Abstract:
The invention provides an aerosol delivery method and system for producing a charged electrohydrodynamic (EHD) aerosol, discharging the aerosol and moving the discharged aerosol in a desired direction without substantial wetting of the device. The delivery system may include a spray nozzle for dispensing the fluid to be aerosolized and negatively charging the aerosol droplets, a discharge electrode generally downstream of the spray nozzle for generating a positive ion stream which intercepts and electrically neutralizes the negative aerosol droplets while also imparting a desired movement on the aerosol in a direction generally away from the discharge electrode and a reference electrode between the spray nozzle and the discharge electrode for modifying the electric field between the spray nozzle and the discharge electrode.

Description:
RELATED APPLICATION 
     This application claims priority from U.S. Provisional Application 60/130,893 filed Apr. 23, 1999. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to devices and methods for controlling the delivery and the delivery direction of an aerosol, and particularly to a method and apparatus for induced aerosol flow in an electrohydrodynamic (EHD) sprayer. 
     2. Background 
     The use of electrohydrodynamic (EHD) apparatus to produce aerosols is well known. Recently, we have recognized that EHD devices are extremely useful to produce and deliver aerosols of therapeutic products. 
     In typical EHE) devices fluid delivery means deliver fluid to be aerosolized to a nozzle maintained at high electric potential. One type of nozzle used in EHD devices is a capillary tube that is capable of conducting electricity. An electric potential is placed on the capillary tube which charges the fluid contents such that as the fluid emerges from the tip or end of the capillary tube a so-called Taylor cone is formed. This cone shape results from a balance of the forces of electric charge on the fluid and the fluid&#39;s own surface tension. Desirably, the charge on the fluid overcomes the surface tension and at the tip of the Taylor cone, a thin jet of fluid forms and subsequently and rapidly separates a short distance beyond the tip into an aerosol. Studies have shown that this aerosol (often described as a soft cloud) has a fairly uniform droplet size and a high velocity leaving the tip but that it quickly decelerates to a very low velocity a short distance beyond the tip. 
     EHD sprayers produce charged droplets at the tip of the nozzle. Depending on the use, these charged droplets can be partially or fully neutralized (with a reference or discharge electrode in the sprayer device) or not. The typical applications for an EHD sprayer without means for discharging or means for partially discharging an aerosol would include a paint sprayer or insecticide sprayer. These types of sprayers may be preferred since the aerosol would have a residual electric charge as it leaves the sprayer so that the droplets would be attracted to and tightly adhere to the surface being coated. However, with EHD apparatus used to deliver therapeutic aerosols, it is preferred that the aerosol be completely electrically neutralized prior to inhalation by the user to permit the aerosol to reach the pulmonary areas where the particular therapeutic formulation is most effective. 
     The preferred orientation of EHD sprayers is with the nozzle vertical and located above the object to receive the aerosol. This nozzle orientation eliminates, for practical purposes, the problems associated with the fluid dispensed from the nozzle tip collecting on or wicking up the outside of the capillary tube and associated fluid delivery means. If the fluid flows up the outside of the nozzle from the tip, it is no longer available to be sprayed and represents a loss in efficiency of the device. Moreover, fluid on the outside surfaces of the capillary tube may accumulate and suddenly flow back to the tip where it may disrupt the Taylor cone. These disruptions and any other disruptions of the Taylor cone may result in a large variation in the size and size distribution of the aerosol droplets which is particularly undesirable in pulmonary drug delivery. 
     When administering pharmaceuticals to a patient these limitations on orientation of the EHD apparatus result in either the patients having to tilt their head backwards or to lie on their back when the aerosol is delivered on axis with the nozzle. Alternatively, the EHD apparatus can deliver the aerosol vertically on axis with the nozzle and an elbow means can change the direction of aerosol flow to deliver the aerosol nearly horizontally. With this change in direction of the aerosol, there often is an appreciable loss in the quantity of the aerosol. The loss in quantity is a result of the fluid impacting and depositing on the walls of the delivery device, particularly in the vicinity of the elbow, instead of reaching the patient. One device for reducing disruptions of the Taylor cone and for reducing the loss in quantity of fluid impacting the walls is described in a co-owned U.S. patent application filed of even date herewith and entitled “High Mass Transfer EHD Aerosol Sprayer”, which application is hereby incorporated by reference. Therefore, an EHD aerosol sprayer is needed where the aerosol delivery direction can be controlled and wherein the Taylor cone can be stabilized to prevent disruption. Of particular need, is an EHD aerosol sprayer that can spray substantially horizontally and deliver the aerosol without appreciable wetting of the delivery device. 
     SUMMARY OF THE INVENTION 
     The invention described herein provides an aerosol delivery method and system for solving the problems discussed above by producing a charged EHD aerosol, discharging the aerosol and inducing a flow in the discharged aerosol in a desired direction without substantial wetting of the device. 
     In a preferred embodiment the delivery system includes a spray nozzle for dispensing the fluid to be aerosolized and negatively charging the aerosol droplets, a discharge electrode generally proximate the spray nozzle for generating a positive ion stream which intercepts and electrically neutralizes the negative aerosol droplets while also imparting a desired movement on the aerosol in a direction generally away from the discharge electrode, and at least one first reference electrode between the spray nozzle and the discharge electrode for modifying the electric field between the spray nozzle and the discharge electrode. Preferably, the discharge electrode is positioned proximate the spray nozzle such that the ion cloud intercepts the aerosol at a short distance, for example less than about 4 centimeters and more preferably less than 2 centimeters from the spray nozzle tip before the aerosol cloud has had a chance to disperse to a large degree. 
     Optionally, at least one second reference electrode may be placed near the discharge electrode on the side opposite of the first electrode. Optionally, at least one third electrode may also be placed near the spray nozzle on the side opposite the first reference electrode. 
     The spray nozzle is usually placed at a potential of between one and twenty kilovolts, with three to six kilovolts being the preferred voltage range. The placing of a negative potential on the spray nozzle results in the aerosol being negatively charged. To electrically discharge the aerosol, a positive potential of between one and twenty kilovolts, and with a preferred voltage of three to six kilovolts, is placed on a discharge electrode. The charges could be reversed on the spray nozzle and the discharge electrode, however, the positive ions from the discharge electrode appear to be much more effective than would negative ions in imparting movement (induced flow) to the aerosol. 
