U.S. patent application number 13/866783 was filed with the patent office on 2013-11-14 for spray ejector device and methods of use.
This patent application is currently assigned to CORINTHIAM OPHTHALMIC, INC.. The applicant listed for this patent is CORINTHIAN OPHTHALMIC, INC.. Invention is credited to Joshua Richard Brown, J. Sid Clements, Matthew Ditrolio, Nathan R. Faulks, Louis Thomas Germinario, Kris Grube, Charles Eric Hunter, James Thornhill Leath, Iyam Lynch, Jonathan Ryan Wilkerson.
Application Number | 20130299607 13/866783 |
Document ID | / |
Family ID | 48471083 |
Filed Date | 2013-11-14 |
United States Patent
Application |
20130299607 |
Kind Code |
A1 |
Wilkerson; Jonathan Ryan ;
et al. |
November 14, 2013 |
SPRAY EJECTOR DEVICE AND METHODS OF USE
Abstract
An ejector device for ejecting droplets of fluid onto a surface
includes an ejector mechanism attached to a fluid reservoir through
a fluid loading plate that is configured to pierce the reservoir
and channel the fluid to a rear surface of the ejector mechanism by
capillary action. The ejector mechanism may have a centro-symmetric
configuration with a lead free piezo actuator and may be covered by
an auto-closing cover.
Inventors: |
Wilkerson; Jonathan Ryan;
(Raleigh, NC) ; Lynch; Iyam; (Boone, NC) ;
Hunter; Charles Eric; (Boone, NC) ; Brown; Joshua
Richard; (Hickory, NC) ; Germinario; Louis
Thomas; (Kingsport, TN) ; Leath; James Thornhill;
(Burlington, NC) ; Faulks; Nathan R.; (Boone,
NC) ; Grube; Kris; (Boone, NC) ; Ditrolio;
Matthew; (Boone, NC) ; Clements; J. Sid;
(Boone, NC) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
CORINTHIAN OPHTHALMIC, INC.; |
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|
US |
|
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Assignee: |
CORINTHIAM OPHTHALMIC, INC.
Raleigh
NC
|
Family ID: |
48471083 |
Appl. No.: |
13/866783 |
Filed: |
April 19, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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61636559 |
Apr 20, 2012 |
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61636565 |
Apr 20, 2012 |
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61643150 |
May 4, 2012 |
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61722611 |
Nov 5, 2012 |
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61722616 |
Nov 5, 2012 |
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Current U.S.
Class: |
239/328 ;
239/302; 239/589 |
Current CPC
Class: |
B05B 17/0646 20130101;
B05B 17/0661 20130101; A61F 9/00 20130101; A61F 9/0008 20130101;
A61M 11/005 20130101; A61M 11/00 20130101; A61M 15/025 20140204;
A61M 2210/0612 20130101; B05B 17/0676 20130101 |
Class at
Publication: |
239/328 ;
239/302; 239/589 |
International
Class: |
A61M 11/00 20060101
A61M011/00 |
Claims
1. An ejector device for ejecting fluid onto a surface, the device
comprising: a housing; a reservoir having a volume (V.sub.t) and
containing or configured to receive a volume of fluid (V.sub.f)
disposed within said housing; a fluid loading plate in fluid
communication said reservoir; and an ejector mechanism in fluid
communication with said fluid loading plate; wherein said fluid
loading plate includes a fluid reservoir interface for attaching to
the reservoir, an ejector mechanism interface for attaching the
fluid loading plate to the ejector mechanism, and one or more fluid
channels for channeling fluid from the fluid reservoir interface to
the ejector mechanism interface, the fluid loading plate being
configured so as to be placed in a parallel arrangement with the
ejector mechanism so as to provide fluid to a rear surface of the
ejector mechanism, said ejector mechanism being configured to eject
a stream of droplets of said fluid through one or more
openings.
2. The ejector device of claim 1, wherein said ejector device is
capable of ejecting said stream of droplets when said ejector
device is tilted.
3. The ejector device of claim 1, wherein said ejector device is
capable of ejecting said stream of droplets when said ejector
device is tilted up to 180 degrees upside-down.
4. The ejector device of claim 1, wherein said reservoir further
comprises a fluid V.sub.f in said volume V.sub.t.
5. The ejector device according to claim 1, wherein said fluid is
for ophthalmic, topical, oral, nasal, or pulmonary use.
6. The ejector device according to claim 4, wherein said reservoir
further comprises a gas of volume V.sub.gas in said volume
V.sub.t.
7. The ejector device of claim 1, wherein said reservoir is
composed of a flexible material.
8. The ejector device of claim 1, wherein said reservoir is
collapsible.
9. The ejector device of claim 8, wherein said collapsible
reservoir is collapsed by volume V.sub.r when filled with a volume
of fluid V.sub.f.
10. The ejector device of claim 8, wherein said collapsible
reservoir is under negative internal pressure.
11. The ejector device of claim 9, wherein said collapsed reservoir
expands in volume V.sub.exp when exposed to a positive pressure
differential, where the pressure inside the reservoir is greater
than ambient pressure.
12. The ejector device of claim 11, wherein said volume V.sub.r is
chosen to be greater than the volume V.sub.exp for a defined
positive pressure differential.
13. The ejector device of claim 1, wherein said reservoir does not
leak through said openings when is the reservoir is exposed to a
positive pressure differential where the pressure inside the
reservoir is greater than ambient pressure.
14. The ejector device of claim 13, wherein said pressure
differential is less than or equal to 40 kPa.
15. The ejector device of claim 1, wherein the ejector mechanism is
configured to eject a stream of droplets having an average ejected
droplet diameter greater than 15 microns, with the stream of
droplets having low entrained airflow so that the pressure of the
stream of droplets onto the surface will be substantially
imperceptible when sprayed against a human or animal body
surface.
16. The ejector device of claim 1, wherein the ejector mechanism
interface of the fluid load plate and the rear surface of the
ejector mechanism are in parallel arrangement so as to form a
capillary separation and generate fluid flow between the fluid load
plate and the ejector mechanism at the rear surface of the ejector
mechanism.
17. The ejector device of claim 16, wherein the fluid load plate
and the ejector mechanism are separated by a distance of about 0.2
mm to about 0.5 mm so as to form capillary separation.
18. The ejector device of claim 1, wherein the ejector mechanism
comprises an ejector plate coupled to a generator plate and a
piezoelectric actuator; the generator plate including a plurality
of openings formed through its thickness, the piezoelectric
actuator being operable to oscillate the ejector plate, and thereby
the generator plate, at a frequency and generate a directed stream
of droplets.
19. The ejector device of claim 8, wherein the fluid load plate
comprises a puncture plate fluid delivery system and a capillary
plate that delivers the fluid from the collapsible reservoir to the
ejector mechanism.
20. The ejector device of claim 19, wherein the puncture plate
fluid delivery system and capillary plate are integrally formed to
define a puncture/capillary plate fluid delivery system.
21. The ejector device of claim 20, wherein the puncture/capillary
plate fluid delivery system includes a fluid retention area and at
least one hollow puncture needle for transferring fluid from the
retention area to the ejector interface.
22. The ejector device of claim 21, wherein the puncture/capillary
plate fluid delivery system includes first and second mating
portions, the flexible reservoir being attached to and in fluid
communication with the second mating portion, the second mating
portion including a puncturable seal to define the retention
area.
23. The ejector device of claim 22, wherein the first mating
portion forms a receptacle for the second mating portion, and
includes the at least one hollow puncture needle for puncturing the
flexible reservoir.
24. The ejector device of claim 23, wherein the first mating
portion and the at least one puncture needle may be integrally
formed.
25. The ejector device of claim 22, wherein the puncturable seal
that is included in the second mating portion comprises a
self-sealing silicone.
26. The ejector device of claim 1, further comprising auto-closing
system for reducing crystallization, evaporation, and contamination
risk, the auto-closing system including a user-activated
slide-plate for covering at least part of the ejector
mechanism.
27. The ejector device of claim 26, wherein the ejector mechanism
defines at least one ejector opening, and the slide-plate is
configured to sealingly engage a gasket or seal formed around the
at least one ejector opening, and is slidable between an open
position in which the at least one ejector opening is exposed, and
a close position in which the at least one ejector opening is
covered by the slide-plate.
28. The ejector device of claim 27, wherein the slide-plate is
biased toward its closed position by means of a spring.
29. The ejector device of claim 27, wherein the slide plate
includes an opening configured to coincide with the at least one
ejector opening in the ejector mechanism when the slide-plate is in
its open position.
30. The ejector device of claim 29, wherein the auto-closing system
includes means to ensure that the slide plate presses with
sufficient pressure against the gasket or seal when in the closed
position.
31. The ejector device of claim 1, wherein the ejector mechanism
comprises an ejector plate coupled to a generator plate and a
piezoelectric actuator, said generator plate including a plurality
of openings formed through its thickness, and said piezoelectric
actuator being operable to oscillate the ejector plate, and thereby
the generator plate, at a resonant frequency of said ejector plate
coupled to said generator plate to generate a directed stream of
droplets.
32. The ejector device of claim 31, wherein the piezoelectric
actuator is made of lead free piezoelectric material.
33. The ejector of claim 32, wherein the piezoelectric material is
selected from the group consisting of a BiFeO.sub.3-based material,
a bismuth sodium titanate (BNT) material, bismuth potassium
titanate (BKT) material, a dual-mode magnetostrictive/piezoelectric
bilayered composite, tungsten-bronze material, a sodium niobate
material, a barium titanate material, and a polyvinylidene fluoride
material.
34. The device of claim 30, having an average ejected droplet
diameter greater than 15 microns, the stream of droplets having low
entrained airflow so that the pressure of the stream of droplets
onto the surface will be substantially imperceptible when sprayed
against a human or animal body target.
35. The device of claim 31, wherein said ejector plate has a
central open region aligned with the plurality of openings of the
generator plate, and the piezoelectric actuator is coupled to a
peripheral region of the ejector plate so as not to obstruct the
plurality of openings of the generator plate.
36. The device of claim 35, wherein said generator plate has a
reduced size relative to said ejector plate, and the size of said
generator plate is determined, at least in part, by the area
occupied by said central open region and the arrangement of said
plurality of openings.
37. The device of claim 36, wherein said ejector plate is circular
and the actuator has an annular configuration, the ejector plate
and the piezoelectric actuator having the same outer diameter.
38. The device of claim of claim 37, wherein said ejector plate is
circular and the actuator has an annular configuration, the ejector
plate has a larger outer diameter than d the piezoelectric
actuator.
39. A device for delivering a fluid to a target, the device
comprising: a housing; a reservoir disposed within the housing for
receiving a volume of fluid or pre-filled with a volume of fluid;
and an centro-symmetric ejector mechanism in fluid communication
with the reservoir and configured to eject a stream of droplets,
said centro-symmetric ejector mechanism comprising an ejector plate
coupled to a generator plate and a piezoelectric actuator, said
generator plate including a plurality of openings formed through
its thickness, and said piezoelectric actuator being operable to
oscillate the ejector plate, and thereby the generator plate, at a
resonant frequency of said ejector plate coupled to said generator
plate to generate a directed stream of droplets.
40. The device of claim 39, wherein said piezoelectric actuator
comprises a lead free piezoelectric material.
41. The device of claim 39, wherein said ejector plate further
comprises a symmetric low order mounting structure.
42. The device of claim 41, wherein said piezoelectric actuator
comprises a lead free piezoelectric material.
43. The device of claim 42, wherein said lead free piezoelectric
material is selected from the group consisting of a
BiFeO.sub.3-based material, a bismuth sodium titanate (BNT)
material, bismuth potassium titanate (BKT) material, a dual-mode
magnetostrictive/piezoelectric bilayered composite, tungsten-bronze
material, a sodium niobate material, a barium titanate material, a
polyvinylidene fluoride material.
44. The device of claim 39, wherein said generator plate is a high
modulus polymeric generator plate.
45. The device of claim 39, wherein the average ejected droplet
diameter is greater than 15 microns, the stream of droplets having
low entrained airflow so that the pressure of the stream of
droplets onto the surface will be substantially imperceptible when
sprayed against a human or animal body target.
46. The device of claim 39, wherein said ejector plate has a
central open region aligned with the plurality of openings of the
generator plate, and the piezoelectric actuator is coupled to a
peripheral region of the ejector plate so as not to obstruct the
plurality of openings of the generator plate.
47. The device of claim 46, wherein said generator plate has a
reduced size relative to said ejector plate, and the size of said
generator plate is determined, at least in part, by the area
occupied by said central open region and the arrangement of said
plurality of openings.
48. The device of claim 47, wherein said ejector plate is circular
and the actuator has an annular configuration, the ejector plate
and the piezoelectric actuator having the same outer diameter.
49. The device of claim of claim 47, wherein said ejector plate is
circular and the actuator has an annular configuration, the ejector
plate has a larger outer diameter than d the piezoelectric
actuator.
50. An ejector mechanism configured to eject a stream of droplets,
the ejector mechanism comprising: an ejector plate coupled to a
generator plate and a piezoelectric actuator; the generator plate
including a plurality of openings formed through its thickness; and
the piezoelectric actuator being operable to oscillate the ejector
plate, and thereby the generator plate, at a frequency and generate
a directed stream of droplets.
51. The ejector mechanism of claim 50, wherein said generator plate
is a high modulus polymeric generator plate.
52. The device of claim 50, wherein said ejector plate further
comprises a symmetric low order mounting structure.
53. The ejector mechanism of claim 50, wherein said piezoelectric
actuator comprises a lead free piezoelectric material.
54. The ejector mechanism of claim 53, wherein said lead free
piezoelectric material is selected from the group consisting of a
BiFeO.sub.3-based material, a bismuth sodium titanate (BNT)
material, bismuth potassium titanate (BKT) material, a dual-mode
magnetostrictive/piezoelectric bilayered composite, tungsten-bronze
material, a sodium niobate material, a barium titanate material,
and a polyvinylidene fluoride material.
55. The ejector mechanism of claim 50, wherein one or more of said
plurality of openings defines an entrance cavity and a capillary
channel.
56. The ejector mechanism of claim 50, wherein said generator plate
is a high modulus polymer generator plate.
57. The ejector mechanism of claim 56, wherein the generator plate
is formed from a material selected from the group consisting of:
ultrahigh molecular weight polyethylene (UHMWPE), polyimide,
polyether ether ketone (PEEK), polyvinylidene fluoride (PVDF), and
polyetherimide.
58. The ejector mechanism of claim 50, wherein said ejector plate
has a central open region aligned with the generator plate, and the
piezoelectric actuator is coupled to a peripheral region of the
ejector plate so as not to obstruct the plurality of openings of
the generator plate.
59. The ejector mechanism of claim 58, wherein said generator plate
has a reduced size relative to said ejector plate and the size of
said generator plate is determined, at least in part, by the area
occupied by said central open region and the arrangement of said
plurality of openings.
60. The ejector mechanism of claim 58, wherein said ejector plate
is circular and the actuator has an annular configuration, said
ejector plate and said piezoelectric actuator having the same outer
diameter.
61. The ejector mechanism of claim 58, wherein said ejector plate
is circular and the actuator has an annular configuration, said
ejector plate has a larger diameter than the piezoelectric
actuator.
62. A reservoir for holding fluid for ejection by an ejector
device, wherein the reservoir is collapsible.
63. The reservoir of claim 62, wherein said fluid is for
ophthalmic, topical, oral, nasal, or pulmonary use.
64. The reservoir of claim 62, wherein said reservoir has a volume
V.sub.t and is provided with a fluid to a volume V.sub.f, which is
less than V.sub.t.
65. The reservoir of claim 64, wherein said collapsible reservoir
is collapsed by volume V.sub.r when filled with the volume of fluid
V.sub.f.
66. The reservoir of claim 65, wherein said collapsible reservoir
is under negative internal pressure.
67. The reservoir of claim 65, wherein said collapsed reservoir
expands in volume V.sub.exp when exposed to a positive pressure
differential, where the pressure inside the reservoir is greater
than ambient pressure.
68. The reservoir of claim 65, wherein said volume V.sub.r is
chosen to be greater than the volume V.sub.exp for a defined
positive pressure differential.
69. An ejector assembly, comprising: a droplet ejector mechanism
for ejecting fluid droplets, a fluid loading plate for channeling
fluid from a reservoir to the droplet ejector mechanism, comprising
a fluid reservoir interface for attaching to the reservoir, an
ejector mechanism interface for attaching the fluid loading plate
to the ejector mechanism, and one or more fluid channels for
channeling fluid from the fluid reservoir interface to the ejector
mechanism interface, the fluid loading plate being configured so as
to be placed in a parallel arrangement with the ejector mechanism
so as to provide fluid to a rear surface of the ejector
mechanism.
70. The fluid loading plate of claim 69, wherein the ejector
mechanism interface of the fluid loading plate and the rear surface
of the droplet ejector mechanism are in parallel arrangement so as
to form a capillary separation and generate fluid flow between the
fluid loading plate and the droplet ejector mechanism to define a
fluid loading area at the rear surface of the droplet ejector
mechanism.
71. The fluid loading plate of claim 70, wherein the fluid loading
plate and the droplet ejector mechanism are separated by a distance
of about 0.2 mm to about 0.5 mm so as to form capillary
separation.
72. The fluid loading plate of claim 70, comprising a puncture
plate fluid delivery system and a capillary plate that delivers the
fluid from a reservoir to the ejector mechanism.
73. The fluid loading plate of claim 72, wherein the puncture plate
fluid delivery system and capillary plate are integrally formed to
define a puncture/capillary plate fluid delivery system.
74. The fluid loading plate of claim 73, wherein the
puncture/capillary plate fluid delivery system includes a fluid
retention area and at least one hollow puncture needle for
transferring fluid from the retention area to the droplet ejector
rear surface.
75. The fluid loading plate of claim 74, wherein the
puncture/capillary plate fluid delivery system includes first and
second mating portions, a flexible reservoir being attached to and
in fluid communication with the second mating portion, the second
mating portion including a puncturable seal to define the fluid
retention area.
76. The fluid loading plate of claim 75, wherein the first mating
portion forms a receptacle for the second mating portion, and
includes the at least one hollow puncture needle for puncturing the
flexible reservoir.
77. The fluid loading plate of claim 76, wherein the first mating
portion and the at least one puncture needle may be integrally
formed.
78. The fluid loading plate of claim 76, wherein the puncturable
seal that is included in the second mating portion comprises a
self-sealing silicone.
Description
RELATED APPLICATIONS
[0001] The present application claims the benefit of the filing
date of U.S. Provisional Application Nos. 61/636,559 filed Apr. 20,
2012; 61/636,565 filed Apr. 20, 2012; 61/643,150 filed May 4, 2012;
61/722,611 filed Nov. 5, 2012, and 61/722,616 filed Nov. 5, 2012,
the contents of which are herein incorporated by reference in their
entireties.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates to ejector devices, and
methods of manufacturing ejector devices. In particular, it relates
to devices and methods for ejecting mists, or sprays of
micro-droplets.
BACKGROUND OF THE INVENTION
[0003] Using spray devices to administer products in the form of
mists or sprays is an area with large potential for safe,
easy-to-use products. A major challenge in providing such a device
is to provide consistent and accurate delivery of suitable doses
and to avoid contamination of the product being delivered.
[0004] An important area where spray devices are needed is in
delivery of eye medications. The application of fluids, as in the
case of eye drops, has always posed a problem, especially for
children and animals, which tend to blink or jerk at the critical
moment of administration, causing the droplet to land on the
eyelid, nose or other part of the face. The impact of a large drop
or drops of fluid on the eyeball, especially when the fluid is at a
different temperature, also tends to produce a blinking reaction.
The elderly also often lose the hand coordination necessary to get
the eye drops into their eyes. Stroke victims have similar
difficulties. Currently, many of these medications are administered
using eye droppers, which often require either the head to be
tilted back, the subject to lie down or provide downward traction
on the lower eyelid, or a combination of traction and tilting,
since the delivery mechanism typically relies on gravity for
applying the medication. This is not only awkward, but involves a
fair amount of coordination, flexibility and cooperation on the
part of the subject to ensure that the medication gets into the eye
while avoiding poking the eye with the dropper tip. In current eye
dropper bottles, the pointed applicator tip poses the risk of
poking the user in the eye, potentially causing physical damage to
the eye, and further, exposing the tip to bacterial contamination
due to contact with the eye. As such, the subject runs the risk of
contaminating the medication in the eye dropper bottle and
subsequently infecting the eye. Additionally, a large volume of the
medication flows out of the eye or is washed away by the tearing
reflex. As a result, this method of administration is also
inaccurate and wasteful. Moreover, the eye dropper does not provide
a satisfactory way of controlling the amount of medication that is
dispensed, nor does it provide a way of ensuring that the
medication that is dispensed actually lands on the eye and remains
on the eye.
[0005] Eye droppers also provide no way of verifying compliance by
a subject. Even if after a week of use the eye dropper bottle could
be checked for the total volume of medication dispensed, e.g., by
weighing the bottle, this does not provide a record of day-to-day
compliance. A subject may have missed one or more doses and
overdosed on other occasions. Also, the poor precision with which
eye droppers deliver drops to the eye makes it difficult to
determine whether the medication is actually delivered into the
eye, even though it may have been dispensed.
[0006] The ability of piezoelectric droplet generation systems to
eject fluid has conventionally been largely limited by the
piezoelectric material properties of the employed ceramic. For many
years, an alternative piezoelectric material system that is lead
free with comparable properties to lead based systems has been
sought in order to meet worldwide regulations. This material system
has yet to surface. An ejector system design which minimizes the
dependency on piezoelectric material properties to allow comparable
ejection with inferior material characteristics is thus highly
desirable.
[0007] Accordingly, there is a need for a delivery device that
delivers safe, suitable, and repeatable dosages to a subject for
ophthalmic, topical, oral, nasal, or pulmonary use.
SUMMARY OF THE INVENTION
[0008] According to the present disclosure there is provided an
ejector device comprising a housing, a reservoir having a volume of
fluid contained within the housing, a fluid loading plate in fluid
communication with the fluid in the reservoir and an ejector
mechanism in fluid communication with the fluid loading plate,
wherein the fluid loading plate provides fluid to a rear surface of
the ejector mechanism, and the ejector mechanism is configured to
eject a stream of droplets of fluid through at least one opening.
The fluid loading plate may be configured to be placed in a
parallel arrangement with the ejector mechanism so as to provide
fluid to a rear ejection surface of the ejector mechanism. The
ejector device of the disclosure is capable of delivering a defined
volume of fluid in the form of droplets having properties that
afford adequate and repeatable high percentage deposition upon
application.
[0009] In this regard, an important consideration according to the
present disclosure is not only to be able to deliver the medication
in an easier to use manner, e.g. by spraying a mist horizontally
onto the surface to be treated, but also to ensure that the
medication is consistently provided to the ejector or delivery
mechanism in any orientation. In some implementations, the ejector
device is capable of ejecting a stream of droplets when the ejector
device is tilted, even if tilted 180 degrees upside-down.
[0010] In certain embodiments, the fluid loading plate may comprise
a capillary plate fluid delivery device for delivering fluid from a
reservoir to an ejector mechanism of an ejector device, and methods
of use for delivering safe, suitable, and repeatable dosages of
fluids to a subject for ophthalmic, topical, oral, nasal, or
pulmonary use. The capillary plate may comprise a fluid reservoir
interface, an ejector mechanism interface, and one or more fluid
channels for channeling fluid to the ejector mechanism by one or
more mechanisms, including capillary action.
[0011] In other embodiments, the fluid loading plate may comprise a
puncture plate fluid delivery system for delivering fluid from a
reservoir to an ejector mechanism of an ejector device. The
puncture plate fluid delivery system, also referred to as a
capillary/puncture plate fluid delivery system, may include a
capillary plate portion comprising a fluid retention area between
the puncture/capillary plate fluid delivery system and a rear
surface of an ejector mechanism for channeling fluid to the ejector
mechanism by one or more mechanisms, including capillary action,
and at least one hollow puncture needle for transferring fluid from
a reservoir to the fluid retention area.
[0012] In certain aspects, the puncture plate fluid delivery system
may include a first and a second mating portion, wherein a
reservoir is attached in fluid communication to the second mating
portion, the second mating portion including a puncturable seal.
