U.S. patent application number 11/487735 was filed with the patent office on 2009-10-22 for microengineered nanospray electrode system.
Invention is credited to Richard Syms.
Application Number | 20090261244 11/487735 |
Document ID | / |
Family ID | 34897486 |
Filed Date | 2009-10-22 |
United States Patent
Application |
20090261244 |
Kind Code |
A1 |
Syms; Richard |
October 22, 2009 |
MICROENGINEERED NANOSPRAY ELECTRODE SYSTEM
Abstract
This invention provides a method of aligning a nanospray
capillary needle, a set of electrodes, and a capillary input to a
mass spectrometer. The electrode system is formed using
microengineering technologies, as an assembly of two separate
chips. Each chip is formed on an insulating plastic substrate. The
first chip carries mechanical alignment features for the capillary
electrospray needle and the API mass spectrometer input, together
with a set of partial electrodes. The second chip carries a set of
partial electrodes. The complete electrode system is formed when
the chips are assembled in a stacked configuration, and consists of
an einzel lens capable of initiating a Taylor cone and separating
ions from neutrals by focusing.
Inventors: |
Syms; Richard; (London,
GB) |
Correspondence
Address: |
MCDERMOTT, WILL & EMERY LLP;Attn: IP Department
227 WEST MONROE STREET, SUITE 4400
CHICAGO
IL
60606-5096
US
|
Family ID: |
34897486 |
Appl. No.: |
11/487735 |
Filed: |
July 17, 2006 |
Current U.S.
Class: |
250/288 |
Current CPC
Class: |
H01J 49/067 20130101;
H01J 49/0018 20130101; H01J 49/165 20130101 |
Class at
Publication: |
250/288 |
International
Class: |
H01J 49/26 20060101
H01J049/26 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 20, 2005 |
GB |
0514843.2 |
Sep 23, 2005 |
GB |
0519439.4 |
Claims
1. A microengineered nanospray ionisation device provided on a
single chip for coupling between a removable capillary nanospray
source input and a separate mass spectrometer, the device
comprising: a first alignment feature for cooperating with the
removable capillary input, the removable capillary input being
receivable into the device and providing for a transport of a fluid
to the ionisation device; a second alignment feature for
cooperating with a capillary output, the capillary output providing
an ion beam to the mass spectrometer; an orifice defining an ion
path between the capillary input and capillary output; at least one
conducting electrode provided in an orientation substantially
perpendicular to the ion path, and wherein each of the first
alignment feature, the second alignment feature, the orifice and
the at least one electrode are integrally formed in the chip, and
wherein the device is configured such that the removable capillary
input is operably provided within the device relative to the at
least one conducting electrode such that operably a potential
difference between the capillary input and the at least one
electrode is provided that ionises fluid on exiting the capillary
input such that it enters into the device in a spray form.
2. The device as claimed in claim 1 wherein the chip is constructed
from two substrates, the substrates being combined in a stack
configuration so as to form the chip.
3. The device as claimed in claim 2 wherein each of the two
substrates are provided with an insulating base, the substrates
being stacked relative to one another such that the resultant chip
has an insulating portion on an outer surface thereof.
4. The device as claimed in claim 2 wherein each of the two
substrates are formed with individual features, the features being
configured such that when the two substrates are brought together
the resultant combination of features define the first alignment
feature, the second alignment feature, the orifice and the at least
one electrode.
5. The device as claimed in claim 4 wherein a first substrate
defines a first grooved alignment feature for receiving the
removable capillary nanospray source input and a second grooved
alignment feature for the capillary output, the substrate
additionally having provided thereon the at least one conducting
electrode with a grooved upright edge arranged normal to the
substrate.
6. The device as claimed in claim 5 wherein the second substrate
has provided thereon at least one conducting electrode with a
grooved upright edge arranged normal to the substrate.
7. The device as claimed in claim 6 wherein on stacking the first
and second substrates relative to one another the at least one
electrodes provided on the first and second substrates form a
contiguous electrode and the electrode grooves combine to form
orifices.
8. (canceled)
9. The device as claimed in claim 1, wherein operably the removable
capillary nanospray source input provides for transportation of the
fluid from a liquid chromatography system.
