CA1227950A - Method and means for vaporizing liquids for detection or analysis - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

Method of vaporizing a solution containing a solvent and molecules of interest for detection or analysis, where the molecules of interest are non-volatile or ionic or thermally labile or a combination thereof. The method involves partially vaporizing the solution in a heated passageway; controlling the temperature of the solution in the passageway to maintain a predetermined degree of vaporization as the flow rate or solu-tion composition varies; spraying the partially vaporized solution through a nozzle to form a thermospray of relatively dry particles entrained in an intense vapor jet; controlling the downstream environment to prevent recondensation of solu-tion of the molecules of interest. The remaining solvent carried by the relatively dry particles is vaporized by internal enthalpy.

Apparatus for the practice of this method is also disclosed.

Description

r`lETHOD AWL) Lyons FOP Vi~PO~I Z IT
LEEDS FOX DETECT OPT Arl~BysIs -Government Support The invention described herein was made in the course of worn under a grant or award from the Department of lo Health and Human Services (formerly Health Education and 1~1elfare).
Field of Invention The present invention relates to the field of analytical chemistry and process flow control, and is 15 particularly adapted to vaporize the fluent from a liquid chromatography so that samples separated by liquid chromatography may be detected and/or analyzed by a mass spectrometer, or other vapor phase detection system or analytical instrument. It is particularly useful for vaporizing non-volatile, ionic or thermally labile samples that need to be separated from a liquid solution without introducing unwanted chemical modification such as pyrolyzes and without materially effecting the temporal distribution of the sample.
BACKGROUND OF THE IMVEMTIO1~
Both analytical chemistry and process flow.
control make wide use of liquid chromatography to analyze solutions. The output of the liquid chromatography may be applied to a mass spectrometer, or any one of a 30 variety of vapor phase detectors such as those utilizing photo ionization, electron capture or flame ionization techniques. Lyon methods are known for vaporizing solids and 1 liquids for use with these devices, but these techniques cannot be generally applied to the vaporization of solutions of non-volatile solutes without producing uncontrolled chemical modification Ox the solute, such as pyrolyzes, or 5 without causing the solute to "salt out" on solid surfaces.
In addition, various techniques applicable to some types of detection and analytical chemistry cannot be applied to others because of solvent interference or matrix effects. In addition, certain large, thermally labile molecules are 10 difficult to vaporize inasmuch as they fragment in an uncontrolled manner when subjected to excessive heat.
The need to convert materials to be analyzed or detected into an ion vapor has been a problem in the field of the analytical chcr~listry for which no completely satisfactory 15 solution has heretofore existed. Gaseous compounds or compounds which can be thermally vaporized without decomposition can usually be converted to an ion vapor relatively easily by heating the compound to vaporize it if it is not a gas, and either bombarding the compound in its 20 gaseous state with a beam of electrons (electron impact ionization) or by introducing chemically-reactive ions into the gas (chemical ionization). However, many compounds are not sufficiently volatile at ambient temperatures to form a gas suitable for either electron impact ionization or 25 chemical ionization, and moreover, may be decomposed when heated so that they cannot be vaporized thermally. Among the compounds which cannot be converted into an ion vapor by these conventional techniques are many itch are of biological, medical and pharmaceutical interest.
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1 A number of special techniques have been developed to generate an ion vapor from compounds of low volatility.
These techniques include field resorption, plasma desorptioll, rapid evaporation from inert surfaces and secondary 5 ionization mass spectrometer. In addition to these, other techniques may be found ion Analytical Chemistry, vow 51, pup AYE (June 1979). None of these techniques is without its limitations, however, and a need still exists for an improved method for obtaining mass spectra of involutely, 10 heat sensitive materials.
The problems of forming an ion vapor of involutely and heat sensitive compounds become particularly acute when it is attempted to use a mass spectrometer to analyze the effluent of a liquid chromatography Liquid chromatography 15 are widely used to separate mixtures into the component compounds, and find particular application when one or more of the component compounds is too involutely to permit the mixture to be separated with a conventional gas chromatography Although mass spectrometers have been widely and successfully interfaced to gas chromatography to permit mass spectra to be taken of compounds in gaseous effluent from the chromatography, efforts to interfacia liquid chromatography to mass spectrometers, have been less successful, in part because compounds eluded from the liquid chromatography are frequently involutely and heat sensitive and thus not amenable to conversion into ion vapor by conventional techniques. Moreover, the compounds to be analyzed from a liquid chromatography are dissolved in a volatile solvent, 30 which tends to reduce the ionization efficiency of 1 the mass spectrometer even further with respect to the solute compouncis of interest since solvent vapor is generally ionized along Whitehall the solute compoul-cls and the solvent is typically in a much greater conceIltratlon then the solute 5 compounds.
one attempt -to interface the mass spectrometer to a liquid chromatography is described in the United States Patent 4,160,161 to Horton. Effluent from a liquid chromatography is injected into an ion chamber maintained at a low pressure by 10 means of a needle which projects into the chamber. The low pressure in the chamber pulls the solvent and solute -through the needle and sprays it into the chamber. A laser or other heat source may be utilized to prevent the effluent from freezing as it flows throucJh the needle and to provide heat 15 to the effluent within the ion chamber. The needle is maintained at a high voltage by a high voltage power supply so that the spray carries a charge. The solvent evaporates in a low pressure environment, reducing tile size of the charge droplets until ideally only the ions remain. However, the application of high voltage in the presence of gases and vapor may cause the vapor phase to break down and become electrically conductive The resultant uncontrolled electrical discharges in the ion charter leads to unstable and erratic behavior.
Another method and apparatus for connecting a liquid chromatography directly to a mass spectrometer was disclosed in US. Patent 4,298,795 to Takeuchi et at. The patent describes a process whereby the liquid effluent is nebulized in a high temperature environment of approximately 300. Tile second capillary tube is utilized to draw the 7~5~1 1 molecules of interest into the mass spectrometer Chile an off axis pump withdraws the bull of the solute that is not drawn into the second capillary. In addition a heating means is provided for the second capillary to prevent recondensation 5 of the effluent on the internal walls of the capillary.
applicants invention may be distinguished from each of the above referellces inasmuch as the present application uses a thermal spray -to partially vaporize a solution. By partially vaporizing the solution within a capillary tube, 10 the expanding vapor phase of the solution is used to create a thermal spray of relatively dry particles in an intense vapor jet itch issues from the capillary nozzle. The vaporization of the solution creates particles of solution tush preferentially contain the molecules of interest to be 15 analyzed. These particles are expelled at velocities up to and including supersonic velocity by the expanding vapor Ed solvent present in the capillary tube.
SIAM OF THE IN~7ENTIOI~
This invention discloses a method and apparatus for vaporizing liquid solutions in order to detect, quantitate, and/or determine physical or chemical properties of samples present in liquid solution. mixtures ma be separated by an on-line liquid chromatographic column and the methods used for detection, quantitation, identification, and/or determination of chemical and physical properties include mass spectrometer, photo ionization, flame ionization, electron capture, optical photometry including US, visible and IT regions of the spectrum, light scattering, light emission, atomic absorption, and any other- technique suitable for detecting or analyzing molecules or particles in a gaseous or vacuum environment.

1 The novel ~hermospra~ method consists of a two-step process. The first step is controlled portly vaporization ox -the solution. Methods are disclosed for controllirlg the degree of partial vaporization and the 5 temperature at which this vaporization occurs, end for maintaining this degree of vaporization essentially constant even though the solvent flow rate and/or composition may vary in either a controlled or an uncontrolled fashion. This thermos pray method allows the solvent to be substantially 10 vaporized -to produce a supersonic fee jet containing a fraction of unvaporized solvent as liquid droplets entrained in an intense vapor jet. Solute molecules of interest which are less volatile than the solvent are preferentially contained in the droplets. Methods are disclosed for controlling the temperature at which this process occurs in order to prevent unwanted chemical modification of the solutes (for example, pvrolysis) and to prevent premature vaporization of the solutes.
Several different methods may be used for the second stage of the vaporization depending on the application and the characteristics of the analytical technique to be employed. Conditions may be chosen in the first stage so that the droplets or particles produced are accelerated to high velocities, in some cases exceeding the local velocity of sound.
Depending on the application, these droplets or particles may be further vaporized by internal enthalpy or by environment interaction in a heated zone; they may be directed onto a relatively cool surface 30 where the less volatile components will stick. while the remainder of the solvent and any volatile components are 1 vaporized. alternatively, sufficient heat may be supplied in the gas phase that all of the solvent and substantial all of tile solute is vaporized without: coming directly in contact with any heated surface. This method is particularly useful for directly coupling a liquid chromatograpll with a mass spectrometer. methods are disclosed for separating the sample particles and molecules of interest from some or substantially all of the solvent vapor prior to significant vaporization of the sample. A method and apparatus are 10 disclosed for producing a high velocity beam of particles contains nonvolatile molecules which may be analyzed by techniques suitable for studying such beams in a vacuum. In some cases the sample, may be analyzed as solids deposited on a surface, in others they may be revaporized in a subsequent step for analysis by a gas phase technique.
The thermos pray method allows controlled vaporization of solutions in such a way that the chemical nature of solutes is not changed by the process even though they may be nonvolatile, ionic, or thermally labile. The technique was originally developed as a means of coupling liquid chromatography to mass spectrometrv, but it has a variety of other potential applications. Some of these are described later in this application. Chile there may be other important applications, the present discussion of the invention describes its application to analytical chemistry.
It is common in a number of analytical situations that the analyze is in the form of a liquid solution. In some cases (e.g. near US and visible photometry) the solute can be detected and analyzed in solution since the properties of the solvent may be sufficiently different from those owe the solute so as not to interfere with the measurement. In other ~2~79~

