Abstract:
A flow conditioner for generating and diluting an aerosol with a first inlet adapted to receive a first volume flow of pressurized gas. A second inlet is adapted to receive a second dilution gas volume flow and a third inlet adapted to receive a fluid to be converted into an aerosol. A nozzle is connected to the first and third inlet and has a nozzle orifice for outputting a first aerosol. A first dilution gas flow partitioner has a first set of openings penetrating the first dilution gas flow partitioner and a second dilution gas flow partitioner that is spaced apart from the first dilution gas partitioner and has a second set of openings penetrating the second dilution gas flow partitioner. The nozzle orifice is positioned in the proximity of the second dilution gas flow partitioner.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a Continuation-in-part patent application claiming the benefit of the U.S. non-provisional patent application Ser. No. 11/315,951 that was filed on Dec. 22, 2005, published under the publication no. US-2007-0144514-A1 on Jun. 28, 2007, and issued as U.S. Pat. No. 7,802,569 on Sep. 28, 2010. This prior non-provisional patent application Ser. No. 11/315,951 is herewith incorporated in its entirety by reference. 
    
    
     GOVERNMENT SUPPORT 
     The present invention was made with U.S. Government support from the National Institutes of Health, National Heart, Lung, and Blood Institute, under grant No. HL78281. The U.S. Government has certain rights in this invention. 
    