10. The device as claimed in claim 1, wherein operably the
removable capillary nanospray source input provides for
transportation of the fluid from a capillary electrophoresis
system.
11. The device as claimed in claim 1 wherein operably the electrode
nearest to the capillary input is used first to create a Taylor
cone to extract ions from fluid contained in the capillary
input.
12. The device as claimed in claim 1 wherein the capillary output
forms the input to a mass spectrometer.
13. The device as claimed in claim 1 including at least two
electrodes and wherein at least a second electrode is used to focus
ions onto the capillary output.
14. The device as claimed in claim 1 where at least one electrode
is electrically heated and used to remove solvent
preferentially.
15. The device as claimed in claim 1, where at least one electrode
is segmented and used to provide a deflecting lateral electric
field to assist in separating ions from neutrals.
16. The device as claimed in claim 15, where the deflecting lateral
field is time varying and used to promote nebulisation.
17. The device as claimed in claim 1 wherein the chip contains at
least one drain hole for fluids.
18. The device as claimed in claim 3, in which at least a first
substrate base contains at least one inlet hole for gases and a
plenum chamber for operably surrounding the received capillary
input.
19. The device as claimed in claim 18, in which the plenum chamber
is arranged to create an axial flow of gas arranged as a sheath to
the spray.
20. The device as claimed in claim 3 wherein the insulating base is
formed in a photo-patternable polymer.
21. The device as claimed in claim 18 in which the substrate-base
perimeter, drain holes and gas inlets are defined by
photopatterning.
22. The device as claimed in claim 1, in which the alignment
features and electrodes are formed in a semiconductor.
23. The device as claimed in claim 22, in which the semiconductor
is silicon.
24. The device as claimed in claim 22, in which the semiconductor
is grooved by anisotropic wet chemical etching down crystal
planes.
25. The device as claimed in claim 22, in which the semiconductor
is grooved by deep reactive ion etching.
26. The device as claimed in claim 22, in which either the
alignment features or the electrodes are formed using deep reactive
ion etching.
27. The device as claimed in claim 3, in which the electrodes or
substrate-bases are formed by sawing.
28. The device as claimed in claim 1, in which the alignment
features and electrodes are formed in a metal.
29. The device as claimed in claim 28, in which the metal is
deposited by electroplating.
30. The device as claimed in claim 3, in which the substrate-bases
are formed in glass.
31. The device as claimed in claim 30 in which the glass is
photopatternable.
32. An integrated package comprising a nanospray source having a
capillary needle at an output thereof, a mass spectrometer having a
capillary needle at an input thereof and a nanospray ionisation
device provided between the source and the mass spectrometer, the
alignment features of the device providing connection ports for the
capillary needles so as to enable a fluid originating from the
source to be ionised and passed to the mass spectrometer.
Description
FIELD OF THE INVENTION
[0001] This invention relates to mass spectrometry, and in
particular to the use of mass spectrometry in conjunction with
liquid chromatography or capillary electrophoresis. The invention
particularly relates to a system and method that is implemented in
a microengineered configuration.
BACKGROUND
[0002] Electrospray is a common method of soft ionisation in
biochemical mass spectrometry (MS), since it allows the analysis of
fluid samples pre-separated by liquid chromatography (LC), the
ionization of complex molecules without fragmentation, and a
reduction in the mass-to-charge ratio of heavy molecules by
multiple charging [Gaskell 1997; Abian 1999]. It may be used in a
similar way with fluid samples pre-separated by other methods such
as capillary electrophoresis (CE).
[0003] The principle is simple. A voltage is applied between an
electrode typically consisting of a diaphram containing an orifice
and a capillary needle containing the analyte. Liquid is extracted
from the tip and drawn into a Taylor cone, from which large charged
droplets are emitted. The droplets are accelerated to supersonic
speed, evaporating as they travel. Coulomb repulsion of the charges
in the shrinking droplet results in fragmentation to ions when the
Rayleigh stability limit is reached. The resulting ions can be
multiply charged.