1 cases, either because of solvent interference or because the analytical method (for example, mass spectrometer) is a gas phase technique, it is necessary to vaporize the solution.
Since the solvent is usually not ox direct interest and also 5 because it may interfere in some way with the desired measurement, it is often necessary or desirable to vaporize the solution in such a way that some, or substantially all, of the solvent is sepclrated from the solute or solutes of interest. It is also very important in many cases that the 10 solute not be chemically modified (for example, by pvrolysis) as a result OX the vaporization process. Whether or not the solvent is removed preferentially, it is important that the solute be efficiently transferred to the analytical instrument if high sensitivity is -to be achieved. Up to now 15 there has been no practical way Okay accomplishing the desired performance, particularly whelp the sample is a non-volatile and/or thermally labile substance in an aqueous solution.
The thermos pray technique is particularly well-suited for these most demanding applications, and also provides a simple, economical, and efficient vaporization -technique for many less difficult applications.
The thermos pray system begins with the vaporizer and its associated control system. This device provides controlled partial vaporization of liquid streams containing solutes which may be nonvolatile, ionic, and/or thermally labile. A supersonic jet of vapor is produced which contains entrained liquid droplets and/or solid particles. Samples whose volatility is less tall that of the solvent are preferentially contained in these droplets or particles.
30 writhed and apparatus are disclosed both for accomplishing the desired degree of vaporization of the liquid stream and for 1 controlling the vaporizer so that this desired degree of partial vaporization is achieved even though the solvent composition or flow rate may vary.
In some cases the thermos pray vaporizer may be 5 combined directly with wel]-kllown analytical techniques to achieve useful results, but in others it is necessary to preheated additional control over the temperature and pressure of the environment surrounding the supersonic jet and downstream of the Mach disk to achieve the desired results.
10 This downstream control system is particularly important in the application to direct LAMS coupling both for analysis of neutral molecules and for direct controlled vaporization of molecular ions from electrically charged droplets and particles. Details of the individual components and combinations into complete systems for various applications will be hereinafter described in detail.
The thermos pray vaporizer uses a small diameter capillary tube through which liquid is forced at essentially constant flow rate, for example, by the ICilldS of pumps typically used in high pressure liquid chromatography.
Depending on the application, the end of this tube may be in gas (for example air) at atmospheric pressure (or higher) or may be in a substantially reduced pressure environment. To produce the thermos pray jet it is necessary to heat the tube sufficiently to produce the desired degree of vaporization.
In earlier experiments, some vaporization was produced by heating the end of the tube with a C02 laser or with an oxy-hydrogen flame. Neither of these techniques was entirely satisfactory since they were difficult to control and required that the tube be heated in a rather small region to rather high temperatures to achieve the required heat input.

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ore resonate, an electrically heated vaporizer was created for this purpose but it was also only partially satisfactory.
The present invention solves the previous problems and provides satisfactory definition and control of the 5 parameters of the vaporizer required to achieve specific results. The invention includes a control system that maintains a desired degree of partial vaporization even though the solvent composition and flow rate may vary in either a controlled or an uncontrolled manner.
The present invention uses two means for supplying the necessary heat to the flowing liquid. One means employs commercial cartridge heaters embedded in a block of material with high thermal conductivity such as copper, which is in intimate thermal contact with the tube. Such thermal contact can be achieved, for example, by silver brazing the tube to the copper block. The second means employs direct ohmic heating of the tube by passing an electrical current through the tube. The first method has the advantage of providing a very stable input of large amounts of heat without introducing any uncontrolled regions of high temperature in contact with the fluid. The disadvantage of the first method is that the thermal mass may make its time response too slow to cope properly with rapid composition or flow changes which sometimes occur. The second method provides a very rapid and efficient method for transferring heat into the flowing liquid. The disadvantage is that the local temperature depends very strongly on the contact with the liquid, and when operated at high degrees of partial vaporization, thermal contact with the fluid ma become poor at the no to end. As a result the -temperature at the nozzle may become such that the "leidenfrost" phenomenon occurs which effectively prevents further contact in this region. This ~;2279~[3 1 can result in a runaway excursion of the temperature near the end of the tune. The electrical connection at the nozzle end of the tube can also introduce an undesirable perturbation of the temperature profile in the capillary. Care must be taken 5 to insure that the tube is heated uniformly right up to the exit. Ideally, the electrical connection should be ox low thermal mass, and any length of unheated capillary at the nozzle end must be minimized.
Either of these techniques can provide satisfactory 10 performance for some applications, particularly if either the flow rate or the composition of the liquid is essentially constant. Satisfactory performance can be achieved merely by controlling the power input at the proper level to produce the desired degree of vaporization. This may be accomplished 15 by sensing the heater power directly or by sensing the temperature of the copper block or the tube itself and controlling the heat input so as to maintain this temperature constant.
When using the copper block vaporizer, better control of -the vaporizer can be achieved by sensing the downstream temperature of the jet. The location of the probe in the jet is not particularly critical since the absolute temperature indicated can be correlated with the desired degree of partial vaporization in separate calibration 25 measurements. To avoid disruption of the free jet expansion it is generally required that this probe be located off the jet axis and downstream of the Mach disk. The power input to the copper block heaters is controlled to maintain the temperature constant at the downstream temperature sensor 30 using a standard proportioning controller. This method of controlling the vaporizer provides satisfactory correction for slow variations in solvent flow rate and composition.

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1 similar approach can also be applied to the vaporizer using direct ohmic heating of the capillary tube, but somewhat better performance is obtained using a temperature sensor attached to the capillary. In this case 5 it is desirable that the sensor be located somewhere along the first one-third of the heated portion of the capillary as measured from the end corresponding to the liquid output.
Typically, this sensor is placed at a point one-fourth to one-sixth of the total heated length from the liquid 10 entrance. This location of the temperature sensor assures that the fluid inside the capillary is still entirely in the liquid state at this point and the temperature at the outer surface of the capillary is a good representation of the temperature of the liquid. By controlling the power applied 15 to the capillary so as to maintain this temperature constant, the desired degree of vaporization may be maintained essentially constant even though the liquid flow rate may vary in either a controlled or an uncontrolled manner.
Furthermore, the response of this system may be sufficiently fast to allow automatic compensation for the rapid flow fluctuations which are sometimes introduced by liquid chromatographic pumping systems.
Alternatively, a combination of the two types of vaporizers may be used. These can be confined in either 25 order, but we have found the most effective connation to be the use of the directly heated capillary vaporizer at the inlet side and the indirectly heated block vaporizer a-t the vaporizer exit. The downstream jet temperature or -the copper block temperature may be used to control the power input to 30 the hock heater and the temperature of the capillary in the region where vaporization has not yet begun can be used to ~27~

1 control the heater power input to the capillary heater. This combination has several important advantages over either alone. Slow variations in liquid flow rate or composition can be compensated for the block heater controlled by the 5 downstream temperature sensor while rapid flow fluctuations can be compensated by the fast response directly heated vaporizer. The downstream temperature sensor may also be used to control heat to both vaporizers; in this case both power supplies can be controlled from a single temperature 10 controller. The temperature sensor attached to the capillary tube can also be used to control both power supplies.
In additions to requiring that the desired degree of vaporization be achieved in the thermos pray vaporizer, most applications require that the temperature and pressure of the 15 vapor surrounding the thermos pray jet be controlled so that vaporization rates of the droplets carried in the jet are in the appropriate range for the particular application. The requirements for this control of the downstream environment depend strongly on what ultimate fate of the droplets or 20 particles is desirable for a particular application. For example, in direct coupling of a liquid chromatography to a mass spectrometer using the thermos pray method, it is desirable to completely toppers the solvent and the solutes by the time the particles reach the ion sampling aperture of 25 the mass spectrometer, while in using thermos pray to deposit nonvolatile sample on a surface it is desirable to vaporize most of the solvent from the particles before they strike the surface but none of the solute.

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1 BRIEF DESCF~IPTIO~ F TAO Drollness Figure 1 is a diagrammatic and partially cross-sectioned view of a thermos pray apparatus constructed in accordarlcc with teachings of the present invention.
Figure is a diagrammatic and partially cross sectioned view of an alternate embodiment of the present invention.
Figure 3 is a diagrammatic and partially cross-sectioned view of a second alternate embodiment of the 10 present invention, Figure it a linear plot of minimum vapor temperature for complete vaporization as a function of liquid velocity for several common solvents.
Figure 5 is a graph illustrating the total ion 15 currents that may be obtained from thermos pray ionization of Old aqueous ammonium acetate, measured as a function of vaporizer temperature and flow rate.
Figure 6 is a mass spectrum of a tetradecapeptide, resin substrate.
Figure 7 is a graph illustrating the fraction of water vaporized as the function of exit temperature calculated or an ambient pressure of 1 elm at various flow rates through a 0.15 mm tube.
Figure 8 is a graph illustrating the absolute temperatures of function of distance downstream from a thermos pray vaporizer for vapor, and for fast and slow particles or droplets.
Figure 9 is a graph illustrating the variations in the vaporizer exit temperature resulting from various control 30 point temperature To, at a flow rate of l.OmL/m.
Figure 10 is a graph illustrating calculated vapor temperatures as a function of power absorbed by the liquid corresponding to a flow rate of 1.0 ml/min through a 0~01~ Mel ID capillary tube.

