WO2000076673A1 - Method for producing an aerosol - Google Patents

Method for producing an aerosol Download PDF

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Publication number
WO2000076673A1
WO2000076673A1 PCT/US2000/015931 US0015931W WO0076673A1 WO 2000076673 A1 WO2000076673 A1 WO 2000076673A1 US 0015931 W US0015931 W US 0015931W WO 0076673 A1 WO0076673 A1 WO 0076673A1
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WO
WIPO (PCT)
Prior art keywords
liquid
exit opening
supply means
gas
exit
Prior art date
Application number
PCT/US2000/015931
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English (en)
French (fr)
Inventor
Joan Rosell
Alfonso Ganan-Calvo
Original Assignee
Aradigm Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Aradigm Corporation filed Critical Aradigm Corporation
Priority to EP00938249.0A priority Critical patent/EP1192009B1/de
Priority to JP2001502989A priority patent/JP2003501257A/ja
Priority to AU53318/00A priority patent/AU767486B2/en
Priority to ES00938249T priority patent/ES2424713T4/es
Priority to CA2374232A priority patent/CA2374232C/en
Publication of WO2000076673A1 publication Critical patent/WO2000076673A1/en

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05BSPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B7/00Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas
    • B05B7/02Spray pistols; Apparatus for discharge
    • B05B7/04Spray pistols; Apparatus for discharge with arrangements for mixing liquids or other fluent materials before discharge
    • B05B7/0416Spray pistols; Apparatus for discharge with arrangements for mixing liquids or other fluent materials before discharge with arrangements for mixing one gas and one liquid
    • B05B7/0441Spray pistols; Apparatus for discharge with arrangements for mixing liquids or other fluent materials before discharge with arrangements for mixing one gas and one liquid with one inner conduit of liquid surrounded by an external conduit of gas upstream the mixing chamber
    • B05B7/0475Spray pistols; Apparatus for discharge with arrangements for mixing liquids or other fluent materials before discharge with arrangements for mixing one gas and one liquid with one inner conduit of liquid surrounded by an external conduit of gas upstream the mixing chamber with means for deflecting the peripheral gas flow towards the central liquid flow
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05BSPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B7/00Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas
    • B05B7/02Spray pistols; Apparatus for discharge
    • B05B7/04Spray pistols; Apparatus for discharge with arrangements for mixing liquids or other fluent materials before discharge
    • B05B7/0416Spray pistols; Apparatus for discharge with arrangements for mixing liquids or other fluent materials before discharge with arrangements for mixing one gas and one liquid
    • B05B7/0483Spray pistols; Apparatus for discharge with arrangements for mixing liquids or other fluent materials before discharge with arrangements for mixing one gas and one liquid with gas and liquid jets intersecting in the mixing chamber

Definitions

  • This application generally relates to the creation of an aerosol created by the directed flow of fluids.
  • BACKGROUND OF THE INVENTION Devices for creating finely directed streams of fluids and/or creating aerosolized particles of a desired size are used in a wide range of different applications, such as, for example, finely directed streams of ink for ink jet printers, or directed streams of solutions containing biological molecules for the preparation of microarrays.
  • the production of finely dispersed aerosols is also important for (1) aerosolized delivery of drugs to obtain deep even flow of the aerosolized particles into the lungs of patients; (2) aerosolizing fuel for delivery in internal combustion engines to obtain rapid, even dispersion of any type of fuel in the combustion chamber; or (3) the formation of uniform sized particles which themselves have a wide range of uses including (a) making chocolate, which requires fine particles of a given size to obtain the desired texture or "mouth feel" in the resulting product, (b) making pharmaceutical products for timed release of drugs or to mask flavors and (c) making small inert particles which are used as standards in tests or as a substrate onto which compounds to be tested, reacted or assayed are coated.
  • a “violent focusing” method comprises the steps of forcing a first liquid through a feeding tube and out of an exit opening of the feeding tube is positioned inside a pressure chamber which is continually filled with a second fluid which may be a second liquid immiscible in the first liquid or a gas.
  • the exit opening of the feeding tube is positioned such that the liquid flowing out of the tube flows toward and out of an exit or discharge orifice of the chamber surrounding the exit opening of the feeding tube.
