Apparatus and method for adjustment of ion separation resolution in FAIMS Number:7,417,225 from the United States Patent and Trademark Office (PTO) owispatent

Title: Apparatus and method for adjustment of ion separation resolution in FAIMS

Abstract: An apparatus for separating ions includes a FAIMS analyzer region having a first ion inlet for introducing ions into the FAIMS analyzer region. An ion outlet from the FAIMS analyzer region is provided for extracting a subset of the ions that is selectively transmitted along an average ion flow path defined through the FAIMS analyzer region. The apparatus also includes an actuator for controllably varying a length of the average ion flow path through the FAIMS analyzer region.

Patent Number: 7,417,225 Issued on 08/26/2008 to Guevremont,   et al.

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Inventors:	Guevremont; Roger (Ottawa, CA), Guevremont; Maria (Ottawa, CA), Kapron; James T. (Ottawa, CA), Thekkadath; Govindanunny (Ottawa, CA), Skotnicki; Greg (Ottawa, CA)
Assignee:	Thermo Finnigan LLC (San Jose, CA)
Appl. No.:	11/285,162
Filed:	November 23, 2005

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Related U.S. Patent Documents

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	Application Number	Filing Date	Patent Number	Issue Date
	10529307	Mar., 2005	7378651
	11068767	Mar., 2005	7223971
	11285162
	11068764		7041969
	PCT/CA03/01350	Sep., 2003
	60630193	Nov., 2004
	60549170	Mar., 2004
	60413162	Sep., 2002

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Current U.S. Class:	250/287 ; 250/281; 250/288; 250/293
Current International Class:	B01D 59/44 (20060101)
Field of Search:	250/281-300

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References Cited [Referenced By]

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U.S. Patent Documents

6653627	November 2003	Guevremont et al.
6690004	February 2004	Miller et al.
6727496	April 2004	Miller et al.
6770875	August 2004	Guevremont et al.
6815668	November 2004	Miller et al.
6815669	November 2004	Miller et al.
2001/0030285	October 2001	Miller et al.
2003/0034449	February 2003	Miller et al.
2003/0146377	August 2003	Miller et al.
2004/0124350	July 2004	Miller et al.

Other References

Guevremont et al. "Atmospheric Pressure Ion Focusing in a High-Field Asymmetric Waveform Ion Mobility Spectrometer", Review of Scientific Instruments, 1999, vol. 70, No. 2, p. 1370-1383. cited by other.

Primary Examiner: Berman; Jack I.
Assistant Examiner: Smyth; Andrew
Attorney, Agent or Firm: Freedman & Associates

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Parent Case Text

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This application is a continuation-in-part of Ser. No. 11/068,767 filed Mar. 2, 2005, the entire contents of which are incorporated herein by reference. This application is also a continuation-in-part of Ser. No. 11/068,764 filed Mar. 2, 2005. the entire contents of which are incorporated herein by reference. This application is also a continuation-in-part of Ser. No. 10/529,307 filed Mar. 25, 2005, the entire contents of which are incorporated herein by reference. This application also claims benefit from U.S. Provisional application 60/630,193 filed Nov. 24, 2004, the entire contents of which are incorporated herein by reference.

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Claims

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What is claimed is:

1. An apparatus for separating ions, comprising: a FAIMS analyzer region having a first ion inlet for introducing ions into the FAIMS analyzer region and having an ion outlet for extracting a subset of the ions that is selectively transmitted along an average ion flow path defined through the FAIMS analyzer region; and, a controller for controllably varying a length of an average ion flow path through the FAIMS analyzer region.

2. An apparatus according to claim 1, wherein the controller comprises an actuator.

3. An apparatus according to claim 2, wherein the FAIMS analyzer region has a second ion inlet for introducing ions into the FAIMS analyzer region.

4. An apparatus according to claim 3, wherein a distance between the first ion inlet and the ion outlet defines a first length of an average ion flow path and wherein a distance between the second ion inlet and the ion outlet defines a second length of an average ion flow path.

5. An apparatus according to claim 4, wherein the actuator comprises an ion inlet selector.

6. An apparatus according to claim 5, wherein the ion inlet selector comprises a selector electrode having an opening defined therethrough, the selector electrode moveable between a first position in which the opening is aligned with the first ion inlet for supporting introduction of ions into the FAIMS analyzer region via the first ion inlet and a second position in which the opening is aligned with the second ion inlet for supporting introduction of ions via the second ion inlet.

7. An apparatus according to claim 3, comprising a first electrode and a second electrode disposed in a spaced-apart relationship one relative to the other, a space between the first electrode and the second electrode defining the FAIMS analyzer region.

8. An apparatus according to claim 7, wherein the first ion inlet is defined through a first portion of the first electrode such that ions introduced via the first ion inlet travel a first length along an average ion flow path between the first ion inlet and the ion outlet, and wherein the second ion inlet is defined through a second portion of the first electrode such that ions introduced via the second ion inlet travel a second length along an average ion flow path between the second ion inlet and the ion outlet.

9. An apparatus according to claim 8, wherein the second length is shorter than the first length.

10. An apparatus according to claim 9, wherein the actuator comprises an ion inlet selector.

11. An apparatus according to claim 10, wherein the ion inlet selector comprises a selector electrode having an opening defined therethrough, the selector electrode moveable between a first position in which the opening is aligned with the first ion inlet for supporting introduction of ions into the FAIMS analyzer region via the first ion inlet and a second position in which the opening is aligned with the second ion inlet for supporting introduction of ions via the second ion inlet.

12. An apparatus according to claim 7, comprising an electrical controller for applying an asymmetric waveform voltage and a direct current compensation voltage between the first electrode and the second electrode.

13. An apparatus according to claim 3, comprising a first ionization source disposed adjacent to the first ion inlet for providing a flow of analyte ions produced from a sample material for introduction via the first ion inlet.

14. An apparatus according to claim 13, comprising a second ionization source disposed adjacent to the second ion inlet orifice for providing a flow of ions produced from the sample material for introduction via the second ion inlet.