Z~2~795~) 1 Figure 11 is a schematic diagram of a mean for providing thermos pray deposition of nonvolatile molecular samples on a moving belt for subsequent detection and/or analysis.
Figure 12 is a schematic diagram of a gas phase technique for separating sample and solvent utilizing the thermos pray apparatus.
Figure 13 is a schematic diagram of a US
photo ionization detector with thermos pray vaporization and 10 gas phase ionization of sample from solvent vapor.
Figure 14 is a schematic diagram or a thermos pray technique for producing supersonic beams of nonvolatile molecules.
Figure 15 is a graph and comparative schematic of a 15 thermos pray device with a movable thermocouple. The graph plots the temperature of the capillary as a function of the flow rate and the linear distance traveled by vaporizing liquid in the capillary.
Figure 16 is a schematic representation of a 20 calculated vaporization at a flow rate of 0.7 mL/min. at 40 watt of input power.
Figure 17 is a graph of control point temperature, To, and vapor exit -temperature corresponding to complete vaporization at the exit.
I Figure 18 it a graph of Ion intensities as functions of power applied to the vaporizer with no downstream heating of the jet.
Figure 19 is a series of mass chromatograms for injections of test solution at vaporization power of 65 watts JO under the conditions illustrated in Figure 18.
Figure 20 is a graph of ion intensities vs. flow at constant vaporizer power with downstream heating of the jet Jo 250C.
Figure 21 is a series of mass chromatograms for 35 major ions observed at 1.4mL/min. under the conditions illustrated in Pique 20.

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1 Figure 22 is a graph o response vs. sample injected for adenosine at optimum sensitivity for the conditions illustrated in Figure I
DETAILED DESCRIPTION OF TIRE PROOFREAD EMBO~I~IEMTS
The operation of the present invention may be summarized with reference to Figures 1-3. A capillary tube if is provided for partially vaporizing a solution or liquid flowing there through. The dimensions of the capillary tube will vary from application to application, but in one lo embodiment, a capillary tube was formed of a few centimeters of stainless steel tubing having a 0.015 mm ID and a 1.5 mm ODE Heat is supplied to the capillary tube to ensure partial vaporization of the liquid solution to be thermos prayed.
Lyle the percentage of solution to be vaporized varies from 15 application to application, the general range of desired vaporization begins at approximately 65~ and extends to nearly Lowe, but 100% vaporization must not occur at a significant distance (i.e., a few nozzle diameters short of the exit).
Heat for the vaporization is provided in one of three ways:
a) by direct ohmic heating of the capillary tube, b) by conductive heating from a heated block c) a combination of both techniques.
25 Figure l illustrates a thermos pray vaporizer having both heating embodiments. Figure 2 illustrates an endowment using only ohmic heating. Figure 3 illustrates an embodiment using only conductive heating.
As illustrated in Figure l, an electric current is 30 provided by power supply 12 by applying a current across a predetermined length of the capillary tube. the output of power supply 12 is applied at the inlet end by contact 16.
At the opposite end of the capillary, the circuit is iffy l complete my means of- contact I to the copper lock 17. The region of the capillary tube heated lies between contact 16 and bloc 17. As illustrated in Figure l, when current is applied by the heater power supply lo, direct ohmic heating 5 is venerated by the capillary 11.
Figure 1 also discloses a conductive heater 17 having first lo and second lo cartridge heaters inserted therein. Block member 17 is preferably a bloc}; of high thermal conductivity material such as copper, which is brazed lo or otherwise intimately secured to capillary tube 11 in a heat conductive manner at the nozzle end 15. A heater power supply aye supplies the power for the two cartridge heaters 18 and 19 which are opera-ted substantially below their rated power output.
In operation, the device may use either a bloc]
heater 17, or the ohmic heating method or a combination of both. The amount of heat necessary to vaporize the liquid solution flowillg through capillary tube 11 will vary depending upon the composition of the liquid solution, and 20 variations in flow rate caused by pump irregularities. Block heater 17 is useful in compensating for wide variances in the overall heating load imposed by compositional changes of the liquid solution. The fast response heater provided by capillary if and power supply 12 is useful for providing rapid changes in power input to compensate for variations in pump flow rate or unexpected variations in composition.
Inasmuch as the device operates with a predetermined partial vaporization of the liquid solution therein, the device has always heated the liquid to its 30 vaporization temperature, and is functioning within the range of power required to provide -the heat of vaporization for the ; quantity of liquid contained within the capillary if. As indicated previously, it is desired to operate between 65~ up ~L22t7~5~

1 to just less than 100~ vaporization. Once 100~ vaporization is achieved, the heat of vaporization is no longer available to absorb the heat supply by the ohmic heater 11, and a high temperature runaway condition will occur. The amount of 5 power supplied by the power supplies 12 and aye is determined by thermocouples 22 and 34 or 17. It is desired to place thermocouple I at a point on capillary 11 before the liquid wherein has been vaporized. As will be hereinafter explained, it has been found that the amount of heat 10 necessary to achieve a predetermined degree of vaporization may be determined from the temperature of the liquid at a fixed point before vaporization has begun.
Figure 15 illustrates the relationship between the flow rate, and the temperature profile along the capillary. A
15 graph has been plotted adjacent to a schematic representation of a thermos pray capillary using the ohmic heating method.
The temperature along the capillary is plotted for a variety of flow rates beginning at 0.7 ml/min and extending to 4.0 ml/min at a constant power input. The sharp upturn of the 0-7 ml/min curve at 8 inches illustrates thermal runaway that may occur if the sample is completely vaporized before eating the nozzle.
In practice, a block heater 17 is particularly useful for process flow control or other analytical or 25 detection procedures wherein a known composition is flowing through capillary 11, with little variation in pump flow rate. The thermal time constant of block heater 11 is relatively slow due to the mass of the block and the cartridge heaters themselves. when used as an analytical instrument to vaporize a wide variety of solvents and compounds of interest, the fast response ohmic heater provided by power supply 12 and capillary tube is more desirable, inasmuch as it has a much faster thermal response time then block heater 17.

1 controlled expansion chamber 20 receives the thermal spray of vapor and particles from nozzle 15 in the cylindrical space 2G. As the particles exit nozzle 15, their internal enthalpy vaporizes some or all of the remaining 5 solvent and some of the molecules of interest into a high speed vapor stream. Cartridge heater 13 supplies additional heat to chamber 20 to prevent recondensation of the solvent around the molecules of interest and to further vaporize any remaining droplets or 10 particles. Cartridge heater 13 receives its power from power supply 24 which is regulated by thermocouple 25 or 31. If desired, the molecules of interest may be ionized by an electron beam or laser passing through chamber 20 as indicated at 26. The vapor jet and molecules of interest are 15 drawn into a pump out line 27 and exhausted. The ionized molecules of interest diffuse through the skimmer nozzle 29 and are directed into a quadruple mass spectrometer generally indicated at 30 by ion lenses 28. Control of the atmosphere in expansion chamber 20 is maintained by means of 20 thermocouple 31 and controller 32 which controls the downstream heater power supply 24. Controller 32 ma also receive incoming liquid pressure information from transducer 33 to monitor variations in flow impedance of the capillary 11. This pressure transducer can also provide a measure of 25 fractional vaporization at constant liquid flow rate for a capillary of known dimensions.
Surprisingly, this system can accommodate vaporizing up to 2 ml/min of liquid directly into the ion source without overloading the pumping systems. This 30 corresponds to a gas flow which is about 100 times larger that that used with the mass spectrometer operated in the conventional I mode. The addition ox the mechanical vacuum pump connected directly to the source would only account for about one order of magnitude of increased capacity normally, 1 but locating the pumping line directly opposite the thermos pray vaporizer allows the supersonic jet to act as its own ejector pump. Thus the conductance of tile pumping aperture is about ten times as high as normal due to the 5 highly directed flow of the jet. It has been found that a 300 loin mechanical pump is more than adequate to maintain stable performance at flow rates to 2ml/min. It is essential that the pump be operated with gas ballast to avoid excess accumulation of liquid in the pump oil. Even then, it is 10 important to service the pump frequently (usually daily) to drain out solvent and add pumping fluid.
This problem can be avoided if the pumping line is fitted with a refrigerated trap, for example, cooled by dry ice or liquid nitrogen. Most of the solvent can then be 15 collected in this trap, thus alleviating these problems with the mechanical pump.
; Figure 2 discloses an alternate embodimellt of the invention utilizing only the ohmic heater comprised of heater power supply 12 and capillary tube 11. The operation of the 20 heating components of this device correspond in operation to Jo the components previously described with respect to Figure 1.
The control circuit, however, utilizes a comparative amplifier 33 to control the heater power supply 12. In addition, a separate temperature indicator I is provided to 25 indicate temperature sensed by the thermocouple on the nozzle end of the capillary. This is used to indicate proper operation of the vaporizer and can be used to trigger an alarm in the event of a thermal runaway. As indicated previously, it has been found that accurate control of the 30 percentage of solvent vaporized may be obtained by placing i the control thermocouple 22 Oil the entrance portion of the capillary where the liquid inside has not yet begun to vaporize.

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1 Figure 3 discloses an alternate embodiment o the invention using only the block heater which comprises copper block 17 and cartridge heaters 18 and 19. us indicated previously, the copper block 17 is brazed, silver soldered, 5 or otherwise intimately secured to capillary tub 11 in a heat conductive manner. The operation of the heating components of this device correspond in operation with the components previously described with respect to Figure 1.
Controller 32 monitors the temperature at the location of 10 thermocouples 21 and 34 to regulate the heater power supply aye In addition, a secondary jet heater and limited expansion volume is defined by chamber 20 which is heated by means of a second block aye and cartridge heater 13.
Controller 32 likewise senses the output of thermocouples 25 15 and 31 to determine the amount of power supplied by downstream heater power supply 24 to the cartridge heater 13.
An illustration of the amount of power applied, and the effect on the fluid temperature at the exit from the thermos pray vaporizer is illustrated in Figure 10. Figure 10 is a graph illustrating the calculated vapor temperatures as a function of power absorbed by the liquid corresponding to a flow rate of 1.0 ml/min through a 0.015 mm ID capillary tube.
The nominal operating point corresponds to a heater block temperature of about 250 C, and is measured ho the 25 thermocouple 21 in Figure 3. Under these conditions, a supersonic jet is produced with about 75% of the total effluent as vapor at the vaporizer exit. The temperature at the exit is approximately 170 C, and the pressure is about 3 elm. As indicated previously, it is essential for most 30 applications of thermos pray that complete vaporization not occur within the vaporizer capillary. This is true both for field assisted vaporization of ions and for transfer of nonvolatile samples to surfaces with efficient solvent 1 removal. Since nonvolatile molecules tend to be concentrated preferentially in the last of the remaining liquid, this prevents thermal degradation of the nonvolatile molecules until their exit from the vaporizer.
As will be discussed hereinafter in more detail, for most applications, it is necessary to supply heat to the vapor jet after it exits the vaporizer into the controlled expansion volume I to prevent recondensation and to complete the vaporization. This requires that the tot not be allowed 10 to expand freely into a vacuum, but rather it must be confined so that adiabatic expansion does not proceed indefinitely. Confinement of the jet is necessary for most applications since otherwise the temperature can become extremely low, causing recondensation and other undesirable 15 effects. As indicated previously, heat is added to the confined volume 20 by means of the cartridge heater 13.
As will be hereinafter described in detail, large nonvolatile molecules are ejected as intact molecular ions which have been ionized in solution by virtue of the ; 20 thermos pray method. This method appears to be consistent with experimental observations to date, and known physical and chemical processes, which involve the following five steps:
1. Nearly complete vaporization of the liquid at 25 the rate with which it is supplied to the vaporizer produces a super heated mist carried in a supersonic jet of vapor.
Nonvolatile molecules are preferentially retained in the droplets of the mist.

