U.S. patent application number 16/396715 was filed with the patent office on 2019-08-22 for chemically modified ion mobility separation apparatus and method.
This patent application is currently assigned to Excellims Corporation. The applicant listed for this patent is Mark A. Osgood, Ching Wu. Invention is credited to Mark A. Osgood, Ching Wu.
Application Number | 20190259595 16/396715 |
Document ID | / |
Family ID | 60660404 |
Filed Date | 2019-08-22 |
View All Diagrams
United States Patent
Application |
20190259595 |
Kind Code |
A1 |
Wu; Ching ; et al. |
August 22, 2019 |
CHEMICALLY MODIFIED ION MOBILITY SEPARATION APPARATUS AND
METHOD
Abstract
An ion mobility spectrometry apparatus and method used to
separate ions and select some of the ions using an AC gate; the
selected ions are further separated along a drift axis of a drift
tube, where the AC gate is controlled using a series of AC voltages
and/or frequencies to select different ions for the drift tube.
Inventors: |
Wu; Ching; (Boxborough,
MA) ; Osgood; Mark A.; (Wilton, NH) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Wu; Ching
Osgood; Mark A. |
Boxborough
Wilton |
MA
NH |
US
US |
|
|
Assignee: |
Excellims Corporation
Acton
MA
|
Family ID: |
60660404 |
Appl. No.: |
16/396715 |
Filed: |
April 28, 2019 |
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Application
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15665421 |
Jul 31, 2017 |
10276358 |
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16396715 |
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14214558 |
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8884221 |
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14537863 |
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13360758 |
Jan 29, 2012 |
8492712 |
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13475993 |
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13360760 |
Jan 29, 2012 |
8492708 |
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13360758 |
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12763092 |
Apr 19, 2010 |
9177770 |
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14214558 |
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12695111 |
Jan 27, 2010 |
8242442 |
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13475993 |
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12577062 |
Oct 9, 2009 |
8217338 |
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12695111 |
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11776392 |
Jul 11, 2007 |
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13475993 |
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11618430 |
Dec 29, 2006 |
7576321 |
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12471101 |
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61801722 |
Mar 15, 2013 |
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61784324 |
Mar 14, 2013 |
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61488438 |
May 20, 2011 |
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61104319 |
Oct 10, 2008 |
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60891532 |
Feb 26, 2007 |
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60807031 |
Jul 11, 2006 |
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60766226 |
Jan 2, 2006 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
H01J 49/061 20130101;
C07B 63/00 20130101; G01N 27/622 20130101; H01J 49/0027
20130101 |
International
Class: |
H01J 49/06 20060101
H01J049/06; G01N 27/62 20060101 G01N027/62; C07B 63/00 20060101
C07B063/00; H01J 49/00 20060101 H01J049/00 |
Claims
1. An ion mobility spectrometer apparatus, comprising: An
ionization source that is in fluid communication with a drift tube;
An AC ion gate, in which at least one power supply applies at least
one AC voltage to at least one grid element of the AC ion gate,
where the AC ion gate is located between the ionization source and
a drift region of the drift tube, and pulses a group of ions into
the drift region where the group of ions are separated along a
drift axis of the drift region; and
2. The AC voltage is controlled with a series of AC voltages and/or
frequencies to select different ions for the drift tube. An ion
mobility spectrometer method, comprising: Forming ions in an
ionization source that is in fluid communication with a drift tube;
Pulsing a group of ions into a drift region of the drift tube using
an AC ion gate; Separating the group of ions along a drift axis of
the drift region; and Controlling the AC ion gate using a series of
AC voltages and/or frequencies to select different ions for the
drift tube.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent
application Ser. No. 15/665,421. Application Ser. No. 15/665,421 is
a continuation-in-part of U.S. patent application Ser. No.
14/992,053, filed on Jan. 11, 2016, which is a continuation of
application Ser. No. 14/214,558, filed on Mar. 14, 2014, which
claims the benefit of and priority to corresponding U.S.
Provisional Patent Application No. 61/784,324, filed on Mar. 14,
2013 and 61/801,722, filed on Mar. 15, 2013, and which is a
continuation-in-part of U.S. patent application Ser. No.
12/763,092, filed on Apr. 19, 2010 and now issued as U.S. Pat. No.
9,177,770; the entire content of these applications are herein
incorporated by reference.
[0002] Application Ser. No. 15/665,421 is also a
continuation-in-part of U.S. patent application Ser. No.
14/537,863, filed on Nov. 10, 2014, which is a continuation of U.S.
patent application Ser. No. 13/475,993, filed May 20, 2012.
Application Ser. No. 13/475,993 is a continuation-in-part of U.S.
patent application Ser. No. 13/360,758, filed Jan. 29, 2012 and now
issued as U.S. Pat. No. 8,492,712, which is a division of
application Ser. No. 12/471,101, filed May 22, 2009, the latter now
issued as U.S. Pat. No. 8,106,352, which is a continuation of U.S.
patent application Ser. No. 11/618,430, filed Dec. 29, 2006, the
latter now issued as U.S. Pat. No. 7,576,321, which claims priority
from Provisional Application 60/766,226, filed Jan. 2, 2006.
Application Ser. No. 13/475,993 is a continuation-in-part of U.S.
patent application Ser. No. 13/360,760, filed Jan. 29, 2012, which
is a division of application Ser. No. 12/471,101, filed May 22,
2009, the latter now issued as U.S. Pat. No. 8,106,352, which is a
continuation of U.S. patent application Ser. No. 11/618,430, filed
Dec. 29, 2006, the latter now issued as U.S. Pat. No. 7,576,321,
which claims priority from Provisional Application 60/766,226,
filed Jan. 2, 2006. Application Ser. No. 13/475,993 is a
continuation-in-part of U.S. patent application Ser. No.
12/695,111, filed Jan. 27, 2010. Application Ser. No. 13/475,993 is
a continuation-in-part of U.S. patent application Ser. No.
12/577,062, filed Oct. 9, 2009, which claims priority from
Provisional Application 61/104,319, filed Oct. 10, 2008.
Application Ser. No. 13/475,993 is a continuation-in-part of U.S.
patent application Ser. No. 11/776,392, filed Jul. 11, 2007, which
claims priority from Provisional Application 60/891,532, filed Feb.
26, 2007 and claims priority from Provisional Application
60/807,031, filed Jul. 11, 2006. Application Ser. No. 13/475,993
also claims the benefit of and priority to corresponding U.S.
Provisional Patent Application No. 61/488,438, filed May 20, 2011.
The entire contents of all of the above applications are
incorporated herein by reference in their entirety.
BACKGROUND OF THE INVENTION
[0003] Many analytical instruments, such as ion mobility
spectrometers (IMS), can require a gating device for turning on and
off a flowing stream of ions and/or other charged particles. IMS
are widely used in field chemical analysis. IMS separate ionic
species based on their ion mobility in a given media (either gas or
liquid). Recent development of the IMS technology results in two
forms of IMS instruments and systems. The time-of-flight (TOF) IMS
separate ions based on their steady state ion mobilities under
constant electric field. High resolving power with IMS has been
achieved with the TOF-IMS instruments. Alternatively, devices that
separate ions based their mobility changes under high field
conditions, such as field asymmetric ion mobility spectrometer
(FAIMS) or differential mobility spectrometer (DMS), can also be
used.
[0004] Even though the gating device is a minor component in the
overall design of an IMS, if manufactured correctly, this component
can improve the IMS resolution and system performance. The gating
device is used to regulate the injection of ion packets into the
analytical instrument. There are many deficiencies with the current
approaches for manufacturing gating devices.
[0005] Traditionally the gating device has been used to regulate
the injection of ion packets into the analytical instrument. Even
though the gating device is a minor component in the overall design
of an IMS, this device is an important part that can improve the
level resolution between peaks in the IMS by providing a compact
ion packet without significant diffusion. Many inventions have been
proposed around the manufacturing and designing the gating device
for improving the resolution without major improvements. The
present invention modifies the gating device in a manner that
improves peak resolution and is able to control which size ions are
injected into the analytical instrument. This novel gating device
significantly reduces the analysis of complex samples with multiple
components such that lower mobility ions are not able to enter the
drift tube.
[0006] Since it was invented in the early 1970's, ion mobility
spectrometry (IMS) has been developed into a powerful analytical
tool used in a variety of applications. There are three major forms
of this instrument including independent chemical detection
systems, chromatographic detectors, or hyphenated IMS mass
spectrometry (MS) systems. As an independent detection system, IMS
qualitatively and quantitatively detects substances in different
forms relying on its capability to ionize the target substance, to
separate the target substance from background based on interactions
with a drift gas (i.e. a carrier gas), and to detect the substance
in its ionized form. As a chromatographic detector, IMS acquires
multiple ion mobility spectra of chromatographically separated
substances. In combined IMS-MS systems, IMS is used as a separation
method to isolate target substances before mass analysis. However,
the resolution of IMS is generally consider low, often regulating
such devices to qualitative use or use in environments with low
levels of interferants with respect to the substances of
interest.
[0007] The basic common components of an IMS system consist of an
ionization source, a drift tube that includes a reaction region, an
ion shutter grid, a drift region, and an ion detector. In gas phase
analysis the sample to be analyzed is introduced into the reaction
region by an inert carrier gas, ionization of the sample is often
completed by passing the sample through a reaction region and/or a
radioactive 63Ni source. The ions that are formed are directed
toward the drift region by an electric field applied to drift rings
that establish the drift region, and a narrow pulse of ions is then
injected into, and/or allowed to enter, the drift region via an ion
shutter grid. Once in the drift region, ions of the sample are
separated based upon their ion mobilities and their arrival time at
a detector is an indication of ion mobility which can be related to
ion mass. However, it is to be understood that ion mobility is not
only related to ion mass, but rather is fundamentally related to
the ion-drift gas interaction potential which is not solely
dependent on ion mass.