     Preferably, the discharge electrode includes a sharp point or edge where a positively charged ion cloud is originated to discharge the aerosol and move it in the desired direction. In a preferred embodiment, the axis of the spray nozzle and the axis of the discharge electrode are at an angle of less than about 120 degrees (between 0 degrees and 180 degrees) and more preferably in the range of 30-90 degrees. Larger angles may also be useful, but at angles approaching 180 degrees (the electrodes thereby being substantially opposed) the movement of the aerosol would be substantially toward the spray nozzle. In most uses, this would not be desirable to direct the charged aerosol substantially toward the discharge electrode, as the droplets are readily attracted to the electrode surface which reduces the aerosol delivery efficiency of the sprayer. If the discharge electrode becomes wetted with aerosol under these conditions, an undesired secondary spray can result at the discharge electrode. It is also undesirable to direct the discharge ion cloud substantially toward the spray nozzle as these ions can disrupt the EHD aerosol generation process. 
     Between the spray nozzle and the discharge electrode is a first reference electrode. The first reference electrode may be a wire, screen, plate or tube, but preferably has a shape that may influence an air stream to move past the spray nozzle. The first electrode may be on but one side of the spray nozzle near the discharge electrode or it may substantially surround the spray nozzle. Preferably, the first reference electrode intersects or breaks the line of sight between the tip of the nozzle and the tip of the discharge electrode to some what de-couple the nozzle&#39;s electric field from the electric field of the discharge electrode. By somewhat de-coupling these two electric fields, the attraction of the negatively charged aerosol to the positively charged discharge electrode is minimized. Consequently, the discharge electrode remains predominantly dry. Thus, the accumulation of the aerosol on the discharge electrode does not present a problem from the standpoint of reducing the quality and quantity of the aerosol delivered to the user. 
     The EHD device is constructed such that gas (generally air) is allowed to enter the device and to then flow near the spray nozzle toward the tip and past the Taylor cone. This gas flow has been found to stabilize the Taylor cone and to move the aerosol away from the tip of the spray nozzle. Moving the charged aerosol away from the tip seems to aid the aerosolization phenomenon at the Taylor cone. Preferably, the corona wind from the discharge electrode is used to assist in inducing the gas flow over the Taylor cone. The positively charged ion cloud downstream from the spray tip readily attracts the negatively charged aerosol droplets away from the nozzle. The motion of the aerosol droplets also induces gas flow over the spray tip and over the Taylor cone. 
     A preferred embodiment of the delivery method includes dispensing a fluid through a negatively charged spray nozzle to produce negatively charged aerosol droplets by the EHD process, generating a positive ion stream from a positively charged discharge electrode generally proximate the spray nozzle such that the ion stream intercepts and electrically neutralizes the negative aerosol droplets downstream of the spray nozzle while also imparting a desired movement on the aerosol in a direction generally away from the discharge electrode, and inserting a reference electrode between the spray nozzle and the discharge electrode for modifying the electric field between the spray nozzle and the discharge electrode. Preferably, the method further includes orienting the axis of the spray nozzle and the axis of the discharge electrode at an angle of less than about 120 degrees and more preferable in the range of 30-90 degrees. Preferably, the ion cloud intercepts the aerosol at a short distance, for example less than about 4 centimeters and more preferably less than 2 centimeters, from the spray nozzle tip before the aerosol cloud has had a chance to disperse to a large degree. 
     Another preferred embodiment of the delivery method includes dispensing a fluid through a negatively charged spray nozzle to produce negatively charged aerosol droplets from a Taylor cone in an EHD process, generating a positive ion stream around a positively charged discharge electrode generally proximate the spray nozzle such that the ion stream intercepts and electrically neutralizes the negative aerosol droplets downstream of the spray nozzle while also imparting a desired movement on the aerosol in a direction generally away from the discharge electrode, inserting a first reference electrode between the spray nozzle and the discharge electrode for modifying the electric field between the spray nozzle and the discharge electrode, providing a gas flow path near the Taylor cone between the spray nozzle and the first reference electrode and inducing gas flow past the spray nozzle along the gas flow path. 
     The EHD apparatus and method is a preferred application of the invention wherein the aerosol is charged. As described earlier, however, the invention is also useful for delivery of many other aerosol products (e.g. fragrances, lubricants, etc). In these other uses it may be useful to move an uncharged aerosol. In this case, the discharge electrode described herein may more accurately be termed an “ionization electrode” because the ions do not discharge the charge on the aerosol, but merely provide the momentum or the corona wind to direct the flow in the desired direction. Apparatus according to the invention would include aerosol source, an ionization electrode for developing the corona wind along a desired path, a reference electrode and a voltage source. 
     In any of the applications of the invention the corona wind could either be a positive or negative ion stream, though the positive stream seems to have some advantages in the drug delivery applications. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The accompanying drawing incorporated in and forming part of the specification illustrates several aspects of the present invention, and together with the description serve to explain the principles of the invention. In the drawings: 
     FIG. 1 is a schematic of an EHD sprayer in accordance with the present preferred embodiment of the invention. 
     FIG. 2 is a schematic of an EHD sprayer in accordance with a second embodiment of the invention. 
     FIG. 3 is a schematic of an EHD sprayer in accordance with a third embodiment of the invention 
     FIG. 4 is an orthographic cutaway view of a multi-nozzle EHD sprayer in accordance with the present invention. 
     FIG. 5 is a side view of the multi-nozzle sprayer shown in FIG. 4 taken at  5 — 5 . 
     FIG. 6 is a front view of the multi-nozzle sprayer shown in FIG.  4 . 
     FIGS. 7A and 7B show cross sectional views of preferred spray tips used in delivering fluid to an EHD sprayer. 
