U.S. patent application number 12/783854 was filed with the patent office on 2010-11-11 for method and system for vacuum driven mass spectrometer interface with adjustable resolution and selectivity.
This patent application is currently assigned to DH Technologies Development Pte Ltd.. Invention is credited to Thomas Covey, BRADLEY SCHNEIDER.
Application Number | 20100282966 12/783854 |
Document ID | / |
Family ID | 44121335 |
Filed Date | 2010-11-11 |
United States Patent
Application |
20100282966 |
Kind Code |
A1 |
SCHNEIDER; BRADLEY ; et
al. |
November 11, 2010 |
METHOD AND SYSTEM FOR VACUUM DRIVEN MASS SPECTROMETER INTERFACE
WITH ADJUSTABLE RESOLUTION AND SELECTIVITY
Abstract
A mass spectrometer system and a method of operating same are
provided. The system comprises a) an ion conduit for receiving
ions; b) a boundary member defining a curtain gas chamber
containing the ion conduit; c) a curtain gas supply for providing a
curtain gas directed by the boundary member to an inlet of the ion
conduit to provide a gas flow into the ion conduit, and a curtain
gas outflow out of a curtain gas chamber inlet; d) a mass
spectrometer at least partially sealed to, and in fluid
communication with, the ion conduit for receiving the ions from the
ion conduit; a vacuum chamber surrounding the mass spectrometer
operable to draw the gas flow including the ions through the ion
conduit and into the vacuum chamber; and, e) a gas outlet for
drawing a gas outflow from the gas flow located between the ion
conduit and the mass spectrometer to increase the gas flow rate
through the ion conduit.
Inventors: |
SCHNEIDER; BRADLEY;
(Bradford, CA) ; Covey; Thomas; (Richmond Hill,
CA) |
Correspondence
Address: |
BERESKIN AND PARR LLP/S.E.N.C.R.L., s.r.l.
40 KING STREET WEST, BOX 401
TORONTO
ON
M5H 3Y2
CA
|
Assignee: |
DH Technologies Development Pte
Ltd.
|
Family ID: |
44121335 |
Appl. No.: |
12/783854 |
Filed: |
May 20, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12473859 |
May 28, 2009 |
|
|
|
12783854 |
|
|
|
|
61057242 |
May 30, 2008 |
|
|
|
61178675 |
May 15, 2009 |
|
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Current U.S.
Class: |
250/282 ;
250/289 |
Current CPC
Class: |
G01N 27/622 20130101;
H01J 49/26 20130101; H01J 49/004 20130101; H01J 49/0468 20130101;
H01J 49/24 20130101; H01J 49/0404 20130101 |
Class at
Publication: |
250/282 ;
250/289 |
International
Class: |
H01J 49/26 20060101
H01J049/26; H01J 49/24 20060101 H01J049/24; H01J 49/02 20060101
H01J049/02 |
Claims
1. A mass spectrometer system comprising: an ion conduit for
receiving ions from an ion source, the ion conduit having an
internal operating pressure; a boundary member defining a curtain
gas chamber containing the ion conduit; a curtain gas supply for
providing a curtain gas directed by the boundary member to an inlet
of the ion conduit to dry and decluster the ions and to provide a
gas flow into the ion conduit, and a curtain gas outflow out of a
curtain gas chamber inlet; a mass spectrometer at least partially
sealed to, and in fluid communication with, the ion conduit for
receiving the ions from the ion conduit; a vacuum chamber
surrounding the mass spectrometer for maintaining the mass
spectrometer at a vacuum pressure lower than the internal operating
pressure, such that the vacuum chamber is operable to draw the gas
flow including the ions through the ion conduit and into the vacuum
chamber; and, a gas outlet for drawing a gas outflow from the gas
flow located between the ion conduit and the mass spectrometer to
increase the gas flow rate through the ion conduit, the gas outlet
being located between the ion conduit and the mass
spectrometer.
2. The mass spectrometer system as defined in claim 1 further
comprising at least one heater for heating at least one of the
curtain gas, the throttle gas, a heated zone upstream of the inlet
of the ion conduit, an inlet of the mass spectrometer and the ion
conduit to decluster the ions.
3. The mass spectrometer system as defined in claim 1 wherein the
gas outlet is adjustable to vary the gas outflow from the gas flow
and vary the increase in the gas flow rate.
4. The mass spectrometer system as defined in claim 1 further
comprising a juncture chamber connecting an outlet of the ion
conduit to an inlet of the mass spectrometer to define an ion path
of travel therebetween, the gas outlet being located in the
juncture chamber.
5. The mass spectrometer system as defined in claim 4 wherein the
outlet of the ion conduit is aligned with the inlet of the mass
spectrometer to transmit the ions substantially along the path of
travel to the inlet of the mass spectrometer; and, the juncture
chamber comprises a side wall spaced from the path of travel.
6. The mass spectrometer system as defined in claim 1 wherein the
ion conduit comprises a differential mobility spectrometer for
receiving ions from the ion source.
7. The mass spectrometer system as defined in claim 1 further
comprising an electrical field generator for providing an
electrical field between the ion conduit and the vacuum chamber,
the electrical field generator being configured to generate an
electrical field to guide the ions into the vacuum chamber and to
impede ions from being drawn out of the gas outlet.
8. The mass spectrometer system as defined in claim 1 wherein the
ion conduit is a differential mobility spectrometer.
9. The mass spectrometer system as defined in claim 2 wherein the
at least one heater is operable to heat the inlet of the ion
conduit to decluster the ions.
10. The mass spectrometer system as defined in claim 3 wherein the
curtain gas supply is adjustable to vary a curtain gas flow rate of
the curtain gas to the inlet of the ion conduit.
11. A mass spectrometer system as defined in claim 10, further
comprising a system controller operable to monitor a gas outflow
rate of the gas outflow out of the gas outlet, and to automatically
adjust the curtain gas flow rate based on the gas flow rate.
12. A mass spectrometer system as defined in claim 11 wherein the
system controller is operable to automatically increase the curtain
gas flow rate when the gas outflow rate of the gas outflow out of
the gas outlet increases, and is further operable to automatically
decrease the curtain gas flow rate when the gas outflow rate of the
gas outflow from the gas outlet decreases.
13. A method of operating a mass spectrometer system including an
ion conduit contained in a curtain gas chamber, and a mass
spectrometer contained in a vacuum chamber at least partially
sealed to, and in fluid communication, with, the ion conduit, the
method comprising: a) maintaining the ion conduit at an internal
operating pressure by directing a curtain gas to an inlet of the
ion conduit to dry and decluster the ions and to provide a gas flow
into the ion conduit; b) providing a curtain gas outflow out of a
curtain gas chamber inlet of the curtain gas chamber; c) providing
ions to the ion conduit; d) maintaining the mass spectrometer at a
vacuum pressure lower than the internal operating pressure to draw
the gas flow including the ions through the ion conduit and into
the vacuum chamber; and, e) drawing a bleed gas at a bleed gas flow
rate from the gas flow between the ion conduit and the mass
spectrometer to increase a gas flow rate through the ion
conduit.
14. The method as defined in claim 13 wherein e) further comprises
varying the bleed gas flow rate to vary the increase in the gas
flow rate.
15. The method as defined in claim 14 further comprising
determining a selected transmission sensitivity; determining an
adjusted gas flow rate to provide the selected transmission
sensitivity; and, varying the bleed gas flow rate to provide the
increase in the gas flow rate to provide the adjusted gas flow rate
to provide the selected transmission sensitivity.
16. The method as defined in claim 15 wherein selecting the
transmission sensitivity and determining the adjusted gas flow rate
to provide the selected transmission sensitivity are substantially
contemporaneous.
17. The method as defined in claim 13 further comprising: providing
the curtain gas at a selected volumetric flow rate to the inlet of
the ion conduit to provide the gas flow through the ion conduit and
into the mass spectrometer, and a curtain gas outflow away from the
inlet of the ion conduit and outside the ion conduit to decluster
the ions; and, adjusting the selected volumetric flow rate of the
curtain gas directly and proportionately with changes in the bleed
gas flow rate to maintain a substantially constant rate of the
curtain gas outflow.
18. The method as defined in claim 13 wherein the ion conduit
comprises a differential mobility spectrometer for receiving ions
from the ion source, the differential mobility spectrometer having
electrodes and at least one voltage source for providing DC and RF
voltages to the electrodes, and the method further comprises
operating the differential mobility spectrometer in transparent
mode such that the RF voltage provided to the electrodes is zero
Volts.
19. The method as defined in claim 18 wherein the DC voltage
provided to the electrodes is zero Volts.
20. The method as defined in claim 13 further comprising heating
the ion conduit to decluster the ions.
21. The method as defined in claim 13 further comprising providing
an electrical field between the ion conduit and the vacuum chamber,
the electrical field being configured to guide the ions into the
vacuum chamber and to impede ions from being drawn out of the gas
flow and into the bleed gas flow.
22. The method as defined in claim 21 wherein the ion conduit is a
differential mobility spectrometer, and the method further
comprises operating the differential mobility spectrometer in
transparent mode with a compensation voltage of zero volts.
23. The method as defined in claim 22 wherein the method further
comprises operating the differential mobility spectrometer in
transparent mode with a separation voltage of zero volts.