[0008] Ion mobility spectrometers (IMS) have become a common tool
for detecting trace amounts of chemical and/or biological
molecules. Compared to other spectrometric chemical analysis
technologies, e.g., mass spectrometry, IMS is a relatively low
resolution technique. The IMS advantages of very high sensitivity,
small size, low power consumption, and ambient pressure operation
are in some cases completely offset, or at a minimum, reduced by
the lack of sufficient resolution to prevent unwanted responses to
interfering chemical and/or biological molecules. The false
positives that result can range from minor nuisances in some
scenarios to major headaches in others. Interfering chemical and/or
biological molecules can have very similar ion mobilities which in
turn can significantly limit detecting and identifying low levels
of the targeted chemical and/or biological molecules in the
sample.
[0009] The present state of the art ion mobility spectrometers lack
the ability to directly reduce the occurrence of interfering
chemical and/or biological molecules in a sample's analysis. It is
the purpose of this invention to overcome these obstacles by making
the use of a cross-directional gas flow in a drift tube and/or
using a segmented drift tube for pre-separation.
SUMMARY OF THE INVENTION
[0010] The present invention generally relates to systems and
methods for transmitting beams of charged particles, and in
particular to such systems and methods that employ defecting at
least one set of grid elements into the same plane, such that the
grid elements are interleaved.
[0011] In one embodiment of the present invention, at least one
electrically substrate (conducting or non-conducting) is used to
deflect at least one set of the grid elements into the same plane,
such that the grid elements are interleaved. The ion gate has a
first and second set of electrically isolated grid elements that
lie in the same plane where the respective sets of grid elements
are applied to alternate potentials. The advanced grid
manufacturing methods and features are disclosed.
[0012] The present invention generally relates to systems and
methods for transmitting beams of charged particles, and in
particular to such systems and methods that let only a portion of
ions to the drift tube of the IMS by employing an AC voltage
(generated by one or more AC power supplies) on the gate wires. By
using an AC voltage there is a reduction in the size of the ion
depletion area in front of the gate when it is closed, thereby
providing a higher peak resolution. In addition the AC gate can be
used to separate ions.
[0013] The present invention relates to a cross-directional drift
tube design for an ion mobility spectrometer wherein the drift gas
flow is in a direction that is substantially neither parallel nor
antiparallel to the drift axis of ions. A cross-directional drift
tube with one or more drift segments allows rapid drift tube clean
up and flexible drift media control. A segmented drift tube is used
for pre-separation of complex sample before separating samples in
the subsequent drift segments. The cross flow design and segmented
drift tube can also be used together for enhanced separation
performance. In another aspect of the present invention, at least
one chemical modifier is added to the drift gas in a
cross-directional gas flow that interacts selectively with at least
one component of the sample in a drift tube. The component may be
impurities and/or interferences in the sample whereby the chemical
modifier enhances sample resolution by shifting the components
drift times. The chemical modifier interaction forces may include
hydrogen bonding, dipole-dipole, and steric hindering effects, but
are not limited to only these.
[0014] The present invention also relates to various aspects of
Multi-Dimensional Ion Mobility Spectrometry (MDIMS) methods and
apparatus. In various embodiments, the MDIMS of the present
inventions differentiate themselves from conventional ion mobility
spectrometry (IMS) by innovatively integrating multiple ion
mobility based separation steps in one device. In various
embodiments, the present invention provides higher resolution and
higher sensitivity than conventional IMS devices and operational
approaches. Various embodiments of the present invention provide an
integrated multiple dimensional time-of-flight ion mobility
spectrometric system that ionizes, separates, and detects chemical
species based on their ion mobilities. These systems generally
include: (a) at least one ionization source, (b) at least two drift
regions, and (c) at least one ion detection device. In various
embodiments, these systems separate ions in one drift dimension
under one set of drift conditions; and subsequently, the separated
ions are introduced into a higher dimension for further separation
under the same or a different set of drift conditions. In various
embodiments, the separation process can be repeated for one or more
additional drift dimensions. Also, in various embodiments, the
first drift dimension is used as one or more of an ionization
source, reaction region or desolvation region, and drift region for
the system. For example, in various embodiments, the electric field
in the first drift dimension (first drift tube) can be used as a
desolvation region for charged droplets.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] The foregoing and other aspects, embodiments, and features
of the inventions can be more fully understood from the following
description in conjunction with the accompanying drawings. In the
drawings like reference characters generally refer to like features
and structural elements throughout the various figures. The
drawings are not necessarily to scale, emphasis instead being
placed upon illustrating the principles of the inventions.
[0016] FIG. 1 shows the completed ion gate from a front view.
[0017] FIG. 2 shows a cross-sectional top view of the ion gate.
[0018] FIGS. 3A and 3B show two different methods to deflect the
grid elements.
[0019] FIG. 4 shows an alternative method to deflect the grid
elements.
[0020] FIGS. 5A-5C illustrates the respective sets of gate
elements.
[0021] FIG. 6 illustrates the process of manufacturing the ion
gate.
[0022] FIG. 7A-7C shows the photo etched edges of the grid
elements.
[0023] FIG. 8 schematically shows a construction of a
Bradbury-Nielsen ion gate using metalized dielectric rings and
parallel wires.
[0024] FIG. 9 is a schematic example of a segmented
Bradbury-Nielson gate.
[0025] FIG. 10 illustrates an operation method of an ion gate.
[0026] FIG. 11 shows an example of a gate using DC voltage.
[0027] FIG. 12 shows an example of a gate using AC voltage.
[0028] FIG. 13 shows the AC gate in the closed position and then
completely open and then closed again.
[0029] FIG. 14 shows an example of an IMS spectrum using 20 parts
per million (ppm) of an L-Tryptophan sample in 80/20 methanol and
water using a DC voltage on the ion gate.
[0030] FIG. 15 shows an example of an IMS spectrum using 20 parts
per million (ppm) of an L-Tryptophan sample in 80/20 methanol and
water using a AC voltage on the ion gate.
[0031] FIG. 16 shows the AC mobility selecting gate in the closed
position having a voltage of 240 and then partially open having a
voltage of 100 and then closed again having a voltage of 240.
[0032] FIG. 17 shows the trajectory of ions using a 67 kHz AC
frequency.
[0033] FIG. 18 shows gate wires that have a large surface area.
[0034] FIG. 19 shows 2 sets of gate wires aligned in phase.
[0035] FIG. 20 shows 4 sets of gate wires in an array that are out
of phase.
[0036] FIG. 21 shows a typical asymmetric waveform used for
differential ion mobility spectrometer or field asymmetric ion
mobility spectrometer.
[0037] FIG. 22 shows an IMS using a cross-flow drift medium
design.
[0038] FIG. 23 shows an IMS using a segmented drift tube for
pre-separation.
[0039] FIG. 24 shows an IMS using a cross-flow drift medium design
combined with a segmented drift tube.
[0040] FIG. 25 shows an IMS using a segmented drift tube design
with cross flow for adding specific modifiers to each segmented
region.
[0041] FIG. 26 shows an IMS using a drift tube design with cross
flow and with an AC gate.
DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS
[0042] The terms ion mobility separator, ion mobility spectrometer,
and ion mobility based spectrometer are used interchangeably in
this invention, often referred to as IMS, including time-of-flight
(TOF) IMS, differential mobility spectrometers (DMS), field
asymmetric ion mobility spectrometers (FAIMS) and their derived
forms. A time of flight ion mobility spectrometer and its derived
forms refers to, in its broadest sense, any ion mobility based
separation device that characterizes ions based on their time of
flight over a defined distance. A FAIMS, a DMS, and their derived
forms separate ions based on their ion mobility characteristics
under high values of normalized electric field.
[0043] The systems and methods of the present inventions may make
use of "drift tubes." The term "drift tube" is used herein in
accordance with the accepted meaning of that term in the field of
ion mobility spectrometry. A drift tube is a structure containing a
neutral gas through which ions are moved under the influence of an
electrical field. It is to be understood that a "drift tube" does
not need to be in the form of a tube or cylinder. As understood in
the art, a "drift tube" is not limited to the circular or
elliptical cross-sections found in a cylinder, but can have any
cross-sectional shape including, but not limited to, square,
rectangular, circular, elliptical, semi-circular, triangular, etc.
In many cases, a drift tube also refers to the ion transportation
and/or ion filter section of a FAIMS or DMS device.
[0044] Neutral gas is often referred to as a carrier gas, drift
gas, buffer gas, etc. and these terms are considered
interchangeable herein. The gas is at a pressure such that the mean
free path of the ion, or ions, of interest is less than the
dimensions of the drift tube. That is, the gas pressure is chosen
for viscous flow. Under conditions of viscous flow of a gas in a
channel, conditions are such that the mean free path is very small
compared with the transverse dimensions of the channel. At these
pressures the flow characteristics are determined mainly by
collisions between the gas molecules, i.e. the viscosity of the
gas. The flow may be laminar or turbulent. It is preferred that the
pressure in the drift tube is high enough that ions will travel a
negligible distance, relative to the longitudinal length of the
drift tube, therefore a steady-state ion mobility is achieved.
[0045] The phrase "and/or," as used herein in the specification and
in the claims, should be understood to mean "either or both" of the
elements so conjoined, i.e., elements that are conjunctively
present in some cases and disjunctively present in other cases.
[0046] Unless otherwise specified in this document the term
"particle" is intended to mean chemical and/or biological single or
plurality of sub-atomic particle, atom, molecule, large or macro
molecule, nanoparticle, or other matters that are vapor, droplets,
aerosol, liquid, solid that follow a mobile medium, where the
medium can be a gas, a liquid, supercritical fluid and/or other
fluidic materials.
[0047] The present invention generally relates to systems and
methods for transmitting beams of charged particles, and in
particular to such systems and methods that employ defecting at
least one set of grid elements into the same plane.
[0048] As used herein, the term "grid element" generally refers to
wire, rod, cable, thin metal foil piece that can be planar, square,
rectangular, circular, elliptical, semi-circular, triangular, but
not limited to these examples. The grid element can be made of any
electrically conducting material.
[0049] The term "gate element" generally refers to a structure that
includes one or more grid elements that can be spatially arranged
with a gap between each other.
[0050] The axis of the drift tube along which ions move under the
influence of the electrical drift field is referred to herein as a
drift axis. The drift axis is often, but not necessarily, a
longitudinal axis of the drift tube.
