U.S. patent application number 10/371152 was filed with the patent office on 2004-01-22 for method and apparatus for an electrospray needle for use in mass spectrometry.
Invention is credited to Park, Melvin A..
Application Number | 20040011954 10/371152 |
Document ID | / |
Family ID | 24564485 |
Filed Date | 2004-01-22 |
United States Patent
Application |
20040011954 |
Kind Code |
A1 |
Park, Melvin A. |
January 22, 2004 |
Method and apparatus for an electrospray needle for use in mass
spectrometry
Abstract
The present invention relates to a spray needle for use in
electrospray ionization (ESI) for mass spectrometry. A spray needle
is disclosed which is constructed to have an opening along its
length such that a sample solution may be more readily introduced
or loaded therein. Further, the design of the spray needle of the
invention is more durable than the prior art spray needles and may
be reusable. Because sample loading is more readily achieved, the
spray needle of the invention is appropriate for use with a fully
automated system for the analysis of samples.
Inventors: |
Park, Melvin A.; (Billerica,
MA) |
Correspondence
Address: |
WARD & OLIVO
708 Third Avenue
New York
NY
10017
US
|
Family ID: |
24564485 |
Appl. No.: |
10/371152 |
Filed: |
September 5, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10371152 |
Sep 5, 2003 |
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09639531 |
Aug 16, 2000 |
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6525313 |
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Current U.S.
Class: |
250/288 |
Current CPC
Class: |
H01J 49/167
20130101 |
Class at
Publication: |
250/288 |
International
Class: |
H01J 049/00; B01D
059/44 |
Claims
What is claimed is:
1. An apparatus for the introduction of sample into a mass
analyzer, comprising: a first component having a first end and a
second end; and a second component having a longitudinal bore
therethrough; wherein said second component is attached to said
second end of said first component such that said first component
and said longitudinal bore of said second component are
coaxial.
2. An apparatus according to claim 1, wherein said second component
has first and second surfaces, and wherein said first surface of
said second component is affixed to said first component at said
second end.
3. An apparatus according to claim 1, wherein said second component
comprises an electrically conducting foil.
4. An apparatus according to claim 1, wherein said second component
is thin.
5. An apparatus according to claim 1, wherein said second component
has a width of approximately 100 microns.
6. An apparatus according to claim 1, wherein said second component
is constructed from a chemically inert material.
7. An apparatus according to claim 6, wherein said chemically inert
material is selected from the group consisting of gold, platinum
and stainless steel.
8. An apparatus according to claim 1, wherein said second component
is shaped and positioned such that said longitudinal bore is
tapered from a first end thereof to a second end thereof.
9. An apparatus according to claim 1, wherein said first component
comprises a rigid material.
10. An apparatus according to claim 1, wherein said first component
comprises an electrically conductive material.
11. An apparatus according to claim 10, wherein said material is
steel.
12. An apparatus according to claim 1, wherein said first component
has a thickness of approximately equal to or less than 400
microns.
13. An apparatus according to claim 1, wherein said first component
has a rectangular cross section.
14. An apparatus according to claim 1, wherein said first component
has a circular cross section.
15. An apparatus according to claim 1, wherein said first component
has a triangular cross section.
16. An apparatus according to claim 1, wherein said second
component is cut at an angle .alpha. to said longitudinal bore
therethrough.
17. An apparatus according to claim 16, such that said angle
.alpha. is within the range of 0 to 90 degrees.
18. An apparatus according to claim 16, such that said angle
.alpha. is within the range of 30 to 60 degrees.
19. An apparatus according to claim 1, wherein said second
component comprises a proximal end and a distal end.
20. An apparatus according to claim 19, wherein said proximal end
is attached to said second end of said first component.
21. An apparatus according to claim 19, wherein said distal end is
constructed by cutting said second component at an angle .alpha. to
said longitudinal bore therethrough.
22. An apparatus according to claim 21, such that said angle
.alpha. is within the range of 0 to 90 degrees.
23. An apparatus according to claim 21, such that said angle
.alpha. is within the range of 30 to 60 degrees.
24. An apparatus according to claim 19, wherein said distal end is
narrower than said proximal end.
25. An apparatus according to claim 19, wherein said distal end has
a width of approximately 200 microns.
26. An apparatus according to claim 19, wherein said distal end has
a width in the range of approximately 20 to 50 microns.
27. An apparatus according to claim 19, wherein said opening has a
width of approximately 5 microns.
28. An apparatus according to claim 19, wherein said distal end
culminates in an angled point tip.
29. An apparatus according to claim 19, wherein said distal end
culminates in an circular tip.
30. An apparatus according to claim 19, wherein sample is
introduced from said spray needle into said mass analyzer at said
distal end.
31. An apparatus according to claim 1, wherein said second
component is coated with a polymer.
32. An apparatus for the introduction of sample into a mass
analyzer, said apparatus comprising a needle having first and
second ends, wherein said needle has an aperture along its length,
parallel to the axis of said needle extending from said second end
toward said first end.
33. An apparatus according to claim 32, wherein said needle
comprises a rigid material.
34. An apparatus according to claim 32, wherein said needle
comprises an electrically conductive material.
35. An apparatus according to claim 32, wherein said needle has a
thickness of approximately 400 microns.
36. An apparatus according to claim 32, wherein said needle has a
circular cross section.
37. An apparatus according to claim 32, wherein said first end
culminates in a tip.
38. An apparatus according to claim 37, wherein said tip comprises
a hole.
39. An apparatus according to claim 38, wherein said hole is
approximately 200 microns in diameter.
40. An apparatus according to claim 38, wherein said hole has a
diameter in the range of approximately 20 to 50 microns.
41. An apparatus according to claim 38, wherein said hole has a
diameter of approximately 5 microns.
42. An apparatus according to claim 32, wherein said second end
culminates in an opening.
43. An apparatus according to claim 32, wherein sample is
introduced from said needle into said mass analyzer at said first
end.
44. An apparatus for the introduction of sample into a mass
analyzer, said apparatus comprising a needle having first and
second ends, wherein said needle has a plurality of apertures along
its length, aligned parallel to said axis of said needle extending
from said second end towards said first end.
45. An apparatus according to claim 44, wherein said needle
comprises a rigid material.
46. An apparatus according to claim 44, wherein said needle
comprises an electrically conductive material.
47. An apparatus according to claim 44, wherein said needle has a
thickness of approximately 400 microns.