Description
[0001] This is a continuation-in-part of U.S. application Ser. No.
12/473,859 filed on May 28, 2009, which in turn claims priority
from U.S. provisional application No. 61/057,242 filed May 30, 2008
and U.S. provisional application No. 61/178,675 filed May 15, 2009.
The contents of U.S. application Ser. Nos. 12/473,859, 61/057,242
and 61/178,675 are incorporated herein by reference.
INTRODUCTION
[0002] The present invention relates generally to methods and
systems involving both a mass spectrometer and a differential
mobility spectrometer.
[0003] In differential mobility spectrometer/mass spectrometer
systems, a drift gas is typically supplied from a compressed gas
source upstream of the differential mobility spectrometer. This
drift gas acts as a carrier gas flow through the differential
mobility spectrometer. The delivery of the drift gas to the
differential mobility spectrometer can be controlled by flow
restriction valves. Sensitivity is related to the transmission
efficiency of the system--what percentage of the ions end up being
actually detected. Selectivity or resolution refers to the
detector's ability to distinguish between similar ions.
[0004] Differential mobility spectrometry, also referred to as high
field asymmetric waveform ion mobility spectrometry (FAIMS) or
Field Ion Spectrometry (FIS), is a variant of ion mobility
spectrometry (IMS). IMS separates ions by the difference in the
time it takes for them to drift through a gas, typically at
atmospheric pressure, in a constant electrostatic field of low
field strength applied along the axial length of a flight tube.
Ions are pulsed into the flight tube and their flight times are
recorded. The time of flight is inversely related to the mobility
of an ion. Ions have a single motion of direction (axial) and are
separated according to their mobility through the gas under these
low field conditions (E<1000V/cm). The drift time and thus
mobility is a function of the size and shape of an ion and its
interactions with the background gas.
[0005] Differential mobility spectrometry differs from IMS in the
geometry of the instrumentation and adds an additional dimension to
the separation theory. RF voltages, often referred to as separation
voltages (SV), are applied across the ion transport chamber,
perpendicular to the direction of the transport gas flow. Ions will
migrate toward the walls and leave the flight path unless their
trajectory is corrected by a counterbalancing voltage, a DC
potential often referred to as a compensation voltage (CV). Instead
of recording the flight time of an ion through the chamber, the
voltage required to correct the trajectory of a particular ion is
recorded. Ions are not separated in time as with an IMS: instead,
the mobility measurement is a function of the compensation voltage
used to correct the tilt in ion trajectory caused by the difference
between high field and low field ion mobilities. As such, ions are
not pulsed into the analyzer but instead introduced in a continuous
fashion and the compensation voltage is scanned to serially pass
ions of different differential mobility or set to a fixed value to
pass only ion species with a particular differential mobility.
SUMMARY OF THE INVENTION
[0006] Typically, there is a tradeoff between selectivity and
sensitivity, both of which are linked to the residence time of the
ions in the differential mobility spectrometer. Specifically,
increasing the residence time of the ions in the differential
mobility spectrometer may increase selectivity, but at the price of
reducing sensitivity.
[0007] As described above, in the description that follows,
sensitivity is related to the transmission efficiency of the
system--what percentage of the ions end up being actually detected.
Selectivity or resolution refers to the detector's ability to
distinguish between similar ions.
[0008] In accordance with an aspect of an embodiment of the
invention, there is provided a mass spectrometer system comprising:
[0009] a) an ion conduit for receiving ions from an ion source, the
ion conduit having an internal operating pressure; [0010] b) a
boundary member defining a curtain gas chamber containing the ion
conduit; [0011] c) a curtain gas supply for providing a curtain gas
directed by the boundary member to an inlet of the ion conduit to
dry and decluster the ions and to provide a gas flow into the ion
conduit, and a curtain gas outflow out of a curtain gas chamber
inlet; [0012] d) a mass spectrometer at least partially sealed to,
and in fluid communication with, the ion conduit for receiving the
ions from the ion conduit; [0013] e) a vacuum chamber surrounding
the mass spectrometer for maintaining the mass spectrometer at a
vacuum pressure lower than the internal operating pressure, such
that the vacuum chamber is operable to draw the gas flow including
the ions through the ion conduit and into the vacuum chamber; and,
[0014] f) a gas outlet for drawing a gas outflow from the gas flow
located between the ion conduit and the mass spectrometer to
increase the gas flow rate through the ion conduit, the gas outlet
being located between the ion conduit and the mass
spectrometer.
[0015] In accordance with an aspect of another embodiment of the
invention, there is provided a method of operating a mass
spectrometer system including an ion conduit contained in a curtain
gas chamber, and a mass spectrometer contained in a vacuum chamber
at least partially sealed to, and in fluid communication, with, the
ion conduit. The method comprises: [0016] a) maintaining the ion
conduit at an internal operating pressure by directing a curtain
gas to an inlet of the ion conduit to dry and decluster the ions
and to provide a gas flow into the ion conduit; [0017] b) providing
a curtain gas outflow out of a curtain gas chamber inlet of the
curtain gas chamber; [0018] c) providing ions to the ion conduit;
[0019] d) maintaining the mass spectrometer at a vacuum pressure
lower than the internal operating pressure to draw the gas flow
including the ions through the ion conduit and into the vacuum
chamber; and, e) drawing a bleed gas at a bleed gas flow rate from
the gas flow between the ion conduit and the mass spectrometer to
increase a gas flow rate through the ion conduit.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] The skilled person in the art will understand that the
drawings, described below, are for illustration purposes only. The
drawings are not intended to limit the scope of the applicant's
teachings in any way.
[0021] FIG. 1, in a schematic diagram, illustrates a differential
mobility spectrometer/mass spectrometer system including a juncture
chamber to which a throttle gas is added between the differential
mobility spectrometer and the mass spectrometer in accordance with
an aspect of a first embodiment of the present invention.
[0022] FIG. 2, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system including a juncture
chamber to which a throttle gas is added between the differential
mobility spectrometer and the mass spectrometer in accordance with
an aspect of a second embodiment of the present invention.
[0023] FIG. 2A, in a graph, plots the signals for various ions
against the DMS offset potential relative to a potential at the
vacuum chamber inlet or mass spectrometer inlet.
[0024] FIG. 3, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system including a juncture
chamber to which a throttle gas is added between the differential
mobility spectrometer and the mass spectrometer, and in which gas
flow into the differential mobility spectrometer is restricted, in
accordance with an aspect of a third embodiment of the present
invention.
[0025] FIG. 4, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system in which a
controlled leak is provided at a juncture of the differential
mobility spectrometer and the mass spectrometer to adjust the gas
flow rate through the differential mobility spectrometer in
accordance with an aspect of a fourth embodiment of the present
invention.
[0026] FIG. 5, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system including a juncture
chamber to which the throttle gas is added between the differential
mobility spectrometer and the mass spectrometer and in which the
differential mobility spectrometer includes a heated tube in
accordance with an aspect of a fifth embodiment of the present
invention.
[0027] FIG. 6, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system similar to that
described in FIG. 2, and in which bubblers are provided for adding
liquid modifiers to the curtain gas provided to the curtain
chamber, in accordance with an aspect of a sixth embodiment of the
present invention.
[0028] FIG. 7, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system similar to that of
FIG. 6, but also including an additional conduit branch for
providing curtain gas directly to the curtain chamber without any
liquid modifiers, in accordance with an aspect of a seventh
embodiment of the present invention.
[0029] FIG. 8, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system including a juncture
chamber to which a throttle gas is added between the differential
mobility spectrometer and the mass spectrometer, and in which
bubblers are provided to add various modifiers to the throttle gas,
in accordance with an aspect of a eighth embodiment of the present
invention.
[0030] FIG. 9, in a schematic view, illustrates a differential
mobility spectrometer/mass spectrometer system including a juncture
chamber from which a bleed gas is drawn between the differential
mobility spectrometer and the mass spectrometer in accordance with
an aspect of a ninth embodiment of the present invention.
[0031] FIG. 10, in a series of graphs, illustrates different
resolutions of a CV scan for separation of a sample containing
ephedrine and pseudoephedrine using a fixed differential mobility
spectrometer geometry with a variable amount of throttle gas added
at the juncture of the differential mobility spectrometer and the
mass spectrometer.
[0032] FIG. 11, in a schematic view, illustrates a mass
spectrometer system including a juncture chamber from which a bleed
gas is drawn between an upstream heated tube and a downstream mass
spectrometer in accordance with an aspect of a tenth embodiment of
the present invention.
[0033] FIG. 12, in a schematic view, illustrates a mass
spectrometer system including a juncture chamber from which a bleed
gas is drawn between an upstream heated tube and a downstream mass
spectrometer, wherein an electric field is provided within the
juncture chamber to guide ions into the mass spectrometer and to
impede ions from being drawn out of the juncture chamber with the
bleed gas in accordance with an aspect of a further embodiment of
the invention.
