Introduction
[0001] This invention relates to aerosol generators.
[0002] Aerosol generators comprising a vibratable member and a plate body operably coupled
to the vibratable member are known. The plate body has a top surface, a bottom surface,
and a plurality of apertures extending from the top surface to the bottom surface.
The apertures may be tapered such that when a liquid is supplied to one surface and
the aperture plate is vibrated using the vibratable member, liquid droplets are ejected
from the opposite surface. Details of such known systems are described for example
in
US6,235,177,
US2007/0023547A, and
US7066398.
[0003] The aperture plate is subjected to a dynamic cyclic stress, flexing inwards and downwards
with liquid passing through the upper portion and ejected through the lower portion
of the aperture plate, through the action of a member comprising a piezoelectric transducer
that is configured to vibrate upon application of an electric signal as described
in Patent
US 7,066,398.
[0004] Such aperture plates are usually vibrated between 100 to 200 kHz, over extended periods
of time. These periods can vary as some nebulizers are reused intermittently for up
to 1 year, (which might equate to approximately 800 x 15 minute nebulisation periods)
and others are used continuously over short periods of up to 1 week.
[0005] Callister D.W, Materials Science and Engineering-An Introduction, John Wiley and sons,
2007, p227-245 describes fatigue as a form of failure that occurs in systems undergoing dynamic
and fluctuating stresses. The term 'fatigue' is used because this type of failure
normally occurs after a lengthy period of repeated stress or strain cycling. Under
these circumstances it is possible for failure to occur at a stress level considerably
lower than the yield strength of the material σ
TS and generally below the yield strength of the material σ
Y.
[0006] The combination of high frequencies and such demanding usage periods place enormous
stresses on the aperture plate. It is therefore not uncommon that the aperture plate
can fail. This problem manifests itself with fractures forming on the aperture plate
surface causing the nebulizer to stop functioning and rendering it impossible to deliver
aerosolised medication to the patient.
[0007] Various attempts have been made to address this but the problem still persists.
[0008] One attempt has been to provide an aperture plate of a non metallic material such
as a flexible polymeric material but such materials generally do not possess the stiffness
required to provide the vibrational amplitude to aerosolise liquids effectively. Other
attempts have been to make the nebulizer head forming the vibrating aperture plate
as a disposable part of the nebulizer which can be replaced on a frequent basis. However,
this presents many economic challenges.
Statements of Invention
[0009] According to the invention there is provided an aperture plate body according to
claim 1.
[0010] The average grain width may be from 0.2 µm to 2.0 µm, in some cases from 0.2 µm to
1.0 µm. In one embodiment the average grain width is approximately 0.5µm.
[0011] In other cases where high temperatures (which may be in the region of 1000°C) are
used in the process to assemble the aperture plate into a nebuliser, the grain width
may be up to 5µm and may even be as high as 8 µm. One typical process which requires
such high temperatures is brazing. Thus, the average grain width may be from 0.2 µm
to 8.0 µm, in some cases from 0.2 µm to 5.0 µm. In some embodiments the average grain
width may be from 1.0 µm to 4.0 µm
[0012] The aperture plate may be of any suitable thickness. In one case the aperture plate
has a thickness of from 59 to 63 microns.
[0013] The aperture plate may have a domed - shaped geometry and the aerosol exits on the
convex side of the dome-shaped plate.
[0014] The invention also provides an aerosol generator comprising an aperture plate of
the invention and means for vibrating the aperture plate.
[0015] The means for vibrating the aperture plate is preferably configured to vibrate the
plate at a frequency of from 125 to 155 kHz. The plate may be vibrated at from 128
to 148 kHz.
[0016] The invention provides an aperture plate in which fatigue life is preserved and extended
to ensure aersolisation over extended periods.
[0017] In one case the aperture plate comprises a plate body having a top surface, a bottom
surface, and a plurality of apertures that taper in a direction from the top surface
to the bottom surface. Liquid is supplied to the top (rear) surface of the aperture
plate, and the aperture plate is vibrated to eject liquid droplets from the bottom
(front) surface. Further, the apertures have an exit angle that is in the range from
about 30° to about 60°, more preferably about 41° to about 49°, and more preferably
at about 45°. The apertures also have a diameter that is in the range from about 1
micron to about 10 microns at the narrowest portion of the taper. Such an aperture
plate is advantageous in that it may produce liquid droplets having a size that are
in the range from about 2µm to about 10µm, at a rate in the range from about 2µl to
about 25µl per 1000 apertures per second. In this way, the aperture plate may be employed
to aerosolise a sufficient amount of a liquid medicament so that a capture chamber
that may otherwise be employed to capture the aerosolised medicament will not be needed.