2. Droplets of the mist are charged positively or 30 negatively according to the statistical expectations for random sampling of a neutral fluid containing discrete positive and negative charges.

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l 3. Molecular ions clustered with a few solvent molecules evaporate from the superheated droplets assisted by the high local electrical folds generated by the charge on the droplet.
I. Cluster ions rapidly equilibrate with the vapor in the ion source to channels available.
5. Ions defusing to the sampling apparatus are then transmitted to the mass analyzer Old other detecting apparatus.
lo 6. Even if the "soft" ionization created by the -thermos pray is insufficient to ionize a desired molecule, additional ionization may be provided by an electron beam or laser as indicated at 26.
Theoretical Considerations This invention is concerned with the process occurring when a flowillg liquid is vaporized as it is forced under pressure through a heated capillary tube. The temperature profiles produced by direct electrical heating of the capillary are illustrated in Figure 15. In this 20 experiment 53 watts was dissipated in the capillary with water flowing through at rates in the range from 0.7 to I
Loin as indicated by the parameter in Figure 15. The experimental result a-t 0.7 mL/min is compared with a calculated profile in Figure 16 where the processes 25 occurring in different regions of the heated capillary are represented schematically. At the inlet end the flowing water is heated until vaporization begins. From this point and downstream the temperature remains nearly constant until 30 vaporization is complete since the heat flu is used to prude the latent heat ox vaporiæatior.. The slight decrease in temperature along -the vaporization region results from the fact that the pressure is ~2~7~35~

1 decreasing toward the eta end. At the point corresponding to complete vaporizatioll the temperature again rises rapidly since only the heat capacity of the vapor is avail be to absorb the 5 input heat. The power output to the capillary is controlled by feedback so as to maintain the temperature, To constant as indicated by a thermocouple 22 attached to the capillary near the inlet end where no vaporization occurs.
The total power which must be coupled into the flowing liquid to vaporize a fraction, f, of a given mass flow F (g/sec) is W - fF~Hv +F(l-f)cL(T2-To) (1) where is the total specific enthalpy (J/y) to convert liquid at the entrance temperature, To , to vapor at exit temperature, T , and CAL is the specific heat capacity of the liquid. The total power coupled into the liquid in the region between the entrance to the vaporization and the location of the thermocouple monitoring To is given by ;

We CL(Tl-To)F (2) where To is the temperature at the control point. If the tube is mounted and insulated so that essentially all of the power dissipated in the tube is coupled into the flowing fluid, then uniform heating of the tube implies that

(3) / L

So 1 where L is the total hotly length, end Lo is the length of the heated portion up to the point monitored by T].
Combining equations (1) through (3) and solving for gives 5 1 I To + Lull TOT
To Jo + Lull ,HV/cL +(l-f)(T2-To)} of<
To = To + (Ll/L)~Hv/cL +(Cv/cL)( 2 0 10 where TV is the specific heat of the vapor and the last term in To represents the heat input required to heat the dry vapor.
Since the flow rate, F, does not appear explicitly in equation (4), this result implies that the indicated 15 temperature, To, is linearly related to the fraction vaporized, I. Thus, by controlling the power input so as to maintain To constant, the fraction vaporized may be maintained at a constant selected value even though the flow rate may change. Furthermore, this equation predicts how the set point required to maintain a certain fractional vaporization depends on the composition of the fluid. As the fluid composition changes, for example, in gradient elusion, the ratio ~Iv/CL changes somewhat. If the set point for To is changed accordingly, then the fraction vaporized may 25 be maintained constant even though the solution composition may vary from pure water, for example, to pure methanol.
To a good approximation, To given by equation

(4), is independent of solvent flow rate but is significantly dependent on solvent composition. A hidden dependence on foe results from the fact that ivy depends on the temperature of the vapor at the exit, Tar, which in turn depends on the slow fate.

~227g5~

l The rate of vaporization of a liquid at temperature T is given by Z = V ) __~ 3_ or

(5) where PUT (T) is the equilibrium vapor pressure at lo temperature T, Pa is the ambient pressure of the vapor, m is the molecular mass, and k is Boltzmann's constant. This expression gives the net flux (no./cm2 sea) evaporating.
It can be transformed into an effective vaporization velocity by multiplying by the molecular mass and dividing by the 15 density of the liquid to Chive (P (T) - ) f m 2 v = (6) If the liquid is completely vaporized, then the vaporization velocity must be at least equal to the liquid flow velocity which is given by YE = FLY
(7) where F is the mass flow (g/sec) and A is the cross sectional 30 area of the flow channel in the capillary tube. For complete vaporization, conservation of mass requires that:
pLvl Pi e (8) ; 35 ~L2;~79~0 ,, 1 where Pi and TV are the density and velocity of the vapor at the exit from the capillary, and Ply and VL are the density and velocity, respectively, of the liquid before it reaches the vaporizer. The maximum velocity with which 5 the vapor can exit the tube is what of the local velocity o-sound in the vapor given by v5 = Kim 2 (9) where = Cp/Cv is the specific heat ratio for the vapor.
Combining equations (8) and (9) and assuming the vapor behaves according to the ideal gas law, we can solve 15 for the pressure of the vapor at the exit from the capillary.
The result is given by Pi = vL~LV5/Y
(10) Substituting the eta pressure for Pa in equation (6) and solving for the liquid velocity gives TV
PLUS J
(11) The temperature at which this equation is satisfied 30 corresponds to the minimum temperature of the fluid at which complete vaporization occurs. This equation can be inverted (at least numerically) to give the minimum temperature for complete vaporization as function of liquid flow. Results for several common solvents are summarized in Figure 4. If the heat supplied to the liquid is more than required to reach this temperature (for a riven flow Nate) vaporization Jill occur prompter and superheated, dry vapor will emerge ~LZZ7~35(:~
-,~

1 from the capillary. It the Hewlett supplied is slightly less that the critical vilely, then a portion of the liquid is not vaporized and will emerge along with the vapor jet as small entrained droplets. For most applications for thermos pray it 5 appears that the best operating point corresponds to a fluid temperature at which partial but nearly complete vaporization occurs. In this range the residual droplets tend to be relatively small and are accelerated to high velocities by the expanding vapor. Since the vapor pressure is a very 10 steep function of the temperature, it is essential to have very precise control of the temperature if a stable fraction vaporized is to be maintained at nearly complete vaporization.
Thus we can calculate for a given ratio L1/L the 15 temperature, To, which corresponds to a certain fractional vaporization of any fluid at any flow rate. Results for water and methanol flowing through a 0.15 mm diameter capillary with Lull = 6 are given in Figure 17. As can be seen from the figure, the dependence on flow rate is rather small, being on the order of 1C for lmL/min change in flow rate of water, hut the dependence on composition is fairly substantial, corresponding to about 15-20C difference between water and methanol at the same flow. or many purposes the low rate dependence may be unimportant; however, if 99% or more vaporization is required in a given application, then the set point must be adjusted whenever large changes in flow rate are made. It is clear, however, that this method of control provides a bets for correcting for the small flow fluctuations introduced by typical LO
30 pumps provided the overall response of the control system and vaporizer is sufficiently fast.

I
I

1 Samples of results on the variation of vaporizer exit temperature with control point temperature, To, are shown in Figure 9 for water at 1 mL/min being vclporized at atmospheric pressure these results were obtainer using a 5 capillary which according to the manufacturer's specifications was between 0.10 and 0.15 mm It. the sharp upward wreak in exit temperature at T1=150C corresponds to complete vaporization (f=1) at -the exit. The downward break at T1=50C indicates the onset of vaporization (f=0). With 10 this particular probe, the fraction vaporized is given by f=T1-50, for 50 To 150~C. After correction for convective losses, these results are generally in good agreement with theoretical expectations, except that the exit temperature (170C) at which f=1 corresponds to a liquid 15 velocity of only about 50 cm/sec. This is about one hat' the velocity expected for 1 mL/min flowing through a 0.15 mm ID
capillary. Subsequent measurements o, the capillary showed that the ID was, in fact, 0.2 mm US indicated by the above results. Performance obtained with the oversized capillary is generally inferior to that obtained with diameter of cay 0.1 to 0.15 mm, presumably because the maximum exit temperature is too low or efficient vaporization of less volatile solutes.
The importance of vaporizer geometry and exit temperatures for efficient vaporization and ionization of nonvolatile molecules is illustrated by the results shown in Figure 18. In this experiment the vaporizer was placed within 0.5 cm of the aperture for sampling ills into the mass analyzer and the ion source heater was turned o f. In this 30 mode of operation almost all of the vaporization and ionization occurs in the vicinity of the vaporizer tip.

