U.S. patent application number 13/419425 was filed with the patent office on 2012-09-13 for apparatus and method for ion mobility spectrometry and sample introduction.
This patent application is currently assigned to Excellims Corporation. Invention is credited to Eugenie Hainsworth, Taeman Kim, Clinton Alawn Krueger, Mark A. Osgood, Ching Wu.
Application Number | 20120228490 13/419425 |
Document ID | / |
Family ID | 46794669 |
Filed Date | 2012-09-13 |
United States Patent
Application |
20120228490 |
Kind Code |
A1 |
Wu; Ching ; et al. |
September 13, 2012 |
APPARATUS AND METHOD FOR ION MOBILITY SPECTROMETRY AND SAMPLE
INTRODUCTION
Abstract
The IMS apparatus and methods described in this invention
involve setting the ion detector at the highest potential of the
drift tube and setting the ionization source at ground or near
ground potential. The methods allow significantly simple sample
introduction without the limitation of the high potential (voltage)
concern of the front end sample delivery. The invention also
describes bringing samples directly into the ion mobility drift
tube. The invention further describes using single syringe for
sample introduction via an electrospray ionization method.
Inventors: |
Wu; Ching; (Acton, MA)
; Osgood; Mark A.; (Brookline, NH) ; Hainsworth;
Eugenie; (Somerville, MA) ; Krueger; Clinton
Alawn; (Milton, MA) ; Kim; Taeman; (Westford,
MA) |
Assignee: |
Excellims Corporation
Acton
MA
|
Family ID: |
46794669 |
Appl. No.: |
13/419425 |
Filed: |
March 13, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61452117 |
Mar 13, 2011 |
|
|
|
Current U.S.
Class: |
250/282 ;
250/288 |
Current CPC
Class: |
H01J 49/165 20130101;
G01N 27/622 20130101; H01J 49/167 20130101; H01J 49/067 20130101;
G01N 27/624 20130101 |
Class at
Publication: |
250/282 ;
250/288 |
International
Class: |
H01J 49/26 20060101
H01J049/26 |
Claims
1. An ion mobility based spectrometer apparatus comprising: a) an
ionization source that is set at a low potential of the
spectrometer; b) an ion detector that is set at a high potential of
the spectrometer; and c) an ion mobility based analyzer that is in
fluid communication with the ionization source on one end and the
ion detector on the other end.
2. The ion mobility based spectrometer apparatus of claim 1,
wherein the low potential is the lowest potential for the
spectrometer at ground or near ground potential.
3. The ion mobility based spectrometer apparatus of claim 1,
wherein the high potential is the highest potential for the
spectrometer.
4. The ion mobility based spectrometer apparatus of claim 1,
wherein the high potential is either positive or negative
potential.
5. The ion mobility based spectrometer apparatus of claim 1,
further comprises a sample inlet.
6. The ion mobility based spectrometer apparatus claim 5, wherein
the sample inlet is set at the lowest potential.
7. The ion mobility based spectrometer apparatus of claim 1,
wherein the ionization source is an electrospray ionization
source.
8. The ion mobility based spectrometer apparatus of claim 7,
wherein the electrospray ionization source comprises a syringe
needle that is used for sampling and as the spray needle.
9. The ion mobility based spectrometer apparatus of claim 7,
further comprises a curtain gas section which has at least two
plates with an opening in the center.
10. The ion mobility based spectrometer apparatus of claim 9,
wherein the plates are positioned to administrator gas flow as
such: a low temperature cooling gas flow enters the center hole of
the first plate on the needle side; a high temperature desolvation
gas flow enters the center hole of the second plate on the
desolvation section side; both gas flows are exhausted at a gas
exit located between the two plates.
11. The ion mobility based spectrometer apparatus of claim 9,
wherein the plates are set at different potentials that guide ions
entering the first plate toward the second plate.
12. The ion mobility based spectrometer apparatus of claim 10,
wherein the gas exit could be used as a gas inlet for the cooling
gas flow and exhaust both cooling gas flow and the desolvation gas
flow from the center hole of the first plate.
13. An ion mobility based spectrometer method comprises: operating
an ion mobility based analyzer that is in fluid communication with
an ionization source on one end and an ion detector on the other
end; setting the ionization source at a low potential of the
spectrometer; and setting the ion detector at a high potential of
the spectrometer.