15. An apparatus according to claim 13, comprising a second ionization source disposed adjacent to the second ion inlet orifice for providing a flow of ions produced from a LockMass calibration compound for introduction via the second ion inlet.

16. An apparatus according to claim 1, wherein the controller comprises an electrical controller.

17. An apparatus according to claim 16, wherein the FAIMS analyzer region comprises: a plurality of first electrode portions, each first electrode portion of the plurality of first electrode portions having a first length and an outer surface that is at least partially curved in a direction transverse to the first length; and, a plurality of second electrode portions interleaved in a repeating sequence with the plurality of first electrode portions, each second electrode portion of the plurality of second electrode portions having a second length and an outer surface that is at least partially curved in a direction transverse to the second length, a space between the outer surface of a first electrode portion and the outer surface of an adjacent second electrode portion defining a portion of the FAIMS analyzer region, wherein the electrical controller is for electrically coupling to at least one of the plurality of first electrode portions and the plurality of second electrode portions, for selectably applying a predetermined asymmetric waveform voltage and direct current voltage between predetermined first and second electrode portions to define a first average ion flow path having a first length, and between different predetermined first and second electrode portions to define a second average ion flow path having a second length that is different than the first length.

18. An apparatus according to claim 17, comprising a second ion inlet into the FAIMS analyzer region, wherein the first average ion flow path is defined between the first ion inlet and the ion outlet, and the second average ion flow path is defined between the second ion inlet and the ion outlet.

19. An apparatus according to claim 17, wherein the first average ion flow path and the second average ion flow path are defined between the first ion inlet and the ion outlet.

20. An apparatus according to claim 19, wherein the plurality of first electrode portions comprises a plurality of first electrode rods, each first electrode rod of the plurality of first electrode rods defining one first electrode portion of the plurality of first electrode portions.

21. An apparatus according to claim 20, wherein the plurality of second electrode portions comprises a plurality of second electrode rods, each second electrode rod of the plurality of second electrode rods defining one second electrode portion of the plurality of second electrode portions.

22. An apparatus according to claim 19, wherein one of the plurality of first electrode portions and the plurality of second electrode portions comprises a formed-electrode.

23. A method for separating ions, comprising: providing a FAIMS analyzer region having a first ion inlet for introducing ions thereto and having an ion outlet for extracting a subset of the ions that is selectively transmitted along an average ion flow path through the FAIMS analyzer region; introducing ions into the FAIMS analyzer region via the first ion inlet; selectively transmitting a subset of the ions through the FAIMS analyzer region along a first length of an average ion flow path; changing an average ion flow path length through the FAIMS analyzer region; and, transmitting ions along the second length of an average ion flow path.

24. A method according to claim 23, comprising providing a second ion inlet for introducing ions into the FAIMS analyzer region, wherein a distance between the first ion inlet and the ion outlet defines the first length and wherein a distance between the second ion inlet and the ion outlet defines the second length.

25. A method according to claim 24, wherein changing an average ion flow path length through the FAIMS analyzer region comprises actuating an ion inlet selector between a first orientation in which an opening of the ion inlet selector is aligned with the first ion inlet for supporting ion introduction therethrough, and a second orientation in which the opening of the ion inlet selector is aligned with the second ion inlet for supporting ion introduction therethrough.

26. A method according to claim 23, wherein transmitting ions along the second length of an average ion flow path comprises selectively transmitting a second subset of the ions.

27. A method according to claim 26, wherein an ion composition of the second subset of ions is substantially the same as an ion composition of the subset of ions.

28. A method for separating ions, comprising: providing a FAIMS analyzer region having an ion inlet end for receiving ions and having an ion outlet for providing a subset of the ions that is selectively transmitted between the ion inlet end and the ion outlet of the FAIMS analyzer region; defining a first average ion flow path length through the FAIMS analyzer region; defining a second average ion flow path length through the FAIMS analyzer region, the second average ion flow path length different than the first average ion flow path length; and, controllably switchably providing ions along the first average ion flow path length and the second average ion flow path length.

29. A method according to claim 28, wherein defining the first average ion flow path length comprises providing a first ion inlet within a portion of the ion inlet end, such that the first average ion flow path length is defined between the first ion inlet and the ion outlet.

30. A method according to claim 29, wherein defining the second average ion flow path length comprises providing a second ion inlet within a different portion of the ion inlet end, such that the second average ion flow path length is defined between the second ion inlet and the ion outlet.

31. An apparatus for separating ions, comprising: a FAIMS analyzer region controllably switchable between a low specificity mode of operation and a high specificity mode of operation and defined by at least a space between a plurality of spaced-apart electrode surfaces, the FAIMS analyzer region in communication with an ionization source for providing a flow of ions including a known ion, and with an ion outlet for extracting ions including the known ion from the FAIMS analyzer region; and, a controller for controllably switching the FAIMS analyzer region between the low specificity mode of operation and the high specificity mode of operation.

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Description

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FIELD OF THE INVENTION

The instant invention relates generally to High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS), and more particularly to an apparatus and method for controllably varying specificity of a FAIMS-based ion separation.

BACKGROUND OF THE INVENTION

High sensitivity and amenability to miniaturization for field-portable applications have helped to make ion mobility spectrometry (IMS) an important technique for the detection of many compounds, including narcotics, explosives, and chemical warfare agents as described, for example, by G. Eiceman and Z. Karpas in their book entitled "Ion Mobility Spectrometry" (CRC, Boca Raton, 1994). In IMS, gas-phase ion mobilities are determined using a drift tube with a constant electric field. Ions are separated in the drift tube on the basis of differences in their drift velocities. At low electric field strength, for example 200 V/cm, the drift velocity of an ion is proportional to the applied electric field strength, and the mobility, K, which is determined from experimentation, is independent of the applied electric field. Additionally, in IMS the ions travel through a bath gas that is at sufficiently high pressure that the ions rapidly reach constant velocity when driven by the force of an electric field that is constant both in time and location. This is to be clearly distinguished from those techniques, most of which are related to mass spectrometry, in which the gas pressure is sufficiently low that, if under the influence of a constant electric field, the ions continue to accelerate.