SUE

1 These results were obtained with 0.1 M aqueous ammonium acetate flowirlg at 1.3 mL/min. A test solution containing concentrations of valise, arginine, adenosine, and quanosine was prepared using the 0.1 I buffer, and 20 us 5 allocates were injected as the power input to the thermos pray vaporizer was varied. The results of Figure I cover the range from 80 to 100~ vaporization of the solvent. The response for both the OH+ ion and the By fragment of adenosine maximize near f--1, while the response for NH4 10 and its clusters with the solvent shows a broad peak at lower input power. The protonated molecular ion for valise (not shown) gives a response similar to that for adenosine. A
very weak signal corresponding to protonated guano sine is observed; this intensity is about 3 orders of magnitude less 15 than that for adenosine. The By fragment of guano sine is more intense, and continues to rise beyond f=1. it appears that this fragment may be produced from unsown which has deposited on the inner surface of the capillary and pyrolyzed. This conclusion is supported by observation of 20 the time profiles of the various ions following the injections at I and above. As shown in Figure 19, the mass chromatograms for valise and adenosine Slow the expected narrow peats, while the guano sine fragment intensity persists for at least a full minute after injectioll. Under these I conditions the MY ion or arginine was not detected, indicating that its response was less than 10 that or adenosine.
By increasing the distance between the vaporizer and the ion sampling aperture and strongly heating the ion source, vaporization of the droplets in the thermosrpay jet can be made to occur downstream from the vaporizer. An ~Z~95~

1 example of results obtained with this more usual mode of operation is shown in Figure I In this experiment the power into the vaporizer was maintained constant at about the level required to completely vaporize 1.2 mL/min end the 5 vaporizer tip was located about 4 cm from the ion exit aperture. The power input to -the source heater was controlled so as to maintain the temperature of the vapor stream at ,50C as monitored by a thermocouple located near the center Ox the flowing stream and at a point about 3 mm 10 downstream from the ion exit aperture. In this case the fraction vaporized at the vaporizer exit varies prom about 1 at 1.2 mL/min down to about 0.6 at 2 mL/min. Adenosine and valise both maximize near f=1, but show a second maximum in the vicinity of I to 1.5 mL/min, which corresponds to 80-85~ vaporization. reunion and guano sine EYE
intensities also maximize in this region as do the fragment ion intensities. In this operating mode, maximum response for arginlne and guano sine are about 10 and owe respectively, of that for adenosine. Mass chromatograms or 20 the major ions obtained at 1.4 mL/min are shown in Figure 21.
A very small amount of tailing is observable on the BH2~
fragments of both adenosine and guano sine, indicating that some pyrolyzes may be occurring, but this effect is very small compared to that shown in Figure 19 for unsown.
The best choice of operating conditions depends to some extent on the properties of the samples and the information desired. For modestly volatile compounds, eye., adenosine and valise, it is possible to accomplish essentially complete vaporization within or just outside the 30 tip of the thermos pray vaporizer and obtain quite high sensitivities us an example, measured responses to a series ~22~g50 l of injections OX adenosine standards under conditions of nearly complete vaporization are illustrated in Figure 22.
In this example the detection limit (SNOW) is abut 20 pi and the linear dynamic range it at least 105. On the other 5 hand, this operating condition is not useful with this particular vaporizer for less volatile samples such as quanosine, asinine and others.
y operating at lower fractions vaporized within the thermos pray and applying copious downstream heat, a more 10 nearly uniform sensitivity is usually obtained. As indicated in Figure 20, some sacrifice in sensitivity for the more volatile compounds may result, but the sensitivity for less volatile components may be significantly improved.
The importance of having the droplets exit with 15 high velocity can be seen by considerillg the effects of the rapid adiabatic expansion that occurs after the vapor and its entrained droplets exit from the vaporizer. For a free jet exit, the Lucia number downstream according to the work ox Chicanos and Sherman is given by:

Al= A l ( ox tip) where A = 3.82, Jo = 0.6d, and d is the nozzle diameter and x is distance from the nozzle in units OX nozzle diameters.
The Mach number is defined as the ratio OX the axial velocity us to the local speed of sound given by equation (91. For an adiabatic expansion we have:

CpT0=(l/2)m us + Cup T (13) ~L~279~

1 which can be inverted to give the temperature downstream as:

T = To my and P = p Yule o (15) where To and PO are the temperature and pressure, respectively, of the vapor at the exit. The adiabatic expansion continues until the pressure in the jet is 15 comparable to the pressure of the background gas.
This is the location ox the Mach disc relative to the nozzle. Beyond this point heat transfer between the jet and the background gas becomes important and the jet undergoes a normal shock with the velocities rapidly relaxed 20 Buick to the local thermal velocity. Between the nozzle and the flack disc, the supersonic vapor stream controls the environment, and any evaporation or the remaining solvent.
Downstream of the Mach disc, the surrounding atmosphere may be controlled.
During the free jet expansioll the entrained liquid droplets Hayakawa highly superheated (relative to the surrounding vapor) and undergo adiabatic vaporization in which the heat of vaporization for the droplet is supplied by its internal enthalpy. The rate of vaporization of a spherical droplet is given by:
dr/dt = TV (16) I o I

1 where the vaporization velocity vet is given by equation (2). Since the process is adiabatic the result is:

do HVP)dV + CL~VdT = 0 (17) Confining these two equations (16) and (17) gives:

do = MY dry (18) which can be integrated to give:

To - T = (~HV/CL) ln(rO/r) (19) If the droplet moves with the velocity up then the foregoing equations (13) and ~15) can be combined and integrated to give an explicit expression relating to the distance x that the particle travels and its temperature. Issue expression is given by:

X = do v T (16) I' o where the vclriations in the particle velocity with distance 30 has been neglected.
Rapid vaporization of the superheated droplets eating the vaporizer capillary causes the temperature of the droplets to initially fall more rapidly than the temperature 2~35(~

1 of the vapor in the supersoilic jet. Within a short distance downstream (about one nozzle diameter or less) conditions are such that recondensation on the droplets may occur. Fast particles cross -through this region sufficiently quickly that 5 very little growth occurs, and throughout the remainder of the free jet expansion the temperature of these particles is above that of the vapor, and the vapor pressure of the particles is above the pressure of the vapor in the surrounding jet. Thus, the fast particles will continue to 10 vaporize throughout the free jet expansion, although slowly because the temperature has been reduced by adiabatic vaporization. Slow particles, on the other hand, will tend to approach equilibrium with the vapor in the jet. In this case, after the initial vaporization, the temperature of the slow particles will follow closely that of the vapor.
; Particle and vapor temperatures as a function of distance from the nozzle are sketched in Figure 8. Figure 8 plots absolute temperature as a function of distance downstream from the vaporizer for vapor and for fast and slow 20 particles or droplets. If the environment surrounding the free jet is heated, then dowllstream of the Mach disk heat transfer from the surrounding medium becomes effective and the temperatures of the vapor and particles rises. In this region the particle temperature will lag behind the vapor temperature, with the lag being largest for the slower and larger particles.
A particle exiting the nozzle with sonic velocity will be rapidly accelerated to supersonic velocity and otherwise will react only weakly with the vapor. The diameter of these particles will decrease monotGnically with distance. High velocity (but subsonic) particles will ; 35 2;279~i~

1 initially vaporize in a shorter- distance, but then ma row slightly as the pass through the supersaturated region.
Slow particles will grow throughout the free jet expansion and will enter the heated region downstream of the Mach disk, 5 much larger and much colder than the smaller droplets. The average droplet diameter is closely correlate with the fraction of the liquid vaporized within the thermospra~
vaporizer. As the fraction vaporized approaches unity the droplet diameter becomes small and the velocity high.
10 Disowned Control of the Thermos pray Vapor sizer From the foregoing -theoretical considerations the thermos pray vaporizer may be designed for any application.
The important design parameters for the vaporizer are the following:
1) The inside diameter of the vaporizer capillary.
) The length of the heated zone.
3) The maximum permissible temperature at the inner surface or the capillary.
4) The thermal time constant of the heater or 20 heaters.
In the foregoing theoretical discussion, it was assumed that the liquid channel is of uniform cross section.
While it significantly complicates the analysis and makes construction somewhat more difficult, it may be advantageous in some cases to have the cross section smaller near -the exit. This would allow higher temperatures and velocities at the exit while allowing lower liquid velocities in the region where the major part of the heat transfer is occurring.
In choosing the optimum values for the above 30 parameters, the following information about the operating conditions is needed:

~L~2~795~

1 1) The solvent flow rate and composition.
2) The degree of vaporization required.
3) The Mom permissible temperature of the fluid in the vaporizer.
I) The magnitude and time constants of uncontrolled variations in flow rate or solvent composition.
The other important considerations in designing a thermos pray system are the methods used for determining the state of the fluid exiting the vaporizer and the way in which 10 this information is used to control the power input to the vaporizer to achieve the desired operating condition.
Design of Thermosprav Vaporizer The range of operating temperatures which are used depends to a great extent on the application and the kinds of samples to be analyzed. or example, it has been found for direct LAMS on nonvolatile compounds, separated by reversed phase HPLC using water-methanol or water-acetonitrile, that vapor temperatures in the range from cay 150 to 250C give good results in most cases. These conditions are compatible 20 with a 0.15 mm capillary and flow rates in the range from I
to 2 ml/min, corresponding to liquid velocities in the range of cay 50 to 200 cm/sec. it these velocities, a heater length on the order of 3 cm is adequate to provide sufficient heat transfer without exceeding the limitations on surface 25 temperature.
To adapt this technique to micro bore liquid chromatography, where the flow rates may be an order of magnitude or more lower, and to maintain comparable operating conditions, the area of the capillary channel must be reduced 30 as the flow rate is reduced in order to maintain a similar range of liquid velocities and corresponding exit I

1 temperatures. In the case of relatively volatile or thermally labile samples, it may be desirable to limit the maximum permissible temperature in the vaporizer. This implies that the liquid flow velocity must be limited, and a 5 given solvent Low rate and composition may dictate an increase in the diameter of the capillary channel.
The ability of the control system to correct for variations in liquid flow or solvent composition depends mainly on the time constant of the temperature sensor and of 10 the vaporizer heater. These time constants are determined by the heat capacities and the rates of energy input and dissipation. To allow correction for rapid changes, for example due to pump imperfections, it is important to keep the masses of the heaters and sensors rather small.
From theoretical consideration of the desired characteristics of the thermos pray vaporizer, the embodiment illustrated in lure 2 using only direct Joule healing of the capillary tube may be superior for some applications.
This approach allows the thermal mass of the heater to be small compared to that o' the flowing liquid, and allows the use of a very short time constant. This approach also requires a power supply with fast response since otherwise a momentary flow stoppage can lead to drastic overheating. One of the practical disadvantages of this approach is that it requires rather high electrical currents and is most conveniently done using a relatively long heated length of capillary. We have wound a stainless steel capillary of 0.015 mm I'D, x 0.15 mm OLD. x 30 cm long to be a convenient choice. Capillaries of smaller dimensions have also been 30 used successfully but these are more difficult to fabricate into practical vaporizers.

