U.S. patent application number 10/649376 was filed with the patent office on 2006-08-03 for aerosol created by directed flow of fluids and devices and methods for producing same.
This patent application is currently assigned to Aradigm Corporation. Invention is credited to Alfonso Ganan-Calvo, Joan Rosell.
Application Number | 20060169800 10/649376 |
Document ID | / |
Family ID | 34216934 |
Filed Date | 2006-08-03 |
United States Patent
Application |
20060169800 |
Kind Code |
A1 |
Rosell; Joan ; et
al. |
August 3, 2006 |
Aerosol created by directed flow of fluids and devices and methods
for producing same
Abstract
A method of creating small particles by a technology referred to
here as "violent focusing" is disclosed, along with devices for
generating such violent focusing. In general, the method comprises
the steps of forcing a first fluid out of an exit opening of the
feeding channel to create a fluid stream. The exit opening is
positioned such that the fluid flowing out of the channel flows
toward and out of an exit orifice of a pressure chamber which
surrounds the exit opening of the feeding channel, and is filled
with an atomizing fluid. An atomizing fluid such as a gas is
directed towards the first fluid stream in approximately orthogonal
directions and surrounding the circumference of the first fluid
stream from all sides. The first fluid flow is broken into
particles which have dimensions which are smaller than the
dimensions of this fluid stream.
Inventors: |
Rosell; Joan; (Castro
Valley, CA) ; Ganan-Calvo; Alfonso; (Sevilla,
ES) |
Correspondence
Address: |
BOZICEVIC, FIELD & FRANCIS LLP
1900 UNIVERSITY AVENUE
SUITE 200
EAST PALO ALTO
CA
94303
US
|
Assignee: |
Aradigm Corporation
|
Family ID: |
34216934 |
Appl. No.: |
10/649376 |
Filed: |
August 26, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09591365 |
Jun 9, 2000 |
|
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10649376 |
Aug 26, 2003 |
|
|
|
60138698 |
Jun 11, 1999 |
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Current U.S.
Class: |
239/418 |
Current CPC
Class: |
B05B 7/0408 20130101;
A61M 11/06 20130101; B05B 7/0433 20130101; F23D 11/104 20130101;
B05B 1/005 20130101; A61M 15/0003 20140204; B05B 7/0458 20130101;
B05B 7/0475 20130101 |
Class at
Publication: |
239/418 |
International
Class: |
F23D 11/10 20060101
F23D011/10 |
Claims
1. A method, comprising: forcing a first fluid through a feeding
supply means and out of an exit opening of the feeding supply means
as a first fluid stream; filling a pressure chamber with a second
fluid which chamber is in fluid connection with the exit opening of
the feeding supply means; forcing the second fluid toward and into
the first fluid stream circumference in a manner which reduces the
circumference of the first fluid stream and breaks the stream into
particles having a diameter less than the diameter of the exit
opening of the first fluid feeding supply means; and allowing the
second fluid to exert force on the first fluid and force particles
of the first fluid out of an exit orifice of the pressure chamber
positioned downstream of a direction of flow of the first fluid
stream.
2. The method of claim 1, wherein the first fluid is a liquid and
the second fluid is a gas.
3. The method of claim 1, wherein the second fluid is forced into
the first fluid stream circumference at an angle in a range of from
about 15.degree. to about 90.degree..
4. The method of claim 1, wherein the second fluid is forced into
the first fluid stream circumference at an angle in a range of from
about 30.degree. to about 90.degree..
5. The method of claim 1, wherein the second fluid is forced into
the first fluid stream circumference at an angle in a range of from
about 45.degree. to about 90.degree..
6. The method of claim 1, wherein the second fluid is forced into
the first fluid stream circumference at an angle in a range of from
about 90.degree..+-.5.degree..
7. The method of claim 1, wherein the first fluid is caused to move
at a speed equal to or greater than the speed of sound in air.
8. The method of claim 1, wherein the second fluid is caused to
move at a speed equal to or greater than the speed of sound in
air.
9. The method of claim 1, wherein the exit opening of the feeding
supply means is about 0.5 to 1.2 times the diameter of the exit
orifice of the pressure chamber.
10. The method of claim 1, wherein the exit opening of the feeding
supply means is about 0.7 to 1.2 times the diameter of the exit
orifice of the pressure chamber.
11. The method of claim 1, wherein the exit opening of the feeding
supply means is about 0.8 to 1.0 times the diameter of the exit
orifice of the pressure chamber.
12. The method of claim 1, wherein the pressure chamber comprises a
channel with a first channel opening at a main portion of the
chamber and second channel opening which encircles an area where
the first fluid stream flows.
13. The method of claim 12, wherein the second channel opening is
less than two times the diameter of the exit orifice of the
pressure chamber.
14. The method of claim 12, wherein the second channel opening is
less than one time the diameter of the exit orifice of the pressure
chamber.
15. The method of claim 12 wherein the ratio of the diameter of the
second channel opening to the diameter of the exit orifice of the
pressure chamber is in a range of from about 0.2 to about 0.7.
16. The method of claim 1, wherein the particles formed have 1/10
or less the mean volume of the particles expected to be formed by
normal Rayleigh breakup.
17. The method of claim 1, wherein the particles formed are
sufficiently small that their surface tension forces substantially
match the amplitude of pressure fluctuations created by the first
fluid and second fluid exiting the pressure chamber.
18. A method, comprising: forcing a liquid through a supply
component and out of circular exit opening of the supply component
as a liquid stream; directing a flow of gas around a circumference
of the liquid stream at an angle of from about 45.degree. to about
90.degree. causing the liquid and gas to physically interact; and
allowing the liquid and gas to escape from an opening positioned
downstream of a direction of flow of the liquid stream and form
liquid particles suspended in the gas.
19. The method of claim 18, wherein the liquid comprises a
pharmaceutically active drug.
20. The method of claim 19, further comprising: inhaling the
particles of liquid suspended in the gas.
21. The method of claim 18, wherein the liquid is comprised of a
hydrocarbon fuel.
22. The method of claim 21, further comprising: igniting the
particles suspended in the gas.
23. A method of creating an aerosol, the method comprising the
steps of: forcing a liquid through a feeding channel and out of an
exit opening of the feeding channel wherein the exit opening of the
feeding channel is positioned such that the liquid flowing out of
the channel flows toward and out of an exit orifice of a chamber
surrounding the exit opening of the feeding channel; forcing a gas
into the chamber and out of the exit orifice of the chamber;
wherein the exit opening of the feeding channel has a diameter in
the range of about 5 to about 10,000 micro-meters and the exit
opening of the channel is positioned at a distance in a range of
from about 5 to about 10,000 micro-meters from an entrance point of
the exit orifice.
24. A method of creating an aerosol, comprising the steps of:
forcing a liquid out of an exit opening of a liquid supply means to
form a liquid stream; forcing a gas into a chamber and out of an
exit orifice of the chamber aligned with a flow path of liquid
flowing out of the exit opening whereby the liquid stream is
focused by the gas to dimensions smaller than dimensions of the
exit opening; wherein the exit opening and exit orifice are
positioned such that particles formed outside the exit orifice have
a size determined by the relationship between the particle surface
tension and the amplitude of turbulent pressure fluctuation outside
the chamber and further wherein that relationship is such that the
particles have dimensions smaller than any dimension of the focused
liquid stream.
25. A method, comprising the steps of: forcing a liquid out of an
exit opening of a liquid supply means; forcing a gas into a
pressure chamber and out of an exit orifice of the chamber; causing
the gas to converge against the liquid exiting the liquid supply
means thereby (a) causing the liquid to assume dimensions smaller
than dimensions of the exit opening of the liquid supply means; (b)
creating a violent interaction between the liquid and the gas; (c)
carrying the liquid away from the exit orifice of the pressure
chamber; and (d) resulting in the liquid forming particles which
are smaller in size than expected based on spontaneous capillary
breakup of the assumed smaller dimensions of the liquid.
26. The method of claim 25, wherein the exit opening of the feeding
supply means has an opening with a cross-sectional configuration
chosen from a circle, an oval, a square and an elongated
rectangular slit.
Description
CROSS-REFERENCES
[0001] This application is a continuation-in-part of application
Ser. No. 09/591,365 filed Jun. 9, 2000 which claims priority to
earlier filed provisional application Ser. No. 60/138,698 filed
Jun. 11, 1999, which applications are incorporated herein by
reference in their entirety.
FIELD OF THE INVENTION
[0002] This application generally relates to the creation particles
created by the directed flow of fluids.
BACKGROUND OF THE INVENTION
[0003] 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.
There are numerous ways of finely breaking up an fluid (typically,
a liquid, an emulsion, or a suspension or a slurry of particles
suspended in a liquid) into droplets. Referring to this fluid as
the first fluid, the present invention pertains to a class of
methods in which a second fluid provides the energy necessary to
finely divide and disperse the first fluid into smaller fragments
or particles. Two characteristics of the size distribution of the
particles are generally sought: an average particle size, and a
dispersion or variability of particle sizes, both of which are
tuned to meet the requirements of a particular application. In
addition, the energy consumption per unit mass of the first fluid,
and the proportion of first and second fluid masses are also of
paramount importance, as are the durability, manufacturability, and
cost of a particular atomizer design.
[0004] In a carburetor of a piston engine with spark ignition, the
liquid is atomized finely to enhance evaporation of the fuel, and
subsequent combustion (Bayvel-Orzechowski, 1993, page 199). In
pulmonary drug delivery via an aerosol, particles with a mass
median aerodynamic diameter typically between 0.5 and 6 micron are
required. In this application, the goal is to generate small enough
particles so that they can be transported to the lung of the
patient via inhalation, and deposited in the desired region of the
lung by inertial impaction or gravitational sedimentation, with
smaller particles depositing more peripherally.