[0004] An electrospray mass spectrometer system contains a number
of key elements: [0005] An electrospray ionisation source capable
of interfacing to an LC or CE system [0006] An interface to couple
ions (in preference to molecules) into a vacuum chamber [0007] An
alignment and/or observation system capable of maximising the
coupling [0008] A mass filter and detector
[0009] Conventionally, the spray is passed from atmospheric
pressure via a chamber held at an intermediate pressure. Several
vacuum interfaces that use differential pumping to match flow rates
to achievable pressures have been developed [Duffin 1992]. The ion
optics normally consist of input and output orifices such as
capillaries, capillary arrays and skimmer electrodes, and
occasionally also a quadrupole lens operating as an ion guide in
all-pass mode. These components are used to maximise the ratio of
coupled ions to neutrals, which would otherwise swamp the
chamber.
[0010] Various methods are used to promote a well-dispersed spray
of small droplets and hence a concentrated flow of analyte ions.
Solvent can be preferentially driven off, by direct heating [Lee
1992]. Advantages may be obtained by the use of a sheath gas flow
[Huggins 1993], and nebulisation may be enhanced by ultrasound
[Hirabayashi 1998].
[0011] Alignment in electrospray is not critical, and the spray may
simply be directed towards the MS input. Alternatively, an off-axis
spray direction may be used to promote the separation of neutrals.
Co-axial lenses mounted directly on the capillary have been
developed to focus the spray [U.S. Pat. No. 6,462,337]; however,
there are limits to the electrode complexity that can be achieved
using such simple mechanical systems.
[0012] In a conventional electrospray system, with capillaries of
=100 .mu.m internal diameter, flow rates are of the order of 1
.mu.l min.sup.-1, and extraction voltages lie in the range 2.5 kV-4
kV. Flow rates and voltages are considerably reduced in so-called
"nanospray systems", based on capillaries having internal diameters
ranging down to =10 .mu.m [Wilm 1996]. Such capillaries are
relatively easy to fabricate, and are available with a range of
diameters and frits. Decreasing the capillary diameter and lowering
the flow rate also tends to create ions with higher mass-to-charge
ratio, extending the applicability further towards
biomolecules.
[0013] Because of the reduced size of the spray cone, alignment of
a nanospray source is more critical. Operation typically involves
mounting the source on a micropositioner and using a video camera
to observe the spray entering the vacuum inlet of an atmospheric
pressure ionisation (API) mass spectrometer. Sources are sold
customised for most popular brands of mass spectrometer. However,
such systems are large, complex and costly.
[0014] To reduce costs, a variety of attempts have been made to
integrate some of the components of nanospray ionisation sources.
Ramsey and Ramsey [1997] showed that a spray could be drawn from
the edge of a glass chip containing an etched capillary. Since
then, integrated capillaries with in-plane flow have been
demonstrated in many materials, especially plastics [Licklider
2000; Svedberg 2003]. In some cases, the fluid has been extracted
from a slot rather than a channel [Le Gac 2003]; in others, from a
shaped surface [Kameoka 2002]. Devices have also been formed in
one-dimensional arrays. Geometries in which the flow is passed
perpendicular to the surface of the chip have also been
demonstrated, often by deep reactive ion etching of silicon
[Schultz 2000; Griss 2002]. Such devices may be formed into
two-dimensional arrays.
[0015] Almost exclusively, the advances above consist of attempts
to integrate system sub-components leading up to the ion emitter.
They concentrate on the fluidic part of the system, ignoring the
problems of separating ions from neutrals, and of aligning the ion
spray to the inlet to the vacuum system. As a result, they are not
suitable for a low cost nanospray system, because accurate
alignment still requires expensive positioning devices.
[0016] There is therefore a need to provide a low cost nanospray
system.
SUMMARY
[0017] The invention addresses these and other problems by
providing a solution to the problems of alignment and electrode
mounting in a low-cost nanospray source by using
microelectromechanical systems technology to form appropriate
mechanical alignment and conducting electrode features on
insulating plastic substrates in an integrated manner. The approach
also allows integration of features for fluid drainage, spray
heating and sheath gas flow.