The first mating portion may form a receptacle for the second
mating portion, and may include the least one hollow puncture
needle for puncturing the puncturable seal. The first mating
portion and the at least one puncture needle may be integrally
formed. The puncturable seal included in the second mating portion
may comprise a self-sealing silicone.
[0013] The reservoir, also referred to herein as an ampoule, may
comprise a collapsible and flexible container. The reservoir may
comprise a container and a lidding wherein the reservoir is
configured so that the lidding and container form a volume capable
of containing a fluid. The reservoir may be configured to be
partially collapsed (at sea level) and capable of expanding to
accommodate expansion of gas within the volume and prevent
leaks.
[0014] The ejector mechanism may comprise an ejector plate coupled
to a droplet generator plate (referred to herein simply as a
generator plate) and a piezoelectric actuator; the generator plate
including a plurality of openings formed through its thickness, and
the piezoelectric actuator being operable to oscillate the ejector
plate and thereby oscillate the generator plate at a frequency to
generate a directed stream of droplets. The ejector plate may have
a central open region aligned with the generator plate, wherein the
piezoelectric actuator is coupled to a peripheral region of the
ejector plate so as not to obstruct the plurality of openings of
the generator plate. The plurality of openings of the generator
plate may be disposed in a center region of the generator plate
that is uncovered by the piezoelectric actuator and aligned with
the central open region of the ejector plate. The three-dimensional
geometry and shape of the openings, including orifice diameter and
capillary length, and spatial array on the generator plate may be
controlled to optimize generation of the directed stream of
droplets. The generator plate may be formed from a high modulus
polymer material, for example, formed from a material selected from
the group consisting of: ultrahigh molecular weight polyethylene
(UHMWPE), polyimide, polyether ether ketone (PEEK), polyvinylidene
fluoride (PVDF), and polyetherimide. The ejector mechanism may be
configured to eject a stream of droplets having an average ejected
droplet diameter greater than 15 microns, with the stream of
droplets having low entrained airflow such that the stream of
droplets deposits on the eye of the subject during use.
[0015] The ejector mechanism may have a centro-symmetric structure
in which the ejector plate includes symmetrically arranged mounting
structures, with a symmetric configuration in which droplets are
ejected from a central region of the symmetrical structure. The
piezoelectric actuator may induce a resonance amplification of the
generator plate coupled to the ejector plate to provide for a
greater variety of piezoelectric constants. The ejector plate may
be made of a high modulus polymeric material, and the piezoelectric
actuator may be lead free, or substantially lead free.
[0016] The droplets may be formed in a distribution of sizes, each
distribution having an average droplet size. The average droplet
size may be in the range of about 15 microns to over 400 microns,
e.g., greater than 20 microns to about 400 microns, about 20
microns to about 200 microns, about 100 microns to about 200
microns, about 20 microns to about 80 microns, about 25 microns to
about 75 microns, about 30 microns to about 60 microns, about 35
microns to about 55 microns, etc. However, the average droplet size
may be as large as 2500 microns, depending on the intended
application. Further, the droplets may have an average initial
velocity of about 0.5 m/s to about 100 m/s, e.g., about 0.5 m/s to
about 20 m/s, about 0.5 to about 10 m/s, about 1 m/s to about 5
m/s, about 1 m/s to about 4 m/s, about 2 m/s, etc. As used herein,
the ejecting size and the initial velocity are the size and initial
velocity of the droplets when the droplets leave the ejector plate.
The stream of droplets directed at a target will result in
deposition of a percentage of the mass of the droplets including
their composition onto the target.
[0017] The ejector mechanism and fluid loading plate may be
assembled to form a unit defining an ejector assembly, the ejector
assembly comprising a fluid loading plate in fluid communication
with an ejector mechanism such that the fluid loading plate
provides fluid to a rear surface of the ejector mechanism, the
ejector mechanism being configured to eject a stream of droplets.
In certain embodiments, the ejector assembly may further comprise a
reservoir in fluid communication with the fluid loading plate.
[0018] The ejector device may further include an auto-closing
system, which generally reduces crystallization, evaporation, and
contamination risk. The auto-closing system may include a
user-activated slide-plate that sealingly engages a gasket or seal
formed to surround at least the holes in the generator plate, and
which is slidable between an open position in which the holes are
exposed and a close position in which the holes are covered by the
slide-plate. The slide-plate may be biased toward its closed
position by means of a spring. The slide plate may include an
opening configured to coincide with the holes in the generator
plate when the slide-plate is in its open position. Means may be
included in the auto-closing system to ensure that the slide plate
presses with sufficient pressure against the seal when in the
closed position.
[0019] Further, according to the disclosure, there is provided an
auto-closing system for a droplet ejection device which generally
reduces crystallization, evaporation, and contamination risk.
[0020] Still further, according to the disclosure, there is
provided a method for the fabrication of a generator plate for
ejecting high viscosity fluids suitable for ophthalmic, topical,
oral, nasal, or pulmonary use, comprising laser micromachining of
materials to form three-dimensional openings through the thickness
of the material, each of the openings defining an entrance cavity
and a capillary channel, wherein the opening comprises an overall
pitch length.
[0021] Still further, according to the disclosure there is provided
a method of delivering a volume of ophthalmic fluid to an eye of a
subject, the method comprising ejecting a directed stream of
droplets of an ophthalmic fluid contained in a reservoir from
openings of an ejector plate, the droplets in the directed stream
having an average ejecting diameter in the range of 5-2500 microns,
e.g., 20-400 microns, e.g., 20-200 microns, and including but not
limited to a range of 100-200, etc., and an average initial
velocity in the range of 0.5-100 m/s, e.g., 1-100 m/s, e.g., 2-20
m/s.
[0022] These and other aspects of the invention will become
apparent to one of skill in the art.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 is a three-dimensional exploded view of the
mechanical parts of one embodiment of an ejector device of the
disclosure;
[0024] FIG. 2 is front view of one embodiment of a an ejector
device of the disclosure;
[0025] FIG. 3 shows one embodiment of a reservoir of the
disclosure;
[0026] FIG. 4 shows another embodiment of a reservoir of the
disclosure;
[0027] FIG. 5 illustrates the variation of atmospheric pressure (p)
with altitude (h);
[0028] FIGS. 6A-6D illustrate various embodiments of components of
a reservoir according to one embodiment of the disclosure;
[0029] FIG. 7 illustrates a form, fill and seal process for
generation of reservoirs in accordance with one embodiment of the
disclosure;
[0030] FIG. 8 shows an embodiment of a reservoir, fluid loading
plate and ejector plate in accordance with an aspect of the
disclosure, illustrating the direction of droplet ejection relative
to attitude angle.
[0031] FIG. 9 shows an embodiment of a testing apparatus for
measuring differential pressure induced leakage in an embodiment of
a reservoir, fluid loading plate and ejector assembly in accordance
with an aspect of the disclosure;
[0032] FIGS. 10A-10E illustrate reservoir expansion following a
decrease in pressure and a determination of the leak point pressure
for embodiments of a reservoir, fluid loading plate and ejector
assembly, in accordance with aspects of the disclosure;
[0033] FIG. 11 illustrates the effect of the volume V.sub.gas
expressed as a percentage of V.sub.t on the differential leakage
pressure value for different embodiments of a reservoir, fluid
loading plate and ejector assembly in accordance with aspects of
the disclosure.
[0034] FIG. 12 illustrates the loss of mass from reservoirs
(ampoules) over time, in accordance with an aspect of the
disclosure;
[0035] FIG. 13 illustrates the attitude insensitivity of an
embodiment of the disclosure having a collapsible and flexible
reservoir (ampoule) compared to an embodiment of the disclosure
having a hard reservoir;
[0036] FIGS. 14 A-C show one embodiment of a capillary plate of the
disclosure;
[0037] FIGS. 15A-C show one embodiment of an ejector mechanism in
relation to an embodiment of a capillary plate of the
disclosure;
[0038] FIGS. 16A-B illustrate the relationship between plate
separation and water height in vertical parallel plates;
[0039] FIGS. 17 A-B show an embodiment of a capillary plate of the
disclosure;
[0040] FIG. 18 shows the effect of resonant frequency on mass
deposition of water with and without a capillary plate;
[0041] FIG. 19 illustrates that an increased water height behind an
ejector plate in the presence of a capillary plate leads to an
increased mass loading effect at a particular frequency;
[0042] FIG. 20 illustrates the downward shift in frequency
associated with a capillary plate used with the delivery of various
fluids;
[0043] FIG. 21 illustrates the reduction in mass loading for fluids
of increasing density and viscosity;
[0044] FIG. 22 illustrates the attitude insensitivity of an ejector
device that includes a capillary plate;
[0045] FIG. 23 shows the main components of one embodiment of an
ejector assembly including a puncture/capillary plate system with
reservoir and ejector mechanism according to the disclosure;
[0046] FIGS. 24 A-B show three dimensional front and back view of
the components of FIG. 23 in assembled form;
[0047] FIGS. 25 A-B show a detailed back and front view of one
embodiment of an ejector mechanism of the disclosure;
[0048] FIG. 26 is a schematic representation outlining fluid flow
through a puncture plate system of the disclosure;
[0049] FIG. 27 is a schematic representation of a puncture plate
system of the disclosure showing the Venturi effect;
[0050] FIG. 28 illustrates the principles of Bernoulli's
equation;
[0051] FIG. 29 illustrates the principles of hydrostatic
pressure;
[0052] FIG. 30 shows schematic representations of different
reservoir configurations of the disclosure;
[0053] FIG. 31 shows schematic representations of further reservoir
configurations of the disclosure;
[0054] FIGS. 32A-B show three dimensional pictures and side view
and front view drawings of two collapsible reservoir embodiments of
the disclosure;
[0055] FIG. 33 shows a back view of one embodiment of a
blow-fill-seal reservoir and puncture plate of the disclosure;
[0056] FIGS. 34 A-B show side views of two blow-fill-seal reservoir
and puncture plate system embodiments of the disclosure;
[0057] FIG. 35 shows different form-fill-seal reservoir embodiments
of the disclosure;
[0058] FIG. 36-37 show an apparatus and set-up to determine the
amount of negative pressure that different reservoir configurations
exert as they are removing fluid;
[0059] FIG. 38 shows the mass per spray and total spray (spray down
performance) of a non-collapse biased reservoir embodiment with
substantial crease formation of the disclosure;
[0060] FIG. 39 shows the mass per spray and total spray (spray down
performance) of various blow-fill-seal reservoir embodiments of the
disclosure;
[0061] FIG. 40 shows two runs of a mass per spray and total spray
(spray down performance) of an LTS/collapse-biased self-sealing RW
weld reservoir embodiment of the disclosure;
[0062] FIG. 41 shows the pull down performance for select round LTS
ampoule designs from FIG. 35.
[0063] FIG. 42 shows the mechanism involved in inverted spray using
a round LTS reservoir;
[0064] FIG. 43 shows the actual spray down performance results of
an LTS reservoir embodiment sprayed down in a complete puncture
system upside down of the disclosure;
[0065] FIG. 44 shows the spray down performance of another puncture
plate configuration with an embodiment of an embodiment an IV bag
reservoir of the disclosure;
[0066] FIG. 45 shows the spray down performance of two different
puncture plate configurations with an embodiment of an IV bag
reservoir of the disclosure in different orientations and with
different spray directions;
[0067] FIG. 46 shows the spray down performance of one embodiment
of a puncture plate configuration with an embodiment of an IV bag
reservoir of the disclosure in different orientations and with
different spray directions and different puncture plate vent
opening options;
[0068] FIG. 47 shows schematically the relationship between
capillary effect and hydrostatic pressure of the reservoir;
[0069] FIG. 48 shows capillary pressure for various sized half
droplets of water;
[0070] FIG. 49 shows capillary pressure for various sized half
droplets of latanaprost;
[0071] FIG. 50 shows capillary rise for various fluid types having
different contact angle values;
[0072] FIG. 51 shows capillary rise for saline in a capillary
channel made of different types of materials;
[0073] FIGS. 52-53 show fluid rise levels between puncture plate
and ejector plate for different materials;
[0074] FIG. 54 shows a test set-up to test for fluid leaking out of
capillary rise hole under different fluid fill locations;
[0075] FIG. 55A shows a cross-sectional view of one embodiment of
an ejector assembly of the disclosure;
[0076] FIG. 55B shows a three dimensional view of one embodiment of
an ejector mechanism of the disclosure;
[0077] FIG. 55C shows a front view of one embodiment of a
centro-symmetric ejector mechanism of the disclosure;
[0078] FIG. 55D shows a dismantled view of one embodiment of an
ejector mechanism of the disclosure;
[0079] FIG. 56 shows the nomenclature of the axis numbering
convention for piezoelectric effects;
[0080] FIG. 57 shows modes of operation of an active region of one
embodiment of generator plate, and digital holographic microscopy
images of oscillation of the generator plate;
[0081] FIG. 58 illustrates a comparison of mass ejection for PZT
and BaTiO.sub.3 (lead free) piezoelectric actuator materials using
an ejector assembly with an inside mounted piezoelectric actuator
according to one embodiment of the disclosure;
[0082] FIG. 59 illustrates a comparison of mass ejection for PZT
and BaTiO.sub.3 (lead free) piezoelectric actuator materials using
an ejector assembly with an edge mounted piezoelectric actuator
according to another embodiment of the disclosure;
[0083] FIG. 60 shows a three dimensional transparent view of one
embodiment of an ejector assembly with auto-closing system of the
disclosure;
[0084] FIG. 61 shows the ejector assembly with auto-closing system
of FIG. 60 in a dismantled state;
[0085] FIG. 62 is a sectional side view of part of the ejector
assembly with auto-closing system of FIG. 60;
[0086] FIG. 63 shows three-dimensional front view of a sliding unit
of the self-closing system of FIG. 60;
[0087] FIG. 64 shows three-dimensional back view of the sliding
unit of FIG. 63;
[0088] FIG. 65 is a front view of the auto-closing unit of FIG. 60
in a closed position;
[0089] FIG. 66 is a sectional side view of the auto-closing unit of
FIG. 60 in a closed position;
[0090] FIG. 67 is a front view of the auto-closing unit of FIG. 60
in an open position;
[0091] FIG. 68 is a sectional side view of the auto-closing unit of
FIG. 60 in an open position;
[0092] FIGS. 69 A-C show transmission light microscopy images over
time of a mesh screen of a generator plate in which the system was
not provided with a capillary plate, and
[0093] FIGS. 70 A-C show transmission light microscopy images over
time of a mesh screen of a generator plate in which the system was
provided with a capillary plate.
DETAILED DESCRIPTION
[0094] The present application relates to ejector devices for
delivering fluid to a surface as an ejected stream of droplets. The
ejector device may for example be as described in U.S. Provisional
Application Nos. 61/569,739, 61/636,559, 61/636,565, 61/636,568,
61/642,838, 61/642,867, 61/643,150 and 61/584,060, and in U.S.
patent application Ser. Nos. 13/184,446, 13/184,468 and 13/184,484,
the contents of which are incorporated herein by reference.
[0095] The ejector device of the present disclosure may, for
example, be useful, in the delivery of fluid for ophthalmic,
topical, oral, nasal, or pulmonary use. However, the disclosure is
not so limited, and may be useful with any ejector devices (e.g.,
printer devices, etc.).
[0096] In certain embodiments, the ejector device may comprise a
housing, a reservoir disposed within the housing for receiving a
volume of fluid, a fluid loading plate, and an, ejector mechanism
configured to eject one or more streams of droplets of a fluid,
wherein the reservoir is in fluid communication with the fluid
loading plate, which is in fluid communication with the ejector
mechanism such that the fluid loading plate provides fluid to a
rear surface of the ejector plate.
[0097] Thus the present disclosure generally relates to an ejector
device for ejecting a fluid onto a surface e.g., the ejection of
ophthalmic fluid onto the eye of a patient. One embodiment
components of the ejector device will be described broadly with
respect to FIG. 1, whereafter some of the elements making up the
device will be discussed in greater detail. It will however be
appreciated that the application is not limited to the particular
embodiments described herein but includes variations and different
combinations of the elements making up the ejector device.
[0098] For purposes of this application, fluid includes, without
limitation, suspensions or emulsions which have viscosities in a
range capable of droplet formation using an ejector mechanism.
[0099] FIG. 1 shows an exploded view of one embodiment of internal
components of an ejector device 100 of the present disclosure, and
includes a reservoir 102, which in this embodiment is a flexible
reservoir made using a self-sealing RF weld technique. The
reservoir 102 is placed into fluid communication with a fluid
loading plate 104 by means of puncturable seal mating 106. The
fluid loading plate supplies the fluid from the reservoir to the
rear face of an ejector mechanism 108 by, e.g., capillary action.
The ejector in this embodiment comprises a piezo ejector mechanism
configured to generate a controllable stream of droplets of fluid.
While the present embodiment describes a fluid loading plate 104,
which is also discussed in greater detail below, other
configurations may be adopted for channeling fluid by capillary
action from the reservoir to the ejector mechanism. In order to
limit evaporation, crystallization and contamination of the fluid,
an auto-closing system 110 is mounted in front of the ejector
mechanism 108. A bracket 112 for supporting a housing 114 for a
targeting LED is configured to clip onto the front face of the
auto-closing system 110.
[0100] As shown in FIG. 2, in certain embodiments, the mechanical
components of the ejector device may be mounted inside a removable
top section 200 of a housing 202, which mates with lower hand-grip
portion 204. The electronics for controlling the ejection of fluid
and power source may be housed inside the lower hand-grip portion
204 of the housing 202.
[0101] The reservoir or ampoule 102 for use with the ejector device
100 may comprise a flexible, or a hard, non-flexible reservoir. In
certain embodiments, the reservoir comprises a collapsible and
flexible reservoir 102 disposed within the top section 200 of the
housing 202, and contains or is adapted to receive a volume of
fluid. Different types of flexible reservoirs made using different
techniques are contemplated by the present disclosure, including
self-sealing, radio frequency (RF) weld reservoirs as shown in FIG.
1. Alternatively, a blow-fill-seal technique can be used to form a
similar configuration reservoir as shown in FIG. 3, or a
form-fill-seal technique can be used to provide a reservoir such as
that shown in FIG. 4. As will become clearer from the discussion
below, the particular configuration of the reservoir may vary from
one embodiment to the next. For example, the shape of the
form-fill-seal reservoirs is not limited to that shown in FIG.
4.
[0102] With reference to FIG. 5, atmospheric pressure varies with
altitude. Specifically, as the altitude increases, the pressure
decreases. In accordance with Boyle's Law, the volume of a gas
increases as the pressure decreases. Similarly, Charles' Law
provides that as the temperature increases, so does the volume of a
gas. In contrast, liquids generally have small changes in volume in
response to changes in pressure and temperature, water being a
notable exception which expands when cooled from 4.degree. C. to
0.degree. C. Thus while a liquid in a reservoir will change little
when the pressure and temperature conditions change, a reservoir
having a volume of liquid and also a volume of gas must be designed
to accommodate decreases in pressure and increases in temperature.
In many cases, the greater concern arises from changes in pressure,
causing significant volume changes in the gas. Changes in altitude
are a common cause of changes in pressure and therefore in the
volume of gases.
[0103] Without intending to be limited by theory, a change in
atmospheric pressure due to changes in altitude can be determined
according to the following equation:
p = p 0 ( 1 - L h T 0 ) g M R L ; ##EQU00001##
Where:
TABLE-US-00001 [0104] Parameter Description Value P.sub.0 sea level
standard atmospheric 101325 Pascal (Pa) pressure L Temperature
lapse rate 0.0065.degree. Kelvin (K)/meter (m) T.sub.0 sea level
standard temperature 288.15.degree. K g Earth-surface gravitational
9.80665 m/sec (s) acceleration M molar mass of dry air 0.0289644
kg/mol R Universal gas constant 8.31447 Joule (J)/(mol
.degree.K)
[0105] An ampoule or reservoir, or a device containing the ampoule
or reservoir may, according to the disclosure, be transported in an
airplane or to a geographic location high above sea level. As
discussed, such changes can lead to pressure differentials from sea
level that can lead to leakage from orifices of an ejector device.
For example, cabins in an airplane can be pressurized for altitudes
from 6000 ft. to 8000 ft. The corresponding pressure differential
from sea level is 20 to 29 kPa, respectively. Ampoules that are not
capable of accommodating for this pressure differential by
expanding often lead to pressure buildup within the ampoule and
subsequent fluid leakage from the device. As used herein, "ambient
pressure" refers to the air pressure to which the reservoir,
ampoule or the device having a reservoir or ampoule is exposed to.
As used herein, "pressure differential" refers to the air pressure
difference between the ambient pressure and the standard air
pressure at sea level (101325 Pascal (Pa)). Thus, the reduced
pressure as found in a plane is the ambient pressure and the
pressure differential is the difference between the ambient
pressure and the standard pressure at sea level (e.g., about 20 kPa
at 6000 ft). Similarly, the pressure differential at an altitude
above sea level is the difference between the standard pressure at
sea level (101325 Pascal (Pa)) and the ambient pressure at that
altitude.
[0106] In other embodiments, the reservoir or ampoule may be a hard
reservoir designed to accommodate expansion of any gas therein. In
some embodiments, the expansion may be suppressed by providing a
pressurized enclosure. In other embodiments, leakage may be
suppressed by sealing any orifice present on the reservoir.
[0107] With reference to FIGS. 6A to 6D, in certain embodiments,
the reservoir (in this case a form-fill-seal reservoir) may
comprise an ampoule having three components, a lidding 601, a
container 602, and optionally a stiffening ring 603. In some
embodiments, the lidding 601 is sealed to the container 602 to form
an enclosed impermeable container. In an embodiment, the sealed
impermeable combination of lidding 601 and container 602 provides
for storage of the liquid. In other embodiments, the container 602
forms a flexible reservoir that can accommodate the expansion of a
gas contained with and trapped by the reservoir. In other
embodiments, the reservoir may be formed of non-pliable materials
to make a stiff reservoir.
[0108] In some aspects according to the present disclosure, the
ampoule or reservoir may be assembled from multiple components so
that the properties of lidding 601, container 602, and stiffening
ring 603 may be adapted according to the needs of the device's
application. In other embodiments, the container 602 and stiffening
ring 603 may be formed together, and lidding 601 applied following
addition of a desired fluid. In an embodiment, the sealed
impermeable combination of lidding 601 and container 602 may be
formed separately. In certain embodiments, the lidding 601 may be
puncturable.
[0109] In certain embodiments, the shape and size of the ampoule or
reservoir may be selected according to the needs of the intended
use. In a non-limiting example, a fluid for ophthalmic use may be
required by a person in need for a short treatment time, and thus
may require fewer doses. Where few doses are indicated, the shape
and size of the ampoule may be scaled appropriately to avoid
unnecessary waste. In other aspects, large volumes may be indicated
where the fluid is required over a long period of time, or may
require multiple daily doses.
[0110] The volume 610 may be controlled by varying the depth 607,
the diameter 604, and the shape 609. In some aspects, for example
for pulmonary use, the diameter 604 may be more than 1 cm in
diameter. In another aspect, the diameter may be 1.5 cm. In a
further embodiment, the diameter may be from 1 to 3 cm. In another
embodiment the diameter may be between 1 and 4 cm, or 1 and 5 cm.
In other embodiments, the diameter 604 may be 3 cm or more, 4 cm or
more, 5 cm or more, 6 cm or more, or 7 cm or more. In other
embodiments, the diameter may be configured for a device, for
example, for ophthalmic applications. For example, the diameter 604
may be 20 mm or less. In other embodiments, the diameter 604 may be
19 mm or less. In another embodiment, the diameter 604 may be 18 mm
or less. In yet another embodiment, the diameter 604 may be 17 mm
or less. In an embodiment, the diameter 604 may be 16 mm or less.
In other embodiments of the present disclosure, the diameter 604
may be from 18 to 19 mm In another embodiment, the diameter may be
from 15 to 20 mm, 16 to 20 mm, 17 to 20 mm, 18 to 20 mm, or 19 to
20 mm. In other embodiments, the diameter 604 may be from 15 to 19
mm, 16 to 19 mm, 17 to 19 mm, or 18 to 19 mm.
[0111] In certain embodiments according the present disclosure, the
shape 609 of the ampoule may be modified to increase or decrease
the volume in view of the diameter 604. In some embodiments, the
shape 609 may be configured so that the diameter decreases toward
the closed end of the container along the depth 607. In certain
aspects, the decreasing diameter may provide for removal of a mold.
