HK1211536B - Ejector device for ejecting fluid onto a surface - Google Patents

Description

Spray device for spraying a fluid onto a surface

Related applications

This application claims the benefit of the filing dates of the following U.S. provisional applications: 61/636,559 filed April 20, 2012, 61/636,565 filed April 20, 2012, 61/643,150 filed May 4, 2012, 61/722,611 filed November 5, 2012, and 61/722,616 filed November 5, 2012, the contents of which are incorporated herein by reference in their entireties.

Technical Field

The present disclosure relates to a spraying device and a method for manufacturing the spraying device. In particular, the present disclosure relates to a device and a method for spraying a fine mist or a micro-droplet spray.

Background Art

The use of spray devices to deliver products in the form of a fine mist or spray is an area with great potential for making products safe and easy to use. The main challenges in providing such devices are providing stable and accurate delivery of the appropriate dose and avoiding contamination of the delivered product.

One important area where spray devices are needed is in the delivery of ophthalmic medications. Applying fluids (e.g., eye drops) is always problematic, especially for children and animals, often causing blinking or twitching at the critical moment of administration, resulting in droplets landing on the eyelids, nose, or other parts of the face. The impact of a large drop or multiple drops of fluid on the eyeball, particularly when the fluids are at different temperatures, can also often cause a blinking reflex. Furthermore, the elderly often lose the coordination necessary to use their hands to get the eye drops into the eye. Stroke patients face similar difficulties. Currently, many such medications are administered using eye droppers, which typically require tilting the head back, having the patient lie down, providing downward traction on the lower eyelid, or a combination of traction and tilting, because the delivery mechanism typically relies on gravity to apply the medication. This is not only awkward but also requires a considerable degree of coordination, flexibility, and cooperation on the part of the patient to ensure the medication enters the eye while preventing the dropper tip from poking the eye. In current eye dropper bottles, the sharp applicator tip poses a risk of poking the user's eye, potentially causing physical damage to the eye, and also exposes the tip to bacterial contamination due to contact with the eye. Likewise, the patient risks contaminating the medication in the eye dropper bottle and subsequently infecting the eye. In addition, a large amount of medication flows out of the eye or is washed away by the tear reflex. As a result, this method of medication administration is also inaccurate and wasteful. Furthermore, eye droppers do not provide a satisfactory way to control the amount of medication dispensed, nor do they provide a way to ensure that the dispensed medication actually lands on the eye and remains on the eye.

Eye droppers also do not provide a way to verify patient compliance. Even after a week of use, the total volume of medication dispensed by the eye dropper bottle can be verified, for example by weighing the bottle, but this does not provide a daily record of compliance. Patients may miss a dose or multiple doses, and in other cases may overdose. Furthermore, eye droppers have poor accuracy in delivering drops to the eye, making it difficult to determine whether the medication was actually delivered to the eye, even if it may have been dispensed.

Traditionally, the ability of piezoelectric droplet generation systems to eject fluids has been largely limited by the properties of the ceramic piezoelectric material used. For years, there has been a search for alternative lead-free piezoelectric material systems with performance comparable to lead-based systems to meet global regulations. However, such material systems remain elusive. Therefore, there is a significant need for ejection system designs that minimize reliance on piezoelectric material properties, thereby enabling similar ejection with less favorable material characteristics.

Therefore, there is a need for a delivery device that can deliver safe, appropriate, and repeatable doses to a patient for ocular, body part, oral, nasal, or pulmonary administration.

Summary of the Invention

According to the present disclosure, a spray device is provided, comprising: a housing; a reservoir containing a volume of fluid within the housing; a fluid loading plate in fluid communication with the fluid in the reservoir; and a spray mechanism in fluid communication with the fluid loading plate, wherein the fluid loading plate provides fluid to a rear surface of the spray mechanism, the spray mechanism being configured to spray a stream of droplets through at least one opening. The fluid loading plate can be configured to be positioned in a parallel arrangement with the spray mechanism so as to provide fluid to a rear spray surface of the spray mechanism. The spray device of the present disclosure is capable of delivering a defined volume of fluid in the form of droplets, with the capability of providing a sufficient and repeatable high percentage of deposition upon application.

In this regard, an important consideration according to the present disclosure is not only the ability to deliver medication in an easy-to-use manner (e.g., by spraying a fine mist onto the surface to be treated), but also the ability to ensure stable delivery of medication to the spray or delivery mechanism in any orientation. In some embodiments, the spray device is capable of spraying a stream of droplets when tilted, even when tilted upside down 180 degrees.

In certain embodiments, a fluid loading plate can include a capillary plate fluid delivery device for delivering fluid from a reservoir to a spraying mechanism of a spraying device, and methods of use for delivering a safe, suitable, and repeatable dose to a patient for ocular, body part, oral, nasal, or pulmonary administration. The capillary plate can include a fluid reservoir interface, a spraying mechanism interface, and one or more fluid channels for directing fluid to the spraying mechanism via one or more mechanisms including capillary action.

In other embodiments, the fluid loading plate may include a piercing plate fluid delivery system for delivering fluid from a reservoir to a spraying mechanism of a spraying device. The piercing plate fluid delivery system, also referred to as a capillary plate/piercing plate fluid delivery system, may include: a capillary plate portion including a fluid retention region located between the piercing plate/capillary plate fluid delivery system and a rear surface of the spraying mechanism, for directing fluid to the spraying mechanism via one or more mechanisms including capillary action; and at least one hollow piercing needle for delivering fluid from the reservoir to the fluid retention region.

In certain aspects, a pierce plate fluid delivery system may include a first mating portion and a second mating portion, wherein a reservoir is fluidically attached to the second mating portion, and the second mating portion includes a pierceable seal. The first mating portion may form a receptacle for the second mating portion and may include at least one hollow piercing needle for piercing the pierceable seal. The first mating portion and the at least one piercing needle may be integrally formed. The pierceable seal included in the second mating portion may include self-sealing silicone.

The reservoir, also referred to herein as an ampoule, may include a collapsible, flexible container. The reservoir may include a container and a lid, wherein the reservoir is configured such that the lid and container form a volume capable of containing a fluid. The reservoir may be configured to partially collapse (at sea level) and expand to accommodate expansion of the gas within the volume and prevent leakage.

The ejection mechanism may include an ejection plate coupled to a droplet generation plate (hereinafter referred to as the generation plate) and a piezoelectric actuator; the generation plate includes a plurality of openings formed through its thickness, and the piezoelectric actuator is operable to oscillate the ejection plate, thereby causing the generation plate to oscillate at a frequency to generate a directional stream of droplets. The ejection plate may have a central open region aligned with the generation plate, wherein the piezoelectric actuator is coupled to a peripheral region of the ejection plate to avoid blocking the plurality of openings of the generation plate. The plurality of openings of the generation plate may be arranged in a central region of the generation plate not covered by the piezoelectric actuator and aligned with the central region of the ejection plate. The three-dimensional geometry and shape of the openings (including orifice diameter and capillary length) and their spatial arrangement on the generation plate may be controlled to optimize the generation of the directional stream of droplets. The generation plate may be formed from a high modulus polymer material, such as a material selected from the group consisting of ultra-high molecular weight polyethylene (UHMWPE), polyimide, polyether ether ketone (PEEK), polyvinylidene fluoride (PVDF), and polyetherimide. The ejection mechanism may be configured to eject a stream of droplets having an average droplet diameter greater than 15 microns, the droplet stream entraining a small amount of air flow such that the droplet stream is deposited on the patient's eye during use.

The ejection mechanism can have a centrally symmetrical structure, wherein the ejection plate includes a symmetrically arranged mounting structure having a symmetrical configuration into which droplets are ejected from a central region of the symmetrical structure. The piezoelectric actuator can induce resonant amplification of a generator plate coupled to the ejection plate to provide a greater variety of piezoelectric constants. The ejection plate can be made of a high-modulus polymer material, and the piezoelectric actuator can be lead-free or substantially lead-free.

The droplets may form a distribution of sizes, each distribution having a mean droplet size. The mean droplet size may range from 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, depending on the intended application, the mean droplet size may reach 2500 microns. Furthermore, the mean initial velocity of the droplets may range from 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 m/s 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, jet size and initial velocity refer to the size and initial velocity of the droplets as they exit the jet plate. A stream of droplets directed towards a target will result in the droplets comprising a majority of their constituents being deposited on the target.

The jetting mechanism and the fluid loading plate can be combined to form a unit defining a jetting assembly, the jetting assembly including the fluid loading plate in fluid communication with the jetting mechanism such that the fluid loading plate provides fluid to a rear surface of the jetting mechanism, the jetting mechanism being configured to eject a stream of droplets. In certain embodiments, the jetting assembly can further include a reservoir in fluid communication with the fluid loading plate.

The spraying device may also include an automatic shutoff system that substantially reduces the risk of crystallization, evaporation, and contamination. The automatic shutoff system may include a user-activated slide that sealingly engages a gasket or seal formed at least around the hole in the generator plate and is slidable between an open position in which the hole is exposed and a closed position in which the hole is covered by the slide. The slide may be biased toward the closed position by a spring. The slide may include an opening configured to coincide with the hole in the generator plate when the slide is in the open position. The automatic shutoff system may include means for ensuring that the slide is pressed against the seal with sufficient pressure when in the closed position.

Further in accordance with the present disclosure, an automatic shutoff system for a droplet ejection device is provided that substantially reduces crystallization, evaporation, and contamination hazards.

Still further, in accordance with the present disclosure, there is provided a method of manufacturing a generating plate for ejecting a high viscosity fluid suitable for use in the eye, body part, mouth, nose, or lungs, comprising laser micromachining a material to form three-dimensional openings through the thickness of the material, each opening defining an entry cavity and a capillary channel, wherein the openings comprise a total pitch length.

Still further, in accordance with the present disclosure, a method of delivering a volume of ophthalmic fluid to an eye of a patient is provided, the method comprising ejecting a directional stream of droplets of the ophthalmic fluid contained in a reservoir from an opening of an ejection plate, the droplets in the directional stream having an average ejection diameter within a range of 5-2500 microns, e.g., 20-400 microns, 20-200 microns, including but not limited to a range of 100-200 microns, etc., and having an average initial velocity within a range of 0.5-100 m/s, e.g., 1-100 m/s, 2-20 m/s.

These and other aspects of the invention will be apparent to those skilled in the art.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG1 is a three-dimensional exploded view of the mechanical parts of an embodiment of a spray device of the present disclosure;

FIG2 is a front view of an embodiment of a spray device of the present disclosure;

FIG3 shows an embodiment of a storage device according to the present disclosure;

FIG4 shows another embodiment of a storage device according to the present disclosure;

Figure 5 shows the variation of atmospheric pressure (p) with altitude (h);

6A-6D illustrate various embodiments of components of a reservoir according to one embodiment of the present disclosure;

FIG7 illustrates a forming, filling, and sealing process for producing a reservoir according to one embodiment of the present disclosure;

8 illustrates an embodiment of a reservoir, fluid loading plate, and ejection plate showing the direction of droplet ejection relative to attitude angle, according to aspects of the present disclosure.

9 illustrates an embodiment of a test apparatus for measuring differential pressure induced leaks in embodiments of a reservoir, fluid loading plate, and jetting assembly according to aspects of the present disclosure;

10A-E illustrate a pressure drop and reservoir expansion after determining a leak point pressure for an embodiment of a reservoir, fluid loading plate, and jetting assembly according to aspects of the present disclosure;

FIG. 11 illustrates the effect of volume V _gas (expressed as a percentage of V _t ) on differential pressure leakage values for various embodiments of reservoirs, fluid loading plates, and jetting assemblies according to various aspects of the present disclosure;

FIG12 illustrates the mass loss of a reservoir (ampoule) over time according to an aspect of the present disclosure;

FIG13 illustrates the gesture insensitivity of an embodiment of the present disclosure having a collapsible flexible reservoir (ampoule) compared to an embodiment of the present disclosure having a rigid reservoir;

14A-14C illustrate one embodiment of a capillary plate of the present disclosure;

15A-15C illustrate one embodiment of a jetting mechanism associated with an embodiment of a capillary plate of the present disclosure;

16A-16B show the relationship between the plate spacing and the water level of vertical parallel plates;

17A-17B illustrate an embodiment of a capillary plate of the present disclosure;

Figure 18 shows the effect of resonance frequency on mass deposition with and without a capillary plate;

Figure 19 shows that the increase in the water level behind the ejector plate in the presence of a capillary plate results in an increase in the mass loading effect at a specific frequency;

FIG20 shows the relationship between frequency and downshift of a capillary plate for conveying various fluids;

Figure 21 shows the relationship between the increase in density and viscosity of the fluid and the decrease in mass loading;

FIG22 illustrates the posture insensitivity of a jetting device including a capillary plate;

FIG23 illustrates the major components of one embodiment of a jetting assembly including a piercing plate/capillary plate system with a reservoir and jetting mechanism according to the present disclosure;

24A-24B show three-dimensional front and rear views of the components of FIG. 23 in assembled form;

25A-25B illustrate detailed rear and front views of one embodiment of a jetting mechanism of the present disclosure;

FIG26 is a schematic diagram of fluid flowing through a piercing plate system of the present disclosure;

FIG27 is a schematic diagram of a piercing plate system of the present disclosure illustrating the Venturi effect;

Figure 28 illustrates the principle of Bernoulli's equation;

Figure 29 shows the static pressure principle;

FIG30 shows schematic diagrams of different reservoir configurations of the present disclosure;

FIG31 shows a schematic diagram of another reservoir configuration of the present disclosure;

32A-32B illustrate three-dimensional side and front views of two collapsible reservoir embodiments of the present disclosure;

FIG33 illustrates a rear view of one embodiment of a blow-fill-seal reservoir and piercing plate of the present disclosure;

34A-34B illustrate side views of two blow-fill-seal reservoirs and piercing plate systems of the present disclosure;

FIG35 illustrates a different form-fill-seal reservoir according to the present disclosure;

36-37 illustrate apparatus and equipment for determining the amount of negative pressure applied by various reservoir configurations as fluid is removed;

FIG38 shows the mass per shot and total shot mass (shoot-down performance) of a non-collapsing biased reservoir embodiment of the present disclosure with a pronounced crease formation;

FIG39 illustrates the mass per shot and the total shot mass (shot-down performance) for various blow-fill-seal reservoir embodiments of the present disclosure;

FIG40 shows two runs of the mass per shot and the total shot mass (shot-down performance) for an LTS/retraction biased self-sealing RW weld reservoir embodiment of the present disclosure;

FIG41 shows the pull-down performance of the circular LTS ampoule configuration selected from FIG35;

Figure 42 shows the mechanisms involved in inverted injection using a circular LTS reservoir;

FIG43 shows actual downward spray performance results of an LTS reservoir embodiment of the present disclosure when the entire piercing system is sprayed with its upper end facing downward;

FIG44 illustrates the downspout performance of another piercing plate configuration with an IV bag reservoir embodiment of the present disclosure;

FIG45 illustrates the spray performance of two different piercing plate configurations with an IV bag reservoir according to an embodiment of the present disclosure in different orientations and spray directions;

FIG46 illustrates the spray performance of one embodiment of a piercing plate configuration with an IV bag reservoir according to the present disclosure in different orientations, different spray directions, and different piercing plate vent selections;

FIG47 schematically illustrates the relationship between the capillary effect and static pressure of a reservoir;

Figure 48 shows the capillary pressure of half drops of water of various sizes;

FIG49 shows the capillary pressure of half-drops of latanaprost of various sizes;

Figure 50 shows capillary rise for various fluid types with different contact angle values;

FIG51 shows the capillary rise of saline in capillary channels made of different materials;

Figures 52-53 show the height of fluid rise between the piercing plate and the ejection plate for different materials;

FIG54 shows a test device for testing fluid leakage of a capillary riser hole at different fluid filling positions;

FIG55A illustrates a cross-sectional view of one embodiment of a jetting assembly of the present disclosure;

FIG55B shows a three-dimensional diagram of one embodiment of a jetting mechanism of the present disclosure;

FIG55C illustrates a front view of a centrally symmetrical ejection mechanism embodiment of the present disclosure;

FIG55D shows a disassembled view of one embodiment of a spray mechanism of the present disclosure;

Figure 56 shows the designations for the axis numbering conventions used for the piezoelectric effect;

FIG57 shows a digital holographic micrograph of the operating mode of the active region of one embodiment of a generating plate and the oscillations of the generating plate;

FIG58 shows a comparison of the quality of PZT and BaTiO ₃ (lead-free) piezoelectric actuator materials ejected using an internally mounted piezoelectric actuator according to one embodiment of the present disclosure;

FIG59 shows a comparison of the quality of PZT and BaTiO ₃ (lead-free) piezoelectric actuator materials ejected using an edge-mounted piezoelectric actuator according to another embodiment of the present disclosure;

FIG60 illustrates a three-dimensional perspective view of one embodiment of a jetting assembly with an automatic shutoff system of the present disclosure;

FIG61 shows the disassembled state of the spray assembly with the automatic closing system of FIG60;

FIG62 is a cross-sectional side view of a portion of the spray assembly with an automatic shutoff system of FIG60;

FIG63 shows a three-dimensional front view of the sliding unit of the automatic closing system of FIG60;

FIG64 shows a three-dimensional rear view of the sliding unit of FIG63;

FIG65 shows a front view of the automatic closing system of FIG60 in the closed position;

FIG66 illustrates a cross-sectional side view of the automatic closing system of FIG60 in a closed position;

FIG67 shows a front view of the automatic closing system of FIG60 in the open position;

FIG68 illustrates a cross-sectional side view of the automatic closing system of FIG60 in an open position;

Figures 69A-69C show transmission optical microscopy images of a mesh of a generating plate over time in a system where no capillary plate is provided; and

70A-70C show transmission optical microscopy images of a mesh of a generating plate where the system is provided with a capillary plate over time.

DETAILED DESCRIPTION

The application relates to the spraying device for delivering fluid to the surface as the droplet stream of injection.Spraying device can be for example at application number be 61/569,739,61/636,559,61/636,565, 61/636,568,61/642,838,61/642,867,61/643,150 and 61/584, the U.S. Provisional Application of 060 and application number be 13/184,446,13/184,468 and 13/184, the spraying device described in the U.S. Patent Application 484, the full contents of these applications are incorporated herein by reference.

The spray device of the present disclosure can be used to deliver fluid for use in the eyes, body parts, mouth, nose or lungs, for example. However, the present disclosure is not limited thereto and can be used with any spray device (e.g., printing device, etc.).

In certain embodiments, a jetting device may include a housing, a reservoir within the housing for receiving a volume of fluid, a fluid loading plate, and a jetting mechanism configured to eject one or more streams of fluid droplets, wherein the reservoir is in fluid communication with the fluid loading plate, which is in fluid communication with the jetting mechanism such that the fluid loading plate provides fluid to a rear surface of the jetting plate.

Thus, the present disclosure generally relates to a spray device for spraying a fluid onto a surface, such as an ophthalmic fluid onto a patient's eye. Referring to FIG. 1 , the various components of one embodiment of the spray device will be generally described, followed by a detailed discussion of some of the components that assemble the spray device. However, it should be understood that the present disclosure is not limited to the specific embodiments described herein, but rather encompasses variations and different combinations of components that assemble the spray device.

For purposes of this application, fluids include, but are not limited to, suspensions or emulsions having a viscosity range capable of being formed into droplets using a spraying mechanism.

