Note: Descriptions are shown in the official language in which they were submitted.
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METHOD FOR PRODUCING AN AEROSOL
FIELD OF THE INVENTION
This application generally relates to the creation of an aerosol created by
the
directed flow of fluids.
BACKGROUND OF THE INVENTION
Devices for creating finely directed streams of fluids and/or creating
aerosolized
particles of a desired size are used in a wide range of different
applications, such as, for
example, finely directed streams of ink for ink jet printers, or directed
streams of solutions
containing biological molecules for the preparation of microarrays. The
production of
finely dispersed aerosols is also important for (1) aerosolized delivery of
drugs to obtain
deep even flow of the aerosolized particles into the lungs of patients; (2)
aerosolizing fuel
for delivery in internal combustion engines to obtain rapid, even dispersion
of any type of
fuel in the combustion chamber; or (3) the formation of uniform sized
particles which
themselves have a wide range of uses including (a) making chocolate, which
requires fine
particles of a given size to obtain the desired texture or "mouth feel" in the
resulting
product, (b) making pharmaceutical products for timed release of drugs or to
mask flavors
and (c) making small inert particles which are used as standards in tests or
as a substrate
onto which compounds to be tested, reacted or assayed are coated.
SUMMARY OF THE INVENTION
A method of creating small particles and aerosols by a technology referred to
here
as "violent focusing" of a liquid to break up and disperse a liquid is
disclosed, along with
devices for generating such violent flow focusing. In general, a "violent
focusing" method
comprises the steps of forcing a first liquid through a feeding tube and out
of an exit opening
of the feeding tube is positioned inside a pressure chamber which is
continually filled with a
second fluid which may be a second liquid immiscible in the first liquid or a
gas. The exit
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opening of the feeding tube is positioned such that the liquid flowing out of
the tube flows
toward and out of an exit or discharge orifice of the chamber surrounding the
exit opening of
the feeding tube. The first liquid exiting the tube is focused to a
substantially reduced
diameter and subjected to a violent action created by the second liquid or
gas, breaking up
the flow into particles substantially smaller than if the reduced diameter
flow underwent
spontaneous capillary breakup. The exit opening of the feeding tube preferably
has a
diameter in the range of about 5 to about 10,000 microns and the exit opening
of the tube is
positioned at a distance in a range of from about 5 to about 10,000 microns,
more preferably
about 15 to about 200 microns from an entrance point of the exit orifice.
A stream of the first liquid flows out of the tube and is focused by the flow
of the
second liquid or gas in the surrounding pressure chamber. The focused stream
then exits out
of the discharge orifice of the pressure chamber, destabilizing and forming
small particles.
The size of the particles of the first liquid is governed by the balance
between the surface
tension forces of the first liquid particle formed, and the amplitude of the
turbulent pressure
fluctuations at, and outside of the exit orifice of the pressure chamber. When
the particles
are sufficiently small that their surface tension forces substantially match
the amplitude of
the pressure fluctuation then the particles are stabilized and will not break
up into still
smaller particles.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a schematic cross-sectional plan view of a nozzle of the
invention;
Figure 2 is another embodiment of the nozzle of Figure 1 showing and labeling
various angles and areas of the nozzle;
Figure 3 is the same embodiment as shown in Figure 1 with various angles and
areas labeled;
Figure 4 is another embodiment of the nozzle of Figure 1 with certain areas
and
angles labeled;
Figure 5 is an embodiment of the nozzle of Figure 1 with various parameters
labeled;
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Figure 6 is a graph of the volume median diameter (VMD) vs the liquid supply
flow rate for four different liquids;
Figure 7 is a graph of the dimensionless volume median diameter (VMD) versus
dimensionless liquid flow rate with a line through the data points showing the
best power-fit;
Figure 8 is a graph of the data with the line shown in Figure 7 compared to a
theoretical line for the Rayleigh breakup prediction of a flow-focused jet;
and
Figure 9 is a graph of data obtained with the different liquids listed of the
geometric standard deviation (GSD) vs. dimensionless liquid flow rates.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
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.