Design and manufacture of molds to form ampoules according to the
present invention having a container 602 are known in the art.
[0112] In certain embodiments of the present disclosure, the
ampoule may comprise a stiffening ring 603 configured to add
stability to the container 602. In some embodiments, the container
602 may be flexible and a stiffening ring 603 may provide for
connection to the devices or housings according to the present
disclosure. The thickness 606 and the diameter 605 may be
determined based on the diameter 604 of the shaped container 602.
In an aspect, the thickness 606 may be determined according to the
material of stiffening ring 603.
[0113] The sealed combination of lidding 601 and container 602, and
optional stiffening ring form an ampoule suitable for holding and
storing a fluid for ophthalmic, topical, oral, nasal, or pulmonary
use until insertion of the ampoule into an ejector device or
ejector device housing. In some embodiments, the sealed ampoule may
be suitable for short-term storage of a fluid for ophthalmic,
topical, oral, nasal, or pulmonary use. In other embodiments, the
sealed ampoule may be suitable for long term storage of a fluid for
ophthalmic, topical, oral, nasal, or pulmonary use.
[0114] In certain implementations, the sealed fluid containing
ampoule may be stored without loss or degradation of the fluid for
1 week. In other embodiments, the sealed ampoule may be stored for
more than 1 week. In some embodiments, the sealed ampoule may
suitable for short term storage including 2 weeks, 3 weeks, or one
month. In certain implementation, the sealed ampoule may be stored
for a month.
[0115] In certain implementations, the sealed fluid containing
ampoule may be stored for longer periods without significant loss
or degradation. In other embodiments, the sealed fluid containing
ampoule may be stored for more than one month. In other
embodiments, the sealed ampoule may be stored for more than two
months. In some embodiments, the sealed ampoule may be suitable for
long-term storage including three months, four months, or more. In
certain implementations, the sealed ampoule may be stored for 5
months. In other embodiments, the sealed ampoule may be stored for
6 months. In some embodiments, the sealed ampoule may suitable for
long-term storage including 7 months, 8 months, or more. In certain
implementations, the sealed ampoule may be stored for 9 months. In
certain implementations, the sealed ampoule may be stored for 10
months. In other embodiments, the sealed ampoule may be stored for
11 months. In some embodiments, the sealed ampoule may be suitable
for long-term storage including 12 months, or more. In certain
implementations, the sealed ampoule may be stored for 1.5 years. In
yet other implementations, the sealed fluid filled ampoule may be
stored for more than 1.5 years.
[0116] The lidding 601, container 602, and stiffening ring 603 may
be formed from any suitable materials for use in the intended
application. By way of example, in ophthalmic applications, any
suitable material for use in pharmaceutical ophthalmic applications
may be used, such as polymer materials that do not chemically react
with or adsorb fluids to be delivered. In other aspects, the
surfaces of the lidding 601, container 602, and stiffening ring 603
that are exposed to the fluid to be delivered may be formed from
materials that provide desired surface properties, including for
example hydrophobicity, hydrophilicity, non-reactivity, stability,
etc. Examples of materials suitable for the lidding 601 and
container 602 include materials presented in, but not limited by,
Table 1.
TABLE-US-00002 TABLE 1 Example lidding and container materials
Manufacturer Product Name Description Sealed Air Nexcel PE based
coextruded film Latitude ML29xxC Sealed Air Nexcel M2930 Sealed Air
Nexcel MF513 Barrier Medical film with oxygen clear barrier
Rollprint Triad "C" Extrusion laminated composite of polyester,
polyethylene, aluminum foil and modified polyolefin sealant Alcan
Pouch laminate High barrier coextruded composite Packaging Product
Code of PET,adhesive, aluminum, Pharmaceutical 92036 polyethylene
Packaging Inc. Texas SV-300X 3 mil nylon, EVOH, poly coex
Technologies SAFC Bioeaze ethyl vinyl acetate film Biosciences
Winpak DF15YG2 Peelable A1-foil based (A1/PE) Winpak WCS100
Flexible packaging laminate composed of PET, LDPE A1, and coex
[0117] In some embodiments according to the present disclosure, the
material for container 602 may be selected for properties
consistent with an FDA-approved medical device. Materials may be
selected by methods and criteria known in the art, for example, ISO
10993-5, Biological Evaluation of Medical Devices--Part 5 US
Pharmacopeia 32, Biological Reactivity Tests, In Vitro; ISO 13485,
Medical Device Quality Management System; and ISO 17025, General
Requirements for the Competence of Testing and Calibration Labs.
For example, the container 602 may be a non-cytotoxic film such as
ML29xxC available from Sealed Air.
[0118] According the present disclosure, material for container 602
may be a polymer. In certain embodiments the polymer may be a
layered polymer. In other embodiments, the polymer may be a
coextruded forming film. In certain embodiments, the polymer may be
a polymer for use in medical devices. In one example according to
the present disclosure, the film may be a polyethylene-based
coextruded forming film. In certain embodiments, the polymer may be
sterilized. In an aspect, the film may be selected according to its
ability to bond to other films. In one example, the other film may
be Tyvek or other coated medical material. In an aspect, the film
may be either clear or opaque. In another aspect, the film may be
resistant to punctures. In yet another aspect, the film may be
resistant to down-gauging.
[0119] In an aspect, the film may formable. Formable films
according to the present disclosure may be selected according to
the requirements of the application. In certain aspects, the film
may be selected based on one or more of the following criteria:
thickness, Young's modulus, elongation, tensile strength, puncture
force, tear and haze. In certain aspects, the flexibility of the
film may provide for a collapsible ampoule. In an aspect, the
collapsible ampoule may provide for the elimination of leakage upon
changes of atmospheric pressure.
[0120] Examples of films compatible with devices and methods of the
present invention include films provided in Table 2. According to
the present disclosure, similar films may be selected based on the
desired properties of Thickness, Young's modulus (MD), Elongation
(MD), Tensile Strength (MD), Puncture, Tear, and Haze.
TABLE-US-00003 TABLE 2 Example films of the present disclosure
Sealed Air Nexcel .RTM. Medical films: Latitude ML29xxC Unit ASTM
30C 45C 60C 70C 80C 10C Thickness* micron 75 112.5 150 175 200 250
Young's modulus kg/cm.sup.2 D882 4967 5059 4995 5002 5016 5023 (MD)
Elongation (MD) % D882 280 340 350 345 374 406 Tensile Strength
kg/cm.sup.2 D882 375 332 329 335 315 296 (MD) Puncture N F1306
13.26 19.39 24.24 28.02 31.70 38.99 Tear g D1004 718 1020 1360 1610
1817 2262 Haze % D1003 12 16 22 31 33 43
[0121] According to some implementations, lidding 601, container
602, and stiffening ring 603 may be a formed of materials suitable
for sterilization. In some aspects lidding 601, container 602, and
stiffening ring 603 may be sterilized together as a unit. In other
aspects, lidding 601, container 602, and stiffening ring 603 may be
sterilized separately, using one or more of the various methods of
sterilization known in the art. In certain aspects of the present
disclosure, one or more sterilization methods may be combined, for
example chemical and irradiation methods as provided below.
[0122] In an aspect, lidding 601, container 602, and stiffening
ring 603 may be formed from materials that are compatible with
sterilization by irradiation. In an aspect, the material may be
compatible with sterilization by gamma irradiation. In other
aspect, the material may be chosen to be compatible with radiation
such as electron beams, X-rays, or subatomic particles.
[0123] In another aspect, the container may be formed from
materials that are compatible with chemical methods of
sterilization. In an embodiment, the material may be compatible
with ethylene oxide (EtO) sterilization. In another embodiment, the
material may be compatible with ozone (O.sub.3) sterilization. In
another embodiment, the material may be compatible with
Ortho-phthalaldehyde (OPA). In a further embodiment, hydrogen
peroxide may be used as a chemical sterilizing agent.
[0124] In some aspects according the present disclosure, lidding
601, container 602, and stiffening ring 603 may be formed from
materials that are compatible with heat sterilization. In an
embodiment, the heat sterilization compatible material may be
resistant to dry heat sterilization. In another embodiment, the
heat sterilization compatible material may be compatible to moist
heat sterilization. In some aspects according the present
disclosure, lidding 601, container 602, and stiffening ring 603 may
be formed from materials that are compatible with
Tyndalization.
[0125] In some aspects, the materials chosen for lidding 601,
container 602, and stiffening ring 603 provide for long term
storage of the liquid. In some embodiments, the sealed ampoule may
comprise impermeable materials. In certain aspects, the
impermeability may be selected on the basis of the fluid. In one
non-limiting example according to the present disclosure, the
fluids for ophthalmic, topical, oral, nasal, or pulmonary use may
require protection from light or air to maintain stability. In
another non-limiting example according to the present disclosure,
the fluids for ophthalmic, topical, oral, nasal, or pulmonary use
may require protection from light and oxygen to maintain stability.
In some embodiments, the materials may be impermeable to gases. In
an embodiment, the gas may be oxygen. In other embodiments, the
material may be impermeable to light. In another embodiment, the
material may be impermeable to gas, for example oxygen, and
impermeable to light.
[0126] In an aspect according to the present disclosure, the
container 602 and lidding 601 material may be selected to be stable
for extended periods. As one aspect, in certain embodiments, one or
more properties including, but not limited to, the tensile
strength, the percent elongation, tear resistance and impact
stability may be used to determine the stability of the
material.
[0127] Referring to FIG. 7, containers containing a fluid of the
present invention may be prepared using a form, fill and seal
process as known in the art. In certain embodiments, the entire
process outlined in FIG. 7 may be performed under sterile
conditions in compliance with applicable regulatory standards for
medical devices and preparations. In one embodiment, a film may be
applied to a mold and then heated and vacuum formed to create a
container of shape 609 and depth 607. By varying the shape 609,
depth 607 and diameter 604, a container or ampoule of a defined
total volume (V.sub.t) may be formed.
[0128] Once formed, the container (e.g., container 602 for
example), may be filled with a fluid and a lidding applied to the
filled container or ampoules. In some embodiments and by way of
example only, a seal is applied to create a leak-proof closure.
Other methods to attach and seal a lidding to the container are
known in the art. Following sealing individual ampoules may be cut
from the form. In other embodiments, the sealing and cutting can
occur simultaneously. The final sealed containers or ampoules are
then suitable for storage, shipping or use in an ejector devise. As
mentioned above, the form-fill-seal process discussed in this
embodiment is only one technique for forming and sealing containers
are known in the art. Other techniques such as blow-fill-seal and
self-sealing RF weld can also be used and do not make use of a
lidding element.
[0129] In some embodiments of the current disclosure, the fluid
(V.sub.f) may fill the entire volume of container 602 (e.g.,
V.sub.t). In other embodiments, the fluid may not completely fill
the volume, leaving a space (V.sub..DELTA.T). In embodiments where
the liquid volume V.sub.f equals V.sub..DELTA.T, applying a lidding
may result in the entrapment of a volume of gas V.sub.gas. In other
embodiments, the volume of container 602 may be decreased by
crushing or deforming up to a volume to reduce the volume by a
volume (V.sub.r). According the present disclosure, the volume of
the sealed container or ampoule will be:
V.sub.t=V.sub.f+V.sub.gas+V.sub.r where
V.sub..DELTA.T=V.sub.gas+V.sub.r
[0130] According to certain aspects of the present disclosure, the
volume V.sub.r provides a capability to the container to expand to
volume Vt, and thereby reduce the tendency of the container to leak
when employed in an ejector device. Similar, the volume V.sub.r can
accommodate an expansion of a volume of an aqueous fluid when
shipped or stored frozen or under conditions where the volume of
liquid may expand. In other embodiments, V.sub..DELTA.T may include
both a volume of gas V.sub.gas and a volume V.sub.r whereby, the
change in gas volume associated with changes in ambient pressure
may be compensated and provide for the preparation of leak free
ejector devices. Similarly, the volume V.sub.r also provides for an
expansion of gas of volume V.sub.exp that may occur during shipping
or storage under conditions of lower ambient pressure.
[0131] In certain aspects according the present disclosure, the
container may contain a volume of gas V.sub.gas. In an aspect, the
gas may be air. In an aspect, the gas may be air that has been
depleted of oxygen. In other aspects the gas may be a non-reactive
gas. In an aspect, the gas may be nitrogen. In another aspect, the
gas may be a noble gas such as helium or argon. In other aspects,
the gas may be CO.sub.2. Any gas may be accommodated according to
the present disclosure.
[0132] In certain embodiments of the disclosure, the reservoirs
provide for attitude insensitivity of ejector devices. In an aspect
the reservoir includes a flexible container. Specifically, as
provided by certain aspects of the present disclosure, the
reservoir provides a consistent amount of fluid to the ejector
mechanism, regardless of the fluid level and device orientation. In
some aspects, an ampoule or reservoir in fluid communication with
an ejector mechanism provides a consistent flow of fluid to the
rear surface of the ejector mechanism so that a consistent volume
of fluid is ejected as droplets. In another aspect, the reservoir
or ampoule is in fluid communication with a capillary plate that
provides for consistent supply and delivery of fluid in a capillary
fluid loading area at a rear ejection surface of an ejector
mechanism. The ampoule provides for attitude insensitivity of the
ejector device and a resistance to leakage as the ambient pressure
is decreased relative to the standard pressure at sea level. Thus
the combination of ampoule, capillary plate and ejector mechanism
provide both reduced attitude and altitude sensitivity to the
device so that a consistent volume of droplets is delivered.
[0133] Referring to FIG. 8, a device of the present disclosure
ejects fluid in a direction 804, perpendicular to the direction of
gravity 805. In an aspect of the present disclosure, the
combination of ampoule 803 and fluid loading plate 802 provide for
a consistent flow of fluid to the ejector plate 801 as the attitude
angle theta (A) is change. For example, as the attitude is
increased, the combination provides for continued consistent flow
of fluid. Accordingly, according to aspects of the present
invention, the device continues to dispense droplets in the
direction 804. In an aspect of the present disclosure, the attitude
angle theta (.theta.) may be arbitrarily increased or decreased
while maintaining a consistent flow of fluid to the ejector plate
801. For instance, the attitude angle theta (.theta.) may be more
or less than 45.degree.. Thus, the attitude angle theta (.theta.)
may be between 0 and 45.degree. or may be between 45.degree. and
90.degree.. The attitude angle theta (.theta.) may also be
90.degree.. The attitude angle theta (.theta.) may also be
180.degree. or may be between 0 and 180.degree..
[0134] In certain implementations according to the present
invention, the containers are flexible containers having a total
volume V.sub.t and contain a volume of liquid V.sub.f and a volume
of gas V.sub.gas, and have a expandable volume V.sub.r. In certain
aspects, the expandable volume V.sub.r provides for and
accommodates the expansion of the gas .DELTA.V.sub.gas due to
changes in pressure while not resulting in an increase in pressure
within the container. Thus, while in transit for example, an
expansion of .DELTA.V.sub.gas does not cause the container to leak.
Similarly, the expansion of an aqueous fluid upon freezing can be
similarly accommodated.
[0135] Many implementations of the invention have been disclosed.
This disclosure contemplates combining any of the features of one
implementation with the features of one or more of the other
implementations. For example, any of the ejector mechanisms or
capillary plates can be used in combination with the container, as
well as any of the housings or housing features, e.g., covers,
supports, rests, lights, seals and gaskets, fill mechanisms, or
alignment mechanisms. Further variations in any of the elements of
any of the embodiments within the scope of ordinary skill are
contemplated by this disclosure. Such variations include selection
of materials, coatings, or methods of manufacturing. Other methods
of fabrication known in the art and not explicitly listed herein
can be used to fabricate, test, repair, or maintain the device.
Example 1
Measurement of Differential Pressure Leak Values
[0136] FIG. 9 shows an assembly that allows an assembly of
container, fluid loading plate and ejector device to be tested for
leakage as the pressure is decreased. The fluid filled container is
mounted onto a leak pressure test apparatus which consists of an
ampoule retaining mount (1), fluid loading plate (2), which
delivers fluid behind the ejector plate (3). The leak pressure test
apparatus is placed within a vacuum chamber that is pumped by a
mechanical pump suitable for attaining 2.75 psi. At this pressure
(2.75 psi) the measured pressure differential between STP (13.23
psi) and the lowest measurable leakage pressure (2.75 psi) is 10.5
psi, or 72.3 kPa. Leakage at this pressure is equivalent to a
pressure differential encountered in traveling from sea level to
31,000 feet. FIG. 9 also illustrates an aspect of the container
having a V.sub.r greater than zero. Thus, the container provides
for expansion of the gas as the ambient pressure is decreased
inside the vacuum chamber. Variation of the V.sub.r can affect the
leak pressure.
[0137] Table 3 provides the results of leak pressure testing
through 40 um holes on a 12 mm deep (e.g., depth 607 of FIG. 6)
flexible container.
TABLE-US-00004 TABLE 3 Leak pressure test through 40 um holes with
12 mm deep flexible container Experiment % Full #: (%) % Air Volume
Delta P (psi) Delta P (kPa) 1 97.20 3.43 1.66 11.43 2 93.20 8.34
2.45 16.91 3 77.38 22.70 0.99 6.80 4 81.89 18.18 1.16 8.00 5 87.72
12.32 3.51 24.18 6 85.28 14.77 1.80 12.41 7 81.17 18.90 1.89 13.05
8 73.31 26.79 1.00 6.89
Table 4 provides the results of leak pressure testing through 20 um
holes on a 20 mm deep flexible container.
TABLE-US-00005 TABLE 4 Leak pressure test through 20 um holes with
20 mm deep flexible container Start Experiment % Air Pressure Leak
Delta P Delta P #: Volume (psi) Pressure (psi) (psi) (kPa): 1 3.13
13.23 2.75 10.48 72.26 2 3.13 13.26 2.95 10.31 71.09 3 15.63 13.26
6.40 6.86 47.30 4 9.38 13.26 5.95 7.31 50.40 5 6.25 13.25 3.75 9.50
65.50 6 12.50 13.25 5.95 7.30 50.33 7 9.38 13.25 5.25 8.00
55.16
Table 5 provides the results of leak pressure testing through 40 um
holes on a 20 mm deep flexible container.
TABLE-US-00006 TABLE 5 Leak pressure test on 20 mm flexible
container with 40 um holes Start Experiment % Air Pressure Leak
Pressure Delta P Delta P #: Volume (psi) (psi) (psi) (kPa): 1 2.3
13.28 2.75 10.53 72.6 2 6.3 13.28 3.18 10.1 69.6 3 9.4 13.28 5.2
8.08 55.7 4 12.5 13.28 5.5 7.78 53.6 5 15.6 13.28 5.9 7.38 50.9 6
18.8 13.27 6.15 7.12 49.1 7 21.9 13.27 6.35 6.92 47.7
Table 6 provides the results of leak pressure testing through 40 um
holes on a 20 mm deep hard container.
TABLE-US-00007 TABLE 6 Leak Pressure Test on Hard container with 40
um holes Start Experiment % Air Pressure Leak Pressure Delta P
Delta P #: Volume (psi) (psi) (psi) (kPa): 1 12.5 13.25 12.85 0.4
2.8 2 4.2 13.25 12.75 0.5 3.4 4 29.2 13.25 12.75 0.5 3.4 5 37.5
13.25 12.7 0.55 3.8 8 20.8 13.25 12.72 0.53 3.7
[0138] FIG. 10 illustrates the results of container expansion as a
mechanism of pressure equalization. As tested in Example 1 and
presented in Table 4, as the pressure is decreased, the gas
expands, causing an expansion of the collapsed volume V.sub.r. As
V.sub.gas approaches the total volume V.sub..DELTA.T the tendency
of the apparatus to leak increases. Smaller volumes of air are
generally associated with lower leak point pressures. Delta P
represents the pressure at which the combination begins to
leak.
[0139] FIG. 11 graphically presents the results of leak pressure
testing of different embodiments of the present disclosure. As
shown, a hard reservoir leaks at low differential pressures that is
independent of the % air volume (e.g., V.sub.air/V.sub.t). The 12
mm deep container (ampoule) requires higher differential pressures
to induce leakage and a maximal pressure of about 25 is observed
for about a 12% air volume. A 20 mm deep container having either
40.times.160 um holes or 20.times.40 um holes, requires the highest
differential pressures to cause leakage. In these embodiments, the
hole number and size were not distinguishable.
Example 2
Measurement of Mass Loss Over Time
[0140] FIG. 12 shows the mass loss from an ampoule (reservoir) over
time to determine the storage ability of ampoules (reservoirs) of
the present disclosure. A series of reservoirs are stored for 72
days and the amount of mass determined. From a total volume of 3.5
ml, a total volume of 50 .mu.l escapes over the time period.
Experiment 3
Measurement of Ejection Volume at Different Attitude Angles
[0141] FIG. 13 shows the ejection volume at differing attitude
angles over a range of frequencies of a piezoelectric ejector
device having either a hard reservoir or a flexible reservoir. The
flexible ampoule design provides more consistent ejection of fluid
volume over a broader frequency range and fill level.
[0142] Although the foregoing describes various reservoir
embodiments by way of illustration and example, the skilled artisan
will appreciate that various changes and modifications may be
practiced within the spirit and scope of the present application.
As used herein, a reservoir may be any object suitable for holding
a fluid. By way of example, the reservoir may be made of any
suitable material capable of containing a fluid. Reservoirs of the
present disclosure may be rigid or flexible and the reservoirs of
the present disclosure may further be collapsible. As used herein,
collapsible refers to a decrease in volume obtainable in a
reservoir achieved by squeezing, folding, crushing, compressing,
vacuuming, or other manipulation, such that total volume enclosed
after collapsing is less than a volume that could be enclosed in a
non-collapsed container. A reservoir may be made of any suitable
material that can formed into a volume capable of holding a volume
of fluid. Suitable materials, for example, may either be flexible
or rigid and may be formable or pre-formed. As used herein a
reservoir, by way of example, may be formed from a film.
[0143] In other aspects, a fluid loading plate of the disclosure
may be integrated into an ejector device between a reservoir and an
ejector mechanism. In certain embodiments, the ejector device may
be for delivering a fluid to an eye of a subject, and may comprise
a housing, a reservoir disposed within the housing for receiving a
volume of fluid, the reservoir being in fluid communication with a
fluid loading plate, the fluid loading plate being in fluid
communication with an ejector mechanism such that the fluid loading
plate provides fluid to a rear ejection surface of an ejector
mechanism, wherein the ejector mechanism is configured to eject a
stream of droplets of a fluid. The ejector mechanism may be
configured to eject a stream of droplets having an average ejected
droplet diameter greater than 15 microns, with the stream of
droplets having low entrained airflow such that the stream of
droplets deposits on the eye of the subject during use.
[0144] In certain embodiments, the ejector mechanism may comprise
an ejector plate and a piezoelectric actuator; the ejector plate
including a plurality of openings formed through its thickness; and
the piezoelectric actuator being operable to oscillate the ejector
plate at a frequency, and generate a directed stream of droplets.
In certain aspects, the ejector plate may be formed from a high
modulus polymer material.
[0145] In certain embodiments, the piezoelectric actuator is
coupled to a peripheral region of the ejector plate so as not to
obstruct the plurality of openings of the ejector plate. The
plurality of openings of the ejector plate may be disposed in a
center region of the plate that is uncovered by the piezoelectric
actuator. In certain embodiments, the three-dimensional geometry
and shape of the openings, including orifice diameter and capillary
length, and spatial array on the ejector plate may be controlled to
optimize generation of the directed stream of droplets.
[0146] By way of example, the fluid loading plate may be integrated
into an ejector device or ejector assembly, or configured to
interface with an ejector mechanism as disclosed, for example, in
the applications: U.S. Application No. 61/591,786, filed Jan. 27,
2012, entitled "High Modulus Polymeric Ejector Mechanism, Ejector
Device, and Methods of Use"; U.S. Application No. 61/569,739, filed
Dec. 12, 2011, entitled "Ejector Mechanism, Ejector Device, and
Methods of Use"; and U.S. application Ser. No. 13/184,484, filed
Jul. 15, 2011, entitled "Drop Generating Device", which
applications are each herein incorporated by reference in their
entireties.