48. An apparatus according to claim 44, wherein said needle has a
circular cross section.
49. An apparatus according to claim 44, wherein said first end
culminates in a tip.
50. An apparatus according to claim 49, wherein said tip comprises
a hole.
51. An apparatus according to claim 50, wherein said hole is
approximately 200 microns in diameter.
52. An apparatus according to claim 50, wherein said hole has a
diameter in the range of approximately 20 to 50 microns.
53. An apparatus according to claim 50, wherein said hole has a
diameter of approximately 5 microns.
54. An apparatus according to claim 44, wherein said second end
culminates in an opening.
55. An apparatus according to claim 44, wherein sample is
introduced from said needle into said mass analyzer at said first
end.
56. An apparatus for the introduction of sample into a mass
analyzer, comprising: a first component having a first end and a
second end; a second component having a longitudinal bore
therethrough; and a plurality of fine elements; wherein said second
component is attached to said second end of said first component
such that said first component and said longitudinal bore of said
second component are coaxial, and wherein said plurality of
elements are positioned within said longitudinal bore of said
second component such that said elements extend therefrom.
57. An apparatus according to claim 56, wherein said second
component has first and second surfaces, and wherein said first
surface of said second component is affixed to said first component
at said second end.
58. An apparatus according to claim 56, wherein said second
component comprises an electrically conducting foil.
59. An apparatus according to claim 56, wherein said second
component is thin.
60. An apparatus according to claim 56, wherein said second
component has a width of approximately 100 microns.
61. An apparatus according to claim 56, wherein said second
component is constructed from a chemically inert material.
62. An apparatus according to claim 61, wherein said chemically
inert material is selected from the group consisting of gold,
platinum and stainless steel.
63. An apparatus according to claim 56, wherein said second
component is shaped and positioned such that said longitudinal bore
is tapered from a first end thereof to a second end thereof.
64. An apparatus according to claim 56, wherein said first
component comprises a rigid material.
65. An apparatus according to claim 56, wherein said first
component comprises an electrically conductive material.
66. An apparatus according to claim 65, wherein said material is
steel.
67. An apparatus according to claim 56, wherein said first
component has a thickness of approximately equal to or less than
400 microns.
68. An apparatus according to claim 56, wherein said first
component has a rectangular cross section.
69. An apparatus according to claim 56, wherein said first
component has a circular cross section.
70. An apparatus according to claim 56, wherein said first
component has a triangular cross section.
71. An apparatus according to claim 56, wherein said second
component is cut at an angle .alpha. to said longitudinal bore
therethrough.
72. An apparatus according to claim 71, such that said angle
.alpha. is within the range of 0 to 90 degrees.
72. An apparatus according to claim 71, such that said angle
.alpha. is within the range of 30 to 60 degrees.
73. An apparatus according to claim 56, wherein said second
component comprises a proximal end and a distal end.
74. An apparatus according to claim 73, wherein said proximal end
is attached to said second end of said first component.
75. An apparatus according to claim 73, wherein said distal end is
constructed by cutting said second component at an angle .alpha. to
said longitudinal bore therethrough.
76. An apparatus according to claim 75, such that said angle
.alpha. is within the range of 0 to 90 degrees.
77. An apparatus according to claim 75, such that said angle
.alpha. is within the range of 30 to 60 degrees.
78. An apparatus according to claim 73, wherein said distal end is
narrower than said proximal end.
79. An apparatus according to claim 73, wherein said distal end has
a width of approximately 200 microns.
80. An apparatus according to claim 73, wherein said distal end has
a width in the range of approximately 20 to 50 microns.
81. An apparatus according to claim 73, wherein said opening has a
width of approximately 5 microns.
82. An apparatus according to claim 73, wherein said distal end
culminates in an angled point tip.
83. An apparatus according to claim 74, wherein said distal end
culminates in an circular tip.
84. An apparatus according to claim 73, wherein sample is
introduced from said spray needle into said mass analyzer at said
distal end.
85. An apparatus according to claim 56, wherein said second
component is coated with a polymer.
Description
TECHNICAL FIELD OF THE INVENTION
[0001] The present invention relates generally to electrospray
ionization for mass spectrometry, and more particularly the
invention relates to an apparatus and method for producing an
electrospray from a sample solution for introduction into mass
spectrometer.
BACKGROUND OF THE PRESENT INVENTION
[0002] Mass spectrometry is an important tool in the analysis of a
wide range of chemical compounds. Specifically, mass spectrometers
can be used to determine the molecular weight of sample compounds.
The analysis of samples by mass spectrometry consists of three main
steps--formation of gas phase ions from sample material, mass
analysis of the ions to separate the ions from one another
according to ion mass, and detection of the ions. A variety of
means exist in the field of mass spectrometry to perform each of
these three functions. The particular combination of means used in
a given spectrometer determine the characteristics of that
spectrometer.
[0003] The present invention relates to the first of these
steps--the formation of gas phase ions from a sample material. More
particularly, the present invention relates to electrospray
ionization (ESI), one such means for producing gas phase ions from
a sample material. Electrospray ionization, was first suggested by
Dole et al. (M. Dole, L. L. Mack, R. L. Hines, R. C. Mobley, L. D.
Ferguson, M. B. Alice, J. Chem. Phys. 49, 2240, 1968). Generally,
in the electrospray technique, analyte is dissolved in a liquid
solution and sprayed from a needle. The spray is induced by the
application of a potential difference between the tip of the needle
and a counter electrode. Specifically, a voltage of several
kilovolts is applied between, for example, a metal capillary and a
flush surface separated by a distance of approximately 20 to 50
millimeters. Under the effect of the electric field, a liquid in
the capillary is dielectrically polarized at the end of the
capillary. The liquid is then pulled out into a cone, known as the
Taylor cone. The surface tension of the liquid at the pointed end
of the cone is no longer able to withstand the attraction of the
electric field, and this causes a small electrically charged
droplet to be detached. The charged droplet flies with great
acceleration to the flush counter electrode, effected by the
inhomogeneous electric field. During the flight of the liquid,
evaporation occurs and the droplets are slowed down. The spray
results in the formation of finely charged droplets of solution
containing analyte molecules. The larger ions become ionized, and
move towards the counter electrode to be transferred into the
vacuum system of a mass spectrometer, for example, through a narrow
aperture or capillary. Very large ions can be formed in this way.
