Reduced pressure FAIMS and dual ion source

Abstract

This specification describes devices, systems, and methods for manipulating ion flows. Aspects of this disclosure describe an ion manifold comprising an ion manifold inlet, an ion repeller manifold, a first ion optical system configured to receive an ion flux through the ion manifold inlet, and a second ion optical system configured to receive an output of the ion flux through the first ion optical system, the second ion optical system having a plurality of outputs for splitting the ion flux into a plurality of ion flows.

Description

Technical Field

[0001] (Cross-Reference to Related Applications) This application claims the benefit of U.S. Provisional Application No. 63 / 592,198, filed October 22, 2023, and U.S. Provisional Application No. 63 / 644,411, filed May 8, 2024, both of which are incorporated herein by reference in their entireties.

Background Art

[0002] Mass spectrometry provides, for example, a rich analysis of the mass-to-charge ratio of one or more molecules in a biological sample, enabling high-precision identification or screening capabilities for a given molecular target. However, mass spectrometric analysis of ionized biological samples is a time-intensive process, requiring on the order of 20 to 40 minutes to analyze a single sample. There exists an unmet need for improved systems that can reduce the time required for mass spectrometric analysis of biological samples without sacrificing measurement resolution. Furthermore, there also exists a need for improved mass spectrometry devices with improved detection, sensitivity, accuracy, and / or precision, particularly when analyzing complex biological samples.

Summary of the Invention

Means for Solving the Problems

[0003] Aspects of the present disclosure describe an ion manifold, the ion manifold comprising an ion manifold inlet, an ion repeller manifold, first ion optics configured to receive an ion flux through the ion manifold inlet, and second ion optics configured to receive an output of the ion flux through the first ion optics, wherein the second ion optics comprises a plurality of outputs that split the ion flux into a plurality of ion streams.

[0004] Provided herein is an ion manifold comprising: (a) an orthogonal ion manifold inlet; (b) a first ion optical system configured to receive an ion flux through the ion manifold inlet, wherein the ion inlet is located inside the first ion optical system; and (c) a second ion optical system configured to receive the output of an ion flux through the first ion optical system, wherein the second ion optical system comprises a plurality of outputs for splitting the ion flux into a plurality of ion streams. Further provided is an ion manifold in which the first and second ion optical systems comprise one or more electrical conduction compartments, each comprising one or more through-holes. Further provided is an ion manifold in which one or more electrical conduction compartments are independently controllable. Further provided is an ion manifold in which one or more electrical conduction compartments are energized with RF and / or DC voltages. Further provided is an ion manifold in which a first ion optical system and a second ion optical system each comprise an electrodynamic ion funnel. Further provided is an ion manifold in which a first ion optical system and a second ion optical system each comprise independently different pressures. Further provided is an ion manifold in which the ion manifold further comprises an inline ion inlet. Further provided is an ion manifold in which the method further includes the step of providing a calibration ion flux into the first ion optical system via an inline ion manifold inlet. Further provided is an ion manifold in which the ion flux from the orthogonal ion inlet and the ion flux from the inline ion manifold inlet are offset by 1 to 5 mm.Further provided is an ion manifold, the ion manifold further comprising an ion repeller manifold, (i) positioned such that an axis along the normal vector of the surface of the ion repeller manifold is perpendicular to the central axis of the ion manifold inlet, and (ii) configured to direct the path of the ion flux into a first ion optical system. Further provided is an ion manifold, the ion manifold having an inline manifold inlet that penetrates the ion repeller manifold. Further provided is an ion manifold, the ion repeller manifold comprising a partitioned plate, the ion repeller manifold configured to allow different voltages. Further provided is an ion manifold, the repeller, the ion manifold inlet, and the first ion optical system are at least partially contained within a first chamber. Further provided is an ion manifold, the second ion optical system is at least partially contained within a second chamber distinct from the first chamber. Furthermore, an ion manifold is provided, wherein a reduced-pressure FAIMS (High Electric Field Asymmetric Waveform Ion Mobility Spectrometer) device is configured to receive ions from a first ion optical system and selectively output ions to a second ion optical system. Furthermore, an ion manifold is provided, wherein a reduced-pressure FAIMS (High Electric Field Asymmetric Waveform Ion Mobility Spectrometer) device is configured to receive ions from a first ion optical system and selectively output multiple-charged ions to a second ion optical system, compared with single-charged ions.

[0005] Provided herein is a method for generating multiple ion streams, comprising the steps of (a) providing an ion flux to the orthogonal ion manifold inlet of an ion manifold, the ion manifold comprising (i) an orthogonal ion manifold inlet, (ii) a first ion optical system configured to receive the ion flux through the ion manifold inlet, the ion inlet comprising a first ion optical system located inside the first ion optical system, and (iii) a second ion optical system configured to receive the output of the ion flux through the first ion optical system, the second ion optical system comprising a Further provided is a method wherein one or more electrical conductor compartments are energized with RF and / or DC voltages. Further provided is a method wherein a first ion optical system and a second ion optical system each comprise an electrodynamic ion funnel. Further provided is a method wherein a first ion optical system and a second ion optical system each comprise different pressures independently. Further provided is a method wherein the ion manifold further comprises an inline ion inlet. Further provided is a method further comprising the step of providing a calibration ion flux into the first ion optical system via an inline ion manifold inlet. Further provided is a method wherein the ion flux from the orthogonal ion inlet and the ion flux from the inline ion manifold inlet are offset by 1 to 5 mm.Further provided is a method comprising an ion repeller manifold, wherein the ion manifold is further positioned such that (i) an axis along the normal vector of the surface of the ion repeller manifold is perpendicular to the central axis of the ion manifold inlet, and (ii) a path of ion flux is directed into a first ion optical system. Further provided is a method wherein the inline manifold inlet penetrates the ion repeller manifold. Further provided is a method wherein the ion repeller manifold comprises a partitioned plate, and the ion repeller manifold is configured to allow different voltages. Further provided is a method wherein the repeller, the ion manifold inlet, and the first ion optical system are at least partially contained within a first chamber. Further provided is a method wherein the second ion optical system is at least partially contained within a second chamber, which is different from the first chamber. Furthermore, a method is provided in which a depressurized FAIMS (High Electric Field Asymmetric Waveform Ion Mobility Spectrometer) device is configured to receive ions from a first ion optical system and selectively output ions to a second ion optical system. Furthermore, a method is provided in which a depressurized FAIMS (High Electric Field Asymmetric Waveform Ion Mobility Spectrometer) device is configured to receive ions from a first ion optical system and selectively output multiple charged ions to a second ion optical system, compared with single-charged ions.

[0006] Provided herein is an ion mobility device comprising: a first substrate plate comprising a coplanar first and second outer electrodes and a first separation electrode; and a second substrate plate comprising a coplanar third and fourth outer electrodes and a second separation electrode, wherein the first and second substrate plates are substantially parallel. Further provided herein is an ion mobility device wherein the distance between the first plate and the second plate is 4 to 12 mm. Further provided herein is an ion mobility device wherein the first, second, third, and fourth outer electrodes are configured as RF confinement electrodes, confining an ion beam to the center of the device. Furthermore, this specification provides an ion mobility device wherein the region surrounding the first and second separation electrodes has a pressure of 20 torr or less. Furthermore, this specification provides an ion mobility device wherein the device is provided with guardrail electrodes on each side of the device. Furthermore, this specification provides an ion mobility device wherein the guardrail electrodes have a DC gradient. Furthermore, this specification provides an ion mobility device wherein a voltage is applied to the first separation electrode. Furthermore, this specification provides an ion mobility device wherein a FAIMS separation voltage is applied to the first separation electrode. Furthermore, this specification provides an ion mobility device wherein a FAIMS separation voltage is applied only to the first separation electrode. Furthermore, this specification provides an ion mobility device wherein a FAIMS separation voltage of at least 800V is applied to at least one separation electrode.Furthermore, provided herein are ion mobility devices wherein a FAIMS separation voltage of at least 2,000 V is applied to at least one separation electrode. Furthermore, provided herein are ion mobility devices wherein a FAIMS separation voltage of at least 2,000 V is applied to at least one separation electrode, and the region surrounding the first and second separation electrodes has a pressure of about 20 torr. Furthermore, provided herein are ion mobility devices wherein the ion manifold comprises the devices disclosed herein.

[0007] Provided herein is a method for spatially separating ions, comprising the steps of: providing an ion flux to an ion mobility device described herein; applying a high-voltage RF waveform to a separation electrode; applying an ion confinement waveform to an outer electrode; and selecting permeable ions based on mobility to generate a mobility-selective ion flow.

[0008] Provided herein is a reduced-pressure electric field asymmetric ion mobility device comprising: a sealed mobility chamber having an ion inlet and an ion outlet located at opposite ends and configured to be filled with an inert gas at a pressure below atmospheric pressure; at least one inner electrode longitudinally positioned between the ion inlet and ion outlet of the sealed mobility chamber; at least one outer electrode longitudinally positioned between the ion inlet and ion outlet of the sealed mobility chamber, the outer electrode being positioned such that the inner electrode is at least partially sealed within the outer electrode; and one or more power sources configured to deliver a waveform to the inner electrode or the outer electrode, the waveform being configured to differentially deflect ions having different ion mobilities based on the interaction of ions with the waveform and the inert gas, the differential deflection being configured to selectively remove ions having a mobility corresponding to a single charged species before the species reaches the ion outlet, and the inner electrode and the outer electrode being substantially planar, one or more power sources. Furthermore, provided herein are reduced-pressure electric field asymmetric ion mobility devices, wherein one or more power sources provide a waveform comprising at least two sinusoidal waves that are phase-shifted relative to each other. Furthermore, provided herein are reduced-pressure electric field asymmetric ion mobility devices, wherein the waveform is delivered to an outer electrode. Furthermore, provided herein are reduced-pressure electric field asymmetric ion mobility devices, wherein the outer electrode comprises at least two ion outlets. Furthermore, provided herein are reduced-pressure electric field asymmetric ion mobility devices, wherein the reduced-pressure electric field asymmetric ion mobility device further comprises one or more sets of ion optics configured to guide ions into an ion inlet, out of an ion outlet, or a combination thereof.Furthermore, provided herein are reduced-pressure electric field asymmetric ion mobility devices in which multiple charged ions are transmitted from the ion inlet to the ion outlet in less than about 100 milliseconds (e.g., less than about 50 ms, 25 ms, 10 ms, 5 ms, or 3 ms). Furthermore, provided herein are reduced-pressure electric field asymmetric ion mobility devices in which the electrodes are configured to be independently controllable. Furthermore, provided herein are reduced-pressure electric field asymmetric ion mobility devices in which the electrodes are located at or near the output.

[0009] Provided herein is a method for separating single-charged ions from multiple-charged ions, comprising the steps of (a) providing an ion flux to the ion inlet of a reduced-pressure electric field asymmetric ion mobility device, the reduced-pressure electric field asymmetric ion mobility device comprising: a sealed mobility chamber having an ion inlet and an ion outlet located at opposite ends and configured to be filled with an inert gas at a pressure below atmospheric pressure; at least one inner electrode longitudinally positioned between the ion inlet and ion outlet of the sealed mobility chamber; at least one outer electrode longitudinally positioned between the ion inlet and ion outlet of the sealed mobility chamber; and one or more power sources configured to deliver a waveform to the inner electrode or the outer electrode, wherein the waveform is transmitted to the ions and A method comprising: (b) using one or more power sources to differentially deflect ions having different ion mobilities based on the interaction of a waveform and an inert gas, wherein the differential deflection is configured to selectively remove ions having a mobility corresponding to a single charge species before the species reaches the ion outlet; (c) using one or more power sources to apply a waveform, thereby substantially preventing ions in an ion flux having a mobility corresponding to a single charge species from reaching the ion outlet of a reduced-pressure electric-field asymmetric ion mobility device; and (d) obtaining a multi-charged ion population at the ion outlet of the reduced-pressure electric-field asymmetric ion mobility device, enriched with ions corresponding to multiple charge species. Further provided herein is a method wherein one or more power sources provide a waveform comprising at least two sinusoidal waves that are phase-shifted relative to each other. Further provided herein is a method wherein the waveform is delivered to an outer electrode. Further provided herein is a method wherein the outer electrode comprises at least two ion outlets. Furthermore, provided herein are methods further comprising one or more sets of ion optical systems configured to guide ions into an ion inlet, out of an ion outlet, or a combination thereof.Furthermore, provided herein are methods wherein multiple charged ions are transmitted from the ion inlet to the ion outlet in less than about 100 milliseconds (e.g., less than about 50 ms, 25 ms, 10 ms, 5 ms, or 3 ms). Furthermore, provided herein are methods wherein the electrodes are configured to be independently controllable. Furthermore, provided herein are methods wherein the electrodes are positioned at or near the output.

[0010] Additional aspects and advantages of this disclosure will be readily apparent to those skilled in the art from the following detailed description, which illustrates and describes only the illustrative embodiments of this disclosure. As will be recognized, other and different embodiments are possible, some of their details of which are modifiable in various obvious ways without departing from this disclosure. Therefore, the drawings and description should be considered illustrative, not restrictive, by their nature. [Brief explanation of the drawing]

[0011] Novel features of the present invention are described in detail in the appended claims. A deeper understanding of the features and advantages of the present invention will be obtained by referring to the following detailed description, which describes illustrative embodiments in which the principles of the present invention are utilized, and to the accompanying drawings (also referred to herein as figures, "Figure" and "FIG").

[0012] [Figure 1] Figure 1 shows an exemplary schematic diagram of an ion manifold, as described in some embodiments of this specification.

[0013] [Figure 2] Figure 2 shows illustrative schematic diagrams of a first ion optical system and a second ion optical system, as described in some embodiments of this specification.

[0014] [Figure 3]Figure 3 shows an exemplary computer system programmed or otherwise configured to implement the methods provided herein, as described in some embodiments of the present specification.

[0015] [Figure 4] Figure 4 shows an exemplary workflow diagram for a method of generating multiple ion streams, as described in some embodiments of the present specification.

[0016] [Figure 5A] Figure 5A shows an example of a planar FAIMS (high-field asymmetric waveform ion mobility spectrometry) configuration, as described in some embodiments of the present specification, showing top and bottom PCBs (printed circuit boards).

[0017] [Figure 5B] Figure 5B shows an example of a planar FAIMS configuration, as described in some embodiments of the present specification, illustrating FAIMS and RF polarities.

[0018] [Figure 6] Figure 6 shows an exemplary cross-sectional schematic diagram of a FAIMS configuration with top and bottom PCBs, as described in some embodiments of the present specification.

[0019] [Figure 7] Figure 7 shows another exemplary cross-sectional schematic diagram of a FAIMS configuration, as described in some embodiments of the present specification.

[0020] [Figure 8] Figure 8 shows an exemplary schematic diagram of a FAIMS configuration with separate segmented electrodes, as described in some embodiments of the present specification.

[0021] [Figure 9A] Figure 9A shows an exemplary front schematic diagram of a device configuration comprising an assembly of FAIMS, as described in some embodiments of the present specification.

[0022] [Figure 9B] FIG. 9B shows an exemplary schematic front view of a device configuration comprising a FAIMS assembly with shared electrodes, as described in some embodiments herein.

[0023] [Figure 10] FIG. 10 shows an exemplary workflow diagram for a front-end interface, as described in some embodiments herein.

[0024] [Figure 11] FIG. 11 shows an exemplary high-level schematic diagram of a planar FAIMS configuration, as described in some embodiments herein.

[0025] [Figure 12A] FIG. 12A shows an isometric top view of a FAIMS front-end interface, as described in some embodiments herein.

[0026] [Figure 12B] FIG. 12B shows an isometric top view of a FAIMS front-end interface, as described in some embodiments herein.

[0027] [Figure 12C] FIG. 12C shows a top view of a FAIMS front-end interface, as described in some embodiments herein.

[0028] [Figure 12D] FIG. 12D shows a bottom view of a FAIMS front-end interface, as described in some embodiments herein.

[0029] [Figure 12E] FIG. 12E shows a side view of a FAIMS front-end interface, as described in some embodiments herein.

[0030] [Figure 12F] Figure 12F shows a side view of the FAIMS front-end interface, as described in some embodiments of this specification.

[0031] [Figure 12G] Figure 12G shows a cross-sectional side view of a FAIMS front-end interface having a planar FAIMS configuration, as described in some embodiments of this specification.

[0032] [Figure 12H] Figure 12H shows an exploded isometric top view of a FAIMS front-end interface having a planar FAIMS configuration, as described in some embodiments of this specification.

[0033] [Figure 13A] Figure 13A shows an isometric top view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0034] [Figure 13B] Figure 13B shows an isometric top view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0035] [Figure 13C] Figure 13C shows a top view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0036] [Figure 13D]Figure 13D shows a bottom view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0037] [Figure 13E] Figure 13E shows a side view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0038] [Figure 13F] Figure 13F shows a rear view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0039] [Figure 13G] Figure 13G shows a cross-sectional side view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0040] [Figure 13H] Figure 13H shows an isometric exploded view of the device, which includes a FAIMS front-end interface coupled to a TWIMS (Traveling Wave Ion Mobility Spectroscopy) interface, as described in some embodiments herein.

[0041] [Figure 14A] Figure 14A shows an exemplary configuration for a FAIMS device.

[0042] [Figure 14B]Figure 14B shows the results of ion isolation with and without the FAIMS device. With the FAIMS device off, the major ions included 621.57, 1,221.25, 1,521.10, and 1,820.95 m / z. With the FAIMS device on (CV=5 volts), the major ions were 921.41 and 621.57.

[0043] [Figure 14C] Figure 14C shows a graph of resolution using experiments with the FAIMS device in the ON (CV=6.5V) or OFF state.

[0044] [Figure 14D] Figure 14D shows a graph of ions measured using a CV lamp. Lamping the CV allows filtering as a function of their mass. High mass transmittances were above an average QToF of 6,600. Varying the CV selectively transmits ions based on their mass; lower CVs transmit higher masses, and higher CVs transmit lower masses.

[0045] [Figure 14E] Figure 14E shows graphs of the CV ramp and its mass dependence, with intensity (cps) plotted against CV (volts).

[0046] [Figure 14F] Figure 14F shows a graph of the CV ramp and its mass dependence, with the relative intensity (percent) plotted against CV (volts).

