Using spray devices to administer products in the form of mists or sprays is an area with large potential for safe, easy-to-use products. An important area where spray devices are needed is in delivery of eye medications. However, a major challenge in providing such a device is to provide consistent and accurate delivery of suitable doses. In addition, a multi-dose spray device may become exposed to possible contamination as a result of interaction with a non-sterile outside environment.
Accordingly, there is a need for a delivery device that delivers safe, suitable, and repeatable dosages to a subject for ophthalmic, topical, oral, nasal, or pulmonary use.
The present disclosure relates, in part, to an ejector mechanism, ejector device and method of delivering safe, suitable, and repeatable dosages to a subject for ophthalmic, topical, oral, nasal, or pulmonary use. The present disclosure relates to an ejector device and fluid delivery system capable of delivering a defined volume of the fluid in the form of a directed stream of droplets having properties that afford adequate and repeatable high percentage deposition of droplets upon application.
According to the disclosure, a piezoelectric ejector device is provided which is designed to minimize the intake of air into the device upon actuation, as explained in further detail herein. The ejector mechanism may include a generator plate and a piezoelectric actuator operable to directly or indirectly oscillate the generator plate, at a frequency to generate a directed stream of droplets of fluid. The generator plate includes a fluid facing surface, a droplet ejection surface, and a plurality of openings formed through its thickness between the surfaces. According to the disclosure, the generator plate and its plurality of openings are configured so as to minimize airflow through the plurality of openings from the droplet ejection surface to the fluid facing surface during oscillation by promoting laminar flow of liquid as it passes from the fluid facing surface to the droplet ejection surface.
The present disclosure generally relates to piezoelectric ejector devices useful, e.g., in the delivery of fluids, such as ophthalmic fluids to the eye. The ejector device may include an ejector assembly including an ejector mechanism and a fluid supply. In certain aspects, the ejector mechanism may comprise a piezoelectric actuator and a droplet generator plate, which are operable to generate a directed stream of droplets of fluid when the actuator is actuated to directly or indirectly oscillate the generator plate. Fluid includes without limitation, suspensions or emulsions which have viscosities in a range capable of droplet formation using an ejector mechanism.
Piezoelectric droplet generation and flow in micro-channels depends on a complex interaction between liquid flow through micro-orifices, fluid-surface interactions, exit orifice diameter, entrant cavity geometry, capillary tube length, ejector material mechanical properties, amplitude and phase of the mechanical displacement, and frequency of displacement of ejector plate. Moreover, fluid properties such as viscosity, density and surface energy play major roles in droplet formation. In accordance with certain aspects of the disclosure, novel ejector hole structures and geometries that optimize droplet generation dynamics and microfluidic flow have been developed. For example, certain embodiments related to computer controlled laser micromachining that provides accurate control of the three-dimensional topography of the ejector surface and nozzle geometry. This provides independent control over fluid velocity amplification, resistance, turbulence and valving of high viscosity fluids.
According to the present disclosure, a piezoelectric ejector device is provided which is designed to minimize the intake of air into the device upon actuation, as explained in further detail herein. As discussed above, the ejector mechanism includes a generator plate and a piezoelectric actuator operable to directly or indirectly oscillate the generator plate, at a frequency to generate a directed stream of droplets of fluid. The generator plate includes a fluid facing surface, a droplet ejection surface, and a plurality of openings formed through its thickness between the surfaces. As described in the various embodiments disclosed in the present disclosure, the generator plate and its plurality of openings are configured so as to minimize airflow through the plurality of openings from the droplet ejection surface to the fluid facing surface during generation of the directed stream of droplets. As explained herein, minimizing of airflow results, in part, in laminar flow of the directed stream of droplets. By way of background, but without intending to be limited by theory, intake of air into the ejector device during operation can result in unpredictable behavior within the device that may not only alter the operation of the device but in many cases may result in failure. Again, without being limiting, the vibrating pump-like action of the ejection area of the ejector mechanism of the disclosure creates pressure gradients that are both in the direction of droplet ejection as well as in the opposite direction of ejection. When the pressure gradient is aligned opposite to the direction of ejection, air within the surrounding region has an opportunity to move into the lower pressure area behind the active area by passing though the ejector openings.
