U.S. patent application number 10/844399 was filed with the patent office on 2005-06-23 for method and apparatus for ion mobility spectrometry.
Invention is credited to Losch, Karsten, Nolting, Bengt.
Application Number | 20050133710 10/844399 |
Document ID | / |
Family ID | 29285148 |
Filed Date | 2005-06-23 |
United States Patent
Application |
20050133710 |
Kind Code |
A1 |
Losch, Karsten ; et
al. |
June 23, 2005 |
Method and apparatus for ion mobility spectrometry
Abstract
Molecular ions are generated by ionization, said molecular ions
are accumulated in an ion reservoir that is external to the drift
chamber. Than said molecular ions are dissociated into fragment
ions (i.e. fragmented ions) with electromagnetic radiation or
electron beams or ion beams, and said fragment ions are
ion-mobility spectrometrically analyzed. In an embodiment the
apparatus comprises additionally a virtual impactor and a
pyrolyzer. The process of fragmentation over time are detected and
analyzed, and this information is used for the differentiation of
hazardous biological samples from non-hazardous biological
samples.
Inventors: |
Losch, Karsten; (Berlin,
DE) ; Nolting, Bengt; (Berlin, DE) |
Correspondence
Address: |
SIEMENS SCHWEIZ
I-44, INTELLECTUAL PROPERTY
ALBISRIEDERSTRASSE 245
ZURICH
CH-8047
CH
|
Family ID: |
29285148 |
Appl. No.: |
10/844399 |
Filed: |
May 13, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10844399 |
May 13, 2004 |
|
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10139635 |
May 7, 2002 |
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6797943 |
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Current U.S.
Class: |
250/282 ;
250/288 |
Current CPC
Class: |
G01N 27/622 20130101;
H01J 49/40 20130101 |
Class at
Publication: |
250/282 ;
250/288 |
International
Class: |
H01J 049/00; B01D
059/44 |
Foreign Application Data
Date |
Code |
Application Number |
May 7, 2002 |
DE |
102 20 269.9 |
Claims
What is claimed is:
1. A method for ion-mobility spectrometry of a sample, comprising
the steps of: (a) generating molecular ions by ionization and
accumulating said molecular ions in an ion reservoir that is
external to a drift chamber of an ion-mobility spectrometer; (b)
exposing said molecular ions in said ion reservoir to a source of
energy for a time sufficient for dissociation of said ions into
fragment ions prior to ion-mobility analysis in the drift chamber
of the ion-mobility spectrometer, wherein said exposing results in
production of multiple charge states of fragment ions. (c)
generating molecular ions from sample molecules by ionization; (d)
accumulating said molecular ions in the ion reservoir that is
external to the drift chamber; (e) applying more than two gating
pulses and performing more than two ion-mobility measurements over
a certain period of time in which sample ions and/or fragment ions
interact with each other before a new sample is injected into an
ionization chamber; and (f) using the occurrence of said
interactions for the analysis of ion-mobility spectra.
2. The method of claim 1, wherein biological material of the sample
is pyrolyzed in a pyrolyzer prior to analysis in said ion-mobility
spectrometer and different concentrations of a chemical are added
to the sample prior to entering the drift chamber of said ion
mobility spectrometer and said added chemical interacts with sample
molecules and/or sample ions and/or fragment ions which causes
transitions of the ion mobility spectra and the spectra and said
transitions of spectra are used for the characterization of the
sample.
3. The method of claim 2, wherein said chemical addition is
HCl.
4. The method of claim 2, wherein said chemical addition is
ammonia.
5. An apparatus for ion mobility spectroscopy, comprising the parts
of: (a) a virtual impactor; (b) a pyrolyzer; and (c) a ion mobility
spectrometer, wherein generated ions of said sample are fragmented
into fragment ions with one of electromagnetic radiation,
electrons, and with ions, and said fragment ions are detected and
analyzed.
6. The apparatus of claim 5, wherein said detected and analyzed
fragment ions are arrived at by using the measurement of
transitions of ion-mobility spectra due to fragmentation for the
distinction of different samples.
7. The apparatus of claim 5, wherein said virtual impactor selects
particles within a size range that lies between about 0.1 .mu.m and
about 20 .mu.m.