[0047] [Figure 14G] Figure 14G shows a graph of CV versus ion population. Varying CV allows for the identification of ions based on their charge state. Here, lower CVs favor single-charged ions over double-charged ions. The opposite was observed for higher CVs.

[0048] [Figure 14H] Figure 14H shows a graph of multiple charged ions with the range m / z 900 to m / z 930 magnified.

[0049] [Figure 15] Figure 15 shows a schematic diagram of an exemplary device described herein, which includes an orthogonal ion manifold inlet, an inline ion manifold inlet, a repeller plate, a reduced-pressure FAIMS, an ion funnel, and a four-branched ion outlet.

[0050] [Figure 16] Figure 16 shows an image of a pair of DC guardrails for use on each side of the FAIMS device described herein. [Modes for carrying out the invention]

[0051] Detailed explanation Various embodiments of the Disclosure are illustrated and described herein, but it will be obvious to those skilled in the art that such embodiments are provided only as examples. Numerous modifications, changes, and substitutions can be conceived by those skilled in the art without departing from the Disclosure. It should be understood that various alternatives to the embodiments of the Disclosure described herein may be adopted. Section headings used herein are for organizational purposes only and should not be construed as limiting the subject matter described herein.

[0052] In some embodiments, the Disclosure describes an ion manifold configured for the multiple detection of one or more ion streams (e.g., derived from a biological sample) using one or more mass spectrometer-based sensors. In some embodiments, the Disclosure describes an ion manifold configured to receive an ion stream and to split or divide the ion stream into multiple ion streams. In some cases, for example, a first ion stream split from the input ion stream may be detected using a first mass spectrometer sensor, and a second ion stream split from the input ion stream may be detected using a second mass spectrometer. By splitting or dividing the input ion stream, the analysis time of the input stream for mass spectrometry can be reduced to at least about 5 seconds, 15 seconds, 20 seconds, 30 seconds, 1 minute, 5 minutes, 10 minutes, 20 minutes, 30 minutes, or at least about 1 hour. In some cases, parallel analysis may provide improved detection, sensitivity, accuracy, and / or precision compared to non-multiplexed methods using the same analysis time. (Example ion manifold)

[0053] In some embodiments, Figure 1 shows an ion manifold 100 comprising an ion manifold inlet 106, an ion repeller manifold 104, a first ion optics system 116, a second ion optics system 118, a port 130, or any combination thereof. In some embodiments, the first ion optics system 116 is configured to receive an ion flux 132 through the ion manifold inlet 106. In some embodiments, the second ion optics system 118 is configured to receive an output of the ion flux through the first ion optics system 116. In some embodiments, the second ion optics system 118 comprises multiple outputs 114 that split or divide the ion flux into multiple ion streams. In some embodiments, the first ion optics system 116, the second ion optics system 118, or a combination thereof is configured to output an ion stream of one or more ions having a range of mass / charge. For example, the second ion optics system may be configured to output ions within a range including about 400 to about 900 mass / charge. In some embodiments, the second ion optical system is configured to transmit at least 50% (e.g., at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%) of the ions received within the second ion optical system. In some embodiments, the first ion optical system 116 and the second ion optical system 118 include an ion funnel. In some embodiments, the first ion optical system 116 and the second ion optical system 118 include one or more electrical conductor compartments 124. In some embodiments, one or more electrical conductor compartments 124 may include a printed circuit board (PCB). In some embodiments, the ion manifold inlet 106 may include a heated ion manifold inlet. In some embodiments, the ion manifold inlet 106 includes a slotted capillary. In some embodiments, the slotted capillary may have a rectangular cross-sectional geometric shape 107. In some cases, the rectangular cross-sectional geometric shape 107 of the slotted capillary tube provides efficient ionization of one or more molecules in a sample to improve the accuracy of ion manifold analysis and detection of one or more molecules or molecular signatures.In some embodiments, the ion manifold inlet 106 has a circular or oval cross-sectional geometric shape. In some embodiments, the capillary has at least one dimension which is less than about 250 microns, less than about 150 microns, or less than about 100 microns. In some embodiments, the capillary has at least one dimension which is less than 250 microns and at least one dimension which is greater than 1 mm. In some embodiments, the capillary has at least one dimension which is less than 150 microns and at least one dimension which is greater than 2 mm.

[0054] In some embodiments, the ion repeller manifold 104, the ion manifold inlet 106, or the first ion optics 116 is at least partially contained within the first chamber 110. In some embodiments, the second ion optics 118 is at least partially contained within the second chamber 112, which is different from the first chamber 110. In some embodiments, the first chamber 110 has a first pressure and the second chamber 112 has a second pressure, with the first pressure being higher than the second pressure. In some embodiments, the first chamber 110 has a first pressure and the second chamber 112 has a second pressure, with the first pressure being lower than the second pressure. In some embodiments, the first chamber 110 has a pressure of at least about 8 torr. In some embodiments, the second chamber 112 has a pressure of at least about 2 torr. In some embodiments, the second chamber 112 has a pressure of about 6 torr or less. In some embodiments, the ion flux 132 is supplied from a multi-emitter array to the ion manifold inlet 106 by electrospray ionization. In some embodiments, the multi-emitter array may be a microfluidic multi-emitter with five or more emitters. In some embodiments, the ion repeller manifold 104 comprises a partitioned plate with one or more compartments (105, 108, 109). In some embodiments, the ion repeller manifold 104 is configured to allow different voltages that can improve the efficiency of delivering ions into the ion funnel. In some embodiments, the partitioned plate (105, 108, 109) comprises at least about two compartments or at least about three compartments. In some embodiments, the central axes of the first and second ion optics 128 are perpendicular to the central axis of the ion manifold inlet 130. In some embodiments, the central axis of the ion manifold inlet 130 is perpendicular to the axis normal to the surface of the ion repeller manifold 128. In some embodiments, the first electrode section 105 of the ion repeller manifold may output a lower voltage than the adjacent second electrode section 108 of the ion repeller manifold 104.In some embodiments, the ion repeller manifold 104 has a voltage gradient across its longitudinal length. In some embodiments, the ion manifold 100 has a port 102 which is fluidly coupled to the ion manifold 100, and the port 102 is configured to pressurize a first chamber 110, a second chamber 112, or a combination thereof. In some embodiments, the central axis of the port 130 is collinear with the central axis of the ion manifold inlet 130. While the primary purpose of the port 102 is to pressurize the first chamber 110, the second chamber 112, or a combination thereof, it has the unexpected benefit of improving the signal and reducing noise by removing the solvent from the ion flux 132 provided at the ion manifold inlet. In some embodiments, the first ion optics 116 or the second ion optics 118 includes a linear DC gradient provided by one or more electrical conduction sections 124 traversing the longitudinal length of the first ion optics 116 or the second ion optics 118. In some embodiments, one or more electrical conduction sections 124 of the first ion optics 116 or the second ion optics 118 include up to about four DC current (DC) conductance limits. In some embodiments, the first electrical conduction section of one or more electrical conduction sections 124 provides a first signal with a first phase, and the second electrical conduction section of one or more electrical conduction sections 124 provides a second signal with the opposite phase of the first phase.

[0055] Figure 1 depicts an ion manifold 100 with an ion manifold inlet 106 configured such that the ion flux 132 enters the ion manifold 100 in a direction perpendicular to the linear axis 128, although the ion manifold inlet 106 may be configured such that the ion flux 132 enters parallel to the linear axis 128. In such a case, the ion repeller manifold 104 may be omitted, and the ion manifold inlet 106 is...

[0056] Those skilled in the art will understand, based on the teachings of this application, that other components may also be included in the ion manifold 100. For example, additional ports may be included to provide different vacuum pressures, and pressure sensors, electrical feedthroughs, and equivalents may be included. In some embodiments, the ion manifold may include a FAIMS device between the first ion optical system and the second optical system, as disclosed herein.

[0057] In some embodiments, the first ion optical system 116 or the second ion optical system 118 comprises one or more electrical conductor compartments 124, as shown in Figure 2. In some embodiments, one or more electrical conductor compartments 124 may comprise one or more through-holes 126. In some embodiments, one or more through-holes 126 may have a circular, oval, polygonal, or square shape, as shown in Figure 2. In some embodiments, one or more electrical conductor compartments 124 may have a center-to-center spacing of at least about 1 millimeter (mm). In some embodiments, one or more through-holes are provided along a linear axis 128 on the surface of one or more electrical conductor compartments 124. In some embodiments, the positioning of two or more through-holes is symmetrical. In some embodiments, two or more through-holes in one or more electrical conductor compartments are adjacent or in contact with each other, as shown in Figure 2. In some embodiments, the first electrical conductor compartment 124 has a first dimension of the through-hole, and the adjacent second electrical conductor compartment 124 has a second dimension that is smaller than the first dimension. In some cases, one or more electrical conductor compartments 124 may form the inner geometry of the first ion optical system 122 and the second ion optical system 123. In some cases, the inner geometry of the first ion optical system 122 and the second ion optical system 123 may comprise one or more compartments. In some cases, one or more compartments of the inner geometry may comprise a linear unsloped compartment, a linear positively sloped compartment, a linear negatively sloped compartment, or any combination thereof, as shown in Figure 2. In some cases, one or more electrical conductor compartments 124 may split or divide the ion flow into multiple ion flows, as described elsewhere in this specification. By splitting the ion flow into multiple ion flows, multiple detection and further processing of individual ion populations, for example, ions within a given mass / charge ratio band, can be isolated, measured, or analyzed. The effect of this ion flow multiplexing and detection is to reduce the time otherwise required to detect molecules in the ion flow. Therefore, an additional component may receive a divided ion flux from a second ion optical system.For example, two or more ion bundles output from the second ion optical system may be operably coupled to different mass spectrometers (e.g., different time-of-flight mass spectrometers).

[0058] In some embodiments, one or more electrical conductor sections 124 may output voltages ranging from approximately 0V to approximately 500V. In some embodiments, one or more electrical conductor sections may output voltages ranging from approximately 0V to approximately 20V, approximately 0V to approximately 40V, approximately 0V to approximately 50V, approximately 0V to approximately 100V, approximately 0V to approximately 150V, approximately 0V to approximately 300V, approximately 0V to approximately 500V, approximately 20V to approximately 40V, approximately 20V to approximately 50V, approximately 20V to approximately 100V, approximately 20V to approximately 150V, approximately 20V to approximately 300V, approximately 20V to approximately 500V, approximately 40V to approximately 50V, and approximately 4 The electrical conductors may output voltages of approximately 0V to 100V, 40V to 150V, 40V to 300V, 40V to 500V, 50V to 100V, 50V to 150V, 50V to 300V, 50V to 500V, 100V to 150V, 100V to 300V, 100V to 500V, 150V to 300V, 150V to 500V, or 300V to 500V. In some embodiments, one or more electrical conductors may output voltages of approximately 0V, 20V, 40V, 50V, 100V, 150V, 300V, or 500V. In some embodiments, one or more electrical conductor sections may output voltages of at least about 0V, about 20V, about 40V, about 50V, about 100V, about 150V, or about 300V. In some embodiments, one or more electrical conductor sections may output voltages of up to about 20V, about 40V, about 50V, about 100V, about 150V, about 300V, or about 500V.

[0059] In some embodiments, one or more electrical conductor compartments 124 may output a current of about 0 μA to about 100 μA. In some embodiments, one or more electrical conductor compartments 124 may output currents of about 0 μA to about 10 μA, about 0 μA to about 20 μA, about 0 μA to about 40 μA, about 0 μA to about 50 μA, about 0 μA to about 80 μA, about 0 μA to about 100 μA, about 10 μA to about 20 μA, about 10 μA to about 40 μA, about 10 μA to about 50 μA, about 10 μA to about 80 μA, about 1 The currents may be output in the range of 0μA to approximately 100μA, approximately 20μA to approximately 40μA, approximately 20μA to approximately 50μA, approximately 20μA to approximately 80μA, approximately 20μA to approximately 100μA, approximately 40μA to approximately 50μA, approximately 40μA to approximately 80μA, approximately 40μA to approximately 100μA, approximately 50μA to approximately 80μA, approximately 50μA to approximately 100μA, or approximately 80μA to approximately 100μA. In some embodiments, one or more electrical conductor compartments 124 may output currents of approximately 0μA, approximately 10μA, approximately 20μA, approximately 40μA, approximately 50μA, approximately 80μA, or approximately 100μA. In some embodiments, one or more electrical conductor compartments 124 may output a current of at least about 0 μA, about 10 μA, about 20 μA, about 40 μA, about 50 μA, or about 80 μA. In some embodiments, one or more electrical conductor compartments 124 may output a current of up to about 10 μA, about 20 μA, about 40 μA, about 50 μA, about 80 μA, or about 100 μA.

[0060] In some embodiments, ion flux is generated through electrospray ionization by applying a voltage of about 0kV to about 5kV. In some embodiments, ion flux is generated through electrospray ionization by applying a voltage of about 0.5kV, about 1kV, about 1.5kV, about 2kV, about 2.5kV, about 3kV, about 3.5kV, about 4kV, about 4.5kV, or about 5kV. In some embodiments, ion flux is generated through electrospray ionization by applying a voltage of at least about 0.5kV, about 1kV, about 1.5kV, about 2kV, about 2.5kV, about 3kV, about 3.5kV, about 4kV, or about 4.5kV. In some embodiments, the ion flux is generated through electrospray ionization by applying voltages of up to approximately 0.5kV, 1kV, 1.5kV, 2kV, 2.5kV, 3kV, 3.5kV, 4kV, 4.5kV, or 5kV.

[0061] In some embodiments, the ion flux is generated through electrospray ionization by utilizing a current of approximately 0 μA to approximately 100 μA. In some embodiments, the ion flux is approximately 0 μA to approximately 10 μA, approximately 0 μA to approximately 20 μA, approximately 0 μA to approximately 40 μA, approximately 0 μA to approximately 50 μA, approximately 0 μA to approximately 80 μA, approximately 0 μA to approximately 100 μA, approximately 10 μA to approximately 20 μA, approximately 10 μA to approximately 40 μA, approximately 10 μA to approximately 50 μA, approximately 10 μA to approximately 80 μA, approximately 10 μA to approximately 100 μA, approximately 20 μA to approximately 40 In some embodiments, ion flux is generated through electrospray ionization by utilizing currents of approximately μA, approximately 20μA to approximately 50μA, approximately 20μA to approximately 80μA, approximately 20μA to approximately 100μA, approximately 40μA to approximately 50μA, approximately 40μA to approximately 80μA, approximately 40μA to approximately 100μA, approximately 50μA to approximately 80μA, approximately 50μA to approximately 100μA, or approximately 80μA to approximately 100μA. In some embodiments, ion flux is generated through electrospray ionization by utilizing currents of approximately 0μA, approximately 10μA, approximately 20μA, approximately 40μA, approximately 50μA, approximately 80μA, or approximately 100μA. In some embodiments, ion flux is generated through electrospray ionization by utilizing currents of at least approximately 0μA, approximately 10μA, approximately 20μA, approximately 40μA, approximately 50μA, or approximately 80μA. In some embodiments, the ion flux is generated through electrospray ionization by utilizing a current of up to approximately 10 μA, 20 μA, 40 μA, 50 μA, 80 μA, or 100 μA.

[0062] In some embodiments, the ion repeller manifold 104 has a DC bias of approximately 0V to approximately 500V for each section (105, 108, 109). In some embodiments, the ion repeller manifold 104 has a DC bias of approximately 0V to approximately 20V, approximately 0V to approximately 40V, approximately 0V to approximately 50V, approximately 0V to approximately 100V, approximately 0V to approximately 150V, approximately 0V to approximately 300V, approximately 0V to approximately 500V, approximately 20V to approximately 40V, approximately 20V to approximately 50V, approximately 20V to approximately 100V, approximately 20V to approximately 150V, approximately 20V to approximately 300V, approximately 20V to approximately 500V, approximately 40 It has a DC bias of approximately V~50V, approximately 40V~100V, approximately 40V~150V, approximately 40V~300V, approximately 40V~500V, approximately 50V~100V, approximately 50V~150V, approximately 50V~300V, approximately 50V~500V, approximately 100V~150V, approximately 100V~300V, approximately 100V~500V, approximately 150V~300V, approximately 150V~500V, or approximately 300V~500V. In some embodiments, the ion repeller manifold 104 has a DC bias of approximately 0V, approximately 20V, approximately 40V, approximately 50V, approximately 100V, approximately 150V, approximately 300V, or approximately 500V for each compartment (105, 108, 109). In some embodiments, the ion repeller manifold 104 has a DC bias of at least approximately 0V, approximately 20V, approximately 40V, approximately 50V, approximately 100V, approximately 150V, or approximately 300V for each compartment (105, 108, 109). In some embodiments, the ion repeller manifold 104 has a DC bias of up to approximately 20V, approximately 40V, approximately 50V, approximately 100V, approximately 150V, approximately 300V, or approximately 500V for each compartment (105, 108, 109).

[0063] In some embodiments, the ion repeller manifold 104 utilizes currents of approximately 0 μA to approximately 100 μA for each compartment (105, 108, 109). In some embodiments, the ion repeller manifold 104 utilizes currents of approximately 0 μA to approximately 10 μA, approximately 0 μA to approximately 20 μA, approximately 0 μA to approximately 40 μA, approximately 0 μA to approximately 50 μA, approximately 0 μA to approximately 80 μA, approximately 0 μA to approximately 100 μA, approximately 10 μA to approximately 20 μA, approximately 10 μA to approximately 40 μA, approximately 10 μA to approximately 50 μA, and approximately 10 μA for each compartment (105, 108, 109). The ion repeller manifold 104 utilizes currents of approximately 0 μA, 10 μA to 100 μA, 20 μA to 40 μA, 20 μA to 50 μA, 20 μA to 80 μA, 20 μA to 100 μA, 40 μA to 50 μA, 40 μA to 80 μA, 40 μA to 100 μA, 50 μA to 80 μA, 50 μA to 100 μA, or 80 μA to 100 μA. In some embodiments, the ion repeller manifold 104 utilizes currents of approximately 0 μA, 10 μA, 20 μA, 40 μA, 50 μA, 80 μA, or 100 μA for each compartment (105, 108, 109). In some embodiments, the ion repeller manifold 104 utilizes a current of at least about 0 μA, about 10 μA, about 20 μA, about 40 μA, about 50 μA, or about 80 μA for each compartment (105, 108, 109). In some embodiments, the ion repeller manifold 104 utilizes a current of up to about 10 μA, about 20 μA, about 40 μA, about 50 μA, about 80 μA, or about 100 μA for each compartment (105, 108, 109).