    
     BACKGROUND OF THE INVENTION 
     The present disclosure relates to a compact portable device for the generation of concentrated respirable dry particles from an aqueous solution or suspension. 
     There is an ever increasing need to deliver large masses of biologics and other agents to the respiratory tract by aerosol. Many devices which generate liquid aerosols may not work well with molecules of high molecular weight or at high concentrations. In addition, some of these devices may degrade the molecules during aerosolization. These limitations, together with the need to reduce the use of fluorocarbons, have lead to the development of dry powder inhalers. In these devices a “blister” or capsule containing the drug is broken and the powdered drug together with the included excipients is dispersed using a vortex caused by inhalation or aerosolized by some other mechanical means such as sonication. Excipients are added to the active agent to aid in the aerosolization of these agglomerates. In some cases, such as Exhubra, they comprise some 70% of the mass of the mixture. The use of excipients results in increased formulation costs, safety pharmacology costs and potential unwanted side effects. These dry powers containing the active agent are most often generated using a spray-drying process. Spray driers have been in common use for many years. Generally they consist of generating an aerosol at the top of a vertical cylindrical tower in which the aerosol spray is diluted with warm gas that may be in the same direction as the spray or in the opposite direction. A cyclone at the output is used to collect the resulting powder. Excipients are added to the collected powders to aid in their dispersion. This mixture is placed in a dry power inhaler, DPI. There are several limitations with this approach: 
     a) The stored resultant dry particles must be stable and preferably resistant to high humidity. 
     b) They must be formulated with excipients such as to be easily dispersed 
     c) The size of the drug particles is generally smaller than that of the excipient particles when the two chemicals are in discrete form. 
     d) The maximum which can be inhaled is limited to the size of the capsule not the volume of the inhalation. 
     e) The spray dry process is likely 60% efficient and the delivery to the lungs by the dry power inhaler 30% efficient resulting in losses of some 80% of the active agent. 
     f) A rapid inhalation results in most of the powder in the capsule being aerosolized but results in high mouth and throat deposition. A slow inhalation can result in higher deep lung deposition but a low efficiency of aerosolization of the powder in the capsule. These issues lead to wide variability in the dose administered leading to both efficacy and safety concerns. 
     These issues can be overcome by a device which generates a liquid aerosol containing the active agent, dries it, concentrates and delivers the residual dry aerosol of the active agent to the lungs in one continuous set of processes such as described in this disclosure. It should be recognized that even the instruments which are of laboratory rather than commercial size are 70 in tall and weigh 50-80 kg. Of note, the spray towers in all these instruments are vertically orientated. A compact clinical device would be best served by a small horizontal drying chamber. 
     Delivery of higher masses to the lungs than can be obtained with solid particles of drug can be achieved with aerosols of the same aerodynamic diameter that have a particle density of less than 1 (Edwards 1996). The formulation of such particles have been the subject of a number of patents, including, U.S. Pat. No. 7,435,408). Large porous particles have been produced by spray drying a mixture of polyester and an active agent such as insulin. These spray dried aerosols have generally been produced by standard spray drying techniques and collected as a powder. To produce particles with a low density, a liquid which has a small molecular weight as compared to a much larger molecular weight additive in the solvent evaporates faster than the diffusion of the large molecular weight component. The resulting particles may be either hollow or have open gas spaces making the geometrical diameter larger than the aerodynamic diameter. These aerosols are generally collected using a cyclone. The powders so produced must later be reaerosolized to be inhaled by the patient. As noted, using such techniques only a small fraction of the original drug is delivered to the lungs. The present disclosure describes how the dilution of a plume of aerosol can be rapidly diluted near to its origin of formation using a heated counter-flow gas jet coaxial in opposite direction to that of the aerosol plume. In addition an annulus of dilution gas transports the aerosol away from the generator along an evaporation chamber to a virtual concentrator. The present disclosure also describes how the evaporation of these aqueous particles in this disturbed plume can be augmented by provision of infrared radiation from a source outside the evaporation chamber. 
     The U.S. non-provisional patent application Ser. No. 11/315,951 filed on Dec. 22, 2005 and published under the publication no. US-2007-0144514-A1 (Yeates et al.), the benefit of which is claimed for the present application, has described a dry power aerosol generator and processing system whereby aqueous solutions of agents are aerosolized, evaporated, concentrated and delivered as a dry power aerosol comprised entirely of the dissolved solute. In the present disclosure are described details of improvements to that system and the subsequent novel findings regarding the generation of pure protein respirable aerosols with a density less than one in a compact device. This device eliminates the need for spray-drying, collection with a cyclone, mixing with excipients and placing in a dry powder inhaler. The improvements to that system are detailed within, The marked reduction of internal gas flow resistance has enabled the use of a blower that is only 2×2×1 inch, thus increasing the portability of the device. Easy to assembly friction fit designs eliminated the use of large O-ring seals on the evaporation chamber making it much easier to assemble by a sick patient. Light weight heaters with resistance to flow as well as a low thermal inertia were developed to allow functionality within a minute of turning on and increase the portability. The counter-flow tube was centered within the concentrator to ensure easy assembly and accurate alignment with the axis of the aerosol jet thus increasing the reliability of its performance. An additional heating element for the warming of the gas for the nozzle and the counter-flow has been included enabling more rapid evaporation of the aerosol plume. Focusing reflectors have been included on the infrared heat source to lower the power needed for the infrared heater. This and the above modifications reduce the overall power used by the device. These and other functional and practical improvements have been disclosed herein. In concert they make the device more portable, more functional, easier and more cost effective to manufacture and provide new possibilities for the generation of novel particles for immediate inhalation that was not previously possible. 
     Virtual impaction has been used as a means to concentrate aerosols (U.S. Pat. No. 4,767,524, Pillai and Yeates, 1994). There have been several modifications of these designs, including the use of slit orifices in place of round orifices (Marple and Robow 1986), Yeates&#39; patent application 200701445 uses this information to design a concentrator with radial slits for a cut-off diameter of 2.5 micron. The present disclosure shows how to concentrate the major mass of particles within the respiratory range. This range is typically 1-5 micron but may cover the range of 0.5-10 micron. According to Marple and Robow, to capture particles above 1 micron a 1 mm orifice slit is required compared to a 2.6 mm slit to concentrate particles above 2.5 micrometers. This potentially increases the pressure head required to accelerate the aerosol through the slits. To reduce the pressure head upstream of the concentrator, parabolic entrances to the orifices were incorporated into the design. It is notable that Seshadri, AAAR 2006, teaches the use of a parabolic entry profile together with a sheath gas flow to reduce wall losses and potentially enhance the concentration factor. As noted, in this present disclosure they are incorporated to reduce the upstream pressure required to operate the concentrator. Shekarrizz, U.S. Pat. No. 7,178,380 describes a concentrator with concave and convex accelerator walls together with a side injector port they claim reduces clogging. That concentrator utilizes input flow rates of 15 liters/minute, just a small fraction of the flow rates in the present device which are typically between 100 and 300 liters per minute but higher and lower flow rates are possible in this disclosed device. The present device does not have, nor does it require, the proposed injector ports to prevent clogging. Alternatively, U.S. Pat. Nos. 7,261,007 and 5,858,043 describe concentric slits to reduce end effects. When concentric slits are used it is much more difficult to exhaust the gas than using the present compact design. 
     A first object of the present disclosure is to provide the means, in a small practical device, to generate an aqueous (or other solvent with a high vapor pressure) aerosol and by dilution and heating, rapidly evaporate aqueous aerosols and thereafter to concentrate the resultant particles and deliver them at flow rates compatible with the full range of normal inspiratory flows. 
     A second object of the present disclosure is to eliminate high pressure couplings so the device can be easily assembled and disassembled for cleaning. 
     A third object of the invention is to lower the resistance to gas flow through the device to enable the construction of a small device using a small blower to provide the dilution gas. 
     A fourth object of the present disclosure is to minimize leakage of gas and/or aerosol between the various components of the device while maintaining structure integrity junction between each of the components. 
     A fifth object of the present disclosure is to facilitate the provision of a counter-flow gas that is precisely coaxial with the aerosol plume and of opposite direction to the aerosol plume. 
     A sixth object of the present disclosure is to provide heated compressed gas to both the nozzle and the counter-flow tube while minimizing heat losses. 
     A seventh object of the present disclosure is to provide, from a source outside the evaporation chamber, localized radiant heat to the newly formed aqueous aerosol particles at the wavelength of the maximum infrared absorption for water. 
     An eighth object of the present disclosure is to allow the device to be used with different easily interchangeable nozzle-holder configurations that enable compressed gas either to be delivered through a central orifice or surround a central fluid stream. 
     A ninth object of the present disclosure is to have these nozzle-holders keyed for use in the flow conditioner and to have the ability to include a compressible fluid reservoir in place of a fluid inlet. 
     A tenth object of the present disclosure is, in a compact device, to provide for a high velocity gas stream to be heated while it flows in one direction and then provide a uniform lower velocity flow in the opposite direction while allowing for the perturbations caused by an aerosol plume and counter-flow gas. 
     An eleventh object of the present disclosure is to efficiently concentrate a respirable aerosol larger than 0.5 micron with minimal pressure drop between the input and the exhaust gas. 
     A twelfth object of the present disclosure is to facilitate easy assembly and disassembly while maintaining axial and rotational high precision alignment. 
     A thirteenth object of the present disclosure is to prevent any aerosol particles in the concentrator exhaust gas stream from contaminating the atmosphere. 
     A fourteenth object of the present disclosure is to minimize any aerosol deposition due to turbulence at the output of the concentrator. 
     A fifteenth object of the present disclosure is to provide an efficient means of delivering the concentrated aerosol at the output by means of the parabolic shaped nature of the output cone. 
     A sixteenth object of the present disclosure is to provide a concentrated aerosol at a small positive pressure to provide a pressure-assist for patients who have trouble generating sufficient inspiratory pressure and flow to trigger some other dry powder inhalers. 
     SUMMARY OF THE INVENTION 
     These and other objects are achieved according to the present invention by a flow conditioner for generating and diluting an aerosol comprising a first inlet adapted to receive a first volume flow of pressurized gas; a second inlet adapted to receive a second volume flow of dilution gas; a third inlet adapted to receive a fluid to be converted into an aerosol; a nozzle connected to the first and third inlet and having a nozzle orifice for outputting a first aerosol; a first dilution gas flow partitioner comprising a first set of openings penetrating the first flow partitioner; and a second dilution gas flow partitioner that is spaced apart from the first dilution gas partitioner and comprises a second set of openings penetrating the second flow partitioner; wherein the nozzle orifice is positioned in the proximity of the second dilution gas flow partitioner. 
     DETAILED DESCRIPTION OF THE INVENTION 
     According to a preferred embodiment of the invention the nozzle is an integral part of a removable nozzle holder that is removably attached to the flow conditioner. This allows replacing the unit comprising the nozzle and nozzle holder for each delivery session to a patient avoiding any contamination issues or delivery of unintended residues of medication. 
     According to another preferred embodiment of the invention the removal nozzle holder with the integral nozzle is a disposable part that is held in the flow conditioner in a centering receptacle comprising a length to width ratio larger than 1. This has the advantage of allowing to center the nozzle exactly as intended and therefore deploy a symmetrical plume of aerosol. In addition, it allows to control that only specific nozzles are inserted into a specific receptacle and therefore avoids using the wrong nozzle. This may particularly be important if the medication is prepackaged into a reservoir that is connected to a disposable nozzle plus nozzle holder as a disposable joint part. However, also other centering designs are possible, either having a longer or shorter length to with ratio than one, or in any other the alternative centering designs that allow a precise orientation of the nozzle. 
     According to another preferred embodiment of the invention the receptacle is an elongated cylindrical hole that extends beyond the first flow partitioner and the nozzle holder is a cylindrical part having an outer cylindrical surface and is inserted snugly into the elongated cylindrical hole that contains ring-shaped grooves accommodating O-rings that are in sealing contact with the outer cylindrical surface the nozzle holder. Preferably, the at least two spaced apart O-rings and a circumferential groove are provided in the elongated cylindrical hole between the two O-rings, wherein at least part of the first volume flow of pressurized gas is introduced via the groove into openings in the nozzle holder that are connected to a nozzle holder pressurized gas channel feeding the nozzle with pressurized gas for forming the first aerosol. Such a design has the advantage that the gas, for instance air, can be supplied in a radial direction, and leaves more space for inserting and removing the nozzle holder in axial direction without any obstruction by a gas supply. Further, it allows unobstructed access in axial direction for connecting it to a fluid supply or inserting an integrated device containing the nozzle, nozzle holder and a fluid reservoir. However, in the alternative, also other designs are possible, for instance an axial or oblique gas supply. 
     According to another preferred embodiment of the invention a first flow divider that is connected to the first inlet divides the first volume flow of pressurized gas into a first partial volume flow that is fed into the removable nozzle holder, and a second partial volume flow that is diverted into a counter-flow tube having a counter-flow tube exit port that is substantially coaxial to the nozzle holder with its integrated nozzle and points into the opposite direction of the nozzle for creating a counter-flow. And advantage of this design is that the initial aerosol formed by the first partial volume flow is arrested by the second partial volume flow. Preferably, before dividing the first volume flow into the first partial and second partial volume flows the first volume flow can be pre-heated. This reduces the number of heaters. However, also other designs are possible, i.e. completely separate sources connected to the nozzle and to the counter-flow tube allowing to heat either one of them, both or none of the volume flows. 
     According to another preferred embodiment of the invention a second flow divider is provided in a space between the first dilution gas flow partitioner and the second dilution gas flow partitioner for dividing the second volume flow of dilution gas into a first partial dilution gas volume flow that is guided to a central area of the second dilution gas flow partitioner where it penetrates the second dilution gas flow partitioner, while the remaining second partial dilution gas volume flow passes the space between the first dilution gas flow partitioner and the second dilution gas flow partitioner where it penetrates the second dilution gas flow partitioner closer to a peripheral area thereof. This design has the advantage of providing a good mixing action of the initially created and then optionally arrested aerosol with the dilution air. The flow in the more peripheral areas achieves that the arrested aerosol plume is not only mixed such that the desired flow profile is created, but also provides more control about this flow profile. This is in particularly desirable for avoiding any depositions of aerosol either on the flow conditioner or on the walls of evaporation chamber. However, also other designs are possible that do not divide the dilution air flow into two partial dilution air flows in the center and in the peripheral area. Several different parameters such as for instance the flow speed and the amount of liquid that has to be aerosolized per minute may determine whether a division into a center and peripheral flow is useful. 
     According to another preferred embodiment of the invention the central area of the second dilution gas flow partitioner comprises a concave shape that is depressed on that side of the second dilution gas flow partitioner where the second partial volume flow of dilution gas exits the second flow partitioner. This design has turned out to be beneficial in avoiding depositions of aerosol on the second dilution gas flow partitioner. However, depending on the parameters, also alternative designs like a plane or even convex shape of the front face of the second dilution gas flow partitioner are possible. 
     According to another preferred embodiment of the invention an outer periphery of the central area of the second dilution gas flow partitioner comprises a rim that protrudes beyond the peripheral area of the second flow partitioner and facilitates easy positioning and removal of the flow partitioner during assembly and disassembly. Preferably, the rim comprises a cylindrical surface with a circular gripping groove. Such a design can particularly be readily accomplished with the aforementioned concave shape allowing the rim of the center portion of the second dilution gas flow partitioner to be elevated over the peripheral portion of the second dilution gas flow partitioner. In the alternative, also other designs for installing and removing the second flow partitioner are possible, for instance discrete protrusions which are spaced apart from each other. 
     According to another preferred embodiment of the invention the second flow divider is ring-shaped and extends through the space between the first dilution gas flow partitioner and the second dilution gas flow partitioner and comprises radial openings through which the first partial dilution gas volume flow penetrates towards the central area of the second dilution gas flow partitioner. Preferably, the first and second dilution gas flow partitioners and the second flow divider form one of a pre-assembled assembly group and an integral component part. This allows a structurally robust design wherein the ring-shaped divider can have the function of a spacer between the first and second flow partitioners or the entire group comprising the first flow partitioner, second flow partitioner and the ring-shaped divider can be integrally formed as one single component part. The cumulative size of the holes provided in the divider determines how much partial dilution air flow is diverted towards the center. In the alternative, also other designs are possible, for example spaced apart columns between the first and second flow partitioner, or any other form or shape of channels that may divide the desired amount of flow towards the center of the second to flow partitioner. 