FIG1 illustrates an exploded view of one embodiment of the internal components of a spray device 100 of the present disclosure, including a reservoir 102, which in this embodiment is a flexible reservoir fabricated using self-sealing RF welding technology. Reservoir 102 is placed in fluid communication with a fluid loading plate 104 via a punctureable seal 106. The fluid loading plate supplies fluid from the reservoir to the rear of a spray mechanism 108, for example, by capillary action. In this embodiment, the sprayer comprises a piezoelectric spray mechanism configured to generate a controllable stream of fluid droplets. While this embodiment depicts a fluid loading plate 104 (described in greater detail below), other configurations for directing fluid from the reservoir to the spray mechanism by capillary action may also be employed. To limit fluid evaporation, crystallization, and contamination, an automatic shutoff system 110 is mounted in front of the spray mechanism 108. A bracket 112, which supports a housing 114 for an alignment LED, is configured to clip onto the front surface of the automatic shutoff system 110.

2 , in some embodiments, the mechanical components of the spray device can be mounted within a removable top portion 200 of a housing 202 that mates with a lower grip portion 204. The electronics and power supply for controlling the fluid spray can be housed within the lower grip portion 204 of the housing 202.

The reservoir or ampoule 102 for use with the spray device 100 can include a flexible reservoir or a rigid, non-flexible reservoir. In certain embodiments, the reservoir includes a collapsible, flexible reservoir 102 disposed within the top 200 of the housing 202 and containing or adapted to receive a volume of fluid. The present disclosure contemplates different types of flexible reservoirs manufactured using different techniques, including a self-sealing radio frequency (RF) welded reservoir as shown in FIG1 . Alternatively, a blow-fill-seal technique can be used to form a reservoir of similar construction as shown in FIG3 , or a blow-fill-seal technique can be used to provide a reservoir as shown in FIG4 . As will be apparent from the discussion below, the specific configuration of the reservoir can vary from embodiment to embodiment. For example, the shape of a blow-fill-seal reservoir is not limited to that shown in FIG4 .

Referring to Figure 5, atmospheric pressure varies with altitude. Specifically, as altitude increases, pressure decreases. According to Boyle's law, the volume of a gas increases as pressure decreases. Similarly, Charles' law dictates that the volume of a gas increases as temperature increases. In contrast, the volume of a liquid generally changes very little in response to changes in pressure and temperature, with the notable exception of water, which expands when cooled from 4°C to 0°C. Thus, although the liquid in a reservoir will change very little when pressure and temperature conditions change, a reservoir with a certain volume of liquid and a certain volume of gas must be designed to accommodate the drop in pressure and the increase in temperature. In many cases, the greater relationship is caused by the change in pressure, which causes the gas volume to change significantly. Changes in altitude are a common cause of changes in pressure, and therefore also a common cause of changes in gas volume.

Without being limited by theory, the change in atmospheric pressure due to a change in altitude can be determined according to the following equation:

in:

parameter illustrate Value Standard atmospheric pressure at sea level 101325 Pascal (Pa) L Temperature drop rate 0.0065°K/meter (m) Standard sea level temperature 288.15°K g Surface gravitational acceleration 9.80665m/s M Molar mass of dry air 0.0289644 kg/mole R Universal gas constant 8.31447 joules (J)/(mole °K)

According to the present disclosure, an ampoule or reservoir, or a device containing an ampoule or reservoir, may be transported by aircraft or to a geographically high altitude. As discussed, this change may cause a pressure differential relative to sea level, which can lead to leakage from the orifice of the injection device. For example, at altitudes between 6,000 and 8,000 feet, the aircraft cabin is pressurized. The corresponding pressure differential relative to sea level is 20 to 29 kPa, respectively. The ampoule cannot accommodate this pressure differential by expanding, often leading to a buildup of pressure inside the ampoule and subsequent leakage of fluid from the device. As used herein, "ambient pressure" refers to the air pressure to which the reservoir, ampoule, or device containing the reservoir or ampoule is exposed. As used herein, "pressure differential" refers to the difference between ambient pressure and standard atmospheric pressure at sea level (101,325 Pascals (Pa)). Therefore, the reduced pressure in the aircraft is the ambient pressure, and the pressure differential is the difference between this ambient pressure and standard pressure at sea level (e.g., approximately 20 kPa at 6,000 feet). Likewise, the pressure differential at an altitude above sea level is the difference between the standard atmospheric pressure at sea level (101,325 Pascals (Pa)) and the ambient pressure at that altitude.

In other embodiments, the reservoir or ampoule can be a rigid reservoir designed to contain the expansion of any gas therein. In some embodiments, expansion can be inhibited by providing a pressurized closure. In other embodiments, leakage can be inhibited by sealing any orifices present in the reservoir.

6A-6D , in certain embodiments, a reservoir (in this case, a form-fill-seal reservoir) may include an ampoule having three components: a lid 601, a container 602, and an optional reinforcement ring 603. In some embodiments, the lid 601 is sealed to the container 602 to form a closed, impermeable container. In one embodiment, the sealed, impermeable combination of the lid 601 and the container 602 provides storage for the liquid. In other embodiments, the container 602 forms a flexible reservoir that can accommodate the expansion of the gas contained and retained by the reservoir. In other embodiments, the reservoir may be formed from a non-flexible material to create a rigid reservoir.

In some aspects of the present disclosure, the ampoule or reservoir can be assembled from multiple components so that the properties of the cap 601, container 602, and reinforcement ring 603 can be tailored to the device application. In other embodiments, the container 602 and reinforcement ring 603 can be formed together, with the cap 601 applied after the desired fluid is added. In one embodiment, the sealed, impermeable combination of the cap 601 and container 602 can be formed separately. In certain embodiments, the cap 601 can be puncturable.

In certain embodiments, the shape and size of the ampoule or reservoir can be selected based on the intended use. In a non-limiting example, a person requiring short-term treatment may require fluid for ocular use and, therefore, may require a smaller dose. In cases where a smaller dose is indicated, the shape and size of the ampoule can be appropriately graduated to avoid unnecessary waste. In other aspects, in cases where the fluid is required for a longer period of time or where a larger daily dose may be required, a larger volume can be indicated.

Volume 610 can be controlled by varying depth 607, diameter 604, and shape 609. In some aspects, such as for pulmonary use, diameter 604 can exceed 1 cm. In another aspect, diameter 604 can be 1.5 cm. In yet another embodiment, diameter 604 can be from 1 cm to 3 cm. In another embodiment, diameter 604 can be between 1 cm and 4 cm, or between 1 cm and 5 cm. In other embodiments, diameter 604 can be greater than 3 cm, greater than 4 cm, greater than 5 cm, greater than 6 cm, or greater than 7 cm. In other embodiments, the diameter can be configured for a device, such as for ophthalmic applications. For example, diameter 604 can be 20 mm or less. In other embodiments, diameter 604 can be 19 mm or less. In another embodiment, diameter 604 can be 18 mm or less. In yet another embodiment, diameter 604 can be 17 mm or less. In one embodiment, diameter 604 can be 16 mm or less. In other embodiments of the present disclosure, diameter 604 can be from 18 mm to 19 mm. In another embodiment, the diameter can be from 15 mm to 20 mm, from 16 mm to 20 mm, from 17 mm to 20 mm, from 18 mm to 20 mm, or from 19 mm to 20 mm. In other embodiments, the diameter 604 can be from 15 mm to 19 mm, from 16 mm to 19 mm, from 17 mm to 19 mm, or from 18 mm to 19 mm.

In certain embodiments according to the present disclosure, the shape 609 of the ampoule can be modified relative to the diameter 604 to increase or decrease the volume. In some embodiments, the shape 609 can be configured such that the diameter decreases along the depth 607 toward the closed end of the container. In certain aspects, this decreasing diameter can provide for mold removal. The construction and manufacture of molds used to form ampoules having a container 602 according to the present disclosure are known in the art.

In certain embodiments of the present disclosure, the ampoule can include a reinforcement ring 603 configured to increase the stability of the container 602. In some embodiments, the container 602 can be flexible, and the reinforcement ring 603 can be provided for connection to a device or housing according to the present disclosure. The thickness 606 and the diameter 605 can be determined based on the diameter 604 of the container 602. In one aspect, the thickness 606 can be determined based on the material of the reinforcement ring 603.

The sealed combination of cap 601 and container 602, and the optional reinforcement ring, forms an ampoule suitable for holding and storing fluid for ocular, body part, oral, nasal, or pulmonary administration until the ampoule is inserted into a spray device or spray device housing. In some embodiments, the sealed ampoule can be suitable for short-term storage of fluid for ocular, body part, oral, nasal, or pulmonary administration. In other embodiments, the sealed ampoule can be suitable for long-term storage of fluid for ocular, body part, oral, nasal, or pulmonary administration.

In certain embodiments, the sealed fluid-containing ampoule can store the fluid for one week without loss or degradation. In other embodiments, the sealed ampoule can be stored for more than one week. In some embodiments, the sealed ampoule can be suitable for short-term storage, including two weeks, three weeks, or one month. In certain embodiments, the sealed ampoule can be stored for one month.

In certain embodiments, the sealed fluid-containing ampoule can be stored for extended periods of time without significant loss or degradation. In other embodiments, the sealed fluid-containing ampoule can be stored for more than one month. In other embodiments, the sealed ampoule can 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 embodiments, the sealed ampoule can be stored for five months. In other embodiments, the sealed ampoule can be stored for six months. In some embodiments, the sealed ampoule may be suitable for long-term storage, including seven months, eight months, or more. In certain embodiments, the sealed ampoule can be stored for nine months. In certain embodiments, the sealed ampoule can be stored for ten months. In other embodiments, the sealed ampoule can be stored for eleven months. In some embodiments, the sealed ampoule may be suitable for long-term storage, including twelve months or more. In certain embodiments, the sealed ampoule can be stored for 1.5 years. In still other embodiments, the sealed fluid-filled ampoule can be stored for more than 1.5 years.

The cover 601, container 602, and reinforcement ring 603 can be formed of any material suitable for the intended application. For example, in ophthalmic applications, any material suitable for treating the eye can be used, such as a polymeric material that does not chemically react with or absorb the fluid to be transported. In other aspects, the surfaces of the cover 601, container 602, and reinforcement ring 603 that are exposed to the fluid to be transported can be formed of materials that provide the required surface properties, including, for example, hydrophobicity, hydrophilicity, non-reactivity, stability, and the like. Examples of materials suitable for the cover 601 and container 602 include, but are not limited to, the materials listed in Table 1.

Table 1: Exemplary lid and container materials

In some embodiments according to the present disclosure, the material used for container 602 can be selected to have properties consistent with those of FDA-approved medical devices. The material can be selected according to methods and specifications known in the art, such as ISO 10993-5, United States Pharmacopoeia 32, Part 5, Biological evaluation of medical devices, Biological response tests, in vitro; ISO 13485, Quality management systems for medical devices; and ISO 17025, General requirements for the qualification of testing and calibration laboratories. For example, container 602 can be a non-cytotoxic film, such as ML29xxC available from Sealed Air.

According to the present disclosure, the material used for container 602 can be a polymer. In certain embodiments, the polymer can be a layered polymer. In other embodiments, the polymer can be a coextruded film. In certain embodiments, the polymer can be a polymer for use in medical devices. In one example according to the present disclosure, the film can be a coextruded film based on polyethylene. In certain embodiments, the polymer can be sterile. In one aspect, the film is selected based on its ability to combine with other films. In one example, the other film can be Tyvek or other coated medical materials. In one aspect, the film is transparent or opaque. In another aspect, the film can be puncture-resistant. In yet another aspect, the film can be resistant to down-gauging.

In one aspect, the film can be formable. Formable films according to the present disclosure can be selected based on the requirements of the application. In some aspects, the film can be selected based on one or more of the following criteria: thickness, Young's modulus, elongation, tensile strength, puncture force, tear, and haze. In some aspects, the flexibility of the film can provide for a collapsible ampoule. In one aspect, a collapsible ampoule can be provided to eliminate leakage when atmospheric pressure changes.

Examples of films that are compatible with the devices and methods of the present invention include the films provided in Table 2. In accordance with the present disclosure, similar films can be selected based on the following desired properties: thickness, Young's modulus (MD), elongation (MD), tensile strength (MD), puncture force, tear, and haze.

Table 2: Exemplary Films of the Disclosure

According to some embodiments, the lid 601, container 602, and reinforcement ring 603 can be formed from materials suitable for sterilization. In some aspects, the lid 601, container 602, and reinforcement ring 603 can be sterilized together as a unit. In other aspects, the lid 601, container 602, and reinforcement ring 603 can be sterilized separately using one or more of various sterilization methods known in the art. In certain aspects of the present disclosure, one or more sterilization methods can be combined, such as chemical and radiation methods as provided below.

In one aspect, the lid 601, container 602, and reinforcement ring 603 can be formed of materials compatible with radiation sterilization. In one aspect, the materials can be compatible with gamma radiation sterilization. In other aspects, the materials can be selected to be compatible with radiation methods such as electron beams, X-rays, or subatomic particles.

In another aspect, the container can be formed from a material compatible with chemical sterilization methods. In one embodiment, the material can be compatible with ethylene oxide (EtO) sterilization. In another embodiment, the material can be compatible with ozone (O ₃ ) sterilization. In another embodiment, the material can be compatible with o-phthalaldehyde (OPA) sterilization. In yet another embodiment, hydrogen peroxide can be used as a chemical sterilant.

In some aspects of the present disclosure, the lid 601, container 602, and reinforcement ring 603 can be formed from materials compatible with heat sterilization. In one embodiment, the heat sterilization-compatible material can resist dry heat sterilization. In another embodiment, the heat sterilization-compatible material can be compatible with moist heat sterilization. In some aspects of the present disclosure, the lid 601, container 602, and reinforcement ring 603 can be formed from materials compatible with Tyndall sterilization.

In some aspects, the materials selected for the lid 601, container 602, and reinforcement ring 603 provide for long-term storage of the liquid. In some embodiments, the sealed ampoule may include an impermeable material. In some aspects, the impermeability may be selected based on the fluid. In one non-limiting example according to the present disclosure, a fluid for use in the eyes, a part of the body, the mouth, the nose, or the lungs may need to be isolated from light or air to remain stable. In another non-limiting example according to the present disclosure, a fluid for use in the eyes, a part of the body, the mouth, the nose, or the lungs may need to be isolated from light and oxygen to remain stable. In some embodiments, the material may be gas-impermeable. In one embodiment, the gas may be oxygen. In other embodiments, the material may be light-impermeable. In another embodiment, the material may be gas-impermeable, such as oxygen, and light-impermeable.

In one aspect of the present disclosure, the container 602 and lid 601 materials can be selected to be long-term stable. As an aspect, in certain embodiments, one or more properties that can be used to determine the stability of a material include, but are not limited to, tensile strength, elongation, tear resistance, and impact stability.

Referring to FIG7 , the fluid-containing container of the present invention can be prepared using forming, filling, and sealing processes known in the art. In certain embodiments, the entire process outlined in FIG7 can be performed under sterile conditions in accordance with applicable regulatory standards for medical devices and preparations. In one embodiment, a film can be applied to a mold, then heated and vacuum formed to produce a container having a shape 609 and a depth 607. By varying the shape 609, depth 607, and diameter 604, a container or ampoule having a defined total volume (V _t ) can be formed.

Once a container (e.g., container 602) is formed, it can be filled with fluid and then a lid is applied to the filled container or ampoule. In some embodiments, by way of example only, a seal is applied to form a leak-proof closure. Other methods for attaching and sealing a lid to a container are also known in the art. After sealing, the ampoules can be cut individually from the template. In other embodiments, sealing and cutting can be performed simultaneously. The final sealed container or ampoule is suitable for storage, transportation, or use in a spray device. As described above, the form-fill-seal process described in this embodiment is only one technique known in the art for forming and sealing containers. Other techniques, such as blow-fill-seal and self-sealing RF welding techniques, which do not use a lid element, may also be used.

In certain embodiments of the present disclosure, the fluid ( _Vf ) may fill the entire volume of the container 602 (e.g., _Vt ). In other embodiments, the fluid may not completely fill the volume, but may leave a void ( _VΔT ). In embodiments where the liquid volume _Vf is equal to _VΔT , application of the cap may result in the entrapment of a volume of gas _Vgas . In other embodiments, the volume of the container 602 may be reduced by squeezing or deformation, such that the volume is reduced by a certain volume ( _Vr ). According to the present disclosure, the volume of a sealed container or ampoule is:

V _t = V _f + V _gas + V _r , where

V _ΔT = V _gas + V _r

According to certain aspects of the present disclosure, volume V _r provides the container with the ability to expand to volume V _t , thereby reducing the container's tendency to leak when used in a spray device. Similarly, volume V _r can also accommodate the expansion of the aqueous fluid volume during transport or storage, or in other situations where the liquid volume may expand. In other embodiments, V _ΔT can include both the gas volume V _gas and volume V _r , thereby compensating for changes in gas volume associated with changes in ambient pressure and thereby creating a leak-proof spray device. Similarly, volume V _r also provides for the gas expansion volume V _exp that may occur during transport or storage under lower ambient pressure conditions.

In certain aspects according to the present disclosure, a container can contain a volume of gas, V _gas . In one aspect, the gas can be air. In another aspect, the gas can be air depleted of oxygen. In other aspects, the gas can be a non-reactive gas. In one aspect, the gas can be nitrogen. In another aspect, the gas can be an inert gas, such as helium or argon. In other aspects, the gas can be CO ₂ . According to the present disclosure, any gas can be contained.

In certain embodiments of the present disclosure, a reservoir provides attitude insensitivity to the ejection device. In one aspect, the reservoir comprises a flexible container. Specifically, as provided in certain aspects of the present disclosure, the reservoir provides a consistent amount of fluid to the ejection mechanism, regardless of the liquid level and the orientation of the device. In some aspects, an ampoule or reservoir in fluid communication with the ejection mechanism provides a consistent fluid flow rate to the rear surface of the ejection mechanism, such 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, which provides a consistent supply and delivery of fluid to the rear ejection surface of the ejection mechanism in a capillary fluid loading region. The ampoule provides attitude insensitivity to the ejection device and provides leak resistance when the ambient pressure decreases relative to the standard pressure at sea level. Thus, the combination of the ampoule, capillary plate, and ejection mechanism provides the device with reduced attitude and altitude sensitivity, enabling the delivery of a consistent volume of fluid.

Referring to Figure 8 , the device of the present disclosure ejects fluid in a direction 804 perpendicular to the direction of gravity 805. In one aspect of the present disclosure, the combination of ampoule 803 and fluid loading plate 802 provides a consistent fluid flow rate to ejection plate 801 as the attitude angle theta (θ) changes. For example, as the attitude angle increases, the combination continues to provide a consistent fluid flow rate. Thus, according to various aspects of the present disclosure, the device continues to dispense droplets along direction 804. In one aspect of the present disclosure, the attitude angle theta (θ) may increase or decrease arbitrarily while maintaining a consistent fluid flow rate to ejection plate 801. For example, the attitude angle theta (θ) may be greater than 45° or less than 45°. Thus, the attitude angle theta (θ) may be between 0 and 45° or between 45° and 90°. The attitude angle theta (θ) may also be 90°. The attitude angle theta (θ) may also be 180° or between 0 and 180°.

In certain embodiments according to the present invention, the container is a flexible container having a total volume _Vt , containing a volume of liquid _Vf and a volume of _gas Vgas, and having an expandable volume _Vr . In certain aspects, the expandable volume _Vr accommodates and accommodates the expansion of the _gas ΔVgas due to pressure changes without causing an increase in pressure within the container. Thus, during transport, for example, the expansion _ΔVgas does not cause the container to leak. Similarly, the expansion of aqueous fluids during freezing can be similarly accommodated.

