U.S. patent application number 11/144843 was filed with the patent office on 2005-10-06 for faims with non-destructive detection of selectively transmitted ions.
This patent application is currently assigned to Ionalytics Corporation. Invention is credited to Barnett, David, Guevremont, Roger, Purves, Randy.
Application Number | 20050218320 11/144843 |
Document ID | / |
Family ID | 27734410 |
Filed Date | 2005-10-06 |
United States Patent
Application |
20050218320 |
Kind Code |
A1 |
Guevremont, Roger ; et
al. |
October 6, 2005 |
FAIMS with non-destructive detection of selectively transmitted
ions
Abstract
Disclosed is a high field asymmetric waveform ion mobility
spectrometer (FAIMS) with optical based detection of selectively
transmitted ions. Light from a light source is directed through an
optical port in an electrode of the FAIMS. A light detector is
provided for receiving light that is one of transmitted and
scattered by the selectively transmitted ions within the FAIMS.
Inventors: |
Guevremont, Roger; (Ottawa,
CA) ; Purves, Randy; (Ottawa, CA) ; Barnett,
David; (Ottawa, CA) |
Correspondence
Address: |
FREEDMAN & ASSOCIATES
117 CENTREPOINTE DRIVE
SUITE 350
NEPEAN, ONTARIO
K2G 5X3
CA
|
Assignee: |
Ionalytics Corporation
Ottawa
CA
|
Family ID: |
27734410 |
Appl. No.: |
11/144843 |
Filed: |
June 6, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11144843 |
Jun 6, 2005 |
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10338859 |
Jan 9, 2003 |
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6917036 |
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60354711 |
Feb 8, 2002 |
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Current U.S.
Class: |
250/292 ;
250/294 |
Current CPC
Class: |
G01N 21/03 20130101;
G01N 21/35 20130101; G01N 27/624 20130101; G01N 21/65 20130101;
Y10T 436/105831 20150115; G01N 21/3504 20130101; Y10T 436/24
20150115 |
Class at
Publication: |
250/292 ;
250/294 |
International
Class: |
H01J 049/28 |
Claims
1. An apparatus for separating ions in the gas phase, comprising: a
high field asymmetric waveform ion mobility spectrometer comprising
two electrodes defining an analyzer region therebetween, the two
electrodes disposed in a spaced apart arrangement for allowing ions
to propagate therebetween and for providing an electric field
within the analyzer region resulting from the application of an
asymmetric waveform voltage to at least one of the two electrodes
and from the application of a compensation voltage to at least one
of the two electrodes, for selectively transmitting a first ion
type in the analyzer region at a given combination of asymmetric
waveform voltage and compensation voltage; and, a probe signal
generator for generating a probe signal which when applied to the
selectively transmitted ions results in light including information
relating to the selectively transmitted ions within the analyzer
region.
2. An apparatus according to claim 1, wherein the probe signal
generator comprises an electrical controller that is in electrical
communication with at least one of the two electrodes for applying
the asymmetric waveform voltage to the at least one of the two
electrodes.
3. An apparatus according to claim 2, comprising an optical port
disposed adjacent to the analyzer region for propagating the light
including information relating to the selectively transmitted ions
therethrough.
4. An apparatus according to claim 3, comprising a light detector
in optical communication with the optical port for detecting light
including information relating to the selectively transmitted
ions.
5. An apparatus according to claim 4, wherein the light detector is
in the form of an infrared light detector.
6. An apparatus according to claim 1, wherein the probe signal
generator comprises a light source in optical communication with a
portion of the analyzer region, for launching incident light having
a wavelength within a predetermined range of wavelengths toward the
selectively transmitted ions within the analyzer region.
7. An apparatus according to claim 6, wherein the analyzer region
includes an inlet orifice and an outlet orifice for introducing a
gas flow between the two electrodes and, wherein, in use, at least
one of the asymmetric waveform voltage, the compensation voltage
and the gas flow are adjustable within the analyzer region, so as
to confine some of the selectively transmitted ions within a
3-dimensional region of space within the analyzer region.
8. An apparatus according to claim 7, comprising an optical port
disposed within a surface of one of the first and second electrodes
for propagating the incident light between the light source and the
3-dimensional region of space within the analyzer region.
9. An apparatus according to claim 8, wherein the light source is
in the form of an infrared light source for providing incident
light within the infrared portion of the electromagnetic
spectrum.
10. An apparatus according to claim 8, wherein the light source is
in the form of a laser light source.
11. An apparatus according to claim 6, wherein the two electrodes
comprise outer and inner generally cylindrical coaxially aligned
electrodes defining a generally annular space therebetween, the
annular space forming the analyzer region.
12. An apparatus according to claim 11, wherein the analyzer region
includes an inlet orifice and an outlet orifice for introducing a
gas flow between the outer and inner generally cylindrical
coaxially aligned electrodes, and wherein, in use, at least one of
the asymmetric waveform voltage, the compensation voltage and the
gas flow are adjustable within the analyzer region, so as to
confine some of the selectively transmitted ions within a
3-dimensional region of space within the analyzer region.
13. An apparatus according to claim 11, comprising an optical port
disposed within a surface of one of the inner and outer generally
cylindrical electrodes for transmitting the incident light between
the light source and the 3-dimensional region of space within the
analyzer region.
14. An apparatus according to claim 13, wherein the optical port is
disposed within a surface of the outer generally cylindrical
electrode at a point along the length of the outer generally
cylindrical electrode that is approximately aligned with the
3-dimensional region of space within the analyzer region.
15. An apparatus according to claim 13, wherein the inner generally
cylindrical electrode includes a curved surface terminus that is
shaped for directing the selectively transmitted ions generally
radially inwardly around the terminus so as to increase the ion
density of the selectively transmitted ions within the
3-dimensional region of space relative to the ion density of the
selectively transmitted ions within an adjacent portion of the
analyzer region, the 3-dimensional region of space being disposed
intermediate the terminus of the inner electrode and an ion outlet
orifice of the analyzer region.
16. An apparatus according to claim 15, including a channel through
the inner generally cylindrical electrode and open at both ends,
the channel forming an opening at the center of the curved surface
terminus that is approximately aligned with the 3-dimensional
region of space.
17. An apparatus according to claim 16, wherein the optical port is
disposed within the opening at the center of the curved
terminus.
18. An apparatus according to claim 1, wherein the probe signal
generator is for supporting a non-destructive analysis of the
selectively transmitted first ion type within the analyzer
region.
19. An apparatus for separating ions in the gas phase, comprising:
a high field asymmetric waveform ion mobility spectrometer
comprising two electrodes defining an analyzer region therebetween,
the two electrodes disposed in a spaced apart arrangement for
allowing a gas flow to pass therebetween and for providing an
electric field within the analyzer region resulting from the
application of an asymmetric waveform voltage to at least one of
the two electrodes and from the application of a compensation
voltage to at least one of the two electrodes, for selectively
transmitting a first ion type in the analyzer region at a given
combination of asymmetric waveform voltage and compensation
voltage, whereby, in use, the asymmetric waveform voltage, the
compensation voltage and the gas flow are adjustable, so as to
confine some of the selectively transmitted ions within a
3-dimensional region of space within the analyzer region; a first
optical port disposed within a surface of one of the two electrodes
and adjacent to a portion of the analyzer region including the
3-dimensional region of space; and, a light source disposed
external to the analyzer region and in optical communication with
the first optical port for providing incident light having a
wavelength within a predetermined range of wavelengths to the
selectively transmitted ions within the 3-dimensional region of
space.
20. An apparatus according to claim 19, comprising a second optical
port disposed within a surface of one of the two electrodes and
adjacent to the portion of the analyzer region including the
3-dimensional region of space, the second optical port for
propagating other light resulting from the passage of the incident
light through the 3-dimensional region of space therethrough.
21-38. (canceled)
Description
[0001] This application claims the benefit of U.S. Provisional
Application No. 60/354,711 filed Feb. 08, 2002.
FIELD OF THE INVENTION
[0002] The instant invention relates generally to high field
asymmetric waveform ion mobility spectrometry (FAIMS), more
particularly the instant invention relates to an apparatus and
method for non-destructive detection of ions separated by
FAIMS.
BACKGROUND OF THE INVENTION
[0003] 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. The drift velocity of an ion is proportional to the
applied electric field strength at low electric field strength, for
example 200 V/cm, 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.
[0004] E. A. Mason and E. W. McDaniel in their book entitled
"Transport Properties of Ions in Gases" (Wiley, N.Y., 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.
[0005] 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. Often, the first
electrode is maintained 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.
[0006] 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
ambient 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 will be
neutralized at the first electrode.
[0007] In order to reverse the transverse drift of the positive ion
in the above example, a constant negative dc voltage called the
"compensation voltage" or CV can be applied to the second
electrode. This dc voltage 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.
[0008] U.S. Pat. No. 5,420,424, issued to Carnahan and Tarassov on
May 30 1995, teaches a FAIMS device having cylindrical electrode
geometry and electrometric ion detection, the contents of which are
incorporated herein by reference. The FAIMS analyzer region is
defined by an annular space between inner and outer cylindrical
electrodes. In use, ions that are to be separated are entrained
into a flow of a carrier gas and are carried into the analyzer
region via an ion inlet orifice. Once inside the analyzer region,
the ions become distributed all the way around the inner electrode
as a result of the carrier gas flow and ion-ion repulsive forces.
The ions are selectively transmitted within the analyzer region to
an ion extraction region at an end of the analyzer region opposite
the ion inlet end. In particular, a plurality of ion outlet
orifices is provided around the circumference of the outer
electrode for extracting the selectively transmitted ions from the
ion extraction region for electrometric detection. Of course, the
electrometric detectors provide a signal that is indicative of the
total ion current arriving at the detector. Accordingly, the CV
spectrum that is obtained using the Carnahan device does not
include information relating to an identity of the selectively
transmitted ions. It is a limitation of the Carnahan device that
the peaks in the CV spectrum are highly susceptible to being
assigned incorrectly. It is another limitation of the Carnahan
device that the ions are consumed upon being detected at the
electrometric detector. Accordingly, it is not possible to perform
further analysis or separation of the ions, or to collect the ions
for other uses.
[0009] Replacing the electrometric detector with a mass
spectrometer detection system provides an opportunity to obtain
additional experimental data relating to the identity of ions
giving rise to the peaks in a CV spectrum. For instance, the
mass-to-charge (m/z) ratio of ions that are selectively transmitted
through the FAIMS at a particular combination of CV and DV can be
measured. Additionally, replacing the mass spectrometer with a
tandem mass spectrometer makes it possible to perform a
full-fledged structural investigation of the selectively
transmitted ions. Unfortunately, the selectively transmitted ions
are difficult to extract from the analyzer region of the Carnahan
device for subsequent detection by a mass spectrometer. In
particular, the orifice plate of a mass spectrometer typically
includes a single small sampling orifice for receiving ions for
introduction into the mass spectrometer. This restriction is due to
the fact that a mass spectrometer operates at a much lower pressure
than the FAIMS analyzer. In general, the size of the sampling
orifice into the mass spectrometer is limited by the efficiency of
the mass spectrometer vacuum system. In principle, it is possible
to align the sampling orifice of a mass spectrometer with a single
opening in the FAIMS outer electrode of the Carnahan device;
however, such a combination suffers from very low ion transmission
efficiency and therefore poor detection limits. In particular, the
Carnahan device does not allow the selectively transmitted ions to
be concentrated for extraction through the single opening.