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.
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.
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
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invention. Further, the dates of publication provided may be different from
the actual
publication dates which may need to be independently confirmed.
GENERAL METHODS
The method is carried out by forcing a liquid from a liquid supply means, e.g.
a
tube. The liquid exits the supply means into a pressure chamber filled with a
second fluid
which is preferably a gas. The chamber has an exit port preferably positioned
directly in
front of and preferably downstream of the flow of liquid exiting the supply
means. The exit
port may be positioned slightly upstream of the liquid supply means exit. The
liquid is
focused by the gas to substantially smaller dimensions as it exits the supply
means e.g. a
tubular stream of liquid one unit in diameter is focused to a stream 1/2 -
1/400 of a unit in
diameter or smaller depending on operating conditions. In this proposed
example, a focused
cylindrical stream of one unit in diameter would be expected to undergo
Rayleigh breakup
and form particles which are about 1.89 times the diameter of the focused
stream. However,
by correctly adjusting parameters (such as positioning the exit of the liquid
supply means
relative to the chamber exit port) the liquid stream is first focused by the
gas flowing out of
the chamber thereby forming a stream with a much smaller diameter. That stream
leaves the
chamber and forms particles which are smaller in diameter than the focused
stream.
Based on the above it will be understood that the nozzles and methods of the
present invention are capable of producing extremely small particles. As an
example,
consider producing particles using a cylindrical liquid supply means having a
diameter of
1000 units. The stream from such a supply means would be expected to undergo
normal
Rayleigh breakup of the 1000 unit diameter stream to form spherical particles
having a
diameter of about 1.89 x 1000 or 1890 units in diameter. If the stream having
a diameter of
1000 units is focused to a stream or jet of smaller dimension by a surrounding
gas the jet
might have a diameter of one tenth that size or 100 units. That 100 unit
diameter focused jet
would be expected to undergo normal Rayleigh breakup to form particles having
a diameter
of 1.89 x 100 or 189 units.
Focusing the diameter of the stream to a narrow focused jet or "stable
microjet" jet
has been referred to as flow focusing technology. When using the flow focusing
technology
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the focused jet has a diameter d, at a given point A in the stream
characterized by the
formula:
\
8p
1
d ,
2II2 LP
gl
wherein d, is the diameter of the stable microjet, indicates approximately
equally to where
an acceptable margin of error is 10%, p, is the density of the liquid and
AP, is change in
gas pressure of gas surrounding the stream at the point A. The diameter of the
jet (d3) can be
any reduced dimension smaller than that of liquid stream exiting the supply
means, e.g. can
have a cross-sectional diameter of from about one half to about 1/100 the area
of the stream
exiting the liquid supply means.
In accordance with the violent flow focusing of the present invention the
liquid
flow exiting the supply means with a diameter of 1000 units is focused as it
leaves the
supply means so that the end of the exiting drop exiting the liquid supply
tube is focused by
the surrounding gas to a reduced dimension (e.g. 1/2 to 1/100 the cross-
sectional diameter of
the liquid supply means). For purposes of example we will say the 1000 unit
stream is
reduced to a diameter of about 100 units. That 100 unit end of the drop is
subjected to
turbulent action by the gas exiting the pressure chamber thereby forming
particles which are
10 units in diameter. Thus, the above proposed examples can be summarized as
follows:
Supply Means Diameter Particle Diameter
Rayleigh 1000 ¨ 1890
Flow Focusing 1000 ¨ 189
Violent Flow Focusing 1000 ¨ 1
Based on the above it will be appreciated that the method of the invention can
produce particles which are substantially smaller than (e.g. 1/2 to 1/100) the
size of particles
produced using flow focusing technology. Further, flow focusing technology can
produce
particles which are substantially smaller than (e.g. 1/2 to 1/100) the size
of particles produced
by normal capillary breakup of a stream.