For example, ions as large as 1 MDa have been detected by ESI in
conjunction with mass spectrometry (ESMS).
[0004] Electrospray, as in the present invention, facilitates the
formation of ions from sample material. It should be noted that the
size of the droplets produced in the ESI technique is dependant
upon the size of the sprayer used. The terms nanospray or micro
spray are used to indicate the use of very small sprayers in
electrospray technique. In other words, a sprayer having an opening
of less than about 10 .mu.m (microns) will produce a nanospray, a
sprayer having an opening of between approximately 10-100 .mu.m
(microns) will produce a micro spray, and a sprayer having an
opening of greater than 100 .mu.m (microns) will produce an
electrospray. For convenience, all three are referred to generally
as "electrospray," in as much as the present invention can be used
with each.
[0005] Referring to FIG. 1, depicted is an ionization source of
copending application Ser. No. 09/570,797 which shows an API source
for generating ions from a sample for subsequent analysis. As
shown, the ionization source 101 comprises spray chamber 1,
transfer region 2, first pumping region 5, second pumping region 4,
hinge 9, flange 10, and source block 16. During normal operation of
the ionization source 101 incorporating an ESI source it is
anticipated that numerous other elements may be used within
ionization source 101 as shown in FIG. 1. These may include vacuum
pump 15, ion transfer devices such as capillary 6 having an
entrance end 7, and exit end 19 and inner channel 8, multipole
devices such as pre-hexapole 11 and hexapole 12, as well as other
ion optic devices such as skimmers 13 and 14 and exit electrodes
17.
[0006] Initially, sample solution is formed into droplets at
atmospheric pressure by spraying the sample solution from a spray
needle 20 into spray chamber 1. The spray may be induced by the
application of a high potential between the tip of spray needle 20
and the capillary entrance end 7 within spray chamber 1. Then,
these sample droplets evaporate while in the spray chamber 1
thereby leaving behind sample ions. These sample ions are
accelerated or directed toward capillary entrance 7 and into
channel 8 by the electric field generated between spray needle 20
and capillary entrance 7. These ions are then transported through
capillary 6 to capillary exit 19, due to the flow of gas created by
the pressure differential between spray chamber 1 and first
transfer region 2.
[0007] The present invention relates particularly to the sprayers
used within electrospray ionization. Presently, known
electrospraying techniques teach that it is necessary to take
active steps to ionize the solution for analysis in the mass
spectrometer. For instance, FIG. 2 depicts a typical prior art
electrospray needle 21. As shown, needle 21 comprises an elongated
capillary structure tapered at one end to form tip 22. Needle 21
includes a plenum 24 to receive the liquid sample. Plenum 24 is
shown having an interval region larger than that of the capillary
section of needle 21. Liquid sample flows from plenum 24 through
upstream inlet 25 into the capillary section of ejection through
tip 26. Plenum 24 may be electrically conductive so that a voltage
applied to the plenum 24 will allow for the transfer of charge into
the liquid stream. Alternatively, a charge can be imposed on the
capillary section of needle 21. The applied voltage produces an
electrical field which is arranged such that it is at its highest
at the tip 26 such that the charge and field at tip 26 are high
enough to form the electrospray (i.e. charged droplets). Such a
prior art apparatus consists only of a single needle which, is a
very thin capillary, producing flow rates on the order of 20
nL/min. Further, such a needle must be loaded through its back end
(i.e. the plenum 24, as shown in FIG. 2), not through the tip 25.
This can be a very time consuming process.
[0008] Typically, nanospray needles are produced by taking a glass
capillary having a relatively large diameter and pulling and/or
machining it to a tip. Then a metal coating is vapor deposited onto
its outer surface, as disclosed in Mann U.S. Pat. No. 5,504,329
(Mann). The needle shown in FIG. 3 is the result of such a process.
Needles such as this are formed by using heat to soften glass
capillary tubing and pulling the tip end to form the needle's
tapered tip 27. These needles are generally single use, and must be
loaded with sample solution using micropipettes or some other means
for loading sample solution through the end 28 of the needle--the
end opposite the spray tip--using a micropipette.
[0009] Such needles are generally single use, and require the
sample to be reloaded through its back end after each use. The
prior art needles breed inaccuracy because the conditions have to
be replicated with each removal and replacement. In addition, the
fragile nature of the needles, combined with their limited use,
makes replacement costs a significant expense for their users.
Also, because these needles are extremely fragile, replacement is
frequent, which is both costly and time consuming.
[0010] Once these prior art needles are formed, a means of making
electrical contact is required. Prior art needles have been made
from small metal tubing (e.g., a steel syringe needle) or
dielectric tubing (e.g., glass, fused silica or polymer tubing). If
the needle is made of an insulating material, there are generally
three ways that the prior art teaches to make a needle capable of
electrical contact: (i) applying thin metal films directly onto the
dielectric tubing, (ii) supporting the dielectric tip inside a
secondary metal tube that contacts the liquid as it exits the
dielectric tubing and (iii) making a direct electric contact with
the solution from a remote position. The most commonly used of
these is the application of a thin metal film (e.g., gold or
platinum) directly onto the dielectric tubing.
[0011] However, due to their relatively inert nature, such metals
often show poor adhesion to the substrate materials, which reduces
ESI stability and eventually leads to ESI tip failure. As the
analyte is sprayed from the tip, the metal coating can rapidly
deteriorate through peeling or flaking. An attempted solution to
this problem has been to apply an interlayer material, such as
chromium or sulfur containing silanes, which adheres to both the
metal and the substrate. However, this has not entirely solved the
problem because such interlayer materials are subject to chemical
attack (i.e., dissolution, in the case of chromium, or bond
cleavage, in the case of silanes).
[0012] Valaskovic U.S. Pat. No. 5,788,166 (Valaskovic), for
example, uses a process of applying a metal overcoating on a
dielectric capillary needle. The capillary needle is constructed by
heating fused-silica tubing with a laser, then pulling the tube
until its internal diameter is in the range of 3 .mu.m. The pulling
process is followed by chemical etching and surface metallization.
The pulling results in formation of slowly tapered capillary edges
and a tip having a very small inner diameter. The chemical etching
process forms the tapered outer wall and a sharp point at the tip
of the needle. The surface metallization applies a thin metal
contact layer on the outer wall of the needle, to allow for
electrical contact. Then an electrically insulating overcoat is
applied. The overcoat essentially fixes the conductive metal
contact layer into place, although the electrically insulating
overcoat does not improve the adhesion of the metal to the
capillary.