The present invention discloses many embodiments. This disclosure foresees that any feature of one embodiment can be combined with one or more features of other embodiments. For example, any one of the ejection mechanism or the capillary plate can be used in combination with any one of the container and the housing or housing features, such as a cover, support, shelf, lamp, seal and gasket, filling mechanism, or alignment mechanism. This disclosure also foresees other variations of any element in any embodiment within the scope of conventional technology. Such variations include the choice of materials, coatings, or manufacturing methods. Other manufacturing methods known in the art and not explicitly listed herein can be used to manufacture, test, repair, or maintain the device.

Example 1: Measurement of differential pressure leakage

Figure 9 shows an assembly that allows the assembly of a container, a fluid loading plate, and an ejection device to test for leakage when pressure is reduced. The fluid-filled container is mounted on a leak pressure test device, which consists of an ampoule holding mount (1) and a fluid loading plate (2) that delivers fluid behind an ejection plate (3). The leak pressure test device is placed in a vacuum chamber that is pumped by a mechanical pump suitable for obtaining 2.75 psi. At this pressure (2.75 psi), the measured pressure difference between STP (13.23 psi) and the lowest measurable leak pressure (2.75 psi) is 10.5 psi or 72.3 kPa. Leakage at this pressure is equivalent to the pressure difference encountered when moving from sea level to 31,000 feet. Figure 9 also shows an aspect of a container where V _r is greater than zero. Thus, the container provides for expansion of the gas inside the vacuum chamber when the external pressure is reduced. Changes in V _r can affect the leak pressure.

Table 3 provides leakage pressure test results for a flexible container having a depth of 12 mm (eg, depth 607 in FIG. 6B ) through a 40 μm hole.

Table 3: Leakage pressure test of 12mm deep flexible container through 40μm hole

Test number Filling percentage (%) Air volume percentage 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 leakage pressure test results of a 20 mm deep flexible container through a 20 μm hole.

Table 4: Leakage pressure test of 20mm deep flexible container through 20μm hole

Test number Air volume percentage Starting pressure (psi) Leakage pressure (psi) Delta P(psi) Delta P(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 leakage pressure test results of a 20 mm deep flexible container through a 40 μm hole.

Table 5: Leakage pressure test of 20mm deep flexible container through 40μm hole

Test number Air volume percentage Starting pressure (psi) Leakage pressure (psi) Delta P(psi) Delta P(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 leakage pressure test results of a 20 mm deep rigid container through a 40 μm hole.

Table 6: Leakage pressure test of rigid container through 40μm hole

Test number Air volume percentage Starting pressure (psi) Leakage pressure (psi) Delta P(psi) Delta P(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

Figure 10 shows the results of container expansion due to the pressure equalization mechanism. As tested in Example 1 and provided in Table 4, when the pressure is reduced, the gas expands, resulting in the contracted volume _Vrexpanding . As _Vgas approaches the total volume _VΔT , the device's tendency to leak increases. Small volumes of air are generally associated with lower leak point pressures. deltaP represents the pressure at which the assembly begins to leak.

FIG11 graphically illustrates the results of leakage pressure tests for various embodiments of the present disclosure. As shown, the rigid reservoir leaked at low differential pressures, regardless of the air volume percentage (e.g., V _air /V _t ). The 12 mm deep container (ampoule) required a high differential pressure to initiate leakage, with the highest pressure observed being approximately 25 μm for an air volume of approximately 12%. The 20 mm deep container, with either 40 × 160 μm pores or 20 × 40 μm pores, required the highest differential pressure to induce leakage. The number and size of pores did not differ across these embodiments.

Example 2: Measurement of mass loss over time :

Figure 12 shows the mass loss of the ampoule (reservoir) over time to determine the storage capacity of the ampoule (reservoir) of the present disclosure. A series of reservoirs were stored for 72 days and the amount of mass was determined. A total volume of 3.5 ml escaped a total of 50 μl of volume during this time period.

Test 3. Measurement of injection volume at different attitude angles:

Figure 13 shows the ejection volume at different attitude angles over the frequency range for a piezoelectric ejection device with either a rigid or flexible reservoir. The flexible ampoule structure provides more consistent ejection volume over a wider frequency range and fill level.

Although various reservoir embodiments have been described above by way of illustration and example, it will be understood by those skilled in the art that various changes and modifications may be made within the spirit and scope of the present application. The reservoir used herein may be any object suitable for holding a fluid. For example, the reservoir may be made of any suitable material capable of accommodating a fluid. The reservoir of the present disclosure may be rigid or flexible, and the reservoir of the present disclosure may also be shrinkable. Shrinkable as used herein means that the reservoir can achieve a reduction in the available volume by squeezing, folding, extruding, compressing, vacuuming or other operations, so that the total volume enclosed after shrinkage is less than the volume that can be enclosed in a non-shrinkable container. The reservoir may be made of any suitable material that can be formed into a volume capable of holding a certain volume of fluid. Suitable materials, for example, may be flexible or rigid and may be formable or preformed. The reservoir used herein may, for example, be formed of a film.

In other aspects, the fluid loading plate of the present disclosure can be integrated into a spray device, between a reservoir and a spray mechanism. In certain embodiments, the spray device can be used to deliver a fluid to a patient's eye and can include a housing, a reservoir disposed within the housing for receiving a volume of fluid, the reservoir being in fluid communication with the fluid loading plate, and the fluid loading plate being in fluid communication with the spray mechanism, such that the fluid loading plate provides the fluid to a rear spray surface of the spray mechanism, wherein the spray mechanism is configured to spray a stream of fluid droplets. The spray mechanism can be configured to spray a stream of droplets having an average droplet diameter greater than 15 microns, the droplet stream being entrained with a small amount of airflow such that the droplet stream is deposited on the patient's eye during use.

In certain embodiments, the ejection mechanism may include an ejection plate and a piezoelectric actuator; the ejection plate including a plurality of openings formed through its thickness; the piezoelectric actuator operable to oscillate the ejection plate at a frequency to generate a directed stream of droplets. In certain aspects, the ejection plate may be formed from a high modulus polymeric material.

In some embodiments, the piezoelectric actuators are coupled to the perimeter of the ejector plate to prevent obstruction of the plurality of openings in the ejector plate. The plurality of openings in the ejector plate can be arranged in a central region of the plate that is not covered by the piezoelectric actuators. In some embodiments, the three-dimensional geometry and shape of the openings (including orifice diameter and capillary length) and their spatial arrangement on the ejector plate can be controlled to optimize the generation of a directed stream of droplets.

For example, the fluid loading plate can be integrated into a jetting device or jetting assembly, or configured to interface with a jetting mechanism such as disclosed in U.S. Application No. 61/591,786, filed January 27, 2012, entitled “High Modulus Polymer Jetting Mechanism, Jetting Device, and Method of Use”; U.S. Application No. 61/569,739, filed December 12, 2011, entitled “Jetting Mechanism, Jetting Device, and Method of Use”; and U.S. Application No. 13/184,484, filed July 15, 2011, entitled “Droplet Generation Device,” the entire contents of which are incorporated herein by reference.

Numerous embodiments and implementations of the present invention are disclosed herein. This disclosure contemplates that any feature of one embodiment can be combined with features of one or more other embodiments. For example, any of the spray mechanisms or reservoirs can be used in combination with a fluid loading plate and any of the housings or housing features discussed in the incorporated references, such as covers, supports, shelves, lights, seals and gaskets, filling mechanisms, or alignment mechanisms. This disclosure also contemplates other variations of any element in any aspect of this disclosure that fall within the conventional art. Such variations include selection of materials, coatings, or manufacturing methods.

14A-14C , in one embodiment, a fluid loading plate may include a capillary plate 1400 including a fluid reservoir interface 1402, a jetting 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 No. 13/184,484, filed July 15, 2011, entitled “Droplet Generation Device,” the entire contents of which are incorporated herein by reference.

In addition, the capillary plate 1400 can selectively include a fastening clip 1412 positioned on the housing mating ring 1410 to secure the capillary plate 1400 to the reservoir housing (not shown). Although exemplary clip configurations and positions are shown, different embodiments and positions can be envisioned, and these are all within the scope of this disclosure. The capillary plate 1400 can also include a puncture protrusion 1414 positioned on the fluid reservoir interface 1402 to facilitate opening various reservoir housing configurations (not shown). Moreover, although exemplary puncture protrusions and positions are shown, different embodiments and positions can be envisioned, and these are all within the scope of this disclosure. For example, the size and shape of the puncture protrusion can be designed to avoid obstructing fluid from flowing through the one or more fluid openings 1406.

15A-15C , in certain embodiments, the ejection mechanism interface 1502 of the capillary plate 1500 is positioned parallel to the rear ejection surface 1506 of the ejection mechanism 1504, thereby forming a space 1508 between the capillary plate and the ejection mechanism and generating a fluid flow 1510 between the capillary plate 1500 and the ejection mechanism 1504 in a capillary fluid loading region 1512 on the rear ejection surface of the ejection mechanism. This fluid flow 1510 allows the capillary plate 1500 to supply fluid to the rear ejection surface 1506 of the ejection plate 1514 of the ejection mechanism. The configuration of the capillary plate provides consistent fluid supply and delivery in the capillary fluid loading region on the rear ejection surface 1506 of the ejection plate 1514. As a result, the ejection mechanism generates droplets of consistent volume, regardless of the fluid level and device orientation (i.e., posture).

16A and 16B , the fluid loading between the capillary plate and the parallel surfaces of the ejection plate depends on the capillary plate separation distance d. As shown in FIG16A , a plate separation of at most 1 mm provides sufficient fluid loading (liquid height) in the capillary fluid loading region. In certain embodiments, a capillary plate-to-ejection mechanism separation distance of between about 0.2 mm and about 0.5 mm, more particularly between about 0.2 mm and about 0.4 mm, or particularly 0.3 mm, can be used.

Without being limited by theory, the general formula for capillary rise between two parallel surfaces is as follows:

in:

h is the liquid height;

γ _1v is the surface tension of the liquid vapor in contact with the surface;

θ is the contact angle between the fluid and the surface;

ρ is the density difference between the fluid and the vapor;

g is the acceleration due to gravity; and

d is the separation distance between the surfaces.

The fluid loading plate can be formed from any material suitable for the intended application. For example, in ophthalmic applications, any material suitable for ocular treatment applications can be used, such as a polymeric material that does not chemically react with or absorb the fluid to be delivered. In certain embodiments, the surface of the fluid loading plate exposed to the fluid to be delivered can be formed from a material that provides desired surface properties, including, for example, hydrophilicity/hydrophobicity, surface energy, etc., to promote wicking and capillary action between parallel surfaces. See, for example, U.S. Patent No. 5,200,248 to Thompson et al., which is incorporated herein by reference.

In certain embodiments, the fluid loading plate can be formed from a single material, such as the material of the capillary plate embodiment. In other aspects, the fluid loading plate can be a composite of more than one material, wherein the surface exposed to the fluid to be transported is selected to have the desired surface properties. For example, the capillary plate can be injection molded or thermoformed as a single piece or as multiple separate pieces. If desired, one or more reservoir mating surfaces can be formed separately or as a single piece with the other components of the capillary plate. Examples, without limitation, include polyamides, including nylons such as nylon-6, HDPE, polyesters, copolyesters, polypropylene, and other suitable pharmaceutical-grade hydrophilic polymers or polymeric structures.

The size and shape of the fluid loading plate can be designed in any suitable manner to interface with the desired ejection mechanism, thereby providing fluid to the ejection mechanism interface between the capillary plate and the rear ejection surface of the ejection mechanism and forming a suitable capillary fluid loading area at the ejection mechanism interface. Referring to Figures 17A and 17B , one embodiment of a capillary plate 1700 is shown. However, the dimensions shown in Figures 17A and 17B are for illustrative purposes only and the present disclosure is not limited thereto. By way of example, the capillary plate 1700 can be substantially square in shape with an edge length of approximately 25 mm. However, other shapes are also contemplated, including substantially circular configurations. Four separate fluid openings 1706 are shown around an annular radius of approximately 4.70 mm, each having an opening width of approximately 2.50 mm and spaced approximately 2 mm apart. The thickness of the fluid flow portion of the capillary plate 1700 (i.e., the portion of the capillary plate 1700 including the fluid openings 1706) can be approximately 0.30 mm, and the thickness of the housing mating ring 1710 of the capillary plate 1700 can be approximately 2 mm. The piercing protrusions 1714 may be, for example, approximately 1.62 mm across and approximately 1.35 mm in length to provide the desired protrusion performance while still allowing fluid flow.

To aid in understanding the present invention, Figures 18-22 illustrate various effects of the use of the fluid loading plate described herein on the performance of the ejection device. The experiments described herein should not be construed as limiting the scope of the present invention, and variations of the present invention within the knowledge of those skilled in the art, now known or later developed, are considered to fall within the scope of the present invention as described herein and hereinafter claimed.

More specifically, Figure 18 illustrates the effect of a capillary plate on the resonant frequency and mass deposition of water using a 160-micron thick NiCo jet plate with 25- and 40-micron holes, showing a downward shift in frequency. Figure 19 shows that as the density (and therefore mass) of the fluid in the resonant system (e.g., the capillary region behind the jet plate) increases, the resonant frequency shifts downward. Figure 20 illustrates the frequency shift associated with a capillary plate used when delivering various fluids using a 160-micron thick NiCo jet plate with 25- and 40-micron holes. Figure 21 shows that both the resonant frequency and amplitude of the resonant structure decrease as the density (ρ) and viscosity (η) of the fluid in the resonant system increase. For example, and not necessarily referring to the specific values shown in the curves of Figure 21, the densities and viscosities of water, ethanol, and propylene glycol are given in the table below the curves. As shown in Figures 18-21, the presence of the capillary plate causes an overall shift in the resonant frequency to lower frequencies. The shift in the liquid jet volume is due to the increase in density and viscosity (for water, ethanol, and propylene glycol).

Figure 22 illustrates the orientation insensitivity of a sprayer including a capillary plate. As shown, the delivered volume (mass) is relatively insensitive to the orientation of the sprayer. This ensures consistent delivery and supply of fluid behind the spray plate. Consequently, droplets of consistent volume are formed and ejected by the spray mechanism, regardless of the fluid level and device orientation.

In other embodiments, the fluid loading plate may include a piercing plate fluid output system, also referred to as a capillary plate/piercing plate fluid delivery system, configured to deliver fluid from a reservoir to a fluid holding area behind the ejection mechanism to deliver a directed stream of droplets via piezoelectric ejection. Without being limited by theory, the piercing plate system may utilize one or more of hydrostatic pressure, capillary pressure, geometric pressure gradient (Venturi effect), and exhaust.

Figures 23-27 illustrate one embodiment of a piercing plate fluid delivery system and its operation. Figures 23A and 23B show front and rear views, respectively, of a jetting mechanism 2300 with five riser holes 2302. As shown in the front view of Figure 23C and the rear view of Figure 23D, the piercing plate fluid delivery system can include a capillary plate portion comprising: a fluid retention region located between the piercing plate/capillary plate fluid delivery system and the rear surface of the jetting mechanism, for directing fluid to the jetting mechanism via one or more mechanisms including capillary action; and at least one hollow puncture needle for transferring fluid from a reservoir to the fluid retention region. In this embodiment, six hollow puncture needles 2306 extend from the rear surface of the capillary plate/piercing plate, with channels extending through the needles to the front of the capillary plate 2304, as indicated by holes 2308. Needle 2306 is surrounded by walls 2310 that define a receptacle for a fitting 2312 (shown in FIG. 23E with a self-sealing silicone sealing element 2314 seated in fitting 2312).

Initially, a fluid-containing reservoir or ampoule 2316 (the two terms are used interchangeably herein) is connected to the fitting and is in fluid communication with an auxiliary reservoir defined by the fitting and silicone sealing element 2314. Capillary plate 2304 is then attached to and in fluid communication with the ejection mechanism 2300. However, prior to use, the piercing plate and ejection mechanism 2300 can be disconnected from the fitting 2312 and reservoir 2316 to prevent fluid exchange. In the initial stage of connection, hollow piercing needle 2302, shown behind the piercing plate image in FIG. 23D , is partially inserted into a self-sealing silicone piercing gasket or grommet 2314 resting within the fitting 2312. The auxiliary reservoir formed in the fitting 2312 is always open to the fluid in the primary ampoule/reservoir 2316. However, at this stage, fluid that has entered the auxiliary reservoir of the fitting 2312 from the primary reservoir will not enter the hollow puncture needle 2306 due to the barrier created by the self-sealing silicone gasket material 2314.

Puncture is achieved by forcing the puncture plate needle through the silicone gasket, which in turn pushes the puncture plate needle through gasket 2314 and into the fluid-filled fitting. This can occur, for example, when the fitting snaps into receptacle 2310 of puncture plate 2304 (indicated by an audible click). Because silicone gasket 2314 is a compliant, self-sealing material, it maintains the seal after puncture. Immediately after puncture, fluid is initially transferred from the reservoir/container through the hollow puncture needle due to a combination of static pressure, the fitting holding/reservoir volume, and fluidic reaction forces from the initial puncture, which drive fluid flow through the capillary channel defined by the hollow needle and the channels in the capillary plate/puncture plate.

Once the fluid flows through the capillary channel, it relies on the surface tension effect to overcome the force of gravity to feed the fluid. As the fluid rises, it removes air from the system by pushing it out from the front of the injection opening or hole. The capillary rise hole 2301 is located on the injection plate 2320 of the injection mechanism above the piezoelectric element 2322, and serves to relieve the pressure of the air in the system. Without these capillary rise holes 2302, the system will be closed in the area above the injection opening. Due to the accumulation of air pressure, the fluid will stop rising, and the air pressure will eventually balance with the capillary pressure. In order to achieve a complete rise, all air needs to be pushed out of the system. The capillary rise hole 2302 (from the rear view of Figure 25A and the front view of Figure 25B) acts as a pressure balance hole. It is set and has an appropriate size (to prevent fluid leakage) to allow the fluid to rise completely, thereby ensuring that no (or very little) air remains in the system. The front view of Figure 24A and the rear view of Figure 24B show the assembled injection assembly.

Figure 26 illustrates a schematic diagram of fluid flow through the piercing plate system after the silicone gasket has been fully punctured. Liquid passes through the piercing system and flows upward along the capillary plate cavity 2600, pushing air out of the ejection openings or holes 2602 and the capillary riser holes 2302. Referring to Figures 23C and 23D , the piercing plate/capillary plate 2304 is shown with six needles having an inner diameter (ID) of 650 microns and an outer diameter (OD) of 1 mm. The number of needles can be as few as one or include multiple needles, for example, eight needles with an ID size range of 500 microns to 3 mm and an OD size range of 600 microns to 4 mm. The riser holes shown in Figures 25A and 25B can also vary from those shown. While the figure shows five riser holes with a diameter of 20 microns, the number of holes can be as few as one or more, for example, eight holes with diameters ranging from 10 microns to 50 microns.

44-46 , the puncture plate can be designed with an elongated needle puncture system. Such a structure can be used, for example, to connect to certain configurations of reservoir structures, such as a vertical rectangular low tensile stress (LTS) reservoir (i.e., an IV bag structure).