E. A. Mason and E. W. McDaniel in their book entitled "Transport Properties of Ions in Gases" (Wiley, New York, 1988) teach that at high electric field strength, for instance fields stronger than approximately 5,000 V/cm, the ion drift velocity is no longer directly proportional to the applied electric field, and K is better represented by K.sub.H, a non-constant high field mobility term. The dependence of K.sub.H on the applied electric field has been the basis for the development of high field asymmetric waveform ion mobility spectrometry (FAIMS). Ions are separated in FAIMS on the basis of a difference in the mobility of an ion at high field strength, K.sub.H, relative to the mobility of the ion at low field strength, K. In other words, the ions are separated due to the compound dependent behavior of K.sub.H as a function of the applied electric field strength.

In general, a device for separating ions according to the FAIMS principle has an analyzer region that is defined by a space between first and second spaced-apart electrodes. The first electrode is maintained at a selected dc voltage, often at ground potential, while the second electrode has an asymmetric waveform V(t) applied to it. The asymmetric waveform V(t) is composed of a repeating pattern including a high voltage component, V.sub.H, lasting for a short period of time t.sub.H and a lower voltage component, V.sub.L, of opposite polarity, lasting a longer period of time t.sub.L. The waveform is synthesized such that the integrated voltage-time product, and thus the field-time product, applied to the second electrode during each complete cycle of the waveform is zero, for instance V.sub.Ht.sub.H+V.sub.Lt.sub.L=0; for example +2000 V for 10 .mu.s followed by -1000 V for 20 .mu.s. The peak voltage during the shorter, high voltage portion of the waveform is called the "dispersion voltage" or DV, which is identically referred to as the applied asymmetric waveform voltage.

Generally, the ions that are to be separated are entrained in a stream of gas flowing through the FAIMS analyzer region, for example between a pair of horizontally oriented, spaced-apart electrodes. Accordingly, the net motion of an ion within the analyzer region is the sum of a horizontal x-axis component due to the stream of gas and a transverse y-axis component due to the applied electric field. During the high voltage portion of the waveform, an ion moves with a y-axis velocity component given by V.sub.H=K.sub.HE.sub.H, where E.sub.H is the applied field, and K.sub.H is the high field ion mobility under operating electric field, pressure and temperature conditions. The distance traveled by the ion during the high voltage portion of the waveform is given by d.sub.H=v.sub.Ht.sub.H=K.sub.HE.sub.Ht.sub.H, where t.sub.H is the time period of the applied high voltage. During the longer duration, opposite polarity, low voltage portion of the asymmetric waveform, the y-axis velocity component of the ion is v.sub.L=KE.sub.L, where K is the low field ion mobility under operating pressure and temperature conditions. The distance traveled is d.sub.L=v.sub.Lt.sub.L=KE.sub.Lt.sub.L. Since the asymmetric waveform ensures that (V.sub.Ht.sub.H)+(V.sub.Lt.sub.L)=0, the field-time products E.sub.Ht.sub.H and E.sub.Lt.sub.L are equal in magnitude. Thus, if K.sub.H and K are identical, d.sub.H and d.sub.L are equal, and the ion is returned to its original position along the y-axis during the negative cycle of the waveform. If at E.sub.H the mobility K.sub.H>K, the ion experiences a net displacement from its original position relative to the y-axis. For example, if a positive ion travels farther during the positive portion of the waveform, for instance d.sub.H>d.sub.L, then the ion migrates away from the second electrode and eventually is neutralized at the first electrode.

In order to reverse the transverse drift of the positive ion in the above example, a constant negative dc voltage is applied to the second electrode. The difference between the dc voltage that is applied to the first electrode and the dc voltage that is applied to the second electrode is called the "compensation voltage" (CV). The CV prevents the ion from migrating toward either the second or the first electrode. If ions derived from two compounds respond differently to the applied high strength electric fields, the ratio of K.sub.H to K may be different for each compound. Consequently, the magnitude of the CV that is necessary to prevent the drift of the ion toward either electrode is also different for each compound. Thus, when a mixture including several species of ions, each with a unique K.sub.H/K ratio, is being analyzed by FAIMS, only one species of ion is selectively transmitted to a detector for a given combination of CV and DV. In one type of FAIMS experiment, the applied CV is scanned with time, for instance the CV is slowly ramped or optionally the CV is stepped from one voltage to a next voltage, and a resulting intensity of transmitted ions is measured. In this way a CV spectrum showing the total ion current as a function of CV, is obtained.

In an analytical instrument that includes (1) a condensed phase separation including for example one of liquid chromatography (LC) or capillary electrophoresis, (2) an atmospheric pressure ionization source including for example electrospray ionization (ESI) or atmospheric pressure photoionization (APPI), (3) an atmospheric pressure gas phase ion separator including for example high-field asymmetric waveform ion mobility spectrometer (FAIMS) and (4) a detection system including for example mass spectrometry (MS), it is advantageous to support switching to convert the function of the intermediate gas phase separation device (FAIMS for example) from a mode of separation to a mode in which the ions are not separated. This non-separating mode is called "total ion transmission mode" (TITM). The TITM is beneficial for reviewing the mixture of ions that are arriving at the intermediate separation device, in order to assess whether any ions are being overlooked by application of the intermediate separation stage. The TITM mode in FAIMS is analogous to the rf-only mode of a quadrupole mass spectrometer, in which mode of operation a wide range of ions is transmitted simultaneously through the quadrupole. This rf-only mode supports tandem arrangement of several quadrupole devices, with one or more of the quadrupole devices operated optionally in non-separation mode so that the separation of ions only occurs in one of the series of tandem quadrupole devices.

SUMMARY OF THE INVENTION

It is an object of at least some embodiments of the instant invention to provide a FAIMS device that is selectively operable in a first separation mode and in a second separation mode, the second separation mode having an ion separation resolution that differs from the first separation mode.

It is a further object of at least some of the embodiments of the instant invention to provide a FAIMS device that is selectively operable in a conventional FAIMS separating mode and in a total ion transmission mode (TITM).

