Patent Grant
8920658
This invention relates generally to techniques and apparatus for desolvating flowing liquid streams while retaining structural integrity and temporal separation of dissolved solutes. More particularly, this invention relates to apparatus and methods for interfacing liquid chromatography with a Fourier transform infrared spectrometer which is applicable to continuous flow use in normal phase, reverse phase and size exclusion separations.
A high degree of compound separation, selectivity and identification is made possible by combining liquid chromatography techniques with molecular detector methods which provide structural information. This approach has been recognized as extremely valuable for the identification of various components of complex chemical mixtures. Particularly, liquid chromatography (LC) has proven to be excellent means for separating a chemical mixture and for determining the individual constituents, either quantitatively or volumetrically. However, LC devices used by themselves have the disadvantage that they do not satisfactorily identify the separated chemical constituents.
On the other hand, the mass spectrometer (MS) is extremely capable and sensitive in identifying single chemical components, but considerable difficulty is experienced in trying to utilize such equipment in identifying the components of a chemical mixture. Consequently, hybrid techniques, which combine chromatography with molecular methods such as mass spectrometry and Fourier transform infrared spectrometry, have been developed and are used extensively for component analysis of complex chemical mixtures.
The high scan speed and sensitivity of Fourier transform infrared (FTIR) spectroscopy have enabled the recording of infrared spectra of individual components of a mixture which have been separated by chromatographic techniques. Coupling of chromatography with FTIR equipment has been successfully accomplished for gas chromatography (GC). However, many chemical compounds and mixtures are not sufficiently volatile for GC separation. Moreover, the sensitivity of a combination GC/FTIR mechanism is reduced for less volatile compounds, making this combination unacceptable. Particularly, the less volatile and/or more polar compounds in a mixture must usually be separated by LC.
Interfacing of LC mechanisms with FTIR devices has not heretofore been substantially successful due to the infrared absorption of the mobile phase of the LC eluent. Generally, solvents which are good mobile phases for LC applications are also usually strong infrared absorbers. To try to address this problem, two general types of systems have been developed: (1) flow cells which take advantage of some mobile phases which have large infrared (IR) windows; and (2) elimination of the mobile phase prior to deposition of the eluate on an appropriate substrate. Each of these approaches, however, have their own problems in achieving a reliable and universal interface arrangement.
For example, all solvents absorb some infrared radiation, and the degree of such absorption defines the maximum path length which a flow cell can have which will allow identifiable spectra to be obtained. Additionally, mobile phases having large IR windows are generally of low polarity and are used only for normal-phase LC. The shorter path lengths which must be used to minimize interference resulting from mobile phase absorption similarly limit the volume of the flow cell, thereby limiting the concentration of the analyte being measured at any one instant, and thus compromising the accuracy of the process overall. The major challenge of interfacing normal-phase and reverse-phase LC to IR techniques is the incompatibility of typical solvents to identification of unknown constituents by IR technology. Consequently, water and other typical mobile phases used in LC separations are best eliminated prior to measuring the IR spectrum of a component.
A variety of methods and devices have been directed toward eliminating solvents prior to FTIR procedures, including flowing effluent from a capillary LC column into a stainless steel wire net designed to eliminate the solvent as a result of a heated gas flow. In this approach, the sample material is suspended between the metal meshing, and the deposits are then analyzed. Griffiths et al. developed a system wherein the LC effluent is deposited on an IR transparent substrate as warm nitrogen induces solvent evaporation prior to IR analysis. An interface was developed by Gagel and Biemann in which deposition of the sample material was to be continuous and where effluent from a microbore LC was continuously sprayed onto a rotating disk as warm nitrogen was passed across the disk to evaporate the solvent. In that procedure, however, the FTIR spectra were measured off-line by fastening the collection device to a reflectance accessory.
A solvent removal interface developed by Kalasinsky for reverse phase LC contemplated the elimination of water by employing a particular chemical (2,2′-dimethoxypropane) to convert the water to methanol and acetone for deposition on a KCl substrate. Such conversion requires specific matching of chemicals and collection substrates, and does not truly remove the solvent but merely converts it to other substances which can independently add interference to analysis results.
Browner and coworkers developed a monodisperse aerosol generator interface for combining LC and FTIR spectrometry known as the MAGIC interface. With this interface, mobile phase elimination was to be accomplished at room temperature, wherein effluent from an LC enters the interface through a 25 micrometer diameter orifice to form a liquid jet. The jet is dispersed by a Helium (He) stream to create a fine aerosol which is directed from a desolvation chamber into first and second momentum separators. In the first momentum separator, evaporated solvent and Helium are removed by vacuum pumps, and the nonvolatile analyte continues into the second momentum separator where any residual volatile material is to be removed. The nonvolatile analyte is then deposited on a KBr (potassium bromide) window which is removed and placed in a beam condenser for IR analysis. Because the solvent is eliminated prior to deposition on the substrate, the isolated analyte can be deposited on a variety of substrates for various IR detection methods.
In U.S. Pat. Nos. 4,814,612 and 4,883,958, which are incorporated herein by reference, M. L. Vestal et at. described similar apparatuses and methods for coupling LC and solid phase detectors, including the use of thermospray vaporizers which vaporize most of the solvent prior to introduction to a desolvation chamber. The device described in the Vestal '958 patent further contemplates passing the vaporized solvent and added carrier gas through one or more solvent removal chambers, which can remove solvent by condensation or diffusion through a membrane to a counterflowing gas stream. This device may further include a momentum separator to concentrate particles relative to the remaining solvent vapor and carrier gas. This patent also teaches the direction of a particle beam for impact with a cryogenically cooled deposition surface. In the Vestal '612 patent, a moving belt is provided for receiving the particle beam, and a temperature transducer is positioned adjacent the belt to maintain the belt at a temperature where no significant amount of the particle sample will be vaporized, yet warm enough that residual liquid solvent is vaporized efficiently in a stream of counterflowing gas which passes over the belt.