     Reference will now be made in detail to the present preferred embodiment of the invention, examples of which are illustrated in the accompanying drawings. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     The invention includes methods and apparatus for directionally controlling the delivery of an aerosol along a desired path. The aerosol may be created by any number of known means (for example, by vaporization, nebulization, electrospraying, expansion through an orifice, and the like) and may have an electrical charge or not. One preferred method of creating the aerosol is by electospraying and particularly by electrohydrodynamic spraying. The purpose of the induced flow electrohydrodynamic (EHD) aerosol sprayer is to provide a device that will permit an operator to consistently spray an aerosol horizontally or in any other arbitrary direction, in the absence of other external airflow. The sprayer utilizes electrical means for stabilizing the Taylor cone with a gas flow near the Taylor cone and for directionally controlling the movement of the charged aerosol generally in a direction controlled by the position and orientation of the discharge electrode and the reference electrode. 
     The aerosol delivery system and method are particularly useful for delivering therapeutic agents by inhalation. They are even more useful for delivering therapeutic agents into the lungs. Therapeutic agents include any materials that are beneficial to the user. Particularly useful therapeutic agents include not only pharmaceuticals but also, for example, chemotherapeutic or chemopreventive agents, vaccines, nucleic acids, proteins and gene therapy agents. 
     Though the invention is described in sufficient detail to enable others to practice it, and though not bound to a description of the manner in which the invention works, nevertheless the inventors believe that the movement of the aerosol away from the discharge electrode is due to the effect of what is termed a corona wind or induced air flow. It is believed that the corona wind works in the following way. The positive charge on the discharge electrode results in corona or ionization of the nearby air molecules producing a positive ion cloud around the electrode. The like-charged ions repel and cause a migration of these ionized air molecules away from the discharge electrode. As is well understood in the art, a sharp point or edge on the discharge electrode (which would be one of our preferred embodiments of the discharge electrode) substantially increases the corona and the movement of the ions away from the point or edge. Since these air molecules have mass, their movement causes a corona wind effect or induced air flow directly away from the discharge electrode (rather axially to a sharp point or edge of the discharge electrode), which then intercepts the aerosol droplets downstream of the tip of the nozzle and redirects them (imparts momentum) generally along the path of the corona wind. As earlier noted, the positively charged air molecules also serve to neutralize/discharge the negative charge on the aerosol. Since the corona wind from the discharge electrode moves along the axis of and away from the discharge electrode, the orientation of the discharge electrode substantially determines the direction taken by the aerosol. 
     By providing an air flow path alongside of the spray nozzle, it has also been found that as the corona wind moves the aerosol away from the spray nozzle, an induced airflow is caused along the spray nozzle and past the Taylor cone. This induced airflow seems to stabilize the Taylor cone, particularly as the EHD device is operated in different orientations. The induced airflow seems to improve the aerosolization process by preventing wicking of the fluid on the outside of the spray nozzle and by transporting the charged aerosol droplets away from the region downstream of the spray nozzle. It may also provide an air curtain that centers the Taylor cone, though this is not proven yet. The induced airflow is beneficial whether the corona wind is created on but one side of the spray nozzle or at several sites or substantially all around the spray nozzle with single or multiple discharge electrodes and reference electrodes. 
     FIG. 1 provides a schematic of the preferred embodiment of the induced flow EHD aerosol sprayer  10 . In this embodiment, the basic sprayer  10  has housing wall  12  terminating in an exit mouthpiece  8 , a spray nozzle  20  having a central axis  24 , a first reference electrode  40 , and discharge electrode  70  having a central axis  74 . The exit mouthpiece  8  generally has a contour allowing the user to bring the aerosol sprayer into contact with the lips or mouth area and receive the aerosol through the mouth for treatment of the lungs. The DC voltage source  30  electrically connects and maintains the spray nozzle  20  at a negative voltage with respect to reference electrode  40 . A second DC voltage source  60  electrically connects and maintains the discharge electrode  70  at a positive voltage with respect to reference electrode  40 . Ground  50  maintains reference electrode  40  at a ground reference voltage, approximately zero volts DC. It will be understood that the reference electrode  40  is conveniently at ground potential, but that it could be at any potential that is negative with respect to the discharge electrode and positive with respect to the spray nozzle. Moreover, the polarity of the charge on the spray nozzle and discharge electrode are conveniently negative and positive respectively, but it is only necessary that the charges are negative and positive with respect to each other (and the reference electrode). 
     Spray nozzle  20  is typically a capillary tube or other tube, plate or any other shape used to deliver fluid in EHD applications. In some embodiments the tube used for spray nozzle  20  may have a spray tip  22  which may be designed specifically for EHD spray applications. These tips promote the formation and stability of the Taylor cone. A stable Taylor cone tends to reduce the deviation in the droplet size in the resulting aerosol. The invention includes apparatus including a single spray nozzle that can produce multiple Taylor cones and apparatus with multiple spray nozzles. 
     One preferred spray nozzle design is shown in FIGS. 7A and 7B. Each spray nozzle  730  includes a round tube having a spray tip  732  at one end and a connection to the source of fluid to be aerosolized at the other end. The spray tip can be merely the open end of the spray nozzle or can optionally include other designs or elements to better promote the formation of Taylor cones. In FIGS. 7A and 7B a partitioning plug  734  is secured in the spray nozzle at the spray tip. The partitioning plug  734  is a cylindrical element terminating in a cone  736  that becomes part of the spray tip for creation of the Taylor cone. The partitioning plug is machined to have four ribs  738  and having therefore a cross section in the shape of a cross to provide four paths for the fluid in the spray nozzle. This has been found to improve the formation of the Taylor cone and to increase the throughput of fluid. Other designs may result in one or more Taylor cones at each spray tip. Multiple nozzles in any useful arrangement may be used in the device. 