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GENERAL DEVICE
The basic device or nozzle of the invention can have a plurality of different
configurations. However, each configuration or embodiment will comprise a
means for
supplying a liquid or first fluid and a means for supplying a second fluid
(preferably a gas) in
a pressure chamber which surrounds at least an exit of the means for supplying
a liquid. The
liquid supply means and pressure chamber are positioned such that turbulent
action takes
place between the liquid exiting the liquid supply means and the second fluid,
a liquid or a
gas, exiting the supply chamber. Preferably, the exit opening of the pressure
chamber is
downstream of and more preferably it is directly aligned with the flow path of
the means for
supplying the liquid. To simplify the description of the invention, the means
for supplying a
liquid is often referred to as a cylindrical tube (tube shape could be varied,
e.g. oval, square,
rectangular). The first fluid or liquid can be any liquid depending on the
overall device
which the invention is used within. For example, the liquid could be a liquid
formulation of
a pharmaceutically active drug used to create dry particles or liquid
particles for an aerosol
for inhalation or, alternatively, it could be a hydrocarbon fuel used in
connection with a fuel
injector for use on an internal combustion engine or heater or other device
which burns
hydrocarbon fuel. Further, for purposes of simplicity, the second fluid is
generally described
herein as being a gas and that gas is generally air or an inert gas. However,
the first fluid is a
liquid and the second fluid may be a gas or a liquid provided the first and
second fluids are
sufficiently different from each other (e.g. immiscible). It is possible to
have situations
wherein the liquid exits either the liquid supply means or the pressure
chamber vaporizes to
a gas on exit. Such is not the general situation. Notwithstanding these
different
combinations of liquid-gas, and liquid-liquid, the invention is generally
described with a
liquid formulation being expelled from the supply means and interacting with
surrounding
gas flowing out of an exit of the pressure chamber. Further, the exit of the
pressure chamber
is generally described as circular in cross-section and widening in a funnel
shape (Fig. 1),
but could be any configuration.
Referring to the figures a cross-sectional schematic view of the nozzle 1 is
shown
in Figure 1. The nozzle 1 is comprised of two basic components which include
the pressure
chamber 2 and the liquid supply means 3. The pressure chamber 2 is pressurized
by fluid
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flowing into the chamber by the entrance port 4. The liquid supply means 3
includes an
inner tube 5 where liquid flows. The inner tube 5 of the liquid supply means 3
is preferably
supplied with a continuous stream of a fluid which fluid is preferably in the
form of a liquid.
The pressure chamber 2 is continuously supplied with a pressurized fluid which
may be a
liquid or a gas. When the fluid is a liquid the liquid is preferably insoluble
and incompatible
with the liquid being provided from the inner tube 5 (e.g. oil and water which
do not readily
mix and form a distinct interface). The inner tube 5 of the liquid supply
means 3 includes an
exit point 6. The pressurized chamber 2 includes an exit point 7. The exit
point 7 of the
pressure chamber is preferably positioned directly downstream of the flow of
liquid exiting
the exit point 6. The liquid supply means exit and the exit of the pressure
chamber are
configured and positioned so as to obtain two effects (1) the dimensions of
the stream exiting
the liquid supply means are reduced by the fluid exiting the pressure chamber;
and (2) the
liquid exiting the liquid supply means and the fluid exiting the pressure
chamber undergo a
violent interaction to form much smaller particles than would form if the
stream of liquid in
reduced dimensions underwent normal capillary instability, e.g. formed
spherical particles
1.89 times the diameter of the cylindrical stream.
Preferably, the exit port of the chamber 2 is directly aligned with the flow
of liquid
exiting the liquid supply means 3. An important aspect of the invention is to
obtain small
particles 8 from the liquid 9 flowing out of the exit port 6 of the inner tube
5. Obtaining the
desired formation of particles 8 is obtained by correctly positioning and
proportioning the
various components of the liquid supply means 3 and the chamber 2 as well as
the properties
of the fluids including the speed of these fluids which flow out of both the
liquid supply
means 3 and the chamber 2. 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.
