Apparatus for interfacing liquid chromatograph with magnetic sector spectrometer

An apparatus and method for combining a liquid chromatograph and a magnetic sector mass spectrometer is described. The liquid chromatograph elution solvent is removed and sample particles relatively free of solvent are transported, without producing an electrical glow discharge, to the magnetic sector mass spectrometer having a chemical ionization source therein.

FIELD OF THE INVENTION 
This invention relates to an improved apparatus and method for interfacing 
a liquid chromatograph with a magnetic sector mass spectrometer. More 
particularly, the present invention is directed to the combined facilities 
of a liquid chromatograph and a high resolution double-focusing magnetic 
sector mass spectrometer having a chemical ionization source. The method 
of the present invention includes nebulizing a liquid chromatograph eluate 
(also known as a liquid chromatograph effluent), separation of a solvent 
liquid (also known as an eluent), and transport of high boiling substances 
of interest to the chemical ionization chamber of the magnetic sector mass 
spectrometer in the form of suspended particles for analysis. 
BACKGROUND OF THE INVENTION 
Mass spectrometric analysis of gas chromatograph fractions is known. It has 
been recognized that certain classes of organic substances while amenable 
to mass spectrometric analysis cannot be separated by passing through a 
gas chromatograph. Therefore, some other means of separating such 
materials is required as preparation for mass spectrum studies and 
identification. 
A common method for separating aforementioned materials is through liquid 
chromatography. Liquid chromatography is typically used in analyzing 
substances comprising large or polar molecules that are unsuitable for gas 
chromatography. 
Liquid chromatography provides a means for separating complex mixtures of 
either organic or inorganic mixtures into their various components, for 
example, compounds that are thermally unstable or nonvolatile under normal 
gas chromatographic conditions. 
Another widely used technique for determining structures of chemical 
species is mass spectrometry. Mass spectrometry identifies an unknown 
species by comparing its mass spectrum with a reference mass spectrum 
obtained from a species of known composition. Mass spectrometers generally 
employ electron impact ionization source for generating ions from the 
sample material supplied to it. 
In liquid chromatography, a chromatographic solvent containing a mixture of 
components in solution, is passed through a chromatographic column. The 
chromatographic column separates the mixture, by differential retention in 
a stationary phase of the column, into its various components. The 
components emerge from the column as distinct bands in a solvent stream 
separated in time and therefore distinguishable by the relative retention 
times. Thus, a liquid chromatograph provides means for sequentially 
separating individual components from an initially complex mixture which 
then may be introduced into a detection device, such as a mass 
spectrometer. 
Even though, liquid chromatography provides means for separating a complex 
mixture into its components, some interfacing means must be provided to 
remove the liquid chromatograph eluent from these components before their 
introduction into a detection device, such as a magnetic sector mass 
spectrometer. Without the removal of the eluent from the component of the 
mixture before its entry into the ionization chamber of the magnetic 
sector mass spectrometer, the mass spectra obtained therefrom cannot be 
used for precise identification of the compounds present in the component. 
The organic liquids used as eluents in liquid chromatograph, if present 
even in minute amounts, constitute a major source of error in any 
subsequent mass spectrometric analysis. Such an error occurs because the 
eluate exiting from the liquid chromatographic column generally contains 
the component in the range of about 10-100 parts per million (ppm). If one 
were to directly introduce the eluate containing the component into the 
ionization chamber of the magnetic sector mass spectrometer, the detection 
system of the magnetic sector mass spectrometer will be overwhelmed by the 
eluent and detection of the component may not occur. Additionally, the 
vacuum system of the magnetic sector mass spectrometer will be inundated 
by the eluent. As a result, an interfacing means and method which removes 
the eluent while efficiently transferring the material of interest to the 
magnetic sector mass spectrometer is needed and is provided by this 
invention. 
However, conventional mass spectrometers having the electron impact mode of 
ionization have limited applications. One of the shortcomings of 
conventional electron impact mass spectrometry is that many types of 
compounds give a very weak signal for the molecular ion being analyzed, 
even when the molecular ion has as high as 1 or 2% relative abundance. 
This often means that a significantly higher quantity of the sample is 
required for determining its molecular weight. As a result, chemical 
ionization mass spectrometry has recently emerged as an important new 
technique to obtain additional information not provided by electron impact 
methods. 