8. The apparatus of claim 5, wherein said pyrolyzer is operated at
a temperature between about 300.degree. C. and about 400.degree.
C.
9. The apparatus of claim 5, wherein said electromagnetic radiation
comprises one of UV light, VUV light, and infrared light.
10. The apparatus of claim 5, wherein the generation of ions of the
sample in said ion-mobility spectrometer is achieved using a
radioactive source comprises one of .sup.3H, .sup.53Ni, .sup.241Am,
UV light, VUV light, an electrical discharge, a corona discharge
and electrospray.
11. The apparatus of claim 5, further comprising means for
generating molecular ions by ionization, said ionization comprising
an ionization of inert-gas molecules of said ion-mobility
spectrometer and clustering of inert-gas ions with sample molecules
or sample-molecule clusters or sample-molecule fragments.
12. The apparatus of claim 5, wherein said ion-mobility
spectrometer includes a drift chamber with a length between about
40 cm and about 60 cm.
13. The apparatus of claim 5, further comprising a gas
chromatograph.
14. The apparatus of claim 13, wherein select output of the
pyrolyzer are transferred to said gas chromatograph.
15. The apparatus of claim 5, further comprising a mass
spectrometer.
16. The apparatus of claim 15, wherein said mass spectrometer
operates in parallel with the ion mobility spectrometer.
17. The apparatus of claim 15, wherein said mass spectrometer
operates in series with the ion mobility spectrometer.
18. The apparatus of claim 5, wherein said analyzed fragment ions
occurs in differentiation between hazardous and non-hazardous
samples.
19. The apparatus of claim 5, wherein the substance which is
analyzed ion-mobility spectrometer is pyrolyzed bioweapons-grade
material.
20. The apparatus of claim 5, wherein the substance which is
analyzed ion-mobility spectrometer is a pathogen.
21. The apparatus of claim 5, wherein biological material of the
sample is pyrolyzed prior to analysis in said ion-mobility
spectrometer and different concentrations of a chemical are added
to the sample prior to entering the drift chamber of the ion
mobility spectrometer and said added chemical interacts with one of
sample molecules, sample ions, and fragment ions, which causes
transitions of the ion mobility spectra and the spectra and said
transitions of spectra are used for the characterization of the
sample.
22. The apparatus of claim 21, wherein said chemical addition
comprises one of HCl and ammonia.
23. The apparatus of claim 5, further comprising means for
detection of micrometer-sized and sub micrometer-sized particles,
said means further comprising: (a) means for generating particle
ions by ionization; (b) means for extracting gas from the drift
chamber in such a way that the movement of said particle ions
towards the collector in the drift chamber of said ion-mobility
spectrometer is increased; and (c) means for measuring and
analyzing the collector current generated by particle ions.
24. The apparatus of claim 23, wherein said particles comprise
bioweapons-grade material.
25. The apparatus of claim 23, wherein said particles have sizes
between about 100 nm and about 10 .mu.m.
26. The apparatus of claim 23, wherein said particles have sizes
between about 2 .mu.m and about 10 .mu.m.
27. The apparatus of claim 23, wherein said particles are
bioweapons-grade micrometer-sized particles with attached spores or
viruses.
28. The apparatus of claim 23, wherein said particles are
bioweapons-grade silicate particles with attached spores or
viruses.
29. The apparatus of claim 23, wherein said particles consist of
inorganic compounds that are partially coated with organic
compounds.
30. The apparatus of claim 23, wherein said means for generating
further comprises a radioactive source comprising one of .sup.3H,
.sup.53Ni, .sup.241Am, UV light, VUV light, an electrical
discharge, a corona discharge, and electrospray.
31. The apparatus of claim 23, wherein said means for generating
further comprises means for an ionization of inert-gas molecules of
said ion-mobility spectrometer and clustering of inert-gas ions
with said particles.
32. The apparatus of claim 5, further comprising a drift chamber
having an electric field with a strength between about 50 V/cm and
about 5000 V/cm.
33. The apparatus of claim 5, further comprising a drift chamber
having an electric field applied by more than 5 electrodes or guard
rings.