According to an aspect of the instant invention, there is provided an apparatus

According to an aspect of the instant invention, there is provided an apparatus

According to an aspect of the instant invention, there is provided a method

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the invention will now be described in conjunction with the following drawings, in which similar reference numerals designate similar items:

FIG. 1 is a simplified block diagram showing a prior art tandem arrangement including an ion source, a FAIMS, and a mass spectrometer;

FIG. 2 is a longitudinal cross-sectional view of an electrospray ion source disposed in fluid communication with an ion inlet of a FAIMS;

FIG. 3 is a longitudinal cross-sectional view of a parallel-plate geometry FAIMS, with a displacement of A between the openings in the top and middle plates and between the openings in the middle and lower plates;

FIG. 4 is a longitudinal cross-sectional view of the FAIMS of FIG. 3 with a displacement of B between the openings in the top and middle plates and between the openings in the middle and lower plates;

FIG. 5 is a longitudinal cross-sectional view of the FAIMS of FIG. 3 with the openings in the top, middle and lower plates vertically aligned;

FIG. 6 is a longitudinal cross-sectional view of a parallel-plate geometry FAIMS including a temperature controller for controlling the temperature of the three plates;

FIG. 7 is a longitudinal cross-sectional view of the FAIMS of FIG. 6 with the openings in the top, middle and lower plates vertically aligned;

FIG. 8a is a perspective view of one of the plates of the FAIMS of FIG. 6, showing the heat-exchange fluid circulation system in greater detail;

FIG. 8b is a plan view of the plate of FIG. 8a;

FIG. 9a is a perspective view of an optional flat plate design, in which the plate is absent sharp edges adjacent the inter-analyzer opening;

FIG. 9b is an enlarged partial side cross-sectional view of the flat plate of FIG. 9a, showing the shape of the inter-electrode opening in greater detail;

FIG. 10a is a side view of a cylindrical geometry FAIMS including a long cylinder surrounding two shorter axially aligned cylinders, and having a source of ions proximate to a gap between the two shorter aligned cylinders;

FIG. 10b is a simplified end view of the FAIMS of FIG. 10a;

FIG. 11 is a side view of the FAIMS of FIG. 10a with the two shorter axially aligned cylinders translated longitudinally so that the gap between these cylinders is approximately adjacent to the ion outlet;

FIG. 12 is a side view of the FAIMS of FIG. 10a with the ion outlet proximate to the gap between the two shorter aligned cylinders;

FIG. 13a is a cross sectional end view of a FAIMS in the form of three electrodes with curved adjacent surfaces, with approximate alignment of the ion inlet, the inter-analyzer opening and the ion outlet;

FIG. 13b is a cross sectional end perspective view of the FAIMS of FIG. 13a with approximate alignment of the ion inlet, the inter-analyzer opening and the ion outlet;

FIG. 14a is a cross sectional end perspective view of the FAIMS of FIG. 13a with a displacement of distance A between the ion inlet and the inter-analyzer opening and between the inter-analyzer opening and the ion outlet;

FIG. 14b is a cross sectional end perspective view of the FAIMS of FIG. 13a with a displacement of distance A between the ion inlet and the inter-analyzer opening and between the inter-analyzer opening and the ion outlet, and showing ions flowing along an average ion flow path between the ion inlet and the ion outlet;

FIG. 15a is a longitudinal cross-sectional view of a parallel-plate geometry FAIMS, with a displacement A between an ion inlet and a transition point and between the transition point and an ion outlet;

FIG. 15b is a longitudinal cross-sectional view of the parallel-plate geometry FAIMS of FIG. 15a, with a displacement B between the ion inlet and the transition point and between the transition point and the ion outlet;

FIG. 15c is a longitudinal cross-sectional view of the parallel-plate geometry FAIMS of FIG. 15a, in a total ion transmission operating mode;

FIG. 16 is a perspective view of the middle plate of the FAIMS system of FIG. 15a disposed in a spaced apart relationship relative to the curved electrode of the FAIMS system of FIG. 15a, and showing an average ion flow path;

FIG. 17 is a simplified flow diagram of a method for controllably varying specificity of a FAIMS-based ion separation according to an embodiment of the instant invention;

FIG. 18 is a simplified flow diagram of another method for controllably varying specificity of a FAIMS-based ion separation according to an embodiment of the instant invention;

FIG. 19 shows a side view of a single-hole selector electrode according to an embodiment of the instant invention;

FIG. 20a is a schematic diagram of a single-hole selector electrode disposed adjacent and parallel to an outer electrode of a FAIMS analyzer, in a condition for introducing ions via a first ion inlet orifice;

FIG. 20b is a schematic diagram of a single-hole selector electrode disposed adjacent and parallel to an outer electrode of a FAIMS analyzer, in a condition for introducing ions via a second ion inlet orifice;

FIG. 21a is a schematic diagram of a single-hole selector electrode disposed adjacent and parallel to an outer electrode of a FAIMS analyzer, in a condition for selectively introducing ions in a FAIMS separation mode via a first ion inlet orifice into the FAIMS analyzer;

FIG. 21b is a schematic diagram of a single-hole selector electrode disposed adjacent and parallel to an outer electrode of a FAIMS analyzer, in a condition for selectively introducing ions in a total ion mode via a second ion inlet orifice into the FAIMS analyzer;

FIG. 22a shows an embodiment of the instant invention including both a rotating selector electrode and a curtain plate, in a first mode of operation;

FIG. 22b shows an embodiment of the instant invention including both a rotating selector electrode and a curtain plate, in a second mode of operation;

FIG. 23 shows patterns of the flow of gases supplied to the curtain region of the system of FIGS. 22a and 22b, when in the second mode of operation;

FIG. 24 shows the system of FIGS. 22a and 22b adapted for the special case of LockSpray.TM.;

FIG. 25 shows a cross sectional view of an ion introduction region of a system according to another embodiment of the instant invention;

FIG. 26a shows the system of FIG. 25 in a first mode of operation;

FIG. 26b shows the system of FIG. 25 in a second mode of operation;

FIG. 27a shows a cross sectional view of an ion introduction region of a system according to another embodiment of the instant invention, in a first mode of operation;