Preferably, the liquid 9 is held within the inner tube 5 which is cylindrical
in
shape. However, the inner tube 5 holding the liquid 9 may be asymmetric, oval,
square,
rectangular or in other configurations including a configuration which would
present a
substantially planar flow of liquid 9 out of the exit port 6. Thus, the nozzle
of the invention
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applies to all kinds of round (e.g., axi-symmetric) and planar (e.g.,
symmetric two-
dimensional) configurations that have a convergent passage for the outer
fluid. For example,
a round but not axi-symmetric geometry would be one in which the surfaces of
the orifice
plate are faceted at different azimuthal angles. Accordingly, the figures
including Figure 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 infinite degrees of freedom of design. For example, corners which
are shown as
sharp could be rounded or finished in different ways.
Formation of the microjet and its acceleration and ultimate particle formation
are
based on the abrupt pressure drop associated with the steep acceleration
experienced by the
liquid on passing through an exit orifice of the pressure chamber which holds
the second
fluid (i.e. the gas).
Without being limited to any one theory, the creation of the violently focused
aerosol (in an axisymmetric configuration) may occur as follows. The strong
radial fluid
flow (10) that exists in the very narrow gap between the points 6 and 7
becomes circulatory
as it passes through and out of the orifice of the exit 7 of the pressure
chamber 2. At the
same time, the liquid (9) meniscus is sucked in towards the center of the exit
point 7 of the
chamber 2. As the gas 10 exits the hole at point 7, its strong circulatory
motion induces the
fluid dynamic effect referred to as a vortex breakdown. This is an instability
in which fluid
particles gain so much centrifugal inertia that they spin off away from the
axis. As a result, a
bubble of gas is created along the axis downstream from this point, in which
the outer fluid
(preferably a gas) flow reverses, flowing upstream back towards the nozzle.
Consequently,
the droplets are accelerated radially outwards resulting in enhanced
dispersion.
Referring now to Figure 2 in order to describe the relationships between some
of
the components shown in Figure 1. First, a dashed line C---C' is shown running
through the
center of the inner tube 5 in which the liquid 9 flows as well as the exit of
the chamber 2. In
symmetric atomizers the line C--C' represents the plane of symmetry
intersection of the
plane of view. The line B--B' represents the bisector of the convergent
passage near the
center of the nozzle. The area referred to as the "convergent passage" is the
region which is
the open area between the terminal face 11 of the liquid supply means 3 and
the front face 12
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of the chamber 2. To obtain desired results with the nozzle of the present
invention the
following characteristics must be present:
(a) a strong convergence of the outer fluid (liquid of gas) in the chamber 2
towards and around the inner fluid 9 coming out of the inner tube 5;
(b) sufficient momentum for the fluid 10 in the chamber 2 before it interacts
with
the fluid 9;
(c) a focusing or compression of the stream of liquid 9 by the surrounding
fluid
10.
The above characteristics (a)-(c) combine with each and with other
characteristics
in order to result in the desired (d) vortex breakdown of the stream of fluid
9 exiting the
inner tube 5. For example, other characteristics will include sonic speeds and
shock waves
(e) when the outer fluid 10 is a gas.
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 outer fluid:
The primary characteristic of the present invention is the facilitation of a
strongly
convergent (imploding) flow of outer fluid 10 towards and around the inner
liquid 9. The
fluid 10 in the pressure chamber should preferably not merely flow parallel to
the liquid 9
exiting the liquid supply means, i.e. should preferably not intersect at a 0
degree angle.
Further, the fluid 10 in the pressure chamber should preferably not flow
directly
perpendicular to the liquid stream 9 exiting the liquid supply means, i.e.
should preferably
not interact at a 90 degree angle or more. Thus, convergence of the two fluids
is preferably
at an angle of more than 0 degrees and less than 90 degrees. However, the
fluid 10 of the
pressure chamber could, in some situations be directed at the liquid 9 from
the liquid supply
means at an angle of 90 degrees or more, i.e., at an angle such that the fluid
10 is flowing
back toward the liquid 9 and is converging on the liquid 9 at an angle of up
to 150 degrees.