[0018] This invention provides a method of aligning a nanospray
capillary needle, a set of electrodes, and the capillary input to
an API mass spectrometer. The electrode system is formed using
microelectromechanical systems technology, as an assembly of two
separate chips. Each chip is formed on an insulating plastic
substrate. The first chip carries mechanical alignment features for
the capillary electrospray needle and the API mass spectrometer
input, together with a set of partial electrodes. The second chip
carries a set of partial electrodes. The complete electrode system
is formed when the chips are assembled in a stacked configuration,
and consists of an einzel lens capable of initiating a Taylor cone
and separating ions from neutrals by focusing.
[0019] Accordingly, the invention provides a system according to
claim 1 with advantageous embodiments provided in the dependent
claims thereto. The invention also provides a method of fabricating
such a system as detailed in the main independent method claim.
[0020] These and other features will be better understood with
reference to the following drawings.
BRIEF DESCRIPTION OF THE DRAWING
[0021] FIG. 1 shows in schematic form a microengineered nanospray
system aligning a nanospray needle with the capillary input to an
atmospheric pressure ionisation mass spectrometer according to an
embodiment of the present invention.
[0022] FIG. 2 shows construction of a microengineered nanospray
system as a stacked assembly of two chips according to an
embodiment of the present invention.
[0023] FIG. 3 is a process flow for construction of a
microengineered nanospray chip according to an embodiment of the
present invention.
[0024] FIG. 4a shows the layout of a lower and FIG. 4b the layout
of an upper substrate of a microengineered nanospray chip according
to an embodiment of the present invention.
[0025] FIG. 5 shows an assembly of a microengineered nanospray chip
according to an embodiment of the present invention.
[0026] FIG. 6 shows electrostatic operation of a microengineered
nanospray chip according to an embodiment of the present
invention.
[0027] FIG. 7 shows operation of the sheath gas inlet of a
microengineered electrospray chip according to an embodiment of the
present invention.
[0028] FIG. 8 shows thermal operation of a microengineered
electrospray chip according to an embodiment of the present
invention.
[0029] FIG. 9 shows electrode configurations realisable using a
stacked electrode assembly with FIG. 9a) being a closed pupil
arrangement, FIG. 9b) a horizontally split pupil, FIG. 9c) a
vertically split pupil and FIG. 9d) a quadrant pupil
arrangement.
DETAILED DESCRIPTION OF THE DRAWINGS
[0030] The invention will now be described with reference to
exemplary embodiments as provided in FIGS. 1 to 9.
[0031] The present inventor has realised that the benefit of MEMS
structures can be extended to nanospray applications. In MEMS,
widely used methods of lithographic patterning, oxidation and
metallisation are combined with specialised techniques such as
anisotropic wet chemical etching [Bean 1978] and deep reactive ion
etching [Hynes 1999] to form three-dimensional features in
crystalline semiconductors such as silicon. UV exposure of
specialised photosensitive polymers such as SU-8 may be used to
form three-dimensional features in plastics [Lorenz 1997]. These
methods may be used to combine insulating substrates, alignment
features and conducting electrodes. The present inventor has
realised that at least potentially, they may therefore form an
integrated nanospray ionisation source at low cost.
[0032] However, further difficulties remain with the realisation
that MEMS technology could be used to provide nanospray devices.
The device must typically operate with high voltages, in a wet
environment, so that electrical isolation and drainage are both
required. The substrate material most commonly used in MEMS,
silicon, is therefore not appropriate; however, other insulating
materials such as glasses are difficult to micromachine. To obtain
a stable spray, an electrode containing an axially aligned orifice
is typically required. To obtain efficient ion separation from
neutrals, electrostatic deflection or focusing is required. For
focusing, further electrodes containing aligned orifices are
needed. If the ion path is itself in the plane of a substrate, such
orifices are extremely difficult to form by in plane patterning
alone. Finally, it is desirable to integrate features capable of
providing a sheath gas around the spray, of promoting nebulisation,
and of preferentially evaporating solvent. For these and other
reasons there has heretofore not been possible an integrated MEMS
nanospray system. However, as will be understood from a review of
FIGS. 1 to 9, the present inventor has addressed these and other
issues.