Accordingly, only a small fraction of the selectively transmitted
ions are extracted from the analyzer region, the vast majority of
the selectively transmitted ions being neutralized eventually upon
impact with an electrode surface.
[0010] Guevremont et al. describe the use of curved electrode
bodies, for instance inner and outer cylindrical electrodes, for
producing a two-dimensional atmospheric pressure ion focusing
effect that results in higher ion transmission efficiencies than
can be obtained using, for example, a FAIMS device having parallel
plate electrodes. In particular, with the application of an
appropriate combination of DV and CV an ion of interest is focused
into a band-like region between the cylindrical electrodes as a
result of the electric fields which change with radial distance.
Focusing the ions of interest has the effect of reducing the number
of ions of interest that are lost as a result of the ion suffering
a collision with one of the inner and outer electrodes.
[0011] In WO 00/08455, the contents of which are incorporated
herein by reference, Guevremont and Purves describe an improved
tandem FAIMS/MS device, including a domed-FAIMS analyzer. In
particular, the domed-FAIMS analyzer includes a cylindrical inner
electrode having a curved surface terminus proximate the ion outlet
orifice of the FAIMS analyzer region. The curved surface terminus
is substantially continuous with the cylindrical shape of the inner
electrode and is aligned co-axially with the ion outlet orifice.
During use, the application of an asymmetric waveform to the inner
electrode results in the normal ion-focusing behavior as described
above, and in addition the ion-focusing action extends around the
generally spherically shaped terminus of the inner electrode. This
causes the selectively transmitted ions to be directed generally
radially inwardly within the region that is proximate the terminus
of the inner electrode. Several contradictory forces are acting on
the ions in this region near the terminus of the inner electrode.
The force of the carrier gas flow tends to influence the ions to
travel towards the ion-outlet orifice, which advantageously also
prevents the ions from migrating in a reverse direction, back
towards the ion source. Additionally, the ions that get too close
to the inner electrode are pushed back away from the inner
electrode, and those near the outer electrode migrate back towards
the inner electrode, due to the focusing action of the applied
electric fields. When all forces acting upon the ions are balanced,
the ions are effectively captured in every direction, either by
forces of the flowing gas, or by the focusing effect of the
electric fields of the FAIMS mechanism. This is an example of a
three-dimensional atmospheric pressure ion trap, as described in
greater detail by Guevremont and Purves in WO 00/08457, the
contents of which are incorporated herein by reference.
[0012] Guevremont and Purves further disclose a near-trapping mode
of operation for the above-mentioned tandem FAIMS/MS device, which
achieves ion transmission from the domed-FAIMS to a mass
spectrometer with high efficiency. Under near-trapping conditions,
the ions that accumulate in the three-dimensional region of space
near the spherical terminus of the inner electrode are caused to
leak from this region, being pulled by a flow of gas towards the
ion-outlet orifice. The ions that are extracted from this region do
so as a narrow, approximately collimated beam, which is pulled by
the gas flow through the ion-outlet orifice and into a smaller
orifice leading into the vacuum system of the mass spectrometer.
Accordingly, such tandem FAIMS/MS devices are highly sensitive
instruments that are capable of detecting and identifying ions of
interest at part-per-billion levels.
[0013] Unfortunately, the tandem FAIMS/MS arrangement suffers from
a number of limitations. In particular, ions that are analyzed by
mass spectrometry cannot be collected or analyzed further. Instead,
the ions are neutralized upon impact with a detector element of the
mass spectrometer, such as for instance an electron multiplier.
Accordingly, it is not possible to analyze ions that are
selectively transmitted by a first FAIMS device before they are
provided to a second FAIMS device for additional separation in a
tandem FAIMS/FAIMS arrangement. Similarly, it is not possible to
provide the mass analyzed ions to a second detector for subsequent
analysis by a complementary technique. Of course, analysis by a
complementary technique provides an opportunity to probe
characteristics of the ions other than mass-to-charge (m/z) ratio.
For example, using an infrared analyzer to obtain the infrared
spectrum of the ions provides information relating to the presence
of specific chemical functional groups, etc.
[0014] Furthermore, the size of the sampling orifice into the mass
spectrometer is very small, being limited by the efficiency of the
mass spectrometer vacuum system. In order to transmit as many ions
as possible from the FAIMS analyzer to the mass spectrometer, it is
necessary to dispose the sampling orifice immediately adjacent to
the ion-outlet orifice, such that widening of the ion beam as a
result of ion diffusion and ion-ion repulsion is minimized. As will
be obvious to one of skill in the art, the insertion of a
non-destructive analyzer, such as for instance the above-mentioned
infrared analyzer, intermediate the sampling orifice and the
ion-outlet orifice results in a longer ion path to the mass
spectrometer, which increases the amount of time for the ion beam
to spread out radially. Of course, the efficiency of introducing
ions into the mass spectrometer decreases as the cross section of
the ion beam increases, and dilute samples may produce insufficient
signal intensity for obtaining meaningful results.
[0015] It would be advantageous to provide a FAIMS apparatus
including a detection system that overcomes the limitations of the
prior art.
SUMMARY OF THE INVENTION
[0016] In accordance with an aspect of the invention there is
provided an apparatus for separating ions in the gas phase,
comprising: a high field asymmetric waveform ion mobility
spectrometer comprising two electrodes defining an analyzer region
therebetween, the two electrodes disposed in a spaced apart
arrangement for allowing ions to propagate therebetween and for
providing an electric field within the analyzer region resulting
from the application of an asymmetric waveform voltage to at least
one of the two electrodes and from the application of a
compensation voltage to at least one of the two electrodes, for
selectively transmitting a first type of ion along an average ion
flow path within the analyzer region at a given combination of
asymmetric waveform voltage and compensation voltage; and, an
optical port disposed adjacent to a portion of the analyzer region
other than a portion including an origin of the average ion flow
path, the optical port formed of a light transmissive material
other than a gas, which material is transmissive to light within a
predetermined range of wavelengths for supporting the propagation
of light having a wavelength within the predetermined range of
wavelengths between the analyzer region and a region that is
external to the analyzer region.
[0017] In accordance with another aspect of the invention there is
provided an apparatus for separating ions in the gas phase,
comprising: a high field asymmetric waveform ion mobility
spectrometer comprising two electrodes defining an analyzer region
therebetween, the two electrodes disposed in a spaced apart
arrangement for allowing a gas flow to pass therebetween and for
providing an electric field within the analyzer region resulting
from the application of an asymmetric waveform voltage to at least
one of the two electrodes and from the application of a
compensation voltage to at least one of the two electrodes, for
selectively transmitting a first type of ion along an average ion
flow path within the analyzer region between an origin of the ion
flow path and an ion outlet orifice of the analyzer region at a
given combination of asymmetric waveform voltage and compensation
voltage, whereby, in use, at least one of the asymmetric waveform
voltage, the compensation voltage and the gas flow are adjustable,
so as to confine some of the selectively transmitted ions within a
3-dimensional region of space within the analyzer region and
adjacent to the ion outlet orifice; and, a first optical port
disposed within a surface of one of the two electrodes and adjacent
to the analyzer region at a point that is generally aligned with
the 3-dimensional region of space within the analyzer region and
adjacent to the ion outlet orifice, the first optical port formed
of a material other than a gas, which material is transmissive to
light within a predetermined range of wavelengths for propagating
light including information relating to the selectively transmitted
ions therethrough.
[0018] In accordance with still another aspect of the invention
there is provided an apparatus for separating ions in the gas
phase, comprising: a high field asymmetric waveform ion mobility
spectrometer comprising two electrodes defining an analyzer region
therebetween, the two electrodes disposed in a spaced apart
arrangement for allowing a gas flow to pass therebetween and for
providing an electric field within the analyzer region resulting
from the application of an asymmetric waveform voltage to at least
one of the two electrodes and from the application of a
compensation voltage to at least one of the two electrodes, for
selectively transmitting a first ion type in the analyzer region at
a given combination of asymmetric waveform voltage and compensation
voltage, whereby, in use, at least one of the asymmetric waveform
voltage, the compensation voltage and the gas flow are adjustable,
so as to confine some of the selectively transmitted ions within a
3-dimensional region of space within the analyzer region; a first
optical port disposed within a surface of one of the two electrodes
and adjacent to a portion of the analyzer region including the
3-dimensional region of space, the first optical port for
propagating incident light along an optical path including the
first optical port and the 3-dimensional region of space; and, a
second optical port disposed within a surface of one of the two
electrodes and adjacent to the portion of the analyzer region
including the 3-dimensional region of space, the second optical
port for propagating other light, resulting from the passage of the
incident light through the 3-dimensional region of space,
therethrough.
[0019] In accordance with yet another aspect of the invention there
is provided an apparatus for separating ions in the gas phase,
comprising: a high field asymmetric waveform ion mobility
spectrometer comprising two electrodes defining an analyzer region
therebetween, the two electrodes disposed in a spaced apart
arrangement for allowing ions to propagate therebetween and for
providing an electric field within the analyzer region resulting
from the application of an asymmetric waveform voltage to at least
one of the two electrodes and from the application of a
compensation voltage to at least one of the two electrodes, for
selectively transmitting a first ion type in the analyzer region at
a given combination of asymmetric waveform voltage and compensation
voltage; and, a probe signal generator for generating a probe
signal which when applied to the selectively transmitted ions
results in light including information relating to the selectively
transmitted ions within the analyzer region.
[0020] In accordance with yet another aspect of the invention there
is provided an apparatus for separating ions in the gas phase,
comprising: a high field asymmetric waveform ion mobility
spectrometer comprising two electrodes defining an analyzer region
therebetween, the two electrodes disposed in a spaced apart
arrangement for allowing a gas flow to pass therebetween and for
providing an electric field within the analyzer region resulting
from the application of an asymmetric waveform voltage to at least
one of the two electrodes and from the application of a
compensation voltage to at least one of the two electrodes, for
selectively transmitting a first ion type in the analyzer region at
a given combination of asymmetric waveform voltage and compensation
voltage, whereby, in use, the asymmetric waveform voltage, the
compensation voltage and the gas flow are adjustable, so as to
confine some of the selectively transmitted ions within a
3-dimensional region of space within the analyzer region; a first
optical port disposed within a surface of one of the two electrodes
and adjacent to a portion of the analyzer region including the
3-dimensional region of space; and, a light source disposed
external to the analyzer region and in optical communication with
the first optical port for providing incident light having a
wavelength within a predetermined range of wavelengths to the
selectively transmitted ions within the 3-dimensional region of
space.