The puncture plate can be constructed of any suitable material such as described and illustrated herein. As non-limiting examples, the puncture plate can be constructed of the following materials: liquid crystal polymer "LCP" (glass filled 0-30%); nylon 6; nylon 6,6; polycarbonate; polyetherimide (Ultem); polyetheretherketone (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 nanocrystalline cobalt phosphate; nanocrystalline 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.

While various embodiments have been described above by way of illustration and example, it will be apparent to those skilled in the art that various changes and modifications may be made within the spirit and scope of the present application. While the terms "capillary plate" and "piercing plate" are used to describe various embodiments, it will be understood that the descriptions are applicable to any fluid loading plate, and need not necessarily be in the form of a plate, but may have any configuration suitable for directing liquid from a reservoir to an ejection mechanism.

The reservoir used herein can be any object suitable for holding a fluid. For example, the reservoir can be made of any suitable material capable of holding a fluid. The reservoir disclosed herein can be rigid or flexible, and the reservoir disclosed herein can also be shrinkable. Shrinkable as used herein means that the reservoir can achieve a reduction in the available volume by squeezing, folding, extruding, compressing, vacuuming or other operations, so that the total volume enclosed after shrinkage is less than the volume that can be enclosed in a non-shrinkable container. The reservoir can be made of any suitable material that can be formed into a volume capable of holding a certain volume of fluid. Suitable materials, for example, can be flexible or rigid and can be formable or preformed. The reservoir used herein can be formed, for example, by a film.

Additionally, the reservoir may be in fluid communication with the 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.

In some aspects, the reservoirs of the systems of the present disclosure can be configured as low tensile stress or "LTS" reservoirs. The LTS reservoirs of the present disclosure are generally designed to minimize or eliminate positive pressures imposed by the reservoir on the system due to memory effects, crease formation, and unbiased contraction. These gradients can cause recovery of the reservoir (volume expansion) which imposes a net pressure differential on the system, drawing air into the system through the injection openings and causing potential failure. In certain aspects, to correct for the pressure differential, the LTS reservoir is configured to be biased to contract to a low, flat resting position, which reduces or eliminates the potential for crease formation.

The LTS reservoir is also constructed of a thin, flexible (low tensile stress) material that is resistant to volume expansion, rebound, and memory effects without compromising inertness and evaporation resistance (see Table 7). As explained above and as explained in further detail below, the LTS reservoir can be constructed in any suitable manner, including, for example, RF welding, blow-fill-seal processes, form-fill-seal processes, and the like.

Without being limited by theory, to assist in transporting fluid from the fluid holding/reservoir through capillary channels during operation, the LTS reservoir can also be geometrically designed to accelerate the fluid by combining the continuity principle shown in FIG. 27 and the Venturi effect described below in the Bernoulli equation for incompressible flow shown in FIG. 28 .

Moreover, without being limited by theory, Figure 28 describes that the reservoir geometry is changed into a convergent profile (large area to small area), and when the fluid moves downward along the reservoir, the speed increase caused by the continuity principle causes the fluid to accelerate. According to Bernoulli's equation, the speed increase caused by the continuity principle will cause a reduction in the pressure in the speed increase area (to maintain continuity). This change in pressure has established a gradient, which helps the fluid to be transported to the accessories and pass through the puncture needle/capillary tube. This convergence area change causes the speed increase, which is called the Venturi effect.

Figure 29 shows that static pressure drives fluid from the LTS ampoule into the fitting and flows through the puncture needle into the fluid reservoir. To maximize static pressure, the ampoule needs to be oriented in an upright position because static pressure is related to height.

Table 7

FIG30 shows schematic diagrams of self-contracting, non-fluid-accelerating LTS reservoir geometries. The vertical rectangle represents a reservoir designed to collapse along its smallest dimension (not shown) (similar to an IV bag). The vertical rectangular reservoir structure is oriented upright to maximize height, which maximizes static pressure. The second image shown is a flattened rectangle that acts similarly to the vertical rectangle, but does not maximize static pressure. The third image shows a square reservoir configuration. FIG31 shows schematic diagrams of fluid-accelerating LTS reservoir geometries.

Referring to Figures 32A and 32B , two examples of circular fluid acceleration LTS reservoirs are shown, one constructed using a blow-fill-seal process (Figure 32A) and the other constructed using RF welding (Figure 32B). As shown, when the reservoir is biased to contract along its smallest dimension (thickness in Figures 32A and 32B), the amount of contraction can be increased. This contraction can significantly prevent crease formation in the reservoir during operation. For vertical reservoir configurations, crease formation can be further prevented during operation of the spray device by enclosing the reservoir in a housing that prevents the reservoir from folding in on itself when emptying. Supporting data for the performance of these reservoirs is provided herein.

Figure 33 shows a piercing plate 3300 and a blow-fill-seal reservoir configuration with the accessories removed. In certain embodiments, when using materials for self-sealing reservoirs, the lower region of the reservoir can be pierced directly. The filling compartment, shown at the bottom of Figure 33, is designed to allow for maximum fluid filling of the auxiliary reservoir. Figures 34A and 34B illustrate alternative piercing mechanisms for blow-fill-seal piercing plate assemblies.

FIG34A shows a side profile of another embodiment of a blow-fill-seal reservoir puncture plate assembly. FIG34A shows a reinforcement mechanism in the form of a plastic housing 3400 that assists in needle puncture of a blow-fill-seal reservoir when the blow-fill-seal reservoir is constructed of a self-sealing material. The right-hand diagram ( FIG34B ) shows a configuration in which the blow-fill-seal reservoir does not self-seal upon puncture and must be connected to an accessory in the same manner as shown in FIG22 and FIG23 . As shown in FIG34B , the needle must pass through the silicone gasket into the area indicated as “Needle puncture here.”

In other embodiments of the present disclosure, Figure 35 shows a geometry that is biased to collapse in a manner that prevents crease formation. The ejection and pull-down processes of these ampoules and their results are disclosed in the following examples.

Example 3: Measurement of downspout and downpull

Static pull-down tests were conducted to determine the amount of negative pressure applied to the system when removing fluid using various reservoir configurations, such as those shown in Figures 30-35. The experimental setup for this test is shown in Figures 36-37. The experimental procedure was as follows: the reservoir was attached to a water column tubing, which was connected to a vacuum regulator, which was connected to a mechanical pump used to extract fluid from the reservoir or ampoule.

Mass deposition tests are performed to determine the mass ejected by the device at a given frequency or frequencies (mass deposition scans). Assuming that some frequencies have very low per-shot masses, which are within the minimum tolerance of the mass-measuring scale, the number of shots at each frequency is varied across samples and then averaged to determine the per-shot volume at each frequency. This also helps eliminate some measurement errors. (The scale used can be measured to tenths of a milligram.) These devices are operated by a laptop computer connected to the scale, a function generator, and an oscilloscope. The ejected mass and electrical characteristics during the ejection (phase and amplitude of voltage and current, and impedance) are recorded. The device is controlled by a LabVIEW program compiled into a LabVIEW executable and run by the laptop. This program allows the user to select the laboratory equipment in the device, the communication port for the scale, and the Universal Serial Bus (USB) identifier for the oscilloscope and function generator. The user also defines the test parameters: voltage, waveform, start frequency, end frequency, step size, number of shots, time between shots, and duration of the ejection. The program communicates with a function generator, sets the frequency and number of injection cycles to achieve the appropriate injection duration, and configures the oscilloscope for a single acquisition from the trigger (voltage probe). The program then instructs the function generator to trigger the waveform. The signal is sent to an operational amplifier, which amplifies it to the appropriate voltage, which is then applied to the device (0 to ±90V). Voltage and current probes are attached to the device to verify the voltage and read the current. A delay is built into the program to allow for calibration time (approximately 8 seconds) before the mass is read from the scale, allowing for determination of each injection mass. The scale is zeroed at the start of the test and at every half-gram. At every half-gram, the scale is reset to zero and the reservoir attached to the device is refilled. This ensures that the device does not run out of fluid and reduces fluid evaporation calibration errors by limiting the amount of fluid that can be evaporated to a scale of 0.5g. The scale is read after each user-defined set of injections (typically 5). The mass of the shot is determined by subtracting the previous value from the current scale reading, thereby accommodating the time required to zero the scale between sets of shots.

FIG38 shows the spray-down performance (24% of the fluid) of a control reservoir that is quite rigid and contracts to form numerous creases that result in negative pressure buildup. FIG39 shows the results for a typical LTS reservoir of the present disclosure, as shown in FIG35 . The results demonstrate that spray-down performance improves with a geometry that creates a biased, controlled contraction, along with the selection of flexible materials and appropriate material caps. The graph shows that most samples (multiple tests of the same ampoule type with the same thickness) allow 80% or more of the fluid to be removed, with a few outliers that remove much less fluid, but still better than the creased control reservoir of FIG38 .

FIG40 illustrates the spray-down performance of two independent runs of one embodiment of a circular LTS reservoir. This reservoir demonstrated significant improvement, with over 90% of the fluid removed. FIG41 illustrates the pull-down of a selected circular LTS ampoule configuration from FIG35. These graphs demonstrate the significant improvement in the negative pressure generated by the system when using a circular LTS reservoir. Without being limited by theory, FIG42 illustrates the mechanisms involved in inverted spraying using a circular LTS reservoir, and FIG43 illustrates actual spray-down performance results for an embodiment of the LTS reservoir of the present disclosure, sprayed with the entire puncture system facing downward.

According to other aspects of the present disclosure, the fluid loading plate can be designed with different needle puncture systems, as shown in Figures 44 to 46. These structures can be used to connect to reservoir structures, such as vertical rectangular LTS reservoirs (ie, IV bag-type structures).

As described above, the system's spray plate can include capillary rise holes to provide additional air pressure relief above the active area (spray opening). This additional air pressure relief can allow for full capillary rise of the fluid, which in turn allows the reservoir/storage chamber to be completely filled with fluid. According to certain aspects of the present invention, it was unexpectedly discovered that if these holes are not placed above the spray opening, the device will not operate effectively once the fluid falls below the level of the spray opening (potentially allowing outdoor air to flow into the system during operation).

When constructing capillary riser holes, it is important to optimize the pore size. These holes are preferably large enough to allow a reasonable discharge rate so that the capillary rise is not too slow, and are preferably small enough so that the fluid does not leak easily when the holes are aligned in the direction of gravity. The leakage of fluid from the riser hole is related to the size of the hole and the surface tension of the fluid. Due to the effect of the strength of the fluid meniscus formed by the fluid in the riser hole (which is related to the surface tension of the fluid), the resistance to leakage of the fluid with a large surface tension increases, which forms a barrier to prevent fluid leakage and air inflow. When the static pressure of the reservoir (ampoule) overcomes the surface tension in the riser hole cavity (Figure 47), the barrier is destroyed.

The fluid loading plate of the present disclosure utilizes capillary action to transport fluid to a location behind the active area of the piezoelectric grid for ejection, for example, as discussed previously with respect to FIG. Capillary rise is a function of the surface tension of the fluid, the surface energy (contact angle) of the surface in contact with the fluid, and the separation distance of the fluid in contact. To achieve optimal performance of the puncture plate system, hydrophilic materials (contact angle between the fluid and the surface is less than 90 degrees) are preferably used for the capillary channels. Furthermore, the material is preferably biocompatible and chemically inert. The separation distance of the surfaces containing the fluid rise is preferably modulated to ensure that the capillary width is much smaller than the capillary length of the fluid, thereby ensuring that surface forces are more dominant than gravity. As shown in FIG. 27 , capillary rise in the system occurs between the puncture plate (capillary plate + needle) and the ejection plate (which includes the active area or opening (piezoelectric grid)).

Example 4: Measurement of capillary rise

Figures 48-49 illustrate the capillary pressure of half a drop of water of various sizes and the exemplary ophthalmic drug latanoprost. Thus, the spacing between the fluid loading plate and the ejection plate is an important parameter for optimizing capillary rise to a certain height above the ejection opening. The spacing between the plates (as well as the viscosity and surface tension of the fluid) also affects the time it takes for the fluid to rise to its final height. As shown in Figure 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 system disclosed herein is not limited thereto, and capillary distances (the spacing between the capillary plate and the ejection plate) of 2.7 mm to 1.7 mm and less than 1.7 mm can be used to achieve greater capillary rise. In certain embodiments, the distance used for the puncture plate system can be between 50 and 200 microns.

In this regard, Figure 51 shows the capillary rise of saline in capillary channels made of different materials. Figure 52 shows the capillary rise between the capillary plate and the puncture plate without the capillary rise holes 2302. In comparison, the capillary rise shown in Figure 53 is better, which shows the rise when the capillary rise holes are included.

Further, Tables 8-10 below show capillary rise data for capillary passages between the fluid loading plate and the rear surface of the ejection mechanism using different numbers and sizes of capillary rise holes 2302. Table 8 shows rise time data for water, Table 9 shows rise time data for latanoprost at room temperature, and Table 10 shows rise time data for latanoprost frozen to 38°F. Although some results must be rejected as invalid due to defects in the capillary rise holes (invalid, no fill through the effective area, blank entries) or show asymmetric fill (marked with an asterisk), the results demonstrate an advantage in rise time when using five capillary holes and show faster rise times as the capillary hole size increases.

1 hole 3 holes 5 holes 5μm Test 1 395s 200s invalid Test 2 370s 155s* invalid 10μm Test 1 No filling through the effective area 70s 23s Test 2 No filling through the effective area 54s 25s 20μm Test 1 22s 8s 6s Test 2 22s 10s 5.5s 50μm Test 1 3s 2s invalid Test 2 3.5s 1.6s Invalid

Table 8

1 hole 3 holes 5 holes 10μm Test 1 No filling through the effective area 60s 26s Test 2 68s* 32s 20μm Test 1 11s 8s 6s Test 2 8s 11s 5s

Table 9

1 hole 3 holes 5 holes 10μm Test 1 25s 28s* Test 2 42s 44s* 20μm Test 1 7s 10s 3.5s Test 2 10s 7s 4.5s

Table 10

Example 5: Fluid Leakage Testing for Selecting Eyedrop and Rising Orifice Sizes

To test for fluid leakage through the capillary riser or vent of one embodiment of the test device, a static pressure test assembly as shown in FIG54 was constructed. The injection plate with the riser and injection assembly was placed below the liquid column defined by the pipe. The test fluid was filled into the pipe directly above the injection plate, and the height of the liquid column was carefully monitored. When the fluid reached the test height (static pressure), at which the fluid was higher than the injection opening, resulting in leakage through the riser and injection opening, the height (equivalent to the pressure value) was recorded and used as a design parameter for optimizing the liftoff dimensions. The results are shown in Tables 11-13 below.

Table 11

Table 12

Table 13

Although various embodiments have been described above by way of illustration and example, it will be apparent to those skilled in the art that various changes and modifications can be made within the spirit and scope of the present application.

As described above, droplets can be formed by a spray mechanism from a fluid contained in a reservoir that is coupled to the spray mechanism. The spray mechanism and reservoir together form a spray assembly that can be configured to be removable to allow the assembly to be discarded or reused. Thus, the components can be removably packaged in a housing, such as the upper section 200 of the housing 202 shown in Figure 2. The housing itself can therefore be disposable, or reusable by being configured to receive a removable spray mechanism. The housing can be handheld, miniaturized, or configured to be coupled to a base and can be adapted to communicate with other devices. The housing can be color-coded or configured to be easily identifiable.

While specific embodiments of an injection mechanism are discussed below, this does not limit the configuration or use of the injection mechanism, nor does it limit the features that may be added to the injection device. In some embodiments, the injection device may include lighting, alignment, temperature control, diagnostics, or other features. Other embodiments may be adapted as part of a larger network of interconnected, interacting devices for patient care and treatment. The injection mechanism may, for example, be a piezoelectric actuator as described herein.

55A-55C , jetting assembly 5500 may include a jetting mechanism 5501 and a reservoir 5520. Jetting mechanism 5501 may include a jetting plate 5502 coupled to a generator plate 5532, which may include one or more openings or apertures 5526. Jetting plate 5502 and generator plate 5532 may be activated by a piezoelectric actuator 5504, which vibrates to transport fluid 5510 contained in reservoir 5520 in the form of ejected droplets 5512 in a direction 5514. Furthermore, the fluid may be an ophthalmic fluid that is ejected toward an eye 5516 of an adult, child, or animal. Furthermore, the fluid may contain an active pharmaceutical ingredient for treating a human or animal ailment, condition, or disease. In some embodiments, the generator plate can be formed of a high modulus polymer generator plate, for example, formed of a material selected from the group consisting of ultra-high molecular weight polyethylene (UHMWPE), polyimide, polyether ether ketone (PEEK), polyvinylidene fluoride (PVDF), and polyetherimide. High modulus polymer generator plates are included.

As shown in FIG55A , the injection plate 5502 is positioned in front of a reservoir 5520 containing a fluid 5510. The rear surface 5525 of the injection plate 5502 is positioned adjacent to the fluid 5510. In this embodiment, the reservoir 5520 has an open end 5538 adjacent to the surface 5525 and attached to the opening 5526. In this embodiment, the surface 5525 seals the fluid 5510 in the reservoir 5520. The reservoir 5520 can be coupled to the injection plate 5502 at a peripheral region 5546 of the surface 5525 of the injection plate 5502 using a suitable seal or coupling. For example, the reservoir 5520 can be coupled via an O-ring 5548a. Although not shown, more than one O-ring can be used. As is known in the art, the O-ring can have any suitable cross-sectional shape. Other couplings, such as polymer seals, ceramic seals, or metal seals, can also be used. Alternatively, a coupling may be omitted entirely, and the reservoir 5520 may be integrally connected to the injection plate 5502, such as by welding or integral molding. In such an embodiment, an opening (not shown) may be provided through which fluid is supplied to the reservoir 5520. In embodiments where a coupling is used, the coupling may be made removable, such as by providing a hinged connection between the reservoir 5520 and the injection plate 5502, or by providing a flexible or non-rigid connector, such as a polymer connector.

The reservoir 5520 can define a multi-part circumferential lip or wall 5550 that covers the injection plate 5502. In the embodiment of Figure 55A, the wall 5550 does not directly contact the injection plate 5502, but is coupled to the O-ring 5548a. Alternatively, the wall 5550 can be directly attached to the injection plate 5502. Conversely, the reservoir can also be directly attached to the injection plate 5502 without the wall 5550 at all.

The configuration of the reservoir, including shape and size, can be selected based on the amount of fluid 5510 to be stored and the geometry of the ejection plate 5502. Alternative forms of the reservoir include gravity-fed, wicking, or collapsible bladders (as described above, which accommodate the pressure differential). These reservoirs can be pre-filled, filled using a micropump, or can be configured to receive a replaceable cartridge. The micropump can fill the reservoir by pumping fluid into a collapsible or non-collapsed container or pumping fluid out of a container. The cartridge can include a container that is loaded into the reservoir. Alternatively, the cartridge itself can be coupled to a disposable jet assembly that is replaced after a specific number of discharges. Examples of reservoirs are shown in U.S. patent application Ser. No. 13/184,484, filed Jul. 15, 2011, the contents of which are incorporated herein by reference.

In some embodiments, the reservoir 5520 includes a plurality of through-holes 5542 (only one is shown in FIG55A ) to allow air to escape or enter the reservoir 5520 and to maintain the fluid 5510 in the reservoir at an appropriate external pressure. The through-holes 5542 have a relatively small diameter so that the fluid 5510 does not leak from the holes. Optionally, no openings are formed in the reservoir 5520, and at least a portion of the reservoir 5520, such as portion 5544 or the entirety, can be collapsible, for example, in the form of a sac, as described in more detail above. Thus, in some embodiments, the entire reservoir can be manufactured in the form of a flexible or collapsible sac. Therefore, when the fluid 5510 is ejected through the opening 5526, the reservoir 5520 changes its shape and volume to follow the changes in the amount of the fluid 5510 in the reservoir 5520.