[0033] FIG. 1 illustrates the concept of a microengineered
nanospray electrode system. A mass spectrometer 101 is provided in
a high-vacuum enclosure 102 pumped (for example) by a
turbomolecular pump 103. Ions are channelled into this chamber via
a further chamber 104 held at an intermediate pressure and pumped
(again, for example) by a rotary pump 105. The inlet to the vacuum
system is assumed to be a capillary 106. The exact configuration of
these components is not, it will be appreciated, important, apart
from the input capillary. For example, the filter element of the
mass spectrometer could be an ion trap, a quadrupole, a magnetic
sector, a crossed-field or a time of flight device. Equally, the
intermediate vacuum chamber could contain a range of components
including further capillaries and skimmer electrodes.
[0034] The overall input to the system is provided by a nanospray
capillary 107. Alignment between the nanospray capillary 107 and
the capillary input to the mass spectrometer 106 is provided by a
microengineered chip 108. The chip contains a first set of
mechanical alignment features 109 for the nanospray capillary and a
second set of alignment features 110 for the capillary input to the
mass spectrometer. The chip also contains a set of electrodes 111
set up perpendicular to the ion path, which may (for example, but
not exclusively) consist of diaphragm electrodes. Other features
may be integrated on the chip, including holes for drainage and gas
inlet.
[0035] FIG. 2 illustrates the main features of the chip 108. The
chip is constructed from two separate substrates, each carrying
microengineered features, which are arranged in a stacked assembly.
The first substrate consists of a base 201 formed in insulating
material and carrying a mechanical alignment feature for the
nanospray capillary corresponding to the feature 109 in FIG. 1,
which may (for example, but not exclusively) consist of a groove
202 etched into a conducting or semiconducting block 203. This
substrate also carries an alignment feature for the capillary input
to the mass spectrometer corresponding to the feature 110 in FIG.
1, which may again for example consist of a further groove 204
etched into a block of similar material 205. This substrate also
carries a set of electrodes corresponding to part of the features
111 in FIG. 1 and consisting of grooves 206 etched into upright
plates of similar material 207.
[0036] The second substrate again consists of a base 208 formed in
insulating material, and carrying a further set of electrodes
corresponding to a further part of the features 111 in FIG. 1 and
consisting of grooves 209 etched into upright plates of conducting
or semiconducting material 210. When the two substrates are stacked
together, the partial electrode sets combine to form complete
diaphragm electrodes with closed pupils 211.
[0037] Using three such electrodes, a so-called `einzel` or
unipotential electrostatic lens is formed. This type of lens allows
focusing of ions passing axially through the stack of electrodes in
a simple and controlled manner, and hence allows the ion spray to
be focused onto the capillary input to the mass spectrometer to
present a concentrated stream of analyte ions.
[0038] It will be appreciated that the alignment grooves 202 and
204, and the electrode grooves 206 and 209, may all be defined by
similar photolithographic processes, and may therefore be
registered together. This aspect provides a solution to the first
problem identified above in the Background to the Invention
section, of constructing an accurately aligned set of mechanical
features and electrodes. It will also be appreciated that the use
of an insulating substrate that may be patterned with drain holes
provides a solution to the problem of maintaining high voltages in
a wet environment. Finally it will be appreciated that a stacked
combination of partial electrodes provides a solution to the
problem of forming diaphragm electrodes arranged normal to a
substrate.
[0039] It will be appreciated by those skilled in the art that a
variety of materials and processes and may be used to realise
structures similar to FIG. 2. FIG. 3 shows a process, which is
intended to be exemplary rather than exclusive. The materials used
are low cost, and only three lithographic steps are required. The
process is based on crystalline silicon substrates on which plastic
virtual substrates are subsequently formed. The individual process
steps are indicated by a set of evolving wafer cross-sections
containing typical features.
[0040] In step 1, a (100)-oriented silicon substrate 301 is first
oxidised to form a SiO.sub.2 layer 302 on both sides. The SiO.sub.2
is patterned and etched to form a channel-shaped opening 303, by
(for example) photolithography and reactive ion etching. In step 2,
the underlying silicon substrate is anisotropically etched down
(111) crystal planes to form a V-shaped groove 304. Commonly an
etchant consisting of potassium hydroxide (KOH), water and
isopropanol (IPA) may be used for this purpose. This step defines
all capillary-mounting grooves and electrode pupils. The front side
oxide is removed, and the wafer is turned over.
