High mass ion detection system and method

An improved ion detection system and method for detection of low or high mass ions having high electron affinity constituent atoms or molecules. A target with a low work function target surface is employed to fragment the incident ions and produce secondary negative ions and electrons. A cesium or barium oxide source is employed to optimally provide a monolayer of cesium or barium oxide on the target surface of a molybdenum or tungsten target. The secondary ions and electrons are detected by a conventional electron multiplier detector. The potential difference between the target surface and electron multiplier detector is chosen to accelerate the secondary ions and electrons to the electron multiplier detector with an energy corresponding to high detection efficiency.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention relates to mass spectrometry. In particular, the 
present invention relates to ion detection systems for mass spectrometry 
of biomolecules and other high molecular weight substances. Additionally, 
the present invention relates to improved ion detection for low molecular 
weight substances. 
2. Background of Related Art 
Accurate mass analysis of substances covering a wide range of molecular 
mass values is of increasing importance. In particular, accurate 
determination of molecular weights of proteins, and other biomolecules, is 
of paramount importance in biochemistry and modern biology. The molecular 
weight of a protein indicates its size, the possible presence of subunits 
(polymeric and monomeric molecular weights), and gives a rough idea of the 
number of component amino acids. An accurate method of high mass molecular 
weight determinations for proteins would be of special importance to the 
biotechnology field, since even rare proteins are now available by 
recombinant DNA techniques, and the first criteria of identity from batch 
to batch is the molecular weight of the protein. 
In general, proteins range in molecular weight from 10,000 to 500,000 amu, 
but this range can be extended to include peptides (below 10,000 amu), or 
certain multimeric proteins (over 500,000 amu). At present, however, no 
accurate and efficient means is available for determination of 
biomolecular mass for the higher portion of the protein mass range, and in 
particular, for masses from 10,000 to 500,000 amu. 
Determination of protein molecular weights by current methodologies, such 
as sedimentation, molecular sieving, gel electrophoresis, etc., present 
various special problems. The method of choice for determining protein 
molecular weights (weight average) has been sedimentation techniques in 
the ultracentrifuge. However, these techniques are technically cumbersome, 
slow and require the determination of other physical properties such as 
the partial specific volume of the protein. The accuracy of these methods 
can sometimes be as precise as to within 1000 mass units for a molecular 
weight of 10,000 amu, but more often are subject to much greater errors. 
Mass spectrometry is one potential method for providing accurate 
determination of molecular weight of biomolecules and other molecules 
spanning a broad mass range. Mass spectrometry employs three functional 
aspects: sample ionization, mass analysis and ion detection. Progress has 
been achieved in all three major areas of mass spectral analysis. As a 
result reasonably effective measurements of certain biomolecules of mass 
below 10,000 amu have been achieved. Mass measurements for proteins as 
large as 25,000 amu have also been made using plasma desorption mass 
spectrometry. Nevertheless, the majority of protein structures have 
molecular weights from 10,000 to 200,000 amu and the need thus exists for 
new and improved methods in mass spectrometry to extend the range of mass 
analysis. 
Presently available ion detection systems are not capable of efficient 
detection of ions in the mass range of from 10,000 to 500,000 amu, and in 
particular in the range of from 25,000 to 500,000 amu. Conventional means 
for detecting ions employed in mass spectrometry employ the impact of the 
ions at high velocity on a surface with the subsequent ejection of 
secondary electrons. These secondary electrons are detected by an electron 
multiplier resulting in an amplified signal pulse. Perhaps the most widely 
adopted method for the detection of low mass ions in mass spectrometry is 
the Channeltron Electron Multiplier (CEM), illustrated schematically in 
FIG. 1. This uses the direct impingement of incident ions on the surface 
of the detector to produce secondary electrons. Problems for the detection 
of high molecular weight ions derive from the well-known measured 
characteristics of these devices; in particular the reduction in the gain 
of CEM's with increasing M/Z of the bombarding ion. Now widely accepted, 
the phenomenon is attributed to the low yield of secondary electrons 
ejected by slow-moving, high mass molecules. R. J. Beuhler and L. 
Friedman, Threshold Studies of Secondary Electron Emission induced by 
Macro-Ion Impact on Solid Surfaces, Nucl. Instrum. Meth., 170, 309 (1980). 