[0021] In accordance with yet another aspect of the invention there
is provided a method for separating ions in the gas phase,
comprising the steps of: separating a mixture of ions including
ions of a first type by selectively transmitting the ions of the
first type through an analyzer region of a high field asymmetric
waveform ion mobility spectrometer along an ion flow path between
an ion inlet end of the analyzer region and an ion outlet end of
the analyzer region; providing a stimulus to the selectively
transmitted ions within at least a portion of the analyzer region
for producing light including information relating to the
selectively transmitted ions; and providing the light including
information relating to the selectively transmitted ions to a light
detector that is external to the analyzer region.
[0022] In accordance with yet another aspect of the invention there
is provided a method for separating ions in the gas phase,
comprising the steps of: separating a mixture of ions including
ions of a first type by selectively transmitting the ions of a
first type through an analyzer region of a high field asymmetric
waveform ion mobility spectrometer along an ion flow path between
an ion inlet of the analyzer region and an ion outlet of the
analyzer region; confining some of the selectively transmitted ions
within a 3-dimensional region of space adjacent to the ion outlet
and within the analyzer region; directing incident light through
the 3-dimensional region of space adjacent to the ion outlet and
within the analyzer region for interacting with the selectively
transmitted ions within the 3-dimensional region of space adjacent
to the ion outlet and within the analyzer region; and, detecting
light including information relating to the selectively transmitted
ions resulting from an interaction between the incident light and
the selectively transmitted ions confined within the 3-dimensional
region of space adjacent to the ion outlet and within the analyzer
region.
[0023] In accordance with yet another aspect of the invention there
is provided a method for separating ions in the gas phase,
comprising the steps of: effecting a first separation of the ions
within a portion of an analyzer region between an ion inlet end of
the analyzer region and a reaction portion of the analyzer region;
affecting the ions within the reaction portion of the analyzer
region so as to induce a structural change of the ions; and,
effecting a second separation of the ions within a portion of an
analyzer region between the reaction portion of the analyzer region
and an ion outlet end of the analyzer region.
[0024] In accordance with yet another aspect of the invention there
is provided an apparatus for separating ions in the gas phase,
comprising: a high field asymmetric waveform ion mobility
spectrometer comprising two electrodes defining an analyzer region
therebetween, the two electrodes disposed in a spaced apart
arrangement for allowing ions to propagate therebetween and for
providing an electric field within the analyzer region resulting
from the application of an asymmetric waveform voltage to at least
one of the two electrodes and from the application of a
compensation voltage to at least one of the two electrodes, for
selectively transmitting a first type of ion along an average ion
flow path within the analyzer region at a given combination of
asymmetric waveform voltage and compensation voltage; an optical
port disposed within a surface of one of the two electrodes and
adjacent to an ion detecting portion of the analyzer region, the
optical port for propagating light including information relating
to the selectively transmitted ions therethrough; and, a light
detector disposed external to the ion detecting portion of the
analyzer region and in optical communication with the optical port
for receiving the light including information relating to the
selectively transmitted ions within the ion detecting portion and
for providing an electrical signal relating to at least an
intensity of the received light.
[0025] In accordance with yet another aspect of the invention there
is provided an apparatus for separating ions in the gas phase,
comprising: a high field asymmetric waveform ion mobility
spectrometer comprising two electrodes defining an analyzer region
therebetween, the two electrodes disposed in a spaced apart
arrangement for allowing ions to propagate therebetween and for
providing an electric field within the analyzer region resulting
from the application of an asymmetric waveform voltage to at least
one of the two electrodes and from the application of a
compensation voltage to at least one of the two electrodes, for
selectively transmitting a first type of ion along an average ion
flow path within the analyzer region at a given combination of
asymmetric waveform voltage and compensation voltage; and, an
optical detector spaced apart from the average ion flow path for
receiving light including information relating to the selectively
transmitted ions within the average ion flow path so as to support
a non-destructive determination of a characteristic of the
selectively transmitted ions.
[0026] In accordance with yet another aspect of the invention there
is provided a method for separating ions in the gas phase,
comprising the steps of: separating a mixture of ions including
ions of a first type by selectively transmitting the ions of the
first type through an analyzer region of a high field asymmetric
waveform ion mobility spectrometer along an average ion flow path
between an ion inlet end of the analyzer region and an ion outlet
end of the analyzer region; detecting light including information
relating to the selectively transmitted ions using a light detector
that is spaced apart from the average ion flow path; and,
determining a characteristic of the selectively transmitted ions
based on the detected light including information relating to the
selectively transmitted ions.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] Exemplary embodiments of the invention will now be described
in conjunction with the following drawings, in which similar
reference numbers designate similar items:
[0028] FIG. 1 is a simplified cross-sectional view of a tandem
FAIMS/MS apparatus;
[0029] FIG. 2a is a side cross-sectional view of a FAIMS device
according to a first embodiment of the instant invention;
[0030] FIG. 2b is a simplified end-on view of the FAIMS device of
FIG. 2a;
[0031] FIG. 2c is an enlarged view of a first optical port
configuration for use with the FAIMS device of FIG. 2a;
[0032] FIG. 2d is an enlarged view of a second optical port
configuration for use with the FAIMS device of FIG. 2a;
[0033] FIG. 2e is an enlarged view of a third optical port
configuration for use with the FAIMS device of FIG. 2a;
[0034] FIG. 2f is an enlarged view of a fourth optical port
configuration for use with the FAIMS device of FIG. 2a;
[0035] FIG. 3a is a side cross-sectional view of another FAIMS
device according to the first embodiment of the instant
invention;
[0036] FIG. 3b is a simplified end-on view of the FAIMS device of
FIG. 3a;
[0037] FIG. 4 is a side cross-sectional view of the FAIMS device
according to the first embodiment of the instant invention coupled
to a mass spectrometer;
[0038] FIG. 5 is a side cross-sectional view of the FAIMS device
according to the first embodiment of the instant invention coupled
to a second FAIMS device and a mass spectrometer;
[0039] FIG. 6a is a side cross-sectional view of a FAIMS device
according to a second embodiment of the instant invention;
[0040] FIG. 6b is a simplified end-on view of the FAIMS device of
FIG. 5a;
[0041] FIG. 7a is a side cross-sectional view of another FAIMS
device according to the second embodiment of the instant
invention;
[0042] FIG. 7b is a simplified end-on view of the FAIMS device of
FIG. 6a;
[0043] FIG. 8 is a side cross-sectional view of a FAIMS device
according to a third embodiment of the instant invention;
[0044] FIG. 9 is a side cross-sectional view of another FAIMS
device according to the third embodiment of the instant
invention;
[0045] FIG. 10 is a simplified flow diagram for a method of
detecting selectively transmitted ions according to the first
embodiment of the instant invention;
[0046] FIG. 11 is a simplified flow diagram for a method of
detecting selectively transmitted ions according to the second
embodiment of the instant invention;
[0047] FIG. 12 is a simplified flow diagram for a method of
affecting the selectively transmitted ions; and,
[0048] FIG. 13 is a simplified flow diagram for a method of
affecting the selectively transmitted ions.
DETAILED DESCRIPTION OF THE DRAWINGS
[0049] 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 the disclosure and in the claims that follow, the term
"light including information relating to the selectively
transmitted ions" is defined as one of scattered light, emitted
light and transmitted incident light having a wavelength within one
of the infrared, ultraviolet and visible regions of the
electromagnetic spectrum, wherein one of the intensity, frequency,
polarization and periodicity of intensity variation of the light is
indicative of, for example, one of an ionic chemical structure, an
ionic conformational state, an ionic density and a relative ionic
density of the selectively transmitted ions within a FAIMS analyzer
region. In addition, the term "average ion flow path" is defined as
the net trajectory of the ions as a result of one of a carrier gas
flow through the analyzer region and an electrical field gradient
within the analyzer region, although the individual ions also
experience an oscillatory motion between the electrodes as a result
of the applied asymmetric waveform voltage.
[0050] Referring to FIG. 1, shown is a simplified cross-sectional
view of a tandem FAIMS/MS apparatus. In particular, a domed-FAIMS
device 2 having cylindrical electrode geometry is shown in fluid
communication with a mass spectrometer 28. The domed-FAIMS device 2
includes inner and outer cylindrical electrodes 4 and 16,
respectively, which are supported by an electrically insulating
material 10 in an overlapping, spaced-apart arrangement. The
generally annular space between the inner electrode 4 and the outer
electrode 16 defines a FAIMS analyzer region 12. The width of the
analyzer region is approximately uniform around the circumference
of the inner electrode 4, and extends around a curved surface
terminus 5 of the inner electrode 4. An ion inlet orifice 11 is
provided through the outer electrode 16 for introducing ions from
an ion source 26 into the analyzer region 12. A flow of a carrier
gas, which is represented in the figure by a series of
closed-headed arrows, is provided within the analyzer region 12 to
carry the ions toward an ion outlet orifice 14 located opposite the
curved surface terminus 5 of the inner electrode 4. An orifice 19
within a curtain plate electrode 17 allows for the flow of a
portion of the carrier gas in a direction that is counter-current
to the direction in which the ions are traveling near the ion inlet
11, so as to desolvate the ions before they are introduced into the
analyzer region 12. The inner electrode 4 is provided with an
electrical contact 8 through the insulating material 10 for
connection to a power supply 6 that during use is capable of
applying a high voltage asymmetric waveform voltage (DV) and a low
voltage dc compensation voltage (CV) to the inner FAIMS electrode
4.
[0051] The mass spectrometer 28 is disposed external to the FAIMS
analyzer region 12, and includes an orifice plate 22 having an
inlet orifice 20 extending therethrough. As will be apparent to one
of skill in the art, the size of the inlet orifice 20 is typically
very small, being limited by the efficiency of the mass
spectrometer vacuum system. The inlet orifice 20 in the orifice
plate 22 is aligned with the ion outlet orifice 14 of the
domed-FAIMS device 2 such that ions being extracted through the ion
outlet orifice 14 enter the mass spectrometer inlet orifice 20.
Those ions that pass through the orifice 20 in the orifice plate 22
travel to a skimmer cone 24 within the differentially pumped region
of the mass spectrometer 28, and are analyzed within a mass
analyzer 18 on the basis of their mass-to-charge ratio. The mass
spectrometer includes a not illustrated detector, such as for
instance an electron multiplier, for providing an electrical signal
that is proportional to a detected ion current.