[0051] As used herein, the term "analytical instrument" generally
refers to ion mobility based spectrometer, MS, and any other
instruments that have the same or similar functions. Unless
otherwise specified in this document the term "mass spectrometer"
or MS is intended to mean any device or instrument that measures
the mass to charge ratio of a chemical/biological compounds that
have been converted to an ion or stores ions with the intention to
determine the mass to charge ratio at a later time. Examples of MS
include, but are not limited to: an ion trap mass spectrometer
(ITMS), a time of flight mass spectrometer (TOFMS), and MS with one
or more quadrupole mass filters.
[0052] One aspect of the invention relates to manufacturing an ion
gate in such a way that the ion gate can be produced in a simple,
reproducible, and reliable manner. FIG. 6 illustrates a
non-limiting process for manufacturing the ion gate. This method
for manufacturing an ion gate for a charged particle stream begins
with the fabrication of the gate elements 603 and 607 that includes
the grid elements. Each of the gate elements 603 and 607 are made
so that the two different pairs of grid elements can be interleaved
without contacting each other. Followed by assembling an insulating
layer (electrically non-conductive, the insulating layer can be any
size and shape, such as a square or a disk with openings, or a
washer, that allows a different potential to the gate elements) 605
between the gate elements 603 and 607 to electrically isolate the
gate elements. The substrate throughout this patent is typically
non-conducting, but can also be a conducting material for some
applications. Then two electrically non-conductive substrates 601
and 609 are added to deflect the grid elements in the gate elements
into the same plane. FIG. 6 shows a non-limiting example, wherein
two electrically non-conductive substrates are used. Similarly, one
electrically non-conductive substrate can also be used to
manufacture the ion gate. Finally, the gate elements are secured
together along with the electrically non-conductive substrates and
the insulating layer. In an alternative embodiment, the gate
elements can be segmented, thus each segment of the grid elements
can be operated independently, i.e. open and close at different
timing, as a segmented ion gate. The method for manufacturing an
ion gate for a charged particle stream, can comprise of
electrically isolated grid elements that lie in the same plane. The
respective sets of grid elements can be applied to alternate
potentials to close the gate and the same potential to open the
gate. For example, the grid element is at 100 volts above and 100
volts below the reference potential. The reference potential is the
potential at the particular location of the gate in the drift tube.
The steps used to manufacture the ion gate can be in any order and
comprise: fabricating at least two gate elements, wherein each gate
element includes at least one set of grid elements; assembling an
insulating layer between the gate elements; deflecting at least one
set of grid elements into the same plane of the other set of grid
elements with at least one substrate; and securing the gate
elements and the non-conductive substrates together.
[0053] A non-limiting example of the completed ion gate is shown in
FIG. 1. The shape of the ion gate can be: square (shown), oval,
circle, semicircle, triangle, rectangle, polygon, octagon, but not
limited to these examples. FIG. 1 shows a front view of the
completed ion gate. The ion gate includes gate elements that
contain the grid elements 103 are held in place with several screws
105. The ion gate apparatus that is used for gating a charged
particle stream comprises: at least two sets of grid elements that
individual voltages can be applied to each set to open and close;
and at least one substrate for deflecting at least one set of grid
elements into the same plane of the other sets of grid elements. In
addition an electrically insulating layer can be added to allow
different voltages to be set to each set of grid elements.
[0054] Another aspect of the invention relates to providing an ion
gate with an effective gating function by applying a uniform
tension on the grid elements, fabricating the gate elements such
that the grid elements are equally spaced, and deflecting the grid
elements into the same plane.
[0055] FIG. 2 shows a cross-sectional top view of the ion gate. The
cross-section shown in FIG. 2 is indicated in FIG. 1 with a cutting
line 107. The ion gate comprises a first and second electrically
isolated gate elements 204 and 206 that each have at least one grid
element 205 and 207. The electrically non-conductive or conductive
substrate 208 deflects the grid element 207 which is part of the
gate element 206 into the same plane as the deflected grid element
205 which is part of the gate element 204. The gate elements 204
and 206 are electrically isolated by placing an insulating layer
(electrically non-conductive or conductive) 210 between these gate
elements. The grid elements are deflected into the same plane 202
and are electrically isolated by interleaving these sets of grid
elements with a gap between each grid element. FIG. 5C illustrates
the respective sets of grid elements in FIG. 5A and FIG. 5B
interleaved. In FIG. 2, the ion gate components are secured
together with a screw fastener 212. In this non-limiting example,
ether an electrically non-conducive material screw fastener may be
used or a conductive material fastener can be contained in an
electrically non-conductive standoff (not shown).
[0056] One embodiment of the present invention, involves using
off-set electrically non-conductive or conductive substrates to
deflect the grid elements. FIG. 3A shows the electrically
substrates 305 and 307 with no off-set 301. FIG. 3B shows
electrically substrates 305 and 307 with an off-set 303. This
off-set design may allow uniform deflection of grid elements and
low cost manufacturing.
[0057] Another embodiment of the present invention, involves the
shape of the electrically non-conductive or conductive substrate to
deflect the grid elements. The portion that deflects the grid
element can be in the shape of a wedge, hexagon, semi-circle, but
not limited to these examples. In addition, the electrically
non-conductive substrate portion that deflects the grid element can
be independent to the secured electrically non-conductive
substrate. A non-limiting example is shown in FIG. 4, where a
circular (not limited to only this shape) substrate 402 deflects
the grid element and the secured substrate 404 holds the substrate
402 in place.
[0058] Yet another embodiment of the present invention is the
fabrication of the gate elements. The grid elements within the gate
elements can be produced by cutting, etching, evaporation or
electroplating, but not limited to these methods. In a non-limiting
example, parallel rows of grid elements are formed by removing
portions of a given thickness of planar metal foil by etching
portions from the foil. This method forms a plurality of grid
elements that are equally spaced. In addition to forming equally
spaced grid elements within the gate element, the grid elements are
made from the same gate element material as a single entity. In
this manner, the grid elements do not need to be fixed to the gate
element through gluing (epoxy), glass soldering, or any other
attaching manner. Fabricating the gate elements by etching the grid
elements is a robust and reproducible method for manufacturing the
grid elements. In addition, since no gluing, soldering, or other
attaching manner is used in fabricating the gate elements, elevated
temperatures and/or thermal expansion of the grid elements are all
uniform. The photo chemical milling (etching) can be performed on
one side or both sides of the material being etched.
[0059] FIG. 7A shows the shape (a pair of opposing concave fillets)
of the grid element etched on both sides of the material, etched
from the top 701 and the bottom 702 of the material. FIG. 7B shows
the shape (a concave fillet) of the grid element etched on one side
of the material, etched from only the top side 704 of the material.
The etched edge distance 703 may be smaller or greater than the
material thickness 705 depending on the layout of the grid
elements. For example, the etched edge distance to the material
thickness ratio is greater than zero, in particular 1-50%, 50-100%,
100-500%. FIG. 7C shows three grid elements that are etched on both
sides of the material. Photo chemical milling can produce uniform
dimensions in grid element width 707 and gap 709 between grid
elements forming a plurality of grid elements that are equally
spaced. When the ion gate is a uniform product, injection of ion
packets into the drift tube are tight packets with limited
background signal, therefore a higher signal to noise ratio can be
achieved. In this embodiment, regardless of manufacturing methods,
the grid element is to be made with a sharp edge, the geometry may
generate a narrow gating electric field region resulting in high
precision gating of charge particles. In an IMS device, a narrow
ion pulse could be generated with precision gate timing control. An
ion gate apparatus for gating a charged particle stream comprises:
at least two sets of electrically insulated grid elements on the
same plane, the evenly spaced grid elements have at least one sharp
edge face to adjacent grid element.
[0060] Another embodiment of the present invention is securing the
gate elements together with non-conductive substrates and the
insulating layer. The ion gate can be secured by clamping,
soldering, screws, pins, but not limited to these examples. The
insulating layer can be made from any non-conductive material such
as, ceramic, aluminum nitrate, but not limited to these
examples.
[0061] An alternative embodiment of manufacturing an "Tyndall" type
of ion gate for a charged particle stream involves two sets of
electrically isolated grid elements, wherein the first set of grid
elements is arranged with an offset in respect to the second set of
the grid elements, such that the gaps of the first grid element is
aligned with the second grid elements; each set of grid elements is
applied to alternate potentials when the gate is closed and same
potential when the gate is opened. The method involves the steps
of: fabricating at least two gate elements by removing portions of
a substantially planar metal foil to form a plurality of grid
elements; wherein each gate element includes at least one set of
grid elements; assembling an insulating layer between the gate
elements; and securing the gate elements together.
[0062] In another embodiment of the invention, a metalized
dielectric structure is used for the Bradbury-Nielsen gate. A
ceramic material is coated with single or multiple layers of
metallization materials. The metallization process is commonly
finished with a thin layer of nickel, gold or other inert metal for
enhanced chemical resistivity. FIG. 8 shows a unique construction
method of a Bradbury-Nielsen ion gate using a metalized ceramic
material. It is built with a frame ring, a tension ring 802 and
parallel wires 805 that are pre-winded on a metal frame. One or the
rings, either the frame ring or the tension ring is metalized 815
with a pattern 810 that connects every other wire to each other. In
one embodiment, the frame ring has metalized contacts 807 that are
1 mm apart (center to center). During the ion gate construction,
the parallel wires are lined up with these contacts and form a firm
contact while the tension ring is pushed down into the frame ring.
As the wire is selected to match the thermal expansion of the frame
ring and tension ring, the wires can be maintained parallel while
the IMS is operated under different temperature conditions. The
gate control voltage(s) are applied to the wires by attaching an
electrical lead to the contact point that is on the outside of the
frame ring. Not only for metalized ceramic tube IMS design, the
Bradbury-Nielsen ion gate can be used for other analytical
instruments.
[0063] In various embodiments for symmetric IMS, an ion focusing
method can be employed to guide ions to a target collection area on
the collector. Suitable focusing methods may include, but are not
limited to, static electric field focusing and ion funnel focusing.