  • the first liquid exiting the tube is focused to a substantially reduced diameter and subjected to a violent action created by the second liquid or gas, breaking up the flow into particles substantially smaller than if the reduced diameter flow underwent spontaneous capillary breakup.
  • the exit opening of the feeding tube preferably has a diameter in the range of about 5 to about 10,000 microns and the exit opening of the tube is positioned at a distance in a range of from about 5 to about 10,000 microns, more preferably about 15 to about 200 microns from an entrance point of the exit orifice.
  • a stream of the first liquid flows out of the tube and is focused by the flow of the second liquid or gas in the surrounding pressure chamber. The focused stream then exits out of the discharge orifice of the pressure chamber, destabilizing and forming small particles.
  • the size of the particles of the first liquid is governed by the balance between the surface tension forces of the first liquid particle formed, and the amplitude of the turbulent pressure fluctuations at, and outside of the exit orifice of the pressure chamber.
  • the particles are sufficiently small that their surface tension forces substantially match the amplitude of the pressure fluctuation then the particles are stabilized and will not break up into still smaller particles.
  • Figure 1 is a schematic cross-sectional plan view of a nozzle of the invention
  • Figure 2 is another embodiment of the nozzle of Figure 1 showing and labeling various angles and areas of the nozzle;
  • FIG. 3 is the same embodiment as shown in Figure 1 with various angles and areas labeled;
  • Figure 4 is another embodiment of the nozzle of Figure 1 with certain areas and angles labeled;
  • Figure 5 is an embodiment of the nozzle of Figure 1 with various parameters labeled;
  • Figure 6 is a graph of the volume median diameter (VMD) vs the liquid supply flow rate for four different liquids,
  • Figure 7 is a graph of the dimensionless volume median diameter (VMD) versus dimensionless liquid flow rate with a line through the data points showing the best power-fit
  • Figure 8 is a graph of the data with the line shown in Figure 7 compared to a theoretical line for the Rayleigh breakup prediction of a flow-focused jet
  • Figure 9 is a graph of data obtained with the different liquids listed of the geomet ⁇ c standard deviation (GSD) vs dimensionless liquid flow rates
  • the method is carried out by forcing a liquid from a liquid supply means, e.g. a tube.
  • the liquid exits the supply means into a pressure chamber filled with a second fluid which is preferably a gas.
  • the chamber has an exit port preferably positioned directly in front of and preferably downstream of the flow of liquid exiting the supply means.
  • the exit port may be positioned slightly upstream of the liquid supply means exit.
  • the liquid is focused by the gas to substantially smaller dimensions as it exits the supply means e.g. a tubular stream of liquid one unit in diameter is focused to a stream 1/2 - 1/400 of a unit in diameter or smaller depending on operating conditions.
  • a focused cylindrical stream of one unit in diameter would be expected to undergo Rayleigh breakup and form particles which are about 1.89 times the diameter of the focused stream.
  • the liquid stream is first focused by the gas flowing out of the chamber thereby forming a stream with a much smaller diameter. That stream leaves the chamber and forms particles which are smaller in diameter than the focused stream.
  • the nozzles and methods of the present mvention are capable of producing extremely small particles.
  • a cylindrical liquid supply means having a diameter of 1000 units.
  • the stream from such a supply means would be expected to undergo normal Rayleigh breakup of the 1000 unit diameter stream to form spherical particles having a diameter of about 1.89 x 1000 or 1890 units in diameter.
  • the stream having a diameter of 1000 units is focused to a stream or jet of smaller dimension by a surrounding gas the jet might have a diameter of one tenth that size or 100 units. That 100 unit diameter focused jet would be expected to undergo normal Rayleigh breakup to form particles having a diameter of 1.89 x 100 or 189 units.
  • Focusing the diameter of the stream to a narrow focused jet or "stable microjet” jet has been referred to as flow focusing technology.
  • the focused jet has a diameter - , at a given point A in the stream characterized by the formula:
  • the diameter of the jet (d-) can be any reduced dimension smaller than that of liquid stream exiting the supply means, e.g. can have a cross-sectional diameter of from about one half to about 1/100 the area of the stream exiting the liquid supply means.
  • the liquid flow exiting the supply means with a diameter of 1000 units is focused as it leaves the supply means so that the end of the exiting drop exiting the liquid supply tube is focused by the surrounding gas to a reduced dimension (e.g. V. to 1/100 the cross-sectional diameter of the liquid supply means).