[0052] During use, ions are produced at the ion source 26 from a
suitable sample containing a species of interest. Typically, a
mixture including a plurality of different ion types is produced
when the sample is ionized. A potential gradient is used in order
to accelerate the ions of the mixture away from the ion source 26,
through the orifice 19 in the curtain plate electrode 17, and
toward the ion inlet orifice 11, where the ions become entrained in
the carrier gas flow and are carried into the FAIMS analyzer region
12. Once inside the FAIMS analyzer region 12, the ions are carried
through an electric field that is formed within the FAIMS analyzer
region 12 by the application of the DV and the CV to the inner
FAIMS electrode 4 via the electrical contact 8. Ion separation
occurs within the FAIMS analyzer region 12 on the basis of the high
field mobility properties of the ions. Those ions of the mixture
that have a stable trajectory for a particular combination of DV
and CV are selectively transmitted through the FAIMS analyzer
region 12, whilst other ions of the mixture collide with an
electrode surface and are lost. Since the electric field also
extends around the curved surface terminus 5, the selectively
transmitted ions tend to be directed generally radially inwardly
towards the ion outlet orifice 14. Near trapping conditions are
created within the analyzer region 12 by adjusting at least one of
the carrier gas flow rate, the carrier gas composition, the applied
CV, the applied DV, the distance between the curved surface
terminus 5 and the ion outlet orifice 14, the potential that is
applied to the orifice plate 22, the temperature of the carrier gas
and the pressure of the carrier gas. Under trapping conditions,
which are created within the analyzer region 12 by adjusting at
least one of the above-mentioned parameters to a different value,
the selectively transmitted ions accumulate within a 3-dimensional
region of space proximate the curved surface terminus 5. Under
near-trapping conditions the ions also accumulate within the
3-dimensional region of space proximate the curved surface terminus
5, except that a lower ion density is achieved when operating under
near-trapping conditions, since the ions are being continually
extracted from the 3-dimensional region of space as an
approximately collimated beam of ions. The extracted ions are
carried by the carrier gas flow through the ion outlet orifice
14.
[0053] Referring now to FIG. 2a, shown is a side cross-sectional
view of a FAIMS device 30 according to a first embodiment of the
instant invention. The FAIMS device 30, in the form of a
domed-FAIMS device, includes inner and outer cylindrical electrodes
32 and 44, respectively, which are supported by an electrically
insulating material 38 in an overlapping, spaced-apart arrangement.
The generally annular space between the inner electrode 32 and the
outer electrode 44 defines a FAIMS analyzer region 40. The width of
the analyzer region is approximately uniform around the
circumference of the inner electrode 32, and extends around a
curved surface terminus 33 of the inner electrode 32. An ion inlet
orifice 35 is provided through the outer electrode 44 for
introducing ions from an ion source 54 into the analyzer region 40.
A flow of a carrier gas, which is represented in the figure by a
series of closed-headed arrows, is provided within the analyzer
region 40 to carry the ions toward an ion outlet orifice 42 located
opposite the curved surface terminus 33 of the inner electrode 32.
An orifice 39 within a curtain plate electrode 37 allows for the
flow of a portion of the carrier gas in a direction that is
counter-current to the direction in which the ions are traveling
near the ion inlet 35, so as to desolvate the ions before they are
introduced into the analyzer region 40. The inner electrode 32 is
provided with an electrical contact 36 through the insulating
material 38 for connection to a power supply 34 that during use is
capable of applying a high voltage asymmetric waveform voltage (DV)
and a low voltage dc compensation voltage (CV) to the inner FAIMS
electrode 32.
[0054] During use, ions are produced at the ion source 54 from a
suitable sample containing a species of interest. Typically, a
mixture including a plurality of different ion types is produced
when the sample is ionized. A potential gradient is used in order
to accelerate the ions of the mixture away from the ion source 54,
through the orifice 39 in the curtain plate electrode 37, and
toward the ion inlet orifice 35, where the ions become entrained in
the carrier gas flow and are carried into the FAIMS analyzer region
40. Once inside the FAIMS analyzer region 40, the ions are carried
through an electric field that is formed within the FAIMS analyzer
region 40 by the application of the DV and the CV to the inner
FAIMS electrode 32 via the electrical contact 36. Ion separation
occurs within the FAIMS analyzer region 40 on the basis of the high
field mobility properties of the ions. Those ions of the mixture
that have a stable trajectory for a particular combination of DV
and CV are selectively transmitted through the FAIMS analyzer
region 40, whilst other ions of the mixture collide with an
electrode surface and are lost. Since the electric field also
extends around the curved surface terminus 33, the selectively
transmitted ions tend to be directed generally radially inwardly
towards the ion outlet orifice 42. Near trapping conditions are
created within the analyzer region 40 by adjusting at least one of
the carrier gas flow rate, the carrier gas composition, the applied
CV, the applied DV, the distance between the curved surface
terminus 33 and the ion outlet orifice 42, the temperature of the
carrier gas and the pressure of the carrier gas. Under trapping
conditions, which are created within the analyzer region 40 by
adjusting at least one of the above-mentioned parameters to a
different value, the selectively transmitted ions accumulate within
a 3-dimensional region of space proximate the curved surface
terminus 33. Under near-trapping conditions the ions also
accumulate within the 3-dimensional region of space proximate the
curved surface terminus 33, except that a lower ion density is
achieved when operating under near-trapping conditions, since the
ions are being continually extracted from the 3-dimensional region
of space as an approximately collimated beam of ions. The extracted
ions are carried by the carrier gas flow through the ion outlet
orifice 42.
[0055] Referring still to FIG. 2a, an infrared light source 50 is
provided for launching infrared light, shown schematically with a
dashed line ending with an open-headed arrow, through a first
optical port 48 in the outer FAIMS electrode 44. For example, the
infrared light source 50 produces infrared light and directs a beam
of the produced infrared light along an optical path including the
first optical port 48. Preferably, the first optical port 48 is
disposed along the length of the outer electrode 44 at a point that
is substantially aligned with the 3-dimensional region of space
proximate the spherical terminus 33. Accordingly, the infrared
light from infrared light source 50 is directed through a region of
higher ion density of the selectively transmitted ions within the
3-dimensional region of space. A second optical port 49 is disposed
within the outer FAIMS electrode 44 at a point that is
approximately opposite the first optical port 48, for receiving the
infrared light after it has passed through the 3-dimensional region
of space proximate the spherical terminus 33. A light detector 52
is provided in optical communication with the second optical port
49 for receiving infrared light propagating therethrough, and for
providing an electrical signal relating to an intensity of the
received infrared light. Of course, the first optical port 48 and
the second optical port 49 are preferably of a size that is
sufficiently large to support the propagation of the infrared light
therethrough. Furthermore, the first optical port 48 and the second
optical port 49 are preferably of a size that is sufficiently small
such that the electric fields within the analyzer region are
substantially unaffected by the discontinuity in the electrode
material.
[0056] During use, trapping conditions are preferably maintained
within the analyzer region as described above, such that the
selectively transmitted ions accumulate within the 3-dimensional
region of space adjacent to the spherical terminus 33 of the inner
electrode 32. This region of space becomes enriched with ions
relative to other regions of space within the analyzer region. The
infrared light beam is passed through the 3-dimensional region of
space, where the accumulated ions may absorb some of the infrared
light. The absorption of infrared light is detected at the light
detector 52. Preferably, the absorption is measured as a function
of frequency of the infrared light. By scanning the frequency of
the infrared light, a fingerprint spectrum is obtained that is
specific for a given compound. A common method for determining the
identity of an unknown compound using solid samples involves
comparing the unknown sample with a library of known compounds and
reporting the most likely matches. A similar library can be
envisioned using gas-phase ions. In this way, the infrared light
beam is used to probe ions within the FAIMS analyzer region 40.
Accordingly, the infrared light source 50 is an example of a probe
signal generator. Of course, light having a wavelength selected
from other regions of the electromagnetic spectrum may also be used
to probe the ions, such as for example ultraviolet light and
visible light. Furthermore, in addition to simply measuring the
amount of light that is absorbed by the ions, probing of the ions
may include any interaction between an incident light beam and the
ions that results in a change to either the ions or the light beam.
For example, probing may result in a conformational change to the
ions, a dissociation of neutral or charged species from cluster
ions, a change of the vibrational state of the ions etc. Further
still, probing may result in one of absorption of a portion of the
incident light beam, scattering of a portion of the incident light
beam, fluorescence by the ions, and emission of light by one of the
ions and the gas molecules in the vicinity of the ions.
[0057] Optionally, the analyzer is operated in the near-trapping
mode so as to continually extract ions from the 3-dimensional
region of space. For example, the extracted ions are provided to
one of a second FAIMS device and a mass spectrometer for additional
separation and detection. Further optionally, the analyzer is
operated in a pulsed trapping mode so as to provide packets of ions
at intervals of time for one of additional separation and
detection.
[0058] Referring now to FIG. 2b, shown is a simplified end-on view
of the FAIMS device of FIG. 2a. Elements labeled with the same
numerals have the same function as those illustrated in FIG. 2a. In
particular, the infrared light source 50 and the light detector 52
are arranged one relative to the other and relative to the FAIMS
outer electrode 44 such that the infrared light travels between the
source 50 and the detector 52 through the 3-dimensional region of
space proximate the spherical terminus 33. As such, the infrared
radiation is used to probe an area of higher ion density within the
FAIMS analyzer region 40. It is an advantage of the apparatus
according to the first embodiment of the instant invention that the
infrared light that is used to probe the accumulated ions does not
result in the ions being consumed or structurally changed.
Accordingly, ions that are detected can be subsequently analyzed or
otherwise manipulated using complimentary analysis methods or
complimentary separation techniques, respectively. Furthermore, the
ability to increase the concentration of ions in the gas phase,
thereby overcoming the natural tendency of the like-charged ions to
repel one-another, makes it possible to perform optical detection
of samples that otherwise would be far too dilute to provide
meaningful results.
[0059] Referring now to FIG. 2c, shown is an enlarged simplified
view of a first optical port configuration for use with the FAIMS
device according to the first embodiment of the instant invention.
A light transmissive window 51c is disposed within the outer
electrode 44. The light transmissive window 51c is constructed of a
material, other than a gas, that is substantially transmissive to
light within a wavelength range of interest. For example, the light
transmissive window 51c is constructed of a material that is
substantially transmissive to light within the infrared region of
the electromagnetic spectrum. Suitable materials for constructing
the light transmissive window 51c will be readily apparent to one
of skill in the art. Some non-limiting examples of suitable window
materials include; sodium chloride (NaCl), potassium bromide (KBr)
and calcium chloride (CaCl.sub.2). Preferably, the first optical
port 48 and the second optical port 49 each include a light
transmissive window 51c that is constructed using similar
materials. Preferably, the light transmissive window 51c forms a
gas tight seal with the outer electrode 44. Preferably, the light
transmissive window 51c includes a first outer surface that is
approximately continuous with an inner surface of the outer
electrode 44, and a second outer surface that is approximately
continuous with an outer surface of the outer electrode 44.