[0041] In step 3, the wafer is spin coated with a thick layer of
the epoxy-based photoresist SU-8 305. This resist may be coated and
exposed in layers of at least 0.5 mm thickness, has excellent
adhesion, and is extremely rugged after curing, allowing it to be
used as a virtual substrate material after processing. The resist
is lithographically patterned to form a dicing groove 306 around
each die, together with any drain holes 307 and gas inlets.
[0042] In step 4, the front side of the wafer is metallised to
increase conductivity, typically with an adhesion layer of Cr metal
and a further thicker layer of Au 308. In step 5, the front side of
the wafer is coated in a photoresist 309. Since the wafer is
non-planar, an electrodeposited resist is used in preference to
spin-coated resist for this step. The resist is patterned to define
the outlines of all electrode and alignment blocks 310, and the
pattern is transferred through the metal. In step 6, the pattern is
transferred through the silicon wafer by deep reactive ion etching,
to form deep separation features 311 between elements. The
photoresist is then removed, and individual dies are separated in
step 7.
[0043] In step 8, two dies are stacked together to form a complete
nanospray chip, by soldering or bonding the metal layers 312
together. Alternatively, a conducting epoxy may be used for this
step. The chip is mounted on a carrier circuit board, and wirebond
connections 313 are made to appropriate features on the lower
substrate.
[0044] It will be appreciated by those skilled in the art that a
first alternative process is offered by forming the conducting
alignment and electrode elements by electroplating a metal inside a
mould, which may itself be formed by a sequence of patterning and
etching steps. However, this alternative requires the separate
formation of a mould, which is a laborious process.
[0045] It will also be appreciated by those skilled in the art that
a second alternative process is offered by forming the alignment
and electrode elements by sawing or otherwise eroding a conducting
layer attached to an insulating substrate. The substrate bases may
be also defined by sawing or by erosion, and the grooves may be
formed, by partial sawing. However, this alternative offers less
flexibility in the range of structures that may be created.
[0046] It will also be appreciated by those skilled in the art that
a third alternative process is offered by forming the substrate
bases from glass, which may be patterned by sawing or (in the case
of a photosensitive glass) by photopatterning. However, these
alternatives again offer less flexibility in the range of structure
that may be created. It will be appreciated that regardless of
their shortcomings that each of the mentioned alternatives may be
considered useful in the context of the present invention for
specific applications.
[0047] FIG. 4 shows the layout of individual substrates that can be
realised using the process of FIG. 3. The larger plastic
substrate-base 401 carries a mounting block 402 for the nanospray
capillary, formed in etched, metallised silicon and having an
etched alignment groove 403. The substrate carries a similar
mounting block 404 for the mass spectrometer input capillary, with
a similar etched alignment groove 405, and a set of partial
electrodes 406 with etched grooves 407. The electrodes are widened
at their extremities to assist in the stacked assembly and to allow
bonding. A large hole 408 through the plastic substrate-base
provides a drain, and a smaller hole 409 provides a channel for
sheath gas to flow into an etched plenum chamber 410. The smaller
plastic substrate-base 411 carries a further set of partial
electrodes 412 and further features 413 defining the sheath gas
plenum.
[0048] FIG. 5 shows assembly. The smaller substrate 501 is
inverted, aligned on top of the larger substrate 502, and the
electrodes are bonded together. The device is mounted on an
external printed circuit board, and wirebond connections 503 are
attached to the alignment features and electrodes. The chip is
aligned and connected electrically to the input capillary 504 of
the mass spectrometer, and the nanospray capillary 505 is inserted
into its input alignment feature and connected electrically. A stop
may be provided on each capillary to ensure that it may only be
inserted into its alignment groove for a fixed distance.
[0049] FIG. 6 shows electrostatic operation of the device. The
capillary input to the mass spectrometer and its alignment feature
601 both are assumed to be at ground potential. Assuming that the
nanospray capillary contains a conducting contact, a large DC
voltage V.sub.1 is applied to the nanospray capillary via its
associated mount 602. Alternatively the voltage may be applied via
a wire passing into the capillary. An intermediate voltage V.sub.2
is applied to the outer electrodes 603, 604 of the lens element and
a further voltage V.sub.3 to the centre element 605. The spray 606
is emitted from a Taylor cone created at the exit of the nanospray
capillary due to the potential difference V.sub.1-V.sub.2. The ion
stream is focused onto the capillary input to the mass spectrometer
607 due to the action of the focus voltage V.sub.3.