Flow convergence improves the transfers of momentum and kinetic energy from
the outer fluid 10 to the inner liquid 9 required to breakup the inner fluid 9
into particles 8.
Improving the efficiency of such transfer results in energy savings for a
given amount of
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inner liquid 9 atomized and a given droplet size requirement. A greater
efficiency of
atomization is achieved by transferring a greater fraction of pressure energy
originally in the
outer fluid 10 per unit mass of the outer fluid to the inner liquid 9.
In order to generate significant convergence in the outer fluid 10 towards the
inner
liquid 9, the outer fluid 10 must be admitted into a path that gives it a
sufficiently high
converging speed. Specifically, the following design constraints shown in
Figure 3 are
preferred.
(1) a convergent passage convergence angle a smaller than 90 degrees,
a < 90 degrees,
(2) the exterior surface 11 of the feeding passage exit should form an angle p
with
center line CC' greater than 45 degrees but smaller than 150 degrees,
150 degrees > r3 > 45 degrees,
and (3) the length of the convergent passage (shown in Figure 3) should be
chosen
such that an optimum is found that encourages a significant bending of the
streamlines
towards the inner fluid 9. In general, DI is required to be at least equal to
1.2 times Do,
DI > 1.2 Do .
(b) Incident momentum in outer fluid:
To ensure sufficient momentum in the outer fluid at the point where it meets
the
inner liquid 9, the convergent passage separation between R and P (see Figure
2) must be
chosen appropriately. This distance can be defined as the distance between
points R and P in
Figure 2. For given conditions of pressure and temperature in the outer fluid
chamber and
outside region, this variable regulates the relative average velocity between
the inner liquid 9
and the outer fluid 10 at the point of encounter (inner rim of tube exit
indicated by point P' in
Figures 2 and 3). For example, a very narrow convergent passage is one in
which frictional
losses dissipate the outer fluid momentum significantly. Widening such a
passage will
encourage coupling between outer fluid 10 and inner liquid 9. On the other
hand, if the
separation between R and P is made too wide, then the effect of efficient
atomization is lost,
because the fastest speed is encountered then in the discharge orifice, not at
the end of the
convergent passage.
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In general, thus, one desires to have as high a momentum as possible in the
outer
fluid 10 for a certain amount of outer fluid mass flow (and pressure and
temperature
conditions). 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
convergent passage). The fastest speed is generally obtained in the narrowest
part of the
outer fluid flow path. Again, if the distance between R and P is too large,
then the
narrowest part will be at the discharge orifice. Thus, if the distance of R to
P is H the largest
value of H compatible with this requirement typically is:
K. =13 Do
For axi-symmetric configurations, 13 equals 0.25; while for planar-two
dimensional
configurations, 13 equals 0.5.
On the other hand, H must be large enough to preclude excessive friction
between
the outer fluid and the convergent passage walls that can slow down the flow
and waste
pressure energy (stagnation enthalpy) into heat (internal energy). An
approximate guiding
principle is that H should be greater than H,o,o, defined as a few times the
thickness of the
viscous boundary layer Si_ that develops inside the outer fluid 10 in its
acceleration through
the convergent passage:
Hmin
¨ 6L
¨ 1 to 10
The thickness of the boundary layer at point P' (Figure 2) for the case when
the
outer fluid is near the speed of sound is approximately given by the following
expression:
6L= (L 1.12 /(P2P02) 5) 5
Here 1l2 is the dynamic viscosity coefficient of the outer fluid 10, p2 is its
density,
and P02 is the pressure of the outer fluid 10 in the upstream chamber. A. is a
numerical factor,
which generally is between 1 and 10. L is the length of the convergent passage
(Figure 3)
L 0.5 (D1-Dt) / sin(13)
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These expressions neglect the presence of liquid in the discharge orifice, or
the
possibility of swirling in the flow. Therefore, the equations provided above
should be
considered as approximate guides, e.g. 30% error factors.