[0060] Referring now to FIG. 2d, shown is an enlarged simplified
view of a second optical port configuration for use with the FAIMS
device according to the first embodiment of the instant invention.
A light transmissive window 51d is disposed within the outer
electrode 44. The light transmissive window 51d is constructed of a
material, other than a gas, that is substantially transmissive to
light within a wavelength range of interest. For example, the light
transmissive window 51d is constructed of a material that is
substantially transmissive to light within the infrared region of
the electromagnetic spectrum. Preferably, the first optical port 48
and the second optical port 49 each include a light transmissive
window 51d that is constructed using similar materials. Preferably,
the light transmissive window 51d forms a gas tight seal with the
outer electrode 44. Preferably, the light transmissive window 51d
includes a first outer surface recessed within an opening through
the outer electrode 44. Since the light transmissive window 51d is
generally constructed from an insulating material, ions colliding
therewith cause a charge buildup that affects the electric field
within the analyzer region due to the applied DV and the applied
CV. The effect of such a charge buildup is expected to diminish
when the window material is recessed relative to the inner surface
of the outer electrode 44.
[0061] Referring now to FIG. 2e, shown is an enlarged simplified
view of a third optical port configuration for use with the FAIMS
device according to the first embodiment of the instant invention.
An optically transmissive portion 51e of, for example, the light
detector 52 is disposed immediately adjacent to the outer surface
of the outer electrode 44. Preferably, the optically transmissive
portion 51e forms a gas-tight seal against the outer surface of the
outer electrode 44. Optionally, the optically transmissive portion
51e is a light transmissive window separate from the light detector
52, which light transmissive window preferably forms a gas-tight
seal against the outer surface of the outer electrode 44.
[0062] Referring now to FIG. 2f, shown is an enlarged simplified
view of a fourth optical port configuration for use with the FAIMS
device according to the first embodiment of the instant invention.
The fourth optical port configuration does not include a
non-gaseous material disposed within an opening through the outer
electrode 44. For example, the fourth optical port configuration
includes an opening through the outer electrode 44 which allows
light to propagate therethrough and which also allows gas and/or
ions to escape from the analyzer region 40. Optionally, the fourth
optical port configuration includes a source of a supplemental gas
flow, as is shown in FIG. 2f, for directing a supplemental gas flow
into the analyzer region via the opening through the outer
electrode 44, in order to prevent the gas and/or ions from escaping
from the analyzer region 40.
[0063] Referring now to FIG. 3a, shown is a side cross-sectional
view of another FAIMS device 61 according to a first embodiment of
the instant invention. Elements labeled with the same numerals have
the same function as those illustrated in FIG. 2a. The FAIMS device
61 includes an outer electrode 53 in the form of a tube having an
approximately uniform cross-section taken at any point along a
longitudinal axis thereof. First and second optical ports 55 and
57, respectively, are provided in the outer electrode 53 for
supporting the propagation of light therethrough. The outer
electrode 53 does not maintain an approximately constant spacing to
the inner electrode 32 about the curved surface terminus 33.
Accordingly, an electrically isolated plate, referred to as the
trapping plate 59, is disposed adjacent to the outer electrode 53.
The trapping plate 59 is used to manipulate the fields in the
trapping region adjacent to the spherical terminus 33 of the inner
electrode 32. An ion outlet orifice 63 in the trapping plate 59 is
provided for extracting ions from the analyzer region 46. The ion
outlet orifice 63 in the trapping plate 59 performs substantially
the same function as the ion outlet orifice 42 in the outer FAIMS
electrode 44 of FIG. 2a. Near-trapping conditions are created
within a 3-dimensional region of space within the FAIMS analyzer
region 46 and adjacent to the curved surface terminus 33, by
adjusting at least one of the carrier gas flow rate, the carrier
gas composition, the applied CV, the applied DV, the distance
between the curved surface terminus 33 and the ion outlet orifice
63, the temperature of the carrier gas, the pressure of the carrier
gas and the potential that is applied to the trapping plate 59.
[0064] Referring now to FIG. 3b, shown is a simplified end-on view
of the FAIMS device of FIG. 3a. Elements labeled with the same
numerals have the same function as those illustrated in FIG. 3a. In
particular, the infrared source 50 and the detector 52 are arranged
relative to each other and relative to the outer electrode 53 such
that infrared light from the source 50 travels through the first
optical port 55, passes through the 3-dimensional region of space
proximate the curved surface terminus 33, and to a first mirror
surface 67. The light is redirected by the first mirror surface 67,
to pass through the 3-dimensional region of space proximate the
curved surface terminus 33 a second time, and to arrive at a second
mirror surface 65. Similarly, the second mirror surface redirects
the light a second time, to pass through the 3-dimensional region
of space proximate the curved surface terminus 33 a third time,
after which the light propagates through the second optical port
57, finally arriving at the light detector 52. For example, the
first and second mirror surfaces 67 and 65, respectively, are
formed by depositing a layer of gold atoms onto the inner surface
of the outer electrode 53. Optionally, the first mirror surface 67
directs the infrared light to the second optical port 57 for
detection at detector 52. Advantageously, using at least a mirror
to redirect the infrared beam increases the effective path length
of the infrared light through the sample, thereby providing
improved signal to noise when used with dilute samples. Optionally,
the infrared source 50 and the detector 52 are arranged relative to
each other and relative to the outer electrode 53 such that
infrared light from the source 50 travels through the first optical
port 55, passes through the 3-dimensional region of space proximate
the curved surface terminus 33, propagates through the second
optical port 57, and is detected at detector 52.
[0065] Referring now to FIG. 4, shown is a side cross-sectional
view of the FAIMS device according to the first embodiment of the
instant invention in a tandem arrangement with a mass spectrometer
60. Elements labeled with the same numerals have the same function
as those illustrated in FIG. 2a. The ability to confine ions near
the spherical terminus 33 of the inner FAIMS electrode 32 supports
the use of complementary methods of detection. Ions that are
selectively transmitted and trapped by the applied DV and CV can be
probed using infrared light, as described with reference to FIG.
2a. Since the infrared analysis does not consume the ions, these
same ions can be extracted into a mass spectrometer 60 for further
analysis. In particular, an orifice plate 56 of the mass
spectrometer 60 is positioned adjacent to the ion outlet orifice 42
in the outer FAIMS electrode 44. Ions that exit from the FAIMS
analyzer region 40 through the ion outlet orifice 42 enter the mass
spectrometer 60 after passing through an orifice 62 in the orifice
plate 56, travel to a skimmer cone 58 within the differentially
pumped region of the mass spectrometer, and are mass analyzed
within a mass analyzer 62.
[0066] In principle, the infrared radiation can also be used to
modify the ions while they are trapped in the 3-dimensional region
of space proximate the spherical terminus 33 of the inner FAIMS
electrode 32. For example, the infrared radiation can be used to
change the conformation of protein ions or to dissociate loosely
held clusters or complexes. Provided that the newly formed
"daughter" ions have a stable trajectory under the ambient CV and
DV conditions, it is then possible to detect the daughter ions
using one of optical and mass spectrometric methods.
[0067] Referring now to FIG. 5, shown is a side cross-sectional
view of the FAIMS device 30 according to the first embodiment of
the instant invention coupled to a second FAIMS device 70 and to a
mass spectrometer 60. Elements labeled with the same numerals have
the same function as those illustrated in FIG. 2a. Ions confined
within the 3-dimensional region of space proximate the spherical
terminus 33 of the inner FAIMS electrode 32 are probed using
infrared radiation launched from source 50 through the first
optical port 48 and received at detector 52 after passing through
second optical port 49. For example, the infrared light source 50
produces infrared light and directs a beam of the produced infrared
light along an optical path including the first optical port 48.
The confined ions are then extracted through the orifice 42 and
into the second FAIMS 70 through inlet 76. The second FAIMS 70 is a
side-to-side FAIMS device, however any other FAIMS electrode
geometry could be used to advantage. The ions are selectively
transported through a second analyzer region 80 between an inner
FAIMS electrode 74 and an outer FAIMS electrode 72. A high voltage
asymmetric waveform and a low voltage dc compensation voltage are
applied by a second power supply (not shown), to the inner FAIMS
electrode 74. Those ions that have stable trajectories under the
ambient conditions of CV and DV within the second FAIMS are passed
through the outlet orifice 78 to the mass spectrometer 60.
Advantageously, a second different separation of the ions can be
achieved in order to eliminate some ions that were co-transported
through the first FAIMS 30. The second different separation is
controlled by varying at least one of the applied DV, the applied
CV, the carrier gas rate, the carrier gas composition, etc. Further
advantageously, the identity of the ions that are transmitted by
the first FAIMS 30 can be confirmed using infrared techniques
before the ions are transported into the second FAIMS 70. This
allows a user to tune the first FAIMS 30 or the second FAIMS 70 to
achieve a desired result.
[0068] Referring now to FIG. 6a, shown is a side cross-sectional
view of a FAIMS device 90 according to a second embodiment of the
instant invention. The FAIMS device 90, in the form of a
domed-FAIMS device, includes inner and outer cylindrical electrodes
92 and 104, respectively, which are supported by an electrically
insulating material 98 in an overlapping, spaced-apart arrangement.
The generally annular space between the inner electrode 92 and the
outer electrode 104 defines a FAIMS analyzer region 100. The width
of the analyzer region 100 is approximately uniform around the
circumference of the inner electrode 92, and extends around a
curved surface terminus 93 of the inner electrode 92. An ion inlet
orifice 95 is provided through the outer electrode 104 for
introducing ions from an ion source 108 into the analyzer region
100. A flow of a carrier gas, which is represented in the figure by
a series of closed-headed arrows, is provided within the analyzer
region 100 to carry the ions toward an ion outlet orifice 102
located opposite the curved surface terminus 93 of the inner
electrode 92. An orifice 99 within a curtain plate electrode 127
allows for the flow of a portion of the carrier gas in a direction
that is counter-current to the direction in which the ions are
traveling near the ion inlet 95, so as to desolvate the ions before
they are introduced into the analyzer region 100. The inner
electrode 92 is provided with an electrical contact 96 through the
insulating material 98 for connection to a power supply 94 that
during use is capable of applying a high voltage asymmetric
waveform voltage (DV) and a low voltage dc compensation voltage
(CV) to the inner FAIMS electrode 92.