     According to another preferred embodiment of the invention an outer periphery of the first dilution gas flow partitioner is formed by merlons that are circumferentially spaced by slots through which the second volume flow of dilution gas penetrates the first dilution gas flow partitioner and enters into the space between the first and second dilution gas flow partitioners. Preferably, the first dilution gas flow partitioner is inserted into a cylindrical housing comprising an inner cylindrical wall and the merlons are fit snugly into the housing such that these are closely adjacent or in contact with the inner wall so that a plurality of openings are defined along the circumference of the second flow partitioner by the slots, the merlons and the cylindrical wall. The space between the first and second dilution gas flow partitioners may function as a pressure equalization chamber. In addition, the spaced apart slots equalize the flow. However, also alternative designs are possible, for instance instead of merlons and grooves discrete holes spaced apart along the circumference of the first dilution gas flow partitioner. 
     According to another preferred embodiment of the invention the counter-flow tube comprises a substantially straight inlet end that extends substantially parallel to the nozzle holder and penetrates the first and second flow partitioners and terminates in an outer end that comprises a 180 degree bend leading to the counter-flow tube exit port. Preferably, the substantially straight inlet end may comprise a positioning plate that can be inserted into a positioning slot. With these measures, it can be guaranteed that the exit port is exactly aligned with the nozzle so that a symmetrical plume of aerosol is formed around the nozzle. 
     According to another preferred embodiment of the invention the at least one of the first inlet port and the second inlet port are connected to at least one of respective pressurized gas and dilution gas heating chambers comprising a respective pressurized gas and dilution gas heater for pre-heating at least one of the first volume flow of pressurized gas and second volume flow of dilution gas. Heating of the various flows can therefore be controlled independently as a desired. However, depending on various parameters such as the amount of liquid to be evaporated per minute, the gas used for evaporation, and the liquid that has to be evaporated, it would be also possible to achieve full in evaporation or evaporation to the desired extent without preheating any of the gas volume flows. 
     According to another preferred embodiment of the invention the dilution gas heaters are elongated infrared bulbs with tapered ends and the respective heating chamber is a tube comprising a respective inner tube wall, and the second volume flow of dilution gas are guided through a gap between the respective infrared bulb and inner tube wall and the flow resistance of this second flow of dilution gas is in the order of 13 mm of water at a flow of 200 liters per minute. This has proven to be a particularly effective heater while providing at the same time a low flow resistance. However, also other forms of heating are possible, for instance electrical heating by convection by surrounding the gas supply tube with an electric resistance heating coil. 
     According to another preferred embodiment of the invention a blower is provided upstream of the dilution gas heating chamber that is connected to the second inlet port for feeding the second volume flow of dilution gas through the heating chamber and into the second inlet port. Such blowers can provide a high volume flow of dilution air. However, also alternative gas sources such as compressors or gas bottles are possible. 
     According to another preferred embodiment of the invention the second volume flow of dilution gas is between 100 and 200 liters per minute and the pressure drop across the flow conditioner from the second inlet is in the order of 2 inches of water at 200 liters per minute. This low pressure drop allows to substitute high-power compressors by a simple blower comprising only a very small fraction of the size and power consumption of a compressor. 
     Herein, this disclosure describes how a relatively high volume (up to 300 liters/minute) of low pressure aerosol is concentrated. The slits are arranged radially such that the exhaust gas is passively expelled radially between the slits. Such a design has many advantages: 
     a) The dilution gas is provided by a small (2 inch×2 inch×1 inch) gas blower or fan. 
     b) The device does not require tight high pressure seals thus enabling easy assembly and disassembly for cleaning and maintenance. 
     c) The exhaust gas requires no negative pressure source and is thus vented at atmospheric pressure. 
     d) The local counter-flow jet is structurally stable with precise reproducible coaxial alignment. 
     e) The localized heated jet and counter-flow gas together with the localized infrared radiation provide rapid drying of the aerosol leading to decreased wall losses and increased efficiency as well as enhancing the ability of the device to create particles with a density lower density than 1 gm/cc. 
     Devices which generate aerosols from liquids with refillable reservoirs have issues regarding the maintenance of their cleanliness. Devices which are used for multiple inhalations may have unpredictable or reduced output as the nozzle or orifices become clogged. This is especially a critical issue when large molecules such as proteins, surface active agents as well and other larger molecules are to be aerosolized. These issues are resolved in the present disclosure through the inclusion of replaceable or disposable cartridges with integrated single-pass nozzles. 
     In the aerosol generator of the present invention, for the purpose of describing the aerosol generator, the following assembly groups can be identified: the nozzle and nozzle-holder with its receptacle, the flow conditioner with its flow partitioners, the counter-flow tube and the evaporation chamber, the virtual impactor the eddy relaxation chamber and the aerosol delivery cone. These assembly groups interact with each other forming a portable compact device for the generation of concentrated dry aerosols from an aqueous (or high vapor pressure solvent) solution or suspension of the substance with the resultant aerosol being a dry concentrated aerosol comprised of the original solute or suspended material. Specifically, it relates to the methodology which demonstrates that this can be achieved in a practical compact portable device. Moreover, this device which enables extremely rapid evaporation of the solvent in close proximity to the base of the aerosol plume facilitates the generation of protein particles with a density of less than one. 
     An overriding design constraint throughout every aspect of the invention was to make the device fully operational using a dilution gas marginally above atmospheric pressure. This has two compelling advantages for a portable concentrated aerosol delivery system for patient use. Firstly, only a very small fan or blower with a limited pressure head is incorporated for size, weight and noise considerations. Secondly, the use of low pressure fittings enables easy assembly and disassembly for cleaning and maintenance. 
     Another design criterion was to provide heated compressed gas to a nozzle and a counter-flow jet so as to effect as rapid evaporation of the solvent as possible. Another design criterion was to incorporate interchangeable removable nozzle-holder and nozzles. This increases the commercial flexibility and functionality of the device. This flow conditioner is compact and has a very low resistance to gas flow. 
     The features of this device include a) a compact two stage flow conditioner with an integral receptacle to accept exchangeable nozzle holders, b) a counter-flow compressed gas divider and counter-flow tube. c) gas heaters with low gas flow resistance and thermal inertia, d) proximal infrared radiation, e) Low resistance, high efficiency aerosol concentrator for particles&gt;0.5 micron, f) a low resistance extracted gas filtering capability, and g) an aerodynamically designed collection “cone” to collect the concentrated output aerosol. An instrument version of this device can be used to tailor the parameters of the aerosol drying process to the specific solute (suspension)/solvent solution to be delivered as a respirable aerosol. The invention can be used to deliver drugs without the need for the use of excipients that are most always required for re-aerosolization of the powdered drug. Biotherapeutics including proteins can be delivered directly to the patient. The particles so produced may have a particle density of less than one or a tap density less than 0.04. 
     Compressed gas is provided via a quick disconnect to a pressure regulator. The compressed gas from this regulator is passed though a heater and then to a port on the manifold of a flow-conditioner. Within the manifold the flow is redirected to two paths, a. to a nozzle-holder and thus to an aerosol generating nozzle and b. to a counter-flow tube whose exit port is aligned along the same axis as the nozzle. A source of low pressure gas at much high flows (100 to 300 liters per minute) is provided by a small blower. (Alternatively a compressed gas source could be used.) This gas is passed though a heater and then it enters through a port on the manifold of the two stage flow-conditioner. This flow-conditioner ensures a uniform flow in an adjoined Pyrex or quartz cylindrical evaporation chamber. The gas from the two stage flow-conditioner enters this evaporation chamber. Infrared radiation from an infrared lamp and reflector adjacent to this evaporation chamber is transmitted through the chamber and reflected by a second focusing reflector on the opposite side of the chamber. This evaporation chamber is connected to a virtual impactor aerosol concentrator. The gas enters through acceleration slit nozzles in an acceleration nozzle plate. A minor fraction of this gas which contains most of the particles exits the concentrator through collection deceleration nozzles in a virtual impaction plate. These deceleration nozzles are precisely aligned with the acceleration nozzles. The resulting aerosol from the deceleration nozzles loses much of its kinetic energy in the form of eddies in the relaxation chamber connected to the exit of the concentrator. From there, the aerosol flows through a tapered aerosol collection cone at the end of which the aerosol exits. The major fraction of the gas flow exits from the gaps between the acceleration nozzles and the deceleration nozzles in the acceleration nozzle plate and the deceleration nozzle plate, respectively. This exhaust gas then flows within a plenum to an optional filter to remove any remaining suspended particles in this exhaust gas. 
     Alternatively, for use where ample supplies of compressed gas are available, a quick disconnect for compressed gas is connected via a tee fitting to two pressure regulators, one for high pressure gas and the other for low pressure gas. The high pressure regulator is connected via a gas heater to the manifold of the two stage flow conditioner as described above. This compressed gas is redirected to two paths as noted above. The low pressure regulator is connected to a dilution gas heater and then to the flow-conditioner as noted above. 
     The compressed gas provides the energy for the aerosolization nozzle as well as for the counter-flow gas. The counter-flow gas flows coaxially and in the opposite direction to an aerosol plume formed by the nozzle such that the counter-flow gas arrests and dilutes the plume. The high pressure gas is heated, according to the desired use, up to 150° C. This temperature is regulated using the thermocouple in the compressed gas stream upstream from the heater using an associated PID controller. This heated compressed gas is delivered to the flow-conditioner manifold via a quick disconnect. This flow is divided within the flow conditioning manifold. One flow goes through a small orifice and on to the counter-flow tube. The diameter of the small orifice determines the gas flow in the counter-flow tube. This flow is typically similar to or a little higher than the gas flow through the nozzle. The other gas flow goes to an annulus surrounding a cylindrical receptacle in the flow conditioner. Ports in a nozzle holder are aligned with this annulus and thus gas flows though the input ports of the nozzle holder though two conducting channels to a small pressure equalization chamber and to then to a nozzle. The fluid is delivered to the nozzle through a central channel. An external pump provides fluid flow rate between 0.1 and 5 ml/minute depending on the application. The aerosol is created by the interaction of the compressed gas with the fluid. The aerosol plume so created is arrested by a jet of gas from the counter-flow tube. The warm dilution gas from the flow-conditioner both enhances the evaporation of the liquid and transports the particles though the evaporation chamber towards the aerosol concentrator. Infrared radiation supplied by the infrared lamp and the corresponding reflector on the opposite side of the chamber augments the evaporation of the liquid from the particles. The particles are then concentrated as they pass through the virtual impactor and delivered via the output cone to the output. The output flow has a small positive pressure and is regulated by the apparatus or person connected to the output. 
     Alternatively, when ample supplies of high pressure as are available, the compressed gas enters the external quick-disconnect fitting and is split into two streams using the tee fitting. One goes to the high pressure regulator and the other to the low pressure regulator. Regulators rather than valves are used to control the gas flows and pressures downstream to these two regulators. This design enables excellent control of these rather diverse flows and pressures while minimizing any changes in these flows and pressures due to fluctuations in the upstream compressed gas pressure or adjustments made with the other regulator. In this preferred embodiment, the upstream pressures are generally between 30 and 100 psi. This does not exclude using higher or lower pressures. The low pressure regulator controls the downstream flow from 100 to 300 liters per minute. 
     To achieve optimal performance, the dilution gas as well as the compressed gas delivered to the nozzle and the counter-flow tube should be both dry and heated. As this device is planned for the respiratory delivery of pharmacologically active aerosols, it should be ready to use within one minute of turning it on. Thus, the temperature of the heated gas must rise to the operating temperature within one minute. This requires heaters with low thermal inertia and which exhibit a high transfer of energy from the heater to the gas flowing through it. Especially in the case of the dilution gas, this heater must offer minimal resistance to gas flow. This facilitates the use of a small gas blower. A heater with low gas flow resistance minimizes the size and pressure-head of the gas mover required. 
     In this disclosure radial slits with large length/width ratios are described to minimize end effects and provide a clear path for the exhaust gas to exit. The use of multiple slit lengths achieves two objectives, a) to maximize the total cumulative length of the slits to minimize the pressure drop across the concentrator and b) to achieve relatively uniform flow at the exit of the evaporation chamber as well as concentrically relatively uniform across the concentrator. 
     These and other advantages of one or more aspects of the invention will become apparent from the consideration of the ensuing description and accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a perspective view of the components for generating dry warm dilution gas and delivering it to the flow conditioner as well as the components for the heating and delivery of hot gas to the nozzle-holder and the counter-flow tube. 
         FIG. 2A  shows a perspective view of a first embodiment of a nozzle-holder. 
         FIG. 2B  shows a longitudinal section of the nozzle-holder shown in  FIG. 2A . 
         FIG. 2C  shows a side view of the nozzle holder shown in  FIG. 2A . 
         FIG. 2D  shows a longitudinal section of a second embodiment of a nozzle holder where the knob on the nozzle holder illustrated in  FIGS. 2A ,  2 B and  2 C is replaced with a cartridge containing the liquid to be aerosolized. 
         FIG. 3A  shows an exploded perspective view of a nozzle body and annulus which fits over the stem protruding from the nozzle body. 
         FIG. 3B  shows a partial longitudinal section denoted T in  FIG. 3D  of the nozzle within a neck section of the barrel of the nozzle holder. 
         FIG. 3C  shows a longitudinal section denoted R-R in  FIG. 3E  of the nozzle holder. 
         FIG. 3D  shows a longitudinal section of the nozzle holder at a 90 degree rotation compared to  FIG. 3C  and in line with the side view illustrated in  FIG. 3F  where this longitudinal section is denoted P-P. 
         FIG. 3E  shows a front end view of the nozzle and barrel and illustrates the section R-R shown in  FIG. 3C . 
         FIG. 3F  shows a side view of the nozzle holder illustrating the section P-P shown in  FIG. 3D . 
         FIG. 4A  shows an exploded perspective view of a flow conditioner manifold and a nozzle holder and the relationship between this nozzle holder and its insertion into the manifold of the flow-conditioner. 
         FIG. 4B  shows a front view of a flow conditioner and illustrates the section shown in  FIG. 4C . 
         FIG. 4C  shows an exploded longitudinal section denoted Y-Y in  FIG. 4B  of the flow conditioner as illustrated in  FIG. 4B  as well as the section of the nozzle holder at the opening of a receptacle to which it is inserted. 
         FIG. 5A  shows a longitudinal section of the flow conditioning manifold and flow partitioners as indicated as section H-H in  FIG. 5B  as well as the relationship between the flow conditioning manifold and walls of the evaporation chamber. The compressed gas flow path to the nozzle holder and counter-flow tube is indicated. 
         FIG. 5B  shows a front view of the flow conditioner shown in  FIG. 5A  and illustrates the section of the flow conditioner shown in  FIG. 5A . 
         FIG. 5C  shows an exploded perspective view of the flow conditioner. It shows the details of the flow conditioner and the counter-flow tube. 
         FIG. 5D  shows a cross longitudinal section denoted F-F in  FIG. 5E  of the flow conditioner together with the evaporation chamber and the acceleration plate of a virtual impactor aerosol concentrator and the interrelationships between these components of the device. 
         FIG. 5E  shows a sectional view of the concentrator illustrating the longitudinal sectional views of the flow conditioner, evaporation chamber and acceleration plate of the concentrator shown in  FIGS. 5D and 5F . 
         FIG. 5F  shows a longitudinal section denoted J-J in  FIG. 5E  of the flow conditioner, evaporation chamber and acceleration plate of the concentrator as indicated in  FIG. 5E . The relationship of the input dilution gas port to the first pressure equalization chamber of the flow conditioner is also shown. 
         FIG. 6A  shows a longitudinal section denoted J-J in  FIG. 6B  of the flow conditioner, evaporation chamber, concentration, output cone, infrared lamp and the reflectors as depicted in  FIG. 6B  showing the interrelationships between each of these components. 
         FIG. 6B  shows a rear view of the flow conditioner, evaporation chamber, concentration, output cone, infrared lamp and the reflectors as shown in  FIG. 6A . 
         FIG. 6C  shows a perspective bottom view of the components enumerated in  FIG. 6A  illustrating their positions in relation to each other. 
         FIG. 6D  shows a perspective top view of the components enumerated in  FIG. 6A  illustrating their positions in relation to each other. 
         FIG. 7A  show a perspective view of the output side of the acceleration plate illustrating the differences in nozzle length and sculptured design as well as a centrally located female indented cross for precise alignment of this acceleration plate with a raised cross on the deceleration plate. 
         FIG. 7B  shows a perspective view of the input side of the deceleration plate showing the respective differences in deceleration nozzle lengths and sculptured design as well as the male raised cross for precise alignment of the deceleration plate with the acceleration plate. A cowling surrounding the deceleration plate is also shown. 
         FIG. 7C  shows a longitudinal section denoted as section K-K in  FIG. 7D  of the evaporation chamber, concentrator and aerosol output cone as indicated in  FIG. 7D  showing the interrelationships of these components. 
         FIG. 7D  shows a side view of the section of the evaporation chamber, concentrator and output cone illustrated in  FIG. 7C . 
         FIG. 7E  shows a sectional rear view of the evaporation chamber, concentrator and output cone illustrated in  FIG. 7F . It also illustrates the sculptured exhaust gas cone and port. 
         FIG. 7F  shows a longitudinal section denoted H-H in  FIG. 7E  of the evaporation chamber, concentrator and output cone. 
     