[0005] Methods in which this second fluid is a gas and the first
fluid is a liquid have a long history. They are known as "pneumatic
atomization", also as "two-fluid atomization" (Gretzinger-Marshall,
1961), and as "twin fluid" atomization. Pneumatic atomization has
been reviewed by Lefebvre (1989), and by Bayvel-Orzechowski (1993).
The first fluid to be atomized (a liquid) is generally passed
through a passage or channel and out of an exit into a region in
which the liquid encounters and interacts with the atomizing fluid,
a gas. The exit end of the channel is thus positioned such that the
liquid coming out of such end encounters gas moving at sufficient
velocity to allow atomization to take place. Pneumatic atomizers
are widely used in applications in which a source of compressed gas
exists, and good dispersion of the particles within the gas is
desired. Some examples are molten metal atomization for the
production of metal strip (Layernia-Wu, page 21), and fuel oil
atomization in boiler furnaces. In the first example, the goal is
to obtain the right metal droplet size at reduced cost, but the
droplets must typically be heavy enough to deposit, gravitationally
or by inertial impaction for example, on a substrate. In the second
example, the object is to generate as small a particle as possible
so that it can evaporate or have enough surface area for the
combustion to proceed to as nearly to completion as possible, to
avoid wasting fuel, and releasing incompletely oxidized fuel into
the environment.
[0006] Pneumatic atomizers have been classified according to low-,
intermediate-, or high-gas pressure (Table 4-3 in
Bayvel-Orzechowski, 1993, p 196). They have also been classified
considering the direction of gas action on the liquid
(Bayvel-Orzechowski, 1993 page 197.) In "swirl-flow atomizers", one
of the two fluids is subjected to swirling before it encounters the
other fluid. In "parallel-flow atomizers", the liquid flow is in
the same mean direction as the gas at the moment of encounter.
Examples of this type are so-called "concentric nebulizers" and
"convergent atomizers" (such as in U.S. Pat. No. 6,166,379, widely
used for inductively coupled plasma mass spectrometry, ICP-MS; or
as shown in Gretzinger-Marshall, 1961.) In "cross-flow atomizers",
liquid jets are introduced into a gas stream, commonly at 90
degrees from a single direction, although angles smaller and
greater than this have been used (Bayvel-Orzechowski, 1993 pages
199-204.) Cross flow atomizers with external action (i.e. where the
gas is impinged on a liquid jet outside the nozzle) are widely used
for the atomization of molten metal (Layernia-Wu, 1996). The active
participation of the air during the disintegration process
distinguishes pneumatic methods from (non-pneumatic) methods in
which the gas flow only serves to disperse the droplets resulting
from the spontaneous disintegration of liquid jets by capillary
instability, thus preventing droplet coagulation or impaction on
solid walls (Schuster et al. 1997). However, the air can
participate to varying degrees.
[0007] Pneumatic atomizers are also referred to by the terms
"Air-assist" and "Airblast". The distinction made is that in air
assist atomization, there is a source of high pressure gas, while
the air velocity in an airblast atomizer is usually limited to 120
m/s. Thus, air assist atomizers are characterized by a relatively
small quantity of high velocity air, while airblast atomizers use a
higher quantity of limited velocity air. Airblast atomizers are
used in aircraft, marine and industrial gas turbines. The need for
an external supply of high pressure air, for example, has ruled out
air-assist atomizers for aircraft applications. (Lefebvre, 1989,
chapter 4)
[0008] Gas can participate in creating atomization in a
mechanistically different way from traditional pneumatic methods.
This is what occurs in the so called "flow focusing" method, in
which a fluid flows out of a chamber through an orifice, and a tube
inside the chamber and supplying a slow stream of another fluid,
which is immiscible in the first fluid, is brought towards the
orifice through which a first fluid is exiting the chamber. As the
first fluid exits the end of the tube, it senses the pressure
gradients that have set up in the flow of the other fluid, and gets
accelerated towards the center of the orifice under the influence
of those pressure gradients, thus attaining a very small stream
width. The break up of the resulting thin stream of first fluid can
proceed via normal Rayleigh capillary instability. [U.S. Pat. No.
6,119,953 and other U.S. patents to Ganan-Calvo.
SUMMARY OF THE INVENTION
[0009] A method of creating small particles, aerosols, and
hydrosols, by a technology referred to here as "violent focusing"
of a fluid, to break up and disperse said fluid is disclosed, along
with devices for generating such violent focusing. The fluid to be
atomized (first fluid) exits from a supply means. A second fluid, a
gas for the generation of aerosols, or a liquid for the generation
of hydrosols, emulsions, and micro-bubbles, surrounds the exit of
the supply means, and is directed with a high speed onto the first
fluid in the region immediately outside and in front of said exit.
Immediately before encountering the first fluid, the direction of
flow of the second fluid is substantially orthogonal to the stream
of first fluid, and the width of the stream of second fluid
directed towards the first fluid is similar or smaller than the
width of the first fluid stream at the exit of the first fluid
supply means. The action of the second fluid on the first fluid is
to cause a focused stream of first fluid to breakup into small
particles, arising both from the pressure gradient forces and shear
stresses that the second fluid exerts on the first fluid. During
the process of atomization, the speed of the stream of second fluid
is higher than the speed of the first fluid stream. In general, the
technique can be expanded to three, four, or any number of fluids.
For example, the second fluid can be used to form a concentric
cylinder around the stream of the first fluid which stream
disassociates resulting in encapsulation of the particles of the
first fluid, and the third fluid can be a gas for aerosolizing the
encapsulated particles, or a liquid for providing a hydrosol of the
encapsulated particles. Such techniques would have utility in the
generation of, for example, timed release formulations of
pharmaceuticals for injection or inhalation. Examples of
appropriate encapsulation media include, but are not limited to
liposomes, polymers, or glycols.
[0010] While pneumatic methods have inherent advantages, successful
applications of pneumatic atomization depend on proper management
of the inherent disadvantages of this form of atomization.
Pneumatic atomizers are disadvantageous relative to non-pneumatic
forms of atomization in their need of a source of compressed gas,
as well as in their generally higher requirements of energy used to
atomize a unit mass of liquid. This higher energy usage is
recognized to be associated with the need to compress gas, but is
also associated with a general low efficiency of energy transfer.
Another disadvantage associated to pneumatic atomizers is their
relatively complex geometry/structure, which makes them more
expensive to manufacture. (Bayvel-Orzechowski, 1993, page 195)
[0011] The needs for improving energy efficiency and for reducing
design complexity are usually conflicting. For example, in order to
improve energy exchange between the gas and the liquid, atomizers
with a complicated design that allows combined internal and
external exposure of the liquid to the air have been devised (FIG.
4-48, and Ref 24 in Bayvel-Orzechowski, 1993, p 199). In another
example, Jennings in U.S. Pat. No. 3,463,404 teaches a system for
maintaining good atomization at a variety of liquid flows. While
this system is simple in design, it requires incurring large energy
losses associated with forcing the gas through a porous plug in the
region immediately preceding the region of encounter of the gas
with the liquid.
[0012] Energy transfer is sometimes facilitated by providing a
narrow passage for the air at the location where the two fluids
meet. This has the effect of raising the local speed (and thus
momentum) at which the second fluid encounters the first fluid, for
a given total mass flow rate of second fluid available. Momentum is
the driving force for these forms of atomization, with higher
momentum leading to greater shear forces that breaks up the first
fluid.
[0013] The air-liquid combination is just one of the fluid
combinations that this disclosure is concerned with. Energy
efficiency is managed in the present invention by a) avoiding
excessive energy losses in the transfer of the fluids from their
high pressure points in the supply lines to their point of
encounter, and b) enhancing the efficiency of transfer of the
energy from the atomizing fluid to the atomized fluid. These
aspects are managed through proper configuration of a simple
atomizer geometry. According to the invention, the energy and
momentum transfer from the air to the liquid is improved, so that
the desired particle size distribution can be achieved with a
smaller consumption of energy. Alternatively, for a given
consumption of energy, the particle size is reduced. This improved
transfer of energy and momentum is achieved by properly arranging
the surfaces confining the liquid and the gas.
[0014] The invention disclosed has the added advantage of ease of
manufacture. In addition, the simplicity of the geometry allows
very small dimensions, thus allowing further reductions in the
particle size by creating an atomizer with reduced dimensions,
which exposes a greater interfacial area of the first fluid to the
second fluid per unit volume of first fluid. Thus, a distinct
advantage of the invention is the simplicity of its geometry, which
allows it to be produced in miniature size (e.g. less than one
kilogram) inexpensively, as might be required for example, for
pulmonary drug delivery applications. Another advantage is the
ability to form aerosols of 1-3 micrometers in diameter, as
required for efficient delivery of pharmaceuticals to the lungs.
Miniature size atomizers can be easily stacked up or combined into
a single unit to obtain a desired amount of delivered atomizate in
a predetermined amount of time. This is particularly important when
the overall size of the unit needs to be small, such as in
pulmonary applications in which the object is to obtain a portable
device having a small overall size. Another advantage of the
geometry disclosed is in its very low deposition of particles on
the solid walls of the atomizer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] The invention is best understood from the following detailed
description when read in conjunction with the accompanying
drawings. It is emphasized that, according to common practice, the
various features of the drawings are not to-scale. On the contrary,
the dimensions of the various features are arbitrarily expanded or
reduced for clarity. Included in the drawings are the following
figures:
[0016] FIG. 1 is a schematic cross-sectional plan view of a nozzle
of the two fluid embodiment of the invention, showing schematically
the first fluid undergoing violent focusing atomization.