[0064] In some embodiments, the heated ion manifold inlet has a DC voltage bias of about 0V to about 500V. In some embodiments, the heated ion manifold inlet has a bias of about 0V to about 20V, about 0V to about 40V, about 0V to about 50V, about 0V to about 100V, about 0V to about 150V, about 0V to about 300V, about 0V to about 500V, about 20V to about 40V, about 20V to about 50V, about 20V to about 100V, about 20V to about 150V, about 20V to about 300V, about 20V to about 500V, about 40V to about 50V, about 4 The DC voltage bias is approximately 0V to 100V, 40V to 150V, 40V to 300V, 40V to 500V, 50V to 100V, 50V to 150V, 50V to 300V, 50V to 500V, 100V to 150V, 100V to 300V, 100V to 500V, 150V to 300V, 150V to 500V, or 300V to 500V. In some embodiments, the heated ion manifold inlet has a DC voltage bias of approximately 0V, 20V, 40V, 50V, 100V, 150V, 300V, or 500V. In some embodiments, the heated ion manifold inlet has a DC voltage bias of at least about 0V, about 20V, about 40V, about 50V, about 100V, about 150V, or about 300V. In some embodiments, the heated ion manifold inlet has a DC voltage bias of up to about 20V, about 40V, about 50V, about 100V, about 150V, about 300V, or about 500V.

[0065] In some embodiments, the heated ion manifold inlet utilizes a current of approximately 0 μA to approximately 100 μA. In some embodiments, the heated ion manifold inlet utilizes currents of approximately 0 μA to approximately 10 μA, approximately 0 μA to approximately 20 μA, approximately 0 μA to approximately 40 μA, approximately 0 μA to approximately 50 μA, approximately 0 μA to approximately 80 μA, approximately 0 μA to approximately 100 μA, approximately 10 μA to approximately 20 μA, approximately 10 μA to approximately 40 μA, approximately 10 μA to approximately 50 μA, approximately 10 μA to approximately 80 μA, approximately The currents used are approximately 10 μA to 100 μA, approximately 20 μA to 40 μA, approximately 20 μA to 50 μA, approximately 20 μA to 80 μA, approximately 20 μA to 100 μA, approximately 40 μA to 50 μA, approximately 40 μA to 80 μA, approximately 40 μA to 100 μA, approximately 50 μA to 80 μA, approximately 50 μA to 100 μA, or approximately 80 μA to 100 μA. In some embodiments, the heated ion manifold inlet uses a current of approximately 0 μA, approximately 10 μA, approximately 20 μA, approximately 40 μA, approximately 50 μA, approximately 80 μA, or approximately 100 μA. In some embodiments, the heated ion manifold inlet utilizes a current of at least about 0 μA, about 10 μA, about 20 μA, about 40 μA, about 50 μA, or about 80 μA. In some embodiments, the heated ion manifold inlet utilizes a current of up to about 10 μA, about 20 μA, about 40 μA, about 50 μA, about 80 μA, or about 100 μA.

[0066] In some embodiments, the first ion optics system 116 and the second ion optics system 118 have RF phases, and the opposite phases have peak voltages of approximately 10 Vp-p to approximately 200 Vp-p. The peak voltages are approximately 50Vp-p, 20Vp-p to 100Vp-p, 20Vp-p to 200Vp-p, 40Vp-p to 50Vp-p, 40Vp-p to 100Vp-p, 40Vp-p to 200Vp-p, 50Vp-p to 100Vp-p, 50Vp-p to 200Vp-p, or 100Vp-p to 200Vp-p. In some embodiments, the first ion optics 116 and the second ion optics 118 have RF phases, and the opposite phases have peak voltages of approximately 10Vp-p, 20Vp-p, 40Vp-p, 50Vp-p, 100Vp-p, or 200Vp-p. In some embodiments, the first ion optics system 116 and the second ion optics system 118 have an RF phase, and the reverse phase has a peak voltage of at least about 10 Vp-p, about 20 Vp-p, about 40 Vp-p, about 50 Vp-p, or about 100 Vp-p. In some embodiments, the first ion optics system 116 and the second ion optics system 118 have an RF phase, and the reverse phase has a peak voltage of up to about 20 Vp-p, about 40 Vp-p, about 50 Vp-p, about 100 Vp-p, or about 200 Vp-p.

[0067] In some embodiments, the first ion optics system 116 and the second ion optics system 118 utilize DC voltages from approximately 0V to approximately 500V. In some embodiments, the first ion optics system 116 and the second ion optics system 118 utilize DC voltages from approximately 0V to approximately 20V, approximately 0V to approximately 40V, approximately 0V to approximately 50V, approximately 0V to approximately 100V, approximately 0V to approximately 150V, approximately 0V to approximately 300V, approximately 0V to approximately 500V, approximately 20V to approximately 40V, approximately 20V to approximately 50V, approximately 20V to approximately 100V, approximately 20V to approximately 150V, approximately 20V to approximately 300V, approximately 20V to approximately 500V, approximately 40V DC voltages of approximately 50V, 40V to 100V, 40V to 150V, 40V to 300V, 40V to 500V, 50V to 100V, 50V to 150V, 50V to 300V, 50V to 500V, 100V to 150V, 100V to 300V, 100V to 500V, 150V to 300V, 150V to 500V, or 300V to 500V are utilized. In some embodiments, the first ion optical system 116 and the second ion optical system 118 utilize DC voltages of approximately 0V, 20V, 40V, 50V, 100V, 150V, 300V, or 500V. In some embodiments, the first ion optics system 116 and the second ion optics system 118 utilize DC voltages of at least about 0V, about 20V, about 40V, about 50V, about 100V, about 150V, or about 300V. In some embodiments, the first ion optics system 116 and the second ion optics system 118 utilize DC voltages of up to about 20V, about 40V, about 50V, about 100V, about 150V, about 300V, or about 500V.

[0068] In some embodiments, the first ion optical system 116 and the second ion optical system 118 utilize currents from about 0 μA to about 100 μA. In some embodiments, the first ion optical system 116 and the second ion optical system 118 utilize currents from about 0 μA to about 10 μA, about 0 μA to about 20 μA, about 0 μA to about 40 μA, about 0 μA to about 50 μA, about 0 μA to about 80 μA, about 0 μA to about 100 μA, about 10 μA to about 20 μA, about 10 μA to about 40 μA, about 10 μA to about 50 μA, and about 10 μA to about 8 The system utilizes currents of 0 μA, approximately 10 μA to 100 μA, approximately 20 μA to 40 μA, approximately 20 μA to 50 μA, approximately 20 μA to 80 μA, approximately 20 μA to 100 μA, approximately 40 μA to 50 μA, approximately 40 μA to 80 μA, approximately 40 μA to 100 μA, approximately 50 μA to 80 μA, approximately 50 μA to 100 μA, or approximately 80 μA to 100 μA. In some embodiments, the first ion optical system 116 and the second ion optical system 118 utilize currents of approximately 0 μA, approximately 10 μA, approximately 20 μA, approximately 40 μA, approximately 50 μA, approximately 80 μA, or approximately 100 μA. In some embodiments, the first ion optics system 116 and the second ion optics system 118 utilize currents of at least about 0 μA, about 10 μA, about 20 μA, about 40 μA, about 50 μA, or about 80 μA. In some embodiments, the first ion optics system 116 and the second ion optics system 118 utilize currents of up to about 10 μA, about 20 μA, about 40 μA, about 50 μA, about 80 μA, or about 100 μA.

[0069] In some embodiments, the first ion optical system 116 or the second ion optical system 118 is configured to selectively transmit ions having a mass of approximately 400 m / z to 900 m / z. For example, the dimensions of the ion optical system and the applied voltage can be configured to selectively transmit a desired mass range while selectively rejecting other mass ranges. In some embodiments, a third ion optical system may be included between the first ion optical system 116 and the second ion optical system 118, and the third ion optical system is configured to selectively transmit ions having a mass of approximately 400 m / z to 900 m / z. In some embodiments, the first ion optical system or the second ion optical system does not selectively transmit ions.

[0070] In some embodiments, the devices provided herein have the configuration shown in Figure 14. In this configuration, the high-pressure ion funnel can be replaced with an RF confinement FAIMS having a 90-degree bending radius for connecting to an orthogonal inlet and a straight section for connecting to an inline inlet. (Example method)

[0071] In some embodiments, the present disclosure describes a method 400 for generating multiple ion streams, as shown in Figure 4. In some embodiments, the method includes the step of providing an ion flux 132 to an ion manifold inlet 106 of an ion manifold 100, the ion manifold comprising an ion manifold inlet, an optional ion repeller manifold 104, a first ion optics system 116 configured to receive the ion flux through the ion manifold inlet 106, and a second ion optics system 118 configured to receive the output of the ion flux through the first ion optics system, the second ion optics system 118 comprising multiple outputs (114) 401, and generating multiple ion streams from the multiple outputs of the second ion optics system as the ion flux passes through the second ion optics system (118) 402. In some embodiments, the central axis of the ion manifold inlet 130 is perpendicular to the central axis of the first ion optics system 128 or the central axis of the second ion optics system 128. In some cases, the central axes of the first ion optics system 128 and the second ion optics system 128 are collinear. In some cases, the ion manifold further includes a port 102 configured to pressurize the ion manifold 100. In some cases, the ion manifold 100 includes a first chamber 110 and a second chamber 112. In some embodiments, the first chamber 110 has a first pressure and the second chamber 112 has a second pressure, with the first pressure being higher than the second pressure. In some embodiments, the first chamber 110 has a first pressure and the second chamber 112 has a second pressure, with the first pressure being lower than the second pressure. In some embodiments, the first ion optics system 116 and the second ion optics system 118 include an ion funnel. In some embodiments, the first ion optics system 116 and the second ion optics system 118 may include one or more electrical conductor compartments 124. In some embodiments, one or more electrical conductor compartments 124 may include printed circuit boards. In some embodiments, the ion manifold inlet 106 may include a heated ion manifold inlet. In some embodiments, the ion manifold inlet 106 includes a slotted capillary tube.In some embodiments, the slotted capillary may have a rectangular cross-sectional geometric shape 107. In some embodiments, the ion manifold inlet 106 has a circular or oval cross-sectional geometric shape. In some embodiments, the ion repeller manifold 104, the ion manifold inlet 106, or the first ion optics 116 is at least partially contained within a first chamber 110. In some embodiments, the first chamber 110 has a pressure of at least about 8 torr (e.g., about 8 to about 12 torr). In some embodiments, the second ion optics 118 is at least partially contained within a second chamber 112, which is different from the first chamber 110. In some embodiments, the second chamber 112 has a pressure of at least about 1 torr (e.g., about 1 torr to about 3 torr). In some embodiments, the ion flux 132 is supplied from the multi-emitter array to the ion manifold inlet 106 by electrospray ionization. In some embodiments, the ion repeller manifold 104 comprises a partitioned plate (105, 108, 109) having one or more compartments. In some embodiments, the partitioned plate (105, 108, 109) comprises at least about two compartments or at least about three compartments. In some embodiments, the central axis of the first ion optical system 128 or the second ion optical system 128 is perpendicular to the central axis of the ion manifold inlet 130. In some embodiments, the central axis of the ion manifold inlet 130 is perpendicular to the axis normal to the surface of the ion repeller manifold 128. In some embodiments, the first electrode compartment 105 of the ion repeller manifold has a lower voltage than the adjacent second electrode compartment 108 of the ion repeller manifold 104. In some embodiments, the ion repeller manifold 104 has a voltage gradient across its longitudinal length. In some embodiments, the ion manifold 100 includes a port 102 that is fluidly coupled to the ion manifold 100, and the port 102 is configured to pressurize a first chamber 110, a second chamber 112, or a combination thereof.In some embodiments, the central axis of port 130 is collinear with the central axis of the ion manifold inlet 130. The primary purpose of port 102 is to pressurize the first chamber 110, the second chamber 112, or a combination of the two, but it has the unexpected benefit of improving the signal and reducing noise by removing the solvent from the ion flow provided from the ion manifold inlet. In some embodiments, the first ion optics 116 or the second ion optics 118 has a linear DC gradient provided by one or more electrical conduction compartments 124 traversing the longitudinal length of the first or second ion optics. In some embodiments, one or more electrical conduction compartments 124 of the first ion optics 116 or the second ion optics 118 have up to about four DC conductance limits. In some embodiments, a first electrical conductor section of one or more electrical conductor sections 124 provides a first signal with a first phase, and a second electrical conductor section of one or more electrical conductor sections 124 provides a second signal with the opposite phase to the first phase.

[0072] In some embodiments, the first ion optical system 116 or the second ion optical system 118 comprises one or more electrical conductor compartments 124, as shown in Figure 2. In some embodiments, one or more electrical conductor compartments 124 may comprise one or more through-holes 126. In some embodiments, one or more through-holes 126 may be circular, oval, polygonal, or square in shape, as shown in Figure 2. In some embodiments, one or more electrical conductor compartments 124 may have a center-to-center spacing of at least about 1 mm. In some embodiments, one or more through-holes are provided along a linear axis 128 on the surface of one or more electrical conductor compartments 124. In some embodiments, two or more through-holes in one or more electrical conductor compartments are adjacent or in contact with each other, as shown in Figure 2. In some embodiments, the first electrical conductor compartment 124 has a first dimension of the through-hole, and the adjacent second electrical conductor compartment 124 has a second dimension that is smaller than the first dimension. In some cases, one or more electrical conductor compartments 124 may form the inner geometry of the first ion optical system 122 and the second ion optical system 123. In some cases, the inner geometry of the first ion optical system 122 and the second ion optical system 123 may comprise one or more compartments. In some cases, one or more compartments of the inner geometry may comprise linear unsloped compartments and linear positively sloped compartments or linear negatively sloped compartments, as shown in Figure 2. In some cases, one or more electrical conductor compartments 124 may split or divide the ion flow into a plurality of ion flows, as described elsewhere in this specification.

[0073] In some embodiments, electrospray ionization may arise from a single source. In some embodiments, electrospray ionization utilizes a voltage adjustable from about 0 kV to about 5 kV. In some embodiments, electrospray ionization is static. In some embodiments, electrospray ionization has a maximum current of 100 μA. In some embodiments, electrospray ionization has accuracy or reliability within at least about 1% of the performance parameters of the electrospray ionization apparatus. In some cases, accuracy may be measured or determined by evaluating the signal intensity of the ions produced by electrospray ionization compared to the expected value or standard signal intensity of the ions produced by electrospray ionization. In some cases, the accuracy of electrospray ionization may be measured by comparing the observed mass-to-charge value of the ions produced by electrospray ionization with the mass-to-charge ratio of a known reference compound produced by electrospray ionization. In some embodiments, electrospray ionization has a voltage readback function. In some embodiments, electrospray ionization has a current readback function. In some embodiments, electrospray ionization has an overcurrent protection function.

[0074] In some embodiments, the ion repeller manifold 104 has a DC bias of approximately 0V to approximately 500V for each section (105, 108, 109). In some embodiments, the ion repeller manifold 104 is static but adjustable. In some embodiments, the ion repeller manifold 104 has an accuracy of 0.1%. In some embodiments, the ion repeller manifold 104 has a voltage readback function. In some embodiments, the ion repeller manifold 104 has a voltage abnormality cutoff function.

[0075] In some embodiments, the heated ion manifold inlet has a DC voltage bias adjustable from approximately 0V to approximately 500V. In some embodiments, the heated ion manifold inlet has a maximum current of 100μA. In some embodiments, the heated ion manifold inlet has a voltage readback function. In some embodiments, the heated ion manifold inlet has a voltage abnormality shutoff function. In some embodiments, the heated ion manifold inlet has a resistance heater operating at 50W. In some embodiments, the heated ion manifold inlet has a TC temperature monitoring and control function. In some embodiments, the heated ion manifold inlet has a temperature control accuracy of 1%. In some embodiments, the heated ion manifold inlet has a nominal temperature of approximately 180°C.

[0076] In some embodiments, the funnel RF is generated using a resonant circuit, and a coil in the RF head resonates with the capacitance of the funnel. In some embodiments, the interphase RF voltages differ by less than 5%. In some embodiments, the RF output level has a readback function and is level-controlled. In some embodiments, the DC gradient across the funnel is made using two resistor dividers, one for each RF phase, with each resistor having a resistance of approximately 500K. In some embodiments, each plate is capacitively coupled to its RF bus. In some embodiments, the coupling capacitor is large relative to the inter-funnel plate capacitance.

[0077] In some embodiments, the first ion optics system 116 and the second ion optics system 118 have an adjustable DC voltage ranging from approximately 0V to approximately 500V. In some embodiments, the first ion optics system 116 and the second ion optics system 118 have an accuracy of 0.1%. In some embodiments, the first ion optics system 116 and the second ion optics system 118 have a maximum current of 100μA. In some embodiments, the first ion optics system 116 and the second ion optics system 118 have a voltage readback function and an anomaly detection function. In some embodiments, the first ion optics system 116 and the second ion optics system 118 have a DC input, a DC output, and a DC conductance limit. In some embodiments, the second ion optics system 118 has four total DC conductance limits. In some embodiments, the DC conductance limit voltage of the second ion optics system 118 is dynamic. In some embodiments, the first ion optical system 116 and the second ion optical system 118 have RF phases, and the opposite phases have peak-to-peak voltages of about 10 Vp-p to about 200 Vp-p. (Exemplary ion mobility spectroscopy process)

[0078] The methods and mass spectrometers described herein utilize one or more ion mobility devices within the ion optics of a mass spectrometer to distinguish and / or separate analyte ions and background ions in an ion bundle prior to analysis using one or more mass spectrometers. The ion mobility systems may include electric field asymmetric ion mobility spectroscopy (FAIMS), traveling wave ion mobility spectroscopy (TWIMS), captured ion mobility spectroscopy (TIMS), drift tube ion mobility spectroscopy (DT-IMS), and / or combinations thereof. In some embodiments, the methods and mass spectrometers include both FAIMS and TWIMS.