The extensive molecular fragmentation observed in the electron impact 
spectra of many compounds results from the fact that during the initial 
electron/molecule interaction, many molecules receive considerable energy 
above the ionization voltage. Typically, the molecule ion undergoes one or 
more bond breaks thereby reducing the intensity of the parent ion. As a 
result it is difficult to determine with certainty the molecular weight of 
the parent ion on the basis of the electron impact spectra. 
When compared, a chemical ionization mass spectrum obtained from an 
unfragmented parent molecule provides fairly precise information about the 
molecular weight of the parent molecule being analyzed. In addition, the 
chemical ionization fragmentation patterns may differ sufficiently from 
the electron impact patterns to reveal other structural features not 
indicated by the conventional mass spectrum. 
One of the major problems encountered in connecting liquid 
chromatograph/mass spectrometer (LC/MS) interfaces to magnetic sector mass 
spectrometers having chemical ionization sources is the presence of a very 
high voltage associated with the ion acceleration process. The high 
voltage between the chemical ionization source and a conventional LC/MS 
interface can result in an electrical glow discharge. This glow discharge 
produces a conductive path, which is very damaging to the highly sensitive 
equipments used in mass spectrometry. 
Dorn et al. in U.S. Pat. No. 4,980,057 disclose the use of a nebulizer 
having a combination ultrasonic/pneumatic nebulizing means, the use of a 
heater directly in the gas stream of the evaporation chamber and the 
control of this heater using a thermocouple located near the inlet of the 
nozzle, the use of a momentum separator in which the skimmers are 
symmetrically pumped from two directions in order to minimize turbulence 
and the use of a three-stage momentum separator which produces 
significantly low pressures at the magnetic sector mass spectrometer while 
maintaining a high yield of sample particles. The use of an ultrasonic 
nebulizer gives much greater flexibility compared to other designs because 
there is no need to readjust the nebulizer temperature when solvents 
change (gradient elution techniques) as with prior art thermospray 
nebulizers. Further, using an ultrasonic nebulizer, the inert gas flow may 
be adjusted at will to accommodate changing liquid chromatograph flow 
rates and solvent volatility. However, no apparatus or method for 
connecting a liquid chromatograph to a magnetic sector mass spectrometer 
having a chemical ionization source therein is disclosed. 
Another interface device utilizing particle beam technology is currently 
marketed by Hewlett-Packard Company. This device, disclosed in U.S. Pat. 
No. 4,863,491 to Brandt et al., uses a pneumatic nebulizer and a two stage 
momentum separator, The stated sensitivity specification for the 
Hewlett-Packard device is a signal/noise ratio of 50:1 on the molecular 
ion of caffeine using a sample size of 20.times.10.sup.-9 g and an LC flow 
of 0.5 ml/min. methanol. 
STATEMENT OF THE INVENTION 
The present invention is directed to an apparatus for interfacing a liquid 
chromatograph with a magnetic sector mass spectrometer having a chemical 
ionization source therein, the apparatus comprising, nebulizing means for 
nebulizing under partial vacuum a chromatograph effluent and dispersing 
the resultant particles by a flow of inert gas to produce an aerosol 
stream of the particles, evaporation means for evaporating liquid 
chromatograph solvent from the stream, the evaporation means having heater 
means therein for maintaining the temperature of the aerosol stream of 
particles and for compensating the cooling of the stream of the effluent 
due to evaporation of the liquid chromatograph solvent, a momentum 
separator connected to the evaporation means, the momentum separator 
having means for providing momentum to sample particles in the stream and 
further having vacuum means for removing the gaseous components present in 
the stream, and restricting means connected to the momentum separator and 
to a chemical ionization block of the chemical ionization source, the 
restricting means having a single opening small enough to restrict the 
outward flow of a reactant gas from the block to the momentum separator 
but large enough to transport the sample particles from the momentum 
separator to the chemical ionization block of the chemical ionization 
source.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
This invention contemplates providing a substantially solvent-free sample 
of a high boiling organic or inorganic chemical species or compound in a 
finely divided particulate form for delivery into the chemical ionization 
source of a magnetic sector mass spectrometer. The invention includes an 
apparatus for interfacing a liquid chromatograph with a high resolution 
double focusing magnetic sector mass spectrometer having a chemical 
ionization source therein. 