In the embodiment of FIG55A, the ejection mechanism 5501 is activated by the vibration of a piezoelectric actuator 5504, which in this embodiment has a ring shape. Two electrodes 5506a and 5506b are formed on opposing surfaces 5536 and 5534 of the piezoelectric actuator 5504, which are parallel to the surface 5522 of the ejection plate 5502. Activating the piezoelectric actuator 5504 causes the ejection plate 5502 and the generator plate 5532 to vibrate. For ease of illustration, the ejection plate 5502 and the generator plate 5532 are shown lying flat in a common plane. However, as discussed in more detail below with respect to FIG55B-55D, the generator plate 5532 in this embodiment is attached to the surface of the ejection plate 5502. The electrodes 5506a and 5506b can be attached to the ejection plate or piezoelectric actuator in any known manner, including by adhesive affixation or other bonding methods. Alternatively, the piezoelectric actuator 5504 may be integrally molded onto the ejection plate 5502 in place. Wires or other conductive connectors may be used to effect the necessary electrical contact between the ejection plate 5502 and the electrodes 5506a, 5506b. Alternatively, the electrodes may be formed on the ejection plate 5502, possibly by plating or other deposition. For example, the electrodes are attached with the aid of a conductive adhesive 5528 applied between the electrode 5506a and the ejection plate 5502 to electrically contact the electrode 5506a with the ejection plate 5502. When a voltage is applied to the electrodes 5506a and 5506b, the piezoelectric actuator 5504 deflects the ejection plate 5502 and, in turn, the generator plate 5532, changing its shape to a more concave or more convex shape.

Therefore, when a voltage is applied to electrodes 5506a and 5506b, the piezoelectric actuator 5504 causes the ejector plate 5502 to flex, and similarly causes the generator plate 5532 to flex, alternating between a more concave and a more convex shape at the resonant frequency of the coupled ejector plate 5502 and generator plate 5532. The ejector plate 5502 and generator plate 5532 flexed at the resonant frequency by the piezoelectric actuator 5504 can amplify the displacement of the coupled ejector plate 5502 and generator plate 5532, thereby reducing the energy input required by the piezoelectric actuator. On the other hand, due to the inherent internal resistance of the annular belt/mesh, the resonant system of the coupled ejector plate 5502 and generator plate 5532 has a damping factor that limits this motion, preventing slippage and sudden failure.

A wide range of voltages corresponding to different piezoelectric materials is known in the art, but for example, a voltage difference between 5V and 60V, or between 30V and 60V, such as 40V or 60V, can be applied to the electrodes. When the direction of the voltage difference is opposite, such as -40 or -60, the plates will deflect in opposite directions. In this way, the piezoelectric actuator 5504 causes the ejection plate 5502 and the generation plate 5532 to oscillate, which constitutes a vibration that causes the fluid 5510 to form droplets 5512. When an AC voltage is applied to the electrodes 5506a and 5506b, the ejection plate 5502 and the generation plate 5532 oscillate, causing the fluid droplets 5512 to accumulate in the opening 5526 and eventually be ejected from the opening 5526 in a direction 5514 away from the reservoir 5520. The frequency and wavelength of the oscillations depend on many factors, including, but not limited to: the thickness, composition, and surface morphology of the ejection plate 5502, as well as its mechanical properties, including its stiffness; the properties of the generator plate 5532; the volume of the openings 5526; the number of openings 5526; the composition and structure of the piezoelectric actuator 5504; the piezoelectric actuation drive voltage, frequency, and waveform; the fluid viscosity; temperature, and other factors. These parameters can be adjusted or selected to produce the desired droplet stream. The frequency of droplet ejection also depends on many factors. In some embodiments, droplets 5512 are ejected at a frequency that is lower than the frequency of the pulses applied to the piezoelectric actuator 5504. For example, droplets 5512 are ejected every 1-1000 cycles of the ejection plate/generator plate vibration (which is the same frequency as the actuator 5504), and more particularly, every 8-12 cycles. In some embodiments, the generator plate comprises a high modulus polymer generator plate.

In one embodiment of the present disclosure, as shown in FIG55C , the ejector plate 5502 can be mounted symmetrically through optional mounting holes 5551 using a symmetrical mounting structure 5555. The symmetrical mounting structure can maximize the constant velocity surface area of the ejector plate 5502, suppress asymmetric wave modes, and mechanically match the piezoelectric material to low-order Bessel modes. In this embodiment, there are four mounting lugs 5555, as shown in FIG55C . In another embodiment, there may be eight mounting lugs 5555. In yet another embodiment, there may be 16 mounting lugs 5555.

In certain aspects, centrosymmetric mounting provides for the use of lead-free piezoelectric materials, such as BaTiO ₃ . In one embodiment of the present disclosure, resonant coupling of ejector plate 5502 with generation plate 5532 and with piezoelectric actuator 5504 provides for the use of piezoelectric materials with smaller displacements than industry standard piezoelectric materials.

According to certain embodiments of the present invention, referring to FIG55A , the jet plate 5502 can be a simple jet plate 5502 having an integrated spawning plate 5532 with a central region 5530 and an opening 5526. In other embodiments of the present disclosure (FIGS. 55B-55D), the jet plate 1602 can be a hybrid jet plate 1602 having coupled spawning plates 5532 with central regions 5530 and openings 5526. The first surface 5522 of the jet plate 5502 can be coupled to the spawning plate 5532. The jet plate 5502 can generally include a central open region 5552 configured to align with the spawning plate 5532. The spawning plate 5532 can then be coupled to the jet plate 5502 such that the central region 5530 of the spawning plate 5532 is aligned with the central open region 5552 of the jet plate 5502. The central region 5530 of the generation plate 5532 can generally include one or more openings or holes 5526, and alignment of the central open region 5552 of the ejection plate 5502 with the central region 5530 of the generation plate 5532 with the one or more openings 5526 allows communication through the one or more openings 5526. In some embodiments, the generation plate comprises a high modulus polymer generation plate.

In some embodiments, the central open area 5552 of the ejection plate 5502 can be smaller than the spawn plate 5532 to provide sufficient overlap of material to allow coupling of the ejection plate 5502 to the spawn plate 5532. However, in such embodiments, the central open area 5552 of the ejection plate 5502 should be sized and shaped so as not to interfere with or block the central area 5530 of the spawn plate 5532 (and thus, not to interfere with or block the one or more openings 5526). As non-limiting examples, the central open area 5552 of the ejection plate can be similar in shape to the spawn plate 5532 and can be sized to have an overlap of approximately 0.5 mm to approximately 4 mm, e.g., approximately 1 mm to approximately 4 mm, or approximately 1 mm to approximately 2 mm, etc., that effectively couples the spawn plate 5532 and the ejection plate 5502 (e.g., overlap on all sides). For example, the shape of the central open area 5552 of the ejection plate can be square, rectangular, circular, oval, etc., generally matching the shape of the generator plate 5532, and its dimensions are such that the central open area 5552 is, for example, about 0.5 mm to about 4 mm smaller in overall dimensions (i.e., the diameter of the circle is about 0.5 mm to about 4 mm smaller, the major and minor axes of the oval are about 0.5 mm to about 4 mm smaller, the side length of the square or rectangle is about 0.5 mm to about 4 mm smaller, etc.). In some embodiments, the generator plate comprises a high modulus polymer generator plate.

In addition to what is described herein, exemplary jetting mechanisms are disclosed in U.S. application Ser. No. 13/712,784, filed on Dec. 12, 2012, entitled “Jetting Mechanism, Apparatus, and Method of Use,” and U.S. application Ser. No. 13/712,857, filed on Dec. 12, 2012, entitled “High Modulus Polymer Jetting Mechanism, Jetting Apparatus, and Method of Use,” the entire contents of which are incorporated herein by reference.

Depending on the materials used, the generation plate 5532 can be coupled to the jet plate 5502 using any suitable means known in the art. Examples of coupling methods include: using adhesives and bonding materials, such as glues, epoxies, bonding agents, and adhesives such as loctite 409 or other suitable superglue; welding bonding methods, such as ultrasonic or thermosonic bonding; thermal bonding; diffusion bonding; or press fitting, among others.

Surface 5522 of jet plate 5502 may also be coupled to piezoelectric actuator 5504, which activates generation plate 5532 to form droplets upon activation. The manner and location of attachment of piezoelectric actuator 5504 to jet plate 5502 influences the operation of jetting assembly 5500 and the formation of the droplet stream. In the embodiment of Figures 55B-55C, piezoelectric actuator 5504 may be coupled to a peripheral region of surface 5522 of plate 5502, while generation plate 5532 is coupled to surface 5522 to align with a central open region 5552 of jet plate 5502, as described above. Piezoelectric actuator 5504 is generally coupled to jet plate 5502 so as not to cover or block central region 5530 of generation plate 5532 (and thus, not to cover or block one or more openings 5526). In this manner, the fluid 5510 can flow through the openings 5526 to form droplets 5512 (as shown in FIG. 55A ).

The structure defined by the ejection plate 5502 and the optionally coupled generation plate 5532 has many eigenmodes, each defining the shape the structure takes when excited. Figure 3 shows examples of eigenmodes. To maximize ejection in any eigenmode, the appropriate shape and position of the piezoelectric actuator 5504 must provide the minimum amount of resistance to deformation of the ejection plate 5502 and the optionally coupled generation plate 5532 in the desired eigenmode. If the piezoelectric actuator 5504 provides a constraint on the shape of a given eigenmode, the stiffness of the piezoelectric actuator 5504 and the bonding layer may damp the mode (provide resistance to continued motion) and force the structure to its limit, depending on the material properties of the piezoelectric actuator 5504. This can limit mass ejection to a value roughly proportional to the properties of the piezoelectric actuator 5504.

In some embodiments, the eigenmodes of the ejector plate 5502 and the optionally coupled generator plate 5532 can be excited so that little or no resistance (other than the internal resistance of the ejector plate 5502 and the optionally coupled generator plate 5532) is generated to continued motion (resonance of the ejector plate 5502 and the optionally coupled generator plate 5532) simply by attaching the piezoelectric actuator 5504 to the edges of the ejector plate 5502 and the optionally coupled generator plate 5532. By attaching the piezoelectric actuator 5504 to the edges of the ejector plate 5502 and the optionally coupled generator plate 5532, the ejector plate 5502 and the optionally coupled generator plate 5532 can be provided with the least possible resistance to motion. In edge-bonded or near-edge-bonded embodiments, limitations on the performance of the piezoelectric actuator 5504 are minimized because the mechanical resistance of the ceramic (e.g., piezoelectric actuator 5504) and the bonded eigenmode shape is less than the resistance of the ejector plate 5502 and the optionally coupled generator plate 5532 themselves.

In certain aspects of the present disclosure, the eigenmodes of the ejector plate 5502 and optionally coupled generator plate 5532 can be optimized by varying the dimensions of the piezoelectric actuator 5504. In one aspect, a given eigenmode can be excited by positioning the driving force (e.g., the piezoelectric actuator 5504) in the right position 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 to lie within the nodes or antinodes of the standing wave (depending on the radial or longitudinal drive waveform). The eigenmodes of the ejector plate 5502 and optionally coupled generator plate 5532 and their shapes can be analytically determined by solving the Sturm-Liouville problem.

While ideal eigenmodels of a membrane (e.g., a rotating drum) can be obtained by solving the Sturm-Liouville problem, in certain aspects of the present disclosure, it is mathematically difficult, or even difficult to analytically determine the eigenmodel shapes, frequencies, and corresponding amplitude coefficients of vibration of the ejector plate 5502 and the optionally coupled generator plate 5532. Analytical limitations arise when loading an ideal membrane, including a driver element, with non-ideal boundary conditions, or involving multiple materials.

In various aspects according to the present disclosure, the ejection plate 5502 and optionally coupled generation plate 5532 can include a load such as a fluid 5510. In other aspects, the ejection plate 5502 and optionally coupled generation plate 5532 can include a piezoelectric actuator 5504 drive element. In another aspect, the ejection plate 5502 can include coupled generation plate 5532 comprising one or more materials. In yet another aspect, the ejection plate 5502 can have a non-uniform thickness. Similarly, in one aspect, the coupled generation plate 5532 can have a non-uniform thickness. In yet another aspect, the generation plate 5532 can have non-uniform openings 5526, potentially resulting in a non-trivial analytical solution.

The analytical limitations caused by non-ideal films can be overcome. In certain aspects of the present disclosure, computing software can be used to divide the entire structure into small discrete elements using the finite element method (FEM). On the one hand, the computing software discretizes the structure into elements that can be half the size of the minimum wavelength (maximum frequency) of the relevant vibration or smaller. In other aspects, the discrete elements can be one-fifth or less of the size of the minimum wavelength (maximum frequency) of the relevant vibration. In other aspects, the discrete elements can be one-tenth or less of the size of the minimum wavelength (maximum frequency) of the relevant vibration. In another aspect of the present disclosure, the discrete elements can be one-fifteenth or one-twentieth or less of the size of the minimum wavelength (maximum frequency) of the relevant vibration. On the one hand, the analytical problem involving partial differential equations can be represented by the central difference at each point of the discrete elements. In another aspect, the partial differential equations can be solved by obtaining the sum of the basis functions that minimize the energy of the system.

In one aspect, using FEM techniques, modal analysis can determine the eigenmode frequencies and shapes for a given set of boundary conditions, such as free, simply supported, clamped, pinned, or some combination thereof. In one aspect, the shape of the piezoelectric actuator 5504 can be determined by the eigenmode shape it is intended to actuate. In certain aspects, the shape of the piezoelectric actuator 5504 is primarily determined by the balance of forces applied per unit area, which is directly related to the area of the piezoelectric actuator 5504 contacting the ejection plate 5502 and optionally coupled generation plate 5532, and the resistance or damping applied to the wave shape by the stiffness of the combined piezoelectric actuator 5504.

In certain embodiments according to the present disclosure, once the position and initial dimensions of the piezoelectric actuator 5504 are determined, a model is created on the ejector plate 5502 and simulated using a voltage applied to the top of the piezoelectric actuator 5504 and grounded at the terminals of the ejector plate 5502 and the optionally coupled generator plate 5532. The ejector plate 5502 and the optionally coupled generator plate 5532 can be simple ejector plates 5502, hybrid ejector plates 5502 with coupled generator plates 5532, simple or hybrid ejector plates 5502 with a four-post structure, an electric field sieve structure, or any other combination of structures. The piezoelectric actuator 5504 excitation frequency is swept during the simulation from near zero frequency up to several hundred kilohertz (kHz), or generally any other frequency. For each frequency swept, the waveform shape, amplitude, and velocity of the displacement experienced by the simple or hybrid ejector plate 5502 are calculated. By applying FEM techniques, the amplitude and velocity of the structure can be determined.

If the jet plate 5502/piezoelectric actuator 5504 system moves with sufficient amplitude and velocity at the desired frequency, the structure is complete. If not, the structure is tuned by reducing the height of the piezoelectric actuator 5504 to change the damping applied by the piezoelectric actuator 5504 to the jet plate 5502. In certain aspects, the lateral/radial thickness of the piezoelectric actuator 5504 can also be tuned to reduce the damping of specific vibration modes or to shift the resonant frequency higher or lower. Given the trend in the size of the piezoelectric actuator 5504, the simulation is repeated until the structure is optimized.

When the jetting assembly 5500 is used to deliver a therapeutic agent or other fluid to a desired target, such as an eye, the jetting assembly 5500 can be designed to prevent contamination of the fluid 5510 contained in the reservoir 5520 and the ejected droplets 5512. In some embodiments, for example, a coating (not shown) can be formed on at least a portion of the exposed surfaces of the piezoelectric actuator 5504, the jetting plate 5502, the generation plate 5532, etc. that are exposed to the fluid. The coating can be used to prevent the piezoelectric actuator 5504 and the electrodes 5506a, 5506b from direct contact with the fluid 5510. The coating can be used to prevent the jetting plate 5502 or the generation plate 5532 from interacting with the fluid. The coating or a separate coating can also be used to protect the piezoelectric actuator 5504 and the electrodes 5506a, 5506b from environmental influences. For example, the coating can be a conformal coating comprising a non-reactive material, such as a polymer comprising polypropylene, nylon, or high-density polyethylene (HDPE), gold, platinum, or palladium, or a coating such as . The coatings are described in more detail herein.

The generation plate 5532 can be a pierced plate comprising at least one opening 5526. The one or more openings 5526 allow droplets to form when the fluid 5510 flows into the opening and is ejected from the generation plate 5532. The generation plate 5532 can include openings of any suitable configuration. An example of a generation plate 5532 comprising a high modulus polymer is described in U.S. Application No. 13/712,857, filed December 12, 2012, entitled "High Modulus Polymer Jetting Mechanism, Jetting Apparatus, and Method of Use," the entire contents of which are incorporated herein by reference for such disclosure.

In some embodiments, the ejection plate 5502 can be formed of a metal, such as stainless steel, nickel, cobalt, titanium, iridium, platinum, palladium, or alloys thereof. Alternatively, the plate can also be formed of other suitable materials, including other metals or polymers, and can be coated, as described above. The plate can be a composite having one or more materials or layers. The plate can be formed, for example, by cutting from a metal sheet, preforming, rolling, casting, or other means. The coating can also be deposited by a suitable deposition technique, such as sputtering, including vapor deposition by physical vapor deposition (PAD), chemical vapor deposition (COD), or electrostatic powder deposition. The protective coating can have a thickness of approximately less than 0.1 μm to approximately 500 μm. It is desirable that the coating attached to the ejection plate 5502 is sufficient to prevent delamination during high frequency vibration.

55B and 55D , in one embodiment, the ejector plate 5502 and the generator plate 5532 can have concentric circular shapes. In some embodiments, the ejector plate can be larger than the generator plate to accommodate coupling with the generator plate and other components described herein (e.g., piezoelectric actuators, etc.). In some embodiments, the overall size or diameter of the generator plate 5532 is determined at least in part by the size of the central region 5530 and the arrangement of the openings 5526. In some embodiments, the generator plate comprises a high modulus polymer generator plate.

However, the two plates can each independently have other shapes, such as oval, square, rectangular, or generally polygonal, and can be the same or different. The overall size and shape can be any suitable size and shape and can be selected based on the structural parameters of the injection device, such as the size and shape of the device housing, etc. In addition, the plates need not be flat and can include surface curvature that makes them concave or convex. The piezoelectric actuator 5504 can have any suitable shape or material. For example, the actuator can have a circular, oval, square, rectangular, or generally polygonal shape. The actuator 5504 can conform to the shape of the injection plate 5502, the generator plate 5532, or the regions 5530 or 5552. Alternatively, the actuator 5504 can have a different shape. Furthermore, the actuator 5504 can be coupled to the injection plate 5502 or the surface 5522 of the injection plate 5502 at one or more sections. In the example shown in Figures 55B-55D, the piezoelectric actuator 5504 is in the shape of a ring that is concentric with the ejection plate 5502, the generation plate 5532, or the region 5530/5552.