[0017] FIG. 2 is a close-up, cross-sectional view of the region of
encounter of the first and second fluids in a generic embodiment,
showing and labeling various angles, points, and areas of the
nozzle (P, R, P' refer to points of geometrically well defined
position; angles are provided or labeled with Greek symbols);
[0018] FIG. 3 is another embodiment of the nozzle of FIG. 1 with
various angles and areas labeled;
[0019] FIG. 4 is a similar embodiment of the nozzle of FIG. 1 with
certain areas and angles labeled;
[0020] FIG. 5 is an embodiment of the nozzle of FIG. 1 with various
parameters labeled;
[0021] FIG. 6 is a graph of the volume median diameter (VMD)
against the first fluid supply flow rate for four different first
fluids;
[0022] FIG. 7 is a graph of the dimensionless volume median
diameter (VMD) versus dimensionless first fluid flow rate with a
line through the data points showing the best power-fit;
[0023] FIG. 8 is a graph of the data with the line shown in FIG. 7
compared to a theoretical line for the Rayleigh breakup prediction
of a flow-focused jet; and
[0024] FIG. 9 is a graph of the geometric standard deviation (GSD)
against dimensionless first fluid flow rates obtained with the
different liquids listed.
[0025] FIG. 10 is a graph of the 85% lower percentile diameter of
the particle volume distribution against the channel width
[0026] FIG. 11 is a graph of the geometric standard deviation
against the channel width
[0027] FIG. 12 is a graph of the same data shown in FIG. 10,
plotted against the (dimensionless) ratio of channel width H over
the first fluid supply means channel width D.sub.o
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0028] Before the present aerosol device and method are described,
it is to be understood that this invention is not limited to the
particular components and steps described, as such may, of course,
vary. It is also to be understood that the terminology used herein
is for the purpose of describing particular embodiments only, and
is not intended to be limiting, since the scope of the present
invention will be limited only by the appended claims.
[0029] It must be noted that as used herein and in the appended
claims, the singular forms "a", "and," and "the" include plural
referents unless the context clearly dictates otherwise. Thus, for
example, reference to "a particle" includes a plurality of
particles and reference to "a fluid" includes reference to a
mixture of fluids, and equivalents thereof known to those skilled
in the art, and so forth.
[0030] Unless defined otherwise, all technical and scientific terms
used herein have the same meaning as commonly understood by one of
ordinary skill in the art to which this invention belongs. Although
any methods and materials similar or equivalent to those described
herein can be used in the practice or testing of the present
invention, the preferred methods and materials are now described.
All publications mentioned herein are incorporated herein by
reference in their entirety to disclose and describe the methods
and/or materials in connection with which the publications are
cited.
[0031] The publications discussed herein are provided solely for
their disclosure prior to the filing date of the present
application. Nothing herein is to be construed as an admission that
the present invention is not entitled to antedate such publication
by virtue of prior invention. Further, the dates of publication
provided may be different from the actual publication dates which
may need to be independently confirmed.
Definitions
[0032] The term "atomization" is used herein to mean any process by
which a fluid is broken up into separate fragments or particles,
typically from a fluid stream, which fragments or particles
typically are much smaller than any dimensions of the stream or
drop of fluid from which they detached.
[0033] The terms "atomizer" and "nozzle" are herein used to refer
to one unit that is capable of atomizing a fluid using another
fluid.
[0034] The terms "energy", "pressure energy" and the like are used
herein to mean mechanical energy in the form of kinetic energy, or
of enthalpy of the fluids, and does not necessarily, but may
include interfacial energy. The term "energy" is herein used
sometimes to refer to the total energy used for pumping the fluids
through the atomization nozzle during operation. The precise
meaning of these terms should be clear from the context to anyone
skilled in the art. The term "energy loss", "frictional losses" and
the like is used herein to mean the amount of mechanical energy
that is transformed into internal energy through known energy
dissipative mechanisms such as viscous action, gas compression
through shock waves, etc. The terms "consumption of energy",
"energy consumption", "energy use" and the like are used herein to
mean the amount of energy used per unit time required to atomize a
unit mass of first fluid (Btu/hr/lb), and generally amounts to the
mechanical energy in the final mixture plus energy losses.
[0035] The terms "first fluid", "first liquid" and the like are
used herein to mean a fluid that is delivered out of a first fluid
supply means into a region where it gets atomized, and in general
is (although is not limited to) a single or multiple phase liquid.
For example, single component liquid; or a multiple component
liquid mixture (comprising one or more liquids and/or solutes); or
a multi-phase liquid, such as an emulsion comprising one or more
liquids emulsified into another liquid; or a suspension or slurry
of solid particles or biological molecules, cells, or liposomes,
suspended in a liquid matrix; or a supercritical fluid; or
combinations of these fluid systems thereof. For pharmaceutical
drug delivery, the first fluid will in general comprise an active
drug or mixture of multiple active drugs, and pharmaceutically
acceptable excipients.
[0036] The terms "particles", "aerosol particles" and the like are
used herein to mean the fragments of fluid or fluids atomized. The
term "particle suspension", "atomizate" and the like are used
herein to mean the collection of the fragments of first fluid,
usually after exiting the nozzle (also called "atomizer"), and in
suspension in a matrix of atomizing fluid.
[0037] The terms "second fluid", "second liquid" and the like are
used herein to mean the fluid directed at the first fluid to
accomplish atomization, and in some embodiment of the invention, to
accomplish such processes as encapsulation of the first fluid. The
second fluid can be (but is not limited to) a liquid, or a gas,
emulsion, suspension, or a supercritical fluid. It will be obvious
to one skilled in the art the second fluid can contain many
components, such as the components listed for the first fluid, or
such things as sugars, polymers or lipids for encapsulation,
glycols including but not limited to poly(ethylene-glycol), or any
number of other compounds. Preferred compounds for encapsulation
include, but are not limited to poloxymers, including
polyoxyethylene, gelatin, and in the preferred embodiment for
pharmaceutical encapsulation is poly(lactic-co-glycolic) acid
[0038] The term "pressure chamber" is used herein to describe a
region of the nozzle, which receives atomizing fluid at high
pressure through a supply means and channels this fluid through a
channel into substantially all areas surrounding the first fluid
immediately exiting a first fluid supply means, and discharges
first and second fluids through a discharge orifice.
[0039] The terms "exit orifice", "discharge orifice", "discharge
opening" and the like are used herein to mean the passage through
which the first and second fluids are discharged out of the
pressure chamber.
[0040] The terms "first fluid supply means", "feeding supply
means", and the like are used herein to describe a structure that
has passages for supplying first fluid from a reservoir to a
specified location in the pressure chamber, which means is
typically in the form of a tube, although in general can have any
shape, including but not limited to non circular cross sections,
ovals, rectangles, concial ends or narrowing funnel shaped
tapers
[0041] The terms "violent mode", "violent focusing", "violent
atomization", "violent focusing atomization" and the like refer to
the process of atomization of a first fluid by the action of a
second fluid which involves impinging of the second fluid onto the
first fluid in all directions substantially orthogonal to the mean
motion of first fluid, that results in both a narrowing of the
first fluid stream, and in a breaking up of the stream into
particles and the particles into smaller particles of first fluid.
It may also involve a vena contracta of the second fluid.
General Methods
[0042] The method is carried out by forcing a first fluid through a
first fluid supply means, e.g., a tube. The fluid exits the supply
means into a pressure chamber filled with a second fluid. The
chamber has an exit port preferably positioned directly in front of
and downstream of the flow of first fluid exiting the first fluid
supply means. A channel inside the pressure chamber directs the
second fluid into trajectories that converge towards the exit of
the first fluid supply means from all sides e.g. all around the
circumference of exit of the first fluid supply means. Downstream
from the channel, the two fluids interact and exchange energy,
which exchange results in the narrowing and atomization of the
first fluid. This turbulent interaction of the two fluids is
generally referred to here as "violent focusing." The first place
of encounter of the two fluids is inside the pressure chamber,
immediately in front of the exit of first supply means, and
directly upstream from the exit of the pressure chamber. The
direction of motion of the second fluid when it encounters the
first fluid is approximately orthogonal to the direction of the
flowing stream of the first fluid at the exit of its supply means.
For example, when the first fluid supply means has symmetric
cylindrical geometry, the second fluid in the second fluid channel
radially converges toward the axis of cylindrical symmetry of the
first fluid supply means. The channel of the second fluid may
narrow in the direction of first fluid motion, and is preferably
unobstructed by other solid or porous surfaces connecting both
walls of the channel.
[0043] The "violent focusing" method comprises the steps of:
[0044] a) forcing a first fluid through a feeding supply means and
out of an exit opening of said feeding supply means as a fluid
stream,
[0045] b) continually filling a pressure chamber with a second
fluid surrounding the exit opening and fluid stream fed
therefrom,
[0046] c) forcing the second fluid through a channel inside the
pressure chamber and out of the channel, in such a way that the
second fluid stream exiting the channel is directed at the first
fluid stream circumference in all directions of flow which are
substantially orthogonal to the mean direction of flow of the first
fluid stream exiting the first fluid supply means; i.e. the second
fluid flows towards the first fluid from all sides at substantially
orthogonal angles.
[0047] d) allowing the first fluid to be focused under the pressure
and shear forces exerted by the convergent flow of the second
fluid, outside and directly in front of the first fluid supply
means; while allowing the second fluid stream to flow faster than
the first fluid stream,
[0048] e) allowing the second fluid to break up the first fluid
stream into particles that are substantially smaller than the width
of the first supply means exit, and
[0049] f) allowing the first and second fluids to exit the pressure
chamber through an exit port of the pressure chamber, positioned
directly in front of the exit of the first fluid supply means.