FIG. 1 shows a block diagram generally indicating the path of travel of the 
material being analyzed in the apparatus of the present invention. The 
material to be tested is initially isolated in the liquid chromatograph. 
The sample solute-containing liquid chromatograph elution solvent then 
passes to nebulizing means, such as an ultrasonic nebulizer for nebulizing 
the liquid chromatograph effluent. The nebulizing means forms an aerosol 
comprising the liquid chromatograph solution of the high boiling material 
in the form of small suspended droplets. After formation in the nebulizing 
means, the aerosol is conveyed to evaporation means by an inert carrier 
gas, such as helium introduced in the nebulizing means. The eluent 
contained in the aerosol is vaporized upon its passage through the 
evaporation means so that the sample material in the form of solid 
particles is carried by the stream of the inert carrier gas to the 
magnetic sector mass spectrometer. Evaporation of the solvent may cause 
cooling of the aerosol sufficient to result in reduced evaporation. Heat, 
as needed, is provided by heating the mixture of the aerosol and the inert 
carrier gas. The heat necessary for vaporization of the solvent can be 
provided by a feedback controlled heater within the evaporation chamber. 
As the particles reach the end of the evaporation chamber, the solid 
particles are almost completely solvent-free when at the entrance to the 
nozzle of the momentum separator. The pumping action of the momentum 
separator causes the solid particles to accelerate to sonic velocities. 
After the aforementioned acceleration, the solvent vapor and carrier gas 
are extracted from the stream by vacuum pumps as described more fully 
below. The solvent-free sample then travels as a bead of particles through 
restricting means into the chemical ionization source of the magnetic 
sector mass spectrometer for analysis. The restricting means are adopted 
to prevent a glow discharge between the chemical ionization source and the 
components of the interface. 
The liquid chromatograph may be of any conventional design such as a Waters 
model 600 MS, supplied by Waters Inc., Milford, Mass. and the 
chromatograph may also include a UV detector such as Waters model 484 MS 
UV detector connected in series just before the nebulizer of the interface 
apparatus. In the preferred embodiment, it is essential that the UV 
detector be capable of operating under sustained back pressures of several 
thousand psi without damage. 
The magnetic sector mass spectrometer may be of any conventional design 
such as model JEOL SX102, supplied by JEOL USA, Peabody, Mass. 
FIG. 2 shows a nebulizing means or a nebulizer 10 and evaporation means or 
evaporation chamber 20. Evaporation means 20 preferably comprises a first 
section 21 and a second section 22, each preferably being about 1.4 in. 
inner diameter tube fitted at each end with flanges. Nebulizer 10 is 
mounted at end 23 of first section 21 of evaporation means 20 and first 
section 21 is further provided with compression type fittings 16, 24 and 
25. For the sake of clarity, FIG. 2 shows nebulizer 10 separated from end 
23 of first section 21. Fitting 24 serves as the connection to a vacuum 
gauge 18 used for monitoring pressure inside evaporation means 20. 
Nebulizing means 10 may be mounted for stability on support means, such as 
on a conventional KF-40 flange (not shown). Nebulizing means 10 can be a 
standard commercial unit obtained from Sonotek Corporation, Poughkeepsie, 
N.Y., such as their model 8700, modified to provide the improved results 
of the present invention. 
It has been found that because the nebulizer must operate in a partial 
vacuum, a conventional method of introducing liquid effluent directly from 
the liquid chromatograph into the nebulizer may produce extensive 
"bumping" of solvent which may result in serious disruption of the 
nebulizer operation. "Bumping" is defined as a violent intermittent 
vaporization of the liquid chromatograph effluent. In order to avoid this 
problem, a very narrow capillary tube is employed to deliver the the 
liquid chromatograph effluent or eluent. The capillary maintains a high 
pressure and prevents bumping. Due to a constriction created by the narrow 
inner diameter of the inlet line, large back pressures are produced at the 
outlet end of the liquid chromatograph. Thus by keeping the liquid 
chromatograph effluent under high pressure until it reaches the tip of 
horn 11, the "bumping" phenomenon, experienced previously, is nearly 
eliminated. 