In some embodiments, the ejection plate 5502 and/or the generation plate 5532 may be coated with a protective coating having anti-contamination and/or antimicrobial properties. The protective coating may be applied to all surfaces of the ejection plate and/or generation plate, including the surface defining the opening 5526. In other embodiments, the protective coating may be applied to selected surfaces, such as surfaces 5522 and 5525, or to selected surface areas, such as portions of these surfaces. The protective coating may be formed from a biocompatible metal such as gold, iridium, rhodium, platinum, palladium, or alloys thereof, or a biocompatible polymer such as polypropylene, HDPE, or PTFE. Antimicrobial materials include metals such as silver, silver oxide, selenium, or polymers such as polyketones. The protective coating may be in direct contact with the fluid 5510 or droplets 5512. The coating may provide an inert barrier around the fluid or prevent bacterial growth, thereby sterilizing the fluid 5510 and/or droplets 5512.

Additionally, one or both of the surface 5522 of the jet plate 5502 and the wetted surface of the generation plate 5532 facing the reservoir 5520 can be coated with a hydrophilic or hydrophobic coating. Furthermore, the coating can be coated with a protective layer. These surfaces can also be coated with a reflective layer. The coating can be both protective and reflective. Optionally, one or more of these surfaces can be formed to be reflective. For example, these surfaces can be made of stainless steel, nickel-cobalt alloy, or other reflective materials. The surfaces can be formed or polished to be reflective. In addition to being reflective, the surfaces can also be backlit on or around their surface. In ophthalmic applications, the reflective surfaces help the user align the jet assembly with the eye.

As desired, the surface of the jet assembly may include a coating preformed by dipping, plating (including electroplating) or other encapsulation methods such as molding or casting. The coating may also be deposited by a suitable deposition technique and, for example, sputtering, including vapor deposition by 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 μm to about 500 μm. It is desirable that the coating attached to the plate is sufficient to prevent delamination during high frequency vibrations.

The piezoelectric actuator 5504 can be formed from any suitable material known in the art. For example, in some embodiments, the piezoelectric actuator can be formed from PZT, barium titanate, or a polymer-based piezoelectric material such as polyvinyl fluoride. Electrodes 5506a and 5506b can be formed from a suitable conductor, including gold, platinum, or silver. Suitable materials for adhesive 5528 can include, but are not limited to, adhesives such as silicone adhesives, epoxies, or silver pastes. An example of a conductive adhesive includes a thixotropic adhesive, such as Dow Corning DA6524 and DA6533. The reservoir 5520 can be formed from a polymer material, some examples of which include rubber, polypropylene, polyethylene, or silicone.

Piezoelectric ceramic materials are isotropic in the unpolarized state, but become anisotropic in the polarized state. In anisotropic materials, both the electric field and the electric displacement must be expressed as vectors in three-dimensional space, similar to mechanical force vectors. This is a direct result of the dependence of the ratio of the dielectric displacement D to the electric field E when the capacitor plates are oriented toward the axis of the crystal (ceramic). This means that the general formula for the electric displacement can be written as a state variable equation:

D _i =ε _ij E _j

Because the electric displacement is always parallel to the electric field, the individual electric displacement vectors D _i are equal to the sum of the field vectors E _j multiplied by their corresponding dielectric constants ε _ij :

D ₁ =ε ₁₁ E ₁ +ε ₁₂ E ₂ +ε ₁₃ E ₃

D ₂ =ε ₂₁ E ₁ +ε ₂₂ E ₂ +ε ₂₃ E ₃

D ₃ =ε ₃₁ E ₁ +ε ₃₂ E ₂ +ε ₃₃ E ₃

Most piezoelectric ceramics have a zero dielectric constant (in contrast to single crystal piezoelectric materials). The only non-zero term is:

ε ₁₁ ＝ε ₂₂ ,ε ₃₃

The piezoelectric effect links mechanical effects with electrical effects. These effects depend significantly on the polar axes they are oriented toward. Figure 56 illustrates the axis numbering scheme. For example, for the electromechanical constant d _ab , where a = electrical direction and b = mechanical direction, the electromechanical constant D ₃₃ = ε ₃₃ E ₃ , in which case the mechanical displacement is in the polar direction Z. Referring to Figure 55A , the Z direction is the direction of ejected droplet 5512, i.e., direction 5514.

Therefore, D ₃₃ is the induced polarization in the direction Z (the polar direction, equivalent to the direction 5514 in FIG. 55A ) parallel to the direction of polarization of the ceramic material.

According to some embodiments of the present invention, a piezoelectric material can be described by a mechanical displacement in a polar direction Z (e.g., direction 5514 in Figure 55A).

In some embodiments, the piezoelectric material may be lead zirconium titanate (PZT) with a D ₃₃ of 330 pC/N. In another embodiment, the piezoelectric material may be a widely used PbTiO ₃ -PbZrO ₃ (PZT)-based multi-component system. Commercially available PZT piezoelectric ceramics include PZT-4 with a D ₃₃ of 225 pC/N, PZT-5A with a D ₃₃ of 350 pC/N, and PZT-5H with a D ₃₃ of 585 pC/N. (PZT)-based piezoelectric actuators may be formed from materials with a D ₃₃ greater than 300 pC/N. In another embodiment, the D ₃₃ of the piezoelectric ceramic may be between 200 pC/N and 300 pC/N. In another embodiment, the D ₃₃ of the piezoelectric ceramic may be between 250 pC/N and 300 pC/N.

In some embodiments, due to safety reasons and FDA/EU requirements, it is desirable to eliminate lead from piezoelectric materials. In one embodiment, a lead-free piezoelectric ceramic having a _D33 of less than 300 pC/N can be used. In another embodiment, the _D33 of the lead-free piezoelectric ceramic can be less than 200 pC/N. In yet another embodiment, the _D33 of the lead-free piezoelectric ceramic can be between 150 pC/N and 200 pC/N. In yet another embodiment, the _D33 of the lead-free ceramic can be less than 150 pC/N. In yet another embodiment, the _D33 of the lead-free piezoelectric ceramic can be between 100 pC/N and 150 pC/N. In yet another embodiment, the _D33 of the lead-free ceramic suitable for piezoelectric actuators can be less than 100 pC/N.

In some embodiments, the piezoelectric device can be made from commercially available materials. As non-limiting examples, the materials listed in Table 14, available from Sunnytec Powder Materials, can be suitable for the piezoelectric device of the present disclosure.

Table 14

In some embodiments, the piezoelectric material may be a BiFeO ₃ -based ceramic. In some embodiments, the ceramic may be selected from the group consisting of: (Bi,Ba)(Fe,Ti)O ₃ , (K,Na,Li)NbO ₃ , (K,Na,Li)NbO ₃ , (K,Na,Li)NbO ₃ , (K,Na,Li)NbO ₃ , Bi(Fe,Mn)O ₃ + BaTiO ₃ , Bi(Fe,Mn)O ₃ +BaTiO ₃ , BiFeO ₃ -NdMnO3-BiA1O3, (Bi,La)(Fe,Mn)O ₃ , (Bi,La)(Fe,Mn)O ₃ ,BiFeMnO ₃ -BaTiO ₃ ,Bi(Fe,Mn)O ₃ - BaZrTiO ₃ , (Bi,La)(Fe,Mn)O ₃ , (Bi,La)(Fe,Mn)O3, (Bi,Ba)(Fe,Ti)O ₃ , Bi(Zn,Ti)O ₃ -La(Zn,Ti)O ₃ -Ba(Sc,Nb)O ₃ (d33=250), BiFeO ₃ , (Ba,M) (Ti,Ni)O ₃ , BiFeO ₃ , Bi(Al,Ga)O ₃ , BT-BiFeO ₃ ,Bi(Fe,Al)O ₃ ,Bi(Fe,Al)O ₃ , Bi(Fe,Co,Mn)O ₃ , BiFeO ₃ -BaTiO ₃ , BiFeO ₃ -BaTiO ₃ , Bi(Al,Ga)O ₃ (d33=150), Bi(Al,Ga)O ₃ , BiFeO ₃ +AD, BiFeO ₃ +BaTiO ₃ , BiFeO ₃ base, BaTiO ₃ -BiFeO ₃ , (Bi,x)(Fe,Mn)O ₃ , (Bi,x)(Fe,Ti,Mn)O ₃ .

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 _0.5 Na _0.5 TiO ₃ -xLaFeO ₃ , (1-x)Bi _0.5 Na _0.5 TiO ₃ -xNaSbO ₃ , (1-x)Bi _0.5 Na _0.5 TiO ₃ -xBiCrO ₃ , (1-x)Bi _0.5 Na _0.5 TiO ₃ -xBiFeO ₃ , Bi _0.5 (Na _1-x K _x ) _0.5 TiO ₃ (BNK T), Bi _0.5 (Na _1-x K _x ) _0.5 TiO ₃ (BNKT), Bi _0.5 (Na _1-x K _x ) _0.5 TiO ₃ (BNKT), Bi _0.5 (Na _1-x K _x ) _0.5 TiO ₃ (BNKT), ((1-x)Bi _1-a Na _a )TiO ₃ -(1-x)LiNbO ₃ ,Bi _0.5 (Na _1-x Li _x ) _0. 5Ti O ₃ ,Bi _0.5 (Na,K) _0.5 [Ti,(Mg,Ta)]O ₃ ,Bi _0.5 (Na,K) _0.5 [Ti,(Al,Mo)]O ₃ ,Bi _0.5 (Na,K ) _0.5 [Ti,(Mg,Nb)]O ₃ ,Bi _0.5 (Na,K) _0.5 [Ti,(M,V)]O ₃ ,Bi _0.5 (Na,K) _0.5 [Ti,(M,V)]O ₃ ,BNT-BT-KNN,(1-x)Bi _0.5 Na _0.5 TiO ₃ -xBaTiO ₃ (BNBT)(d33＝100×10 ^-12 pC/N or larger), BNT-BKT-BT (d33＝158pC/N), BNT-BKT-BT+PT (d33＝127), BNT-KN, Bi _0.5 Na _0.5 TiO ₃ -BaTiO ₃ (BNBT) (d33＝253pC/N), NGK2,BNT-BKT-BT,NGK,BNT-BKT-BT,NGK4,Bi _0.5 Na _0.5 TiO ₃ -BaTiO ₃ -CaTiO ₃ -Ba(Zn _1/3 Nb _2/3 )O ₃ +Y ₂ O ₃ ,MnO,(1-v)[(Li _{1- y} Na _y )zNbO ₃ ]-v[Bi _0.5 Na _0.5 TiO ₃ ,(1-vx)[(Li _1-y Na _y )zNbO ₃ ]-xLMnO ₃ -v[Bi _0.5 Na _0.5 TiO ₃ ],Bi _0.5 Na _0.5 Ti O ₃ ,BNT-BT,BNT-BT,xBi _0.5 Na _0.5 TiO ₃ -y[MNbO ₃ )-(Z/2)(Bi ₂ O ₃ -Sc ₂ O ₃ )(M＝ K,Na),BNT-BKT-Bi(Mg _2/3 Ta _1/3 )O ₃ ,[(Bi _0.5 Na _0.5 )xMy]z(TiuNv)O ₃ (M＝Ba, Mg,Ca,Sr,(Bi _0.5 K _0.5 ))(N＝Zr,Hf),[(Bi _0.5 Na _0.5 )xMy]z(TiuNv)O ₃ (M＝Ba,Mg,Ca,Sr,(Bi _0.5 K _0.5 ), other) (N=Zr, Hf, other), BNT-BKT-BT-CT-NaNbO ₃ , BNT-BKT-Bi(Ni,Ti)O ₃ ,BNT-BKT-Bi(Ni,Ti)O ₃ ,BNT-BKT-BT,BNT-BT-ST,BNT-BKT-BT,BNT-BKT-AgNbO ₃ ,BNT-BKT-BT,BT-BKT,BNT-BT-Bi(Fe _0.5 Ti _0.5 ) ₃ ,BNT-BKT-Bi(Zn _0.5 Zr _0.5 )O ₃ ,BNT-BKT-Bi(Fe _0.5 Ta _0.5 )O ₃ ,BNT -BKT-Bi(Ml,M2)O ₃ ,BNT-BKT,BNT-BT,BNT-BKT,Bi _0.5 K _0.5 TiO ₃ (BKT) and Bi _0.5 Na _0.5 TiO ₃ -(1-x)ABO ₃ .

In some embodiments, the piezoelectric material may be a dual-mode magnetostrictive/piezoelectric bilayer composite, a tungsten bronze material, a sodium niobate material, a barium titanate material, and a polyvinyl fluoride material. Examples of suitable materials for the piezoelectric actuators of the present disclosure include: A2Bi4Ti5O18(A＝Sr,Ca,(Bi _0.5 Na _0.5 ),(Bi _0.5 Li _0.5 ),(Bi _0.5 Li _0.5 ),(Al-xBix)2Bi4 Ti5O18(A＝Sr,Ca,(Bi _0.5 Na _0.5 ),(,(Bi _0.5 Li _0.5 ),(Bi _0.5 Li _0.5 ),Bi4Ti3O12-x(Srl-a Aa)TiO3(A＝Ba,Bi _0.5 Na _0.5 ,Bi _0.5 K _0.5 ,Bi _0.5 Li _0.5 ),Bi4Ti3O12-(Ba,A)TiO3,Bi4 Ti3O12-x{(Srl-aA'a)TiO3-ABO3}(A'＝Ba,Bi _0.5 Na _0.5 ,Bi _0.5 K _0.5 ,Bi _0.5 Li _0.5 ,A ＝Bi,Na,K,Li,B＝Fe,Nb),(A1-xBix)Bi4Ti4O15(A＝Sr,Ba),BaBi4Ti4O15,( Sr2-aAa)x(Nal-bKb)y(Nb5-cVc)O15(A＝Mg,Ca,Ba)d33＝80pC/N or higher,Tc＝150℃ or higher,(Sr2-aAa)x(Nal-bKb)y(Nb5-cVc)O15, (Na _0.5 Bi _0.5 )1-xMxBi4Ti4O15,Bi4Ti3O12,SrBi2(Nb,W)O9,(Srl-xMlx)Bi 2(Nb1-zWy)2O9,(Sr,Ca)NdBi2Ta2O9+Mn,(Srl-xMx)(Bi,Nd)(Nb,Ta)2O 9,Bi2(Srl-xMx)Nb2O9(M=Y,La),(Sr2CaK)Nb5O15(d33=120).

In an embodiment of the present disclosure, the niobate material may be selected from the following materials: (Sn, K)(Ti, Nb)O3, KNbO3-NaNbO3-LiNbO3-SrTiO3-BiFeO3, KNbO3- NaNbO3-LiNbO3, KNbO3- NaNbO3-LiNbO3, xLiNbO3-yNaNbO3-zBa Nb2O6, NaxNbO3-AyBOf(A＝K, Na, Li, BiB＝Li, Ti, Nb, Ta, Sb), (1-x)(Na1-a Mna)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＝Nb,Ta,Sb,L＝Y,Er,Ho,Tm,Lu,Yb),(LixNa1-x-yKy) z-2wMa2wNbl-wMbwO3(Ma＝ ²⁺ metal A, Mb＝ 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).

Barium titanate is an inorganic compound with the chemical formula _BaTiO₃ . Barium titanate also contains other elements in substoichiometric amounts. Examples of other elements in _BaTiO₃ include rare earth elements and alkaline earth metals. Substoichiometric amounts of other elements alter the piezoelectric properties of the _BaTiO₃ material. Doping the _BaTiO₃ material refers to the inclusion of other elements in substoichiometric amounts.

Examples of suitable single crystal barium titanate materials also include:

{(Bi1/2,Na1/2)1-xA1x}TiO3(A1＝Ba,Ca,Sr),{(Bi1/2,Na1/2)1-x(Bi1/2,A2 1/2)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-x NaxNb5O15,La3Ga5SiO14,MgBa(CO3)2,NdCa40(BO3)3(Ml＝rare earth element, M2＝alkaline earth metal),LaTiO2N.

In some embodiments, the ejection plate 5502 can be formed from a suitable material, where the suitable material is selected based on the direction 5514 of the out-of-plane displacement. The displacement Z of the ejection plate 5502 (e.g., movement in direction 5514) depends on the diameter of the ejection plate 5502 and the thickness of the ejection plate 5502. The suitable material can also be selected based on the Young's modulus and Poisson's ratio of the ejection plate 5502. The Young's modulus and Poisson's ratio are intrinsic properties of the material, and the material can be selected to determine the desired displacement. For an appropriate material for the ejection plate 5502, the displacement Z can be increased by reducing the thickness of the ejection plate 5502.

A suitable material of the ejection plate 5502 having a displacement in direction 5514 can be coupled to the frequency of the piezoelectric actuator 5504, thereby matching the resonant frequency of the ejection plate 5502. By coupling the displacement of the ejection plate 5502 to the piezoelectric actuator 5504 in a resonant system, the piezoelectric actuator can be used to achieve ejection of liquid through the apertures of the generator plate 5532 without being limited by D33.

55C, the manner and location in which the piezoelectric actuator 5504 is attached to the jetting plate 5502 can affect the operation of the jetting assembly 5500 and the formation of the droplet stream.

As described above, whether as a simple jet plate 5502 or as a hybrid jet plate 5502 coupled to a generator plate 5532, the jet plate 5502 can have a number of eigenmodes, each defining the shape the structure takes when the wave mode is excited. As provided above, the eigenmodes of the jet plate 5502 and optionally coupled generator plate 5532 can be calculated using, for example, FEM techniques to determine the desired amplitude and velocity of the eigenmodes.

In one embodiment, the piezoelectric actuator 5504 is edge-mounted on the ejection plate 5502, where the distance 5554 is zero. This edge-mounted configuration is a special case where the internal resistance to the wave pattern being excited is near zero. When the circular piezoelectric actuator 5504 is attached to the edge of the circular ejection plate 5502 (e.g., where the distance 5554 is zero or near zero), the ejection plate 5502 is significantly stiffened where the rigid piezoelectric actuator 5504 is located. However, the portion of the ejection plate 5502 within the inner diameter 5557 of the piezoelectric actuator 5504 remains free to move, limited only by its own elastic limit and not by the piezoelectric actuator 5504. Similarly, the hybrid ejection plate 5502 with its coupled generator plate 5532 remains free to move, limited only by the combined elastic limit and not by the piezoelectric actuator 5504. If the edges of the piezoelectric actuator 5504 are pinned or clamped, the jet plate 5502 behaves effectively as if it were the diameter of the inner diameter 5557 of the piezoelectric actuator 5504 with ideal (edge-driven) radial and longitudinal excitation. Other wave modes associated with the overall size of the jet plate 5502 are suppressed due to the stiffness of the piezoelectric actuator 5504. In certain embodiments, the stiffness of the piezoelectric actuator 5504 can be modulated by increasing or decreasing the thickness of the piezoelectric actuator 5504. Example 5 below provides an example of piezoelectric actuator 5504 modulation.

In other embodiments according to the present disclosure, the mounting configuration of the piezoelectric actuator 5504 on the ejection plate 5502 can affect the displacement and velocity of the ejection plate 5502 and the generator plate 5532. Generally speaking, within a given waveform, the displacement amplitude and velocity of the ejection plate 5502 are a balance between the force determined primarily by the piezoelectric material's motion per unit voltage ( _D33 ) and the piezoelectric's damping/resistance to the motion of the ejection plate 5502. Increasing the stiffness of the piezoelectric material increases both damping and resistance. For piezoelectric materials with larger _D33 , such as materials like PZT, the damping/resistance of the piezoelectric material plays a less significant role in the displacement amplitude. In other embodiments with smaller _D33 , such as _BaTiO3 , the performance of the droplet ejection system degrades significantly with increasing damping/resistance. The performance degradation of the jetting assembly 5500 is directly proportional to the _D33 of the material used to fabricate the piezoelectric actuator 5504.