     Discharge electrode  70  typically has a sharp discharge tip  72  or a knife-edge or other sharp points or other protrusions. As is known in the art, these sharp shapes tend to promote the formation of ions. Alternatively, any tip shape that is capable of ionizing air molecules may be utilized. The discharge electrode is generally elongated and has a fairly easily definable central axis  74 . Whether elongated or not, however, the tip  72  will have a geometry which allows significant ionization in the neighborhood of one or more sites on the discharge electrode and movement of the ions away from these sites in a direction which is predictable and reproducible. When the central axis is easily definable, the direction of movement of the ions and ultimately the aerosol is generally parallel with this axis. When the axis is not easily definable, the direction of movement of the ions and the aerosol is predictable and reproducible away from the sites in a direction that we will define as axial to the discharge sites. Discharge electrodes with multiple ionization sites and multiple discharge electrodes (with or without multiple spray nozzles) are within the scope of the invention. 
     The discharge electrode is located sufficiently close to the spray nozzle  20  and to the spray tip  22  and is oriented with respect thereto such that the ions from the discharge electrode may intercept the aerosol downstream of the spray tip  22 . If the interception point is remote from the spray tip at a point where the aerosol has had sufficient time to become quite disperse, the effect of the ion cloud to move the aerosol in the desired direction is diminished. Therefore, the discharge electrode is preferably located sufficiently close to the spray nozzle  20  and to the spray tip  22  and is oriented with respect thereto such that the ions from the discharge electrode may intercept the aerosol proximate the spray tip  22  before the aerosol has dispersed to any great degree. 
     A reference electrode  40  is located between spray nozzle  20  and discharge electrode  70 . This reference electrode can be a wire, screen, plate, tube or other shape with modifies the field between the spray nozzle and the discharge electrode. When used for influencing the flow of air near the spray nozzle and the Taylor cone, the reference electrode preferably has a shape and size sufficient for that purpose. In some embodiments, the spray end  42  of reference electrode  40  may be located proximate but not intersecting the line LOS that connects the spray tip  22  to discharge tip  72 . In other embodiments, the spray end  42  of reference electrode  40  may be located to barely intersect the line LOS. In a preferred embodiment, however, the reference electrode  40  is positioned so that it crosses line LOS and the spray end  42  is past the line LOS but not substantially within the region of the aerosol spray downstream of the spray nozzle during use. With the reference electrode in this preferred position, the electric field generated between the spray nozzle  20  and reference electrode  40  is substantially de-coupled from the electric field generated between the discharge electrode  70  and reference electrode  40 . Thus, changes in the relative position of the spray nozzle  20  with respect to reference electrode  40  or changes in the electric field strength generated between the spray nozzle  20  and reference electrode  40  have little, if any, impact on the electric field generated between the discharge electrode  70  and the reference electrode  40 . Similarly, changes in the relative position of the discharge electrode  70  with respect to reference electrode  40  or changes in the electric field strength generated between the discharge electrode  70  and reference electrode  40  have little, if any, impact on the electric field generated between the spray nozzle  20  and the reference electrode  40 . 
     However, the existence and the position of the reference electrode contribute with the discharge electrode to controlling the direction of the aerosol delivery. Without the reference electrode, the charged aerosol would tend to be attracted toward the tip of the discharge electrode. The positive ions from the tip of the discharge electrode would also be attracted toward the aerosol and the spray nozzle and the spray nozzle tip. The aerosol and the positive ions would then tend to meet substantially in between the spray nozzle and the discharge electrode. The reference electrode is positioned such that it reduces this tendency so that the aerosol and the positive ions intersect more near the intersection of their respective central axes downstream of the electrodes. In FIG. 1, the discharge electrode is positioned such that the aerosol is moved generally in the direction of the positive ion flow and toward the exit mouthpiece  8  and the user. 
     The discharge electrode  20  and the reference electrode  40  are fixed in the EHD device in such a manner and with respect to the spray nozzle  20  such that a gas flow path (such as at  18  and/or  28 ) is provided alongside the spray nozzle. For example, in FIG. 1, the electrodes are fastened such that air may enter the EHD device through the mouthpiece  8  in the housing  12  and move along the inside of the housing wall at  16  and then along the gas flow path at  18  and/or  28 . When used to deliver therapeutic agents by inhalation, the user&#39;s mouth would typically cover the mouthpiece so that additional openings  13  may be necessary in the housing  12  to allow entry of gas or air. The position of the openings  13  may be moved to allow more or less gas to move along the gas flow paths  18  and  28 . This air movement along the gas flow path  18  and/or  28  has been found to contribute to a very stable Taylor cone at the tip  22 . The airflow also helps move the aerosol to the location where the positive ions from the discharge electrode impact the aerosol. The airflow along the path  18  and/or  28  appears to be at least partially induced by the corona wind from discharge electrode  70 . 
     Preferably, reference electrode  40  and spray nozzle  20  are positioned such that the electric field intensity is largest between spray tip  22  and spray end  42 , as for example when they are angled toward each other and the spray tip  22  and the spray end  42  are relatively closer together than other parts of the electrodes. This relative position of spray nozzle  20  and reference electrode  40  minimizes any tendency for the dispensed fluid to coat or collect on the outside of spray nozzle  20 . It also has some positive effect on the induced air flow past at  18  and/or  28  due to the corona wind. Collection of fluid on the outside of spray nozzle  20  (with the spray nozzle fairly vertical and the nozzle tip at substantially the lowest point) is most likely when the spray nozzle  20  dispenses the aerosol in the upward direction and is least likely when the spray nozzle  20  dispenses the aerosol in the downward direction. Collection of fluid reduces the quantity of the fluid that is converted into an aerosol. Additionally, this fluid collection has the potential to disrupt or interfere with the Taylor cone. Any disruption or interference with this cone affects the aerosol droplet size and the droplet size distribution. This relative position of spray nozzle  20  and reference electrode  40  also minimizes the tendency for the aerosol to coat or collect on the reference electrode  40 . Any collection of the aerosol on the reference electrode  40  reduces the quantity of aerosol delivered to the user from the EHD aerosol sprayer  10 . 
     For the above mentioned reasons it is desirable to orient the spray nozzle more in a vertical orientation (generally above the horizontal) so that the fluid is restrained by gravity from wicking up the nozzle and the aerosol generally moves downward away from the tip. This also suggests that the movement of the corona wind is most beneficially away from the nozzle tip  22  such as when the central axis  74  of the discharge electrode is oriented parallel to the central axis  24  of the nozzle or at some acute angle. Of course, the corona wind must intercept the aerosol in some manner to affect the direction of the aerosol. 
