Spray ejector device and methods of use.

(54) Title: SPRAY EJECTOR DEVICE AND METHODS OF USE. (54) Title: SPRAY EJECTOR DEVICE AND METHODS OF USE.

(57) Summary

An ejector device for ejecting small drops of fluid onto a surface includes an ejector mechanism attached to a fluid reservoir through a fluid loading plate that is configured to pierce the reservoir and channel fluid to a posterior surface of the ejector mechanism. by capillary action; the ejector mechanism may have a center-symmetrical configuration with a lead-free piezo-actuator and may be covered by a self-closing cover.

(57) Abstract

An ejector device (100) for ejecting droplets of fluid onto a surface ineludes an ejector mechanism (108) attached to a fluid reservoir (102) through a fluid loading píate (104) that is configured to pierce the reservoir and channel the fluid to a rear surface of the ejector mechanism (108) by capillary action. The ejector mechanism (108) may have a centro-symmetric configuration with a lead free piezo actuator and may be covered by an auto-closing cover.

SPRAY EJECTOR DEVICE AND METHODS OF USE

RELATED REQUESTS

This application claims the benefit of the filing date of the US Provisional Applications. No. 61 / 639,559 filed on April 20, 2012; 61 / 636,565 filed on April 20, 2012; 61 / 643,150 filed on May 4, 2012; 61 / 722,611 filed on November 5, 2012, and 61 / 722,616 filed on November 6, 2012, the contents of which are incorporated herein by reference in their entireties.

TECHNICAL FIELD

The present description relates to ejector devices, and 15 methods of making ejector devices. In particular, it refers to devices and methods for expelling mists, or micro-droplet sprays.

BACKGROUND OF THE INVENTION

Using spray devices to administer products in the form of mists or sprays is an area with great potential for safe, easy-to-use products. A greater challenge in providing such a device is to provide consistent and accurate delivery of adequate doses and to avoid contamination of the product being supplied.

An important area where spray devices are needed is in the supply of eye medications. The application of fluids, as in the case of eye drops, has always posed a problem, especially for children and animals, which tend to blink or shake at the critical time of administration, causing the droplet to land on the eyelid, nose or another part of the face. The impact of a large drop or drops of fluid on the eyeball, especially when the fluid is at a different temperature, also tends to produce a flicker reaction. Older people also frequently lose the hand coordination necessary to introduce the eye drops into their eyes. Stroke victims have similar difficulties.

Currently, many of these medications are administered using eye droppers, which frequently require the head to be tilted back, the subject to lie down or provide downward traction on the Lower Eyelid, or a combination of tilt traction, as the mechanism Delivery times typically rely on the severity to apply the medication. This is not only difficult, but involves a good amount of coordination, flexibility, and cooperation on the part of the subject to ensure that the medication enters the eye while avoiding stinging the eye with the tip of the dropper. In current eye dropper bottles, the pointed applicator tip poses the risk of itching the user in the eye, potentially causing physical damage to the eye, and further exposing the tip to bacterial contamination due to contact with the eye. As such, the subject runs the risk of contaminating the medication in the eye dropper bottle and subsequently infecting the eye. Additionally, a large volume of medication flows out of the eye or is washed out by the drip reflex. As a result, this method of administration is also imprecise and wasteful. Furthermore, the eye dropper does not provide a satisfactory way to control the amount of medicine being delivered, nor does it provide a way to ensure that the medicine being delivered actually lands on the eye and stays on the eye.

Eyedroppers also provide no way to verify compliance with a subject. Even if after one week of use the eye dropper bottle can be checked for the total volume of medicine delivered, for example, by weighing the bottle, this does not provide a day-to-day compliance record. A subject may have missed one or more doses and taken an excessive dose at other times. Also, the poor precision with which the eye droppers deliver drops to the eye makes it difficult to determine if the medication is actually delivered into the eye, even though it may have been delivered.

The ability of a piezoelectric droplet generation system to expel fluid has conventionally been very limited by the piezoelectric material properties of the ceramic used. For many years, an alternative lead-free piezoelectric material system with properties comparable to lead-based systems has been sought in order to satisfy global regulations. This material system has yet to emerge. An ejector system design that minimizes dependency on piezoelectric material properties to allow for comparable ejection with inferior material characteristics thus desirable.

Accordingly, there is a need for a delivery device that delivers safe, adequate, and repeatable dosages to a subject for ophthalmic, topical, oral, nasal, or pulmonary use.

BRIEF DESCRIPTION OF THE INVENTION

In accordance with the present disclosure there is provided an ejector device comprising a housing, a reservoir having a volume of fluid contained within the housing, a fluid loading plate in fluid communication with the fluid in the reservoir, and an ejector mechanism in communication fluid with the fluid charging plate, where the fluid charging plate provides fluid to a posterior surface of the ejector mechanism, and the ejector mechanism is configured to eject a stream of fluid droplets through at least one opening. The fluid loading plate may be configured to be placed in parallel with the ejector mechanism to supply fluid to a rear ejection surface of the ejector mechanism. The disclosure ejector device is capable of supplying a defined volume of fluid in the form of droplets that have properties that allow unrepeatable adequate high percentage deposition with application.

In this regard, an important consideration in accordance with the present disclosure is not only capable of delivering the drug in an easier to use form, for example by spraying a mist horizontally on the surface to be treated, but also to ensure that medication is consistently delivered to the delivery ejector mechanism in any orientation. In some implementations, the ejector device is capable of expelling a stream of droplets when the ejector device is tilted, even if it is tilted 180 degrees reversed.

In certain embodiments, the fluid loading plate may comprise a capillary plate fluid supply device for supplying fluid from a reservoir to an ejector mechanism of an ejector device, and methods of use for supplying adequate, safe fluid dosages, and Repeatable to a subject for ophthalmic, topical, oral, nasal, or pulmonary use. The capillary plate may comprise a fluid reservoir interface, an ejector mechanism interface, and one or more fluid channels for channeling fluid to the ejector mechanism through one or more mechanisms, including capillary action.

In other embodiments, the fluid loading plate may comprise a puncture plate fluid supply system for supplying fluid from an ejector mechanism reservoir of an ejector device. The puncture plate fluid supply system, also denoted as a puncture / capillary plate fluid supply system, may include a capillary plate portion comprising a fluid retention area between the fluid supply system of puncture / capillary plate and a posterior surface of an ejector mechanism to channel fluid to the ejector mechanism by one or more mechanisms, including capillary action, and at least one hollow puncture needle to transfer fluid from a reservoir to the fluid retention area.

In certain aspects, the puncture plate fluid supply system may include a first and a second coupling portion, where a reservoir is joined in fluid communication to the second coupling portion, the second coupling portion includes a pierceable seal . The first coupling portion can form a receptacle for the second coupling portion, and can include the at least one hollow puncture needle to pierce the pierceable seal. The first coupling portion and the at least one puncture needle can be integrally formed. The pierceable seal included in the second coupling portion may comprise a self-sealing silicone.

The reservoir, also indicated herein as a vial, may comprise a collapsible and flexible container. The container may comprise a container and a layer where the reservoir is configured so that the lid and the container form a volume capable of containing a fluid. The reservoir may be configured to partially fold (at sea level) and capable of expansion to incorporate gas expansion within the volume and prevent leakage.

The ejector mechanism may comprise an ejector plate coupled to a droplet generating plate (referred to herein simply as a generating plate) and a piezoelectric actuator; the generating plate includes a plurality of openings formed through its thickness, and the piezoelectric actuator is operable to oscillate the ejector plate and thereby oscillate the generating plate at a frequency to generate a directed stream of droplets. The ejector plate may have a central open screed aligned with the generator plate, wherein the piezoelectric actuator is coupled to a peripheral region of the ejector plate so as not to obscure the plurality of openings in the generator plate. The plurality of openings of the generating plate can be arranged in a central region of the generating plate which is discovered by the piezoelectric actuator and

I aligned with the central open region of the ejector plate. The geometry and three-dimensional shapes of the openings, including hole diameter and capillary length, and spatial arrangement on the generating plate can be controlled to utilize directed stream generation of droplets. The generating plate can be formed from a high modulus polymer material, for example, formed from 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 ejector mechanism may be configured to expel a stream of droplets having an average ejected droplet diameter greater than 15 microns, with the droplet stream having low entrained airflows so that the droplet stream is deposited on the subject's eye. during use.

The ejector mechanism may have a centro-symmetrical structure in which the ejector plate includes symmetrically arranged mounting structures, with a symmetrical configuration in which droplets are ejected from a central region of the symmetrical structure. The piezoelectric actuator can induce resonance amplification of the generator plate coupled to the ejector plate to allow for a greater variety of piezoelectric constants. The ejector plate may be made of a high modulus polymeric material, and the piezoelectric actuator may be lead free, or substantially lead free.

The droplets can be formed in a size distribution, each distribution has an average droplet size. The average droplet size may be in the range of about 15 microns to over 400 microns, for example, greater than 20 microns to approximately 400 microns, approximately 20 microns to approximately 200 microns, approximately 100 microns to approximately 200 microns, approximately 20 microns. micras at approximately 80 micras, approximately 25 micras at approximately 75 micras, approximately 30 micras at approximately 60 micras, approximately 35 micras at approximately 60 micras, etc. However, the average droplet size can be as large as 2500 microns, depending on the desired application. Also, the droplets can have an average initial velocity of about 0.5 m / s to about 100 m / s, for example, about 0.5 m / s to about 20 m / s, about 0.5 to about 10 m / s, about 1 m / s about 5 m / s, about 1 m / s, about 4 m / s, about 2 m / s, etc. As used here, the ejection size and initial velocity are the initial size and velocity of the droplets when the droplets leave the ejector plate. The droplet current directed at a target will result in deposition of a percentage of the mass of the droplets including their composition on the target.

The ejector mechanism and fluid charge plate can be assembled to form a unit defining an ejector assembly, the ejector assembly comprises a fluid charge plate in fluid communication with an ejector mechanism such that the fluid charge plate provides fluid To a rear surface of the ejector mechanism, the ejector mechanism is configured to eject a stream of droplets. In certain embodiments, the ejector assembly may further comprise a reservoir in fluid communication with the fluid loading plate.

The ejector device may further include a self-closing system, which generally reduces crystallization, evaporation, and risk of contamination. The self-closing system may include a user-activated sliding plate that is sealedly coupled to a gasket or seal formed to surround at least the holes in the generating plate, and is slidable between an open position in which the holes They are exposed and a closed position in which the holes are covered by the sliding plate. The sliding plate can be deflected into its closed position by means of a spring. The slide plate can include an opening configured to match the holes in the generating plate when the slide plate is in its open position. Means may be included in the self-closing system to ensure that the slide plate is pressed with sufficient pressure against the seal when in the closed position.

Furthermore, in accordance with the description, a self-closing system is provided for a droplet ejection device that generally reduces crystallization, evaporation, and risk of contamination.

Furthermore, in accordance with the disclosure, there is provided a method of manufacturing a generator plate for expelling high-viscosity fluid suitable for ophthalmic, topical, oral, nasal, or pulmonary use, comprising laser micro-turning of materials to form openings. Three-dimensional through the thickness of the material, each of the openings defines an entrance cavity and a capillary channel, where the opening comprises a general inclination length.

Furthermore, in accordance with the disclosure, there is provided a method of supplying a volume of ophthalmic fluid to a subject's eye, the method comprising expelling a directed stream of droplets from a fluid "

one ophthalmic contained in a reservoir from ejector plate openings, the droplets in the directed stream have an average expulsion diameter in the range of 5-2500 microns, for example, 20-400 microns, for example, 20-200 microns, and including but not limited to a range of 100-200, etc., and an average initial velocity in the range of 0.5-100 m / s, for example, 1-100 m / s, for example, 2-20 m / s .

These and other aspects of the invention will become apparent to one skilled in the art.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 is a three-dimensional exploded view of the mechanical parts of one embodiment of an ejector device of the disclosure;

Figure 2 is a front view of one embodiment of an ejector device of the description.

Figure 3 shows an embodiment of a tank of the description;

Figure 4 shows another embodiment of a tank of the description;

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

Figures 6A to 6D illustrate various modalities of components of a reservoir in accordance with one embodiment of the description;

Figure 7 illustrates a forming, filling and sealing process for generating deposits in accordance with one embodiment of the disclosure;

Figure 8 shows an embodiment of a reservoir, fluid charge plate and ejector plate in accordance with one aspect of the disclosure, illustrating the direction of droplet ejection relative to angle of inclination.

Figure 9 shows an embodiment of a test apparatus for measuring differential pressure induced leakage in an embodiment of a reservoir, fluid charge plate, and ejector assembly in accordance with one aspect of the disclosure;

Figures 10A to 10E illustrate reservoir expansion after a decrease in pressure in a modal filtration point pressure determination of a reservoir, fluid charge plate and ejector assembly, in accordance with aspects of the disclosure;

Figure 11 illustrates the effect of volume V_gas expressed as a percentage of V-ι over the differential filtration pressure value for different modalities of a tank, fluid charge plate and ejector assembly in accordance with aspects of the description.

Figure 12 illustrates loss of deposit mass (vial) over time, in accordance with one aspect of the disclosure;

Figure 13 illustrates the tilt insensitivity of an embodiment of the disclosure having a collapsible and flexible reservoir (vial) compared to an embodiment of the disclosure having a hard reservoir;

Figures 14A to 14C show an embodiment of a capillary plate of the description;

Figures 15A to 15C show an embodiment of an ejector mechanism relative to an embodiment of a capillary plate of the disclosure;

Figures 16A to 16B illustrate the relationship between plate spacing and water height on vertical parallel plates;

Figures 17A to 17B show an embodiment of a capillary plate of the description;

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

Figure 19 illustrates that an increased height of water behind an ejector plate in the presence of a capillary plate leads to an increased mass loading effect at a particular frequency;

Figure 20 illustrates the downward frequency shift associated with a capillary plate used with the supply of various fluids;

Figure 21 and Table A illustrate the reduction in mass load for fluids of increasing density and viscosity;

Figure 22 illustrates the tilt insensitivity of an ejector device including a capillary plate;

Figures 23A through 23F show the main components of one embodiment of an ejector assembly including a capillary / puncture plate system with reservoir and ejector mechanism in accordance with the description;

Figures 24A to 24B show three-dimensional front and rear views of the components of Figures 23A to 23F in assembled form;

Figures 25A to 25B show a detailed front and rear view of one embodiment of an ejector mechanism of the disclosure;

Figure 26 is a schematic representation outlining fluid flow 10 through a puncture plate system of the disclosure;

Figure 27 is a schematic representation of a lancing plate system of the disclosure showing the Venturi effect;

Figure 28 illustrates the principles of the Bernoulli equation; Figure 29 illustrates the principles of hydrostatic pressure;

Figure 30 shows schematic representations of different tank configurations from the description;

Figure 31 shows schematic representations of additional tank configurations from the description;

Figures 32A to 32B show three-dimensional and side view and front view image figures 20 of two modalities of collapsible tank of the description;

Figure 33 shows a rear view of one embodiment of a blow-fill-seal reservoir and puncture plate of the disclosure;

Figures 34A to 34B show side views of two embodiments of the blow-fill-seal reservoir system and lancing plate of the disclosure;

Figure 35 shows two forms of filling-sealing form-5 tank of the description;

Figures 36 to 37 show an apparatus and configuration for determining the amount of negative pressure that different reservoir configurations exert as they are removing fluid;

Figure 38 shows the mass by spray and total spray 10 (downward spray performance) of a non-collapsible deflected tank embodiment with substantial fold formation of the disclosure;

Figure 39 shows the mass by spray and total spray (descending spray performance) of various modalities of the blow-fill-seal tank of the disclosure;

Figure 40 shows two executions of a spray mass and total spray (falling spray performance) of a self-sealing low tensile stress (LTS) weld deposit / collapsible deviation form of the disclosure;

Figure 41 shows the downward traction performance for selected round LTS ampoule designs from Figure 35.

Figure 42 shows a mechanism involved in inverted spraying using a round LTS tank;

Figure 43 shows the actual downward spray performance results of a down sprayed LTS reservoir mode on a full inverted puncture system of the disclosure;

Figure 44 shows the downward spraying performance of another lancing plate configuration with one embodiment of an IV bag reservoir embodiment of the disclosure;

Figure 45 shows the downward spraying performance of two different puncture plate configurations with one embodiment of an IV bag reservoir of the disclosure in different orientations and with different spray directions;

Figure 46 shows the downward spraying performance of one embodiment of a lancing plate configuration with an IV bag reservoir embodiment of the disclosure in different orientations and with different spraying directions and different venting plate vent options. puncture;

Figure 47 schematically shows the relationship between capillary effect and hydrostatic pressure of the tank;

Figure 48 and Table B show capillary pressure for half droplets of various water sizes;

Figure 49 and Table C show capillary pressure for half droplets of various sizes of latanaprost;

Figure 50 and Table D show capillary augmentation of various types of fluid having different contact angle values;

Figure 51 and Table E show capillary augmentation for saline in a capillary channel made of different types of materials;

Figures 52 to 53 show fluid increase levels between puncture plate and ejector plate for different materials;

Figure 54 shows a test setup for testing fluid leakage out of the capillary augmentation port under different fluid fill locations;

Figure 55A shows a cross-sectional view of one embodiment of an ejector assembly of the disclosure;

Figure 55B shows a three-dimensional view of one embodiment of an ejector mechanism of the disclosure.

Figures 55C shows a front view of one embodiment of a center-symmetric ejector mechanism of the disclosure;

Figure 55D shows a disassembled view of one embodiment of an ejector mechanism of the disclosure;

Figure 56 shows the nomenclature of the axis numbering convention for piezoelectric effects;

Figure 57 shows modes of operation of an active region of a generator plate modality, and oscillation digital holographic microscopy images of the generator plate;

Figures 58 illustrates a comparison of mass ejection for lead zirconate titanate PZT piezoelectric actuator materials and BaT¡0₃ (lead free) utilizing an ejector assembly with an internally mounted piezoelectric actuator in accordance with one embodiment of the disclosure;

Figure 59 illustrates a comparison of mass ejection for piezoelectric actuator materials from PZT and BaT¡0₃ (lead free) using an ejector assembly with an edge mounted piezoelectric actuator in accordance with another embodiment of the disclosure;

Figure 60 shows a three-dimensional transparent view of an embodiment of an ejector assembly with self-closing system of the description;

Figure 61 shows the self-closing ejector assembly of Figure 60 in a dismantled state;

Figure 62 is a sectional side view of part of the ejector assembly with self-closing systems of Figure 60;

Figure 63 shows a three-dimensional front view of a sliding unit of the self-closing system of Figure 60;

Figure 64 shows a three-dimensional rear view of the sliding unit of Figure 63;

Figure 65 is a front view of the self-closing unit of Figure 60 in a closed position;

Figure 66 is a sectional side view of the self-closing unit 20 of Figure 60 in a closed position;

Figure 67 is a front view of a self-closing unit of Figure 60 in an open position;

Figure 68 is a sectional side view of the self-closing unit19 of Figure 60 in an open position;

Figures 69A to 69C show light transmission microscopy images over time of a mesh screen of a generator plate in which the system is not provided with a capillary plate, and Figures 70A to 70C show light microscopy images transmission over time of a sieve mesh of a generator plate in which the system was provided with a capillary plate.

DETAILED DESCRIPTION OF THE INVENTION

The present application relates to ejector devices for supplying fluid to a surface as a stream expelled from droplets. The ejector device, for example, can be as described in the

US Provisional Requests not. 61 / 569,739, 61 / 636,559, 61 / 636,565,

61 / 636,568, 61 / 642,838, 61 / 642,867, 61 / 643,150 and 61 / 584,060, and US Patent Applications. No. 13 / 184,446, 13 / 184,468 and 13 / 184,484, the contents of which are incorporated herein by reference.

The ejector device of the present disclosure may, for example, be useful in supplying fluid for ophthalmic, topical, oral, nasal or pulmonary use. However, the description is not so limited, and may be useful with any of the ejector devices (eg, printer devices, etc.).

In certain embodiments, the ejector device may comprise a housing, a reservoir arranged within the housing to receive a volume of fluid, a fluid loading plate, and an ejector mechanism configured to eject one or more droplet streams from a fluid, in where the reservoir is in fluid communication with the fluid charging plate, which is in fluid communication with the ejector mechanism such that the fluid loading plate provides fluid to a rear surface of the ejector plate.

Thus, the present disclosure generally relates to an ejector device for expelling fluid onto a surface, for example, expelling ophthalmic fluid onto a patient's eye. Components of one embodiment of the ejector device will be described extensively with respect to Figure 1, thereafter some of the elements that make up the device will be discussed in greater detail. However, it will be appreciated that the application is not limited to the particular modalities described herein, but includes variations and different combinations of the elements that make up the ejector device.

For purposes of this application, the fluid includes, without limitation, suspensions or emulsions having viscosities in a range capable of droplet formation using an ejector mechanism.

Figure 1 shows an exploded view of an embodiment of internal components of an ejector device 100 of the present disclosure, and Includes a reservoir 102, which in this embodiment is a flexible reservoir made of a self-sealing RF welding technique. Reservoir 102 is placed in fluid communication with fluid loading plate 104 via pierceable seal coupling 106. The fluid loading plate supplies fluid from the reservoir to the rear face of an ejector mechanism 108, for example, by capillary action. The ejector in this embodiment comprises a piezoejector mechanism configured to generate a controllable stream of fluid droplets. Although the present embodiment describes a fluid loading plate 104, which is also discussed in greater detail below, other configurations can be adopted to channel fluid by capillary action from the reservoir to the ejector mechanism. In order to limit vaporization, crystallization, and fluid contamination, a self-closing system 110 is mounted in front of the ejector mechanism 108. A bracket 112 to support a housing 114 for a focus LED is configured to clip onto the front face of the self-locking system

110.

As shown in Figure 2, in certain embodiments, the mechanical components of the ejector device can be mounted within a removable upper section 200 of a housing 202, which engages with the lower handle portion 204. Electronic components to control expulsion. of fluid and power source can be accommodated within lower grip portion 204 in housing 202.

The reservoir or vial 102 for use with the ejector device

100 it can comprise a flexible deposit, or a hard, non-flexible one. In certain embodiments, the reservoir comprises a collapsible and flexible reservoir 102 disposed within the upper section 200 of housing 202, and contains or is adapted to receive a volume of fluid. Different types of flexible tanks made using different techniques are contemplated by the present description, including self-sealing, radio frequency (RF) welding tanks as shown in Figure 1. Alternatively, a blow-fill-seal technique can be used to form a reservoir of similar configuration as shown in Figure 3, or a form-fill-seal technique can be used to provide a reservoir such as that shown in Figure 4. As will be clarified from the discussion below, the particular configuration of the tank may vary from one modality to the next. For example, the shape of the form-fill-seal tanks is not limited to that shown in Figure 4.