[0050] The exit opening of the first fluid supply means preferably
has a diameter in the range of about 5 to about 10,000
micro-meters, more preferably about 15 to 300 micro-meters. The
exit opening of the pressure chamber preferably has a diameter in
the range of about 5 to about 10,000 micro-meters, more preferably
about 15 to 400 micro-meters, and the exit opening of the supply
means is positioned at a distance from the pressure chamber exit
opening in a range of from about 5 to about 10,000 micro-meters,
more preferably about 15 to about 300 micro-meters. In general, the
width of the second fluid stream at the channel exit is less than 2
times the width of the first fluid supply means exit, preferably
less than 1.5 times the width of the first fluid supply means exit,
more preferably less than 1 times the first fluid supply means
exit, and most preferably from 0.2 to 0.7 times the width of the
first fluid supply means exit.
[0051] The first fluid can be (but is not limited to) a liquid, an
emulsion, or a suspension or slurry comprising solid particles
suspended in and/or partially dissolved in a liquid. The second
fluid can be but is not limited to a liquid, a gas, or a
supercritical fluid. The second fluid can in general be of any
composition, including but not limited to liquids, suspensions,
solutions, aerosols, supercritical fluids, but in the preferred
embodiment is a gas or a fluid substantially immiscible in the
first fluid. Any gas or gas mixture could be used, including but
not limited to air, nitrogen, carbon dioxide, helium, argon, or any
other acceptable gas or mixture of gasses.
[0052] Depending on the application, the two fluids may be
immiscible or completely miscible, or miscible to varying degrees.
For example, this invention can be used to enhance transport
processes that are aided by an increased interfacial area between
the two phases, including dissolution of poorly miscible liquids,
or evaporation of a liquid first fluid (e.g. fuel) into a gaseous
second fluid (e.g. air). For encapsulation applications, in general
the two fluids will be immiscible or poorly miscible. There may be
applications where one or both of the fluids are mixtures of
components, some of which are miscible and some of which are
immiscible in one or several of the components of the other. It
will be obvious to one skilled in the art that many combinations of
miscibility/immiscibility could have utility.
[0053] The walls that define the channel leading the second fluid
or gas to the stream of the first fluid do not have to be
connected. However, these walls generally present a clear path for
flow of the second fluid to the stream of first fluid. While said
walls may be connected inside the channel by solid objects such as
(but not limited to) porous objects, ribs, fins, etc., the channel
preferably comprises an open passage. Having an open channel
minimizes energy losses as the second fluid flows through the
channel, allowing for a more efficient process. The pressure
driving the flow of second fluid is such that sufficiently high
velocity is imparted on the second fluid at the exit of the channel
to bring about the atomization. The flow of second fluid encounters
the first fluid in the pressure chamber at an angle to the
direction of flow of the first fluid inside the supply means near
the exit which is preferably equal to about 90 degrees +/-about 45
degrees, preferably 90 degrees +/-about 30 degrees, still more
preferably 90 degrees +/-about 15 degrees, most preferably 90
degrees +/-5 degrees.
[0054] The separation between the walls defining the channel
determines the amount of mass of second fluid consumed given a
velocity of second fluid, and thus affects the quantity of energy
spent. However, the present invention is a particularly
advantageous configuration in terms of energy use, and therefore
allows a separation between the walls that is quite small, and in
general comparable to the width of the first fluid supply
means.
[0055] Based on the above it will be seen that very small particles
can be created, and that particles much smaller than the dimensions
of the first fluid supply means and the channel can be created.
This can be very important for many applications. For example, for
the pulmonary delivery of drugs, particles in the range of 0.1 to
10 micro-meters are required, and for efficient delivery particles
of 0.5 to 6 micro-meters, or preferably 1 to 3.5 micro-meters, are
required. When the dimensions of the supply means are comparable to
the dimensions of the particles, blockage of the very small
structures can occur. This problem can be reduced or obviated by
the current invention. In addition, the relative large dimensions
of the supply means and channel will allow for efficient delivery
of suspensions.
[0056] The invention can in general be expanded to include a third,
fourth, fifth, or any number of fluids, each similar to the
previously described first fluid or second fluid, wherein if it is
similar to the previously described first fluid, its supply means
will in general be concentrically positioned around and containing
the first fluid supply means and the flow will be parallel to the
first fluid. Thus, a cylinder in a cylinder, etc. If it is similar
to the previously described second fluid, it will comprise a
distinct channel for directing said fluid toward the exit of the
previous fluid's pressure chamber. These subsequent fluids can have
any of the properties of the first and second fluids disclosed
above. For example, the first fluid could comprise a formulation
containing a pharmaceutically active compound, the second fluid
could be used to coat or encapsulate particles of said formulation,
and the third fluid could be a gas used to disperse said coated or
encapsulated particles as an aerosol. Any number of fluids could be
used to create any number of desirable properties. It is also
possible to use a first and second fluids in the nozzle which then
discharge out of the nozzle into a bath of a third fluid.
[0057] To help better appreciate the importance of atomizer design
in the atomization of fluids, we note that the energy spent in
accelerating the second fluid to the site of atomization increases
directly with the total momentum carried by that fluid at that
location. It is reminded that atomization is achieved when such
momentum is transferred effectively to the first fluid, resulting
in its breakup. Therefore, the key to not wasting energy
unnecessarily lies in making use of the available momentum (that
carried by the second fluid) for atomizing first fluid to the
extent possible, and that is done through adequate atomizer design.
In other words, increasing the extent of atomization can be done by
the brute force method of increasing the total momentum in the
second fluid. However, this approach results in a proportional
increase in the energy spent.
[0058] To support the claim that the energy is proportional to the
total momentum, we present the following simplified analysis, which
considers incompressible fluids. A pump or pressure source of
second fluid provides the energy consumed for the process (the
first fluid generally carries a negligible source of energy). The
energy consumed by the pump or the pressure source is equal to the
work per unit time, K, which is the product of the pressure p times
the flow rate of second fluid Q: K=pQ
[0059] p is generally measured relative to a point in the system,
taken here to be the site of atomization. In the absence of viscous
losses, the Bernouilli theorem allows us to express p in terms of
the velocity at the site of atomization. p is in fact equal to 0.5
times the momentum flux at the site of atomization (Kg/m/s.sup.2):
p=0.5.times.(momentum flux)=0.5(.rho.V.sup.2)
[0060] Here .rho. is the density of the second fluid and V its
velocity (assumed uniform at the site of atomization). Q is the
volume rate associated with the flow of second fluid. Because an
incompressible second fluid is considered, its density is constant,
and the volume rate at the pump is the same as the volume rate at
the site of atomization, expressed as the product of the cross
sectional area A which the second fluid flows through with velocity
V at the site of atomization: Q=VA
[0061] Combining the expressions for Q and for p, the energy spent
can be expressed as K=0.5(.rho.V.sup.2)VA
[0062] The total rate of momentum P carried by the second fluid at
the site of atomization is expressed in units of (kg m/s.sup.2),
and is represented by the product of the total mass per unit time
Q.rho.(kg/s) of second fluid times its momentum per unit mass or
speed V (m/s) at the site of atomization. Thus,
P=.rho.QV=.rho.V.sup.2A and K=0.5P.sup.3/2/(.rho.A).sup.1/2
[0063] It can thus be seen that raising the momentum P by applying
more pressure at the pump, will result in more units of momentum
carried at the site of atomization. Although this will result in
more units transferred to the first fluid, it will also result in
an increase in the amount of energy spent K.
General Device
[0064] The basic device or nozzle of the invention can have a
plurality of different embodiments. However, each configuration or
embodiment will comprise a means for supplying a first fluid
(preferably a liquid) 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 first fluid. The first fluid
supply means and pressure chamber are positioned such that
mechanical interaction resulting in atomization of the first fluid
takes place between the first fluid exiting the first fluid supply
means and the second fluid exiting the supply chamber. The exit
opening of the pressure chamber is downstream of and preferably it
is directly aligned with the flow path of the means for supplying
the first fluid.
[0065] To simplify the description of the invention, the means for
supplying a first fluid is often referred to as a cylindrical tube.
However, tube shape could be varied, e.g. oval, square,
rectangular, and can be of uniform cross section or tapered. For
example the exit of the first fluid supply means may be a slit
defined by two walls or surfaces, and having a long dimension and a
short dimension. The first fluid can be any fluid depending on the
application. For example, the fluid could be a liquid formulation
comprising a pharmaceutically active drug used to create dry
particles or liquid particles for an aerosol for inhalation,
suspensions for injection, or other pharmaceutical applications.
Alternatively, it could be a hydrocarbon fuel used in connection
with a fuel injector for use on, for example, an internal
combustion engine, turbine, heater, or other device which burns
hydrocarbon fuel. In general, the first fluid could be (but is not
limited to) a single or multiple phase liquid. For example, it can
be a single component liquid; or a multiple component liquid
mixture (comprising one or more liquids and/or solutes); or a
multi-phase liquid, such as an emulsion comprising one or more
liquids emulsified into another liquid; or a suspension or slurry
of solid particles or biological molecules, cells, or liposomes,
suspended in a liquid matrix; or combinations of these liquid
systems thereof. The second fluid can be any fluid, as described
previously, but preferably is a gas and that gas is generally air
or an inert gas, such as carbon dioxide, or gas mixtures of inert
gases. The two fluids are generally immiscible or mildly miscible.
However, on some applications, violent focusing can be used to
enhance mixing between two poorly miscible fluids or phases, thanks
to the large interfacial area between the two phases of fluids that
is created during violent focusing.
[0066] An example is dissolution of poorly miscible liquids.
Another is evaporation of fuel into air or another oxidizing gas
e.g. oxygen. Here evaporation can be viewed as a form of mixing of
a liquid's constituent molecules into a gaseous solvent, the
oxidizing atmosphere. It is possible to have situations wherein the
liquid upon exiting either the first fluid 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, such as
cylindrical, or have other shapes consistent with an entrance and
an exit, which entrance represents the exit point of the pressure
chamber.