  • a reduced dimension e.g. V. to 1/100 the cross-sectional diameter of the liquid supply means.
  • the 1000 unit stream is reduced to a diameter of about 100 units. That 100 unit end of the drop is subjected to turbulent action by the gas exiting the pressure chamber thereby forming particles which are 10 units in diameter.
  • the method of the invention can produce particles which are substantially smaller than (e.g. Vi to 1/100) the size of particles produced using flow focusing technology.
  • flow focusing technology can produce particles which are substantially smaller than (e.g. Vi to 1/100) the size of particles produced by normal capillary breakup of a stream.
  • each configuration or embodiment will comprise a means for supplying a liquid or first fluid and a means for supplying a second fluid (preferably a gas) in a pressure chamber which surrounds at least an exit of the means for supplying a liquid.
  • the liquid supply means and pressure chamber are positioned such that turbulent action takes place between the liquid exiting the liquid supply means and the second fluid, a liquid or a gas, exiting the supply chamber.
  • the exit opening of the pressure chamber is downstream of and more preferably it is directly aligned with the flow path of the means for supplying the liquid.
  • the means for supplying a liquid is often referred to as a cylindrical tube (tube shape could be varied, e.g. oval, square, rectangular).
  • the first fluid or liquid can be any liquid depending on the overall device which the invention is used within.
  • the liquid could be a liquid formulation of a pharmaceutically active drug used to create dry particles or liquid particles for an aerosol for inhalation or, alternatively, it could be a hydrocarbon fuel used in connection with a fuel injector for use on an internal combustion engine or heater or other device which bums hydrocarbon fuel.
  • the second fluid is generally described herein as being a gas and that gas is generally air or an inert gas.
  • the first fluid is a liquid and the second fluid may be a gas or a liquid provided the first and second fluids are sufficiently different from each other (e.g. immiscible). It is possible to have situations wherein the liquid exits either the liquid supply means or the pressure chamber vaporizes to a gas on exit. Such is not the general situation. Notwithstanding these different combinations of liquid-gas, and liquid-liquid, the invention is generally described with a liquid formulation being expelled from the supply means and interacting with surrounding gas flowing out of an exit of the pressure chamber. Further, the exit of the pressure chamber is generally described as circular in cross-section and widening in a funnel shape (Fig. 1), but could be any configuration.
  • the nozzle 1 is comprised of two basic components which include the pressure chamber 2 and the liquid supply means 3.
  • the pressure chamber 2 is pressurized by fluid flowing into the chamber by the entrance port 4.
  • the liquid supply means 3 includes an inner tube 5 where liquid flows.
  • the inner tube 5 of the liquid supply means 3 is preferably supplied with a continuous stream of a fluid which fluid is preferably in the form of a liquid.
  • the pressure chamber 2 is continuously supplied with a pressurized fluid which may be a liquid or a gas.
  • a pressurized fluid which may be a liquid or a gas.
  • the inner tube 5 of the liquid supply means 3 includes an exit point 6.
  • the pressurized chamber 2 includes an exit point 7.
  • the exit point 7 of the pressure chamber is preferably positioned directly downstream of the flow of liquid exiting the exit point 6.
  • the liquid supply means exit and the exit of the pressure chamber are configured and positioned so as to obtain two effects (1) the dimensions of the stream exiting the liquid supply means are reduced by the fluid exiting the pressure chamber; and (2) the liquid exiting the liquid supply means and the fluid exiting the pressure chamber undergo a violent interaction to form much smaller particles than would form if the stream of liquid in reduced dimensions underwent normal capillary instability, e.g. formed spherical particles 1.89 times the diameter of the cylindrical stream.
  • the exit port of the chamber 2 is directly aligned with the flow of liquid exiting the liquid supply means 3.
  • An important aspect of the invention is to obtain small particles 8 from the liquid 9 flowing out of the exit port 6 of the inner tube 5.
  • Obtaining the desired formation of particles 8 is obtained by correctly positioning and proportioning the various components of the liquid supply means 3 and the chamber 2 as well as the properties of the fluids including the speed of these fluids which flow out of both the liquid supply means 3 and the chamber 2.