FIG. 27b shows the system of FIG. 27a in a second mode of operation;

FIG. 28a shows a top view of a single-hole selector electrode;

FIG. 28b shows a top view of a multiple-hole selector electrode;

FIG. 28c shows a top view of a notched selector electrode;

FIG. 28d shows a top view of an eccentrically mounted multiple-hole selector electrode;

FIG. 29 is a simplified flow diagram of a method of separating ions according to an embodiment of the instant invention;

FIG. 30 is a simplified flow diagram of another method of separating ions according to an embodiment of the instant invention;

FIG. 31a shows a system according to an embodiment of the instant invention for selecting ions from two ion sources located adjacent to a FAIMS analyzer, while in a first mode of operation;

FIG. 31b shows the system of FIG. 31a in a second mode of operation

FIG. 32 is a simplified schematic view of a FAIMS analyzer including an array of rod-shaped electrodes according to an embodiment of the instant invention, taken along a first direction;

FIG. 33 is a schematic view of a portion of the FAIMS analyzer of FIG. 32, taken along the first direction;

FIG. 34 illustrates the effect of electric fields within the FAIMS analyzer of FIG. 32 on the trajectory of ions;

FIG. 35a is a simplified schematic view of another FAIMS analyzer including an array of rod-shaped electrodes according to another embodiment of the instant invention, taken along the first direction;

FIG. 35b is a simplified schematic view of another FAIMS analyzer including an array of rod-shaped electrodes according to another embodiment of the instant invention, taken along the first direction;

FIG. 36 is a simplified schematic view of yet another FAIMS analyzer including an array of rod-shaped electrodes according to yet another embodiment of the instant invention, taken along the first direction;

FIG. 37a is a simplified schematic view of a FAIMS analyzer according to an embodiment of the instant invention including a plurality of wire electrodes;

FIG. 37b is a simplified schematic view of a FAIMS analyzer according to an embodiment of the instant invention including an array of rod-shaped electrodes in a first closest packing arrangement;

FIG. 37c is a simplified schematic view of a FAIMS analyzer according to an embodiment of the instant invention including an array of rod-shaped electrodes in a second closest packing arrangement;

FIG. 37d is a simplified schematic view of a FAIMS analyzer according to an embodiment of the instant invention including a two-dimensional layered array of rod-shaped electrodes;

FIG. 37e is a simplified schematic view of a FAIMS analyzer according to an embodiment of the instant invention including a three-dimensional layered array of rod-shaped electrodes;

FIG. 38 is a simplified exploded view of yet another FAIMS analyzer including an array of rod-shaped electrodes according to the instant invention including two sets of electrode rods;

FIG. 39a is an exploded isometric view of the FAIMS analyzer of FIG. 38;

FIG. 39b is an isometric view of the FAIMS analyzer of FIG. 38;

FIG. 40a is a simplified schematic view of a FAIMS analyzer including a formed electrode according to another embodiment of the instant invention, taken along a first direction; and,

FIG. 40b is a simplified schematic view of the FAIMS analyzer of FIG. 40a taken along a direction normal to the first direction.

DESCRIPTION OF EMBODIMENTS OF THE INVENTION

The following description is presented to enable a person skilled in the art to make and use the invention, and is provided in the context of a particular application and its requirements. Various modifications to the disclosed embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments and applications without departing from the spirit and the scope of the invention. Thus, the present invention is not intended to be limited to the embodiments disclosed, but is to be accorded the widest scope consistent with the principles and features disclosed herein.

Throughout much of the following discussion it is assumed that the FAIMS electrodes are operating at atmospheric pressure, but the discussion is equally applicable at pressures below ambient atmospheric pressure and at pressures exceeding ambient atmospheric pressure. Furthermore, because ion separation and ion transmission in FAIMS is susceptible to changes in temperature it is desirable to operate FAIMS at a selected temperature setting. For example, a rise in temperature leads to a decrease in the number density of the gas (N, molecules per cc) and therefore the operating electric field (E/N) increases with rising temperature. Similarly an increase in gas pressure increases N and therefore decreases the effective E/N conditions. In order that experiments give consistent results when repeated, it is assumed that the temperatures and pressures are maintained at selected conditions, within selected tolerance limits.

It is also assumed that the physical conditions in the analyzer region of FAIMS do not significantly change the CV of the transmission of the ion of interest while it is passing through the analyzer region to a degree that prevents its transmission. For example, if conditions in different areas of the analyzer region differ substantially, those ions that are initially being successfully transmitted near the ion inlet region likely are lost to the electrode walls at a later time during their passage through the FAIMS analyzer region. This occurs, for instance, when conditions near the ion inlet are in a balanced state for a selected ion type, and the selected ion type is being transmitted near the ion inlet, but at a location elsewhere in the analyzer region the conditions are sufficiently different that the same selected ion type is migrating to the electrode walls and is being lost. Temperature, pressure, composition of the carrier gas and spacing between the electrodes, are a few non-limiting examples of the physical conditions, assuming constant applied voltages, that affect the CV of transmission of an ion. For example, a substantial difference in the electrode spacing near the ion inlet and near the ion outlet results in the field E/N near the inlet and near the outlet being different from each other. In some instances, moderate changes are beneficial for improving the resolution, or specificity, of ion separation, but larger changes that the ion experiences for longer times may result in complete loss of transmission of the ion. The term specificity is intended to describe the number of different ion types actually transmitted through a FAIMS device relative to the number of different ion types that are introduced via an ion inlet of the FAIMS. High specificity indicates that few or only one type of ion is actually being transmitted through the FAIMS, whereas low specificity indicates that many or all types of ion are actually being transmitted through the FAIMS. Of course, ion transmission efficiency may vary significantly with ion type, or may be relatively constant for different ion types. Thus, a total ion transmission mode (TITM) is by definition a low specificity mode of operation in which at least some fraction of many or all types of ions that are introduced via an ion inlet are transmitted through the FAIMS device to an ion outlet.

