Mass spectrometers work by ionizing molecules and then
sorting and identifying the molecules based on their mass-to-charge (m/z)
ratios. Several different types of ion sources are available for mass spectrometers.
Each ion source has particular advantages and disadvantages for different types
of molecules to be analyzed.
Much of the advancement in liquid chromatography (LC/MS)
over the last ten years has been in the development of ion sources. The introduction
of techniques that are performed at atmospheric pressure have been of particular
interest. These techniques do not require the use of complex pumps and pumping techniques
to create a vacuum. Common techniques include and are not limited to electrospray
ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric
pressure photoionization (APPI).
ESI is the oldest and most studied of the above-mentioned
techniques. Electrospray ionization works by a technique that relies in part on
chemistry of the molecules to generate analyte ions in solution before the analyte
reaches the mass spectrometer. The liquid eluent is sprayed into a chamber at atmospheric
pressure. The analyte ions are then spatially and electrostatically separated from
More recently, there has been a trend toward developing
ion sources that use low flow rates and sample amounts. Nanospray devices work by
being able to emit small amounts of analyte at low flow rates. At such flow rates
the properties effecting molecules are different from standard electrospray techniques.
However, at low flow rates and with analyte at very low levels it is often difficult
to detect certain ions. It would, therefore, be desirable to provide an apparatus
that can detect various ions at very low levels with increased sensitivity. These
and other problems have been overcome by the present invention.
SUMMARY OF THE INVENTION
The invention provides a mass spectrometry system, comprising
a nanospray ion source for providing radiative heating to an ionization region.
The nanospray ion source comprises a nanospray ionization device for producing ions
and a conduit adjacent to the ionization device for receiving ions from the ionization
device, the conduit comprising a a conductive material for providing radiative heating
to the ionization region and a detector downstream from the nanospray ion source
for detecting ions produced by the nanospray ion source.
The invention also provides a nanospray ion source for
providing radiative heating to an ionization region. The nanospray ion source comprises
a nanospray ionization device for producing ions and a conduit adjacent to the ionization
device for receiving ions from the ionization device, the conduit comprising a conductive
material for providing radiative heating to the ionization region.
The invention also provides a method for heating and desolvating
an analyte and sample in an ionization region of a nanospray ion source. The method
comprises radiating heat from a conductive conduit into the ionization region and
desolvating the analyte in the ionization region.
BRIEF DESCRIPTION OF THE DRAWINGS
- FIG. 1 shows a general block diagram of a mass spectrometry system of the present
- FIG. 2 shows a general block diagram of a second mass spectrometry system.
- FIG. 3 shows a side elevation of a first embodiment of the invention.
- FIG. 4 shows the side elevation view of FIG. 3 with added field lines.
- FIG. 5 shows a second embodiment of the present invention.
- FIG. 6A shows a third embodiment of the present invention.
- FIG. 6B shows a fourth embodiment of the present invention.
- FIG. 7 shows another embodiment of the present invention.
Before describing the invention in detail, it must be noted
that, as used in this specification and the appended claims, the singular forms
"a," "an," and "the" include plural referents unless the context clearly dictates
otherwise. Thus, for example, reference to "an emitter" includes more than one "emitter".
Reference to a "nanospray ionization device" or a "conduit" includes more than one
"nanospray ionization device" or "conduit". In describing and claiming the present
invention, the following terminology will be used in accordance with the definitions
set out below.
The term "adjacent" means near, next to or adjoining. Something
adjacent may also be in contact with another component, surround (i.e. be concentric
with) the other component, be spaced from the other component or contain a portion
of the other component. For instance, an "emitter" that is adjacent to a electrode
may be spaced next to the electrode, may contact the electrode, may surround or
be surrounded by the electrode or a portion of the electrode, may contain the electrode
or be contained by the electrode, may adjoin the electrode or may be near the electrode.
The term "analyte" refers to any sample including one or
more solvents mixed with the sample for analysis.