With reference to Figure 5, atmospheric pressure varies with altitude. Specifically, as altitude increases, pressure decreases. In accordance with Boyle's law, the volume of a gas increases as the pressure decreases. Similarly, Charles's Law allows that as the temperature increases, so does the volume of a gas. In contrast, liquids generally have small changes in volume in response to changes in pressure and temperature, with a notable exception being a gap that expands when cooled from 4 ° to 0 °. Thus, while a liquid in a reservoir will change little when the pressure and temperature conditions change, a reservoir must be designed that has a volume of the liquid and also a volume of gas to incorporate decreases in pressure and increases in temperature. In many cases, the greatest concern arises from changes in pressure, causing significant volume changes in the gas. Changes in altitude are a common cause of changes in pressure and therefore in the volume of gases.

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

P = Po · Μ .........

\ & z

Where:

<td>Parameter</td><td>Description</td><td>Value</td>

<td>Po</td><td>Atmospheric pressure standard at sea level</td><td>101325 Pascal (Pa)</td>

<td>L</td><td>temperature span index</td><td>-273.14 ° C (0.0065 ° Kelv¡n) / meter (m)</td>

<td>To</td><td>standard temperature at sea level</td><td>15 ° C (288.15 ° K)</td>

<td>G</td><td>acceleration gravitational of land surface</td><td>9.80665 m / (s)</td>

<td>M</td><td>molar mass of dry air</td><td>0.0289644 kg / mol</td>

<td>R</td><td>gas constant universal</td><td>8.31447 Joule (J) / mol ° K)</td>

An ampule or reservoir, or a device containing the ampoule or reservoir may, in accordance with the description, be transported on an airplane or to a geographic location well above sea level. As discussed, such changes can lead to pressure differentials from sea level that can lead to leakage from holes in an ejector device. For example, cockpits on an airplane can be pressurized for altitudes from 1828.8 m (6000 ft) to 2438.4 m (8000 ft). The corresponding pressure differential from sea level is 20 to 29 kilo paséales, respectively. Ampoules that are unable to accommodate for this temperature differential through frequent expansion lead to pressure build-up within the ampoule and subsequent fluid leakage from the device. As used herein, "ambient pressure" refers to the air pressure to which the reservoir, bulb, or device having a reservoir or bulb is exposed. As used here, "pressure differential" refers to the difference in air pressure between ambient pressure and standard air pressure at sea level (101325 paséales (PA)). Thus, the reduced pressure as found in an environment is the ambient pressure and the pressure differential is the difference between the ambient pressure and the standard pressure at sea level (for example, approximately 20 kilograms at 1828.8 m (6000 feet)). Similarly, the pressure differential at an altitude above sea level is the difference between the standard pressure at sea level (101325 Paséales (PA)) and the ambient pressure at that altitude.

In other embodiments, the reservoir or vial may be a hard reservoir designed to incorporate expansion of any gas there. In some embodiments, expansion can be suppressed by providing a pressurized compartment. In other embodiments, leakage can be suppressed by sealing any holes present in the reservoir.

Referring to Figures 6A through 6D, in certain embodiments, the reservoir (in this case a form-fill-seal reservoir) may comprise a vial having three components, a cap 601, a container 602, and optionally a reinforcing ring 603. In some embodiments, lid 601 is sealed to container 602 to form a closed waterproof container. In one embodiment, the sealed waterproof combination of lid 601 and container 602 provides storage of the liquid. In other embodiments, container 602 forms a flexible reservoir that can incorporate the expansion of a gas contained with and trapped by the reservoir. In other embodiments, the reservoir can be forced from non-folding materials to make a rigid reservoir.

In some respects in accordance with the present disclosure, the vial or reservoir can be assembled from multiple components so that the container, cap 601 properties

602, and reinforcing ring 603 can be adapted according to the needs of the device application. In other embodiments, container 602 and reinforcing ring 603 can be formed together, and cap 601 applied after addition after a desired fluid. In one embodiment, the sealed waterproof condition of lid 601 and container 602 can be formed separately. In certain embodiments, cover 601 may be pierceable.

In certain modalities, the shape and size of the vial and reservoir can be selected according to the needs of the desired use. In a non-limiting example, a fluid for ophthalmic use may be required by a person who needs a short treatment time, and thus may require fewer doses. Where fewer doses are indicated, the shape and size of the vial can be scaled appropriately to avoid unnecessary waste. In other aspects, large volumes may be indicated where fluid is required for an extended period of time, or multiple daily doses may be required.

Volume 610 can be controlled by varying depth 607, diameter 604, and shape 609. In some respects, for example for lung use, diameter 604 may be greater than 1 cm in diameter. In another aspect, the diameter can be 1.5 cm. In a further embodiment, the diameter can be from 1 to 3 cm. In another embodiment the diameter can be between 1 and 4 cm, or 1 and 6 cm. In other embodiments, the diameter 604 may be 3 cm or more, 4 cm or more, 5 cm or more, 6 cm or more, or 7 cm or more. In other embodiments, the diameter may be configured for a device, for example, for ophthalmic applications. For example, diameter 604 can be 20mm or less. In other embodiments, diameter 604 may be 19mm or less. In another embodiment, diameter 604 can be 18mm or less.

Even in another embodiment, diameter 604 can be 17 mm or less. In one embodiment, diameter 604 can be 16mm or less. In other embodiments of the present disclosure, diameter 604 can be from 8 to 19 mm. In another embodiment, the diameter may be from 15 to 20mm, 16 to 20mm, 17 to 20mm, 18 to 20mm, or 19 to 20mm. In other embodiments, diameter 604 can be from 15 to 19mm, 16 to 19mm, 17 to 19mm, or 18 to 19mm.

In certain embodiments in accordance with the present disclosure, the vial shape 609 may be modified to increase or decrease the volume in view of the diameter 604. In some embodiments, the shape 609 may be configured so that the diameter decreases toward the closed end of the container along depth 607. In certain respects, the decreasing diameter may allow removal of a mold. Design and manufacture of molds for forming ampoules in accordance with the present invention having a container 602 are known in the art.

In certain embodiments of the present disclosure, the vial may comprise a reinforcing ring 603 configured to add stability to container 602. In some embodiments, container 602 may be flexible and a reinforcing ring 603 may allow connection to devices or housings. in accordance with the present description. The thickness 606 and diameter 605 can be determined based on the diameter 604 of the container 602 formed. In one aspect, thickness 606 can be determined in accordance with the material of reinforcing ring 603.

The sealed combination of cap 601 and container 602, and optional reinforcing rings form a vial suitable for retaining and storing a fluid for ophthalmic, topical, oral, nasal, or lung use until insertion of the vial into an ejector device or housing ejector device. In some embodiments, the sealed vial may be suitable for short-term storage of a fluid for ophthalmic, topical, oral, nasal, or pulmonary use. In other embodiments, the sealed vial may be suitable for long-term storage of a fluid for ophthalmic, topical, oral, nasal, or pulmonary use.

In certain implementations, the vial containing sealed fluid can be stored without loss of fluid graduation for one week. In other modalities, the sealed vial can be stored for more than a week. In some embodiments, the sealed vial may be suitable for short-term storage including 2 weeks, 3 weeks, or one month. In a certain Implementation, the sealed vial can be stored for one month.

In certain implementations, the vial containing sealed fluid can be stored for longer periods without significant loss or degradation. In other modalities, the vial containing sealed fluid can be stored for more than a month. In other modalities, the sealed vial can be stored for more than 2 months. In some embodiments, the sealed vial may be suitable for long-term storage, including 3 months, 4 months, or more. In certain implementations, the sealed vial can be stored for 5 months.

In other modalities, the sealed vial can be stored for 6 months. In some embodiments, the sealed vial may be suitable for long-term storage, including 7 months, 8 months, or longer. In certain implementations, the sealed vial can be stored for 9 months. In certain implementations, the sealed vial can be stored for 10 months. In other modalities, the sealed vial can be stored for 11 months. In some embodiments, the sealed vial may be suitable for long-term storage, including 12 months, or longer. In certain implementations, the sealed vial can be stored for 1.5 years. Even in other implementations, the fluid filled sealed vial can be stored for more than 1.5 years.

Lid 601, container 602, and reinforcing ring 603 can be formed from any of the materials suitable for use in the desired application. By way of example, in ophthalmic applications, any material suitable for use in pharmaceutical ophthalmic applications may be used, such as polymer materials that do not chemically react with or absorb fluids to be supplied. In other aspects, the surfaces of the lid 601, container 602, and reinforcing ring 603 that are exposed to the fluid to be supplied can be formed from materials that provide desired surface properties, including, for example, hydrophobicity, hydrophilicity. , null reactivity, stability, etc. Examples of suitable materials for lid 601 and container 602 include materials presented in, but not limited to, the

Table 1.

TABLE 1

Illustrative lid and container materials

<td>Maker</td><td>Name of product</td><td>Description</td>

<td>Sealed Air</td><td>Nexcel Latitude ML.29xxC</td><td>PE-based co-extruded film</td>

<td>Sealed Air</td><td>Nexcel M2930</td><td></td>

<td>Sealed Air</td><td>Nexcel MF513 transparent</td><td>Medical barrier film with oxygen barrier</td>

<td>Rollprint</td><td>Triad "C"</td><td>Extruded laminated compound of polyester, polyethylene, aluminum foil and modified polyolefin sealant</td>

<td>Alean Packaging Pharmaceutical Packaging Inc.</td><td>Bag Rolled Product Code 92036</td><td>Co-extruded high barrier PET compound, adhesive, aluminum, polyethylene</td>

<td>Texas Technologies</td><td>SV-300X</td><td>3 mils (0.008 cm) nylon, EVOH, poly coex</td>

<td>SAFO Biosciences</td><td>Bioeaze</td><td>Ethyl vinyl acetate film</td>

<td>Winpak</td><td>DF15YG2</td><td>Removable Al foil based (AI / PE)</td>

<td>Winpak</td><td>WCS100</td><td>PET Composite Flexible Packaging Laminate, LDPE Al, and coex</td>

In some embodiments in accordance with the present disclosure, the material for container 602 can be selected for properties consistent with an FDA approved medical device. Materials can be selected by methods and criteria known in the art, for example, ISO 10993-5, Biological Evaluation of Devices

Physicians-US Pharmacopeia 32 from USA Part 5, Biological Reactivity Tests, in vitro; ISO 13485, Medical Device Quality Management System; and ISO 17025, General Requirements for the Testing and Calibration Laboratories Competition. For example, container 602 may be a non-cytotoxic film such as ML29xxC available from Sealed

Air.

In accordance with the present description, the material for container 602 can be a polymer. In certain embodiments, the polymer may be a layered polymer. In other embodiments, the polymer can be a co-extruded forming film. In certain embodiments, the polymer can be a polymer for use in medical devices. In one example, in accordance with the present disclosure, the film may be a polyethylene-based co-extruded forming film. In certain embodiments, the polymer can be sterilized. In one aspect, the film can be selected in accordance with its ability to link to other films. In one example, the other film may be a Tyvek-coated or other medical material. In one aspect, the film can be transparent or opaque. In another aspect, the film may be puncture resistant. In yet another respect, the film can be down-calibration resistant.

In one aspect, the film may be formable. Formable films in accordance with the present description can be selected in accordance with the application requirements. In certain respects, the film may be selected based on one or more of the following criteria: thickness, Young's modulus, elongation, tensile strength, puncture force, tear, and haze. In certain aspects, the flexibility of the film can allow for a collapsible vial. In one aspect, the collapsible ampoule can allow leakage removal with changes in atmospheric pressure.

Examples of films compatible with devices and methods of the present invention include films provided in Table 2. In accordance with the present description, similar films can be selected based on the desired properties of Thickness, modulus (MD) of

Young, Elongation (MD), Tensile Strength (MD), Puncture, Tear, and Mist.

TABLE 2

Illustrative films of the present description

<td colspan="2">H medical films</td><td>excel® d</td><td colspan="2">e Sealed air:</td><td colspan="4">attitude ML29xxC</td>

<td></td><td>Unit</td><td>ASTM</td><td>30C</td><td>45C</td><td>60C</td><td>70C</td><td>80C</td><td>10C</td>

<td>Thickness*</td><td>Miera</td><td></td><td> 75</td><td> 112.5</td><td> 150</td><td> 175</td><td> 200</td><td> 250</td>

<td>Young's Modulus (MD)</td><td>kg / cm²</td><td>D882</td><td> 4967</td><td> 5059</td><td> 4995</td><td> 5002</td><td> 5016</td><td> 5023</td>

<td>Elongation (MD)</td><td> %</td><td>D882</td><td> 280</td><td> 340</td><td> 350</td><td> 345</td><td> 374</td><td> 406</td>

<td>Tensile strength (MD)</td><td>kg / cm²</td><td>D882</td><td> 375</td><td> 332</td><td> 329</td><td> 335</td><td> 315</td><td> 296</td>

<td>Puncture</td><td>N</td><td>F1306</td><td> 13.26</td><td> 19.39</td><td> 24.24</td><td> 28.02</td><td> 31.70</td><td> 38.99</td>

<td>Tear</td><td>G</td><td>D1004</td><td> 718</td><td> 1020</td><td> 1360</td><td> 1610</td><td> 1817</td><td> 2262</td>

<td>Mist</td><td> %</td><td>D1003</td><td> 12</td><td> 16</td><td> 22</td><td> 31</td><td> 33</td><td> 43</td>

In accordance with the implementations, the lid 601, container 602, and reinforcing ring 603 can be formed of materials suitable for sterilization. In some aspects, the lid 601, container 602, and reinforcing ring 603 can be sterilized together as a unit. In other aspects, the lid 601, container 602, and reinforcing ring 603 can be sterilized separately, using one or more of the various sterilization methods known in the art. In certain aspects of the present disclosure, one or more sterilization method, for example chemical and irradiation methods, may be combined as provided below.

In one aspect, lid 601, container 602, and reinforcing ring 603 can be formed from materials that are compatible with irradiation sterilization. In one aspect, the material may be compatible with gamma irradiation sterilization. In another aspect, the material can be chosen to be compatible with radiation such as electron beams, X-rays, or subatomic particles.

In another aspect, the container can be formed from materials that are compatible with chemical sterilization methods. In one embodiment, the material may be compatible with ethylene oxide (EtO) sterilization. In another embodiment, the material may be compatible with ozone sterilization (OR₃). In another embodiment, the material may be Ortho-Phthaladehyde (OPA) compatible. In a further embodiment, hydrogen peroxide can be used as a chemical sterilizing agent.

In some respects in accordance with the present disclosure, cap 601, container 602, and reinforcing ring 603 can be formed from materials that are compatible with heat sterilization. In one embodiment, the heat sterilization compatible material may be resistant to dry heat sterilization. In another embodiment, the compatible heat sterilization material may be compatible with moist heat sterilization. In some respects in accordance with the present disclosure, cap 601, container 602, and reinforcing ring 603 can be formed from materials that are compatible with tinting.

»

In some respects, the materials chosen for cap 601, container 602, and reinforcing ring 603 allow for long-term storage of the liquid. In some embodiments, the sealed vial can comprise impervious materials. In certain aspects, impermeability can be selected on the basis of the fluid. In a non-limiting example in accordance with the present disclosure, fluids for ophthalmic, topical, oral, nasal, or pulmonary use may require light or air protection to maintain stability. In another non-limiting example in accordance with the present disclosure, fluids for ophthalmic, topical, oral, nasal, or pulmonary use may require protection from light and oxygen to maintain stability. In some embodiments, the materials may be gas impervious. In one embodiment, the gas can be oxygen. In other embodiments, the material may be light impermeable. In another embodiment, the material may be gas impermeable, eg oxygen, and light impermeable.

In one aspect in accordance with the present disclosure, container material 602 and lid 601 can be selected to be stable for extended periods. As an aspect, in certain embodiments, one or more properties that include, but are not limited to, tensile strength, percent elongation, tear strength, and impact stability can be used to determine material stability.

Referring to Figure 7, the containers containing a fluid of the present invention can be prepared using a form, fill and seal process as known in the art. In certain embodiments, the entire process described in Figure 7 can be performed under sterile conditions in compliance with applicable regulatory standards for medical devices and preparations. In one embodiment, a film can be applied to a mold and then heated and vacuum formed to create a 609 shape and 607 depth container. By varying shape 609 and 607 depth and 604 diameter, a volume container or vial can be formed. total (V_t) defined.

Once formed, the container (eg, container 602, for example), can be filled with a fluid and a cap applied to the container or filled ampoules. In some embodiments and by way of example only, a seal is applied to create a leak-proof lid. Other methods of attaching and sealing a lid to the container are known in the art. After sealing, individual ampoules can be cut from the shape. In other modalities, sealing and cutting can occur simultaneously. The final sealed containers or ampoules are then suitable for storage, shipping or use in an ejector device. As mentioned above, the form-fill-seal process discussed in this embodiment is solely a technique for forming and sealing containers that are known in the art. Other techniques such as blow-fill-seal and self-sealing RF welding can also be used and do not make use of a cap element.

In some embodiments of the present disclosure, fluid (Vf) can fill the entire volume of container 602 (eg, V_t). In other modalities, the fluid may not completely fill the volume, leaving a gap (V_AT). In modalities where the liquid volume V_F equals ν_ΔΤapplying a cap can result in entrapment of a volume of gas V_gas. In other embodiments, the container volume 602 can be decreased by compression or deformation to a volume to reduce the volume by a volume V_r. In accordance with this description, the volume of the sealed container or vial shall be:

V_T = Vf + V_gas + V_r where V / \ T ⁼ Vgas ⁺ Vr

In accordance with aspects of the present description, volume V_r provides an ability for the container to expand to volume V_t, and thereby reduce the tendency of the container to leak when used in an ejector device. Similar, volume V_r it can incorporate an expansion of a volume of an aqueous fluid when shipped or stored frozen or under conditions where the volume of the liquid can expand. In other modalities, ν_ΔΤ can include both a volume of gas V_gas as a volume V_r whereby, the change in gas volume associated with changes in ambient pressure can be compensated and allow the preparation of leak-free ejector devices. Similarly, volume V_r also allows for gas expansion of volume V_exp which can occur during shipping or storage under conditions of lower ambient pressure.

In certain aspects in accordance with the present description, the container can contain a volume of gas V_gas. In one aspect, the gas may be air. In one aspect, the gas may be air that has been depleted of oxygen. In other respects the gas may be a nonreactive gas. In one aspect, the gas may be nitrogen. In another aspect, the gas can be a noble gas such as helium or argon. In other respects, the gas may be CO₂.

Any gas can be incorporated in accordance with the present description.

In certain embodiments of the disclosure, the shells allow for tilt insensitivity of ejector devices. In one aspect the reservoir includes a flexible container. Specifically, as provided by certain aspects of the present disclosure, the reservoir provides a consistent amount of fluid to the ejector mechanism, regardless of the fluid level and orientation of the device. In some respects, a vial or reservoir in fluid communication with an ejector mechanism provides consistent fluid flow to the posterior surface of the ejector mechanism so that a consistent volume of fluid is expelled as droplets. In another aspect, the reservoir or vial is in fluid communication with a capillary plate that allows for consistent supply or distribution of fluid in a capillary fluid loading area at a posterior ejection surface of an ejector mechanism. The vial allows for Inclination Insensitivity of the ejector device and resistance to seepage as the ambient pressure decreases in relation to the standard pressure at sea level. Thus, the combination of ampule, capillary plate and ejector mechanism allow both inclination and reduced altitude sensitivity to the device so that a consistent volume of droplets is delivered.

Referring to Figure 8, a device of the present disclosure ejects fluid in one direction 804, perpendicular to the direction of gravity 805. In one aspect of the present disclosure, the combination of vial 803 and fluid loading plate 802 allow a consistent flow of fluid to ejector plate 801 as the angle of inclination theta (Θ) is changed. For example, as the incline increases, the combination allows for continued consistent fluid flow. Accordingly, in accordance with aspects of the present invention, the device continues to supply droplets in the 804 direction. In one aspect of the present disclosure, the angle of inclination theta (Θ) can be arbitrarily increased or decreased while maintaining consistent fluid flow to ejector plate 801. For example, the angle of inclination theta (Θ) may be greater or less than 45 °. Thus, the angle of inclination theta (Θ) can be between 0 and 45 ° or it can be between 45 ° and 90 °. The angle of inclination theta (Θ) can also be 90 °. The angle of inclination theta (Θ) can also be

180 ° or it can be between 0 and 180 °.

In certain implementations in accordance with the present invention, the containers are flexible containers having a total volume V_t and they contain a volume of the liquid V_F and a volume of gas V_gas, and have an extensible volume V_r. In some respects, the extensible volume V_r allows and incorporates the expansion of ÁV gas_gas due to changes in pressure although it does not result in an increase in pressure within the container. Thus, although an AV expansion is in transit, for example_gas it does not cause the container to leak. Similarly, the expansion of a freezing aqueous fluid can be similarly incorporated.

Many implementations of the invention have been described. This description contemplates combining any of the characteristics of an implementation with the characteristics of one or more of the other implementations. For example, any of the ejector mechanisms or capillary plates can be used in combination with the container, as well as any of the housings or housing features, for example covers, supports, supports, lights, seals and gaskets, filling mechanisms, or alignment mechanisms. Additional variations of any of the elements of any of the modalities within the scope of basic knowledge are contemplated by this description. Such variations include selection 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

Differential pressure filtration value measurement

Figure 9 shows an assembly that allows a container assembly, fluid loading plate, and ejector device to be tested for filtration as pressure decreases. The fluid filled container is mounted on a filtration pressure testing apparatus consisting of a mounting retaining vial (1), fluid loading plate (2) supplying fluid behind the ejector plate (3). The filtration pressure testing apparatus is placed inside a vacuum chamber that is pumped by a suitable mechanical pump to achieve 18.96 kilo pascals (2.75 psi). At this pressure (18.96 kilo pascals (2.75 psi)) the pressure differential measured between STP (91.21 kilo pascals (13.23 psi)) and the lowest average setting pressure (18.96 kilo pascals (2.75 psi)) is 10.5 psi or 72.3 kilo pascals. Filtering this pressure is equivalent to a pressure differential found when traveling from sea level to 31,000 feet (9448.8 m). Figure 9 also illustrates an aspect of the container that has a V_rgreater than zero. In this way, the container allows gas expansion as the environmental pressure decreases within the vacuum chamber. The variation of the V_r it can affect the filtration pressure.

Table 3 provides leakage pressure test results through 40 um holes on a 12mm deep flexible container (eg, depth 607 of Figure 6B).