[0067] Referring to the figures a cross-sectional schematic view of
the nozzle 1 is shown in FIG. 1. The nozzle 1 is comprised of two
basic components which include the pressure chamber 2 and the first
fluid supply means 3. The pressure chamber 2 is pressurized by the
second fluid 10 flowing into the pressure chamber via the entrance
port 4. The first fluid supply means 3 includes an inner wall 5
defining an inner passage wherein the first fluid 9 flows. The
first fluid supply means 3 can have any composition and
configuration, including layers of dissimilar materials, voids, and
the like, but is preferably a tube constructed of a single
material. The inner wall 5 of the fluid supply means 3 is
preferably supplied with a continuous stream of a first fluid 9
which first fluid 9 can be any liquid or gas but is preferably in
the form of a liquid, suspension, or emulsion.
[0068] The pressure chamber 2 is continuously supplied with a
pressurized second fluid 10 which can be any liquid or gas but is
preferably a gas, or a supercritical fluid. The inner wall 5 of the
first fluid supply means 3 includes an exit point 6. The
pressurized chamber 2 includes an exit point 7, which marks the
entrance to the discharge opening 15. The exit point 7 of the
pressure chamber is preferably positioned directly downstream of
the flow of first fluid exiting the exit point 6. The pressure
chamber 2 includes channel 13 surrounding the exit 6 of supply
means 3. The first fluid supply means exit 16, the channel 17, and
the exit 18 of the pressure chamber 2 are configured and positioned
so as to obtain two effects (1) the dimensions of the stream
exiting the first fluid 9 supply means 3 are reduced by the second
fluid 10 exiting the channel so that a focused stream 14 is formed;
and (2) the first fluid 9 exiting the first fluid supply means 3
and the second fluid 10 exiting the channel 13 undergo a violent
interaction to form much smaller particles 8 than would form if the
stream of first fluid in reduced dimensions underwent normal
capillary instability, e.g. formed spherical particles
approximately 1.89 times the diameter of the first fluid
stream.
[0069] The position of the exit port 18 could be in any location
that allows the efficient "violent mode" atomization of the first
fluid and efficiently delivers the resulting particles, but
preferably, the exit port 18 of the chamber 2 is substantially
directly aligned with the flow of first fluid exiting the first
fluid supply means 3. An important aspect of the invention is to
obtain small particles 8 from the interaction of the first fluid 9
and the second fluid 10, the first fluid 9 flowing out of the exit
port 16 of the first fluid supply means 3. The desired formation of
particles 8 is obtained by correctly positioning and proportioning
the various components of the first fluid supply means 3 and the
pressure chamber 2 and thus correctly proportioning the channel 13
as well as the properties of the fluids, including but not limited
to the pressure, viscosity, density and the like, determining the
mass flow, momentum flow, and energy flow of the first fluid fluids
which flows out of both the first fluid supply means 3, of the
second fluid which flows through the channel 13, and of the
resultant mixed flow of combined streams of first and second fluids
that flow out of exit 18, the result being particles 8.
Specifically, there are some important geometric parameters that
define the nozzle 1 of the present invention. Those skilled in the
art will adjust those parameters using the information provided
here in order to obtain the most preferred results depending on a
particular situation.
[0070] Preferably, the first fluid 9 is held within an inner wall 5
which is cylindrical in shape. However, the inner wall 5 holding
the first fluid 9 may be tapered (e.g. funnel shaped) or have other
varying cross section, asymmetric, oval, square, rectangular or in
other configurations including a configuration which would present
a substantially planar flow of first fluid 9 out of the exit port
16. Thus, the nozzle of the invention applies to all kinds of
configurations that have a channel for the second fluid 10
surrounding the first fluid means exit 16. Accordingly, the
figures, including FIG. 1, are used only to define the variables
but are not intended to imply any restrictions on the type of
geometry or the specific details of the design of the nozzle 1 of
the present invention. There are many degrees of freedom of design.
For example, corners which are shown as sharp could be rounded or
finished in different ways. Similarly, solid surfaces which are
shown straight in the figures, could be curved, and could be
patterned or admit different types of finishes, in order to
obtained certain additional effects or optimize the design.
[0071] The focusing of the stream of first fluid 9 and its ultimate
particle formation are based on the violent focusing experienced by
the first fluid 9 on passing through and out of exit 16 and through
exit 18 of the pressure chamber 2 which holds the second fluid
10.
[0072] Without being limited to any one theory, creation of
particle 8 may occur as follows. The particular arrangement of the
channel 13 causes a focusing of the first fluid 9 stream, as well
as possibly a vena contracta of the second fluid stream, and a
breaking up of the fluid stream into particles:
[0073] A) Focusing of first fluid 9 stream: The second fluid 10
attains a large momentum per unit volume in channel 13 exit at
points 6 and 7. This rate of momentum flow can be described by the
total momentum carried by the second fluid 10 per unit time at the
exit of channel 13, which can be expressed in units of (kg/s) times
(m/s), and be estimated as the product of the total mass flow rate
(kg/s) of second fluid times the average speed (m/s) of second
fluid at channel exit (defined in FIG. 1 by points 6 and 7).
[0074] Because a momentum per unit time received by an object
represents a force on that object, and the second fluid 10 stream
is incident on the first fluid 9, a portion of said rate of
momentum flow is experienced by first fluid 9 as a force exerted by
the second fluid 10 exiting channel 13. However, the net momentum
of the whole of the second fluid 10 stream exiting channel 13 has a
vectorial sum of zero or nearly zero in the plane of second fluid
motion, because said fluid flow toward the first fluid 9 is evenly
distributed around all sides surrounding the first fluid 9. Each
portion of second fluid 10 having a specific direction of motion in
channel 13 carries momentum, and thus exerts a force on the portion
of first fluid 9 that said portion of second fluid impinges on. The
net effect is a distributed force onto each portion of first fluid
9 towards inwards, resulting in a squeeze inward of the first fluid
9 stream. Such squeezing actions combined with the steady supply of
first fluid results in a focused stream 14 of first fluid 9, such
as the one illustrated in FIG. 1. In addition, the second fluid
creates shears on the first fluid as it rushes over that first
fluid. Such shear forces also tend to accelerate the first fluid
away from the first fluid supply means, and this acceleration thus
also tends to reduce the cross section of the first fluid 9 stream,
as shown by focused stream 14 in FIG. 1.
[0075] B) Vena contracta of second fluid: As the streamlines of
second fluid 10 that graze point 7 and bound the second fluid
stream leave channel 13, a component of their velocity points
towards the first fluid 9, and these streamlines detach from the
walls of the channel at exit point 7. After detachment, the stream
of second fluid 10 slows down in the direction of the channel 13
and accelerates in the axial direction (first fluid 9 flow
direction), but the total width of the second fluid 10 stream
surrounding the first fluid 9 stream becomes narrower than the
width of the pressure chamber exit port 7. We are referring to this
reduced cross section as the vena contracta of second fluid. As a
result of the reduced cross section associated with such vena
contracta, the average speed of second fluid is greater than the
lower speed that would result if the second fluid stream could fill
the entire width of the pressure chamber exit port 7. This
augmented speed is associated with an augmented flow of momentum,
and therefore, is more effective than a lower speed at breaking up
the first fluid 9 into particles 8.
[0076] Based on the above it will be understood that when a vena
contracta of second fluid 10 is present, configuring the system to
have an angle between the second and first fluid streams of about
90 degrees has the advantage over other configurations having a
much smaller angle. It will be further understood that the stream
of second fluid carrying a desired speed and momentum is
significantly narrower in width than either the pressure chamber
exit port or the first fluid exit port.
[0077] C) Breaking up of first fluid into particles: Except for a
very thin viscous boundary layer of fluid adjacent to the interface
of first fluid 9 exposed to second fluid 10, the second fluid 10
flowing over the first fluid 9 does so at a faster speed than the
first fluid 9. This difference creates a shear force in the
direction parallel to the interface. This shear force tends to
create undulations or waves on the surface of the first fluid 9,
which grow and ultimately break off, resulting in fragments that
detach from the main body of first fluid 9. Such fragments can
themselves undergo subsequent fragmentation upon further
interaction with the second fluid 10, and other fragments or
portions of first fluid 9. Even under steady conditions of the
flows of first and second fluids in their respective supply means,
it is nearly inevitable that these instabilities and unsteady flows
will take place, including an instability in which said viscous
boundary layer becomes turbulent. Actions A), B) and C) described
above can take place concomitantly, partially concurrently, or
separately.
[0078] We refer now to FIGS. 2 and 3 in order to describe the
relationships between some of the components shown in FIG. 1.
First, a dashed line C-C' is shown running through the center of
the exit port 16 in which the first fluid 9 flows as well as the
exit port 18 of the chamber 2. In symmetric planar atomizers, for
example, the line C-C' represents the plane of symmetry intersected
by the plane of view. In cylindrically symmetric atomizers, this
line represents the axis of cylindrical symmetry. The dashed line
B-B' represents the bisector of the second fluid channel 13 near
its exit end. The area that has been referred to as the second
fluid "channel" 13 is the open passage that lies in between the
terminal face 11 of the first fluid supply means 3 and the front
face 12 of the chamber 2. The exit of the channel 13 is defined by
edges P and P' (appearing as points on the cross sectional view of
FIGS. 2 and 3). However, the width of the second fluid stream upon
exiting channel 13, also called "channel exit width", or simply
"channel width", is taken as the distance between points P and R of
FIG. 2, and is also referred to by symbol H. Other geometric
parameters of critical importance are D.sub.t, which is the first
fluid exit width; D.sub.o, which is the width of the pressure
chamber exit; and the channel length, which will be quantified
using the related parameter D.sub.1, which is the full width of the
first fluid supply means defined as the full separation between
channel entrance points Q and Q'as shown in FIG. 3. In order for
violent atomization to take place, these angles and certain ratios
of these dimensions must be satisfied, as will be described and
quantified in the following.