[0018] The aperture plate body is constructed from a palladium nickel alloy. Such an alloy
is corrosion resistant to many corrosive materials particularly solutions for treating
respiratory diseases by inhalation therapy, such as an albuterol sulfate and ipratropium
solution, which is used in many medical applications. Further, the palladium nickel
alloy has a low modulus of elasticity and therefore a lower stress for a given oscillation
amplitude.
[0019] Also described is a method for aerosolizing a liquid. According to the method, an
aperture plate is provided that comprises a plate body having a top surface, a bottom
surface, and a plurality of apertures that taper in a direction from the top surface
to the bottom surface. The apertures have an exit angle that is in the range from
about 30° to about 60°, preferably in the range from about 41° to about 49°, more
preferably at about 45°. The apertures also have a diameter that is in the range from
about 1 micron to about 10 microns at the narrowest portion of the taper. A liquid
is supplied to the top (rear) surface of the aperture plate, and the aperture plate
is vibrated to eject liquid droplets from the bottom (front) surface.
[0020] Typically, the droplets have a size in the range from about 2µm to about 10µm. Conveniently,
the aperture plate may be provided with as many apertures as possible, typically at
least about 1,000 apertures so that a volume of liquid in the range from about 2µl
to about 25µl may be produced within a time of less than about one second. In this
way, a sufficient dosage may be aerosolized so that a patient may inhale the aerosolized
medicament without the need for a capture chamber to capture and hold the prescribed
amount of medicament.
[0021] In one particular case, the liquid that is supplied to the top surface is held to
the top surface by surface tension forces until the liquid droplets are ejected from
the bottom surface.
Brief Description of the Drawings
[0022] The invention will be more clearly understood from the following description of an
embodiment thereof, given by way of example only, with reference to the accompanying
drawings, in which:
Fig. 1(a) is a micrograph of an aperture plate according to the invention with a fracture
free, fine equiaxed microstructure (with a trench milled out);
Fig. 1(b) is a micrograph taken from the milled out trench showing a fracture free,
fine equiaxed microstructure;
Fig. 1(c) is a micrograph of an aperture plate according to the invention showing
a microstructure which is somewhat larger than that of Figs 1a and 1b, and caused
by higher temperatures used in the process to assemble the aperture plate into a functioning
nebuliser;
Fig. 2 is an FEA model of a vibrating aperture plate of the invention;
Fig. 3 illustrates a direct relationship between the thickness of the plate and natural
frequency;
Fig. 4 illustrates an inverse relationship between the dome diameter of the plate
and natural frequency;
Fig. 5 is a side view of an aperture plate;
Fig. 6 is a cross-sectional side view of a portion of the aperture plate of Fig. 5;
Fig. 7 is a more detailed view of one of the apertures of the aperture plate of Fig
6;.
Fig. 8 is a graph illustrating the flow rate of liquid through an aperture as the
exit angle of the aperture is varied;
Fig. 9 is a top perspective view of a mandrel having nonconductive islands to produce
an aperture plate in an electroforming process;
Fig. 10 is a side view of a portion of the mandrel of Fig. 9 showing one of the nonconductive
islands in greater detail;
Fig. 11 is a flow chart illustrating one method for producing an electroforming mandrel;
Fig. 12 is a cross-sectional side view of the mandrel of Fig. 11 when used to produce
an aperture plate using an electroforming process;
Fig. 13 is flow chart illustrating one method for producing an aperture plate;
Fig. 14 is a cross-sectional side view of a portion of an alternative aperture plate;
Fig. 15 is a side view of a portion of an alternative electroforming mandrel when
used to form the aperture plate of Fig. 14; and
Fig. 16 illustrates the aperture plate of Fig. 5 when used in an aerosol generator
to aerosolize a liquid.
Detailed Description
[0023] In the invention, an aperture plate is formed from a palladium nickel alloy comprising
about 89% palladium and about 11% nickel. As illustrated in Fig. 1 there is a generally
fine substantially equiaxed grain microstructure throughout the thickness of the aperture
plate. The average grain width (W) is in the range of from 0.2 µm to 2.0 µm, in some
cases from 0.2 µm to 1.0 µm. For optimum results the average grain width is approximately
0.5 µm. However grain widths up to 5 µm and possibly up to 8 µm will also provide
sufficient fracture resistance.
[0024] Because the grain structure is equiaxed (L/W =1) the grain length (L) is the same
as the grain width.
[0025] The grain width was obtained from SEM (Scanning Electron Microscope) pictures using
the line intercept method for calculating the average grain size:
where:
D is the average grain size,
C is the total length of the test line used,
N is the number of grain boundary intercepts on the line,
M is magnification of the micrograph
[0026] The grain structure was investigated with a Focused Ion Beam Microscope (FIB) and
a FIB FEI 200 machine. Using a gallium source (Ga
+), with a primary ion beam of +30keV, a trench was milled 10µm in width X 20µm length
X 6µm depth. The sample was then tilted at 45° and imaged at a magnification of 20,00X
and the grain size, shape, and distribution observed.