The Vestec Universal Interface incorporates many of the features described in the Vestal patents mentioned above, and was commercially available in the industry from Vestec Corporation of Houston, Tex.
An apparatus combining LC technology with mass spectrometry is described in U.S. Pat. No. 4,980,057, which is incorporated herein by reference, issued to S. B. Dorn, et al. The Dorn '057 device includes a nebulizer which volatilizes the LC eluate to form an aerosol which passes through a desolvation chamber. The nebulizer introduces an inert gas which helps vaporize the solvent and carries the aerosol to a momentum separator which accelerates the particles to sonic velocities. The momentum separator includes three vacuum pumping stages, wherein the first two stages are defined by conical skimmer nozzles, and the third chamber includes a long inlet tube which provides the vacuum pumping restriction. The resulting particle beam is provided to the MS ion source for analysis.
Another approach to this analysis problem is the LC-IR sample delivery system developed by S. Bourne based on ultrasonic nebulization followed by evaporation. Versions of this system have been available from Bourne Scientific, Nicolet and Bio-Rad corporations, as described in U.S. Pat. Nos. 5,045,703; 5,039,614; 5,238,653 and 4,552,723, which are incorporated herein by reference.
LC sample delivery by pneumatic, thermal or ultrasonic nebulization, followed by evaporation and deposition at atmospheric pressure or in a vacuum onto a rotating germanium disk is a technique developed by Lab Connections. The germanium disk is then transferred to, and read by an FTIR, as described in U.S. Pat. Nos. 5,772,964 and 4,823,009, which are incorporated herein by reference.
In U.S. Pat. No. 5,538,643, which is incorporated herein by reference, Kallos describes an LC-FTIR interface sample handling process consisting of nebulizing an LC eluent, removing the solvent by a combination membrane-and-momentum separator, followed by focused deposition onto a cryogenic surface with subsequent thermal manipulation of this surface to remove remaining solvent.
Consequently, while a great number of investigations and techniques have been attempted heretofore, LC/FTIR interfaces have thus far shown only limited success in providing interpretable IR spectra from normal-phase and reverse-phase separations, due to inadequate solvent elimination and/or limited applicability to IR analysis. Although many of these previously developed systems generate aerosols from the liquid stream, and partially desolvate the stream, none of them effectively, reliably and robustly separates the solvent vapor and non-condensable carrier gas from the particulate stream.
These and other deficiencies in or limitations of the prior art are overcome in whole or at least in part by the apparatus and related methods of this invention. As described hereinafter, the present invention successfully and effectively removes interfering materials, thus enabling applications of the particle stream, such as for analysis, which would otherwise be prevented or limited.
Accordingly, it is a principal object of this invention to provide improved treatment techniques and apparatus for desolvating flowing liquid streams containing one or more solutes while retaining the chemical and structural integrity and temporal separation of such solutes.
A specific object of the present invention is to provide methods and apparatus to continuously remove the solvents from a fluid mixture comprising liquid components and solute components and deposit the resolved, concentrated, structurally integral solutes on a surface for subsequent infrared absorption analysis.
In general, methods and apparatus of the present invention consist of a series of process steps or stages, and related apparatus components, that comprise a novel spray drier system for processing a flowing liquid stream containing low-volatility components by removing the liquid solvent component and leaving the low-volatility solute components. The spray drier system of this invention preserves the chemical and structural integrity, as well as the temporal resolution, of the low volatility components (the solutes) while desolvating the liquid stream. The dried solute may be further processed, deposited onto a solid surface, or collected as a solid, powder or liquid. In one preferred embodiment, the liquid stream is a chromatographic effluent and the dried solute is deposited as a small spot or stripe on a surface for infrared spectrographic analysis. The term “solute” as used in this disclosure is hereby defined as and intended to include dispersed and suspended, as well as dissolved, solids and relatively low vapor pressure liquids.
The novel spray drier system of this invention comprises in part a nebulizer which converts the liquid stream into a high speed aerosol jet which can then be directed circumferentially around the inside surface of a hot, generally cylindrical cavity of a chamber. As used herein, the term “aerosol” is hereby defined to include liquid droplets and/or solid particles suspended or entrained in a gas-phase fluid. Centrifugal force, which can be provided by the jet velocity, causes the larger liquid droplets to travel along the outer diameter of the cavity. The cavity inner surface is heated to a temperature of at least 20° C., preferably at least 50° C., more preferably at least 100° C., above the boiling point of the liquid component of the fluid stream, to cause the droplets approaching that surface to “film boil.” Film boiling rapidly evaporates solvent from the droplets. In film boiling, the rapid release of freshly evaporated solvent vapor creates a gas layer adjacent the heated surface that prevents droplet contact with the cavity wall, thereby retaining the solute in the droplets. To ensure that the phenomenon of “film boiling” occurs in the chamber cavity, the heated inner surface of the cavity should be maintained at a temperature that is at least 20° C., preferably at least 50° C., and more preferably at least 100° C., hotter than the boiling point of the liquid component of the fluid stream being treated. The solute is protected from thermal damage by the combination of a short residence time and by being inside the droplet, which is cooled by solvent evaporation.