(C) Flow-focusing of the inner liquid:
In the presence of airflow, the inner liquid 9 coming out of the inner tube 5
gets
funnel-shaped into a jet that gets thinner as it flows downstream. The jet can
have a variety
of different configurations, e.g. a circular cross-section, or a flat planar
one. Any
configuration can be used which provides flows through the center of the
discharge orifice 7,
and can become much thinner as it enters the discharge orifice 7 than at the
exit 6 of the
inner tube 5. This phenomenon has previously been termed "flow-focusing" (see
WO
99/31019 published June 24, 1999). The forces responsible for the shaping of
the inner
liquid 9 are believed to arise from the pressure gradients that set within the
outer fluid 10 as
it flows through the discharge orifice 7. For example, in axi-symmetric
configurations, a
round inner liquid jet is expected to attain a diameter dj determined by the
V2 power law with
liquid flow rate Q (in volume per unit of time, e.g. cubic meter per second):
¨ (8pV (7r2Apg))1/4 Q1/2
pi is the inner liquid density, ir is pi, and APg is the pressure drop in the
outer fluid
between the upstream value and the value at the point where di is taken and ¨
means
approximately equal to with about a 10% error margin. This equation will be
herein
referred to as the "flow-focusing" formula and only applies for a uniform
velocity
distribution along the inner liquid jet radius.
A notable consequence of flow-focusing is that the inner liquid is stabilized
towards the center of the discharge orifice. For example, in one of the
preferred device
embodiments (Figure 5), the exit of both the inner tube 5 and the chamber 2 at
point 7 were
of equal diameter. However, in all the tests done the inner liquid 9 was
observed to flow
through the center of the discharge orifice without impacting or wetting its
side walls. (Due
to the random nature of the drop trajectories under conditions of very high
inner liquid flow
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rates used for violent focusing, a small degree of wetting has indeed been
detected, but is
associated with an insignificant fraction of the inner liquid.)
(d) Vortex breakdown:
A theoretical model based on the existence of a vortex cell near the region of
breakup is proposed to explain the effectiveness of atomization obtained by
the present
invention in the case of axi-symmetric geometries. In such cases, it is
hypothesized that the
strong radial forces provided by the outer fluid flow between the orifice body
and the liquid
dispenser (a cylindrical tube in its simplest form) result in a violent swirl
in the outer fluid.
The swirling motion results in a vortex which breaks down near the region of
breakup. Such
breakdown is the centrifugal explosion of the fluid streamlines due to their
rapid spinning
motion. The entrained particles and filaments of the inner liquid are spun
away and
dispersed before they get a chance to coalesce (two or more particles forming
one). The
benefits of vortex breakdown in promoting liquid breakup and drop dispersion
have
previously been reported. In the new invention any swirling of the outer fluid
is not created
upstream by means of swirling vanes or other shapes of the atomizer body.
Instead, the
swirling is induced locally by the strong converging motions forced by the
very simple
geometry of the atomizer.
(e) Gas sonic speeds and shock waves:
Sonic speeds and shock waves take place when the outer fluid is a gas. In all
tests
to date using that configuration, 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.
Characteristics of supersonic flow such as shock waves may improve
atomization.
However, such are not believed to be required.
Unique characteristics of the present invention include: (f) High frequency of
droplet generation, (g) Low requirements on liquid pressure, (h) Low
sensitivity of drop size
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to inner liquid flow rate, (i) Little apparent effect of atomizer size on
droplet size. These
characteristics are described further below.