[0027] The aperture plate also has a generally equiaxed, randomly oriented grain microstructure
with an average grain width approximately 0.5µm in size - Fig. 1, through the whole
thickness of the aperture plate. The plate has a metallurgical configuration that
is highly resistant to fatigue crack initiation and crack propagation.
[0028] For aperture plates that require higher processing temperatures (possibly in the
region of 1000°C) in the assembly process to incorporate the aperture plate into a
nebuliser, the Focused Ion Beam Microscope (FIB) was unsuitable as the average grain
size was much larger that for those aperture plates that did not experience such high
temperatures in the assembly process. A more suitable technique for the estimation
of grain size is the used of Surface Scanning Electron Microscopy. Fig 1 (c) (i) shows
a micrograph of the bottom surface and Fig 1 (c) (ii) shows a micrograph of the top
surface. The lines that are visible on the surface show the grain boundaries. The
scale bar shows 50 µm, which is a measure of the magnification used.
[0029] In conjunction with the microstructure, in the invention the total number of vibrational
cycles and the aperture plate geometrical characteristics are optimised to ensure
a fracture free vibrating plate and a prolonged fatigue life for the nebuliser.
[0030] We have found that the natural frequency (NF) of the aperture plate plays an important
role in determining the fatigue life of the aperture plate. The statistical analysis
was successful with a 'p square' value of 0.025 and we have shown that lowering the
vibrational frequency response of the aperture plate (NF) prolongs the fatigue life
of the nebuliser.
[0031] During a life test, an aperture plate undergoes an approximately 810 nebulisation
periods with each nebulisation period of 15 minutes duration. For example, for a vibrational
frequency of 142 kHz, the total number of the aperture plate's vibrational cycles
per life of a nebuliser is:
142,000cycles/second*15*60seconds*810≈1.04*1011 cycles
[0032] Thus, the total number of vibrational cycles over the life time of a nebuliser is
very high and this places considerable stress on the aperture plate.
[0033] It was determined that by reducing the vibrational frequency from 142 kHz to 133
kHz (a decrease of only 9 kHz), a decrease of 7*10
9 vibrational cycle will takes place:-
133,000cycles/second*15*60seconds*810≈9.7*1010 cycles
142kHz-133kHz=9kHz=1.04*1011 cycles - 9.7*1010 cycles=7*109 cycles
[0034] It is known from Literature that the circular plates have characteristic sets of
vibration modes. Bower [Bower A., Applied Mechanics of Solids, CRC Press, 2010, p
694], when analysing the vibrational modes and natural frequencies of a circular membrane,
showed that the natural frequencies of vibrations are given by the solutions to the
equation:
where:
Jn is the Bessel function,
ω(m,n) is the natural frequency,
R-is the radius of the membrane,
h is the thickness of the membrane,
p is the mass density,
To is the radial force per unit length.
[0035] From this equation the natural frequencies of the vibrating plate can be determined.
For example, the first natural frequency denoted ω
(0,1) will have the formula:
[0036] Thus, the natural frequency is dependent on the vibrational plate's geometrical characteristics,
ie thickness and plate radius (or diameter).
[0037] A FEA (Finite Element Analysis) modal analysis was conducted to simulate the vibrating
behaviour of the aperture plate of the invention and to determine and predict the
influence of the main factors on the vibrational characteristic of the aperture plate
- mode shape and natural frequency (NF) - Figure 2.
[0038] Our simulation results showed that there is a direct relationship between the thickness
of the plate and the natural vibrational frequency (NF) - Fig. 3, and an inverse relationship
between the plate dome diameter and the natural vibrational frequency (NF) - Fig.6
and this correlates with our experimental findings.
[0039] In order to lower the vibrational response (NF) of the plate, the thickness of the
aperture plate can be reduced or the dome diameter can be increased.
[0040] For example, decreasing the plate thickness by 3µm will decrease the natural frequency
up to 9 kHz and that will contribute to an increase in the fatigue life of the vibrational
plate as described above.
[0041] In the invention we provide an aperture plate with a generally equiaxed microstructure.
The fatigue life may be further enhanced using a lower specification of the thickness
and natural frequency range.
[0042] An increase in the fatigue life of the vibrating aperture plate, provides suitable
aersolisation over extended periods of time.
[0043] The invention provides an improved aperture plate that:-
extends the life of nebulisers;
eliminates the risk of premature and unpredictable failure of a nebuliser in service;
eliminates the risk of product returns from hospitals and patients; and
eliminates the possible risk of fragments of the aperture plate breaking free from
the nebulizer.