  • the liquid 9 is held within the inner tube 5 which is cylindrical in shape.
  • the inner tube 5 holding the liquid 9 may be asymmetric, oval, square, rectangular or in other configurations including a configuration which would present a substantially planar flow of liquid 9 out of the exit port 6.
  • the nozzle of the invention applies to all kinds of round (e.g., axi-symmetric) and planar (e.g., symmetric two- dimensional) configurations that have a convergent passage for the outer fluid.
  • a round but not axi-symmetric geometry would be one in which the surfaces of the orifice plate are faceted at different azimuthal angles.
  • Formation of the microjet and its acceleration and ultimate particle formation are based on the abrupt pressure drop associated with the steep acceleration experienced by the liquid on passing through an exit orifice of the pressure chamber which holds the second fluid (i.e. the gas).
  • the creation of the violently focused aerosol may occur as follows.
  • the strong radial fluid flow (10) that exists in the very narrow gap between the points 6 and 7 becomes circulatory as it passes through and out of the orifice of the exit 7 of the pressure chamber 2.
  • the liquid (9) meniscus is sucked in towards the center of the exit point 7 of the chamber 2.
  • the gas 10 exits the hole at point 7 its strong circulatory motion induces the fluid dynamic effect referred to as a vortex breakdown. This is an instability in which fluid particles gain so much centrifugal inertia that they spin off away from the axis.
  • a dashed line C — C is shown running through the center of the inner tube 5 in which the liquid 9 flows as well as the exit of the chamber 2.
  • the line C— C represents the plane of symmetry intersection of the plane of view.
  • the line B--B' represents the bisector of the convergent passage near the center of the nozzle.
  • the area referred to as the "convergent passage” is the region which is the open area between the terminal face 11 of the liquid supply means 3 and the front face 12 of the chamber 2.
  • the primary characteristic of the present invention is the facilitation of a strongly convergent (imploding) flow of outer fluid 10 towards and around the inner liquid 9.
  • the fluid 10 in the pressure chamber should preferably not merely flow parallel to the liquid 9 exiting the liquid supply means, i.e. should preferably not intersect at a 0 degree angle.
  • the fluid 10 in the pressure chamber should preferably not flow directly perpendicular to the liquid stream 9 exiting the liquid supply means, i.e. should preferably not interact at a 90 degree angle or more.
  • convergence of the two fluids is preferably at an angle of more than 0 degrees and less than 90 degrees.
  • the fluid 10 of the pressure chamber could, in some situations be directed at the liquid 9 from the liquid supply means at an angle of 90 degrees or more, i.e., at an angle such that the fluid 10 is flowing back toward the liquid 9 and is converging on the liquid 9 at an angle of up to 150 degrees.
  • Flow convergence improves the transfers of momentum and kinetic energy from the outer fluid 10 to the inner liquid 9 required to breakup the inner fluid 9 into particles 8. Improving the efficiency of such transfer results in energy savings for a given amount of inner liquid 9 atomized and a given droplet size requirement.
  • a greater efficiency of atomization is achieved by transferring a greater fraction of pressure energy originally in the outer fluid 10 per unit mass of the outer fluid to the inner liquid 9.
  • the outer fluid 10 In order to generate significant convergence in the outer fluid 10 towards the inner liquid 9, the outer fluid 10 must be admitted into a path that gives it a sufficiently high converging speed. Specifically, the following design constraints shown in Figure 3 are preferred.
  • the length of the convergent passage should be chosen such that an optimum is found that encourages a significant bending of the streamlines towards the inner fluid 9.
  • D is required to be at least equal to 1.2 times D 0 ,
  • the convergent passage separation between R and P must be chosen appropriately.
  • This distance can be defined as the distance between points R and P in Figure 2.
  • this variable regulates the relative average velocity between the inner liquid 9 and the outer fluid 10 at the point of encounter (inner rim of tube exit indicated by point P' in Figures 2 and 3).
  • a very narrow convergent passage is one in which frictional losses dissipate the outer fluid momentum significantly. Widening such a passage will encourage coupling between outer fluid 10 and inner liquid 9.
  • 0.25; while for planar-two dimensional configurations, ⁇ equals 0.5.
  • H must be large enough to preclude excessive friction between the outer fluid and the convergent passage walls that can slow down the flow and waste pressure energy (stagnation enthalpy) into heat (internal energy).