[0079] Combining FAIMS with TWIMS or another secondary ion mobility separation device can reduce or eliminate the need for high-resolution FAIMS separation. The reduced resolution requirement allows FAIMS to operate under reduced pressure, which reduces ion flux loss, typically associated with ion-neutral particle collisions and / or ion-ion recombination. In some cases, FAIMS can be used as a filter. For example, a set of conditions can be applied to the passage of a selected class of ions, and ions outside the permeation conditions (e.g., unselected ions) are removed. FAIMS devices can operate under reduced pressure, e.g., 1-4 torr, with sufficient resolution for the separation of two aggregate classes of ions, e.g., between single-charged chemical background species and multi-charged peptide ions. Single-charged ions can be removed, reducing the total ion flux and allowing them to pass through to downstream analysis, enriching multi-charged ions, preserving the ion of interest, and improving the performance of subsequent TWIMS separation, which can be used to improve the utilization of the mass spectrometer by separating peptides over time. In some cases, the traveling wave ion mobility device comprises multiple RF electrodes and protective electrodes, positioned within a vacuum system, configured to maintain a pressure within the traveling wave ion mobility device that is less than the pressure of the inert gas in the mobility chamber containing the reduced-pressure electric field asymmetric ion mobility device. In some embodiments, the high-pressure ion funnel in the device configuration provided herein is replaced by a FAIMS device.

[0080] In some embodiments, the disclosure provides implementations for high-field asymmetric waveform ion mobility spectroscopy (FAIMS). At a high level, FAIMS may involve separating or characterizing ions based on differences in their mobility under high and low electric fields. In practice, FAIMS may enable increased filtering and separation of ions in mass spectroscopic analysis.

[0081] High-field asymmetric waveform ion mobility spectroscopy (FAIMS) can separate gas-phase ions at atmospheric pressure. In FAIMS, ions can be introduced into a mobility region ("FAIMS region"), through which a radio frequency (RF) waveform (its magnitude is called the dispersion voltage (DV)) is applied so that the ions are alternately exposed to high and low electric fields. The waveform can be asymmetric; for example, a high electric field may be applied for a certain time unit, and then a low electric field of the opposite polarity (half the high electric field component) may be applied for twice the length. For example, the RF voltage can be the sum of two separate RF voltages, one of which is a sine function and the other is the same but π / 2 phase-shifted sine function. The result is a double sine waveform with low and high periods, with a duration ratio of 3:1. Other ratios are also possible. The electric field-dependent change in ion mobility causes the ions to drift towards the walls of the separation region. Because the dependence of ion mobility on electric field strength can be ion-specific, different types of ions can be separated ion by ion, a separation that may be referred to as FAIMS separation. To allow the ion of interest to pass through FAIMS, an appropriate DC current compensation voltage (CV) can be applied to compensate for the drift of the ion of interest toward the analyzer wall. By varying the CV, different ions can be selectively transmitted (or selectively removed) through the FAIMS device. Described herein is a novel FAIMS device that is capable of producing such separation at sub-atmospheric pressure without significant loss of ion flux, resulting in high ion transmittance.

[0082] These high-voltage asymmetric waveforms may be in the radio frequency (RF) range. Ions can migrate towards one of the two electrodes based on the ratio of high-field to low-field mobilities of each ion. Therefore, ions with mobilities outside a certain range cannot pass through the FAIMS device, while ions with mobilities within a certain range can pass through the FAIMS device. In some cases, FAIMS can be achieved using a double sinusoidal waveform (e.g., Vp-p 1,000V, CV -60V~0V, 2MHz). In some cases, a flyback transformer waveform is used in the method described herein.

[0083] In some cases, one or more power sources provide waveforms comprising a sinusoidal, square, triangular, sawtooth, or a combination of one or more of these. In some cases, one or more power sources provide waveforms comprising at least two waveforms that are phase-shifted relative to each other. In some cases, the phase shift between waveforms is about 30° to about 120° (e.g., about 30°, about 45°, about 60°, about 90°, or about 120°). In some cases, at least two waveforms are sinusoidal. In some cases, at least two waveforms have different amplitudes.

[0084] The frequencies of any of the waveforms used herein may independently range from 100 kHz to about 2 MHz (e.g., about 100 kHz, about 500 kHz, about 750 kHz, about 1 MHz, about 1.5 MHz, or about 2 MHz). In some embodiments, the frequencies are about 100 kHz to about 1,000 kHz. In some embodiments, the frequencies are about 100 kHz to about 200 kHz, about 100 kHz to about 300 kHz, about 100 kHz to about 400 kHz, about 100 kHz to about 500 kHz, about 100 kHz to about 750 kHz, about 100 kHz to about 1,000 kHz, about 200 kHz to about 300 kHz, about 200 kHz to about 400 kHz, about 200 kHz to about 500 kHz, about 200 kHz to about 750 kHz, and about 200 kHz. The frequencies are approximately 1,000 kHz, 300 kHz to 400 kHz, 300 kHz to 500 kHz, 300 kHz to 750 kHz, 300 kHz to 1,000 kHz, 400 kHz to 500 kHz, 400 kHz to 750 kHz, 400 kHz to 1,000 kHz, 500 kHz to 750 kHz, 500 kHz to 1,000 kHz, or 750 kHz to 1,000 kHz. In some embodiments, the frequencies are approximately 100 kHz, 200 kHz, 300 kHz, 400 kHz, 500 kHz, 750 kHz, or 1,000 kHz. In some embodiments, the frequencies are at least approximately 100 kHz, 200 kHz, 300 kHz, 400 kHz, 500 kHz, or 750 kHz. In some embodiments, the frequency is up to about 200 kHz, about 300 kHz, about 400 kHz, about 500 kHz, about 750 kHz, or about 1,000 kHz. In some embodiments, the frequency is about 1 MHz to about 2 MHz. In some embodiments, the frequency is about 1 MHz to about 1.25 MHz, about 1 MHz to about 1.5 MHz, about 1 MHz to about 1.75 MHz, about 1 MHz to about 2 MHz, about 1.25 MHz to about 1.5 MHz, about 1.25 MHz to about 1.75 MHz, about 1.25 MHz to about 2 MHz, about 1.5 MHz to about 1.75 MHz, about 1.5 MHz to about 2 MHz, or about 1.75 MHz to about 2 MHz.In some embodiments, the frequency is approximately 1 MHz, approximately 1.25 MHz, approximately 1.5 MHz, approximately 1.75 MHz, or approximately 2 MHz. In some embodiments, the frequency is at least approximately 1 MHz, approximately 1.25 MHz, approximately 1.5 MHz, or approximately 1.75 MHz. In some embodiments, the frequency is at most approximately 1.25 MHz, approximately 1.5 MHz, approximately 1.75 MHz, or approximately 2 MHz.

[0085] The absolute value of the maximum amplitude of any of the waveforms used may be approximately 100V to approximately 2,000V (e.g., approximately 250V to approximately 1,750V, approximately 500V to approximately 1,500V, approximately 750V to approximately 1,000V, approximately 100V, approximately 300V, approximately 500V, approximately 700V, approximately 800V, approximately 1,000V, approximately 1,500V, or approximately 2,000V). In some cases, the voltages used for FAIMS as described herein are 200-3,000V, 200-2,000V, 500-2,000V, 750-3,000V, 1,000-3,000V, 750-2,000V, or 1,000-2,000V. In some cases, the voltage used for the FAIMS described herein is at least 250, 300, 500, 600, 750, 800, 900, 1,000, 1,200, 1,500, 1,700, 2,000, or at least 2,500V.

[0086] Any reduced-pressure electric field asymmetric ion mobility device may have an overall duty cycle of waveform delivered by one or more power sources, which is about 5% to about 90% (e.g., about 5%, about 10%, about 20%, about 30%, about 50%, or about 90%). In some embodiments, the duty cycle is about 5% to about 90%. In some embodiments, the duty cycle is about 5% to about 10%, about 5% to about 20%, about 5% to about 30%, about 5% to about 50%, about 5% to about 60%, about 5% to about 80%, about 5% to about 90%, about 10% to about 20%, about 10% to about 30%, about 10% to about 50%, about 10% to about 60%, about 10% to about 80%, about 10% to about 90%, about 20% The duty cycle is approximately 30%, approximately 20% to approximately 50%, approximately 20% to approximately 60%, approximately 20% to approximately 80%, approximately 20% to approximately 90%, approximately 30% to approximately 50%, approximately 30% to approximately 60%, approximately 30% to approximately 80%, approximately 30% to approximately 90%, approximately 50% to approximately 60%, approximately 50% to approximately 80%, approximately 50% to approximately 90%, approximately 60% to approximately 80%, approximately 60% to approximately 90%, or approximately 80% to approximately 90%. In some embodiments, the duty cycle is approximately 5%, approximately 10%, approximately 20%, approximately 30%, approximately 50%, approximately 60%, approximately 80%, or approximately 90%. In some embodiments, the duty cycle is at least approximately 5%, approximately 10%, approximately 20%, approximately 30%, approximately 50%, approximately 60%, or approximately 80%. In some embodiments, the duty cycle is approximately 10%, 20%, 30%, 50%, 60%, 80%, or 90% at most.

[0087] The waveforms used in the devices and methods described herein may be independently delivered to or otherwise applied to the inner electrode or the outer electrode.

[0088] The ion inlet and ion outlet of this disclosure can be aligned with axes that are substantially perpendicular to each other. In some cases, the ion inlet is aligned along a first axis and the ion outlet is aligned along a second axis, and the first and second axes are aligned substantially parallel to each other.

[0089] In some cases, the ion inlet is aligned along a first axis, and the ion outlet is aligned along a second axis, and the first and second axes are aligned such that they form an angle of about 40° to about 120° (e.g., about 45°, about 60°, about 75°, about 100°, or about 120°) at their intersection. In some cases, the inert gas used is nitrogen, helium, or argon. In some cases, the reduced-pressure electric field asymmetric ion mobility device is configured for the permeation of ions having m / z values ​​of about 400 to about 900. In some cases, the reduced-pressure electric field asymmetric ion mobility device is configured for the permeation of ions having m / z values ​​greater than about 400 m / z. In some cases, the reduced-pressure electric field asymmetric ion mobility device is configured to remove ions having m / z values ​​less than about 350 m / z. In some cases, the ion inlet extends substantially parallel to the direction of ion movement between the inner and outer electrodes. In some cases, the ion inlet extends at an angle to the direction of ion movement between the inner and outer electrodes, with an angle of approximately 20° to 70° (e.g., approximately 30° to 60°, or approximately 40° to 50°). In other cases, the ion outlet extends approximately parallel to the direction of ion movement between the inner and outer electrodes. In other cases, the ion outlet extends at an angle to the direction of ion movement between the inner and outer electrodes, with an angle of approximately 60° to 120° (e.g., approximately 70° to 110°, or approximately 80° to 90°). In other cases, the ion inlet and ion outlet are approximately aligned along a common axis.

[0090] The reduced-pressure electric field asymmetric ion mobility devices of this disclosure may be configured to remove at least about 80% of a single charged ion (e.g., at least about 85%, at least about 90%, at least about 95%, at least about 98%, or at least about 99%). In some cases, at least about 80% of a single charged ion is removed within the first 50% of the distance between the inlet and outlet.

[0091] In some embodiments, the single charged ion current passing through the FAIMS device of the Disclosure is reduced by about 50% to about 99.5%, or redirected to an alternative outlet of the device. In some embodiments, the single charged ion current passing through the FAIMS device of this disclosure is approximately 50% to approximately 60%, approximately 50% to approximately 70%, approximately 50% to approximately 80%, approximately 50% to approximately 95%, approximately 50% to approximately 90%, approximately 50% to approximately 95%, approximately 50% to approximately 99%, approximately 50% to approximately 99.5%, approximately 60% to approximately 70%, approximately 60% to approximately 80%, approximately 60% to approximately 95%, approximately 60% to approximately 90%, approximately 60% to approximately 95%, approximately 60% to approximately 99%, approximately 60% to approximately 99.5%, approximately 70% to approximately 80%, approximately 70% to approximately 95%, approximately 70% to approximately Reduced by 90%, approximately 70% to 95%, approximately 70% to 99%, approximately 70% to 99.5%, approximately 80% to 95%, approximately 80% to 90%, approximately 80% to 95%, approximately 80% to 99%, approximately 80% to 99.5%, approximately 95% to 90%, approximately 95% to 95%, approximately 95% to 99%, approximately 95% to 99.5%, approximately 90% to 95%, approximately 90% to 99%, approximately 90% to 99.5%, approximately 95% to 99%, approximately 95% to 99.5%, or approximately 99% to 99.5%, or redirected to an alternative exit for this device. In some embodiments, the single charged ion current passing through the FAIMS device of the Disclosure is reduced by about 50%, about 60%, about 70%, about 80%, about 95%, about 90%, about 95%, about 99%, or about 99.5%, or redirected to an alternative outlet of the device. In some embodiments, the single charged ion current passing through the FAIMS device of the Disclosure is reduced by at least about 50%, about 60%, about 70%, about 80%, about 95%, about 90%, about 95%, or about 99%, or redirected to an alternative outlet of the device. In some embodiments, the single charged ion current passing through the FAIMS device of the Disclosure is reduced by up to about 60%, about 70%, about 80%, about 95%, about 90%, about 95%, about 99%, or about 99.5%, or redirected to an alternative outlet of the device.

[0092] The FAIMS device of this disclosure may be configured to decompose single-charged ions from multiple-charged ions radially about the central axis of the enclosed mobility chamber. In some cases, the radial resolution of multiple-charged species from single-charged species is, on average, at least about 2 mm (e.g., at least 2 mm, at least 5 mm, at least 10 mm, at least 12 mm, or at least 20 mm) when measured at the ion outlet.

[0093] In some cases, a reduced-pressure electric field asymmetric ion mobility device comprises one or more sets of ion optics configured to guide ions into an ion inlet and out of an ion outlet, or a combination thereof. Each of the one or more sets of ion optics may independently comprise one or more ion funnels, one or more DC lenses, or a combination of two or more of these. In some cases, one or more sets of ion optics are configured to guide ions from the ion outlet into a traveling wave ion mobility device.

[0094] In some cases, the average ion transmission efficiency of multiple charged ions from the ion inlet to the ion outlet is at least about 50% (e.g., at least about 50%, at least about 70%, at least about 80%, at least about 90%, or at least about 95%). In other cases, the average ion transmission efficiency of single charged ions from the ion inlet to the ion outlet is about 50% or less (e.g., about 50% or less, about 30% or less, about 10% or less, about 5% or less, or about 1% or less).

[0095] In some cases, multiple charged ions are permeated from the ion inlet to the ion outlet in less than approximately 100 milliseconds (e.g., less than approximately 50 ms, 25 ms, 10 ms, 5 ms, or 3 ms). In other cases, multiple charged ions are permeated from the ion inlet to the ion outlet in approximately 0.1 ms to 10 ms, approximately 0.5 ms to 5 ms, or approximately 1 ms to 3 ms. In some cases, the gas pressure at the inlet is approximately 0.1 torr to 10 torr (e.g., approximately 0.5 torr to 8, approximately 1 torr to 5 torr, or approximately 1 torr to 3 torr) higher than the gas pressure at the outlet.

[0096] In some cases, the differential deflection is configured to selectively remove ions having a mobility corresponding to a single charged species having a mass of about 400 Da or less (e.g., about 300 Da or less, about 200 Da or less, or about 100 Da or less). In some cases, the single charged species is a solvent used for electrospray ionization of a sample. In some cases, about 5% to 50%, about 10% to 40%, or about 20% to 35% of the ions are selectively removed by the ion mobility device. In some cases, the gas moves through the ion mobility device at a speed of about 10 m / s to about 300 m / s, or about 50 m / s to about 200 m / s. In some cases, the ion mobility device includes a gradient DC bias for moving the ions and does not include gas flow, as further disclosed below.

[0097] In some embodiments, FAIMS may be used as a separation operation in conjunction with mass spectrometry analysis. FAIMS can enable, for example, improved detection of peptides in complex samples, filtering out "chemical noise," filtering out interfering ions, and selection of charge states for analysis. In some embodiments, FAIMS may be used to select ions that are low in abundance in a sample and would otherwise be unanalyzable (e.g., due to limitations in the duty cycle of the mass spectrometer). For example, by selectively removing more abundant ions, FAIMS may help distinguish ions with similar mass-to-charge ratios and prevent more abundant ions from masking the presence of less abundant ions.

[0098] In some embodiments, the FAIMS device includes one or more guardrail electrodes that are charged with either RF or DC to assist in ion confinement. An embodiment of DC guardrails is shown in Figure 15.

[0099] Figure 10 shows an exemplary workflow diagram 1000 for a front-end interface. Specifically, Figure 10 shows an embodiment of a method in which FAIMS may be integrated into one or more implementations for ion manifolds disclosed herein. Workflow diagram 1000 may include electrospray ionization at 1010, ion funnel treatment at 1020, application of FAIMS at 1030, and split ion funnel treatment at 1040.

[0100] Workflow diagram 1000 may, in some embodiments, begin with electrospray ionization (ESI) in 1010. For example, ESI may use electrical energy to assist in the transport of ions from the solution into the gas phase before the ions are exposed to mass spectrometry analysis. The electrical energy may include a high voltage applied across the liquid and may produce an aerosol. ESI in 1010 may include a soft ionization technique (e.g., with minimal or no fragmentation) used for the production of gas-phase ions. In some embodiments, the electrospray in 1010 may be identical or similar to one or more of the electrospray techniques disclosed herein.

[0101] In some embodiments, ESI at 1010 may provide multiple ions to an ion funnel at 1020. The ion funnel can focus the ion flow. For example, the ion funnel can focus the ion flow using one or more electrodes with decreasing inner diameters (e.g., stacked ring electrodes). In some embodiments, the ion funnel can focus ions and efficiently transmit them to lower pressure areas. This can help address a challenge arising from ESI where ions may be generated at atmospheric pressure but analyzed at lower pressures, resulting in ion loss due to Joule expansion or free-jet expansion. Focusing and transmitting ions by the ion funnel can help offset the expansion of the ion cloud, limiting the amount of ions reaching the detector. Workflow diagram 1000 illustrates the ion funnel at 1020 before FAIMS at 1030, but in some embodiments, the ion funnel may be positioned after FAIMS at 1030, either in addition or as an alternative. In some embodiments, the ion funnel in 1020 may be identical or similar to one or more ion funnels disclosed herein. In some embodiments, the ion funnel may be operated at a pressure of at least 8 torr (e.g., about 8 torr to about 12 torr).