Below a certain threshold velocity, detection may not be possible at all. 
In an attempt to avoid the limitations on the primary ion source 
accelerating voltage, post-acceleration of the ions was introduced to 
increase the velocity of high mass ions. One approach to providing 
post-acceleration of high mass ions employs application of high voltages 
across the electron multipliers to accelerate the ions above the 
threshold. This is impractical, however, for voltages in excess of 3 to 4 
kV due to intolerably low signal-to-noise levels. The disadvantages of 
such systems also include size, cost and complexity associated with 
bringing detector signals at high voltage to ground potential. 
Another approach to post-acceleration ion detection for mass spectrometry 
is illustrated in FIG. 2. Post-acceleration of incident ion beams is 
provided by an intermediate conversion electrode (dynode) which can 
operate at high voltages. This circumvents one of the major problems 
associated with floating detectors at high voltages; for example, coupling 
the detector output signal to ground level electronics. Instead of 
directly bombarding the detector surface, the primary ions impact the 
dynode surface with an energy given by the voltage (V): 
EQU V=V.sub.a +V.sub.d 
where V.sub.a is the ion source accelerating voltage and V.sub.d is the 
voltage applied to the dynode. Secondary electrons ejected from the dynode 
surface are subsequently detected by conventional multipliers. Detection 
of high mass ions (50,000-100,000 amu) by post-acceleration methods still 
require dynode voltages of the same magnitude. 
Various post-acceleration detector configurations have been reported and 
are commercially available from some manufacturers of magnetic 
instruments. One such detector is manufactured by JEOL Ltd. and is 
described in Evaluation of Post Acceleration Type High Sensitive Ion 
Detector For Mass Spectrometer, JEOL News, 21A (No. 2), 34 (1985). 
One disadvantage of post-acceleration detectors, related to the energy of 
the electrons impinging on the final detector surface, represents a form 
of "Catch-22" for detector efficiency. High dynode voltages are required 
to accelerate high mass ions to an energy sufficient to produce secondary 
electrons, however, for high dynode voltages, the secondary electrons 
impinge on the multiplier with energies higher than the energy for maximum 
detection efficiency. This is illustrated by FIG. 3 which shows the CEM 
response as a function of the incident electron energy. (Taken from E. 
Kurz, Channel Electron Multipliers, American Laboratory (March 1979).) 
Inspection of FIG. 3 shows that for electrons of energy E=40 KeV, the 
detection efficiency has dropped to approximately 60% from a peak of 90% 
at E=500 eV. Therefore, the gain in secondary emission at the conversion 
dynode is offset in part by the decrease in detector efficiency at the 
higher incident electron energies. 
Another disadvantage of post acceleration, and other detectors, is that to 
detect negative sample ions, existing detectors must rely on the ejection 
of lower yield, secondary positive ions. Consequently, the detection of 
high mass, negative ions is usually less sensitive than the detection of 
positively charged high mass ions. One approach to a post acceleration 
positive ion detector is shown in U.S. Pat. No. 4,423,324 to Stafford. 
Various other approaches have been attempted to resolve one or more of 
these problems. E.g., N. R. Daly, Scintillation Type Mass Spectrometer Ion 
Detector, Rev. Sci. Instrum., 31, 264 (1960); I. Katakuse, H. Nakabushi, 
T. Ichihara, Y. Fujita, T. Matsuo, T. Sukurai and H. Matsuda, Post 
Acceleration For Heavy Molecule Ion Detector, Mass Spectrometry, 33, 145 
(April, 1985). The usefulness of such approaches for yielding effective 
high mass resolution has not been demonstrated, however. 
Thus at present high mass ion detection in mass spectrometry instruments 
remains limited by ion acceleration voltages at the source. 
SUMMARY OF THE INVENTION 
The present invention provides an ion detection system and method with 
greatly improved sensitivity in detection of high mass ions. 
The present invention further provides an ion detection system and method 
capable of detecting high mass ions without requiring high ion source 
acceleration voltages. 
The present invention further provides an ion detection system and method 
capable of detection of high mass ions without employing high 
post-acceleration voltages. 
The present invention further provides an ion detection system and method 
with improved sensitivity for detection of low mass ions. 
The present invention further provides an ion detection system and method 
equally effective for detecting positive or negative incident ions. 
The present invention further provides an ion detection system having 
improved wear characteristics. 