    
    
     DETAILED DESCRIPTION OF THE DRAWINGS 
     Referring to  FIG. 1 , for the purpose of describing the aerosol generator, the following assembly groups can be identified: a) the dilution gas drying chamber, blower and heater, b) the compressed gas heater c) the flow conditioner manifold and d) the counter-flow tube. 
     Input Gas Conditioning 
     Low pressure gas to dilute and evaporate the liquid aerosol travels through the flowing components. A gas dryer  1002  contains a desiccant  1003  such as, but not limited to, aluminum oxide pellets. This chamber  1002  is connected a gas filter  1021  and a fitting  1022  to a miniature blower  1001  or equivalent gas mover. The blower is connected via a flow measurement device  1023  to a dilution flow heater  1004 . The flow measurement device may be a pneumotac, hot wire anemometer, mass flow meter or other low resistance device. The heater  1004  is comprised of a heat tolerant cylinder (1.0 inch OD 0.75 inch ID)  1005 . In a preferred configuration, this cylinder is made of ceramic. Centrally located within the tube is a rapidly heating infrared bulb  1006 . In a preferred configuration this rapidly responding infrared bulb  1006 , has tapered ends to reduce gas flow resistance. This ceramic heating tube  1005  fits snugly in a fitting  1007  which has a right angled lumen. The other opening of fitting  1007  has a tapered receptacle (not shown). This enables easy placement a similarly tapered male fitting (not shown) on a flow conditioner manifold  1020 . In a preferred configuration, the tapers on this port and receptacle are standard 22 mm respiratory tapers. There is an iron-constantan thermocouple (not shown) placed in the gas stream within the lumen of the right angle channel of the fitting  1007 . This thermocouple is connected to a temperature regulating device  1008 . In a preferred embodiment, the temperature regulating device is a PID controller which regulates the power supplied to the infrared bulb  1006 . 
     High pressure gas to both generate an aerosol of the fluid in a cartridge  1101  with a nozzle  1024  and provide a co-axial counter-flow though counter-flow tube  1102  to arrest the aerosol plume comprises of the following components. The compressed gas enters a fitting  1019  and is warmed in heater  1011 . In a preferred configuration, this heater comprises of a 0.75 inch OD 0.56 inch ID ceramic tube  1009  in which is placed an infrared bulb  1010 . An iron-constantan thermocouple is located in the exit gas stream (not shown) on the female piece of a quick disconnect  1032  or other convenient location downstream from the heater  1011 . This thermocouple is connected to a temperature regulating device such as a PID controller  1012 . This quick disconnect is connected via a Teflon tube  1031  to a right angle fitting  1013 . For illustration purposes a tube  1060  has been inserted to demonstrate the connectivity of the compressed gas flow to the inlet  4028  (see  FIG. 4C ) of the flow conditioner manifold  1020 . Other configurations which achieve the desired functions are possible. 
     Input Gas Conditioning 
     Up to 300 liters of dilution gas is provided by the miniature blower  1001  or equivalent gas mover. When the relative humidity of the room gas is higher than desirable for the aerosolized volume of fluid to be dried, this dilution gas may be passed though the gas drying chamber  1002  containing the desiccant  1003 . This dry gas passes through the filter  1021  to protect the blower from wear (due to any desiccant dust) via the fitting  1022  to the blower  1001 . This dry gas is propelled by the blower  1001  through the flow meter or flow measuring device  1023  to the dilution flow heater  1004 . The gas is heated in heater  1004  as it passes between the infrared bulb  1006  and the inside wall of the heat tolerant cylinder  1005  in the form of a ceramic tube. The temperature of the gas exiting the tube is measured with the iron-constantan thermocouple (not shown) placed directly in the gas-flow and the gas is maintained at the desired temperature, typically 35-45° C. using the temperature regulating device  1008  such as a PID controller which regulates the power supplied to the heater bulb  1006 . 
     Similarly, the compressed gas, used for the nozzle and counter-flow gas is passed through the heater  1011 . The gas is heated as it passes between the infrared heater  1010  and the walls of the ceramic tube  1009 . The temperature of the gas exiting the tube is measured with the iron-constantan thermocouple (not shown) and maintained at the desired temperature typically 100-140° C. using the second PID controller  1012 . This PID controller regulates the power in the infrared bulb  1010 . 
     In another preferred configuration of this invention, compressed gas can be used as the source of dilution gas. In this case a pressure regulator would replace the dilution gas blower  1001 . Compressed gas, or other gas, generally has had most, if not all, of its moisture removed. In this case an input high pressure fitting is connected via a high pressure tube and T piece to two gas pressure regulators (not shown). One regulator controls the gas flow to the compressed gas heater  1011  and the other controls the gas flow via the flow measuring device  1023  now placed between the regulator and the dilution flow heater  1004 . 
     Replaceable Nozzle Holder and Nozzle 
     A schematic figure showing the features of a preferred configuration of a nozzle-holder is shown in  FIG. 2A  to  FIG. 2C . The nozzle holder is comprised of an aerosol generating nozzle  1024  mounted with in a fitting  2112  on a neck  2003  at the end of a barrel  2001 . A narrowing from the barrel to the neck  2003  enables gas to streamline along the neck adjacent to the nozzle. This minimizes any deposition of particles on the face of the nozzle through eddy currents that would be induced by a large flat surface near the nozzle. The nozzle  1024  in  FIG. 2B  is contiguous with a small pressure equalization chamber  2105  which in turn is connected to two channels which terminate at one or more ports  2008 . A tube  2104  in close proximity to the nozzle and coaxial with the nozzle orifice is connected to another channel  2103  and  2107  to a connector  2005 . At the other end of the barrel is a knob  2006  with several circumferential grooves to permit easy insertion and withdrawal of the nozzle holder into a receptacle (see  4030   FIG. 4A  and  FIG. 4C ) within the flow conditioner manifold  1020 . The connector  2005  at the opposite end to the nozzle enables the attachment a fluid line (not shown). In a preferred configuration this is a Luer connector. Ports  2008  in the barrel  2001  interface with compressed gas supply groove (see  2071   FIG. 4C ) in the flow-conditioning manifold  1020 . According to the invention, these nozzle holders must be inserted into the flow conditioner. This feature essentially eliminates the indiscriminant use of this nozzle holder by a patient. This protects the patient and helps ensure the proper delivery of the contents of the cartridge. In one preferred nozzle-holder configuration  FIGS. 2A ,  2 B,  2 C and  2 D the nozzle  1024  requires both high pressure gas and high pressure fluid to generate a satisfactory aerosol. The fluid port  2005  is connected via a channel  2007  to the channel  2103  and to a tube  2104 . In a preferred configuration, this tube  2104  has and internal diameter of 0.03 inches and is has a port  2110  that is positioned one to 1-2 diameters from a 0.014 in diameter orifice in the nozzle  1024 . These dimensions are not provided to exclude other diameters and distances but rather as working examples. The nozzle  1024  is contained within in the fitting  2112  to ensure that the orifice and the tube  2104  are precisely coaxial. This design is provided as an example. Similar configurations can be achieved with other designs. The compressed gas intake ports  2008  are on the side of the barrel  2001  of the nozzle holder. The ports  2008  are connected to one or more channels  2101  to the pressure distribution chamber  2105 . This chamber  2105  extends into the nozzle body to facilitate even gas flow around the tube  2104  to the orifice in the nozzle. A liquid aerosol plume  2106  is formed at the exit of the nozzle  1024 . The knob,  2006  acts as a stop to limit the distance that the barrel  2001  is inserted into the receptacle  4030   FIG. 4A  and  FIG. 4C  in the flow conditioner manifold  1020 . The circumferential grooves on knob  2006  facilitate easy insertion of the nozzle holder into the barrel of the flow conditioner and well as its removal from the flow conditioner. 
     In this configuration of the nozzle-holder, fluid is supplied by an external pump (not shown) through the port  2005  on the nozzle holder. The fluid stream flows through the channel  2007  and through the center channel  2103  along the center of the nozzle barrel  2001 . The tube  2104  transports this fluid to its port  2110 . Compressed gas enters through the ports  2008  on either side of the barrel  2001 . This compressed gas enters channel(s)  2101  on either side of the central channel  2103 . These outer channels transport the compressed gas to the pressure equalization chamber  2105 . The compressed gas in the chamber  2105  flows around the tube  2104  causing the fluid to flow through the center of the orifice of the nozzle  1024  without the fluid coming in contact with the orifice. The aerosol is created by focusing the flow of this fluid through this nozzle  1024 . At the down-stream side of the orifice, the liquid aerosol plume  2106  is formed. 
     In another preferred configuration  FIG. 2D , a cylindrical cartridge  2020  is incorporated into the nozzle holder in place of the knob  2006  and connector  2005  shown in  FIGS. 2A ,  2 B and  2 C. The fluid to be aerosolized is contained within a chamber  2021  in this cartridge  2020 . The chamber  2021  of this cartridge has a piston  2022  which can be translated down the inside of chamber. This chamber is connected to the channel  2103 . This piston  2202  can be depressed with a plunger  2023  attached so it can be used multiple times or it can be depressed using a rod that is not attached to the piston such that it can be a single use nozzle system. The plunger or rod can be depressed with a servomotor or other means. Several circumferential grooves around the cartridge  2020  facilitate the easy insertion into, and removal of this cartridge-nozzle holder from the receptacle  4030  (see  FIG. 4A  and  FIG. 4C ) of the flow conditioner  1020 . 
     Alternative Nozzle-Holder and Nozzle 
       FIGS. 3A ,  3 B,  3 C,  3 E,  3 F show a nozzle and nozzle-holder which uses high pressure gas in the center of a low pressure fluid flow. This second nozzle and nozzle holder are used as an illustration of the breadth of the utility of the design of the receptacle  4030  (see  FIG. 4 ) within the flow conditioner manifold  1020  to incorporate nozzles with quite different operational functionality. This alternative nozzle-holder has external features and functionality in common although its configuration and nature of aerosol generation are quite different. These nozzles are both single pass nozzles, i.e. all the liquid is aerosolized on passage through the nozzle. None of this fluid is recirculated. Both nozzles, however, share the distinction that the aerosol is generated through the shear forces between the liquid and the gas. In neither case is the aerosol generated through the shear of the liquid on a solid. This reduces the possibility of high shear forces causing shear degradation of any large molecules dissolved in, or suspended in, the fluid to be aerosolized. 