[0102] In some embodiments, the ion funnel at 1020 may allow the focused ion flow to pass through into the FAIMS at 1030. In some embodiments, the FAIMS at 1030 may be a FAIMS device. For example, the FAIMS device may be a planar FAIMS device, as disclosed herein. In another embodiment, the FAIMS device may be a non-planar FAIMS device (e.g., having a curved or rounded structure), as described in PCT / US2024 / 027512 (which is incorporated as a whole by reference). Several embodiments of a planar FAIMS device are illustrated herein in Figures 5A-8. In some embodiments, the ion funnel may be integrated into the FAIMS device at 1030 in addition to, or as an alternative to, an external ion funnel (e.g., an ion filter at 1020 or a splitting ion funnel at 1040). In some embodiments, at 1030, the FAIMS device may separate ions from the ion flow based on their differential mobility in an asymmetric (e.g., oscillating) electric field. Therefore, the FAIMS in 1030 may output a filtered ion flow.

[0103] In some embodiments, the ion stream filtered from the FAIMS at 1030 may be fed into a splitting ion funnel at 1040. The splitting ion funnel may have some similarity to, for example, the ion funnel at 1020. In some embodiments, the splitting ion funnel may split the filtered ion stream into a plurality of filtered ion streams. The splitting ion funnel at 1040 may perform a splitting operation that is identical or similar to one or more of the splitting techniques disclosed herein. The operation may be performed on each of the filtered ion streams in the plurality of filtered ion streams. For example, the operation may be identical for at least two (or, for example, each) of the plurality of filtered ion streams. In another embodiment, the operation may be different for at least two (or, for example, each) of the plurality of filtered ion streams. Multiplexing may be made possible when enabling the operation to be applied to a plurality of filtered ion streams. For example, multiplexed mass spectroscopy may be performed by performing mass spectroscopy separately (for example, at least partially, overlapping on the time axis) using one or more of the plurality of filtered ion streams. This multiplexing can enable faster and more efficient mass spectrometry analysis (e.g., in terms of time, computing resources, network traffic, materials, etc.). Multiplexing can also enable improved detection, sensitivity, accuracy, and / or precision.

[0104] In some embodiments, the first ion optical system comprises an electric field asymmetric waveform ion mobility spectrometer and a traveling wave ion mobility spectrometer (TWIMS) or a captured ion mobility spectrometer (TIMS). In some embodiments, the electric field asymmetric waveform ion mobility spectrometer is upstream of the traveling wave ion mobility spectrometer (TWIMS) or the captured ion mobility spectrometer (TIMS). In some embodiments, the electric field asymmetric waveform ion mobility spectrometer is designed to operate below atmospheric pressure (e.g., less than 100 torr, less than 50 torr, less than 20 torr, less than 10 torr, or less than 5 torr). In some embodiments, the electric field asymmetric waveform ion mobility spectrometer is designed to operate at about 3 to about 8 torr. In some embodiments, the electric field asymmetric waveform ion mobility spectrometer is designed to operate at about 4 to about 6 torr. In some embodiments, the electric field asymmetric waveform ion mobility spectrometer is configured to preferentially remove ions with a net charge of +1. In some embodiments, the second ion optical system further comprises at least one collision cell and at least one upstream mass filter, each corresponding to at least one mass spectrometer. In some embodiments, the second ion optical system further comprises a second collision cell and / or a second mass filter, each corresponding to at least one mass spectrometer. (Example implementation of reduced-pressure planar ion mobility spectroscopy)

[0105] Figure 5A shows an example of a planar FAIMS (High Electric Field Asymmetric Waveform Ion Mobility Spectroscopy) configuration (front view) 501, and Figure 5B shows an example of a planar FAIMS configuration (rear view) 502, showing the FAIMS and RF (outer electrode) polarity for electrodes on the upper and lower substrate plates. Figure 5A is a front view, as can be seen from the flow of ions entering the device. Figure 5B is a rear view, as can be seen from the flow of ions exiting the device. The upper PCB 503a comprises outer electrodes 505a and 505b. The bottom PCB 503a comprises outer electrodes 506a and 506b. In Figure 5B, the upper PCB 503a comprises an upper RF+ electrode 505a, an upper FAIMS+ separation electrode 507a, and an upper RF- electrode 505b. The bottom PCB 503b comprises an upper RF electrode 506a, an upper FAIMS separation electrode 507b, and an upper RF+ electrode 506b. In some embodiments, the outer electrodes may function as a quadrupole and be configured together to guide ions through the planar FAIMS. The electrodes may be constructed from any suitable material commonly used in the art. In some cases, the electrodes comprise gold-plated copper.

[0106] Figure 6 shows an exemplary top schematic view of one planar substrate used in the FAIMS configuration 600. A second planar substrate with the same design may be installed above the first planar substrate (for example, as depicted in Figures 5A and 5B). Directional flow of ions is indicated as 605. In some embodiments, the FAIMS may operate using a fluid (e.g., an inert gas) that flows across the FAIMS. For example, as shown in Figure 6, the fluid may flow from left to right. The fluid may flow across one or more substrate plates 620. In some embodiments, one or more substrate plates comprise a PCB (board). In some cases, the substrate plates have mounting points 601 / 602 to the device chassis. In some cases, the mounting points 601 and 602 are staggered on the upper and lower substrate plates. The substrate plates may extend to at least a portion of the length of the FAIMS region 603. As shown, the FAIMS region does not have to extend along the entire length of the device. For example, the FAIMS region may be located with space on the left side of the device, as shown. This space may allow ions to travel through for deceleration before entering the FAIMS region, for example. In some embodiments, the FAIMS region may operate under reduced pressure. For example, the FAIMS region may operate using low pressure (e.g., about 5 torr). In some embodiments, the FAIMS region may be defined as a region within a quadrupole. The quadrupole may be driven by one or more outer electrodes. In addition, or alternatively, the quadrupole may be driven by SD electrodes acting as guardrails. The FAIMS region may include an inner electrode 625. In some cases, the substrate plate is surrounded, or integrated with, at least partially, one or more ion funnels (see Figure 1-2, 10).

[0107] In some embodiments, the FAIMS may include one or more substrate plates with a length (maximum linear dimension) of about 10 mm to about 1,000 mm.In the globe embodiment, FAIMS are approximately 10mm to 50mm, 10mm to 100mm, 10mm to 150mm, 10mm to 200mm, 10mm to 250mm, 10mm to 300mm, 10mm to 350mm, 10mm to 400mm, 10mm to 450mm, 10mm to 500mm, 10mm to 1,000mm, 50mm to 100mm, 50mm to 150mm, 50mm to 200mm, 50mm to 250mm, 50mm to 300mm, 50mm to 350mm, and 50mm~approx. 400mm, approx. 50mm~approx. 450mm, approx. 50mm~approx. 500mm, approx. 50mm~approx. 1,000mm, approx. 100mm~approx. 150mm, approx. 100mm~approx. 200mm, approx. 100mm~approx. 250mm, approx. 100mm~approx. 300mm, approx. 100mm~approx. 350mm, approx. 100mm~approx. 400mm, approx. 100mm~approx. 450mm, approx. 100mm~approx. 500mm, approx. 100mm~approx. 1,000mm, approx. 150mm~approx. 200mm, approx. 150mm~approx. 250mm, approx. 150mm~approx. 300mm, approx. 150mm~approx. 350mm, approx. 150mm ~400mm, 150mm~450mm, 150mm~500mm, 150mm~1,000mm, 200mm~250mm, 200mm~300mm, 200mm~350mm, 200mm~400mm, 200mm~450mm , about 200mm to about 500mm, about 200mm to about 1,000mm, about 250mm to about 300mm, about 250mm to about 350mm, about 250mm to about 400mm, about 250mm to about 450mm, about 250mm to about 500mm, about 250mm to about 1,000mm, about 300m It may include one or more substrate plates with lengths of approximately m to 350 mm, approximately 300 mm to 400 mm, approximately 300 mm to 450 mm, approximately 300 mm to 500 mm, approximately 300 mm to 1,000 mm, approximately 350 mm to 400 mm, approximately 350 mm to 450 mm, approximately 350 mm to 500 mm, approximately 350 mm to 1,000 mm, approximately 400 mm to 450 mm, approximately 400 mm to 500 mm, approximately 400 mm to 1,000 mm, approximately 450 mm to 500 mm, approximately 450 mm to 1,000 mm, or approximately 500 mm to 1,000 mm.In some embodiments, the FAIMS may include one or more substrate plates having lengths of about 10 mm, about 50 mm, about 100 mm, about 150 mm, about 200 mm, about 250 mm, about 300 mm, about 350 mm, about 400 mm, about 450 mm, about 500 mm, or about 1,000 mm. In some embodiments, the FAIMS may include one or more substrate plates having lengths of at least about 10 mm, about 50 mm, about 100 mm, about 150 mm, about 200 mm, about 250 mm, about 300 mm, about 350 mm, about 400 mm, about 450 mm, or about 500 mm. In some embodiments, the FAIMS may include one or more substrate plates with lengths of up to approximately 50 mm, 100 mm, 150 mm, 200 mm, 250 mm, 300 mm, 350 mm, 400 mm, 450 mm, 500 mm, or 1,000 mm.

[0108] In some embodiments, the FAIMS comprises a first substrate plate and a second substrate plate. In some cases, the distance between the first plate and the second plate is 0.1 to 20 mm, 0.3 to 20 mm, 0.5 to 20 mm, 1 to 20 mm, 2 to 20 mm, 5 to 20 mm, 0.5 to 10 mm, 0.1 to 10 mm, 0.5 to 12 mm, 3 to 10 mm, 4 to 8 mm, 5 to 10 mm, or 5 to 10 mm. In some cases, the distance between the first plate and the second plate is 0.1, 0.2, 0.3, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15 mm or less, or 20 mm or less. In some cases, the distance between the first plate and the second plate is at least 0.1, 0.2, 0.3, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, or at least 20 mm.

[0109] Some embodiments suggest that the FAIMS may have a pressure of approximately 0.1 torr to approximately 100 torr. Some embodiments suggest that the FAIMS may have a pressure of approximately 0.1 torr to approximately 0.5 torr, approximately 0.1 torr to approximately 1 torr, approximately 0.1 torr to approximately 2 torr, approximately 0.1 torr to approximately 4 torr, approximately 0.1 torr to approximately 6 torr, approximately 0.1 torr to approximately 8 torr, approximately 0.1 torr to approximately 10 torr, approximately 0.1 torr to approximately 15 torr, approximately 0.1 torr to approximately 20 torr, approximately 0.1 torr to Approximately 40 torr, approximately 0.1 torr to approximately 100 torr, approximately 0.5 torr to approximately 1 torr, approximately 0.5 torr to approximately 2 torr, approximately 0.5 torr to approximately 4 torr, approximately 0.5 torr to approximately 6 torr, approximately 0.5 torr to approximately 8 torr, approximately 0.5 torr to approximately 10 torr, approximately 0.5 torr to approximately 15 torr, approximately 0.5 torr to approximately 20 torr, approximately 0.5 torr to approximately 40 torr, approximately 0.5 to 100 torr, 1 to 2 torr, 1 to 4 torr, 1 to 6 torr, 1 to 8 torr, 1 to 10 torr, 1 to 15 torr, 1 to 20 torr, 1 to 40 torr, 1 to 100 torr, 2 to 4 torr, 2 to 6 torr, 2 tons orr~approx. 8 torr, approx. 2 torr~approx. 10 torr, approx. 2 torr~approx. 15 torr, approx. 2 torr~approx. 20 torr, approx. 2 torr~approx. 40 torr, approx. 2 torr~approx. 100 torr, approx. 4 torr~approx. 6 torr, approx. 4 torr~approx. 8 torr, approx. 4 torr~approx. 10 torr, approx. 4 torr~approx. 15 torr, approx. 4 torr~approx. 20 torr, approx. 4 torr~approx. 40 torr, approx. 4 tors orr ~ approximately 100 torr, approximately 6 torr ~ approximately 8 torr, approximately 6 torr ~ approximately 10 torr, approximately 6 torr ~ approximately 15 torr, approximately 6 torr ~ approximately 20 torr, approximately 6 torr ~ approximately 40 torr, approximately 6 torr ~ approximately 100 torr, approximately 8 torr ~ approximately 10 torr, approximately 8 torr ~ approximately 15 torr, approximately 8 torr ~ approximately 20 torr, approximately 8 torr ~ approximately 40 torr, approximately 8 torr ~ approximately 100 torr The pressures may be approximately 10 torr to 15 torr, approximately 10 torr to 20 torr, approximately 10 torr to 40 torr, approximately 10 torr to 100 torr, approximately 15 torr to 20 torr, approximately 15 torr to 40 torr, approximately 15 torr to 100 torr, approximately 20 torr to 40 torr, approximately 20 torr to 100 torr, or approximately 40 torr to 100 torr. Some advantages are that the FAIMS may have pressures of approximately 0.1 torr, approximately 0.5 torr, approximately 1 torr, approximately 2 torr, approximately 4 torr, approximately 6 torr, approximately 8 torr, approximately 10 torr, approximately 15 torr, approximately 20 torr, approximately 40 torr, or approximately 100 torr. In some embodiments, the FAIMS may have a pressure of at least about 0.1 torr, about 0.5 torr, about 1 torr, about 2 torr, about 4 torr, about 6 torr, about 8 torr, about 10 torr, about 15 torr, about 20 torr, or about 40 torr. In some embodiments, the FAIMS may have a maximum pressure of about 0.It may have a pressure of 5 torr, approximately 1 torr, approximately 2 torr, approximately 4 torr, approximately 6 torr, approximately 8 torr, approximately 10 torr, approximately 15 torr, approximately 20 torr, approximately 40 torr, or approximately 100 torr.

[0110] The length of the FAIMS region (for example, the length of the FAIMS region 603) is at least about 10 mm, at least about 50 mm, at least about 100 mm, or at least about 150 mm. In some embodiments, the length of the FAIMS region is about 750 mm or less, about 500 mm or less, about 400 mm or less, or about 300 mm or less. In some embodiments, the length of the FAIMS region is about 100 mm to about 400 mm.

[0111] Figure 7 shows an exemplary top schematic view of a FAIMS configuration 700 in which the FAIMS region 603 and FAIMS electrode 507a extend almost the entire length of the device.

[0112] Figure 8 shows an exemplary top schematic of a FAIMS configuration 800 in which the FAIMS region 603 extends to almost the entire length (longest linear dimension) of the device and utilizes separate compartmentalized electrodes (components 801, 802, etc.). Any number of compartments, such as at least 2, 3, 4, 6, 8, 12, 16, 20, 24, or at least 32, may be used for the FAIMS electrodes. In some cases, the FAIMS electrodes comprise 2, 3, 4, 6, 8, 12, 16, 20, 24 or fewer, or 32 or fewer. In some cases, the FAIMS electrodes comprise 2-32, 2-24, 2-16, 2-8, 4-32, 4-16, 4-12, 8-32, 8-24, 8-16, or 12-32 compartments. In some cases, the compartments superimpose a DC gradient to drive ions through the FAIMS region. In some embodiments, the compartments superimpose a DC gradient to drive ions through the FAIMS region without gas flow. In some cases, the compartments are positioned in a meandering pattern to minimize device size while increasing distance.

[0113] Those skilled in the art will understand, based on the teachings of this application, that various features of the planar FAIMS disclosed herein may be combined. For example, the FAIMS configuration 600 may include compartmentalized electrodes and be modified to drive ions without gas flow.

[0114] Figure 9A shows an exemplary front schematic view of a FAIMS configuration 900. A stack of PCBs 905 is integrated into a single assembly. The exit ion funnel is shown as 901. In some cases, the PCB 905 is a double-sided structure (with electrodes on both the top and bottom sides of the single board). Any number of substrate plates, such as 2, 3, 4, 5, 6, 8, 10, 12, 15, 20, 30, or more, may be integrated into the assembly. In some cases, the substrate plates are arranged in a one-dimensional array (e.g., 1×2, 1×3, 1×4, and equivalents) or a two-dimensional array (e.g., 2×2, 2×3, 3×2, 2×4, 3×3, 4×4, or 2×5 configurations and equivalents). The substrate plates may be PCBs, but other suitable materials may be used. Figure 9B shows an exemplary front schematic view of a FAIMS configuration 903. In some cases, adjacent outer electrodes (904a / 904b) are shared between FAIMS devices.

[0115] Figure 11 shows a schematic diagram of a device configuration 1100 comprising an ion funnel 1020, a planar FAIMS 1030, an ion funnel 1035, a splitting ion funnel 1040, and a splitting ion output 1050. Part of the planar FAIMS device may be located within the second ion funnel, as shown, or the planar FAIMS device may be spaced apart from the second ion funnel. In some embodiments, the ion funnel 1035 may be a rectangular ion funnel having a rectangular cross-sectional opening for funneling ions.

[0116] Figures 12A–12H depict the front-end ion manifold 1200 described herein, which includes an ion inlet 1206. Ports such as sensors 1201a–c (for monitoring conditions such as pressure, temperature, or other conditions), electrical connections 1203a–b, vacuum ports 1204a–b, the ion inlet 1206, and one or more (e.g., splitter) ion outlets 1205 may be present within one or more chambers of the device. Figure 12G shows a cross-sectional view of the device configuration 1200 described herein, which includes an ion inlet and an ion funnel chamber 1020, a FAIMS chamber 1030 (with an ion funnel 1035), and a splitting ion funnel chamber 1040. Ions flow from left to right. The cross-section is obtained along plane 7, as depicted in Figure 12C. Ports such as ports for sensors 1201a-c (for monitoring conditions such as pressure, temperature, or other conditions), electrical connections 1203, vacuum ports 1204, ion inlets, and one or more (e.g., splitter) ion outlets 1205 may be present in one or more chambers of the device. The FAIMS chamber 1030 comprises a planar FAIMS with upper 503a and bottom 503b PCBs, and an ion funnel 1035. The front-end device 1200 also comprises a first ion funnel 116 and a splitting ion funnel 118.