Referring now to FIG. 1, shown is a simplified block diagram of a prior art tandem arrangement including a condensed phase separation system 102, an ionization source 104, an ion desolvation region 106, a FAIMS 108, and a mass spectrometer 110. A power supply 112 applies voltages including an asymmetric waveform voltage and a compensation voltage to not illustrated electrodes of the FAIMS 108 via electrical connection 114. In FIG. 1 the ionization source 104 is shown, by way of non-limiting example, in the form of an electrospray ionization source. However, many other suitable ion sources are known, including photoionization sources, APCI sources, atmospheric pressure MALDI, radioactivity based sources, corona discharge sources, and other rf-based discharge sources, to name just a few non-limiting examples. The components 104, and 106 optionally are at elevated temperature to assist in desolvation of the ions, whereas 102, 108, and 110 are optionally at room temperature.

Referring still to FIG. 1, sample is provided from the condensed phase separation system 102 to ionization source 104. Ions produced from the sample are introduced into FAIMS 108 via desolvation region 106, and are separated according to the FAIMS principle. Ions that are transmitted through FAIMS 108 then travel to mass spectrometer 110 to be analyzed further or detected.

Referring now to FIG. 2, shown is a longitudinal cross-sectional view of an ESI-FAIMS-MS tandem system, shown generally at 200. An electrospray ionization needle 202 is disposed in fluid communication with an ion inlet 204 of a FAIMS 206. The inner electrode 208 and the outer electrode 210 are supported in a spaced-apart arrangement by an insulating material 212 with high dielectric strength to prevent electrical discharge. Some non-limiting examples of suitable materials for use as the insulating material 212 include Teflon.TM. and PEEK. A passageway 214 for introducing a curtain gas is shown by dashed lines in FIG. 2, but often is omitted in later figures for simplicity of interpretation of the figures.

In FIG. 2, the ions are formed near the tip of electrospray needle 202 and drift towards a curtain plate 216. The curtain gas, introduced below the curtain plate 216 via the passageway 214, divides into two portions, one of which flows through an aperture 218 in the curtain plate 216, so as to prevent neutrals and droplets from entering the curtain plate aperture 218. Ions are driven against this flow of gas by a voltage gradient that is established between the needle 202 and the curtain plate 216. A field generated by a voltage difference applied between the curtain plate 216 and the FAIMS outer electrode 210 pushes ions that pass through the aperture 218 in the curtain plate 216 towards the ion inlet 204 of FAIMS 206. The second portion of the curtain gas flows into the ion inlet 204 and carries the ions along the length of the FAIMS electrodes to an ion outlet 220, and into a not illustrated mass spectrometer or other post-FAIMS analyzer/detector.

A high voltage asymmetric waveform is applied by electrical controller 222 to the inner electrode 208 of FAIMS 206, to produce an electric field that causes ions within an annular space between the inner electrode 208 and the outer electrode 210, which annular space is referred to as the analyzer region 224, to oscillate between the inner electrode 208 and the outer electrode 210. The waveform is generated in such a way to cause the ions to move in a first direction in a strong field for a short time, followed by motion in the other direction in a weaker field for a longer time. Absent any change in ion mobility between the high field and low field portions of this applied asymmetric waveform, after each cycle of the waveform the ion returns to its original position relative to the surface of the electrodes, without consideration of diffusion or ion-ion repulsion. In practice however, the mobility of many ions is different in strong and weak electric fields and for these ions the ion's position after one cycle of the waveform is not identical to its starting position relative to the electrode surfaces. A second, direct current voltage, which is referred to as the compensation voltage (CV), is applied to eliminate or compensate for this change of position. If the compensation voltage is of a magnitude that eliminates or compensates for the change of position that otherwise occurs absent the compensation voltage, the ion returns to the same relative location after each cycle of the waveform. Thus the ion does not migrate towards one or the other of the electrodes, and is transmitted through FAIMS 206. Other ions, for which the compensation voltage is too high or too low to compensate for the net displacement of the ion relative to the electrodes during one cycle of the waveform, drift towards an electrode and are unable to pass through FAIMS 206.

Still referring to FIG. 2, the cylindrical electrode geometry also permits ion focusing of the ion for which the asymmetric waveform voltage and compensation voltages are appropriate for transmission through FAIMS. This ion focusing mechanism means that ions, for which the compensation voltage exactly balances the change in position noted above, do not travel parallel to the walls of the electrodes as they are transported by the gas along the analyzer region 224. Under conditions of focusing, the ions that were originally near the electrode walls migrate to an optimum radial location between the electrodes. The ion cloud therefore tends to be located around this optimum radial location, thus `focusing` the ions into a band within the space between the electrodes. Of course this cloud occupies a finite amount of space because the focusing is not strong and because diffusion, ion-ion electrostatic repulsion and other mechanical and chemical activity, including turbulence of the gas, tends to cause the ion cloud to spread out in space. At equilibrium the forces expanding the cloud are balanced by the focusing action of the electric fields in the analyzer region of FAIMS. This focusing effect is a result of the gradient of electric field E/N between the electrodes. In this example the gradient is generated because the electrodes are of cylindrical geometry, one of the possible physical geometries of electrodes that gives rise to non-constant E/N in space between the electrodes.

Two approaches are discussed for operating FAIMS 206 in total ion transmission mode. In a first approach the asymmetric waveform is deactivated and the inner electrode 208 and the outer electrode 210 are held at a same voltage. In a not illustrated second approach the asymmetric waveform is deactivated and the inner electrode 208 is retracted, or translated, so that the tip of the hemispherical end of the inner electrode 208 is no longer between the ion inlet 204 and the ion outlet 220. The voltages applied to the inner electrode 208 and to the outer electrode 210 are established empirically, to produce optimized ion transmission. In both of these approaches the mixture of ions that enters through ion inlet 204 is not separated by the FAIMS mechanism, and some of the non-separated mixture of ions exits through the ion outlet 220. The extent to which the ions are transmitted is influenced also by other mechanisms for relative selectivity of ion transmission, for example the relative rates of loss of various types of ions via diffusion. It is also important to note that the ion focusing properties of FAIMS are not operative absent the asymmetric waveform, since the variation in E/N in the radial direction is not sufficient for focusing, so that the ions are lost by mechanisms that include diffusion and ion-ion electrostatic mutual repulsion. Unfortunately, when operating in this optional non-separating mode, the length of the ion path between the ion inlet 204 and the ion outlet 220 is long, and the efficiency of transmission of the ions between the ion inlet 204 and the ion outlet 220 is low.