     When used to deliver therapeutic agents by inhalation, it is also desirable to deliver an aerosol horizontally to the user&#39;s mouth. This desire suggests that it would be more beneficial to shift the direction of the aerosol by up to 90 degrees so that it is delivered substantially horizontally to the user. Both of these desires may be accomplished by maintaining an angle  30  between the nozzle central axis  24  and the discharge electrode central axis  74  between about 0 and 120 degrees. The invention will continue to work at angles in excess of 120 degrees, but it will be understood that the aerosol will be redirected by the corona wind more in the general direction of the nozzle at these higher angles. Ultimately, at 180 degrees, the corona wind would be moving substantially parallel to the nozzle central axis and may substantially defeat the purpose of the invention as described earlier. The aerosol is most preferably directed by the discharge electrode toward the mouthpiece  8  and ultimately to the user contacting the mouthpiece. It may be useful when the angle  30  is a large number to use more than one reference electrode  40  between the spray nozzle and the discharge electrode. 
     Also, the best results in inducing airflow past the Taylor cone have been observed when the discharge electrode is oriented so that the corona wind moves in a direction substantially away from the spray nozzle. This may be accomplished by maintaining an angle  30  between the nozzle central axis  24  and the discharge electrode central axis  74  between about 0 and 90 degrees, preferably between 0 and 60 degrees. 
     The discharge electrode tip  72  may be located either upstream or downstream of the spray tip  22 . As mentioned earlier, in this upstream or downstream position proximate spray tip  22 , the ions from the discharge electrode may intercept the aerosol a short distance downstream of the spray tip  22  before the aerosol has dispersed to any great degree. Preferably, the discharge electrode is positioned proximate the spray nozzle such that the ion cloud intercepts the aerosol at a distance of less than about 4 centimeters and more preferably less than 2 centimeters from the spray nozzle tip before the aerosol cloud has had a chance to disperse to a large degree. By the term “upstream” of the spray tip  22 , we mean that when the spray nozzle is in a vertical orientation, the discharge electrode tip is above a plane through the spray tip  22  perpendicular to the nozzle central axis  24 . By the term “downstream” we mean that the discharge electrode tip would be below the perpendicular line under the above conditions. Whether the discharge electrode is positioned upstream or downstream of the spray nozzle, the discharge electrode should be located outside of the spray path of the aerosol. As mentioned, this spray path tends to enlarge greatly as the aerosol disperses downstream of the spray nozzle. 
     Preferably, reference electrode  40  and discharge electrode  70  are positioned such that the electric field intensity is largest between spray end  42  and discharge tip  72 . This relative position of discharge electrode  70  and reference electrode  40  minimizes the quantity of ionized air molecules that flow to the ground electrode  40 . Thus, this configuration maximizes the number of ionized air molecules (corona wind) available to discharge the aerosol. Additionally, this configuration also tends to maximize the aerosol quantity that moves with the corona wind and the induced air flow past the Taylor cone. 
     DC voltage source  30  electrically connects spray nozzle  20  to reference electrode  40  and maintains spray nozzle  20  at a negative potential. DC voltage source  60  electrically connects discharge electrode  70  to reference electrode  40  and maintains discharge electrode  70  at a positive potential. A positive potential is preferred on the discharge electrode  70  to form the corona wind discussed above. A negative voltage on the discharge electrode  70  would more readily form an ion stream. However, these negative ions (electrons) have a higher mobility (velocity) than air molecules, but they also have a very small mass. Thus, electrons have far less momentum than air molecules so that using electrons to discharge the aerosol would have relatively little impact on the movement of the aerosol but in some applications may be useful. 
     The positive voltage on the discharge electrode  70  strips an electron from an air molecule leaving the air molecule with a positive charge. Consequently, the ionized air molecule will move by repulsion away from the discharge electrode  70 . Additionally, the ionized air molecules are attracted to the negative charge on the aerosol. In the embodiments where the reference electrode  40  does not cross line LOS, the ionized air molecule will also be attracted to the negative voltage on the spray nozzle  20 . Due to the aerosol&#39;s closer proximity most, if not all, of the ionized air interacts with the aerosol. Thus, the predominate motion direction of the ionized air molecules is determined by the orientation of the ionization sites on the discharge electrode, which is typically directly away from the discharge electrode  70  and generally parallel to the central axis  74 . Consequently, the aerosol also moves in the same direction as determined by the characteristics and/or position/orientation of the discharge electrode  70 . 
     Voltage sources  30  and  60  typically provide between one and twenty kilovolts, with the preferred voltage being between three and six kilovolts. The best voltage for aerosolizing a particular fluid depends on the fluid&#39;s properties, principally the conductivity/resistivity, viscosity, surface tension, and flow rate. Additionally, the relative positions of the spray nozzle  20 , reference electrode  40 , and discharge electrode  70  will typically have some influence on the best voltage(s) to be applied to the spray nozzle  20  and discharge electrode  70 . Furthermore, the type of nozzle tip  22  and the aerosol droplet size will also influence the ideal voltage utilized in a particular application. To some extent, the magnitude of the voltage may be used to control the velocity of the ions from the discharge electrode. The person of ordinary skill in the art of designing and using EHD sprayers is familiar with typical voltages utilized for specific fluids and equipment geometry. 
     In some embodiments, the addition of a resistance in series with the voltage sources  30  and/or  60  may be required to prevent arcing between the spray nozzle  20  and reference electrode  40 , or between reference electrode  40  and discharge electrode  70 . The resistance is intended to limit current so that arcing is either minimized or cannot be maintained. To be effective without overly limiting the current to the electrodes, the resistance should have a value of hundreds of kilohms to hundreds of megohms. In a preferred embodiment and operating at preferred voltages, the resistance has a value between about ten and twenty megohms. 