[0117] Figures 13A–13H depict device 1300, which comprises both a front-end device 1200 and a TWIMS (Traveling Wave Ion Mobility) device 1301. In some cases, the front-end device comprises the FAIMS interface shown in Figures 12A–12H. Figure 13G shows a cross-section along plane 14, as depicted in Figure 13C. The TWIMS device 1301 includes a substrate 1305 (e.g., a PCB board) with electrodes that separate ions based on ion mobility using traveling waves. Each output from a splitting ion funnel (e.g., ion outlet 1205, depicted in Figure 12G) may be fed into a separate region of the TWIMS device for ion mobility separation before exiting through the TWIMS outlet 1310. In cases where the splitting ion funnel has four outlets, an additional substrate may be included for ion mobility separation before exiting through an optional TWIMS outlet 1315. As disclosed herein, in some embodiments, two or more of the TWIMS outlets may be operably coupled to different mass spectrometers for multiplex analysis.

[0118] In some embodiments, the plate, used in conjunction with a FAIMS configuration, may be flexible. The flexibility of the support described herein (e.g., a circuit board) may be measured using Young's modulus. Young's modulus measures the resistance of a material to elastic (recoverable) deformation under load. A list of Young's moduli for the stiffness of the exemplary materials described herein is provided below, namely, nylon (3 GPa), nitrocellulose (1.5 GPa), polypropylene (2 GPa), silicon (150 GPa), polystyrene (3 GPa), agarose (1-10 GPa), polyacrylamide (1-10 GPa), and polydimethylsiloxane (PDMS) (1-10 GPa). The solid support described herein may have Young's moduli of 1-500, 1-40, 1-10, 1-5, or 3-11 GPa. The solid supports described herein may have a Young's modulus of about 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 20, 25, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 400, 500 GPa, or greater. The relationship between flexibility and rigidity is inverse to each other, with flexible materials having a low Young's modulus and significantly changing their shape under load. In some cases, the flexibility of a support refers to a support that, when bent according to a radius of curvature of 100, 50, 30, 20, 10, or 5 mm or more (compared to a planar substrate), is able to maintain the structural integrity of the substrate of the support.

[0119] Those skilled in the art will understand, based on the teachings of this application, that the splitting ion funnel disclosed herein may be arranged in various locations relative to other components. For example, the splitting ion funnel may be positioned in front of a FAIMS device such that each output of the splitting ion funnel can be operably coupled to a different FAIMS device (e.g., four outlets are fed into four separate FAIMS devices). In another embodiment, the splitting ion funnel 118 may have independently controllable electrodes positioned in or near each of the outputs 114. This allows for adjustment of the voltage at each output and control of the relative flow of ions between the outputs. The voltage may be adjusted for each output to have substantially the same ion flux, or alternatively, the voltage may be adjusted to bias more ion flux toward a certain output. In some cases, this can be dynamically controlled during the operation of the device. In another embodiment, the splitting ion funnel may receive ions separated by ion mobility from a TWIMS device. This has the advantage of using only one TWIMS device. Other configurations are also possible and within the scope of this application. (Example computer system)

[0120] This disclosure provides a computer system programmed to implement the methods described herein. Figure 3 shows a computer system 201 programmed or otherwise configured to implement the methods and systems described herein. The computer system 201 may be a computer system located remotely from a user's electronic device or an electronic device. The electronic device may be a mobile electronic device.

[0121] The computer system 201 includes a central processing unit (CPU, also referred to herein as "processor" and "computer processor") 205, which may be a single-core or multi-core processor, or multiple processors for parallel processing. The computer system 201 also includes memory or memory locations 210 (e.g., random-access memory, read-only memory, flash memory), an electronic storage unit 215 (e.g., a hard disk), a communication interface 220 for communicating with one or more other systems (e.g., a network adapter), and peripheral devices 225 such as caches, other memories, data storage devices, and / or electronic display adapters. The memory 210, storage unit 215, interface 220, and peripheral devices 225 communicate with the CPU 205 through a communication bus (solid line), such as a motherboard. The storage unit 215 may be a data storage unit (or data repository) for storing data. The computer system 201 can be operationally coupled to a computer network ("network") 230 with the help of the communication interface 220. Network 230 may be the Internet, an intranet, and / or an extranet, or an intranet and / or extranet communicating with the Internet. Network 230 may, in some cases, be a telecommunications and / or data network. Network 230 may include one or more computer servers that can enable distributed computing, such as cloud computing. Network 230 may, in some cases, implement a peer-to-peer network that, with the help of computer system 201, can enable devices coupled to computer system 201 to behave as clients or servers.

[0122] The CPU 205 can execute a sequence of machine-readable instructions, which may be embodied in a program or software. Instructions may be stored in a memory location, such as memory 210. Instructions can be directly directed to the CPU 205, which can then be programmed or otherwise configured to implement the methods of this disclosure. Embodiments of operations performed by the CPU 205 may include fetching, decoding, executing, and writing back.

[0123] CPU205 may be part of a circuit such as an integrated circuit. One or more other components of system 201 may be included in the circuit. In some cases, the circuit is an application-specific integrated circuit (ASIC).

[0124] The storage unit 215 can store files such as drivers, libraries, and saved programs. The storage unit 215 can also store user data, such as user preferences and user programs. The computer system 201 may include one or more additional data storage units located outside the computer system 201, such as on a remote server that communicates with the computer system 201 via an intranet or the internet.

[0125] Computer system 201 can communicate with one or more remote computer systems via network 230. For example, computer system 201 can communicate with a user's remote computer system. Embodiments of remote computer systems include personal computers (e.g., portable PCs), slate or tablet PCs (e.g., Apple® iPad®, Samsung® Galaxy Tab), telephones, smartphones (e.g., Apple® iPhone®, Android®-enabled devices, Blackberry®), or personal digital assistants. Users can access computer system 201 via network 230.

[0126] The methods described herein can be implemented using machine-executable code (e.g., a computer processor) stored on an electronic storage location of the computer system 201, such as memory 210 or an electronic storage unit 215. The machine-executable or machine-readable code can be provided in the form of software. During use, the code can be executed by the processor 205. In some cases, the code can be read from the storage unit 215 and stored on memory 210 for quick access by the processor 205. In some situations, the electronic storage unit 215 can be omitted, and the machine-executable instructions are stored on memory 210.

[0127] The code can be pre-compiled and configured for use with machines that have processors adapted to run the code, or it can be compiled during runtime. The code can be supplied in a programming language, which may be chosen to allow the code to be executed in a pre-compiled form or in a post-compiled form.

[0128] Aspects of the systems and methods provided herein, such as computer system 201, can be embodied in programming. Various aspects of the technology can typically be considered “products” or “manufactured goods” in the form of machine (or processor) executable code and / or associated data carried on or embodied thereon on a certain type of machine-readable medium. Machine-executable code can be stored on electronic storage units such as memory (e.g., read-only memory, random-access memory, flash memory) or hard disks. The “storage” type medium can include any or all of the tangible memory of a computer, processor, or equivalent, or its associated modules such as various semiconductor memories, tape drives, disk drives, and equivalents, which can provide non-transient storage at any given time for software programming. All or part of the software may be communicated from time to time via the Internet or various other telecommunication networks. Such communication may enable, for example, the loading of software from one computer or processor to another, for example, from a management server or host computer to an application server computer platform. Therefore, other types of media that may hold software elements include optical, electrical, and electromagnetic waves, such as those used across physical interfaces between local devices, through wired and optical fixed networks, and via various air links. Physical elements that carry such waves, such as wired or wireless links, optical links, or equivalents, may also be considered media that hold software. Unless limited to non-transient tangible “storage” media as used herein, the terms computer or machine “readable media,” etc., refer to any medium involved in providing instructions to a processor for execution.

[0129] Therefore, machine-readable media such as computer executable code may take many forms, but are not limited to, tangible storage media, carrier media, or physical transmission media. Non-volatile storage media include optical or magnetic disks, such as any storage device in any computer or equivalent, which may be used to implement a database as shown in the drawings. Volatile storage media include dynamic memory, such as the main memory of such a computer platform. Tangible transmission media include copper wires and optical fibers, including coaxial cables and wires that form buses in computer systems. Carrier media may take the form of electrical or electromagnetic signals, or acoustic or optical waves, such as those generated between radio frequency (RF) and infrared (IR) data communications. Common forms of computer-readable media include, for example, floppy disks, flexible disks, hard disks, magnetic tapes, any other magnetic media, CD-ROMs, DVDs or DVD-ROMs, any other optical media, punch cards, paper tapes, any other physical storage media with perforation patterns, RAM, ROMs, PROMs and EPROMs, FLASH®-EPROMs, any other memory chips or cartridges, carriers for transferring data or instructions, cables or links for transferring such carriers, or any other media from which a computer can read programming code and / or data. Many of these forms of computer-readable media may be involved in transporting one or more sequences of one or more instructions to a processor for execution.

[0130] The computer system 201 includes, or can communicate with, an electronic display 235, which for example provides a user interface (UI) 240 for selecting ion manifold implantation parameters. Embodiments of the UI include, but are not limited to, a graphical user interface (GUI) and a web-based user interface.

[0131] The methods and systems of this disclosure can be implemented using one or more algorithms. The algorithms can be implemented using software in response to execution by the central processing unit 205. The algorithms can implement, for example, a method for characterizing an eardrum. Embodiment