     In this alternate preferred configuration, the nozzle-holder and the nozzle are shown in  FIGS. 3A ,  3 B,  3 C,  3 D,  3 E and  3 F. As noted, this configuration enables the aerosol is generated using compressed gas though a central channel together with a low pressure fluid flow to the perimeter of the compressed gas nozzle. The fluid port  2005  (see  FIG. 3C ) is situated on the end of the nozzle holder. In a preferred configuration of the invention, this port  2005  is a Luer fitting. This port  2005  is connected via channel  2007  and a small distributive reservoir  3208  to one or more channels  3203  (see  FIG. 3C ) and so to an annular cavity  3206  surrounding a base  3204  of the nozzle body  3300  (see  FIG. 3A ). In this case, the nozzle is comprised of two components, a nozzle body  3300  and a nozzle annulus  3205 . The nozzle body  3300  is seated within a neck  3220  of the nozzle barrel  3001  (see  FIG. 3C ) with the base of the nozzle body  3204  sealed to the barrel of the nozzle holder. The annular cavity  3206  (see  FIG. 3B ) is connected via grooves, e.g. grooves  3210  (see  FIG. 3A) and 3212  in a crown  3211  of the nozzle body  3300  to a miniature reservoir  3213  (see  FIG. 3B ) formed between a concave indentation  3216  in the crown  3211  and the annulus  3205  seated atop of the crown  3211 . This reservoir  3213  is contiguous with an annular cavity  3230  between a stem  3214  on the nozzle body  3300  and the annulus  3205 . The annulus  3205  is seated within and at the end of a neck  3220  of the nozzle barrel  3001  (see  FIGS. 3C and 3D ) such that a central hole  3233  in the annulus  3205  is positioned concentrically around the nozzle stem  3214  (see  FIG. 3B ). The distance between the nozzle stem and the annulus is small enough such that surface tension rather than gravity dominates the movement of fluid. The diameter difference between the inner annulus diameter and the outer stem diameter is between 0.006 and 0.8 mm, resulting in an annular gap width between the 0.003 and 0.4 mm. The stem  3214  which is in a preferred configuration is 1.75 mm but may vary from 0.5 mm to 3 mm has an orifice  3209  which in a preferred configuration is about 0.5 mm in diameter although other nozzle dimensions from 0.05 to 1 mm may be used. The orifice exits at the apex of a hollow cone  3240  within the orifice stem  3214 . A lip  3215  on the cone  3240  is either level with the outer surface of the annulus  3205  or protrudes slightly from this surface, potentially up to 1 mm. The nozzle body  3300  is comprised of machined ceramic or other material which is wettable by the solution or suspension to be aerosolized. In the case of an aqueous based solution, the nozzle should have a high surface energy to improve wettability. This may be achieved by applying a hydrophilic agent or other means. The outer surface of the annulus  3205  is coated with a hydrophobic agent to prevent an aqueous fluid from spreading across this annulus. The barrel of the nozzle-holder  3001  has one or more ports  2008  which are connected via a channel  3201  to a channel  3202  (see  FIG. 3D ). The channel  3202  in turn is contiguous with a channel  3234  of similar diameter within the nozzle body  3300 . This is contiguous with the orifice channel  3209 . In a preferred configuration, the nozzle barrel  3001  and a knob  3301  (see  FIG. 3F ) are constructed of either polysulphone or ultem although other materials may be used. 
     Generating an Aerosol by the Nozzle-Holder and Nozzle Shown in  FIGS. 3A-F   
     In this preferred configuration of the nozzle-holder shown in  FIGS. 3A ,  3 B,  3 C,  3 D,  3 E, and  3 F the aerosol is generated by supplying compressed gas to the central orifice  3209  within the nozzle. The fluid to be aerosolized is fed at a low pressure through the annular cavity  3206 , reservoir  3213  and the annular channel  3230  to the outer surface of the nozzle and by capillary action within the cone  3240  towards the orifice  3209 . The fluid to be aerosolized is supplied to port  2005  by an external pump (not shown). The fluid is pumped into the port  2005  and into channels  3203  to the annular space  3206  surrounding a base of the orifice body  3204 . This fluid distributes itself to each of the grooves  3210  in the side of the crown  3211  of the nozzle and through the grooves  3212  to the miniature reservoir  3213 . The top of the crown is concave to ensure the fluid is presented uniformly to the cavity  3230  surrounding the central orifice stem  3214 . The fluid flows evenly through the space  3230  between stem the annulus to the lip  3215  of the nozzle. In a preferred configuration, the nozzle stem  3206  may protrude some 0 to 0.050 inches through the annulus. The fluid flows over this lip  3215  to form a thin film on the inner surface of the cone  3240  within the orifice stem  3214 . The compressed gas enters through the ports  2008  in the side of the nozzle barrel  2001 . The gas flows through the central coaxial channel  3202  to the channel  3234  along the axis of the orifice body  3300 . The compressed gas then goes through the orifice  3209 . Aerosolization occurs at the junction formed by interaction of the fluid flowing into the cone and the gas jet at the perimeter of the orifice  3209  at the apex of the cone  3240 . In this way large shear stressed between any solid surface and the fluid are avoided. A plume of aerosol is generated which has particle free center. The negative pressure within the cone caused by the gas jet aids in the formation of a thin fluid film on the inner surface of the cone. For optimal function the cone apex should subtend a solid angle of about 45 and preferably between 15 and 80 degrees. However, other angles between 10 and 80 degrees may be possible. It is noted that all the surface through or over which the fluid is designed to flow should have high surface energies, i.e. be wettable by the fluid. The fluid flows over the lip of the cone by capillary forces. These forces increase as the fluid flows into and towards the apex of the cone. As noted, the maintenance of this thin fluid layer is also aided by the negative pressure created by the jet of gas exiting the orifice  3209 . 
     For optimal function, it is important that the surfaces of the nozzle body, including the crown and nozzle stem as well as the internal surface of the annulus have a high surface energy such that they are readily wettable by an aqueous based fluid. On the other hand, the top surface of the annulus  3205  has a hydrophobic coating to stop any fluid flow across the annulus. The distance between the nozzle stem and the annulus is small enough, for instance ˜0.17 mm such that surface tension rather than gravity dominates the movement of fluid. As the nozzle stem has a high surface energy, the fluid forms a meniscus between the lip  3215  of the cone  3240  on the stem  3214  of the nozzle and the annulus. 
     Positioning of the Nozzle Holder for Insertion into the Flow Conditioner 
     The positioning of the nozzle holder for insertion into the flow conditioner is shown in  FIGS. 4A ,  4 B and  4 C. The nozzle holder is aligned with a central axial receptacle  4030  in the flow conditioner manifold  1020  (See  FIG. 4A  and  FIG. 4C ). The barrel  2001  or  3001  of the nozzle holder is inserted in this receptacle  4030  of the flow-conditioner  1020 . When the nozzle holder is fully inserted, ports  2008  for the compressed gas, used for aerosolization, align with the circular groove  4071  in the flow conditioner  1020 . There is an O-ring  4033  on each side of this groove to prevent leakage of the compressed gas from the groove  4071 . The compressed gas enters the circular groove  4071  through a channel  4036  which in turn is connected to a compressed gas input  4028 . In the center of the manifold is a pillar  4040 . This pillar  4040  facilitates the inclusion of the receptacle  4030  which has a 4:1 length to width ratio. This ensures both a snug positioning of the nozzle barrel  2001  or  3001  and its precise axial alignment. This is important as the aerosol plume must be precisely aligned with the axis of the counter-flow gas for efficient performance. 
     Flow Conditioner Design 
     Exploded and cross-sectional views showing the individual components which comprise the flow conditioner which affects the flow profiles of the dilution gas flow are shown in  FIGS. 5A ,  5 B,  5 C,  5 D,  5 E and  5 F. In  FIG. 5A  an adjoining evaporation chamber  5100  is also denoted. To augment the rapid evaporation of the liquid aerosol in a confined space, the aerosol plume formed by either one of the nozzles described must be rapidly dispersed and diluted while providing sufficient thermal energy to evaporate the liquid. The flow conditioner must provide a uniform flow of gas through the evaporation chamber  5100  while again having a minimal pressure drop. This is made more challenging by the presence of the aerosol plume  2106  (See  FIG. 5A ) and the jet of gas  5120  (see  FIG. 5D ) from a counter-flow tube  1102 . As noted, this must be achieved with minimal pressure drop across flow conditioner to minimize the power and size of the fan required. A small compact flow-conditioner which is inexpensive to manufacture and is easy to assemble and disassemble for cleaning clearly makes the end product more commercially attractive. The flow partitioners are designed to reduce the radial velocity of the incoming dilution gas and to distribute the gas such that at the exit of the evaporation chamber the gas has a near uniform velocity. These components of the flow conditioner are constructed for easy assembly and disassembly while maintaining full functionality. 
     The exploded rendition of the components used to transform a relatively high velocity dilution gas flow entering a port  5122  (see  FIG. 5B ) to a lower velocity gas flow that is relatively uniform at the exit of an evaporation chamber  5100  is shown detail in  FIG. 5C . A cross-section of the assembled parts together with a head-on view of the flow conditioner indicating the location of the port  5122  for the dilution gas and port  4028  for the compressed gas is contained in  FIGS. 5A and 5B . The flow conditioner consists of four primary components; a manifold  1020 , two flow partitioners  5102 ,  5103 , and a counter-flow tube  1102 . As shown in  FIG. 4A  and  FIG. 4C  the manifold  1020  has the input for compressed gas  4028 , the input for dilution gas  5122 , the receptacle  4030  into which the nozzle holder is inserted, the central stabilization pillar  4040 , a receptacle for a counter-flow tube  4041  and two circumferential steps  4011 , and  4012  as well a step  4013  on the end of the pillar  4040 . These steps facilitate the firm localization of the two flow partitioners  5103  and  5102  (see  FIG. 5C ). Of course these two flow conditioners  5103  and  5102  could be manufactured integrally as one piece. The manifold  1020  of the flow-conditioner is comprised of Ultem or other strong heat resistant non-conductive material, with excellent dimensional stability; as are the two flow partitioners  5102  and  5103 . The flow partitioners remain in place as shown in  FIG. 5  during normal operation and handling. They are easy to remove and replace. This functionality is achieved through specific design features subsequently described. The entry port on the flow conditioner for dilution gas  5122  is made with a 22 mm standard respiratory male taper. This port fits into the corresponding female taper (not shown) in fitting  1007  (see  FIG. 1 ). Thus, the flow conditioner is held snugly in position by gravity. 
     The port  4028  for compressed gas is located within the flow conditioning manifold  1020 . The compressed gas flowing through this port is divided into two. One flow is directed though the channel  4036  to the annular groove  4071  within the central receptacle  4030 . There are O-rings  4033  in grooves on either side of the annular groove  4071  in the central coaxial receptacle  4030 . The flow divider is also connected to a restriction  4024  which in turn in connected via the counter-flow receptacle  4041  to the counter-flow tube  1102 . 
     The counter-flow tube  1102  has a 180 degree bend  5016  which reverses the direction of gas flow and directs it towards the oncoming aerosol plume  2106  generated by the nozzle  1024 . The counter-flow has a small plate  5029  attached to the side which, when inserted into the flow conditioner interacts with a slot  5031  in the pillar  4040  of the flow conditioner such that when the counter-flow tube is seated, the counter-flow tube is precisely coaxial with the nozzle  1024 . In a preferred configuration, the counter-flow tube is comprised of 12 gauge stainless steel tubing. In a preferred configuration, outlet of the counter-flow tube is 2 inches from the nozzle  1024 . This does not exclude other combinations of tube diameters and nozzle to counter-flow distances but rather forms an example. 
     The two flow partitioners  5102  and  5103  are designed to reduce the radial velocity of the incoming dilution gas and to distribute the gas such that at the exit of the evaporation chamber  5100  has a near uniform velocity. These components of the flow conditioner are constructed for easy assembly and disassembly while maintaining full functionality. These two flow partitioners  5102  and  5103  divide the chamber of the manifold  1020  into two pressure/flow equalization chambers,  5021  and  5222 . The flow partitioner  5102  is of slightly larger diameter than the circumference of flow partitioner  5103 . The flow partitioner  5103  has a “chimney”  5134  with circumferentially placed holes  5009 . The top of the chimney has a circumferential ledge  5007  which provides a means of stabilization for the second flow conditioner. Flow partitioner  5103  is inserted into the chamber of the flow-conditioning manifold such that it seats on the stepped circumferential step  4012  on the inside of the flow conditioner as well as the circumferential step  4013  on the central pillar  4040  of the manifold  1020 . The flow partitioner  5102  is inserted into the chamber of the flow manifold  1020  such that the flow partitioner seats on the step  4011  in the manifold. 