[0044] Vibrating mesh nebulisers are in common use today for the treatment of a range of
respiratory ailments which require the aersolisation of medication to the lungs.
[0045] As described in
US20070023547A the aperture plates of the invention are constructed of a relatively thin plate that
may be formed into a desired shape and includes a plurality of apertures that are
employed to produce fine liquid droplets when the aperture plate is vibrated. Techniques
for vibrating such aperture plates are described generally in
U.S. Pat. Nos. 5,164,740;
5,586,550; and
5,758,637. The aperture plates are constructed to permit the production of relatively small
liquid droplets at a relatively fast rate. For example, the aperture plates of the
invention may be employed to produce liquid droplets having a size in the range from
about 2 microns to about 10 microns, and more typically between about 2 microns to
about 5 microns. In some cases, the aperture plates may be employed to produce a spray
that is useful in pulmonary drug delivery procedures. As such, the sprays produced
by the aperture plates may have a respirable fraction that is greater than about 70%,
preferably more than about 80%, and most preferably more than about 90% as described
in
U.S. Pat. No. 5,758,637. In some embodiments, such fine liquid droplets may be produced at a rate in the
range from about 2 microliters per second to about 25 microliters per second per 1000
apertures. In this way, aperture plates may be constructed to have multiple apertures
that are sufficient to produce aerosolized volumes that are in the range from about
2 microliters to about 25 microliters, within a time that is less than about one second.
Such a rate of production is particularly useful for pulmonary drug delivery applications
where a desired dosage is aerosolized at a rate sufficient to permit the aerosolised
medicament to be directly inhaled. In this way, a capture chamber is not needed to
capture the liquid droplets until the specified dosage has been produced. In this
manner, the aperture plates may be included within aerosolisers, nebulizers, or inhalers
that do not utilise elaborate capture chambers.
[0046] The aperture plate may be employed to deliver a wide variety of drugs to the respiratory
system. For example, the aperture plate may be utilized to deliver drugs having potent
therapeutic agents, such as hormones, peptides, and other drugs requiring precise
dosing including drugs for local treatment of the respiratory system. Examples of
liquid drugs that may be aerosolized include drugs in solution form, e.g., aqueous
solutions, ethanol solutions, aqueous/ethanol mixture solutions, and the like, in
colloidal suspension form, and the like. The invention may also find use in aerosolizing
a variety of other types of liquids, such as insulin.
[0047] The palladium nickel alloy aperture plates of the invention may be used with a variety
of liquids without significantly corroding the aperture plate. Examples of liquids
that may be used and which will not significantly corrode such an aperture plate include
albuterol, chromatin, and other inhalation solutions that are normally delivered by
jet nebulizers, and the like.
[0048] The palladium nickel alloy has a low modulus of elasticity. The stress for a given
oscillation amplitude is proportional to the amount of elongation and the modulus
of elasticity. By providing the aperture plate with a lower modulus of elasticity,
the stress on the aperture plate is significantly reduced.
[0049] To enhance the rate of droplet production while maintaining the droplets within a
specified size range, the apertures may be constructed to have a certain shape. More
specifically, the apertures are preferably tapered such that the aperture is narrower
in cross section where the droplet exits the aperture. In one case, the angle of the
aperture at the exit opening (or the exit angle) is in the range from about 30° to
about 60°, more preferably from about 41° to about 49°, and more preferably at about
45°. Such an exit angle provides for an increased flow rate while minimizing droplet
size. In this way, the aperture plate may find particular use with inhalation drug
delivery applications.
[0050] The apertures of the aperture plates will typically have an exit opening having a
diameter in the range from about 1 micron to about 10 microns, to produce droplets
that are about 2 microns to about 10 microns in size. In another case, the taper at
the exit angle is preferably within the desired angle range for at least about the
first 15 microns of the aperture plate. Beyond this point, the shape of the aperture
is less critical. For example, the angle of taper may increase toward the opposite
surface of the aperture plate.
[0051] The aperture plates of the invention may be formed in the shape of a dome as described
generally in
U.S. Pat. No. 5,758,637. As described above, for optimum performance the aperture plate is vibrated at a
frequency in the range from about 125 kHz to about 155 kHz when aerosolising a liquid.
Further, when aerosolising a liquid, the liquid may be placed onto a rear surface
of the aperture plate where the liquid adheres to the rear surface by surface tension
forces. Upon vibration of the aperture plate, liquid droplets are ejected from the
front surface as described generally in
U.S. Pat. Nos. 5,164,740,
5,586,550 and
5,758,637.