~L~2~9sai -3q-1 The rather tong heated length normally used in the directly heated capillary vaporizers may cause some loss in efficiency for direct thermos pray vaporization of ions from solution since a significant number of ions may be produced 5 inside the capillary and lost due to either gas phase or wall recombination. Another problem with these vaporizers is that it is difficult to make the required electrical connection at the nozzle end without leaving a small portion which is not sufficiently heated. This allows the temperature of the 10 vapor to drop before exiting the nozzle and may also cause some loss in efficiency.
One approach to combing the best features of both vaporizers is shown in the embodiment shown in Figure 1. In this case the heater power is split between the two 15 vaporizers with typically 1/3 to 2/3 being supplied by the ohmic capillary heater and the remained by the black heater.
The capillary heater is usually considerably longer (cay. 30 cm) than the block hector (cay. 3 cm). This combination allows the fast response of the capillary heater to be employed to correct for flow variations while the block heater assures that the vaporizer temperature is properly controlled at the exit nozzle and that the final portion of the vaporization within the capillary occurs near the nozzle.
The performance of all of these vaporizer configurations depends strongly on the control system used and the location of the sensors used for determining the state of the fluid exiting the vaporizer. One of the most effective approaches it the use of a temperature sensor attached to the capillary vaporizer in the region within 30 which vaporization has not yet begun. This sensor is useful with both the directly heated capillary and with the combination described above. If the vaporizer heater power supply is controlled ho feedback from this sensor so as to I
-on-1 maintain this temperature constant, then very stable operation is obtained even though much larger flow variations may occur.
temperature sensor located in the vapor jet 5 downstream of the Mach disk may be used in a surlier manner to control any of these vaporizers. Isle this approach is somewhat more generally applicable, it is somewhat affected by other parameters such as the heat supplied to thy ion source block; thus it is not as directly related to fractional vaporization and is neither as reliable nor as stable as the former.
Another way of monitoring the performance of the vaporizer is the measure the pressure in the liquid upstream of the vaporizer as indicated at 33 in Figure 1. This 15 pressure corresponds to the pressure drop due to flow of liquid through the tube plus the pressure produced by the vaporization. Variations of pressure with temperature are dominated by the second contribution; and for a given liquid composition and flow velocity it is uniquely related to fraction vaporized. One of the potential problems with this approach is that the relationship between pressure and temperature may change, for example, due to fluctuation in the LO pump or from partial occlusion of the liquid channel.
It such an occlusion occurs upstream, the pressure would increase due to a change in liquid flow impedance even though the vaporization conditions had not changed, and the pressure indication would not provide the correct input for control of the vaporizer. On the other hand, if partial occlusion occurs at or near the exit of the vaporizer, both the exit temperature and the pressure will rise together at constant ;

2~9S() 1 power input (and constant fraction vaporized). If -the power is adjusted to keep either the exit temperature or upstream pressure constant, the fraction vaporized will decline as the vapor velocity increases due to an occlusion at or near the 5 tip. it a constant flow rate and solvent composition, this condition can be detected by monitoring the power input to the heater.
The exit temperature, the upstream pressure, and power input are related to the liquid flow velocity and 10 fractional vaporization as discussed above. The liquid flow rate and solvent composition are nominally controlled by the liquid pumping system. If the liquid flow rate and composition, power input, liquid pressure, and exit temperature are all monitored, then the fractional 15 vaporization is uniquely determined independent of any uncontrolled changes in effective vaporizer diameter which might occur as a result of partial occlusion. Since modern liquid chromatographic pumps are often operated under control of a microprocessor, it appears feasible to select the 20 desired solvent flow rate, composition and fractional vaporization, and to program the microprocessor to automatically adjust conditions so that the fraction vaporization is maintained constant both with changes in solvent composition and flow rate and with uncontrolled 25 changes in vaporizer characteristics which might be introduced by pump variations or partial occlusion of the flow channel. In the event that such occlusions causes the exit temperature or liquid pressure to exceed preset limits, an alarm showing incipient failure could be triggered.

~;2279~C) 1 applications . . _ The extent of vaporization which is desirable depends to some extent on the particular application, but it appears that most applications which we have considered so 5 far involve operation at substantial vaporization where both the particle velocities and the temperatures of the droplets and vapor are highest. As the jet undergoes an adiabatic expansion, the temperatures of hot the vapor and the droplets decrease rapidly leading eventually to complete 10 quenching of further vaporization. For most applications it appears desirable to limit the duration of the adiabatic expansion so that the temperature in the jet does not get too low. In many cases additional heat is added downstream of the Mach disk to effect further vaporization. Individual ; 15 cases are discussed below.
l. Direct Production of Ions in On-Line LAMS
. . . _ . .
If the droplets or particles produced in the thermos pray vaporizer are charged sufficiently, then ions as well as neutrals may be vaporized. If the solution being 20 vaporized contains ions in solution, then the droplets are charted by the symmetric charging mechanism. Other charging mechanisms may also be involved, and other methods of adding charge (e.g. electrical discharge) may also be employed.
While a completely satisfactory theory of field-assisted 25 vaporization of ions from liquid surfaces is not yet available, it appears that surface field strengths on the order of 108 V/m are required for evaporation rates for ions to be comparable to those Son neutrals. It appears that some of the droplets produced when thermos praying aqueous 30 electrolytic solutions (e.g. 0.1 M ammonium acetate) may initially be small enough and highly enough charged to emit ions as they eta the vaporizer nozzle. Ivory, due to the ~LZ~9~) I

1 rapid cooling that results from evaporation of the droplets during thy adiabatic expansion, tilts ion emission will not persist unless some additional heat is added downstream to assist in further vaporization of both ions and neutrals.
The efficiency of thermos pray ionization is very sensitive to vaporizer conditions. Total ion currents obtained from thermos pray ionization of l aqueous ammonium acetate measured as a function o vaporizer temperature and flow rate are summarized in Figure 5. These 10 results were obtained by operating the quadruple with only RF excitation so as to transmit all of the ions and by collecting the ions on a Faraday cup at the quad exit. No external source of ionization was used for these experiments and no electrical fields were employed inside the ion source.
15 These results were obtained for positive ions, jut approximately equal intensities of negative ions are also produced and their behavior with temperature and flow rate is similar.
These results correlate well with visual 20 observations. The maximum current corresponds to production of a relatively dry mist in an intense vapor jet; the temperatures corresponding to the maxima in Figure 5 are in excellent agreement with the optimum temperature vs. flow rate results obtained visually. Also the temperature at 25 which the current vanishes on the high temperature side correlates with disappearance the mist while the low temperature threshold for current production correlates with the minimum temperature for jet formation. lass spectra obtained by thermos pray ionization of aqueous ammonium 30 acetate show that the positive ion spectra consist almost entirely of NH4+ and its clusters with water, ammonia, and acetic acid while the negative ion spectra consists of the acetate ion clustered with one or two acetic acid molecules.
;

9 joy 1 Thermospra~ ionization appears to provide intact molecular ions for any molecule which its ionized in solution and the efficiency of producing these ions scorns nearly independent of the molecular weight and volatility of sample.
5 As an example, a spectrum of the tetradecapep-~ide resin substrate is shown in Figure 6. This is one of the largest molecules which has been successfully detected using thermos pray ionization to date and is near the upper mass limit of our quadruple as presently configured. The mass 10 resolution is too low and the mass scale calibration too uncertain in this high mass range to assign with certainty the peaks corresponding approximately to doubly and triple charged ions. From recent results on field resorption of large peptizes with multiple ionizable side chains, it is 15 suggested that these are probably doubly and triple protonated molecules. Similar results have been obtained on other molecules with molecular weights in excess of 1000 am including vitamin B12, grammicidin, and several peptizes.
We have recently developed a technique for separating the sample from the solvent uslny thermos pray vaporization with a flowing gas system which involves no moving parts and does not require a vacuum system. This concept is illustrated schematically in Figure 12. In this concept the thermos pray jet sprays into a gas stream as illustrated at 40~., 40b (which could be clean air) at atmospheric or higher pressure. The flow of gas is sufficient to sweep away most of the solvent vapor as it is ; thermalized downstream of the Mach disk, but not so high as to significantly deflect the beam of high velocity particles 30 and droplets generated by the thermos pray. The beam of particles passes through a first small aperture 36 into a second region where further separation of solvent vapor and sample particles occur. The gas entering each region may be ~L;22~7~5~
~45-1 heated as required to effect additional vaporization of solvent from the droplets or particles. Figure 12 shows two stages of separation, aye, 40b, separated by aperture baffles 38 and 39 but depending on the degree of solvent 5 removal required, the number of staves could be reduced to one or increased to as many as is required. At the exit of the solvent separator the particles pass through a final aperture 37 in-to a suitable detector or analyzer 35. The gas flowing into the detector may be the same as the gas used in 10 the separator or may be different depending on the application.
An example of the use of this gas phase sample/solvent separator with a photo ionization detector is shown in Figure 13. In this case air is used as the carrier 15 gay in the separation region 40 and helium is used as the flow gas in the detector 41. In most cases smell concentrations of air or solvent vapor will not interfere with the photo ionization detector, particularly if relatively long wave-length radiation is used. In the version shown in 20 Figure 3 the particle beam impacts on a heated metal surface 42 where final sample vaporization occurs. Gas phase sample molecules or small clusters are then photo ionized and collected at 43. The ion collector may be biased by deflector 44 relative to the hot surface so as to detect ions 25 produced in the gas phase but not those produced directly at the hot surface I Alternatively, the collector may be used to monitor ion currents produced directly as the result of particle impact with the heated surface 42 with the US lamp 45 turned off. Both modes of operation may be of significant 30 utility. In some cases, it may be possible to efficiently vaporize the particles in the beam aye merely by contact with hot gas in the detector; in this case the heated surface is not required.