The performance of edge-mounted embodiments of piezoelectric actuator 5504/jet plate 5502 can be exploited to mitigate the effects of smaller material movements. Specifically, when jet plate 5502 is excited into a mechanical waveform where, due to a certain force per unit area applied by piezoelectric actuator 5504, only its own resistance limits its movement, piezoelectric D33 can be scaled down without sacrificing performance for the same electrical input, up to a minimum force per unit area. Figure 8 illustrates this property: if the force per unit area is above a certain threshold, the increase in jet plate 5502 movement is minimal. Below this threshold, the jet plate 5502 decreases linearly with the force per unit area.

For the jet plate 5502 of the present disclosure, low-order modes are typically excited at the lowest frequencies on structures where the wavelength of the standing wave is an integer multiple of half the wavelength. The frequency and wavelength of these modes are determined by the material properties of the jet plate 5502 and its radial dimensions. Because the eigenmode shape always has nodes for these modes at the edges of the jet plate 5502 and a maximum at the center of the membrane, only two piezoelectric locations are relevant for exciting these modes in a fluid ejection system.

In embodiments according to the present disclosure, piezoelectric actuator 5504 can be placed in the center of ejection plate 5502 to stimulate maximum motion. However, because there is always an area in the center of ejection plate 5502 where fluid ejection is directly performed, this mounting position is not optimal for this application. Performance must be sacrificed to allow fluid ejection.

Piezoelectric actuators 5504 can also be placed on the edge of the ejection plate 5502 to stimulate maximum motion at low frequencies in the center of the ejection plate 5502. In this configuration, resistance to the inherent motion of the wave modes is minimized, allowing these wave modes to produce large displacements at low frequencies, improving mass deposition. Generally, these wave modes are conducive to continuous fluid injection due to their generally constant shape and velocity distribution across the injection area. In addition, by loading the center of the ejection plate 5502 with mass, such as a hybrid ejection plate 5502 with an attached generator plate 5532, low-order wave mode displacements are enhanced due to the inertia of the central mass (e.g., generator plate 5532).

In some embodiments, edge-mounted piezoelectric actuators 5504 cause ejection plates 5502, coupled to generation plates 5532, to oscillate at the resonant frequency of the ejection plates coupled to the generation plates. In one embodiment, by matching the resonant frequencies, the displacement requirements of the piezoelectric material are reduced. In one embodiment, by matching the resonant frequencies, a directional stream of droplets can be generated using piezoelectric materials with a D ₃₃ less than 200. In another embodiment, by matching the resonant frequencies, a directional stream of droplets can be generated using piezoelectric materials with a D ₃₃ less than 15 or less than 1250. In yet another embodiment, by matching the resonant frequencies, a directional stream of droplets can be generated using piezoelectric materials with a D ₃₃ less than 100 or less than 75.

In another embodiment, the piezoelectric actuator 5504 is slightly smaller than an edge-mounted (e.g., internally mounted) configuration on the ejection plate 5502, wherein 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.

In other embodiments according to the present disclosure, the piezoelectric actuator 5504 is internally mounted on the jet plate 5502, wherein the distance 5554 is greater than zero and the outer diameter of the piezoelectric actuator 5504 is smaller than the outer diameter of the jet plate 5502. In one embodiment, the piezoelectric actuator 5504 is internally mounted on the jet plate 5502 and is 1% smaller than the diameter of the jet plate 5502. In one embodiment, the piezoelectric actuator 5504 is internally mounted on the jet plate 5502 and is 1.5% smaller than the diameter of the jet plate 5502. In one embodiment, the piezoelectric actuator 5504 is internally mounted on the jet plate 5502 and is 2% smaller than the diameter of the jet plate 5502. In one embodiment, the piezoelectric actuator 5504 is internally mounted on the jet plate 5502 and is 3% smaller than the diameter of the jet plate 5502. In one embodiment, the piezoelectric actuator 5504 is internally mounted on the jet plate 5502 and is 4% smaller than the diameter of the jet plate 5502. In one embodiment, the piezoelectric actuator 5504 is mounted internally to the ejection plate 5502 and is 5% smaller than the diameter of the ejection plate 5502. In one embodiment, the piezoelectric actuator 5504 is mounted internally to the ejection plate 5502 and is 7.5% smaller than the diameter of the ejection plate 5502.

In some embodiments according to the present disclosure, piezoelectric actuator 5504 is internally mounted on ejection plate 5502, wherein distance 5554 is greater than zero and the inner diameter of the annular piezoelectric actuator is selected such that low frequency edge modes of ejection plate 5502 are damped or eliminated.

In certain embodiments of the present disclosure, the ejection mechanism can be configured to facilitate a piezoelectric actuator actuation of the ejection plate 5502, and thereby the generator plate 5532. As described above, the generator plate 5532 can be configured to optimize ejection of the fluid of interest. For example, the aspect ratio of the opening of the generator plate can be selected based in part on the fluid properties, such that the overall thickness of the generator plate 5532 ranges from approximately 50 μm to approximately 200 μm, as described above. Without being limited by theory, in certain embodiments, direct actuation of thicker generator plates, while feasible, is not optimal. In some embodiments, the generator plate comprises a high modulus polymer generator plate.

Similarly, in certain embodiments, utilizing a configuration including a generator plate coupled to a jet plate as described herein can optimize actuation of the jet mechanism. Furthermore, by reducing the surface area of the generator plate 5532 (i.e., a central area having one or more openings), production costs are also reduced, potential manufacturing defects are reduced, and manufacturing efficiency and yield are improved. In certain embodiments, the size and shape of the jet plate can be designed to facilitate actuation of the jet mechanism (i.e., facilitate actuation of the jet plate, and thus facilitate actuation of the generator plate 5532). For example, the configuration of the jet plate facilitates actuation of the jet mechanism by selecting properties (e.g., size, shape, material, etc.) that facilitate flexure of the jet plate, thereby facilitating vibration of the generator plate. For example, the thickness of the jet plate 5532 can generally range from approximately 10 μm to approximately 400 μm, from approximately 20 μm to approximately 100 μm, from approximately 20 μm to approximately 50 μm, or from approximately 30 μm to approximately 50 μm, etc. Also, without being limited by theory, in certain embodiments, direct actuation may be better with a thinner ejection plate 5502 (compared to the generation plate 5532). In some embodiments, the generation plate 5532 comprises a high modulus polymer generation plate.

According to certain embodiments of the present invention, the configuration of the ejector plate 5502 and the generator plate 5532 can be selected such that the central region of the generator plate 5532, including the opening (the "active region" of the generator plate), produces symmetrical oscillations having a normal oscillation pattern. Without being limited by theory, in certain embodiments, the configuration of the ejector plate 5502 and the generator plate 5532 can be selected such that oscillations of the 0,2 normal pattern and the 0,3 normal pattern can be observed in the active region of the generator plate. The pattern is related to the maximum amplitude and displacement of the active region, and is labeled (d, c), where d is the number of nodal diameters and c is the number of nodal circles.

By controlling the voltage pulses applied to electrodes 5506a and 5506b, for example, a voltage difference of 40V or 60V can be applied to the electrodes, the amplitude and frequency of the vibration of ejector plate 5502 can also be controlled. As described above, this voltage difference creates a pulse that causes ejector plate 5502 to deflect, thereby causing generator plate 5532 to deflect. In some embodiments, one of electrodes 5506a or 5506b is grounded, while a voltage pulse, such as a bipolar pulse, is applied to the other electrode 5506a or 5506b to cause ejector plate 5502 to vibrate. For example, in one embodiment, the resonant frequency of piezoelectric actuator 5504 can be between approximately 5 kHz and approximately 1 MHz, such as between approximately 10 kHz and approximately 160 kHz, such as between approximately 50-120 kHz, approximately 50-140 kHz, or approximately 108-130 kHz, etc. The frequency of the applied voltage pulses can be lower than, higher than, or the same as the resonant frequency of piezoelectric actuator 5504.

In certain embodiments, the droplet delivery time is from about 0.1 ms to about several seconds. Without wishing to be bound by theory, it is believed that a human eye blink takes about 300 ms to about 400 ms. Therefore, for embodiments where delivery is desired within the duration of a blink, the delivery time may be from about 50 ms to about 300 ms, more particularly 25 ms to 200 ms. In one embodiment, the delivery time is from 50 ms to 100 ms. This allows the ejected droplets to be effectively delivered and deposited in the eye during a single blink cycle. In some embodiments, such as saline dispensers legally available over the counter, the delivery time may be as long as several seconds, for example, 3-4 seconds, spanning several blink cycles. Alternatively, a single dose may be administered over several pulses of droplet ejection. Furthermore, without wishing to be bound by theory, pulsing can be used to reduce the peak amplitude of the droplet airflow by stretching the pulsation outward over time. This can thereby reduce the ejection pressure on the target. Furthermore, pulsing can also reduce droplet coalescence, resulting in less entrained air. For example, 25 ms pulses may be administered with a 25 ms rest period between pulses. In one embodiment, the pulses may be repeated for a total of 150 ms.

As described herein, the spray devices and spray mechanisms of the present disclosure can be configured to spray fluids having a generally low viscosity to a relatively high viscosity as a droplet stream. For example, a fluid suitable for use with the spray device can have an extremely low viscosity, such as 1 cP of water, or less, such as 0.3 cP. Alternatively, the fluid can have a viscosity ranging up to 600 cP. More particularly, the viscosity of the fluid can range from approximately 0.3 to 100 cP, 0.3 to 50 cP, 0.3 to 30 cP, 1 cP to 53 cP, and so on. In some embodiments, the spray device can be used to spray fluids having a relatively low viscosity as a droplet stream, such as fluids having a viscosity greater than 1 cP, ranging from approximately 1 cP to approximately 600 cP, approximately 1 cP to approximately 200 cP, approximately 1 cP to approximately 100 cP, approximately 10 cP to approximately 100 cP, and so on. In some embodiments, a solution or drug having a suitable viscosity and surface tension can be used directly in the reservoir without modification. In other embodiments, additional materials may be added to adjust fluid parameters. For example, some fluids are listed in Table 15 below:

Table 15. Viscosity measured at 20°C

From the above discussion, it should be understood that different configurations and materials will result in different properties. To help understand some of the properties of several selected embodiments of the injection mechanism, experiments were conducted to compare certain embodiments. Of course, the experiments described herein should not be considered as specific limitations of the present invention, and various variations of the present invention within the knowledge of those skilled in the art, whether currently known or developed in the future, are considered to fall within the scope of the present invention as described herein and hereinafter claimed.

Example 6: Measurement of mass deposition

To measure mass deposition of the spraying device, the spraying device was held horizontally and sprayed toward the ground, with the polar direction Z, as shown in FIG56 , pointing toward the ground (e.g., parallel to gravity). Referring to FIG55A , the direction 5514 of the sprayed droplet 5512 was toward the ground. The ground and positive leads of the device were connected to an operational amplifier, and the current and voltage probes were connected to an oscilloscope.

The frequency range provided for device jetting was initially determined by frequency sweeping from 2 kHz to 500 kHz. Electrical data, including voltage and current, was recorded and stored. During analysis, the jetting range was selected for mass deposition determination. The results were plotted to provide a mass jetting curve as shown in Figure 58.

To determine mass deposition, the frequency and voltage are set to, for example, a 90 V peak-to-peak (90 Vpp) sine wave at a frequency of 50 kilohertz (kHz), and five jets from the jetting device are measured on a 24 mm x 60 mm No. 1 glass cover slip, using a scale with a sensitivity of 1 milligram (mg) and calibrated with a traceable 1 mg first-stage weight. For each measurement, the cover slip is placed on the scale and the scale is zeroed. The slide is placed under the jetting device and the voltage is applied for a defined period of time. The slide is returned to the scale and the mass is determined and recorded. Before each measurement, the cover slip is cleaned and the scale is re-zeroed. A total of five measurements are recorded for each frequency. This process is repeated while varying the frequency incrementally according to a predetermined step size (typically 1 kHz).

Example 7: Comparison of PZT and _BaTiO3 using an internally mounted jet assembly.

The mass deposition curve for a jetting device with an internally mounted jetting assembly was determined using the method described in Experiment 6 above to determine the frequency range over which the device jetted. For both piezoelectric materials, PZT and BaTiO ₃ , the piezoelectric actuator 5504 had an outer diameter of 16 mm, an inner diameter of 8 mm, and a height of 550 μm. It was mounted on a 50 μm thick, 20 mm diameter circular jetting plate 5502. In this example, several samples of PZT were directly compared to BaTiO ₃ . Based on the approximate ratio of the materials' d 33 coefficients, PZT jetted more fluid than BaTiO ₃ . Figure 59 shows the only significant jetting pattern.

At distances 5554 greater than zero (here, 2 mm), PZT material offers a wider range of effective frequencies compared to _BaTiO . The maximum ejected mass of the PZT ejector is more than twice the output of the _BaTiO ejector. While not as efficient, _BaTiO offers a maximum ejected mass of approximately 6 mg between 115 kHz and 102 kHz.

7a: Comparison of PZT and _BaTiO3 using edge-mounted jetting assembly.

Using the method of Experiment 6, the ejection mass was determined at various frequencies, starting from 10 kHz to 500 kHz with a frequency step of 1 kHz. Plotting the deposited mass in milligrams versus frequency, Figure 58 shows the deposited mass versus frequency for edge-mounted PZT and BaTiO ₃ piezoelectric actuators with an outer diameter of 20 mm, an inner diameter of 14 mm, and a height of 550 μm, mounted on a 20 mm diameter, 50 μm thick circular ejection plate 5502. In this case, several samples of PZT were directly compared to BaTiO _3. Even though the materials' d33 coefficients differed significantly, PZT and BaTiO ₃ were ejected almost identically (adjusted to account for sample variations). It is also apparent from Figure 58 that many modes were excited and that the material properties were identical.

When the PZT and _BaTiO3 piezoelectric actuators 5504 are edge-mounted (i.e., distance 5554 is zero or near zero), jetting quality occurs over a discrete frequency range corresponding to the resonant coupling between the piezoelectric actuator and the associated jetting plate 5502 and generator plate. Although the PZT device has a _D33 of 330 pC/N and the _BaTiO3 has a _D33 of 160 pC/N, the jetting curves and efficiencies are very similar. The centrosymmetric structure and edge-mounting of the piezoelectric actuator overcome this displacement difference, allowing a wide variety of piezoelectric materials to be incorporated into the jetting device.

7b: Effect of reducing the diameter of the piezoelectric actuator 5504 relative to the ejection plate 5502

As the piezoelectric actuator 5504 is translated inward from the edge of the ejection plate 5502 (e.g., as the distance 5554 increases from zero), performance is lost because the ejection pattern is increasingly damped by the piezoelectric stiffness. In one embodiment, the piezoelectric outer diameter is 20 mm, the inner diameter is 14 mm, the optimal thickness is 250 μm, and the ejection plate diameter is 20 mm. This demonstrates jetting that exceeds all other cases by 20-33%. In another embodiment, the piezoelectric outer diameter is changed to 19 mm, the ejection plate diameter is changed to 21 mm, and the optimal thickness is 200 μm. The jetting frequency remains virtually the same, but in contrast to the edge-mounted case, the jetting per pattern decreases even with the optimal piezoelectric thickness (tested in the lab at 25 μm increments from 150 μm to 550 μm). In this third embodiment, the piezoelectric outer diameter remains at 19 mm, the inner diameter remains at 14 mm, but the ejection plate is changed to 23 μm. Again, the thickness was optimized to 175 μm to reduce the stiffness, but all modes were severely suppressed, with performance reduced by more than 80%.

Example 8: Comparison of BaTiO ₃ piezoelectric materials

BaTiO ₃ materials with different properties were distinguished using scanning electron microscopy (SEM). SEM images of two exemplary BaTiO ₃ materials were taken, with the first sample showing a uniform particle size of approximately 2 to 5 microns in diameter and the second sample showing a fused structure with particles tens of microns in diameter. Although both samples had similar D ₃₃ values, the smaller particle size improved performance by lowering the resonant frequency.

Example 9: Eigenmodel Modulation

For a circular ejection plate 5502 excited by a piezoelectric actuator 5504, increasing the stiffness of the piezoelectric actuator 5504 results in suppression of high-frequency eigenmodes. To test the effect of increasing the stiffness of the piezoelectric actuator 5504, a first piezoelectric actuator 5504, 200 μm thick, 20 mm outer diameter, and 14 mm inner diameter (20 mm × 14 mm), and a second piezoelectric actuator 5504, 400 μm thick (20 mm × 14 mm), were attached to an ejection plate 5502 with a 20 mm outer diameter (e.g., edge-mounted). The normalized displacements of the two ejection mechanisms were simulated or tested over a frequency range from 1 Hz to 3 × 10 ⁵ Hz. The thinner piezoelectric actuator 5504 exhibits greater flexibility, allowing for complex eigenmodes at higher frequencies. In contrast, a thicker, stiffer piezoelectric actuator 5504 restricts the eigenmodes to low frequency modes that are localized to the region of the ejection plate 5502 that is within the inner diameter of the piezoelectric actuator 5504 (eg, the inner 14 mm).

It should be understood that the jetting assemblies described herein can be incorporated into jetting devices and systems. Exemplary jetting devices and systems are described in U.S. Application No. 13/712,784, filed December 12, 2012, entitled “Jeting Mechanism, Apparatus, and Method of Use,” U.S. Application No. 13/712,857, filed December 12, 2012, entitled “High Modulus Polymer Jetting Mechanism, Jetting Apparatus, and Method of Use,” and U.S. Application No. 13/184,484, filed July 15, 2011, entitled “Droplet Generation Device,” the entire contents of which are incorporated herein by reference.

When a fluid is exposed to an air interface, it evaporates into the air, causing the fluid volume to be lost over time. If the fluid retains any mineral elements, the composition of the mixture changes over time, leading to crystallization at the air-fluid interface. However, if the small volume of air surrounding the fluid-air interface is sealed, the evaporation and crystallization rates are reduced to the leak rate of the seal, thereby reducing or eliminating evaporation and crystallization. As long as the device is open to the environment, it can be contaminated.

To partially address these problems, the present disclosure provides an automatic shut-off system for use with a droplet ejection device that prevents the device from being open to the environment for a period longer than the actual droplet ejection cycle, which greatly reduces the risk of contamination. In certain embodiments, the automatic shut-off system is compact in size along the fluid ejection path, uses a minimum of components, and provides a consistent seal even when there are dimensional variations in the components. The system provides a closed sealing position and an open working position for fluid ejection. The transition between the closed position and the open position can be configured to be manually actuated by the user, or can be configured to be power actuated. In certain embodiments, the system can provide a manual configuration using a small actuation force. In addition, the movement between the sealing position and the open position can be configured to be linearly actuated or rotary actuated. For example, certain embodiments provide a linear actuation configuration for use in conjunction with a user-operated, hinged activation button.

Figures 60-65 illustrate one embodiment of the automatic closing system of the present disclosure. Figure 60 illustrates a compact, linearly actuated embodiment of the automatic closing system of the present disclosure, and Figure 61 illustrates an exploded assembly view of the major components of this embodiment.