DESCRIPTION OF VARIOUS EMBODIMENTS
[0034] Referring to FIG. 1, there is illustrated in a schematic
view, a differential mobility spectrometer/mass spectrometer system
200 in accordance with an aspect of a first embodiment of the
present invention. The differential mobility spectrometer/mass
spectrometer system 200 comprises a differential mobility
spectrometer 202 and a first vacuum lens element 204 of a mass
spectrometer (hereinafter generally designated mass spectrometer
204). Mass spectrometer 204 also comprises mass analyzer elements
204a downstream from vacuum chamber 227. Ions can be transported
through vacuum chamber 227 and may be transported through one or
more additional differentially pumped vacuum stages prior to the
mass analyzer indicated schematically as mass analyzer elements
204a. For instance in one embodiment, a triple quadrupole mass
spectrometer may comprise three differentially pumped vacuum
stages, including a first stage maintained at a pressure of
approximately 2.3 Torr, a second stage maintained at a pressure of
approximately 6 mTorr, and a third stage maintained at a pressure
of approximately 10.sup.-5 Torr. The third vacuum stage may contain
a detector, as well as two quadrupole mass analyzers with a
collision cell located between them. It will be apparent to those
of skill in the art that there may be a number of other ion optical
elements in the system that have not been described. This example
is not meant to be limiting as it will also be apparent to those of
skill in the art that the differential mobility spectrometer/mass
spectrometer coupling described can be applicable to many mass
spectrometer systems that sample ions from elevated pressure
sources. These may include time of flight (TOF), ion trap,
quadrupole, or other mass analyzers as known in the art.
[0035] The differential mobility spectrometer 202 comprises plates
206 and an electrical insulator 207 along the outside of plates
206. The plates 206 surround a drift gas 208 that drifts from an
inlet 210 of the differential mobility spectrometer to an outlet
212 of the differential mobility spectrometer 202. The insulator
207 supports the electrodes and isolates them from other conductive
elements. For example, the insulator may be fabricated from ceramic
or Teflon.TM.. The outlet 212 of the differential mobility
spectrometer 202 releases the drift gas into a juncture or baffle
chamber 214 defined by baffles 216, which juncture chamber 214
defines a path of travel for ions between the differential mobility
spectrometer 202 and the mass spectrometer 204. In some
embodiments, the outlet 212 of the differential mobility
spectrometer 202 is aligned with the inlet of the mass spectrometer
204 to define the ion path of travel therebetween, while the
baffles 216 are spaced from this path of travel to limit
interference of the baffles 216 with the ions 222 traveling along
the path of travel.
[0036] The differential mobility spectrometer 202 and juncture
chamber 214 are both contained within a curtain chamber 218,
defined by curtain plate (boundary member) 219 and supplied with a
curtain gas from a curtain gas source 220. The curtain gas source
220 provides the curtain gas to the interior of the curtain chamber
218. Ions 222 are provided from an ion source (not shown) and are
emitted into the curtain chamber 218 via curtain chamber inlet 224.
The pressure of the curtain gas within the curtain chamber 218
provides both a curtain gas outflow 226 out of curtain gas chamber
inlet 224, as well as a curtain gas inflow 228 into the
differential mobility spectrometer 202, which inflow 228 becomes
the drift gas 208 that carries the ions 222 through the
differential mobility spectrometer 202 and into the juncture
chamber 214. The curtain plate 219 may be connected to a power
supply to provide an adjustable DC potential to it.
[0037] As illustrated in FIG. 1, the first vacuum lens element 204
of the mass spectrometer 204 is contained within a vacuum chamber
227, which can be maintained at a much lower pressure than the
curtain chamber 218. In accordance with an aspect of an embodiment
of the present invention, the vacuum chamber 227 can be maintained
at a pressure of 2.3 Torr by a vacuum pump 230 while the curtain
chamber 218 and an internal operating pressure of the differential
mobility spectrometer 202 can be maintained at a pressure of 760
Torr. As a result of the significant pressure differential between
the curtain chamber 218 and the vacuum chamber 227, the drift gas
208 is drawn through the differential mobility spectrometer 202,
the juncture chamber 214 and, via vacuum chamber inlet 229, into
the vacuum chamber 227 and first vacuum lens element 204. As shown,
the mass spectrometer 204 can be sealed to (or at least partially
sealed), and in fluid communication with the differential mobility
spectrometer, via the juncture chamber, to receive the ions 222
from the differential mobility spectrometer 202.
[0038] As shown, the baffles 216 of the curtain chamber comprise a
controlled leak or gas port 232 for admitting the curtain gas into
the juncture chamber 214. Within the juncture chamber 214, the
curtain gas becomes a throttle gas that throttles back the flow of
the drift gas 208 through the differential mobility spectrometer
202. Specifically, the throttle gas within the juncture chamber 214
modifies a gas flow rate within the differential mobility
spectrometer 202 and into the juncture chamber 214, thereby
controlling the residence time of the ions 222 within the
differential mobility spectrometer 202. By controlling the
residence time of the ions 222 within the differential mobility
spectrometer 202, resolution and sensitivity can be adjusted. That
is, increasing the residence times of the ions 222 within the
differential mobility spectrometer 202 can increase the resolution,
but can also result in additional losses of the ions, reducing
sensitivity. In some embodiments it can therefore be desirable to
be able to precisely control the amount of throttle gas that is
added to the juncture chamber 214 to provide a degree of control to
the gas flow rate through the differential mobility spectrometer
202, thereby controlling the tradeoff between sensitivity and
selectivity. In the embodiment of FIG. 1, the inflow of throttle
gas from the curtain chamber 218 can be controlled by controlling
the size of the leak provided by the gas port 232.
[0039] The baffles can be configured to provide a randomizer
surface member, and the gas port 232 can be oriented to direct the
throttle gas at least somewhat against the baffles 216 and
randomizer surface to disburse the throttle gas throughout the
juncture chamber 214. In one embodiment, the gas port 232
introduces the throttle gas without disrupting the gas streamlines
between the differential mobility spectrometer 202 and the mass
spectrometer inlet 229.
[0040] As described above and as known in the art, RF voltages,
often referred to as separation voltages (SV), can be applied
across an ion transport chamber of a differential mobility
spectrometer perpendicular to the direction of drift gas 208 (shown
in FIG. 1). The RF voltages may be applied to one or both of the
DMS electrodes comprising the differential mobility spectrometer.
The tendency of ions to migrate toward the walls and leave the path
of the DMS can be corrected by a DC potential often referred to as
a compensation voltage (CV). The compensation voltage may be
generated by applying DC potentials to one or both of the DMS
electrodes comprising the differential mobility spectrometer. As is
known in the art, a DMS voltage source (not shown) can be provided
to provide both the RF SV and the DC CV. Alternatively, multiple
voltage sources may be provided.
[0041] Similarly, a DC declustering or inlet potential can be
provided to the vacuum chamber inlet 229 (again as shown in FIG. 1)
by an inlet potential voltage source (not shown), again as known in
the art. This vacuum chamber inlet may be a orifice, or,
alternatively, may be a capillary, heated, capillary or an ion
pipe.
[0042] In embodiments of the present invention in which the vacuum
chamber inlet 229 is smaller then an outlet of the differential
mobility spectrometer 202, it can be advantageous to provide a
braking potential to the vacuum chamber inlet 229 relative to the
differential mobility spectrometer 202. This braking potential can
be provided by providing a DMS DC offset voltage to the plates or
electrodes of the DMS relative to the declustering or inlet
potential provided to the vacuum chamber inlet 229. By slowing down
the ions prior to them entering the vacuum chamber 229, the braking
potential can increase the extent to which these ions are entrained
within the gas flows, thereby increasing the likelihood that the
ions will actually pass through the vacuum chamber inlet, instead
of impacting on the sides of the vacuum chamber inlet 229.
[0043] Alternatively, in some embodiments of the present invention,
such as, for example without limitation, embodiments in which the
vacuum chamber inlet 229 is larger relative to the slit or outlet
from the differential mobility spectrometer 202, it can be
desirable to adjust the DMS DC offset voltage. In particular this
DC offset voltage may actually be positive to speed up ions as they
pass through the vacuum chamber inlet 229, if it is not desirable
to slow them down to improve transmission from the differential
mobility spectrometer 202 into the vacuum chamber 227.
[0044] This DMS DC offset can also be adjusted based on a mass of
the ions being selected in a differential mobility spectrometer
202. This could be part of a two-stage process. Specifically, the
declustering voltage provided to the vacuum chamber inlet 229 can
first be adjusted based on the mass of the ions being selected in
the differential mobility spectrometer 202. Then, relative to this
declustering potential provided to the vacuum chamber inlet 229,
the DMS DC offset voltage could be adjusted to enhance transmission
from the differential mobility spectrometer 202 through the vacuum
chamber inlet 229. Alternatively, the DMS offset DC potential may
be selected for a given ion. In some embodiments, a voltage source
controller can be set to automatically adjust the DMS electrode DC
offsets to maintain the same potential difference relative to the
orifice potential. Then the declustering potential or inlet
potential may be adjusted, That is, in these embodiments the DMS
offset voltage is merely the difference between the DC potential
applied to the electrodes as an offset and the inlet voltage. Say,
for example, that a preferred DMS offset voltage is -3 V. Then,
when the inlet voltage is tuned, the control system can, in these
embodiments, maintain that -3 V offset regardless of the current
inlet voltage. For instance, if the inlet potential is initially 50
V, the DC potential on the DMS electrodes can be automatically
maintained at 47 V (CV=0 situation). If the inlet potential is
tuned up to 100 V, the DC applied to the DMS electrodes can be
automatically changed to 97 V. The CV=0 situation means that an ion
high and low field mobility are either the same, or extremely
similar. This may occur if the separation voltage is 0 V, or under
some conditions with the separation voltage applied.
