-11C, all of the ions within the third dashed-line box 188 have inter-peak arrival times that are greater than the required switching time period 180. Additionally, as shown in FIGS. 11A and 11C, detector 106 does not need to perform scans for the arrival time ranges of 160 ms to 260 ms and 625 ms to 975 ms. This is because all of the ions within those arrival time ranges could be detected during the first and second scans, as shown in Figures 9A, 9C, 10A, and 10C.

[0070] 12A-12C are detailed views of the graphs of FIG. 7 that identify data acquired by the fourth scan of detector 106 within a fourth dashed-line box 190. FIG. 12A is a first portion of the graph of FIG. 7 showing data for the arrival time range of 160 ms to 260 ms, FIG. 12B is a second portion of the graph of FIG. 7 showing data for the arrival time range of 260 ms to 400 ms, and FIG. 12C is a third portion of the graph of FIG. 7 showing data for the arrival time range of 625 ms to 975 ms. As can be seen in FIGS. 12A-12C, all of the ions within the fourth dashed-line box 190 have inter-peak arrival times that are greater than the required switching time period 180. Additionally, as shown in FIGS. 12A and 12C, detector 106 does not need to perform scans for the arrival time ranges of 160 ms to 260 ms and 625 ms to 975 ms. This is because all of the ions within those arrival time ranges could be detected during the first and second scans, as shown in Figures 9A, 9C, 10A, and 10C.

[0071] 13A-C are detailed views of the graph of FIG. 7 identifying the data acquired by all four scans of detector 106 within first, second, third, and fourth dashed boxes 184, 186, 188, 190. FIG. 13A is a first portion of the graph of FIG. 7 showing data for a reach time range of 160 ms to 260 ms, FIG. 13B is a second portion of the graph of FIG. 7 showing data for a reach time range of 260 ms to 400 ms, and FIG. 13C is a third portion of the graph of FIG. 7 showing data for a reach time range of 625 ms to 975 ms.

[0072] In operation, the detector 106 performs a first scan on a first set of ions that have undergone ion mobility separation, e.g., a first packet of ions that have been pulsed into the IMS device 104 and separated on the basis of mobility, by switching to detect a different predefined mass-to-charge ratio at the determined arrival time, e.g., a mass-to-charge ratio and arrival time corresponding to the first dashed box 184 in Figures 9A-9C and 13A-13C. The detector 106 then performs a second scan on a second set of ions that have undergone ion mobility separation, e.g., a second packet of ions that have been pulsed into the IMS device 104 after the first packet has been scanned and separated on the basis of mobility, by switching to detect a different predefined mass-to-charge ratio at the determined arrival time, e.g., a mass-to-charge ratio and arrival time corresponding to the second dashed box 186 in Figures 10A-10C and 13A-13C. The detector 106 then performs a third scan on a third set of ions that have undergone ion mobility separation, e.g., a third packet of ions pulsed to the IMS device 104 after the second packet has been scanned and separated based on mobility, by switching to detect a different predefined mass-to-charge ratio at the determined arrival time, e.g., a mass-to-charge ratio and arrival time corresponding to the third dashed box 188 in Figures 11A-11C and 13A-13C. Finally, the detector 106 performs a fourth scan on a fourth set of ions that have undergone ion mobility separation, e.g., a fourth packet of ions pulsed to the IMS device 104 after the third packet has been scanned and separated based on mobility, by switching to detect a different predefined mass-to-charge ratio at the determined arrival time, e.g., a mass-to-charge ratio and arrival time corresponding to the fourth dashed box 190 in Figures 12A-12C and 13A-13C. The first, second, third, and fourth scans are then aggregated to generate a multi-analyte target IMS-MS data plot. Thus, the system 100 is capable of detecting multiple ions with different mass-to-charge ratios and different or similar mobilities.

[0073] It should be understood that more than four scans or fewer than four scans can be performed on a group of ions, depending on the mass-to-charge ratio, mobility, and arrival time of the ions. Additionally, it should be understood that the detector 106 can be configured to detect particular ions multiple times in multiple scans and repeat the analysis of those ions to increase the acquisition rate and sensitivity for those analytes. For example, ions detected in a first scan can also be detected again in, e.g., a second, third, fourth, etc. scan, if possible, if they overlap with ions detected in those scans and do not adversely affect the detection of those ions. As another example, all of the ions shown in Figures 13A and 13B that are detected in the first scan (shown in the first dashed box 184) can be detected a second time during the third scan (shown in the third dashed box 188) because none of those ions overlap with ions in the third scan.