FIG. 3 is a longitudinal cross-sectional view of a parallel plate FAIMS 300 including three stacked plates 302, 304 and 306, disposed in a spaced-apart relationship. The plates 302, 304 and 306 are stacked along a first direction, referred to as the stacking direction, such that a first electrode surface along plate 302 faces one side of the intermediate electrode plate 304, and a second electrode surface along plate 306 faces a side of the intermediate electrode plate 304 that is opposite the one side. Ions that are produced by ion source 308 drift along the first direction toward a curtain plate 310. A flow of a curtain gas 312, introduced below the curtain plate 310, divides into two portions, one of which flows outwardly through an aperture 314 in the curtain plate 310, so as to prevent neutrals and droplets from entering the curtain plate aperture 314. Ions are driven against this flow of gas by a voltage gradient that is established between the ion source 308 and the curtain plate 310. A field generated by a voltage difference between the curtain plate 310 and the FAIMS plate 302 pushes ions that pass through the aperture 314 in the curtain plate 310 towards the ion inlet 316 of FAIMS 300. The second portion of the curtain gas flows into the ion inlet 316 and carries the ions along the length of the FAIMS electrodes through the analyzer region 318a, along a second direction that is normal to the first direction. A second carrier gas flow 320 is optionally provided to assist in carrying the ions along the analyzer region 318a.

The ions travel along an average ion flow path, as is described hereinbelow. In particular, the ions travel an approximate distance along the average ion flow path indicated as "A" from the inlet 316 to an orifice, referred to as inter-analyzer aperture 322. The ions are carried by the flow of gas through the inter-analyzer aperture 322 into a second analyzer region 318b, and travel a second approximate distance "A" along the average ion flow path to the ion outlet 324. Accordingly, the inter-analyzer aperture defines a transition point, for changing the direction of ion flow along the average ion flow path. Since the asymmetric waveform and dc offset voltage is applied to the plate 304 from power supply 326, and assuming that the distance between plate 302 and 304 and between plate 304 and 306 are approximately equal, both analyzer regions 318a and 318b operate to separate ions in a substantially equivalent way. Optionally, to improve ion separation resolution, slightly different conditions are imposed in these analyzer regions 318a and 318b, for instance by varying electrode spacing or by application of different dc voltages to plates 302 and 306.

FIG. 4 is a longitudinal cross-sectional view of the FAIMS of FIG. 3, with the inter-analyzer aperture 322 located at a distance "B" from the ion inlet 316. This system is designed such that the position of the inter-analyzer aperture 322 is selectable relative to the ion inlet 316 and the ion outlet 324. For instance, a controller including an actuator 328 is provided for translating the intermediate electrode plate 304 along the second direction, so as to translate the transition point as defined by the inter-analyzer aperture 322, and thereby controllably vary a length of the average ion flow path. The actuator 328 is optionally one of manually operable and automatically operable. For instance, the actuator 328 optionally includes a thumb-screw, an adjustable wheel or knob, or some other manually operable control mechanism for supporting manual adjustment of the inter-analyzer aperture 322 position. Alternatively, the actuator 328 optionally includes a motor that drives the electrode 304 in one of a continuous and a stepped manner via a linkage member.

FIG. 4 illustrates that this arrangement of electrodes provides the benefit of an adjustable ion transit time, allowing the separation of ions and the efficiency of ion transmission to be established empirically by adjusting the position of the inter-analyzer aperture 322 relative to the ion inlet 316 and the ion outlet 324. If the gas flow rate is sufficiently high that the ion residence time is too short to achieve a desired degree of separation of one type of ion from another type of ion, the distance B between the ion inlet 316 and the inter-analyzer aperture 322 is increased, for instance to distance "A" as shown previously in FIG. 3. Optionally this distance is adjusted by mechanical horizontal translation of plate 304, however, those knowledgeable in the field will appreciate that this distance is readily adjusted in many different ways.

In principle, the device as configured in either of FIG. 3 and FIG. 4 optionally is operated in a non-separating TITM by removal of the asymmetric waveform and the dc compensation voltage. In this condition the device shown in FIG. 3 and FIG. 4 passes a mixtures of ions without active FAIMS-based separation however the mixture of ions is required to travel some distance between the closely spaced electrodes/plates and ion transmission efficiency from the ion source to the post-FAIMS detector/analyzer is expected to be reduced.

It is an unforeseen benefit of the system shown in FIG. 3 and FIG. 4 that the distances "A" or "B" are optionally reduced effectively to zero, as shown in FIG. 5. This also has the advantage of de-activating the FAIMS, and thereby providing a readily available mechanism for total ion transmission mode (TITM). Referring now to FIG. 5, by aligning the ion inlet 316, the inter-analyzer aperture 322 and the ion outlet 324, the ion separation mechanism of FAIMS is minimized, so that the majority of ions passing through ion inlet 316 exit through the ion outlet 324. The transmission of ions is significantly higher with the alignment of the ion inlet 316, the inter-analyzer aperture 322 and the ion outlet 324, than if the inter-analyzer aperture 322 remained located at distance "A" or "B" as shown in FIGS. 3 and 4 with the asymmetric waveform and the dc compensation voltage removed. Furthermore, in FIG. 5 the ion transmission may be also controlled by removal of the applied asymmetric waveform and replacement of the dc voltages applied to plates 302, 304 and 306 with dc voltages that are determined empirically to maximize the efficiency of transport of ions from the ion inlet 316 to the ion outlet 324.