[0045] Referring to FIG. 2, there is illustrated in a schematic
view, a differential mobility spectrometer/mass spectrometer system
300 in accordance with an aspect of a second embodiment of the
present invention. For clarity, the same reference numerals used in
FIG. 1, with 100 added, are used in FIG. 2 to designate elements
analogous to the elements of FIG. 1. For brevity, the description
of FIG. 1 is not repeated with respect to FIG. 2.
[0046] It is important to note that due to the compensation voltage
provided to the plates or electrodes of the differential mobility
spectrometer, the actual DC potential of one or both of the
electrodes of the differential mobility spectrometer may not differ
by the DMS DC offset amount from the declustering potential applied
to vacuum chamber inlet element. For example, say that a
declustering potential is applied to vacuum chamber inlet element
329. This declustering potential (DP) is determined based on the
m/z of the ion being selected by the differential mobility
spectrometer, and this determination of the DP is known in the art.
Then, a DC offset voltage is applied to the plate or electrodes 306
of the differential mobility spectrometer 302. In addition, the CV
will be applied to the electrodes 306. Application of a CV may
proceed in different ways. For example, say that there is a CV of
10 volts, then 5V can be applied to one electrode, while -5V are
applied to the other electrode. Alternatively, 10V can be applied
to one electrode and no volts to the other electrode.
[0047] Consider an example where all of the CV is applied to one
electrode. Then, say that a DP of 100V is first determined for the
vacuum chamber inlet. The offset between the vacuum chamber inlet
and the differential mobility spectrometer is determined to be -5V.
The CV for the differential mobility spectrometer is 10V. Then, one
electrode of the differential mobility spectrometer would have a
potential of 100V-5V+10V or 105V, while the other electrode would
have a potential of 100V-5V=95V.
[0048] As noted above, the DC offset voltage need not be negative.
Specifically, where the orifice or inlet dimension more closely
matches the slit dimension for the differential mobility
spectrometer, there may be no need to slow the ions down to
properly entrain them in the gas flow so that they can flow through
the orifice. Instead, it could even be desirable to speed the ions
up.
[0049] Referring to FIG. 2A, the effectiveness of braking
potentials applied to electrodes of dimension 1.times.10.times.30
mm is plotted in a graph for various mass to charge ratios. For all
the ions tested, the optimal DMS offset voltage appears to be
negative--that is, the optimal DMS potential should be slightly
lower than the vacuum chamber inlet potential to establish a
braking potential. The magnitude of the optimal offset voltage and
the widths of the optimal voltage range both increase with the mass
to charge ratio of the ion of interest, likely reflecting the known
decrease in the ion mobility constant for higher m/z ions. The data
plotted in FIG. 2A demonstrates that the transfer of ions from a
slotted DMS analyzer to a circular mass spectrometer or vacuum
chamber inlet may be improved by slowing down the ions to give them
a longer time period in which to be influenced by the bending gas
streams converging on the inlet, thereby reducing losses in the
interface region or juncture of the differential mobility
spectrometer and mass spectrometer.
[0050] As with the system 200 of FIG. 1, in the system 300 of FIG.
2 drift gas 308 can be drawn through the differential mobility
spectrometer 302 and into the vacuum chamber 327 and the first
vacuum lens element 304 by the much lower pressure maintained in
the vacuum chamber 327. As with the system 200 of FIG. 1, the
vacuum chamber 327 of the system 300 can be maintained, say, at a
pressure of 2.3 Torr, for example, while the pressure in the
curtain chamber 318 can be maintained at a pressure of 760
Torr.
[0051] As with the system 200 of FIG. 1, the resolution or
selectivity of system 300 can be adjusted by adding a throttle gas
to a juncture chamber 314 between the differential mobility
spectrometer 302 and the vacuum chamber inlet 329. In the system
300 of FIG. 2, a common source is provided for both the curtain gas
and the throttle gas; however, separate sources may also be
provided. For example, this gas could be nitrogen. The throttle gas
flows through a conduit branch 320a into the juncture chamber 314.
Again, this gas is called a throttle gas because it throttles back
the flow through the differential mobility spectrometer. In some
embodiments, the gas can be added in a coaxial manner to reduce the
likelihood of a cross beam of the throttle gas interfering with the
ion beam trajectory or ion path of travel between the differential
mobility spectrometer 302 and the mass spectrometer, as
interference with this ion beam trajectory could potentially
diminish transmission efficiency. For example, as shown in FIG. 2,
gas ports 332 are oriented or inclined such that the throttle gas
flows into the juncture chamber 314 at an orientation that is
toward the vacuum chamber 327 and away from the differential
mobility spectrometer 302. Optionally, the juncture chamber 314 can
be enlarged or may include extra structures to reduce the linear
velocity of the throttle gas to reduce its interference with the
ion beam at the point of entry into the mass spectrometer. Further,
the gas ports 332 may optionally be oriented such that the throttle
gas flows along the sidewalls of the juncture chamber, somewhat
parallel to the ion path of travel. In another embodiment, the
juncture chamber may be designed with a much larger diameter than
the diameter of the insulator, and the gas port may be oriented
such that the gas stream through the inlet is directed along the
wall.
[0052] Please note that schematic FIGS. 1-9 are not to scale. That
is, from a functional perspective the juncture chamber can be made
substantially larger than what is shown in the figures, to reduce
the risk of the throttle gas inflow disrupting ion flow through the
juncture chamber. Further, the throttle gas can be introduced so as
to be directed along the wall, thereby reducing disruption, and
increasing sensitivity, as compared to the case in which the
throttle gas is provided in a cross-flow to the ion motion in the
juncture chamber.
[0053] Conduit branch 320a comprises a controllable valve 320b that
can be used to control the rate of flow of the throttle gas into
the juncture chamber 314. For example, to increase resolution or
selectivity, at the price of an acceptable loss in sensitivity, the
controllable valve 320b could be opened to admit more throttle gas
into the juncture chamber 314 via conduit branch 320a to reduce the
gas flow rate within the differential mobility spectrometer 302.
This, in turn, can increase the residence time of the ions 322
within the differential mobility spectrometer. The increased
residence time manifests itself as narrower mobility peak widths,
and therefore, improved selectivity. At the same time, the
increased residence time lowers sensitivity somewhat due to
increased diffusion losses. At the same time, because of the
increased residence time within the differential mobility
spectrometer, more of the ions can be lost.
[0054] As shown, FIG. 2 also can comprise a valve 320c for
controlling the rate of flow of the curtain gas into the curtain
chamber 318. It is important to control the curtain gas flow rate
to ensure proper declustering of ions upstream of to the DMS.
Clusters can have different mobilities than dry ions, and can
therefore have different compensation voltage (CV) values. These
clusters can be filtered and lost while transmitting an ion of
interest, leading to reduced sensitivity. As shown in FIG. 2, the
system may comprise a common gas supply to provide both the curtain
gas and the throttle gas flows. The curtain gas outflow 326 from
the curtain plate 319 aperture can be defined by the sum of the
volumetric flow rates for the curtain gas and the throttle gas
minus the volumetric flow rate through the gas conductance limiting
aperture 329. The curtain gas outflow 326 is typically optimized
for a given compound and set of conditions. Therefore, with the
configuration illustrated in FIG. 2, the curtain gas outflow 326
may be maintained constant regardless of what portion of the total
flow is provided through passage 320 (curtain gas) or 320a
(throttle gas), provided that the total volumetric flow rate is
constant.
[0055] As the differential mobility spectrometer 302 is sealed, or
at least partially sealed (no seal is perfect) to the mass
spectrometer, or at least to the first vacuum chamber 327, The mass
spectrometer can comprise a circular orifice to receive the ions
322 from the differential mobility spectrometer 302. This is
enabled by the streamlines resulting from sealing the differential
mobility spectrometer 302 to the mass spectrometer. The gas
streamlines exiting the differential mobility spectrometer 302
converge on the orifice inlet 329, and these bending streamlines
can transport ions through the inlet 329. It can be desirable to
maintain a circular orifice to ensure high transmission efficiency
through subsequent vacuum stages and lenses.
[0056] Referring to FIG. 3, there is illustrated in a schematic
view, a differential mobility spectrometer/mass spectrometer system
400 in accordance with an aspect of a third embodiment of the
present invention. For clarity, the same reference numerals used in
FIG. 2, with 100 added, are used in FIG. 3 to designate elements
analogous to the elements of FIG. 2. For brevity, the descriptions
of FIGS. 1 and 2 are not repeated with respect to FIG. 3.
[0057] As with the system 300 of FIG. 2, the resolution or
selectivity of system 400 of FIG. 3 can be adjusted by adding
throttle gas to a juncture chamber 414 between the differential
mobility spectrometer 402 and the vacuum chamber inlet 429. As with
system 300 of FIG. 2, a common source can be provided for both the
curtain gas and the throttle gas.