When the droplets have evaporated to a sufficiently small size, Stokes drag forces from the exiting solvent vapor will exceed the centrifugal force and carry the droplets out of the chamber, for example along the central axis of the cylindrical cavity. For convenience, the term “cyclone” will be used herein for the chamber/cylindrical cavity assembly as described above. After the droplets leave the cyclone inner surface, heat exchange with the superheated solvent vapor further dries the droplets. If not already present, a small amount of non-condensable gas may be added. This added gas helps to maintain the dried droplets in an aerosol suspension during and after the removal of solvent vapor. Solvent vapor is removed by condensation onto a cooled surface in a first-stage condenser unit. Operating this first-stage condenser unit above the freezing point of the solvent produces a liquid condensate that can be continuously drained. The amount of remaining solvent vapor may be further reduced by an optional second condenser stage operated at a lower temperature than the first-stage condenser unit. A solvent freeze point reducing agent, such as methanol, may be added to the second condenser stage. For a preferred chromatographic application, the dried droplet aerosol suspension flows through an orifice that focuses the dried droplets into a narrow beam. An optical surface is placed under the beam to collect the solute. The deposition surface is typically positioned in an evacuated chamber and is temperature controlled to condense or freeze liquid solutes while preventing condensation or allowing sublimation of any residual solvent. To prevent “bouncing” of the dried particle off of the optical surface, a solvent or other adhesion-improving agent may be added to the deposition region. The optical surface is then moved into the focus of the infrared microscope beam for analysis of the solute collected on the surface.
The following discussion is intended to convey the inventors' present understanding concerning how this invention operates, but such discussion should not be interpreted to limit the validity or scope of the claims. Much of the uniqueness and advantage of the cyclone apparatus of this invention is its ability to accept a wide range of starting droplet sizes, and to automatically by virtue of its operation deliver only enough heat to each droplet as needed to evaporate the predominant portion of the solvent in each droplet. Evaporative cooling effects with this apparatus limit the maximum droplet temperature to roughly the solvent boiling point at the cyclone operating pressure. Each individual droplet remains in the cyclone only long enough to shrink to a relatively uniform and very small size. Because the residence time of a droplet in the cyclone is inversely related to the starting droplet size, the result is minimal exposure of each droplet to high temperature, potentially thermally degrading or volatile-solute evaporating conditions. The balance between opposing centrifugal force and the drag forces within the cyclone from the exiting solvent vapor determines what that droplet size will be. The concentrated droplets are removed from proximity to the cyclone surface while they still contain a relatively small amount of solvent. Because the exiting droplets have a relatively narrow homogeneous size distribution, the amount of additional heat required to thereafter complete the evaporative removal of residual solvent is similar for each droplet. Heat transfer from the super heated solvent vapor in this system provides this relatively uniform additional amount of heat to effectively complete the evaporation process. At the same time evaporation of this residual solvent continues to protect the sample (solute) for most of this drying step. Because the droplets are already leaving the cyclone before they can reach full dryness, the duration of droplet exposure to conditions without evaporative cooling protection is minimal thereby minimizing opportunities for thermal degradation of the sample.
Unlike most prior art processes in this field, the cyclone of this invention evaporates the solvent without the addition of and dilution by, a drying gas. In most prior art techniques in this field, the problem of supplying sufficient heat to complete evaporation has required either: (1) a large mass of drying gas; (2) a very long residence time to allow a low temperature differential to transfer sufficient heat through the gas to the liquid; (3) exposure of the sample to excessively high temperatures; or (4) a combination of these approaches. Worst of all, in the prior art, is the duration of exposure of all the solute to these drying conditions for the relatively long time needed to dry the largest of the droplets. All smaller droplets are thereby exposed to excessive drying conditions that the present invention avoids. By contrast, the methods and apparatus of this invention do not require any of these prior art drying techniques and thereby avoid the associated disadvantages.
As will be apparent from the following description, the methods and apparatus of this invention may be practiced in a number of different ways, all of which are considered to be within the scope of the invention. At the present time, it is envisioned that there will be certain preferred embodiments, especially in connection with liquid chromatography. Among such preferred invention embodiments are the following:
(1) Apparatus for evaporating liquid from an inlet fluid stream comprising liquid and solute components, said apparatus comprising in combination:
(2) An apparatus according to paragraph (1) above wherein said fluid vortical direction imparting element is selected from the group consisting of: (i) a fluid inlet that directs an inlet fluid stream so as to have a net tangential component relative to the cylindrical-shaped cavity side wall; (ii) a rotating element in said chamber cavity on which an inlet fluid stream impinges and at least a portion of which fluid stream is thereby directed outwards toward the cavity side wall with a net circumferential directional component; (iii) a source of moving gas in said chamber cavity that imparts motion having a net circumferential component to an inlet fluid stream; and, (iv) a rotational device that rotates the chamber cavity.
(3) An apparatus according to paragraph (1) above wherein the source of heat that heats the cavity side wall is selected from the group consisting of: (i) an electric resistance heater; (ii) an electric cartridge heater; (iii) a surface mounted electric resistance heater; (iv) a deposited film electrically conductive resistance heater; (v) an electrically conductive heater deposited on the cylindrical-shaped surface; (vi) a radio frequency electrical induction heater; (vii) a microwave heater; (viii) a flame; (ix) an infrared radiant heater; (x) a high temperature gas; and, (xi) a high temperature liquid.
(4) An apparatus according to paragraph (1) above wherein said fluid vortical direction imparting element is capable of causing an inlet fluid stream to rotate within the chamber cavity at a sufficient velocity to maintain the fluid stream traveling substantially circumferentially adjacent said cylindrical-shaped cavity side wall.