[0013] Because the pulling process is used on fused silica tubing,
the extra step of metallization is required. The pulling process
results in slowly tapered edges, which culminate in a sharp point.
This point is then etched to create a narrow diameter opening at
the distal end (or tip) of the pulled tubing (i.e., forming a
needle). A needle such as this has the disadvantage of the
formation of "bubbles" in the solution within the needle, which
interferes with the spray of the solution--in fact, it may even
stop flow of the solution from the needle. In other words, having
such a narrow diameter at the distal end (or tip) of the needle
permits air pockets to form at the base of the tip. That is,
solution near the distal end may begin to evaporate, thereby
forming air pockets. These air pockets then permeate through the
solution toward the proximal end (due to the larger space
available), effectively "blocking" the spray of solution from the
needle. The glass structure of the needle also contributes to the
formation of these air pockets, as the solution is held within the
needle due to capillary action. In other words, the solution grips
the inner surface of the needle as the air pockets permeate through
the interior of the needle.
[0014] Other forms of electrospray include pneumatic assisted,
thermal assisted, or ultrasonic assisted, or the addition of arc
suppression gases so that higher voltages can be applied during
electrospray formation. Pneumatically assisted sprayers typically
have a much larger tip (greater than 100 .mu.m) than, for example,
nanosprayers (around 5 .mu.m) (See FIG. 4 for an example of a
nanospray needle). When using pneumatically assisted sprayers,
sample solution is typically pumped (for example, via a syringe
pump) into the sprayer. Sample aliquots can then be injected into
this solution stream either manually or automatically (i.e., by a
robot or other machine). However, the conventional process of
injecting sample into sprayers by machines is cumbersome, as the
process is difficult to control. That is, filling the needle
through its proximal end is not practical--since the opening at the
proximal end is so small. The glass capillary, with the opening at
the end, provides a measure of resistance during filling, and
therefore must be performed carefully with a micropipette.
[0015] Accordingly, prior to the present invention, a need has
existed for a multiple use, robust, spray needle and sprayer having
a geometry that eases the elimination of voids or bubbles. It is a
purpose of the invention to provide such a spray needle and
sprayer, as well as a method of operating a mass spectrometer using
a spray needle and sprayer to produce an electrospray formed from a
sample solution. It is also a purpose of the present invention to
provide a means and method of operating a mass spectrometer which
utilizes the apparatus with a variety of ionization techniques
(i.e., ESI, MALDI, etc.)
SUMMARY OF THE INVENTION
[0016] One aspect of the present invention is to provide an
apparatus and method of facilitating the introduction of a liquid
sample into a mass spectrometer for subsequent analysis. To address
the foregoing problems, the present invention provides a sprayer
which is reusable, robust, and easy to load. Furthermore, the
present invention provides a spray needle and sprayer which has a
geometry that minimizes the formation of voids or bubbles, thereby
providing improved results in the analysis of the sample solution,
as demonstrated in the mass spectra of FIG. 10 obtained in a mass
analysis performed using the spray needle according to the
preferred embodiment disclosed herein.
[0017] Specifically, one embodiment of the present invention
comprises a two component spray needle (i.e., a support and a tip).
Advantages of a spray needle having this configuration include ease
of sample loading, minimization of bubble formation or voids,
durability, reusability, ease of automation, ease of replacement,
increased reproduction of analysis results, etc. For example, if
after repeated uses the tip is no longer functional, a new tip may
be constructed, and attached to the intact support.
[0018] Another embodiment of the present invention provides a
single component spray needle and sprayer having an opening along
its length to facilitate the introduction or loading of a sample
solution into the needle. In other words, the spray needle can be
filled with the solution through its an elongated slit along its
length by merely dipping the needle into the sample solution. This
allows for the liquid to be drawn in through the tip into the body
of the spray needle via capillary action. At the same time, this
may limit the droplet size upon ejection of the sample from the
needle. The opening also provides for unique spraying capabilities
due to its geometry and length. Furthermore, because the spray
needle does not need to be loaded via the rear opening (or proximal
end), the spray needle can be easily employed within automated
systems.
[0019] Yet another embodiment of the present invention comprises a
single unit spray needle having a slit along its length as well as
having the tip end diagonally cut (as shown in FIGS. 7A-7C). The
construction of this embodiment provides a robust needle which
facilitates the introduction of sample solution into the spray
needle through its proximal end (or tip) as well as facilitates the
production of very small sample droplets for ionization. In
addition, the spray needle of this embodiment can be loaded through
a dipping process, making it ideal for use with an automated
process. The needle of this embodiment also minimizes the formation
of bubbles or voids in the sample solution.
[0020] Yet a further embodiment of the invention comprises a
multi-tip spray needle (as shown in FIGS. 11A-C). Such a spray
needle preferably embodies the structure of the preferred
embodiment shown in FIGS. 5A-C, but alternatively, may embody the
alternative structures shown in FIGS. 6A-C and 7A-C. Specifically,
a multi-tip spray needle according to the invention may comprise a
plurality of (e.g., 20, 50, 100, etc.) very fine (i.e., on the
order of 50 .mu.m or less) elements at the needle's distal end. An
advantage of such a multi-tip structure is the facilitation of the
spray of extremely fine droplets, having the effect of maximizing
the introduction of sample ions into the mass analyzer from the
source region.
[0021] Other objects, features, and characteristics of the present
invention, as well as the methods of operation and functions of the
related elements of the structure, and the combination of parts and
economies of manufacture, will become more apparent upon
consideration of the following detailed description with reference
to the accompanying drawings, all of which form a part of this
specification.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] A further understanding of the present invention can be
obtained by reference to a preferred embodiment set forth in the
illustrations of the accompanying drawings. Although the
illustrated embodiment is merely exemplary of systems for carrying
out the present invention, both the organization and method of
operation of the invention, in general, together with further
objectives and advantages thereof, may be more easily understood by
reference to the drawings and the following description. The
drawings are not intended to limit the scope of this invention,
which is set forth with particularity in the claims as appended or
as subsequently amended, but merely to clarify and exemplify the
invention.