However, the intake of air through the ejector openings may be prevented by the presence of fluid behind the ejector openings, thereby blocking the air from entering the system. In certain instances, air may enter the system through paths formed from gaps created during processes that interfere with proper symmetric fill conditions. These processes create chaotic turbulent regions between the liquid and air, which allow overpressures to occur that encapsulate the air that has moved into the openings to create bubbles.
One way in which air can enter the system by overcoming the resistance of generator plate openings is by fluid turbulence on the fluid side of the ejector mechanism created from an abrupt transition in fluid flow, for example, as fluid enters the fluid reservoir side of the generator plate. Rapidly moving fluid experiences a sudden change in flow due to a large and sudden change in slope at a transition point. With reference to
With reference to
The present disclosure generally relates to ejector devices useful, e.g., in the delivery of fluid for ophthalmic, topical, oral, nasal, or pulmonary use, more particularly, for use in the delivery of ophthalmic fluid to the eye. In one embodiment, the ejector device includes an ejector assembly including an ejector mechanism which generates a controllable stream of droplets of fluid. The ejector mechanism may be a charge isolated mechanism. Fluid includes, without limitation, suspensions or emulsions which have viscosities in a range capable of droplet formation using an ejector mechanism. Fluids may include pharmaceutical and medicament products.
As explained in further detail herein, the ejector mechanism may form a directed stream of droplets, which may be directed toward a target. The droplets may be formed in a distribution of sizes, each distribution having an average droplet size. The average droplet size may be in the range of about 15 microns to over 400 microns, greater than 20 microns to about 400 microns, about 20 microns to about 80 microns, about 25 microns to about 75 microns, about 30 microns to about 60 microns, about 35 microns to about 55 microns, about 20 microns to about 200 microns, about 100 microns to about 200 microns, etc. However, the average droplet size may be as large as 2500 microns, depending on the intended application. Further, the droplets may have an average initial velocity of about 0.5 m/s to about 100 m/s, e.g., about 0.5 m/s to about 20, e.g., 0.5 to 10 m/s, about 1 m/s to about 5 m/s, about 1 m/s to about 4 m/s, about 2 m/s, etc. As used herein, the ejecting size and the initial velocity are the size and initial velocity of the droplets when the droplets leave the ejector plate. The stream of droplets directed at a target will result in deposition of a percentage of the mass of the droplets including their composition onto the target.
As described herein, the ejector device and ejector mechanism of the disclosure may be configured to eject a fluid of generally low to relatively high viscosity as a stream of droplets. By way of example, fluids suitable for use by the ejector device can have very low viscosities, e.g., as with water at 1 cP, or less, e.g. 0.3 cP. The fluid may additionally have viscosities in ranges up to 600 cP. More particularly, the fluid may have a viscosity range of about 0.3 to 100 cP, 0.3 to 50 cP, 0.3 to 30 cP, 1 cP to 53 cP, etc. In some implementations, the ejection device may be used to eject a fluid having a relatively high viscosity as a stream of droplets, e.g., a fluid having a viscosity above 1 cP, ranging from about 1 cP to about 600 cP, about 1 cP to about 200 cP, about 1 cP to about 100 cP, about 10 cP to about 100 cP, etc. In some implementations, solutions or medications having a suitable viscosity and surface tensions can be directly used in the reservoir without modification. In other implementations, additional materials may be added to adjust the fluid parameter.