     Of note, there are four surfaces of contact between the flow conditioner manifold  1020  and the first flow partitioner  5103  (see  FIG. 4C  and  FIG. 5A ). It is these surfaces that provide stable seating of the flow partitioner within the housing. Again, these multiple surface contacts facilitate the easy seating of this second flow conditioner yet secure it in place so that it does not fall out or move during normal handling and operation of the device. Also it is notable that through the use of these multiple steps, the gas flow is directed though holes  5013 ,  5023  and slots  5012  in the flow partitioners  5102  and  5103  (see  FIG. 5C ) rather than “leak” through the contact areas between the flow partitioners and the manifold  1020 . In this way, the flow is controlled by the size of the flow channels rather than leaks. The use of O-rings is avoided. The use of such large O-rings would make the parts too difficult to assemble by a patient or end user. This minimizes aerosol deposition on this flow partitioner. The flow partitioner  5102  has a central hole  5014  through which the nozzle neck  2003  protrudes. It has a near rectangular hole  5015  to facilitate the insertion of the counter-flow tube  1102 . A central part  5017  of the flow partitioner  5102  is raised. This facilitates the inclusion of a circumferential groove  5018 . This groove enables a user to grip the outer flow partitioner with their fingers for easy removal and insertion to and from the flow-conditioner manifold  1020 . The raised center of the flow conditioner has a concave surface to reduce aerosol deposition on its surface. 
     The flow conditioning manifold performs multiple functions central to the successful operation of the device. These include a) the locating of the nozzle holder precisely on the central axis of the receptacle of the manifold; b) the delivery and partitioning of compressed gas to the inlet ports  2008  (see  FIG. 2B ) on the barrel  2001  of the nozzle holder as well as to the counter-flow tube  1102  (see  FIG. 4C ) and c) the intake and redistribution of dilution gas to achieve near uniform gas flow at the exit of the evaporation chamber  5100  (see  FIG. 5A ). 
     Partitioning of the Compressed Gas 
     In  FIG. 5A  it can be seen that the compressed gas is connected via a quick-disconnect fitting  5019  and the Teflon tube  1031  through the right angle fitting  1013  on the manifold of the flow conditioner  1020 . To simplify the practicality and use of the device, there is only one connector on the flow-conditioning manifold for the compressed gas  4028 . The compressed gas flow is partitioned using an internally located flow divider within the flow conditioner manifold. One flow is directed to an annular groove through the channel  4036  to the annular groove  4071  within the central receptacle that provides the compressed gas to the nozzle holder. O-rings  4033  in grooves on either side of the annular groove  4071  in the central receptacle  4030  seal against leakage of the compressed gas. The other flow passes through a restriction  4024  which limits the flow rate of the counter-flow gas at a similar or slightly larger volumetric flow rate as that coming through the aerosolization nozzle  1024 . The liquid aerosol plume  2106  is arrested by the co-axial counter-flow jet of gas  5120  from a port  5026  of the counter-flow tube  1102  such that a stagnation point  5300  is midway between the nozzle and the counter-flow port  5026  (see  FIG. 5A ). 
     Functions Performed by the Dilution Gas Flow Conditioner 
     The input gas flow from the entry port  5122  (see  FIG. 5B ) is directed circumferentially is the pressure equalization channel  5021  around the center pillar  4040  (see  FIG. 4C ) of the first stage of the flow-conditioner. This first stage is a hollow “donut” of low gas flow resistance. The rotational velocity of the gas is reduced as it moves perpendicularly through the slots  5012  (see  FIG. 5C ) located circumferentially between the merlons  5042  on the flow partitioner  5103 . These slots form a gas flow path of higher resistance than that of the channel forming this first donut-shaped pressure equalization chamber  5021 . The gas enters the second stage of the flow conditioner through these slots  5012 , into a second donut-shaped pressure equalization channel  5022  with low flow resistance. From this channel, it is distributed in two ways; a) through holes  5009  around a ‘chimney’  5008  and subsequently through holes  5223  in the center portion of the second flow-partitioner and b) through the concentric holes  5013  in the outer region of the second flow partitioner  5102 . The positions and sizes of these holes (or slits) achieve a uniform flow profile at the virtual impactor face plate while minimizing deposition of aerosol on the second flow partitioner  5103  and the walls of evaporation chamber  5100 . The gas flow to the center of the evaporation chamber in-part is regulated by the size of the holes  5009  in this ‘chimney’. 
     The Evaporation Chamber 
     The features of the evaporation chamber  5100  see  FIG. 5A  are shown in  FIGS. 6A ,  6 B,  6 C and  6 D. The evaporation chamber  5100  fits between the flow conditioning manifold  1020  and an aerosol concentrator  6100 . In a preferred configuration the evaporation chamber is comprised of a 275 inch outer diameter 2.56 inch internal diameter tube 6 inches long that is transparent to infrared radiation. Other similar dimensions are possible. In preferred configurations, this tube can be made of quartz or borosilicate glass. This tube is inserted into the open end of the flow-conditioner manifold  1020  until it abuts the flow partitioner  5102  (see  FIG. 5A ). The dimensions of the manifold opening and the tube are such that a friction fit is sufficient to a) support the tube and b) prevent any substantial gas leak from the inside of the chamber to the atmosphere. The other end of evaporation chamber is inserted into a circumferential groove  6055  (see  FIG. 6A  and  FIG. 7C ) on an acceleration plate  6110  (see  FIG. 6A ) of the virtual impactor type aerosol concentrator  6100 . Again this is a snug friction fit. Alternatively, lip seals or tapered ends of this tube  5100  and corresponding female tapers on the manifold  1020  and the concentrator acceleration plate  6110  could be used to eliminate any gas leakage between the evaporation chamber  5100  and the flow conditioner manifold or the aerosol concentrator  6100 , respectively. 
     On one side of and adjacent to the evaporation chamber is a 125 W rapidly heating infrared lamp  6001 . A preferably parabolic infrared reflector  6002  is placed behind the bulb such that the center of the bulb is in the focal plane of the reflector. In addition an infrared reflector  6003  on the opposite side of the evaporation chamber  5100  again increases the infrared radiation flux within the evaporation chamber. In a preferred configuration these infrared reflectors are made of polished aluminum. The infrared reflector  6003  may also be comprised of a gold coating on the evaporation tube. Also the reflector  6002  may be replaced with gold coating on the infrared lamp  6001 . 
     To augment the rate of evaporation, the aerosol flowing through the evaporation chamber  5100  is heated with infrared radiation. Heat transfer by convection is proportional to the temperature gradient. However, heat transfer by radiant heat is proportional to the fourth power of the temperature differential. Water has strong absorption bands in the infrared region. Thus, the rapidly responding infrared lamp  6001  is located below the evaporation chamber  5100 . The infrared reflector  6002  increases the infrared radiation flux within the chamber  5100 . The quartz or borosilicate glass of the evaporation chamber, being transparent to infrared enables the infrared radiation to enter the chamber  5100 . This infrared radiation is absorbed by water in the aerosol particles. This energy is then dispelled as the latent heat of evaporation. Also the second infrared reflector  6003  placed or the opposite side of the evaporation chamber enhances the transfer of infrared energy to the aqueous aerosol particles in transit through the evaporation chamber  5100 . 
     The Counter-Flow Tube 
     The evaporation chamber  5100  also contains the counter-flow tube  1102  (see  FIG. 1  and  FIG. 5A ). The counter-flow tube is positioned in receptacle  4041  (see  FIG. 4C  and  FIG. 5A ) with a small plate  5029  (see  FIG. 5C ) attached to the counter-flow tube positioned in a slot  5031  in the pillar  4040  (see  FIG. 4C ) of the manifold  1020 , This tube, which receives gas from the flow divider,  5052  (see  FIG. 5A ) has a 180 degree bend followed by a short straight section. The curvature of this bend is such that when the small plate  5029  (see  FIG. 5C ) is correctly inserted into the slot  5031  in the manifold  1020  the port  5026  of the counter-flow tube is precisely coaxial with the center of the chamber and the orifice  1024  of the aerosol nozzle. 
     The compressed gas from the flow divider  5052  flows through the counter-flow tube and exits the counter-flow port  5026 . The jet of gas so created is coaxial with but of opposite direction to the aerosol plume. The short straight section of the counter-flow tube  1102  ensures a symmetrical jet of counter-flow gas. The flow rate in this gas jet is such that the aerosol plume  2106  is arrested midway  5300  between the nozzle orifice  1024  and the port  5026  of the counter-flow tube  1102 , 
     The Aerosol Concentrator 
     The virtual impactor shown in detail in  FIGS. 7A ,  7 B,  7 C,  7 D,  7 E and  7 F is used to concentrate the output aerosol from the evaporation chamber  5100 . As shown In  FIG. 7C , the borosilicate/quartz tube of the evaporation chamber  5100  forms a snug fit into the circumferential groove  6055  in the acceleration plate  6110  of the virtual impactor  6100 . Turning back to  FIG. 7A , the virtual impactor is comprised of the acceleration plate  6110  containing long acceleration slit nozzles  7002 , medium slit nozzles  7102  and short acceleration slit nozzles  7202  and a virtual impaction deceleration plate  7020  (see  FIG. 7B ) containing long  7003  and medium  7103  and short  7203  complementary deceleration slit nozzles. Attached to a deceleration plate  7120  is an exhaust gas cowling  7021  and exhaust port  7022  (see  FIGS. 7D and 7E ). A plenum  7004  formed by the acceleration face plate  6110 , the deceleration plate  7020  and the exhaust gas cowling  7021  provides a low resistance flow path for the exhaust gas that emanates from a gap  7300  between the tips of the acceleration nozzles  7002 ,  7102 ,  7202  and the receptor slits on the deceleration nozzles  7003 ,  7103  and  7203 . The acceleration plate  6110  fits snuggly into the virtual impactor deceleration plate  7020  such that the long  7002 , medium  7102  and short  7202  acceleration nozzles are accurately aligned with the long  7003  and medium  7103  and short  7203  deceleration nozzles, respectively. There is a small gap  7300  between the orifices of these acceleration nozzles and the complementary deceleration nozzles. The slits of the acceleration nozzles are 1.1 mm wide. The receptor slits are 1.4 mm wide and positioned such that the gap  7300  between the between the slits of the acceleration nozzles and the deceleration nozzles is 1.3 mm. These are mentioned as a practical solution but are not intended to exclude other similar dimensions. To prevent particles entrained in the exhaust gas from entering the atmosphere, a filter (not shown) may be attached on the exit port  7022 . 
     Although virtual impactor aerosol concentrators have previously been described, this concentrator has specific novel features which make the invention ideally suited to its proposed function. The concentrator was optimized to deliver the largest mass fraction of respirable aerosol generated by the nozzle  1024  (see  FIG. 1 ) to the output. The concentrator is thus optimized to work best within the respiratory range, i.e. 1 to 5 micron aerodynamic diameter. Thus, for the purposes of this invention, this output aerosol can be considered to comprise of particles greater than 0.5 micrometers aerodynamic diameter. Thus, the virtual impactor should concentrate as many particles as possible which are smaller than or equal to 5 micrometers aerodynamic diameter. This, together with the requirements for a minimal pressure drop across the concentrator and the absence of any negative gas pressure to remove the exhaust gas from the gaps between the nozzles and the receiving slits required several novel design features to be incorporated. 
     1. The sixteen acceleration slit nozzles  7002 ,  7102  and  7202  are arranged radially as shown in  FIG. 7A . The design is chosen so the exhaust gas exits the concentrator radially with minimal interference with the jet of aerosol passing between the acceleration nozzles  7002 ,  7102  and  7202  and the deceleration nozzles  7003 ,  7103 ,  7203  The shorter slit nozzles  7102 ,  7202  are designed to keep the flow across the evaporation chamber and the concentrator as uniform as possible. Note this configuration also maximizes the total cumulative length of the slits of the acceleration and deceleration nozzles. The total cumulative length of the accelerator nozzles is a preferred design is 18 cm although other cumulative lengths from 10 to 25 cm are possible.
 