[0023] For a more complete understanding of the present invention,
reference is now made to the following drawings in which:
[0024] FIG. 1 depicts an atmospheric pressure ionization (API)
source block for introducing ions from an ionization source (e.g.,
ESI, etc.) into a mass analyzer for subsequent analysis;
[0025] FIG. 2 shows a lengthwise cross-sectional view of a prior
art nanospray needle as shown in Myers U.S. Pat. No. 5,975,426;
[0026] FIG. 3 shows a lengthwise cross-sectional view of a prior
art nanospray needle according to Mann U.S. Pat. No. 5,504,329;
[0027] FIG. 4 is a microphotograph showing a prior art nanospray
needle;
[0028] FIG. 5A shows a side view of a preferred embodiment of a
spray needle according to the present invention;
[0029] FIG. 5B shows an end view of the spray needle depicted in
FIG. 5A;
[0030] FIG. 5C shows a top plan view of the spray needle depicted
in FIG. 5A;
[0031] FIG. 6A shows a top plan view of an alternate embodiment of
the spray needle in accordance with the present invention;
[0032] FIG. 6B shows an end view of the spray needle shown in FIG.
6A;
[0033] FIG. 6C shows a side view of the spray needle shown in FIG.
6A;
[0034] FIG. 7A shows a top plan view of another alternate
embodiment of the spray needle according to the present
invention;
[0035] FIG. 7B shows a side view of the spray needle shown in FIG.
7A;
[0036] FIG. 7C shows an end view of the spray needle shown in FIG.
7A;
[0037] FIG. 8 depicts the electrospray needle shown in FIGS. 5A-C
integrated within an electrospray assembly according to the present
invention;
[0038] FIG. 9 depicts the electrospray assembly showing in FIG. 8
integrated into an ionization source block;
[0039] FIG. 10 shows a mass spectra obtained in a mass analysis
performed using the spray needle of FIGS. 5A-C in accordance wit
the present invention; and
[0040] FIG. 11A shows a side view of a yet another alternate
embodiment of a spray needle according to the present
invention;
[0041] FIG. 11B shows an end view of the spray needle depicted in
FIG. 11A;
[0042] FIG. 11C shows a top plan view of the spray needle depicted
in FIG. 11A.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
[0043] As required, a detailed illustrative embodiment of the
present invention is disclosed herein. However, techniques, systems
and operating structures in accordance with the present invention
may be embodied in a wide variety of forms and modes, some of which
may be quite different from those in the disclosed embodiment.
Consequently, the specific structural and functional details
disclosed herein are merely representative, yet in that regard,
they are deemed to afford the best embodiment for purposes of
disclosure and to provide a basis for the claims herein which
define the scope of the present invention. The following presents a
detailed description of a preferred embodiment (as well as some
alternative embodiments) of the present invention.
[0044] Referring initially to FIG. 5A, shown is a side view of a
preferred embodiment of spray needle 31 according to the present
invention. As shown, spray needle 31 according to the preferred
embodiment of the invention comprises two component parts, support
30 and foil 33.
[0045] Support 30 is preferably constructed from a rigid and
electrically conductive material (e.g., steel, etc.). It is also
preferred that the support 30 be a solid yet thin structure (i.e.,
on the order of 400 .mu.m or less in thickness). The thickness of
the support contributes to the determination of the loading and
spray properties of the sprayer (i.e., how fast the solution will
flow into the sprayer, the potential at which the sprayer must be
operated, the optimal distance between the sprayer and ESI orifice,
and the solution flow rate during spray etc.), because the
thickness of support 30 determines the size of foil 33. It is
further preferred, as shown in FIG. 5B, that support 30 have a
rectangular cross section. This geometry eases the elimination of
voids or bubbles which interfere with the spray of the solution.
Alternatively, support 30 may have a different cross-sectional
shape (e.g., triangular, circular, hexagonal, etc.). Such change in
the shape of support 30, however, may alter the spray properties of
the sprayer. Thus, different structures may be ideal for different
sample solutions.
[0046] Generally, foil 33 may be constructed using a piece of
electrically conducting "foil" which is cut at an angle .alpha., as
shown in FIG. 5A. In the preferred embodiment, the foil 33 is
attached to the outer surface of support 30 and is in direct
contact with a portion of one end of support 30, as depicted in
FIGS. 5A and 5C. Foil 33 is attached such that it is in electrical
contact with support 30. Preferably, an adhesive is used to attach
foil 33 to support 30, but other means for attaching the foil 33 to
support 30 may be used, such as soldering. Foil 33 is preferably
constructed from a chemically inert and easily cleaned material
(e.g., gold, copper, platinum, stainless steel (because of its
limited reactivity to certain compounds), etc.). For example,
certain species are not readily protonated, but will accept, for
example, silver or copper ions as adducts. Therefore, use of such
different materials for foil 33 may alter the life and spray
properties of the spray needle 31 (i.e., durability, sample loading
flow rate, the potential at which the spray needle must be
operated, the optimal distance spray needle 31 is positioned from
the capillary orifice (see FIG. 9), the spray flow rate, etc.)
[0047] Alternatively, other materials might be used in the
construction of foil 33, depending on the particular
electrochemical or reactive properties desired. For example, the
utilization of copper instead of gold as the material for foil 33
will result in the formation of copper ions, and has the potential
for forming complexes with analyte species. Some of such complexes
have been known to enhance signal intensity in certain
analyses.
[0048] Preferably, foil 33 is constructed from a very thin piece of
metal (i.e., about 100 .mu.m in thickness). However, the thickness
of foil 33 may be chosen such that needle 31 obtains certain
properties (i.e., durability, formation, spray type, etc.). In
fact, the choice of thickness of foil 33 may depend on the material
from which foil 33 is constructed (e.g., gold, copper, etc.).
[0049] In the preferred embodiment of the spray needle 31 of the
present invention as shown in FIGS. 5A-5C, tip 32 may be formed by
wrapping or folding a portion of foil 33 around a portion of
support 30 and adhering foil 33 to support 30. Once wrapped or
folded, the exposed end of foil 33 is preferably cut at an angle
.alpha. 34, as shown in FIG. 5A, thereby forming tip 32. Foil 33 is
preferably attached to support 30 in such a way that it conforms to
the shape of support 30 (e.g., if support 30 is rectangular, then
foil 33 would conform to this rectangular shape (i.e., it would
resemble a straight edged `U` shape)).