This is accomplished by means of a supply tube which is directed 
substantially perpendicular or at an acute angle with respect to the flow 
of inert gas. In a typical commercial unit, such as the one mentioned 
above, the liquid effluent is supplied axially to the tip of horn 11, via 
a compression fitting at the rear of the unit. Tube assembly 15 preferably 
comprises a stainless steel outer portion having about 1.6 mm outer 
diameter and about 0.230 mm inner diameter and an inner portion comprising 
capillary tube 13, preferably of fused silica having an inner diameter of 
about 0.1 mm. The outer portion serves to support and align fused silica 
tube 13. The stainless steel outer portion preferably extends to within 
about 2 mm of the tip of nebulizer horn 11, while fused silica tube 13 
extends beyond the stainless steel outer portion preferably to within 
about 0.5 mm of the tip of nebulizer horn 11 when nebulizer 10 is inserted 
in place in first section 21 of evaporation chamber 20. Fused silica tube 
13 is connected to an output end of the liquid chromatograph for 
transporting the liquid chromatograph effluent into evaporation means 20. 
In nebulizing means 10 of the present invention, the liquid chromatograph 
effluent is delivered obliquely or orthogonally to a tip of an ultrasonic 
horn 11 rather than axially as is the case in commercial nebulizers. 
Prior art nebulization methods are either pneumatic or thermal (i.e. 
thermospray). In the present invention, the nebulizing means is a hybrid 
which is both ultrasonic and pneumatic. Accordingly, the nebulizing means 
is far less solvent dependent than the prior art nebulizers. 
The invention may also include means for adding a second solvent stream 
directly at the tip of horn 11 by means of a second tube assembly 17 and 
compression fittings similar to those of tube assembly 15. To those 
skilled in the art, it would be obvious to provide more than two tube 
assemblies for delivering chromatograph effluents from several liquid 
chromatographs. The nebulizers used in the prior art generally need to 
combine solvent streams before reaching the nebulizer. As a result, there 
exists the possibility of solvent/solute incompatibility that can result 
in a precipitation of solute. Such a precipitation can clog the lines. The 
present invention solves this problem by mixing on the surface of 
nebulizer 10. The mixing of a second flow of solvent also may be used to 
reduce peak broadening by providing a rinsing function of the nebulizer 
surface without loss of sensitivity. 
Addition of the second solvent stream near nebulizing means 10 itself, 
instead of at some earlier point, ensures that the added solvent or 
solvent plus additive would not have detrimental effects on the UV 
detector response and would not cause precipitation of solute in the 
detector or in the interconnecting lines. 
In order to disperse an aerosol produced by nebulizer 10, the original 
liquid supply connection of nebulizer 10 is used to supply a jet of an 
inert gas, such as helium, from a tank to the tip of horn 11. This may be 
accomplished by providing a tube 14, preferably of fused silica having 
about 0.32 mm inner diameter, inside nebulizer's original axial supply 
orifice at a point approximately 1 cm back from the tip of horn 11. Fused 
silica tube 14 is preferably held in a well centered position within the 
original axial supply tubing by a compression union. The inside diameter 
of the central portion of the union is reduced for inserting fused silica 
tube 14 therein. Fused silica tube 14 provides enough restriction to give 
a high gas velocity at the desired flow rates of the inert gas. The 
preferred inert gas flow rate is about 1 liter/min. However, rates ranging 
from 300 ml to several liters per minute can be used. 
A coiled heater within the evaporation means is considerably more effective 
and permits more accurate temperature control through the use of a 
feedback temperature controller than conventional evaporation means used 
in the prior art. A heater 27, preferably a coiled heater such as a 3 foot 
long by 1/16 in. calrod type stainless steel heater, enters through 
fitting 25 and is then positioned in the free space inside first and 
second sections 21 and 22 respectively. 
Second section 22 of evaporation means 20 may be fitted with a sealed glass 
section 29 near its center to allow a visual evaluation of the relative 
dryness of the aerosol being produced within evaporation means 20. In 
addition, this part of evaporation means 20 is preferably fitted with a 
suitable compression fitting 30 for mounting of a thermocouple probe 31, 
preferably just in front of an entrance to a nozzle of the momentum 
separator shown in FIG. 3. The thermocouple is used to sense the 
temperature of the gas just before the nozzle of the momentum separator. 