The present invention provides an ion detection system and method based on 
the measurement of secondary negative ions and electrons produced by the 
impact of incident ions having high electron affinity constituents on a 
cesiated, or similarly low work function, target surface. In a preferred 
embodiment the ion detection system of the present invention is employed 
in conjunction with a source of biomolecular ions, which ions are typified 
by high electron affinity constituents, and in particular, carbon, 
hydrogen and oxygen constituent atoms. The biomolecular ion beam is 
collimated by a shield and accelerated to a target by a predetermined bias 
potential applied to the target, which is chosen to be negative or 
positive depending upon the polarity of the incident ions. The target 
includes a target surface coated with a monolayer of a low work function 
material such as cesium or barium oxide. The monolayer of cesium, or other 
low work function material, may be provided by the utilization of a 
reservoir of such material adjacent the target surface which is 
periodically heated to vaporize the material to allow a monolayer to form 
on the target surface. A heater is also employed to heat the target to a 
temperature which enhances emission of electrons upon impact of the 
incident ions. The heated, low work function, target surface, in 
conjunction with the high electron affinity of the fragments produced by 
impacting the primary, incident biomolecules results in high yields of 
secondary negative ions and electrons. The negative ions are comprised 
primarily of relatively small molecules comprised of carbon, hydrogen 
and/or oxygen constituents. 
A conventional electron multiplier detector may be employed to detect the 
secondary ions and electrons. The secondary ion fragments are accelerated 
from the target to the electron multiplier detector by the difference in 
bias potential of the target and electron multiplier detector. Due to the 
relatively low mass of the secondary fragment ions and electrons, these 
secondary negatively charged particles are accelerated to a velocity 
sufficient to create a strong signal on the electron multiplier detector.

DESCRIPTION OF THE PREFERRED EMBODIMENT 
FIG. 4 illustrates schematically the structural features of a mass 
spectrometer employing the high mass ion detection system of the present 
invention. A beam of ions (positive or negative) is provided by an ion 
source 10. As discussed in more detail below, optimum efficiency of the 
ion detection system requires that the ion beam be composed of ions which 
dissociate on impact to provide fragments with high electron affinities. 
Biomolecules possess such high electron affinity constituent atoms and 
molecules, therefore in one preferred application a beam of biomolecular 
ions is provided by ion source 10. Several types of ion sources suitable 
for providing a beam of biomolecular ions are described in A. 
Benninghoven, ed., Ion Formation From Organic Solids, Springer-Verlag 
(1983), pp. 32 and 90. Due to the increased sensitivity of the detector of 
the present invention, the ion source acceleration voltage may be 
considerably less than that required for other high mass ion detection 
systems. 
Before arriving at the high mass ion detection system, illustrated in FIG. 
5, the ion beam passes through a mass analyzer 12, shown in FIG. 4, which 
separates the ions based on their charge to mass ratios. Such mass 
analyzer 12 may be of the quadrupole type, magnetic sector type, or time 
of flight (TOF) type. Both the quadrupole and magnetic sector mass 
analyzer systems have inherent limitations, however, due to the 
requirements of increased mass analyzer size for increased ion mass. 
Accordingly, a TOF mass analyzer is preferred for very high mass 
biomolecule spectrometry. Such a suitable TOF mass analyzer is described 
in Erich W. Blauth, Dynamic Mass Spectrometers, Elsevier (1965), p. 71. 
Quadrupole and magnetic sector analyzers may also be employed, however, 
and are described at p. 140 and p. 1 of Blauth, respectively. After 
leaving the mass analyzer 12 the ion beam arrives at the detector 14. In, 
for example, a TOF system, the timing of the signal from the detector 14 
will serve to indicate the mass of the ions. 
Referring to FIG. 5, a preferred embodiment of the ion detection system 14 
of FIG. 4 is shown. The incident biomolecular ion beam provided from the 
ion source 10 and mass analyzer 12 first passes through a detector shield 
16 shown in FIG. 5. The detector shield serves to collimate the ion beam 
and to shield portions of the detector from the beam. Various detector 
configurations may require modification of the position and shape of the 
detector shield 16. 
After passing through the detector shield 16, the biomolecular ion beam 
impacts on the target 18. The target 18 comprises a target substrate 20 
with a planar first major surface 22 configured so as to intercept the ion 
beam. 