TABLE 3

Filtration pressure test through 40 um holes with 12mm deep flexible container

<td>Experiment #</td><td>% Full (%)</td><td>% of Air Volume</td><td>Delta P (psi)</td><td>Delta P (kPa)</td>

<td> 1</td><td> 97.20</td><td> 3.43</td><td> 1.66</td><td> 11.43</td>

<td> 2</td><td> 93.20</td><td> 8.34</td><td> 2.45</td><td> 16.91</td>

<td> 3</td><td> 77.38</td><td> 22.70</td><td> 0.99</td><td> 6.80</td>

<td> 4</td><td> 81.89</td><td> 18.18</td><td> 1.16</td><td> 8.00</td>

<td> 5</td><td> 87.72</td><td> 12.12</td><td> 3.51</td><td> 24.18</td>

<td> 6</td><td> 85.28</td><td> 14.77</td><td> 1.80</td><td> 12.41</td>

<td> 7</td><td> 81.17</td><td> 18.90</td><td> 1.89</td><td> 13.05</td>

<td> 8</td><td> 73.31</td><td> 26.79</td><td> 1.00</td><td> 6.89</td>

Table 4 provides the filtration pressure test results through 20 um holes on a 20mm deep flexible container.

TABLE 4

Filtration pressure test through 20 um holes with 20mm deep flexible container

<td>Experiment #</td><td>% of Air Volume</td><td>Initial pressure (kPa) (PS¡)</td><td>Filtration pressure (kPa) (psi)</td><td>Delta P (psi)</td><td>Delta P (kPa)</td>

<td> 1</td><td> 3.13</td><td> 91.21 (13.23)</td><td> 19.16 (2.75)</td><td> 10.48</td><td> 72.26</td>

<td> 2</td><td> 3.13</td><td> 91.42 (13.26)</td><td> 20.33 (2.95)</td><td> 10.31</td><td> 71.09</td>

<td> 3</td><td> 15.63</td><td> 91.42 (13.26)</td><td> 44.12 (6.40)</td><td> 6.86</td><td> 47.30</td>

<td> 4</td><td> 9.38</td><td> 91.42 (13.26)</td><td> 41.02 (5.95)</td><td> 7.31</td><td> 50.40</td>

<td> 5</td><td> 6.25</td><td> 91.35 (13.25)</td><td> 25.85 (3.75)</td><td> 9.50</td><td> 65.50</td>

<td> 6</td><td> 12.50</td><td> 91.35 (13.25)</td><td> 41.02 (5.95)</td><td> 7.30</td><td> 50.33</td>

<td> 7</td><td> 9.38</td><td> 91.35 (13.25)</td><td> 36.19 (5.25)</td><td> 8.00</td><td> 55.16</td>

Table 5 provides the leak pressure test results through 40 um holes on a 20mm deep flexible container.

TABLE 5

Filter pressure test on 20mm flexible container with 40um holes

<td>Experiment #</td><td>% of Air Volume</td><td>Initial pressure (kPa) (PS¡)</td><td>Filtration pressure (kPa) (psi)</td><td>Delta P (psi)</td><td>Delta P (kPa)</td>

<td> 1</td><td> 2.3</td><td> 91.56 (13.28)</td><td> 19.16 (2.75)</td><td> 10.53</td><td> 72.6</td>

<td> 2</td><td> 6.3</td><td> 91.56 (13.28)</td><td> 21.92 (3.18)</td><td> 10.1</td><td> 69.6</td>

<td> 3</td><td> 9.4</td><td> 91.56 (13.28)</td><td> 35.8 (5.2)</td><td> 8.08</td><td> 55.7</td>

<td> 4</td><td> 12.5</td><td> 91.56 (13.28)</td><td> 37.9 (5.5)</td><td> 7.78</td><td> 53.6</td>

<td> 5</td><td> 15.6</td><td> 91.56 (13.28)</td><td> 40.6 (5.9)</td><td> 7.38</td><td> 50.9</td>

<td> 6</td><td> 18.8</td><td> 91.49 (13.27)</td><td> 42.40 (6.15)</td><td> 7.12</td><td> 49.1</td>

<td> 7</td><td> 21.9</td><td> 91.49 (13.27)</td><td> 43.78 (6.35)</td><td> 6.92</td><td> 47.7</td>

Table 6 provides the leak pressure test results through 40 um holes on a 20mm deep hard container.

TABLE 6

Filtration Pressure Test on hard container, 40 um holes

<td>Experiment #</td><td>Air Volume%</td><td>Initial pressure (kPa) (psi)</td><td>Filtration pressure (kPa) (psi)</td><td>Delta P (psi)</td><td>Delta P (kPa)</td>

<td> 1</td><td> 12.5</td><td> 91.35(13.25)</td><td> 88.59 (12.85)</td><td> 0.4</td><td> 2.8</td>

<td> 2</td><td> 4.2</td><td> 91.35(13.25)</td><td> 87.90 (12.75)</td><td> 0.5</td><td> 3.4</td>

<td> 4</td><td> 29.2</td><td> 91.35(13.25)</td><td> 87.90 (12.75)</td><td> 0.5</td><td> 3.4</td>

<td> 5</td><td> 37.5</td><td> 91.35(13.25)</td><td> 87.5 (12.7)</td><td> 0.55</td><td> 3.8</td>

<td> 8</td><td> 20.8</td><td> 91.35 (13.25)</td><td> 87.70 (12.72)</td><td> 0.53</td><td> 3.7</td>

Figures 10A to 10E illustrate the results of container expansion as a pressure equalizing mechanism. As tested in Example 1 and presented in Table 4, as the pressure decreases, the gas expands, causing an expansion of the collapsed volume V_r. As V_gas approaches the total volume ν_ΔΤ, increases the tendency of the apparatus to leak. Smaller volumes of air are generally associated with lower filtration point pressures. Delta P represents the pressure at which the combination begins to filter.

Figure 11 graphically presents the filtration pressure test results in different modalities of the present description. As shown, a hard deposit is filtered at low differential pressures that is independent of the percentage of air volume (for example, V_toReA / t). The 12mm deep container (vial) requires higher differential pressures to reduce seepage and a maximum pressure of approximately 25 is observed for approximately 12% air volume. A 20mm deep container having either 160 um or 20 x 40 um holes requires the highest differential pressures to cause seepage. In these modalities, the number and size of holes were not distinguishable.

EXAMPLE 2

Measurement of mass loss over time

Figure 12 shows the loss of mass of a vial (reservoir) over time to determine the storage capacity of the ampoules (reservoir) of the present disclosure. A series of tanks is stored for 72 days and the amount of dough is determined. From a total volume of 3.5 ml, a total volume of 50 μΙ escapes during the time period.

Experiment 3. Measurement of ejection volume at different angles of inclination:

Figure 13 shows the ejection volume at different angles of inclination over a frequency range of a piezoelectric injector device having either a hard tank or a flexible tank. The flexible vial design provides more consistent expulsion of fluid volume over a wider frequency range and fill level.

Although the foregoing describes various modes of deposit by way of illustration and example, the skilled artisan will appreciate that various changes and modifications may be practiced within the spirit and scope of the present application. As used herein, a reservoir can be any object suitable for retaining a fluid. By way of example, the reservoir can be made of any suitable material capable of containing a fluid. Tanks of the present description can be rigid or flexible and the tanks of the present description can also be foldable. As used herein, collapsible refers to a decrease in volume obtainable in a tank achieved by compression, pressure, bending, crushing, compression, vacuum, or other manipulation, such that the total volume covered after folding is less than a volume that could be contained in an unfolded container. A reservoir can be made of any suitable material that can be formed into a volume capable of holding a volume of fluid. Suitable materials, for example, can be flexible or rigid, or can be formable or preformed.

As used herein, a reservoir, by way of example, can be formed from a film.

In other aspects, a fluid loading plate of the disclosure can be integrated into an injector device between a reservoir and an ejector mechanism. In certain embodiments, the ejector device may be for supplying fluid to a subject's eye, and may comprise a housing, a reservoir disposed within the housing to receive a volume of fluid, the reservoir which is in fluid communication with a plate of fluid charge, the fluid loading plate is in fluid communication with an ejector mechanism such that the fluid loading plate provides fluid to the rear ejection surface of an ejector mechanism, where the ejector mechanism is configured to expel a stream of droplets of a fluid. The ejector mechanism may be configured to expel a stream of droplets having an average expelled droplet diameter greater than 15 microns, with the stream of droplets having low entrained air flow such that the droplet stream is deposited on the subject's eye. during use.

In certain embodiments, the ejector mechanism may comprise an ejector plate and a piezoelectric actuator, the ejector plate includes a plurality of openings formed through its thickness; and the piezoelectric actuator is operable to oscillate the ejector plate at a frequency, and generate a directed stream of droplets. In certain aspects, the ejector plate can be formed from a high modulus polymer material.

In certain embodiments, the piezoelectric actuator is coupled to a peripheral region of the ejector plate so as not to obstruct the plurality of openings in the ejector plate. The plurality of openings in the ejector plate can be arranged in a central rim of the plate that is exposed by the plezoelectric actuator. In certain embodiments, the three-dimensional geometry and shape of the openings, including orifice diameter and capillary length, and spatial arrangement of the ejector plate can be controlled to optimize generation of directed stream of droplets.

As an example, the fluid loading plate can

Integrate into an ejector device or ejector assembly, or be configured to interface with an injector mechanism as described, for example, in the applications: US Application. No. 61 / 591,786, filed on

27 January 2012, titled “Hlgh Modulus Polymerlc Ejector Mechanlsm,

Devlce Ejector, and Methods of Use ”; US request No. 61 / 569,739, filed December 12, 2011, titled "Ejector Mechanlsm, Ejector Devlce, and Methods of Use," and US Application. No. 13 / 184,484, filed on July 15, 2011, titled “Drop Generatlng Device”, whose applications are incorporated herein by reference in their entirety.

Many modalities and implementations of the invention are described here. This description contemplates combining any of the characteristics of one modality with the characteristics of one or more of the other modalities. For example, any of the ejector mechanisms or tanks can be used in combination with the fluid charging plate, as well as any of the housings or housing features discussed in the built-in references, eg covers, brackets, necks, lights, seals and gaskets, filling mechanisms, or alignment mechanisms. Additional variations in any of the elements of any of the aspects of the present description that are within the scope of basic knowledge are contemplated by this description. Such variations include selection of materials, coatings, or manufacturing methods.

Referring to Figures 14A through 14C, in one embodiment, the fluid loading plate may comprise a capillary plate 1400 that includes a fluid reservoir interface 1402, an Ejector Mechanism Interface 1404, and one or more fluid openings 1406 . If desired, capillary plate 1400 may optionally include a reservoir housing coupling ring 1410 to facilitate connection to various reservoir housing configurations (not shown) as described in US Application. No. 13 / 184,484, filed on July 15, 2011, titled "Drop Generating Device", which is incorporated herein by reference in its entirety.

In addition, capillary plate 1400 may optionally include holding clips 1412 on housing mating ring 1410 to secure capillary plate 1400 to a reservoir housing (not shown). Although illustrative fastener configurations and positions are shown, different modalities and positions are envisioned if they are within the scope of the description. Capillary plate 1400 may also include perforation projections 1414 on fluid reservoir interface 1402 to facilitate opening of various reservoir housing configurations (not shown).

Again, while illustrative projections and drilling positions are shown, different modalities and positions are envisioned and are within the scope of the disclosure. For example, perforation projections may be sized and formed so as not to hinder fluid flow through the one or more fluid openings 1406.

Referring to Figures 15A-15C, in certain embodiments, the ejector mechanism interface 1502 of the capillary plate 1500 is arranged in parallel with a rear ejection surface 1506 of the ejector mechanism 1404 to form a gap 1508 between the capillary plate and the ejector mechanism, and generating fluid flow 1510 between capillary plate 1500 and ejector mechanism 1504 in capillary fluid loading area 1512 on the rear ejection surface of the ejector mechanism. This fluid flow 1510 allows capillary plate 1500 to supply fluid to rear ejection surface 1506 of ejector plate 1514 of the ejector mechanism. The capillary plate configuration allows for consistent supply and distribution of fluid in the capillary fluid loading area at the rear ejection surface 1506 of the ejector plate 1514. As a result, a consistent volume of droplets is generated by the ejector mechanism, regardless of the fluid level and orientation of the device (i.e.

Inclination).

Referring to Figures 16A through 16B, the fluid load between the parallel surfaces of the capillary plate and the ejector plate is dependent on the distance d of the capillary plate gap. As shown in

Figure 16A, plate gap up to 1mm provides adequate fluid load (liquid height) in capillary fluid loading area. In certain embodiments, a separation distance between the capillary plate and the ejector mechanism of between about 0.2mm and about 0.25mm, more particularly between about 0.2 and about 0.4mm, or more particularly about 0.3mm, can be used.

Without intending to be limited by theory, general expressions for capillary augmentation between two parallel surfaces are described below:

2 and_{t&gt;cos (0) h ™ -------------------- * ---------- 10

Where:

h is the height of the liquid;

Θ is the surface tension of liquid vapor in contact with a surface;

γ-ΐν is the contact angle between the fluid and the surface; p is the difference in density between fluid and vapor; g is acceleration due to gravity; and d is the separation distance between surfaces.

The fluid loading plate can be formed from any of the materials suitable for use in the desired application. By way of example, in ophthalmic applications, any material suitable for use in pharmaceutical ophthalmic applications can be used, such as polymeric materials that do not chemically react with or absorb fluids to be supplied. In certain embodiments, the surfaces of the fluid loading plate that are exposed to the fluid to be supplied can be formed from materials that provide desired surface properties, including hydrophilic / hydrophobic properties, surface energy, etc., to facilitate wicking and capillary action between the parallel surfaces. For example, see US Patent No. 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 an Individual material, for example, in a capillary plate embodiment. In other aspects, the fluid loading plate may be a compound formed from more than one material where the surfaces that are exposed to the fluid to be supplied are selected to have desired surface properties. By way of example, a capillary plate can be injection molded or thermoformed as a unitary piece as separate pieces. If desired, one or more reservoir mating surfaces can be formed separately, or formed as a unitary piece with other components of the capillary plate. Without being limiting, and by way of example, materials include: pollamides Including nylon such as nylon-6, HDPE, polyesters, co-polyesters, polypropylene, and other suitable pharmaceutical grade hydrophilic polymers or polymeric structures.

The fluid loading plate can be dimensioned and formed in any suitable way to interface with the desired ejector mechanism so that fluid is provided to and a suitable capillary fluid loading zone is formed at the ejector mechanism interface between the capillary plate and the rear ejector surface of the ejector mechanism. Referring to Figures 17A and 17B, one embodiment of a capillary plate 1700 is illustrated. However, the sizes given in Figures 17A and 17B are for illustration purposes only, and the description is not so limited. By way of example, capillary plate 1700 may be generally square in shape and have an edge length of approximately 25mm. However, other shapes are envisaged, including generally circular configurations, etc. Four fluid openings 1706 are shown spaced around a radius instead of about 4.70mm, having an overall opening width of about 2.50mm and a spacing of about 2mm. The thickness of the capillary plate fluid flow portion 1700 (i.e., the capillary plate portion 1700 includes a fluid opening 1706) may be approximately 0.30 mm, and the thickness of the capillary plate housing coupling ring 1710 1700 can be about 2mm. Drill projections 1714 can be, for example, approximately 1.62 mm wide and approximately 1.35 mm long to allow for desired protrusion properties while still allowing fluid flow.

To help understand the present invention, Figures 18 illustrate various effects of the use of a fluid loading plate described herein on the performance of the ejector device. The experiments described herein should not be construed as specifically limiting the invention and such variations of the invention, now known or later developed, which would be within the purview of one skilled in the art are considered to fall within the scope of the invention as described herein. and is claimed here in later.

More specifically, Figure 18 illustrates the effects of a capillary plate on resonant frequency and water mass deposition using a 160 micron thick NiCo ejector plate with holes 25 to 40 microns, showing a downward frequency shift. The

Figure 19 illustrates that as the density (and therefore the mass) of a fluid increases in a resonant system (such as the capillary region behind the ejector plate), there is a downward shift in the resonant frequency. Figure 20 illustrates the downward frequency shift associated with a capillary plate used with supplying various fluids using a 160 micron thick NiCo ejector plate with 25-40 micron holes. Figure 21 and Table A illustrate both a reduction in resonant frequency and amplitude of the resonant structure as the density (p) and viscosity (η) of the fluid in the resonant system increases. As an example, and not necessarily related to the particular values ​​in the graph of Figure 21, the densities and viscosities of water, ethanol and propylene glycol are provided in the table below. As shown in Figures 18 to 21 and Table A, the presence of a capillary plate leads to a general shift in resonance frequency, at lower frequencies. The displacement in spray volume for liquids is a sequence of increased density and viscosity, (water, ethanol, and propylene glycol).

TABLE A

<td>Liquid</td><td>Density (r) (g / cm²)</td><td>Viscosity (h) (cP)</td>

<td>Water</td><td> 0.998</td><td> 1.002</td>

<td>Ethanol</td><td> 0.789</td><td> 1.62</td>

<td>Propylene glycol</td><td> 1.036</td><td> 50</td>

Figure 22 illustrates the tilt insensitivity of an ejector device that includes a capillary plate. As shown, delivered volume (mass) is relatively insensitive to the orientation of the ejector device. This ensures a constant supply and distribution of fluid behind the ejector plate. As a result, a consistent volume of droplets is formed and sprayed by the ejector mechanism, regardless of fluid level and device orientation.

In other embodiments, the fluid loading plate may comprise a puncture plate fluid supply system, also denoted as a puncture / capillary plate fluid supply system, which is configured to supply fluid from the reservoir to a Fluid retention area at the rear of the ejector mechanism for delivery as a directed stream of droplets through piezoelectric ejection. Without wishing to be bound by theory, the puncture plate system may use one or more gradients of hydrostatic pressure, capillary pressure, geometric pressure (Venturi effect), and air exhaustion.

An embodiment of a puncture plate fluid supply system and its operation is shown in Figures 23A to 27. Figures 23A and 23B show a front view and a rear view, respectively, of an ejector mechanism 2300 with five delivery holes. elevation 2302. As shown in the front view in Figure 23C and a rear view in Figure 23D, the puncture plate fluid supply system may include a capillary plate portion comprising a fluid retention area between the supply system of capillary / puncture plate fluid and a posterior surface of an ejector mechanism for channeling fluid to the ejector mechanism by one or more mechanisms, including capillary action, and at least one hollow puncture needle to transfer fluid from a reservoir to the fluid retention area. In this embodiment, six hollow puncture needles 2306 extend from the posterior surface of the capillary / puncture plate, channels through the needles extend through the front face of capillary plate 2304 as shown by the holes 2308. Needles 2306 are surrounded by a wall 2310 defining a receptacle for a coupling 2312 (shown in Figure 23E along with a self-sealing 2314 sllicone sealing element that is housed in coupling 2312).

Initially, the fluid-containing reservoir or ampoule 2316 (these terms are used interchangeably herein) connects to the coupling and is in fluid communication with a secondary reservoir defined by the coupling and silicone sealing element 2314. Capillary plate 2304, in turn , is attached to and in fluid communication with the ejector mechanism 2300. However, prior to use, the puncture plate and ejector mechanism 2300 may be provided in a disconnected state from coupling 2312 and reservoir 2316 to prevent fluid exchange. During the Initial stage of connection the hollow puncture needles 2302 shown on the back of the puncture plate image in Figure 23B are partially inserted into the 2314 self-sealing silicone puncture ring or packing that rests within the coupling 2312. The secondary reservoir formed in coupling 2312 is constantly open to fluid in the vial / primary reservoir 2316. At this stage, fluid from the primary reservoir that has been moved into secondary reservoir of coupling 2312 does not enter the hollow puncture needles 2306, however, due to the barrier created by the 2314 self-sealing silicone packing material.

Puncture is accomplished by pressing the puncture plate needles all the way through the 2314 gasket in fluid filled coupling by forcing the needles through the silicone gasket. This may occur, for example, when the coupling is snapped shut (indicated by a clicking sound) into receptacle 2310 of puncture plate 2304. A seal is maintained after puncture because silicone gasket 2314 is a compatible material in and self-sealing. Initial fluid transfer from the reservoir / container through the hollow puncture needles immediately after puncture results from a combination of hydrostatic pressure, coupling retention / reservoir volume, and the fluid reaction force from the initial puncture that drives fluid through capillaries defined by needles and hollow channels in the capillary / puncture plate.

Once the fluid passes through the capillary tubes, surface tension effects dominate the increase in fluid against gravity. As the fluid rises, it removes air from the system by pushing it out of the front of the ejector openings or holes. Capillary lifting holes 2301 are placed on the ejector plate 2320 of the ejector mechanism on the piezoelectric element 2322 which serves as a pressure release for air in the system. In the absence of these capillary lift holes 2302, the system would close in the region over the ejector openings and the fluid would stop rising due to the increasing build-up in air pressure which eventually becomes balanced with the capillary pressure. In order to achieve full lift, all air needs to be pushed out of the system. Capillary lift holes 2302 (shown from the rear in Figure 25A and from the front in Figure 25B) act as pressure equalizing holes and are properly positioned and sized (to prevent fluid seepage) and allow the fluid rises completely thereby ensuring that no (or very little) air remains in the system. The assembled ejector assembly is shown from the front in Figure 24A and from the rear in

Figure 24B.

Figure 26 illustrates a schematic describing fluid flow through the puncture plate system after complete puncture through the silicone gasket. Liquid flows through the puncture system and up the capillary plate chamber 2600, pushing air out of the ejector ports or openings 2602 and capillary lift holes 2302. Referring to Figures 23C and 23D, the puncture / capillary plate 2304 illustrates a six-needle design with an inside diameter (ID) from 150 microns and an outside diameter (OD) ) 1 mm. The number of needles can be as small as one needle but can also include more needles, for example, eight needles with ID dimensions ranging from 500 microns-3mm and OD dimensions ranging from 600 microns-4mm. The lifting holes shown in Figures 25A and 25B may also vary from what is presented in this figure. This

Figure shows five 20 micron diameter dimensioned lifting holes, however the number of holes can be as low as one hole but can also include more holes, for example eight holes with hole diameter ranging from 10 micron -50 microns.

Alternatively, referring to Figures 44 through 46, the puncture plate may be designed with an elongated needle puncture system. Such designs, for example, can be used in connection with certain reservoir design configurations such as standing rectangular Low Tensile Effort Reservoirs (ie, IV bag designs).

The puncture plate to be constructed from any suitable material, as described and illustrated here. By way of non-limiting example, the puncture plate may be constructed of: liquid crystal polymer "LSP" (0-30% filled glass); Nylon 6;

Nylon 6, 6; Polycarbonate; polyetherimide (Ultem); Polyether Ether Ketone (PEEK); Polyimide (Kapton); 316L Stainless Steel; Diamond-Like Carbon Coated Stainless Steel (DLC) (300 series); diamond-like carbon coated aluminum (DLC); diamond-like carbon clad copper (DLC); diamond-like carbon-coated nanocrystalline cobalt phosphate (DLC); Nanocrystalline Cobalt Phosphate (nCoP); Gold Plated Stainless Steel (300 series); Polymer Coated Stainless Steel (Polymers listed above) (300 series); Polymer Coated Copper (Polymers listed above) (300 series); Polymer-coated aluminum (Polymers listed above) (300 series), etc.