The temperature of the gas at that point is used to control the current 
applied to heater 27. The output of thermocouple 31 is monitored by a 
temperature controller 33 to modulate the current supplied to heater 27 
mounted in evaporation means 20. The temperature of the inert gas/solvent 
vapor mix is usually set at a temperature of about 80.degree. to 
90.degree. F. by using temperature controller 33. First and second 
sections 21 and 22 respectively are joined by flange means 32, O-rings 34 
and centering rings (not shown). 
Turning to FIG. 3, evaporation chamber 22 is preferably mounted directly 
onto a momentum separator, generally indicated by numeral 40, by means of 
an end flange 41 and O-ring 38. Momentum separator 40 preferably comprises 
identical tubular sections 42 and 43 having flange 48 at each end, and an 
end section 44 having flange 48 at one end and a vacuum flange 55 at the 
other end. Tubular sections 42 and 43 are preferably made of stainless 
steel tubing and are sealably connected to each other along flanges 48. 
Tubular sections 42 and 43 each, are respectively provided with oppositely 
disposed tubes 45, 46, 47 and 49, each preferably having about 14 mm inner 
diameter. Tubular section 44 is preferably provided with a tube 52, having 
about 23 mm inner diameter. Vacuum means are connected to tubes 45, 46, 47 
and 49 that serve as connecting lines to vacuum pumps, such as rotary 
vacuum pumps (not known) used for evacuating the various stages of 
momentum separator 40. The vacuum means further comprise a vacuum pump, 
such as a high speed and high volumetric capacity turbomolecular vacuum 
pump (not shown) preferably having a pumping capacity of about 190 
liters/second and connected to tube 52. Preferably tube 52 has a larger 
diameter than tubes 45, 46, 47 and 49 for handling higher volumetric rates 
of gaseous components. Momentum separator 40 preferably comprises first, 
second and third stages, respectively formed by tubular sections 42, 43 
and 44. On the first and second stage, the two pumping lines are connected 
to a common 20 cubic foot per minute rotary vacuum pump where each line 
can be isolated from the pump by means of a conventional vacuum valve, 
installed in each line. The first stage may be also fitted with a 
compression fitting, not shown, that allows the installation of an 
internal heater, used for heating the first stage if icing becomes a 
problem. 
The third stage vacuum line connected to a large inner diameter tube 52 of 
momentum separator 40 is used to reduce pressures to a range necessary to 
prevent formation of a conducting path that may produce a glow discharge 
between the chemical ionization source and momentum separator 40. Third 
section 44 of momentum separator 40 comprises a stainless steel tube 
fitted at one end with a KF-40 flange 48 and at the other end with an "O" 
ring sealed vacuum flange 55 arranged to mate with a similar flange on the 
housing of the magnetic sector mass spectrometer. A pumping restriction 
between the third pumping stage and the chemical ion source of the 
magnetic sector mass spectrometer is provided by restricing means 
typically formed by a long inlet line 50. The "O" ring flange, fitted with 
an internal axially-positioned compression type fitting 61 serves as a 
mount for inlet line 50 of the restricting means, used for transporting 
the particle stream from momentum separator 40 to the chemical ionization 
chamber of the magnetic sector mass spectrometer. 
Momentum separator 40 comprises three arranged to mount inside of and be 
firmly attached to centering rings of flanges 48. The three parts are a 
nozzle 60, a cone shaped first skimmer 62, and a cone shaped second 
skimmer 64. Nozzle 60 is preferably provided with an inside diameter of 
about 0.5 mm and a length of about 12.7 mm. First skimmer 62 is preferably 
provided with a centrally disposed opening of about 0.5 mm at the tip. In 
addition, the angle observed at the tip of a conic section which bisects 
first skimmer 62 is preferably about 67 degrees. Second skimmer 64 is 
preferably provided with a centrally disposed opening of about 1.0 mm at 
the tip. The angle observed at the tip of a conic section which bisects 
second skimmer 64 is preferably about 16 degrees. Nozzle 60 and the 
openings on first skimmer 62 and second skimmer 64 are positioned and 
aligned to transport the stream of particles from momentum separator 40 to 
the chemical ionization source of the magnetic sector mass spectrometer. 
Inlet line 50, preferably a glass tube, mounts in fitting 61 at the "O" 
ring flange end of vacuum flange 55. 