Convertor targets may employ Ti, W, Cu, Al, Au and stainless steel. Mo 
provides a higher yield of negative ion production, however. Therefore, 
preferably, either Mo (or W) are employed as target materials. 
Upon impacting the target surface 22, the incident biomolecular ions will 
fragment, i.e. dissociate into various size constituent. The extent of 
fragmentation will depend largely upon the incident ion velocity, however, 
significant fragmentation will occur for even relatively low impact 
velocity. Due to the characteristics of the atomic and molecular 
constituents of the incident biomolecules, in combination with the 
characteristics of the target surface, both of which are described in more 
detail below, the biomolecular fragments will have a tendency to become 
negatively ionized irrespective of the charge on the incident ion beam. 
Such negatively charged ions may be backscattered upon collision or may be 
later desorbed from the target surface 22 by subsequent collisions. Also, 
the impact of the ions will cause electrons to be given off from the 
target surface 22. Such backscattered and desorbed ions and electrons are 
collectively illustrated in FIG. 5 as negative charges 24 being emitted 
from target surface 22. 
The target surface 22 is coated with a partial monolayer of cesium 26. 
Alternatively, BaO or other low work function material may be employed. As 
described in more detail below, the low work function properties of the 
cesium, or other low work function material, coated on the target surface 
enhances the production of negative ions. The cesium monolayer may be 
provided by a cesium dispenser 28. The cesium dispenser 28 may take the 
form of a reservoir of cesium, or cesium compound, positioned adjacent the 
target surface 22 but out of the incident ion beam. The reservoir of 
cesium is periodically heated to vaporize the cesium 30 to thereby provide 
the desired monolayer of cesium on the target surface. Suitable cesium 
dispensers are manufactured by SAES GETTERS/USA, INC., for example their 
Model NF Series. 
The target substrate 20 is coupled to a target biasing potential 32. The 
target biasing potential will be positive or negative depending upon the 
charge of the incident ions. A potential of -2.5 kV would be suitable for 
incident positive ions and a potential of +2.0 kV would be suitable for 
incident negative ions. 
The target 18 is preferably provided with a heater 34 for heating the 
target 18 to a predetermined temperature. As described in more detail 
below, such heating increases the efficiency of electron emission from the 
target in response to the collision of the incident ions. The optimum 
temperature for detector efficiency is interrelated with the work function 
of the target surface and the electron affinity of the impacting ions. In 
an embodiment with a cesiated target surface 22, or other low work 
function surface having a work function of approximately 3 eV or less, and 
an incident beam of biomolecules, a suitable temperature range for the 
target 18 is 0.degree.-400.degree. C. This range assumes a background 
electron emission level of 10.sup.-15 A which would correspond to an 
acceptable signal to noise level. 
The secondary negative ions and electrons 24 emitted from target surface 22 
are detected by detector 36, which may be a CEM (Channeltron Electron 
Multiplier) detector. The CEM detector 36 may be of a type manufactured by 
Galileo Electro Optics Corp. such as their model 4000 Series. The CEM 
detector 36 is preferably positioned in a manner such that it is shielded 
from the incident ion beam by shield 16 and is only a few centimeters from 
target 18. 
The CEM detector operates in a conventional manner, i.e., ions and 
electrons impacting on a target at the anode end 40 of the detector 36 
trigger an avalanche of secondary electrons which is multiplied through 
repeated collisions within the detector 36. The detector anode biasing 
potential 38 is chosen to provide a potential difference between the anode 
end 40 of the detector 36 and the target 18 sufficient to accelerate the 
low mass negative fragment ions 24 to velocities above the threshold for 
detection and electrons to an energy corresponding to their maximum 
detection efficiency. Such energy should thus correspond generally to the 
peak shown in FIG. 3, i.e., approximately 500 eV. Therefore, for a -2.5 kV 
target potential (suitable for positive incident ions), the detector 
biasing potential 38 may be chosen to be approximately -2.0 kV. The 
cathode end of CEM detector 36 will preferably be coupled to ground 42. A 
detection signal will be provided along line 44 in a conventional manner. 