[0069] During use, ions are produced at the ion source 108 from a
suitable sample containing a species of interest. Typically, a
mixture including a plurality of different ion types is produced
when the sample is ionized. A potential gradient is used in order
to accelerate the ions of the mixture away from the ion source 108,
through the orifice 99 in the curtain plate electrode 97, and
toward the ion inlet orifice 95, where the ions become entrained in
the carrier gas flow and are carried into the FAIMS analyzer region
100. Once inside the FAIMS analyzer region 100, the ions are
carried through an electric field that is formed within the FAIMS
analyzer region 100 by the application of the DV and the CV to the
inner FAIMS electrode 92 via the electrical contact 96. Ion
separation occurs within the FAIMS analyzer region 100 on the basis
of the high field mobility properties of the ions. Those ions of
the mixture that have a stable trajectory for a particular
combination of DV and CV are selectively transmitted through the
FAIMS analyzer region 100, whilst other ions of the mixture collide
with an electrode surface and are lost. Since the electric field
also extends around the curved surface terminus 93, the selectively
transmitted ions tend to be directed generally radially inwardly
towards the ion outlet orifice 102. Near trapping conditions are
created within the analyzer region 100 by adjusting at least one of
the carrier gas flow rate, the carrier gas composition, the applied
CV, the applied DV, the distance between the curved surface
terminus 93 and the ion outlet orifice 102, the temperature of the
carrier gas and the pressure of the carrier gas. Under trapping
conditions, which are created within the analyzer region 100 by
adjusting at least one of the above-mentioned parameters to a
different value, the selectively transmitted ions accumulate within
a 3-dimensional region of space proximate the curved surface
terminus 93. Under near-trapping conditions the ions also
accumulate within the 3-dimensional region of space proximate the
curved surface terminus 93, except that a lower ion density is
achieved when operating under near-trapping conditions, since the
ions are being continually extracted from the 3-dimensional region
of space as an approximately collimated beam of ions. The extracted
ions are carried by the carrier gas flow through the ion outlet
orifice 102.
[0070] According to the second embodiment of the instant invention,
the detection of ions confined in the trapping region of a FAIMS
device is performed using a light scattering technique. Raman
spectroscopy is a non-limiting example of a light scattering
technique suitable for use with the second embodiment of the
instant invention. If, during a collision between a photon and an
ion in the gas phase, the energy of the photon corresponds to an
energy difference between the state that the ion is in and a higher
state, the photon may be absorbed. However, no matter what the
energy of the photon is, the photon-ion collision may scatter the
photon, thereby changing the photon's direction of motion. Most of
the scattered photons undergo no change in frequency and energy. A
small fraction however, exchange energy with the ion during the
collision process. The resulting increase or decrease in energy of
the scattered photons is the Raman effect.
[0071] Referring still to FIG. 6a, a light source 110 is provided
for launching substantially monochromatic light, shown
schematically with a dashed line ending with an open-headed arrow,
through a first optical port 112 in the outer FAIMS electrode 104.
For example, the light source 110 produces substantially
monochromatic light and directs a beam of the produced
substantially monochromatic along an optical path including the
first optical port 112. Preferably, the light source 110 is in the
form of a laser light source for providing laser light of any
convenient frequency v.sub.o, where v.sub.o usually lies in the
visible or near-UV region. Preferably, the first optical port 112
is disposed along the length of the outer electrode 104 at a point
that is substantially aligned with the 3-dimensional region of
space proximate the spherical terminus 93. Accordingly, the light
from light source 110 is directed through a region of higher ion
density within the 3-dimensional region of space. A second optical
port 114 is disposed within the outer FAIMS electrode 104 at a
point that is approximately opposite the first optical port 112.
Light that is not scattered by ions within the 3-dimensional region
of space proximate the spherical terminus 93 is transmitted out of
the FAIMS device 90 through the second optical port 114.
Optionally, a beam stop is provided in optical communication with
the second optical port 114.
[0072] Referring now to FIG. 6b, shown is a simplified end-on view
of the FAIMS device of FIG. 6a. Elements labeled with the same
numerals have the same function as those illustrated in FIG. 6a. A
detector 118 is provided in optical communication with a third
optical port 117 for receiving the light, shown as a wavy dotted
line, that is scattered from the ions confined within the
3-dimensional region of space proximate the curved terminus 93 of
the inner FAIMS electrode 92. The third optical port 117 is
constructed to be substantially transmissive to the scattered
light. Preferably, the third optical port 117 is disposed such that
the incident laser light is substantially precluded from impinging
upon the detector 118 whilst the scattered light is being observed.
The detector 118 provides an electrical signal relating to an
intensity of the scattered light. Of course, the first optical port
112 and the third optical port 117 are preferably of a size that is
sufficiently large to support the propagation of the incident laser
light and the scattered light, respectively, therethrough.
Furthermore, the first optical port 112, the second optical port
114 and the third optical port 117 are preferably of a size that is
sufficiently small such that the electric fields within the
analyzer region are substantially unaffected by the discontinuity
in the electrode material. Optionally, one of the optical port
configurations described with reference to FIGS. 2c to 2f may be
used with the FAIMS device 90 according to the second embodiment of
instant invention.
[0073] During use, trapping conditions are maintained within the
analyzer region 100 as described above, such that the selectively
transmitted ions accumulate within the 3-dimensional region of
space adjacent to the spherical terminus 93 of the inner electrode
92. This region of space becomes enriched with ions relative to
other regions of space within the analyzer region. The incident
laser light is passed through the 3-dimensional region of space,
where the accumulated ions may scatter some of the laser light. Of
course, the scattering cross section of ions is very small, hence a
sufficiently high ion density and an intense laser beam are
necessary in order to achieve an amount of scattering that can be
detected at detector 118.
[0074] Optionally, the analyzer is operated in the near-trapping
mode so as to continually extract ions from the 3-dimensional
region of space. For example, the extracted ions are provided to
one of a second FAIMS device and a mass spectrometer for additional
separation and detection. Further optionally, the analyzer is
operated in a pulsed trapping mode so as to provide packets of ions
at intervals of time for one of additional separation and
detection.
[0075] Referring now to FIG. 7a, shown is a side cross-sectional
view of another FAIMS device 120 according to the second embodiment
of the instant invention. The FAIMS device 120, in the form of a
domed-FAIMS device, includes inner and outer cylindrical electrodes
122 and 136, respectively, which are supported by an electrically
insulating material 128 in an overlapping, spaced-apart
arrangement. The generally annular space between the inner
electrode 122 and the outer electrode 136 defines a FAIMS analyzer
region 132. The width of the analyzer region 132 is approximately
uniform around the circumference of the inner electrode 122, and
extends around a curved surface terminus 123 of the inner electrode
122. An ion inlet orifice 130 is provided through the outer
electrode 136 for introducing ions from an ion source 140 into the
analyzer region 132. A flow of a carrier gas, which is represented
in the figure by a series of closed-headed arrows, is provided
within the analyzer region 132 to carry the ions toward an ion
outlet orifice 134 located opposite the curved surface terminus 123
of the inner electrode 122. An orifice 129 within a curtain plate
electrode 127 allows for the flow of a portion of the carrier gas
in a direction that is counter-current to the direction in which
the ions are traveling near the ion inlet 130, so as to desolvate
the ions before they are introduced into the analyzer region 132.
The inner electrode 122 is provided with an electrical contact 126
through the insulating material 128 for connection to a power
supply 124 that during use is capable of applying a high voltage
asymmetric waveform voltage (DV) and a low voltage dc compensation
voltage (CV) to the inner FAIMS electrode 122.
[0076] During use, ions are produced at the ion source 140 from a
suitable sample containing a species of interest. Typically, a
mixture including a plurality of different ion types is produced
when the sample is ionized. A potential gradient is used in order
to accelerate the ions of the mixture away from the ion source 140,
through the orifice 129 in the curtain plate electrode 127, and
toward the ion inlet orifice 130, where the ions become entrained
in the carrier gas flow and are carried into the FAIMS analyzer
region 132. Once inside the FAIMS analyzer region 132, the ions are
carried through an electric field that is formed within the FAIMS
analyzer region 132 by the application of the DV and the CV to the
inner FAIMS electrode 122 via the electrical contact 126. Ion
separation occurs within the FAIMS analyzer region 132 on the basis
of the high field mobility properties of the ions. Those ions of
the mixture that have a stable trajectory for a particular
combination of DV and CV are selectively transmitted through the
FAIMS analyzer region 132, whilst other ions of the mixture collide
with an electrode surface and are lost. Since the electric field
also extends around the curved surface terminus 123, the
selectively transmitted ions tend to be directed generally radially
inwardly towards the ion outlet orifice 134. Near trapping
conditions are created within the analyzer region 132 by adjusting
at least one of the carrier gas flow rate, the carrier gas
composition, the applied CV, the applied DV, the distance between
the curved surface terminus 123 and the ion outlet orifice 134, the
temperature of the carrier gas and the pressure of the carrier gas.
Under trapping conditions, which are created within the analyzer
region 132 by adjusting at least one of the above-mentioned
parameters to a different value, the selectively transmitted ions
accumulate within a 3-dimensional region of space proximate the
curved surface terminus 123. Under near-trapping conditions the
ions also accumulate within the 3-dimensional region of space
proximate the curved surface terminus 123, except that a lower ion
density is achieved when operating under near-trapping conditions,
since the ions are being continually extracted from the
3-dimensional region of space as an approximately collimated beam
of ions. The extracted ions are carried by the carrier gas flow
through the ion outlet orifice 134.
[0077] Referring still to FIG. 7a, the FAIMS inner electrode 122
has a channel 142 extending therethrough. A first optical port 144
is disposed within the channel 42, proximate the curved surface
terminus 123. A light source 146 is provided for launching
substantially monochromatic light, shown schematically with a
dashed line ending with an open arrow, into the channel 142 and
through the first optical port 144 in the inner FAIMS electrode
122. For example, the light source 146 produces substantially
monochromatic light and directs a beam of the produced
substantially monochromatic light along an optical path including
the first optical port 144. Preferably, the light source 146 is in
the form of a laser light source for providing laser light of any
convenient frequency v.sub.o, where v.sub.o usually lies in the
visible or near-UV region. Ions that are confined in the trapping
region scatter a portion of the incident radiation with a portion
thereof going to a detector 148 after passing through a second
optical port 150 in the outer FAIMS electrode 136. Light that is
not scattered by ions within the 3-dimensional region of space
proximate the spherical terminus 123 is transmitted out of the
FAIMS device 120 through the ion outlet orifice 134. Optionally, a
beam stop is provided in optical communication with the ion outlet
orifice 134. Of course, the first optical port 144 and the second
optical port 150 are preferably of a size that is sufficiently
large to support the propagation of the incident laser light and
the scattered light, respectively, therethrough. Furthermore, the
first optical port 144 and the second optical port 150 are
preferably of a size that is sufficiently small such that the
electric fields within the analyzer region are substantially
unaffected by the discontinuity in the electrode material.
Optionally, one of the optical port configurations described with
reference to FIGS. 2c to 2f may be used with the FAIMS device 120
according to the second embodiment of instant invention.
[0078] Referring now to FIG. 7b, shown is a simplified end-on view
of the FAIMS device of FIG. 7a. Elements labeled with the same
numerals have the same function as those illustrated in FIG. 7a.