[0079] To obtain desired results with the nozzle of the present
invention the following characteristics must be present:
[0080] (a) a strong convergence of the streamlines of the second
fluid 10 (liquid or gas) in the chamber 2 towards and surrounding
the first fluid 9 coming out of the exit port 16;
[0081] (b) efficient utilization of the momentum in second fluid
10;
[0082] (c) a focusing or narrowing of the stream of the first fluid
9 by the surrounding fluid 10 from the channel 13.
[0083] The above characteristics (a)-(c) combine with each and with
other characteristics in order to result in the desired (d) violent
focusing of the stream of fluid 9 exiting the exit port 16. For
example, other characteristics may include the fluid 9 and/or 10
obtaining sonic speeds and shock waves (e) when the second fluid 10
is a gas, and may also include a vena contracta of the second fluid
stream after it has come in contact with the first fluid
stream.
[0084] In order to more fully understand the invention, each of the
characteristics (a)-(e) referred to above are described in further
detail below.
(a) Strong Convergence of Second Fluid:
[0085] The primary characteristic of the present invention is the
facilitation of a strongly convergent (imploding) flow of second
fluid 10 towards and surrounding the first fluid 9. The fluid 10 in
the pressure chamber 2 should preferably not flow parallel to the
first fluid 9 exiting the first fluid supply means, i.e. the two
fluids should preferably not intersect at a 0 degree or small
angle. Further, the second fluid 10 in the pressure chamber should
preferably flow substantially directly perpendicular to, or with a
similar large angle relative to the flow of, the first fluid stream
9 exiting the first fluid supply means 3.
[0086] In order to generate significant convergence in the second
fluid 10 toward the first fluid 9, the second fluid 10 should be
admitted into a path that directs it towards the first fluid at a
high angle. Specifically, the following design constraints based on
the parameters shown in FIGS. 2 and 3 are preferably:
[0087] (1) a second fluid channel tapering angle .alpha. smaller
than 90 degrees, preferably smaller than 30, more preferably
between 0 and 10 degrees, but a is most preferably about 0
degrees.
[0088] (2) the wall 11 of the channel 12 should form an angle
.beta. (FIGS. 2 and 3) with center line C-C' greater than 45
degrees but smaller than 135 degrees, preferably between 75 and 105
degrees, and most preferably, of about 90 degrees; and
[0089] (3) the length of the second fluid channel 13, defined as
the distance between points Q and P.sup.1 (shown in FIG. 3), should
be adjusted based on the other factors. The channel 13 should be
long enough to facilitate the bending of the streamlines of second
fluid 10 towards a path defined by the channel bisector B-B', which
is substantially orthogonal to the first fluid 9 flow direction.
Thus, in general, D.sub.1 is required to be at least equal to 1.5
times the greater of D.sub.o and D.sub.t, and is preferably more
than 1.5 times the greater of D.sub.o and D.sub.t, most preferably
more than 2 times the greater of D.sub.o and D.sub.t. However, the
channel 13 should not be so long that frictional losses between the
second fluid and the walls of the channel become unacceptably high
for the application in question, or so long that the viscous
boundary layer becomes turbulent in the channel. This requirement
also depends on other properties, generally combined into a
Reynolds number. Those skilled in the art, reading this disclosure
will be able to determine which combinations of those parameters
lead to unacceptably high losses in a particular application.
(b) Efficient Utilization of Second Fluid Momentum:
[0090] To ensure efficient utilization for atomization of the
momentum that the second fluid 10 carries at the point where it
meets the first fluid 9, two independent conditions should be
satisfied for two ratios involving geometric parameters defined
earlier, namely D.sub.t/D.sub.o and H/D.sub.o. H is a measure of
the width of the exit of the channel 13, and equals the distance
between points R and P in FIG. 2. D.sub.o is the width of the
pressure chamber exit, and D.sub.t is the width of the first fluid
supply means exit. In general, none of these three dimensions can
be much greater or smaller than the other two. For example, a very
large D.sub.o in comparison to D.sub.t (regardless of H) would, for
example, permit the escape of second fluid and the corresponding
momentum from the pressure chamber through regions of its exit port
cross section that are far from the first fluid stream, and,
therefore, the majority of the momentum carried by the second fluid
10 at the exit of the channel at point P would not be delivered
towards, and utilized for shearing and atomizing, the first fluid
9. This underutilization of the momentum ultimately represents an
unnecessary energy loss, which is avoided by the violent focusing
method. On the other hand, it is conceivable for violent focusing
to be able to take place for a D.sub.t that is quite large compared
to D.sub.o, so long as H stays comparable to D.sub.o. The ratio of
D.sub.t/D.sub.o should be greater than 0.5 and preferably between
0.7 and 1.2, and most preferably between 0.8 and 1.0. It is worth
noting that values under unity allow for visual inspection of the
alignment of the first fluid channel from a line of sight from
outside the nozzle into the pressure chamber exit port, and thus
present a manufacturing advantage over ratios greater than
unity.
[0091] The efficient utilization of momentum of the second fluid 10
also depends on the ratio H/D.sub.o. This ratio governs where in
the second fluid flow path (which includes the channel exit of
width H, and the pressure chamber exit of width D.sub.o) the speed
of second fluid reaches its highest value. In general, the
narrowest cross section in said flow path carries second fluid at,
or approximately near, the highest speed. For example, when
H/D.sub.o is close to unity, both the exit of the channel and the
pressure chamber exit carry second fluid at or near the maximum
speed attained along said flow path. However, if H/D.sub.o had a
value much greater than unity, then the speed at the exit of the
channel would be much smaller than the speed attained near the
pressure chamber exit. This condition is undesirable, because the
energy used to pump second fluid through the pressure chamber is
employed to accelerate the second fluid inside the pressure chamber
exit, thus after, rather than right before, it encounters the first
fluid. Reducing width H would automatically cause an increase in
speed, thus momentum, of the second fluid at the channel exit,
right before it encounters the first fluid. This would be done with
little change in the overall energy use, but with a great
difference in the extent of atomization of the first fluid 9.
[0092] If, on the other hand, H/D.sub.o had a value much smaller
than unity, then the speed at the exit of the pressure chamber
would be much smaller than at the channel exit. This condition is
generally undesirable because maintaining the second fluid at high
speed improves atomization during the exiting of the streams from
the pressure chamber and ensures a thorough degree of atomization
without an undue expense of energy. A very small H, could impact
energy use also by bringing about unnecessary frictional losses in
the channel, due to excessive friction between the second fluid 10
and channel walls 11 and 12. It should be noted however, that those
losses are a function of other quantities, such as channel length,
already discussed, or such as density (kg/m.sup.3) and dynamic
viscosity (kg/m/s) of the second fluid. Systematic studies
described under Examples for experiment 5 demonstrate that there is
an optimum range of ratios of channel widths to pressure chamber
exit width, for the particular set of conditions studied. In
general, the width of the second fluid stream at the channel exit
(H) is less than 2 times the diameter of the pressure chamber exit
(D.sub.o), preferably less than 1.5 times the width of the pressure
chamber exit, more preferably less than 1 times the pressure
chamber exit, and most preferably from 0.2 to 0.7 times the width
of the pressure chamber exit.
[0093] In general, aside from the requirements on these geometric
ratios, it is desirable to have as high a momentum as needed in the
second fluid 10 for a certain amount of second fluid mass flow and
for given conditions of pressure and temperature. The ratio between
momentum and mass fluxes is similar to its average speed (in fact,
is very nearly such value when variations in local speed are
negligibly small across the second fluid channel exit). Both for
compressible as well as incompressible fluids, the fastest speed is
generally obtained in the narrowest part of the second fluid flow
path, which includes the channel, the pressure chamber discharge
opening, and the space in between where the two fluids first
encounter each other. Again, if the distance between points R and P
(FIG. 2) is too large, then the narrowest point in the flow path
will be at the exit orifice. In the presence of the first fluid 9,
such analysis implicitly assumes that the interface between not yet
atomized first fluid 9 and second fluid 10, acts as part of the
boundary that limits and defines the flow path for the second
fluid. Thus, ignoring the space occupied by first fluid 9, a
typical value of H compatible with the requirement of high speed at
either the exit of the channel 13 or of the pressure chamber 2, is:
H=.beta.D.sub.o
[0094] For axi-symmetric configurations, .beta. equals 0.25; while
for planar-two dimensional configurations, .beta. equals 0.5. These
values are consistent with the most preferred ranges for H/D.sub.o
provided earlier.
[0095] H must be large enough to preclude excessive friction
between the second fluid 10 and the second fluid channel 13 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.sub.min, defined as a
few times the thickness of the viscous boundary layer .delta..sub.L
that develops inside the second fluid 10 in its acceleration
through the second fluid channel 13:
H.sub.min.about..lamda..delta..sub.L .lamda..about.1 to 10
[0096] The thickness of the boundary layer at point P' (FIG. 2) for
the case when the second fluid is a gas and its speed is near the
speed of sound (at the exit of the channel or at the exit of the
pressure chamber) is approximately given by the following
expression:
.delta..sub.L=(L.mu..sub.2/(.rho..sub.2P.sub.o2).sup.0.5).sup.0.5
[0097] Here .mu..sub.2 is the dynamic viscosity coefficient of the
second fluid 10, .rho..sub.2 is its density, and P.sub.o2 is the
pressure of the second fluid 10 in the upstream chamber. .lamda. is
a numerical factor, which generally is between 1 and 10. L is the
length of the second fluid channel Q-P' (FIG. 3)
L=0.5(D.sub.1-D.sub.t)/sin(.beta.)
[0098] These expressions neglect the reduction in effective exit
area due to the presence of first fluid in the exit orifice.
Therefore, the equations provided above should be considered as
approximate guides, e.g. .+-.30% error factors or less.