34. The apparatus of claim 5, further comprising: (a) an ionization
chamber for the generation of particle ions by ionization; and (b)
drift chamber and collector; wherein a pump extracts gas from the
drift chamber in such a way that the movement of said particle ions
towards the collector in the drift chamber is increased, a
collector current generated by particle ions is measured, and a
spectrum of particle ions is used for detection and
characterization of micrometer-sized particles.
35. The apparatus of claim 5, further comprising at least one
filter in place of said virtual impactor.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to an improved method and
apparatus for ion mobility spectrometry. In particular the
invention provides a method and apparatus that yield a higher
information content of the obtained ion-mobility spectra and a
better probability of correct identification of hazardous
substances and a better distinction between hazardous and
non-hazardous chemical and biological agents. The method and
apparatus of the invention can be used for the analysis of ions of
macromolecules for environmental screening, e.g. the detection of
proteins and lipids that occur in hazardous biological agents. In
particular the improved method and apparatus for ion mobility
spectrometry are useful for the detection of biological weapons
made from viruses or bacterial spores and inorganic and organic
surfactants and other chemicals, e.g. micrometer-sized dust-forming
silicate particles.
[0002] Ion mobility spectrometry is a powerful analytical tool for
the detection of chemical and biological hazards. Typically, in an
ion mobility spectrometer (IMS) the sample is ionized, passed
through an electric field and the time-of-flight of the different
sample ions at atmospheric pressure is detected by an electrode
detector. The disadvantage of these prior art IMS is that the false
alarm rate for the detection of some chemical and biological
hazards is too high for many important civil applications. Some
mass spectrometers (MS) have better false alarm rates, but MS are
very expensive since they require complicated vacuum technology
(see e.g. U.S. Pat. No. 6,342,393). The purpose of this invention
lies in an improved method and apparatus for ion mobility
spectrometry to obtain a significantly improved accuracy of
detection.
BRIEF SUMMARY OF THE INVENTION
[0003] In a first embodiment, an IMS is set out wherein molecular
ions of the sample are dissociated into fragment ions, and in which
the spectra of the fragment ions and the process of fragmentation
over time are analyzed. For example, electromagnetic or electron
beams may create fragmentation which increases the number of
different ions that are detected by the detector of the
ion-mobility spectrometer. For detection of biological hazards, the
sample may be collected by a virtual impactor, partially chemically
decomposed in a pyrolyzer and separated into fractions in gas
chromatograph before being analyzed in the IMS. In a further
embodiment of the methods and apparatuses of the invention, the
interaction of the sample ions with each other over time is
monitored and used to achieve a higher information content. Beyond
this, in one embodiment of the methods and apparatuses of the
invention, a chemical that interacts with the sample is added to
the inert gas of the ion mobility spectrometer and the changes of
the ion mobility spectra are monitored and used for obtaining a
higher information content. This chemical can e.g. be a
pH-modifier. Beyond this, in another embodiment of the methods and
apparatuses of the invention, larger particles are detected with an
ion-mobility spectrometer by using the reversion of the flow of the
inert gas relative to the common direction and thereby dragging
large particles towards the collector electrode, and using this
detection to obtain a higher information content about the sample,
e.g. about the presence of weapons-typical additions to spores and
viruses. In the embodiments which comprise multiple gatings, before
injecting a new sample into the ionization chamber, a higher yield
of collected ions may be achieved which may lead to a further
improvement of signal/noise ratios. Said ion mobility spectrometers
may be operated in the positive or negative ion mode or in both ion
modes. The ionization of a target compound of the sample can be
done directly by an ionization source that emits energy that
interacts with and ionizes the target compound. Alternatively or
additionally, a target compound of the sample can be indirectly
ionized by an ionization source which emits energy that interacts
with and ionizes an intermediate compound which, in turn, interacts
with and ionizes the target compound. It should be understood that
this invention has been disclosed so that one skilled in the art
may appreciate its features and advantages, and that a detailed
description of specific components and the spacing and size of the
components is not necessary to obtain that understanding. Many of
the individual components of the ion mobility spectrometers are
conventional in the industry, and accordingly are only
schematically depicted. The disclosure and description of the
invention and the examples are thus explanatory, and various
details in the construction of the equipment are not included.