[0052] The aperture plates of the invention may be constructed using an electro-deposition
process where a metal is deposited from a solution onto a conductive mandrel by an
electrolytic process. In one example, the aperture plates are formed using an electroforming
process where the metal is electroplated onto an accurately made mandrel that has
the inverse contour, dimensions, and surface finish desired on the finished aperture
plate. When the desired thickness of deposited metal has been attained, the aperture
plate is separated from the mandrel. Electroforming techniques are described generally
in
E. Paul DeGarmo, "Materials and Processes in Manufacturing" McMillan Publishing Co.,
Inc., New York, 5.sup.th Edition, 1979.
[0053] The mandrels that may be utilised to produce the aperture plates may comprise a conductive
surface having a plurality of spaced apart nonconductive islands. In this way, when
the mandrel is placed into the solution and current is applied to the mandrel, the
metal material in the solution is deposited onto the mandrel.
[0054] A variety of other techniques may be employed to place a pattern of nonconductive
material onto the electroforming mandrel. Examples of techniques that may be employed
to produce the desired pattern include exposure, silk screening, and the like. This
pattern is then employed to control where plating of the material initiates and continues
throughout the plating process. A variety of nonconductive materials may be employed
to prevent plating on the conductive surface, such as a photoresist, plastic, and
the like. As previously mentioned, once the nonconducting material is placed onto
the mandrel, it may optionally be treated to obtain the desired profile. Examples
of treatments that may be used include baking, curing, heat cycling, carving, cutting,
molding or the like. Such processes may be employed to produce a curved or angled
surface on the nonconducting pattern which may then be employed to modify the angle
of the exit opening in the aperture plate.
[0055] Referring now to Fig. 5, one aperture plate 10 will be described. Aperture plate
10 comprises a plate body 12 into which are formed a plurality of tapered apertures
14. Plate body 12 is constructed of a palladium nickel alloy as described above. The
plate body 12 may be configured to have a dome shape as described generally in
U.S. Pat. No. 5,758,637. Plate body 12 includes a top or front surface 16 and a bottom or rear surface 18.
In operation, liquid is supplied to rear surface 18 and liquid droplets are ejected
from front surface 16.
[0056] Referring to Fig. 6, the configuration of apertures 14 will be described in greater
detail. Apertures 14 are configured to taper from rear surface 18 to front surface
16. Each aperture 14 has an entrance opening 20 and an exit opening 22. With this
configuration, liquid supplied to rear surface 18 proceeds through entrance opening
20 and exits through exit opening 22. As shown, plate body 12 further includes a flared
portion 24 adjacent exit opening 22. As described in greater detail hereinafter, flared
portion 24 is created from the manufacturing process employed to produce aperture
plate 10.
[0057] As best shown in Fig.7, the angle of taper of apertures 14 as they approach exit
openings 22 may be defined by an exit angle θ. The exit angle is selected to maximize
the ejection of liquid droplets through exit opening 20 while maintaining the droplets
within a desired size range. Exit angle θ may be constructed to be in the range from
about 30° to about 60° more preferably from about 41° to about 49°, and most preferably
around 45°. Also, exit opening 22 may have a diameter in the range from about 1 micron
to about 10 microns. Further, the exit angle θ preferably extends over a vertical
distance of at least about 15 microns, i.e., exit angel θ is within the above recited
ranges at any point within this vertical distance. As shown, beyond this vertical
distance, apertures 14 may flare outward beyond the range of the exit angle θ.
[0058] In operation, liquid is applied to rear surface 18. Upon vibration of aperture plate
10, liquid droplets are ejected through exit opening 22. In this manner, the liquid
droplets will be propelled from front surface 16. Although exit opening 22 is shown
inset from front surface 16, it will be appreciated that other types of manufacturing
processes may be employed to place exit opening 22 directly at front surface 16.
[0059] Fig. 8 is a graph containing aerosolisation simulation data when vibrating an aperture
plate similar to aperture plate 10 of Fig. 1. In the graph of Fig. 8, the aperture
plate was vibrated at about 180 kHz when a volume of water was applied to the rear
surface. Each aperture had an exit diameter of 5 microns. In the simulation, the exit
angle was varied from about 10° to about 70°. (noting that the exit angle in Fig.
8 is from the center line to the wall of the aperture). As shown, the maximum flow
rate per aperture occurred at about 45°. Relatively high flow rates were also achieved
in the range from about 41° to about 49°. Exit angles in the range from about 30°
to about 60° also produced high flow rates. Hence, in this example, a single aperture
is capable of ejecting about 0.08 microliters of water per second when ejecting water.
For many medical solutions, an aperture plate containing about 1000 apertures that
each have an exit angle of about 45° may be used to produce a dosage in the range
from about 30 microliters to about 50 microliters within about one second. Because
of such a rapid rate of production, the aerosolized medicament may be inhaled by the
patient within a few inhalation manoeuvres without first being captured within a capture
chamber.