Although the foregoing describes several by way of illustration and example, those skilled in the art will appreciate that various changes and modifications may be practiced within the spirit and scope of the present application. Even though the term "capillary plate" and "puncture plate" are used to describe various modalities, it will be appreciated that the description is applicable to any fluid loading plate, without needing to take the form of a plate, and may have any configuration suitable for channeling fluid from the reservoir to the ejector mechanism.

As used herein, a reservoir can be any object suitable for retaining a fluid. By way of example, the reservoir can be made of any suitable material capable of containing a fluid. Tanks of the present description can be rigid and flexible and the tanks of the present description can also be collapsible. As used herein, collapsible refers to a decrease in volume that can be obtained in reservoir achieved by pressure, bending, crushing, compression, vacuum, or other manipulation, such that the total volume covered after folding is less than one volume. which could be covered in an unfolded container. A reservoir can be made of any suitable material that can be formed into a volume capable of holding a volume of fluid. Suitable materials, for example, can be flexible or rigid and can be formable or pre-formed. As a reservoir is used here, by way of example, it can be formed from a film.

Furthermore, the reservoir may be in fluid communication with a fluid charging plate to form a fluid reservoir interface, and in certain embodiments the fluid charging plate may optionally include a reservoir or ring mating surface to facilitate connection. with various fluid reservoir configurations.

In some aspects, the system reservoir of the disclosure may be configured as a low tensile stress reservoir or "LTS". An LTS reservoir of the disclosure is generally designed to minimize or eliminate positive pressure gradients imposed on the system by the reservoir created from memory effects, crease formation, and unwanted crease. Such a gradient can result in the restoration of the reservoir (volume expansion) that exerts a net pressure differential on the system, resulting in potential failure to draw air into the system through the ejector openings. In certain aspects, to correct the pressure differential, the LTS reservoir is configured to deflect to fold over its own low position support position, which reduces or eliminates the possibility of crease formation.

The LTS reservoir is also constructed from thin, flexible 10 materials (low tensile stress) that withstands volume expansion, rebound, and memory effects without compromising inertia and evaporation resistance (see Table 7). LTS tanks, as explained above and in further detail below, can be constructed in any suitable way, for example, including RF welding, blow-fill-seal processes, blow-fill seal processes, seal processes form-fill, etc.

Without intending to be theoretically limited, to aid in additional transport from the fluid / reservoir retention and through the capillary tubes during operation, the LTS reservoir may also be genetically engineered to accelerate fluid by incorporating the principle of continuity and the effect of Venturl as described in Figure 7 as described below in the Bernoulli equation for non-compressible flows, and shown in Figure 28.

Again, without intending to be bound by theory, Figure 28 describes how altering the reservoir geometry to a convergent profile (larger area to smaller area) results in the fluid accelerating as it moves down the reservoir due to increased in speed resulting from the principle of continuity. According to Bernoulli's equation, an increase in velocity from the principle of continuity will result in a decrease in pressure in the region of increased velocity (in order to maintain continuity). This change in pressure creates a gradient that helps transport fluid in the coupling and through the puncture needles / capillary tubes. This increase in velocity that results from a change of convergent area is known as the Venturl effect.

Figure 29 illustrates how hydrostatic pressure drives fluid from the LTS vial into the coupling and through the puncture needles into the fluid reservoir. To maximize hydrostatic pressure the bulb needs to be oriented in the vertical position since the hydrostatic pressure is a function of height.

TABLE 7

<td>Ampoule type</td><td>Ampoule material</td><td>Thickness</td>

<td>RF welded</td><td>Polyurethane (PU), PU / Polyvinylidene Chloride (PVDC) / PU, Ethylene-Vinyl Acetate (EVA) Thermal Plastic Polyurethane (TPU) PU / Ethylene Vinyl Alcohol (EVOH) / PU Isoplast® ETPU</td><td>0.005 -0.03 cm (2-12 thousandths of an inch)</td>

<td>Sealed by sopiadollenado</td><td>Low Density Polyethylene (LDPE) LDPE with EVA (10% -50%) EVA (100%)</td><td>2-15 thousandths of an inch (0.005-0.038 cm)</td>

<td>Sealed by form filled</td><td>Vietrex (LDPE with oxygen barrier layer) TPU</td><td>2-12 thousandths of an inch (0.005-0.03 cm)</td>

Figure 30 shows a schematic representation of fluid-free acceleration LTS reservoir geometries that fold over themselves. The foot rectangle represents a reservoir (similar to an IV bag) that is designed to fold along its minimum dimension (not shown). The foot rectangle tank design is vertically oriented to maximize height so as to maximize the effect of hydrostatic pressure. The second image shown is the horizontal rectangle that works in a similar way to the standing rectangle, but without maximizing the hydrostatic pressure effect. The third image shows a square tank configuration. Figure 31 shows schematic representations of fluid acceleration LTS reservoir geometries.

Referring to Figures 32A and 32B, two examples of a circular fluid acceleration LTS reservoir are illustrated, one constructed by blow-fill-seal processes (Figure 32A) and the other by brazing.

RF (Figure 32B). As shown, the amount of fold can be improved when the reservoir is deflected to fold along the minimum dimension, which in Figures 32A and 32B is the thickness. This type of fold largely prevents the formation of folds in the tank during operation. For standing tank designs, additional protection against crease formation can be created during operation of an ejector device by enclosing the tank in a housing that prevents it from bending over as it is being emptied. Supporting data on the performance of these deposits is provided here.

Figure 33 shows a configuration of a puncture plate

3300 and a blow-fill-seal tank with the coupling removed.

In certain embodiments, where self-sealing reservoir materials are used, puncture can occur directly through the lower region of the reservoir. The fill compartment shown at the bottom of Figure 33 is designed to allow maximum fluid fill from the secondary reservoir. Alternative puncture mechanisms for the blow-fill-seal puncture plate assembly are shown in Figures 34A and 34B.

Figure 34A shows a side profile of another embodiment of the puncture plate assembly of the blow-fill-seal reservoir. The

Figure 34A shows a reinforcing mechanism in the form of a 3400 plastic shell used to aid in needle puncture through the brine-fill reservoir when constructed of a self-sealing material. The Figure to the right (Figure 34B) shows the configuration when the blow-fill-seal tank does not self-seal with the puncture and must be connected to the coupling in the same way as in Figures 22 and 23A through 23F. As shown in Figure 34B, the needles need to pass through the silicone gasket within the region shown as "Needle Puncture Here".

Even in another embodiment of the disclosure, Figure 35 illustrates 10 deposit geometries that are offset to fold in a certain direction to prevent crease formation. Down spray and down pull procedures and results of these vials are described in the example below.

EXAMPLE 3

Down spray and down pull measurement

Static down pull tests were performed to determine the amount of negative pressure that different reservoir configurations, for example shown in Figures 30 through 35, exert on the system as they are removing fluid. The experimental setup for this test is shown in Figures 36 to 37. The experimental procedure is as follows: a reservoir is attached to a water column tube that is connected to a vacuum regulator connected to a mechanical pump used to extract fluid from the reservoir or vial.

Mass deposition test was performed to determine the mass of a spray from a device at a given frequency with multiple frequencies (mass deposition sweep). Since some frequencies have a very low spray mass, which may be at the lower tolerance of the scale used to measure the mass, the spray number is varied per sample at each frequency, so it was averaged to determine a spray volume at each frequency. This also helped eliminate the same measurement error. (The scale used could be read to the tenth of 1 mg). These settings were executed by a laptop computer, which communicated with the scale, a function generator, and an oscilloscope. The mass of the pressures is recorded as well as the electrical characteristics (pass and magnitude of voltage and current, and impedance) during spraying. The configuration was controlled by an executable labview program and run from the laptop. This program allows the user to select the laboratory equipment in the configuration, the communication port for the scale, and the Universal Serial Bus (USB) identification for the oscilloscope and function generator. Users also defined the test parameters: voltage, waveform, start frequency, end frequency, step size, number of sprays, time between sprays, and duration of spray; the program communicated with the function generator, configuring the frequency for expression and number of cycles to achieve the appropriate spray duration, and set the oscilloscope to individual acquisition from a trigger (Voltage Probe). The program then instructed the function generator to activate the waveform. The signal was sent to an operational amplifier to boost the signal to the appropriate voltage, which was then applied to the device (0 to ± 90V). On the device, voltage and current probes were attached to verify the voltage and to read the current. A delay was written in the program to allow the time for the scale to swing out ("8s) before reading the mass of the scale and determining the mass by spray. The scale was zeroed at the start of the test and every half gram. In each half gram when zero is placed on the scale, the scale was cleaned and the tank attached to the device was filled. This ensured that the device was not depleted of fluid, and decreased the evaporation error of the fluid on the scale by limiting the amount of fluid on the scale that could evaporate to 0.5g. The scale was read after each group of sprays as defined by the user (usually 5). The mass of the sprays was determined by subtracting the previous volume from the current scale reading, thereby eliminating the time required to zero the scale between spray groups.

Figure 38 shows descending spray performance (24% fluid) of a control reservoir that is quite rigid and folds to form many folds resulting in negative pressure build-up. Figure 39 shows the results for a representative LTS deposit from the description, as illustrated in Figure 35. This shows an improvement in downward spray performance when creating a deflected geometry to fold in a controlled direction as well as choosing flexible materials and the appropriate material thickness. The graph shows that most samples (multiple tests of the same type of vial with the same thickness) allowed 80% or more of the fluid to be removed, with few outliers, which were removed much less but better than the control reservoir , folded from Figure 38.

Figure 40 shows the downward performance of spray 10 from two separate runs with a round LTS tank modality. That deposit showed marked improvement, with more than 90% of the fluid removed. Figure 41 shows the drops for selected round LTS vial designs from Figure 35. These charts show a great improvement in the negative pressure generated from the system when using the round LTS reservoir. Without intending to be bound by theory, Figure 43 shows the mechanism involved in inverted spraying using a round LTS reservoir, although Figure 43 shows the actual downward spray performance results of a downward spray LTS reservoir in a complete puncture system invested.

In accordance with other aspects of the description, the fluid loading plate can be designed with different needle puncture systems, as illustrated in Figures 44 to 46. Such designs can be used in connection with reservoir designs, for example Standing, rectangular LTS tanks (i.e. IV bag style designs).

As discussed above, a system ejector plate can include capillary lift holes to provide additional air pressure release over the active area (ejector openings). This additional air pressure release can thereby allow complete capillary lift of the fluid, allowing the retention / reservoir to be completely filled with fluid. In accordance with certain aspects of the invention, it was unexpectedly found that if these holes are not placed over the ejector openings, the device may not operate efficiently once the fluid falls below the level of the ejector openings (thereby potentially allowing outside air to move into the system during operation).

When building capillary lift holes, optimization of the hole size is important. The holes are preferably large enough to allow a reasonable ventilation speed so that the capillary lift is not too slow, and are preferably small enough so that the fluid does not easily leak when the hole is aligned in the direction of gravity. The leakage of the fluid out of the lift hole is a function of the hole size as well as the surface tension of the fluid. Fluids with higher surface tensions have increased resistance to seepage due to the force of the fluid's meniscus (which is a function of the fluid's surface tension) formed within the lift port by the fluid, which creates a fluid barrier that it filters out and air that enters. The barrier is broken when the hydrostatic pressure of the reservoir (vial) exceeds the surface tension within the lift hole cavity (see Figure 47).

The fluid loading plate of the disclosure uses capillary action 5 to transport fluid to a location behind the active area of ​​the piezoelectric mesh for ejection, for example, as previously discussed with respect to Figure 27. Capillary lift is a function of the surface tension of the fluid, surface energy of the surfaces in contact with the fluid (contact angle), and the separation distance of the surfaces in contact with the fluid. To achieve optimum performance for the puncture plate system, a hydrophilic material (contact angle between the fluid and the surface less than 90 degrees) is preferably used for the capillary channels. Furthermore, the material is preferably chemically inert and blocompatible. The separation distance of the surfaces is that they contain the fluid lift they are preferably tuned to ensure that the capillary width is considerably less than the capillary length of the fluid thereby ensuring that the surface forces are more significant than those of gravity. As shown in Figure 27, capillary lift in the system occurs between the puncture plate (capillary plate plus needles) and the ejector plate (which includes the active area or openings (piezoelectric sieve mesh).

EXAMPLE 4

Capillary elevation measurement

Figure 48 and Table B and Figure 49 and Table C illustrate capillary pressure for half droplets of various sizes of water and an illustrative eye medication, latanaprost. Thus, the separation distance of the fluid loading plate from the ejector plate is an important parameter for optimizing capillary lift at a certain height above the ejector openings. This plate separation distance (along with viscosity and fluid surface tension) also impacts the time for the fluid to rise to the final height. As shown in Figure 50 and Table D, a device designed to spray water and saline can operate with a capillary distance less than or equal to 2.5 mm. However, the systems of the disclosure are not so limited, and a capillary distance (separation between capillary plate and ejector plate) from 2.7mm-1.7mm, and below 1.7mm can be used to achieve greater capillary lift. In certain embodiments, a distance to the puncture plate system can be between 50-200 pm.

TABLE B

<td>Droplet size (m) Radius</td><td>Water</td><td>Water</td><td>Water</td>

<td></td><td>P</td><td>P a</td><td></td>

<td></td><td>PSI value</td><td>P_atm ()</td><td>P / P_a</td>

<td>1.00E-07</td><td> 105.8159</td><td> 14.69595</td><td> 7.200345</td>

<td>5.00E-07</td><td> 21.16318</td><td> 14.69595</td><td> 1.440069</td>

<td>1.00E-06</td><td> 10.58159</td><td> 14.69595</td><td> 0.720035</td>

<td>5.00E-06</td><td> 2.116318</td><td> 14.69595</td><td> 0.144007</td>

<td>1.00E-05</td><td> 1.058159</td><td> 14.69595</td><td> 0.072003</td>

<td>5.00E-05</td><td> 0.211632</td><td> 14.69595</td><td> 0.014401</td>

<td>1.00E-04</td><td> 0.105816</td><td> 14.69595</td><td> 0.0072</td>

<td>5.00E-04</td><td> 0.021163</td><td> 14.69595</td><td> 0.00144</td>

<td>1.00E-03</td><td> 0.010582</td><td> 14.69595</td><td> 0.00072</td>

<td>5.00E-03</td><td> 0.002116</td><td> 14.69595</td><td> 0.000144</td>

<td>1.00E-02</td><td> 0.001058</td><td> 14.69595</td><td>7.2E-05</td>

<td>5.00E-02</td><td> 0.000212</td><td> 14.69595</td><td>1.44E-05</td>

<td>1.00E-01</td><td> 0.000106</td><td> 14.69595</td><td>4.2E-06</td>

<td>5.00E-01</td><td>2.12E-05</td><td> 14.69595</td><td>1.44E-06</td>

<td>1.00E + 00</td><td>1.06E-05</td><td> 14.69595</td><td>7.2E-07</td>

psi = 6.89 kPa

TABLE C

<td>Droplet size (m) Radius</td><td>Latanoprost</td><td>Latanoprost</td><td>Latanoprost</td>

<td></td><td>P</td><td>P a</td><td></td>

<td></td><td>PSI value</td><td>P atm ()</td><td>P / P a</td>

<td>1.00E-07</td><td> 41.13995</td><td> 14.69595</td><td> 2.799408</td>

<td>5.00E-07</td><td> 8.227991</td><td> 14.69595</td><td> 0.559882</td>

<td>1.00E-06</td><td> 4.113995</td><td> 14.69595</td><td> 0.279941</td>

<td>5.00E-06</td><td> 0.822799</td><td> 14.69595</td><td> 0.055988</td>

<td>1.00E-05</td><td> 0.4114</td><td> 14.69595</td><td> 0.027994</td>

<td>5.00E-05</td><td> 0.08228</td><td> 14.69595</td><td> 0.005599</td>

<td>1.00E-04</td><td> 0.04114</td><td> 14.69595</td><td> 0.002799</td>

<td>5.00E-04</td><td> 0.008228</td><td> 14.69595</td><td> 0.00056</td>

<td>1.00E-03</td><td> 0.004114</td><td> 14.69595</td><td> 0.00028</td>

<td>5.00E-03</td><td> 0.000823</td><td> 14.69595</td><td>5.6E-05</td>

<td>1.00E-02</td><td> 0.000411</td><td> 14.69595</td><td>2.8E-05</td>

<td>5.00E-02</td><td>8.23E-05</td><td> 14.69595</td><td>5.6E-06</td>

<td>1.00E-01</td><td>4.11E-05</td><td> 14.69595</td><td>2.8E-06</td>

<td>5.00E-01</td><td>8.23E-06</td><td> 14.69595</td><td>5.6E-07</td>

<td>1.00E + 00</td><td>4.11E-06</td><td> 14.69595</td><td>2.8E-07</td>

psi = 6.89 kPa

TABLE D

<td colspan="2">Values ​​calculated at room temperature</td>

<td>Drug</td><td>Capillary length (mm)</td>

<td>Saline solution</td><td> 2.736762</td>

<td>Latanoprost</td><td> 1.716383</td>

<td>Restasis</td><td> 2.090882</td>

<td>Timolol</td><td> 1.9827</td>

<td>Tropicamide</td><td> 1.971853</td>

<td>Water</td><td> 2.726606</td>

Regarding this, Figure 51 and Table E show capillary elevation for saline in capillary channels made of different materials. Figure 52 shows capillary lift between capillary plate and puncture plate without a capillary lift hole 2302. This is contrasted with the much better capillary lift shown in Figure 53, which shows the elevation when a capillary lift hole is included.

TABLE E

<td>Drug</td><td>Surface</td><td>Contact angle Measured (degrees)</td>

<td>Saline solution</td><td>Gold</td><td> 61</td>

<td>Saline solution</td><td>Diamond-like carbon (DLC)</td><td> 67</td>

<td>Saline solution</td><td>Liquid Crystal Polymer (30% filled glass)</td><td> 76</td>

<td>Saline solution</td><td>PEEK</td><td> 80</td>

In addition, Tables 8-10 below show capillary lift data in the capillary channel between the fluid loading plate and the rear surface of the ejector mechanism as a result of using different numbers and sizes of capillary lift holes 2302. The

Table 8 shows the data for elevation time for water, Table 9 shows elevation time for Latanaprost at room temperature, and Table 10 shows an elevation time for Latanaprost refrigerated at 3.33 ° C (38 ° F). Some results have to be discarded as in operation (In-Ορ, Active Area Past Not filled, blank entry) due to effects on capillary lift holes, or showed asymmetric filling (marked with an asterisk), but results indicated benefits in lift time when using five capillary holes, and showed faster lift times with increasing capillary hole size.

TABLE 8

<td></td><td></td><td>1 hole</td><td>3 Holes</td><td>5 Holes</td>

<td>5 um</td><td>Test 1</td><td>395s</td><td>200s</td><td>In-Op</td>

<td></td><td>Test 2</td><td>370s</td><td>155s *</td><td>In-Op</td>

<td>10 um</td><td>Test 1</td><td>Past Active Area Without Fill</td><td>70s</td><td>23s</td>

<td></td><td>Test 2</td><td>Past Active Area Without Fill</td><td>54s</td><td>25s</td>

<td>20 a</td><td>Test 1</td><td>22s</td><td>8s</td><td>6s</td>

<td></td><td>Test 2</td><td>22s</td><td>10s</td><td>5.5s</td>

<td>50 um</td><td>Test 1</td><td>3s</td><td>2s</td><td>In-Op</td>

<td></td><td>Test 2</td><td>3.5s</td><td>1.6s</td><td>In-Op</td>

TABLE 9

<td></td><td></td><td>1 hole</td><td>3 Holes</td><td>5 Holes</td>

<td>10 um</td><td>Test 1</td><td>AA Past Unfilled</td><td>60 s</td><td>26 s</td>

<td></td><td>Test 2</td><td></td><td>68 s *</td><td>32 s</td>

<td>20 um</td><td>Test 1</td><td>11s</td><td>8 s</td><td>6s</td>

<td></td><td>Test 2</td><td>8s</td><td>11 s</td><td>5s</td>

TABLE 10

<td></td><td></td><td>1 hole</td><td>3 Holes</td><td>5 Holes</td>

<td>10 um</td><td>Test 1</td><td></td><td>25 s</td><td>28 s *</td>

<td></td><td>Test 2</td><td></td><td>42 s</td><td>44 s *</td>

<td>20 um</td><td>Test 1</td><td>7 s</td><td>10s</td><td>3.5 s</td>

<td></td><td>Test 2</td><td>10s</td><td>7s</td><td>4.5 s</td>

---- EXAMPLE 5

Fluid Filtration Test for Selected Eye Drugs and

Lifting Hole Sizes

To test leakage of fluid out of capillary lift holes or ventilation holes of a device modality, a hydrostatic pressure test assembly was constructed as shown in Figure 54. The ejector plate with the lift holes and the Ejector was placed under the fluid column defined by the tube. The test fluid was filled into the tube oriented directly on the ejector plate with the height of the fluid column carefully monitored. When the fluid reached test heights (hydrostatic pressure) at which the fluid over the ejector openings caused filtration through the lift ports and the ejector openings, the heights (corresponding to the pressure values) were recorded and used. and were used as a design parameter to optimize lift hole dimensions. The results are shown in Tables 11-13 below.