[0132] The following are exemplary embodiments of the disclosures herein. Embodiment 1. An ion manifold, (a) Ion manifold inlet and (b) A first ion optical system configured to receive an ion flux through the inlet of an ion manifold, (c) A second ion optical system configured to receive the output of an ion flux through a first ion optical system, the second ion optical system having multiple outputs for splitting the ion flux into multiple ion streams, An ion manifold equipped with this feature. Embodiment 2. A method for generating multiple ion flows, (a) A step of providing an ion bundle to the ion manifold inlet of an ion manifold, the ion manifold is i. Ion manifold entrance and ii. A first ion optical system configured to receive an ion flux through the inlet of an ion manifold, iii. A second ion optical system configured to receive the output of an ion flux through a first ion optical system, the second ion optical system having multiple outputs, It has steps, (b) When the ion flux passes through the second ion optical system, the step of generating multiple ion streams from multiple outputs of the second ion optical system, Methods that include... Embodiment 3. An ion manifold or method according to any of the prior embodiments, wherein the first ion optical system and the second ion optical system include an ion funnel. Embodiment 4. An ion manifold or method according to any of the prior embodiments, wherein the first ion optical system and the second ion optical system comprise one or more electrical conductor compartments. Embodiment 5. An ion manifold or method according to any of the prior embodiments, wherein one or more electrical conductor compartments are provided with one or more through holes. Embodiment 6. An ion manifold or method according to any of the prior embodiments, wherein one or more through-holes are circular, oval, polygonal, or square in shape. Embodiment 7. An ion manifold or method according to any of the prior embodiments, wherein one or more electrical conductor compartments include a printed circuit board. Embodiment 8. An ion manifold or method according to any of the prior embodiments, wherein one or more electrical conductor compartments have a center-to-center distance of at least about 1 mm. Embodiment 9. An ion manifold or method according to any of the prior embodiments, wherein one or more through-holes are provided along a linear axis on the surface of one or more electrical conductor compartments. Embodiment 10. An ion manifold or method according to any of the prior embodiments, wherein two or more through-holes in one or more electrical conductor compartments are adjacent to or in contact with each other. Embodiment 11. An ion manifold or method according to any of the prior embodiments, wherein the ion manifold inlet comprises a heated ion manifold inlet. Embodiment 12. An ion manifold or method according to any of the prior embodiments, wherein the ion manifold inlet comprises a slotted capillary tube. Embodiment 13. An ion manifold or method according to any of the prior embodiments, wherein the slotted capillary has a rectangular cross-sectional geometric shape. Embodiment 14. An ion manifold or method according to any of the prior embodiments, wherein the ion manifold inlet has a circular or oval cross-sectional geometric shape. Embodiment 15. An ion manifold or method according to any of the prior embodiments, wherein the repeller, ion manifold inlet, and first ion optical system are at least partially contained within the first chamber. Embodiment 16. An ion manifold or method according to any of the prior embodiments, wherein the first chamber has a pressure of at least about 8 torr (e.g., about 8 torr to about 12 torr). Embodiment 17. An ion manifold or method according to any of the prior embodiments, wherein the second ion optical system is contained within the second chamber, at least partially different from the first chamber. Embodiment 18. An ion manifold or method according to any of the prior embodiments, wherein the second chamber has a pressure of at least about 1 torr (e.g., about 1 torr to about 3 torr). Embodiment 19. An ion manifold or method according to any of the prior embodiments, wherein the first chamber has a first pressure and the second chamber has a second pressure, and the first pressure is higher than the second pressure. Embodiment 20. An ion manifold or method according to any of the prior embodiments, wherein an ion bundle is provided from a multi-emitter array to the ion manifold inlet by electrospray ionization. Embodiment 21. An ion manifold or method according to any one of the prior embodiments, further comprising an ion repeller manifold, wherein (i) an axis along the normal vector of the surface of the ion repeller manifold is positioned perpendicular to the central axis of the ion manifold inlet, and (ii) an ion flux path is directed into the first ion optical system. Embodiment 22. An ion manifold or method according to any of the prior embodiments, comprising a partitioned plate, and optionally comprising at least about two compartments or at least about three compartments. Embodiment 23. The compartmentalized ion repeller manifold according to Embodiment 22, wherein the compartmentalized ion repeller is configured to allow different voltages in order to improve the efficiency of ion delivery into the ion funnel. Embodiment 24. An ion manifold or method according to any of the prior embodiments, wherein the central axes of the first ion optical system and the second ion optical system are perpendicular to the central axis of the ion manifold inlet. Embodiment 25. An ion manifold or method according to any of the prior embodiments, wherein the central axis of the ion manifold inlet is perpendicular to the axis normal to the surface of the ion repeller manifold. Embodiment 26. An ion manifold or method according to any of the prior embodiments, wherein the first electrode compartment of the ion repeller manifold has a lower voltage than the adjacent second electrode compartment of the ion repeller manifold. Embodiment 27. An ion manifold or method according to any of the prior embodiments, wherein the ion repeller manifold has a voltage gradient across the longitudinal length of the ion repeller manifold. Embodiment 28. An ion manifold or method according to any of the prior embodiments, comprising a port fluidly coupled to the ion manifold, wherein the port is configured to pressurize a first chamber, a second chamber, or a combination thereof. Embodiment 29. An ion manifold or method according to any of the prior embodiments, wherein the central axis of the port is collinear with the central axis of the ion manifold inlet. Embodiment 30. An ion manifold or method according to any of the prior embodiments, wherein the first or second ion optical system comprises a linear DC gradient provided by one or more electrical conductor compartments across the longitudinal length of the first or second ion optical system. Embodiment 31. An ion manifold or method according to any of the prior embodiments, wherein one or more electrical conductor compartments of the first or second ion optical system have up to four DC conductance limits. Embodiment 32. An ion manifold or method according to any of the prior embodiments, wherein a first electrical conductor compartment of one or more electrical conductor compartments provides a first signal with a first phase, and a second electrical conductor compartment of one or more electrical conductor compartments provides a second signal with the opposite phase to the first phase. Embodiment 33. An ion manifold or method according to any of the prior embodiments, wherein the first ion optical system, the second ion optical system, or a combination thereof is configured to output one or more ion streams of ion fluxes provided to the ion manifold inlet in the range of about 400 to about 900 mass / charge. Embodiment 34. An ion manifold or method according to any of the prior embodiments, wherein a reduced-pressure FAIMS (high electric field asymmetric waveform ion mobility spectrometer) device is configured to receive ions from a first ion optical system and selectively output ions to a second ion optical system. Embodiment 35. The ion manifold or method according to Embodiment 34, wherein the reduced-pressure FAIMS device is a planar FAIMS device comprising two substrates, each having an outer electrode and a separation electrode. Embodiment 36. Ion mobility device, a. A first substrate plate, i. Coplanar first outer electrode and second outer electrode, ii. The first separation electrode and, A first substrate plate comprising, b. A second substrate plate, i. Coplanar third and fourth outer electrodes, ii. The second separation electrode, A second substrate plate comprising, A device comprising a first substrate plate and a second substrate plate that are substantially parallel. Embodiment 37. The device further comprises an inlet configured for gas flow, as described in Embodiment 36. Embodiment 38. The device according to Embodiment 36 or 37, wherein the longest linear dimension of the first substrate plate and the second plate is 100 to 300 mm. Embodiment 39. The device according to any one of Embodiments 36-38, wherein the distance between the first plate and the second plate is 0.5 to 12 mm. Embodiment 40. The device according to any one of Embodiments 36-38, wherein the distance between the first plate and the second plate is approximately 6 mm. Embodiment 41. The device according to any one of Embodiments 36-40, wherein the region surrounding the first and second separation electrodes has a pressure of 20 torr or less. Embodiment 42. The device according to any one of Embodiments 36-40, wherein the region surrounding the first and second separation electrodes has a pressure of 5 to 15 torr. Embodiment 43. The device according to any one of Embodiments 36-42, wherein a portion of either the first or second separation electrode is surrounded at least partially by an ion funnel. Embodiment 44. The device according to Embodiment 43, wherein the ion funnel comprises a rectangular ion funnel (RIF). Embodiment 45. The device according to any one of Embodiments 36-44, wherein the longest linear dimension of the separation electrode is shorter than the longest linear dimension of the outer electrode. Embodiment 46. The device according to Embodiment 45, wherein the separation electrode is positioned distal to the ion flow relative to the outer electrode. Embodiment 47. The separation electrode is partitioned, as described in any one of Embodiments 36-46. Embodiment 48. The device according to Embodiment 47, wherein at least a portion of the partitions is independently addressable. Embodiment 49. The device according to Embodiment 47 or 48, wherein the isolation electrode comprises at least two compartments (e.g., 2 to 40 compartments). Embodiment 50. The device according to Embodiment 47 or 48, wherein the compartments are arranged in a substantially linear configuration. Embodiment 51. The device according to Embodiment 47 or 48, wherein the compartments are arranged in a meandering configuration. Embodiment 52. The device according to any one of Embodiments 36-51, wherein the substrate plate comprises a printed circuit board (PCB). Embodiment 53. The device according to any one of Embodiments 36-52, wherein the substrate plate further comprises electrodes configured to provide ion mobility separation using traveling wave ion mobility spectroscopy (TWIMS) or captured ion mobility spectroscopy (TIMS). Embodiment 54. A device assembly comprising a plurality of ion mobility devices as described in any one of Embodiments 36-53. Embodiment 55. The device assembly according to Embodiment 54, wherein two or more adjacent outer electrodes are shared on a substrate plate. Embodiment 56. The device assembly according to Embodiment 54 or 55, comprising a 2×1, 1×2, 2×2, 2×3, 3×2, 2×4, 3×3, 4×4, or 2×5 array of ion mobility devices (rows × columns). Embodiment 57. The device assembly is the device assembly according to any one of Embodiments 54-56, comprising at least four ion mobility devices. Embodiment 58. An ion manifold or method according to any one of Embodiments 1-34, comprising the device described in any one of Embodiments 36-57. Embodiment 59. The ion manifold or method according to Embodiment 59, wherein the device according to any one of Embodiments 36-57 is installed between a first ion optical system and a second ion optical system. Embodiment 60. The ion manifold or method according to Embodiment 58 or 59, wherein the pressure in the ion funnel of the first ion optical system is higher than the pressure in the ion mobility device. Embodiment 61. A method for separating ions, a. The step of providing an ion bundle to an ion mobility device according to any one of embodiments 36-57, b. The step of applying a high-voltage RF waveform to the isolation electrode, c. The step of applying an ion confinement waveform to the outer electrode, d. A step of selecting permeable ions based on mobility and generating a mobility-selective ion flow, Methods that include... Embodiment 62. The method according to Embodiment 61, wherein the RF waveform is a flyback transformer waveform. Embodiment 63. The method according to Embodiment 62 or 63, wherein the carrier gas is flowed into the inlet of the ion mobility device. Embodiment 64. The method according to Embodiment 62 or 63, wherein the isolation electrode is partitioned and has a DC gradient. Embodiment 65. A reduced-pressure electric field asymmetric ion mobility device, iii. A sealed mobility chamber located at the opposite end, having an ion inlet and an ion outlet, and configured to be filled with an inert gas at a pressure below atmospheric pressure, iv. At least one inner electrode positioned longitudinally between the ion inlet and ion outlet of the sealed mobility chamber, v. At least one outer electrode positioned longitudinally between the ion inlet and ion outlet of a sealed mobility chamber, wherein the outer electrode is positioned such that the inner electrode is at least partially sealed within the outer electrode, vi. One or more power sources configured to deliver a waveform to an inner electrode or an outer electrode, wherein the waveform is configured to differentially deflect ions having different ion mobilities based on the interaction of ions with the waveform and an inert gas, the differential deflection is configured to selectively remove ions having a mobility corresponding to a single charged species before the species reaches the ion outlet, and the inner and outer electrodes are substantially planar, A device equipped with the following features. Embodiment 66. A method for separating single-charged ions from multiple-charged ions, e. A step of providing an ion flux to the ion inlet of a reduced-pressure electric field asymmetric ion mobility device, wherein the reduced-pressure electric field asymmetric ion mobility device is 1. A sealed mobility chamber, located at the opposite end, having an ion inlet and an ion outlet, and configured to be filled with an inert gas at a pressure below atmospheric pressure, 2. At least one inner electrode is positioned longitudinally between the ion inlet and ion outlet of the sealed mobility chamber, 3. At least one outer electrode is positioned longitudinally between the ion inlet and ion outlet of the sealed mobility chamber, 4. One or more power sources configured to deliver a waveform to an inner or outer electrode, wherein the waveform is configured to differentially deflect ions having different ion mobilities based on the interaction of ions, the waveform, and an inert gas, and the differential deflection is configured to selectively remove ions having a mobility corresponding to a single charge species before the species reaches the ion outlet, It has steps, f. The step of applying a waveform using one or more power sources to substantially prevent ions in an ion flux having mobility corresponding to a single charge type from reaching the ion outlet of a reduced-pressure electric field asymmetric ion mobility device, g. A step of obtaining a multi-charged ion population enriched with ions corresponding to multiple charge species at the ion outlet of a reduced-pressure electric field asymmetric ion mobility device, Methods that include... Embodiment 67. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the gas pressure is less than about 700 torr (e.g., less than about 100 torr, less than about 10 torr, or less than about 5 torr). Embodiment 68. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the distance between the ion inlet and ion outlet is about 10 mm to about 700 mm (e.g., about 100 mm to about 500 mm, about 200 mm to about 400 mm, or about 250 mm to about 350 mm). Embodiment 69. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the distance from the central axis of the enclosed mobility chamber to the outer surface of at least one outer electrode is about 7 mm to about 50 mm (e.g., about 10 mm to about 40 mm, or about 15 mm to about 25 mm). Embodiment 70. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the distance from the central axis of the enclosed mobility chamber to the outer surface of at least one inner electrode is about 0.2 mm to about 20 mm (e.g., about 1 mm to about 15 mm, or about 3 mm to about 10 mm). Embodiment 71. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the distance from the outer surface of at least one inner electrode to the inner surface of at least one outer electrode is about 5 mm to about 40 mm (e.g., about 5 mm to about 30 mm, about 8 mm to about 20 mm, or about 10 mm to about 15 mm). Embodiment 72. One or more power sources comprising a waveform that provides a sinusoidal waveform, a square waveform, a triangular waveform, a sawtooth waveform, or a combination of one or more thereof, according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 73. One or more power sources provide a waveform comprising at least two sinusoidal waves that are phase-shifted relative to each other, according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 74. The method according to Embodiment 73 or a reduced-pressure electric field asymmetric ion mobility device, wherein the phase shift is approximately 30° to approximately 120° (e.g., approximately 30°, approximately 45°, approximately 60°, approximately 90°, or approximately 120°). Embodiment 75. The method according to any one of Embodiments 73-74 or a reduced-pressure electric field asymmetric ion mobility device, wherein the frequency of at least one of the at least two sine waves is about 100 kHz to about 2 MHz (e.g., about 100 kHz, about 500 kHz, about 750 kHz, about 1 MHz, about 1.5 MHz, or about 2 MHz). Embodiment 76. The method according to any one of Embodiments 73-75 or a reduced-pressure electric field asymmetric ion mobility device, wherein the absolute value of the maximum amplitude of the waveform is about 100V to about 2,000V (e.g., about 250V to about 1,750V, about 500V to about 1,500V, about 750V to about 1,000V, about 100V, about 300V, about 500V, about 700V, about 1,000V, about 1,500V, or about 2,000V). Embodiment 77. The method according to any one of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the overall duty cycle of the waveform delivered by one or more power sources is about 5% to about 90% (e.g., about 5%, about 10%, about 20%, about 30%, about 50%, or about 90%). Embodiment 78. A waveform is delivered to an inner electrode using the method of any one of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 79. A waveform is delivered to an outer electrode in the manner of any one of Embodiments 65-77 or in a reduced-pressure electric field asymmetric ion mobility device. Embodiment 80. An ion inlet extending substantially parallel to the direction of ion movement between the inner electrode and the outer electrode, according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 81. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the ion inlet extends at an angle with respect to the direction of ion movement between the inner electrode and the outer electrode, the angle being about 20° to about 70° (e.g., about 30° to about 60°, or about 40° to about 50°). Embodiment 82. An ion outlet extending substantially parallel to the direction of ion movement between the inner electrode and the outer electrode, according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 83. The ion outlet extends at an angle with respect to the direction of ion movement between the inner electrode and the outer electrode, the angle being about 60° to about 120° (e.g., about 70° to about 110°, about 80° to about 90°), according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 84. An ion inlet and ion outlet substantially aligned along a common axis, according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 85. An ion inlet and ion outlet are axially aligned, substantially perpendicular to each other, in the manner of any of Embodiments 65-79 or in a reduced-pressure electric field asymmetric ion mobility device. Embodiment 86. The method according to any of Embodiments 65-79 or a reduced-pressure electric field asymmetric ion mobility device, wherein the ion inlet is aligned along a first axis, the ion outlet is aligned along a second axis, and the first and second axes are aligned substantially parallel to each other. Embodiment 87. The method according to any of Embodiments 65-79 or a reduced-pressure electric field asymmetric ion mobility device, wherein the ion inlet is aligned along a first axis and the ion outlet is aligned along a second axis, and the first and second axes are aligned such that the first and second axes form an angle of about 40° to about 120° (e.g., about 45°, about 60°, about 75°, about 100°, or about 120°) at their intersection. Embodiment 88. An ion mobility device according to any one of Embodiments 65-87 or a reduced-pressure electric field asymmetric ion mobility device, wherein at least one outlet is operably coupled to at least one ion optical system. Embodiment 89. An external electrode comprising at least two ion outlets, the method according to any one of Embodiments 65-88 or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 90. The method according to Embodiment 89 or a reduced-pressure electric field asymmetric ion mobility device, wherein at least two ion outlets are operably coupled to a common ion optical system. Embodiment 91. The method according to Embodiment 89 or 90 or a reduced-pressure electric field asymmetric ion mobility device, wherein at least two ion outlets are independently operably coupled to different common ion optical systems. Embodiment 92. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the inert gas is nitrogen, helium, or argon. Embodiment 93. A reduced-pressure electric field asymmetric ion mobility device is configured for ion permeation, having an m / z value of about 400 to about 900, according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 94. A reduced-pressure electric field asymmetric ion mobility device configured to remove at least about 80% of a single charged ion within the first 50% of the distance between the inlet and outlet (e.g., at least about 85%, at least about 90%, at least about 95%, at least about 98%, or at least about 99%), according to any of Embodiments 68-93 or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 95. A reduced-pressure electric field asymmetric ion mobility device configured to decompose single-charged ions from multiple-charged ions radially around the central axis of a sealed mobility chamber, according to any of Embodiments 70-93 or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 96. The method according to Embodiment 95 or a reduced-pressure electric field asymmetric ion mobility device, wherein the radial resolution of multiple charged species from a single charged species is, on average, at least about 2 mm (e.g., at least 2 mm, at least 5 mm, at least 10 mm, at least 12 mm, or at least 20 mm) when measured at the ion outlet. Embodiment 97. A reduced-pressure electric field asymmetric ion mobility device further comprises one or more sets of ion optical systems configured to guide ions into an ion inlet, out of an ion outlet, or a combination thereof, according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device. Embodiment 98. The method according to Embodiment 97 or a reduced-pressure electric field asymmetric ion mobility device, wherein one or more sets of ion optics each independently comprises one or more ion funnels, one or more DC lenses, or a combination of two or more thereof. Embodiment 99. The method according to Embodiment 98 or a reduced-pressure electric field asymmetric ion mobility device, wherein one or more sets of ion optics are configured to guide ions from the ion outlet into the traveling wave ion mobility device. Embodiment 100. The traveling wave ion mobility device comprises a plurality of RF electrodes and protective electrodes, located in a vacuum system configured to maintain a pressure within the traveling wave ion mobility device that is less than the pressure of the inert gas in the mobility chamber containing the reduced-pressure electric field asymmetric ion mobility device, or the reduced-pressure electric field asymmetric ion mobility device. Embodiment 101. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the average ion transmission efficiency of multiple charged ions from the ion inlet to the ion outlet is at least about 50% (e.g., at least about 50%, at least about 70%, at least about 80%, at least about 90%, or at least about 95%). Embodiment 102. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the average ion transmission efficiency of a single charged ion from the ion inlet to the ion outlet is about 50% or less (e.g., about 50% or less, about 30% or less, about 10% or less, about 5% or less, or about 1% or less). Embodiment 103. A method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein multiple charged ions are transmitted from the ion inlet to the ion outlet in less than about 100 milliseconds (e.g., less than about 50 ms, 25 ms, 10 ms, 5 ms, or 3 ms). Embodiment 104. A method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein multiple charged ions are transmitted from the ion inlet to the ion outlet within approximately 0.1 ms to approximately 10 ms, approximately 0.5 ms to approximately 5 ms, or approximately 1 ms to approximately 3 ms. Embodiment 105. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the gas pressure at the inlet is about 0.1 torr to about 10 torr (e.g., about 0.5 torr to about 8, about 1 torr to about 5 torr, or about 1 torr to about 3 torr) higher than the gas pressure at the outlet. Embodiment 106. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, configured to selectively remove ions having a differential deflection corresponding to a single charged species having a mass of about 400 Da or less (e.g., about 300 Da or less, about 200 Da or less, or about 100 Da or less). The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the single charged species is a solvent used for electrospray ionization of a sample. Embodiment 107. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein about 5% to 50%, about 10% to 40%, or about 20% to 35% of the ions are selectively removed by the ion mobility device. Embodiment 108. The method according to any of the prior embodiments or a reduced-pressure electric field asymmetric ion mobility device, wherein the gas moves through the ion mobility device at a speed of about 10 m / s to about 300 m / s, or about 50 m / s to about 200 m / s. [Examples]

[0133] (Example 1) Generation of multiple ion flows using an orthogonal implantation ion manifold An ion manifold is used to generate multiple ion streams from an input ion stream of a biological sample, as described elsewhere in this specification. The biological sample is prepared for ionization by purifying and concentrating it and removing salts, buffers, or contaminants that may interfere with the ionization process. Once the biological sample is purified and concentrated, it is digested or decomposed to produce analyte molecules (e.g., protein peptides) suitable for ionization and analysis by one or more mass spectrometers. The digested or decomposed biological sample is then mixed with a solvent (e.g., a water-acetonitrile mixture) to improve the solubility of the analyte molecules and facilitate ionization. The biological sample in the solvent is then ionized by electrospray ionization and supplied to the ion manifold inlet of an ion manifold as described elsewhere in this specification. In some cases, liquid chromatography may be performed to separate the sample before ionization. The ion flowing within the ion manifold interacts with the ion repeller manifold, which is positioned such that its axis along the normal vector of the surface of the ion repeller manifold is perpendicular to the central axis of the ion manifold inlet. The ion flow is pushed or removed by the ion repeller manifold moving, shifting, or directing the path of the ion flow into the first and second ion optics, as described elsewhere herein, and the central axes of the first and second ion optics are also perpendicular to the central axis of the ion manifold inlet. As the ion flow exits the second ion optics, the ion flow splits or divides into multiple ion flows based on at least one through-hole geometric feature of one or more electrical conductor compartments of the second ion optics. The multiple ion flows exiting the second ion optics are then directed or supplied to one or more mass spectrometer sensors to analyze a biological sample analyte. (Example 2) Generation of multiple ion flows using an orthogonal implantation ion manifold

[0134] Following the general procedure of Example 1, the ion stream is pushed or removed by an ion repeller manifold moving, shifting, or directing the path of the ion stream into a first ion optical system, a FAIMS device (e.g., a planar FAIMS device), and a second ion optical system, as described elsewhere herein, and the central axes of the first and second ion optical systems are also perpendicular to the central axis of the ion manifold inlet. As the ion stream exits the second ion optical system, it is split or divided into multiple ion streams based on at least one through-hole geometric feature of one or more electrical conductor compartments of the second ion optical system. The multiple ion streams exiting the second ion optical system are then directed or supplied to one or more ion mobility devices operably coupled to a mass spectrometer for analysis of a biological sample analyte. (Example 3) Combined use of a planar FAIMS device and QToF6600

[0135] The device has a front-end configuration as shown in Figure 14: It was constructed to have a spray system → axial capillary tube → funnel → FAIMS → 6mm orifice lens → QToF6600.

[0136] Sample Sciex PPG calibration mixture, Sciex "Electrospray" mixture, and Sciex ESI mixture were analyzed using this configuration. Two FAIMS models were tested: (1) FAIMS + lateral RF (6 mm orifice between FAIMS and 6600Qjet) and (2) FAIMS + DC gradient (6 mm orifice between FAIMS and 6600Qjet). Lateral RF versus lateral DC refers to the RF or DC guardrail for confinement, respectively. Pressure parameters are shown in Table 1. [Table 1]

[0137] Lateral DC, used to accelerate ions within FAIMS, was improved by applying a very low voltage (up to 10 volts across the resistor). For optimal ion transmission in this experiment, the pressure within the ion funnel was lower.

[0138] The following FAIMS conditions, namely frequency = 750 kHz, Vp-p = 650 volts (4 mm gap between FAIMS electrodes, approximately 1.65 kV / cm), and CV = 6.5 volts (isolation of m / z 922), were used in combination with the sample AG mixture to investigate m / z isolation. The results are shown in Figures 14B-14C. Notably, 30,000 FWHM was maintained with both the FAIMS electrodes on and off.

[0139] Ion transmittance versus CV was measured using a sample PPG mixture (Figure 14D). Ramping CV allowed filtering as a function of ion mass. High mass transmittance was good, exceeding an average QToF of 6600. Varying CV selectively permeated ions based on their mass, with lower CVs permeating higher masses and higher CVs permeating lower masses (Figures 14E-14F). Varying CV also allowed ion discrimination based on their charge state. Here, lower CVs preferred single-charged ions over double-charged ions. The opposite was observed with higher CVs (Figure 14G).

[0140] Multiple-charged ions were also investigated at 900 m / z–930 m / z (Figure 14H). Data were collected using a PPG mixture, and Vp-p was set to 350 volts only (due to arc discharge at higher values). Increasing the CV allowed for the discrimination of single-charged ions at m / z 907 from dual-charged ions at approximately m / z 927. Increasing the RF amplitude is expected to further improve ion discrimination. (Example 4) Planar FAIMS + TWIMS

[0141] The general method described in Example 3 was followed, but with a modification: a TWIMS device was added between the FAIMS device and the mass spectrometer. (Example 5) Reduced pressure FAIMS

[0142] The general method described in Example 3 was followed, but with a modification, the device was configured as shown in Figure 15, and the high-pressure ion funnel was replaced with a reduced-pressure FAIMS device. Specific definitions and additional considerations

[0143] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which this disclosure belongs. All patents and publications referenced herein are incorporated by reference.

[0144] Whenever the terms “atleast,” “greater than,” or “greater than or equal to” precede the first number in a series of two or more numbers, those terms apply to each of the numbers in that series. For example, “greater than or equal to 1, 2, or 3” is equivalent to “greater than or equal to 1,” “greater than or equal to 2,” or “greater than or equal to 3.”