[0058] In addition, gas restriction plates 434 are provided at an
inlet 410 of the differential mobility spectrometer 402. These gas
restriction plates 434 can facilitate tuning the pressure of the
differential mobility spectrometer 402 for further optimization of
selectivity, in an analogous fashion to Nazarov et al. (Nazarov E
G, Coy S L, Krylov E V, Miller A R, Eiceman G., Pressure Effects in
Differential Mobility Spectrometry, Anal. Chem., 2006, 78,
7697-7706). Specifically, when the gas restriction plates 434 are
provided to restrict the flow of drift gas into the differential
mobility spectrometer 402, pumping at the back of the differential
mobility spectrometer 402, by providing the lower pressure in the
vacuum chamber 427, can lower the pressure within the differential
mobility spectrometer to provide an extra degree of selectivity or
an extra parameter to adjust for tricky separations. The diameter
of the aperture in the gas restriction plate 434 can be adjustable
to allow an operator to tune the pressure within the differential
mobility spectrometer 402 for the vacuum draw established with a
fixed mass spectrometer inlet diameter.
[0059] Referring to FIG. 4, there is illustrated in a schematic
view a differential mobility spectrometer/mass spectrometer system
500 in accordance with an aspect of a fourth embodiment of the
present invention. For clarity, the same reference numerals used in
FIG. 1, with 300 added, are used in FIG. 4 to designate elements
analogous to the elements of FIG. 1. For brevity, the descriptions
of FIGS. 1 to 3 are not repeated with respect to FIG. 4.
[0060] The system 500 of FIG. 4 is a hybrid of the systems 200 and
300 of FIGS. 1 and 2 respectively. That is, similar to the system
200 in FIG. 1, the curtain gas supply 520 provides a curtain gas to
the curtain chamber 518, and a controlled leak 532 is provided from
the curtain chamber 518 into the juncture chamber 514. However,
similar to the system 300 of FIG. 2, the flow of throttle gas into
the juncture chamber 514 of the system 500 of FIG. 4 can be
controlled independently of the pressure of the curtain gas within
the curtain chamber 518 by adjusting gas flow restrictors 533. That
is, gas flow restrictors 533 can be adjusted to adjust the size of
controlled leak 532, thereby adjusting the amount of throttle gas
sucked into the juncture chamber 514, without mechanically breaking
the seal with the mass spectrometer 504. In contrast, the
controlled leak 232 of the system 200 of FIG. 1 is provided by
mechanically altering the leak provided by the seal with the mass
spectrometer as shown in FIG. 1. Specifically, baffles 216 of the
system 200 of FIG. 1 are adjustable to control the size of the leak
shown in FIG. 1.
[0061] Referring to FIG. 5, there is illustrated in a schematic
view, a differential mobility spectrometer/mass spectrometer system
600 in accordance with an aspect of a fifth embodiment of the
invention. For clarity the same reference numerals used in FIG. 2,
with 300 added are used in FIG. 5 to designate elements analogous
to the elements of FIG. 2. For brevity, the descriptions of FIGS. 1
and 2 are not repeated with respect to FIG. 5.
[0062] In a system 600 of FIG. 5, a heated tube 602a is installed
at the inlet 610 of the differential mobility spectrometer 602. The
heated tube 602a can be sealed to the inlet 610 of the differential
mobility spectrometer 602. The heated tube 602a can facilitate
additional declustering of the ions 622 prior to the ions 622
entering the differential mobility spectrometer. During use with
high flow rate high performance liquid chromatography (HPLC), for
example clusterring can be a problem that decreases sensitivity.
This additional declustering can also help with other ion sources,
such as atmospheric pressure matrix-assisted laser
desorption/ionization (AP-MALDI), atmospheric pressure chemical
ionization (APCI), Desorption electrospray ionization (DESI), and
Direct Analysis in Real Time (DART), for example. While these
sources have been provided as examples, it will be apparent to
those of skill in the art that this approach can improve
performance for any ionization source that generates ions as well
as clusters. The heated tube 602a can also facilitate laminar flow
conditions, and increase the uniformity of the electric field at
the inlet 610 of the differential mobility spectrometer 602, and by
doing so can facilitate ion transmission into the differential
mobility spectrometer 602.
[0063] In some embodiments of the present invention, such as the
system 600 illustrated in FIG. 5, increases in the volumetric flow
of throttle gas into the juncture chamber 614 can be balanced by
corresponding reductions in the volumetric flow rate of curtain gas
into the curtain chamber 618. For example, the total rate of flow
of, say, nitrogen, into both the curtain chamber and the juncture
chamber (the curtain gas flow rate and the throttle gas flow rate
respectively) can be kept substantially constant by balancing
changes in one of the curtain gas flow rate and the throttle gas
flow rate with opposite changes in the other of these flow rates.
This can be desirable.
[0064] Specifically, if the flow of throttle gas into the juncture
chamber is increased while the flow of curtain gas into the curtain
chamber is kept constant, then the outflow of curtain gas away from
the inlet of the differential mass spectrometer can be expected to
increase. This can be undesirable. That is, as shown in FIG. 5 for
example, a particular outflow 626 of curtain gas, in the opposite
direction to the flow of gas through the differential mobility
spectrometer and into the mass spectrometer, may have been selected
for a particular group of ions sharing a common m/z to decluster
these ions. Thus, the curtain gas outflow rate desired may depend
on the group of ions of interest and what counterflow is desired to
help to decluster them. If the flow of throttle gas into the
juncture chamber 614 is increased, then, other things equal, the
outflow 626 from the boundary member 619 can also be expected to
increase beyond what was selected, which can be undesirable.
Accordingly, in some embodiments it can be desirable to reduce the
inflow of the curtain gas into the curtain chamber proportionally
to balance an increase in the inflow of throttle gas into the
juncture chamber.
[0065] FIG. 5 illustrates one way in which this can be achieved.
Specifically, for system 600 a common source is shown for both the
curtain gas and the throttle gas. Thus, for example, if a greater
flow from this common source is used to increase the rate at which
throttle gas flows into the juncture chamber, then there may be a
corresponding reduction in the flow rate of the curtain gas from
this common source into the curtain chamber. This reduction of the
flow rate of curtain gas into the curtain chamber can help to
balance the increase in the rate of flow of throttle gas into the
juncture chamber, such that the outflow 626 of curtain gas away
from the inlet of differential mass spectrometer 602 is
substantially unchanged.
[0066] This balancing of increases in throttle gas flow with
proportional decreases in curtain gas flow can also be achieved
using other means in connection with other embodiments of the
present invention. For example, in the case of the system 500 of
FIG. 4, increasing the curtain gas flow rate into the curtain
chamber 518 could, on its own, also increase the rate at which
throttle gas flows into the juncture chamber 514, resulting in a
significant increase in the outflow 526 from the boundary member
519 relative to the outflow initially selected. However, this
effect can be overcome, and the rate at which throttle gas flows
into the juncture chamber even reduced, by adjusting gas flow
restrictors 533 to reduce the flow of throttle gas into the
juncture chamber 514 via controlled leak 532. Of course, where the
throttle gas flow rate decreases, the curtain gas flow into the
curtain chamber can be proportionally increased, to maintain the
outflow of curtain gas away from the inlet of the differential mass
spectrometer substantially constant.
[0067] Referring to FIG. 6, there is illustrated in a schematic
view a differential mobility spectrometer/mass spectrometer system
700 in accordance with an aspect of a sixth embodiment of the
present invention. For clarity, the same reference numerals used in
FIG. 2, with 400 added, are used in FIG. 6 to designate elements
analogous to the elements of FIG. 2. For brevity the descriptions
of preceding Figures, including FIGS. 1 and 2, are not repeated
with respect to FIG. 6.
[0068] As shown in FIG. 6, the system 700 is quite similar to the
system 300 of FIG. 2. However, the system 700 of FIG. 6 comprises
additional elements. Specifically, as with the system 300 of FIG.
2, a curtain gas supply 720 comprises a controllable valve 720b
that can be used to control the rate of flow of the throttle gas
into the juncture chamber 714 via conduit branch 720a. Conduit or
curtain gas supply 720 also comprises a valve 720c for controlling
the rate of flow of the curtain gas that will ultimately end up in
the curtain chamber 718. The flow of the curtain gas downstream of
valve 720c is divided into two branches 720d and 720e. The flow of
the curtain gas within branch 720d is controlled by valve 720f.
Similarly, the flow of the curtain gas within branch 720e is
controlled by valve 720g.