TABLE 11

<td></td><td></td><td colspan="4">Water column for the mesh side</td><td colspan="4">Water column directly on the mesh</td>

<td></td><td></td><td colspan="2">Ventilation holes (centimeters of water) (inches of water)</td><td colspan="2">Mesh holes (inches of water) (inches of water)</td><td colspan="2">Ventilation holes (centimeters of water) (inches of water)</td><td colspan="2">Mesh Holes (inches of water) (inches of water)</td>

<td>Ring Ventilation Holes</td><td>Condition of Mounting</td><td>Average</td><td>Deviation Standard</td><td>Average</td><td>Deviation Standard</td><td>Average</td><td>Deviation Standard</td><td>Average</td><td>Deviation Standard</td>

<td rowspan="2">1 x 5um</td><td> 1</td><td> 81.28 (32)</td><td></td><td> 78.74 (31)</td><td> 5.08 (2)</td><td> 55.88 (22)</td><td> 7.22 (3)</td><td> 73.66 (29)</td><td> 10.16(4)</td>

<td> 2</td><td> 71.12 (28)</td><td> 7.22 (3)</td><td> 98.74(31)</td><td></td><td> 58.42 (23)</td><td> 7.22 (3)</td><td> 98.74 (31)</td><td></td>

<td rowspan="2">3 x 5um</td><td> 1</td><td> 71.12 (28)</td><td></td><td> 68.58 (27)</td><td> 5.08 (2)</td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 66.04 (26)</td><td> 7.22 (3)</td><td> 73.66 (29)</td><td> 7.22 (3)</td><td></td><td></td><td></td><td></td>

<td rowspan="2">5 x 5um</td><td> 1</td><td></td><td></td><td></td><td></td><td colspan="2">No filtration</td><td> 68.58 (27)</td><td> 15.24 (6)</td>

<td> 2</td><td></td><td></td><td></td><td></td><td colspan="2">No filtration</td><td> 71.12 (28)</td><td> 15.24 (6)</td>

<td rowspan="2">1 x 10um</td><td> 1</td><td> 58.42 (23)</td><td> 25.4(10)</td><td> 68.58 (27)</td><td> 7.22 (3)</td><td> 38.1 (15)</td><td> 2.54 (1)</td><td> 63.5 (25)</td><td> 10.16(4)</td>

<td> 2</td><td> 55.88 (22)</td><td> 10.16(4)</td><td> 68.58 (27)</td><td> 5.08 (2)</td><td> 45.72(18)</td><td> 5.08 (2)</td><td> 58.42 (23)</td><td> 127(5)</td>

<td rowspan="2">3 x 10um</td><td> 1</td><td> 38.1 (15)</td><td> 2.54 (1)</td><td> 63.5(25)</td><td> 10.16 (4)</td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 35.56 (14)</td><td> 5.08 (2)</td><td> 66.74(26)</td><td> 127(5)</td><td> 33.02 (13)</td><td> 7.22 (3)</td><td> 58.42 (23)</td><td> 127(5)</td>

<td rowspan="2">3 x 20um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 55.88 (22)</td><td> 5.08 (2)</td><td> 58 42 (23)</td><td> 127(5)</td><td></td><td></td><td></td><td></td>

<td rowspan="2">1 x 50um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td></td><td></td><td></td><td></td><td> 30.48 (12)</td><td> 10 16 (4)</td><td colspan="2">No filtration</td>

<td rowspan="2">3 x 50um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td colspan="2">I</td>

<td> 2</td><td></td><td></td><td></td><td></td><td> 35.56 (14)</td><td> 7.22 (3)</td><td colspan="2">No filtration</td>

<td rowspan="2">5 x 50um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td colspan="2"> I-</td>

<td> 2</td><td></td><td></td><td></td><td></td><td> 33.02(13)</td><td> 10.16 (4)</td><td colspan="2">No filtration</td>

TABLE 12

<td></td><td></td><td colspan="4">Tropicamide column next to the mesh</td><td colspan="4">Tropicamide column directly on the mesh</td>

<td></td><td></td><td colspan="2">Ventilation holes (inches of tropicamide) (inches of tropicamide)</td><td colspan="2">Mesh holes (centimeters of tropicamide) (inches of tropicamide)</td><td colspan="2">Ventilation holes (inches of tropicamide) (inches of tropicamide)</td><td colspan="2">Mesh Holes (inches of tropicamide) (inches of tropicamide)</td>

<td>Ring Ventilation Holes</td><td>Condition of Mounting</td><td>Average</td><td>Deviation Standard</td><td>Average</td><td>Deviation Standard</td><td>Average</td><td>Deviation Standard</td><td>Average</td><td>Deviation Standard</td>

<td rowspan="2">1 x 5um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 17.78 (7)</td><td> 3.8(1.5)</td><td> 17.27 (6.8)</td><td> 2.54(1)</td><td></td><td></td><td></td><td></td>

<td rowspan="2">1 x 10um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 12.19(4,8)</td><td> 2.28 (0.9)</td><td> 15.24 (6)</td><td> 1.77 (0.7)</td><td> 17,78 (7)</td><td></td><td> 14.22 (5.6)</td><td> 3.04(1.2)</td>

<td rowspan="2">3 x 10um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td colspan="2">n / a</td><td> 16(3.5)</td><td> 3.30(1.3)</td><td colspan="2">n / a</td><td> 12.29 (4.8)</td><td> 1.27 (0.5)</td>

<td rowspan="2">3 x 20um</td><td> 1</td><td colspan="2">I</td><td></td><td></td><td colspan="2">I</td><td></td><td></td>

<td> 2</td><td colspan="2">n / a</td><td> 20.57 (8.1)</td><td> 4.86(16)</td><td colspan="2">n / a</td><td> 9.65 (3.8)</td><td> 2.08 (0.8)</td>

<td rowspan="2">1 x 50um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 10.16 (4)</td><td> 2.28 (0.9)</td><td> 15.24 (6)</td><td> 3.02 (1 3)</td><td></td><td></td><td></td><td></td>

<td rowspan="2">3 x 50um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 12.19 (4 8)</td><td> 1.77 (0.7)</td><td> 16.25 (6.4)</td><td> 2.08 (0.8)</td><td></td><td></td><td></td><td></td>

TABLE 13

<td></td><td></td><td colspan="4">Latanoprost column next to the mesh</td><td></td>

<td></td><td></td><td colspan="2">Ventilation holes (Latanoprost centimeters) (Latanoprost inches)</td><td colspan="2">Mesh Holes (Latanoprost Centimeters) (Latanoprost Inches)</td><td></td>

<td>Ring Ventilation Hole</td><td>Condition of Mounting</td><td>Average</td><td>Standard deviation</td><td>Average</td><td>Standard deviation</td><td></td>

<td rowspan="2">1 x 5um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td colspan="2">n / a</td><td> 9.39 (3.7)</td><td> 1.52 (0.6)</td><td></td>

<td rowspan="2">1 x 10um</td><td> 1</td><td colspan="2">I</td><td></td><td></td><td></td>

<td> 2</td><td colspan="2">n / a</td><td> 8.89 (3.5)</td><td> 1 52 (0.6)</td><td></td>

<td rowspan="2">1 x 50um</td><td> 1</td><td></td><td></td><td></td><td></td><td></td>

<td> 2</td><td> 8.38 (3.3)</td><td> 1.77 (0.7)</td><td> 9.39 (3.7)</td><td> 1.52 (0.6)</td><td></td>

Although the foregoing describes various embodiments by way of illustration and example, the skilled artisan will appreciate that various changes and modifications may be practiced within the spirit and scope of the present application.

As mentioned above, droplets can be formed by an ejector mechanism from fluid contained in a reservoir that is coupled to the ejector mechanism. The ejector and reservoir mechanism, which together form an ejector assembly, can be configured to be removable to allow the assembly to be discarded or reused. In that way, the components can be packed in a housing, for example, the upper section 200 of the housing 202 shown in Figure 2, in a removable form. The housing itself may therefore be disposable, or may be reusable when configured to receive a removable ejector mechanism. The housing can be portable, miniaturized, or formed to fit a base, and can be adapted for communication with other devices. Housings can be color coded or configured for easy identification.

Although specific modalities of the ejector mechanism are discussed below, this does not limit the configuration or use of the ejector mechanism or the features that may be added to the ejector device. Ejector devices, in some implementations, may include lighting means, alignment means, temperature control means, diagnostic means, and other features. Other implementations may be part of a larger network of interconnected and interacting devices used for treatment and subject care. The ejector mechanism, for example, may be a piezoelectric actuator as described herein.

Referring to Figures 55A through 55C, an ejector assembly 5500 may include an ejector mechanism 5501 and a reservoir 5520. Ejector mechanism 5501 may include an ejector plate 5502 coupled to a generator plate 5532 that includes one or more openings or holes 5526. Ejector plate 5502 and generator plate 5532 which can be activated by a piezoelectric actuator 5504 which lives to supply a fluid 5510, contained in reservoir 5520, in the form of droplets 5512 ejected along a direction 5514. Again, the fluid it may be an ophthalmic fluid that is expelled into an eye 5516 of an adult, human child, or animal. Additionally, the fluid may contain an active pharmacist to treat a human or animal discomfort, condition, or disease. In some implementations, the generating plate is a high modulus polymer generating plate, for example, formed from a material selected from the group consisting of: ultra high molecular weight polyethylene (UHMWPE), polyimide, polyether ether ketone ( PEEK), polyvinyldene fluoride (PVDF), and polyetherimide, comprises a high modulus polymeric generator plate.

As shown in Figure 55A, ejector plate 5502 is disposed on the front of reservoir 5520 containing fluid 5510. The rear surface 5525 of ejector plate 5502 is arranged to be adjacent to fluid 5510. In this embodiment, therefore, reservoir 5520 has an open end 5538 that is attached adjacent surface 5525 and opening 5526. In this embodiment, surface 5525 encloses fluid 5510 in reservoir 5520. Reservoir 5520 may be coupled to ejector plate 5502a on a peripheral screed 5546 of surface 5525 of ejector plate 5502 using a suitable seal or coupling. By way of example, reservoir 5520 can be attached to a 5548a toned ring. Although not shown, more than one O-ring can be used. As known in the art, tonk rings can have any suitable transverse shape.

In addition, other couplers such as polymeric, ceramic, or metal seals can be used. Alternatively, the coupling can be completely removed and reservoir 5520 can be integrally connected to ejector plate 5502, for example by welding or overmolding. In such an implementation, an opening through which fluid is supplied to reservoir 5520 may be provided (not shown). In embodiments where couplings are used, the couplings may be removably made, for example, by providing a hinged connection between the reservoir 5520 and the ejector plate 5502, or by providing a flexible or non-rigid connector, eg, polymeric connector.

Reservoir 5520 can define a rim or peripheral wall

5550 covering portions of the ejector plate 5502. In the implementation of Figure 55A, the wall 5550 does not directly contact the ejector plate 5502, rather it is coupled to 5548A toning rings. Alternatively, the wall

5550 can be attached directly to ejector plate 5502. Instead, the reservoir can be attached directly to ejector plate 5502, and wall 5550 may be omitted entirely.

The reservoir configuration, including shape and dimension, 5 can be selected based on the amount of fluid 5510 being stored, as well as the geometry of the ejector plate 5502. Alternative forms of reservoirs include collapsible, gravity-fed collapsible bags. wick (as discussed above and incorporating pressure differentials). These reservoirs can be prefilled, filled using a micropump, or can be configured to receive a replaceable cartridge. The micropump can fill the reservoir by pumping fluid into or out of a collapsible or non-collapsible container. The cartridge can include a container that is loaded inside the tank. Alternatively, the same cartridge can be attached to a disposable ejector assembly which is then replaced after a specified number of discharges. Examples of filing are illustrated in US Patent Application. No. 13 / 184,484, filed on July 15, 2011, the contents of which are incorporated herein by reference.

In some implementations, reservoir 5520 includes through ports 5542 (only one shown in Figure 55A) to allow air to escape from or enter reservoir 5520 and maintain fluid 5510 in the reservoir at the appropriate ambient pressure. The through holes 5542 have a small diameter so that fluid 5510 does not leak from the holes.

Alternatively, none of the openings can be formed in reservoir 5520, and at least a portion, for example, portion 5544, or the entire reservoir 5520 may be collapsible, for example, in the form of a bag, as discussed in more detail above. In this way, the entire tank can, in some embodiments, be made in the form of a flexible or collapsible bag. Accordingly, as fluid 5510 is expelled through openings 5526, reservoir 5520 changes its shape and volume to allow for changes in the amount of fluid 5510 in reservoir 5520.

In the embodiment of Figure 55A, the ejector mechanism 5501 is activated by being vibrated by a piezoelectric actuator 5504, which in this embodiment has an annular shape. Two electrodes 5506a and 5506b are formed on two opposite surfaces 5536 and 5534 of the piezoelectric actuator 5504 that are parallel to the surface 5522 of the ejector plate 5502 and active of the piezoelectric actuator 5504 to vibrate the ejector plate 5502 and a generator plate 5532. For ease of representation, ejector plate 5502 and generator plate 5532 are shown lying on a common plane. However, as discussed in greater detail below with respect to Figures 55B to 55D, the generator plate 5532 in this embodiment is attached to a surface of the ejector plate 5502.

Electrodes 5506a and 5506b can be attached to the piezoelectric ejector or actuator plate in any known way including adhesive fixation or other bonding. They can also be overmoulded in place for ejector plate 5502. Wires or other conductive connectors can be used to affect necessary electrical contact between ejector plate 5502 and electrodes 5506a and 5506b. Alternatively, the electrodes can be formed on the ejector plate 5502 by coating or otherwise by deposit. By way of example, the electrodes are joined by means of electrically conductive adhesive 5528 which is applied between electrode 5506a and ejector plate 5502 to place electrode 5506a in electrical contact with ejector plate 5502. When a voltage is applied across electrodes 5506a and 5106b, plezoelectric actuator 5504 deflects ejector plate 5502 and similarly generator plate 5532 to change the shape to a more concave or connected shape.

By conscious, when a voltage is applied across electrodes 5106a and 5106b, plezoelectric actuator 5504 deflects ejector plate 5502 and similarly generator plate 5502 to change shape to be alternatively more concave or connected to the resonant frequency of ejector plate 5502 and generator plate 5532 coupled. The coupled ejector plate 5502 and generator plate 5532 deflected by the plezoelectric actuator 5504 at the resonant frequency can amplify the displacement of the coupled ejector plate 5502 and generator plate 5532 thereby decreasing the power requirements of the piezoelectric actuator input. In a further aspect, the damping factor of the resonator system of the ejector plate 5502 and generator plate 5532 coupled due to the inherent internal resistance of the ring / mesh limits movement to prevent a leak condition and prevent catastrophic failure.

An extensive range of voltages corresponding to different piezoelectric materials are known in the art, but by way of example, a voltage differential of between 5 and 60V, or 30 and 60V, for example, 40 or 60V can be applied to the electrodes. When the direction of the voltage differential is reversed, for example to -40 or -60, the plate will skew in the opposite direction. In this way, the plezoelectric actuator 5504 causes oscillation of the ejector plate 5502 and generating plate 5524 which constitutes the release resulting in the formation of droplets 5512 of fluid 5510. As alternating voltage is applied to electrode 5506a and 5506b, ejector plate 5502 and generator plate 5532 oscillate, causing fluid droplets 5512 to accumulate in openings 5526 and eventually eject from openings 5526 along the address 5514 away from tank 5520. The oscillation frequency and wavelength can depend on many factors, including but not limited to, the thickness, composition and morphology and mechanical properties of the ejector plate 5502, including its hardness, the properties of the 5532 generator plate, the volume of openings 5526, the number of openings 5526, composition and structure of piezoelectric actuator 5504, voltage driving piezoelectric actuator, frequency and waveform, fluid viscosity, temperature and other factors. These parameters can be adjusted or selected to create the desired droplet current. The frequency of droplet expulsion also depends on many factors. In some implementations, particles 5512 are ejected at a frequency less than the pulse frequency applied to the piezoelectric damper 5504. For example, droplets 5512 are ejected every 1-1000 cycles, and more specifically 8-12 cycles, from ejector plate / generator plate vibration (which vibrate at the same frequency as actuator 5504). In some implementations, the generating plate comprises a high modulus polymeric generating plate.

In one embodiment of the present disclosure, as illustrated in Figure 55C, the ejector plate 5502 can be centro-symmetrically mounted by symmetrical mounting frames 5555 through optional mounting holes 5551. Symmetrical mounting structures can maximize area constant velocity surface of ejector plate 5502, suppress anti-symmetric modes and mechanically match piezoelectric material to low-order Bessel modes. In this mode there are four 5555 mounting tabs as shown in

Figure 55C. In another mode, there can be eight 5555 mounting tabs. Even in another mode, there can be 16 5555 mounting tabs.

In certain respects, center-symmetrical mounting allows the use of piezoelectric materials that are lead-free, for example, BaTiCb. In one embodiment of the disclosure, resonance coupling of ejector plate 5502 to a generator plate 5532 and piezoelectric actuator 5504 allows the use of piezoelectric materials having smaller displacements than industry standard piezoelectric materials.

In accordance with certain embodiments of the description, referring to Figure 55A, an ejector plate 5502 may be a simple ejector plate 5502 having an integrated generator plate 5532 having a central region 5530 and apertures 5526. In other embodiments of the description (Figures 55B to 55D) the ejector plate 1602 may have hybrid ejector plate 1602 having an attached generator plate 5532 having a central region 5530 and openings 5526. The first surface 5522 of the ejector plate 5502 can be coupled to the generator plate 5532. The ejector plate 5502 can generally comprise a central open region

5532 configured to align with the generator plate 5532. The generator plate 5532 can then be coupled with the ejector plate 5502 so that a central region 5530 of the generator plate 5532 aligns with the central open ruler 5552 of the ejector plate 5502. The central ruler 5530 of generator plate 5532 may generally include one or more openings or holes 5526. Alignment of the central open region 5552 of the ejector plate 5502 or the central region 5530 of the generating plate 5532 with its one or more openings 5526 allows for passing communication of the one or more openings 5526. In some embodiments, the generating plate comprises a high modulus polymeric generating plate.

In certain embodiments, the central open region 5552 of ejector plate 5502 may be smaller than generator plate 5532 to provide sufficient overlap of material to allow coupling of ejector plate 5502 and generator plate 5532. However, the central open screed 5552 of the ejector plate 5502 must, in some embodiments, be sized and formed so as not to interfere with or obstruct the central region 5530 (and with it one or more openings 5526) of the generator plate 5532. By way of non-limiting example, the central open region 5552 of the ejector plate can be formed in a similar way to the generator plate 5532, and can be dimensioned to obtain, for example, about 0.5mm to about 4mm, for example, about 1 mm to about 4 mm, or about 1 mm to about 5 mm, etc., of overlapping material available for coupling the generator plate 5532 to the ejector plate 5502 (for example, overlap on all sides). For example, the central open region 5552 of the ejector plate may be formed as a square, a rectangle, a circle, an oval, etc., in a shape to generally coincide with the shape of the 5532 generator plate, and dimensioned such that the central open region 5552 is, for example, about 0.5 mm to about 4 mm smaller in overall dimensions (i.e. the diameter of a circle is about 0.5 to about 4 mm smaller, the major and minor axes of an oval are approximately 0.5 to approximately 4 mm smaller, the length of the sizes of a rectangle square are approximately 0.5 to approximately 4 mm smaller, etc.). In some embodiments, the generating plate comprises a high modulus polymeric generating plate.

Except as otherwise described herein, illustrative ejector mechanisms are described in US Applications. No. 13 / 712,784, filed December 12, 2012, titled “Ejector Mechanisms, Devices, and Methods of Use,” and 13 / 712,857, filed December 12, 2012, titled “Hlgh Modulus Polymeric Ejector Mechanism,

Ejector Device, and Method of Use ”, the contents of which are incorporated herein by reference in their entirety.

Generator plate 5532 may be coupled to ejector plate 5502 using any suitable shape known in the art, depending on the materials in use. Examples of coupling methods include the use of adhesive and bonding materials, eg, glues, epoxies, bonding agents, and adhesives such as loctite 409 or other suitable superglue, welding and bonding processing, eg, ultrasonic or thermosonic bonding , thermal bond, diffusion bond, or press fit, etc.

The surface 5522 of the ejector plate 5502 can also be coupled to a piezoelectric actuator 5504, which activates the generator plate 5532 to form the droplets with activation. The shape and location of attachment of the piezoelectric actuator 5504 to the ejector plate 5502 affects the operation of the ejector assembly 5500 and the creation of the droplet current.

In the embodiment of Figures 55B to 55C, the piezoelectric actuator 5504 can be coupled to a peripheral region of the surface 5522 of the plate 5502, while the generator plate 5532 is coupled to the surface 5522 to align with the central open region 5532 of the ejector plate

5502, as described above. Piezoelectric actuator 5504 is generally coupled to ejector plate 5502 so as not to cover or obstruct central region 5530 (and thereby one or more openings 5526) of generator plate 5532. In this way, fluid 5510 can pass through the openings 5526 to form droplets 5512 (as shown in Figure 55A).

The structure defined by the ejector plate 5502 and generating plate 5532 optionally coupled has a large number of vibration modes that define, for each vibration mode, the shape that the structure will take when said structure is stimulated. Examples of vibration modes are presented in Figure 3. For maximum ejection in any of these vibration modes, the piezoelectric actuator 5504 should be properly shaped and positioned in a position that provides the least amount of deformation resistance of ejector plate 5502 and generator plate 5532 optionally coupled in vibration mode wanted. The piezoelectric actuator 5504 provides a constraint on the shape of a given vibration mode, the hardness of the piezoelectric actuator 5504 and the link layer can dampen the mode (provide resistance to continuous motion), and can force movement of the structure to be extremely dependent on the material properties of the 5504 piezoelectric actuator. This can limit mass ejection to approximately the ratio of the properties of the piezoelectric actuator.

5504.

In some implementations, Vibration modes of ejector part 5502 and optionally coupled 5532 generator plate can be stimulated with low or no resistance (other than Inside resistance of ejector plate 5502 and optional 5532 generator plate attached) to continuous motion (plate resonance ejector 5502 and generating plate 5532 optionally attached) simply by mounting piezoelectric actuator 5504 to the edge of ejector plate 5502 and generating plate 5532 optionally docked. By linking piezoelectric actuator 5504 to the edge of ejector plate 5502 and generating plate

5532 optionally coupled, the least possible resistance to movement of ejector plate 5502 and generator plate 5532 optionally coupled can be provided. In an edge bonded or near edge bonded embodiment, limitations on the properties of the piezoelectric actuator 5504 are minimized, since the mechanical resistance offered by the hardness of the ceramic (for example, the piezoelectric actuator 5504) and bonding to the forms of Vibration mode is less than the same ejector plate 5502 and the optionally coupled generator plate 5532.

In certain aspects of the present disclosure, the vibration modes of the ejector plate 5502 and optionally coupled 5532 generator plate can be optimized by varying the dimensions of the piezoelectric actuator 5502. In one aspect, a given vibration mode can be stimulated by mounting the driving force (eg, piezoelectric actuator 5504) in the correct location, relative to the foot wave on ejector plate 5502 and generator plate 5532 optionally coupled, and restricting the dimensions of the piezoelectric actuator 5504, within the foot wave node or anti-node (depending on dominant radial or longitudinal pulse mode). The vibration modes of an optionally coupled ejector plate 5502 and generator plate 5532 and their shapes can be found analytically by solving the Sturm-Liouville problem.

Although Idealized vibration modes of a membrane (eg, a drum) can be found by solution to the Sturm10 Liouville problem, in certain aspects of the present description it becomes mathematically difficult or even intractable to analytically solve the vibration mode forms, frequencies, and corresponding amplitude coefficients of vibration of an ejector plate 5502 and generator plate 5532 optionally coupled. Analytical limitations to obtain a solution to the Sturm-Liouville problem arise when an idealized membrane is loaded, includes an impulse element, such as a non-ideal limit condition, or comprises multiple materials.