  • An approximate guiding principle is that H should be greater than H mm , defined as a few times the thickness of the viscous boundary layer ⁇ L that develops inside the outer fluid 10 in its acceleration through the convergent passage:
  • ⁇ L (L ⁇ 2 /(p 2 P o2 ) 05 ) 05
  • ⁇ 2 is the dynamic viscosity coefficient of the outer fluid 10
  • p 2 is its density
  • P o2 is the pressure of the outer fluid 10 in the upstream chamber
  • is a numerical factor, which generally is between 1 and 10.
  • L is the length of the convergent passage ( Figure 3)
  • the inner liquid 9 coming out of the inner tube 5 gets funnel-shaped into a jet that gets thinner as it flows downstream.
  • the jet can have a variety of different configurations, e.g. a circular cross-section, or a flat planar one. Any configuration can be used which provides flows through the center of the discharge orifice 7, and can become much thinner as it enters the discharge orifice 7 than at the exit 6 of the inner tube 5. This phenomenon has previously been termed "flow-focusing" (see WO 99/31019 published June 24, 1999).
  • the forces responsible for the shaping of the inner liquid 9 are believed to arise from the pressure gradients that set within the outer fluid 10 as it flows through the discharge orifice 7.
  • a round inner liquid jet is expected to attain a diameter dj determined by the V. power law with liquid flow rate Q (in volume per unit of time, e.g. cubic meter per second; Ganan-Calvo A. M., 1998):
  • Vortex breakdown A theoretical model based on the existence of a vortex cell near the region of breakup is proposed to explain the effectiveness of atomization obtained by the present invention in the case of axi-symmetric geometries.
  • the strong radial forces provided by the outer fluid flow between the orifice body and the liquid dispenser result in a violent swirl in the outer fluid (Shtern and Hussain 1999).
  • the swirling motion results in a vortex which breaks down near the region of breakup.
  • Such breakdown is the centrifugal explosion of the fluid streamlines due to their rapid spinning motion.
  • any swirling of the outer fluid is not created upstream by means of swirling vanes or other shapes of the atomizer body. Instead, the swirling is induced locally by the strong converging motions forced by the very simple geometry of the atomizer.
  • Characteristics of supersonic flow such as shock waves may improve atomization. However, such are not believed to be required.
  • Unique characteristics of the present invention include: (f) High frequency of droplet generation, (g) Low requirements on liquid pressure, (h) Low sensitivity of drop size to inner liquid flow rate, (i) Little apparent effect of atomizer size on droplet size.
  • the inner liquid 9 does not have to be pushed out of its inner tube 5 with a sufficiently high pressure capable of maintaining a stable liquid jet in the absence of outer fluid flow and solid surfaces in its way. It is not necessary for the inner liquid to form a stable microjet structure. Further, pre-existent inner liquid jet structure coming directly out of the exit opening 6 is not required because, a explained in (c), the liquid meniscus is focused by the action of the outer fluid pressure forces.
  • Figures 6-9 show results for aerosols produced by methods of the present invention using dry air and dry nitrogen as outer fluids 10, and a range of liquids as inner fluids 9: distilled water, 2-propanol, 20 % (v/v) by volume of ethanol in water
  • Figure 6 is a graph of the volume median diameter (VMD) vs the liquid supply flow rate for four different liquids.
  • VMD / d 0 5.60 (Q/Q 0 ) 0208
  • Figure 8 graphs the new fit characteristic of the new method together with the one which would correspond to the Rayleigh breakup of a flow focused jet at the same conditions of liquid properties, flow rate, and gas pressure (thus equal d 0 , Q, and Q 0 ).
  • the results shown in Figure 8 are based on the theoretical assumption that Rayleigh breakup of a flow-focused jet would result in droplets of uniform diameter (VMD) equal to 1.89 times the jet diameter (Brodkey 1995). Applying the equation for the jet diameter given earlier leads to:
  • VMD 1.89 (8p,/ ( ⁇ 2 ⁇ P Practice))" 4 Q 1/2
  • VMD / d 0 1.89 (8/ ⁇ 2 ) 1/4 (Q/Q 0 ) 1 2
  • the proposed atomization system obviously requires delivery of the liquid to be atomized and the gas to be used in the resulting spray. Both should be fed at a rate ensuring that the system lies within the desired parameter window. Multiplexing is effective when the flow-rates needed exceed those obtained for an individual cell. More specifically, a plurality of feeding sources 3 or holes therein forming tubes 3 may be used to increase the rate at which aerosols are created. The flow-rates used should also ensure the mass ratio between the flows is compatible with the specifications of each application.