[0050] Alternatively, support 30 may comprise an opening on one of
its ends for accepting an end of foil 33 and securing foil 33
therein. Among other things angle .alpha. 34 and the thickness of
foil 33 each contribute to the determination of the loading and
spray properties of the sprayer (i.e., the rate at which the
solution will flow into the sprayer, the potential at which the
sprayer must be operated, the optimal distance between the sprayer
and ESI orifice, and the solution flow rate is during spray, etc.)
Preferably, angle .alpha. 34 is approximately 45 degrees. This
provides optimum performance of the spray needle 31 during
operation. Of course, angle .alpha. 34 may be any angle between
zero and ninety degrees, but importantly, the specific angle
.alpha. 34 used will affect the properties and/or performance of
spray needle 31. Specifically, angle .alpha. 34 aids in determining
the flow rate of the spray, and, in turn, the accuracy and
exactness of the mass analysis results. Also, choice of angle
.alpha. 34 for optimum results may vary in accordance with the
sample or technique being used, the material used for foil 33, the
potentials being applied, the distance between the needle 31 and
the ESI orifice, etc.
[0051] Of course, the relative dimensions of support 30 and foil 33
may differ from that shown in FIGS. 5A-C. Specifically, the
geometry of support 30 (and therefore the assumed geometry of foil
33 when attached to support 30) may differ from the geometry of
foil 33 at the spraying end. For example, foil 33 at support 30 as
shown in FIG. 5A, is rectangular, while foil 33 at tip 32 may be
slightly "crushed" so as to produce a gap narrower than the
thickness of support 30. Although this may reduce the solution flow
rate throughout the sample loading and spray process, it will
importantly allow for the spray of smaller droplets of the sample
solution during the ESI process and result in enhanced performance
of the ESI.
[0052] The construction of the apparatus and attachment of foil 33
to support 30 is unique because the opening in the resulting
invention is along the length. This allows sample to be loaded into
the needle 31 anywhere along the aperture (as indicated by 33A)
along its length by a simple dipping process. Further, the needle
31 maintains the ability to produce very small droplets (or larger
ones), can be extremely robust, is reusable, convenient for use in
fully automated systems, etc.
[0053] More specifically in the preferred embodiment shown in FIGS.
5A-C, the sample solution may be loaded into needle 31 aperture
33A. To load the sample, the invention may be held vertically, and
tip 32 lowered into a sample solution. The sample solution will be
drawn into foil 33 via capillary action, thereby filling the
internal cavity within foil 33 (created when foil 33 is wrapped or
folded around support 30). Due to the case of filling foil 33 with
sample, and its heightened durability over prior art needles, the
invention may be repeatedly cleaned and reused.
[0054] This reusability, coupled with the geometric structure of
the needle (which eases the elimination of interfering voids or
bubbles) may be especially important in an alternative embodiment
which utilizes the invention for the fully automated analysis of
samples in conjunction with a robot. Another variation uses the
invention to accomplish sequential analysis of a multitude of
samples.
[0055] Importantly, use of a spray needle according to the
preferred embodiment disclosed herein provides improved results in
the analysis of a sample solution, as demonstrated by the mass
spectra 50 shown in FIG. 10 obtained in a mass analysis performed
using the spray needle according to the preferred embodiment.
[0056] Referring next to FIGS. 6A-6C, shown is an alternate
embodiment of a spray needle 41 in accordance with the present
invention. In particular, shown in FIG. 6A is a top plan view of
spray needle 41 comprising an elongated structure having an inner
channel there through. Spray needle 41 further includes a tapered
end 36 which culminates into an opening at tip 42. This embodiment
of the invention further comprises an opening 35 (or slit) which
extends along substantially the entire length of needle 41 (i.e.,
from tapered end 36 all the way to the other end of needle 41). Of
course, optionally, the opening 35 may extend for only a short part
of needle 41. Also, opening 35 may be a series of holes or openings
aligned lengthwise along needle 41 rather than a single continuous
slit, as shown. Opening 35 (or a series of openings) provides the
user with an improved method of loading the sample solution into
the spray needle, as well as providing a variety of options as to
controlling the spray of the sample from the needle. For example,
opening 35 provides a greater area for the sample to be drawn into
the spray needle 41, and therefore enhances the loading
characteristics and abilities of needle 41. That is, needle 41 may
be loaded quickly and efficiently, allowing the user to load sample
via an automated process.
[0057] As shown, needle 41 is preferably cylindrical in structure.
Of course, other structures may be used (i.e., rectangular, square,
triangular, etc.). It is also preferred that needle 41 be
constructed from a solid, yet thin material (i.e., on the order of
400 .mu.m or less in thickness). It is also preferred that needle
41 include an opening at tip 42 having a diameter (if needle 41 is
cylindrical) of between about 20 .mu.m and 50 .mu.m. Alternatively,
needle 41 may be used in an nanospray ionization source, and
therefore would preferably include an opening at tip 42 having a
diameter (if needle 41 is cylindrical) of approximately 5 .mu.m. As
the above demonstrates, the opening in tip 142 determines the spray
properties of the needle (i.e., flow rate etc.).
[0058] Turning next to FIG. 7A, shown is a top plan view of yet
another alternate embodiment of a spray needle according to the
present invention. Specifically, shown is spray needle 43
comprising an elongated body 42 (shown here as being cylindrical,
but other shapes may be used) having an inner channel therethrough.
Spray needle 43 further includes an opening 39 along the length of
body 42 is cut at an angle b 44 (as shown in FIG. 7C) such that a
substantial opening 37 is created at the spray end of needle 43.
Also, opening 37 is such that a narrow sharp tip 38 is created at
the end of needle 42. Tip 38 provides a means for distributing
sample droplets in a variety of different sizes (i.e., a larger
opening at tip 38 would produce larger droplets). For example, a
high electric field maintained at tip 38 may result in the solution
being discharged from tip 38 in the form of a Taylor Cone.
[0059] The embodiments of a spray needle according to the invention
shown in FIGS. 5-7 may also be treated on the internal area of the
spray end of the needle of FIGS. 5A, 6A or 7A with polypropylene or
some other polymer coating. This treatment allows a needle to be
more readily cleaned, while not interfering with the functionality
of the needle. Further, this treatment makes the inner surface of
the needles spray end inert with respect to the sample solution
being tested and will therefore prevent any negative effects which
may be caused by the substance used for the body of the needle
(i.e., gold, copper, stainless steel, etc.).