In aspects in accordance with the present disclosure, the 5502 ejector plate and optionally coupled 5532 generator plate may include loads such as 5510 fluid. In other aspects, the 5502 ejector plate and optionally coupled 5532 generator plate may include a piezoelectric actuator drive element. 5504. In another aspect, the ejector plate 5502 may include the coupled generator plate 5532 comprising one or more materials. In a further aspect, ejector plate 5502 may be of non-uniform thickness. Similarly, in one aspect, the coupled generator plate 5532 may be of non-uniform thickness. In yet another aspect, the 5532 generator plate can have openings 5526 that are non-uniform and can lead to non-trivial analytical solutions.

The analytical limitations that arise from a non-idealized membrane can be overcome. In certain respects in accordance with the present disclosure, computer software may be used to divide a structure into smaller discrete elements using Finite Element Methods (FM). In one aspect, computer software discretizes the structure into elements that may be half or less the size of the minimum wavelength (maximum frequency) of vibratory interest. In other respects the discrete elements may be one fifth or less of the size of the minimum wavelength (maximum frequency) of vibratory interest. In another aspect of the present disclosure, the discrete elements may be one fifteenth or one twelfth or less the size of the minimum wavelength (maximum frequency) of vibratory interest. In one aspect, the analytical problem involving a partial differential equation can then be represented by the central differences at each point of the discrete elements. In another aspect, the partial differential equation can be solved by finding a sum of base functions that minimize the energy of the system.

In one aspect, using EMF techniques, vibration mode frequencies and shapes can be determined through modal analysis for a given group of boundary conditions, such as free, simply supported, clamped, buckled, or some hybrid conditions. the limit. In one aspect, the shape of the piezoelectric actuator 5504 can be determined by the shape of the vibration mode it is intended to drive. In certain aspects, the shape of the 5504 piezoelectric actuator is largely determined by the counterbalance of force applied per unit area, which is directly related to the area of ​​the piezoelectric actuator 5504 in contact with the ejector plate 5502 and generating plate 5532 optionally coupled, and the resistance or damping applied to the mode shape by the hardness of the bonded 5504 piezoelectric actuator.

In certain embodiments in accordance with the present disclosure, once the location and initial size of the piezoelectric actuator 5504 is determined, it is modeled on the ejector plate 5502 and simulated with a voltage applied to the top of the piezoelectric actuator 5504 and grounded on ejector plate 5502 and generator plate terminal 5532 optionally attached. Optionally attached 5502 ejector plate and 5532 generator plate may be a single 5502 ejector plate, a hybrid 5502 ejector plate having a 5532 coupled generator plate, or a single or hybrid 5502 ejector plate having a four post structure, field filtered structure electrical, or any other combination of structures. The stimulation frequency of the piezoelectric actuator 5504 is swept in the simulation from frequencies close to zero to several hundred kilohertz (kHz), or more generally any frequency. The mode shape, amplitude of displacement, and speed experienced by the single or hybrid ejector plate 5502 are calculated for each frequency in the sweep. By applying EMF techniques, the amplitude and speed of a design can be evaluated.

If the 5502 ejector plate / 5504 piezoelectric actuator system is moving at the appropriate amplitude and speed at the desired design frequency it is complete. If not, the design tuned to slim or thicken the height of the 5504 piezoelectric actuator in order to alter the damping of the ejector plate 5502 applied by the piezoelectric actuator 5504. In certain respects, the 5504 piezoelectric actuator can also be tuned in lateral / radial thickness in order to reduce damping in specific ways or to change resonant frequencies either higher or lower. Simulations are repeated given the trend in the dimensioning of the 5504 piezoelectric actuator until design optimization is complete.

Since the 5500 ejector assembly is used to deliver therapeutic agents or other fluids to the desired target, for example, the eye, the 5500 ejector assembly may be designed to prevent fluid 5510 contained in reservoir 5520 and ejected droplets 5512 become contaminated. In some implementations, for example, a coating (not shown) may be formed on at least a portion of the exposed surface (s) of the piezoelectric actuator 5504, the ejector plate 5502, the generator plate 5532, etc. ., which are exposed to fluids. The coating can be used to prevent direct contact of the piezoelectric actuator

5504 and electrodes 5506a and 5506b with fluid 5510. The coating can be used to prevent interaction of ejector plate 5502 or generator plate 5532 with the fluid. The liner or a separate liner can also be used to protect the piezoelectric actuator 5504 and electrodes 5506a and 5106b from the environment. For example, the coating may be a conformal coating that includes a non-reactive material, for example, polymers including polypropylene, nylon, or high-density polyethylene (HDPE), gold, platinum, or palladium, or coatings such as Teflon®. Coatings are described in further detail here.

Generator plate 5532 may be a perforated plate containing at least one opening 5526. The one or more openings 5526 allow droplets to form as fluid 5510 is passed into the openings and ejected into the generating plate 5532. Generator board 5532 can include any suitable configuration of openings. Examples of 5532 generating plates comprising high modulus polymers are illustrated in US Application. No. 13 / 712,857, filed December 12, 2002, entitled "High Modulus Polymeric Ejector Mechanism, Ejector Device, And Methods Of Use", the contents of which are incorporated herein by reference in their entirety for the purpose of such descriptions.

In some implementations, ejector plate 5502 can be formed of a metal, for example, stainless steel, nickel, cobalt, titanium, iridium, platinum, or palladium or alloys thereof. Alternatively, the plate can be formed of another suitable material, including other metals or polymers, and can be coated as described herein. The plate can be a composite of one or more materials or layers. The plate can be manufactured, for example, by cutting from a metal foil, pre-forming, rolling, melting or thereby forming. Coatings can also be deposited by suitable deposition techniques such as spraying, vapor deposition including physical vapor deposition (PAD), chemical vapor deposition (COD), or deposition of electrostatic powder. The protective coating can have a thickness of about less than 0.1 pm to about 500 pm. It is desirable that the coating adhere to the ejector plate 5502 enough to prevent delamination when vibrating at a high frequency.

Referring to Figures 55B and 55D, in one implementation, ejector plate 5502 and generator plate 5532 may have concentric circular shapes. In certain embodiments, the ejector plate may be larger than the generator plate, to Incorporate generator plate coupling and other components (eg, piezoelectric actuator, etc.) described herein. In certain embodiments, the overall size or diameter of the generator plate 5532 may be, at least in part, determined by the size of the central region 5530 and by the arrangement of openings 5526. In some embodiments, the generator plate comprises a polymeric generator plate high modulus.

However, both plates can independently have 5 other shapes, for example, an oval, square, rectangular, or generally polygonal shape, or they can be the same or different. The general size and shape can be any suitable size and shape, and can be selected based on ejector device design parameters, eg, size and shape of an outer device housing, etc.

Additionally, the plates need not be flat, and may include a surface curvature making it concave or connected. The piezoelectric actuator 5504 can be of any suitable shape or material. For example, the actuator can have a circular, oval, square, rectangular, or a generally polygonal shape. Actuator 5504 can adapt to the shape of ejector plate 5502, generating plate 5532, or regions 5532 or 5552. Alternatively, actuator 5504 may have a different shape. Furthermore, actuator 5504 can be coupled to ejector plate 5502 or surface 5522 of ejector plate 5502 in one or more sections. In the example shown in Figures 55B to 55D, the piezoelectric actuator 5504 is in the form of a ring that is concentric to the ejector plate 5502, generator plate 5532, and regions 5530/5552.

In some implementations, ejector plate 5502 and / or generator plate 5532 may be coated with a protective coating that has anti-contamination and / or anti-microbial properties. The protective coating can conform to all other surfaces of the ejector plate and / or generating plate, including surfaces that define openings 5526. In other implementations, the protective coating can be applied to selected surfaces, for example, surfaces 5522, 5525, or surface regions, for example, parts of such surfaces. The protective coating can be formed of a biocompatible material, eg, gold, iridium, rhodium, platinum, palladium, or alloys thereof, or a biocompatible polymer, eg, polypropylene, HDPE, or Teflon®.

Antimicrobial materials include metals such as silver, silver oxide, selenium, or polymers such as polka ketones. The protective coating can be in direct contact with the 5510 fluid or 5512 droplets. The coating can provide an inert barrier around the fluid or can inhibit microbial growth and sanitize the 5510 fluid and / or the droplets

5512.

Additionally, one or both of ejector plate surface 5522 5502 and generator plate moistened surface 5532 facing reservoir 5520 may be coated with a hydrophilic or hydrophobic coating. Additionally, the liner can be coated with a protective layer. Surfaces can also be coated with a reflective layer. A coating layer can be both protective and reflective. Alternatively, one or more of the surfaces have been formed to be reflective. For example, the surfaces may be made of steel, nickel-cobalt, or other reflective material. A surface can then be shaped or polished to be reflective. In addition to making the reflective surface, the surface can also be feedback on its surface and around its perimeter. In ophthalmic applications, a reflective surface helps the user to align the ejector assembly with the eye.

If desired, the ejector assembly surfaces can include coatings that can be preformed by dipping, coating, including electrocoating, or otherwise encapsulating, such as by molding or casting. The coatings can also be deposited by suitable deposition techniques such as spraying, vapor deposition, including physical vapor deposition (PAD) and chemical vapor deposition (COD), or electrostatic powder deposition. The protective coating can have a thickness of less than 0.1 pm to approximately 500 pm. It is desirable that the coating adhere to the plate enough to prevent delamination when vibrating at a high frequency.

The piezoelectric actuator 5504 can be formed from any suitable material known in the art. By way of example, in some implementations, the piezoelectric actuator may be formed of PZT, barium titanate, or polymer-based piezoelectric materials, such as polyvinylidene fluoride. Electrodes 5506a and 5506b can be formed from suitable conductors include gold, platinum, or silver. Materials suitable for use as the 5528 adhesive may include, but are not limited to, adhesives such as silicone adhesive, epoxies, or silver paste. An example of a conductive adhesive includes thixotropic adhesive such as Dow Corning DA6524 and DA6533. Reservoir 5520 can be formed from a polymer material, some examples of which include Teflon®, rubber, polypropylene, polyethylene, or silicone.

Piezoelectric ceramic materials are isotropic in the non-polarized state, but they also become anisotropic in the polarized state. In anisotropic materials, both the electric field and the electric displacement must be represented as three-dimensional vectors in a similar way as the mechanical force vector. This is a direct result of the dependence of the dielectric displacement ratio, D, on the electric field, E, with the orientation of the capacitor plate to the glass (or ceramic driven) axes. This means that the general equation for electric displacement can be written as a variable equation of state:

D¡ - s¡j Ej

The electric displacement is always parallel to the electric field, in this way each electric displacement vector, D, is equal to the sum of the field vectors Ex, multiplied by its corresponding dielectric constant, sj:

Di = ε-ι-ι E-ι + εΐ2 E₂ + ε₁₃ AND₃

D₂ - ε₂ι Ei + ε₂₂ AND₂ + ε₂₃ AND₃

100

D₃ = ε₃ι Ει + ε₃2 Ε2 + ε₃₃ Ε₃

Most dielectric constants for piezoelectric ceramics (as opposed to Individual glass piezoelectric materials) are zero. The only non-zero terms are:

Cu = 822 · ε₃₃

The piezoelectric effect refers to electrical effects. These effects are highly dependent on their orientation to the driven axis. The axis numbering scheme is shown in Figure 56. For example, for the constant the electro-mechanical d_tob, a = electric direction; b = mechanical direction and for electro-mechanical constant D₃₃ = ε₃₃ AND₃ with mechanical displacement in the driven section, Z in this case. Referring to Figure 55A, the Z direction is the direction of the ejected droplets 5512, direction 5512.

Therefore, D₃₃ is the induced polarization in the Z 15 direction (driven direction, corresponding to direction 5514 in Figure 55A) that is parallel to the direction in which the ceramic material is polarized.

In accordance with certain embodiments of the disclosure, piezoelectric materials may be excluded by mechanical displacement in the driven direction, Z (eg, direction 5514 of Figure 55A).

In some embodiments, the piezoelectric material may be a lead zl-titanate titanate (PZ) having D₃₃ = 330 pC / N. In another embodiment, the piezoelectric material may be a type of PbTiO3-PbZrO3 (PZT) based multiple component system that is widely used. Ceramics

101 commercially available PZT piezoelectrics Include PZT-4 which has a D₃₃ 255 pC / N, PZT-5A that has a D₃₃ 350 pC / N, and PZT-5H that has a D₃₃ 585 pC / N. The piezoelectric throttle based on (which from PZT) can be formed from a material having a D₃₃ greater than 300 pC / N).

In another embodiment, piezoelectric ceramic can have a D₃₃ from 200 pC / N to 300 pC / N. In another embodiment, piezoelectric ceramic can have a D₃₃from 250 pC / N to 300 pC / N.

In some implementations, it may be desirable to remove lead from the piezoelectric material for safety and compliance reasons.

FDA / EU. In one implementation, a lead free piezoelectric ceramic can be used having a D₃₃ less than 300 pC / N. In another embodiment, a lead-free piezoelectric ceramic can have a D33 of less than 200. Even in another embodiment, a lead-free piezoelectric ceramic can have a D33 of between 150 pC / N and 200 pC / N. Even in another embodiment, the D33 of the lead-free ceramic may be less than 150 pC / N. Even in another embodiment, a lead-free piezoelectric ceramic can have a D33 of between 100 and 150 pC / N. Even in another embodiment, the 150 pC / N of a lead-free ceramic suitable for a piezoelectric damper may be less than 100 pC / N.

In some embodiments, the piezoelectric device can be prepared from commercially available materials. For a non-limiting example, available materials from Sunnytee Powder Materials presented in Table 14 may be suitable for devices

02 Piezoelectric Description.

TABLE 14

<td colspan="2" rowspan="2">Physical materials and properties</td><td>S-42</td><td>S-44</td><td>S-44-2</td><td>S-81</td><td>S-51</td><td>S-52</td><td>S-53</td><td>S-54</td><td>S-55</td><td>S101-D</td><td>S101-F</td>

<td>P-42</td><td>FM-2-1</td><td>SP-12-4</td><td>P.8</td><td>P-5A</td><td>FT-3</td><td>FT-4</td><td>P-5H</td><td>TK-4800</td><td>S101-D</td><td>S101-F</td>

<td>Density (grams / cm)</td><td>P</td><td> 7.6</td><td> 7.7</td><td> 7.7</td><td> 7.6</td><td> 7.6</td><td> 7.56</td><td> 7.56</td><td> 7.6</td><td> 7.7</td><td> 7.55</td><td> 7.6</td>

<td>Curie temperature (• C)</td><td>Tea</td><td> 305</td><td> 300</td><td> 280</td><td> 320</td><td> 260</td><td> 280</td><td> 250</td><td> 180</td><td> 170</td><td> 185</td><td> 165</td>

<td>Dielectric Constants</td><td>33 IZO</td><td> 1450</td><td> 1550</td><td> 1600</td><td> 1030</td><td> 2300</td><td> 2200</td><td> 3200</td><td> 3800</td><td> 4600</td><td> 1200</td><td> 4200</td>

<td>Dissipation Factor (%)</td><td>Tgo</td><td> 0.4</td><td> 0.4</td><td> 0.5</td><td> 0.3</td><td> 1.5</td><td> 1.8</td><td> 1.8</td><td> 1.7</td><td> 2</td><td> 1.6</td><td> 1.6</td>

<td rowspan="3">Coefficients of Coupling (%)</td><td>Kp</td><td> 65</td><td> 68</td><td> 66</td><td> 58</td><td> 71</td><td> 80</td><td> 81</td><td> 77</td><td> 81</td><td> 72</td><td> 68</td>

<td>Kt</td><td> 48</td><td> 48</td><td> 47</td><td> 46</td><td> 51</td><td> 51</td><td> 52</td><td> 52</td><td> 51</td><td> 50</td><td> 46</td>

<td>K31</td><td> 33</td><td> 34</td><td> 35</td><td> 30</td><td> 38</td><td> 43</td><td> 44</td><td> 42</td><td> 45</td><td> 38</td><td> 36</td>

<td rowspan="3">Frequency Constants (MHz)</td><td>N_P</td><td> 2230</td><td> 2250</td><td> 2220</td><td> 2300</td><td> 2080</td><td> 1960</td><td> 1950</td><td> 1980</td><td> 1950</td><td> 2030</td><td> 2100</td>

<td>Nt</td><td> 2050</td><td> 2050</td><td> 2080</td><td> 2050</td><td> 2040</td><td> 2030</td><td> 2045</td><td> 2040</td><td> 2020</td><td> 2040</td><td> 2100</td>

<td>NL</td><td> 1650</td><td> 1630</td><td> 1630</td><td> 1655</td><td> 1545</td><td> 1420</td><td> 1420</td><td> 1500</td><td> 1465</td><td> 1510</td><td> 1545</td>

<td>Quality factor Mechanics</td><td>Qm</td><td> 600</td><td> 1400</td><td> 1200</td><td> 1000</td><td> 80</td><td> 70</td><td> 65</td><td> 65</td><td> 55</td><td> 100</td><td> 70</td>

<td rowspan="2">Load constants Piezoelectric (X1012M / V)</td><td>d33</td><td> 320</td><td> 330</td><td> 330</td><td> 250</td><td> 450</td><td> 550</td><td> 640</td><td> 650</td><td> 750</td><td> 620</td><td> 650</td>

<td>d31</td><td> -155</td><td> -135</td><td> -140</td><td> -110</td><td> -200</td><td> -260</td><td> -300</td><td> -290</td><td> -300</td><td> -250</td><td> -265</td>

<td rowspan="2">Voltage Constants Piezoelectric (X10-3V m / N)</td><td>g33</td><td> 25.8</td><td> 23.4</td><td> 23 2</td><td> 27.4</td><td> 22.1</td><td> 28.2</td><td> 22.6</td><td> 19.3</td><td> 18.4</td><td> 21.8</td><td> 17.4</td>

<td>g31</td><td> -12.5</td><td> -10.5</td><td> -10.2</td><td> -9.8</td><td> -11.1</td><td> -11.5</td><td> -10.8</td><td> -8.6</td><td> -7.5</td><td> -8.5</td><td> -7.1</td>

<td rowspan="2">Elastic constants (X10-12m2 / N)</td><td>SE11</td><td> 11.5</td><td> 12.5</td><td> 12.1</td><td> 12.1</td><td> 13.8</td><td> 16.2</td><td> 16.5</td><td> 14.1</td><td> 15.2</td><td> 14.5</td><td> 13.7</td>

<td>SD11</td><td> 10.2</td><td> 11.2</td><td> 11.1</td><td> 10.9</td><td> 11.8</td><td> 13.3</td><td> 13.2</td><td> 11.6</td><td> 12.9</td><td> 12.3</td><td> 11.8</td>

In some embodiments, the piezoelectric material may be a BiFeO3-based ceramic. In some embodiments, ceramics can be selected from the group consisting of (Bi, Ba) (Fe, Ti) OR₃, (K, Na, Li) NbO₃, (K, Na, Li) NbO₃, (K, Na, Li) NbO₃, (K, Na, Li) NbO3, Bi (Fe, Mn) O₃+ BaTiO₃, Bi (Fe, Mn) O₃+ BaTiO₃, B¡FeO₃-NdMnO₃-BiA103, (Bi, La) (Fe, Mn) O₃, (Bi, La) (Fe, Mn) O3, BiFeMnO3-BaTiO₃, B¡ (Fe, Mn) O3-BaZrT¡0₃, (Bi, La) (Fe, Mn) O₃, (B¡, La) (Fe, Mn) O₃, (B¡, Ba) (Fe, Ti) O₃, B¡ (Zn, Ti) 0₃-La (Zn, T¡) 0₃Ba (Sc, Nb) O₃ (d33 = 250), BiFeO₃, (Ba, M) (Ti, Ni) O₃, BiFeO₃, Bi (AI, Ga) O₃BTBiFeO₃, Bi (Fe, AI) O₃, Bi (Fe, AI) O₃, BI (Fe, Co, Mn) OR₃, BiFeO₃-BaTIO₃, BiFeO₃BaTiO₃, Bi (AI, Ga) O₃ (d33 = 150), Bi (AI, Ga) O₃, BiFeO + AD, BiFeO + BaTiO,

BiFeO-based, BaTiO-BiFeO, (Bi, x) (Fe, Mn) O, and (Bi, x) (Fe, Ti, Mn) O₃.

In some embodiments, the piezoelectric material can be a bismuth sodium titanate (BNT) material or a

103 Bismuth Potassium Titanate (BKT) material. BNT or BKP material can be selected from the group consisting of (1x) B¡₀.5Nao.₅T¡03- xLaFeO₃, (1-x) B¡o.5Nao.₅T¡0₃- xNaSbO₃, Bio ^ Na ^ xKxjo.sTiOs (BNKT), B¡o.5 (Na-i-xKx) o.5T¡0₃ (BNKT), B¡o.5 (Nai-xKx) o.5Ti0₃ (BNKT), B¡os (Nai5 χΚχ)₀.₅ΤίΟ₃ (BNKT), ((1-x) B¡i „_toNa_to) T¡0₃- (1-x) LiNbO₃, B¡o 5 (Nai.xLix) or.₅Ti0₃, B¡₀.₅(Na, K)₀.₅[Ti, (Mg, Ta)] O₃, Bío.₅(Na, K) o.₅[You, (AI, Mo)] O₃, Bío.₅(Na, K) o.₅[T¡, (Mg, Nb)] O₃, Bio.₅(Na, K) o.5 [Ti, (M, V)] 0₃, Bi₀.5 (Na, K) o.₅[Ti, (M, V)] 0₃, BNT-BT-KNN, (1x) Bi₀₅Nao.₅Ti0₃-xBaT¡0₃ (BNBT) (d₃₃= 100x10 '¹²C / N or more), BNT-BKT-BT (d₃₃= 158pC / N), BNT-BKT-BT + PT (d₃₃= 127), BNT-KN, B¡₀₅Na_{0 5}Uncle₃-BaTIO₃ (BNBT) (d₃₃ = 253pC / N), NGK2, BNT-BKT-BT, NGK, BNT-BKT-BT, NGK4, B¡o sNao 5T¡0₃-BaT¡0₃-CaT03 Ba (Zni /₃Nb2 /₃)OR₃ + Υ₂Ο₃, MnO, (1 — v) [(Li-r_ _andNay) zNb0₃] -v [B¡o.5Nao.₅T¡0₃], Bio.₅Nao.5T¡0₃, BNT-BT, BNT-BT, xB¡o.5Nao.5T¡0₃-y (Mnb0₃) - (Z / 2) (B¡₂0₃-Sc20₃) (Μ = K, Na), BNT-BKTBi (Mg2 / 3Ta1 / 3) O3, [(Bio.₅Na₀5) xMy] z (T¡uNv) 0₃ (M = Ba, Mg, Ca, Sr, (BÍ0.5K0.5)) (N = Zr, Hf), [(B¡o.5Nao.₅) xMy] z (T¡uNv) 0₃ (M = Ba, Mg, Ca, Sr, (BÍ0.5K0.5), others) (N = Zr, Hf, others), BNT-BKT-BT-CT-NaNbO₃, BNT-BKT-Bi (Ni, Ti) O₃, BNT-BKTBi (Ni, Ti) O₃, BNT-BKT-BT, BNT-BT-ST, BNT-BKT-BT, BNT-BKT-AgNbO₃, BNT-BKT-BT, BT-BKT, BNT-BT-Bi (Fe0.5T¡0.5) 3, BNT-BKT-Bi (Zn0.5Zr0.5) 03, BNT-BKT-Bi (Fe0.5Ta0.5 ) 03, BNT-BKT-Bi (MI, M2) O3, BNT-BKT, BNT-BT,

BNT-BKT, BÍ0.5K0 ₅Uncle₃ (BKT) and Bio.sNao.sTiOs- (1 -x) ABO₃.