14. The ion mobility based spectrometer method of claim 13, wherein
the low potential is set at the lowest potential for the
spectrometer at ground or near ground potential.
15. The ion mobility based spectrometer method of claim 13, wherein
the high potential is set at the highest potential for the
spectrometer.
16. The ion mobility based spectrometer method of claim 13, wherein
the high potential is set at either positive or negative
potential.
17. The ion mobility based spectrometer method of claim 13, further
comprises setting a sample inlet at the lowest potential.
18. The ion mobility based spectrometer method of claim 13, further
comprises electrospraying a sample from a syringe needle.
19. The ion mobility based spectrometer method of claim 18, further
comprises using the needle for sampling and spraying.
20. The ion mobility based spectrometer method of claim 13, further
comprises administering gas flows in the curtain gas section as
such: a low temperature cooling gas flow enters a center hole of a
first plate on the needle side; a high temperature desolvation gas
flow enters the center hole of a second plate on the desolvation
section side; both gas flows are exhausted at a gas exit between
the first and second plate.
Description
[0001] The present application claims the benefit of and priority
to corresponding U.S. Provisional Patent Application No.
61/452,117, filed Mar. 13, 2011 respectively, the entire content of
the application is herein incorporated by reference.
BACKGROUND OF THE INVENTION
[0002] The needle in some commercial electrospray ionization (ESI)
sources is operated at kilovolt potentials during electrospray
operation. For such ESI sources, a longer dielectric liquid
transfer line of several inches is typically configured between the
ground potential injector valve and the ESI needle to allow a
gradual drop in kilovolt potential through the sample solution. A
high electric field gradient in the transfer tube is avoided to
minimize sample heating, electrophoretic and electrolysis effects
during Flow injection analysis (FIA). Liquid transfer lines can be
reduced in length when an ESI source in configured with a grounded
needle, however, even with grounded ESI needles, the dead volume
due to the transfer lines cannot be entirely eliminated. For ion
mobility spectrometer (IMS) applications where small amounts of
sample are available for injection, sample dilution or losses due
to injector valve, connector and transfer line dead volumes and
surfaces may compromise the limit of detection.
SUMMARY OF THE INVENTION
[0003] The IMS apparatus and methods described in this invention
involve setting the ion detector at the highest potential of the
drift tube and setting the ionization source at ground or near
ground potential. The methods allow significantly simple sample
introduction without the limitation of the high potential (voltage)
concern of the front end sample delivery. The invention also
describes bringing samples directly into the ion mobility drift
tube. The invention further describes using single syringe for
sample introduction via an electrospray ionization method.
[0004] This invention reduces or eliminates cross contamination,
solvent consumption, liquid dead volume, and waste by having the
sampling and spray needle the same apparatus. The sampling and
spray needle configured with an auto injector apparatus, continuous
infusion syringe pump, or used in manual injection is introduced
directly into the IMS. Such a sampling and spray needle eliminates
the need for injector valves, transfer lines or additional fluid
delivery systems into IMS instruments. The injector needle and an
ESI source has been configured such that the sample solution can be
sprayed directly from the injector needle tip. The injector needle
does not need to be introduced into the ESI source region through a
guide. The needle can be configured as a reusable or disposable
tip. The liquid spray flow rate is set by the auto or manual
injector sample injection flow rate. This flow rate can be set to
optimize IMS analysis and sample throughput. In addition,
automation of the direct spray needle can be achieved by setting up
array of the spray needles that are loaded in a manner that rotates
and/or moves to the next spray needle in the ESI source region.
[0005] The invention comprises a reusable or disposable needle
configured in an auto-injector or a manual injector which serves as
the means to remove a sample solution from a container and
transport such solution to an atmospheric pressure ionization (API)
source (such as ESI or APCI) wherein the needle is to deliver
sample directly into the API source and/or desolvation region. Such
fixed or disposable needle, when introduced into an API source,
becomes the liquid introduction channel or tube in the nebulizer
probe of an APCI source, the nebulizer apparatus of a pneumatically
assisted Electrospray probe or an Electrospray tip in an unassisted
ESI ion source probe. Ions produced from samples introduced through
such sprayers into an API source are subsequently directed into a
desolvation region of the IMS. Auto injectors may be configured
with multiple injector needles configured for direct delivery of
sample into an API source through one or more probes. Such multiple
needle auto injectors may deliver samples in a sequential or
multiplexed manner to such single or multiple direct injection API
source ports or probes to maximize sample throughput. In one
embodiment of the invention, a reusable or disposable sampling and
spray injection needle may be packed with material, such as C18
coated beads, to aid in desalting, sample cleanup or the separation
of sample compounds in solution during the sample pickup, delivery
and spray steps. Different solvent composition layers can be pulled
sequentially into such packed sampling and spray needles with
attached reservoirs prior to sample pickup. The sample can then be
sprayed into an API source from such a loaded injection needle
using solvent gradients to aid in sample desalting, additional
cleanup or sample compound separation during spraying.