[0099] The purpose of providing all of these geometrical
constraints is to make an efficient utilization of the momentum of
second fluid for the purpose of atomizing first fluid, and
ultimately making efficient use of the energy consumed. This
purpose would be partially defeated by the presence of porous
materials located inside channel 13, in which it is well known that
the mechanical energy (enthalpy) in the second fluid converts into
heat (internal energy of the system). Therefore, channel 13 may
include, but preferably will not include, such porous structures,
or other materials that may incur significant energy loss.
(c) Focusing of the First Fluid:
[0100] In the presence of second fluid flow, the first fluid 9
exiting the first fluid supply means 3 gets funnel-shaped into a
jet that generally 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 such as a fluid sheet for
example. Any configuration can be used which provides flows through
the center of the exit orifice 7, and can become much thinner as it
enters the exit orifice 7 than it is at the exit 6 of the supply
means 3. The forces responsible for the shaping of the first fluid
9 are believed to arise from two sources: a) the pressure gradients
that set within the second fluid 10 as it flows out of channel 13
and around the exit orifice 7; and b) shear stresses that are
transferred from the faster moving second fluid to the slower
moving first fluid. When the source of the forces is pressure
gradients alone, for example, in axi-symmetric configurations, a
round first fluid jet is expected to attain a diameter d.sub.j
determined by the 1/2 power law with liquid flow rate Q (in volume
per unit of time, e.g. cubic meter per second; Ganan-Calvo A. M.,
1998):
d.sub.j.about.(8.rho..sub.1/(.pi..sup.2.DELTA.P.sub.g)).sup.1/4Q.sup.1/2
[0101] .rho..sub.1 is the first fluid density, .pi. is pi, and
.DELTA.P.sub.g is the pressure drop in the second fluid between the
upstream value (taken at the supply means exit 16) and the value at
the point where d.sub.j is measured (for example, at the pressure
chamber exit 18, or at a point inside the pressure chamber
discharge opening 15, or outside the nozzle) and .about.means
approximately equal to with about a .+-.10% or less error margin.
This equation will be herein referred to as the "flow-focusing"
formula and only applies for a uniform velocity distribution along
the first fluid jet radius. A similar equation exists for other
geometries. The presence of shear stresses will in general, cause
the jet to accelerate more than would otherwise be under the action
of pressure gradients alone, and conservation of mass demands that
its width will be smaller than that predicted by such
"flow-focusing" equations.
[0102] A notable consequence of the fact that the first fluid 9 is
surrounded by the second fluid 10, and that all portions of the
second fluid are accelerated approximately equally towards towards
the first fluid, is that the first fluid is stabilized towards the
center 14 of the pressure chamber exit orifice 18. For example, in
one of the preferred device embodiments (FIG. 5), the exit 16 and
the exit 18 are allowed to be of equal diameter. In all of the
tests done with such embodiment the first fluid 9 was observed to
flow through the center 14 of the exit orifice 18 without impacting
or wetting its side walls such as at the point 7. (Due to the
random nature of the particle trajectories under conditions of very
high first fluid flow rates, a small degree of wetting has indeed
observed, but was associated with an insignificant fraction of the
first fluid 9.)
(d) Violent Focusing:
[0103] The violent focusing of the stream of fluid 9 exiting the
first fluid supply means 3 is characterized by a stream of first
fluid entering the exit 18 to the pressure chamber 2 which is
narrower than the width of the stream of first fluid exiting the
first fluid supply means 3. It is also characterized by a flow of
second fluid 10 exiting the pressure chamber 2 which surrounds the
first fluid everywhere, such second fluid stream having a higher
speed than the first fluid stream. The violent focusing of the
stream of first fluid 9 is further characterized by a rapid
disintegration of such fluid over a region that spans between the
exit of the first fluid supply means 3 and a nearby point in the
region outside the atomizer.
(e) Gas Sonic Speeds and Shock Waves:
[0104] Sonic speeds and shock waves may take place when the second
fluid is a gas. In all tests to date using such fluid choice, the
pressure drop across the atomizer was such that the gas attained
sonic and supersonic speeds. Under these conditions shock waves are
also expected to be present.
[0105] Characteristics of supersonic flow such as shock waves may
improve atomization, and may be required for optimal atomization in
some cases.
[0106] 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 first fluid flow
rate, (i) Little apparent effect of atomizer size on droplet size.
These characteristics are described further below.
(f) High Frequency of Droplet Generation:
[0107] When the second fluid 10 is a gas and the first fluid 9 a
liquid, experimental data demonstrate that the droplets are much
smaller than predicted from the spontaneous capillary breakup, such
as Rayleigh breakup in axi-symmetric configurations; (Rayleigh
1882) of an first fluid column of size d.sub.j equal to that
predicted by the flow-focusing formula discussed earlier. Or, what
is the same, for given values of the liquid properties and
operational variables (such as flow rates and pressures), the final
size of the droplets is many times smaller than such flow-focusing
diameter d.sub.j. As a result, the frequency of droplet production
is much higher than predicted by spontaneous capillary breakup of
the focused jet. Accordingly, particles formed via the method
described here are substantially smaller (e.g. 1/2 the size or less
or 1/20 the size or less) than would be obtained due to spontaneous
capillary break-up of the stream exiting the chamber 2 at the exit
18. (See graph of FIG. 7)
(g) Low Requirements on Liquid Pressure:
[0108] The first fluid 9 does not have to be pushed out of its
supply means 3 with a sufficiently high pressure capable of
maintaining a stable liquid jet outside the tube exit 6 in the
absence of second fluid flow or pressure chamber. In other words,
it does not need to be pushed under pressures exceeding the
so-called jetting pressure. A pre-existent first fluid jet
structure coming directly out of the exit opening 6 is not required
because, a explained above in (c), the first fluid meniscus is
focused by the action of the second fluid pressure forces, and is
thus drawn out into a continuous stream by the accelerating forces
of the second fluid (pressure gradients and shear stresses).
(h) Low Sensitivity of Drop Size to First Fluid Flow Rate:
[0109] In the cases tested thus far, a low sensitivity of droplet
size on flow rate has been observed. The dependence is close to a
power law with exponent 1/5 of the liquid flow rate.
(i) Small Apparent Effect of Atomizer Size:
[0110] Based on the experimental data available, the drop size
dependence with first fluid flow rate, second fluid pressure, and
first fluid mechanical properties does not appear to involve
variables characterizing the size of the atomizer. (See the below
EXAMPLES.) However, under certain conditions of operation, for
example at high flow rates that lead to a large fraction of the
exit orifice occupied by the liquid, one would expect a certain
dependence.
EXAMPLES
[0111] The following examples are put forth so as to provide those
of ordinary skill in the art with a complete disclosure and
description of how to make and use the present invention, and are
not intended to limit the scope of what the inventors regard as
their invention nor are they intended to represent that the
experiments below are all or the only experiments performed.
Efforts have been made to ensure accuracy with respect to numbers
used (e.g. amounts, temperature, etc.) but some experimental errors
and deviations should be accounted for. Unless indicated otherwise,
parts are parts by weight, molecular weight is weight average
molecular weight, temperature is in degrees Centigrade.
Examples 1-5
[0112] FIGS. 6-12 show results for aerosols produced by methods of
the present invention using dry air and dry nitrogen as second
fluids 10, and a range of liquids as first fluids 9: distilled
water, 2-propanol, 20% (v/v) by volume of ethanol in water ("20%
EtOH"), and 0.1% weight in volume (w/v) Polysorbate-20 in distilled
de-ionized water ("0.1% Tween"). Tests were performed in four
separate experiments with different atomizers. The atomizers were
of an axi-symmetric type and had dimensions as specified below in
Table A for variables defined in FIGS. 4 and 5. Specifically, the
pressure chamber discharge opening was conveniently created by
drilling a straight-through hole through a plate of thickness
T.
[0113] In experiments 1-4, the droplet size was determined by phase
Doppler anemometry (Lefebvre 1989; Bayvel and Orzechowski 1993)
along the axis of the aerosol plume a few centimeters downstream
from the exit of the atomizer. This measurement technique led to
notoriously low rates of validated counts, i.e. low rates of
detected light pulses ("bursts"). This problem appears to result
from a combination of high droplet concentrations and high
velocities. Validation count rates lower than 50% have been
excluded from the sets of data presented here. As a consequence,
all of the droplet size measurements in experiments 3 and 4 with
were excluded from the graphs. Nevertheless, atomizer dimensions
have been included in table A to indicate that stable aerosols were
obtained in a third and fourth experiment with an atomizer of
similar characteristics as in experiment 2, but otherwise of a very
different design.
Table A
[0114] Atomizer geometric dimensions (in micrometers unless
indicated) used in the experiments (refer to figure for key);
typical tolerance +/-15%; (.alpha.=0 degrees +/-5 degrees;
.beta.=90 degrees +/-5 degrees) (Refer to FIGS. 4 and 5 for meaning
of symbols.) TABLE-US-00001 Experi- ment D.sub.o D.sub.t D.sub.l H
T .PHI., degrees .theta., degrees 1 62 50 90 19 50 13 +/- 7 60 2
200 200 400 35 75 0 0 3 200 200 400 50 75 0 0 4 200 200 400 50-80
75 0 0 5 100 100 410 10-135 75 0 0 6 150 150 410 13.5-160 75 0
0
[0115] FIG. 6 is a graph of the volume median diameter (VMD) versus
the liquid supply flow rate for four different liquids.