[0060] Apparatus and methods used for electroforming that may be used to construct the aperture
plate are described in
US2007/0023547A. Referring to Fig. 9, one embodiment of an electroforming mandrel 26 that may be
employed to construct aperture plate 10 of Fig. 5 will be described. Mandrel 26 comprises
a mandrel body 28 having a conductive surface 30.The mandrel body 28 may be constructed
of a metal, such as stainless steel. As shown, conductive surface 30 is flat in geometry.
However, in some cases it will be appreciated that conductive surface 30 may be shaped
depending on the desired shape of the resulting aperture plate. Disposed on conductive
surface 30 are a plurality of nonconductive islands 32. Islands 32 are configured
to extend above conductive surface 30 so that they may be employed in electroforming
apertures within the aperture plate as described in greater detail hereinafter. Islands
32 may be spaced apart by a distance corresponding to the desired spacing of the resulting
apertures in the aperture plate. Similarly, the number of islands 32 may be varied
depending on the particular need.
[0061] Referring now to Fig. 10, construction of islands 32 will be described in greater
detail. As shown, island 32 is generally conical or dome shaped in geometry. Conveniently,
island 32 may be defined in terms of a height h and a diameter D. As such, each island
32 may be said to include an average angle of incline or slope that is defined by
the inverse tangent of 1/2 (D)/h. The average angle of incline may be varied to produce
the desired exit angle in the aperture plate as previously described.
[0062] As shown, island 32 is constructed of a bottom layer 34 and a top layer 36. As described
in greater detail hereinafter, use of such layers assists in obtaining the desired
conical or domed shape. However, it will be appreciated that islands 32 may in some
cases be constructed from only a single layer or multiple layers.
[0063] Referring to Fig.11, one method for forming nonconductive islands 32 on mandrel body
28 will be described. As shown in step 38, the process begins by providing an electroforming
mandrel. As shown in step 40, a photoresist film is then applied to the mandrel. As
one example, such a photoresist film may comprise a thick film photoresist having
a thickness in the range from about 7 to about 9 microns. Such a thick film photoresist
may comprise a Hoechst Celanese AZ P4620 positive photoresist. Conveniently, such
a resist may be pre-baked in a convection oven in air or other environment for about
30 minutes at about 100°C. As shown in step 42, a mask having a pattern of circular
regions is placed over the photoresist film. As shown in step 44, the photoresist
film is then developed to form an arrangement of nonconductive islands. Conveniently,
the resist may be developed in a basic developer, such as a Hoechst Celanese AZ 400
K developer. Although described in the context of a positive photoresist, it will
be appreciated that a negative photoresist may also be used as is known in the art.
[0064] As shown in step 46, the islands are then treated to form the desired shape by heating
the mandrel to permit the islands to flow and cure in the desired shape. The conditions
of the heating cycle of step 46 may be controlled to determine the extent of flow
(or doming) and the extent of curing that takes place, thereby affecting the durability
and permanence of the pattern. In one case, the mandrel is slowly heated to an elevated
temperature to obtain the desired amount of flow and curing. For example, the mandrel
and the resist may be heated at a rate of about 2° C per minute from room temperature
to an elevated temperature of about 240° C. The mandrel and resist are then held at
the elevated temperature for about 30 minutes.
[0065] In some cases, it may be desirable to add photoresist layers onto the nonconductive
islands to control their slope and further enhance the shape of the islands. Hence,
as shown in step 48, if the desired shape has not yet been obtained, steps 40-46 may
be repeated to place additional photoresist layers onto the islands. Typically, when
additional layers are added, the mask will contain circular regions that are smaller
in diameter so that the added layers will be smaller in diameter to assist in producing
the domed shape of the islands. As shown in step 50, once the desired shape has been
attained, the process ends.
[0066] Referring now to Figs. 12 and 13, a process for producing aperture plate 10 will
be described. As shown in step 52 of Fig. 13, a mandrel having a pattern of nonconductive
islands is provided. Conveniently, such a mandrel may be mandrel 26 of Fig. 9 as illustrated
in Fig. 12. The process then proceeds to step 54 where the mandrel is placed in a
solution containing a material that is to be deposited on the mandrel. As one example,
the solution may be a Pallatech PdNi plating solution, commercially available from
Lucent Technologies, containing a palladium nickel that is to be deposited on mandrel
26. As shown in step 56, electric current is supplied to the mandrel to electro deposit
the material onto mandrel 26 and to form aperture plate 10. As shown in step 56, once
the aperture plate is formed, it may be peeled off from mandrel 26.