An ion collector can be segmented to facilitate, collection of ions
with specific ion mobility (drift time) or a certain range of
mobilities on to different segment of the ion collectors. A
segmented Bradbury-Nielson gate can be used to enhance the
separation and collection.
[0064] In various embodiments of IMS instruments, wherein the
Bradbury-Nielson gate can be segmented. A variety of geometries,
including but not limited to parallel, rectangular, concentric ring
shape, can be used for the segmentation, referring to FIG. 9,
various embodiments can use parallel segmentation. Each segment of
the ion gate, for example, 901, 903, and 905, can be controlled to
open at a different time. Such a segmented ion gate can be used as
either first or second ion gate in a time-of-flight type ion
mobility separator. While it is used as the second ion gate in a
IMS, multiple portions of ions with different drift time are
allowed to pass through segmented ion gate, thus collected on
different sections of ion collectors, and recovered separately if
desired.
[0065] In various embodiments, an apparatus of ion gate for an ion
mobility separator comprising a segmented Bradbury-Nielson that
contains multiple sections of Bradbury-Nielson gate. The segmented
Bradbury-Nielson gate can be used as a second gate in a
time-of-flight type ion mobility separator. The segmented
Bradbury-Nielson gate comprises a variety of geometries which may
include but is not limited to: parallel, rectangular, concentric.
The ion mobility separator further comprises a segmented ion
collector where a plurality of sections of ion collector is inline
with the sections of the segmented Bradbury-Nielson gate.
[0066] This invention further describes a method and apparatus of
ion gate operation. In one embodiment, an AC voltage is used to
close the gate. In a common operation of the Bradbury-Nielson gate,
the ion gate is open when the adjacent grid elements are at the
same potential and the ion gate is closed when a DC voltage, e.g.
30V, 50V, 100V, 200V, or -30V, -50V, -100V, -200V are applied on
the adjacent grid elements. The voltage creates an electric field
that pushes ions toward the grid element that is a lower potential,
thus preventing ions from penetrating through the ion gate when
closed.
[0067] During ion mobility measurements, the ion gate is opened for
a short period of time, e.g. 100 microseconds, and then closed for
a period of time, e.g. 20 millisecond, while ions are traveling in
the drift tube. FIG. 10 illustrates a closed ion gate. When the
applied voltage is higher than the reference potential, a `+` is
shown for the gate wire (i.e. grid element) and when the applied
voltage is lower than the reference potential, a `-` is shown for
the gate wire. The voltage difference between the adjacent wires
causes positive ions to be collected on the (-) wire and negative
ions to be collected on the (+) wire. By repeating wire layout
pattern of (+) and (-) wires, a large area is covered and ions are
prevented to pass through the ion gate. In this embodiment, an AC
voltage instead of DC voltage is applied the gate wires. In this
case, the potential of each wire is constantly changing. The
potential on wire 1003 is `+` and wire 1004 is `-` at the state
1001, and then the potential on wire 1003 is `-` and wire 1004 is
`+` at the state 1002. The state 1001 and 1002 repeats at certain
frequency. The voltage and frequency of the AC applied to the
adjacent wires is optimized to completely close the ion gate. The
ion gate is opened by setting all gate wires at the same potential.
The new gate configuration and operational method is not limited to
be used for ion mobility spectrometer, but can be used for any
device that needs to shut off a stream of charged particles.
[0068] In a variety of the embodiments, a method for operating an
ion gate for a charged particle stream involves opening the ion
gate by setting adjacent gate wires (grid elements) at the same
potential; closing the ion gate by setting adjacent gate wires at
different potentials by applying an AC voltage to the adjacent
wires. The AC voltage can be controlled to provide a given
frequency and amplitude that that is most suitable for the intended
operation. The frequency can be a constant and/or controlled to
cover a broad range during a period when the ion gate is closed.
Similarly, the amplitude can be a constant and/or controlled in a
range during a period of closing the gate. The AC voltage may be a
symmetric or asymmetric waveform (for example, a waveform is used
for DMS and/or FAIMS, a typical example of the waveform is shown in
FIG. 21). In a variety of operation modes, the AC powered ion gate
can be operated as such, conducting a series of ion mobility
measurements under a series of different frequencies and/or
amplitudes, and then integrating the series of ion mobility
measurement data into an ion mobility spectrum using common data
processing algorithms, such as summing.
[0069] A Bradbury-Nielson gate is traditionally used for injecting
short pulses of ions into TOF mass spectrometers and ion mobility
spectrometers to improve the mass resolution of TOF instruments by
reducing the initial pulse size as compared to other methods of ion
injection. Therefore the precise control of the ion pulse width
admitted to the drift tube can be controlled. However, the means
for controlling the size of ions entering the drift tube using a
Bradbury-Nielson gate has not been proposed to date.
[0070] One embodiment of the present invention is to use an AC
voltage instead of the commonly used DC voltage to control the
amount of a ion pulses generated and let through the gate. In a
common operation of the Bradbury-Nielson gate, the ion gate is open
when the adjacent grid elements are at the same potential and the
ion gate is closed when a DC voltage, e.g. 30V, 50V, 100V, 200V, or
-30V, -50V, -100V, -200V are applied on the adjacent grid elements.
The voltage creates an electric field that pushes ions toward the
grid element that is a lower potential, thus preventing ions from
penetrating through the ion gate when closed. FIG. 11 shows an
example of a gate using DC voltage. Negative sample ions 1101
travel toward the ion gate wires 1105 and 1006 of the gate in a
relatively straight line according the applied filed in the
reaction region (desolvation region) 1103 until they come close to
the gate wires where they are pulled toward the positive wires 1105
and are neutralized on the positive wires 1105 if the gate is not
in the open state. Since DC voltage is being used to control the
gate, each adjacent wire has a different polarity, either positive
or negative. Therefore gate wires 1105 are positive and gate wires
1106 are negative. During ion mobility measurements the ion gate is
opened for a short period of time, e.g. 100 microseconds, and then
closed for a period of time, e.g. 20 millisecond, thereby letting a
pulse of ions travel in the drift tube 1108. During the closed
state of the gate an ion depletion area is formed 1110. The larger
the area of the ion depletion area the longer the gate needs to be
opened to let ions through, since there is a low population of
ions. In order to get higher resolution peaks in the IMS spectrum,
a shorter opening period of time is preferred in order to get a
narrow pulse of ions through with limited diffusion. By using an AC
voltage instead of a DC voltage to close the gate the ion depletion
area can be reduced, in particular, by a half. The ion depletion
area can be reduced by an percentage by using an AC voltage.
[0071] In a variety of the embodiments, a method for operating an
ion gate for a charged particle stream involves opening the ion
gate by setting adjacent gate wires (grid elements) at the same
potential; closing the ion gate by setting adjacent gate wires at
different potentials by applying an AC voltage to the adjacent
wires. The AC voltage can be controlled to provide a given
frequency and amplitude that that is most suitable for the intended
operation. The frequency can be a constant and/or controlled to
cover a broad range during a period when the ion gate is partially
open and/or closed. Similarly, the amplitude can be a constant
and/or controlled in a range during a period of closing the gate.
The AC voltage may be a symmetric or asymmetric waveform. The
waveform can be, but not limited to: sine, square, triangle, and
sawtooth. In a variety of operation modes, the AC powered ion gate
can be operated as such, conducting a series of ion mobility
measurements under a series of different frequencies and/or
amplitudes, and then integrating the series of ion mobility
measurement data into an ion mobility spectrum using common data
processing algorithms, such as summing. FIG. 12 shows an example of
a gate using AC voltage. Negative sample ions 1201 travel toward
the ion gate wires 1205 of the gate according to the AC applied
field until they come close to the gate wires where they are pulled
toward the gate wires 1205 and are neutralized if the gate is not
in the open state. Since AC voltage is being used to control the
gate, each adjacent wire has a different polarity, which alternates
between positive or negative. Therefore the gate wires 1205 are
positive and are negative according to the applied AC voltage.
During ion mobility measurements, the ion gate is opened for a
short period of time, e.g. 100 microseconds, and then closed for a
period of time, e.g. 20 millisecond, while ions are traveling in
the drift tube 1208. During the closed state of the gate an ion
depletion area is formed 1210. By using an AC voltage instead of a
DC voltage to close the gate the ion depletion area is minimized,
in particular, can be reduced by a half thereby improving the
operation of the ion gate. There is little or no space charge using
the AC voltage as compared to DC voltage. Since the ion gate can
create tighter ion pulses when it is opened the resolution of the
peaks traveling through the drift tube 1208 are significantly
increased. FIG. 13 shows the AC gate in the closed position 1301
and then completely open 1303 and then closed again 1305. The open
1303 position is for a shorter period of time than that when using
a DC voltage.
[0072] Another embodiment of the present invention is to use an AC
voltage instead of DC voltage on an ion gate to filter ions
according to their size and/or ion mobility. An apparatus and
method is used to filter ions according to their ion mobility by
varying the AC potential on a segmented Bradbury-Nielson gate. Some
of the components of the charged particle stream have a smaller
size and/or shape (or ion mobility) compared to the other
components of the charged particle stream. The present invention
controls the AC voltage on a segmented Bradbury-Nielson gate in
order to filter small ions from larger ions from an ionized sample
before they enter the drift tube. FIG. 14 shows an example of an
IMS spectrum using 20 parts per million (ppm) of an L-Tryptophan
sample in 80/20 methanol and water using a DC voltage on the ion
gate. The reactant ion peak (RIP) and L-Tryptophan (L-Trp) are
shown as peaks in the spectrum. When AC voltage is used on the ion
gate smaller sized ions such as the RIP peaks can be substantially
eliminated as shown in FIG. 15. The AC frequency can be tuned to
control the specific ion mobility that is excluded from being
transmitted from the ionized sample into the drift tube. For
example, an AC frequency of 67 kHz and a 100-240 voltage range
between the gate wires would exclude small ions having a 100
molecular weight size from the other ions in the sample that have a
larger molecular weight greater than 100. FIG. 16 shows the AC
mobility selecting gate in the closed position 1601 having a
voltage of 240 and then partially open 1603 having a voltage of 100
and then closed again 1605 having a voltage of 240. In this mode,
when the gate is open 1603, only larger molecular weight (low ion
mobility) components of the sample can get through the gate without
getting neutralized on the gate wires. The AC mobility selecting
gate works by tuning the AC frequency in the reaction region
(desolvation region) 1705 as shown in FIG. 17. When components of a
sample have different ion mobilities, sizes or molecular weights,
the AC frequency has a stronger or weaker effect on the components
travel. For example, for two negative ions where one 701 has a
molecular weight of 100 and the other ion 1703 has a molecular
weight of 200 the trajectory using a 67 kHz frequency is
substantially different as shown in FIG. 17. The smaller (high
mobility) ion 1701 has a larger oscillation 1708 than the larger
(low mobility) ion's oscillation 1706. When the AC gate is only
partially open as in FIG. 16 the larger ion 1703 passes the gate
wires onto the drift tube 1708 and the smaller ion 1701 is
neutralized on the gate wire.