~Z2~79~

1 The thermos pray vaporizer can also be used with gas Crow separation of solvent vapor to produce a molecular beam of nonvolatile molecules or small clusters as shown in Figure 14. If the thermos pray jet is directed into a vacuum 50 5 without solvent removal, the rapid adiabatic cooling will cause recondensation of the vapor onto the particles or droplets. While this technique can probably be used to produce a supersonic particle beam, the particles produce will tend to be rather large and very cold. By using the gas 10 flow separator aye and 40b it is possible to first separate most of the solvent vapor from the sample particles and then pass the particles through a second heated capillary 51.
downstream of the capillary 51 is a conventional supersonic beam system consisting of a skimmer 52 and collimator 53 with 15 the chambers in between these components separately pumped by large vacuum pumps. As the particles pass through the heated capillary 51 further rapid vaporization can be made to occur resulting in a supersonic "seeded" beam of nonvolatile molecules 54. Depending on the conditions used in the heated 20 capillary 51 , it should be possible to achieve either complete or partial vaporization as required.
Efficient removal of solvent appears to be quite straightforward by this technique, but maintaining efficient sample transfer requires very close control of both the 25 vaporizer and the downs ream environment. For efficient sample transfer it is essential to have the sample contained in the droplets and also have the droplets moving with relatively high velocity. In some cases this may be accomplished simply by proper control of the 30 vaporizer. For example, we have succeeded in obtaining essentially 100% transfer of amino acids in aqueous solution ; 35 ~279S~) 1 by thermos prying at atmospheric pressure with no control on the downstream environment. On the other hand when operating at lower ambient pressures it appears necessary to confine the vaporization region so that the adiabatic expansion does 5 not continue indefinitely. A schematic diagram of a system for thermos pray transfer of samples to a moving heft 62 at atmospheric pressure is shown in Figure 11. In this system the exit temperature is controlled by feedback control of the vaporizer heater using a temperature sensor 23 attached at or 10 near the end of the capillary 15. The temperature at or near the surface of the belt at the point of jet impact is monitored by a second temperature sensor 60 which controls the input to a heater/cooler 61 attached to the housing surrounding the jet. Depending on the nature of the solvent 15 and sample it may be necessary in some cases to either heat or cool this region to maintain the surface of the belt at an appropriate temperature. This temperature should be low enough that no significant amount of sample is vaporized vet high enough that any residual liquid solvent is vaporized efficiently in a stream of counter-current flowing gas 63 which passes over the belt and exits with the vapor to the exhaust system I
The foregoing description of the several embodiments of the thermos pray vaporizer and its application is presented for the purpose of illustrating the invention, and is not intended to be exhaustive or to limit the invention to the specific embodiments or means illustrated.
They were chosen and described in order to explain the principles of the invention and their practical application to enable those skilled in the art to use the invention. The scope of the invention is to be defined in accordance with the following appended claims.

Claims (60)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. An ion vapor source for obtaining an ion vapor from a liquid sample, said sample having ions of interest therein, the source comprising:
(a) a capillary tube for receiving said sample, said tube defining a nozzle on one end thereof, (b) a means for supplying a liquid sample containing ions of interest to said capillary tube, (c) a heating means for partially vaporizing the liquid sample passing through said capillary tube, (d) a control means for controlling the temperature of the sample within the capillary to maintain a predetermined fraction of the sample in liquid form as it is ejected from the nozzle as a thermospray of minute particles entrained in an intense vapor jet whereby ions of interest are vaporized from the particles as a consequence of an electrical charge on the particles and the internal enthalpy of the particles.

2. An ion source as claimed in claim 1 in which the liquid sample contains additional ions which are not themselves of interest but which serve to increase the charge on the particles in the thermospray thereby increasing the efficiency with which ions of interest are produced.

3. An ion vapor source for obtaining ion vapor from a liquid sample, said sample having molecules of interest contained therein, said source comprising:
(a) a capillary tube for receiving said sample, said tube defining a nozzle on one end thereof, (b) a means for supplying a liquid sample containing molecules of interest to said capillary, (c) a heating means for partially vaporizing the liquid sample passing through said capillary tube, (d) a control means for controlling the temperature of the sample within the capillary to maintain a predetermined fraction of the sample in liquid form as it is ejected from the nozzle as a thermospray of minute particles entrained in on intense vapor jet, (e) a means for ionizing the selected molecules of interest after ejection from said nozzle.

4. An ion source as claimed in claim 3 wherein the liquid sample contains additional ions which are not themselves of interest but which may transfer their ionization to molecules of interest by ion-molecule collision processes thereby providing an additional means of ionizing molecules of interest.

5. An ion vapor source as claimed in claim which further includes a means for controlling the downstream environment beyond the capillary nozzle for controlling the temperature and pressure of the downstream environment.

6. An ion vapor source as claimed in claim 5 wherein said means for controlling the downstream environment further includes a heat source and a temperature sensitive transducer.

7. An ion vapor source as claimed in claim 5 wherein said means for controlling the downstream environment further includes a vacuum pump for withdrawing said vapor.

8. An ion vapor source as claimed in claim 5 wherein said means for controlling the downstream environment further includes a flow constricting aperture located upstream of the ion sampling aperture but downstream of the main source of heat or the jet.

9. An ion vapor source as claimed in claim ]
wherein said heating means comprises a heated metal block intimately secured in a heat conductive relationship around said capillary tube.

10. An ion vapor source as claimed in claim 1 wherein said capillary is electrically conductive and said heating means includes a circuit for applying electrical energy to a predetermined length of said tube for direct resistance heating.

11. An ion vapor source as claimed in claim 9 wherein the control means for controlling the temperature includes a temperature sensor mounted in thermal contact with the capillary at a point where the entire sample is still in the liquid state.

12. An ion vapor source as claimed in claim 10 wherein said heating means also includes a heated metal block intimately secured to the downstream side of said directly heated portion of said capillary in a heat conductive relationship therewith.

13. An ion vapor source as claimed in claim 11 wherein the control means for controlling the temperature further includes a temperature sensor in the vapor stream downstream from the vaporizer wherein said temperature sensor is used with said control means to compensate for gradual changes in composition or flow rate of said sample.

14. An ion vapor source as claimed in claim 12 wherein said control means controls said heated block to compensate for gradual changes in composition or flow rate of said sample and control said direct resistance heating to compensate for rapid fluctuations in flow rate.

15. An ion vapor source for obtaining an ion vapor from a liquid sample having large, thermally labile molecules therein, said source comprising, (a) a metal capillary tube for receiving said sample, said tube defining a nozzle portion at one end thereof, (b) a heating means for said capillary tube to vaporize a predetermined fraction of the sample passing there through, (c) control means for said heating means to control the temperature of the sample within the capillary and maintain from 1% to 35% of the sample in liquid form as it is ejected from the nozzle as a thermospray of minute particles entrained in an intense vapor stream, (d) a means for controlling the downstream vaporization of the remaining sample after ejection from said nozzle, whereby the remaining fraction of the sample is vaporized by contact with heated vapor to thereby suspend said thermally liable molecules in said vapor stream, (e) a means for ionizing said thermally liable molecules into ions of interest for further analysis.

16. An ion vapor source as claimed in claim 15 wherein said means for controlling the downstream environment further includes a heat source and a temperature sensitive transducer.

17. An ion vapor source as claimed in claim 15 wherein said means for controlling the downstream environment further includes a vacuum pump for withdrawing said vapor.

18. An ion vapor source as claimed in claim 15 wherein said vapor stream is directed to an exhaust means downstream of said nozzle, said source also comprising an ion lens for extracting said ions of interest.

19. An ion vapor source as claimed in claim 15 wherein said heating means further comprises first and second heating means, said first means responding to gradual changes in the composition or flow rate of said sample, and said second heating means responding to smaller rapid fluctuations in flow rate.

20. A thermospray device for vaporizing a liquid sample containing a solvent and large molecules of interest for future analysis, said device comprising:
(a) a metal capillary tube for receiving said sample, said tube defining a nozzle portion at one end thereof, (b) a heating means for said capillary tube to vaporize a predetermined fraction of the sample passing there through, (c) a control means for said heating means to control the temperature of the sample within the nozzle and maintain from 1% to 35% of the sample in liquid form as it is ejected from the nozzle as a particle beam of minute particles entrained in an intense vapor jet, (d) a means for purging the solvent from said vapor stream as said molecules are selected for further analysis.

21. A thermospray device as claimed in claim 20 wherein said device further includes a moving belt which is arranged to receive said particle beam, said purging means having a chamber surrounding said belt and means for admitting a purging gas in a countercurrent relationship thereto.