The black dot in FIG. 7b indicates from this view that the laser
radiation is coming out of the page toward the reader. In this
case, the scattered light is observed at right angles to the
incident laser light. Of course, the scattered light may be
observed at any appropriate angle. The detector 148 provides an
electrical signal relating to an intensity of the scattered
light.
[0079] In addition to the incident light being scattered by
interactions with the ions confined within the FAIMS analyzer,
light scattering also occurs if the ions heat a small volume of the
surrounding bath gas. The photons of the incident light scatter as
they pass into a hot gas because such a heated "bubble" of gas has
a different refractive index than the cooler surrounding gas. One
way of inducing the ions to heat a small volume of the surrounding
bath gas is to adjust the asymmetric waveform that is applied to
the inner electrode of a FAIMS device. Since the application of the
asymmetric waveform results in the ions oscillating back and forth
in approximately a same region of space, the gas that surrounds an
ion becomes heated around the trajectory of the ion. This
oscillation requires energy, and this energy is dissipated to
create a region in the vicinity of the ion where the gas is hotter
than the bulk of the gas in the FAIMS device. This region of heated
gas is significantly larger in size than the ion, and is more
likely to scatter the light than the relatively small ion itself.
Of course, the oscillation of any ion present in the trapping
region gives rise to heating of the bath gas. In other words, the
ions that are detected may not be the ion of interest, despite the
fact that they are transmitted at the same CV value. Accordingly,
there may not be as much specificity as there would be in looking
at the scattered light from the ion itself, as described above.
Tandem FAIMS devices may be more appealing for studying gas phase
ions based on the heating of the bath gas because of the extra
specificity as opposed to a single FAIMS device. Alternatively, the
non-destructive nature of the detection method supports the
combination of light scattering detection methods with mass
spectrometry in order to achieve more specificity if desired.
[0080] The FAIMS device 90 that was described with reference to
FIGS. 6a and 6b, as well as the FAIMS device 120 that was described
with reference to FIGS. 7a and 7b, is suitable for detecting ions
based upon the scattering of incident light as a result of bath gas
heating by the ions. Application of a high voltage, high frequency
asymmetric waveform to the ions in the analyzer region of FAIMS
causes the ions to move rapidly back and forth through the gas in
an oscillatory motion. The energy provided to the ions to cause
this motion is dissipated, effectively by the equivalent of
friction, to the gas and causes heating of the gas in the vicinity
of the ion. This heated gaseous region becomes a lens of different
refractive index than the bulk gas, and can scatter incident light.
If the ion is being carried along the analyzer region of FAIMS, the
ion and the heated region remain together as they move in concert
along the length of the analyzer. The heat produced by the ion
therefore continues to heat the same volume of gas, whose
temperature continues to rise. On the other hand, if the ion enters
a trapping or near trapping region of FAIMS this condition changes.
The ion is constrained by the focusing effects of the electric
fields, and the gas flows past the ion. In this case the heat
generated by the oscillating ion is applied to continuously new
volumes of gas that flow past the ion, and the heat is carried away
by the flow of gas.
[0081] For example, in FIG. 7a, an ion A is flowing along with the
gas as described in the first case in the previous paragraph. This
maximizes the temperature of the gas in the vicinity of ion A. On
the other hand an ion B, which is located within the 3-dimensional
region of space proximate the curved surface terminus 123 of the
inner electrode 122, feels the contrary forces of the electric
fields and gas flows, and some of the heat produced by the ion B is
carried away by the gas out of the orifice 134.
[0082] Referring now to FIG. 8, shown is a side cross-sectional
view of a FAIMS device 160 according to a third embodiment of the
instant invention. The FAIMS device 160, in the form of a
domed-FAIMS device, includes inner and outer cylindrical electrodes
162 and 176, respectively, which are supported by an electrically
insulating material 168 in an overlapping, spaced-apart
arrangement. The generally annular space between the inner
electrode 162 and the outer electrode 176 defines a FAIMS analyzer
region 172. The width of the analyzer region 172 is approximately
uniform around the circumference of the inner electrode 162, and
extends around a curved surface terminus 163 of the inner electrode
162. An ion inlet orifice 170 is provided through the outer
electrode 176 for introducing ions from an ion source 180 into the
analyzer region 172. A flow of a carrier gas, which is represented
in the figure by a series of closed-headed arrows, is provided
within the analyzer region 172 to carry the ions toward an ion
outlet orifice 174 located opposite the curved surface terminus 163
of the inner electrode 162. An orifice 169 within a curtain plate
electrode 167 allows for the flow of a portion of the carrier gas
in a direction that is counter-current to the direction in which
the ions are traveling near the ion inlet 170, so as to desolvate
the ions before they are introduced into the analyzer region 172.
The inner electrode 162 is provided with an electrical contact 166
through the insulating material 168 for connection to a power
supply 164 that during use is capable of applying a high voltage
asymmetric waveform voltage (DV) and a low voltage dc compensation
voltage (CV) to the inner FAIMS electrode 162.
[0083] During use, ions are produced at the ion source 180 from a
suitable sample containing a species of interest. Typically, a
mixture including a plurality of different ion types is produced
when the sample is ionized. A potential gradient is used in order
to accelerate the ions of the mixture away from the ion source 180,
through the orifice 169 in the curtain plate electrode 167, and
toward the ion inlet orifice 170, where the ions become entrained
in the carrier gas flow and are carried into the FAIMS analyzer
region 172. Once inside the FAIMS analyzer region 172, the ions are
carried through an electric field that is formed within the FAIMS
analyzer region 172 by the application of the DV and the CV to the
inner FAIMS electrode 162 via the electrical contact 166. Ion
separation occurs within the FAIMS analyzer region 172 on the basis
of the high field mobility properties of the ions. Those ions of
the mixture that have a stable trajectory for a particular
combination of DV and CV are selectively transmitted through the
FAIMS analyzer region 172, whilst other ions of the mixture collide
with an electrode surface and are lost. Since the electric field
also extends around the curved surface terminus 163, the
selectively transmitted ions tend to be directed generally radially
inwardly towards the ion outlet orifice 174. Near trapping
conditions are created within the analyzer region 172 by adjusting
at least one of the carrier gas flow rate, the carrier gas
composition, the applied CV, the applied DV, the distance between
the curved surface terminus 163 and the ion outlet orifice 174, the
temperature of the carrier gas and the pressure of the carrier gas.
Under trapping conditions, which are created within the analyzer
region 173 by adjusting at least one of the above-mentioned
parameters to a different value, the selectively transmitted ions
accumulate within a 3-dimensional region of space proximate the
curved surface terminus 163. Under near-trapping conditions the
ions also accumulate within the 3-dimensional region of space
proximate the curved surface terminus 163, except that a lower ion
density is achieved when operating under near-trapping conditions,
since the ions are being continually extracted from the
3-dimensional region of space as an approximately collimated beam
of ions. The extracted ions are carried by the carrier gas flow
through the ion outlet orifice 174.
[0084] The applied high voltage asymmetric waveform causes an ion
within the analyzer region 173 to experience a rapid oscillatory
motion that leads to energetic collisions with the surrounding bath
gas. These collisions result in "heating" of an ion as it moves
through the bath gas, as was described in more detail above. Ions
that are heated by the high electric fields in the FAIMS device may
also emit some of their energy. For example, molecules that absorb
infrared radiation are also capable of emitting characteristic
infrared wavelengths when heated for example by collisions with the
bath gas molecules. This emitted radiation can be monitored to
probe the ions confined in the trapping region of the FAIMS device.
Accordingly, the power supply 164 is another example of a probe
signal generator.
[0085] Referring still to FIG. 8, the FAIMS device 160 includes an
optical port 182 in the outer FAIMS electrode 176. The optical port
182 supports the propagation of infrared light, including infrared
light having a wavelength within a wavelength range of interest,
therethrough. Preferably, the optical port 182 is disposed along
the length of the outer electrode 176 at a point that is
substantially aligned with the 3-dimensional region of space
proximate the spherical terminus 163. Accordingly, the infrared
light emitted by the ions that are confined within the
3-dimensional region of space passes through the optical port 182
to a light detector 184. The detector 184 is in optical
communication with the optical port 182 for receiving the emitted
infrared light propagating therethrough, and for providing an
electrical signal relating to an intensity of the emitted infrared
light having a wavelength within the wavelength range of interest.
Of course, the optical port 182 is of a size that is sufficiently
large to transmit the emitted infrared light. Furthermore, the
optical port 182 is sufficiently small such that the electric
fields within the analyzer region 172 are substantially unaffected
by the discontinuity in the electrode material. Optionally, one of
the optical port configurations described with reference to FIGS.
2c to 2f may be used with the FAIMS device 160 according to the
third embodiment of instant invention.
[0086] Referring still to FIG. 8, the detector 184 is preferably
placed proximate the trapping region. Having the detector 184 in
the region near the gas outlet 174 reduces the effect of the
emission of ions other than the ions of interest compared with
having the detector in the region near the ion inlet 170. In
addition, the ion density in the trapping region proximate the
spherical terminus 163 of the inner FAIMS electrode 162 can be
significantly higher than the ion density in the analyzer region
when the operating parameters are selected to optimize ion
trapping. The higher ion density results in more radiation being
emitted from the trapping region and therefore a more intense
signal is acquired. The amount of heating required by the
application of the asymmetric waveform to trigger characteristic
emission events in an ion may be variable. Consequently, emission
spectra may be acquired as a function of the DV to give multiple
fingerprint spectra that are specific for a given analyte, as a
function of DV, since the emission is specific to the structure of
the species. As was described above, a common method for
determining the identity of an unknown compound using IR detection
involves comparing the unknown sample with a library of known
compounds and reporting the most likely matches. For this example,
however, the emission spectra may change as a function of the
applied waveform voltage. Thus, reference spectra at different
applied waveform voltages should be used for comparative
purposes.
[0087] Optionally, the analyzer is operated in the near-trapping
mode so as to continually extract ions from the 3-dimensional
region of space. For example, the extracted ions are provided to
one of a second FAIMS device and a mass spectrometer for additional
separation and detection. Further optionally, the analyzer is
operated in a pulsed trapping mode so as to provide packets of ions
at intervals of time for one of additional separation and
detection.