Alternative embodiments and operating techniques will become
apparent to those skilled in the art in view of this disclosure,
and such modifications should be considered within the scope of the
invention, which is defined by the claims. The invention described
can of-course also be used in combination with the known prior art
variants of ion-mobility spectrometry.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0004] The invention will be described in conjunction with certain
drawings which are for the purpose of illustrating the preferred
and alternate embodiments of the invention only, and not for the
purpose of limiting the same, and wherein:
[0005] FIG. 1 is a schematic structural view showing of an
apparatus for ion mobility spectroscopy with a infrared laser for
fragmentation;
[0006] FIG. 2 is a schematic structural view showing of an
apparatus for ion mobility spectroscopy with a UV lamp for
fragmentation;
[0007] FIG. 3 is a schematic structural view showing of an
apparatus for ion mobility spectroscopy with a infrared laser for
fragmentation and with several gating pulses;
[0008] FIG. 4 is a schematic structural view showing of an
apparatus for ion mobility spectroscopy with a infrared laser for
fragmentation and interaction with chemical additions;
[0009] FIG. 5 is a block diagram of an apparatus for ion mobility
spectroscopy;
[0010] FIG. 6 is a schematic structural view showing of an
apparatus for ion mobility spectroscopy with 30 guard rings and 2
pumps; and
[0011] FIG. 7 is a schematic structural view showing of an
apparatus for ion mobility spectroscopy with an impactor and a
pyrolyzer.
DETAILED DESCRIPTION OF THE INVENTION
[0012] FIG. 1 shows a schematic structural view showing of an
apparatus for ion mobility spectroscopy with a infrared laser for
fragmentation. The sample 1 is injected into the ionization chamber
2 and ionized by the source of ionization 3 which may be e.g. a
radioactive source such as .sup.3H, .sup.53Ni, or .sup.241Am, UV or
VUV light, or an electrical discharge (non-radioactive electron
source). For example, when using a .sup.53Ni foil as source of
ionization and air as drift gas, the primary ions are mainly
short-living N.sub.2.sup.+, NO.sup.+ and O.sub.2.sup.-. These
N.sub.2.sup.+, NO.sup.+ and O.sub.2.sup.- rapidly react with traces
of water in the drift gas to form clusters of the types
N.sub.2.sup.+(H.sub.2O).sub.x, NO.sup.+(H.sub.2O).sub.y, and
O.sub.2.sup.-(H.sub.2O).sub.z, which then cluster with the
molecules and clusters of the sample. The ionization chamber 2
serves as ion reservoir. After injection of the sample into the
ionization chamber 2, some of the sample molecules and sample ions
start to dissociate into fragment molecules and fragment ions due
to interaction with the light from an infrared LASER 4. With the
help of a gating pulse which is applied to the gate 5, the fragment
ions 6 from the ionization chamber 2 are transferred into the drift
chamber 7 where the fragment ions 6 are accelerated by an electric
field 8. The time of flight of the fragment ions 6 in the gaseous
phase is measured with the help of a collector 9. Since different
fragment ions 6 have different mobilities in the gas of the drift
tube, they result in distinct peaks in the IMS spectrum 10. Several
measurements, without interrupting the dissociation reaction caused
by the LASER 4, are done before injecting a new sample into the
ionization chamber 2. The indicated time points, 0, 100 ms, and 200
ms, respectively, refer to the time after application of a gating
pulse. In order to reduce the noise, the ion mobility spectrometer
is enclosed in a grounded copper foil. The collector 9 is connected
with a 10.sup.10-V/A pre-amplifier via a cable of only a few mm
length. The feedback resistor of the pre-amplifier was selected for
a low noise level. The voltage supply for the guard rings of the
drift tube is stabilized to better than 0.1% rms, a) after a short
period of time for fragmentation, e.g. 1 second, b) after a long
time of fragmentation, e.g. 5 seconds: significant fragmentation
has occurred and accordingly characteristic changes of the heights
of some peaks in the ion-mobility spectra are observed. The
information of the spectra at the beginning, i.e. when the sample
is still non-fragmented, and the characteristic changes of spectra
over time due to fragmentation are used to characterize the sample.
In particular, the sample is evaluated for a hazardous biological
content. For example, the measured spectra are correlated with a
data base which contains spectra of non-fragmented samples and
their changes due to fragmentation wherein the correlation
procedure includes the use of small distortions of the drift time
of the spectra.
