System for studying a sample of material using a heavy ion induced mass spectrometer source

A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The invention relates to a plasma desorption mass spectrometer source. In 
particular, the invention relates to a plasma desorption mass spectrometer 
source which contains a pulsed neutron generator to provide an appropriate 
neutron flux in the direction of a fissionable material producing a pulsed 
source of heavy ions in order to desorb and ionize large molecules from a 
material for mass analysis. 
2. Description of the Related Art 
Accurate determination of molecular weights of biomolecules, such as 
proteins, is very important in biochemistry and industrial polymer 
applications as an analytical tool for molecular characterization. The 
molecular weight is a useful parameter, since it is indicative of the size 
of a biomolecule and gives an approximation of the number and type of 
subunits constituting the biomolecule. Of particular importance is the 
analysis of special proteins used in recombinant DNA research, where the 
paramount criteria of identity from one protein to another protein is the 
molecular weight of each protein. 
The molecular weight of proteins ranges from 10,000 atomic mass units (amu) 
to over 500,000 amu. Mass spectrometry is one method used for providing an 
accurate determination of weights of biomolecules involving large masses. 
However, conventional mass spectrometers are only useful for measuring 
molecular weights up to about 25,000 amu. 
Mass spectrometry involves three distinct functions: sample ionization, 
mass analysis and ion detection. FIG. 1 illustrates the high-level 
structural features of a mass spectrometer, whereby an ion beam 10-1 is 
provided by an ion source 20-1. The ion beam then passes through a mass 
analyzer 30-1, which separates the ions based on their charge-to-mass 
ratios. Such a mass analyzer 30-1 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 larger mass analyzer size for measuring larger 
ion masses. TOF mass analyzers allow for high molecular mass range, high 
ion transmission, and have the ability to record ions of different mass 
simultaneously. Therefore, TOF mass analyzers are preferred devices for 
analyzing large mass biomolecules. After passing through the TOF mass 
analyzer 30-1, the ion beam 10-1 arrives at the ion detector 40-1. For TOF 
spectrometers, the time that an ion arrives at the detector ion 40-1 
serves as an indication of the mass of the ion. 
Based on improvements in each of the three distinct functions of a mass 
spectrometer, accurate results can be achieved for measurements of 
biomolecules of masses below 10,000 amu, and reasonably effective 
measurements have been performed using Plasma Desorption Mass Spectrometry 
(PDMS), Matrix Assisted Laser Desorption Mass Spectrometry (MALDI), and 
Electro-Spray Mass Spectrometry (ESMS), for proteins as large as 25,000 
amu. However, at present, both MALDI and ESMS are experiencing technical 
evolutions to allow for the detection of ions in the mass range of 
25,000-500,000 amu. 
The original method used in mass spectrometry for detecting heavy molecules 
utilized primary ions from a radioactive source that traveled at high 
velocities and which subsequently impacted on a thin film of a sample of 
interest. This impact then caused a subsequent ejection, or desorption, of 
secondary ions from that thin film. The term "desorption" means the 
removal of ions from a surface. These secondary ions were subsequently 
mass differentiated and detected. PDMS is the original large molecule 
detecting mass spectrometry technique. A general background of this 
technology is given by Robert Cotter, in Plasma Desorption Mass 
Spectrometry: Coming of Age, in Analytical Chemistry, Vol. 60, No. 13, 
Jul. 1, 1988. A block diagram of a plasma desorption mass spectrometer is 
shown in FIG. 2. The typical ionization source that is utilized is a 
10-.mu.Ci sample of .sup.252 Cf (californium), which is held between two 
thin sheets of nickel foil. The ionization source is held at the same 
electrical potential (around 20 kV) as the sample to be analyzed. .sup.252 
Cf is used as the source since it has a high probability for spontaneous 
fission. 
.sup.252 Cf decays with a half-life of 2.65 years, of which 97% is decayed 
as alpha particles and 3% is decayed by spontaneous fission. That is, 3% 
is decayed as two charged fragments simultaneously emitted in opposite 
directions, 180 degrees apart from each other. Typically, such a decay 
involves .sup.106 Tc and .sup.142 Ba, with a total energy of about 200 
million electron volts (MeV) and with a total mass of about 200 amu. 
At the start of each timing cycle, one of the fission fragments hits a 
start detector 10-2, which is constructed as a grounded foil that emits 
secondary electrons collected by a dual channel plate detector 20-2. The 
output pulse from the detector 20-2 is amplified by amplifier 30-2, passed 
through a constant fraction discriminator 40-2, and recorded as the start 
pulse by a time-to-digital converter 50-2. The detector foil 10-2 and the 
discriminator 40-2 are designed to distinguish fission fragments from 
lower energy alpha particles, which emit about 6.1 MeV of energy per alpha 
particle. Discriminator 40-2 only provides an output for energies above 
the alpha particle energy and is thus responsive selectively to the 
fission fragments. 