[0060] Turning next to FIG. 8, shown is one embodiment of the
integration of the spray needle of FIGS. 5A-C within an
electrospray assembly according to the present invention. Of
course, similarly, the alternative embodiments of a spray needle
according to the invention (i.e., as shown in FIGS. 6A-C, 7A-C and
11A-C) may be integrated with an electrospray assembly as shown in
FIGS. 8 and 9. As shown, hole 105 in entrance cap 97 is designed
especially to receive the tip of spray needle 93. During operation,
spray needle 93 and entrance cap 97 are at different electrical
potentials--by about 1000 V. It is this potential difference which
induces the spray process. However, the strength of the field at
tip 104 of spray needle 93 is of critical importance in producing a
spray and subsequently ions. The potential difference between
needle 93 and cap 97 might be 1000 V without inducing a spray. If
needle 93 is too far from entrance cap 97 then the field strength
at tip 104 of needle 93 will be too low and no spray will be
formed. If needle 93 is to close to entrance cap 97 then an arc
will form between needle 93 and cap 97--and no spray will be
formed. Hole 105 of entrance cap 97 is designed to ease the
positioning of needle 93 with respect to cap 97. Because hole 105
is cylindrical and significantly greater in length than in
diameter, tip 104 of needle 93 can be located in a range of
positions in hole 105 without great influence on the strength of
the field at tip 104. That is, because hole 105 is cylindrical,
there is a range of positions along the axis of hole 105 within
which the distance between these positions and the nearest point on
the surface of hole 105 is a constant. Assuming the potential
difference between cap 97 and needle 93 is a constant, and the
distance between tip 104 and cap 97 is a constant within the above
mentioned range of positions, the strength of the field at tip 104
will also be a constant.
[0061] The positioning of needle 93 with respect to capillary
section 98 (as seen in FIG. 9) is thus one dimensional (i.e., along
the longitudinal axis 106 of needle 93). The position of needle 93
is fixed in the plane perpendicular to axis 106 by the mechanical
alignment of components 91 through 100 in assembly 90. Along axis
106, there is a range of needle positions over which spray and ions
are readily formed. It has been observed that needle 93 should
extend approximately 7 mm (+/-1 mm), from the end of retainer 96 in
order to provide a useable ion current.
[0062] The positioning of needle 93 is eased further in that needle
93 is positioned within assembly 90 independent of the remainder of
the source and instrument. That is, to exchange spray needles
and/or samples, assembly 90 is first extracted from the source.
Then, on the bench, base 91--together with union 94, retainer 96,
and needle 93--is extracted from assembly 90. Retainer 96 is
loosened by partially unscrewing it thus allowing needle 93 to be
removed. A new nanospray needle is produced or obtained from a
manufacturer. Analyte solution is loaded into the new needle via
micropipette from the distal end of the needle. The new needle 93
is then inserted into retainer 96 so that it extends about 7 mm,
+/-1 mm, beyond retainer 96. Retainer 96 is then tightened, and
base 91--together with union 94, retainer 96, and needle 93--is
reinserted into cylinder 92 to complete assembly 90. Assembly 90 is
finally reinserted into the source.
[0063] An embodiment of the complete assembly 90, as inserted into
spray chamber 240, is depicted in FIG. 9. Notice that spray chamber
cover 107 includes a number of ports, three of which--108, 109, and
110--are shown. This spray chamber is designed in accordance with
co-pending application IONIZATION CHAMBER FOR ATMOSPHERIC PRESSURE
IONIZATION MASS SPECTROMETRY. Further, adapter 111 with electrical
contact spring 112 is fitted over port 109. Nanospray assembly 90
is inserted through adapter 111 and port 109 until finally coming
into contact with and fitting over capillary section 233. At this
point o-ring 100 forms a seal between capillary section 233 and
union 99. In this way multiple part capillary 235 is formed from
capillary sections 98 and 233 in accordance with copending
application METHOD AND APPARATUS FOR A MULTIPLE PART CAPILLARY
DEVICE FOR USE IN MASS SPECTROMETRY. Notice that assembly 90 can be
inserted and extracted from spray chamber 240, without tools, by
simply pushing and pulling respectively assembly 90 through port
109 along axis 106.
[0064] When inserted into spray chamber 240, nanospray assembly 90
is supported on one end by adapter 111 and port 109 and is
supported on the other end by capillary 233. In the preferred
embodiment, cover 107 is electrically grounded by contact with the
rest of the source (not shown). Adapter 111 is grounded by contact
with cover 107. And base 91--together with union 94, spray needle
93, and retainer 96--is grounded by contact with adapter 111 via
spring contact 112. Capillary section 98 together with cap 97 and
union 99 are held at a high potential via metal coating 30A on
capillary section 233.
[0065] Depicted in FIG. 10 is nanospray assembly 90 as it is
inserted into spray chamber 240 of a complete ionization source
designed according to co-pending application IONIZATION SOURCE FOR
MASS SPECTROMETRY. During normal operation of preferred embodiment
nanospray assembly 90, sample solution is formed into droplets at
atmospheric pressure by spraying the sample solution from spray
needle 93 into spray chamber 240. The spray is induced by the
application of a high potential between spray needle 93 and
entrance cap 97 within spray chamber 240. Sample droplets from the
spray evaporate while in spray chamber 240 thereby leaving behind
an ionized sample material (i.e., sample ions). These sample ions
are accelerated toward capillary inlet 126 of capillary section 98
by the electric field between spray needle 93, entrance cap 97 and
inlet 126 of first section 98 of capillary 235 and by the flow of
gas towards and into inlet 126. The design of entrance cap 97
provides the additional advantage over prior art nanospray devices
that the gas flow through hole 105 tends to focus ions into inlet
126. That is, gas flow in the nanospray assembly according to the
present invention is well controlled. All gas entering channel 113
must flow through hole 105. Because needle tip 104 is inserted into
hole 105 for normal operation, ions produced at tip 104 are
immediately entrained in the gas flow and transported to and
through channel 113. As a result, the position of spray needle 93
within the assembly is again less critical than in prior art
devices.
[0066] The ions are transported through first channel 113 into and
through second channel 232 to capillary outlet 234. As described
above first section 98 is joined to second section 233 in a sealed
manner by union 99. The flow of gas created by the pressure
differential between spray chamber 240 and first transfer region
245 further causes ions to flow through the capillary channels from
the spray chamber toward exit elements 255 and the mass analyzer
(not shown).