Still referring to FIG. 5, assuming the widths of the analyzer regions 318a and 318b are each 2 mm, the distance from the ion inlet 316 to the ion outlet 324 is now only 4 mm plus the thickness of the plate 304. The efficiency of transport of ions through this non-separating FAIMS is significantly higher than that of the system in the state shown in FIG. 3 or FIG. 4 operated in non-separating mode by removal of the waveform voltages, since for example in the system of FIG. 3 the ions travel twice the distance "A". Additionally, when operating in a non-separating mode the ions are difficult to transport unless the dc voltages applied to the plates 302, 304 and 306 are substantially equal, since any voltage difference adds an electric field that tends to force the ions to collide with one of the plates. Referring again to FIG. 5, the dc voltages applied to the plates 302, 304 and 306 are helpful in pulling the ions through the three co-aligned openings, namely ion inlet 316, inter-analyzer aperture 322 and ion outlet 324.

Although the system shown in FIGS. 3 through 5 include three separate electrode plates 302, 304 and 306, optionally the plates 302 and 306 are replaced by a single formed electrode having a generally "C-shaped" structure, such that a first electrode surface portion of the formed electrode faces one side of the intermediate electrode plate 304, and a second electrode surface portion of the same formed electrode faces a side of the intermediate electrode plate 304 that is opposite the one side.

Of course, the parallel plate version of FAIMS that is shown in FIGS. 3 through 5 is known to lack focusing properties, other than at the edges of the plates, in the absence of temperature gradients or any other conditions creating an electric field gradient between the electrodes. Fortunately, when temperature conditions between the parallel plate electrodes are established to mimic the E/N gradient in cylindrical geometry FAIMS, a beneficial focusing effect occurs. The transmission of ions at a fixed CV requires control of the temperature in the analyzer region, such that the CV conditions for transmission of a selected ion do not change significantly as the ion travels along the space between the electrodes. By controlling the temperature of the carrier gas and by controlling the temperature of each of the electrodes to create a temperature gradient in the gas between the electrodes, ion focusing conditions are established in the parallel plate version of FAIMS.

FIG. 6 illustrates a FAIMS system 600 similar to that shown in FIGS. 3 through 5, however a temperature controller is provided to control the relative temperatures of each of the three plates 602, 604 and 606. Three flows 608, 610 and 612 of a heating/cooling fluid, referred to more generally as a heat-exchange fluid, are delivered to channels in the plates 602, 604 and 606 respectively. The heat-exchange fluid passes through channels in the plate and exits from the three plates as flows 608b, 610b and 612b from plates 602, 604 and 606 respectively. Preferably these three heat-exchange fluid flows are circulated and temperature controlled independently. The heat-exchange fluid flows are used to adjust and stabilize the temperatures of the three plates, with the benefit of producing temperature gradients between the electrodes. The temperature gradient produces a gradient of E/N between the plates during application of the asymmetric waveform and dc offset voltages between the electrodes. The gradient of E/N is beneficially controlled to maximize the ion transmission through the analyzer regions 614a and 614b.

Referring still to FIG. 6, ions that are produced by ion source 616 drift toward a curtain plate 618. A flow of a curtain gas 620, introduced below the curtain plate 618, divides into two portions, one of which flows outwardly through an aperture 622 in the curtain plate 618, so as to prevent neutrals and droplets from entering the curtain plate aperture 622. Ions are driven against this flow of gas by a voltage gradient that is established between the ion source 616 and the curtain plate 618. A field generated by a voltage difference between the curtain plate 618 and the FAIMS plate 602 pushes ions that pass through the aperture 622 in the curtain plate 618 towards the ion inlet 624 of FAIMS 600. The second portion of the curtain gas flows into the ion inlet 624 and carries the ions along the length of the FAIMS electrodes through the analyzer region 614a. A second carrier gas flow 626 is optionally provided to assist in carrying the ions along the analyzer region 614a.

The ions travel along an average ion flow path, as is described hereinbelow. In particular, the ions travel an approximate distance along the average ion flow path indicated as "A" from the inlet 624 to an orifice in the intermediate electrode plate 604, which is referred to as inter-analyzer aperture 628. The ions are carried by the flow of gas through the inter-analyzer aperture 628 into a second analyzer region 614b, and travel a second approximate distance "A" along the average ion flow path to the ion outlet 630. Accordingly, the inter-analyzer aperture 628 defines a transition point, for changing the direction of ion flow along the average ion flow path. Since the asymmetric waveform and dc offset voltage is applied to the plate 604 from power supply 632, and assuming that the distance between plate 602 and 604 and between plate 604 and 606 are approximately equal, both analyzer regions 614a and 614b operate to separate ions in a substantially equivalent way. Optionally, to improve resolution, slightly different conditions are imposed in these analyzer regions 614a and 614b, for instance by electrode spacing variation or by application of different dc voltages to plates 602 and 606.

FIG. 7 illustrates the same system that is shown in FIG. 6, but with the inter-analyzer aperture 628 located in alignment with the ion inlet 624 and the ion outlet 630. For instance, a controller including an actuator 634 is provided for translating the intermediate electrode plate 604 along a direction parallel to the plates 602 and 606, so as to translate the transition point as defined by the inter-analyzer aperture 628, and thereby controllably vary a length of the average ion flow path. The actuator 634 is optionally one of manually operable and automatically operable. For instance, the actuator 634 optionally includes a thumb-screw, an adjustable wheel or knob, or some other manually operable control mechanism for supporting manual adjustment of the inter-analyzer aperture 628 position. Alternatively, the actuator 634 optionally includes a motor that drives the intermediate electrode plate 604 in one of a continuous and a stepped manner via a linkage member. With alignment of the three openings the ions that are delivered to ion inlet 624 pass without separation to the ion outlet 630, with the device acting in total ion transmission mode. In this mode of operation, it is preferable that the asymmetric waveform be deactivated, and dc potentials placed on all three plates 602, 604 and 606. The dc potentials are selected to maximize the efficiency of transmitting ions from ion inlet 624 to ion outlet 630.

FIGS. 8a and 8b illustrate one approach to passing a heat-exchange fluid through the plates 602, 604 or 606 of the system shown in FIG. 6 and FIG. 7. In the specific example that is shown in FIGS. 8a and 8b, a flow of the heat-exchange fluid enters plate 604 through a fluid inlet 802, and having passed along a channel 804 within the plate, the fluid exits from f