     Ground  50  maintains the reference electrode  40  at a reference voltage. Preferably, this reference voltage is approximately zero volts. Preferably, the reference electrode is electrically paired with the nozzle and the discharge electrode. However, in some applications, the “reference electrode” is not an electrode at all and may instead be made of a dielectric material. This may promote wetting of the dielectric “reference electrode” by charged aerosol; however, if the application is one that only requires a short burst of aerosol (perhaps several seconds), then this dielectric “reference electrode” may still function. 
     FIG. 2 illustrates a second EHD sprayer  200  configured to control the aerosol discharge direction. Sprayer  200  employs a spray nozzle  220  that is electrically connected to a reference electrode  240  with a voltage source  230 . Discharge electrode  224  is connected to reference electrode  240  with a voltage source  260 . The spray nozzle  220  and the discharge electrode  224  are similar to spray nozzle  20  and the discharge electrode  70  discussed above. Voltage sources  230  and  260  are also similar to voltage sources  30  or  60  described above. Ground  250  provides the same function and reference voltage to that disclosed above for ground  50 . The reference electrode  240  has been modified so that the electric field produced between spray nozzle  220  and reference electrode  240  is symmetric around the outside surface of spray nozzle  220 . An airflow path at  218  is created by the reference electrode  240  (which is open to intake airflow at the upstream end nearest the voltage supply and opposite the spray tip  222 ) and the spray nozzle  220 . Air may move up the housing walls  212  at  216  and thence down the flow path  218  past the Taylor cone. When used to deliver therapeutic agents by inhalation, the user&#39;s mouth would typically cover the mouthpiece so that additional openings (similar to the openings  13  in FIG. 1) may be necessary in the housing  212  to allow entry of gas or air. 
     Preferably, reference electrode  240 , the spray nozzle  220  and the discharge tip  226  are positioned such that the electric field intensity is largest between spray tip  222  and spray end  242  and between the spray end  242  and the discharge tip  226 . This relative position of spray nozzle  220  and ground electrode  240  minimizes any tendency for the fluid dispensed to coat or collect on the outside of spray nozzle  220 . The fluid collection on the outside of spray nozzle  220  is most likely when the spray nozzle  220  dispenses the aerosol in the upward direction, and is least likely when the spray nozzle  220  dispenses the aerosol in the downward direction. The collection of fluid reduces the quantity of the fluid that is converted into an aerosol. Additionally, this fluid collection has the potential to disrupt or interfere with the Taylor cone. Any disruption or interference with this cone affects the aerosol droplet size and the droplet size distribution. 
     The positioning of the spray tip  222  with respect to spray end  242  of the reference electrode  240  is fairly important in minimizing the tendency for the aerosol to coat or collect on the ground electrode  240 . A preferred position of the reference electrode would be such that the spray end is approximately on the line of sight between the spray nozzle tip  222  and the discharge tip  226 . Positioning the reference electrode a short distance from this line of sight is still useful and part of the invention; however, as the position of the reference electrode is changed (back toward the voltage source in FIG. 2) to expose more of the spray nozzle, the aerosol tends to move toward the discharge electrode and to neutralize and coat the discharge electrode more. If the position of the reference electrode is changed to more cross over the line of sight (that is, to more surround the spray nozzle tip and shield it from the discharge electrode) the tendency is for the aerosol to coat the inside of the reference electrode. 
     The preferred shape for spray nozzle  220  is a cylindrical tube. Consequently, the preferred shape for the reference electrode  240  is a truncated cone with the smaller diameter opening forming spray end  242 . This configuration of sprayer  200  provides an approximately conical electrical field between spray tip  222  and spray end  242 . Other sprayer  200  geometry could also generate symmetric diverging electric fields. These electric fields cause the aerosol to move away from sprayer  200 , with the motion direction aligned generally with the longitudinal axis of spray nozzle  220 . 
     FIG. 3 illustrates a third EHD sprayer  300  configured to control the aerosol discharge direction and stabilize the Taylor cone. Sprayer  300  employs a spray nozzle  320  that is electrically connected to a first reference electrode  340  with a voltage source (not shown) to provide a negative charge on the spray nozzle with respect to the first reference electrode  340 . Discharge electrode  370  is connected to a voltage source (not shown) which places a positive charge on the discharge electrode with respect to the first reference electrode  340 . The spray nozzle  320  and the discharge electrode  370  are similar to spray nozzle  20  and the discharge electrode  70  discussed above. The voltage sources are also similar to voltage sources  30  or  60  described above. Positive ions are created at the tip  372  of the discharge electrode and a corona wind is created in a direction substantially along the axis  374  toward the mouthpiece  308  of the device. 
     The embodiment of FIG. 3 also incorporates a second reference electrode  342  near the discharge electrode on the side opposite the first reference electrode  340  and a third reference electrode  344  near the spray nozzle on the side opposite the first reference electrode. Reference electrodes  340 ,  344  and spray nozzle  320  create an air flow path at  318  and  328  respectively. Air is induced at least partially by the corona discharge to move down the flow path  318  and  328  past the Taylor cone to provide stability. Furthermore, reference electrodes  340 ,  344  and spray nozzle  320  provide greater symmetry in the electric field or spray tip  342  than what can be achieved in spray nozzle  20 . Likewise, reference electrodes  340 ,  342  and discharge electrode  370  provide symmetry in the electric field at discharge tip  372  so that positive ions are more likely to move along axis  374  than in the sprayer shown in FIG.  1 . 
     The EHD sprayers shown in FIGS. 1-3 may be arranged into an EHD sprayer employing multiple spray nozzles. Utilizing multiple spray nozzles permits an EHD sprayer to aerosolize greater volumes of fluid required in many aerosol sprayer applications. These spray nozzles may be arranged in any shape or array desired as long as the electric field interactions are taken in to account. The nozzles may be arranged in circles, lines, multiple stacked lines or random stacks may be used, for example. 