[0067] To obtain the desired exit angle and the desired exit opening on aperture plate 10,
the time during which electric current is supplied to the mandrel may be varied. Further,
the type of solution into which the mandrel is immersed may also be varied. Still
further, the shape and angle of islands 32 may be varied to vary the exit angle of
the apertures as previously described. Merely by way of example, one mandrel that
may be used to produce exit angles of about 45° is made by depositing a first photoresist
island having a diameter of 100 microns and a height of 10 microns. The second photoresist
island may have a diameter of 10 microns and a thickness of 6 microns and is deposited
on a center of the first island. The mandrel is then heated to a temperature of 200°
C for 2 hours.
[0068] Referring now to Fig. 14, an alternative embodiment of an aperture plate 60 will
be described. Aperture plate 60 comprises a plate body 62 having a plurality of tapered
apertures 64 (only one being shown for convenience of illustration). Plate body 62
has a rear surface 66 and a front surface 68. Apertures 64 are configured to taper
from rear surface 66 to front surface 68. As shown, aperture 64 has a constant angle
of taper. Preferably, the angle of taper is in the range from about 30° to about 60°,
more preferably about 41° to about 49°, and most preferably at about 45°. Aperture
64 further includes an exit opening 70 that may have a diameter in the range from
about 2 microns to about 10 microns.
[0069] Referring to Fig. 15, one method that may be employed to construct aperture plate
62 will be described. The process employs the use of an electroforming mandrel 72
having a plurality of non-conductive islands 74. Conveniently, island 74 may be constructed
to be generally conical or domed-shaped in geometry and may be constructed using any
of the processes previously described herein. To form aperture plate 60, mandrel 72
is placed within a solution and electrical current is applied to mandrel 72. The electroplating
time is controlled so that front surface 68 of aperture plate 60 does not extend above
the top of island 74. The amount of electroplating time may be controlled to control
the height of aperture plate 60. As such, the size of exit openings 72 may be controlled
by varying the electroplating time. Once the desired height of aperture plate 60 is
obtained, electrical current is ceased and mandrel 72 may be removed from aperture
plate 60.
[0070] Referring now to Fig. 16, use of aperture plate 10 to aerosolise a volume of liquid
76 will be described. Conveniently, aperture plate 10 is coupled to a cupped shaped
member 78 having a central opening 80. Aperture plate 10 is placed over opening 80,
with rear surface 18 being adjacent liquid 76. A piezoelectric transducer 82 is coupled
to cupped shaped member 78. An interface 84 may also be provided as a convenient way
to couple the aerosol generator to other components of a device. In operation, electrical
current is applied to transducer 82 to vibrate aperture plate 10. Liquid 76 may be
held to rear surface 18 of aperture plate 10 by surface tension forces. As aperture
plate 10 is vibrated, liquid droplets are ejected from the front surface as shown.
[0071] As previously mentioned, aperture plate 10 may be constructed so that a volume of
liquid in the range from about 4 microliters to about 30 microliters may be aerosolized
within a time that is less than about one second per about 1000 apertures. Further,
each of the droplets may be produced such that they have a respirable fraction that
is greater than about 90 percent. In this way, a medicament may be aerosolized and
then directly inhaled by a patient.
[0072] The invention is not limited to the embodiments hereinbefore described which may
be varied in construction and detail.
1. Lochplattenkörper (12) mit mehreren Löchern (14), die zwischen einer ersten Oberfläche
(18) und einer zweiten Oberfläche (16) konisch zulaufen, wobei die Löcher einen Austrittswinkel
(θ) in dem Bereich von 30° bis 60° aufweisen, dadurch gekennzeichnet, dass die Platte (12) aus einer Palladium-Nickel-Legierung gebildet ist, die ungefähr 89
% Palladium und ungefähr 11 % Nickel umfasst und eine allgemein feine, zufällig orientierte
im Wesentlichen gleichachsige Kornmikrostruktur über die gesamte Dicke der Lochplatte
(12) aufweist.
2. Lochplatte nach Anspruch 1, wobei die durchschnittliche Kornbreite von 0,2 µm bis
2,0 µm beträgt.
3. Lochplatte nach Anspruch 1 oder Anspruch 2, wobei die durchschnittliche Kornbreite
von 0,2 µm bis 1,0 µm beträgt.
4. Lochplatte nach einem der Ansprüche 1 bis 3, wobei die durchschnittliche Kornbreite
ungefähr 0,5 µm beträgt.
5. Lochplatte nach Anspruch 1, wobei die durchschnittliche Kornbreite von 0,2 µm bis
8,0 µm beträgt.
6. Lochplatte nach Anspruch 1 oder Anspruch 2, wobei die durchschnittliche Kornbreite
von 0,2 µm bis 5,0 µm beträgt.