[0006] Washing or flushing of a packed or open disposable injection
needle, according to the invention, is not required between
injections allowing an increase in sample throughput. In one
embodiment of the invention, sample solution may be drawn up into a
packed or open disposable injection needle. The injection needle is
subsequently introduced into the API source and sample solution is
sprayed from the injection needle tip with or without a solvent
gradient to elute sample from any packed material. Alternately, a
sample solution can be loaded into a non-disposable or reusable
needle and the needle is then inserted into and forms a seal with a
packed disposable injection needle. The packed injection needle is
then introduced into an API source and the sample solution and any
solvent gradient flows from the non-disposable needle through the
packed disposable needle. The resulting solvent and sample solution
is sprayed from the disposable needle tip into an API source. The
packing material in the disposable tip serves to desalt or further
clean the sample solution as well as to provide some sample
component separation due to solvent gradient flow, if desired.
Depending on the requirements of a specific analytical application,
packing material may be replaced by filter media according to the
invention to aid in sample cleanup with a minimum of dead
volume.
[0007] The invention eliminates the need for sample injector valves
or transfer lines into an API source, reducing sample dilution,
loss and contamination due to sample handing and transfer. When a
reusable needle is configured in the invention, the needle inner
bore and outer surface can be washed in between each sample
delivery and spraying step to reduce or eliminate, chemical noise,
cross talk or carry over from one sample to the next. The use of
disposable needles, configured according to the invention,
eliminates sample to sample cross talk or contamination without a
wash step between sample injections into the API source. Faster
cycle times or more rapid sample injection throughput can be
achieved by eliminating wash steps. Alternatively, a wash step can
be run for one or more reusable injection needles while sample
delivery and spraying is occurring with another injection needle or
needles. The invention reduces apparatus costs, sample losses,
sample contamination, and sample handling and minimizes solvent
consumption and waste while increasing sample throughput in flow
injection analysis with Atmospheric pressure ion sources. A direct
injection needle apparatus may be configured with other API inlets
in the same API source chamber as a means to increase analytical
flexibility within one API source apparatus. Ions produced from the
API source may be analyzed by an apparatus other than MS including
but not limited to ion mobility analyzers.
[0008] This invention also describes an apparatus and method for
operating the ionization source and/or sample inlet at ground or
near ground potential. The configuration will enable the direct
electrospray and allow simple interface to API and other sample
introduction methods, such as interface a thermal desorber, in this
case the thermal desorption process can happen in the ionization
region.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] 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.
[0010] FIG. 1 shows schematic diagram of the prior state of the art
IMS system.
[0011] FIG. 2 shows schematic diagram of the IMS apparatus of this
invention.
[0012] FIG. 3 shows the single syringe electrospray for IMS.
[0013] FIGS. 4A-B shows an embodiment of the electrospray
ionization source that could use a curtain gas section for heat
isolation of high temperature drift gas from the electrospray
needle.
DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS
[0014] Unless otherwise specified in this document the term "ion
mobility based spectrometer" is intended to mean any device that
separates ions based on their ion mobilities and/or mobility
differences under the same or different physical and/or chemical
conditions, the spectrometer may also include detecting the ions
after the separation process. Many embodiments herein use the time
of flight type IMS as examples; the term ion mobility based
spectrometer shall also include many other kinds of spectrometers,
such as differential mobility spectrometer (DMS) and field
asymmetric ion mobility spectrometer (FAIMS). Unless otherwise
specified, the term ion mobility spectrometer or IMS is used
interchangeable with the term ion mobility based spectrometer
defined above.
[0015] 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
[0016] 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.
[0017] 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.