[0073] In yet another embodiment, the wires of the AC gate can be
configured to enhance the size selection. As shown in FIG. 18, the
wires 1815 can be made rectangular such that certain small ions
would have a larger surface area in the direction that is parallel
to the charged particle stream to be neutralized on and the
frequency tuning could be established such that the small and large
ions are within a few molecular weight units and still be
differentiated. Alternatively, the wires 1815 in FIG. 18 can be 2
or more that are aligned in phase as shown in FIG. 19 or 2 or more
are out of phase in any array as shown in FIG. 20. When 2 or more
wires are used in an array that are out of phase a specific
component ion mobility can be filtered out thereby letting the
other components through the gate. The configuration shown in FIG.
20 provides the ability eliminate one specific sample component
from traveling through the gate to the drift tube 2008. This is
different from other configurations where they operate as a cut-off
whereby all small size and/or shape ions are eliminated at a
certain point. In a variety of the embodiments, a method for
operating an AC ion gate for charged particles stream involves,
applying an AC voltage to 2 or more wires; the AC voltage are out
of phase, selectively eliminating one or more sample components
from the charged particle stream while partially opening the ion
gate; conducting ion mobility and/or mass measurement. The
operating method may further include applying a series of AC
voltages in certain sequence during ion mobility measurement. Such
sequence may include AC voltage that selectively eliminating sample
component ions in the charge particle stream from high ion mobility
to low ion mobility; or from low mobility to high mobility; or
selectively for one or more targeted sample components with certain
ion mobilities. The frequency and/or amplitude of the AC voltages
in such sequence may be altered in a continuous or discrete
fashion.
[0074] In a variety of the embodiments, a method for operating an
AC ion gate for a charged particle stream involves; applying an AC
voltage to one or more of the gate wires to partially open and/or
close the ion gate, partially opening the ion gate with an AC
voltage that is greater than 0 but less than the AC voltage used to
close the ion gate, and filtering a percentage of some components
of the charged particle stream from the other components of the
particle stream by neutralizing such components on the ion gate
wires. The frequency and/or amplitude of the AC voltage can be
controlled in a range or held constant during a period of closing
the gate. The AC voltage can be a symmetric or asymmetric waveform.
The percentage of some components of the charged particle stream
being filtered from the other components can be 0 to 100%, in
particular, 100%, greater than 75%, greater than 50%, greater than
25%, greater than 10%, or a small percentage being greater than
0%.
[0075] In one embodiment, the method of operating an AC gate may
include a series of pulse of ions that allow different components
of charged particle stream to pass through the AC gate; and analyze
the components of charged particle stream based on their ion
mobility and/or mass to charge ratio.
[0076] In one preferred embodiment of a time of flight ion mobility
spectrometer include an ionization source located on one end of the
ion mobility spectrometer is used to ionize the samples. An
electric field is used to guide the ionized sample toward an ion
gate. On the ion gate, at least one AC voltage is applied to the
gate elements where at least one pulse of the ionized sample is
passed into a drift tube. The ionized sample is then guided by
another electric field to guide the pulse(s) of ions toward an ion
detector. The ion detector is commonly located at the other end of
the spectrometer. The AC voltage can be composed using one or more
waveform. The AC voltage has a waveform that is substantially same
as the asymmetric waveform used in differential/field asymmetric
ion mobility spectrometers, an example of such waveform is shown in
FIG. 21. The time of flight ion mobility spectrometer can offer two
separation mechanisms in one integrated structure. The ionized
sample mixture is first filtered by the AC ion gate based on their
ion mobility differential under high electric field condition
between grid elements; only selected ions under a given AC voltage
condition can pass the ion gate as a pulse of ions, and then, the
pulse of ions are further separated ion the drift tube of the time
of flight ion mobility spectrometer based on their low field ion
mobility. The AC gate can sweep through a range of AC voltages to
select ions with different high field mobility to be pulsed into
the drift tube for further separation. With this measurement, a 3D
separation plot could be generated with one axis of low field ion
mobility, or drift time, and another axis of compensation voltage
of the asymmetric waveform for DMS/FAIMS, and the third as axis of
ion intensity.
[0077] Even though many embodiments and examples given in this
disclosure refer to ion gate for general IMS device, these devices
can be operated under low vacuum, ambient or high pressure
conditions. Alternatively, the ion gate can be operated in liquid
for liquid phase IMS or other devices, such as electrophoretic
devices, where packets of ions need to be formed. The ion gate can
also be used under vacuum conditions for generating ion packets for
mass spectrometers, such as a time of flight mass spectrometer.
This invention discloses gating methods and apparatuses that can be
used for any device where packets of charged particles need to be
formed.
[0078] In various aspects, the present invention provides
multi-dimensional ion mobility spectrometry (MDIMS) systems,
preferably with multi-dimensional electric field designs in one
integrated spectrometer, and methods of operating such systems. In
various embodiments, the MDIMS systems and/or methods provide
improved sensitivity and resolution compared to conventional single
dimension drift tubes. In various embodiments, improved sensitivity
can be achieved by using the first dimension as an ion storage
region to improve system duty cycle. In various embodiments the
MDIMS systems and/or methods provide improved mobility resolution.
In various embodiments, improvements can be achieved by the use of
drift regions which can further separate ions that are or have
already been separated based on their mobilities. In various
embodiments, as ion species are being separated in the first
dimension, the columbic repulsion among them is reduced by
transferring them to a second IMS dimension (e.g., using a kickout
pulse). Thus, in various embodiments, higher mobility resolution
can be experienced in the second dimension. In various embodiments,
the first dimension can be used as an ion reaction region where
further ion conversion can be achieved. In various embodiments of a
MDIMS, and appropriate electric field application, a MDIMS can be
used to detect both positive and negative ions substantially
simultaneously.
[0079] In various embodiments of the MDIMS, it is understood that a
preferred embodiment is to arrange the drift axis of each dimension
in orthogonal geometry, however, the drift axis can be arranged in
parallel, anti-parallel or with an angle in between to achieve
similar results.
[0080] It is to be understood, that the electrical drift field
strength-to-gas number density ratio (E/N value, often expressed in
units of Townsend) in all IMS dimensions of the present MDIMS
apparatus and methods is chosen to establish a steady-state drift
environment, sometimes referred to as a low field environment.
[0081] With the MDIMS of the present inventions, the ion mobility
spectrum can be represented, e.g., in a 2-D or 3-D plot, and can
use a non-linear detection window. Chemicals can be identified in
their 1-D, 2-D or 3-D mobility profile. This mobility profiling
method can provide additional information and thus, can provide
greater confidence for chemical (e.g., explosive)
identification.
[0082] In various embodiments a Dual Polarity Ion Extraction (DPIE)
operational mode can be conducted using the first dimension as a
flow through cell where both positive and negative ions are brought
into the first drift chamber by gas flow while the drift voltage in
the first dimension is turned off (i.e., substantially no drift
field is present). At a predetermined time ions are and kicked out
into the second dimension, preferably such that the positive and
negative ions in the first dimension are substantially
simultaneously extracted into two separated drift chambers in the
second dimension. After ions are separated in the second dimension,
they can be further separated and detected in the third or higher
dimensions.
[0083] In various embodiments, ionized samples are guided into
and/or formed in the first drift region and subject to a first
order separation based on mobility (resembling conventional IMS).
At a given predetermined time, separated ions in the first
dimension (first drift tube) are kicked out into the second drift
dimension drift region where they are separated in the direction
that is substantially perpendicular to the first drift direction.
The same process can be continued in the higher dimensions if
desired with further dimensions of IMS.
[0084] In one embodiment, the three walls in the first dimension
are at 1,000 V and the gate grids are set at 0 V and 2,000 V
respectively. The sample gas flow used to carry ions through the
first dimension can be exhaust, e.g., behind the first dimension
detector. After ions are separated in the second dimension, a kick
out voltage can be applied to bring the separated ions into the
third dimension. In a continuous sample detection scenario, the
sequence will repeat. For a chemical mixture that may form both
positive and negative ions, various embodiments of the DPIE
technique can extract more than 50% of both positive and negative
ions into the second dimension.
[0085] In various embodiments, the MDIMS devices can transport ions
between each dimension without significantly losing resolving
power. In various embodiments, when ions are separated in the first
dimension; they can look like a thin plate. To move them into the
direction that is perpendicular to the first dimension, voltages
are changed on the appropriate electrodes (typically an electrode
opposite the inlet, the inlet itself, or both) within a microsecond
range. The electric field during these kick out moments can be
manipulated to create temporary high and low electric field zones.
The thin plate in the high field zone can be compressed into a thin
line in the low field zone of the second dimension.
[0086] In various embodiments, a MDIMS comprises an ionization
source to, for example, (a) generate reactant ions and a reaction
region where reactant ions can react with samples and form product
ions to be detected for sample identification; (b) generate sample
ions for detection, (c) or both. The reaction region can be guarded
by ion guides that generate a substantially continuous electric
field to, e.g., lead the ions to the first dimension drift region
(first drift tube).