Referring now to FIGS. 3 and 4, there is shown the chemical ionization 
source of the magnetic sector mass spectrometer, generally indicated by 
numeral 70. Chemical ionization source 70 preferably comprises a 
hermetically sealed housing 72 which encloses a chemical ionization block 
or chemical ionization chamber 74. The interior of chemical ionization 
housing 72 is kept under vacuum, preferably at about 5.times.10-.sup.6 
Torr, by means of a vacuum system (not shown). An entrance end 51 of inlet 
line 50 aligned and positioned near the opening at the tip of second 
skimmer 64 is connected to chamber 74 for transporting the particle stream 
from momentum separator 40 into chamber 74 of chemical ionization source 
70. Inlet line 50 is provided with a significantly larger inner diameter, 
preferably about 3 mm, than inner diameter of about 0.2 mm provided in 
inlet lines of the conventional chemical ionization sources. Such a large 
diameter facilitates entry of the sample particles into chamber 74. It 
should be apparent to those skilled in the art to provide inlet line 50 
with a demountable coupling to allow uncoupling of inlet line 50 from the 
chemical ionization source 70 for performing repairs or inspection. Inner 
diameter of inlet line 50 also acts as a restriction for isolating the 
final pumping stage of momentum separator 40 from the relatively high 
pressure (about 0.3-3.0 Torr) required by the chemical ionization process. 
Chemical ionization source 70 further comprises a filament 76 used for 
supplying a beam 86 of electrons into chamber 74 through a window 88. 
Filament 76 is heated by an electrical source 78 for producing beam 86. 
The electrical lines used for supplying power to filament 76 are insulated 
from housing 72 by the insulators 80. Chamber 74 is provided with an exit 
orifice 90 for conveying an ion beam 94 of sample material produced in 
chemical ionization source 70 to the magnetic sector mass spectrometer. A 
reactant gas, such as a volatile hydrocarbon, may be introduced through an 
inlet 89 into chamber 74. Suitable hydrocarbon, such as methane or 
isobutane, is introduced through a pressure regulated gas line 82 
connected to a reactant gas source 84. The aforementioned pressure of 
about 0.3 to 3.0 Torr is maintained within chamber 74 by keeping inner 
diameter of inlet line 50 small enough to restrict the outward flow of the 
reactant gas from chamber 74 and by regulating the flow rate of the 
reactant gas into chamber 74. Thus, a single opening provided by the inner 
diameter of inlet line 50 is sufficient to restrict the outward flow of 
the inert gas into tubular section 44 of momentum separator 40. However 
the single opening is large enough to transport the sample particles. 
In accordance with a further aspect of the invention, chamber 74 of 
chemical ionization source 70 is provided with a target 100, preferably 
positioned in opposition to the stream of sample particles exiting from 
inlet line 50. Target 100 is preferably made of metal, such as copper and 
it is preferably heated by electrical means (not shown) for facilitating 
vaporization of sample particles. 
Also in accordance with the invention, chemical ionization source 70 is 
provided with a series of plates 92 for accelerating and focussing ion 
beam 94 before it enters through a passage 96 into the magnetic sector 
mass spectrometer (not shown). Plates 92 are electrically insulated and 
are supplied with a variable voltage that may be regulated to provide a 
properly focussed ion beam 94 to the magnetic sector mass spectrometer. 
Chemical ionization housing 72 is grounded through a ground 98 and chamber 
74 is connected to a high voltage source (not shown) capable of providing 
voltages in the range of about 8-10 KeV. Since inlet line 50 is connected 
to chamber 74, it is also subjected to high voltages. If entrance end 51 
of inlet line 50 is too close to a component of momentum separator 40, 
such as the inner wall of skimmer 64, an electrical glow discharge may 
occur between the two. Such a discharge is very damaging to the equipment. 
The aforementioned problem is solved in the present invention by 
sufficiently separating the inner wall of skimmer 64 and entrance end 51 
of inlet line 50 to prevent the electrical glow discharge. 
It should be apparent to those skilled in the art to combine chemical 
ionization source 70 of the present invention with a conventional electron 
impact ionization source, if required. 
When all of the mechanical components are connected using KF type flanges, 
each of the parts can be readily demounted for adjustment or modification. 