For negative incident ions, the target 18 should be maintained at a 
positive bias potential 32, for example, +2.0 kV. The anode end 40 of 
detector 36 should then be biased more positive, for example, by an anode 
biasing potential 38 of +2.5 kV. Cathode potential 42 should then be 
approximately +4.5 kV. Unlike conventional post-acceleration ion 
detectors, for either positive or negative incident ions, however, 
efficient production of secondary ions will be provided. Also, there is no 
problem in accelerating the secondary ions and electrons to velocities 
exceeding the threshold required to eject secondary electrons upon impact 
with CEM detector 36, due to the very low mass of the secondary fragment 
ions and electrons. 
Referring to FIG. 6, an alternate embodiment of the ion detection system is 
shown. The detection system of FIG. 6 differs from that of FIG. 5 in that 
target 18 is positioned perpendicular to the direction of the ion beam 
rather than at an angle as shown in FIG. 5. Also, an annular, on-axis CEMA 
(Channeltron Electron Multiplier Array) detector 46 is employed in place 
of the off-axis detector 36 of FIG. 5. The CEMA detector 46 may be of the 
type manufactured by Galileo Electro Optics Corp., such as their model 
LPD-25. The configuration of FIG. 6 may be advantageously employed in 
applications where space limitations are present. 
As mentioned above, in contrast to conventional ion detectors, the high 
mass ion detection system of the present invention exploits the 
physio-chemical properties inherent in the structure of large biomolecules 
as well as the electronic material properties of the target surface 22. 
The negative ion production efficiency is a function of the difference 
between the work function (.phi.) of the impacted surface and the electron 
affinity (E.sub.a) of the fragmented species: (.phi.-E.sub.a). For optimum 
efficiency, a low work function surface must be combined with an atom or 
molecule with high electron affinity. Target heating may also enhance 
negative ion and electron production efficiency. 
The significance of target surface work function and temperature and 
incident ion electron affinity on negative ion conversion efficiency 
relates to the physical processes underlying negative ion formation on the 
target surface 22. Negative ions can be generated from ion beams incident 
on target surface 22 through one or more surface conversion processes. The 
conversion processes most significant in detecting high mass ions are the 
following: 
(1) Desorption of negative ions (e.g. H.sup.-, OH.sup.-, O.sup.-, 
O.sub.2.sup.-), present as background impurities or residual fragments 
from prior biomolecule deposition, from the surface by energetic ion 
impact. 
(2) Backscattering or reflection of secondary particles from the surface in 
the form of negative ions after dissociation or fragmentation of 
biomolecular ions. 
(3) Electron production by thermionic emission from the target surface. 
The relationship between work function, temperature, electron affinity and 
negative ion production efficiency can be illustrated more specifically by 
using an incident hydrogen ion beam as an example. From the well known 
Saha-Langmuir relationship, the ratio (R) of the negative ion flux leaving 
a surface to the total impingement rate of H+ions can be estimated by: 
EQU R=[1+(g.sub.o /g.sub.-)exp[(.phi.-E.sub.a)/kT]].sup.-1 
where (g.sub.o /g.sub.-) is the ratio of the statistical weight of the 
atomic and ionic states, k is the Boltzmann constant and T is a 
temperature term. The temperature term T is interpreted as an effective 
temperature which exists around the incident particle for a short time due 
to conversion of some fraction of the impact energy into heat. An 
analogous relationship between target surface work function and effective 
temperature exists for thermionic emission of electrons and is described 
by the well known Richardson equation. 
By combining a surface of low work function with an incident ion species 
having a high electron 
affinity, the value of the (.phi.-E.sub.a) energy term in the exponent is 
minimized and the negative ion production efficiency is enhanced. 
Additionally, increasing the temperature term T by heating the target will 
enhance efficiency. Such heating is limited, however, by a temperature at 
which thermionic electron emission will be continuous thereby giving 
undesired background noise. 
The present invention exploits the high electron affinity characteristics 
of the primary biomolecule constituents to enhance negative ion production 
efficiency. Large, biomolecules consist mostly of elements that possess 
high electron affinities, for example, hydrogen (0.77 eV), carbon (1.25 
eV) and oxygen (1.46 eV). Additionally, organic fragments of low molecular 
weight commonly formed by collisions (such as OH, C.sub.2, CH.sub.2, 
C.sub.2 H.sub.2, CO, CHO, COOH and others) also possess high electron 
affinities. 
Table I lists the formulas and nominal masses of some peptides under mass 
10,000 amu. 