[0145] Whenever the terms “no more than,” “less than,” or “less than or equal to” precede the first number in a set of two or more numbers, the terms “no more than,” “less than,” or “less than or equal to” apply to each of the numbers in that set. For example, “less than or equal to 3, 2, or 1” is equivalent to “less than or equal to 3,” “less than or equal to 2,” or “less than or equal to 1.”

[0146] One embodiment of the invention described herein considers a numerical range. Where a range exists, the range includes its endpoint. In addition, all subranges and values ​​within the range exist as if explicitly described.

[0147] The terms “about” or “approximately” may mean within an acceptable margin of error for a particular value, which will in part depend on how the value is measured or determined, for example, the limits of the measurement system. For example, “about” may mean within 1 or a standard deviation greater than 1, according to practice in the art. Alternatively, “about” may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Where a particular value is described in this application and claims, unless otherwise stated, the term “about” may be assumed to mean within an acceptable margin of error for that particular value.

[0148] As used herein, “or” is intended to mean “inclusive OR,” also known as “logical OR,” and when used as a logical description, the expression “A or B” is true if either A or B is true or if both A and B are true; and when used as a list of elements, the expression “A, B, or C” is intended to include any combination of the elements enumerated in the expression, e.g., any element selected from the group consisting of A, B, C, (A, B), (A, C), (B, C), and (A, B, C), and if additional elements are enumerated, they are also intended to include them. Thus, any reference to “or” herein is intended to include “and / or” unless otherwise stated.

[0149] When an element such as a layer, region, or substrate is said to be "on" or "extending onto" another element, it should be understood that it may be directly on or extend directly onto the other element, or intervening elements may also be present. In contrast, when an element is said to be "directly on" or "extending directly onto" another element, no intervening elements are present. Similarly, when an element such as a layer, region, or substrate is said to be "over" or "extending over" another element, it should be understood that it may be directly over the other element, or extend directly over it, or intervening elements may also be present. In contrast, when an element is said to be "directly over" or "extending directly over" another element, no intervening elements are present. Furthermore, when an element is described as "connected" or "coupled" to another element, it should be understood that it may be directly connected or coupled to the other element, or an intermediary element may be present. In contrast, when an element is described as "directly connected" or "directly coupled" to another element, no intermediary element is present.

[0150] Relative terms such as "below," "above," "upper," "lower," "horizontal," or "vertical" may be used herein to describe the relationship between one element, layer, or region and another, as illustrated in the figures. It should be understood that these terms and those discussed above are intended to encompass different orientations of the device, in addition to the orientation depicted in the figures.

[0151] The terms “first,” “second,” “third,” etc., may be used in this specification to describe various elements, but it should be understood that these elements should not be limited by these terms. These terms are used solely to distinguish one element from another. For example, the first element may be referred to as the second element without departing from the scope of this disclosure, and similarly, the second element may be referred to as the first element.

[0152] As used herein, “ion optic” generally refers to any device or combination of devices capable of directing the path of an ion flux in a controlled manner. Non-limiting embodiments include AC or DC lenses, quadrupoles, collision cells, and equivalents.

[0153] As used herein, “mass analyzer” generally refers to a device capable of determining the mass-to-charge ratio and intensity or the number of counts per second of one or more ions arriving at a detector configured within the analyzer.

[0154] The term "molecule" can refer to any biological component that may be involved in corona formation, including, but is not limited to, proteins, polypeptides, polysaccharides, sugars, lipids, lipoproteins, metabolites, oligonucleotides, metabolomes, or combinations thereof. It is considered that distinctly different particle biomolecular coronas may contain some of the same biomolecules, distinctly different biomolecules with respect to other sensor elements, or that the level or quantity, type, or conformation of the biomolecules binding to each sensor element may differ. In one embodiment, the biomolecules are selected from the group consisting of proteins, nucleic acids, lipids, and metabolomes.

[0155] The “ion manifold” described herein is a device that, in a configurable manner, can direct an ion flux to enter multiple outlets through an inlet by, for example, splitting the ion flux between selected outlets of the ion manifold. The ion manifold comprises a series of ion optics capable of directing or splitting the ion flow.

[0156] Preferred embodiments of the present invention are shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided only as examples. Numerous modifications, alterations, and substitutions will be conjured upon those skilled in the art without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be adopted when practicing the present invention. The following claims define the scope of the present invention, and methods and structures within the scope of these claims, as well as their equivalents, are intended to be covered thereby.

[0157] The steps of the methods described and claimed herein illustrate or describe each of the methods or sets of operations according to the embodiments, but those skilled in the art will recognize many variations based on the teachings described herein. The steps may be completed in different orders. The steps may be added or omitted. Some of the steps may include substeps. Many of the steps may be repeated as many times as beneficial. One or more steps may be performed simultaneously.

[0158] One or more of each step of this method or set of operations may be carried out using one or more processors or logic networks, such as a programmable array logic for a field-programmable gate array, as described herein. The network may be programmed to provide one or more of each step of this method or set of operations, and the program may include program instructions stored in computer-readable memory, or programmed steps of a logic network, such as a programmable array logic or a field-programmable gate array.

[0159] Throughout this specification, multiple instances may implement a component, operation, or structure described as a single instance. While the individual operations of one or more methods are illustrated and described as separate operations, one or more of these operations may be performed in parallel, and it is not required that the operations be performed in the order they are illustrated. Structures and functionalities presented as separate components in exemplary configurations may be implemented as combined structures or components. Similarly, structures and functionalities presented as single components may be implemented as separate components. These and other variations, modifications, additions, and improvements are within the scope of the subject matter of this specification.

[0160] In addition, certain embodiments disclosed herein include logic or several routines, subroutines, applications, or instructions. These may constitute either software (e.g., code embodied on a machine-readable medium) or hardware. In hardware, routines, etc., may be tangible units capable of performing certain operations, and may be configured or arranged in a certain manner. In exemplary embodiments, one or more computer systems (e.g., standalone, client, or server computer systems) or one or more hardware modules of a computer system (e.g., a processor or group of processors) may be configured as hardware modules that operate by software (e.g., an application or application portion) to perform certain operations as disclosed herein.

[0161] In various embodiments, hardware modules may be mechanically or electronically implemented. For example, a hardware module may comprise a dedicated network or logic that is permanently configured to perform a certain operation (e.g., as a special-purpose processor such as a field-programmable gate array (FPGA) or application-specific integrated circuit (ASIC)). A hardware module may also comprise a programmable logic or network that is temporarily configured by software to perform a certain operation (e.g., contained within a general-purpose processor or other programmable processor). It should be understood that the decision to mechanically implement a hardware module within a dedicated and permanently configured network or a temporarily configured network (e.g., configured by software) may be determined by cost and time considerations.

[0162] Therefore, a hardware module may encompass a tangible entity that is physically constructed to operate in a certain manner or to perform certain operations disclosed herein, is permanently configured (e.g., wired), or is temporarily configured (e.g., programmed). In embodiments where a hardware module is temporarily configured (e.g., programmed), each hardware module does not need to be configured or instantiated at any given point in time. For example, a hardware module may comprise a general-purpose processor configured using software, and the general-purpose processor may be configured as separate, different hardware modules at different points in time. The software, therefore, may configure the processor to configure a particular hardware module at one point in time and different hardware modules at different points in time.

[0163] Hardware modules may provide information and receive information from other hardware modules. Therefore, the hardware modules described can be considered to be communicatively coupled. If multiple such hardware modules exist simultaneously, communication may be achieved through signal transmission (e.g., via appropriate circuits and buses) connecting the hardware modules. In embodiments where multiple hardware modules are configured or instantiated at different times, communication between such hardware modules may be achieved, for example, through the storage and retrieval of information in a memory structure to which multiple hardware modules have access. For example, one hardware module may perform an operation and store the output of that operation in a memory device to which it is communicatively coupled. Furthermore, the hardware module may then, at a later time, access the memory device and read and process the stored output. Hardware modules may also initiate communication with input or output devices and act on resources (e.g., sets of information). Elements described as bonded and / or connected can refer to two or more elements that work together or interact with each other, whether in direct contact (e.g., direct physical contact) or not (e.g., electrically connected, communicatively bonded, etc.).

[0164] Various operations of the exemplary methods disclosed herein may be performed, at least in part, by one or more processors that are temporarily (e.g., by software) or permanently configured to perform the relevant operations. Whether temporarily or permanently configured, such processors may constitute a processor implementation module that operates to perform one or more operations or functions. In some exemplary embodiments, the modules referred to herein may comprise a processor implementation module.

[0165] Similarly, any methods or routines disclosed herein may be processor implementations, at least in part. For example, at least some of the operations of a method may be performed by one or more processors or processor implementation hardware modules. The performance of certain operations may not reside solely within a single machine, but may be distributed among one or more processors and deployed across several machines. In some exemplary embodiments, a processor or processor may be located in a single location (e.g., in a home environment, an office environment, or as a server farm), while in other embodiments, the processors may be distributed across several locations.

[0166] The performance of a certain operation may not reside solely within a single machine, but may be distributed across one or more processors and deployed across several machines. In some exemplary embodiments, one or more processors or processor implementation modules may be located within a single geographical location (e.g., a home environment, an office environment, or a server farm). In other exemplary embodiments, one or more processors or processor implementation modules may be distributed across several geographical locations.

Claims

1. It is an ion manifold, (a) Orthogonal ion manifold inlet, (b) A first ion optical system configured to receive an ion flux through the ion manifold inlet, wherein the ion inlet is located inside the first ion optical system, (c) A second ion optical system configured to receive the output of the ion flux through the first ion optical system, wherein the second ion optical system has a plurality of outputs for splitting the ion flux into a plurality of ion streams. An ion manifold equipped with this feature.

2. A method for generating multiple ion flows, wherein the method is (a) Providing an ion flux to the orthogonal ion manifold inlet of an ion manifold, the ion manifold is (i) The orthogonal ion manifold inlet and (ii) A first ion optical system configured to receive the ion flux through the ion manifold inlet, wherein the ion inlet is located inside the first ion optical system, (iii) A second ion optical system configured to receive the output of the ion flux through the first ion optical system, wherein the second ion optical system has a plurality of outputs and To be equipped with, (b) When the ion bundle passes through the second ion optical system, the plurality of ion streams are generated from the plurality of outputs of the second ion optical system. Methods that include...

3. The ion manifold or method according to any one of the claims, wherein the first ion optical system and the second ion optical system each comprise one or more electrical conductor compartments, and each of the one or more electrical conductor compartments comprises one or more through holes.

4. The ion manifold or method according to any one of the claims, wherein one or more electrical conductor compartments are independently controllable.

5. The ion manifold or method according to any one of the claims, wherein one or more electrical conductor compartments are energized with RF and / or DC voltages.

6. The ion manifold or method according to any one of the claims, wherein the first ion optical system and the second ion optical system each comprise an electrodynamic ion funnel.

7. The ion manifold or method according to any one of the claims, wherein the first ion optical system and the second ion optical system each independently have different pressures.

8. The ion manifold according to any one of the claims, further comprising an inline ion inlet.

9. The method according to any one of the claims, further comprising providing a calibration ion flux into the first ion optical system via an inline ion manifold inlet.

10. The ion manifold or method according to any one of the claims, wherein the ion flux from the orthogonal ion inlet and the ion flux from the inline ion manifold inlet are offset by 1 to 5 mm.

11. The ion manifold further comprises an ion repeller manifold, the ion repeller manifold being positioned such that (i) an axis along the normal vector of the surface of the ion repeller manifold is perpendicular to the central axis of the inlet of the ion manifold, and (ii) a path of the ion flux is directed into the first ion optical system, according to any one of the claims.

12. The ion manifold or method according to any one of the claims, wherein the inline manifold inlet penetrates the ion repeller manifold.

13. The ion repeller manifold comprises a partitioned plate, and the ion repeller manifold is configured to allow different voltages, according to any of the claims, an ion manifold or method.

14. The ion manifold or method according to any one of the claims, wherein the repeller, the ion manifold inlet, and the first ion optical system are at least partially contained within the first chamber.

15. The ion manifold or method according to any of the claims, wherein the second ion optical system is at least partially contained within a second chamber different from the first chamber.

16. An ion manifold or method according to any one of the claims, wherein a reduced-pressure FAIMS (high electric field asymmetric waveform ion mobility spectrometer) device is configured to receive ions from the first ion optical system and selectively output ions to the second ion optical system.

17. An ion manifold or method according to any one of the claims, wherein a reduced-pressure FAIMS (high electric field asymmetric waveform ion mobility spectrometer) device is configured to receive ions from the first ion optical system and selectively output multiple charged ions to the second ion optical system by comparing them with single-charged ions.

18. An ion mobility device, (a) A first substrate plate, i. Coplanar first outer electrode and second outer electrode, ii. The first separation electrode and A first substrate plate comprising, (b) A second substrate plate, i. Coplanar third and fourth outer electrodes, ii. Second separation electrode and A second substrate plate comprising A device comprising the first substrate plate and the second substrate plate being substantially parallel.

19. The device according to claim 18, wherein the distance between the first plate and the second plate is 4 to 12 mm.

20. The device according to claim 18, wherein the first external electrode, the second external electrode, the third external electrode, and the fourth external electrode are configured as RF confinement electrodes, confining the ion beam to the center of the device.

21. The device according to any one of claims 18-20, wherein the region surrounding the first separation electrode and the second separation electrode has a pressure of 20 torr or less.

22. The device according to any one of claims 18-20, wherein the device is provided with guardrail electrodes on each side of the device.

23. The device according to claim 22, wherein the guardrail electrode has a DC gradient.

24. The device according to claim 18, wherein a voltage is applied to the first isolation electrode.

25. The device according to claim 18, wherein the FAIMS separation voltage is applied to the first separation electrode.

26. The device according to claim 18, wherein the FAIMS separation voltage is applied only to the first separation electrode.

27. The device according to any one of claims 18-26, wherein a FAIMS isolation voltage of at least 800V is applied to at least one isolation electrode.

28. The device according to any one of claims 18-26, wherein a FAIMS isolation voltage of at least 2,000 V is applied to at least one isolation electrode.

29. The device according to any one of claims 18-26, wherein a FAIMS isolation voltage of at least 2,000 V is applied to at least one isolation electrode, and the region surrounding the first isolation electrode and the second isolation electrode has a pressure of about 20 torr.

30. The ion manifold or method according to any one of claims 1-17, comprising the device according to any one of claims 18-24.

31. A method for spatially separating ions, (a) to provide an ion flux to the ion mobility device according to any of the above claims, (b) Applying a high-voltage RF waveform to the separation electrode, (c) Applying the ion confinement waveform to the outer electrode, (d) Selecting permeated ions based on mobility and generating a mobility-selective ion flow. Methods that include...

32. A reduced-pressure electric field asymmetric ion mobility device, A sealed mobility chamber having an ion inlet and an ion outlet located at opposite ends, and configured to be filled with an inert gas at a pressure below atmospheric pressure, At least one inner electrode is arranged longitudinally between the ion inlet and the ion outlet of the sealed mobility chamber, At least one outer electrode is longitudinally positioned between the ion inlet and the ion outlet of the sealed mobility chamber, wherein the outer electrode is positioned such that the inner electrode is at least partially sealed within the outer electrode, One or more power sources configured to deliver a waveform to the inner electrode or the outer electrode, wherein the waveform is configured to differentially deflect ions having different ion mobilities based on the interaction of the ions with the waveform and the inert gas, the differential deflection is configured to selectively remove ions having a mobility corresponding to a single charged species before the species reaches the ion outlet, and the inner electrode and the outer electrode are substantially planar, and the power source and A device equipped with the following features.

33. A method for separating single-charged ions from multiple-charged ions, wherein the method is (a) To provide an ion flux to the ion inlet of a reduced-pressure electric field asymmetric ion mobility device, the reduced-pressure electric field asymmetric ion mobility device is A sealed mobility chamber having an ion inlet and an ion outlet located at opposite ends, and configured to be filled with an inert gas at a pressure below atmospheric pressure, At least one inner electrode is arranged longitudinally between the ion inlet and the ion outlet of the sealed mobility chamber, At least one outer electrode is arranged longitudinally between the ion inlet and the ion outlet of the sealed mobility chamber, One or more power sources configured to deliver a waveform to the inner electrode or the outer electrode, wherein the waveform is configured to differentially deflect ions having different ion mobilities based on the interaction of the ions with the waveform and the inert gas, and the differential deflection is configured to selectively remove ions having a mobility corresponding to a single charged species before the species reaches the ion outlet. To be equipped with, (b) Applying the waveform using one or more power sources to substantially prevent ions of the ion flux having mobility corresponding to a single charge type from reaching the ion outlet of the reduced-pressure electric field asymmetric ion mobility device, (c) At the ion outlet of the reduced-pressure electric field asymmetric ion mobility device, obtain a multi-charged ion population enriched with ions corresponding to multiple charge species. Methods that include...

34. The method according to any of the claims or a reduced-pressure electric field asymmetric ion mobility device, wherein the one or more power sources provide a waveform comprising at least two sinusoidal waves that are phase-shifted relative to each other.

35. The waveform is delivered to the outer electrode, according to the method of any one of claims 32-34 or a reduced-pressure electric field asymmetric ion mobility device.

36. The method according to any one of claims 32-35 or a reduced-pressure electric field asymmetric ion mobility device, wherein the outer electrode comprises at least two ion outlets.

37. The reduced-pressure electric field asymmetric ion mobility device further comprises one or more sets of ion optical systems, the one or more sets of ion optical systems configured to guide ions into the ion inlet, guide them out of the ion outlet, or a combination thereof, according to any one of the claims or the reduced-pressure electric field asymmetric ion mobility device.

38. The method according to any of the claims or a reduced-pressure electric field asymmetric ion mobility device, wherein multiple charged ions are transmitted from the ion inlet to the ion outlet in less than about 100 milliseconds (e.g., less than about 50 ms, 25 ms, 10 ms, 5 ms, or 3 ms).

39. The electrode is configured to be independently controllable, according to the method or reduced-pressure electric field asymmetric ion mobility device according to any one of the claims.

40. The electrode is positioned at or near the output, according to the method of any one of the claims or a reduced-pressure electric field asymmetric ion mobility device.

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