[0147] Many embodiments and implementations of the invention are
disclosed herein. This disclosure contemplates combining any of the
features of one embodiment with the features of one or more of the
other embodiments. For example, any of the ejector mechanisms or
reservoirs can be used in combination with the fluid loading plate,
as well as any of the housings or housing features discussed in the
incorporated references, e.g., covers, supports, rests, lights,
seals and gaskets, fill mechanisms, or alignment mechanisms.
Further variations on any of the elements of any of the aspects of
the present disclosure that are within the scope of ordinary skill
are contemplated by this disclosure. Such variations include
selection of materials, coatings, or methods of manufacturing.
[0148] With reference to FIGS. 14A-14C, in one embodiment, the
fluid loading plate may comprise a capillary plate 1400 including a
fluid reservoir interface 1402, an ejector mechanism interface
1404, and one or more fluid openings 1406. If desired, the
capillary plate 1400 may optionally include a reservoir housing
mating ring 1410 to facilitate connection with various reservoir
housing configurations (not shown), as described in U.S.
application Ser. No. 13/184,484, filed Jul. 15, 2011, entitled
"Drop Generating Device", which is herein incorporated by reference
in its entirety.
[0149] In addition, the capillary plate 1400 may optionally include
fastening clips 1412 on the housing mating ring 1410 to secure
capillary plate 1400 to a reservoir housing (not shown). Although
exemplary clip configurations and positions are shown, different
embodiments and positions are envisioned and within the scope of
the disclosure. Capillary plate 1400 may also include piercing
projections 1414 on the fluid reservoir interface 1402 to
facilitate opening of various reservoir housing configurations (not
shown). Again, although exemplary piercing projections and
positions are shown, different embodiments and positions are
envisioned and within the scope of the disclosure. For instance,
the piercing projections may be sized and shaped so as not to
hinder fluid flow through the one or more fluid openings 1406.
[0150] With reference to FIGS. 15A-15C, in certain embodiments, the
ejector mechanism interface 1502 of the capillary plate 1500 is
placed in parallel arrangement with a rear ejection surface 1506 of
the ejector mechanism 1504 so as to form a separation 1508 between
the capillary plate and the ejector mechanism, and generate fluid
flow 1510 between the capillary plate 1500 and the ejector
mechanism 1504 in the capillary fluid loading area 1512 at the rear
ejection surface of the ejector mechanism. This fluid flow 1510
allows the capillary plate 1500 to provide fluid to the rear
ejection surface 1506 of the ejector plate 1514 of the ejector
mechanism. The configuration of the capillary plate provides for
consistent supply and delivery of fluid in the capillary fluid
loading area at the rear ejection surface 1506 of the ejector plate
1514. As a result, a consistent volume of droplets is generated by
the ejector mechanism, regardless of fluid level and device
orientation (i.e., attitude).
[0151] With reference to FIGS. 16A and 16B, the fluid loading
between the parallel surfaces of the capillary plate and the
ejector plate is dependent upon distance d of the capillary plate
separation. As is shown in FIG. 16A, plate separation of up to 1 mm
provides adequate fluid loading (liquid height) in the capillary
fluid loading area. In certain embodiments, a separation distance
between the capillary plate and the ejector mechanism of between
about 0.2 mm and about 0.5 mm, more particularly between about 0.2
and about 0.4 mm, or more particularly of 0.3 mm may be used.
[0152] Without intending to be limited by theory, general
expressions for capillary rise between two parallel surfaces are
set out below:
h = .gamma. lv ( cos ( .theta. 1 ) + cos ( .theta. 2 ) ) .rho. y d
; ##EQU00002## h = 2 .gamma. lv cos ( .theta. ) .rho. gd
##EQU00002.2##
[0153] where:
[0154] h is the liquid height;
[0155] .gamma..sub.lv is the liquid vapor surface tension in
contact with a surface;
[0156] .theta. is the contact angle between the fluid and the
surface;
[0157] .rho. is density difference between fluid and vapor;
[0158] g is acceleration of gravity; and
[0159] d is the separation distance between surfaces.
[0160] The fluid loading plate may be formed from any suitable
materials for use in the intended application. By way of example,
in ophthalmic applications, any suitable material for use in
pharmaceutical ophthalmic applications may be used, such as
polymeric materials that do not chemically react with or adsorb
fluids to be delivered. In certain embodiments, the surfaces of the
fluid loading plate that are exposed to the fluid to be delivered
may be formed from materials that provide desired surface
properties, including hydrophilic/hydrophobic properties, surface
energy, etc., so as to facilitate wicking and capillary action
between the parallel surfaces. For example, see U.S. Pat. No.
5,200,248 to Thompson et al., which is herein incorporated by
reference.
[0161] In certain embodiments, the fluid loading plate may be
formed from a single material, e.g., in a capillary plate
embodiment. In other aspects, the fluid loading plate may be a
composite formed from more than one material wherein the surfaces
that are exposed to the fluid to be delivered are selected so as to
have desired surface properties. By way of example, a capillary
plate may be injection molded or thermoformed as a unitary piece or
as separate pieces. If desired, one or more reservoir mating
surfaces may be separately formed, or formed as a unitary piece
with other components of the capillary plate. Without intending to
be limiting, and by way of example, materials include: polyamides
including nylons such nylon-6, HDPE, polyesters, co-polyesters,
polypropylene, and other suitable pharmaceutical grade hydrophilic
polymers or polymeric structures.
[0162] The fluid loading plate may be sized and shaped in any
suitable manner so as to interface with the desired ejector
mechanism such that fluid is provided to and a suitable capillary
fluid loading zone is formed at the ejector mechanism interface
between the capillary plate and the rear ejector surface of the
ejector mechanism. With reference to FIG. 17A and 17B, one
embodiment of a capillary plate 1700 is illustrated. However the
sizes given in FIGS. 17A and 17B are for illustration purposes
only, and the disclosure is not so limited. By way of example,
capillary plate 1700 may be generally square shaped and have an
edge length of about 25 mm. However, other shapes are envisioned,
including generally circular configurations, etc. Four separated
fluid openings 1706 are shown about an annular radius of about 4.70
mm, having a general opening width of about 2.50 mm and a spacing
of about 2 mm. The thickness of the fluid flow portion of capillary
plate 1700 (i.e., the portion of capillary plate 1700 including
fluid opening 1706) may be about 0.30 mm, and the thickness of the
housing mating ring 1710 of capillary plate 1700 may be about 2 mm.
Piercing projections 1714 may be, e.g., about 1.62 mm across and
about 1.35 mm in length to provide for desired protrusion
properties while still allowing for fluid flow.
[0163] To assist in understanding the present invention, FIGS.
18-22 illustrate various effects of the use of a fluid loading
plate described herein on the performance of an ejector device. The
experiments described herein should not be construed as
specifically limiting the invention and such variations of the
invention, now known or later developed, which would be within the
purview of one skilled in the art are considered to fall within the
scope of the invention as described herein and hereinafter
claimed.
[0164] More specifically, FIG. 18 illustrates the effects of a
capillary plate on resonant frequency and mass deposition of water
using a 160 micron thick NiCo ejector plate with 25 and 40 micron
holes, showing a downward shift in frequency. FIG. 19 illustrates
that as the density (and therefore the mass) of a fluid in a
resonant system (such as the capillary region behind the ejector
plate) increases, so there is a downward shift in the resonant
frequency. FIG. 20 illustrates the downward shift in frequency
associated with a capillary plate used with the delivery of various
fluids using a 160 micron thick NICO ejector plate with 25 and 40
micron holes. FIG. 21 illustrates both a reduction in resonant
frequency and amplitude of the resonant structure as the density
(.rho.) and viscosity (.eta.) of the fluid in the resonant system
are increased. By way of example, and not necessarily related to
the particular values in the graph of FIG. 21, the densities and
viscosities of water, ethanol and propylene glycol are given in the
table below the graph. As shown in FIGS. 18-21, the presence of a
capillary plate leads to an overall shift in resonance frequency,
to lower frequencies. The shift in volume sprayed for liquids is a
consequence of increased density and viscosity, (water, ethanol,
and propylene glycol).
[0165] FIG. 22 illustrates the attitude insensitivity of an ejector
device that includes a capillary plate. As shown, volume (mass)
delivered is relatively insensitive to ejector device orientation.
This insures a constant delivery and supply of fluid behind the
ejector plate. As a result, a consistent volume of droplets is
formed and sprayed by the ejector mechanism, regardless of fluid
level and device orientation.
[0166] In other embodiments, the fluid loading plate may comprise a
puncture plate fluid delivery system, also referred to as a
capillary/puncture plate fluid delivery system, which is configured
to deliver fluid from the reservoir to a fluid retention area at
the back of the ejector mechanism for delivery as a directed stream
of droplets via piezoelectric ejection. Without intending to be
limited by theory, the puncture plate system may utilize one or
more of hydrostatic pressure, capillary pressure, geometrical
pressure gradients (Venturi effect), and air exhaustion.
[0167] One embodiment of a puncture plate fluid delivery system and
its operation is shown in FIGS. 23-27. FIGS. 23A and B show a front
view and a back view, respectively, of an ejector mechanism 2300
with 5 rise holes 2302. As shown in front view in FIG. 23C and in
back view in FIG. 23D, the puncture plate fluid delivery system may
include a capillary plate portion comprising a fluid retention area
between the puncture/capillary plate fluid delivery system and a
rear surface of an ejector mechanism for channeling fluid to the
ejector mechanism by one or more mechanisms, including capillary
action, and at least one hollow puncture needle for transferring
fluid from a reservoir to the fluid retention area. In this
embodiment, 6 hollow puncture needles 2306 extend from the back
surface of the capillary/puncture plate, the channels through the
needles extending through to the front face of the capillary plate
2304 as shown by the holes 2308. The needles 2306 are surrounded by
a wall 2310 defining a receptacle for a fitment 2312 (shown in FIG.
23E together with a self-sealing silicone sealing element 2314 that
is housed in the fitment 2312).
[0168] Initially, the fluid containing reservoir or ampoule 2316
(these terms are used interchangeably herein) is connected to the
fitment and is in fluid communication with a secondary reservoir
defined by the fitment and the silicone sealing element 2314. The
capillary plate 2304 is, in turn, attached to and in fluid
communication with the ejector mechanism 2300. However, prior to
use, the puncture plate and ejector mechanism 2300 may be provided
in a disconnected state from the fitment 2312 and reservoir 2316 to
prevent fluid exchange. During the initial stage of connection the
hollow puncture needles 2302 shown on the back of the puncture
plate image in FIG. 23D are partially inserted into the
self-sealing silicone puncture gasket or grommet 2314 that rests
inside the fitment 2312. The secondary reservoir formed in the
fitment 2312 is constantly open to the fluid in the primary
ampoule/reservoir 2316. At this stage, fluid from the primary
reservoir that has moved into the secondary reservoir of the
fitment 2312 does not enter into the hollow puncture needles 2306,
however, due to the barrier created by the self-sealing silicone
gasket material 2314.
[0169] Puncture is accomplished by pressing the puncture plate
needles all the way through the gasket 2314 into the fluid filled
fitment by forcing the needles through the silicone gasket. This
may occur, e.g., when the fitment snap-fits (indicated by a
clicking sound) into the receptacle 2310 of the puncture plate
2304. A seal is maintained after puncture because the silicone
gasket 2314 is a compliant and self-sealing material. The initial
transfer of fluid from the reservoir/container through the hollow
puncture needles immediately after puncture results from a
combination of hydrostatic pressure, fitment retention/reservoir
volume, and the fluid reaction force from initial puncture which
drives the fluid through the capillary tubes defined by the hollow
needles and channels in the capillary/puncture plate.
[0170] Once the fluid passes through the capillary tubes, surface
tension effects dominate the rise of the fluid against gravity. As
the fluid rises, it removes air from the system by pushing it out
of the front of the ejector openings or holes. Capillary rise holes
2301 are placed on the ejector plate 2320 of the ejector mechanism
above the piezoelectric element 2322 that serves as a pressure
relief for the air in the system. In the absence of these capillary
rise holes 2302, the system would be closed in the region above the
ejector openings and the fluid would cease to rise due to the
increasing build up in air pressure that eventually equalizes with
the capillary pressure. In order to achieve complete rise, all of
the air needs to be pushed out of the system. The capillary rise
holes 2302 (shown from the back in FIG. 25A and from the front in
FIG. 25B) act as pressure equalizing holes and are placed and
properly sized (to prevent fluid leaking) and allow the fluid to
rise completely thereby ensuring that no (or very little) air
remains in the system. The assembled ejector assembly is shown from
the front in FIG. 24A and from the rear in FIG. 24B.
[0171] FIG. 26 illustrates a schematic outlining fluid flow through
the puncture plate system after complete puncture through the
silicone gasket. The liquid flows through the puncture system and
up the capillary plate chamber 2600, pushing air out of the ejector
openings or holes 2602 and capillary rise holes 2302. With
reference to FIGS. 23 C and D, the puncture/capillary plate 2304
illustrates a design with 6 needles with an inner diameter (ID) of
650 microns and an outer diameter (OD) of 1 mm. The number of
needles can be as small as 1 needle but can also include more
needles, e.g., 8 needles with ID dimensions ranging from 500
microns-3 mm and OD dimensions ranging from 600 microns-4 mm. The
rise holes shown in FIG. 25 can also vary from what is displayed in
this figure. This FIG. 5 shows 20 micron diameter sized rise holes
however the number of holes can be as low as 1 hole but can also
include more holes e.g., 8 holes with the diameter of the holes
ranging from 10 microns-50 microns.
[0172] Alternatively, with reference to FIGS. 44-46, the puncture
plate may be designed with an elongate needle puncture system. Such
designs may, for instance, be used in connection with certain
configurations of reservoir designs such as standing rectangular
Low Tensile Stress (LTS) reservoirs (i.e., IV bag designs).
[0173] The puncture plate may be constructed from any suitable
material, such as described and illustrated herein. By way of
non-limiting example, the puncture plate may be constructed from:
Liquid crystal polymer "LCP" (glass filled 0-30%); Nylon 6; Nylon
6,6; Polycarbonate; Polyetherimide (Ultem); Polyether ether ketone
(PEEK); Kapton; Polyimide (Kapton); Stainless Steel 316L;
Diamond-like carbon (DLC) coated Stainless Steel (300 series);
Diamond-like carbon (DLC) coated aluminum; Diamond-like carbon
(DLC) coated copper; Diamond-like carbon (DLC) coated
nano-crystalline cobalt phosphate; Nano crystalline cobalt
phosphate (nCoP); Gold coated Stainless Steel (300 series); Polymer
coated (Polymers listed above) Stainless Steel (300 series);
Polymer coated (Polymers listed above) Copper (300 series); Polymer
coated (Polymers listed above) aluminum (300 series), etc.
[0174] Although the foregoing describes various embodiments by way
of illustration and example, the skilled artisan will appreciate
that various changes and modifications may be practiced within the
spirit and scope of the present application. Even though the term
"capillary plate" and "puncture plate" is used to describe various
embodiments, it will be appreciated that the description is
applicable to any fluid loading plate, need not take the form of a
plate and can have any configuration suitable for channeling the
liquid from the reservoir to the ejector mechanism.
[0175] As used herein, a reservoir may be any object suitable for
holding a fluid. By way of example, the reservoir may be made of
any suitable material capable of containing a fluid. Reservoirs of
the present disclosure may be rigid or flexible and the reservoirs
of the present disclosure may further be collapsible. As used
herein, collapsible refers to a decrease in volume obtainable in a
reservoir achieved by squeezing, folding, crushing, compressing,
vacuuming, or other manipulation, such that total volume enclosed
after collapsing is less than a volume that could be enclosed in a
non-collapsed container. A reservoir may be made of any suitable
material that can formed into a volume capable of holding a volume
of fluid. Suitable materials, for example, may either be flexible
or rigid and may be formable or pre-formed. As used herein a
reservoir, by way of example, may be formed from a film.
[0176] Furthermore the reservoir may be in fluid communication with
a fluid loading plate to form a fluid reservoir interface, and in
certain embodiments the fluid loading plate may optionally include
a reservoir mating surface or ring to facilitate connection with
various fluid reservoir configurations.
[0177] In some aspects, the reservoir of the system of the
disclosure may be configured as a low tensile stress or "LTS"
reservoir. An LTS reservoir of the disclosure is generally designed
to minimize or eliminate positive pressure gradients imposed on the
system by the reservoir created from memory effects, crease
formation, and unbiased collapse. Such gradients may result in a
restoration of the reservoir (expansion in volume) that exerts a
net pressure differential on the system, resulting in potential
failure by drawing air into the system through the ejector
openings. In certain aspects, to correct for the pressure
differential, the LTS reservoir is configured so as to be biased to
collapse into its low lying rest position, which reduces or
eliminates the possibility of crease formation.
[0178] The LTS reservoir is also constructed from thin, flexible
(low tensile stress) materials that resists volume expanding,
rebounding, and memory effects without compromising the inertness
and evaporation resistance (see Table 7). LTS reservoirs, as
explained above and in further detail below, may be constructed in
any suitable manner, e.g., including RF-welding, blow-fill seal
processes, form-fill seal processing, etc.
[0179] Without intending to be limited by theory, to aid in fluid
transport from the fluid retention/reservoir and through the
capillary tubes during operation, the LTS reservoir may also be
geometrically designed to accelerate the fluid by incorporating the
principle of continuity and the Venturi effect as shown in FIG. 27
and as described below in the Bernoulli equation for incompressible
flows, and shown in FIG. 28.
[0180] Again, without intending to be limited by theory, FIG. 28
describes how altering the reservoir geometry to a convergent shape
profile (larger area to smaller area) results in the fluid
accelerating as it moves down the reservoir due to the increase in
velocity resulting from the continuity principle. According to the
Bernoulli equation, an increase in velocity from the continuity
principle will result in a decrease in pressure in the region of
increased velocity (in order to maintain continuity). This change
in pressure creates a gradient that aids in transporting the fluid
into the fitment and through the puncture needles/capillary tubes.
This increase in velocity resulting from a converging area change
is known as the Venturi effect.
[0181] FIG. 29 illustrates how hydrostatic pressure drives fluid
from the LTS ampoule into the fitment and through the puncture
needles into the fluid reservoir. To maximize hydrostatic pressure
the ampoule needs to be oriented in the upright position since
hydrostatic pressure is a function of height.
TABLE-US-00008 TABLE 7 Ampoule Type Ampoule Material Thicknesses
RF-Welded Polyurethane (PU), 2-12 mils PU/Polyvinylidene Chloride
(PVDC)/PU, Ethylene-Vinyl Acetate (EVA) Thermal Plastic
Polyurethane (TPU) PU/Ethylene-Vinyl Alcohol (EVOH)/PU Isoplast
.RTM. ETPU Blow fill seal Low-Density Polyethylene 2-15 mils (LDPE)
LDPE w/ EVA (10%-50%) EVA (100%) Form fill seal Victrex (LDPE w/
oxygen 2-12 mils barrier layer) TPU
[0182] FIG. 30 shows schematic representations of non-fluid
accelerating LTS reservoir geometries, which collapse into
themselves. The standing rectangle represents a reservoir (similar
to an IV bag) that is designed to collapse along its minimum
dimension (not shown). The standing rectangle reservoir design is
oriented upright to maximize the height such that the effect of
hydrostatic pressure is maximized. The second image shown is the
lying rectangle which functions in a similar way to the standing
rectangle, but without maximizing the effect of hydrostatic
pressure. The third image shows a square reservoir configuration.
FIG. 31 shows schematic representations of fluid accelerating LTS
reservoir geometries.
[0183] With reference to FIG. 32, two examples of a circular fluid
accelerating LTS reservoir are illustrated, one constructed by
blow-fill-seal processes (FIG. 32A) and the other by RF-welding
(FIG. 32B). As shown, the amount of collapse may be enhanced when
the reservoir is biased to collapse along the minimum dimension,
which in FIG. 32 is the thickness. This type of collapse largely
prevents the formation of creases in the reservoir during
operation. For standing reservoir designs, further protection
against crease formation during operation of an ejector device may
be created by enclosing the reservoir in a housing that prevents it
from folding over itself as it is emptying. Supporting data of the
performance of these reservoirs is provided herein.
[0184] FIG. 33 shows a configuration of a puncture plate 3300 and a
blow-fill-seal reservoir with the fitment removed. In certain
embodiments, where for self-sealing reservoir materials are used,
the puncture can occur directly through the lower region of the
reservoir. The fill compartment shown at the bottom of FIG. 33 is
designed to allow for maximal fluid fill of the secondary
reservoir. Alternative puncture mechanisms for the blow fill seal
puncture plate assembly are shown in FIG. 34.
[0185] FIG. 34 A shows a side profile of another embodiment of the
blow fill seal reservoir puncture plate assembly. FIG. 34A shows a
stiffening mechanism in the form of a plastic shell 3400 used to
aid in needle puncture through the blow fill reservoir when it is
constructed from a self-sealing material. The figure to the right
(FIG. 34B) shows the configuration when the blow fill seal
reservoir does not self-seal upon puncture and must be connected to
the fitment in the same manner as in FIGS. 22 and 23. As is shown
in FIG. 34B, the needles need to pass through the silicon gasket
into the region shown as "Needles puncture through here".
[0186] In yet other embodiments of the disclosure, FIG. 35
illustrates geometries of reservoirs that are biased to collapse a
certain way to prevent crease formation. Spray down and pull down
procedures and results for these ampoules are disclosed in the
example below.
Example 3
Measurement of Spray Down and Pull Down
[0187] Static pull down tests were performed to determine the
amount of negative pressure that different reservoir
configurations, e.g., as shown in FIGS. 30-35, exert on the system
as they are removing fluid. The experimental setup for this test is
shown in FIGS. 36-37. The experimental procedure is as follows: a
reservoir is attached to a water column tube that is connected to a
vacuum regulator connected to a mechanical pump used to draw fluid
from the reservoir or ampoule.
[0188] Mass deposition testing was performed to determine the mass
of a spray from a device at a given frequency or multiple
frequencies (mass deposition sweep). Given that some frequencies
have a very low mass per spray, which may be at the lower tolerance
of the scale used for measuring the mass, the number of sprays were
varied per sample at each frequency, then averaged to determine a
per spray volume at each frequency. This also helped eliminate some
error in the measurement. (The scale used could read to the tenth
of a milligram.) These setups were run by a laptop computer, which
communicated with the scale, a function generator, and an
oscilloscope. The mass of the sprays was recorded as well as the
electrical characteristics (phase and magnitude of the voltage and
the current, and the impedance) during the spray. The setup was
controlled by a labview program that was compiled into a labview
executable program and run from the laptop. This program allowed
the user to select the lab equipment in the setup, the com port for
the scale, and Universal Serial Bus (USB) identification for the
oscilloscope and function generator. The user also defined the
testing parameters: voltage, wave form, start frequency, end
frequency, step size, number of sprays, time between sprays, and
spray duration. The program communicated with function generator,
setting the frequency for the spray and the number of cycles to
achieve the appropriate spray duration, and set the oscilloscope to
single acquisition from a trigger (Voltage Probe). The program then
instructed the function generator to trigger the wave form. The
signal was sent to an operational amplifier to boost the signal to
the appropriate voltage, which was then applied to the device (0 to
.+-.90V). At the device, voltage and current probes were attached
to verify the voltage and to read the current. A delay was written
into the program to allow time for the scale to balance out
(.apprxeq.8 sec) before reading the mass from the scale and
determine the mass per spray. The scale was zeroed at the start of
the test and at every half gram. At every half gram when zeroing
the scale, the scale was cleaned and the reservoir attached to the
device was refilled. This insured that the device did not run out
of fluid, and lowered the error from evaporation of the fluid on
the scale by limiting the amount of fluid on the scale that could
evaporate to 0.5 g. The scale was read after each set of sprays as
defined by the user (normally 5). The mass of the sprays was
determined by subtracting the previous value from the current scale
reading, thereby eliminating the time required to zero the scale
between sets of sprays.
[0189] FIG. 38 shows spray down performance (24% of the fluid) of a
control reservoir that is fairly rigid and collapses to form many
creases that result in a buildup of negative pressure. FIG. 39
shows the results for a representative LTS reservoir of the
disclosure, as illustrated in FIG. 35. This shows an improvement in
spray down performance when creating a geometry biased to collapse
in a controlled direction as well as choosing flexible materials
and the appropriate material thickness. The graph shows that the
majority of the samples (multiple tests of the same ampoule type
with the same thicknesses) allowed 80 percent or more of the fluid
to be removed, with a few outliers, which removed much less but
better than the creased, control reservoir of FIG. 38.