Droplets may be formed by an ejector mechanism from fluid contained in a reservoir coupled to the charge isolated ejector mechanism. The charge isolated ejector mechanism and reservoir may be disposable or reusable, and the components may be packaged in a housing of an ejector device, such as those described in U.S. Provisional Application Nos. 61/569,739, 61/636,559, 61/636,565, 61/636,568, 61/642,838, 61/642,867, 61/643,150 and 61/584,060, and in U.S. patent application Ser. Nos. 13/184,446, 13/184,468 and 13/184,484, the contents of which are incorporated herein by reference. More particularly, exemplary ejector devices and ejector mechanism are illustrated in U.S. Application No. 61/569,739, filed Dec. 12, 2011. entitled “Ejector Mechanism, Ejector Device, and Methods of Use,” U.S. Application No. 61/636,565, filed Apr. 20, 2012, entitled “Centro-Symmetric Lead Free Ejector Mechanism, Ejector Device, and Methods of Use” and U.S. Application No. 61/591,786, filed Jan. 27, 2012, entitled “High Modulus Polymeric Ejector Mechanism, Ejector Device, And Methods Of Use,” each of which are herein incorporated by reference in their entirety.
In accordance with certain embodiments of the disclosure, the openings of a generator plate of the disclosure are configured to have a shape with a gradual slope of change from the fluid facing surface to the droplet ejection surface. By way of background, without intending to be limited by theory, for fluid traveling in one dimension, the optimal function is linear (e.g., a pipe) and turbulence in the system is related to the Reynolds number, which is a function of the velocity, pipe diameter, density of fluid, and the viscosity of the fluid. The Reynolds number is a ratio of between inertial and viscous forces and is thus a dimensionless quantity. The flow is generally considered to be laminar when the Reynolds number is less than 2300 and is considered turbulent for values above 4000. In the region between 2300 and 4000 the flow is considered to be “transitional” which means that both laminar and turbulent flows are possible.
Where Re is the Reynolds number,
ρ is the density of the fluid,
v is the velocity of the fluid,
L is the pipe diameter, and
η is the viscosity of the liquid.
To minimize the presence of turbulent regions formed from quick transitions (steps) in the shape of an opening, the curvature may be a function with a small second derivative. In accordance with one aspect of the disclosure, the second order curve which provides a minimum value for the second derivative is the shape of a circle whose function is shown below. In this regard, such curvatures comprise a shape having an external entry radius of curvature having a circular shape from the fluid facing surface to the droplet ejection surface.
Where R is the external radius of the curve.
With reference to
Thus, laminar flow openings in accordance with the present disclosure may be configured with gradually changing circular curvature, which encourages laminar flow by minimizing voracity and eliminating the presence of vortices. With reference to
In accordance with one aspect of the disclosure, the ratio σ (ratio of size of the radius of curvature to the size of the opening at the droplet ejection surface) defines the proper conditions for constructing laminar ejectors. In one embodiment, when the opening at the droplet ejection surface is greater than about 40 μm a σ was chosen to be equal to or greater than about 2.5. In another embodiment, the ratio σ of size of the radius of curvature to the size of the opening at the droplet ejection surface was chosen to be greater than about 5, when the opening at the droplet ejection surface was less than about 40 μm. It should be noted that the height or thickness of the mesh (defined by the generator plate) is not necessarily limited to the dimensions illustrated in
According to another aspect, generator plate openings are configured so as to have an entrance length or generator plate thickness which facilitates the creation of a laminar flow region. By way of background, but without intending to be limited by theory, fluid entering a pipe (i.e., in the context of the present disclosure, fluid entering the opening of a generator plate) undergoes a period (length) in which laminar flow is not possible due to the initial boundary conditions between the fluid and the surface of the pipe/opening. This is illustrated in
The results are shown in Table 1 below:
As was discussed above, the Reynolds number is a ratio between inertial and viscous forces and flow is generally considered to be laminar when the Reynolds number is less than 2300 and is considered turbulent for values above 4000. In the region between 2300 and 4000 the flow is considered to be “transitional” which means that both laminar and turbulent flows are possible. However, as is demonstrated by the results in Table 1 and as shown in
In the embodiment of
The benefits from screening the system from additional air intake include continued operation of the device without failure occurring from excess air in the system, which causes unpredictable changes of pressure within the system. The excess air can also contaminate the fluid within the system, which is undesirable when delivering pharmaceutical compositions, particularly low preservative and preservative free pharmaceutical compositions.