22. A thermospray device as claimed in claim 20 wherein said purging means further comprises a plurality of apertured baffles with the apertures aligned along an axis defined by said particle beam, said purging means including means for providing a sweep gas between said baffles for removing solvent vapor.

23. A thermospray device as claimed in claim 22 wherein the purging means also includes a heated surface suspended within a heated chamber for receiving the particle beam.

24. A thermospray device as claimed in claim 22 wherein the purging means further includes:
(a) a second heated capillary beyond said baffles for receiving said particle beam, (b) a collimator means aligned with said second capillary for selecting particles along a predefined axis, (c) a vacuum pump means for withdrawing any remaining solvent vapor between said second capillary and said collimator.

25. A thermospray vaporizer for vaporizing a solution containing a solvent and molecules of interest for detection or analysis, wherein the molecule(s) of interest are non-volatile or ionic or thermally labile or a combination thereof, said vaporizer comprising:
(a) a capillary tube for heating a solution to be vaporized, (b) a means for pumping said solution through said capillary, (c) a means for heating the capillary tube to partially vaporize a solution passing therethrough, (d) a means for controlling the temperature of the capillary tube to vaporize a predetermined fraction of the solution passing therethrough, (e) a nozzle portion at the end of said capillary for spraying the partially vaporized solution to form a thermospray of relatively dry particles entrained in an intense vapor jet, (f) a means for controlling the downstream environment to prevent recondensation of solvent on the molecules of interest, whereby any remaining solvent carried by the relatively dry particles is vaporized beyond the nozzle by internal enthalpy.

26. A thermospray vaporizer as claimed in claim 5 which further includes means for ionizing the molecules of interest.

27. A thermospray vaporizer as claimed in claim 25 which further includes means to control the temperature of the downstream environment beyond the nozzle.

28. A thermospray vaporizer as claimed in claim 25 which further includes a vapor pumping means having a vapor inlet positioned downstream of said nozzle and aligned generally therewith.

29. A thermospray vaporizer as claimed in claim 28 which further includes an ionizing means for ionizing said molecule of interest between said nozzle and said vapor inlet.

30. A thermospray vaporizer as claimed in claim 25 which further includes a two stage heating means for heating the capillary tube, with the first stage responsive to variations in the composition of the solution, and a second stage responsive to variations in the flow rate of the solution.

31. A thermospray vaporizer as claimed in claim 25 which further includes a means for detecting a specific molecule of interest.

32. A thermospray vaporizer as claimed in claim 25 which further includes a means for analyzing the mass of the molecules of interest.

33. A thermospray vaporizer as claimed in claim 25 wherein the size of the nozzle and the temperature of the capillary are selected to create a supersonic vapor jet.

34. A method of vaporizing a solution containing a solvent and molecules of interest for detection or analysis, wherein the molecules of interest are non-volatile or ionic or thermally labile or a combination thereof, said method comprising:
(a) partially vaporizing the solution in a heated passageway, (b) controlling the temperature of the solution in the passageway to maintain a predetermined degree of vaporization as the flow rate or solution composition varies, (c) spraying the partially vaporized solution through a nozzle to form a thermospray of relatively dry particles entrained in an intense vapor jet, (d) controlling the downstream environment to prevent recondensation of solution of the molecules of interest, whereby the remaining solvent carried by the relatively dry particles is vaporized by internal enthalpy.

35. A method of vaporization as claimed in claim 34 wherein the intense vapor jet exits the nozzle at a supersonic velocity and the remaining solvent is vaporized between the nozzle and a Mach disk downstream of the nozzle beyond a Mach disk.

36. A method of vaporization as claimed in claim 34 wherein the molecules of interest are ionized.

37. A method of vaporization as claimed in claim 34 wherein the temperature of the solution is controlled with a two stage heater, with the first stage responding to variations of composition and the second stage responding to variations in flow rate.

38. A method of vaporization as claimed in claim 34 which further includes the step of removing the solvent vapor with a vacuum pump along a first axis generally aligned with said passageway and directing ionized molecules of interest along a second axis generally perpendicular to said first axis.

39. A method of vaporization as claimed in claim 35 which further includes the step of detecting a particular molecule of interest.

40. A method of vaporization as claimed in claim 39 wherein the detection step is selected from one of the following:
(1) photoionization, (2) flame ionization, (3) electron capture, (4) optical photometry, or (5) atomic adsorption, (6) optical emission.

41. A method of vaporization as claimed in claim 35 which further includes the step of analyzing mass of said molecules of interest.

42. A method of partially vaporizing a liquid sample containing a solvent and non-volatile molecules of interest for further analysis, said method comprising, (a) supplying a liquid sample containing said molecules to a capillary tube having a nozzle at one end thereof, (b) heating the capillary tube to partially vaporize the sample flowing therein, (c) spraying the sample from the nozzle as a spray of minute particles entrained in an intense vapor jet, said particles preferentially containing the molecules of interest, (d) controlling the temperature of the sample in said capillary to maintain from 1% to 35% of the sample in liquid form as it is sprayed from the nozzle, (e) purging the vapor stream of solvent vapor before analyzing said molecules.

43. A method as claimed in claim 42 which further includes the step of ionizing the molecules after they have been sprayed from said nozzle.

44. A method as claimed in claim 42 which further includes the step of ionizing the molecules of interest with chemical ionization before said sample is sprayed.

45. An ion vapor source for obtaining an ion vapor from a liquid sample, the source comprising:
(a) a capillary nozzle for heating and partially vaporizing a liquid sample passing there through, (b) means for heating the capillary nozzle, (c) means for supplying a liquid sample to said nozzle (d) means for sensing the fluid pressure of said liquid sample upstream of said capillary nozzle and using said pressure to control the temperature of the sample within the nozzle to maintain a predetermined fraction of the sample in liquid form as it is ejected from the nozzle, (e) an ionization chamber for receiving at least a portion of the sample discharged from said nozzle.

46. An ion vapor source as claimed in claim 1 which further comprises means for regulating the temperature of the discharge sample to regulate the subsequent adiabatic expansion of the sample.

47. A method of vaporizing a sample containing nonvolatile molecules for an ion vapor source, said method comprising:
(a) supplying a liquid sample containing said molecules at a selected fluid pressure to a capillary nozzle, (b) heating the nozzle to achieve a partial vaporization of the sample within the nozzle, (c) regulating the fluid pressure of the sample upstream of the nozzle, (d) controlling the temperature and pressure of the sample in said nozzle to maintain a predetermined fraction of the sample in liquid form as it is ejected from the nozzle, (e) ionizing the vaporized sample.

48. A method of vaporizing a sample as claimed in claim 47 wherein said method further includes the step of regulating the temperature of the sample after it has been discharged from said nozzle to control the adiabatic expansion of the sample.

49. An ion analyzer for obtaining and analyzing vapor from a liquid sample, said sample having ions of interest therein, the source comprising:
(a) a capillary tube for receiving said sample, said tube defining a nozzle on one end thereof, (b) a means for supplying a liquid sample containing ions of interest to said capillary tube, (c) a heating means for partially vaporizing the liquid sample passing through said capillary tube, (d) a control means for controlling the temperature of the sample within the capillary to maintain a predetermined fraction of the sample in liquid form as it is ejected from the nozzle as a thermospray of minute particles entrained in an intense vapor jet, (e) means for separating the ions of interest as they are vaporized from the particles as a consequence of an electrical charge on the particles and the internal enthalpy of the particles, (f) means for analyzing the separated ions of interest.

50. An ion analyzer as claimed in claim 9 in which the liquid sample contains additional ions which are not themselves of interest but which serve to increase the charge on the particles in the thermospray thereby increasing the efficiency with which ions of interest are produced.

51. An ion analyzer as claimed in claim 49 in which the means for analyzing the separated ions is a mass spectrometer.

52. An ion analyzer for obtaining and analyzing ion vapor from a liquid sample, said sample having molecules of interest contained therein, said source comprising:
(a) a capillary tube for receiving said sample, said tube defining a nozzle on one end thereof, (b) a means for supplying a liquid sample containing molecules of interest to said capillary, (c) a heating means for partially vaporizing the liquid sample passing through said capillary tube, (d) a control means for controlling the temperature of the sample within the capillary to maintain a predetermined fraction of the sample in liquid form as it is ejected from the nozzle as a thermospray of minute particles entrained in an intense vapor jet, (e) a means for ionizing the selected molecules of interest after ejection from said nozzle.
(f) means for analyzing the selected molecules after ionization.

53. An ion analyzer as claimed in claim 52 wherein the liquid sample contains additional ions which are not themselves of interest but which may transfer their ionization to molecules of interest by ion-molecule collision processes thereby providing an additional means of ionizing molecules of interest.

54. An ion analyzer as claimed in claim 49 in which the means for analyzing the selected molecule is a mass spectrometer.

55. An ion vapor source as claimed in claim 49 or 52 wherein said heating means comprises a heated metal block intimately secured in a heat conductive relationship around said capillary tube.

56. An ion vapor source as claimed in claim 49 wherein said capillary is electrically conductive and said heating means includes a circuit for applying electrical energy to a predetermined length of said tube for direct resistance heating.

57. An ion vapor source as claimed in claim 56 wherein said heating means also includes a heated metal block intimately secured to the downstream side of said directly heated portion of said capillary in a heat conductive relationship therewith.

58. An ion vapor source as claimed in claim 52 wherein the control means for controlling the temperature includes a temperature sensor mounted in thermal contact with the capillary at a point where the entire sample is still in the liquid state.

59. An ion vapor source as claimed in claim 58 wherein the control means for controlling the temperature further includes a temperature sensor in the vapor stream downstream from the vaporizer wherein said temperature sensor is used with said control means to compensate for gradual changes in composition or flow rate of said sample.

60. An ion vapor source as claimed in claim 57 wherein said control means controls said heated block to compensate for gradual changes in composition or flow rate of said sample and control said direct resistance heating to compensate for rapid fluctuations in flow rate.