[0190] FIG. 40 shows the spray down performance of two separate
runs with one embodiment of a round LTS reservoir. This reservoir
showed a marked improvement, with over 90 percent of the fluid
removed. FIG. 41 shows the pull downs for select round LTS ampoule
designs from FIG. 35. These graphs show a large improvement in the
negative pressure generated from the system when using the round
LTS reservoir. Without intending to be limited by theory, FIG. 42
shows the mechanism involved in inverted spray using a round LTS
reservoir, while FIG. 43 shows the actual spray down performance
results of an LTS reservoir sprayed down in a complete puncture
system upside down.
[0191] In accordance with other aspects of the disclosure, the
fluid loading plate may be designed with a different needle
puncture systems, as illustrated in FIGS. 44-46. Such designs may
be used in connection with reservoir designs, e.g., standing
rectangular LTS reservoirs (i.e., IV bag style designs).
[0192] As discussed above, an ejector plate of the system may
include capillary rise holes to provide additional air pressure
relief above the active area (ejector openings). This additional
air pressure relief may thereby allow for complete capillary rise
of the fluid, which allows the retention/reservoir to be completely
filled with fluid. In accordance with certain aspects of the
invention, it was unexpectedly found that if these holes are not
placed above the ejector openings, the device may not operate
efficiently once the fluid falls below the level of the ejector
openings (thereby potentially allowing outside air to move into the
system during operation).
[0193] When constructing capillary rise holes, optimization of hole
size is of importance. The holes are preferably large enough to
allow a reasonable venting rate so that the capillary rise is not
too slow, and are preferably small enough so that the fluid does
not readily leak when the hole is aligned in the direction of
gravity. Leaking of the fluid out of the rise hole is a function of
the size of the hole as well as the surface tension of the fluid.
Fluids with higher surface tensions have increased resistance to
leaking due to the strength of the fluid meniscus (which is a
function of the surface tension of the fluid) formed within the
rise hole by the fluid, which creates a barrier from fluid leaking
out and air moving in. The barrier is breached when the hydrostatic
pressure of the reservoir (ampoule) overcomes the surface tension
within the rise hole cavity (see FIG. 47).
[0194] The fluid loading plate of the disclosure utilizes capillary
action to transport fluid to a location behind the active area of
the piezoelectric mesh for ejection, e.g., as discussed earlier
with respect to FIG. 27. Capillary rise is a function of the
surface tension of the fluid, surface energy of the surfaces in
contact with the fluid (contact angle), and the separation distance
of the surfaces in contact with the fluid. To achieve optimal
performance for the puncture plate system a hydrophilic material
(contact angle between the fluid and the surface less than 90
degrees) is preferably used for the capillary channels. In addition
the material is preferably biocompatible and chemically inert. The
separation distance of the surfaces containing the fluid rise are
preferably tuned to ensure that the capillary width is considerably
less than the capillary length of the fluid thereby ensuring that
the surface forces are more significant than that of gravity. As
shown in FIG. 27, capillary rise in the system occurs between the
puncture plate (capillary plate+needles) and the ejector plate
(which includes the active area or openings (piezoelectric mesh
screen).
Example 4
Measurement of Capillary Rise
[0195] FIGS. 48-49 illustrate capillary pressure for various sized
half droplets of water and an exemplary ocular medication,
latanaprost. Thus, the fluid loading plate separation distance from
the ejector plate is an important parameter for optimization of
capillary rise to a certain height above the ejector openings. This
plate separation distance (along with viscosity and surface tension
of the fluid) also impacts the time for the fluid to rise to the
final height. As shown in FIG. 50, a device designed to spray water
and saline can operate with a capillary distance less than or equal
to 2.7 mm. However, the systems of the disclosure are not so
limited, and a capillary distance (separation between capillary
plate and the ejector plate) from 2.7 mm-1.7 mm, and below 1.7 mm
may be utilized to achieve greater capillary rise. In certain
embodiments, a distance for the puncture plate system may be
between 50-200 micrometers.
[0196] In this regard, FIG. 51 shows capillary rise for saline in
capillary channels made of different materials. FIG. 52 shows
capillary rise between capillary plate and puncture plate without a
capillary rise hole 2302. This is contrasted with the much better
capillary rise shown in FIG. 53, which shows the rise when a
capillary rise hole is included.
[0197] Further, Tables 8-10 below show capillary rise data in the
capillary channel between the fluid loading plate and the rear
surface of the ejector mechanism as a result of using different
numbers and sizes of capillary rise holes 2302. Table 8 shows the
data for rise time for water, Table 9 shows rise time for
Latanaprost at room temperature, and Table 10 shows the rise time
for Latanaprost refrigerated to 38.degree. F. Some results had to
be discarded as in operative (In-Op, No Fill Past Active Area,
blank entry) due to defects in the capillary rise holes, or showed
asymmetric fill (marked with an asterisk), but the results
indicated the benefits in rise time when using 5 capillary holes,
and showed faster rise times with increase capillary hole size.
TABLE-US-00009 TABLE 8 1 Hole 3 Holes 5 Holes 5 um Test 1 395 s 200
s In-Op Test 2 370 s 155 s* In-Op 10 um Test 1 No Fill Past 70 s 23
s Active Area Test 2 No Fill Past 54 s 25 s Active Area 20 um Test
1 22 s 8 s 6 s Test 2 22 s 10 s 5.5 s 50 um Test 1 3 s 2 s In-Op
Test 2 3.5 s 1.6 s In-Op
TABLE-US-00010 TABLE 9 1 Hole 3 Holes 5 Holes 10 um Test 1 No Fill
past 60 s 26 s A.A. Test 2 68 s* 32 s 20 um Test 1 11 s 8 s 6 s
Test 2 8 s 11 s 5 s
TABLE-US-00011 TABLE 10 1 Hole 3 Holes 5 Holes 10 um Test 1 25 s 28
s* Test 2 42 s 44 s* 20 um Test 1 7 s 10 s 3.5 s Test 2 10 s 7 s
4.5 s
Example 5
Fluid Leak Testing for Select Ocular Drugs and Rise Hole Sizes
[0198] To test for fluid leaking out of capillary rise holes or
vent holes of one embodiment of the device, a hydrostatic pressure
test assembly was constructed as shown in FIG. 54. The ejector
plate with the rise holes and the ejector assembly was placed
beneath the fluid column defined by the tube. The test fluid was
filled into the tube oriented directly above the ejector plate with
the height of the fluid column carefully monitored. When the fluid
reached test heights (hydrostatic pressure) at which the fluid
above the ejector openings caused leakage through the rise holes
and the ejector openings, the heights (corresponding to the
pressure values) were recorded and used as a design parameter for
optimizing rise hole dimensions. Results are shown in Tables 5-7
below.
TABLE-US-00012 TABLE 11 Water column to side of mesh Water column
directly above mesh Vent Holes Mesh Holes Vent Holes Mesh Holes
(inches water) (inches water) (inches water) (inches water) Annulus
Mounting Standard Standard Standard Standard Vent Hole Condition
Average Deviation Average Deviation Average Deviation Average
Deviation 1 .times. 5 um 1 32 31 2 22 3 29 4 2 28 3 31 23 3 31 3
.times. 5 um 1 28 27 2 2 26 3 29 3 5 .times. 5 um 1 No leak 27 6 2
No leak 28 6 1 .times. 10 um 1 23 10 27 3 15 1 25 4 2 22 4 27 2 18
2 23 5 3 .times. 10 um 1 15 1 25 4 2 14 2 26 5 13 3 23 5 3 .times.
20 um 1 2 22 2 23 5 1 .times. 50 um 1 2 12 4 No leak 3 .times. 50
um 1 2 14 3 No leak 5 .times. 50 um 1 2 13 4 No leak
TABLE-US-00013 TABLE 12 Tropicamide column to side of mesh
Tropicamide column directly above mesh Vent Holes Mesh Holes Vent
Holes Mesh Holes (inches Tropicamide) (inches Tropicamide) (inches
Tropicamide) (inches Tropicamide) Annulus Mounting Standard
Standard Standard Standard Vent Hole Condition Average Deviation
Average Deviation Average Deviation Average Deviation 1 .times. 5
um 1 2 7 1.5 6.8 1 1 .times. 10 um 1 2 4.8 0.9 6 0.7 7 5.6 1.2 3
.times. 10 um 1 2 n/a 6.3 1.3 n/a 4.8 0.5 3 .times. 20 um 1 2 n/a
8.1 1.6 n/a 3.8 0.8 1 .times. 50 um 1 2 4 0.9 6 1.3 3 .times. 50 um
1 2 4.8 0.7 6.4 0.8
TABLE-US-00014 TABLE 13 Latanoprost column to side of mesh Vent
Holes Mesh Holes (inches Latanoprost) (inches Latanoprost) Annulus
Mounting Standard Standard Vent Hole Condition Average Deviation
Average Deviation 1 .times. 5 um 1 2 n/a 3.7 0.6 1 .times. 10 um 1
2 n/a 3.5 0.6 1 .times. 50 um 1 2 3.3 0.7 3.7 0.6
[0199] Although the foregoing describes various embodiments by way
of illustration and example, the skilled artisan will appreciate
that various changes and modifications may be practiced within the
spirit and scope of the present application.
[0200] As mentioned above, droplets may be formed by an ejector
mechanism from fluid contained in a reservoir that is coupled to
the ejector mechanism. The ejector mechanism and reservoir, which
together form an ejector assembly, may be configured to be
removable to allow the assembly to be disposed of or reused. Thus
the components may be packaged in a housing, e.g., the upper
section 200 of the housing 202 shown in FIG. 2, in a removable
manner. The housing itself may therefore be disposable, or may be
reusable by being configured to receive a removable ejector
mechanism. The housing may be handheld, miniaturized, or formed to
couple to a base, and may be adapted for communication with other
devices. Housings may be color-coded or configured for easy
identification.
[0201] While specific embodiments of the ejector mechanism are
discussed below, this does not limit the configuration or use of
the ejector mechanism nor the features that may be added to the
ejector device. Ejector devices, in some implementations, may
include illumination means, alignment means, temperature control
means, diagnostic means, or other features. Other implementations
may be part of a larger network of interconnected and interacting
devices used for subject care and treatment. The ejector mechanism
may, for example, be a piezoelectric actuator as described
herein.
[0202] Referring to FIGS. 55 A-C, an ejector assembly 5500 may
include an ejector mechanism 5501 and a reservoir 5520. The ejector
mechanism 5501 may include an ejector plate 5502 coupled to a
generator plate 5532 that includes one or more openings or holes
5526. The ejector plate 5502 and generator plate 5532 that can be
activated by a piezoelectric actuator 5504 which vibrates to
deliver a fluid 5510, contained in the reservoir 5520, in the form
of ejected droplets 5512 along a direction 5514. Again, the fluid
may be an ophthalmic fluid that is ejected towards an eye 5516 of a
human adult, child, or animal. Additionally, the fluid may contain
an active pharmaceutical to treat a discomfort, condition, or
disease of a human or an animal. In some implementations, the
generator plate is a high modulus polymer generator plate, e.g.,
formed from a material selected from the group consisting of:
ultrahigh molecular weight polyethylene (UHMWPE), polyimide,
polyether ether ketone (PEEK), polyvinylidene fluoride (PVDF), and
polyetherimide. comprises a high modulus polymeric generator
plate.
[0203] As shown in FIG. 55A, ejector plate 5502 is disposed over
the front of the reservoir 5520 which contains fluid 5510. The rear
surface 5525 of ejector plate 5502 is arranged to be adjacent to
the fluid 5510. In this embodiment, the reservoir 5520 therefore
has an open end 5538 which is attached adjacent to surface 5525 and
to openings 5526. In this embodiment, surface 5525 encloses the
fluid 5510 in the reservoir 5520. The reservoir 5520 may be coupled
to the ejector plate 5502 at a peripheral region 5546 of the
surface 5525 of the ejector plate 5502 using a suitable seal or
coupling. By way of example, the reservoir 5520 may be coupled via
an O-ring 5548a. Although not shown, more than one O-ring can be
used. As known in the art, the O-rings may have any suitable
cross-sectional shape. Furthermore, other couplers such as
polymeric, ceramic, or metallic seals can be used. Alternatively,
the coupling can be eliminated altogether and reservoir 5520 may be
integrally connected to ejector plate 5502, for example by welding
or over molding. In such an implementation, an opening through
which fluid is supplied to reservoir 5520 may be provided (not
shown). In embodiments where couplings are used, the couplings may
be made removable, e.g., by providing a hinged connection between
the reservoir 5520 and the ejector plate 5502, or by providing a
flexible or non-rigid connector, e.g., polymeric connector.
[0204] The reservoir 5520 may define a peripheral lip or wall 5550
covering portions of the ejector plate 5502. In the implementation
of FIG. 55A, the wall 5550 does not directly contact the ejector
plate 5502, rather it is coupled to O-rings 5548a. Alternatively,
the wall 5550 can be directly attached to ejector plate 5502.
Instead, the reservoir can be directly attached to the ejector
plate 5502 and the wall 5550 can be omitted altogether.
[0205] The configuration of the reservoir, including the shape and
dimension, can be selected based on the amount of fluid 5510 to be
stored, as well as the geometry of the ejector plate 5502.
Alternative forms of reservoirs include gravity-fed, wicking, or
collapsible bladders (as discussed above and which accommodate
pressure differentials). These reservoirs may be prefilled, filled
using a micro-pump or may be configured to receive a replaceable
cartridge. The micro pump may fill the reservoir by pumping fluid
into or out of a collapsible or non-collapsible container. The
cartridge may include a container which is loaded into the
reservoir. Alternatively, the cartridge itself may be coupled to a
disposable ejector assembly which is then replaced after a
specified number of discharges. Examples of reservoirs are
illustrated in U.S. patent application Ser. No. 13/184,484, filed
Jul. 15, 2011, the contents of which are herein incorporated by
reference.
[0206] In some implementations, the reservoir 5520 includes through
holes 5542 (only one shown in FIG. 55A) to allow air to escape from
or enter the reservoir 5520 and keep the fluid 5510 in the
reservoir at the appropriate ambient pressure. The through holes
5542 have a small diameter so that the fluid 5510 does not leak
from the holes. Alternatively, no openings may be formed in the
reservoir 5520, and at least a portion, e.g., the portion 5544, or
the entire reservoir 5520 can be collapsible, e.g., in the form of
a bladder, as is discussed in greater detail above. Thus the entire
reservoir may, in some embodiments, be made in the form of a
flexible or collapsible bladder. Accordingly, as the fluid 5510 is
ejected through the openings 5526, the reservoir 5520 changes its
shape and volume to follow the changes in the amount of fluid 5510
in the reservoir 5520.
[0207] In the embodiment of FIG. 55A, the ejector mechanism 5501 is
activated by being vibrated by a piezoelectric actuator 5504, which
in this embodiment has an annular shape. Two electrodes 5506a and
5506b are formed on two opposite surfaces 5536 and 5534 of the
piezoelectric actuator 5504 that are parallel to the surface 5522
of the ejector plate 5502 and activate the piezoelectric actuator
5504 to vibrate the ejector plate 5502 and a generator plate 5532.
For ease of representation the ejector plate 5502 and generator
plate 5532 are shown lying in a common plane. However, as is
discussed in greater detail below with respect to FIGS. 1B-1D, the
generator plate 5532 in this embodiment is attached to a surface of
the ejector plate 5502. The electrodes 5506a and 5506b can be
attached to the ejector plate or piezoelectric actuator in any
known manner including fixing by adhesive or otherwise bonding.
They may also be overmolded in place to ejector plate 5502. Wires
or other conductive connectors can be used to affect necessary
electrical contact between the ejector plate 5502 and the
electrodes 5506a and 5506b. Alternatively, the electrodes may be
formed on the ejector plate 5502 by plating or otherwise
depositing. By way of example, the electrodes are attached by means
of electrically conductive adhesive 5528 which is applied between
the electrode 5506a and the ejector plate 5502 to place the
electrode 5506a in electrical contact with the ejector plate 5502.
When a voltage is applied across the electrodes 5506a and 5506b,
the piezoelectric actuator 5504 deflects ejector plate 5502 and
likewise generator plate 5532 to change the shape to a more concave
or convex shape.
[0208] Accordingly, when a voltage is applied across the electrodes
5506a and 5506b, the piezoelectric actuator 5504 deflects ejector
plate 5502 and likewise generator plate 5532 to change shape to be
alternately more concave or convex at the resonance frequency of
the coupled ejector plate 5502 and generator plate 5532. The
coupled ejector plate 5502 and generator plate 5532 deflected by
the piezoelectric actuator 5504 at the resonant frequency may
amplify the displacement of the coupled ejector plate 5502 and
generator plate 5532 thereby decreasing the power requirements of
the piezoelectric actuator input. In a further aspect, the damping
factor of the resonance system of the coupled ejector plate 5502
and generator plate 5532 due to the inherent internal resistance of
the annulus/mesh limits the movement to prevent a runaway condition
and prevent catastrophic failure.
[0209] An extensive range of voltages corresponding to different
piezoelectric materials are known in the art, but by way of
example, a voltage differential of between 5 and 60 V, or and 60 V,
e.g., 40 or 60 V may be applied to the electrodes. When the
direction of the voltage differential is reversed, for example to
-40 or -60, the plate will deflect in the opposite direction. In
this way, the piezoelectric actuator 5504 causes oscillation of
ejector plate 5502 and generator plate 5532 which constitutes the
vibration that results in formation of the droplets 5512 from fluid
5510. As the alternating voltage is applied to electrodes 5506a and
5506b, the ejector plate 5502 and the generator plate 5532
oscillate, causing the fluid droplets 5512 to accumulate in the
openings 5526 and eventually to be ejected from the openings 5526
along the direction 5514 away from the reservoir 5520. The
frequency and wavelength of oscillation may depend on many factors,
including but not limited to, the thickness, composition and
morphology and mechanical properties of the ejector plate 5502,
including its stiffness, the properties of the generator plate
5532, the volume of the openings 5526, the number of openings 5526,
composition and structure of the piezoelectric actuator 5504,
piezoelectric actuation driving voltage, frequency and waveform,
the viscosity of the fluid, temperature and other factors. These
parameters may be adjusted or selected to create the desired
droplet stream. The frequency of droplet ejection also depends on
many factors. In some implementations, the droplets 5512 are
ejected at a frequency lower than the pulse frequency applied to
the piezoelectric actuator 5504. For example, the droplets 5512 are
ejected every 1-1000 cycles, and more specifically 8-12 cycles, of
the ejector plate/generator plate vibration (which vibrate at the
same frequency as the actuator 5504). In some implementations, the
generator plate comprises a high modulus polymeric generator
plate.
[0210] In one embodiment of the present disclosure, as illustrated
in FIG. 55 C, the ejector plate 5502 may be centro-symmetrically
mounted by symmetric mounting structures 5555 through optional
mounting holes 5551. Symmetric mounting structures may maximize the
constant velocity surface area of ejector plate 5502, suppress
anti-symmetric modes and mechanically match the piezoelectric
material to the low order Bessel modes. In this embodiment there
are four mounting tabs 5555 as shown in FIG. 1C. In another
embodiment, there may be eight mounting tabs 5555. In yet another
embodiment, there may be 16 mounting tabs 5555.
[0211] In certain aspects, the centro-symmetrical mounting provides
for the use of piezoelectric materials that are lead free, e.g.,
BaTiO.sub.3. In one embodiment of the disclosure, the resonance
coupling of the ejector plate 5502 to a generator plate 5532 and to
the piezoelectric actuator 5504 provides for the use of
piezoelectric materials having smaller displacements than industry
standard piezoelectric materials.
[0212] In accordance with certain embodiments of the disclosure,
with reference to FIG. 55A, an ejector plate 5502 may be a simple
ejector plate 5502 having an integrated generator plate 5532 having
a center region 5530 and openings 5526. In other embodiments of the
disclosure (FIGS. 55B-D) the ejector plate 1602 may be hybrid
ejector plate 1602 having a coupled generator plate 5532 having a
center region 5530 and openings 5526. The first surface 5522 of the
ejector plate 5502 may be coupled to the generator plate 5532. The
ejector plate 5502 may generally comprise a central open region
5552 configured to align with the generator plate 5532. The
generator plate 5532 may then be coupled with the ejector plate
5502 such that a center region 5530 of the generator plate 5532
aligns with the central open region 5552 of the ejector plate 5502.
The center region 5530 of the generator plate 5532 may generally
include one or more openings or holes 5526, and alignment of the
central open region 5552 of the ejector plate 5502 with the central
region 5530 of the generator plate 5532 with its one or more
openings 5526 allows for through communication of the one or more
openings 5526. In some embodiments, the generator plate comprises a
high modulus polymeric generator plate.
[0213] In certain embodiments, the central open region 5552 of the
ejector plate 5502 may be smaller than the generator plate 5532 to
provide sufficient overlap of material so as to allow for coupling
of the ejector plate 5502 and the generator plate 5532. However,
the central open region 5552 of the ejector plate 5502 should, in
such embodiments, be sized and shaped so as to not interfere with
or obstruct the center region 5530 (and thereby one or more
openings 5526) of the generator plate 5532. By way of non-limiting
example, the central open region 5552 of the ejector plate may be
shaped in a manner similar to the generator plate 5532, and may be
sized so as to have, for example, about 0.5 mm to about 4 mm, e.g.,
about 1 mm to about 4 mm, or about 1 mm to about 2 mm, etc., of
overlap material available for coupling of the generator plate 5532
to the ejector plate 5502 (e.g., overlap on all sides). For
instance, the central open region 5552 of the ejector plate may be
shaped as a square, a rectangle, a circle, an oval, etc., in a
manner to generally match the shape of the generator plate 5532,
and sized such that the central open region 5552 is, for example,
about 0.5 mm to about 4 mm smaller in overall dimensions (i.e., the
diameter of a circle is about 0.5 to about 4 mm smaller, the major
and minor axes of an oval are about 0.5 to about 4 mm smaller, the
length of the sides of a square or rectangle are about 0.5 to about
4 mm smaller, etc.). In some embodiments, the generator plate
comprises a high modulus polymeric generator plate.
[0214] Except as otherwise described herein, exemplary ejector
mechanisms are disclosed in U.S. application Ser. Nos. 13/712,784,
filed Dec. 12, 2012, entitled "Ejector Mechanisms, Devices, and
Methods of Use", and 13/712,857, filed Dec. 12, 2012, entitled
"High Modulus Polymeric Ejector Mechanism, Ejector Device, and
Methods of Use," the contents of which are herein incorporated by
reference in their entireties.
[0215] The generator plate 5532 may be coupled to the ejector plate
5502 using any suitable manner known in the art, depending on the
materials in use. Examples of coupling methods include the use of
adhesive and bonding materials, e.g., glues, epoxies, bonding
agents, and adhesives such as loctite 409 or other suitable super
glue, welding and bonding processing, e.g., ultrasonic or
thermosonic bonding, thermal bonding, diffusion bonding, or
press-fit etc.
[0216] Surface 5522 of ejector plate 5502 may also be coupled to a
piezoelectric actuator 5504, which activates generator plate 5532
to form the droplets upon activation. The manner and location of
attachment of the piezoelectric actuator 5504 to the ejector plate
5502 affects the operation of the ejector assembly 5500 and the
creation of the droplet stream. In the embodiment of FIGS. 55B-C,
the piezoelectric actuator 5504 may be coupled to a peripheral
region of surface 5522 of plate 5502, while generator plate 5532 is
coupled to surface 5522 so as to align with the central open region
5552 of ejector plate 5502, as described above. The piezoelectric
actuator 5504 is generally coupled to the ejector plate 5502 so as
to not cover or obstruct the central region 5530 (and thereby one
or more openings 5526) of the generator plate 5532. In this manner,
fluid 5510 may pass through the openings 5526 to form droplets 5512
(as shown in FIG. 55A).