At the same time that the first fission fragment impinges the detector foil 
10-2, the second fission fragment penetrates sample stage 60-2 (typically 
made of aluminum) on which sample 70-2 has been deposited on the reverse 
side thereof. 
As a result of their masses and high velocities, the fission fragments 
emitted from the .sup.252 Cf source are able to deposit large amounts of 
energy as they impinge on the sample 70-2 on the foil 60-2, allowing for 
the desorption of high molecular weight species from the sample 70-2. 
Typically, from 1 to 10 high molecular weight secondary ions are desorbed 
from the sample 70-2 and accelerated toward a grid 80-2 held at ground 
potential, where the secondary ions enter a long (15 cm to 3 m) drift 
region 90-2 with velocities inversely proportional to the square root of 
their masses. The amount of time needed to travel through the drift region 
90-2 is a function of the mass of each particle desorbed from the sample 
70-2. 
These particles are then detected by a detector 100-2; the detector output 
signals are amplified by an amplifier 110-2, and passed through a constant 
fraction discriminator 120-2. The output signal from the discriminator is 
fed to the time-to-digital converter 50-2. The data from the first and 
second fission fragments are then sent to a processor, such as a computer 
130-2, which determines a mass spectrum based on this data. 
As noted above, a californium source produces heavy ions, but it does so in 
a not-very-predictable manner. Another limitation of using the californium 
source is the low yield of molecular ions. Still another problem with 
using the californium source is that, since the alpha particles that are 
emitted are of much lower momentum than the particles emitted by 
spontaneous fission, the alpha particles greatly increase the number of 
fragmented ions, and since there is no time correlation for the alpha 
particle-initiated events, the signal-to-noise ratio levels are markedly 
decreased. All of these problems contribute to long acquisition times and 
decreased molecular ion sensitivity. 
Therefore, it is desired to find a better source for use in a plasma 
desorption mass spectrometer, and especially a source useful in measuring 
molecular weights greater than 25,000 amu. 
SUMMARY OF THE INVENTION 
According to the invention, a pulsed neutron generator and a uranium foil 
are used with a plasma desorption mass spectrometer to increase the 
detection characteristics of large size molecules being analyzed. 
Accordingly, an object of the invention is to provide a heavy ion generator 
comprising a fissionable material having an n,f reaction cross-section 
greater than a predetermined value, and a pulsed neutron generator 
positioned to bombard the fissionable material with neutrons thereby 
producing heavy ions emitted from the fissionable material in a fashion 
following the pulse form of the neutron burst. 
Another object of the invention is to provide a heavy ion generator as 
described above, wherein the pulsed neutron generator has an adjustable 
repetition rate for generating pulses. 
The invention is directed toward a system for studying a sample of 
material. This system comprises a heavy ion generator which further 
comprises a pulsed neutron generator and a fissionable material having an 
n,f reaction cross-section greater than a predetermined value. The pulsed 
neutron generator is positioned to bombard the fissionable material with 
neutrons to thereby produce heavy ions emitted from the fissionable 
material. At least some of the heavy ions propagate toward and fall 
incident upon the sample of material, thereby inducing desorption of the 
sample. 
The invention is also directed toward a method for studying a sample of 
material. The first step of the method involves placing a 238 isotope of 
uranium (.sup.238 U) in a path of a pulsed neutron generator. The second 
step involves placing the sample of material near the .sup.238 U source. 
The third step involves generating one or more neutron pulses by the 
neutron pulse generator, thereby causing at least one or more heavy ions 
to be emitted from the .sup.238 U source, and thereby causing at least one 
of the one or more heavy ions to fall incident upon the sample of 
material, which induces desorption of at least one ion off the sample of 
material.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
As noted above, a californium source produces heavy ions in a 
not-so-predictable manner. Thus, a feature of the invention is the 
generation of heavy molecular ions in a predictable or controllable way. 
According to the invention, a uranium 238 (.sup.238 U) foil is bombarded 
with neutrons from a pulsed neutron generator. The neutrons contact the 
foil and because of the high (n,f) reaction cross-section (neutron to 
fission fragment cross-section) of .sup.238 U, heavy ions come off. The 
pulsed neutron generator has an adjustable repetition rate, or pulse rate, 
such that timing information that correlates the masses of heavy molecular 
ions can be extracted. With this timing information, the heavy molecular 
ion generation can be characterized and used more effectively in studying 
a substance. 