7. Lochplatte nach einem der Ansprüche 1 bis 3, wobei die durchschnittliche Kornbreite
von 1,0 µm bis 4,0 µm beträgt.
8. Lochplatte nach einem der Ansprüche 1 bis 7, wobei die Lochplatte (12) eine Dicke
von 59 bis 63 Mikrometern aufweist.
9. Lochplatte nach einem der Ansprüche 1 bis 8, die eine kuppelförmige Geometrie aufweist.
10. Lochplatte nach einem der Ansprüche 1 bis 9, wobei der Austrittswinkel (θ) in dem
Bereich von 40° bis 45° liegt.
11. Lochplatte nach einem der Ansprüche 1 bis 10, wobei der Austrittswinkel (θ) ungefähr
45° beträgt.
12. Lochplatte nach einem der Ansprüche 1 bis 11, wobei die Löcher (14) einen Durchmesser
in dem Bereich von 1 Mikron bis 10 Mikron aufweisen.
13. Aerosolgenerator, umfassend eine Lochplatte (12) nach einem der Ansprüche 1 bis 12
und ein Mittel (82) zum Vibrieren der Lochplatte (12).
14. Aerosolgenerator nach Anspruch 13, wobei das Mittel (82) zum Vibrieren der Lochplatte
(12) dazu ausgebildet ist, die Platte (12) mit einer Frequenz von 125 bis 155 kHz
zu vibrieren.
15. Aerosolgenerator nach Anspruch 13 oder Anspruch 14, wobei das Mittel zum Vibrieren
der Lochplatte (2) dazu ausgebildet ist, die Platte (12) mit einer Frequenz von 128
bis 148 kHz zu vibrieren.
1. Corps de plaque d'ouvertures (12) comportant une pluralité d'ouvertures (14) diminuant
progressivement entre une première surface (18) et une seconde surface (16), les ouvertures
ayant un angle d'émergence (θ) qui est dans la plage allant de 30° à 60°, caractérisé en ce que la plaque (12) est formée d'un alliage de palladium et nickel comprenant environ
89% de palladium et environ 11% de nickel et ayant une microstructure de grains généralement
fins, à l'orientation aléatoire, sensiblement équiaxiques à travers toute l'épaisseur
de la plaque d'ouvertures (12).
2. Plaque d'ouvertures selon la revendication 1, dans laquelle la largeur moyenne des
grains est de 0,2 µm à 2,0 µm.
3. Plaque d'ouvertures selon la revendication 1 ou la revendication 2, dans laquelle
la largeur moyenne des grains est de 0,2 µm à 1,0µm.
4. Plaque d'ouvertures selon l'une quelconque des revendications 1 à 3, dans laquelle
la largeur moyenne des grains est approximativement de 0,5 µm.
5. Plaque d'ouvertures selon la revendication 1, dans laquelle la largeur moyenne des
grains est de 0,2 µm à 8,0 µm.
6. Plaque d'ouvertures selon la revendication 1 ou la revendication 2, dans laquelle
la largeur moyenne des grains est de 0,2 µm à 5,0 µm.
7. Plaque d'ouvertures selon l'une quelconque des revendications 1 à 3, dans laquelle
la largeur moyenne des grains est de 1,0 µm à 4,0 µm.
8. Plaque d'ouvertures selon l'une quelconque des revendications 1 à 7, la plaque d'ouvertures
(12) ayant une épaisseur de 59 à 63 microns.
9. Plaque d'ouvertures selon l'une quelconque des revendications 1 à 8, laquelle a une
géométrie en forme de dôme.
10. Plaque d'ouvertures selon l'une quelconque des revendications 1 à 9, dans laquelle
l'angle d'émergence (θ) est dans la plage allant de 40° à 45°.
11. Plaque d'ouvertures selon l'une quelconque des revendications 1 à 10, dans laquelle
l'angle d'émergence (θ) est approximativement de 45°.
12. Plaque d'ouvertures selon l'une quelconque des revendications 1 à 11, dans laquelle
les ouvertures (14) ont un diamètre dans la plage allant de 1 micron à 10 microns.
13. Générateur d'aérosol comprenant une plaque d'ouvertures (12) selon l'une quelconque
des revendications 1 à 12 et un moyen (82) pour faire vibrer la plaque d'ouvertures
(12).
14. Générateur d'aérosol selon la revendication 13, dans lequel le moyen (82) pour faire
vibrer la plaque d'ouvertures (12) est configuré pour faire vibrer la plaque (12)
à une fréquence de 125 à 155 kHz.
15. Générateur d'aérosol selon la revendication 13 ou la revendication 14, dans lequel
le moyen pour faire vibrer la plaque d'ouvertures (2) est configuré pour faire vibrer
la plaque (12) à une fréquence de 128 à 148 kHz.