[0067] Still referring to FIG. 9, first transfer region 245 is
formed by mounting flange 248 on source block 254 where a vacuum
tight seal is formed between flange 248 and source block 254 by
o-ring 258. Capillary 235 penetrates through a hole in flange 248
where another vacuum tight seal is maintained (i.e., between flange
248 and capillary 235) by o-ring 256. A vacuum is then generated
and maintained in first transfer 245 by a pump (e.g., a roughing
pump, etc., not shown). The inner diameter and length of capillary
235 and the pumping speed of the pump are selected to provide as
high a rate of gas flow through capillary 235 as reasonably
possible while maintaining a pressure of 1 mbar in the first
transfer region 245. A higher gas flow rate through capillary 235
will result in more efficient transport of ions.
[0068] Next, as further shown in FIG. 9, first skimmer 251 is
placed adjacent to capillary exit 234 within first transfer region
245. An electric potential between capillary outlet end 234 and
first skimmer 251 accelerates the sample ions toward first skimmer
251. A fraction of the sample ions then pass through an opening in
first skimmer 251 and into second pumping region 243 where
pre-hexapole 249 is positioned to guide the sample ions from the
first skimmer 251 to second skimmer 252. Second pumping region 243
is pumped to a lower pressure than first transfer region 245 by
pump 253. Again, a fraction of the sample ions pass through an
opening in second skimmer 252 and into third pumping region 244,
which is pumped to a lower pressure than second pumping region 243
via pump 253.
[0069] Once in third pumping region 244, the sample ions are guided
from second skimmer 252 to exit electrodes 255 by hexapole 250.
While in hexapole 250 ions undergo collisions with a gas (i.e., a
collisional gas) and are thereby cooled to thermal velocities. The
ions then reach exit electrodes 255 and are accelerated from the
ionization source into the mass analyzer (not shown) for subsequent
analysis.
[0070] Referring lastly to FIGS. 11A-C, shown is yet another
alternative embodiment of a spray needle according to the
invention, wherein spray needle 131 further comprises a multiple
element tip (or "multi-tip"). As shown, spray needle 131, similar
to the preferred embodiment of the invention shown in FIGS. 5A-C,
comprises two component parts, support 130 and foil 133. Support
130 is preferably constructed from a rigid and electrically
conductive material (e.g., steel, etc.). It is also preferred that
the support 30 be a solid yet thin structure (i.e., on the order of
400 .mu.m or less in thickness). The thickness of the support
contributes to the determination of the loading and spray
properties of the sprayer (i.e., how fast the solution will flow
into the sprayer, the potential at which the sprayer must be
operated, the optimal distance between the sprayer and ESI orifice,
and the solution flow rate during spray etc.), because the
thickness of support 130 determines the size of foil 133. It is
further preferred, as shown in FIG. 11B, that support 130 have a
rectangular cross section. This geometry eases the elimination of
voids or bubbles which interfere with the spray of the solution.
However, support 30 may have a different cross-sectional shape
(e.g., triangular, circular, hexagonal, etc.). Such change in the
shape of support 130, however, may alter the spray properties of
the sprayer. Thus, different structures may be ideal for different
sample solutions.
[0071] Generally, foil 133 may be constructed using a piece of
electrically conducting "foil" which is cut at an angle .alpha., as
shown in FIG. 11A. In this embodiment, foil 133 is attached to the
outer surface of support 130 at one end of support 130, as depicted
in FIGS. 11A and 11C. Foil 133 is attached such that it is in
electrical contact with support 130. Preferably, an adhesive is
used to attach foil 133 to support 130, but other means for
attaching foil 133 to support 130 may be used, such as soldering,
etc.
[0072] Foil 133 is preferably constructed from a chemically inert
and easily cleaned material (e.g., gold, copper, platinum,
stainless steel (because of its limited reactivity to certain
compounds), etc.). For example, certain species are not readily
protonated, but will accept, for example, silver or copper ions as
adducts. Therefore, use of such different materials for foil 133
may alter the life and spray properties of the spray needle 131, as
described above with respect to the preferred embodiment. Of
course, other materials might be used in the construction of foil
133, depending on the particular electrochemical or reactive
properties desired (e.g., the use of copper instead of gold for
foil 133 may result in the formation of copper ions, thus having
the potential for forming complexes with analyte species) in order
to enhance signal intensity in certain analyses.
[0073] As described above for the preferred embodiment, it is
preferred that foil 133 be constructed from a very thin piece of
metal (i.e., about 100 .mu.m in thickness). However, the thickness,
particular metal, etc., used for foil 133 may be chosen based on
the desired properties (i.e., durability, formation, spray type,
etc.).
[0074] Importantly, spray needle 131 according to this alternate
embodiment of the invention, as shown in FIGS. 11A-C, comprises tip
132 which, as previously described, may be formed by wrapping or
folding a portion of foil 133 around one end of support 130 and
affixing foil 133 thereto. Once wrapped or folded, the exposed end
of foil 133 is preferably cut at an angle .alpha. 134 as shown in
FIG. 11A, thereby forming tip 132. In addition, tip 132 may have a
plurality of (i.e., 26, 50, 100, etc.) extremely fine elements 136
(i.e., on the order of 50 .mu.m or less) extending slightly
therefrom. Preferably, these fine elements 136 are individual
elements positioned lengthwise within foil 133, as shown in FIG.
11C. During use of such spray needle 131, the sample solution is
sprayed from each of these individual fine elements 136, thereby
resulting in a very fine spray of sample solution, which minimizes
the amount of solution lost (i.e., not introduced into the
analyzer). Alternatively, tip 132 may be designed such that it
comprises a plurality of tips, rather than the additional fine
elements 136 being positioned withing foil 133. Alternatively, the
individual fine elements 136 may be incorporated into the
embodiments depicted in FIGS. 6A-C & 7A-C in a manner similar
to that shown and described for FIGS. 11A-C.
[0075] While the present invention has been described with
reference to one or more preferred embodiments, such embodiments
are merely exemplary and are not intended to be limiting or
represent an exhaustive enumeration of all aspects of the
invention. The scope of the invention, therefore, shall be defined
solely by the following claims. Further, it will be apparent to
those of skill in the art that numerous changes may be made in such
details without departing from the spirit and the principles of the
invention. It should be appreciated that the present invention is
capable of being embodied in other forms without departing from its
essential characteristics.
* * * * *