[0217] The structure defined by the ejector plate 5502 and
optionally coupled generator plate 5532 possesses a large number of
eigenmodes which define, for each eigenmode, the shape the
structure will take when said structure is excited. Examples of
eigenmodes are presented in FIG. 3. For maximum ejection at any of
these eigenmodes, the piezoelectric actuator 5504 must be shaped
properly and placed in a position that provides the least amount of
resistance to the deformation of the ejector plate 5502 and
optionally coupled generator plate 5532 in the desired eigenmode.
If the piezoelectric actuator 5504 provides a restriction on the
shape of a given eigenmode the stiffness of the piezoelectric
actuator 5504 and bonding layer may damp the mode (provide
resistance toward continued movement), and may force the movement
of the structure to be extremely dependent on the piezoelectric
actuator 5504 material properties. This can limit the mass ejection
in approximately the ratio of the piezoelectric actuator 5504
properties.
[0218] In some implementations, the ejector plate 5502 and
optionally coupled generator plate 5532 eigenmodes can be excited
with low or no resistance (other than the internal the ejector
plate 5502 and optionally coupled generator plate 5532 resistance)
to continued movement (ejector plate 5502 and optionally coupled
generator plate 5532 resonance) simply by mounting the
piezoelectric actuator 5504 to the edge of the ejector plate 5502
and optionally coupled generator plate 5532. By bonding the
piezoelectric actuator 5504 to the edge of the ejector plate 5502
and optionally coupled generator plate 5532, the least possible
resistance to ejector plate 5502 and optionally coupled generator
plate 5532 movement can be provided. In an edge bonded, or near
edge bonded embodiment, limitations of the piezoelectric actuator
5504 properties are minimized, as the mechanical resistance offered
by the stiffness of the ceramic (e.g., the piezoelectric actuator
5504) and bonding to the eigenmode shapes is less than that of the
ejector plate 5502 and optionally coupled generator plate 5532
itself.
[0219] In certain aspects of the present disclosure, the eigenmodes
of the ejector plate 5502 and optionally coupled generator plate
5532 may be optimized by varying the dimensions of the
piezoelectric actuator 5504. In an aspect, a given eigenmode may be
excited by mounting the driving force (e.g., piezoelectric actuator
5504) at the right location, relative to the standing wave on the
ejector plate 5502 and optionally coupled generator plate 5532, and
constraining the dimensions of the piezoelectric actuator
5504-within the standing wave node or anti-node (depending on
dominant radial or longitudinal drive mode). The eigenmodes of a
ejector plate 5502 and optionally coupled generator plate 5532 and
their shape can be found by solution of the Sturm-Liouville problem
analytically.
[0220] While idealized eigenmodes of a membrane (e.g., a drum) may
be found by solution of the Sturm-Liouville problem, in certain
aspects of the present disclosure it becomes mathematically
difficult or even intractable to analytically solve for the
eigenmode shapes, frequencies, and corresponding amplitude
coefficients of the vibration of an ejector plate 5502 and
optionally coupled generator plate 5532. Analytical limitations to
obtaining a solution to the Sturm-Liouville problem arise when an
idealized membrane is loaded, includes a driving element, has a
non-ideal boundary condition, or comprises multiple materials.
[0221] In aspects according to the present disclosure, the ejector
plate 5502 and optionally coupled generator plate 5532 may include
loads such as fluid 5510. In other aspects, the ejector plate 5502
and optionally coupled generator plate 5532 may include a
piezoelectric actuator 5504 driving element. In another aspect, the
ejector plate 5502 may include the coupled generator plate 5532
comprising one or more materials. In a further aspect, the ejector
plate 5502 may be of non-uniform thickness. Similarly, in an
aspect, the coupled generator plate 5532 may be of non-uniform
thickness. In yet another aspect, the generator plate 5532 may have
openings 5526 that are non-uniform and may lead to non-trivial
analytical solutions.
[0222] The analytic limitations arising from a non-idealized
membrane may be overcome. In certain aspects according to the
present disclosure, computational software may be used which
divides an entire structure into smaller discrete elements using
Finite Element Methods (FEM). In an aspect, the computational
software discretizes the structure into elements that may be one
half or less of the size of the minimum wavelength (maximum
frequency) of vibrational interest. In other aspects the discrete
elements may be one fifth or less of the size of the minimum
wavelength (maximum frequency) of vibrational interest. In other
aspects, the discrete elements may be one tenth or less of the size
of the minimum wavelength (maximum frequency) of vibrational
interest. In another aspect of the present disclosure, the discrete
elements may be one fifteenth or one twentieth or less of the size
of the minimum wavelength (maximum frequency) of vibrational
interest. In an aspect, the analytical problem comprising a partial
differential equation may then be represented by the central
differences at each point of the discrete elements. In another
aspect the partial differential equation may be solved by finding a
sum of basis functions that minimize the system energy.
[0223] In an aspect, using FEM techniques, the eigenmode
frequencies and shapes may be determined through modal analysis for
a given set of boundary conditions, such as free, simply supported,
clamped, pinned, or some hybrid of these boundary conditions. In an
aspect, the shape of the piezoelectric actuator 5504 may be
determined by the eigenmode shape it is meant to drive. In certain
aspects, the shape of the piezoelectric actuator 5504 is largely
determined by the counterbalance of applied force per unit area,
which is directly related to the area of the piezoelectric actuator
5504 in contact with the ejector plate 5502 and optionally coupled
generator plate 5532, and the resistance or damping applied to the
mode shape by the stiffness of the bonded piezoelectric actuator
5504.
[0224] In certain embodiments according to the present disclosure,
once the piezoelectric actuator 5504 location and initial size is
determined, it is modeled on the ejector plate 5502 and simulated
with a voltage applied to the top of the piezoelectric actuator
5504 and grounded on the ejector plate 5502 and optionally coupled
generator plate 5532 terminal. The ejector plate 5502 and
optionally coupled generator plate 5532 can be a simple ejector
plate 5502, a hybrid ejector plate 5502 having a coupled generator
plate 5532, a simple or hybrid ejector plate 5502 having a 4 post
structure, electric field screened structure, or any other
combination of structures. The piezoelectric actuator 5504
excitation frequency is swept in the simulation from near zero
frequency up to several hundred kilohertz (kHz), or more generally
any frequency. The mode shape, amplitude of the displacement and
velocity the simple or hybrid ejector plate 5502 experiences are
computed for each frequency in the sweep. By applying FEM
techniques, the amplitude and velocity of a design may be
assessed.
[0225] If the ejector plate 5502/piezoelectric actuator 5504 system
moves with adequate amplitude and velocity at the desired frequency
the design is complete. If not, the design is tuned by thinning or
thickening the piezoelectric actuator 5504 height in order to alter
the damping of the ejector plate 5502 applied by the piezoelectric
actuator 5504. In certain aspects, the piezoelectric actuator 5504
can also be tuned in lateral/radial thickness in order to reduce
the damping of specific modes or to shift resonant frequencies
either higher or lower. Simulations are repeated given the trending
of the piezoelectric actuator 5504 sizing until design optimization
is complete.
[0226] As the ejector assembly 5500 is used for delivering
therapeutic agents or other fluids to the desired target, e.g., the
eye, the ejector assembly 5500 may be designed to prevent the fluid
5510 contained in the reservoir 5520 and the ejected droplets 5512
from being contaminated. In some implementations, for example, a
coating (not shown) may be formed over at least a portion of the
exposed surface(s) of the piezoelectric actuator 5504, the ejector
plate 5502, the generator plate 5532, etc., that are exposed to the
fluids. The coating may be used to prevent direct contact of the
piezoelectric actuator 5504 and the electrodes 5506a and 5506b with
the fluid 5510. The coating may be used to prevent interaction of
the ejector plate 5502 or generator plate 5532 with the fluid. The
coating or a separate coating may also be used to protect the
piezoelectric actuator 5504 and electrodes 5506a and 5506b from the
environment. For example, the coating can be a conformal coating
including a nonreactive material, e.g., polymers including
polypropylene, nylon, or high density polyethylene (HDPE), gold,
platinum, or palladium, or coatings such as Teflon.RTM.. Coatings
are described in further detail herein.
[0227] The generator plate 5532 may be a perforated plate that
contains at least one opening 5526. The one or more openings 5526
allow the droplets to form as fluid 5510 is passed into the
openings and ejected from generator plate 5532. The generator plate
5532 may include any suitable configuration of openings. Examples
of generator plates 5532 comprising high modulus polymers are
illustrated in U.S. application Ser. No. 13/712,857, filed Dec. 12,
2012, entitled "High Modulus Polymeric Ejector Mechanism, Ejector
Device, And Methods Of Use", the contents of which are herein
incorporated by reference in its entirety for the purpose of such
disclosures.
[0228] In some implementations, the ejector plate 5502 may be
formed of a metal, e.g., stainless steel, nickel, cobalt, titanium,
iridium, platinum, or palladium or alloys thereof. Alternatively,
the plate can be formed of other suitable material, including other
metals or polymers, and may be coated as described herein. The
plate may be a composite of one or more materials or layers. The
plate may be fabricated for example by cutting from sheet metal,
pre-forming, rolling, casting or otherwise shaping. The coatings
may also be deposited by suitable deposition techniques such as
sputtering, vapor deposition including physical vapor deposition
(PAD), chemical vapor deposition (COD), or electrostatic powder
deposition. The protective coating may have a thickness of about
less than 0.1 .mu.m to about 500 .mu.m. It is desirable that the
coating adhere to the ejector plate 5502 sufficiently to prevent
delamination when vibrating at a high frequency.
[0229] Referring to FIGS. 55B and 55D, in one implementation, the
ejector plate 5502 and generator plate 5532 may have concentric
circular shapes. In certain embodiments, the ejector plate may be
larger than the generator plate, so as to accommodate coupling of
the generator plate and other components (e.g., piezoelectric
actuator, etc.) described herein. In certain embodiments, the
overall size or diameter of the generator plate 5532 may be, at
least in part, determined by the size of central region 5530 and by
the arrangement of openings 5526. In some embodiments, the
generator plate comprises a high modulus polymeric generator
plate.
[0230] However, both plates may independently have other shapes,
e.g., an oval, square, rectangular, or generally polygonal shape,
and may be the same or different. Overall size and shape may be any
suitable size and shape, and may be selected based on ejector
device design parameters, e.g., size and shape of an outer device
housing, etc. Additionally, the plates need not be flat, and may
include a surface curvature making it concave or convex. The
piezoelectric actuator 5504 may be of any suitable shape or
material. For example, the actuator may have a circular, oval,
square, rectangular, or a generally polygonal shape. The actuator
5504 may conform to the shape of the ejector plate 5502, generator
plate 5532, or regions 5530 or 5552. Alternatively, the actuator
5504 may have a different shape. Furthermore, the actuator 5504 may
be coupled to the ejector plate 5502 or surface 5522 of the ejector
plate 5502 in one or more sections. In the example shown in FIGS.
55B-D, the piezoelectric actuator 5504 is in the shape of a ring
that is concentric to the ejector plate 5502, generator plate 5532,
and regions 5530/5552.
[0231] In some implementations, the ejector plate 5502 and/or
generator plate 5532 may be coated with a protective coating that
has anti-contamination and/or anti-microbial properties. The
protective coating can be conformal over all surfaces of the
ejector plate and/or generator plate, including surfaces defining
the openings 5526. In other implementations, the protective coating
can be applied over selected surfaces, e.g., the surfaces 5522,
5525, or surface regions, e.g., parts of such surfaces. The
protective coating can be formed of a biocompatible metal, e.g.,
gold, iridium, rhodium, platinum, palladium or alloys thereof, or a
biocompatible polymer, e.g., polypropylene, HDPE, or Teflon.RTM..
Antimicrobial materials include metals such as silver, silver
oxide, selenium or polymers such as polyketones. The protective
coating can be in direct contact with the fluid 5510 or the
droplets 5512. The coating may provide an inert barrier around the
fluid or may inhibit microbial growth and sanitize the fluid 5510
and/or the droplets 5512.
[0232] Additionally, one or both of the surface 5522 of ejector
plate 5502 and the wetted surface of generator plate 5532 that
faces the reservoir 5520 may be coated with a hydrophilic or
hydrophobic coating. Additionally, the coating may be coated with a
protective layer. The surfaces may also be coated with a reflective
layer. A coating layer may be both protective and reflective.
Alternatively, one or more of the surfaces may have been formed to
be reflective. For example, the surfaces may be made of stainless,
nickel-cobalt, or other reflective material. A surface may have
been formed or polished to be reflective. In addition to making the
surface reflective, the surface may also be backlit on its surface
or around its perimeter. In ophthalmic applications, a reflective
surface aids the user in aligning the ejector assembly with the
eye.
[0233] If desired, surfaces of the ejector assembly may include
coatings that may be pre-formed by dipping, plating, including
electroplating, or otherwise encapsulating, such as by molding or
casting. The coatings may also be deposited by suitable deposition
techniques such as sputtering, vapor deposition, including physical
vapor deposition (PAD) and chemical vapor deposition (COD), or
electrostatic powder deposition. The protective coating may have a
thickness of less than 0.1 .mu.m to about 500 .mu.m. It is
desirable that the coating adhere to the plate sufficiently to
prevent delamination when vibrating at a high frequency.
[0234] Piezoelectric actuator 5504 may be formed from any suitable
material known in the art. By way of example, in some
implementations, the piezoelectric actuator can be formed from PZT,
barium titanate or polymer-based piezoelectric materials, such as
polyvinylidine fluoride. The electrodes 5506a and 5506b can be
formed of suitable conductors including gold, platinum, or silver.
Suitable materials for use as the adhesive 5528 can include, but is
not be limited to, adhesives such as silicone adhesives, epoxies,
or silver paste. One example of a conductive adhesive includes
Thixotropic adhesive such as Dow Corning DA6524 and DA6533. The
reservoir 5520 may be formed of a polymer material, a few examples
of which include Teflon.RTM., rubber, polypropylene, polyethylene,
or silicone.
[0235] Piezoelectric ceramic materials are isotropic in the
unpolarized state, but they become anisotropic in the polarized
state. In anisotropic materials, both the electric field and
electric displacement must be represented as vectors with three
dimensions in a fashion similar to the mechanical force vector.
This is a direct result of the dependency of the ratio of
dielectric displacement, D, to electric field, E, upon the
orientation of the capacitor plate to the crystal (or poled
ceramic) axes. This means that the general equation for electric
displacement can be written as a state variable equation:
D.sub.i=.di-elect cons..sub.ijE.sub.j
[0236] The electric displacement is always parallel to the electric
field, thus each electric displacement vector, D.sub.i, is equal to
the sum of the field vectors, E.sub.j, multiplied by their
corresponding dielectric constant, .di-elect cons..sub.ij:
D.sub.1=.di-elect cons..sub.11E.sub.1+.di-elect
cons..sub.12E.sub.2.di-elect cons..sub.13E.sub.3
D.sub.2=.di-elect cons..sub.21E.sub.1+.di-elect
cons..sub.22E.sub.2.di-elect cons..sub.23E.sub.3
D.sub.3=.di-elect cons..sub.31E.sub.1+.di-elect
cons..sub.32E.sub.2.di-elect cons..sub.33E.sub.3
[0237] The majority of the dielectric constants for piezoelectric
ceramics (as opposed to single crystal piezoelectric materials) are
zero. The only non-zero terms are:
.di-elect cons..sub.11=.di-elect cons..sub.22,.di-elect
cons..sub.33
[0238] The piezoelectric effect relates mechanical effects to
electrical effects. These effects are highly dependent upon their
orientation to the poled axis. The axis numbering scheme is shown
in FIG. 56. For example, for the electro-mechanical constant
d.sub.ab, a=electrical direction; b=mechanical direction and for
electro-mechanical constant D.sub.33=.di-elect cons..sub.33 E.sub.3
with mechanical displacement in the poled direction, Z in this
case. Referring to FIG. 55A, the Z direction is the direction of
the ejected droplets 5512, direction 5514.
[0239] Accordingly, D.sub.33 is the induced polarization in
direction Z (poled direction, corresponding to direction 5514 in
FIG. 55A) which is parallel to the direction in which the ceramic
material is polarized.
[0240] In accordance with certain embodiments of the disclosure,
piezoelectric materials may be described by mechanical displacement
in the poled direction, Z (e.g. direction 5514 of FIG. 55A).
[0241] In some embodiments, the piezoelectric material may be a
lead Zirconium titanate (PZT) having a D.sub.33=330 pC/N. In an
another embodiment, the piezoelectric material may be a type of a
PbTiO3-PbZrO3 (PZT)-based multi-component system that is widely
used. Commercially available PZT piezoelectric ceramics include
PZT-4 having a D.sub.33 of 225 pC/N, PZT-5A having a D.sub.33 of
350 pC/N, and PZT-5H having a D.sub.33 of 585 pC/N. The (PZT)-based
piezoelectric actuator can be formed from a material having a
D.sub.33 of greater than 300 pC/N. In another embodiment, the
piezoelectric ceramic may have a D.sub.33 of 200 pC/N to 300 pC/N.
In another embodiment, the piezoelectric ceramic may have a
D.sub.33 of 250 pC/N to 300 pC/N.
[0242] In some implementations, it may be desirable to eliminate
lead from the piezoelectric material for safety reasons and FDA/EU
compliance. In an implementation, a lead free piezoelectric ceramic
may be used having a D.sub.33 of less than 300 pC/N. In another
embodiment, a lead free piezoelectric ceramic may have a D33 of
less than 200. In yet another embodiment, a lead free piezoelectric
ceramic may have a D.sub.33 of between 150 pC/N and 200 pC/N. In
yet another embodiment, the D33 of the lead free ceramic may be
less than 150 pC/N. In yet another embodiment, a lead free
piezoelectric ceramic may have a D.sub.33 of between 100 and 150
pC/N. In yet another embodiment, the D.sub.33 of a lead free
ceramic suitable for a piezoelectric actuator may be less than 100
pC/N.
[0243] In some embodiments the piezoelectric device may be prepared
from commercially available materials. For a non-limiting example,
materials available from Sunnytec Powder Materials presented in
Table 14 may be suitable for piezoelectric devices of the
disclosure.
TABLE-US-00015 TABLE 14 Materials Physical & S-42 S-44 S-44-2
S-81 S-51 S-52 S-53 S-54 S-55 S101-D S101-F Properties P-42 FM-2-1
SP-12-4 P-8 P-5A FT-3 FT-4 P-5H TK-4800 S101-D S101-F Density
(g/cm.sup.3) p 7.6 7.7 7.7 7.6 7.6 7.56 7.56 7.6 7.7 7.55 7.6 Curie
Tc 305 300 280 320 260 280 250 180 170 185 165 temperature
(.degree. C.) Dielectric 33 T/0 1450 1550 1600 1030 2300 2200 3200
3800 4600 3200 4200 constants Dissipation tgo 0.4 0.4 0.5 0.3 1.5
1.8 1.8 1.7 2 1.6 1.6 factor (%) Coupling K.sub.p 65 68 66 58 71 80
81 77 81 72 68 Coefficients Kt 48 48 47 46 51 51 52 52 51 50 46 (%)
K31 33 34 35 30 38 43 44 42 45 38 36 Frequency N.sub.p 2230 2250
2220 2300 2080 1960 1950 1980 1950 2030 2100 constants Nt 2050 2050
2080 2050 2040 2030 2045 2040 2020 2040 2100 (MHz) NL 1650 1630
1630 1655 1545 1420 1420 1500 1465 1510 1545 Mechanical Qm 600 1400
1200 1000 80 70 65 65 55 100 70 quality factor Piezoelectric d33
320 330 330 250 450 550 640 650 750 620 650 Charge d31 -155 -135
-140 -110 -200 -260 -300 -290 -300 -250 -265 Constants
(.times.10-12 M/V) Piezoelectric g33 25.8 23.4 23.2 27.4 22.1 28.2
22.6 19.3 18.4 21.8 17.4 voltage g31 -12.5 -10.5 -10.2 -9.8 -11.1
-11.5 -10.8 -8.6 -7.5 -8.5 -7.1 constants (.times.10-3 Vm/N)
Elastic constants SE11 11.5 12.5 12.1 12.1 13.8 16.2 16.5 14.1 15.2
14.5 13.7 (.times.10-12 m2/N) SD11 10.2 11.2 11.1 10.9 11.8 13.3
13.2 11.6 12.9 12.3 11.8
[0244] In some embodiments, the piezoelectric material may be a
BiFeO.sub.3-based ceramic. In some embodiments, the ceramic may be
selected from the group consisting of (Bi,Ba)(Fe,Ti)O.sub.3,
(K,Na,Li)NbO.sub.3, (K,Na,Li)NbO.sub.3, (K,Na,Li)NbO.sub.3,
(K,Na,Li)NbO3, Bi(Fe,Mn)O.sub.3+BaTiO.sub.3,
Bi(Fe,Mn)O.sub.3+BaTiO.sub.3, BiFeO.sub.3--NdMnO.sub.3--BiAlO3,
(Bi,La)(Fe,Mn)O.sub.3, (Bi,La)(Fe,Mn)O3, BiFeMnO3--BaTiO.sub.3,
Bi(Fe,Mn)O3-BaZrTiO.sub.3, (Bi,La)(Fe,Mn)O.sub.3, (Bi,La)(Fe,Mn)O3,
(Bi,Ba)(Fe,Ti)O.sub.3,
Bi(Zn,Ti)O.sub.3--La(Zn,Ti)O.sub.3--Ba(Sc,Nb)O.sub.3 (d33=250),
BiFeO.sub.3, (Ba, M)(Ti,Ni)O.sub.3, BiFeO.sub.3, Bi(Al,Ga)O.sub.3,
BT-BiFeO.sub.3, Bi(Fe,Al)O.sub.3, Bi(Fe,Al)O.sub.3,
Bi(Fe,Co,Mn)O.sub.3, BiFeO.sub.3--BaTiO.sub.3,
BiFeO.sub.3--BaTiO.sub.3, Bi(Al,Ga)O.sub.3 (d33=150),
Bi(Al,Ga)O.sub.3, BiFeO.sub.3+AD, BiFeO.sub.3+BaTiO.sub.3,
BiFeO.sub.3-based, BaTiO.sub.3--BiFeO.sub.3, (Bi, x)(Fe,Mn)O.sub.3,
and (Bi, x)(Fe, Ti,Mn)O.sub.3.