The positions of each of the skimmers, the nozzle and the glass inlet line 
are all adjustable horizontally along the axis of the momentum separator 
by axially sliding skimmers 62 and 64 on the inner diameter of tubular 
section 43 and 44. The preferred positions of the various components are 
as follows: 
1) Tip of first skimmer 62 about 3 mm behind the tip of the nozzle 60; 
2) Tip of second skimmer 64 about 5 mm behind the nearest point of contact 
on the inside wall of first skimmer 62; and 
3) Entrance end 51 of inlet line 50 about 15 mm behind the nearest point of 
contact on the inside wall of second skimmer 64 for preventing an 
electrical glow discharge. 
Minor adjustments in the axial alignments of the nozzle and the various 
skimmers are possible because of slight side play where the centering 
rings make contact with the flanges. Using this adjustment, the alignments 
have been optimized optically to ensure that the orifices are strictly 
concentric with each other. 
When operating, nebulizer 10 is supplied with the effluent output of the 
liquid chromatograph and with a flow of helium amounting to about 1000 
ml/min. With an applied power of about 3.8 watts, ultrasonic nebulizer 10 
produces an aerosol with particle sizes ranging from about 10-50 microns. 
These particles are dispersed by the helium jet and travel into 
evaporation chamber 20. In evaporation chamber 20, the eluent from these 
aerosol particles is evaporated. This process of evaporation causes 
cooling of the droplet which, if not compensated, can cease evaporation. 
Such a cooling is compensated by providing a heated carrier gas, e.g., 
helium. The helium itself is heated by coiled heater 27 described above. 
Sufficient heat input is ensured by monitoring the temperature of the gas 
at the end of evaporation chamber 20. A significant number of aerosol 
particles does not impact on heater 27 because as a particle approaches 
heater 27 it tends to lose solvent more quickly on the heated side thereby 
generating an asymmetrical force on the particle with a net vector sum 
directed away from the hot surface. Under most conditions, the vacuum in 
evaporation chamber 20 is about 508 Torr. Care must be taken not to allow 
the pressure to become too low because this may inhibit drying of the 
particles by reducing the contact time between the particles and the 
helium. 
In passing through evaporation chamber 20, the aerosol is evaporated and it 
arrives at the entrance to nozzle 60 as a mixture of helium, solvent 
vapor, and small dry particles of the sample. The strong pumping pressure 
provided by the vacuum pumps connected to momentum separator 40 generates 
a high velocity flow through nozzle 60 by providing momentum to the sample 
particles. This accelerates the sample particles to sonic velocities. 
Because the sample particles are much more massive than the associated 
inert gas, usually helium gas, and solvent vapor, these particles have 
much greater momentum and tend to travel in a straight line after leaving 
nozzle 60. On the other hand, the gaseous components exiting from the 
nozzle jet tend to be pumped away by the action of the rotary vacuum pumps 
connected to momentum separator 40 and also due to the cone shapes of 
skimmers 62 and 64 respectively. Most of the gas (about 97%) is removed in 
the first stage of momentum separator 40. The later stages serve to remove 
the last traces of solvent vapor and helium gas, leaving the sample 
particles to continue their trip to chemical ionization source 70 
effectively free of solvent vapor. Due to large inner diameter of inlet 
line 50, the reactant gas from chamber 74 tends to exit out of inlet line 
50 into third section 44 of momentum separator 40. Such an escaped 
reactant gas should be evacuated rapidly to prevent formation of 
conducting paths that create electrical glow discharge between entrance 
end 51 of inlet line 50 and the inner side of skimmer 64. By connecting to 
tube 52 of the third section of momentum separator 40 the high volumetric 
rate turbomolecular vacuum pump and by maintaining vacuum therein of about 
3.times.10.sup.-2 Torr, possibility of the electrical glow discharge is 
significantly reduced. Additionally, by allowing the outward flow of the 
reactant gas into third section 44 of momentum separator 40 and not in the 
interior of chemical ionization chamber 74, the vacuum system of the 
magnetic sector mass spectrometer is not burdened. 