[0087] In Multiple Step Separation (MSS) mode operation, a pulse of
ions are generated by opening an ion gate, to introduce them into
the first dimension drift region; the ions are separated based on
their mobilities under the guidance a substantially continuous
electric drift field in the first drift tube. In one embodiment,
the electric field is generated by a series of ion guides. Each ion
guide can comprise one or more electrodes; and different voltages
can be applied on each electrode to establish the potential
difference across the first drift tube. For example, four
electrodes can be used for each of the first dimension ion
guides.
[0088] In various embodiments of MSS mode operation, as a first
group of ions reaches the first dimension detector matrix, a kick
out voltage can be applied to generate a high electric field that
is perpendicular to the first dimension drift field, thus the ions
separated in the first dimension are moved into the second
dimension drift region. An electric field separator screen can be
used to help define the electric field in the second dimension.
Ions introduced into the second field will continue to drift across
the second dimension drift region and further separation can be
achieved. The ion guides in the second dimension can be arranged
similarly to the first dimension ion guides, for example, if a
third dimension of separation is desired. If a third dimension is
desired, complete square electrodes can be used as the ion guides.
Ions separated in the second dimension can be detected by the
detector. The detector can comprise multiple detectors according to
required special resolution of the spectrometer or a single
detector.
[0089] In various embodiments, a partial kick out operation can be
performed when ions are introduced from the first dimension to the
second dimension. If only a portion of the ions are kicked out, the
mobility measurement in the first dimension can be resumed after
the kick out. Thus, an ion mobility spectrum can also be acquired
independently in the first dimension. As a complete kick out can
increase the sensitivity in the second dimension, alternating
between these operation methods can be beneficial. In addition, a
clean up operation, e.g., remove all ions in the drift chambers by
an applied "kick out" electric field for an extended period of
time, can also be added between detection cycles.
[0090] The low dimension operation of the spectrometer can be used
as fast screening method to generate a quick survey of the ionic
species from the ionization source. In combination with the normal
operation of the MSS mode, the survey of the ionic species can be
used as an index to guide upper dimension operations. The survey
mode operation can also be used to selectively kick out ions of
interest, simplifying higher dimension spectra, and saving total
analysis.
[0091] Different drift/separation conditions can be established
independently for each dimension, e.g., different drift gases may
be used in each dimension or different drift gas temperatures in
each dimension.
[0092] The MDIMS can be operated in a fashion where a number of
multiple dimensional positive ion mobility data is collected
followed by a number of multiple dimensional negative ion mobility
data. The sequence can be realized, e.g., by alternation the
polarities of electric fields in the spectrometer.
[0093] During MSS mode operation, the directions of the drift gas
flow can be set to be counter to or across from the ion movement.
The size of each gas port can be selected depending on the flow
required to achieve the flow pattern inside the spectrometer and
preferably the drift flow sweeps the entire drift region and
removes excessive sample molecules and any other reactive neutral
molecules.
[0094] One aspect of the present invention is a method and
apparatus for using a cross flow IMS apparatus for effectively
removing neutral molecules from drift tube. In a time of flight
type ion mobility spectrometer, the cross gas flow is used in a
manner that is similar to conventional uni- or counter-directional
drift gas flow, the drift gas flow does not substantially affect
the ion separation along the drift axis. Compared to prior art
counter- and uni-direction drift flow design, the cross flow design
allows neutral molecule(s) to only travel a short distance and less
time in a drift region. A non-limiting example is shown in FIG. 22
where a drift segment is used. However more than one drift segment
can be used. The drift tube 2201 comprises: an ionization source
2202, a desolvation region 2210 and an analytical segment (drift
region) 2205 separated by an ion gate 2207. After a sample is
introduced into one end of the IMS (in this particular case an ESI
source 2202 is used; any other ionization source could be used),
the ionized sample and solvent ions are formed in the desolvation
region 2210, a narrow pulse on the ion gate 2207 introduces the ion
mixture into the separation segment 2205. This configuration has
the drift gas flow 2215 (comprised of drift flow for desolvation
2219 and separation 2217) in a direction that is substantially
perpendicular to the drift axis of the ions; the drift axis
generally represent the averaged ion path in the drift tube. With
cross flow configuration, neutral molecules that travel with the
drift and desolvation gas flow are not mixed across desolvation and
drift region. Neutral fragments that are generated during drift and
desolvation process in the drift tube are effectively removed from
the drift tube avoiding further gas phase ion molecular interaction
in the drift tube. The cross-directional drift gas can be in a
direction that is between greater than 0.degree. to less than
180.degree. to that of the drift axis of the ions. The
cross-directional drift gas is applied to a substantial portion of
the desolvation and/or drift region. In many cases the
cross-directional drift gas is applied over the entire drift axis.
In addition, the cross-directional gas flow 2215 can be a drift
medium that comprises various components. The components may be a
plurality chemical modifiers and/or a plurality of drift gases. The
cross-directional flow can comprise different drift medium in the
different segments and/or regions of the IMS. For example, as shown
in FIG. 22, drift gas flow 2219 can comprise the same and/or
different drift medium as drift gas flow 2217.
[0095] In various embodiments, the cross flow configuration for the
IMS can be combined with counter or uni-direction flow
configurations. For example, if the drift region has a cross flow
arrangement as shown in FIG. 22, a portion the drift flow could be
exhausted into the desolvation region and then pumped away from the
end of the desolvation region, given the desolvation region is
using a counter direction gas flow arrangement.
[0096] In another aspect of the present invention a multiple
segmented IMS apparatus is used for pre-separation of the sample. A
non-limiting example is shown in FIG. 23 where two drift segments
are used. However more than two drift segment can be used. The
drift tube 2301 comprises: a pre-separation segment 2303 and an
analytical segment 2305 separated by an ion gate 2307. The
pre-separation segment 2303 resembles the pre-separation column
used in chromatography. After a sample is introduced into one end
of the IMS (in this particular case an ESI source is used, any
other ionization source could be used), the ionized sample and
solvent ions are formed in the desolvation region 2310, a narrow
pulse on the first ion gate 2312 introduces the ion mixture into
the pre-separation segment 2303. The second ion gate 2307 is timed
to open so that only components of the sample are allowed to enter
the analytical segment 2305. Elimination of the solvent avoids
ion-molecule reactions in the analytical segment 2305 of the drift
tube 2301.
[0097] In various embodiments the two gate IMS apparatus and
method, the first gate transmits packets of ions and these ions
move to the second gate. Part of the ions from the first gate will
be transmitted through to the second gate and the transmitted ions
will be further separated through the drift region. Ions at the
second gate have low density and the space charge effect can be
reduced and the IMS will have enhanced separation. The IMS
separated ions can be detected by a faraday plate and can be
transported to a mass analyzer for further analysis.
[0098] In another embodiment of the two gate IMS apparatus and
method, the first gate transmits narrow ion packets. Higher ion
mobility ions take a shorter time to get to the second gate than
lower mobility ions. By controlling the second gate timing, certain
mobility ions are transmitted through the second gate. The first
gate can be controlled to transmit the second, third, fourth, etc.
ion packet before the first packet reaches the detector. The first
and second gate will be operated synchronously with different
start-on time and width of opening. Ions transmitted through the
second gate will be separated while traveling through the drift
region and being detected by the detector or being transported to
the mass analyzer. The first gate opening will have a specific
period which was determined not to mix ions of different packets. A
grid in front of the detector can be replaced by an exit gate to
further limit the ions with specific ion mobility.
[0099] A segmented drift tube with multiple ion gates can be used
with cross flow design for easy application of different drift
media in different segments, however, segmented drift tube design
could be used with one drift media, and/or with conventional uni-
or counter-direction drift gas flow designs.
[0100] In another aspect of the present invention a multiple
segmented planar IMS apparatus combined with a cross flow can be
used to enhance separation of components of a sample. In this case,
solvent ions as well as solvent neutrals are eliminated from the
analytical segment. A non-limiting example is shown in FIG. 24
where two drift segments are used. However more than one drift
segment can be used. The drift tube 2401 comprises: a
pre-separation segment 2403 and an analytical segment 2405
separated by an ion gate 2407. The pre-separation segment 2403
resembles the pre-separation column used in chromatography. After a
sample is introduced into one end of the IMS (in this particular
case an ESI source is used, any other ionization source could be
used), the ionized sample and solvent ions are formed in the
desolvation region 2410, a narrow pulse on the first ion gate 2412
introduces the ion mixture into the pre-separation segment 2403.
The second ion gate 2407 is timed to open so that only components
of the sample are allowed to enter the analytical segment 2405.
Elimination of the solvent avoids ion-molecule reactions in the
analytical segment 2405 of the drift tube 2401. This configuration
has the drift gas flow 2415 in a direction that is substantially
perpendicular to the drift axis of the ions, the drift axis
generally represent the averaged ion path in the drift tube. With
cross flow configuration, neutral molecules that travel with the
drift and desolvation gas flow are not mixed across desolvation and
drift region. Neutral fragments that are generated during drift and
desolvation process in the drift tube are effectively removed from
the drift tube avoiding further gas phase ion molecular interaction
in the drift tube. The cross-directional drift gas can be in a
direction that is between greater than 0.degree. to less than
180.degree. to that of the drift axis of the ions. The
cross-directional gas flow can be a drift medium that comprises
various components. The components may be a plurality chemical
modifiers and/or a plurality of drift gases. The cross-directional
flow can comprise different drift medium in the different segments
of the IMS. For example, as shown in FIG. 24, drift gas flow 2419
can comprise the same and/or different drift medium as drift gas
flow 2417.
[0101] A separation apparatus, comprising: an ionization source
ionizing a sample that contain a least one component in front of an
ion gate; a drift tube that has a drift axis along which ions are
separated; and a drift flow in a direction that is greater than
zero but less than one hundred and eighty degrees from the drift
axis. The apparatus can further comprise at least one chemical
modifier that is added to the drift flow for separation
enhancement. In one embodiment, a separation apparatus comprising:
an ionization source ionizing a sample that ionizes samples; a
drift tube has a drift axis along which ions are separated, wherein
the drift tube has greater than or equal to, two drift segments in
which the ions are separated, and a ion gate that is placed between
drift segments. The separation apparatus may further comprises at
least one chemical modifier that is added to the drift flow.