[0245] In some embodiments, the piezoelectric material may be a
bismuth sodium titanate (BNT) material or a bismuth potassium
titanate (BKT) material. The BNT or BKT material may be selected
from the group consisting of
(1-x)Bi.sub.0.5Na.sub.0.5TiO.sub.3-xLaFeO3,
(1-x)Bi.sub.0.5Na.sub.0.5TiO.sub.3-xNaSbO.sub.3,
(1-x)Bi.sub.0.5Na.sub.0.5TiO.sub.3-xBiCrO.sub.3,
(1-x)Bi.sub.0.5Na.sub.0.5TiO.sub.3-xBiFeO.sub.3,
Bi.sub.0.5(Na.sub.1-xK.sub.x).sub.0.5TiO.sub.3(BNKT),
Bi.sub.0.5(Na.sub.1-xK.sub.x).sub.0.5TiO.sub.3(BNKT),
Bi.sub.0.5(Na.sub.1-xK.sub.x).sub.0.5TiO.sub.3(BNKT),
Bi.sub.0.5(Na.sub.1-xK.sub.x).sub.0.5TiO.sub.3(BNKT),
((1-x)Bi.sub.1-aNa.sub.a)TiO.sub.3-x(1-x)LiNbO.sub.3,
Bi.sub.0.5(Na.sub.1-xLix).sub.0.5TiO.sub.3,
Bi.sub.0.5(Na,K).sub.0.5[Ti, (Mg, Ta)]O.sub.3,
Bi.sub.0.5(Na,K).sub.0.5[Ti,(Al, Mo)]O.sub.3,
Bi.sub.0.5(Na,K).sub.0.5[Ti,(Mg, Nb)]O.sub.3,
Bi.sub.0.5(Na,K).sub.0.5[Ti,(M,V)]O.sub.3,
Bi.sub.0.5(Na,K).sub.0.5[Ti,(M,V)]O.sub.3, BNT-BT-KNN,
(1-x)Bi.sub.0.5Na.sub.0.5TiO.sub.3-xBaTiO.sub.3 (BNBT)
(d.sub.33=100.times.10.sup.-12 C/N or more), BNT-BKT-BT
(d.sub.33=158 pC/N), BNT-BKT-BT+PT (d.sub.33=127), BNT-KN,
Bi.sub.0.5Na.sub.0.5TiO.sub.3--BaTiO.sub.3 (BNBT) (d.sub.33=253
pC/N), NGK2, BNT-BKT-BT, NGK, BNT-BKT-BT, NGK4,
Bi.sub.0.5Na.sub.0.5TiO.sub.3-BaTiO.sub.3-CaTiO.sub.3-Ba(Zn.sub.1/3Nb.sub-
.2/3)O.sub.3+Y.sub.2O.sub.3, MnO,
(1-v)[(Li.sub.1-yNay)zNbO.sub.3]-v[Bi.sub.0.5Na.sub.0.5TiO.sub.3,
(1-v-x)[(Li.sub.1-yNa.sub.y)zNbO.sub.3]-xLMnO.sub.3-v[Bi.sub.0.5Na.sub.0.-
5TiO.sub.3], Bi.sub.0.5Na.sub.0.5TiO.sub.3, BNT-BT, BNT-BT,
xBi.sub.0.5Na.sub.0.5TiO.sub.3-y(MNbO.sub.3)--(Z/2)(Bi.sub.2O.sub.3--Sc.s-
ub.2O.sub.3) (M=K, Na), BNT-BKT-Bi(Mg2/3Ta1/3)O3,
[(Bi.sub.0.5Na.sub.0.5)xMy]z(TiuNv)O.sub.3 (M=Ba, Mg, Ca, Sr,
(Bi.sub.0.5K.sub.0.5)) (N.dbd.Zr, Hf),
[(Bi.sub.0.5Na.sub.0.5)xMy]z(TiuNv)O.sub.3 (M=Ba, Mg, Ca, Sr,
(Bi.sub.0.5K.sub.0.5), others) (N.dbd.Zr, Hf, others),
BNT-BKT-BT-CT-NaNbO.sub.3, BNT-BKT-Bi(Ni,Ti)O.sub.3,
BNT-BKT-Bi(Ni,Ti)O.sub.3, BNT-BKT-BT, BNT-BT-ST, BNT-BKT-BT,
BNT-BKT-AgNbO.sub.3, BNT-BKT-BT, BT-BKT, BNT-BT-Bi(Fe0.5Ti0.5)3,
BNT-BKT-Bi(Zn0.5Zr0.5)O3, BNT-BKT-Bi(Fe0.5Ta0.5)O3,
BNT-BKT-Bi(M1,M2)O3, BNT-BKT, BNT-BT, BNT-BKT,
Bi.sub.0.5K.sub.0.5TiO.sub.3(BKT) and
Bi.sub.0.5Na.sub.0.5TiO.sub.3-(1-x)ABO.sub.3.
[0246] In some implementations, the piezoelectric material may be a
dual-mode magnetostrictive/piezoelectric bilayered composite,
tungsten-bronze material, a sodium niobate material, a barium
titanate material, and a polyvinylidine fluoride material. Examples
of suitable materials for the piezoelectric actuator of the
disclosure include A2Bi4Ti5O18 (A=Sr,
Ca,(Bi.sub.0.5Na.sub.0.5),(Bi.sub.0.5Li.sub.0.5),(Bi.sub.0.5Li.sub.0.5),
(A1-xBix).sub.2Bi4Ti5O18 (A=Sr,
Ca,(Bi.sub.0.5Na.sub.0.5),(Bi.sub.0.5Li.sub.0.5),(Bi.sub.0.5Li0.5),
Bi4Ti3O12-x(Sr1-aAa)TiO3 (A=Ba, Bi.sub.0.5Na0.5, Bi.sub.0.5K0.5,
Bi.sub.0.5Li0.5), Bi4Ti3O12-(Ba, A)TiO3,
Bi4Ti3O12-x{(Sr1-aA'a)TiO3-ABO3} (A'=Ba, Bi.sub.0.5Na0.5,
Bi.sub.0.5K0.5, Bi0.5Li0.5, A=Bi,Na,K,Li, B.dbd.Fe,Nb),
(A1-xBix)Bi4Ti4O15 (A=Sr,Ba),
BaBi4Ti4O15,(Sr2-aAa)x(Na1-bKb)y(Nb5-cVc)O15 (A=Mg, Ca, Ba) d33=80
pC/N or more, Tc=150.degree. C. or more,
(Sr2-aAa)x(Na1-bKb)y(Nb5-cVc)O15, (Na0.5Bi.sub.0.5)1-xMxBi4Ti4O15,
Bi4Ti3O12, SrBi2(Nb,W)O9, (Sr1-xM1x)Bi2(Nb1-zWy)2O9, (Sr,
Ca)NdBi2Ta2O9+Mn, (Sr1-xMx)(Bi, Nd)(Nb, Ta)2O9, Bi2(Sr1-xMx)Nb2O9
(M=Y, La), (Sr2CaK)Nb5O15 (d33=120).
[0247] In implementations according to the disclosure, the niobate
material may be selected from (Sn,K)(Ti,Nb)O3,
KNbO3-NaNbO3-LiNbO3-SrTiO3-BiFeO3, KNbO3-NaNbO3-LiNbO3,
KNbO3-NaNbO3-LiNbO3, xLiNbO3-yNaNbO3-zBaNb2O6, NaxNbO3-AyBOf
(A=K,Na,Li,Bi B.dbd.Li,Ti,Nb,Ta,Sb),
(1-x)(Na1-aMna)b(Nb1-aTia)O3-xMbTiO3
(M=(Bi1/2K1/2),Bi1/2Na1/2),(Bi1/2Li1/2), Ba, Sr,
(K,Na,Li)NbO3-Bi(Mg,Nb)O3-Ba(Mg,Nb)O3,
(1-x)[(Li1-yNay)zRO3]-xLMnO3(R.dbd.Nb,Ta,Sb, L=Y,Er,Ho,Tm, Lu, Yb),
(LixNa1-x-yKy)z-2wMa2wNb1-wMbwO3 (Ma=.sup.2+ metal A, Mb=.sup.3+
metal B), NN-BT d33=164, K1-xNaxNbO3+Sc2O3,
[(K1-xNax)1-yAgy]NbO3-z[Ma+][O2-] (M=additive), Li(K,Na)(Nb,Sb)O3,
KNbO3-NaNbO3 (d33=200), (Li,Na,K)(Nb,Ta,Sb)O3, (K,Na,Li)NbO3,
KNbO3+MeO3 (MnWO3.etc.) (d33=130).
[0248] Barium titanate material is an inorganic compound with the
chemical formula BaTiO.sub.3. Barium titanate materials include
BaTiO.sub.3 materials that further comprise substoichiometric
amounts of other elements. Examples of other elements that are
included in BaTiO.sub.3 materials include rare earth elements and
alkaline earth metals. The substoichiometric amounts of other
elements modify the piezoelectric properties of the BaTiO.sub.3
materials. Doping of BaTiO.sub.3 materials refers to the inclusion
of substoichiometric amounts of other elements.
[0249] Examples of suitable single crystal barium titanate
materials further include {(Bi1/2,Na1/2)1-xA1x}TiO3 (A1=Ba, Ca,
Sr), {(Bi1/2,Na1/2)1-x(Bi1/2, A21/2)xTiO3 (A1=Ba, Ca, Sr, A2=Li, K,
Rb) (Single crystal), (Sr,Ba)3TaGa3Si2O14,
La3-xSrxTayGa6-y-zSizO14, (Ba, Ca)TiO3, LiNbO3, LiTaO3,
(K3Li2)1-xNaxNb5O15, La3Ga5SiO14, MgBa(CO3)2, NdCa4O(BO3)3 (M1=rare
earth elements, M2=alkaline earth metals), LaTiO2N.
[0250] In some implementations, the ejector plate 5502 may be
formed of a suitable material where the suitable material is
selected based on out of plane displacement, direction 5514. The
ejector plate 5502 displacement Z (e.g. movement in the direction
5514), depends on the diameter of the ejector plate 5502 and the
thickness of the ejector plate 5502. The suitable material may also
be selected in view of the Young's Modulus and Poisson's Ratio of
the ejector plate 5502. The Young's Modulus and Poison's Ratio are
intrinsic properties of the material and conforming materials can
be selected to determine a desired displacement. For a suitable
material for the ejector plate 5502, displacement Z may be
increased by decreasing the thickness of the ejector plate
5502.
[0251] Suitable materials for ejector plate 5502, having a
displacement in direction 5514 can be coupled to the frequency of
the piezoelectric actuator 5504 so that the resonant frequency of
the ejector plate 5502 is matched. By coupling the displacement of
the ejector plate 5502 with the piezoelectric actuator 5504 in a
resonance system, the ejection of liquid through the holes of the
generator plate 5532 can be accomplished with piezoelectric
actuator that are not limited by D.sub.33 values.
[0252] Referring to FIG. 55C, the manner and location of attachment
of the piezoelectric actuator 5504 to the ejector plate 5502 may
affect the operation of the ejector assembly 5500 and the creation
of the droplet stream.
[0253] As discussed above, the ejector plate 5502, whether as a
simple ejector plate 5502 or as a hybrid ejector plate 5502 coupled
to a generator plate 5502, may possess a large number of eigenmodes
which define, for each eigenmode, the shape the structure will take
when said mode is excited. As provided above, using for example FEM
techniques, the eigenmodes of an ejector plate 5502 and optionally
coupled generator plate 5532 may be calculated and the desired
amplitude and velocity of the eigenmodes determined.
[0254] In one embodiment, the piezoelectric actuator 5504 is
edge-mounted on the ejector plate 5502 where the distance 5554 is
zero. An edge mount design is a special case which has near zero
inherent resistance to modes it is designed to excite. When a
circular piezoelectric actuator 5504 is bonded to the edge of a
circular ejector plate 5502 (e.g., the distance 5554 is at or near
zero) the ejector plate 5502 is stiffened considerably where a
stiff piezoelectric actuator 5504 is placed, but the portion of the
ejector plate 5502 on the inside of the piezoelectric actuator 5504
inner diameter 5557 is left to move freely, restricted only by its
own limits of elasticity rather than the piezoelectric actuator
5504. Similarly, hybrid ejector plates 5502 having a coupled
generator plate 5532 would also be left to move freely, restricted
only by the combined limits of elasticity rather than the
piezoelectric actuator 5504. If the edges of the piezoelectric
actuator 5504 are pinned or clamped, the ejector plate 5502 behaves
virtually as though it was the diameter of inner diameter 5557 of
the piezoelectric actuator 5504 with ideal (edge driven) radial and
longitudinal excitation. Other modes relevant to the entire size of
the ejector plate 5502 are suppressed due to the stiffness of the
piezoelectric actuator 5504. In certain embodiments, the stiffness
of the piezoelectric actuator 5504 may be modulated by increasing
or decreasing the thickness of a piezoelectric actuator 5504.
Embodiments illustrating the modulation of piezoelectric actuator
5504 are presented in Example 5 below.
[0255] In other embodiments according to the present disclosure,
the mounting configuration of the piezoelectric actuator 5504 to
the ejector plate 5502 effects the displacement and velocity of the
ejector plate 5502 and the generator plate 5532. In general, the
amplitude of displacement and the velocity of the ejector plate
5502 in a given mode is a balance between the force, largely
determined by the movement per unit voltage (D.sub.33) of the
piezoelectric material, and the damping/resistance that a
piezoelectric presents to the ejector plate 5502 movement.
Increasing stiffness of the piezoelectric material increases the
damping and resistance. For embodiments of the present disclosure
having piezoelectric materials having a large D.sub.33, for example
materials like PZT, the damping/resistance of the piezoelectric
material plays a less significant role in the amplitude of
displacement. In other embodiments with a lower D.sub.33, for
example BaTiO.sub.3, the performance of a droplet ejector system
may be significantly decreased by the damping/resistance. The
performance of an ejector assembly 5500 reduces in direct
proportion to the D.sub.33 of the material used to prepare a
piezoelectric activator 5504.
[0256] The properties of an edge mounted embodiment of a
piezoelectric actuator 5504/ejector plate 5502 can be used to
bypass the effects of lower material movement. Specifically, when
the ejector plate 5502 is excited in a mechanical mode where only
its own resistance limits its movement due to a given force per
unit area applied by the piezoelectric actuator 5504, the
piezoelectric D.sub.33 can be scaled down with no impact on
performance for the same electrical input until a minimum force per
unit area value is reached. This property is illustrated in FIG. 8,
where if the force per unit area is above a certain threshold, the
increase in ejector plate 5502 movement is very small. Below this
threshold, the ejector plate 5502 movement decreases linearly with
force per unit area.
[0257] For ejector plates 5502 of the present disclosure, low order
modes are generally excited at the lowest frequencies on a
structure where the wavelength of the standing wave is an integer
multiple of a half wavelength. The frequency and wavelength of this
mode is determined by the material properties of the ejector plates
5502 and its radial dimension. As the eigenmode shape always
possesses a node at the edges of the ejector plates 5502 for these
modes and a maximum at the center of the membrane, only two
piezoelectric locations are relevant for exciting these modes in a
fluid ejection system.
[0258] In an embodiment according to the present disclosure, a
piezoelectric actuator 5504 can be placed in the center of the
ejector plate 5502 in order to excite maximum movement. However,
because there must be an area directly in the center of the ejector
plate 5502 for fluid ejection to take place, this mounting position
is not optimum for this application. Performance must be sacrificed
to allow fluid ejection.
[0259] A piezoelectric actuator 5504 can likewise be placed at the
edge of the ejector plate 5502 to excite maximum movement in the
center of the ejector plate 5502 at low frequencies. In this
configuration, minimum resistance to the natural movement of the
mode occurs, allowing large displacements at low frequencies and
enhanced mass depositions in these modes. Generally, these modes
are favorable for continuous fluid ejection due to their nearly
constant shape and velocity distribution over the ejection area.
Furthermore, loading the center of the ejector plate 5502 with a
mass, such as in a hybrid ejector plate 5502 having a coupled
generator plate 5532, enhances low order mode displacement due to
the inertia of the center mass (e.g. generator plate 5532).
[0260] In some embodiments, the edge-mounted piezoelectric actuator
5504 oscillates the ejector plate 5502 coupled to the generator
plate 5532 at the resonant frequency of the ejector plate coupled
to said generator plate. In one embodiment, matching the resonant
frequency decreases the displacement requirement of the
piezoelectric material. In one embodiment, the resonant frequency
matching provides for the generation of a directed stream of
droplets using a piezoelectric material having a D.sub.33 of less
than 200. In another embodiment, the resonant frequency matching
provides for the generation of a directed stream of droplets using
a piezoelectric material having a D.sub.33 of less than 150 or less
than 125. In yet another embodiment, the resonant frequency
matching provides for the generation of a directed stream of
droplets using a piezoelectric material having a D.sub.33 of less
than 100 or less than 75.
[0261] In another embodiment, the piezoelectric actuator 5504 is
slightly less than edge mounted (e.g., inside mounted) on the
ejector plate 5502 where the distance 5554 is greater than zero. In
one embodiment, the distance 5554 may be 0.05 mm. In another
embodiment, the distance 5554 may be 0.01 mm. In yet another
embodiment, the distance 5554 may be 0.25 mm. In yet another
embodiment, the distance 5554 may be 0.5 mm. In further
embodiments, the distance 5554 may be 0.75 mm, or 1.0 mm, or may be
greater than 1.0 mm.
[0262] In other embodiments according to the present disclosure,
the piezoelectric actuator 5504 is inside mounted on the ejector
plate 5502 where the distance 5554 is greater than zero and the
outer diameter of piezoelectric actuator 5504 is smaller than
ejector plate 5502. In an embodiment, the piezoelectric actuator
5504 is inside mounted on the ejector plate 5502 and is 1% smaller
than the diameter of ejector plate 5502. In an embodiment, the
piezoelectric actuator 5504 is inside mounted on the ejector plate
5502 and is 1.5% smaller than the diameter of ejector plate 5502.
In an embodiment, the piezoelectric actuator 5504 is inside mounted
on the ejector plate 5502 and is 2% smaller than the diameter of
ejector plate 5502. In an embodiment, the piezoelectric actuator
5504 is inside mounted on the ejector plate 5502 and is 3% smaller
than the diameter of ejector plate 5502. In an embodiment, the
piezoelectric actuator 5504 is inside mounted on the ejector plate
5502 and is 4% smaller than the diameter of ejector plate 5502. In
an embodiment, the piezoelectric actuator 5504 is inside mounted on
the ejector plate 5502 and is 5% smaller than the diameter of
ejector plate 5502. In an embodiment, the piezoelectric actuator
5504 is inside mounted on the ejector plate 5502 and is 7.5%
smaller than the diameter of ejector plate 5502.
[0263] In some embodiments according to the present disclosure, the
piezoelectric actuator 5504 is inside mounted on the ejector plate
5502 where the distance 5554 is greater than zero and the inner
diameter of the annular piezo actuator is selected so that the low
frequency edge mode of the ejector plate 5502 is damped or
eliminated.
[0264] In certain embodiments of the disclosure, the ejector
mechanism may be configured so as to facilitate actuation of the
ejector plate 5502, and thereby the generator plate 5532, by the
piezoelectric actuator. As described above, the generator plate
5532 may be configured to optimize ejection of a fluid of interest.
For example, the aspect ratio of the openings of the generator
plate may be selected based, in part, on fluid properties, such
that the general thickness of the generator plate 5532 ranges from
about 50 .mu.m to about 200 .mu.m, as described above. Without
being limited by theory, in certain implementations, direct
actuation of a relatively thick generator plate, though possible,
may be less optimal. In some implementations, the generator plate
comprises a high modulus polymeric generator plate.
[0265] As such, in certain implementations, actuation of the
ejector mechanism may be optimized using configurations including a
generator plate coupled to an ejector plate, as described herein.
In addition, reducing the surface area of the generator plate 5532
(i.e., the central region having one or more openings) likewise
reduces manufacturing costs, reduces potential manufacturing
defects, and increases manufacturing efficiencies and output. In
certain embodiments, the ejector plate may be sized and shaped in a
manner to facilitate actuation of the ejector mechanism (i.e.,
actuation of the ejector plate and thereby the generator plate). By
way of example, configurations of the ejector plate may effectuate
actuation of the ejector mechanism through selection of properties
(e.g., size, shape, material, etc.) that facilitate flex of the
ejector plate, and thereby vibration of the generator plate. For
instance, the ejector plate 5532 may have a thickness generally
ranging from about 10 .mu.m to about 400 .mu.m, from about 20 .mu.m
to about 100 .mu.m, from about 20 .mu.m to about 50 .mu.m, or from
about 30 .mu.m to about 50 .mu.m, etc. Again, without being limited
by theory, in certain implementations, direct actuation of a
relatively thinner ejector plate 5502 (compared to the generator
plate 5532), may be more optimal. In some implementations, the
generator plate 5532 comprises a high modulus polymeric generator
plate.
[0266] In accordance with certain implementations of the
disclosure, the configuration of the ejector plate 5502 and the
generator plate 5532 may be selected such that the center region of
the generator plate 5532 including openings (the "active region" of
the generator plate) produces a symmetric oscillation with a normal
mode of oscillation. Without being limited by theory, in certain
implementations, configurations of the ejector plate 5502 and
generator plate 5532 may be selected such that 0.2 normal mode and
0.3 normal mode of oscillation of the active region of the
generator plate is observed. The mode is associated with a maximum
amplitude and displacement of the active region, wherein the mode
is designated as (d,c) where d is the number of nodal diameters and
c is the number of nodal circles.
[0267] The magnitude and frequency of the ejector plate 5502
vibration can also be controlled by controlling the voltage pulses
applied to the electrodes 5506a, 5506b, e.g., a voltage
differential of 40 or 60 V may be applied to the electrodes. As
discussed above, the pulses are created by voltage differentials
that deflect the ejector plate 5502, and thereby generator plate
5532. In some implementations, one of the electrodes 5506a or 5506b
is grounded and voltage pulses, e.g., bipolar pulses, are applied
to the other one of the electrodes 5506a or 5506b e.g., to vibrate
the ejector plate 5502. By way of example, in one implementation,
the piezoelectric actuator 5504 can have a resonant frequency of
about 5 kHz to about 1 MHz, e.g., about 10 kHz to about 160 kHz,
e.g., about 50-120 kHz or about 50-140 kHz, or about 108-130 kHz,
etc. The applied voltage pulses can have a frequency lower, higher,
or the same as the resonant frequency of the piezoelectric actuator
5504.
[0268] In certain implementations, delivery time of the droplets is
about 0.1 ms to about several seconds. Without wishing to be bound
by theory, it is believed that human eyes take about 300 ms to
about 400 ms for a blink. Therefore, for implementations where
delivery is desired to be within the duration of a blink, the
delivery time may be about 50 ms to about 300 ms and more
particularly 25 ms to 200 ms. In one implementation, the delivery
time is 50 ms to 100 ms. In this way, the ejected droplets can be
effectively delivered and deposited in the eye during a blinking
cycle of the eye. In some implementations, for example
over-the-counter saline dispensers, the delivery time can be as
long as several seconds, e.g., 3-4 seconds, spanning several blink
cycles. Alternatively, a single dosage can be administered over
several bursts or pulses of droplet ejection. Additionally, and not
intending to be limited by theory, pulsing may be used to reduce
the peak amplitude of the droplet airstream by spreading the
impulse out over time. Therefore, the pressure of the ejection on
the target may be mitigated. Furthermore, pulsing may also reduce
droplet agglomeration and result in less entrained air generation.
By way of example, pulses of 25 ms can be administered with stop
times of 25 ms separating the pulses. In one implementation, the
pulses may be repeated for a total of 150 ms.
[0269] As described herein, the ejector device and ejector
mechanism of the disclosure may be configured to eject a fluid of
generally low to relatively high viscosity as a stream of droplets.
By way of example, fluids suitable for use by the ejector device
can have very low viscosities, e.g., as with water at 1 cP, or
less, e.g. 0.3 cP. The fluid may instead have viscosities in ranges
up to 600 cP. More particularly, the fluid may have a viscosity
range of about 0.3 to 100 cP, 0.3 to 50 cP, 0.3 to 30 cP, 1 cP to
53 cP, etc. In some implementations, the ejector device may be used
to eject a fluid having a relatively high viscosity as a stream of
droplets, e.g., a fluid having a viscosity above 1 cP, ranging from
about 1 cP to about 600 cP, about 1 cP to about 200 cP, about 1 cP
to about 100 cP, about 10 cP to about 100 cP, etc. In some
implementations, solutions or medications having the suitable
viscosities and surface tensions can be directly used in the
reservoir without modification. In other implementations,
additional materials may be added to adjust the fluid parameter. By
way of example, certain fluids are listed below in Table 15:
TABLE-US-00016 TABLE 15 Viscosity measured at 20.degree. C.
drugs/fluids dynamic viscosity (cP) kinematic viscosity (cP)
density water 1.017 1.019 0.99821 Xalatan .TM. 1.051 1.043 1.00804
Tropicamide 1.058 1.052 1.00551 Restasis .TM. 18.08 17.98
1.00535
[0270] From the above discussion it will be appreciated that
different configurations and material will result in different
attributes. In order to assist in understanding some of these
attributes in a few select embodiments of the ejector mechanism,
experiments were conducted to compare certain embodiments. The
experiments described herein should not, of course, be construed as
specifically limiting the invention and such variations of the
invention, now known or later developed, which would be within the
purview of one skilled in the art are considered to fall within the
scope of the invention as described herein and hereinafter
claimed.
Example 6
Measurement of Mass Deposition
[0271] To measure the mass deposition of an ejector device, the
ejector devise is clamped horizontally to eject material towards to
the ground where the poled direction Z, as shown in FIG. 56, is
toward to the ground (e.g., parallel to gravity). Referring to FIG.
55A, the direction 5514 of the ejected droplets 5512 is towards to
the ground. A ground wire and positive wire of the device is
connected to an operational amplifier and a current probe and
voltage probe are connected to an oscilloscope.
[0272] The frequency region that provides for device spraying is
initially determined by a frequency sweep through the range of 2
kHz to 500 kHz. The electrical data, including the voltage and
current, are recorded and stored. Upon analysis, the spray ranges
for mass deposition determination are selected. The results are
plotted to provide a mass ejection profile as shown in FIG. 58, for
example.