(5) An apparatus according to paragraph (1) above wherein said source of heat heats the cavity side wall to a temperature high enough to establish and maintain film boiling of the fluid stream adjacent said cavity side wall.
(6) An apparatus according to paragraph (1) above wherein the chamber outlet is located in said lower region of the chamber cavity such that a fluid stream leaving the chamber through the chamber outlet must pass through a region that is closer to the chamber axis than to the cavity side wall.
(7) An apparatus according to paragraph (1) above wherein the chamber forms a sealed enclosure capable of operating at a pressure different than the surrounding environment.
(8) An apparatus according to paragraph (1) above wherein film boiling prevents the fluid stream from contacting the cavity side wall and the apparatus operates without leaving any substantial portion of the solute component on the cavity side wall.
(9) An apparatus according to paragraph (1) above further comprising a fluid stream in said chamber cavity wherein the inlet fluid stream is an aerosol stream containing discrete liquid droplets.
(10) An apparatus according to paragraph (1) above wherein the liquid portion of a fluid stream exiting the chamber cavity has a concentration of solute that is at least ten times the concentration of solute in the inlet fluid stream.
(11) An apparatus according to paragraph (1) above wherein the inlet fluid stream is caused to rotate within the chamber cavity by its inlet velocity and the orientation of the fluid stream chamber inlet.
(12) An apparatus according to paragraph (1) above wherein the inlet fluid stream is caused to rotate within the chamber cavity by being impacted by a stream of solvent vapor, other liquid vapor, other gas, sample-containing liquid, other liquid, liquid droplets or a combination thereof.
(13) An apparatus according to paragraph (1) above further comprising a conduit that connects an outlet of a liquid chromatograph to the fluid stream chamber inlet.
(14) An apparatus according to paragraph (1) above further comprising a conduit that directs concentrated solute droplets or substantially dry particles coming from the chamber outlet directly or via another treatment component, such as a reactor, to a light scattering detector, optical absorbance analyzer, infrared spectrometer, mass spectrometer, nuclear magnetic resonance spectrometer, atomic emission spectrometer, atomic absorbance spectrometer or flame ionization detector.
(15) Apparatus for converting a fluid steam comprising liquid and solute components into a nebulized stream comprising gas, vapor and/or aerosol, said apparatus comprising in combination:
(16) An apparatus according to paragraph (15) above further comprising an electrical resistance measuring device connected between the respective ends of the capillary tube for generating an output to assess the sufficiency of the heat supplied to the capillary tube.
(17) An apparatus according to paragraph (16) above further comprising a control mechanism electrically connected to the electrical resistance measuring device, whereby the control mechanism regulates the electrical supply from the electric current source in accordance with the output generated by the electrical resistance measuring device in order to maintain the capillary tube at a sufficiently high average temperature along its length to produce a nebulized steam at the capillary tube discharge end.
(18) An apparatus according to paragraph (15) above wherein the capillary tube has a length of about 1 to 20 cm and an inside diameter of about 0.05 to 0.2 mm.
(19) An apparatus according to paragraph (15) above wherein the thermal mass of the capillary tube is less than 5 times that of a liquid inside the capillary tube.
(20) An apparatus according to paragraph (15) above further comprising an electric power control mechanism which senses a need for a change in the electric power being delivered to the capillary tube and substantially effects such an adjustment in a time of 100 milliseconds or less.
(21) A system for generating and desolvating a nebulized fluid stream wherein a nebulized fluid stream emerging from the capillary tube discharge end of the capillary tube according to paragraph (15) above is sent to a fluid stream inlet of an evaporating apparatus for evaporating liquid from the nebulized fluid stream, said evaporating apparatus comprising in combination:
(22) A system for separating liquid from a fluid stream comprising liquid and solute components, said system comprising an evaporation apparatus according to paragraph (1) above in combination with a condenser apparatus, wherein the condenser apparatus comprises:
(23) A system according to paragraph (22) above wherein said condenser surface is cooled to condense the condensable gas component.
(24) A system according to paragraph (22) above wherein said condenser region comprises the interior of a condenser tube, the outside of which is in direct or indirect contact with a cooling fluid at a temperature low enough to provide the required cooling effect.
(25) A system according to paragraph (22) above wherein said source of providing cooling comprises air cooling followed by Peltier cooling.
(26) A system according to paragraph (22) above wherein the condenser apparatus comprises a single-stage condenser.
(27) A system according to paragraph (22) above wherein the condenser apparatus comprises a multi-stage condenser.
(28) A system according to paragraph (21) above further comprising a condenser apparatus wherein the condenser apparatus comprises:
(29) A system for generating and desolvating a fluid stream comprising liquid and solute components, said system comprising in combination:
(30) A system for separating liquid from a fluid stream comprising liquid and solute components, said system comprising in combination:
(31) A system for generating and desolvating a fluid stream comprising liquid and solute components, said system comprising in combination:
(32) A method for evaporating liquid from an inlet fluid stream comprising liquid and solute components, said method comprising the steps of:
(33) The method according to paragraph (32) above wherein the step of imparting a rotational direction to the inlet fluid stream is effected by: (i) a fluid inlet that directs an inlet fluid stream so as to have a net tangential component relative to the cylindrical-shaped cavity side wall; (ii) a rotating element in said chamber cavity on which an inlet fluid stream impinges and at least a portion of which fluid stream is thereby directed outwards toward the cavity side wall with a net circumferential directional component; (iii) a source of moving gas in said chamber cavity that imparts motion having a net circumferential component to an inlet fluid stream; or, (iv) a rotational device that rotates the chamber cavity.
(34) The method according to paragraph (32) above wherein the step of maintaining the cyclone side wall at a suitable temperature is effected by a heating element selected from the group consisting of: (i) an electric resistance heater; (ii) an electric cartridge heater; (iii) a surface mounted electric resistance heater; (iv) a deposited film electrically conductive resistance heater; (v) an electrically conductive heater deposited on the cylindrical-shaped surface; (vi) a radio frequency electrical induction heater; (vii) a microwave heater; (viii) a flame; (ix) an infrared radiant heater; (x) a high temperature gas; and, (xi) a high temperature liquid.
(35) The method according to paragraph (32) above wherein the step of imparting a rotational direction to the inlet fluid stream causes the inlet fluid stream to rotate within the cyclone side wall at a sufficient velocity to maintain the fluid stream traveling substantially circumferentially adjacent said cyclone side wall.
(36) The method according to paragraph (32) above wherein the cyclone side wall is maintained at a temperature high enough to establish and maintain film boiling of the fluid stream adjacent the cyclone side wall.
(37) The method according to paragraph (32) above further comprising the step of having a fluid stream with an elevated concentration of solute leave the lower portion of the cyclone region through an outlet that is closer to an axis of the cyclone region than it is to the cyclone side wall.
(38) The method according to paragraph (32) above wherein said inlet fluid stream is an aerosol containing discrete liquid droplets.
(39) The method according to paragraph (32) above wherein the liquid portion of a fluid stream exiting the lower portion of the cyclone region has a concentration of solute that is at least ten times the concentration of solute in the inlet fluid stream.
(40) The method according to paragraph (32) above wherein the inlet fluid stream comes from the outlet of a liquid chromatograph.
(41) The method according to paragraph (32) above wherein a fluid stream exiting the lower portion of the cyclone region is sent directly, or via another treatment component, to a light scattering detector, optical absorbance analyzer, infrared spectrometer, mass spectrometer, nuclear magnetic resonance spectrometer, atomic emission spectrometer, atomic absorbance spectrometer or flame ionization detector.
(42) A method for converting a fluid stream comprising liquid and solute components into a nebulized stream comprising gas, vapor and/or aerosol, said method comprising the steps of:
(43) The method according to paragraph (42) above further comprising the step of regulating the electrical power supply to the capillary tube based on a measurement of the electrical resistance of the capillary tube.
(44) A method for generating and desolvating a nebulized fluid stream comprising the steps of:
(45) A method for separating liquid from a fluid stream comprising liquid and solute components, said method comprising the steps of:
(46) A method according to paragraph (44) above further comprising the steps of:
(47) A method for generating and desolvating a nebulized fluid stream, said method comprising the steps of:
(48) A method for separating liquid from a fluid stream comprising liquid and solute components, said method comprising the steps of:
In some applications of this invention, the low-volatility components will be temporally and spatially separated from each other in the same relation as they were in the original untreated stream. The fluid stream may, for example, consist essentially of a liquid solvent that may change in composition as treatment in accordance with this invention progresses. The fluid stream may carry a variety of dissolved and/or dispersed solid and/or liquid components, each of which is typically carried in a short section of the stream, frequently as the only dissolved component in that section. The solvent portion of the stream may be comprised of any suitable liquid.
Among other applications, this invention may specifically be applied to treating the eluate from a high-pressure liquid chromatograph instrument, with typical liquid flow rates ranging from about 0.1 to 2 ml per minute. All of such LC eluate may be processed according to the present invention. Alternatively, a portion of such LC eluate may be treated in accordance with this invention, while another portion may be directed to another instrument, such as a mass spectrometer, or collected for other purposes, or not utilized at all. In a typical liquid chromatography application, the liquid consists essentially of organic solvents, or water mixed with a varying concentration of one or more miscible organic solvents, and may additionally contain varying concentrations of one or more additives. The water, organic solvents, and volatile additives, if present, can all be substantially removed or separated from the low-volatility components by the methods and apparatus of this invention.
This invention is based on the principle that a flowing fluid stream can be treated according to the invention to produce a treated flowing gas stream that carries the originally dissolved components (solutes) as particulate matter, but at a mass concentration substantially higher, e.g., a 10 fold increase in concentration, than that in the original fluid stream. The invention thus enables further processing of the particulate stream, especially types of processing that would be rendered difficult or impossible by the continued presence of the liquid. One example of such further processing which is facilitated by this invention involves directing the particulate stream onto a window or another optically transparent or translucent surface or onto a porous surface such as a porous membrane, where the particulate matter collects in a configuration which is favorable for observation, for example by an infrared spectrometer using microscope optics. Another example of such further processing that is facilitated by this invention involves directing the particulate stream through a reaction chamber, and thence into a detector designed for gas chromatography, thus allowing the application of gas chromatography detectors to liquid chromatography eluents.
In alternate embodiments, this invention may also be used for other applications outside of this liquid flow rate range or where maintaining temporal separation of solute components is not important. In applications of this invention that are unrelated to chromatography, temporal resolution may not be important, such as in small scale and general-purpose spray drying of specialty chemicals, foods or other dissolved or suspended materials.
These and other benefits, advantages and applications for the methods and apparatus of this invention will be better understood by the following detailed description and the accompanying drawings.
The present invention discloses methods and apparatus as schematically illustrated in
Referring now to
Liquid Stream Generation Step (10):
In step (10), a flowing liquid sample stream containing dissolved and/or dispersed materials in various sections of the stream is generated. The liquid sample stream to be treated in accordance with this invention might originate, for example, as the eluate from a liquid chromatograph column 2610, or from a flow injection apparatus (pump 2510 and injector 2600), or as a stream of relatively steady composition from a pump or a pressurized source such as a manufacturing process.
Nebulization Step (20):
In step (20) the flowing liquid sample stream, or a portion thereof, is nebulized, which converts the liquid stream into a gas and/or solvent vapor plus sample containing solvent droplet aerosol stream. A flow of a substantially inert non-condensable gas (such as air, nitrogen or helium), or a condensable gas (such as water or other solvent vapor) may be added to assist in the nebulization process. Various types of known nebulizer devices may be used in this step, including pneumatic nebulizers of either concentric flow or cross flow geometry, electrospray nebulizers, sonic and ultrasonic nebulizers, spinning rotary disk nebulizers, thermal nebulizers or combination nebulizers. The nebulizer selected needs to be of suitable size relative to the flow rate of the liquid stream to be treated. A particularly preferred embodiment for purposes of this invention is a thermal nebulizer without a gas addition, or a combined thermal and concentric pneumatic nebulizer using a volume of non-condensable gas substantially less that the resultant solvent vapor volume. If large volumes of gas are needed for nebulization, a condensable gas such as water or solvent vapor can be used. In one preferred embodiment, thermal nebulizer is a short heated capillary tube 1700 (as seen in
In the present invention, a preferred way to provide heat input to a thermal nebulizer is to make it of a corrosion resistant conductive metal capillary tube such as stainless steel or nickel and passing electrical current from power supply 1300 (as shown in
If the thermal nebulizer is used without a thermal feedback control system, the maximum desirable power input is determined so any drop in flow rate and reduction in sensible and latent heat capacity due to solvent composition change will not cause 100% evaporation, as the solids will then precipitate out of solution and may plug the nebulizer. Even if plugging does not occur, when all the solvent evaporates the nebulizer temperature increases and the solute may be damaged by exposure to the high resulting temperature. In the extreme case where liquid flow stops and the power is not reduced, the metal capillary may melt. The minimum desirable power is determined to maintain good nebulization when any flow rate increase or increase in sensible and latent heat capacity occurs. In the prior art, a thermal nebulizer used with gradient LC requires changes in control settings as the gradient progresses.
The prior art typically controlled either the power input or the temperature of a relatively large block of metal that the capillary passed through. It is speculated that this resulted in a significant thermal lag and a large temperature gradient between the temperature controlled location and the inner capillary surface. The temperature gradient resulted in a substantially different temperature at the control point and the capillary inner surface that transfers heat to the eluent stream. Therefore the temperature set point was typically substantially higher than the actual capillary inner surface temperature, which was not determinable. Empirically, any eluent change (composition or flow) required a change in control set point. Therefore sophisticated thermal nebulizers used with LC gradients would incorporate preprogrammed changes in set points that were correlated to the gradient conditions.
According to the present invention, automatic stable nebulizer performance over large changes in both solvent composition and flow rate can be obtained by a control system that substantially maintains the total electrical resistance of the capillary nebulizer near to a predetermined value. To assist in understanding, a theory of why this works will be presented, although validity of the invention should not be predicated on correctness of this theory. Because the electrical resistance of the capillary tube varies approximately linearly with temperature over the control range, maintaining a constant total capillary electrical resistance is believed to be tantamount to maintaining a stable average capillary temperature. The temperature distribution along the capillary length may vary, but the (resistance weighted) temperature average along the length of the capillary is maintained substantially constant. The low heat capacity of the capillary allows the control loop to respond rapidly to changing solvent conditions. The heat capacity of the capillary should be substantially less than the heat capacity of the fluid contained in the capillary. For example, the heat capacity of the capillary might advantageously be less than 1/10th that of the fluid in the capillary, preferably less than 1/100th, more preferably less than 1/1,000th. The thin wall of the capillary results in a relatively small temperature difference the bulk of the capillary where the heat is generated and the inner capillary surface where the heat is transferred to the solvent stream. In the present invention, which desirably uses a capillary having a wall thickness of a fraction of a millimeter, more desirably having a wall thickness between about 0.1 mm and 0.02 mm, or in the example given having a wall thickness of 0.05 mm, it is believed that each location along the length of the capillary, has a relatively small temperature difference between average across the wall and the inner surface. In the present invention it is found that a single control setting results in stable nebulizer operation over the varying solvent composition and flow conditions that occur during typical gradient LC separations. A reversed phase separation from 100% water to 100% organic solvent such as methanol or acetonitrile (including perturbations resulting from pump pulsations, solvent viscosity variations, etc. as well as programmed flow changes) can be dramatically improved by automatically varying the voltage (and resulting current) to the nebulizer in a manner that maintains the nebulizer electrical resistance nearly constant. Convenient electrical contact to the capillary can either be through dedicated electrical high temperature soldered or crimp on connectors 1710 or through conductive compression fittings that support and hydraulically connect the capillary. When using the compression fittings for electrical contact, electrical isolation of the nebulizer can be provided by electrically floating either the LC system or the cyclone, or making a section of the interconnecting capillary tube 2600 of insulating material well know to those skilled in the art, such as PEEK or fused silica. The low thermal inertia of the capillary tube makes the energy input to the stream nearly instantaneously determined by the electrical power applied to the capillary. This allows a feed back control to maintain the % evaporation within acceptable limits, even under conditions of rapidly changing flow and solvent composition. Adjustable control resistor 1720 sets the desired electrical resistance (temperature) of the nebulizer tube. If the nebulizer tube cools the nebulizer resistance becomes lower causing the operational amplifier 1750 output to call for more voltage from the DC power supply. This higher voltage increases the current through the nebulizer until the nebulizer has heated up sufficiently to increase its resistance sufficiently to balance the bridge and reduce the call for more voltage.
In the instant example, it is found that a single setting of the control circuit automatically adjusts the nebulizer power to accommodate wide changes in solvent composition (from pure water to pure organic solvent) and flow rate (from 0.2 to 2 ml per minute). The DC power supply output 1760 automatically adjusts from about 0 to 15 volts and can deliver up to 40 watts to the nebulizer. This allows operation up to 2 ml per minute of any solvent. A desirable way to set the nebulizer operating condition (electrical resistance) is to flow a known solvent at a known flow rate through the nebulizer. The control resistor 1720 is then adjusted until the power dissipated in nebulizer 1700 is the desired % of the theoretical sensible plus latent heat required for total evaporation. At one milliliter per minute, the approximate theoretical power required to fully evaporate some typical LC solvents are: chloroform 8 watts, acetonitrile 9 watts, tetrahydrafuran 10 watts, isooctane 11 watts, isopropyl alcohol 15 watts, methanol 22 watts, trichlorobenzene 25 watts, DMSO 35 watts and water 44 watts. It is experimentally found that a good power to adjust to is about 4 watts less than the theoretical 50% evaporation requirement. It is speculated that this empirical 4 watt offset is because of heat transferred to the nebulizer 1700 by thermal conduction from the cyclone body. In the instant example, solvents like chloroform and pure acetonitrile can be successfully nebulized with no applied electrical power. When operating LC gradients, the nebulizer power is best set using that gradient's highest power requirement composition and flow conditions. For a water to acetonitrile gradient at 1 ml per minute, the power should be set to about 18 watts while flowing at initial conditions of 1 ml per minute of 100% water. The desired power calculation for this example is: 50% of 44 watts for 100% evaporation of water at 1 ml per minute which is 22 watts, less 4 watts gives 18 watts for the set point. Empirically it is found that good results can be obtained over a fairly wide range of set points. It is also empirically found that after setting the nebulizer power, the automatic control protects the nebulizer from damage even if the flow totally stops.
Desolvation/Evaporation Step (30):
In step (30), the next process step, evaporation in the cyclone converts the aerosol in the nebulized stream to vapor plus highly concentrated, typically dry particles of the low-volatility component(s). The high-speed aerosol jet from the nebulizer 1700 is directed circumferentially around the hot, generally cylindrical shaped outer diameter of the cavity 705 inside of the cyclone. In one embodiment, the cyclone was designed with the cylindrical cavity having a reduced width exhaust passageway from cavity 705 to the central gas exit, which results in an overall toroidal-like cavity. The central core of the toroid shown in
One desirable place to add the non-condensable gas is as a sheathing flow 2915 around the inside diameter of the condenser feed line inlet 2911. This maximizes the particle suspension in the condenser while minimizing the total amount of non-condensable gas required for particle suspension. Alternative preferred cylindrical cyclone evaporators are shown in
Electrostatic charge can dramatically effect the droplet size distribution both during the nebulization process and during the droplet shrinking process as the solvent is evaporated, as discussed for example in “Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles” by William C. Hinds (second edition 1999, John Wiley & Sons, Inc.) which is incorporated herein by reference. The number of droplets can be partially controlled by controlling the electrostatic charge present on droplets. When charged droplets evaporate, they shrink until the electrostatic repulsion forces become great enough to cause a coulomb explosion creating a large number of smaller droplets. Since the disclosed cylindrical film boiling cyclone ejects partially desolvated droplets at a relatively fixed size independent of the number of droplets present, the ratio of droplet mass to super heated solvent vapor is affected by the number of droplets. Electrospray nebulizers produce small charged droplets by electrostatic repulsion of the liquid from the needle. High speed liquid streams (thermospray) strip the electrostatic double layer out of their delivery tube (called streaming current) and can result in charged droplets. Increasing the electrostatic charge on the nozzle can increase the degree of droplet charging during nebulization, which through coulombic explosion produces more droplets each containing less solute. The electrostatic charge on the droplets can also cause droplet and dried droplet loss to the walls. Adjustable 4000 volt bipolar DC solvent charging power supply 1600 controls the potential of, or current to the thermospray inlet to the cyclone. In
Another way to affect electrostatic charge is by the addition of volatile buffers that readily produce gas phase ions. These ions are capable of transferring charge from droplets. Ammonium acetate is an example.
Concentration Step (40):
In step (40), the bulk of the condensable gas is removed from the desolvated flowing stream while retaining a significant portion of the dried particles entrained in that stream. Solvent vapor is removed by condensation onto the inside of a condenser tube 2900 cooled by ice water bath 3000 (
It is presently believed that there are trade offs in optimizing the operating pressure, condenser geometry, and condenser temperature(s). Generally it is desirable to minimize analyte dilution from both con-condensable gas and residual solvent vapor, and to minimize analyte loss due to aerosol particle diffusion to condenser walls, sample transfer line walls and poor adhesion to the optical disk. It is also desirable to minimize the deposition spot area on the disk since this maximizes thickness and detection sensitivity. The design and operational tradeoffs to achieve these result in compromises. The following theoretical discussion is intended to convey the present understanding of the inventors, and the accuracy of theoretical mechanisms of operation should not be used to limit the scope or validity of the invention claims. The atomized particles are held in suspension by the gas viscosity, which is roughly independent of aerosol particle size until the particle size decreases to the order of magnitude of the mean free path of the gas molecules. This transition from what is commonly called the continuum flow regime to the molecular flow regime results in significantly less viscous drag on, and much more rapid diffusion of the particles resulting in increased losses to the passageway surfaces. A practical lower operating pressure limit is set by the need to maintain the particles in suspension as they travel through the system. This lower pressure limit depends on the duration the particles need to held in suspension, and the particle size. For the instant apparatus the lower pressure limit is the order of magnitude of 0.1 atmospheres and 0.5 atmospheres is preferable for dried particles of about 0.01 microns, which is speculated to be the approximate size of particle generated by the pure thermal nebulizer with LC effluents approaching the current system's detection threshold. The partial pressure of residual solvent vapor leaving the last condenser is set by the temperature to which vapor equilibrated with condensate. The colder this temperature is, the less remaining solvent. A desirable operating pressure for LC eluent droplets nebulized by a pure thermal nebulizer is preferably between 0.1 and 2 atmospheres pressure, and more preferably between 0.3 and 1 atmosphere pressure. Using a colder condenser also desirably reduces the residual solvent vapor, but if the trap is below the freezing point of the solvent, volume must be supplied to store the frozen solvent. Therefore it is desirable to remove the bulk of the solvent as liquid drained to a location or locations outside the flow path. It is also desirable to minimize the volume of the cyclone, condenser and transfer lines as this minimizes residence time and chromatographic band spreading. Minimizing the total path length from the first-stage condenser to the optical disk minimizes drop out of aerosol particles.
For mixed solvent and gradient operation, a multi-stage liquid condenser can desirably be used.
A preferred technique (
In
Methanol is a good freezing point depressant solvent. Other material potentially useful as freezing point depressant solvents in the present invention include other alcohols, acetonitrile an other materials which are mutually miscible with all the mobile phase solvents. For water containing gradients, the methanol can lower the condensate freezing point of water from 0 Celsius to less than −90 Celsius. This allows the second-stage condenser to operate much colder without risk of freezing, thereby greatly reducing the residual solvent vapor pressure and mass of residual solvent that accompanies the sample. The equilibrium vapor pressure of water at its freezing point of 0 Celsius is over 4 Torr while the vapor pressure of methanol at its freezing point of −98 Celsius is much less than 1 Torr. Any residual methanol can be readily evaporated or sublimed from the cold optical disk that the sample is deposited on at a much lower temperature than water ice can be sublimed at. This allows a much colder optical sample disk that allows better capture, particularly of samples that are liquid at room temperature.
A convenient way to control the freezing point depressant vapor addition is to sparge a carrier gas such as dry nitrogen through it at the reduced pressure of the condenser. Regulating the flow of its carrier gas regulates the freezing point depressant vapor addition. Better regulation of flow, and less dilution with carrier gas can be achieved by typically elevated temperature regulation of the freezing point depressant bottle and flow path.
Deposition/Application Step (50):
In step (50), the concentrated particle stream is now ready for use in a variety of applications. This stage can be a direct detection on a measurement surface 3600, processing of the desolvated particle stream followed by detection, or collection of the particle stream for other use. A preferred embodiment is deposition of the particulates onto a controlled temperature cryogenic window, preferably under vacuum conditions, followed by examination using infrared spectroscopy or Raman spectroscopy. In this embodiment sensitivity can be increased by maximizing the deposit thickness and using microscope optics for examination. The aerosol suspension is sucked through a nozzle 3500 that focuses the dried droplets into a narrow high-speed beam. An optical surface is placed under the beam to collect the solute. The deposition surface is typically in a vacuum chamber 3900 evacuated by roughing pump 4600. The deposition surface is typically temperature controlled to freeze or condense liquid solutes while avoiding significant condensation of residual solvent vapor, and desirably allowing sublimation of any residual solvent which did condense. The optical surface is then moved into the focus of the infrared microscope beam for analysis.
Another preferred embodiment is deposition of the particulates on a surface with the addition of a matrix material, either into the original liquid stream, into the particulate stream, or on the deposition surface. This matrix material can be to assist the transmission of trace quantities of analytes for FTIR, or to add compounds essential to the subsequent use. An example of the latter is deposition onto the surface, followed by analysis of the deposit by Matrix Assisted Laser Desorption Ionization using a time of flight mass spectrometer for detection. Another preferred embodiment is direct transmission of the particle stream into a mass spectrometer for analysis. Another preferred embodiment is conversion of the particulate stream into a gas stream through reaction or pyrolysis, and thence directing the stream into a gas detector, such as an ion mobility detector or a detector commonly used for gas chromatography. In another embodiment, the dried aerosol may be collected for off line use.
Although the foregoing description of this invention has been by reference to particular process steps using particular apparatus components, it will be understood by those of ordinary skill in the art that these illustrative embodiments can be readily modified in a variety of ways to adapt this invention to treat different flowing liquids under different conditions, and each of such modifications is considered to be within the scope of this invention.
This application is a Division of U.S. Ser. No. 12/312,890 filed May 29, 2009 (now pending), which is a Sec. 371 of PCT/US2007/025,207 filed Dec. 8, 2007, which claims the benefit of the filing dates of U.S. Provisional patent applications U.S. Ser. No. 60/873,848 filed Dec. 8, 2006 and U.S. Ser. No. 60/927,646 filed May 4, 2007. Each of these earlier related applications is incorporated herein by reference.
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| Number | Date | Country | |
|---|---|---|---|
| 20140224638 A1 | Aug 2014 | US |
| Number | Date | Country | |
|---|---|---|---|
| 60873848 | Dec 2006 | US | |
| 60927646 | May 2007 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 12312890 | US | |
| Child | 14186649 | US |