[0050] FIG. 7 shows operation of the sheath gas inlet. Sheath gas
is passed through the lower substrate-base 701 of the assembly via
an inlet hole 702. The gas flows into a plenum 703 formed in the
nanospray capillary mount 704. The gas leaks from the plenum around
the capillary, because it does not fully seal the orifice formed by
the grooves in the upper and lower nanospray capillary mount.
However, the natural taper of the capillary 705 ensures that the
majority of the leakage takes place in a forward axial direction
706, forming a sheath around the spray.
[0051] FIG. 8 shows a mode of thermal operation. A current I is
passed through one or more of the electrodes 801 to provide local
heating, which may preferentially evaporate more volatile
components in the spray such as a carrier solvent, thus enriching
the analyte ion stream.
[0052] FIGS. 9a-9d shows different possible electrode cross
sections. In the simplest realisation (FIG. 9a), the assembly of
two plates 901 and 902 with grooves formed by anisotropic wet
chemical etching will create electrodes with a diamond-shaped pupil
903. The edges of the pupil will be defined by the (111) crystal
plane angle .theta.=cos.sup.-1(1/ 3)=54.73.degree. of silicon. The
size of the pupils may be controlled, by varying the width of the
initial etched groove either continually or in discrete steps along
the axis. It will be appreciated by those skilled in the art that
other fabrication methods such as deep reactive ion etching may be
used to form U-shaped alignment grooves and electrode grooves,
which have greater inherent symmetry.
[0053] It will also be appreciated by those skilled in the art that
the electrodes may be segmented horizontally using additional
spacing 904 as shown in FIG. 9b, or segmented vertically using
additional etching 905 as shown in FIG. 9c. Both methods of
segmentation may be combined as shown in FIG. 9d. Segmented
electrodes of this type may be used to provide one- or two-axis
electrostatic deflection in addition to focusing. These additional
degrees of freedom offer the potential to improve the separation of
ions from neutrals, for example by inserting a bend or a dog-leg
into the ion path that neutrals cannot follow.
[0054] It will also be appreciated that the ability to provide
transverse electrostatic forces using segmented electrodes allows
the spray to be deflected in a time-varying manner. If the spray is
oscillated using a sinoidally varying lateral force, a periodic
perturbation may be induced in the spray flow. If the spatial
frequency of this perturbation is chosen to coincide with the
spatial frequency of Rayleigh instability in the flow pattern, the
flow will be encouraged to fragment into droplets, thus promoting
nebulisation.
[0055] What has been described herein is a microengineered
nanospray device. While advantageous embodiments have been
described it will be appreciated that certain integers and
components are used to illustrate exemplary embodiments and it is
not intended to limit the invention in any way except as may be
deemed necessary in the light of the appended claims. Furthermore
where the invention is described with reference to specific figures
it will be appreciated that components or features of one figure
can be freely interchanged with those of other figures without
departing from the scope of the invention.
[0056] While the reference to the miniature nature of the device of
the present invention has been made with reference to MEMS
technology it will be appreciated that within the context of the
present invention that the term MEMS is intended to encompass the
terms microengineered or microengineering and is intended to define
the fabrication of three dimensional structures and devices with
dimensions in the order of microns. It combines the technologies of
microelectronics and micromachining. Microelectronics allows the
fabrication of integrated circuits from silicon wafers whereas
micromachining is the production of three-dimensional structures,
primarily from silicon wafers. This may be achieved by removal of
material from the wafer or addition of material on or in the wafer.
The attractions of microengineering may be summarised as batch
fabrication of devices leading to reduced production costs,
miniaturisation resulting in materials savings, miniaturisation
resulting in faster response times and reduced device invasiveness.
Wide varieties of techniques exist for the microengineering of
wafers, and will be well known to the person skilled in the art.