(a High frequency of droplet generation:
When the outer fluid is a gas and the inner fluid a liquid, the data
demonstrate that
the droplets are much smaller than predicted from the spontaneous capillary
breakup, such as
Rayleigh breakup in axi-symmetric configurations; of an inner liquid column of
size dj 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, the final
size of the droplets is
many times smaller than the flow-focusing diameter dj discussed earlier. As a
result, the
frequency of droplet production is much higher than predicted by spontaneous
capillary
breakup of the flow 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 tube
5 and chamber
2. (See Figure 7)
(g) Low requirements on liquid pressure:
The inner liquid 9 does not have to be pushed out of its inner tube 5 with a
sufficiently high pressure capable of maintaining a stable liquid jet in the
absence of outer
fluid flow and solid surfaces in its way. It is not necessary for the inner
liquid to form a
stable microjet structure. Further, pre-existent inner liquid jet structure
coming directly out
of the exit opening 6 is not required because, a explained in (c), the liquid
meniscus is
focused by the action of the outer fluid pressure forces.
(h) Low sensitivity of drop size to inner liquid flow rate:
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.
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_ .
(i) Small apparent effect of atomizer size:
Based on the experimental data available thus far (reported later herein), the
drop
size dependence with inner liquid flow rate, outer fluid pressure and inner
liquid physical
properties does not seem to involve any variables characterizing the size of
the atomizer.
(See the EXAMPLES.) However, under certain conditions of operation, for
example at high
flow rates that lead to a large fraction of the discharge orifice occupied by
the liquid, one
would expect certain dependence.
EXAMPLES
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.
Figures 6-9 show results for aerosols produced by methods of the present
invention
using dry air and dry nitrogen as outer fluids 10, and a range of liquids as
inner fluids 9:
distilled water, 2-propanol, 20 % (v/v) by volume of ethanol in water
("20%Et0H"), 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.
The droplet size was determined by phase Doppler anemometry 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
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. .
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
Atomizer geometric dimensions (in micron unless indicated) used in the
experiments (refer to figure for key); typical tolerance +1-15%, (a=0 degrees;
13=90 degrees)
Experiment Do Dt Dl H T c, degrees 0,
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
Figure 6 is a graph of the volume median diameter (VMD) vs the liquid supply
flow rate for four different liquids.
In Figure 7 the volume median diameter and liquid flow rates have been
non-dimensionalized using similar variables to those identified in the flow-
focusing
literature, do and Q.:
do YIAPg
and
Q. = c74 / (pi Apg3 )1/2
where a is the interfacial tension of the liquid-gas interface (newton/meter).
However, the
definition of the pressure drop APg used here is based not on the upstream
(stagnation) and
downstream (ambient) values of the pressure, but on the upstream value Po and
the value P*
at the sonic point. The sonic pressure was computed using the well-known
isentropic
expression:
P* = Po (2/(k+1))"k-1)
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where k is the heat capacity ratio of the gas (equal to 1.4 for dry air and
dry nitrogen).
Therefore
APg = Po - P* = Po (1 - (2/(k+1))kl(k-1) )
Thus, for both dry air and nitrogen,
APg = 0.4717 Po
In these experiments Po was varied between 200 kPa and 700 kPa.
The best power law fit to the available data (Figure 7) is:
VMD / do = 5.60 (Q/Q00 208
Figure 8 graphs the new fit characteristic of the new method together with the
one which
would correspond to the Rayleigh breakup of a flow focused jet at the same
conditions of
liquid properties, flow rate, and gas pressure (thus equal do, Q, and Qo). The
results shown in
Figure 8 are based on the theoretical assumption that Rayleigh breakup of a
flow-focused jet
would result in droplets of uniform diameter (VMD) equal to 1.89 times the jet
diameter.
Applying the equation for the jet diameter given earlier leads to:
VMD = 1.89 (80 (lr2Apg))1/4 Q1/2
This expression can be cast into dimensionless form using the definitions of
do and Qo:
VMD / d, = 1.89 (8/7c2)1/4 ("0)1/2
In Figure 8 the "Rayleigh breakup" line has been represented 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,
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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.
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 appears
to be relatively insensitive to the scale of the atomizer.