[0069] The flow of the curtain gas through branch 720d passes into
a bubbler 720h, which can be used to add a modifier liquid to the
curtain gas/drift gas, which passes through branch 720d and will
ultimately be pumped into the differential mobility spectrometer
702 by the vacuum maintained in the vacuum chamber 727. Similarly,
a separate modifier can be added to the curtain gas flowing through
branch 720e in bubbler 720i. The curtain gas outflows from the
bubblers 720h and 720i can be controlled by outlet valves 720j and
720k respectively, after which the two branches 720d and 720e merge
and then release the curtain gas with the modifiers into the
curtain chamber 718. As noted above, the curtain gas and drift gas
are one and the same; thus, adding the modifiers to the curtain gas
adds simplicity to the system 700. Modifiers can be vapors that
provide selectivity by clustering with ions to different degrees,
thereby shifting the differential mobility. Examples of modifiers
can include alcohols such as isopropyl alcohol, water, as well as
hydrogen and deuterium exchange agents, such as deuterated water or
methanol, which can be used, amongst other things, to count the
number of exchangeable protons on a molecule. In general, a
modifier may be defined as any additive to the drift gas that
changes the observed compensation voltage for a peak at a given AC
amplitude. The compensation voltage is related to the ratio of high
to low field mobility. Modifiers can act in other ways as well as
clustering phenomena. For instance, changing the polarizability of
the drift gas can also change the observed compensation voltage.
Clustering and polarizability changes are two examples of
mechanisms that modifiers may use to change compensation voltage
optima; however, there may also be many other mechanisms.
[0070] Referring to FIG. 7, there is illustrated in a schematic
view a differential mobility spectrometer/mass spectrometer system
800 in accordance with an aspect of a seventh embodiment of the
present invention. For clarity, the same reference numerals used in
FIG. 6 with 100 added are used in FIG. 7 to designate elements
analogous to the elements of FIG. 6. For brevity the descriptions
of preceding figures, including FIGS. 1, 2 and 6, are not repeated
with respect to FIG. 7.
[0071] As shown in FIG. 7, the system 800 is very similar to the
system 700 of FIG. 6. However the system 800 of FIG. 7 comprises an
additional conduit branch 821. Conduit branch 821 can provide
curtain gas, nitrogen in the present case, directly to the curtain
chamber 818 without passing through bubblers 820h and 820i for
modifier liquids to be added. Alternatively conduit branch 821 can
provide curtain gas directly to chamber 818, while an additional
gas fraction can also be added containing one or more
modifiers.
[0072] Referring to FIG. 8, there is illustrated in a schematic
view a differential mobility spectrometer/mass spectrometer system
900 in accordance with an aspect of an eighth embodiment of the
present invention. For clarity, the same reference numerals used in
FIG. 2, with 600 added, are used in FIG. 8 to designate elements
analogous to the elements of FIG. 2. For brevity, the descriptions
of preceding figures, including FIGS. 1 and 2 are not repeated with
respect to FIG. 8.
[0073] As shown in FIG. 8, the system 900 is quite similar to the
system 300 in FIG. 2. However, the system 900 in FIG. 8 comprises
additional elements. Specifically, as with the system 300 of FIG.
2, a curtain gas supply 920 comprises a controllable valve 920c for
controlling the rate of flow of the curtain gas into curtain
chamber 918. However, unlike the embodiments of FIGS. 2 and 7,
separate sources are provided for the curtain gas and the throttle
gas. Specifically, the system 900 further comprises a throttle gas
source 940 that divides into two branches 942 and 944. The flow of
the throttle gas within conduit branch 942 is controlled by
controllable valve 946. Similarly, the flow of the throttle gas
within branch 944 is controlled by valve 948. Optionally, as
described below, auxiliary supplies for supplying auxiliary
substances to the juncture chamber via the gas port 932 can be
provided.
[0074] The flow of throttle gas through branch 942 passes into a
bubbler 950, which can be used to add a modifier liquid to the
throttle gas passing through branch 942. Similarly, a separate
liquid modifier can be added to the throttle gas flowing through
branch 944 by bubbler 952. The throttle gas/liquid modifier
outflows from the bubblers 950 and 952 can be controlled by outlet
valves 954 and 956 respectively, after which the two branches 942
and 944 merge into common branch 958. The flow of the throttle gas
and modifier liquids added by bubblers 950 and 952 through conduit
958 and eventually into juncture chamber 914 can be controlled by
controllable valve 960.
[0075] The various controllable valves 946, 948, 954 and 956 enable
liquid modifiers to be added to the throttle gas by bubblers 950
and 952 in a controlled manner to facilitate selectivity by
clustering and reacting ions to different degrees thereby shifting
their masses observed in the mass spectrometer 904. As described
above, the modifiers added may also include hydrogen and deuterium
exchange agents, such as deuterated water or methanol, used,
amongst other things, to count the number of exchangeable protons
on the ions prefiltered with the differential mobility
spectrometer.
[0076] In the differential mobility spectrometer/mass spectrometer
systems of FIGS. 1 to 8, the differential mobility spectrometers
can be dimensioned to provide, initially, a relatively short
residence time for the ions within the differential mobility
spectrometer, and a relatively high gas flow rate of the drift gas
within the differential mobility spectrometer. This initial bias of
the differential mobility spectrometer in favor of sensitivity at
the expense of selectivity can be subsequently offset by providing
a throttle gas to the juncture chambers as described above to
decrease the flow rate of the drift gas. In the aspects of the
embodiments illustrated in FIG. 9, the opposite approach is
taken.
[0077] Referring to FIG. 9, there is illustrated in a schematic
view a differential mobility spectrometer/mass spectrometer system
1000 in accordance with an aspect of ninth embodiment of the
present invention. For clarity, the same reference numerals used in
FIG. 1, with 800 added, are used in FIG. 9 to designate elements
analogous to the elements of FIG. 1. For brevity, the description
of preceding figures, including FIG. 1, are not repeated with
respect to FIG. 9.
[0078] As shown in FIG. 9, the system 1000 is quite similar to the
systems 200 and 300 of FIGS. 1 and 2 respectively. However, instead
of adding a throttle gas to the juncture chamber 1014, the system
1000 of FIG. 9 comprises a gas outlet 1032 including a vacuum pump
1040 for drawing a bleed gas out of the juncture chamber 1014. As
the quantity of bleed gas drawn out of the juncture chamber 1014
increases, the gas flow rate of the drift gas 1008 within the
differential mobility spectrometer 1002 will increase, which can
diminish selectivity and resolution, while, at the same time,
increasing sensitivity. For this reason, in the system 1000 of FIG.
9, the differential mobility spectrometer 1002 can be dimensioned
to provide, initially, a relatively long residence time for the
ions 1022 within the differential mobility spectrometer 1002, and a
relatively low gas flow rate of the drift gas 1008 within the
differential mobility spectrometer 1002. This initial bias of the
differential mobility spectrometer 1002 in favor of selectivity at
the expense of sensitivity can be subsequently offset by increasing
a vacuum draw provided by vacuum pump 1040 to increase the rate at
which bleed gas is drawn from the juncture chamber 1014 to increase
the flow rate of the drift gas.
[0079] The bleed gas may also be useful for DMS/MS systems where
the mass spectrometer inlet is sized to provide either a
discontinuous gas flow into vacuum, or a very low gas flow rate. As
known in the art, a very small diameter orifice can provide a very
low gas flow rate into the vacuum system, and an inlet diaphragm or
adjustable orifice dimension may provide a discontinuous or
variable gas flow into the mass spectrometer vacuum system. Under
these conditions, as described below in more detail, the bleed gas
draw can provide a continuous flow of carrier gas through the DMS
cell regardless of the flow rate into the vacuum system of the mass
spectrometer system.
[0080] For example, drawing a bleed gas from the juncture of a
differential mobility spectrometer and a mass spectrometer can be
used to match the higher flow capacity of the differential mobility
spectrometer with the lower flow capacity of a low-flow, low-cost,
portable mass spectrometer. Because pumping capacity can be the
primary limitation in reducing the size and weight of a mass
spectrometer, this pumping capacity can be sacrificed to provide a
smaller mass spectrometer. To compensate for this lower pumping
capacity, a shutter can be provided at the orifice or inlet to the
vacuum chamber. This shutter might have a duty cycle of, say, 1%,
so that it is open for 10 milliseconds, and then closed for one
second (1000 milliseconds), to reduce the load on the vacuum
pump.
[0081] However, the flows through the differential mobility
spectrometer can be, and preferably are, continuous. Thus, to avoid
turbulence or other problems, as shown in FIG. 9 a bleed gas can be
drawn from the juncture of the differential mobility spectrometer
with the mass spectrometer. By extracting gas from this juncture
region, a high fraction of the differential mobility
spectrometer-filtered ions can enter the vacuum chamber inlet,
while excess flow through the differential mobility spectrometer
can be exhausted as bleed gas. This bleed gas flow can prevent or
reduce turbulence in the differential mobility spectrometer and
maintain a constant differential mobility spectrometer
resolution.
[0082] Referring to FIG. 10, there is illustrated in a series of
graphs, the effect of throttle gas on the resolution and peak width
for a sample containing ephedrine and pseudoephedrine. The
differential mobility spectrometer electrode dimension was
1.times.10.times.300 mm. RF was set to approximately 4000 V peak to
peak amplitude. In each graph, CV voltage is plotted on the x axis,
while original signal intensity is plotted on the y axis normalized
to the signal intensity achieved with no throttle gas provided.
[0083] As shown the compensation voltage peak width decreases
(improved selectivity) as more throttle gas is added to the
juncture chamber, while sensitivity correspondingly diminishes.