[0018] The term ion mobility separator, and ion mobility
spectrometer, and ion mobility based spectrometers 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 their derived forms refers to, in its broadest
sense, any ion mobility based separation device that characterize
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. The IMS systems may operate in different drift
media, such as gas and/or liquid, in their pure or mixture forms.
The operating pressure may vary from low vacuum to a plurality of
atmospheric pressures.
[0019] 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 is also referred to the ion
transportation and/or ion filter section of a FAIMS or DMS
device.
[0020] 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. An
IMS can be used at different pressure conditions.
[0021] The apparatus and methods used for flow injection analysis
typically include an injector valve, transfer lines, fluid line
connections, an addition fluid delivery pump, a sprayer probe with
internal volume for ESI and APCI sources and a switching valve when
multiple injector valves are configured. Each of these elements
adds to the dead volume or mixing volume encountered when
delivering a sample solution into an API source in flow injection
analysis. Added dead or mixing volumes can cause sample dilution
due to diffusion or mixing of the sample with solvent during sample
solution flow into an API source. Sample can adsorb to the walls of
the valve, transfer line and probe transfer tube. Dilution of
sample and loss of sample to the inner surfaces of the flow pathway
results in reduced ion signal and analytical sensitivity. As liquid
flow rates are reduced the sample solution spends more time in the
transfer dead volumes. Increased transfer time results in increased
sample dilution and loss to transfer surfaces. Adsorbed sample can
bleed off valve, transfer line, connector and probe surfaces in
subsequent injections, contributing chemical noise and interference
peaks to acquired mass spectrum. Chemical noise or interference
peaks due to contamination from prior injected sample can reduce
the accuracy of quantitative measurements and compromise the limits
of detection. Increased valve, connector, transfer line and probe
surfaces require increased solvent flushing or cleaning time in
between sample injections to minimize subsequent sample carry over
or bleed. This required flushing increases solvent consumption and
increases the time between injections. Increased cleaning time
between injections decreases the number of samples that can be
injected in a given time period, reducing sample throughput.
[0022] The invention allows rapid flow injection analysis over a
wide range of liquid flow rates while minimizing solvent
consumption and waste and eliminating all injector valves, fluid
line connectors, transfer lines, probe liquid transfer tubes and
additional liquid flow delivery system apparatus. Sample dilution
or adsorption losses and solvent consumption are minimized with the
invention and apparatus costs are reduced by elimination of
components. Sample carry over or cross talk can be minimized with
washing of reusable injection needles or eliminated with disposable
or removable injection needles configured according to the
invention. The invention comprises the configuration and use of an
injector needle to draw up sample solution from a sample vial or
container into the injector needle and attached solvent reservoir,
transfer of the sample solution to an API source probe, passing of
the injector needle through the API source probe channel and
spraying of the sample solution from the tip of the injector needle
into an API source. Ions are produced from the sprayed solution in
the API source and are directed into the IMS where they are
analyzed. API sources may include but are not limited to ESI, APCI
or Inductively Coupled Plasma (OCP) ion sources.
[0023] Commercially available auto-injectors such as the Leap HTS
PAL system are configured with syringes for the uptake, movement
and injection of samples into injector valves. The syringes and
attached injector needles are typically mounted to a programmable
x-y-z position translator arm. Under pre-programmed control, sample
solution is removed from a selected sample vial or vials, the
loaded injector needle is moved to a position directly in-line with
the bore of an ESI probe assembly and the injector needle is
introduced through the bore of the ESI probe assembly in an ESI
source. Some commercially available auto-injectors are configured
with multiple syringes. FIA sample throughput can be increased
according to the invention when such multiple syringe
auto-injectors are used. Such a multiple syringe auto-injector
configuration can be operated whereby one syringe is spraying
sample solution into ES source while a second syringe is being
flushed and cleaned prior to loading the next sample solution to be
sprayed into the second injector needle and syringe. The syringes
can be partially or completely filled with sample solution for each
FIA run. The fill and spray liquid flow rates are determined by the
syringe size used and the plunger movement rate as programmed in
the auto-injector. Commercially available auto-injectors are
configured to flush the internal bore of the syringe and injection
needle and wash the injection needle external surface.