2. The tapered surfaces of the input of the acceleration nozzles are designed with parabolic profiles  7008  (see  FIG. 7C ) to minimize the pressure differential required to accelerate the aerosol to nozzle velocity while minimizing aerosol deposition on the face of the acceleration plate  6110  of the concentrator  6100 .
 
3, Likewise, the output cones of the deceleration nozzles  7003 ,  7103  and  7203  also are parabolically sculptured, having parabolic-like profiles  7009  (see  FIG. 7C ) to lower the resistance though the concentrator and minimize the turbulence of the aerosol at the output of the concentrator.
 
4. In addition, the downstream surfaces of the acceleration nozzles  7002 ,  7102  as well as the upstream surfaces of the deceleration nozzles  7003 ,  7103  are sculptured to lower the resistance of the exhaust gas between these nozzles. The sculptured shape leaves a gap of 1 cm or even more between the acceleration plate and deceleration plate at those locations where the sculptured acceleration and deceleration channels are not provided, i.e. leaves wide radial channels for the separated exhaust volume flow of low particle concentration to flow through these channels towards the cowling and eventually leave the system through the exhaust port  7022  (see  FIG. 7E ). Again, this enables the exhaust volume flow to be removed with minimal perturbation of the aerosol jets. The contours of these upstream and downstream surfaces which are designed to minimize both flat surfaces and sharp acute angles are critical to the overall performance of the concentrator. Of note, the downstream contours of the deceleration nozzles were shown to markedly increase the efficiency of the concentrator compared to slits within a flat virtual impaction plate.
 
5. To facilitate precise alignment of the acceleration nozzles  7002 ,  7102 ,  7202  with their respective deceleration nozzles,  7003 ,  7103 ,  7203 , a location cylinder  7010  (see  FIG. 7A ) and a close fitting male cylinder  7011  ensure the coaxial alignment of the concentrator jet plate with the receptor plate. This together with a male cross  7115  and close fitting female cross shaped receptacle  7013  ensure that the jet slits are aligned precisely with the receptor slits of the deceleration nozzles.
 
6. The acceleration plate  6110  and deceleration plate  7120  are easily separable using a centrally placed heli-coil  7014  and screw  7015  (see  FIG. 7F ). This facilitates multiple assemblies and disassemblies and the cleaning of any aerosol deposited on the inner surfaces of the plates.
 
7. A cavity  7016  (see  FIG. 7C ) on the downstream side of the concentrator is designed to allow the turbulence from the receptor slits to decay and thus reduce unwanted aerosol deposition on the output cone.
 
8. The cowling  7021  (see  FIG. 7E ) has a sculptured exit channel  7106  and the exit port  7022  has a standard 22 mm taper which facilitates the connection of a disposable filter (not shown).
 
     The aerosol at the output of the evaporation chamber  5100  is concentrated using the virtual impactor shown in  FIGS. 7A ,  7 B,  7 C,  7 D,  7 E and  7 F. The aerosol from the evaporation chamber  5100  is accelerated as it passes through the acceleration nozzles  7002  and  7102  and  7202 . In this case, the resistance to flow is minimized by using the long  7002  medium  7102  and short  7202  slit nozzle configuration. As the aerosol particles have considerably higher momentum than the gas and water vapor molecules in which they are suspended, the particles cross the gap  7300  and enter the deceleration nozzles  7003 ,  7103  and  7203 . The aerosol flow rate of the output of the concentrator is generally only ⅕ th  to 1/10 th  that of the input flow rate. The gas flow rate difference between the input gas flow rate and the output gas flow rate is exhausted through the gap  7300  (see  FIG. 7C ) between the slits and into the plenum  7004 . The concentrated aerosol at the output is funneled through an aerodynamically designed output cone  7006  to be delivered to the patient or for other desired purposes. 
     In a preferred configuration, on an outer wall of the output the cavity  7016  of the concentrator there is 1 to 2 cm broad flange  7030 . This facilitates the placement of the output cone  7006  which has a matching internal diameter at its inlet and a step  7031  so that there are no flow discontinuities. The output of the cone has a standard 22 mm respirator taper  7032  (see  FIG. 7F ) to permit easy connection to an inhalation tube or filter (not shown). 
     EXAMPLES 
     The flow resistance of the dilution heater was found to be 0.12, 0.3 and 0.5 inches of water at 100, 150 and 200 liters per minute, respectively. The flow resistance of the flow conditioner was determined to be 1 inch of water at 150 liters per minute and 1.8 inches of water at 200 liters per minutes. The flow resistance of the aerosol concentrator was determined to be less than 1 mm of water at all tested input flow rates below 300 liters/minute when the concentrator output flow rate was 40 liters per minute. The pressure inside the evaporation chamber was 0.3, 0.8, 1.4, 2.2 and 2.7 inches of water at chamber flow rates of 100, 150, 200, 250 and 300 liters/minute, respectively when the output flow rate of the concentrator was 40 liters/min. 
     A solution of 16% bovine serum albumin was fed to the nozzle using an infusion pump and aerosolized at 1 ml/minute. The nozzle pressure was 20 to 24 psi and the dilution gas flow 200 liters/minute. The resultant dry aerosol downstream from the concentrator was measured for two minutes at 40 liters/minute. The mass collected was determined gravimetrically. Typically 180 to 210 mg was collected. Thus the output of the device is about 100 mg per minute. 
     The overall efficiency of the throughput of the device was found to be 64%. The efficiency of the concentrator alone was found to be 85%. 
     Red food dye number 4 (0.2%) was added as a tracer to the 16% albumin solution. Under similar conditions an albumin aerosol was sampled at 30 liters per minute by a Marple Miller cascade impactor. Each stage of the impactor was washed 3 times with water and the relative mass on each stage was determined spectrophotometrically at 508 nanometers. The cumulative mass was plotted on log-probability paper. The mass median diameter was found to be 3.4 μm. Eighty five percent of the collected aerosol was found to be in the respirable range, i.e. the sum of all stages up to and including 5 micron. 
     To determine if the aerosolized protein was degraded by passing through the nebulizer, porcine trypsin was aerosolized and collected. A solution of this trypsin was placed on a confluent cell culture. The cells were seen to detach from the substrate. No difference could be seen between the results of a similar concentration of trypsin which has not been aerosolized. 
     To evaluate the shape and surface characteristics of the albumin particles produced, particles at the output were collected on a 12 mm diameter Millipore filter. The filter was placed at the center of a larger filter with similar flow characteristics. This filter was then mounted on an electron microscope stud and stored upright in a desiccator. Each sample was sputtered with palladium-gold and random images recorded on a SEM at magnification of 1500. The albumin particles were found to be spherical with a smooth surface. 
     The embodiments described in the specifications of this disclosure provide practical compact portable devices for the generation of dry concentrated respirable particles from and liquid solution or suspension. This present disclosure provides the means, in a small practical clinical device, to generate and by dilution and heating, rapidly evaporate aqueous aerosols and thereafter to concentrate the resultant particles and deliver them at flow rates compatible with the full range of normal inspiratory flows. 
     Herein are described the inclusion of many valuable features in the embodiments which i. enable improved function, ii. facilitate the practical use of the embodiments and iii. have clinical advantages. 
     Among other advantages, the embodiment of the invention achieves the following: 
     a) Provides from a source directly adjacent to the evaporation chamber, localized radiant heat to the newly formed aqueous aerosol particles at the wavelengths of the maximum infrared absorption for water. 
     b) Allows the device to be used with different nozzle-holder configurations and for these to be easily interchangeable. These nozzle-holders enable either compressed gas delivered to a central orifice or around a central fluid stream. These nozzle-holders are keyed to the flow conditioner and may or may not include a compressible fluid reservoir.
 