     An exemplary multiple nozzle configuration is illustrated in FIGS. 4-6. These figures illustrate a linear spray nozzle array in a device for pulmonary delivery of drugs in a clinical setting where the source of fluid to be aerosolized is remote from the EHD sprayer. An EHD sprayer is housed in a device  100  remote from the source of fluid. The EHD sprayer  100  shown in FIGS. 4-6 includes a housing  110 , air inlet  112 , spray nozzles  120 , reference electrodes  140 , discharge electrodes  170 , spray electrodes  180 , and manifold  190 . A DC voltage source (see FIG. 1) electrically connects and maintains the spray nozzles  120  at a negative voltage with respect to reference electrodes  140 . A second DC voltage source (see FIG. 1) electrically connects and maintains the discharge electrodes  170  at a positive voltage with respect to reference electrodes  140 . Ground (see FIG. 1) maintains reference electrodes  140  at a ground reference voltage (approximately zero volts DC). The housing  110  contains and supports the spray nozzles  120 , ground electrodes  140 , discharge electrodes  170 , spray electrodes  180 , and manifold  190 . All of these elements are supported by the housing  110  so that air can enter the housing such as at  114  and through holes in perforated plate  118  so as to be available above the reference electrodes  140  to be induced by the corona wind along the gas flow path  116  past the spray nozzles  120  and past the Taylor cones produced at the tip  122  of the spray nozzles. Additionally, housing  110  may contain the voltage source(s) or provide connections for external voltage source(s). 
     Each spray nozzle  120  is typically a capillary tube or other tube, electrode or other shape used to deliver fluid in EHD applications. In some embodiments the tube used for a spray nozzle  120  may have a spray tip  122  designed specifically for EHD spray applications. This tip promotes the Taylor cone formation. Additionally, this tip may stabilize the Taylor cone, which consequently tends to reduce the deviation in the droplet size in the resulting aerosol. The induced airflow along the gas flow path  116  additionally stabilizes the Taylor cone. 
     Each discharge electrode  170  typically has a knife edge or needle like discharge tip  172 . These tip shapes tend to promote the formation of ionized air molecules. Alternatively, any tip shape that is capable of ionizing air molecules may be utilized. 
     In many uses it is desirable to maintain an angle between the spray nozzle and the discharge electrodes between about 0 and 120 degrees. The invention will continue to work at angles in excess of 120 degrees, but it will be understood that the aerosol will be redirected by the corona wind more in the general direction of the nozzle at these higher angles. Ultimately, at 180 degrees, the corona wind would be moving substantially parallel to the nozzle central axis and would potentially move the aerosol back to the nozzle. This would substantially defeat the purpose of the invention. When using multiple spray nozzles and discharge electrodes, it is useful to maintain substantially the same angle between all the spray nozzles and all the discharge electrodes; however, it is sufficient to maintain that angle between any of them such that the overall effect of the corona wind is to move the aerosol away from the spray nozzles toward the desired target/user and/or to induce the flow of air along the gas flow path  116  past the Taylor cone. The spray nozzles and discharge electrodes need not be paired in any one to one relationship. 
     Also, the best results in inducing airflow past the Taylor cone have been observed when the discharge electrodes are oriented so that the corona wind moves in a direction substantially away from the spray nozzle. This may be accomplished by maintaining an angle between a plane cutting through the nozzles and a plane cutting through the discharge electrodes between about 0 and 90 degrees, preferably between 0 and 60 degrees. And the discharge electrode tips  172  may be located either upstream or downstream of the spray tips  122 . As mentioned earlier, in this position upstream or downstream proximate the spray tips  122 , the ions from the discharge electrode may intercept the aerosol a short distance from the spray tips  122  before the aerosol has dispersed to any great degree. By the term “upstream” of the spray tips  122 , we mean that when the spray nozzles are in a vertical orientation, the discharge electrode tips are above a line drawn through the spray tips  122  perpendicular to a central axis of the spray nozzles. By the term “downstream” we mean that the discharge electrode tips would be below the perpendicular line under the above conditions. 
     In the embodiment shown, there are three reference electrodes  140   a ,  140   b , and  140   c . Other embodiments may use different configurations of reference electrodes  140  as required to develop and shape the electric fields desired for a particular application. Reference electrode  140   a  is located above spray nozzles  120 . 
     Preferably, reference electrodes  140   a  and  140   b  and spray nozzles  120  are positioned such that the electric field intensity is largest between spray tips  122  and spray ends  142   a  and  142   b . This relative position of spray nozzles  120  and reference electrodes  140   a  and  140   b  minimizes any tendency for the fluid to coat or collect on the outside of spray nozzles  120 . The collection of fluid on the outside of spray nozzles  120  is most likely when the spray nozzles  120  dispense aerosol in the upward direction, and is least likely when the spray nozzles  120  dispense aerosol in the downward direction. The collection of fluid reduces the quantity of the fluid that is converted into an aerosol. Additionally, this fluid collection has the potential to disrupt or interfere with the Taylor cone. Any disruption or interference with this cone affects the aerosol droplet size and the droplet size distribution. This relative position of spray nozzles  120  and reference electrodes  140   a  and  140   b  also minimizes the tendency for the aerosol discharged to coat or collect on the reference electrodes  140   a  and  140   b . Any collection of the aerosol on the reference electrodes  140   a  and  140   b  reduces the quantity of aerosol discharged from the EHD aerosol sprayer  100 . 
     Reference electrode  140   b  is also located between spray nozzles  120  and discharge electrodes  170 . In some embodiments, the spray end  142   b  of reference electrode  140   b  may be located to intersect the line LOS (see FIG. 1) that connects a spray tip  122  to a discharge tip  172 . In the preferred embodiment, however, the reference electrode  140   b  is positioned so that reference electrode  140   b  crosses line LOS (see FIG.  1 ). With the reference electrode in the preferred position, the electric field generated between the spray nozzles  120  and reference electrode  140   b  is substantially de-coupled from the electric field generated between the discharge electrodes  170  and reference electrode  140   b . Thus, changes in the relative position of the spray nozzles  120  with respect to reference electrode  140   b , or changes in the electric field strength generated between the spray nozzles  120  and reference electrode  140   b  have minimal impact on the electric field generated between the discharge electrodes  170  and the reference electrode  140   b . Similarly, changes in the relative position of the discharge electrodes  170  with respect to reference electrode  140   b , or changes in the electric field strength generated between the discharge electrodes  170  and reference electrode  140   b  have minimal impact on the electric field generated between the spray nozzles  120  and the reference electrode  140   b.    