[0102] In another embodiment of the present invention, a chemical
modifier can be added to different segments or regions of the IMS
in order to target specific interactions with various components of
the sample. Two or more segments can be used, but for
simplification a two segment design will be discussed. Therefore
two or more different chemical modifiers can be used in the IMS
without substantially interfering with each other. 0 to 100% of
modifier can be used in each of the different segments or regions
of the IMS. The cross flow drift design is one way to add the
modifier, but it is not necessary to use cross flow in order to add
the modifiers to each segment or region in the IMS. The different
segments or regions can be isolated from each other by a number of
ways which include but are not limited to; using gates in between
or a small opening, slits or pinholes. In this configuration, a
modifier that targets one functional group can be added to the
first region of the IMS and a second type of modifier can be added
to the next region that interacts with a different functional
group. Unlike previous methods where a transforming agent,
immobilizing agent, or chiral molecule is added to the sample
components prior to ionization, in this process, the sample
components are modified in the drift tube in discrete sections
according to the desired interaction. For example, in order to
separate a pair of enantiomers in a sample, a chiral modifier added
to the cross flow drift gas in the first region of the drift tube
which forms diastereomer components that are then interacted by a
second modifier added to the cross flow drift gas in a second
region of the drift tube to enhance separation.
[0103] FIG. 25 shows an IMS where the sample is ionized in the
desolvation region 2510. The drift tube 2501 consists of two
regions 2503 and 2505 that have an applied electric field (not
shown) and are separated by a gate 2507. Another gate separates the
desolvation region 2510 from the drift tube 2501 with a gate 2512.
In the case of a sample that has two enantiomer components, this
enantiomer pair is ionized in the desolvation region 2510 and is
then allowed to travel into the first separation region 2503
whereby 0-100% of a chiral modifier is added to the cross drift
flow 2513 which interacts with the enantiomer pair. Diastereomers
are then formed and are let into the second separation region 2505.
These diastereomers are then separated in the second separation
region with enhanced separation by using 0-100% of a modifier that
is added to the cross drift flow 2517.
[0104] One embodiment of this invention is to rigidify the
molecules (limit the number of conformations) by adding an
immobilizing agent to the first drift region of the drift tube. The
immobilizing agent stabilizes the gas phase structure of analytes
in order to enhance the interaction of the modifier in the second
region of the drift tube in order to enhance separation. In variety
of embodiments, a modifier that can frame (affix) the higher order
structure of a gas phase analyte molecule is used to achieve
well-defined gas phase mobility of the analytes. Forming complexes
with metals and/or other molecules is a non-limiting example of
this method. Another embodiment of this invention is to add at
least one transforming agent as a modifier to the first drift
region, which bonds/binds (interacts) to at least one component of
the sample. The bonding interactions or attraction forces may
include; hydrogen bonds, van der Waals forces, dipole-dipole,
steric hindering effects, coordinate covalent bond, metallic bond,
ionic bond, non-covalent bond, covalent bond, weak covalent nature,
antibonding, short-lived metastable, clusters, but is not limited
to only these. A second chemical modifier is added to the second
region of the drift tube that interacts selectively with the
component of the sample and/or transforming agent which
resolves/separates the component from other components of the
sample based on their measured ion mobility characteristics.
[0105] When using a modifier, the modifier can interact with
solvent ions and for additional ions; the modified solvent ions can
overwhelm the signal from the ions of interest. By using an AC
gate, this invention allows the removal of the solvent ions before
the drift tube separation region where the modifier is introduced
to. A non-limiting example is shown in FIG. 26 where a drift
segment is used. However more than one drift segment can be used.
The drift tube 2601 comprises: an ionization source 2602, a
desolvation region 2610 and an analytical segment (drift region)
2605 separated by an AC ion gate 2607. After a sample is introduced
into one end of the IMS (in this particular case an ESI source 2602
is used; any other ionization source could be used), the ionized
sample and solvent ions are formed in the desolvation region 2610.
The AC gate 2607 is operated to reject the low molecular weight
solvent ions, and a pulse on the AC ion gate introduces the rest of
the ion mixture into the separation segment 2605. This
configuration has the drift gas flow 2615 (comprised of drift flow
for desolvation 2619 and separation 2617) in a direction that is
substantially perpendicular to the drift axis of the ions; the
drift axis generally represents the averaged ion path in the drift
tube. The cross-directional drift gas can be in a direction that is
between greater than 0.degree. to less than 180.degree. to that of
the drift axis of the ions. The cross-directional drift gas is
applied to a substantial portion of the desolvation and/or drift
region. In many cases the cross-directional drift gas is applied
over the entire drift axis. In addition, the cross-directional gas
flow 2615 can be a drift medium that comprises various components.
The components may be a plurality chemical modifiers and/or a
plurality of drift gases. The cross-directional flow can comprise
different drift medium in the different segments and/or regions of
the IMS. For example, as shown in FIG. 26, drift gas flow 2619 can
comprise the same and/or different drift medium as drift gas flow
2617.
[0106] In another embodiment, the AC ion gate 2607 is operated as
FAIMS (DMS) device, for example, using elongated gate elements as
shown in FIG. 18 and applying a waveform such as the example shown
in FIG. 21. In this embodiment, a pulse of ions that are
characterized by a single FAIMS compensation voltage are allowed
through the AC gate; these ions are then separated in the drift
region 2605. This configuration has the drift gas flow 2615
(comprised of drift flow for desolvation 2619 and separation 2617)
in a direction that is substantially perpendicular to the drift
axis of the ions; the cross-directional drift gas can be in a
direction that is between greater than 0.degree. to less than
180.degree. to that of the drift axis of the ions. The
cross-directional drift gas is applied to a substantial portion of
the desolvation and/or drift region, or over the entire drift axis.
In addition, the cross-directional gas flow 2615 can be a drift
medium that comprises various components. The components may be a
plurality chemical modifiers and/or a plurality of drift gases. The
cross-directional flow can comprise different drift medium in the
different segments and/or regions of the IMS. For example, as shown
in FIG. 26, drift gas flow 2619 can comprise the same and/or
different drift medium as drift gas flow 2617.
[0107] An ion mobility spectrometer apparatus can have an
ionization source that is in fluid communication with a drift tube;
an AC ion gate that located between the ionization source and the
drift tube pulses a group of ions into the drift tube where the
group of ions are separated along a drift axis, and at least one
drift gas that flows substantially in a direction that is greater
than zero but less than one hundred and eighty degrees from the
drift axis. The group of ions are pre-separated by an AC ion gate
comprising applying at least one AC voltage to at least one of the
grid elements of the AC ion gate to pass a pulse of selected ions
into the drift tube. The AC voltage has an asymmetric waveform as
used in an DMS. the drift gas can also use different drift gases or
by adding chemicals into the drift gas. The drift tube is a
segmented drift tube. The group of ions are pre-separated by a
previous section of a segmented drift tube. The segmented drift
tube is divided by the AC gates positioned between each segments
only allowing selected ions to pass the ion gates. The segment of
the drift tube uses different gas compositions. The group of the
ions is a mixture of solvent(s) and sample(s). The pre-separation
is to eliminate solvent ions for the group of ions.
[0108] An ion mobility spectrometer method can be operated by
forming ions in an ionization source that is in fluid communication
with a drift tube; pulsing a group ions that into a drift tube;
separating the group of ions along a drift axis of the drift tube,
and; providing at least one drift gas that flows substantially in a
direction that is greater than zero but less then one hundred and
eighty degrees from the drift axis. The group of ions are
pre-separated by an AC ion gate comprising applying at least one AC
voltage to at least one of the grid elements of the AC ion gate to
pass a pulse of selected ions into the drift tube. The AC voltage
has an asymmetric waveform as used in an DMS. The drift gas further
comprises adding chemicals into the drift gas. The drift tube is a
segmented drift tube. The group of ions are pre-separated by a
previous section of a segmented drift tube. The segmented drift
tube are divided by the AC gates positioned between each segments
only allowing selected ions to the ion gates. Each segment of the
drift tube uses different gas compositions. The group of the ions
is a mixture of solvent(s) and sample(s). The pre-separation is to
eliminate solvent ions.
[0109] A separation method, comprising ionizing a sample with at
least one component; separating the ionized sample along a drift
axis of a drift tube, and proving a drift flow in a direction that
is greater than zero but less than one hundred and eighty degrees
from the drift axis. The separation method may further comprise
removing neutral molecules in the drift tube along with the drift
flow; the neutral molecules could be, but not limited to, one
component of the sample; fragment of a sample molecule;
contaminants in the apparatus. In one embodiment, a separation
method comprising: ionizing a sample with at least one component;
providing the sample to an ion mobility based spectrometer with
greater than or equal to, two drift segments separated by an ion
gate between the drift segments; transporting the ionized sample as
a ion packet along a drift axis; and pre-separating the ion packet
in one of the drift segments prior to further separation in other
separation segments. This separation method may further comprises;
adding at least one chemical modifier to a drift gas flow that is
in a direction to that of the drift axis of the ions that is
between greater than 0 degrees to less than 180 degrees.
[0110] In various embodiments, the drift gas can be supplied to the
higher dimension in the direction that is in substantially parallel
to the lower dimension. Under linear flow conditions and the
parallel flow pattern, for example, limited mixing of drift gas
near the dimension interface is expected.
[0111] In SBA mode operation, the sample is provided into the
spectrometer through an inlet port. Through the ionization source,
the ionized the samples are brought into the first dimension drift
region by gas flow. In various embodiments of the SBA operational
mode, the first dimension drift tube can be used as ion storage
device to, e.g., increase the duty cycle of the device.
[0112] In various embodiments of Continuous First Dimension
Ionization (CFDI) mode operation, the samples are introduced to the
spectrometer as pulses of gas. The sample gas pulse can be formed
in a wide variety of ways, for example, by thermally desorbing
chemicals from a surface, as the eluent of a chromatographic
separation, by pumping the sample into the spectrometer for a short
period of time, introduction through a pulsed valve, etc. In many
embodiments, the flow under a linear flow condition, and a "plug"
of gas phase sample is directed from the inlet port towards the
ionization source by gas flow. Pulses of reactant ions (preferably
at high density) are generated by the ionization source and guided
by the electrical drift field to drift towards the sample "plug".