c) Provides the means for a heated high velocity gas counter-flow stream in one direction as well as a uniform lower velocity flow in the opposite direction while allowing for the perturbations caused by an aerosol plume and counter-flow gas. This is achieved with minimal pressure drop using a two stage flow conditioner.
 
d) Efficiently concentrates a respirable aerosol with minimal pressure drop between the input and the exhaust gas using a variable length slit concentrator with radial input slits about 1.1 mm wide and output slits 1.4 mm wide with both input and output cones being parabolic in nature on both upstream and downstream surfaces.
 
e) Minimizes any aerosol deposition due to turbulence at the output of the concentrator by including a cavity to allow these vortexes to relax.
 
f) Provides an efficient means of delivering the concentrated aerosol at the output by utilizing an internally parabolic-shaped output cone.
 
g) Eliminates high pressure couplings on large diameters so the device can be easily assembled and disassembled for cleaning.
 
h) Lowers the resistance to gas flow so as to enable the construction of a small device using a small blower to provide the dilution gas.
 
i) Minimizes leakage of gas and/or aerosol between the various components of the device while maintaining structure integrity junction between each of the components by including at least two and preferably 3 or 4 mutually perpendicular surfaces.
 
j) Facilitates the provision of a removable counter-flow gas that is precisely coaxial with the aerosol plume and of opposite direction to the aerosol plume a counter-flow tube was keyed into a flow conditioner.
 
k) Provides heated compressed gas to both the nozzle and the counter-flow tube while minimizing heat losses by incorporating a flow divider and flow regulating orifice into the flow conditioner.
 
l) Facilitates easy and precise assembly and disassembly the concentrator plates by having a raised male cylindrical protrusion and cross and reciprocal female indents in the center of the concentrator. These provide both axial and rotational high precision alignment.
 
m) Prevents any aerosol particles in the exhaust gas stream from contaminating the atmosphere by use of a cowling and filter port.
 
n) Provides a concentrated aerosol at a small positive pressure as pressure-assist for patients who have trouble generating sufficient inspiratory pressure and flow to trigger some other dry powder inhalers.
 
o) Generates dries and concentrates near sterile aerosols by the use of sterilizable components of the embodiments together with the positive pressure inside the device.
 
     In the following, the embodiment according to the present invention is summarized. 
     Generation of an Aerosol 
     The liquid to be aerosolized is fed into the input port  2005  in the nozzle holder and conducted via channels to the nozzle  1024 . The compressed gas required to aerosolize a liquid to be aerosolized is provided to fitting  1019 . It passes though the heater  1011  where it is warmed to the temperature required. This temperature is measured with the thermocouple and the heater regulated using a PID controller. This heated gas is divided into two flows. One flow is directed though a flow limiting orifice  5024  to the counter-flow tube  1102 . The remaining flow proceeds into the annular groove  4071  and from there into the barrel ports  2008 ,  3008  and thence to the nozzle  1024 . The interaction of the liquid to be aerosolized and the high pressure gas in the nozzle causes the production of a plume  2106  of liquid aerosol. This warm gas in the counter-flow tube is directed into the aerosol plume coaxial with but in opposite direction to the plume. This gas flow arrests the aerosol plume midway between the nozzle and the end of the counter-flow tube. The injection of this heated gas into the aerosol plume enhances the rapid evaporation of the liquid solvent. 
     As Shown in  FIG. 1  the aerosol processing system contains two gas heaters, one gas heater  1011  to warm the compressed gas to generate the aerosol and provide a counter-flow  5120  (see  FIG. 5A ) to arrest the aerosol plume  2106  and the other gas heater  1004  to warm the gas to dilute the aerosol. These warm gas flows are distributed to their respective functions within a flow-conditioner. Within the flow conditioner manifold  1020  (see  FIG. 5A ), the compressed warm gas is divided into two components, one is routed through the barrel of the nozzle holder  2001  to generate the aerosol at the tip of the nozzle and the other to form the counter-flow gas stream  5120  coaxial with but of opposite direction to the nozzle plume  2106 . The evaporation of the aerosol as it transits an evaporation chamber  5100  is augmented by the use of a radiant heater  6001  together with its associated  6002  and  6003  reflectors. The aerosol is accelerated through nozzles  7002 ,  7102  and  7202  in the acceleration plate  6110  (see  FIG. 7A ) of the low resistance virtual impactor. The particles that have a much higher momentum than the gas molecules traverse a gap and pass through the slits of the deceleration nozzles,  7003 ,  7103  and  7203  in the deceleration plate  7120  into the output collection cones. When the aerosol flow rate at the output of the virtual impactor is lower than the flow rate when entering the virtual impactor, the residual gas is exhausted between the acceleration plate  6110  and deceleration plate  7120 . The majority of the particles pass through the slits in the deceleration plate  7120  and thus comprise the output aerosol. 
     Schematics of the gas input and conditioning components of the invention are depicted in  FIG. 1 . An optional gas drying chamber  1002  is provided for use as needed. The chamber of this dryer is filled with the desiccant  1003 . A miniature blower  1001  is connected, through the flow measurement device  1023  to a dilution gas heater  1004 . This heater  1004  is connected via the right angle fitting  1013  to the inlet  4028  on the flow conditioner manifold  1020 . A thermocouple (not shown) is situated in the lumen of this right angle fitting. The flow conditioner has the two donut shaped channels  5021 ,  5022  separated by the flow partitioner  5103  with slots  5012  that allow gas to pass from one channel  5021  to the other channel  5022 . The second stage of the flow conditioner is connected to an evaporation chamber  5100  through the holes  5013 ,  5023  in this second flow conditioner  5102 . The evaporation chamber  5100  is positioned between the flow conditioner manifold  1020  and an aerosol concentrator  6110 . The aerosol concentrator has radially arranged acceleration nozzles  7002 ,  7102 ,  7202  which also are connected to the exhaust plenum  7004 . The deceleration nozzles  7003 ,  7103  and  7203  are in close proximity to and are aligned with the acceleration nozzles  7002 ,  7102  and  7202 , respectively. The downstream ends of these deceleration nozzles are contiguous with the turbulence decay cavity  7016  and aerosol collection and cone  7006 . This collection cone is connected to an output device or person (not shown) that regulates the output flow as desired. 
     Compressed gas is provided to fitting  1019 . This fitting is connected to the compressed gas heater  1011 . This is connected to an input port  4028  on the flow conditioner manifold  1020 . This port  4028  is connected to a flow divider. One side of this divider is connected via a flow limiting orifice  5024  to the counter-flow tube  1102 . The other side of this divider is connected to an annular groove  4071 . This annular groove interfaces with ports  2008  on the nozzle holder. These ports are connected through channels to the nozzle  1024 . The fluid port  2005 , in a preferred configuration is a Luer fitting. This port  2005  is connected though channels to the nozzle  1024 . 
     The invention incorporates a novel easily replaceable integral nozzle holder and nozzle  1024 . The barrel  2001 ,  3001  of this nozzle holder is inserted into the cylindrical receptacle  4030  along the center axis of the flow conditioning manifold  1020 . As noted, a circumferential groove  4071  in this manifold is contiguous with ports  2008  on the barrel on the nozzle holder  2001 ,  3001 . 
     The gas to dilute and help evaporate the liquid aerosol is provided by a small blower  1001 . The flow of this gas is measured as it passes though the flowmeter  1023 . This gas is heated as it passes through the heater  1004 . This high velocity warm gas passes through the right angled channel  1007  to the inlet  5122 . This gas flow is transformed into a flow of relatively uniform velocity as it passes though the pressure equalization chambers  5021 ,  5222  and the flow partitioners  5103 ,  5102 . This high velocity dilution gas is transformed by this very low resistance flow conditioner to provide an even gas flow in the evaporation chamber  5100  such the velocity of the output aerosol as it enters the acceleration plate  6110  (see  FIG. 6A ) of the virtual impactor illustrated in  FIGS. 7A ,  7 B,  7 C,  7 D,  7 E,  7 F is relatively uniform. 
     The aerosol is entrained within and further evaporated by the dilution gas as it flows through the evaporation chamber. This evaporation is augmented by the infrared radiation from the infrared lamp  6001 . The now solid phase aerosol enters the acceleration nozzles  7002 ,  7102 ,  7202  to form aerosol jets. Most of the aerosol in these jets enters the deceleration nozzles  7003 ,  7103 ,  7203  and is presented to the output cone  7006 . Most of the gas (which has much less momentum than the particles) is exhausted through the exhaust plenum  7004 . 
     To facilitate rapid drying of the aqueous aerosol in a confined space, the aerosol plume from the compressed gas-powered nozzle is preferably arrested and mixed with dilution gas. This dilution gas should be warmed. US Patent application 200701445 teaches the use of a coaxial counter-flow jet to arrest an aerosol plume. However, neither was the jet gas nor the counter-flow gas heated; let alone to over 100 degrees Celsius. This hot gas provides the latent heat of evaporation to facilitate extremely rapid evaporation of the aerosol droplets. Notwithstanding this high input gas temperature, the temperature within the plume is generally less than 30° C. The particles are cooled by the latent heat of evaporation. Thus the provision of this hot gas does not result in the denaturing of any protein in the aerosol generated 
     Horizontal System 
     The virtual impactor concentrator described in US Patent application 200701445 has a cut-off of 2.5 micrometers. That prior art system obviated the necessity of collecting and re-suspending the dry power mixture; a time consuming and potentially wasteful procedure. However, that liquid to dry powder aerosol generator used up to 300 liters of dilution gas at relatively high pressure (20-50 psi). This required a 5 horsepower compressor and a tank of pressurized gas. Such a large and expensive compressors and/or the access to large compressed gas tanks makes that prior art device impractical for home use. 
     Some of the novel features of the system according to the present invention are the flow conditioner and the virtual impactor and the exchangeable cartridge/nozzle, In addition, further advances were achieved by reducing the pressure drops through the gas heaters and the inter-connecting parts. 
     This facilitates the generation, dilution, evaporation and concentration of protein aerosol with a density less than 1 which provides a highly concentrated aerosol of particles of a size of about 1 micrometer and above for delivery to the respiratory tract. This is a compact device whose dilution gas can be at a pressure drop in the entire volume flow of only 1-3 inches of water through the device downstream from the dilution air blower. This requires a substantial reduction of the pressure drops inherent within the previous system US patent application publication no. 200701445.