     Preferably, reference electrodes  140   b  and  140   c  and discharge electrodes  170  are positioned such that the electric field intensity is largest between spray ends  142   b  and  142   c  and discharge tips  172 . This relative position of discharge electrodes  170  and reference electrodes  140   b  and  140   c  minimizes the quantity of ionized air molecules that flow to the reference electrodes  140   b  and  140   c .Thus, this configuration maximizes the number of ionized air molecules (corona wind) available to discharge the aerosol. Additionally, this configuration also tends to maximize the aerosol quantity that moves with the corona wind. Preferably, reference electrodes  140   b  and  140   c  are also positioned symmetrically to discharge electrodes  170 . This geometric symmetry promotes symmetry in the electric field at discharge tips  172  which tends to promote ionized air flow across the plane intersecting the discharge electrodes. 
     A DC voltage source (see FIG. 1) electrically connects spray nozzles  120  to reference electrodes  140   a  and  140   b  and maintains spray nozzles  120  at a negative potential. A second DC voltage source (see FIG. 1) electrically connects discharge electrodes  170  to reference electrodes  140   b  and  140   c  and maintains discharge electrodes  170  at a positive potential. 
     A positive potential is preferred on the discharge electrodes  170  to form the corona wind discussed above. A negative voltage on the discharge electrodes  170  would form an ion stream easier; however, as described above these negative ions (electrons) have a very low momentum. Thus, using electrons to discharge the aerosol has relatively little impact on the movement of the aerosol as compared with the effect of positive ions. However, as stated above, in some applications it may actually be useful to have a negative charge on the discharge electrode, though it is not preferred in the drug delivery application. 
     The positive voltage on the discharge electrodes  170  strips an electron from an air molecule leaving the air molecule with a positive charge. Subsequently, the ionized air molecule will move away from the discharge electrodes  170 . Additionally, the ionized air molecules are attracted to the negative charge on the aerosol. In the embodiments where the reference electrode  140   b  does not cross line LOS (see FIG.  1 ), the ionized air molecule will also be attracted to the negative voltage on the spray nozzles  120 . Due to the closer proximity of the aerosol most, if not all, of the ionized air interacts with the aerosol. The addition of lower reference electrode  140   c  and the resulting impact on the electric field or discharge tips  172  provide a symmetry to the ionizing field. Thus, the predominate motion direction of the ionized air molecules is directly away from the discharge electrodes  170  and along the direction that the discharge electrodes  170  are pointing. Consequently, the aerosol also moves in the direction that the discharge electrode is pointing. Preferably, this direction is generally toward the device exit which, in the drug delivery application is toward the mouth of the user. In any event, the motion direction of the aerosol is principally controlled by the position/orientation of the discharge electrodes  170 . 
     In some applications, it may be useful to begin the corona discharge and the corona wind just prior to production of aerosol. This may assist in more completely moving the aerosol droplets away from the spray nozzle. Typically, when the voltage to the discharge electrode and the spray nozzle are applied at the same time, the positive corona begins prior to the aerosolization of the fluid because the electron stripping process is more rapid than the EHD droplet formation process. However, at times, it is useful to apply the voltage to the discharge electrode just prior to applying the voltage to the spray nozzle. 
     When the spray nozzles are arranged in an array, it may be necessary to add spray electrodes to the array to balance and/or shape the electric fields experienced by the other spray nozzles. A spray electrode may be a spray nozzle that is plugged, blocked, or not provided with fluid. Alternatively, the spray electrode may be shaped similarly to a discharge electrode. Additionally, spray nozzle spacing may serve a similar function. 
     When using a linear array as shown in FIGS. 4-6 for sprayer  100 , spray electrodes  180  are placed at each end of the linear array. These spray electrodes  180  tend to balance and/or even out the electric field without having to adjust the voltages on individual spray nozzles  120 , so that the adjacent spray nozzle  124  is subject to a similar electric field as the other spray nozzles  120 . With each spray nozzle  120  subject to similar electric fields, each Taylor cone will then behave in a predictable manner. Consequently, the aerosol droplet size and size distribution can be predicted and controlled. 
     Spray nozzles  120  may be joined to manifold  190  that is supported by housing  110 . Manifold  190 , if employed, provides a fluid connection between a fluid source (not shown) and each spray nozzle  120 . Additionally, manifold  190  interconnects each spray nozzle  120 . Thus, each spray nozzle should experience approximately the same fluid pressure and each spray nozzle should experience similar fluid flow rates. Similar fluid flow rates also promote similar Taylor cone behavior. Consequently, the aerosol droplet size and size distribution can be predicted and controlled. 
     Manifold  190 , if manufactured from a conducting material, can also electrically connect the voltage source to each spray nozzle  120  and to each spray electrode  180  installed. Due to the relatively large size of manifold  190  as compared to a spray nozzle  120  onto spray electrode  180 , the voltage provided to each spray nozzle  120  or each spray electrode  180  should be similar. Consequently, the Taylor cone behavior can be predicted with greater certainty. 
     We have disclosed the preferred EHD apparatus and method in detail. As described earlier, the invention is also useful for delivery of many other aerosol products (e.g. fragrances, lubricants, etc). In these other uses it may be useful to move an uncharged aerosol. In this case, the discharge electrode described herein may more accurately be termed an “ionization electrode” because the ions do not discharge the charge on the aerosol, but merely provide the momentum to the corona wind to direct the flow in the desired direction. This corona wind could either be a positive or negative ion stream. Apparatus according to the invention would include aerosol source, an ionization electrode for developing the corona wind along a desired path, a reference electrode and a voltage source. 
     In summary, numerous benefits have been described which result from employing the concepts of the invention. The foregoing description of the invention&#39;s preferred embodiment has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Obvious modifications or variations are possible in light of the above teachings. These embodiments were chosen and described to best illustrate the principles of the invention and its practical application, to thereby enable one of ordinary skill in the art to best utilize the invention in various embodiments and with various modifications, as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto.