Converging-diverging supersonic shock disruptor for fluid nebulization and drop fragmentation

A disruptor apparatus comprises a nozzle comprising: a converging section; a diverging section; and a throat between the converging section and the diverging section. The disruptor apparatus also comprises a holder configured to receive a fluid conduit, which comprises an outlet located in the converging section; and a channel disposed about the holder and configured to guide a gas past the outlet of the fluid conduit, through the converging section, through the throat and into the diverging section where the gas travels at supersonic speed and establishes a standing shock wave in the diverging section. A mass spectrometer and a method are also described.

BACKGROUND

Chemical and biological separations are routinely performed in various industrial and academic settings to determine the presence and/or quantity of individual species in complex sample mixtures. There exist various techniques for performing such separations.

One particularly useful analytical process is chromatography combined with mass spectroscopy, which encompasses a number of methods that are used for separating ions or molecules for analysis. Liquid chromatography (“LC”) is a physical method of separation wherein a liquid ‘mobile phase’ carries a sample containing a mixture of compounds or ions for analysis (analytes) through a separation medium or ‘stationary phase.’ Fluid from the LC device, which comprises both the analytes and the mobile phase, is provided the analytes to an ion source of a mass spectrometer (MS) for spectroscopic analysis.

Often an electro-spray system is used in the interface between the LC device and a mass spectrometer. In electro-spray systems, a voltage is applied to the mobile phase to charge the fluid, and a gas may be provided to assist in nebulizing the fluid. As the fluid comprising the mobile phase and analytes exits a tube or channel annular gas flow around the tube or channel exit forms drops from the fluid. The fluid drops have a charge and, as the mobile phase begins to evaporate, the charge can be transferred to the analytes.

Unfortunately, and among other shortcomings, known drying methods are comparatively low-energy processes and therefore require the drops to travel a significant distance to desolvate. Moreover, repulsion of ions due to known space charge repulsion causes rarefaction. Decreased sample density translates to a comparatively small fraction of the sample ions entering the MS and, hence, reaching a detector in the MS. As such, the efficiency of the MS is reduced.

What is needed, therefore, is a method and apparatus for providing analytes from an LC column to a mass analyzer that overcomes at least the drawbacks of known devices and methods described above.

DEFINED TERMINOLOGY

It is to be understood that the terminology used herein is for purposes of describing particular embodiments only, and is not intended to be limiting.

As used in the specification and appended claims, the terms ‘a’, ‘an’ and ‘the’ include both singular and plural referents, unless the context clearly dictates otherwise. Thus, for example, ‘a device’ includes one device and plural devices.

DETAILED DESCRIPTION

In the following detailed description, for purposes of explanation and not limitation, representative embodiments disclosing specific details are set forth in order to provide a thorough understanding of the present teachings. Descriptions of known systems, devices, materials, methods of operation and methods of manufacture may be omitted so as to avoid obscuring the description of the example embodiments. Nonetheless, systems, devices, materials and methods that are within the purview of one of ordinary skill in the art may be used in accordance with the representative embodiments.

FIG. 1shows a simplified schematic diagram of a mass spectrometer100in accordance with a representative embodiment. The block diagram is drawn in a more general format because the present teachings may be applied to a variety of different types of mass spectrometers. As should be appreciated as the present description continues, devices and methods of representative embodiments may be used in connection with the mass spectrometer100. As such, the mass spectrometer100is useful in garnering a more comprehensive understanding of the functions and applications of the devices and method of the representative embodiments, but is not intended to be limiting of these functions and applications. The mass spectrometer100includes an ion source101, a mass analyzer102and a detector103. The mass spectrometer100comprises additional apparatuses, such as electrostatic and RF lenses, as well as other apparatuses not shown. Such apparatuses are known and are not described in detail to avoid obscuring the description of representative embodiments.

The ion source101comprises a disruptor apparatus104. The disruptor apparatus104is configured to receive fluid from an LC device105and inert gas from a gas source106and functions as an interface between the LC device105and the mass spectrometer100. As described in more detail below, the disruptor apparatus104nebulizes the fluid from the LC device105to generate drops and then fragments the drops to form droplets (not shown inFIG. 1). The droplets are desolvated leaving analyte ions and gas molecules. The resulting analyte ions (not shown inFIG. 1) are provided to mass analyzer102. The mass analyzer102may include a conduit such as a sleeve, transport device, dispenser, capillary, nozzle, hose, pipe, pipette, port, connector, tube, orifice, orifice in a wall, coupling, container, housing, structure or other apparatus used to transport analyte ions from the ion source101to the detector103. The mass analyzer102may be one of a number of known devices used to filter ions based on a charge-to-mass ratio. Illustratively, the mass analyzer comprises one of a quadrupole mass analyzer, an ion trap, a tune-of-flight device, among others. The detector103may be a known ion detector used to detect the analyte ions that are collected and separated by the mass analyzer102according to their mass-to-charge ratio. The detector103typically also includes known hardware, software or firmware, or a combination thereof useful in detecting analytes.

FIG. 2Ashows a cross-sectional view of disruptor apparatus104in accordance with a representative embodiment. The disruptor apparatus104comprises a first portion201, a second portion202and a third portion203. The first portion201defines a nozzle204that extends axially through the first portion. The nozzle204comprises a converging section205, a throat206and a diverging section207in order, in tandem. The second portion202comprises a holder208, and the first portion201is configured to receive a part of the holder208remote from the throat206and diverging section207. The holder208maintains an outlet211of a fluid conduit209in a position to facilitate nebulization. The fluid conduit209is connected at one end to an output of an LC column210and provides fluid at the outlet211for nebulization as described more fully below.

In the embodiment shown inFIG. 2A, the holder208maintains the fluid conduit209in a position such that the outlet211is located in the first portion201at a position in the converging section205of the nozzle204to facilitate nebulization. In an alternative embodiment, the fluid conduit209could be extended through the throat206so that the outlet211is located in the diverging section207of the nozzle204.

The third portion203is coupled to the second portion202. In the example shown, a part of the third portion203accommodates a part of the second portion202. The third portion203receives a gas212from a gas control and supply213. Typically, the gas212is an inert gas such as nitrogen. The LC column210is connected to the fluid conduit209via a connection in the third portion203, and as described provides LC fluid (not shown inFIG. 2A) to the fluid conduit209there through.

The second portion202comprises an axial gas conduit214disposed about the fluid conduit209, and comprises orifices215that extend radially from the axial gas conduit214to a channel216, which is illustratively formed by and between the first portion201and the second portion202. The axial gas conduit214is configured to direct the gas212toward the orifices215. The orifices215are configured to direct the gas212into the channel216of the first portion201where the gas212propels drops (not shown inFIG. 2A) of fluid resulting from nebulization of the fluid provided at the outlet211. As described more fully herein, the drops are propelled by the gas212through the converging section205and the throat206, and into the diverging section207. The drops are then propelled by the gas212into a standing shock wave218established by the flow of gas212through nozzle204.

The fluid provided at the outlet211of the fluid conduit209is nebulized by known methods. Notably, in representative embodiment, the fluid provided at the outlet211is nebulized by known electrospray methods; or by gas-assisted nebulization, by or electrospray with gas-assisted nebulization. The gas212may be used to effect gas-assisted nebulization, or in electrospray with gas-assisted nebulization. If electrospray is used as the sole method of nebulization, the gas212would not be used in the nebulization of the fluid to form drops, but only to propel the drops through the nozzle204and into the standing shock wave218.

In a representative embodiment, the orifices215are arranged at 90° intervals about a longitudinal axis217through the disruptor apparatus104. In another representative embodiment, the orifices215are arranged at 120° intervals about the longitudinal axis217. In still other representative embodiments there are more than four orifices, while in other embodiments there are three or fewer orifices. The regular spacing of the intervals is merely illustrative, and irregular spacing of the orifices215is contemplated.

In representative embodiments, the material used for the first portion201and the fluid conduit209is electrically conducting, while the material used in the second portion202is electrically insulating. The third portion203may be either electrically conducting or insulating. Illustratively, the electrically conducting material comprises one or more of a metal, a metal alloy, an electrically conducting composite material, or a coated plastic material. Similarly, the insulating material is illustratively a polymer (e.g., plastic), a composite material or other suitable electrical insulator. As will become clearer as the present description continues, the conducting and insulating materials are selected to facilitate establishing an electrical potential difference between the first portion201and the fluid conduit209.

In accordance with a representative embodiment, in operation, the disruptor apparatus104first nebulizes fluid from the LC column210by electrospray with gas-assisted nebulization of fluid provided at the outlet211disposed in the converging section205, and by passing the gas212past the outlet211. Alternatively, the nebulization occurs solely by gas assisted nebulization of fluid at the outlet211by passing the gas212past the outlet211. Next, the drops (not shown inFIG. 2A) formed by the nebulization are propelled by the gas212through the throat206and into the diverging section207. As described more fully herein, the drops attain a substantially greater velocity than the velocity attained by known nebulization methods, and impact on a standing shock wave218located in the diverging section or at or near an exit219of the diverging section207. The impact of the drops with the standing shock wave218fragments the drops into droplets (not shown inFIG. 2A) by imparting at least three (3) orders of magnitude and as much as approximately four (4) orders of magnitude more energy into the drops than known practice gas assisted nebulization.

The gas212is provided at an upstream pressure P0that is chosen to establish the standing shock wave218. As described more fully herein, the Mach number of the standing shock wave218, which refers to the standing shock wave caused by gas212having a velocity of the same Mach number upon entering the standing shock wave218, is dependent upon the ratio of the upstream pressure (P0) to the ambient pressure ratio (P3) at the outlet of the diverging section205. In representative embodiments, the ratio P0/P3is selected to be on the order of approximately 4.0 or higher to attain a desired Mach number to ensure suitable fragmentation of drops of nebulized fluid. It is noted that the upstream pressure P0is more readily controlled than the ambient pressure P3, which is, for example, the pressure of a chamber of the ion source101and is normally atmospheric pressure.

In accordance with representative embodiments, the disruptor apparatus104significantly desolvates or substantially completely desolvates the mobile phase of the LC fluid leaving analyte ions. Among other benefits, the disruptor apparatus104produces a comparatively high density cloud of analyte ions near the entrance of the mass analyzer102. By contrast, and as alluded to above, because of the time and distance required to desolvate the fluid drops formed by known low energy drop formation, current nebulizers produce a low-density cloud of analyte ions. As such, using known nebulizers, the nebulizer outlet must be placed comparatively far from the inlet to the mass analyzer. The extra time and distance resulting from this separation allow space charge forces to cause the analyte ions to move apart and become less dense. Therefore, by known methods and apparatuses fewer analyte ions are provided to the mass analyzer102.

In certain embodiments such as described below in connection with connectionFIG. 3, the disruptor apparatus104is a component of the ion source101. In other embodiments such as described below in connection withFIG. 4, the disruptor apparatus104functions as the ion source101and is coupled directly to a conduit to a mass analyzer102. Thus, whether the disruptor apparatus104is a component of the ion source101or functions as the ion source101of the mass spectrometer100, the disruptor apparatus104comprises an interface between the LC column and the mass spectrometer.

FIG. 2Bis a cross-sectional view showing a part of the first portion201of the disruptor apparatus104, which is shown in an enlarged view to facilitate the description of the nozzle204. As shown, the throat206is situated between the converging section205and the diverging section207; and the throat206is a part of nozzle204in which the cross-sectional area of the nozzle204in the x-z plane orthogonal to the longitudinal axis217is a minimum. Notably, the dashed lines delineating the boundaries of the converging section205, the throat206and the diverging section207are set in approximate position. Generally, the converging section205, as its name implies, is a section where the cross-sectional area of the nozzle204in the x-z plane orthogonal to the longitudinal axis217decreases with respect to the axial position (+x-direction) towards the throat. The diverging section207is a section where the cross-sectional area of the nozzle in the x-z plane orthogonal to the longitudinal axis217increases with axial position (+x direction) away from the throat206. Moreover, while the throat206comprises a region of the nozzle204, it is a point at which the cross-sectional area of the nozzle204is a minimum.

As noted above, the holder208maintains the outlet211of the fluid conduit209at a location in the first portion201at a position in the converging section205of the nozzle204to facilitate nebulization. Fluid222from the LC column210flows through the fluid conduit209and the gas212converges about the outlet211as it traverses the converging section205. The gas212converging near the outlet211assists in nebulizing the fluid222at the outlet211via shear forces to generate drops220.

The gas212propels the drops220through the converging section205, through the throat206and into the diverging section207. The ratio of the upstream pressure to ambient pressure (P0/P3), dimensions of the converging section205, the throat206, and diverging section207of the nozzle204of disruptor apparatus104are selected so that the gas212flowing through the nozzle204creates a standing shock wave218at a selected location within the nozzle204. In certain embodiments, the standing shock wave is positioned at the exit219of the diverging section207. In other embodiments, the standing shock wave218is positioned within the diverging section207, but comparatively close to the exit219of the diverging section207. As described more fully below, the positioning of the standing shock wave218away from the throat206affords sufficient distance for the drops220to be accelerated by the gas212and thereby attain a comparatively high velocity before the drops220impact the standing shock wave218. By similar analysis, standing shock wave218should not be located in proximity to the throat206because the drops220will not have sufficient distance to attain a sufficient velocity for acceptable fragmentation of the drops220to occur. As such, the pressure ratio (P0/P3) and dimensions of the components of the nozzle204are selected to avoid locating the standing shock wave218in proximity to the throat206.

The gas212attains a velocity of at least approximately Mach 1.2 in the diverging section207. In certain embodiments, the gas212attains a velocity of at least approximately Mach 3.0 in the diverging section207; and in certain embodiments, the gas212attains a velocity of at least approximately Mach 4.0. The comparatively high velocity of the gas212serves to propel the drops220through the diverging section207at comparatively high velocity as well. As they traverse the diverging section207, the drops220can attain a velocity nearing that of the gas212. The velocity of the drops220relative to the gas212depends on the distance between the throat206and the standing shock wave218. In representative embodiments, by providing a diverging section207of suitable length, drop velocities of 80% relative to the gas velocity are readily attainable. The drops220attain their maximum velocity in the diverging section207and impact the standing shock wave218at substantially normal incidence. The combination of the comparatively high speed attained by the drops220and their substantially normal incidence to the standing shock wave218fosters efficient fragmentation of the drops220.

The normal incidence of the drops220to the standing shock wave218is more disruptive than a network of weak oblique shocks as provided in certain known nebulizers. As the drops220enter the standing shock wave218, the standing shock wave218will flatten the drops220; deposit a comparatively large vortex ring around the periphery of the drops220; and create a comparatively large instantaneous difference between the drop speed and the ambient gas speed, generating shear, which will cause the drops220to fission. Drops220fragment into droplets221, and after emerging from the standing shock wave218, the droplets221enter a region at an ambient pressure P3, and the velocity of the droplets221reduces very rapidly to ambient gas velocities. This rapid change in velocity imparts energy to the droplets221in the form of heat. Accordingly, in a representative embodiment, as the fluid.222from the LC column210travels through the disruptor apparatus104, it undergoes a gas-assisted nebulization upon mixing with the gas212in the converging section205; and a high-energy fragmentation caused by accelerating the drops220along a direction normal to and through the highly energetic shock wave218. By way of comparison, the energy imparted to the drops220by the disruptor apparatus104is on the order of 103to 104greater than the energy imparted by known nebulizer apparatuses and methods for similar upstream and ambient pressures, and inert gas flow rates of inert gas. Illustratively, the energy imparted to the drops220with the velocity of gas212in the diverging section207of approximately Mach 3.0 or greater is sufficient to substantially completely desolvate the droplets221.

As noted previously, the fluid conduit209and the first portion201are electrically conductive and the holder208is electrically insulating. The insulator allows an optional voltage (designated V inFIG. 2B) to be maintained between the fluid conduit209and the first portion201that there exists an electrical potential gradient that charges the drop220as they exit the fluid conduit209. In a representative embodiment, the fluid conduit209is maintained at a ground potential and a positive voltage is applied to the first portion. The present teachings contemplate foregoing the establishing of a voltage as just described. Rather, aiding in the imparting of electric charge to drop220by the application of an electric field at the outlet211may be unnecessary as droplets221resulting from the fissioning may comprise charged analyte ions after passing through the standing shock wave218.

Thus, in accordance with a representative embodiment, the disruptor apparatus104provides smaller droplets as droplets221. The droplets221require a comparatively shorter desolvation time in a drying stage of the ion source. A reduced desolvation time beneficially results in a higher density analyte ion cloud near the inlet to the mass analyzer102. Ultimately, this higher analyte ion density produces a greater ion current into the mass analyzer102, which in turn leads to higher sensitivity and lower detection levels.

Referring toFIGS. 2A and 2B, and as alluded to above, in the converging/diverging nozzle of disruptor apparatus104, the ratio of pressures, P0/P3and the dimensions of the exit219of diverging section207and the throat206of the nozzle204dictate the conditions for both supersonic flow of gas212and the location of the standing shock wave218. In accordance with representative embodiments, the gas212traveling through the nozzle204of the disruptor apparatus104can readily attain a velocity in the diverging section207of at least M=1.2 and more typically in the range of approximately M=3 to approximately M=4. By way of quantitative example, a minimum pressure ratio of P0/P3that must be exceeded to achieve supersonic speeds is 1.89 where the gas212is air or, likewise, nitrogen. As such, with the a pressure ratio P0/P3of approximately 2 or greater, the gas212can attain supersonic speeds in the diverging section207, the standing shock wave218can be established, and the fragmentation of drops220into droplets221can be achieved.

As noted above, the cross-sectional area of the exit219of the diverging section207and the cross-sectional area of the throat206impact the position of the standing shock wave218. A given specified upstream pressure P0and downstream post-shock pressure P3determine the ratio of the area of the exit219of the diverging section207to the area of the throat206that ensures that the standing shock wave218exists and is situated at the exit219of the diverging section207. By creating the nozzle204with this area ratio, or substantially with this area ratio, a standing shock wave218substantially normal to the longitudinal axis217is formed at the exit219. For example, selecting ambient pressure P0to be approximately 4 atm, which can be readily achieved, a design Mach number is required so that the pre-shock wave static pressure P1begets the post-shock pressure P2that is substantially equal to the ambient pressure P3, which is illustratively 1 atm.

Many details of attaining supersonic gas flow in a convergent/divergent nozzle and the positioning of a standing shock wave are known. Such details, can found, for example, in Section 7.2 of C. J. Chapman, “High Speed Flow”, Cambridge University Press (2000), ISBN 0-521-66647-3. The disclosure of this section of this text is specifically incorporated herein by reference.

In known methods of nebulization used in many LC applications, the predominant mechanism causing drop fissioning is not kinetic energy (KE) deposition resulting from the interaction of the drops with a standing shock wave according to the representative embodiments described above, but rather electrostatic repulsion/fissioning of drops as the mobile phase evaporates. In known apparatuses and systems, space charge, which is a term used to describe mutual electrostatic repulsion of analyte particles and drops, limits maximum transmission not to a fraction of the total number of analyte particles, but to a maximum absolute quantity. That is, the space charge limit is reached for ions in a particular device, attempts to increase analyte throughput does not help. In contrast, during the comparatively rapid fragmentation of drops220into droplets221, the droplets221acquire a static electric charge due to non-uniform distribution of charge in the original drop as well as the splitting of polarized molecules. Moreover, one way to mitigate space charge quenching of analyte current is to decrease the residency time ions spend in desolvation. Therefore, by desolvating the droplets221more rapidly and providing the ions into the mass analyzer more quickly, the maximum current (in absolute value) is increased. In embodiments described herein, because the droplets221are comparatively small, a comparatively greater area-to-volume ratio is attained and the speed of desolvation is increased compared to known methods and apparatuses. As described below, the nozzle of disruptor apparatus104beneficially improves the speed of desolvation, increasing the space-charge-limited current and allowing more analytes to be passed into the mass spectrometer device. These and other beneficial aspects of the apparatus are described presently in connection with representative embodiments shown inFIGS. 3 and 4.

FIG. 3is a cross-sectional view of ion source101in accordance with a representative embodiment. The ion source101comprises a housing300and the disruptor apparatus104, which extends through the housing300into a chamber301bounded by the housing300. Droplets221emerge from the diverging section207of the nozzle204of disruptor apparatus104and enter the chamber301. In a representative embodiment, the diverging section207is oriented along a longitudinal axis302that is substantially orthogonal to a conduit longitudinal axis303of a conduit304. While the orthogonal arrangement may be used, it is not essential. A variety of angles (obtuse and acute) may be defined between the longitudinal axis302and the conduit longitudinal axis303of the conduit304. Alternatively, the longitudinal axis302may be aligned with the conduit longitudinal axis303of the conduit304. Illustratively, the pressure in the chamber301is maintained at about 20 Torr to about 2000 Torr. Operation at atmospheric pressure (around 760 Torr) and non-atmospheric pressure is thus possible.

The mass analyzer102includes the conduit304or any number of capillaries, conduits or devices for receiving and moving the analyte ions from the chamber301to the detector103. The conduit304extends into the housing300downstream from the disruptor apparatus104. The conduit304may comprise a skimmer (not shown inFIG. 3) that guides the analyte ions to the conduit304, which in turn guides the analyte ions to the detector into the mass analyzer102and ultimately to the detector103(not shown inFIG. 3). Optionally, a gas conduit309may direct a drying gas305into the chamber301toward the droplets221in the chamber301. The drying gas305is heated and assists further in desolvating droplets221.

In a representative embodiment, the droplets221that emerge from the disruptor apparatus104are electrically charged. A voltage is established between the disruptor apparatus104and the conduit304so that the charged analyte ions are directed to the conduit304along trajectories306. Most of the droplets221that are not provided to the conduit304continue to travel in the direction of the longitudinal axis302and are expelled at an exhaust port308along with gases307.

As described above, providing droplets221of a smaller volume fosters more efficient separation of the mobile phase from the analytes. This is because the amount of time it takes for a droplet221to desolvate the mobile phase is directly related to the size of the drop: drops of lesser volume desolvate more rapidly than drops of greater volume. Faster desolvation time in turn means not only that a larger fraction of analyte ions are desolvated, but also means the distance that droplets221travel from outlet211until they are desolvated is shorter. In many known methods and apparatuses, many analyte ions are not ultimately provided to the mass analyzer102, but rather are lost such as through an exhaust port308. Often in known devices, the drops are lost before separation of the mobile phase and analytes occurs. By contrast, the droplets221are desolvated more rapidly and in a shorter distance, or in a smaller volume in the ion source101ofFIG. 3. This facilitates more efficient transfer of analyte ions into the mass analyzer102by reducing space charge effects, which are the mutual electrostatic repulsion of ions as well as charged droplets221.

Because disruptor apparatus104fragments the drops220(FIG. 2B) into droplets221of a comparatively small volume and the desolvation process occurs more rapidly. In certain embodiments, the droplets221may be provided directly to the conduit304and thus directly to the mass analyzer102. In this manner, the disruptor apparatus104functions as an interface between the LC column and the mass spectrometer. Representative embodiments illustrating the use of the apparatus as such an interface are described presently in conjunction withFIG. 4.

FIG. 4shows cross-sectional views of the disruptor apparatus104provided to a conduit to a mass analyzer in accordance with representative embodiments. Many of the details provided in connection with the description of representative embodiments ofFIGS. 1,2A,2B and3are germane to the presently described embodiments, and are not repeated in order to avoid obscuring the description of the embodiment ofFIG. 4.

Specifically,FIG. 4shows a cross-sectional view of a part of the first portion201of the disruptor apparatus104and a conduit403to a mass analyzer (not shown inFIG. 4) in accordance with a representative embodiment. Notably, the housing300, the chamber301, and similar components described in connection with representative embodiments in connection withFIG. 3are not included in the presently described embodiment. Rather, the droplets221provided from the diverging section207of the nozzle204, travel generally along a trajectory401, and are provided directly to the conduit304to the mass analyzer. In this manner, the disruptor apparatus104functions as the ion source101. As described in detail above, because the drops220have been fragmented into droplets221of comparatively small volumes, the time required for desolvation is reduced; and the distance that droplets221need to travel until the droplets221are desolvated is shorter. As such, the nozzle204of disruptor apparatus104may be provided directly to the conduit304to the mass analyzer102.

In the present embodiment, the nozzle204and the conduit403share a common axis of symmetry402, which is co-axial with the trajectory401of the droplets221passing from the nozzle204to the conduit403. The nozzle204and the conduit403may be integral. Illustratively, the drops220from the outlet211traverse the throat206and are fragmented into droplets221by the standing shock wave216as described above. The droplets221are substantially completely desolvated, travel down the conduit403and are provided to the mass analyzer. Because of the comparatively short distance required for desolvation to occur, a greater portion of the analyte ions from the desolvated droplets221are provided to the conduit403, and then to the mass analyzer through the comparatively direct connection of the nozzle to the conduit403.

FIG. 5shows a flow-chart of a method500in accordance with a representative embodiment. Many of the details provided in connection with the description of representative embodiments ofFIGS. 1,2A,2B,3and4are germane to the presently-described embodiment, and are not repeated in order to avoid obscuring the description of the illustrative method.

At501, the method comprises introducing a gas into the converging section of the nozzle at an upstream pressure. At502, the method comprises subjecting the diverging section of the nozzle to an ambient pressure so that a ratio of the upstream pressure to the ambient pressure creates a standing shock wave in the diverging section. At503, the method comprises mixing a fluid comprising an analyte with the gas to form drops directed towards the standing shock wave. The mixing is done in the converging section.

In view of this disclosure it is noted that the methods and devices can be implemented in keeping with the present teachings. Further, the various components, materials, structures and parameters are included by way of illustration and example only and not in any limiting sense. In view of this disclosure, the present teachings can be implemented in other applications and components, materials, structures and equipment to needed implement these applications can be determined, while remaining within the scope of the appended claims.