The invention as described herein takes advantage of the n,f reaction in 
the 238 isotope of uranium. In doing so, the reliance on the random 
break-up of californium is removed. In the system according to the 
invention, fission fragment generation is directly related to the neutron 
burst. That is, the time mark for the secondary desorption event, which 
corresponds to the desorption of ions from the sample, can be related to 
the timing of the neutron pulse that caused the primary emission event. A 
burst of neutrons from a pulsed neutron generator is allowed to impinge on 
a .sup.238 U foil, causing multiple fission events. Of these, a 
considerable number of fission fragments called primary ions will 
propagate toward and fall incident on the thin-film sample target, thereby 
inducing desorption of the sample target. These multiple fission events 
occur at a rate of several orders of magnitude (i.e., hundreds or 
thousands), and cause desorption of the heavy ions from the sample target. 
This results in multiple, time-correlated events instead of the single 
time-correlated event of a spontaneous fission using the californium 
source. In some cases, it will be possible to reduce acquisition times 
from hours to minutes or even seconds by using the .sup.238 U source. 
Also, it is possible to optimize TOF windows, as well as the number of 
pulse cycles, by varying pulse parameters appropriately. 
According to one embodiment of the invention, a mass spectrometer source 
contains a pulsed neutron generator with associated control electronics to 
provided an appropriate neutron flux in the direction of a fissionable 
material with a high-enough n,f reaction cross-section. The preferred 
fissionable material is .sup.238 U. Resultant fission fragments, hereafter 
referred to as primary ions, are then used to desorb heavy molecular ions 
from a target. The desorbed ions are hereinafter referred to as secondary 
ions. These secondary ions are then analyzed by a TOF mass discriminator. 
The timing sequence allowing for TOF mass discrimination, and any decay 
particle suppressions are associated with the timing sequence of the 
neutron pulses, resulting in a significantly improved degree of 
correlation between primary ion generation, secondary ion generation, and 
detection. 
A block diagram of a preferred embodiment of the invention is given in FIG. 
3. Neutron pulses are sent to a .sup.238 U source 110-3 by a neutron 
generator 10-3. The number and rate of the neutron pulses 120-3 emitted 
from the neutron source 10-3 are controlled by pulse out signals 180-3 
sent by the control electronics 20-3. The control electronics 20-3 are 
controlled by control signals 130-3 sent by a computer/analyzer 40-3. By 
way of example but not by way of limitation, in the preferred embodiment, 
the computer/analyzer 40-3 can be an IBM-compatible personal computer. As 
a result of the bombardment of the .sup.238 U source 110-3 by the neutron 
pulses 120-3, heavy mass ions (also called fission fragments) 140-3 are 
emitted from the .sup.238 U source 110-3 at a controllable and predictable 
rate. There is no need to use a complement particle as a time mark (as is 
done with californium as the radioactive source), since a time zero mark 
signal 150-3 is sent from the control electronics 20-3 to a 
Time-to-Digital Converter (TDC) 100-3 in coincidence with each burst of 
neutron pulses 120-3 emitted from the neutron generator 10-3. The fission 
fragments 140-3 emitted from the .sup.238 U source 110-3 due to the 
neutron pulses 120-3 hit the sample stage 60-3. These fission fragments 
140-3 then pass through the sample stage 60-3, and impinge on the thin 
film sample 50-3 attached on one side of the sample stage 60-3. The sample 
stage 60-3 is positioned close to the .sup.231 U source 110-3, such that a 
substantial majority of the fission fragments 140-3 emitted from the 
.sup.238 U source 110-3 will impinge on the sample 50-3. With the 
closeness in location between the .sup.238 U source and the sample stage 
60-3, the solid angle of the dispersal of the fission fragments 140-3 
being ionized from the .sup.238 U source will not present a problem with 
respect to a certain percentage of the fission fragments 140-3 missing the 
sample stage 60-3. 
As a result of their masses and high velocities, some of the fission 
fragments emitted from the .sup.238 U source are able to deposit large 
amounts of energy as they impinge on the thin film sample 50-3, allowing 
for the desorption of high molecular weight species from the sample 50-3. 
Molecules 160-3 are desorbed off the thin film sample 50-3 and accelerate 
toward a grid 90-3 held at a fixed potential, typically a ground 
potential. The grid 90-3 may be made of any of several standard types of 
grid material, such as a screen material. The desorbed molecules 160-3 
then enter a drift region 70-3 with velocities inversely proportional to 
the square root of their masses. The amount of time needed to travel 
through the drift region 70-3 determines the mass of each particle 
desorbed from the thin film sample 50-3. When the desorbed molecules 160-3 
exit from the sample 50-3, each of the desorbed molecules 160-3 have a 
relatively small amount of energy associated with them, typically around 
100 electron volts (eV) of kinetic energy. These low energy particles will 
typically be desorbed off the sample 50-3 in various directions. However, 
as these desorbed molecules 160-3 get pulled into the drift region 70-3 by 
the attraction to the high potential at the grid 90-3, the desorbed 
molecules 160-3 will be pulled in line, so that the desorbed molecules 
160-3 will travel through the drift region 70-3 in essentially parallel 
paths with respect to each other. The high potential at the grid 90-3 
causes the desorbed molecules 160-3 to be accelerated towards the grid 
90-3, where the desorbed molecules 160-3 then pass through the grid 90-3, 
and enter a field-free region, also known as the drift region 70-3. In the 
drift region 70-3, there are no forces acting upon the desorbed molecules 
160-3, and so the heavier ones of the desorbed molecules 160-3 lag behind 
the lighter ones of the desorbed molecules 160-3, due to the fact that 
each of the desorbed molecules 160-3 enters the drift region 70-3 with the 
same kinetic energy, and since kinetic energy=1/2*mass*velocity.sup.2, the 
heavier mass ions will have slower velocities than the lighter mass ions 
as these ions pass through the drift region 70-3. 