  • the gas and liquid can be dispensed by any type of continuous delivery system (e.g. a compressor or a pressurized tank the former and a volumetric pump or a pressurized bottle the latter). If multiplexing is needed, the liquid flow-rate should be as uniform as possible among cells; this may entail propulsion through several capillary needles, porous media or any other medium capable of distributing a uniform flow among different feeding points.
  • a compressor or a pressurized tank the former and a volumetric pump or a pressurized bottle the latter e.g. a compressor or a pressurized tank the former and a volumetric pump or a pressurized bottle the latter.
  • liquid supply means 3 may be planar with grooves therein, but need not be strictly planar, and may be a curved feeding device comprised of two surfaces that maintain approximately the same spatial distance between the two pieces of the liquid supply means.
  • curved devices may have any level of curvature, e.g. circular, semicircular, elliptical, hemi-elliptical, etc.
  • a device of the invention may be used to provide particles for drug delivery, e.g.
  • the device would produce aerosolized particles of a pharmaceutically active drug for delivery to a patient by inhalation.
  • the device is comprised of a liquid feeding source such as a channel to which formulation is added at one end and expelled through an exit opening.
  • the feeding channel is surrounded by a pressurized chamber into which gas is fed and out of which gas is expelled from an opening.
  • the opening from which the gas is expelled is positioned directly in front of the flow path of liquid expelled from the feeding channel.
  • Various parameters are adjusted so that pressurized gas surrounds liquid flowing out of the feeding channel in a manner so as to reduce the dimension of the flow which is then broken up on leaving the chamber.
  • the aerosolized particles are inhaled into a patient's lungs and thereafter reach the patient's circulatory system.
  • the method of the invention is also applicable in the mass production of dry particles.
  • Such particles are useful in providing highly dispersible dry pharmaceutical particles containing a drug suitable for a drug delivery system, e.g. implants, injectables or pulmonary delivery.
  • the particles formed of pharmaceutical are particularly useful in a dry powder inhaler due to the small size of the particles (e.g. 1-5 microns in aerodynamic diameter) and conformity of size (e.g. 3 to 30%> difference in diameter) from particle to particle.
  • Such particles should improve dosage by providing accurate and precise amounts of dispersible particles to a patient in need of treatment.
  • Dry particles are also useful because they may serve as a particle size standard in numerous applications.
  • the first fluid is preferably a liquid
  • the second fluid is preferably a gas, although two liquids may also be used provided they are generally immiscible.
  • Atomized particles are produced within a desired size range (e.g., 1 micron to about 5 microns).
  • the first fluid liquid is preferably a solution containing a high concentration of solute.
  • the first fluid liquid is a suspension containing a uniform concentration of suspended matter. In either case, the liquid quickly evaporates upon atomization (due to the small size of the particles formed) to leave very small dry particles.
  • the device of the invention is useful to introduce fuel into internal combustion engines by functioning as a fuel injection nozzle, which introduces a fine spray of aerosolized fuel into the combustion chamber of the engine.
  • the fuel injection nozzle has a unique fuel delivery system with a pressure chamber and a fuel source.
  • Atomized fuel particles within a desired size range e.g., 5 micron to about 500 microns, and preferably between 10 and 100 microns
  • Atomized fuel particles within a desired size range are produced from a liquid fuel formulation provided via a fuel supply opening. Different size particles of fuel may be required for different engines.
  • the fuel may be provided in any desired manner, e.g., forced through a channel of a feeding needle and expelled out of an exit opening of the needle.
  • a second fluid e.g. air
  • a pressure chamber which surrounds at least the area where the formulation is provided (e.g., surrounds the exit opening of the needle) is forced out of an opening positioned in front of the flow path of the provided fuel (e.g. in front of the fuel expelled from the feeding needle).