The proposed atomization system obviously requires delivery of the liquid to
be
atomized and the gas to be used in the resulting spray. Both should be fed at
a rate ensuring
that the system lies within the desired parameter window. Multiplexing is
effective when the
flow-rates needed exceed those obtained for an individual cell. More
specifically, a plurality
of feeding sources 3 or holes therein forming tubes 3 may be used to increase
the rate at
which aerosols are created. The flow-rates used should also ensure the mass
ratio between
the flows is compatible with the specifications of each application.
The gas and liquid can be dispensed by any type of continuous delivery system
(e.g. a compressor or a pressurized tank the former and a volumetric pump or a
pressurized
bottle the latter). If multiplexing is needed, the liquid flow-rate should be
as uniform as
possible among cells; this may entail propulsion through several capillary
needles, porous
media or any other medium capable of distributing a uniform flow among
different feeding
points.
Although a single liquid supply means 3 is shown in Figures 1-5 it, of course,
is
possible to produce a device with a plurality of feeding members where each
feeding
member feeds fluid to an array of outlet orifices in a single surrounding
pressure chamber.
In addition, the liquid 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 liquid
supply means.
Such curved devices may have any level of curvature, e.g. circular,
semicircular, elliptical,
hemi-elliptical, etc.
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DRUG DELIVERY DEVICE
A device of the invention may be used to provide particles for drug delivery,
e.g.
the pulmonary delivery of aerosolized pharmaceutical compositions. The device
would
produce aerosolized particles of a pharmaceutically active drug for delivery
to a patient by
inhalation. The device is comprised of a liquid feeding source such as a
channel to which
formulation is added at one end and expelled through an exit opening. The
feeding channel
is surrounded by a pressurized chamber into which gas is fed and out of which
gas is
expelled from an opening. The opening from which the gas is expelled is
positioned directly
in front of the flow path of liquid expelled from the feeding channel. Various
parameters are
adjusted so that pressurized gas surrounds liquid flowing out of the feeding
channel in a
manner so as to reduce the dimension of the flow which is then broken up on
leaving the
chamber. The aerosolized particles are inhaled into a patient's lungs and
thereafter reach the
patient's circulatory system.
PRODUCTION OF DRY PARTICLES
The method of the invention is also applicable in the mass production of dry
particles. Such particles are useful in providing highly dispersible dry
pharmaceutical
particles containing a drug suitable for a drug delivery system, e.g.
implants, injectables or
pulmonary delivery. The particles formed of pharmaceutical are particularly
useful in a dry
powder inhaler due to the small size of the particles (e.g. 1-5 microns in
aerodynamic
diameter) and conformity of size (e.g. 3 to 30% difference in diameter) from
particle to
particle. Such particles should improve dosage by providing accurate and
precise amounts of
dispersible particles to a patient in need of treatment. Dry particles are
also useful because
they may serve as a particle size standard in numerous applications.
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 microns). The first fluid liquid is preferably a solution
containing a high
concentration of solute. Alternatively, the first fluid liquid is a suspension
containing a
uniform concentration of suspended matter. In either case, the liquid quickly
evaporates
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upon atomization (due to the small size of the particles formed) to leave very
small dry
particles.
FUEL INJECTION APPARATUS
The device of the invention is useful to introduce fuel into internal
combustion
engines by functioning as a fuel injection nozzle, which introduces a fine
spray of
aerosolized fuel into the combustion chamber of the engine. The fuel injection
nozzle has a
unique fuel delivery system with a pressure chamber and a fuel source.
Atomized fuel
particles within a desired size range (e.g., 5 micron to about 500 microns,
and preferably
between 10 and 100 microns) 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.
Fuel injectors of the invention have two significant advantages over prior
injectors. First, fuel generally does not contact the periphery of the exit
orifice from which it
is emitted because the fuel stream is surrounded by a gas (e.g. air) 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.
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MICROFABRICATION
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 nonbiological
structures with
dimensions as small as 1 to 100 nanometers, and having molecular weights of
104 to 101
daltons. Microelectro-deposition and microetching can also be used in
microfabrication of
objects having distinct, patterned surfaces.
Atomized particles within a desired size range (e.g., 0.001 micron to about
0.5
microns) 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.
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.
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