In some implementations, the piezoelectric material may be a dual-mode magento-strict / piezoelectric double-layer compound, tungsten-bronze material, a sodium niobate material, a

104 barium titanate material, and a polyvinylidene fluoride material. Examples of materials suitable for the piezoelectric actuator of the disclosure include A2BÍ4TÍ5018 (A = Sr, Ca, (B¡o.₅Nao.5), (BÍ0.5LÍ0.5), (B¡o.₅The.₅), (A1-xBix) 2B¡4T¡5018 (A = Sr, Ca, (B¡o.5Nao.5), (, (B¡o.5Nao.5), (Bio.5L¡o 5), BÍ4TÍ3O125 x (Sr1-aAa) T¡03 (A = Ba, B¡o.₅Nao.₅, BÍ0.5K0.5, B¡₀ sLio.s), Bi4T¡3012- (Ba, A) T¡03, B¡4T¡3012-x {(Srl-aA'a) TiO3-AB03} (A-Ba, Bi_or.₅NaO.5, Bi₀₅KO.5, Bi_O5Li0.5, A = Bi, Na, K, L¡, B = Fe, Nb), (AI-xBix) B¡4Ti4O15 (A = Sr, Ba), BaBi4T¡4015, (Sr2aAa) x (Nal-bKb ) and (Nb5-cVc) O15 (A = Mg, Ca, Ba) d33 = 80pC / N or more, Te = 150 ° C. or more, (Sr2-aAa) x (Nal-bKb) and (Nb5-cVc) O15, (Bio.sNaos)! 10 xMxB¡4Ti4O15, BÍ4TÍ3012, SrB¡2 (Nb, W) O9, (Srl-xMlx) Bi2 (Nbl-zWy) 2O9, (Sr, Ca) NdBi2Ta209 + Mn, (Srl-xMx) (B¡, Nd) (Nb, Ta) 209, Bi2 (Srl-xMx) Nb2O9 (M = Y, La), (Sr2CaK) Nb5015 (d33 = 120).

In implementations in accordance with the description, the niobate material can be selected from (Sn, K) (Ti, Nb) O3, KNbO315 NaNbO3-LiNbO3-SrTiO3-BiFeO3, KNb03-NaNb03-LiNb03, KNbO3NaNbO3-L¡NbO3, yNaNbO3-zBaNb2O6, NaxNbO3-AyBOf (A = K, Na, Li, B¡ B = Li, Ti, Nb, Ta, Sb), (1-x) (Nal-aMna) b (Nbl-aTia) O3 -xMbT ¡03 (M = (Bil / 2KI / 2), Bil / 2Nal / 2), (Bil / 2Lil / 2), Ba, Sr, (K, Na, Li) NbO3-Bi (Mg, Nb) O3Ba (Mg , Nb) O3, (lx) [(Lil-yNay) zRO3j- xLMnO3 (R = Nb, Ta, Sb, L = Y, Er, Ho, Tm,

Lu, Yb), (LixNal-x-yKy) z-2wMa2wNbl-wMbwO3 (Ma =²⁺ metal A, Mb = ³⁺ metal B), NN-BT d33 = 164, KI-xNaxNbO3 + Sc2O3, [(KI-xNax) l-yAgy] NbO3z [Ma +] [02-] (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.)

105 (d33 = 130).

Barium titanate material is an inorganic compound with the chemical formula BaTiO₃. Barium titanate materials include BaTiO materials₃which also comprise substoichiometric amounts of other elements. Examples of other elements that are so included in BaT¡0 materials₃ they include rare earth elements and ferrous alkali metals. Sub-stoichiometric amounts of other elements modify the plezoelectric properties of BaT¡0 materials₃. Doping of BaTiO materials₃ it refers to the inclusion of substoichiometric amounts of other elements.

Examples of suitable single crystal barium titanate materials further include Bil / 2, Nal / 2) l-xAlx} T¡03 (AI = Ba, Ca, Sr), {(Bil / 2, Nal / 2) lx ( Bil / 2, A21 / 2) xTiO3 (AI = Ba, Ca, Sr, A2 = Li, K, Rb) (single crystal), (Sr, Ba) 3TaGa3S¡2014, La3-xSrxTayGa6-y-zSizO14, (Ba , Ca) T¡03,

L¡NbO3, L¡TaO3, (K3L¡2) l-xNaxNb5O15, La3Ga5S¡014, MgBa (C03) 2,

NdCa40 (B03) 3 (M1 = rare earth metals, M2 = alkaline earth metals),

LaTiO2N.

In some implementations, ejector plate 5502 can be formed of a suitable material where the suitable material is selected based on out-of-plane offset, direction 5514. The offset Z of ejector plate 5502 (eg movement in direction 5514) depends on the ejector plate diameter 5502 and ejector plate thickness 5502. The suitable material can also be selected in

106 View of Young's Modulus and Poisson's Ratio from ejector plate 5502. Young's Modulus and Poison's Ratio are intrinsic properties of the material and forming materials can be selected to determine a desired displacement. For a suitable material for ejector plate 5502, the Z offset can be increased by decreasing the thickness of the ejector plate 5502.

Suitable materials for ejector plate 5502, having an offset in direction 5514, can be coupled to the frequency of piezoelectric actuator 5504 to match the resonant frequency of ejector plate 5502. By coupling the displacement of the ejector plate 5502 with the piezoelectric actuator 5504 in a resonance system, the expulsion of the liquid through the holes of the generator plate 5532 can be achieved with piezoelectric actuators that are not limited by values ​​of D₃₃.

Referring to Figure 55C, the shape and attachment location of the piezoelectric actuator 5504 to the ejector plate 5502 may affect the operation of the ejector assembly 5500 and the creation of the droplet current.

As discussed above, the 5502 ejector plate, either as a simple 5502 ejector plate or as a hybrid 5502 ejector plate coupled to a 5502 generator plate, can possess a large number of vibration modes that define, for each vibration mode, the shape the structure will take when this mode is stimulated. How I know

07 previously provided, using for example EMF techniques, the vibration modes of an optionally coupled ejector plate 5502 and generator plate 5532 can be calculated and the desired amplitude and velocity of the vibration modes determined.

In one embodiment, piezoelectric actuator 5504 is edge mounted on ejector plate 5502 where distance 5554 is zero. An edge mount design is a special case that has almost zero inherent resistance for modes that is designed to stimulate. When a circular piezoelectric actuator 5504 is bonded to the edge of the circular ejector plate 5502 (for example, the distance from 5554 is at or near zero) the ejector plate 5502 is considerably hardened where a hard piezoelectric actuator 5504 is placed, but the portion of the ejector plate 5502 on the inside diameter 5557 of the piezoelectric actuator 5504 is allowed to move freely, restricted only by its own elastic limits in place of the piezoelectric actuator 5504. Similarly, hybrid ejector plates 5502 having an attached generator plate 5532 would also be allowed to move freely, restricted only by the combined elastic limits rather than the piezoelectric actuator 5504. If the edges of the piezoelectric actuator 5504 are buckled or clamped, the ejector plate 5502 behaves as thought to be virtually as difficult as the ID 5557 diameter of the piezoelectric actuator 5504 with ideal radial and longitudinal (edge-driven) stimulation. Other modes relevant to the entire size of the

108 Ejector plate 5502 is suppressed due to the hardness of the piezoelectric actuator 5504. In certain embodiments, the hardness of the piezoelectric actuator 5504 can be modulated by increasing or decreasing the thickness of a piezoelectric actuator 5504. Modes are presented which illustrate the modulation of the piezoelectric actuator. 5504 in Example 5 below.

In other embodiments in accordance with the present disclosure, the mounting configuration of the piezoelectric actuator 5504 to the ejector plate 5502 effected the displacement and velocity of the ejector plate 5502 and the generating plate 5532. In general, the displacement amplitude and the velocity of ejector plate 5502 in a given mode is a balance between force, largely determined by movement by unit voltage (D₃₃) of the piezoelectric material, and the damping / resistance that a piezoelectric presents to the movement of the ejector plate 5502. Increasing the hardness of the piezoelectric material increases the damping and resistance. For embodiments of the present disclosure having piezoelectric materials having a D₃₃ Large, for example materials like PZT, the damping / resistance of the piezoelectric material plays a less significant role in amplitude of displacement. In other modalities with a D₃₃ lower, for example BaT¡O₃, the performance of a droplet ejector system can be significantly decreased by damping / resistance. The performance of a 5500 ejector assembly is reduced in direct proportion to D₃₃ of the material used to prepare a

109 piezoelectric activator 5504.

The properties of an edge mounted embodiment of a piezoelectric actuator 5504 / ejector plate 5502 can be used to avoid the effects of lower material movement. Specifically, when the ejector plate 5502 is stimulated in a mechanical mode where only its own resistance limits its movement due to a force given per unit area applied to the piezoelectric actuator 5504, the D₃₃Piezoelectric can scale down without any performance impact for the same electrical input until a minimum force per unit area is reached. This property is illustrated by Figure 8, where if the force per unit area is above a certain threshold, the increase in movement of ejector plate 5502 is very small. Below this threshold, ejector plate motion 5502 is linearly decreased with force per unit area.

For ejector plates 5502 of the present disclosure, low order modes are generally stimulated at the lowest frequencies in a structure where the wavelength of the foot wave is an integer multiple of an average wavelength. The frequency and wavelength are thus determined by the material properties of the ejector plates 5502 and their radial dimension. Since the vibration mode shape always has a node at the edges of the ejector plates 5502 for these modes and a maximum at the center of the membrane, only two piezoelectric locations are relevant for stimulating these modes in a

110 fluid expulsion system.

In an embodiment in accordance with the present description, a piezoelectric actuator 5504 can be placed in the center of the ejector plate 5502 in order to stimulate maximum movement. However, because there must be an area directly in the center of ejector plate 5502 for fluid ejection to take place, this mounting position is not optimal for this application. Performance must be sacrificed to allow fluid expulsion.

A similarly shaped piezoelectric actuator 5504 can be placed on the edge of ejector plate 5502 to stimulate maximum movement in the center of ejector plate 5502 at low frequencies. In this configuration, minimal resistance to the natural movement of the mode occurs, allowing large shifts at low frequencies and improved mass depositions in these modes. Generally, these modes are favorable for continuous fluid ejection due to their almost constant shape and velocity distribution over the ejection area. Also, loading the center of the ejector plate 5502 with a mass, such as a hybrid 5502 ejector plate having a 5532 generator plate attached, improves low order mode shift due to the inertia of the center mass (eg, generator plate 5532).

In some embodiments, the edge mounted piezoelectric actuator 5504 oscillates the ejector plate 5502 coupled to the generator plate 5532 at the resonant frequency of the ejector plate coupled to

one 1 said generating plate. In one embodiment, matching the resonant frequency decreases the displacement requirement of the piezoelectric material. In one embodiment, the resonant frequency equalization allows the generation of a directed stream of droplets using a piezoelectric material having a D₃₃ less than 200. In another embodiment, resonant frequency equalization allows generation of a directed droplet current using a piezoelectric material having a D₃₃ less than 150 or less than 125. Even in another embodiment, the resonant frequency equalization frequency allows the generation of a directed stream of droplets using a piezoelectric material having a D₃₃ less than 100 or less than 75.

In another embodiment, the piezoelectric actuator 5504 is slightly smaller than edge mounted (eg, interior mounted) on ejector plate 5502 where distance 5554 is greater than zero. In one embodiment, the distance 5554 can be 0.05 mm. In another embodiment, the distance 5554 can be 0.01 mm. Even in another mode, the distance 5554 can be 0.25 mm. Even in another mode, the distance 5554 can be 0.5 mm. In additional modes, the distance 5554 can be 0.75mm, or 1.0mm, or it can be greater than 1.0mm.

In other embodiments in accordance with the present disclosure, the piezoelectric actuator 5504 is mounted inside on the ejector lever 5502 where the distance 5554 is greater than 0 and the outer diameter of the piezoelectric actuator 5504 is less than the plate

112 ejector 5502. In one embodiment, the piezoelectric actuator 5504 is mounted inside on the ejector plate 5502 and is 1% smaller than the diameter of the ejector plate 5502. In one embodiment, the piezoelectric actuator 5504 is mounted inside on the plate ejector 5502 and it's

1.5% smaller than the diameter of the ejector plate 5502. In one embodiment, the piezoelectric actuator 5504 is mounted internally on the ejector plate 5502 and is 2% smaller than the diameter of the ejector plate 5502. In one embodiment, the Piezoelectric actuator 5504 is mounted inside on ejector plate 5502 and is 3% smaller than the diameter of ejector plate 5502. In one embodiment, the piezoelectric actuator 5504 is mounted on the inside of the ejector plate 5502 and is 4% smaller than the diameter of the ejector plate 5502. In one embodiment, the piezoelectric actuator 5504 is mounted on the inside of the ejector plate 5502 and it is 5% smaller than the diameter of the ejector plate 5502. In one embodiment, the piezoelectric actuator 5504 is mounted on the inside of the ejector plate 5502 and is 7.5% smaller than the diameter of the ejector plate 5502.

In some embodiments in accordance with the present disclosure, the piezoelectric actuator 5504 is mounted to the Interior on the ejector plate 5502 where the distance 5554 is greater than zero and the inner diameter of the annular piezo actuator is selected such that the edge mode of Low frequency of ejector plate 5502 is damped or removed.

113

In certain embodiments of the description, the ejector mechanism may be configured to facilitate actuation of ejector plate 5502, and thereby generator plate 5532, by the piezoelectric actuator. As described above, the 5532 generator plate can be configured to optimize ejection of a fluid of interest. For example, the aspect ratio of the generator plate openings can be selected based, in part, on fluid properties, such that the overall thickness of the 5532 generator plate varies from about 50 pm to about 200 pm, as previously described. Without being theoretically limited, in certain implementations, direct actuation of a relatively thick generator plate, while possible, may be less optimal. In some implementations, the generating plate comprises a high modulus polymeric generating plate.

As such, in certain implementations, the drive of the ejector mechanism can be optimized using configurations including a generator plate coupled to an ejector plate, as described herein. Furthermore, by reducing the surface area of ​​generating plate 5532 (i.e., the central region having one or more openings) similarly reduces manufacturing costs, reduces potential manufacturing effects, and increases manufacturing efficiencies and performance. In certain embodiments, the ejector plate can be sized and shaped to facilitate actuation of the ejector mechanism (i.e., actuation of the ejector plate and thereby the generating plate). As an example,

14 Ejector plate configurations can effect actuation of the ejector mechanism through selection of properties (eg, size, shape, material, etc.) that facilitate flexing of the ejector plate, and thereby vibration of the ejector plate. For example, the ejector plate 5532 may have a thickness generally ranging from about 10 pm to

<td>approximately</td><td> 400</td><td>pm from</td><td>approximately</td><td> 20</td><td>p.m</td><td>until</td>

<td>approximately</td><td> 100</td><td>pm from</td><td>approximately</td><td> 20</td><td>p.m</td><td>until</td>

<td>approximately</td><td> 50</td><td>pm, or from</td><td>approximately</td><td> 30</td><td>p.m</td><td>until</td>

about 50 pm etc. Again, without being theoretically limited, in certain implementations, direct actuation of a relatively thinner ejector plate 5502 (compared to the 5532 generator plate) may be more optimal. In some implementations, the 5532 generator plate comprises a high modulus polymeric generator plate.

In accordance with certain implementations of the description, the configuration of the ejector plate 5502 and the generator plate 5532 can be selected so that the central region of the generator plate 5532 that includes openings (the "active region" of the generator plate) produces a symmetrical oscillation with a normal oscillation mode. Without being theoretically limited, in certain implementations, ejector plate configurations

5502 and generator plate 5532 can be selected such that 0.2 normal mode and 0.3 normal mode of oscillation of the active region of the generator plate is observed. The mode is associated with a maximum amplitude and displacement of the active region, where the mode is designed as (d, c) where d is the number of nodal diameters and c is the number of nodal circles.

The magnitude and frequency of ejector plate vibration 5502 can also be controlled by controlling the voltage pulses applied to electrodes 5506a, 5506b, for example, a voltage differential of 40 to 60V can also be applied to the electrodes. As discussed above, pulses are created by voltage differentials that deflect ejector plate 5502, and thereby generator plate 5532. In some implementations, one of electrodes 5506a and 5506b is grounded and voltage pulses, eg, bipolar pulses, are applied to another of electrodes 5106a or 5506b, for example, to vibrate ejector plate 5502. By way of example, in one implementation, the piezoelectric actuator 5504 may have a resonant frequency, from about 5 kHz to about 1 MHz, for example, about 10 kHz to about 160 kHz, for example, about 50-120 kHz or about 50 -140 kHz, or approximately 108-130 kHz, etc. The applied voltage pulses may have a lower, higher, or the same frequency as the resonant frequency of the piezoelectric actuator 5504.

In certain implementations, the delivery time of the droplets is approximately 0.1 ms to approximately several seconds. Without wishing to be bound by theory, it is believed that human eyes take approximately 300 ms to 400 ms for a blink. Therefore, for

16 For deployments where supply is desired to be within the duration of one blink, the delivery time can be from about 50ms to about 300ms and more particularly from 25ms to 200ms. In one implementation, the delivery time is 50 ms at

100 ms. In this way, the ejected droplets can be effectively delivered and deposited in the eye during an eye blink cycle. In some implementations, for example over-the-counter saline dispensers, the delivery time may be as long as several seconds, for example 3-4 seconds, spanning multiple blink cycles.

Alternatively, an Individual dosage can be administered over several bursts or droplet expulsion pulses. Additionally, and not intended to be limited in theory, pulsation can be used to reduce the peak amplitude of the droplet air stream by dispersing the Impulse outward over time. Therefore, the pressure of the ejection on the target can be mitigated. In addition, pulsation can also reduce droplet agglomeration and result in less entrained air generation. As an example, 25 ms pulses can be delivered with 25 ms stop times by separating the pulses. In one implementation, the pulses can be repeated for a total of 150 ms.

As described herein, the ejector device and ejector mechanism of the disclosure may be configured to eject a generally low to relatively high viscosity fluid such as a droplet stream. By way of example, fluids suitable for use by the ejector device may have very low viscosities, for example, as with water at 1 cP, or less, for example, 0.3 cP. In turn, the fluid can have viscosities in ranges of up to 600 cP. More particularly, the fluid can have a viscosity range of about 0.3 to 100 cP, 0.3 to 50 cP, or

0.3 to 30 cP, 1 cP to 53 cP, etc. In some implementations, the ejector device can be used to expel a fluid that has a relatively high viscosity such as a droplet stream, for example, a fluid that has a viscosity above 1 cP, ranging from about 1 cP to about 600 cP , about 1 cP to about 200 cP, about 1 cP about 100 cP, about 10 cP to about 100 cP, etc. In some implementations, solutions or medications that have adequate viscosities and surface tensions can be used directly in the reservoir without modification. In other implementations, additional materials can be added to adjust the fluid parameter. As an example, certain fluids are listed below in Table 15:

18

TABLE 15

Viscosity measured at 20 ° C

<td>Drugs / fluids</td><td>Viscosity dynamic (cP)</td><td>Viscosity kinematics (cP)</td><td>Density</td>

<td>Water</td><td> 1.017</td><td> 1.019</td><td> 0.997821</td>

<td>Xalatan ™</td><td> 1.051</td><td> 1.043</td><td> 1.00804</td>

<td>Tropicamide</td><td> 1.058</td><td> 1.052</td><td> 1.00551</td>

<td>Subtas is ™</td><td> 18.08</td><td> 17.98</td><td> 1.00535</td>

From the previous discussion it will be appreciated that different configurations and material will result in different attributes. In order to understand some of these attributes in selected modalities of the ejector mechanism, experiments are known to purchase certain modalities. The experiments herein described of course should not be construed as specifically limiting the invention and such variations of the invention, now known or later developed, which would be within the purview of one skilled in the art, are considered to fall within the scope of the Invention as described herein and as claimed hereinafter.

EXAMPLE 6

Mass Deposition Measurement

To measure the mass deposition of an ejector device, the

119 Ejector device is held horizontally to eject materials towards the ground where the driven direction Z, as shown in Figure 56, is towards the ground (eg parallel to gravity). Referring to Figure 55A, the direction 5514 of the ejected droplets 5502 is toward the earth. A ground wire and positive wire from the device are connected to an operational amplifier, and a current probe and voltage zone are connected to an oscilloscope.

The frequency ruler that allows device spraying is initially determined by a frequency sweep across the range of 2 kHz to 500 kHz. Electrical data, including voltage and current, is recorded and stored. With analysis, the spray ranges are selected for determination of mass deposition. The results are plotted to provide a mass ejection profile as shown in Figure 58, for example.

To determine the mass deposition, a frequency and voltage are set, for example, at a peak to peak sine wave of 90V (90Vpp) at a frequency of 50 kilohertz (kHz) and the spray is from the ejector device is measured five Times on a 24mm x 60mm No. 1 glass coverslip using a scale with a sensitivity of 1mg (mg) and calibrated to a Class 1 weight of 1mg with a traceable certificate. For each measurement, the coverslip is placed on the scale and the scale is zeroed. The slide is placed under the ejector device and the voltage applied for a defined period of time. The slide is returned to the

120 scales and the mass is determined and recorded. The coverslip is cleaned, the scale is zeroed before each measurement. A total of five measurements are recorded for each frequency. The process is repeated with the frequency increasingly changed based on a predetermined step size (typically 1 kHz).

EXAMPLE 7

Comparison of PZT to BaTiO₃ using internally mounted ejector assemblies

The mass deposition profile of ejector devices having an interior mounted ejector assembly is determined using the method described in Experiment 6 above to determine the frequency region for device spray. For both piezoelectric materials PZT and BaTiO3, the piezoelectric actuator 5504 has an outer diameter of 16mm by an inner diameter of 8mm, with a height of 550um, mounted to a circular ejector plate 5502 of diameter 20mm thick 50 um. In this modality, several examples of PZT are compared directly to BaTiO₃ with PZT that expels more fluid than

BaT¡O₃ approximately in the ratio of the d33 coefficients of the materials. The only significant ejection mode is shown in Figure

59.