[0088] Referring now to FIG. 9, shown is a side cross-sectional
view of another FAIMS device according to the third embodiment of
the instant invention. Elements labeled with the same numerals have
the same function as those illustrated in FIG. 8. The FAIMS device
190, in the form of a domed-FAIMS device, includes an outer FAIMS
electrode 192 having an optical port 194 that is disposed along a
length thereof at a point that is intermediate the ion inlet 170
and the curved surface terminus 163. Of course, heating of the ions
occurs throughout the FAIMS device 190 when the asymmetric waveform
is operated at high voltage. Thus, the FAIMS device 190 does not
require a light source in order to excite the ions within the
analyzer region 172, which simplifies the set-up and reduces the
cost to produce the apparatus. In addition, the heating of the ions
is not restricted to the ions that are confined in the trapping
region, but instead ions throughout the FAIMS device experience
heating. Thus, the placement of the detector is not as restricted
as it is in the first and second embodiments of the instant
invention. For the FAIMS device 190, the optical port 194 in the
outer FAIMS electrode 192 may be disposed at one of a plurality of
locations along the outer FAIMS electrode 176 in the region between
the ion inlet and ion outlet. Of course, locating the optical port
194 too close to the ion inlet 170, however, may result in a
condition in which there is a greater contribution to the
background because of emission from ions other than the ion of
interest. This occurs if ions other than the ions of interest have
not had sufficient time to be lost to the walls of the FAIMS device
190. That is, ions other than the ion of interest, which transmit
at CV values other than the optimal CV value of the ion of
interest, require a finite time after they enter the ion inlet
before they collide with an electrode wall. This time is dependent
upon several parameters that include, but are not limited to, the
voltage and frequency of the asymmetric waveform, the CV of the ion
in comparison with the ion of interest, etc.
[0089] For improved detection specificity, the invention described
with reference to FIG. 8 or 9 is optionally combined with mass
spectrometry based detection. The non-destructive method of
measuring the radiation emitted from the ion of interest enables
the ion to be further studied using mass spectrometry based
techniques.
[0090] Optionally, the FAIMS device shown in FIG. 9 is constructed
using other than cylindrical electrode geometry. For instance, a
trapping region is not required, and therefore FAIMS devices
having, for instance, one of parallel plate electrodes, curved
plate electrodes and spherical electrodes are suitable.
Furthermore, the so-called side-to-side FAIMS devices could also be
used to advantage with the invention as it is described with
reference to FIG. 9.
[0091] In addition to detecting selectively transmitted ions, the
above-mentioned devices are also suitable for affecting a property
of the selectively transmitted ions. In principle, the IR light can
be used to modify the ions, for example change the conformation of
protein ions, or dissociate loosely held clusters or complexes,
while the precursors are trapped in the FAIMS device. The newly
formed "daughter" ions that are formed from these precursor ions
can be detected by optical or mass spectrometric methods.
Similarly, bath gas heating resulting from the application of
strong electric fields within the FAIMS analyzer region provides
the energy that is required to affect the conformation or
dissociate clusters within the selectively transmitted ions. Of
course, changing the structure of a selectively transmitted ion
affects its high field ion mobility properties. As such, a parent
ion that has a stable trajectory under a particular combination of
applied DV and CV may form a daughter ion that is lost due to a
collision with an electrode under identical DV and CV
conditions.
[0092] Referring now to FIG. 10, shown is a simplified flow diagram
for a method of detecting selectively transmitted ions using an
optical based detection technique. At step 300, a mixture of ions
including an ion type of interest is introduced into a FAIMS
analyzer region of, for example, one of the above-mentioned FAIMS
devices 30, 61, 90, 120, 160 and 190. Optionally, the ions are
produced within the analyzer region from a suitable sample using,
for example, a laser-based ionization technique. At step 302,
appropriate conditions are provided within the FAIMS analyzer
region for effecting a separation of the ions, to selectively
transmit the ion type of interest to a detection portion of the
analyzer region. For optical based detection techniques involving
one of an absorption and a scattering of incident radiation by the
selectively transmitted ions, it is most preferable to confine the
selectively transmitted ions within a 3-dimensional region of space
overlapping with the detection portion. Confining the selectively
transmitted ions within the 3-dimensional region of space results
in a higher ion density within the detection portion of the
analyzer region, which produces a better response from the light
detector. For optical based detection techniques involving bath gas
heating, it is preferable to probe the ions in a portion of the
analyzer region other than the 3-dimensional region of space
proximate the curved surface terminus of the inner electrode. Once
ions are being selectively transmitted through the analyzer region
to the detection portion, a stimulus is provided at step 304 to the
selectively transmitted ions. For example, providing the stimulus
includes one of directing an incident beam of infrared light
through the detection portion, directing an incident beam of laser
light through the detection portion, and applying a strong electric
field within the detection portion. Optionally, a combination
including two or more of the above-mentioned stimuli is provided.
The stimulus is provided such that light including information
relating to the selectively transmitted ions results from an
interaction between the stimulus and the selectively transmitted
ions. The light including information relating to the selectively
transmitted ions depends upon the nature of the stimulus, and
includes transmitted infrared light, light that is scattered by one
of the selectively transmitted ions and the carrier gas in the
vicinity of a selectively transmitted ion, and infrared light
emitted by the selectively transmitted ions as a result of bath gas
heating of the ions under the influence of strong electric fields
within the analyzer region. At step 306 the light including
information relating to the selectively transmitted ions is
received at a light detector. Preferably, the light is propagated
through an optical port to a detector that is disposed external to
the FAIMS analyzer region. At step 308, at least an intensity of
the light including information relating to the selectively
transmitted ions is determined. In this case, the information
provides a measure of the ion concentration or of the ion density
within the detection portion of the analyzer region. Preferably,
the intensity determination is performed as a function of
wavelength, in which case the information also relates to a
structural identification of the selectively transmitted ions.
Optionally, the selectively transmitted ions are provided to a
different analyzer or to a mass spectrometer after optical based
detection.
[0093] Referring now to FIG. 11, shown is a simplified flow diagram
for another method of detecting selectively transmitted ions using
an optical based detection technique. At step 310, a mixture of
ions including an ion type of interest is introduced into a FAIMS
analyzer region of, for example, one of the above-mentioned FAIMS
devices 30, 61, 90 and 120. Optionally, the ions are produced
within the analyzer region from a suitable sample using, for
example, a laser-based ionization technique. At step 312,
appropriate conditions are provided within the FAIMS analyzer
region for effecting a separation of the ions, to selectively
transmit the ion type of interest to a detection portion of the
analyzer region. At step 314, some of the selectively transmitted
ions are confined within a 3-dimensional region of space
overlapping with the detection portion. Confining the selectively
transmitted ions within the 3-dimensional region of space results
in a higher ion density within the detection portion of the
analyzer region, which produces a better response from the light
detector. At step 316, incident light is directed through the
3-dimensional region of space within the analyzer region. For
example, light from one of an infrared light source and a laser
light source is directed through a first light transmissive optical
port in a direction toward the 3-dimensional region of space. At
step 318 the incident light is allowed to interact with the
selectively transmitted ions confined within the 3-dimensional
region of space, to result in light including information relating
to the selectively transmitted ions. At step 320, the light
including information relating to the selectively transmitted ions
is detected. For example, the light propagates from the
3-dimensional region of space to a light detector via a second
light transmissive optical port. Optionally, the light is detected
after propagating through one of the first light transmissive
optical port and the ion outlet orifice from the FAIMS analyzer
region.
[0094] Referring now to FIG. 12, shown is a simplified flow diagram
for a method of affecting the selectively transmitted ions. At step
322, a mixture of ions including an ion type of interest is
introduced into a FAIMS analyzer region of, for example, one of the
above-mentioned FAIMS devices 30, 61, 90, 120, 160 and 190.
Optionally, the ions are produced within the analyzer region from a
suitable sample using, for example, a laser-based ionization
technique. At step 324, appropriate conditions are provided within
the FAIMS analyzer region for effecting a separation of the ions,
to selectively transmit the ion type of interest to at least a
portion of the analyzer region. At step 326, the ions are affected
in order to induce a change therein. For example, a stimulus is
provided to the selectively transmitted ions at step 326. Some
non-limiting examples of suitable forms of stimuli include:
directing an incident beam of infrared light through the at least a
portion; directing an incident beam of laser light through the at
least a portion; and, applying a strong electric field within the
at least a portion. Optionally, a combination including two or more
of the above-mentioned stimuli is provided. Changes that are
induced by the stimulus include but are not limited to:
conformational changes; dissociation of weakly bound molecules;
and, chemical bond breakage. Ions formed when the selectively
transmitted ions undergo such a change are referred to herein as
"daughter ions" . At step 328 the daughter ions are detected. Of
course, daughter ions may only be detected if they have high field
mobility properties that are suitable for transmitting the daughter
ions within the FAIMS analyzer region under the ambient conditions
of applied CV, applied DV, carrier gas flow rate, etc. Optionally,
the daughter ions are detected using one of an optical based
detection technique, a mass spectrometric detection technique and
electrometric detection.
[0095] Referring now to FIG. 13, shown is a simplified flow diagram
for another method of affecting the selectively transmitted ions.
At step 330, a mixture of ions including an ion type of interest is
introduced into a FAIMS analyzer region of, for example, one of the
above-mentioned FAIMS devices 30, 61, 90 and 120. Optionally, the
ions are produced within the analyzer region from a suitable sample
using, for example, a laser-based ionization technique. At step
332, appropriate conditions are provided within the FAIMS analyzer
region for effecting a separation of the ions, to selectively
transmit the ion type of interest to a reaction portion within the
analyzer region. At step 334, some of the selectively transmitted
ions are confined within a 3-dimensional region of space
overlapping with the reaction portion. Confining the selectively
transmitted ions within the 3-dimensional region of space results
in a higher ion density within the reaction portion of the analyzer
region. At step 336, incident light is directed through the
3-dimensional region of space within the analyzer region. For
example, light from one of an infrared light source and a laser
light source is directed through a first light transmissive optical
port in a direction toward the 3-dimensional region of space. At
least one of the intensity and the frequency of the incident light
is selected to affect the ions within the 3-dimensional region of
space. At step 338 the incident light is allowed to interact with
the selectively transmitted ions confined within the 3-dimensional
region of space, to produce daughter ions. The daughter ions are
formed from the selectively transmitted ions as a result of
structural changes that include but are not limited to:
conformational changes; dissociation of weakly bound molecules;
and, chemical bond breakage. The daughter ions are detected at step
340. Of course, daughter ions may only be detected if they have
high field mobility properties that are suitable for transmitting
the daughter ions within the FAIMS analyzer region under the
ambient conditions of applied CV, applied DV, carrier gas flow
rate, etc. Optionally, the daughter ions are detected using one of
an optical based detection technique, a mass spectrometric
detection technique and electrometric detection.
[0096] Some non-limiting examples of optional features that may be
employed in conjunction with the various embodiments of the instant
invention will now be described briefly. The light transmissive
window material that is used to form an optical port is optionally
one of a light focusing element and a light dispersing element.
Further optionally, a reflective surface is provided within the
FAIMS analyzer region for directing light that propagates from a
light source though an optical port back through the optical port
to a detector element. Advantageously, the path length of the light
through the gaseous sample is increased and only a single optical
port is required.
[0097] Numerous other embodiments may be envisaged without
departing from the spirit and scope of the invention.
* * * * *