[0024] In one alternative embodiment, samples can be prepared using
the same syringe and direct sprayed into the IMS device for
analysis. The IMS device could be used to analyze complex samples
using simple step sample preparation methods on the fly. These
methods may include, but are not limited to, solid phase
microextraction (SPME) and microextraction by packed sorbent
(MEPS). A SPME fiber can be used to extract and preconcentrate
gaseous or aqueous analytes; the analytes will then be desorbed
into electrospray solvent for direct injection into the IMS for
analysis. Alternatively, volatile and semi-volatile analytes could
be thermally desorbed into the device and ionized in the
desolvation region via SESI or other API methods. MEPS is a
extraction technique that allows rapid sample preparation using
in-syringe solid phase extraction. The syringe would then be
directly inserted into the IMS for analysis. A variety of sorbents
are commercially available.
For prior art IMS systems, the Faraday detectors are operated at
ground or near-ground potential, and thus the other end of the
drift tube, the ion source end, is set at high voltage. For
positive ion detection, a positive voltage is applied at the ion
source end; similarly for negative ion detection, a negative
voltage is applied. State of art portable IMS systems have been
generally developed for gas monitoring only, since the gas-phase
sample can be guided into the ionization source via a
non-conductive flow path. For an ESI source, the liquid sample
needs to be delivered to the electrospray needle, and the liquid
sample is generally conductive. This fact makes the handheld
ESI-IMS challenging, since sample handling and injection pose a
safety hazard. Developing a floating pre-amplifier that could be
operated at high voltage allows the current invention to set the
ionization source at ground and the Faraday detector at a high
potential of the opposite polarity, i.e. positive potential for
negative ions and negative potential for positive ions.
[0025] FIG. 1 shows the prior art IMS systems, the ionization
source 100 is operated at the highest potential 101 of the drift
tube and the Faraday ion detector 102 is operated at the lowest
potential, substantially at ground potential 103. In various
embodiments, a time of flight type of ion mobility spectrometer
uses a ionization source 100, sample inlet, in case electrospray
ionization source, the sample inlet is also the ionization source
100, desolvation/ionization (reaction) region 104, ion gate 105,
drift region 107, aperture grid, ion detector 102, and
pre-amplifier 109 that are organized on a continuous potential
gradient connected with a resister chain. In case of prior art IMS,
the ionization source or sample inlet are at high potential and ion
detector is at low potential of this gradient. The current
invention describes using an ion detector 202 (typically a Faraday
plate) and a pre-amplifier 209 that operates at a high voltage 201,
such as high voltage (potential) can either be positive or negative
potential as shown in FIG. 2, in a range of 200-40000 V, in
particular 1000V, 5000 V, 10,000 V with similar gain and rise time
as the state-of-the-art amplifiers operating at near ground
potential (such as the Keithley 428-PROG Programmable Current
Amplifier, Cleveland, Ohio). In this non-limiting example, FIG. 2
shows a desolvation/ionization (reaction) region 204, ion gate 205,
drift region 207, and a sample inlet port 215. This invention
allows the ionization source 200, e.g. ESI or APCI source, and
components that may need to be accessible during the analysis
procedure to be set at substantially low voltage, such as, at
ground potential 203. It will isolate users from high voltage
components so that they can directly handle and inject samples into
the IMS.
[0026] Basic operation of the IMS system will involve obtaining a
sample and directly introducing the sample into the IMS device via
direct syringe spray or other API source. The main advantages of
the syringe direct spray include: 1) rapid testing, since a sample
could be analyzed within one minute; 2) no cross contamination,
since there is no carry-over from previous samples as the sample is
directly delivered from the syringe to the desolvation region of
the detector. Flow rates for common ESI methods are typically at
about 1-10, 10-100, and can be substantially increase to 100-1000,
1000-5000 .mu.L/min, etc., and each test may be completed in a
time-span ranging from several milliseconds seconds a minute,
depending on the amount of signal averaging required. This means
that very little solvent is required. If the analyte is
sufficiently concentrated such that direct measurement is possible,
an aqueous sample may be directly diluted with organic solvents,
such as methanol, for stable electrospray. The sample preparation
method may involve: a 10 .mu.L syringe may be preloaded with 1
.mu.L methanol; subsequently 1 .mu.L of aqueous sample would be
drawn up, and the syringe would then be inserted into the ESI
source for direct measurement. A thermal desorber/secondary
electrospray ionization (SESI) source module could also be used,
which would allow analysis of gas phase and solid phase samples.
SESI involves spraying electrospray solvent to deliver charged
solvent droplets into the desolvation region; the charged solvent
droplets are then used to ionize gas-phase samples.
[0027] In one embodiment, the direct syringe spray method uses a
single syringe that has a needle in the diameter that could be used
to directly spray sample into the spectrometer. For this purpose,
there is an electrical contact that is attached to the syringe
needle, but no other assembly component is needed for this
ionization source. The syringe is used to draw samples from a
liquid reservoir (sampling) and then spraying the sample into the
spectrometer using the same or a replacement needle. The single
syringe needle spray ionization source can be used with an prior
art ion mobility based spectrometer or the ion mobility based
spectrometer that the ionization source is at ground or near ground
potential.
[0028] The IMS system with the ionization source at near ground
potential will not only benefit the direct analysis of liquid
samples, but also allow easier sample introduction of gas and solid
sample. With a thermal desorber, it can also be used to analyze gas
phase and solid phase samples (first evaporated with the thermal
desorber) and then ionize using SESI or other API methods. The
combined thermal desorber/SESI subsystem will allow the user to
switch between a direct liquid injection mode and a thermal
desorption/gas sampling mode in-situ. The gas-phase sample, either
directly from the surrounding environment or from thermal
desorption of the solid-phase sample, is pulled into the
desolvation region via the gas inlet and ionized by the charged
droplets.
[0029] In various embodiments, the ground potential can also be
located in the middle of a drift tube, such as the sample inlet
before the ion gate. In this case, for positive ion measurement,
the ionization source is positive potential, the sample inlet port
location is at ground, and the Faraday detector is at negative
potential; the potential gradient will be reversed for negative ion
measurement. Setting the sample port at ground potential allow
users directly insert sample into the sampling port without safety
concerns.
[0030] In one embodiment of direct syringe spray ion mobility
spectrometer, as shown in FIG. 3 the liquid sample in syringe 301
is directly electrosprayed into the desolvation/reaction region 302
of the ion mobility spectrometer (where the curtain gas section is
not shown). In addition, a gas sample inlet port could be added to
the desolvation region where the gas phase sample could be ionized
undergoing secondary electrospray ionization. In case the syringe
needle 301 is replace by other ionization sources operated at
ground or near ground potential, the ionization process of the gas
phase sample will undergo other secondary ionization processes.
Ions formed in the desolvation region or reaction region are
analyzed by ion mobility analyzer 304 in the drift gas that is
preheated or mixed to designated temperature and/or other
conditions using the gas preheating/mixer subsystem 305.
[0031] In one embodiment of the ESI-IMS system, the electrospray
ionization source comprises an electrospray needle, curtain
(cooling) gas section and desolvation region and other components
of IMS. The ionization source is operated at substantially at
atmosphere pressure. The curtain section is placed between
desolvation region and electrospray needle (the ionization source),
the curtain section is to substantially thermally isolate the
electrosprayer needle from heated gas of desolvation region
(desolvation gas).
[0032] The electrospray ionization source consists of an
electrospray needle, curtain gas section and desolvation region.
The ionize source is operated at substantially at atmosphere
pressure. The lowered gas temperature at electrospray needle region
will provide a favorable environment for electrospraying by
avoiding boiling of the analyte solution in the electrospray needle
and at the tip of electrospray needle, by high temperature gas. It
is beneficial to have this curtain gas section to separate the
electrospray needle from the high temperature desolvation,
especially when a syringe needle is used as the electrospray needle
without other additional components surround the bare needle tip.
The electrospray needle is at a high electrical potential relative
to the adjacent electrodes to generate charged droplets. The
charged droplets generated from the electrospray needle will be
transported to the desolvation region through the curtain gas
section and desolvated at desolvation region and ions will be
generated. The ions in the desolvation region will be gated to the
drift region for ion mobility analysis. The ions in the desolvation
region can be further transported to high vacuum to be analyzed by
mass spectrometer. The curtain gas section provides positive or
negative gas flow. For positive cooling gas flow, the cooling gas
will be at lower temperature than the gas at the desolvation
region, and will lower the gas temperature at the electrospray
needle region. For negative cooling gas flow, the cooling gas flow
will lower the gas temperature at the electrospray needle region
than the gas temperature without negative cooling gas flow.
[0033] One embodiment of the invention is an ion mobility based
spectrometer apparatus comprising: an ionization source that is
connect to a first end drift tube and an detector that is connected
to the second end of the drift tube; a high potential is applied to
operate the spectrometer; at least one section of the ionization
source is set at ground or substantially near ground potential; and
at least one section of the detector and/or the preamplifier is set
at the high potential by connecting to an high voltage power
supply. The end of the ionization source is set at near ground
potential that is a voltage that is substantial safe to touch. The
high potential can be either positive or negative high potential.
The ion mobility based spectrometer has a sample introduction port.
The ground or near ground potential can be set at the sample
introduction port. The sample introduction port may locate inside
the ionization source or substantially downstream from the
ionization source toward the ion detector.
[0034] In various embodiments, an ion mobility based spectrometer
(FIG. 4A and 4B is shown as an example) does not necessary use an
electrospray ionization source. FIG. 4A and 4B shows a
desolvation/ionization (reaction) region 403, ion gate 410, drift
region 401, electrospray needle 405, drift gas flow 412, (optional)
aperture grid 414 and a detector 415. FIG. 4A shows a non-limiting
example of a curtain gas 407 at negative flow and FIG. 4B has a
curtain gas 407 at positive flow. The curtain gas section could be
used as a universal interface to bring charged particles or ions
into the ion mobility based spectrometer. All ionization sources
that are suitable the ion mobility based spectrometers could be
used. Such sources could be, but not limited to, secondary
electrospray ionization, DART ionization, DESI, MALDI, APCI, corona
discharge, radioactive ionization.
[0035] One embodiment of the ion mobility based spectrometer
apparatus has the ionization source set at a low potential for the
spectrometer and the ion detector is set at a high potential
whereby the ionization source on one end and the ion detector on
the other end are in fluid communication. The low potential is the
lowest potential for the spectrometer at ground or near ground
potential whereby the high potential is the highest potential for
the spectrometer. The high potential can be either positive or
negative potential. The ion mobility based spectrometer can
optionally have sample inlet which can be set at the lowest
potential. The ionization source can be various, such as
electrospray, DART, corona discharge, electron beam, radioactive
.sup.63Ni, but not limited to only these examples. When using
electrospray ionization, a fixed needle can be used as well as a
needle that is used for sampling and as the spray needle.
Therefore, the ion mobility based spectrometer can be operated
where an ionization source on one end is in fluid communication
with an ion detector on the other end; setting the ionization
source at a low potential of the spectrometer; and setting the ion
detector at a high potential of the spectrometer. The low potential
is set at the lowest potential for the spectrometer at ground or
near ground potential. The high potential is set at the highest
potential for the spectrometer and can be set at either positive or
negative potential. The spectrometer can be operated using a sample
inlet as well whereby the sample inlet is set at the lowest
potential. The sample can be electrosprayed from a needle which can
be used for sampling and spraying.
[0036] Another embodiment of the ion mobility based spectrometer
apparatus has a curtain gas section which has at least two plates
with an opening in the center. The plates are positioned to
administrator gas flow as such: a low temperature cooling gas flow
enters the center hole of the first plate on the needle side; a
high temperature desolvation gas flow enters the center hole of the
second plate on the desolvation section side; both gas flows are
exhausted at a gas exit located between the two plates. The plates
can be set at different potentials that guide ions entering the
first plate toward the second plate. The gas exit could be used as
a gas inlet for the cooling gas flow and exhaust both cooling gas
flow and the desolvation gas flow from the center hole of the first
plate. Therefore, the ion mobility based spectrometer administers a
curtain gas wherein the curtain gas flow is administered as such: a
low temperature cooling gas flow enters a center hole of a first
plate on the needle side; a high temperature desolvation gas flow
enters the center hole of a second plate on the desolvation section
side; both gas flows are exhausted at a gas exit. The plates can be
set at different potentials that guide ions entering the first
plate toward the second plate. The cooling gas flow can be used as
a gas inlet and exhaust whereby both the cooling gas flow and the
desolvation gas flow from the center hole of the first plate.
[0037] It is recognized that modifications and variations of the
invention disclosed herein will occur to those of ordinary skill in
the art and it is intended that all such modifications and
variations be included within the scope of the appended claims. The
contents of all of the patents and literature articles cited herein
are incorporated into this specification by reference.
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