These particles are then detected by a detector 80-3 at the end of the 
drift region 70-3, and the instant in time when each particle arrives at 
the detector 80-3 is recorded as a multi-stop signal 170-3. By way of 
example but not by way of limitation, in the preferred embodiment, the 
detector 80-3 can be a Dual Microchannel Plate, #C-701, manufactured by R. 
M. Jordan Company. Other types of detectors 80-3 may be used in the 
invention by one of ordinary skill in the art in keeping within the scope 
of the invention. The information concerning the particles passes through 
the Multi-stop Time-to-Digital Converter (TDC) 100-3, and arrives at the 
computer/analyzer 40-3. Also, by way of example but not by way of 
limitation, in the preferred embodiment, the TDC 100-3 can be a TOF2 
manufactured by Schmidt Industries, a division of SI Diamond Technology. 
Note that other similar devices may be substituted for the TDC 100-3 as 
used in the preferred embodiment and still keep within the scope of the 
invention. 
The time it takes the particles to travel through the drift region 70-3 and 
impinge on detector 80-3 is compared against a time zero mark as 
determined by the time zero mark signal 150-3 received from the control 
electronics 20-3, and the time difference determines the mass of each of 
the desorbed particles. This time difference corresponds to the instant in 
time of a particular neutron pulse being emitted from the neutron 
generator 10-3 subtracted from the instant in time of an ion being 
detected at the detector 80-3, wherein the ion detected at the detector 
80-3 was desorbed off the sample 50-3 due to the particular neutron pulse. 
The time determination and comparison can be performed in the 
computer/analyzer 40-3, or any type of processor as otherwise convenient. 
As mentioned above, each time zero mark as determined by the time zero 
mark signals 150-3 are correlated to a corresponding one of the bursts of 
neutron pulses 120-3. The above-mentioned structure performs the TOF mass 
discrimination. 
As described earlier, the californium source provides a significant primary 
ion yield, but is not actively controllable. The present invention uses a 
pulsed neutron generator to provide an adequate neutron flux to a suitable 
fissionable material. .sup.238 U is one such suitable fissionable 
material, since it has a relatively high n,f reaction cross section, which 
is approximately 1.2 barns for 14 MeV neutrons. Based on this, one can 
obtain reasonably high fission fragment yields. These fission fragment 
yields are strongly dependent on the neutron flux applied to the .sup.238 
U by a neutron generator, which can be highly controlled by using current 
neutron tube technology. 
One such neutron tube that can be used for implementing the present 
invention is a pulsed neutron tube developed by Martin Marietta Specialty 
Components, Inc., which can deliver neutron fluxes in a pulsed mode. In 
one embodiment, the neutron pulses would each cause about 10000 fission 
fragments due to a burst of approximately 5-100 nanoseconds. The burst 
repetition rate would be on the order of 2000 bursts/second. The burst 
repetition rate can be controlled by appropriate control signals 130-3 
sent by the computer/analyzer 40-3 to the control electronics 20-3. Based 
on the control signals 130-3 received, the control electronics 20-3 sends 
pulse out signals 160-3 to the neutron generator 10-3 at instants in time 
corresponding to the desired neutron pulse repetition rate. 
Using an approach according to the invention, what previously took hours to 
perform mass spectrometry could be done in a manner of minutes or even 
seconds. The ion source would then be coupled to a TOF mass discriminator, 
allowing mass analyzing capability up to 100,000 amu, which is well beyond 
the range of current conventional mass spectrometers. The time zero mark 
for the TOF analysis can be derived from the electronics used to drive the 
neutron generator. 
Another advantage of a system according to the invention is that all of the 
fission fragments generated would be synchronized. As a result, the 
background noise due to fission fragments that produce ions while the ions 
from the previous fission fragments are being analyzed can be eliminated, 
since these fission fragments associated with the background noise do not 
have a time mark associated with them. 
While preferred embodiments of the invention have been described, 
modifications of the described embodiments may become apparent to those of 
ordinary skill in the art, following the teachings of the invention, 
without departing from the scope of the invention as set forth in the 
appended claims.