Chemical ionization mass spectra result from the ionmolecule reactions that 
occur between the sample particles at low pressure and the primary ions of 
a high pressure reactant gas. Typical pressures in chemical ionization 
chamber 74 vary between about 0.3-3.0 Torr for the reactant gas. Both gas 
upon introduction into chemical ionization chamber 74, are bombarded by 
electron beam 86. Since the amount of the sample material in chemical 
ionization chamber 74 is significantly less than the amount of the 
reactant gas, virtually all of the primary ionization by electron beam 86 
occurs to the reactant gas. The ionized reactant gas undergoes 
ion-molecule reactions with itself to form a steady-state plasma which in 
turn reacts chemically with the sample particles. The process results in 
ionizing the sample particles. If methane is used as the reactant gas, the 
most important ions in the reaction plasma are CH.sub.5.sup.+ and C.sub.2 
H.sub.5.sup.+ which together make up to about 90% of the ionic content. It 
is believed, even though no reliance thereon is intended, that these ions 
are formed by a reaction of the normal electron impact products with the 
excess of CH.sub.4 in the chemical ionization chamber 74. Thus: 
EQU CH.sub.4 +e.fwdarw.CH..sub.4.sup.+ +2e 
EQU CH.sub.4 .fwdarw.CH.sub.3.sup.+ +H. 
EQU CH..sub.4.sup.+ +CH.sub.4 .fwdarw.CH.sub.5.sup.+ +CH..sub.3 
EQU CH.sub.3.sup.+ +CH.sub.4 .fwdarw.C.sub.2 H.sub.5.sup.+ +H.sub.2 
In the presence of a good proton acceptor, such as dipropyl phthalate 
(1,2-benzenedicarboxylic acid dipropyl ester, C.sub.14 H.sub.18 O.sub.4), 
the ions CH.sub.5.sup.+ and C.sub.2 H.sub.5.sup.+ act as Bronsted acids 
and protonate the molecule: 
EQU CH.sub.5.sup.+ +C.sub.14 H.sub.18 O.sub.4 .fwdarw.[C.sub.14 H.sub.18 
O.sub.4 ].sup.+ H+CH.sub.4 
EQU C.sub.2 H.sub.5.sup.+ +C.sub.14 H.sub.18 O.sub.4 .fwdarw.[C.sub.14 H.sub.18 
O.sub.4 ].sup.+ H+C.sub.2 H.sub.4 
These reactions are typical of those observed for alcohols, aldehydes, 
esters, etc., and also for many biochemical compounds, typically 
encountered in recent chemical ionization applications. 
Additional fragmentation occurs in chamber 74 to give a mass spectral 
pattern that is similar in appearance to the electron impact spectrum of a 
hydrocarbon, but the abundance of the quasi-parent ion is greatly 
increased relative to the fragment ions. 
The increased relative abundance of the quasi-parent ion has proven to be 
of great value in many studies, particularly with relatively complex 
bioorganic molecules. As studies of the fragmentation patterns are 
extended and the various effects of different reactant gases are 
understood and applied, chemical ionization spectra have proven to have 
increased value. One of the important reasons that this increased 
quasi-parent ion abundance is so useful is that the overall mass spectral 
sensitivity is of the same order of magnitude as the sensitivity obtained 
for electron impact spectra. High sensitivity occurs due in part, to the 
fact that the electron beam is fully utilized because of the considerable 
increase in the partial pressure of reactant gas in chamber 74. The 
reactant gas or ion plasma, in turn, has a high probability of reactive 
collision with the unknown sample; thus the overall sensitivity is quite 
comparable to that obtained by conventional electron impact ionization 
source. 
The present invention will be further understood from the illustration of 
specific examples which follow. These examples are intended for 
illustrative purposes only and should not be construed as limitation upon 
the broadest aspects of the invention. 
EXAMPLES 
Relative abundance of dipropyl phthalate having a molecular weight of 250 
was analyzed by using the improved interface of the present invention 
having the chemical ionization source therein. FIG. 5 shows the mass 
spectrum of dipropyl phthalate. As seen in FIG. 5, the molecular 
fragmentation of dipropyl phthalate is significantly minimized and 
spectral lines indicating its presence is clearly shown. 
FIG. 6 shows the mass spectrum of dipropyl phthalate obtained by using 
conventional electron impact ionization source. FIG. 6 shows significant 
molecular fragmentation of dipropyl phthalate and as a result hardly any 
spectral lines are present at 250 which would have indicated presence of 
dipropyl phthalate.