[0013] The operation of the apparatus in FIG. 2 is similar to FIG.
1, but here the fragmentation is done with light from an UV or
vacuum-UV (VUV) lamp 11. Alternatively, the fragmentation may be
done with electron beams (electron-ionization or electron
bombardment) or ion beams (ion bombardment) or other methods. For
example, electron beams may be generated in vacuum and released
into the gaseous medium of the ionization chamber 2 through a thin
membrane. The indicated time points, 0, t.sub.1, and t.sub.2,
respectively, refer to the time after application of a gating
pulse. Depending on the methods of ionization and fragmentation,
the amount of humidity in the drift chamber 7 may greatly affect
the sensitivity of the spectrometer. That is why in some variants
of this design, the humidity may be controlled by pumping the drift
gas through a molecular sieve. After a short period of time for
fragmentation (a), the spectra show little change. After a long
time of fragmentation (b), significant fragmentation has occurred
and accordingly characteristic changes of the heights of some peaks
in the ion-mobility spectra are observed. The operation of the
spectrometer may comprise the following steps: (i) The sample is
continuously collected from different locations via a pump and
several tubes with 2 mm diameter and a few m length. (ii) The
sample 1 is passed through a virtual impactor which selects a size
range of 0.5-8 .mu.m and discards particle sizes which are smaller
than 0.5 .mu.m and larger than 8 .mu.m. (iii) The collected sample
is stored in a container having a 20 mL volume. (iv) After 2
minutes of collection and storage, the complete sample is
transferred from the container into a pyrolyzer which causes
partial decomposition of the sample. (v) The product of the
pyrolyzation reaction at 350.degree. C. within the time range of 5
s-8 s after transfer to the pyrolyzer is transferred to the
ionization chamber of the ion-mobility spectrometer. (vi) In the
ionization chamber 2, the sample is ionized and fragmented. (vii)
The first gating pulse is applied a few milliseconds after transfer
of the sample to the gate 5. (viii) The first ion-mobility spectrum
is recorded and stored on a computer. This spectrum corresponds to
the essentially non-fragmented sample. (ix) Several more
ion-mobility measurements are performed on the sample over a period
of 30 seconds. The spectra obtained correspond to different degrees
of fragmentation of the sample and are also stored on the computer.
(x) By this way the spectra of the sample with different degrees of
fragmentation, from essentially non-fragmented to essentially
completely fragmented, are obtained. (xi) The information from the
spectrum of the almost non-fragmented sample and the information
from the transitions of several peaks in the course of
fragmentation are used for the analysis of the sample. In
particular neuronal networks are used for the distinction between
hazardous and non-hazardous samples. Because the information
content of the spectra is much higher than in the prior art ion
mobility spectrometry of biological agents, the false alarm rate is
significantly reduced.
[0014] FIG. 3 shows a schematic structural view showing of an
apparatus for ion mobility spectroscopy with a infrared laser for
fragmentation and with several gating pulses. The sample is
injected into the ionization chamber 2 and ionized by the source of
ionization 3 which may be e.g. a radioactive source such as e.g.
.sup.3H, .sup.53Ni, or .sup.241Am, UV or VUV light, or an
electrical discharge (non-radioactive electron source). After
ionization, some of the sample ions start to interact with each
other 12. After the fragmentation several gating pulses are applied
to the gate 5 and several measurements of ion-mobility spectra 10
are made before a new sample is injected into the ionization
chamber 2. Thus, successive ion-mobility spectra follow the
interaction of ions in the ionization chamber 2. This change of the
spectra over time is used for a better characterization of the
sample, a) after a short period of time of interaction, b) after a
long time of interaction in the ionization chamber 2,
characteristic changes of the heights of some peaks in the
ion-mobility spectra are observed and used for the identification
of the sample.