[0074] 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 shown in the accompanying drawings are non-limiting exemplary embodiments, and that the scope of the present disclosure is defined only by the claims. Features shown or described in connection with one exemplary embodiment may be combined with features of other embodiments. Such modifications and variations are intended to be encompassed within the scope of the present disclosure. Furthermore, in this disclosure, like-named components of embodiments have generally similar configurations, and therefore, within the scope of a particular embodiment, each configuration of each like-named component will not necessarily be described in full detail.

[0075] The subject matter described herein can be implemented in digital electronic circuitry, or in computer software, firmware, or hardware, including the structural means disclosed herein and their structural equivalents or combinations thereof. The subject matter described herein can be implemented as one or more computer program products, such as one or more computer programs tangibly embodied in an information carrier (e.g., in a machine-readable storage device) or embodied in a propagated signal, for execution by or to control the operation of a data processing apparatus (e.g., a programmable processor, a computer, or multiple computers). Computer programs (also known as programs, software, software applications, or code) can be written in any form of programming language, including compiled or interpreted languages, and can be implemented as stand-alone programs or in any form including modules, components, subroutines, or other units suitable for use in a computing environment. A computer program does not necessarily correspond to a file. A program can be stored as a portion of a file that holds other programs or data, in a single file dedicated to the program, or in multiple cooperating files (e.g., a file storing one or more modules, subprograms, or code portions). A computer program can be implemented to be executed on one computer or on multiple computers at one site, or can be distributed across multiple sites and interconnected by a communications network.

[0076] The processes and logic flows described herein, including the method steps of the subject matter described herein, can be performed by one or more programmable processors running one or more computer programs to perform the functions of the subject matter described herein by operating on input data and generating output. The processes and logic flows can also be performed by, and apparatus of the subject matter described herein can be implemented as, special purpose logic circuitry, such as an FPGA (field programmable gate array) or an ASIC (application-specific integrated circuit).

[0077] Processors suitable for executing a computer program include, by way of example, both general-purpose and special-purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, a processor can receive instructions and data from a read-only memory or a random-access memory, or both. The essential elements of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data. Generally, a computer can also include one or more mass storage devices, such as magnetic, magneto-optical, or optical disks, for storing data, or be operatively coupled to receive and / or transmit data from such mass storage devices. Information carriers suitable for carrying computer program instructions and data include all forms of non-volatile memory, including, by way of example, semiconductor memory devices (e.g., EPROM, EEPROM, and flash memory devices); magnetic disks (e.g., internal hard disks or removable disks); magneto-optical disks; and optical disks (e.g., CD and DVD disks). The processor and memory can be incorporated by or in special-purpose logic circuitry.

[0078] To provide for user interaction, the subject matter described herein can be implemented on a computer having a display device, such as a CRT (cathode ray tube) or LCD (liquid crystal display) monitor, for displaying information to the user, as well as a keyboard and pointing device (e.g., a mouse or trackball) through which the user can provide input to the computer. Other types of devices can also be used to provide for user interaction as well. For example, feedback provided to the user can be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback), and input from the user can be received in any form, including acoustic, vocal, or tactile input.

[0079] The techniques described herein may be implemented using one or more modules. As used herein, the term "module" refers to computing software, firmware, hardware, and / or various combinations thereof. However, at a minimum, a module should not be interpreted as software not implemented on hardware, firmware, or recorded on a non-transitory processor-readable recordable storage medium (i.e., a module is not software itself). In practice, a "module" should always be interpreted to include at least some physical, non-transitory hardware, such as a processor or part of a computer. Two different modules may share the same physical hardware (e.g., two different modules may use the same processor and network interface). The modules described herein may be combined, integrated, separated, and / or duplicated to accommodate various applications. Additionally, functionality described herein as being performed by a particular module may be performed by one or more other modules and / or by one or more other devices instead of or in addition to the functionality performed by that particular module. Furthermore, modules may be implemented across multiple devices and / or other components, local or remote from each other. Additionally, modules can be moved from one device and added to another device and / or included in both devices.

[0080] The subject matter described herein can be implemented in a computing system that includes back-end components (e.g., data servers), middleware components (e.g., application servers), or front-end components (e.g., client computers having a graphical user interface or web browser through which a user can interact with an implementation of the subject matter described herein), or any combination of such back-end, middleware, and front-end components. The components of the system can be interconnected by any form or medium of digital data communication, e.g., a communications network. Examples of communications networks include local area networks ("LANs") and wide area networks ("WANs"), e.g., the Internet.