As the pulse of reactant ions and samples intercept in the first
dimension, a portion of the samples are ionized. As the sample
encounters multiple reactant ion pulses in the same acquisition
period, chemicals in the sample "plug" are ionized. Chemicals with
different properties (e.g., charge affinity) can thus be separated
and detected at different locations on the detector matrix. This
gas phase titration method can improve ionization efficiency of ion
mixture where chemicals with different properties coexist. By this
means chemicals that can not be detected in conventional IMS can be
detected.
[0113] In various embodiments, the CFDI can also be performed in
the reaction region. A plurality of pulses of reactant ion is
generated by pulsing the ion gate while pulsed samples are
introduced to the spectrometer from a gas port. In this
implementation, the ion ion gate is removed or kept open. Pulse of
ions generated in the reaction region are separated in the first
dimension drift region, and then the separated ions are extracted
in a higher dimension drift region for further ion mobility
analysis if so desired. In various embodiments, the CFDI method can
be used as an independent ionization source directly interfaced to
spectrometers, such as a differential mobility spectrometer, ion
mobility spectrometer or a mass spectrometer, either inline or
perpendicular to the direction of the drift electric field. In
embodiments where CFDI is used for a single IMS, a shutter grid
will be used. The ionized chemical species continue to drift in the
drift region after formation in the reaction region. Similarly,
interfaces to other spectrometers, such as differential ion
mobility spectrometers and mass spectrometers, can also be realized
by placing the sample inlet of these instruments directly after the
reaction region.
[0114] The CFDI mode can be performed using reactant ions with
different chemical properties. For example, modifying the ion
chemistry using a variety of chemical reagents that react with
initial reactant ions can generates reactant ions with different
chemical properties. These ionic species can be used, e.g., to
ionize samples introduced to the spectrometer. Similar effects can
be achieved, e.g., by using an ionization source that can generate
different ionic species or charged particles/droplets. In various
embodiments, altering the ionization chemistry can be used to
achieve substantially selective ionization of targeted chemicals in
the sample. For example, a series of ion pulse with different
chemical properties can be used to ionize chemicals with compatible
ionization properties in the sample.
[0115] In Selective Ion Introduction (SII) mode operation, one or
multiple groups of selected ions are kicked out into a higher
dimension. The selective kick out can be realized by applying a
kick out voltage at a predetermined time to the region where ions
of interests are traveling through at a given timing. In various
embodiments, the kick out pulse is not necessarily applied to a
selected region of the lower dimension, but the higher dimension
drift chamber does not intercept the lower dimension only over a
portion of length of the lower dimension; thus, e.g., a selected
location can be designed only to allow a small group of ions to be
kick out into the second dimension. A similar result as described
with respect to MSS mode can be achieved by controlling the kick
out timing and performing multiple acquisition cycles.
[0116] In various embodiments of MDIMS systems, the higher
dimension drift region, such as the second dimension region, can be
operated in different phases of drift media, e.g. gas or liquid.
The liquid phase drift cell can be constructed with two parallel
plates or grids instead of a conventional drift tube design. The
liquid phase drift cell can be a thin layer of liquid that has an
electric field across the layer. The higher order dimension drift
cell has drift axis that is substantially parallel or substantially
perpendicular to the first dimension drift axis. The higher
dimension drift cell has multiple compartments (channels) that are
substantially perpendicular to the lower dimension drift axis. The
higher dimension drift cell can be used for selectively collecting
samples separated in the lower dimension drift tube. The higher
dimension drift cell can be further interface to other separation
and detection apparatus, including but not limited to
electrophoresis, chromatography, UV absorption and other
spectroscopic apparatus.
[0117] In various embodiments of MDIMS systems of the present
inventions, different drift gases are used in different drift tubes
and/or dimensions of the MDIMS to separate ionic species in a
higher dimension (e.g., a second dimension) that are not
sufficiently separated in the drift gas in a lower dimension (e.g.,
the first dimension). It is to be understood that the drift gas can
be a mixture of two or more gases. Similar separations can also be
done by varying other drift chamber conditions.
[0118] Various embodiments that can be used to realize the SII mode
operation with IMS.sup.n. By reducing the physical size of the
higher dimensions and controlling the timing of the kick out pulse,
a selected group of ions that drifted into the kick out region can
be brought into a higher dimension drift chamber where they can be
further separated. The same process can be continued until the nth
separation performed in different drift chambers. The geometry of
the interconnected drift chambers can be two dimensional or three
dimensional, thus the number of times a higher order mobility
separation can be conducted is not necessarily limited by the
physical space available for the spectrometer.
[0119] In various embodiments, a three dimensional MDIMS can be
used for SII mode operation. When gas phase sample is introduced
into the reaction region of the first dimension drift tube, between
two ion gates, the sample is ionized by either CFDI or conventional
ionization methods with reactant ions created by the ionization
source. The sample ions mixed with reactant ions are pulsed into
the first drift region. Under the guidance of the electric field
generated by ion guide, the ion mixture separates in the first
dimension. At a predetermined timing when ions of interest drift
into the kick out region, a kick out voltage can be applied to a
set of electrodes (including a split ion guide and grids) to
extract ions into the second dimension. As ions are compressed in
the interface between the kick out region and a second dimension
drift region, narrow pulses of plural separated ions are created at
the beginning of the second dimension drift region. The ions pulses
are separated in the drift region that is guarded by ion guides.
The further separated ions are extracted from second ion kick out
region into the third drift chamber that has a drift direction that
is orthogonal to the first and second dimension. The extracted ions
repeat the process described above in the third dimension or
higher.
[0120] In various embodiments, a MDIMS can operate in SII mode with
a two dimensional structure. One peak that is isolated by the first
dimension drift tube is extracted into second dimension, and then
one peak isolated by the second dimension drift tube is extracted
into the third dimension having a drift direction that is
substantially perpendicular to the second dimension and
substantially anti-parallel to the first dimension. In this
example, the drift axes of all dimensions are on the same
plane.
[0121] For example, in various embodiments, this configuration can
be interfaced to other detectors, such as a mass spectrometer.
IMS-MS systems are commonly used to achieve mobility based
separation before mass analysis. The interface to a mass
spectrometer can be in-line with ion drifting direction behind the
detector matrix. An interface to a mass spectrometer can be through
an opening on the second dimension detector matrix, or
perpendicular to the drifting direction using a kick out pulse to
push ions into the interface. Higher ion transportation efficiency
is expected in the latter case.
[0122] In various embodiments of the MDIMS, a compact MDIMS device
can be configured with three dimensions, including one first
dimension chamber, two second dimension drift chambers, and two
third dimension chambers, with a largest dimension of <10 cm.
The configuration is to realize both CFDI and DPIE with SII mode.
In CFDI operation, the reactant ions are formed in ion source and
pulsed into the reaction region to selectively ionize the pulsed
sample. Ionized samples are separated in the first dimension drift
region and then further separated in a higher dimension drift
region.
[0123] In DPIE operation, both positive and negative ions formed in
the ionization source and reaction region are carried into the
first dimension by carrier flow without effluence of the electric
field. The positive and negative ions are extracted in to the
second dimension drift chambers. The sample ions are detected on
the detector matrix in the first dimension, second dimension or
third dimension depending on the instrument usage and it is
software controlled. For fast screening operation, ions are
detected at lower dimension detectors for high throughput. For
highest resolution, ions are measured at the third dimension
detectors. The practical unit includes a sample inlet, a sample
inlet control valve, an ionization source, and a first dimension
drift region. The drift flow is designed to sweep cross the second
drift region and third drift region. At the drift gas inlet, a flow
distribution system is used to assure even drift flow across the
entire drift chambers.
[0124] A portable system package can include a pneumatic system,
electronics and computer controls, a user interface and display,
battery power, and a MDIMS.
[0125] A modularized design approach is preferably used in the
MDIMS of the present inventions to facilitate the provision of
future upgrades. For example, a different ionization source may be
desired for different applications. Such sources may be, e.g., a
corona discharge, electrospray ionization or desorption
electrospray ionization. The provision of a modular design can
facilitate the changing of the ion source.
[0126] In another aspect, the functionality of one or more of the
methods described above may be implemented as computer-readable
instructions on a general purpose processor or computer. The
computer may be separate from, detachable from, or may be
integrated into a MDIMS system. The computer-readable instructions
may be written in any one of a number of high-level languages, such
as, for example, FORTRAN, PASCAL, C, C++, or BASIC. Further, the
computer-readable instructions may be written in a script, macro,
or functionality embedded in commercially available software, such
as EXCEL or VISUAL BASIC. Additionally, the computer-readable
instructions could be implemented in an assembly language directed
to a microprocessor resident on a computer. For example, the
computer-readable instructions could be implemented in Intel 80x86
assembly language, if it were configured to run on an IBM PC or PC
clone. In one embodiment, the computer-readable instructions can be
embedded on an article of manufacture including, but not limited
to, a computer-readable program medium such as, for example, a
floppy disk, a hard disk, an optical disk, a magnetic tape, a PROM,
an EPROM, or CD-ROM (or any other type of data storage medium).
[0127] All literature and similar material cited in this
application, including, but not limited to, patents, patent
applications, articles, books, treatises, and web pages, regardless
of the format of such literature and similar materials, are
expressly incorporated by reference in their entirety. In the event
that one or more of the incorporated literature and similar
materials differs from or contradicts this application, including
but not limited to defined terms, term usage, described techniques,
or the like, this application controls.
[0128] The section headings used herein are for organizational
purposes only and are not to be construed as limiting the subject
matter described in any way.
[0129] The claims should not be read as limited to the described
order or elements unless stated to that effect. While the present
inventions have been described in conjunction with various
embodiments and examples, it is not intended that the present
inventions be limited to such embodiments or examples. On the
contrary, the present inventions encompass various alternatives,
modifications, and equivalents, as will be appreciated by those of
skill in the art.
[0130] It is recognized that modifications and variations of the
invention disclosed herein will be apparent to those of ordinary
skill in the art and it is intended that all such modifications and
variations be included with the scope of the appended claims.
* * * * *