The techniques may be divided into those related to the removal of
material and those pertaining to the deposition or addition of
material to the wafer. Examples of the former include:
[0057] Wet Chemical Etching (Anisotropic and Isotropic) [0058]
Electrochemical or photo assisted electrochemical etching [0059]
Dry plasma or reactive ion etching [0060] Ion beam milling [0061]
Laser Whereas examples of the latter include: [0062] Evaporation
[0063] Thick film deposition [0064] Sputtering [0065]
Electroplating [0066] Chemical vapour deposition (CVD) [0067]
Epitaxy
[0068] These techniques can be combined with wafer bonding to
produce complex three-dimensional, examples of which are the
interface devices provided by the present invention.
[0069] The words comprises/comprising when used in this
specification are to specify the presence of stated features,
integers, steps or components but does not preclude the presence or
addition of one or more other features, integers, steps, components
or groups thereof.
REFERENCES
[0070] Gaskell S. J. "Electrospray: Principles and practice" J.
Mass Spect. 32, 677-688 (1997) [0071] Abian J. "The coupling of gas
and liquid chromatography with mass spectrometry" J. Mass Spectrom.
34, 157-168 (1999) [0072] Duffin K. L., Wachs T., Henion J. D.
"Atmospheric-pressure ion-sampling system for liquid-chromatography
mass-spectrometry analyses on a benchtop mass-spectrometer" Anal.
Chem. 64, 61-68 (1992) [0073] Lee E. D., Henion J. D.
"Thermally-assisted electrospray interface for
liquid-chromatography mass-spectrometry" Rapid Comm. in Mass Spect.
6, 727-733 (1992) [0074] Huggins T. G., Henion J. D. "Capillary
electrophoresis mass-spectrometry determination of inorganic ions
using an ion spray-sheath flow interface electrophoresis" 14,
531-539 (1993) [0075] Hirabayashi A., de la Mora J. F. "Charged
droplet formation in sonic spray" Int. J. Mass Spect. 175, 277-282
(1998) [0076] Li G., Yin H. "Mass spectrometer electrospray
ionization" U.S. Pat. No. 6,462,337 [0077] Wilm M., Mann M.
"Analytical properties of the nanoelectrospray ion source" Anal.
Chem. 68, 1-8 (1996) [0078] Ramsey R., Ramsey J. "Generating
electrospray from microchip devices using electro-osmotic pumping"
Anal. Chem. 69, 1174-1178 (1997) [0079] Licklider L., Wang X. Q.,
Desai A., Tai Y. C., Lee T. D. "A micromachined chip-based
electrospray source for mass spectrometry" Anal Chem. 72, 367-75
(2000) [0080] Svedberg M., Petterson A., Nilsson S., Bergquist J.,
Nyholm L., Nikolajeff F., Markides K. "Sheathless electrospray from
polymer microchips" Anal Chem. 75, 3934-3940 (2003) [0081] Le Gac
S., Arscott S., Rolando C. "A planar microfabricated
nanoelectrospray emitter tip based on a capillary slot"
Electrophoresis 24, 3640-3647 (2003) [0082] Kameoka J., Orth R.,
Czaplewski D., Wachs T., Craighead H. G. "An electrospray
ionization source for integration with microfluidics" Anal. Chem.
74, 5897-5901 (2002) [0083] Schultz G. A., Corso T. N., Prosser S.
J., Zhang S. "A fully integrated monolithic microchip electrospray
device for mass spectrometry" Anal. Chem. 72, 4058-4063 (2000)
[0084] Griss P., Melin J., Sjodahl J., Roeraade J., Stemme G.
"Development of micromachined hollow tips for protein analysis
based on nanoelectrospray ionization mass spectrometry" J.
Micromech. Microeng. 12, 682-687 (2002) [0085] Bean K. E.
"Anisotropic etching of silicon" IEEE Trans. Electron Devices
ED-25, 1185-1193 (1978) [0086] Hynes A. M., Ashraf H., Bhardwaj J.
K., Hopkins J., Johnston I., Shepherd J. N. "Recent advances in
silicon etching for MEMS using the ASE.TM. process" Sensors and
Actuators 74, 13-17 (1999) [0087] Lorenz H., Despont M., Fahrni N.,
LaBianca N., Renaud P., Vettinger P. "SU-8: a low-cost negative
resist for MEMS" J. Micromech. Microeng. 7, 121-124 (1997)
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