[0081] Throughout this specification and the claims, approximation language can be used to modify any quantitative expression that can vary within acceptable limits without causing a change in the relevant basic function. Thus, values ​​modified by one or more terms such as "about" and "substantially" are not limited to the exact value specified. In at least some cases, approximation language can correspond to the precision of an instrument for measuring the value. Throughout this specification and the claims, range limits can be combined and / or interchanged, and such ranges are identified and include all subranges contained within them, unless the context or language dictates otherwise.

Claims

1. 1. A system for acquiring full resolution ion mobility data comprising: an ion mobility separation device configured to receive the stream of ions, direct at least a portion of the stream of ions through the ion mobility separation device, and separate the ions in the portion based on ion mobility; an ion detector configured to receive the portion of the stream of ions from the ion mobility separation device, detect ions having a predetermined mass-to-charge ratio during the dwell time, and generate one or more signals in response to detecting ions having the predetermined mass-to-charge ratio; a data acquisition system configured to receive one or more signals from the ion detector and generate a time-dependent ion signal based on the one or more signals received from the ion detector, the time-dependent ion signal representing the intensity of the one or more signals at a plurality of different arrival time periods during a dwell time; The system includes an ion mobility separation device, an ion detector, and a controller in communication with a data acquisition system.

2. 10. The system of claim 1, wherein the data acquisition system is a high bandwidth data acquisition system.

3. 3. The system of claim 2, wherein the high bandwidth data acquisition system is an analog-to-digital converter and the one or more signals produced by the ion detector are analog signals.

4. 4. The system of claim 3, wherein the analog-to-digital converter has a resolution of at least 8 bits.

5. 2. The system of claim 1, wherein the data acquisition system is configured to separate the dwell time into a plurality of sub-time periods, separately sum the received one or more signals for each of the plurality of sub-time periods, and generate a time-dependent ion signal based on the sum and the plurality of sub-time periods.

6. 6. The system of claim 5, wherein the data acquisition system has a bandwidth greater than 1 kHz.

7. 10. The system of claim 1, wherein the ion mobility separation device is configured to generate a travelling driving potential configured to guide ions through the ion mobility separation device and separate the ions based on ion mobility.

8. 10. The system of claim 1, wherein the ion mobility separation device includes an accumulation region and an ion mobility separation path, the accumulation region configured to accumulate ions into one or more ion packets and pulse the one or more ion packets into the ion mobility separation path.

9. 1. A method for acquiring full resolution ion mobility data, comprising: introducing a stream of ions into an ion mobility separation device; directing, by an ion mobility separation device, at least a portion of the stream of ions through the ion mobility separation device to an ion detector; separating the portion of ions based on ion mobility with an ion mobility separation device; receiving the ions by an ion detector; detecting ions having a predetermined mass-to-charge ratio during the dwell time with an ion detector; generating, by the ion detector, one or more signals in response to detection of ions having a predetermined mass-to-charge ratio; receiving, by a data acquisition system, one or more signals from the ion detector; and generating, by a data acquisition system, a time-dependent ion signal based on the one or more signals received from the ion detector, the time-dependent ion signal representing the intensity of the one or more signals at a plurality of different arrival time periods during the dwell time.

10. The method of claim 9 , comprising a controller in communication with the ion mobility separation device, the ion detector, and the data acquisition system.

11. 10. The method of claim 9, wherein the data acquisition system is a high bandwidth data acquisition system.

12. 12. The method of claim 11, wherein the high bandwidth data acquisition system is an analog-to-digital converter and the one or more signals produced by the ion detector are analog signals.

13. 13. The method of claim 12, wherein the analog-to-digital converter has a resolution of at least 8 bits.

14. Separating the dwell time into a plurality of sub-time periods by a data acquisition system; separately summing the received one or more signals for each of a plurality of sub-time periods; generating a time-dependent ion signal based on the sum and the plurality of sub-time periods; 10. The method of claim 9, comprising:

15. 15. The method of claim 14, wherein the data acquisition system has a bandwidth greater than 1 kHz.

16. generating a travel driving potential with an ion mobility separation device that guides ions through the ion mobility separation device and separates the ions based on ion mobility; 10. The method of claim 9, comprising:

17. 10. The method of claim 9, wherein the ion mobility separation device includes an accumulation region and an ion mobility separation path, the accumulation region configured to accumulate ions into one or more ion packets and pulse the one or more ion packets into the ion mobility separation path.

Images