  • Various parameters are adjusted to obtain a fuel-fluid interface and an aerosol of the fuel, which allow formation of atomized fuel particles on exiting the opening of the pressurized chamber.
  • Fuel injectors of the invention have two significant advantages over prior injectors. First, fuel generally does not contact the periphery of the exit orifice from which it is emitted because the fuel stream is surrounded by a gas (e.g.
  • the fuel exits the orifice and forms very small particles which may be substantially uniform in size, thereby allowing faster and more controlled combustion of the fuel.
  • Molecular assembly presents a 'bottom-up' approach to the fabrication of objects specified with enormous precision.
  • Molecular assembly includes construction of objects using tiny assembly components, which can be arranged using techniques such as microscopy, e.g. scanning electron microspray.
  • Molecular self-assembly is a related strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions as small as 1 to 100 nanometers, and having molecular weights of 10 4 to 10 10 daltons.
  • Microelectro-deposition and microetching can also be used in microfabrication of objects having distinct, patterned surfaces.
  • Atomized particles within a desired size range can be produced to serve as assembly components to serve as building blocks for the microfabrication of objects, or may serve as templates for the self-assembly of monolayers for microassembly of objects.
  • the method of the invention can employ an atomizate to etch configurations and/or patterns onto the surface of an object by removing a selected portion of the surface.
PCT/US2000/015931 1999-06-11 2000-06-09 Method for producing an aerosol WO2000076673A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP00938249.0A EP1192009B1 (de) 1999-06-11 2000-06-09 Verfahren zur erzeugung eines aerosols
JP2001502989A JP2003501257A (ja) 1999-06-11 2000-06-09 エーロゾルを生成する方法
AU53318/00A AU767486B2 (en) 1999-06-11 2000-06-09 Method for producing an aerosol
ES00938249T ES2424713T4 (es) 1999-06-11 2000-06-09 Método para producir un aerosol
CA2374232A CA2374232C (en) 1999-06-11 2000-06-09 Method for producing an aerosol

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US13869899P 1999-06-11 1999-06-11
US60/138,698 1999-06-11

Publications (1)

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WO2000076673A1 true WO2000076673A1 (en) 2000-12-21

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EP (1) EP1192009B1 (de)
JP (1) JP2003501257A (de)
AU (1) AU767486B2 (de)
CA (1) CA2374232C (de)
ES (1) ES2424713T4 (de)
WO (1) WO2000076673A1 (de)

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WO2004002627A2 (en) * 2002-06-28 2004-01-08 President And Fellows Of Harvard College Method and apparatus for fluid dispersion
US6682716B2 (en) 2001-06-05 2004-01-27 Alexza Molecular Delivery Corporation Delivery of aerosols containing small particles through an inhalation route
US6716415B2 (en) 2001-05-24 2004-04-06 Alexza Molecular Delivery Corporation Delivery of sedative-hypnotics through an inhalation route
US6737043B2 (en) 2001-05-24 2004-05-18 Alexza Molecula Delivery Corporation Delivery of alprazolam, estazolam, midazolam or triazolam through an inhalation route
US6759029B2 (en) 2001-05-24 2004-07-06 Alexza Molecular Delivery Corporation Delivery of rizatriptan and zolmitriptan through an inhalation route
US6805853B2 (en) 2001-11-09 2004-10-19 Alexza Molecular Delivery Corporation Delivery of diazepam through an inhalation route
WO2004091763A2 (en) * 2003-04-10 2004-10-28 President And Fellows Of Harvard College Formation and control of fluidic species
WO2006037823A1 (es) 2004-09-30 2006-04-13 Universidad De Sevilla Dispositivo para la atomización neumática de líquidos mediante flujo implosivo de gas
EP1663499A2 (de) * 2003-08-26 2006-06-07 Aradigm Corporation Durch ausgerichtete fluidströmung erzeugtes aerosol und diese erzeugende vorrichtungen und verfahren
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EP1192009A1 (de) 2002-04-03
ES2424713T4 (es) 2014-01-23
EP1192009B1 (de) 2013-05-01
AU5331800A (en) 2001-01-02
JP2003501257A (ja) 2003-01-14
CA2374232C (en) 2013-08-20
CA2374232A1 (en) 2000-12-21
EP1192009A4 (de) 2006-10-18
AU767486B2 (en) 2003-11-13

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