The term "atmospheric pressure ionization source" refers
to the common term known in the art for producing ions. The term has further reference
to ion sources that produce ions at ambient temperature and pressure ranges. Some
typical ionization sources may include, but are not be limited to electrospray,
APPI and APCI ion sources.
The term "charged droplet" or "charged droplet formation"
refers to the production of molecules comprising a mixture of analyte, solvent and/or
The term "conductive" or "conductive conduit" refers to
an apparatus that is thermally conductive, or may hold or radiate heat.
The term "conduit" refers to any sleeve, capillary, transport
device, dispenser, nozzle, hose, pipe, plate, pipette, port, orifice, orifice in
a wall, connector, tube, coupling, container, housing, structure or apparatus that
may be used to receive or transport ions or gas.
The term "conduit electrode" refers to an electrode that
may be employed to direct ions into a conduit. The electrode may be used to collect
ions in the conduit for further processing.
The term "corona needle" refers to any conduit, needle,
object, or device that may be used to create a corona discharge.
The term "detector" refers to any device, apparatus, machine,
component, or system that can detect an ion. Detectors may or may not include hardware
and software. In a mass spectrometer the common detector includes and/or is coupled
to a mass analyzer.
The term "electrospray ionization source" refers to an
emitter and associated parts for producing electrospray ions. The emitter may or
may not be at ground potential. Electrospray ionization is well known in the art.
The term "emitter" refers to any device known in the art
that produces small droplets or an aerosol from a liquid.
The term "first electrode" refers to an electrode of any
design or shape that may be employed for directing ions or for increasing or creating
a field to aid in charged droplet formation or movement.
The term "second electrode" refers to an electrode of any
design or shape that may be employed to direct ions or for increasing or creating
a field to aid in charged droplet formation or movement.
The terms "first electric field", "second electric field"
and "third electric field" refer to contributions to the total electric field by
individual electrodes as specified. The contribution to the electric field from
a particular electrode is regarded as the field due to the charges on that electrode
only (and the charges they induce on other electrodes). By the principle of superposition,
the total electric field at any point is the sum of the contributions to the field
at that point from all the electrodes present with the given applied voltages.
The term "ionization region" refers to an area between
any ionization source and the conduit.
The term "ion source" or "source" refers to any source
that produces analyte ions.
The term "molecular longitudinal axis" means the theoretical
axis or line that can be drawn through the region having the greatest concentration
of ions in the direction of the spray. The above term has been adopted because of
the relationship of the molecular longitudinal axis to the axis of the conduit.
In certain cases a longitudinal axis of an ion source or electrospray emitter may
be offset from the longitudinal axis of the conduit (For example if the axes are
orthogonal but not intersecting). The use of the term "molecular longitudinal axis"
has been adopted to include those embodiments within the broad scope of the invention.
To be orthogonal means to be aligned perpendicular to or at approximately a 90 degree
angle. For instance, the "molecular longitudinal axis" may be orthogonal to the
axis of a conduit. The term substantially orthogonal means 90 degrees ± 20
degrees. The invention, however, is not limited to those relationships and may comprise
a variety of acute and obtuse angles defined between the "molecular longitudinal
axis" and longitudinal axis of the conduit.
The term "nanospray ionization source" refers to an emitter
and associated parts for producing ions. The emitter may or may not be at ground
potential. The term should also be broadly construed to comprise an apparatus or
device such as a tube with an electrode that can discharge charged particles that
are similar or identical to those ions produced using nanospray ionization techniques
well known in the art. Nanospray emitters at low liquid flow rates use flow rates
ranging from 0.001 x 10-9 to 5000.0 x 10-9 L/Min. An emitter
tip orifice ranges from 5.0 x 10-6 to 50.0 x 10-9 meters in
The term "nebulizer" refers to any device known in the
art that produces small droplets or an aerosol from a liquid.
The term "non-pneumatic" refers to the production of charged
droplet formation by some method other than gas flow assistance nebulization. For
instance, electric or magnetic fields may be employed to aid in the formation of
charged droplets from emitter(s).
The term "pneumatic" refers to the use of gas flow assistance
in charged droplet formation.
The term "sequential" or "sequential alignment" refers
to the use of ion sources in a consecutive arrangement. Ion sources follow one after
the other. This may or may not be in a linear arrangement.
The invention is described with reference to the figures.
The figures are not to scale, and in particular, certain dimensions may be exaggerated
for clarity of presentation.
FIG. 1 shows a general block diagram of a mass spectrometry
system. The block diagram is not to scale and is drawn in a general format because
the present invention may be used with a variety of different types of mass spectrometers.
A mass spectrometer system 1 of the present invention comprises an ion source 3,
a transport system 5 and a detector 7.
The invention in its broadest sense provides an ion source
that produces a spectrum at low sample flow rates. The ion source 3 may comprise
a variety of different types of ion sources that emit ions. For instance, a nanospray
ionization source 4 with low sample flow rates. These ionization sources may in
certain instances be different from electrospray ion sources because of the differing
physical and chemical properties at the nanoscale level and consequential differences
in ion production mechanisms. In addition, often times the low flow rates used in
nanospray do not require a gas assist in production of charged droplet formation.
These low flow rates, therefore, allow for application of electric or magnetic fields
in the formation and collection of charged droplets.
Referring now to FIGS. 1-3, the nanospray ionization source
4 comprises a first emitter 9 and a first electrode 11 adjacent to the first emitter
9. The first emitter 9 and the first electrode 11 may be disposed anywhere in the
nanospray ionization source 4. FIG. 1 shows the option of having a housing 6 disposed
in the nanospray ionzation source 4. The housing 6 may be designed similar to a
faraday cage or shield. In this design a single potential may be applied to the
housing 6 so that it acts similar to an electrode. This electrode may then be used
in charged droplet formation after the analyte has been emitted from one or more
of the emitters. This is not a requirement of the system or nanospray ionization
source 4. Other housings, enclosures, electrodes, walls or devices may be employed
that are known in the art.
FIG 2 shows a second general block diagram of the invention.
In this embodiment of the invention, additional electrodes and emitters are shown.
For instance, the figure shows the first emitter 9, a second emitter 10, and a third
emitter 12. Each of the emitters are employed for emitting ions. Each of the emitters
9, 10 and 12 may be placed in various positions in and about the nanospray ionization
source 4. In addition, the figure shows the application of a variety of electrodes.
For instance, the figure shows the first electrode 11, a second electrode 13 and
a third electrode 15. The invention may comprise any number and combination of electrodes
and emitters. Note the figure shows the first electrode 11, the second electrode
13, and the third electrode 15 are adjacent to each other. This is not a requirement
of the invention. Each of the electrodes and emitters may be placed in various positions
and orientations about the housing 6.
FIG. 3 shows a side elevation view of a portion of the
present invention. The diagram is not to scale and is provided for illustration
purposes only. FIG. 3 shows the ion source 3 in a nanospray configuration. The nanospray
ionization source 4 comprises the first electrode 11, the second electrode 13, the
first emitter 9, and the second emitter 10. Also displayed is a conduit electrode
17. The first electrode 11 produces a first electric field for moving and directing
ions. The conduit electrode 17 is designed for creating a second electric field
that collects ions and directs them into transport system 5. Transport system 5
then directs the ions to the mass detector 7 (See FIGS. 1-3).
The first electrode 11, the second electrode 13 and the
conduit electrode 17 may be disposed in the housing 6. In other embodiments of the
invention the first electrode 11, the second electrode 13 and the conduit electrode
17 may comprise the housing 6. In this embodiment of the invention a single potential
is applied to the entire housing 6. The housing 6 may direct ions toward the conduit
19 and/or shield ions from the conduit 19. It should be noted that when the housing
6 is operating like an electrode ions are ejected from the second emitter 10 where
they travel toward the bottom of the housing 6. The spray becomes bifurcated due
to the strong electric fields produced by the housing 6 or the combination of the
conduit electrode 17 with the first electrode 11 and second electrode 13. The process
provides overall improved production of charged droplet formation. In addition,
the design and process separates gas phase ions from charged droplets that comprise
solvent, analyte and/or mobile phase. This is accomplished by the fact that the
gas phase ions are shed first from the spray that is emitted from the emitter. They
can then be immediately collected, whereas the charged droplets travel in different
directions from the conduit 19 or to the bottom of the housing 6 where they are
not then collected by the conduit 19. This provides for a simple and effective process
for collecting of gas phase ions without the other contaminating charged droplets
that would lower overall instrument signal to noise ratio or sensitivity.
More than one emitter may be employed with the present
invention. The first emitter 9, the second emitter 10 and the third ion emitter
12 may be disposed anywhere within the housing 6. Each emitter is designed so as
to emit ions at low flow rates into the ionization region 22. The emitter 9 comprises
a body portion 14 and an emitter tip 16. In FIG. 3 the first emitter 9 and the second
emitter 10 are positioned opposite each other. They are also adjacent to the first
electrode 11 and the second electrode 13. The conduit electrode 17 may comprise
a portion of the conduit 19 or may be separate from the conduit 19. The conduit
electrode 17 comprises a body portion 30 and an end portion 32. The conduit electrode
17 may be designed in the form of a flange (See FIG. 3).
In certain instances the end portion 32 of the conduit
electrode 17 may be blunt or pointed. In either case, the conduit electrode 17 may
be designed to aid in the collection of ions into the conduit 19. The conduit electrode
17 is connected to a voltage source that is designed to create a third electric
field (voltage source not shown in diagrams). The conduit electrode 17 creates a
third electric field for drawing ions into the conduit 19 for detection by detector
FIG. 3 shows the first electrode 11 and the second electrode
13 in an adjacent position disposed in the nanospray ionization source 4. In FIG.
3 they are also positioned adjacent to the first emitter 9 and the second emitter
10 and opposite the conduit electrode 17. The figure only shows a pair of electrodes.
However, a number or plurality of electrodes may be employed with the present invention.
The electrodes and emitters may also be positioned in other various locations and
FIG. 4 shows a side elevation of the same embodiment shown
in FIG. 3, but with exemplary equipotential lines produced as a result of the electrodes.
It should be noted that as the ions are emitted and flow from one or more emitters
toward the conduit 19, they are aided by the fields produced by the first electrode
11, the second electrode 13 and the conduit electrode 17. Different potentials may
be applied to each of the electrodes. However, when the first electrode 11 and the
second electrode 13 are connected to the conduit electrode 17, a single housing
is defined. A single potential can be applied to the single housing 6 to aid in
the formation and collection of ions from one or more ion emitter. In addition,
the housing 6 is designed in such a way that if the ions are not taken into the
conduit 19, they pass out of the ionization region 22 (See FIG. 3 and 4) and are
collected on various positions on the conduit electrode 17 or circulated to position
33 and can not re-circulate to contaminate the aerosol. In certain instances, these
are unwanted ions or ions of a particular mass to charge ratio that are not of interest
to the user. This provides for improved overall sensitivity of the device.
FIG. 5 shows a second embodiment of the present invention.
In this embodiment of the invention an electric heater 25 may be employed with the
present invention. The electric heater 25 may be stand-alone or comprise a portion
of the conduit electrode 17. The electric heater may also be positioned in any number
of directions and may be located in any number of locations in or on the conduit
electrode 17. The electric heater 25 may have its own internal voltage source or
may be electrically connected to an external source. The electric heater 25 is designed
for being able to provide direct irradiation to the ionization region 22. In addition,
an optional thermocoupl, closed feedback loop, computer and output screen may be
in connection with the electric heater 25. This feedback loop would allow for regulation
of the amount of radiative heat provided by the electric heater 25 to the ionization
region 22. This helps in the regulation of desolvation of the analyte and sample
that has been nanosprayed into the area.
FIGS. 6A and 6B show other embodiments of the present invention.
In these embodiments of the invention, a second conduit 40 may be employed with
the present invention. The second conduit 40 is designed for receiving and directing
heated gas toward the conduit electrode 17 as well as the ionization region 22.
The gas travels down the second conduit 40 and exists adjacent to the conduit electrode
17. The heated gas heats the conduit electrode 17 and is conducted toward the end
of the conduit so that heat may irradiate into the ionization region 22. The irradiative
heating provides for improved desolvation and concentration of the analyte ions
that enter the conduit electrode 17.
FIG. 7 shows an additional embodiment of the present invention
where an additional passageway 50 may be employed t direct heated gas toward the
ionization region 22.
Having described the apparatus of the present invention,
a description of the method of the present invention is now in order. A few different
methods of ionizing the analyte of the present invention are possible. The method
of ionizing the analyte in an ionization region of the nanospray ions source comprises
applying heat to a conductive conduit and radiating heat from the conductive conduit
to desolvate the analyte in the ionization region. A second method comprises radiating
heat from the end of a conductive conduit into an ionization region and then desolvating
the analyte in the ionization region.
Referring to FIGS. 5-6, the method of the invention will
now be described. FIG. 5 shows an embodiment of the invention that employs an electric
heater 25. Initially, the sample is introduced into the mass spectrometry system
1. It is then subject to ionization by the nanospray ionization source 4. The analyte
typically comprises solvent mixed with a sample. The analyte is subjected to nanospray
after it has traveled through the first emitter 10 and has been ejected into the
ionization region 22. Once the ions have entered the ionization region 22 they are
subject to the electric fields produced by the conduit electrode 17, the first electrode
11, and the second electrode 13. Typically, the analyte that is ejected into the
ionization region 22 comprises a large amount of solvent. It is desirable to reduce
the solvent as much as possible as the ions are produced from the first emitter
10. This can be accomplished using either a direct or indirect heating methodology.
These methods will now be discussed in more detail.
As mentioned, FIG. 5 shows the application of an electric
heater 25. The electric heater 25 provides a direct source of heat into the ionization
region 22. The irradiated heat then desolvates and dries the analyte and concentrates
it before it enters the conduit 19. As mentioned above, an optional feedback loop
may also be employed. In this case scenario an optional thermocouple 27, closed
feedback loop 29, computer 31 and output screen 35 may be in connection with the
electric heater 25 (not shown if FIGS.). This feedback loop would allow for regulation
of the amount of radiative heat provided by the electric heater 25 to the ionization
region 22. This helps in the regulation of desolvation of the analyte and sample
that has been nanosprayed into the area. This is accomplished by the optional thermocouple
27 sensing the surrounding ionization region 22 and then providing feedback to the
heater 25 by way of a closed feedback loop 29. A computer 31 and output screen 35
may be employed for a user to interact with the instrument feedback loop. The design
and method provides for an efficient way for desolvating and ionizing a sample and
FIG. 6 shows another embodiment of the present invention
and method. In this embodiment of the invention indirect heating and desolvation
of the analyte and sample is accomplished. Gas source 43 provides heated gas to
the system. The heated gas is injected so as to contact and heat the conduit 19.
In particular, the heated gas causes heating of the conduit body portion 30. The
heat is then conducted down the conduit body portion 30 to the conduit end portion
32. The conduit end portion 32 then irradiates the excess heat into the ionization
region 22 to heat the region as well as the analyte. Typically, this then provides
for desolvation of the analyte and sample. This concentrates the ions and improves
the overall sensitivity and detection of the instrument.
It is to be understood that while the invention has been
described in conjunction with the specific embodiments thereof, that the foregoing
description as well as the examples that follow are intended to illustrate and not
limit the scope of the invention. Other aspects, advantages and modifications within
the scope of the invention will be apparent to those skilled in the art to which
the invention pertains.
All patents, patent applications, and publications
infra and supra mentioned herein are hereby incorporated by reference
in their entireties.