That is, the top trace in FIG. 10, trace 100, shows that data
generated when the DMS electrode set is optimized for sensitivity,
and no throttle gas is provided. In this case, the mobility peaks
for pseudoephedrine and ephedrine are merged to give a single peak
with very broad half width. As the volumetric flow of throttle gas
increases, from the trace 102 representing a throttle gas flow rate
of 0.4 L/min, to trace 104, representing a throttle gas flow rate
of 0.8 L/min two distinct peaks begin to become apparent as a
result of the selectivity improvement achieved by narrowing each of
the mobility peaks. When the throttle gas is set to approximately
1.4 L/min, the peak centers are sufficiently resolved to achieve
separation of these two components, although the sensitivity has
decreased by approximately a factor of 2. Further increases in the
throttle gas flow provide higher resolution, although the
sensitivity loss also becomes greater, as shown in trace 108,
representing a throttle gas flow rate of 1.8 L/min.
[0084] Accordingly, according to some aspects of these embodiments
of the present invention, a throttle gas can be added to the
juncture chamber until an acceptable compromise between sensitivity
and selectivity is reached, such that sensitivity remains at a
level to enable the peaks to be discerned, while selectivity has
been improved to enable the peaks to be readily distinguished.
[0085] According to some aspects of some other embodiments of the
present invention, in which no throttle gas is provided, but
instead a bleed gas is drawn from the juncture chamber, the initial
mass spectrum obtained may show peaks that are distinguishable, but
which represent very faint signals, given the loss of sensitivity
due to the very high residence times within the differential
mobility spectrometer. According to these aspects of the present
invention, increasing amounts of bleed gas can be drawn from the
juncture chamber to increase the gas flow rate through the
differential mobility spectrometer, thereby reducing the residence
time of ions within the differential mobility spectrometer (the
electrode geometry having been selected to provide this long
residence time). As this occurs, the peak height will increase,
representing the greater sensitivity, but may also become broader
and overlap. By observing this process, an operator can stop
increasing the bleed gas flow rate at a point where the peaks are
still readily distinguishable and sensitivity is still
acceptable.
[0086] According to some aspects of various embodiments of the
present invention, a method of operating mass spectrometer systems
as defined above is provided in which the differential mobility
spectrometer is maintained at an internal operating pressure (the
curtain chamber operating pressure), while the mass spectrometer is
maintained at a vacuum pressure that is substantially lower than
the internal operating pressure. The differential mobility
spectrometer is also in fluid communication with the mass
spectrometer to draw a gas flow, including ions provided to the
differential mobility spectrometer, through the differential
mobility spectrometer and into a vacuum chamber containing the mass
spectrometer. A gas flow between the differential mobility
spectrometer and the mass spectrometer can be modified to change
the gas flow rate within the differential mobility spectrometer
without changing the total volumetric flow rate into the mass
spectrometer. As described above, this gas flow rate can be
modified, for example, by adding a throttle gas at a throttle gas
flow rate to the gas flow between the differential mobility
spectrometer and the mass spectrometer to decrease the gas flow
rate through the differential mobility spectrometer. Optionally,
the throttle gas flow rate can be varied to vary the decreases in
the gas flow rate.
[0087] Optionally the method further comprises detecting the ions
drawn into the mass spectrometer to provide a mass spectrum.
Initially, the electrode geometry of the differential mobility
spectrometer may be selected to provide good sensitivity but poor
selectivity. Then, an operator can select a selected resolution for
the mass spectrum and determine and then adjust the gas flow rate
to provide the selected resolution. The operator can then vary the
throttle gas flow rate to decrease the gas flow rate to provide the
adjusted gas flow rate to provide the selected resolution for the
mass spectrum, by increasing a residence time of the ions within
the differential mobility spectrometer. This can also have the
result of decreasing sensitivity somewhat, however.
[0088] Optionally, an outlet of the differential mobility
spectrometer can be connected to an inlet of the mass spectrometer
to define an ion path of travel for ions therebetween using a
juncture chamber. In such embodiments, the throttle gas can be
directed into the juncture chamber and away from the ion path of
travel to reduce disruption of the ion path of travel by the
throttle gas. Alternatively, the throttle gas can simply be
dispersed throughout the juncture chamber.
[0089] Optionally, the selected resolution for the mass spectrum
and the adjusted gas flow rate for providing this selected
resolution can be determined substantially contemporaneously. For
example, these steps can be performed substantially
contemporaneously with the step of varying the throttle gas flow
rate, whereby an operator can simply observe how the resolution of
the mass spectrum changes (along with the sensitivity) as the
throttle gas flow rate is increased. Then, after an operator
reaches an acceptable resolution (while retaining acceptable
sensitivity), the throttle gas flow rate can be maintained at a
constant level, thereby determining the adjusted gas flow rate to
provide the selected resolution of the mass spectrum.
[0090] According to aspects of other embodiments of the present
invention, instead of supplying a throttle gas to a juncture
chamber between the differential mobility spectrometer and the mass
spectrometer, a bleed gas can be drawn from the gas flow between
the differential mobility spectrometer and the mass spectrometer at
a bleed gas flow rate to increase a gas flow rate through the
differential mobility spectrometer. The bleed gas flow rate can be
varied to vary the increase in the gas flow rate. That is, in
embodiments in which a bleed gas is drawn from the gas flow between
the differential mobility spectrometer and the mass spectrometer,
an electrode geometry of the differential mobility spectrometer can
initially be selected to provide good selectivity at the price of
poor or very poor sensitivity. Then, sensitivity can be improved,
while selectivity is diminished, by increasing the bleed gas flow
rate of the bleed gas drawn from the gas flow between the
differential mobility spectrometer and the mass spectrometer.
[0091] According to some aspects of some embodiments of the present
invention, an operator can determine a selected transmission
sensitivity, determine an adjusted gas flow rate to provide the
selected transmission sensitivity, and vary the bleed gas flow rate
to provide the increase in the gas flow rate to provide the
adjusted gas flow rate to provide the selected transmission
sensitivity. Optionally, the steps can be performed altogether.
That is, an operator can gradually increase a vacuum pump speed
connected to the juncture chamber to increase the bleed gas flow
rate, observing at the same time from the mass spectrum how the
selected transmission sensitivity improves. Then, once an
acceptable transmission sensitivity has been reached (and while
selectivity is still acceptable) the bleed gas flow rate can be
maintained to provide the adjusted gas flow rate to provide the
selected transmission sensitivity. For example, for a given
separation, an operator may try to optimize the sensitivity by
seeing how much selectivity is required to eliminate an
interference, and then maximizing the sensitivity while still
removing the interference.
[0092] Referring to FIG. 11, there is illustrated in a schematic
view, a mass spectrometer system 1100 in accordance with an aspect
of a tenth embodiment of the present invention. The mass
spectrometer system 1100 comprises a first vacuum lens element 1104
of a mass spectrometer (hereinafter generally designated mass
spectrometer 1104), but does not include a differential mobility
spectrometer. Lens element 1104 is contained within a vacuum
chamber 1127. The mass spectrometer 1104 also comprises mass
analyzer elements 1104a downstream from the vacuum chamber 1127.
Ions can be transported through the vacuum chamber 1127 and may be
transported through one or more additional differentially pumped
vacuum stages prior to the mass analyzer indicated schematically as
mass analyzer 1104a, as described, for example, with respect to the
embodiment of FIG. 1.
[0093] A heated tube 1102 can be provided upstream of vacuum
chamber 1127. Similar to the plates of the differential mobility
spectrometers of the embodiments described above, the heated tube
1102 can surround a drift gas 1108 that can drift from an inlet
1110 of the heated tube 1102 to an outlet 1112 of the heated tube
1102. The outlet 1112 of the heated tube 1102 can release a drift
gas 1108 into a juncture chamber 1114. The juncture chamber 1114
defines a path of travel for ions between the heated tube 1102 and
the mass spectrometer 1104. In some embodiments the outlet of 1112
of the heated tube 1102 can be aligned with the inlet of the mass
spectrometer 1104 to define an ion path of travel therebetween,
while walls of the juncture chamber 1114 can be spaced from this
path of travel to limit interference with the ions 1122 traveling
along the path of travel.
[0094] The heated tube 1102 and juncture chamber 1114 are both
contained within a curtain chamber 1118 defined by a curtain plate
(boundary member) 1119 and supplied with a curtain gas from a
curtain gas source 1120. The curtain gas source 1120 can provide
the curtain gas to the interior of the curtain chamber 1118. Ions
1122 can be provided from an ion source (not shown) and can be
emitted into the curtain chamber 1118 via curtain chamber inlet
1124. The curtain gas can be supplied to the curtain chamber at a
rate sufficient to provide both a curtain gas outflow out of the
curtain chamber inlet, as well as a curtain gas inflow into the
heated tube. The diameter of the inlet 1110 of the heated tube 1102
can be substantially larger than a vacuum chamber inlet (or mass
spectrometer inlet) 1129, such that the heated tube 1102 does not
restrict gas flow. The pressure of the curtain gas within the
curtain chamber 1118 can provide both a curtain gas outflow 1126
out of the curtain gas chamber inlet 1124, as well as a curtain gas
inflow 1128 into the heated tube 1102, which inflow 1128 can become
the drift gas 1108 for carrying the ions 1122 through the heated
tube 1102 and into the juncture chamber 1114. The curtain plate
1119 may be connected to a power supply to receive an adjustable DC
potential.