As shown in Figures 60 and 61, a slide element 6000 with an orifice 6002 is held between an injection system 6004 to be sealed and a retaining plate 6006. The injection system is shown schematically, with internal features hidden from view. The face of the injection system has a circular orifice 6010 surrounded by a circular elastomeric face seal 6012. This face seal resides in a gland or groove 6014 on the face of the injector. In one embodiment, the slide element is pressed against the face seal by a flexure 6020 integral to the slide element. Alternatively, the flexure can be seated on the retaining plate or incorporated into a separate component. In one position of the slide element (open position), the slide orifice 6002 is aligned with the injection orifice 6010, allowing fluid to be dispensed. In the closed position, the slide element orifice 6002 and the injection system orifice 6010 are completely misaligned, sealing the injection system. A hinged activation button 6030 (Figure 60) pivots about a fulcrum 6031 connected to the housing (not shown). Button 6030 is operated by the user's finger, which actuates the slide element in a downward direction and opens the seal. When the user's finger pressure is removed, compression spring 6032 returns the slide element 6000 to the closed sealing position.

Figure 62 shows a schematic cross-sectional view of the automatic closure system, illustrating the basic sealing principle. An axial force F presses the slider element against the elastomeric face seal within the gland located on the face of the injection system. The face seal surface protrudes from the face of the injection system by approximately 20% of the seal cross-section. The maximum expected internal pressure in the injection system is resisted by this axial compressive force F, such that the compressive force exceeds the internal pressure given by the product of the internal pressure P and the sealing area A. For this embodiment, the axial force is selected to be approximately twice the expected internal pressure. In a preferred embodiment, the axial compressive force is provided by a compact flexure 6020, as shown in Figures 63 and 64. Flexure 6020 provides a consistent force on the seal, which is less susceptible to component manufacturing dimensional variations. By integrating the flexure with the slider element, a minimal stack height is provided from the injection system to the retaining plate orifice, allowing the face of the injection system to be closer to the final delivery point. To minimize actuation forces, the face seal 6012 is formed from pre-lubricated silicone. To prevent wear, the slider element 6000 is always in contact with the seal. All edges of the slider element 6000 do not extend away from the seal 6012, but rather rest against it; only the edge of the slider orifice crosses the face seal. To further prevent wear and reduce actuation forces, the slider orifice edge 6040 is rounded, as is the top edge of the face seal. To maintain parallelism between the slider element and the face seal, a small slider 6042 is provided on the slider element, as shown in Figures 63 and 64.

In the preferred embodiment, the slider element is injection molded from an antimicrobial thermoplastic. However, the present disclosure is not limited thereto, and any suitable material may be used. As discussed, the flexure 6020 integrated into the slider 6000 provides a preload on the face seal. The flexure geometry is selected to provide the required axial force without excessively stressing the thermoplastic. Specifically, the maximum stress at full flexure of the flexure is selected to be below the long-term creep limit of the selected thermoplastic. This ensures that the required face seal preload is achieved long after the device is assembled, without stress relaxation in the flexure. For compactness, the compression spring 6032 for automatically closing the device is nestled within a slot 6044 within the perimeter of the slider element 6000. As described above, two sliders 6042 are positioned on the slider element 6000 to maintain parallelism between the slider element 6000 and the face seal when the exposed face seal surface protrudes above the guide surface of the injection system, which constrains the rear side of the slider element 6000.

As mentioned above, the axial force on the face seal is selected to exceed the expected internal pressure force by a certain safety margin. In cases where the required axial force exceeds the force provided by the small plastic buckling joint, an alternative approach is to use a separate spring component, which can be formed from steel. Steel leaf springs do not suffer from long-term creep issues and can increase the applied force, providing important advantages, but this comes at the cost of increased cost and the space required due to the separate component. One solution to this problem is to use a compression spring 6032, also serving a secondary purpose. The primary purpose of the compression spring is to provide the device with an automatic closing feature. When the user removes finger pressure from the activation button, the compression spring passively returns the device to the closed, sealing position without manual intervention. To maintain the device fully closed, the device geometry is configured such that the compression spring is preloaded when the slider element is in the fully closed position. This preload serves the secondary purpose of increasing the axial force on the face seal, a feature employed in this embodiment.

As shown in Figure 66, in the closed position, the activation button 6030 interacts with the slide element on an angled surface 6050. This angle creates 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. This fulcrum is a small lifting portion that interacts with the front of the slide element. In the presence of a horizontal force vector, the slide element 6000 pivots about the fulcrum, causing the lower portion of the slide element 6000 to pivot toward the face seal, thereby increasing the axial force on the face seal. This improves seal integrity without adding additional components or increasing space requirements. In addition, the axial force on the face seal is no longer solely dependent on the flexure joint, allowing a wider range of thermoplastics with low modulus (hardness) values to be selected.

Figures 65-68 show a complete set of schematic diagrams of an embodiment utilizing all of the features described above in the closed (left) position (Figures 65 and 66) and the open (right) position (Figures 67 and 68). In certain embodiments, the automatic closing system includes an umbrella valve or other suitable pressure relief device used in conjunction with a retaining plate (also referred to herein as a compression plate) to address vapor pressure buildup. As non-limiting examples, alternative pressure relief systems may include: a duckbill valve; an umbrella/duckbill two-way valve; other suitable pressure relief valves; a pinhole valve in a silicone sheet; a slit valve in a silicone sheet; a single pinhole/vent hole in a rigid material (e.g., a 50 micron diameter hole in 50 micron thick stainless steel); an array of vent holes; or any other suitable pressure relief device capable of quickly and adequately restoring pressure equilibrium while preventing excessive evaporation due to vapor pressure. Various aspects of the umbrella valve or pressure relief device will be discussed in greater detail herein.

Example 10: Measurement of crystallization, evaporation, and sealing

Crystallization occurs particularly in small holes where the evaporation rate is high, and the crystallization rate inhibits the operation of the droplet ejection device. If crystallization occurs, it prevents the droplets from being ejected from the ejection opening by blocking the flow.

According to one embodiment, for a generation plate with a 50 micron deep, 20 μm wide hole that is not punctured/capillary and is openly exposed to the environment, Figures 69A-69C show crystal growth of an isotonic saline solution over time. In Figure 69A, at the start of the timing, the injection opening is shown (the fluid has just been placed in a hard reservoir that is sealed to a spray grid that defines a plurality of injection openings), and no crystallization is shown. The laminated compression plate is sealed to the mesh screen by means of an O-ring, and the other opposite surface of the mesh screen is attached to the reservoir via the O-ring, and the assembly is held together by screws and nuts. 50 seconds after the fluid was placed, as shown in Figure 69B, a large amount of crystals began to form in the nozzle (hole). At 3 minutes, as shown in Figure 69C, many injection openings or holes were completely blocked, and several nozzles (holes) showed crystal growth. These images were obtained by transmitted light microscopy, wherein the crystals blocked the transmitted light through-openings.

To illustrate the role of the fluid loading plate, a system was also constructed consisting of a mesh screen with a generator plate containing pores 50, each 50 microns deep and 20 μm wide. However, in this case, a capillary plate was added, which was exposed to the environment. Figures 70A-70C show crystal growth over time in an isotonic saline solution. In Figure 70A, at the start of the timer, the injection openings are shown (the fluid has just been placed into the rigid reservoir, which is sealed to the injection grid via the following: laminated compression plate, O-ring, mesh screen, O-ring, piercing/capillary plate, O-ring, reservoir, all held together by screws and nuts). No crystals have formed. At 5 minutes, as shown in Figure 70B, no crystals have formed. At 6 hours, as shown in Figure 70C, many of the injection openings or pores are completely blocked, and several injection openings show crystal growth. Although the piercing/capillary plate does not reduce evaporation, it does reduce crystallization. By delivering a constant supply of fluid, the rate of crystallization is reduced by preventing mineral deposits from being immersed in the fluid.

In certain applications, evaporation may cause changes in drug strength and efficacy, for example, water loss, resulting in changes in concentration. Evaporation may also cause crystallization at the injection opening. Table 16 shows a comparison of the evaporation rate of the automatic closing system of the present invention and the evaporation rate of two umbrella valves with different opening pressures set in the fluid loading plate. The evaporation rate shown is the evaporation rate presented due to the pressure fluctuation valve not being opened, using one valve for isotonic saline and different valves for latanoprost and isotonic saline. Both valves showed very high evaporation rates. In contrast, depending on the fluid tested, the automatic closing system of the present invention resulted in a 7-10 times reduction in evaporation rate. Compared with the puncture plate/capillary plate and umbrella valve alone, this also resulted in a 7-10 times extension of the crystallization time between two injections.

Table 16: Evaporation rates for an umbrella valve compared to an ideal face seal using an automatic shutoff system.

In certain aspects of the present disclosure, an automatic shutoff system is utilized to prevent large pressure excursions from forcing fluid out of the injection system.If the pressure exceeds the cracking pressure, the valve compensates for the pressure almost instantly.

Alternatives to umbrella valves are also within the scope of this disclosure. In this regard, any suitable method for equalizing pressure while preventing evaporation can be utilized, such as 50 μm and 100 μm vent solutions with antimicrobial, fluid-resistant membrane filters incorporated into the vents. This solution also equalizes air pressure almost instantly, at 10 psi/.25 cc per second, and reduces evaporation rates 10-20 times compared to umbrella valves, as shown in Table 17. Table 17 also shows the leak rates for pressure equalization (without evaporation).

Table 17: Evaporation and leakage rates for pressure equalization of filter vents

The automatic closing system provides the air pressure barrier needed to prevent fluid evaporation, which could otherwise cause crystallization of the ejection opening. The purpose of this experiment is to determine the normal force required to produce a seal for an automatic closing system capable of sealing at a pressure of 1.00 PSI.

The weight of a plastic sealing element on a silicone face seal ring is used to determine the face seal quality in relation to the normal force. The ABS/polycarbonate plastic sealing element is attached to the bottom of the nozzle, allowing water to be added to vary the mass. A self-lubricating silicone seal is placed inside a compression plate, to which a pressure regulator and pressure gauge are attached. The variable-mass sealing element is balanced on the silicone seal, and fluid is added to the nozzle. Pressure data is recorded in relation to the face seal normal force.

As gauge pressure approaches 1.00 PSI, the seal quality of the automatic shutoff system increases. Normal forces of 40 grams and greater typically seal at pressures of 0.9 PSI or greater. Since this is significantly higher than the 0.2 PSI umbrella valve outlet pressure, it is considered an acceptable seal.

Another identification condition is that the friction force of the closing slide on the automatic closing system should be less than the restoring force of the automatic closing spring. This condition can be met by selecting a spring with a sufficiently large spring constant and displacement.

To measure the sealing quality provided by the internal automatic closing system seal during a series of multiple slide actuations, the automatic closing system according to the present disclosure was attached to an air pressure regulator and a pressure gauge. The regulator was set to 1.00 PSI using an ideal seal, which was then removed. The automatic closing was actuated to provide a seal, and the gauge pressure inside the seal was increased until a maximum pressure was reached. This maximum equilibrium pressure was recorded as the sealing pressure for that test.

The maximum equilibrium pressure was recorded for 20 tests, after which the automatic closing system was actuated 100 times. This process was repeated three or more times, resulting in four sets of 20 test data, with 100 actuations between each set. This was designed to allow for repeated testing of the automatic closing system over a total of 380 slide actuations. The average sealing pressure for each set of data is shown in Table 18.

Table 18: Automatic Closing Face Seal 380 Actuation Test

The 1.00 PSI seal was identified as an acceptable face seal because it provided a safety margin above the 0.2 PSI umbrella valve outlet. Over a total of 380 actuations, the data from this test was always within 6-7% of the target sealing pressure.

Many embodiments of the invention disclosed in this application and the aforementioned applications incorporated herein by reference have been disclosed. This disclosure contemplates that any feature of one embodiment or example can be combined with one or more features of other embodiments or examples. For example, any of the spray mechanisms or reservoirs can be used in combination with any of the disclosed housings or housing features, such as covers, supports, shelves, lights, seals and gaskets, filling mechanisms, or alignment mechanisms.

This disclosure also contemplates other variations of any element in any invention within the conventional art. Such variations include the choice of materials, coatings, or manufacturing methods. Any electrical and electronic technology may be used in any embodiment without limitation. Furthermore, any networking, remote access, patient monitoring, e-health, data storage, data mining, or Internet functionality is applicable to and implemented in conjunction with any and all embodiments. Furthermore, diagnostic functionality, such as performance testing or physiological parameter measurement, may also be incorporated into the functionality of any embodiment. As part of its diagnostic functionality, the device may perform a glaucoma performance test or other eye tests. Other manufacturing methods known in the art and not specifically listed here may be used to manufacture, 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 establish a unique identifier that matches the device to the user and is positioned between the eyes. Alternatively, the device or base may be coupled to or include any suitable advanced imaging device for photography or radiation.

Claims (31)

1. A jetting device for spraying fluid onto a surface, the jetting device comprising: case; A reservoir disposed within the housing, the reservoir having a certain volume _Vt and containing or configured to receive a certain volume _Vf of fluid; A fluid loading plate in fluid communication with the storage device; and An injection mechanism in fluid communication with the fluid loading plate; The fluid loading plate includes: a fluid reservoir interface for attachment to the reservoir; a jetting mechanism interface for attaching the fluid loading plate to the jetting mechanism; and one or more fluid channels for guiding fluid from the fluid reservoir interface to the jetting mechanism interface. The fluid loading plate is configured to be arranged parallel to the jetting mechanism to provide fluid to the rear surface of the jetting mechanism. The jetting mechanism is configured to jet a droplet stream of the fluid through one or more openings, and is configured to jet a droplet stream having an average droplet diameter greater than 15 micrometers, and the droplet stream carries a small amount of airflow so that when jetted onto a human or animal body surface, the pressure of the droplet stream on the surface will be substantially imperceptible. The fluid loading plate's injection mechanism interface and the injection mechanism's rear surface are arranged parallel to form a capillary gap, and fluid flow is generated on the injection mechanism's rear surface between the fluid loading plate and the injection mechanism; and The fluid loading plate includes a puncture plate fluid delivery system and a capillary plate, the puncture plate fluid delivery system and the capillary plate being integrally formed to deliver fluid from the reservoir to the injection mechanism, the puncture plate fluid delivery system including a fluid holding area and at least one hollow puncture needle for transferring fluid from the fluid holding area to the injection mechanism interface. 2. The spraying device as claimed in claim 1, wherein the spraying device is capable of spraying the droplet stream when the spraying device is tilted. 3. The spraying device as claimed in claim 1, wherein the spraying device is capable of spraying the droplet stream when the spraying device is tilted to an inverted position of 180 degrees. 4. The spraying device of claim 1, wherein the fluid is intended for use in the eyes, mouth, nose or lungs. 5. The injection device as claimed in claim 1, wherein the storage container further includes a certain volume of gas V_{_gas} in the volume V_{_t} . 6. The injection device as claimed in claim 1, wherein the reservoir is made of a flexible material. 7. The injection device of claim 1, wherein the reservoir is retractable. 8. The injection device as claimed in claim 7, wherein when a certain volume _Vf of fluid is filled, the retractable reservoir shrinks to a volume _Vr . 9. The injection device of claim 7, wherein the retractable reservoir is under negative internal pressure. 10. The injection device of claim 8, wherein when exposed to a positive pressure differential, the contracted reservoir expands by a volume V _exp , wherein the pressure inside the reservoir is greater than the external pressure. 11. The injection device of claim 10, wherein, for a defined positive pressure differential, the volume V_{_r} is selected to be greater than the volume V_{_exp} . 12. The injection device of claim 1, wherein the reservoir does not leak through the opening when exposed to a positive pressure differential, wherein the pressure inside the reservoir is greater than the external pressure. 13. The injection device as claimed in claim 12, wherein the positive pressure difference is less than or equal to 40 kPa. 14. The injection device of claim 1, wherein the fluid loading plate and the injection mechanism are spaced apart by a distance of 0.2 mm to 0.5 mm to form the capillary gap. 15. The spraying device of claim 1, wherein the spraying mechanism comprises a spraying plate and a piezoelectric actuator connected to a generating plate, the generating plate comprising a plurality of openings formed through its thickness, the piezoelectric actuator being operable to cause the spraying plate to oscillate at a certain frequency, thereby causing the generating plate to oscillate at a certain frequency and generating a directional flow of droplets. 16. The injection device of claim 1, wherein the puncture plate fluid delivery system includes a first mating portion and a second mating portion, the retractable reservoir being attached to and in fluid communication with the second mating portion, the second mating portion including a puncture-resistant seal for defining the fluid retention area. 17. The injection device of claim 16, wherein the first mating portion forms an insertion hole for the second mating portion, and includes the at least one hollow puncture needle for puncturing the retractable reservoir. 18. The injection device of claim 17, wherein the first mating portion and the at least one hollow puncture needle are integrally formed. 19. The spraying device of claim 16, wherein the puncture-resistant seal included in the second mating portion comprises a self-sealing silicone. 20. The spraying device of claim 1, further comprising an automatic shut-off system for reducing the risk of crystallization, evaporation and contamination, the automatic shut-off system including a user-activated slide plate for covering at least a portion of the spraying mechanism. 21. The spraying device of claim 20, wherein the spraying mechanism defines at least one spray opening, the slide plate is configured to hermetically engage a gasket or seal formed around the at least one spray opening, and the slide plate is slidable between an open position exposing the at least one spray opening and a closed position in which the at least one spray opening is covered by the slide plate. 22. The jetting device of claim 21, wherein the slide plate is biased toward its closed position by means of a spring. 23. The spraying device of claim 21, wherein the slide plate includes an opening configured to coincide with at least one spray opening in the spraying mechanism when the slide plate is in its open position. 24. The spraying device of claim 23, wherein the automatic shut-off system includes means for ensuring that sufficient pressure is applied to press the slide plate against the gasket or seal when the device is in the shut-off position. 25. The spraying device of claim 1, wherein the spraying mechanism includes a spraying plate coupled to a generating plate and a piezoelectric actuator, the generating plate including a plurality of openings formed through its thickness, the piezoelectric actuator being operable to cause the spraying plate to oscillate at a resonant frequency of the spraying plate coupled to the generating plate, thereby causing the generating plate to oscillate at the resonant frequency of the spraying plate coupled to the generating plate to generate a directional flow of droplets. 26. The jetting device of claim 25, wherein the piezoelectric actuator is made of lead-free piezoelectric material. 27. The jetting device of claim 26, wherein the lead-free piezoelectric material is selected from the group consisting of: _BiFeO3- based materials, sodium bismuth titanate (BNT) materials, potassium bismuth titanate (BKT) materials, bimodal magnetostrictive/piezoelectric bilayer composites, tungsten bronze materials, sodium niobate materials, barium titanate materials, or polyvinylidene fluoride materials. 28. The spraying device of claim 25, wherein the spraying plate has a central opening region aligned with a plurality of openings of the generating plate, and the piezoelectric actuator is coupled to a peripheral region of the spraying plate to prevent obstruction of the plurality of openings of the generating plate. 29. The spraying device of claim 28, wherein the generating plate has a reduced size relative to the spraying plate, the size of the generating plate being determined at least in part by the area occupied by the central opening region and the arrangement of the plurality of openings. 30. The spraying device of claim 29, wherein the spraying plate is circular, the piezoelectric actuator has an annular structure, and the spraying plate and the piezoelectric actuator have the same outer diameter. 31. The spraying device of claim 29, wherein the spraying plate is circular, the piezoelectric actuator has an annular structure, and the spraying plate has an outer diameter larger than that of the piezoelectric actuator.