[0116] In FIG. 7 the volume median diameter and liquid flow rates
have been non-dimensionalized using similar variables to those
identified in the flow-focusing literature (Ganan-Calvo 1998),
d.sub.o, and Q.sub.o: d.sub.o=.sigma./.DELTA.P.sub.g and
Q.sub.o=(.sigma..sup.4/(.rho..sub.1.DELTA.P.sub.g.sup.3).sup.1/2
[0117] where .sigma. is the interfacial tension of the liquid-gas
interface (Newton/meter). The definition of the pressure drop
.DELTA.P.sub.g is based on the upstream (stagnation) value P.sub.o,
estimated to be a fair representation of the pressure at the exit
of first fluid supply means 6 (FIG. 5), and the value P* at the
sonic point, expected to be located at exit 18 of the pressure
chamber 3. The sonic pressure P* was computed using the well-known
isentropic expression: P*=P.sub.o(2/(k+1)).sup.k/(k-1)
[0118] where k is the heat capacity ratio of the gas (equal to 1.4
for dry air and dry nitrogen; White 1994). Therefore
.DELTA.P.sub.g=P.sub.o-P*(1.about.(2/(k+1)).sup.k/(k-1))
[0119] Thus, for both dry air and dry nitrogen,
.DELTA.P.sub.g=0.4717P.sub.o
[0120] In experiments 1 through 4, P.sub.o was varied between 200
kPa and 700 kPa.
[0121] The best power law fit to the available data (FIG. 7) is:
VMD/d.sub.o=5.60 (Q/Q.sub.o).sup.0.208
[0122] FIG. 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.sub.o, Q, and
Q.sub.o in each case). The results shown in FIG. 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), and on applying the
flow-focusing equation for the jet diameter given earlier, to
estimate VMD as follows: VMD=1.89
(8.rho..sub.1/(.pi..sup.2.DELTA.P.sub.g)).sup.1/4Q.sup.1/2
[0123] This expression has been cast into dimensionless form using
the definitions of d.sub.o and Q.sub.o: VMD/d.sub.o=1.89
(8/.pi..sup.2).sup.1/4(Q/Q.sub.o).sup.1/2
[0124] In FIG. 8 the "Rayleigh breakup" line, based on this
expression, has been graphed between the limits believed to occur
in reality. If this expression could be extrapolated to higher Q/Qo
values, it would predict larger drop sizes at equal conditions of
Q/Qo and do. But, more importantly, because the dependence with
Q/Qo is much less pronounced than for flow-focused jets, the range
of liquid flow rates over which a certain band of desired drop
sizes can be generated is much wider than from Rayleigh breakup of
flow-focused jets. These conclusions should apply as well when a
comparison is being made to non-Rayleigh breakup of flow-focused
jets, provided the droplet diameters become similar to the jet
diameter.
[0125] Another notable result is that data from dissimilar
atomizers seems to follow the same scaling law. In other words,
based on currently available data, the scaling law (at least its
exponent of approximately 1/5) appears to be relatively insensitive
to the scale of the atomizer. However, in general, differences from
this behavior may be encountered, when practicing the methods
disclosed.
[0126] The proposed atomization system obviously requires delivery
of the first fluid 9 to be atomized and the second fluid 10 to be
used in the resulting suspension of particles. Both fluids should
be fed at a rate ensuring that the system lies within a desired
parameter window. For example, not exceeding a certain ratio of
second to first fluid mass flow rates is generally an important
consideration. Multiplexing a number of atomizers is effective when
the total amount of first fluid flow-rate needed exceeds that
obtained from an individual atomizer or cell. More specifically, a
plurality of feeding sources 3 or holes therein forming tubes in
the first fluid supply means 3 may be used to increase the overall
rate at which particle suspensions are created. The flow-rates used
should also ensure the mass ratio between the flows is compatible
with the specifications of each application.
[0127] The second fluid and first fluid 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 of atomizers is needed, the
first fluid 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.
[0128] Although a single first fluid supply means 3 is shown in
FIGS. 1-5, it is, of course, possible to produce a device with a
plurality of feeding members 3 where each feeding member feeds
fluid to an array of outlet orifices 18 in a single surrounding
pressure chamber 2. These feeding members can be separate solid
bodies, or can share one or more solid components. For example, a
row of feeding channels to supply first fluid 9 can be created by
joining two halves, each patterned with a series of half channels
needed to supply the first fluid. In addition, the first fluid
supply means 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 first fluid supply means. Such curved
devices may have any level of curvature, e.g. circular,
semicircular, elliptical, hemi-elliptical, etc.
Example 6
[0129] FIGS. 10, 11, and 12 report results from a separate
experiment in which the aerosol size distribution was carefully
measured as a function of the distance between the first fluid
supply means and the pressure chamber, H. Aerosol size
distributions were measured outside the atomizer using a standard
aerosol measurement technique called laser diffraction (using a
Sympatec HELOS system). A device was designed having a
configuration as that shown on FIG. 5. The geometric parameters for
this system are recorded in the last line of TABLE A above.
Measurements of the particle size distribution were made with
de-ionized water as first fluid and dry nitrogen as second fluid,
at a water flow rate of 35 ml/hr and a pressure in the pressure
chamber measured upstream from channel 13 relative to the room into
which the aerosol was discharged, of 10 bar. Presented are two
statistics that define the particle size: d85 and GSD. d85
represents the diameter under which is represented 85% of the
volume of the aerosol measured. (For example, using this
nomenclature, the volume median diameter VMD described earlier
would be expressed as d50.) GSD is a measure of the width of the
distribution in droplet sizes, and is equal to the so-called
geometric standard deviation.
[0130] FIG. 10 graphs d85 as a function of the channel with H. It
can be seen that d85 is large at the largest values of H, but it is
quite small at smaller values of H, and then rises again for even
lower values of H. The transition seen at intermediate values of H
represents a transition from a certain mode of atomization to
another, more efficient violent focusing mode. All tests represent
conditions of approximately constant second fluid flow rate (given
that the pressure upstream, and the geometry of the pressure
chamber exit where the sonic condition determining the mass flow
rate is assumed to exist are kept constant.) Interestingly, the
width of the distribution is not worsened when this transition
takes place. In fact, FIG. 11 shows that the GSD stays nearly
constant throughout the entire range of conditions tested. FIG. 12
shows d85 versus the ratio of H to the inner diameter of the liquid
supply channel (D.sub.t).
Drug Delivery Device
[0131] A device of the invention may be used to provide particles
for drug delivery, e.g. the pulmonary delivery of aerosolized
pharmaceutical compositions comprised of a drug alone or with a
pharmaceutically acceptable carrier. The device would produce
aerosolized particles of a pharmaceutically active drug for
delivery to a patient by inhalation. The device is comprised of a
first fluid 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
second fluid is fed and out of which second fluid is expelled from
an opening. The opening from which the second fluid is expelled is
positioned directly in front of the flow path of first fluid
expelled from the feeding channel. Various parameters are adjusted
so that pressurized second fluid surrounds first fluid 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. Examples of the
second fluid used are air, nitrogen, carbon dioxide, etc., and
mixtures thereof. Examples of first fluid are a drug dissolved or
suspended in an aqueous formulation, ethanolic formulation, etc.,
and mixtures thereof.
Production of Dry Particles
[0132] 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 micro-meters 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.
[0133] For the formation of dry particles, the first fluid is
preferably a liquid, and 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 micro-meters). The first fluid is
preferably a solution containing a volatile solvent and a high
concentration of solute drug. Alternatively, the first fluid is a
suspension containing a uniform concentration of suspended matter.
In either case, the liquid solvent quickly evaporates upon
atomization (due to the small size of the particles formed) to
leave very small dry particles.
Fuel Injection Apparatus
[0134] 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 micro-meters, and preferably between 10 and
100 micro-meters) 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.
Simultaneously, a second fluid, e.g. air, contained in 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.
[0135] 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 an oxidizing gas (e.g. air
or oxygen) which flows into the exit orifice. Thus, clogging of the
orifice is eliminated or substantially reduced. In addition,
formation of carbon deposits around the orifice exit is also
substantially reduced or eliminated. Second, 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.
Microfabrication
[0136] Molecular assembly presents a `bottom-up` approach to the
fabrication of objects specified with incredible 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 non-biological structures with dimensions
as small as 1 to 100 nanometers, and having molecular weights of
10.sup.4 to 10.sup.10 daltons. Microelectro-deposition and
microetching can also be used in microfabrication of objects having
distinct, patterned surfaces.
[0137] Atomized particles within a desired size range (e.g., 0.001
micron to about 0.5 micro-meters) 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. In
addition, 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.
REFERENCES
[0138] 1. Schuster, J. A., Rubsamen, R. M., Lloyd, P. M. and Lloyd,
L. J. (1997) "The AERx Aerosol Delivery System." Pharmaceutical
Research vol 14 (3) pp 354-357 [0139] 2. A. M. Ganan-Calvo (1998)
"Generation of Steady Liquid Microthreads and Micron-Sized
Monodisperse Sprays in Gas Streams." Physical Review Letters, vol
80 (2) pp 285-288 [0140] 3. U.S. Pat. No. 6,119,953, "A Liquid
Atomization Procedure", A. Ganan Calvo, A. Barrero Ripoll [0141] 4.
Bayvel L. and Z. Orzechowski, (1993) Liquid Atomization. Taylor and
Francis, Washington D.C. [0142] 5. Lavernia E. J. and Y. Wu, (1996)
Spray Atomization and Deposition. John Wiley & Sons Ltd,
Chichester, West Sussex, England. [0143] 6. Lefebvre A. H. (1989)
Atomization and Sprays. Hemisphere Publ. Co., New York. [0144] 7.
Gretzinger-Marshall, (1961) "Characteristics of Pneumatic
Atomization" A. I. Ch. E. Journal, June 1961, pages 312-318.
[0145] The instant invention is shown and described herein in a
manner which is considered to be the most practical and preferred
embodiments. It is recognized, however, that departures may be made
therefrom which are within the scope of the invention and that
obvious modifications will occur to one skilled in the art upon
reading this disclosure.
* * * * *