Where the distance 5554 is greater than 0 (here, 2 mm), the

121 PZT material provides a wider range of effective frequencies when compared to BaTiO3. The maximum mass ejection of the PZT based ejector is more than double the BaTiO ejector output₃. Although less efficient, BaT¡0₃ Provides maximum mass expulsion between 115 and 102 kHz of approximately 6 mg.

7a: Comparison of PZT and BaTiOgjj using edge mounted ejector assemblies

Using the method of Experiment 6, mass ejection at different frequencies is determined using a frequency step size of 1 kHz, starting at 10 kHz to 500 kHz. The deposited mass in milligrams is plotted against frequency and is shown in Figure 58 for PZT and BaTiO piezoelectric actuators₃ edge mounted having an outside diameter of 20mm by 14mm piezoelectric inside diameter 550um height on a 20mm thick 5502 circular ejector plate 50um. In this case, several PZT samples are directly compared to BaTiO₃ with expulsion of PZT and BaT¡O₃ almost equivalently (adjusted for sample variation) even with very different material coefficients of 33. As is also evident from Figure 58, many modes are stimulated with equivalent performance between materials.

When PZT and BaTiO piezoelectric actuators₃ are edge-mounted (i.e. distance 5554 is at or near zero), occurs

122 expulsion of mass at discrete ranges of frequencies corresponding to the resonance coupling between the piezoelectric actuator and the ejector plate 5502 coupled and generating plate. Although the PZT based device has a D₃₃ = 330 pC / N and BaTIO₃ has a D₃₃ = 160 pC / N, the expulsion and efficiency profiles are very similar. The center-symmetrical design and edge mounting of the piezoelectric actuator overcomes differences in displacement by allowing a wide variety of piezoelectric materials to be incorporated into the ejector device.

7b: Effect of decreasing piezoelectric actuator diameter

5504 in relation to ejector plate 5502

As the piezoelectric actuator 5504 is displaced from the edge of the ejector plate 5502 (for example, the distance 5554 increased from zero), performance is lost as the ejection modes are increasingly damped by the piezoelectric hardness. In one embodiment the piezoelectric was 20mm outside diameter by 14mm inside diameter with an optimized thickness of 250um and an ejector plate diameter of 20mm. Expulsion was shown that exceeds all other cases by 20 to 33%. In another embodiment the outer diameter of the piezoelectric was altered to 19mm and the ejector plate diameter changed to 21mm with an optimized thickness of 200um. Ejection frequencies are usually the same, but opposite the edge-mounted case, ejection is reduced through each mode even when optimizing the

123 piezoelectric thickness, (thicknesses from 150 um to 550 um were used in the laboratory in increments of 25 um). In the third embodiment, the piezoelectric remained at 19 mm outside diameter and 14 mm inside diameter, but the ejector plate changed to 23 um. Again, the thickness was optimized to 175 um to reduce hardness for all modes they were highly suppressed and performance degraded by more than 80%.

EXAMPLE 8

Comparison of BaTiO piezoelectric materials₃

BaTiO materials were distinguished₃ that have different properties using Scanning Electron Microscopy (SEM). SEM images of two BaTiO materials were obtained₃ illustrative and showed a uniform particle size of approximately 2 to 5 microns in diameter in the first sample and a structure fused with particles of tens of microns in diameter in the second example. Although both examples had D values₃₃ Similarly, the smaller grain size improves performance by lowering the resonant frequencies.

EXAMPLE 9

Vibration Modes Modulation

For a circular ejector plate 5502 stimulated by a

24 Piezoelectric Actuator 5504, increasing the hardness of the Piezoelectric Actuator 5504 resulted in its pressure of high frequency vibration modes. To test the effects of increasing the hardness of the piezoelectric actuator 5504, a first piezoelectric actuator 5504 of thickness

twenty um having an outer diameter of 20mm and an inner diameter of 14 (20mm x 14mm) and a second piezoelectric actuator 5504 of thickness 400um (20mm x 14mm) were bonded to a ejector plate 5502 with a diameter 20mm exterior (for example, edge mounted). The normalized displacement of the two ejector mechanisms were [molded or measured] at a frequency range from 1 Hz to 3 x 10⁵ Hz. The increased flexibility of the slimmer 5504 piezoelectric actuator enables complex high-frequency vibration modes. In contrast, the thicker, stiffer 5504 piezoelectric actuator limits vibration modes to low-frequency modes limited to ejector plate region 5502 within the inside diameter of piezoelectric actuator 5504 (eg, within 14mm).

It will be understood that the ejector assembly described herein can be incorporated into an ejector device and system. Illustrative ejector devices and systems are illustrated in 3 / 712,784, filed December 12, 2012, titled "Ejector Mechanisms, Devices, and Methods of Use", filed December 12, 2012, and titled "High Modulus Polymeric Ejector Mechanism , Ejector Device, and Methods of Use ”and 13 / 184,484, filed on July 15, 2011, entitled“ Droplet Generator Device ”, whose

125 Contacts are incorporated here by reference in their totalities.

When fluid is exposed to an air interface, it will evaporate into the air, causing a loss of fluid volume over time. If the fluid has any of the elements and minerals left behind, the mix contents change over time resulting in crystallization at the air-fluid interface. However, if a small volume of air is sealed around the fluid-air interface, the evaporation rate and crystallization rate drop to the seal filtration rate, thereby reducing or eliminating evaporation and crystallization. Contamination is also possible any time a device is opened to the environment.

Partly to address these problems, the present disclosure provides a self-closing system for use with a droplet ejection device, which prevents the device from opening to the environment for longer than the actual droplet ejection period, which greatly reduces the risk of contamination. In certain embodiments, the self-closing system is dimensionally compact along the fluid ejection path, uses a minimum of components, and provides a consistent seal in the presence of component dimensional variance. The system allows a closed, sealed position and an open, active position used for fluid expulsion. The switch between closed and open positions can be configured for manual actuation by a user, or can be configured for energized actuation. In certain modalities, the system can

126 provide a manual configuration with low actuation force. In addition, movement between sealed and open positions can be configured for linear actuation or rotary actuation. For example, certain modalities provide a linear actuation configuration used in conjunction with a user-activated, flip-action button.

Figures 60 to 65 show an embodiment of a self-closing system of the description. Figure 60 shows a compact, linearly driven embodiment of a self-closing system of the disclosure, and Figure 61 shows an exploded assembly view of the main components of this embodiment.

As shown in Figures 60 and 61, a sliding element

6000 with an opening 6002 it is retained between the expulsion system 6004 to be sealed and a retaining plate 6006. The expulsion system is shown schematically without reference to internal features. The face of the ejection system has a 6010 round opening surrounded by a round, elastomeric face seal 6012. The face seal resides in a sleeve or groove 6014 on the ejector face. In one embodiment, the sliding element is pressed against the face seal by flexes 6020 integrated into the sliding element. The flexures could alternatively be located on the retaining plate or can be incorporated as a separate component. In one position of the sliding element (the open position) the sliding opening 6002 is aligned with the ejector opening 6010 for fluid supply. In the closed position the sliding element opening

127

6002 and ejection system opening 6010 are not fully aligned and the ejection system is sealed. A hinged activation button 6030 (Figure 30) rotates around a fulcrum 6031 connected to a housing (not shown). The button 6030 is finger operated by the user and operates the slider in the downward direction to open the seal. With removal of user finger pressure, a compression spring 6032 returns slide member 6000 to the closed and sealed position.

Figure 62 shows a schematic cross-sectional view of the self-closing system and demonstrates the basic sealing principle. An axial force, F, presses the sliding element against the elastomeric face seal located within the sleeve on the face of the ejection system. The face seal surface protrudes from the ejection system surface by approximately 20% of the seal cross section. The maximum anticipated internal pressure in the ejection system is counteracted by the axial pressure force, F, so that the pressure force extends the internal pressure force given by the product of the internal pressure P and the seal area A. For this modality, the axial force was chosen to be approximately 2X the anticipated internal pressure force. In the preferred embodiment, the axial pressing force is provided by compact bends 6020 as shown in Figures 63 and 64. Bends 6020 provide a consistent force on the seal that is not sensitive to manufacturing variance in component dimensions. . Having the flexes integrated into the sliding element provides a height of

128 minimal stacking from the ejection system to the opening of the retaining plate, allowing the face of the ejection system to be closer to the final supply point. To minimize actuation force the face seal 6012 is formed from a pre-lubricated silicone. To prevent abrasion, sliding element 6000 is always in contact with the seal. No element edge of distant element 6000 moves off and back on element 6012; only the sliding opening edges pass through the face seal. To further prevent abrasion and reduce actuation force, sliding opening edge 6040 is rounded and the top edges of the face seal are surrounded. To keep the sliding element parallel to the face seal, small sliding protrusions 6042 are provided on the sliding element as shown in Figures 63 and 64.

The sliding element in the preferred embodiment is injection molded from an antimicrobial thermoplastic. However, the description is not limited in that way, and any suitable material may be used. As discussed, the 6020 sliding 6000 flexes provide the pre-load force on the face seal. The bending geometry is chosen to provide the desired axial force without overstressing the thermoplastic. In particular, the maximum flexural stress when fully deflected is chosen to be below the long-term yield limit of the chosen thermoplastic. This ensures that the desired face seal preload is achieved long-term, after the device has been assembled,

129 no relaxation of tension in the lessons. For compactness, the device's self-closing compression spring 6032 is located in a groove

6044 within the boundaries of the sliding element 6000. As mentioned above, two sliding protuberances 6042 are located on the sliding element 6000 to keep the sliding element 6000 parallel to the face seal, as the exposed face seal surface protrudes on the guide surface on the ejection system that restricts the rear side of the sliding element 6000.

As previously described, the axial force on the face seal is chosen to access the anticipated internal pressure force by some margin of safety. In the event that the required axial force exceeds the force that can be provided by small plastic bends, an alternative method is used for the use of a separate spring component, which could be formed of steel. Long-term influx problems are not present with a steel sheet spring and the force exerted can be increased to provide significant advantages, but with an increase in cost and space required due to the separate part. One method of addressing this problem is to use compression spring 6032 for a secondary purpose as well. The primary purpose of the compression spring would be to provide the self-closing feature of the device. When user pressure is removed from the trigger button, the compression spring returns the device to the closed and passively sealed position without user interaction. To maintain a device

130 Fully closed, the geometry of the device is set such that the compression spring is in a preloaded state when the sliding element is in its fully closed position. This preload can be used for the secondary purpose of increasing axial force on the face seal as a feature employed in the present embodiment.

As shown in Figure 66, the closed position of the trigger button 6030 interacts with the sliding element on a sloped, void surface 6050. This angle results in a horizontal outward force component acting on top of slide member 6000. A small fulcrum feature (not shown) is integrated within the top of the retention plate. The fulcrum is a small raised portion that interacts with the front face of the sliding element. In the presence of the horizontal force vector, the sliding element 6000 rotates around the fulcrum causing the bottom of the sliding element 6000 to rotate toward the face seal thereby increasing axial force on the face seal. This increases the integrity of the seal without the addition of added parts or increased space requirement. In addition, the axial force on the face seal is no longer solely flexurally dependent, allowing for a wider choice of thermoplastics with lower modulus (hardness) values.

Figures 65 to 68 show a complete schematic representation of an embodiment in both closed (left) positions (Figures

131 and 66) and open (right) (Figures 67 to 68), with implementation of all the characteristics described above. In certain embodiments, the self-closing system includes umbrella valves or other suitable pressure relief means used in connection with the retaining plate (also referred to herein as a compression plate) in order to address vapor pressure build-up . By way of non-limiting example, alternative pressure release systems may include: duckbill valves; two-way umbrella / duckbill valves; other suitable pressure relief valves; perforation valve in a silicone sheet;

recess valve in silicone sheet; individual perforation / vent hole of a rigid material (eg 50 micron diameter hole in 50 micron stainless steel); an arrangement of ventilation holes; or any other suitable pressure release means that can restore pressure balance fast enough, while also preventing excessive evaporation due to vapor pressure. Aspects of umbrella valves or pressure release means are discussed here in further detail.

EXAMPLE 10

Crystallization, Evaporation, and Sealing Measurement

Crystallization occurs, especially in small holes where the evaporation rate is high, at speeds that can be

132 prohibitive for operation of a droplet ejector device. If crystallization occurs, it prevents droplet ejection out of the ejector openings by blocking flow.

Pursuant to an embodiment for a generator plate 5 with 20 um wide and 50 micron deep holes without any puncture / capillary plate and openly exposed to the environment, Figures 69A to 69C show crystal growth over time for solution saline isotonic. In Figure 69A, the ejector openings are shown in zero time (the fluid has just been inserted into a hard reservoir that is sealed to the ejector mesh (defining multiple ejector openings) and shows no crystallization. A stack compression plate is sealedly attached to the screen mesh by means of a tonco ring and the opposite surface of the screen mesh is attached through an O-ring to a reservoir, the assembly is held together with screws and nuts. At 50 seconds after the Fluid is inserted, shown in Figure 69B, noticeable crystallization begins to form in the ejector nozzles (holes). Within 3 minutes, shown in Figure 69C, a number of ejector openings or holes are completely clogged and several ejector nozzles (holes) exhibit crystal growth. The images were acquired by transmission light microscopy, where crystals obstruct light transmitted through openings.

In order to demonstrate the effect of a fluid loading plate, a system was similarly configured, consisting of a mesh screen of

133 a generator plate with holes 20 um wide and 50 microns deep, but in this case a capillary plate was added and it was openly exposed to the environment. Figures 70A to 70C show crystal growth over time for isotonic saline. In Figure 70A, the ejector openings are shown in zero time (noise has just been inserted into a hard reservoir that is sealed to the ejector mesh through the following: a stack compression plate, O-ring, mesh sieve, O-ring, puncture / capillary plate, O-ring, reservoir held together with screws and nuts) and no crystallization has occurred. At 5 minutes, shown in Figure 70B, no crystallization has yet formed. Within 6 hours, shown in Figure 70C, a number of ejector openings are completely clogged and several ejector openings exhibit crystal growth. Although the puncture / capillary plate cannot reduce evaporation, it reduces crystallization. The decrease in crystallization rate is obtained by supplying a constant fluid supply, and by preventing mineral deposits not immersed in fluid.

Evaporation in certain applications can lead to changes in drug strength and potency, for example, through loss of water and resulting changes in concentration. Evaporation can lead to crystallization in ejector openings. Table 16 shows evaporation rates of the self-closing system of the present description versus evaporation rates with two types of umbrella valves with different cracking pressures provided on the loading plate of

134 fluid. Evaporation rates shown are those exhibited without valve cracking due to pressure fluctuation for isotonic saline using one type of valve, and isotonic saline using a different valve. Both valves showed very high evaporation rates. In contrast, the self-closing systems of the present disclosure resulted in a decrease in evaporation rate by a factor of 7-10, depending on the test fluid. This also resulted in a crystallization time extension by a factor of 7 -10 between sprays compared to the puncture / capillary plate and umbrella valves alone.

TABLE 16

Evaporation rates of umbrella valve against perfect face seal using self-closing system

<td>Fluid</td><td>Umbrella valve</td><td>Mass lost in 1 day (mg)</td><td>Expected Mass Lost in 30 days (mg)</td><td>% of fluid expected, lost from 2.0 ml vial in 30 days</td>

<td>Isotonic saline solution</td><td rowspan="3">5.3 mm (0.61.3 kilopascals (0.1-0.2 psi) vent pressure)</td><td> 23.6</td><td> 707</td><td> 35%</td>

<td>Isotonic saline solution</td><td> 18.0</td><td> 539</td><td> 27%</td>

<td>Isotonic saline solution</td><td> 20.4</td><td> 613</td><td> 31%</td>

<td>Latanoprost</td><td rowspan="3">5.8 mm (ventilation pressure of 1.32.06 kilopascals (0.2-0.3 psi))</td><td> 3.5</td><td> 104</td><td> 5%</td>

<td>Latanoprost</td><td> 8.6</td><td> 258</td><td> 13%</td>

<td>Isotonic saline solution</td><td> 11.7</td><td> 351</td><td> 18%</td>

<td>Latanoprost</td><td rowspan="3">Perfect stamp</td><td> 7.5</td><td> 224</td><td> 11%</td>

<td>Isotonic Saline Solution</td><td> 2.4</td><td> 72</td><td> 4%</td>

<td>Latanoprost</td><td> 2.6</td><td> 79</td><td> 4%</td>

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In certain aspects of the description, self-closing systems are used in order to prevent large pressure excursions that force fluid out of the ejector system. Valves equalize pressure almost instantaneously without the presence of cracking pressure.

Alternatives to umbrella valves are within the scope of the present description. In this regard, any suitable way to equalize pressure while preventing evaporation can be used, for example, a 50 um and 100 um vent port solution with a bacteria resistant membrane filter already fluidized with the vent port . This solution also equals pressure almost instantaneously, 68.9 kilo pascals (10 psi) /0.25cc per second of air, but also reduces evaporation rates 10-20 times below those of umbrella valves, as shown in Table 17. Filtration rates for pressure equalization (not evaporation) are also shown in Table 17.

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TABLE 17

Evaporation and filtration rates for pressure equalization of filtered vents

<td>Condition</td><td>Average mass loss per day (mg)</td><td>Standard deviation (mg)</td><td>Number of samples</td>

<td>50um hole</td><td> 1.3</td><td> 0.3</td><td> 4</td>

<td>50 um hole and 1.2 um membrane</td><td> 0.9</td><td> 0.2</td><td> 3</td>

<td colspan="4">Orifice filtration rates 50um in SS316 steel, 50um thick (sample size: N = 10 for each condition)</td>

<td>Condition</td><td>Average filtration speed (cm^TO3 / s)</td><td>Corrected Filtration Rate (cm^TO3 / s)</td><td>Standard deviation (cm^TO3 / s)</td>

<td>No 50um hole (SS316 plate)</td><td> 0.035</td><td> 0</td><td> 0.004</td>

<td>50um hole</td><td> 0.431</td><td> 0.40</td><td> 0.08</td>

<td>50um hole and 1.0um membrane (PTFE on non-woven polyester LHOP backing)</td><td> 0.428</td><td> 0.39</td><td> 0.06</td>

<td>50um hole and 1.2um membrane (acrylic copolymer on non-woven nylon backing</td><td> 0.473</td><td> 0.44</td><td> 0.13</td>

The self-closing system provides an air and pressure barrier necessary to prevent evaporation of fluid that could lead to crystallization in the ejector openings. The purpose of this experiment was to determine the normal force required to produce a self-sealing system seal capable of sealing at 6.8 kilo pascals (1.00 PSI).

By using the gravitational force of a plastic sealing element with the silicone face seal ring to determine face seal quality as a function of normal force. An ABS / Polycarbonate plastic seal element was attached to the bottom of a laboratory beaker so that water for variable mass could be added. The self-lubricating silicone seal was housed inside the compression plate, with a regulator

137 pressure and pressure gauge attached to the inside of the compression plate. The variable mass sealing element was balanced with the silicone seal, and fluid was added to the laboratory beaker. Pressure data was recorded as a function of normal face seal force.

As the gauge pressure approached 6.8 kilo paséales (1.00 PSI), the self-closing system seal mass increased. Normal forces of 40 g and greater were typically sealed at 6.20 kilo paseales (0.20 PSI) or more. This was identified as an acceptable seal in that it is significantly higher than the umbrella valve ventilation pressure of 1.3 kilo pascals (0.2 PSI).

Another identified condition was that the friction force of the closing slide with the self-closing system must be less than the restoring force of the self-closing spring. This condition was met by choosing a spring with sufficient spring constant and displacement.

To measure the seal quality provided by the internal self-closing system on a sequence of multiple sliding drives. A self-closing system in accordance with the description was attached to an air pressure regulator and pressure gauge. The regulator was set at 6.8 kilo pascals (1.00 PSI) with a perfect seal, and then the perfect seal was removed. In self-closing it was actuated to provide a seal, and the gauge pressure within the seal increased until it reached maximum pressure. The maximum equilibrium pressure is recorded as the seal pressure for that test.

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The maximum equilibrium pressure was recorded for 20 tests, after which the self-closing system was operated 100 times. This process was repeated three more times, resulting in four data sets of 20 tests, with 100 drives between each data set. This was designed to test the self-closing system repeatability system on a total of 380 slip drives. The average seal pressure for each data set is shown in Table 18.

TABLE 18

Self-closing face seal test on 380 drives

<td>Data Set # (N = 20 drives)</td><td>Average Seal Pressure (Kilo Pascals) (PSI)</td>

<td> 1</td><td> 6.481 ± 0.041 (0.940 ± 0.006)</td>

<td> 2</td><td> 6.460 + 0.048 (0.937 ± 0.007)</td>

<td> 3</td><td> 6.439 ± 0.034 (0.934 ± 0.005)</td>

<td> 4</td><td> 0.453 ± 0.034 (0.936 ± 0.005)</td>

<td colspan="2">Note: Maximum seal pressure is 6.8 kilo pascals (1.00 PSI) due to regulator</td>

A 6.8 kilo paséales (1.00 PSI) seal was identified as an acceptable face seal because it provides a safe margin on umbrella valve ventilation of 2.06 kilo paséales (0.2 PSI). The data from this test was consistent within 6-7% of this target sealing pressure over 380 total actuations.

In many implementations of the inventions described in the present application and the previous applications that are incorporated by reference

139 have been described. This description contemplates combining any of the characteristics of an implementation or modality with the characteristics of one or more of the other implementations or modalities. For example, any of the ejector mechanisms or reservoirs can be used in combination with any of the described housings or housing features, for example, covers, supports, supports, lights, seals and gaskets, filling mechanisms, or alignment mechanisms.

Additional variations on any of the elements of any of the inventions within the scope of basic skill are contemplated by this description. Such variations include selection of materials, coatings, or manufacturing methods. Any of the electrical and electronic technology can be used with any of the implementations without limitation. Furthermore, any network, remote access, subject monitoring, electronic health, data storage, data extraction, or Internet functionality is applicable to any and all implementations and can be practiced with this. Furthermore, additional diagnostic functions such as test performance or physiological parameter measurements can be incorporated into the functionality of any of the implementations. Glaucoma performance or other eye tests can be performed by the devices as part of their diagnostic functionality. Other manufacturing methods known in the art and not explicitly listed here can be used to manufacture, test, repair, or maintain the device. In addition, the device can include mechanisms of

140 more sophisticated imaging or alignment. For example, the device or base can be equipped, or attached to a retina scanner or disc to create a unique identification to attach a device to a user, and to delineate between eyes. Alternatively, the base device can be attached to or include images from sophisticated imaging devices for any suitable type of photography or radiology.

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