[0095] Similar to the embodiment of FIG. 1, the vacuum chamber 1127
can be maintained at a much lower pressure than the curtain chamber
1118. In accordance with an aspect of an embodiment of the present
invention, the vacuum chamber 1127 can be maintained at a pressure
of 2.3 Torr via vacuum pump 1130. In an example, an internal
pressure of the heated tube 1102 can be maintained at a pressure of
760 Torr. As a result of the significant pressure difference
between the curtain chamber 1118 and the vacuum chamber 1127, the
drift gas 1108 can be drawn through the heated tube 1102, the
juncture chamber 1114 and vacuum chamber inlet 1129 into the vacuum
chamber 1127 and the first vacuum lens element 1104.
[0096] From the foregoing, it can be seen that the mass
spectrometer system 1100 of the FIG. 11 is, in some respects, quite
similar to the systems 200 and 300 of FIGS. 1 and 2 respectively.
However, instead of adding a throttle gas to the juncture chamber
1114, the system 1100 of FIG. 11 comprises a gas outlet 1132
including an additional vacuum pump 1140 for drawing a bleed gas
out of the juncture chamber 1114. The gas flow drawn from gas
outlet 1132 by additional vacuum pump 1140 can draw a larger
fraction of ions into the heated tube 1102. The increased gas flow
through the heated tube 1102 can also lower the residence time for
ions within the heated tube 1102, thereby lowering diffusion losses
and increasing sensitivity as mentioned above. The curtain gas flow
rate can be increased proportionately to the vacuum pump flow rate
to ensure that sufficient gas to provide an outflow from gas
chamber inlet 1124.
[0097] In these respects, the system 1100 is quite similar to the
system 1000 of FIG. 9. However, the system 1100 differs from the
system 1000 in FIG. 9 in that the system 1100 does not include a
differential mobility spectrometer. Instead, the differential
mobility spectrometer has simply been replaced with a heated tube
1102.
[0098] In accordance with an aspect of an embodiment of the
invention, the system 1100 of FIG. 11 can also comprise a
controller 1141. Controller 1141 can comprise a computer processor,
together with suitable user input/output modules. In one
embodiment, a user can adjust vacuum pump 1140 (which can be any
suitable device for drawing a gas flow) to adjust a rate at which
bleed gas is drawn out of the juncture chamber 1114. In this
embodiment, controller 1141 can monitor the rate at which vacuum
pump 1140 draws bleed gas out of the juncture chamber 1114, and
then can calculate a suitable increase in curtain gas flow to be
provided by curtain gas source 1120, and can adjust a curtain gas
flow meter 1121 to provide this increase in curtain gas flow.
Alternatively vacuum pump 1140 can be maintained at a constant
rate, and a adjustable restriction such as an aperture may be
located between pump 1140 and the juncture chamber. According to
some embodiments, an increase in bleed gas flow rate will be
matched by an equal increase in curtain gas inflow rate. According
to other embodiments, recognizing that some of this increase in
curtain gas inflow may increase flow 1126 out of curtain chamber
inlet 1124, the curtain gas inflow may be increased by more than
the increase in the bleed gas flow rate.
[0099] According to another embodiment of the invention, vacuum
pump 1140 may not be directly controlled by an operator. Instead,
an operator can control vacuum pump 1140 via controller 1141, and
controller 1141 could then determine, using for example, a computer
processor, a suitable corresponding adjustment to be made to the
curtain gas flow rate.
[0100] According to some embodiments in which bleed gas is drawn
from the juncture chamber, ions may tend to follow streamlines
directed out of the bleed gas outlet in the juncture chamber.
Referring to FIG. 12, there is illustrated in a schematic diagram a
portion of a mass spectrometer system 1200 in accordance with an
aspect of another embodiment of the invention. The mass
spectrometer system 1200 comprises an upstream heated tube 1202 and
a juncture chamber 1214. The juncture chamber 1214 is located
downstream of the heated tube 1202 to receive drift gas entrained
ions 1208 from the heated tube 1202. As illustrated, a bleed gas
can be drawn through bleed gas port 1232 to increase the drift gas
flow rate of drift gas 1208 through heated tube 1202. On its own,
the gas outlet 1232 might tend to create streamlines of bleed gas
that could entrain ions and draw them out through gas port 1232. To
impede this, a suitable electric field 1205 can be provided around
the drift gas 1208 where the drift gas 1208 enters the juncture
chamber. The electric field can be configured to guide the
entrained ions within streamlines drawn into a vacuum chamber (not
shown) and to impede the ions from being drawn by other streamlines
through the bleed gas port 1232. Suitable ion optical elements,
known to those of skill in the art, such as, for example, a single
or multiple ion lens elements with DC or RF potentials applied, can
be used to provide the electric field 1205. More generally, and
referring to FIG. 11, a potential difference between the heated
tube outlet 1112 and vacuum chamber inlet 1129 can help direct ions
across the gap between the outlet 1112 and the mass spectrometer
inlet. The ions can exit the heated tube 1102, traveling on-axis
with respect to the downstream inlet orifice, while the bleed gas
can be drawn radially away from the inlet. In this configuration, a
potential difference between the tube outlet 1112 and vacuum
chamber inlet 1129 can help to keep ions moving in the axial
direction with the gas flow into vacuum chamber 1127.
Experimental Results
[0101] The operation of the mass spectrometer system 1100 of FIG.
11, which lacks a DMS, can be simulated to some extent by operating
a mass spectrometer system similar to the system 1100, except that
this mass spectrometer system comprises a DMS. This DMS can be run
in transparent mode to allow all of the ions to be transmitted
without discrimination, when the separation voltage is turned off,
or set sufficiently low to prevent differential mobility
separations, and the compensation voltage is set to 0.
Additionally, in this mode of operation the DMS can simultaneously
transmit ions of both polarities and subject each to separation
based on their differential mobility constants.
[0102] According to an aspect of an embodiment of a present
invention, a mass spectrometer system similar to the mass
spectrometer system 1000 of FIG. 9 was operated in transparent
mode, with separation voltage and compensation voltage set to 0
volts. The dimensions of the tube or DMS cell were
1.times.10.times.30 mm (while the cross section was rectangular for
the collection of these data, any suitable cross-section could have
been be used, such as a typical circular cross section for a tube).
The gas flow into the vacuum, drawn through the tube, was 2.8
L/minute. The curtain gas inflow was set to 3.3 L/minute to provide
a 0.5 L/minute outflow from the curtain plate. Operating this mass
spectrometer system in this manner results in the DMS cell
essentially acting as a tube with two conductive walls and two
insulating walls.
[0103] Initially, the vacuum pump for drawing bleed gas from the
juncture chamber was off. In this mode of operation, the DMS-MS
signal provided by the mass analyzer elements downstream of the
mass spectrometer was approximately 100000 cps (counts per second).
Subsequently, after about a minute, the vacuum pump for drawing the
bleed gas out of the juncture chamber was turned on to draw an
additional flow of 3.7 L/minute out from the juncture chamber.
Adding this 3.7 L/minute bleed gas outflow, to the 2.8 L/minute gas
flow through the tube resulting from the pressure differential
between vacuum chamber 1127 and the internal pressure of the DMS,
resulted in a total gas flow through the "tube" of 6.5 L/minute.
The curtain gas inflow was not increased at this point, thereby
eliminating the beneficial outflow from the curtain plate.
Nonetheless, the signal provided at the downstream mass analyzer
elements increased to 540000 cps.
[0104] Subsequently the curtain gas inflow was re-optimized to 7.1
L/minute (to take into account the bleed gas drawn out) and to once
again provide an outflow of approximately 0.6 L/minute (7.1
L/minute inflow--6.5 L/minute outflow through the "tube"). As a
result, the signal increased to 760,000 cps. These results show
significant gains when pumping at the exit of the "tube" (i.e.
drawing the bleed gas out from the juncture chamber). These gains
may be partially due to reduced residence time and diffusion within
the "tube" or DMS, and possibly, more significantly due to
amplifying the inlet gas flow to draw more ions into the "tube" and
reduce losses at the inlet.
[0105] Similar experimental results were obtaining using this mass
spectrometer system, while varying the pump speed of the vacuum
pump for drawing the bleed gas from the juncture chamber. When the
vacuum pump was off, such that a 2.8 L/minute transport gas flow
including minoxidil was drawn through the "tube", the signal for a
sample of minoxidil was 124,000 cps as measured at the downstream
mass analyzer element This signal intensity was improved when the
bleed gas was drawn at 3.7 L/minute, to provide a total transport
gas flow through the "tube", of 6.5 L/minute. At that transport
flow rate, the signal intensity increased to 620000 cps. Further
improvements in the signal intensity were observed when the bleed
gas flow rate was increased 4.9 L/minute to give a total transport
flow rate through the "tube" of 7.7 L/minute. At that transport gas
flow through the signal intensity increased further to 730000 cps.
In all of these cases, the curtain gas inflow was increased
directly and proportionately with the increases in bleed gas flow
to provide a relatively constant curtain gas outflow out of the
curtain gas chamber inlet.
[0106] While the Applicant's teachings are described in conjunction
with various embodiments, it is not intended that the Applicant's
teachings be limited to such embodiments.
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