TABLE I 
______________________________________ 
Peptide Molecules 
Peptide Nominal Mass Formula 
______________________________________ 
Leu-Enkephalin 
556 C.sub.28 H.sub.38 N.sub.5 O.sub.7 
Angiotensin II 
1046 C.sub.50 H.sub.72 N.sub.13 O.sub.12 
Fibrinopeptide A 
1520 C.sub.64 H.sub.102 N.sub.19 O.sub.24 
B-Lipotropin 
2175 C.sub.98 H.sub.139 N.sub.26 O.sub.29 S.sub.1 
Glucagon 3480 C.sub.153 H.sub.226 N.sub.43 O.sub.49 S.sub.1 
Bovine Insulin 
5727 C.sub.254 H.sub.377 N.sub.65 O.sub.75 S.sub.6 
Human Proinsulin 
9378 C.sub.410 H.sub.638 N.sub.114 O.sub.127 
______________________________________ 
S.sub.6 
Over 90% of the total atoms in each molecule listed consists of the atomic 
constituents C, H, and O. This percentage is likely to persist for larger 
molecules up to and exceeding 100,000 amu. Due to the large number of 
atoms with high electron affinities in an incident, energetic beam of 
biomolecular ions, a high percentage of the resulting fragments will have 
a high electron affinity for virtually any class of biomolecular ions. 
For maximum conversion efficiency a target surface work function of about 
1.45 eV is preferred. This corresponds to an optimum cesium coverage of 
half a monolayer. To achieve such a half monolayer of cesium on the target 
surface, consecutive or continuous cesium depositions may be made by 
alternately heating and cooling a dispenser containing a cesium compound 
which releases free cesium upon heating. 
The negative ion conversion efficiency is also dependent on the ion beam 
angle of incidence with respect to the target normal. For low mass 
incident ions, such as H+, this dependence is most pronounced. Negative 
ion yields from a planar target may be improved using a serrated or 
saw-toothed target surface 22 as shown in FIG. 7. Notching the surface of 
the target provides a high angle of incidence while retaining the 
flexibility for off or on-axis detector positioning as shown in FIGS. 5 
and 6. 
For conventional impact schemes, the yield of negative ions formed can be 
lower than that for positive fragment ions. This limitation is not present 
in the detection system of the present invention where high mass 
biomolecular ions are impacted on a low work function surface. 
Accordingly, high sensitivity ion detection is provided for positive or 
negative incident ions. 
The survival probability of negative ions once formed is further enhanced 
by the following features: a relatively small separation between the 
target surface 22 and CEM detector 36; absence of intermediate surfaces 
where collisions could result in the destruction of the negative ions 
formed at the target surface; and low background particle densities. 
While the present invention has been described in terms of the presently 
preferred embodiment, it will be appreciated that the present invention is 
equally applicable to a wide variety of alternate embodiments. For 
example, while the ion detection system of the present invention has been 
described in a preferred application in an improved mass spectrometry 
system employing a source of ionized biomolecules, or other ion source 
providing ions with high electron affinity constituents, it should be 
appreciated that significant improvements may also be achieved in mass 
spectrometry applications involving other types of ions, and in various 
applications involving detection of a wide range of ion types and masses 
outside of the mass spectrometry field. Additionally, while the preferred 
embodiment has been described in terms of a specific configuration of 
detector, target and electron multiplier in relation to the ion beam and 
with respect to each other, many different configurations are possible. 
Similarly, while specific preferred voltage values have been described for 
the target bias potential and the electron multiplier detector bias 
potential, considerable variation in these values is possible while still 
remaining within the scope of the present invention. Specifically, the 
optimum potential difference between the target and electron multiplier 
detector will vary with the specific electron multiplier detector employed 
and with the specific biomolecules analyzed. Similarly, the temperature to 
which the target is heated may be varied through a considerable range 
while giving substantial enhancement to the detector efficiency. 
Additionally, with respect to the manner in which a low work function 
target surface is created, whether by forming a monolayer of low work 
function material, such as cesium or barium oxide, or by forming a low 
work function alloy or composite film (such as oxygenated cesium), many 
modifications are possible while remaining within the scope of the present 
invention. 
It will be apparent to those skilled in the art that other changes in the 
details of the preferred embodiment described may be made and such 
alternate embodiments are within the scope of the present invention.