[0273] To determine the mass deposition, the frequency and voltage
are set, for example, to a 90V peak to peak (90 Vpp) sine wave at a
frequency of 50 kilohertz (kHz) and the spray from the ejector
device is measured 5 times on a 24 mm.times.60 mm No. 1 glass
coverslip using a scale with a 1 milligram (mg) sensitivity and
calibrated with a 1 mg class 1 weight with traceable certificate.
For each measurement, the coverslip is placed on the scale and the
scale is zeroed. The slide is place underneath the ejector device
and the voltage applied for a defined period of time. The slide is
returned to the scale and the mass is determined and recorded. The
coverslip is cleaned, the scale re-zeroed before each measurement.
A total of 5 measurements are recorded for each frequency. The
process is repeated with the frequency incrementally changed based
on a predetermined step size (normally 1 kHz).
Example 7
Comparison of PZT to BaTiO.sub.3 Using an Inside Mount Ejector
Assemblies
[0274] The mass deposition profile of ejector devices having an
inside mounted ejector assembly are determined using the method
described in Experiment 6 above to determine the frequency region
for device spraying. For both the PZT and BaTiO.sub.3 piezoelectric
materials, the piezoelectric actuator 5504 has a 16 mm outer
diameter by 8 mm inner diameter, with a height of 550 um, mounted
to a 20 mm diameter circular ejector plate 5502 50 um thick. In
this embodiment, several samples of PZT are compared directly to
BaTiO.sub.3 with PZT ejecting more fluid than BaTiO.sub.3 in
approximately the ratio of the d33 coefficients of the materials.
The only significantly ejecting mode is shown in FIG. 59.
[0275] Where the distance 5554 is greater than zero (here, 2 mm),
the PZT material provides a broader range of effective frequencies
when compared to BaTiO.sub.3. The maximal mass ejection of the
PZT-based ejector is more than twice the output of the BaTiO.sub.3
ejector. While less efficient, the BaTiO.sub.3 provides maximal
mass ejection between 115 and 102 kHz of about 6 mg.
7a
Comparison of PZT and BaTiO.sub.3 Using Edge Mounted Ejector
Assemblies
[0276] Using the method of Experiment 6, mass ejection at different
frequencies is determined using a frequency step size of 1 kHz,
beginning at 10 kHz to 500 kHz. The mass deposited in milligrams is
plotted versus the frequency and is shown in FIG. 58 for edge
mounted PZT and BaTiO.sub.3 piezoelectric actuators having a 20 mm
outer diameter by 14 mm inner diameter of 550 um height
piezoelectric on a 20 mm circular 50 um thick ejector plate 5502.
In this case, several samples of PZT are compared directly to
BaTiO.sub.3 with PZT and BaTiO.sub.3 ejecting nearly equivalently
(adjusted for sample variation) even with vastly different material
d.sub.33 coefficients. As is also apparent from FIG. 58, many modes
are excited with equivalent performance between materials.
[0277] When PZT and BaTiO.sub.3 piezoelectric actuators are edge
mounted (that is, the distance 5554 is at or near zero), mass
ejection occurs at discrete ranges of frequencies corresponding to
the resonance coupling between the piezoelectric actuator and the
coupled ejector plate 5502 and generator plate. While the PZT based
device has a D.sub.33=330 pC/N and the BaTiO.sub.3 has a
D.sub.33=160 pC/N, the ejection profiles and efficiencies are very
similar. The centro-symmetric design and edge mounting of the
piezoelectric actuator overcomes the differences in displacement
allowing a wide variety of piezoelectric materials to be
incorporated into the ejection device.
7b
Effect of Decreasing Piezoelectric Actuator 5504 Diameter Relative
to Ejector Plate 5502
[0278] As the piezoelectric actuator 5504 is shifted in from the
edge of the ejector plate 5502 (e.g., the distance 5554 is
increased from zero), performance is lost as the ejecting modes are
increasingly damped by the piezoelectric stiffness. In one
embodiment the piezoelectric was 20 mm outer diameter by 14 mm
inner diameter with an optimized thickness of 250 um and an ejector
plate diameter of 20 mm. It showed ejection exceeding all other
cases by 20-33%. In another embodiment the outer diameter of the
piezoelectric was altered to 19 mm and the ejector plate diameter
was changed to 21 mm with an optimized thickness of 200 um. The
ejection frequencies remain virtually the same, but opposed to the
edge mounted case, ejection is reduced across every mode even
though piezoelectric thickness is optimized, (thicknesses from 150
um to 550 um were lab tested in 25 um increments). In the third
embodiment, the piezoelectric remained at 19 mm outer diameter and
14 mm inner diameter but the ejector plate was changed to 23 um.
Once again, the thickness was optimized to 175 um to reduce
stiffness but all modes are severely suppressed and performance was
degraded over 80%.
Example 8
Comparison of BaTiO.sub.3 Piezoelectric Materials
[0279] BaTiO.sub.3 materials having differing properties were
distinguished using Scanning Electron Microscopy (SEM). SEM images
of two exemplary BaTiO.sub.3 materials were obtained and showed a
uniform particle size about 2 to 5 microns in diameter in the first
sample and a fused structure with particles tens of microns in
diameter in the second sample. While both samples had similar
D.sub.33 values, the smaller grain size improves performance by
lowering the resonance frequencies.
Example 9
Modulation of Eigenmodes
[0280] For a circular ejector plate 5502 excited by a piezoelectric
actuator 5504, increasing the stiffness of the piezoelectric
actuator 5504 resulted in suppression of high frequency eigenmodes.
To test the effects of increasing the stiffness of the
piezoelectric actuator 5504, a first piezoelectric actuator 5504 of
200 um thickness having an outer diameter of 20 mm and an inner
diameter of 14 (20 mm.times.14 mm) and a second piezoelectric
actuator 5504 of 400 um thickness (20 mm.times.14 mm) were bonded
to an ejector plate 5502 with an outer diameter of 20 mm (e.g.,
edge mounted). The normalized displacement of the two ejector
mechanisms were [modeled or measured] at a frequency range from 1
Hz to 3.times.10.sup.5 Hz. The greater flexibility of the thinner
piezoelectric actuator 5504 allows for high frequency complex
eigenmodes. In contrast, the thicker, stiffer piezoelectric
actuator 5504 limits the eigenmodes to low frequency modes limited
to the region of the ejector plate 5502 within the inner diameter
of the piezoelectric actuator 5504 (e.g., inside 14 mm)
[0281] It will be understood that the ejector assembly described
herein may be incorporated into an ejector device and system.
Exemplary ejector devices and systems are illustrated in Ser. No.
13/712,784, filed Dec. 12, 2012, entitled "Ejector Mechanisms,
Devices, and Methods of Use", Ser. No. 13/712,857, filed Dec. 12,
2012, entitled "High Modulus Polymeric Ejector Mechanism, Ejector
Device, and Methods of Use", and Ser. No. 13/184,484, filed Jul.
15, 2011, entitled "Droplet Generator Device", the contents of
which are herein incorporated by reference in their entireties.
[0282] When fluid is exposed to an air interface, it will evaporate
into the air, causing a loss over time of fluid volume. If the
fluid has any mineral elements that are left behind, the mixture
contents change over time which results in crystallization at the
air-fluid interface. However, if a small air volume around the
fluid-air interface is sealed, the evaporation rate and
crystallization rate drop to the leak rate of the seal, thereby
reducing or eliminating evaporation and crystallization.
Contamination is also possible whenever a device is open to the
environment.
[0283] In part to address these issues, the present disclosure
provides an auto-closing system for use with a droplet ejection
device, which prevents the device from being open to the
environment for any longer that the actual droplet ejection period,
which greatly reduces the risk of contamination. In certain
embodiments, the auto-closing system is dimensionally compact along
the path of fluid ejection, uses a minimum of components, and
provides a consistent seal in the presence of component dimensional
variance. The system provides for a closed, sealed position and an
open, active position used for fluid ejection. The change between
closed and open positions can be configured for manual actuation by
a user, or can be configured for powered actuation. In certain
embodiments, the system may provide a manual configuration with low
actuation force. Furthermore, movement between sealed and open
positions can be configured for linear actuation or for rotary
actuation. For instance, certain embodiments provide a linear
actuation configuration used in conjunction with a user-operated,
hinged activation button.
[0284] FIGS. 60-65 show one embodiment of an auto-closure system of
the disclosure. FIG. 60 shows a compact, linearly actuated
embodiment of an auto-closing system of the disclosure, and FIG. 61
shows an exploded assembly view of the main components of this
embodiment.
[0285] As shown in FIGS. 60 and 61, a slide element 6000 with an
aperture 6002 is retained between the ejection system 6004 to be
sealed and a retaining plate 6006. The ejection system is shown
schematically without reference to internal features. The face of
the ejection system has a round aperture 6010 surrounded by a
round, elastomeric face seal 6012. The face seal resides in a gland
or groove 6014 in the face of the ejector. In one embodiment, the
slide element is squeezed against the face seal by flexures 6020
integral to the slide element. The flexures could alternatively be
located on the retaining plate or could be incorporated as a
separate component. In one position of the slide element (the open
position) the slide aperture 6002 is aligned with the ejector
aperture 6010 for fluid dispensing. In the closed position the
slide element aperture 6002 and ejection system aperture 6010 are
fully non-aligned and the ejection system is sealed. A hinged
activation button 6030 (FIG. 60) pivots about a fulcrum 6031
connected to a housing (not shown). The button 6030 is finger
operated by the user and actuates the slide element in the downward
direction to open the seal. Upon removal of user finger pressure, a
compression spring 6032 returns the slide element 6000 to the
closed and sealed position.
[0286] FIG. 62 shows a schematic cross-sectional view of the
auto-closing system and demonstrates the basic sealing principle.
An axial force, F, presses the slide element against the
elastomeric face seal located within the gland on the face of the
ejection system. The face seal surface protrudes from the surface
of the ejection system by approximately 20% of the seal cross
section. The maximum anticipated internal pressure in the ejection
system is countered by the axial squeezing force, F, such that the
squeeze force exceeds the internal pressure force given by the
product of the internal pressure P and the seal area A. For this
embodiment, the axial force was chosen to be approximately 2.times.
the anticipated internal pressure force. In the preferred
embodiment, the axial squeeze force is provided by compact flexures
6020 as shown in FIGS. 63 and 64. The flexures 6020 provide a
consistent force on the seal that is not sensitive to manufacturing
variance in the dimensions of the components. Having the flexures
integral to the slide element provides a minimum stack-up height
from the ejection system to the aperture of the retaining plate,
allowing the face of the ejection system to be closer to the final
delivery point. To minimize actuation force the face seal 6012 is
formed from a pre-lubricated silicone. To prevent abrasion, the
slide element 6000 is always in contact with the seal. No edge of
the slide element 6000 travels off and back onto the seal 6012;
only the slide aperture edges traverse the face seal. To further
prevent abrasion and reduce actuation force, the slide aperture
edge 6040 is rounded and the top edges of the face seal are
rounded. To keep the slide element parallel to the face seal, small
glide nubs 6042 are provide on the slide element as shown in FIGS.
63 and 64.
[0287] The slide element in the preferred embodiment is injection
molded from an anti-microbial thermoplastic. However, the
disclosure is not so limited, and any suitable material may be
used. As discussed, flexures 6020 integral to the slide 6000
provide the pre-load force on the face seal. Flexure geometry is
chosen to provide the desired axial force without over-stressing
the thermoplastic. In particular, the maximum stress in the flexure
when fully deflected is chosen to be below the long-term creep
limit of the chosen thermoplastic. This ensures that the desired
face seal pre-load is achieved long-term, after the device has been
assembled, without stress relaxation in the flexures. For
compactness, the compression spring 6032 for auto-closing the
device is located in a slot 6044 within the bounds of the slide
element 6000. As mentioned above, two glide nubs 6042 are located
on the of the slide element 6000 to keep the slide element 6000
parallel to the face seal, as the exposed face seal surface
protrudes above the guide surface on the ejection system that
constrains the back side of the slide element 6000.
[0288] As described above, the axial force on the face seal is
chosen to exceed the anticipated internal pressure force by some
margin of safety. In the event the axial force required exceeds the
force that can be provided by small plastic flexures, an
alternative approach is to use a separate spring component, which
could be formed from steel. Long term creep issues are not present
with a steel leaf spring and the exerted force can be increased to
provide significant advantages, but with an increase in the cost
and space required due to the separate part. One approach to
address this problem is to use the compression spring 6032 for a
secondary purpose as well. The primary purpose of the compression
spring would be to provide the auto-closing feature of the device.
When user finger pressure is removed from the activation button,
the compression spring returns the device to the closed and sealed
position, passively, without user interaction. To maintain a fully
closed device, the geometry of the device is set such that the
compression spring is in a pre-loaded state when the slide element
is in its fully closed position. This pre-load can be used for the
secondary purpose of increasing the axial force on the face seal, a
feature employed in the present embodiment.
[0289] As shown in FIG. 66, in the closed position the activation
button 6030 interacts with the slide element on an angled, inclined
surface 6050. This angle results in a horizontal outward force
component acting on the top of the slide element 6000. A small
fulcrum feature (not shown) is integrated into the top of the
retaining plate. The fulcrum is a small raised portion interacting
with the front face of the slide element. In the presence of the
horizontal force vector, the slide element 6000 pivots about the
fulcrum causing the lower part of the slide element 6000 to pivot
toward the face seal to thereby increase the axial force on the
face seal. This increases the seal integrity without the addition
of added parts or increased space requirement. Furthermore, the
axial force on the face seal is no longer solely dependent on the
flexures, allowing a wider choice of thermoplastics with lower
modulus (stiffness) values.
[0290] FIGS. 65-68 show a complete schematic representation of one
embodiment in both closed (left) (FIGS. 65 and 66) and open (right)
(FIGS. 67 and 68) positions, with implementation of all features
described above. In certain embodiments, the auto-closing system
includes umbrella valves or other suitable pressure relief means
utilized in connection with the retention plate (also referred to
herein as a compression plate) in order to address vapor pressure
build-up. By way of non-limiting example, alternative pressure
relief systems may include: duckbill valves; umbrella/duckbill
2-way valves; other suitable pressure release valves; pinhole valve
in a silicone sheet; slit valve in silicone sheet; single
pinhole/vent hole in a rigid material (e.g., 50 micron diameter
hole in 50 micron thick stainless steel); an array of vent holes;
or any other suitable pressure relief means that can restore
pressure equilibrium quickly enough, while also preventing excess
evaporation due to vapor pressure. Aspects of the umbrella valves
or pressure relief means are discussed in further detail
herein.
Example 10
Measurement of Crystallization, Evaporation, and Sealing
[0291] Crystallization occurs, especially in small holes where the
evaporation rate is high, at rates that can be prohibitive to
operation of a droplet ejector device. If crystallization occurs,
it prevents droplet ejection out of ejector openings by blocking
flow.
[0292] In accordance with one embodiment, for a generator plate
with of 20 um wide holes 50 microns deep with no puncture/capillary
plate and openly exposed to the environment, FIGS. 69 (a)-(c) shows
the crystal growth over time for isotonic saline solution. In FIG.
69(a), the ejector openings are shown at time zero (fluid has just
been inserted into a hard reservoir that is sealed to the ejector
mesh (which defines multiple ejector openings) and shows no
crystallization. A stack compression plate sealingly engages the
mesh screen by means of an O-ring and the opposite surface of the
mesh screen is attached via an O-ring to a reservoir, the assembly
being held together with screws and nuts. At 50 seconds after fluid
is inserted, shown in FIG. 69(b), noticeable crystallization begins
to form in the ejector nozzles (holes). At 3 minutes, shown in FIG.
69(c), a number of ejector openings or holes are completely
occluded and several ejector nozzles (holes) exhibit crystal
growth. The images were acquired by transmission light microscopy,
wherein crystals occlude transmitted light through openings.
[0293] In order to demonstrate the effect of a fluid loading plate,
a system was similarly set up, composed of a mesh screen of a
generator plate with 20 um wide holes 50 microns deep, but in this
case a capillary plate was added and openly exposed to the
environment. FIGS. 70(a)-(c) show the crystal growth over time for
isotonic saline solution. In FIG. 70(a), the ejector openings are
shown at time zero (fluid has just been inserted into a hard
reservoir that is sealed to the ejector mesh via the following: a
stack compression plate, O-ring, mesh screen, O-ring,
puncture/capillary plate, O-ring, reservoir held together with
screws and nuts) and no crystallization has occurred. At 5 minutes,
shown in FIG. 70(b), still no crystallization has formed. At 6
hours, shown in FIG. 70(c) a number of ejector openings are
completely occluded and several ejector openings exhibit crystal
growth. Although the puncture/capillary plate cannot reduce the
evaporation, it reduces crystallization. The decrease in
crystallization rate is obtained by delivering a constant fluid
supply, and preventing mineral deposits not immersed in fluid.
[0294] Evaporation may in certain applications lead to changes in
drug strength and potency, e.g., through loss of water and
resulting change in concentration. Evaporation can also lead to
crystallization in ejector openings. Table 16 shows evaporation
rates from the auto-closure system of the present disclosure versus
evaporation rates with two types of umbrella valves with different
cracking pressures provided in the fluid loading plate. The
evaporation rates shown are those exhibited without valve cracking
due to pressure fluctuation for isotonic saline using one type of
valve, and for latanoprost and isotonic saline using a different
valve. Both valves showed very high evaporation rates. In contrast,
the auto-closure systems of the present disclosure resulted in a
decrease in evaporation rate by a factor of 7-10, depending on the
test fluid. This also resulted in an extension of crystallization
time by a factor of 7-10 in between sprays compared to the
puncture/capillary plate and umbrella valves alone.
TABLE-US-00017 TABLE 16 Umbrella valve evaporation rates versus
perfect face seal using auto-closure system. Predicted Predicted %
fluid Mass Lost Mass Lost lost from Umbrella in 1 day in 30 days
2.0 mL ampoule Fluid Valve (mg) (mg) in 30 days Isotonic 5.3 mm
23.6 707 35% Saline (0.1-0.2 PSI Isotonic vent pressure) 18.0 539
27% Saline Isotonic 20.4 613 31% Saline Latanoprost 5.8 mm 3.5 104
5% Latanoprost (0.2-0.3 PSI 8.6 258 13% Isotonic vent pressure)
11.7 351 18% Saline Latanoprost 7.5 224 11% Isotonic Perfect Seal
2.4 72 4% Saline Latanoprost 2.6 79 4%
[0295] In certain aspects of the disclosure, auto-closure systems
were utilized in order to prevent large pressure excursions from
forcing fluid out of the ejector system. Valves equalize pressure
nearly instantly if the pressure exceeds the cracking pressure.
[0296] Alternatives to umbrella valves are within the scope of the
present disclosure. In this regard, any suitable manner for
equalizing pressure while preventing evaporation may be utilized,
e.g., a 50 um and 100 um vent hole solution with a bacteria and
fluid resistant membrane filter bonded over the vent hole. This
solution also equalizes pressure almost instantly, 10 psi/0.25 cc
per second of air, but also reduces evaporation rates 10-20 times
below that of the umbrella valves, as shown in Table 17. Leak rates
for pressure equalization (not evaporation) are also shown in Table
17.
TABLE-US-00018 TABLE 17 Evaporation and Leak rates for pressure
equalization of filtered vent holes Average Standard Number mass
loss Deviation of Condition per day (mg) (mg) samples 50 um hole
1.3 0.3 4 50 um hole & 0.9 0.2 3 1.2 um membrane Leak rates
from 50 um hole in SS316 steel, 50 um thick (Sample size: N = 10
for each condition) Average Corrected Standard Leak Rate Leak Rate
Deviation Condition (cm{circumflex over ( )}3/sec) (cm{circumflex
over ( )}3/sec) (cm{circumflex over ( )}3/sec) No 50 um hole (SS316
0.035 0 0.004 plate) 50 um hole 0.431 0.40 0.08 50 um hole &
0.428 0.39 0.06 1.0 um membrane (PTFE on non-woven polyester LHOP
support) 50 um hole & 0.473 0.44 0.13 1.2 um membrane (acrylic
copolymer on non-woven nylon support)
[0297] The auto-closure system provides an air and pressure barrier
necessary to prevent evaporation of fluid which could lead to
crystallization in the ejector openings. The purpose of this
experiment was to determine the normal force necessary to produce
an auto-closure system seal capable of sealing at 1.00 PSI.
[0298] Using the gravitational force of a plastic sealing element
upon the silicone face sealing ring to determine face seal quality
as a function of normal force. An ABS/Polycarbonate plastic seal
element was attached to the bottom of a beaker so that water could
be added for variable mass. The self-lubricating silicone seal was
housed inside the compression plate, with a pressure regulator and
pressure gauge attached to the inside of the compression plate. The
variable mass sealing element was balanced upon the silicone seal,
and fluid was added to the beaker. Pressure data was recorded as a
function of face seal normal force.
[0299] As gauge pressure approached 1.00 PSI, the auto-closure
system seal mass was increased. Normal forces of 40 grams and
larger typically sealed at 0.90 PSI or greater. This was identified
as an acceptable seal because it is significantly higher than the
0.2 PSI umbrella valve venting pressure.
[0300] Another identified condition was that the frictional force
of the closing slider upon the auto-closure system should be less
than the restoring force of the auto-closure spring. This condition
was fulfilled by choosing a spring with a sufficient spring
constant and displacement.
[0301] To measure the seal quality provided by the interior
auto-closure system seal over a sequence of multiple sliding
actuations. An auto-closure system according to the disclosure was
attached to an air pressure regulator and pressure gauge. The
regulator was set to 1.00 PSI with a perfect seal, and then the
perfect seal is removed. The auto-closure is actuated to provide a
seal, and the gauge pressure inside the seal increased until it
reached a maximum pressure. This maximum equilibrium pressure is
recorded as the seal pressure for that trial.
[0302] The maximum equilibrium pressure was recorded for 20 trials,
whereafter the auto-closure system was actuated 100 times. This
process was repeated 3 more times, resulting in 4 data sets of 20
trials, with 100 actuations between each data set. This was
designed to test the auto-closure system repeatability over a total
of 380 slide actuations. The average seal pressure for each data
set is shown in Table 18.
TABLE-US-00019 TABLE 18 Auto-closure face seal testing over 380
actuations Data Set # (N = 20 actuations) Average Seal Pressure
(PSI) 1 0.940 .+-. 0.006 2 0.937 .+-. 0.007 3 0.934 .+-. 0.005 4
0.936 .+-. 0.005 Note: Maximum seal pressure is 1.00 PSI because of
regulator
[0303] A 1.00 PSI seal was identified as an acceptable face seal
because it provides a safety margin above the 0.2 PSI umbrella
valve vent. The data from this test was consistently within 6-7% of
this target sealing pressure over 380 total actuations.
[0304] Many implementations of the inventions disclosed in the
present application and the above applications that are
incorporated by reference have been disclosed. This disclosure
contemplates combining any of the features of one implementation or
embodiment with the features of one or more of the other
implementations or embodiments. For example, any of the ejector
mechanisms or reservoirs can be used in combination with any of the
disclosed housings or housing features, e.g., covers, supports,
rests, lights, seals and gaskets, fill mechanisms, or alignment
mechanisms.
[0305] Further variations on any of the elements of any of the
inventions within the scope of ordinary skill are contemplated by
this disclosure. Such variations include selection of materials,
coatings, or methods of manufacturing. Any of the electrical and
electronic technology can be used with any of the implementations
without limitation. Furthermore, any networking, remote access,
subject monitoring, e-health, data storage, data mining, or
internet functionality is applicable to any and all of the
implementations and can be practiced therewith. Furthermore,
additional diagnostic functions, such as performance of tests or
measurements of physiological parameters may be incorporated into
the functionality of any of the implementations. Performance of
glaucoma or other ocular tests can be performed by the devices as a
part of their diagnostic functionality. Other methods of
fabrication known in the art and not explicitly listed here can be
used to fabricate, test, repair, or maintain the device.
Furthermore, the device may include more sophisticated imaging or
alignment mechanisms. For example, the device or base may be
equipped with or coupled to an iris or retina scanner to create a
unique identification to match a device to the user, and to
delineate between eyes. Alternatively, the device or base may be
coupled to or include sophisticated imaging devices for any
suitable type of photography or radiology.
* * * * *