[0015] FIG. 4 shows a schematic structural view showing of an
apparatus for ion mobility spectroscopy with a infrared laser for
fragmentation and interaction with chemical additions. The
biological sample is injected into the ionization chamber 2 and
ionized by the source of ionization 3 which may be a radioactive
source such as e.g. .sup.3H, .sup.53Ni, or .sup.241Am, UV or VUV
light, or an electrical discharge (non-radioactive electron
source). A chemical addition was added to the inert gas of the IMS
or already to the sample in the pyrolysis tube. The chemical
addition may be e.g. HCl or NH.sub.3. This chemical addition can
interact 13 with the sample molecules and sample ions and thereby
causing specific changes of the ion-mobility spectra 3 of the
fragmentation ions. In particular, in the presence of some water
vapor, NH.sub.3 can bind to fatty acids of virus envelopes. Acidic
additions, e.g. HCl, and basic additions in the presence of some
water vapor, can change the pH of proteins and polypeptides, and
consequently their charge state and thus their ion-mobility
spectra. The changes of the ion-mobility spectra caused by the
presence of the chemical additions help to identify and
characterize the sample.
[0016] FIG. 5 shows a block diagram of an apparatus for ion
mobility spectroscopy. A virtual impactor 20 is e.g. continuously
operated and serves for selecting and concentrating a certain size
range of particles, e.g. 0.2 .mu.m (e.g. single influenza virus or
other pathogen) to 10 .mu.m (e.g. several spores of anthrax bound
to a dust particle or other pathogen). Particle size and size
distribution offer too little information to unambiguously identify
biological hazards in the presence of significant amounts of
interferrents of non-hazardous substances. That is why the
biological agents are collected and, from time to time, injected
into a pyrolyzer 21 where they are partially decomposed into
chemical components. The output from the pyrolyzer 21 is then
transferred to the ion mobility spectrometer (IMS) 22 where it is
ionized and further decomposed. In this way a very detailed
ion-mobility spectrum with a large number of peaks is obtained
which represents a fingerprint of the biological agent. Sample
injection into the pyrolyzer and sample transfer from the pyrolyzer
to the IMS are organized in such a way that a chemical
pre-selection is performed, i.e. that only some of the products of
the pyrolysis are analyzed in the IMS, e.g. lipids, polysaccarides,
and weapons-typical additions to bacterial spores. A computer 23
analyzes the IMS spectra and as well their changes due to
fragmentation of ions. In this way a large amount of information
about the biological agents is obtained which allows the
distinction between hazardous and non-hazardous agents.
[0017] FIG. 6 shows an ion mobility spectrometer with 30 guard
rings 32 and 2 pumps. A first pump 30 conveys the sample into the
ionization chamber 2. The operation of an inert gas pump 34 at the
other end of the drift chamber 7 can be reversed which leads to the
possibility of detection of very large particles, e.g.
weapons-typical micrometer-sized additions to bacterial spores. The
insulating layers between the guard rings 32 are made from an inert
polymer. Guard rings 32 and insulating layers are held together
with 3 screws which each attached to a spring in order to exert a
constant pressure on the guard rings 32 and insulating layers.
[0018] FIG. 7 shows a schematic structural view showing of an
apparatus for ion mobility spectroscopy with an impactor and a
pyrolyzer. For example, a two-stage virtual impactor 20 is operated
with a flow rate of a few 100 L/min and collects and concentrates
particles with sizes from about 0.2 to 10 micrometers. The
concentrated aerosol is transferred to the pyrolyzer 21 which is
operated at about 350.degree. C. After application of a few seconds
of pyrolysis, the partially decomposed sample enters the ionization
chamber 2 of the ion-mobility spectrometer 22. The source of
ionization 3, e.g. a .sup.53Ni foil, serves for the ionization of
the partially decomposed sample. The sample ions formed by this
process are then fragmented with electron beams which are generated
by the electron beam generator 14. Sample ions and fragment ions
interact with each other and form various clusters. The
fragmentation and clustering processes cause specific changes of
the ion-mobility spectra 10 over time. Several ion-mobility spectra
in the positive and negative ion modes are recorded before a new
sample is injected into the ionization chamber 2. The specific
changes of the spectra over time are used for the automatized
differentiation of hazardous from non-hazardous samples with the
help of software and computer 23.
[0019] The invention being thus described, it will be obvious that
the same may be varied in many ways. Such variations are not to be
regarded as a departure from the spirit and scope of the invention,
and all such modifications as would be obvious to one skilled in
the art are intended to be included within the scope of the
following claims.
* * * * *