In additional aspects, in order to avoid build-up of liquid on the ejection surface of the droplet generator plate, the ejection surface may also be configured to define trenches around at least a portion of one or more ejector hole(s) as shown in
To further counteract the effects of fluid beading on the ejection surface and the build-up of fluid, certain aspects further relate to the use of coatings on the surface of the ejector plate, e.g., gold coatings, silver coating, antimicrobial coatings, etc. In certain embodiments, coatings, e.g., gold coatings may be deposited on a generator plate, e.g., a PEEK generator plate to modify the surface (higher surface energy to increase he hydrophilicity) so that fluids flow more easily, to reduce fluid beading on the surface, etc.
In yet other aspects, the thickness of the droplet generator plate may also affect laminar flow parameters, with better laminar flow being obtained from thicker plates with longer capillary tube length, while also affecting the oscillation of the plate, with thinner plates displaying better fluid ejection at higher frequencies. One embodiment was found to work well with a capillary tube length of 125 μm. The capillary tube or channel 1500 in relation to the flute intake 1502 for laminar flow is shown in
The ejector assembly, which may include an ejector plate coupled to a droplet generator plate and a piezo actuator.
In some applications, ophthalmic fluid may be ejected toward an eye 1616, for example in a human adult or child, or an animal. The fluid may contain a pharmaceutical agent to treat a discomfort, condition, or disease of the human or an animal, either in the eye or on a skin surface, or in a nasal or pulmonary application.
The attachment of ejector 1604 to ejector plate 1602 may also affect operation of ejection assembly 1600, and the creation of single droplets or streams thereof. In the implementation of
Central region 1630 of ejector plate 1602 includes droplet generator region 1632 with one or more openings 1626, through which fluid 1610 passes to form droplets 1612. Ejection region (or droplet generator) 1632 may occupy a portion of central region 1630, for example the center, or the ejection hole pattern of droplet generator region 1632 may occupy substantially the entire area of central region 1630. Further, open region 1638 of reservoir housing 1608 may correspond substantially to the size of ejection region 1632, or open region 1638 may be larger than ejection region 1632.
In this regard, the location of the openings may affect mass deposition, with ejection hole patterns near the center of central region 1630 generally being preferred. Further, the configuration and location of the piezoelectric actuator 1604 may impact operation, including the inner and outer diameters of the ejector plate 1602, and the thickness of the actuator 1604. In one embodiment a 19 mm outer diameter, 14 mm inner diameter, 250 microns thick actuator may be used in a non-edge mounted application.
As shown in
Prior to excitation, ejector assembly 1600 is configured in a resting state. When a voltage is applied across electrodes 1606a and 1606b on opposite surfaces 1634 and 1636 of (e.g., piezoelectric) actuator 1604, ejector plate 1602 deflects to change between relatively more concave shape 1700 and relatively more convex shape 1701, as shown in
When driven with an alternating voltage, actuator 1604 operates to reverse the convex and concave shapes 1700 and 1701 of ejector plate 1602, inducing periodic movement (oscillation) of ejector plate 1602 in ejection region (droplet generator) 1632. Droplets 1612 are formed at apertures or openings 1626, as described above, with the oscillatory motion of ejection region 1632 causing one or more droplets 1612 to be ejected along fluid delivery (ejection) direction 1614, for example in a single-droplet (droplet on demand) application, or as a stream of droplets.
The drive voltage and frequency may be selected for improved performance of the ejection mechanism, as described above. In certain embodiments the oscillation frequency of actuator 1604 may be selected at or near a resonance frequency of the fluid filled ejector mechanism, or at one or more frequencies selected to oscillate ejector plate 1602 at such a resonance via superposition, interference, or resonant coupling.
When operated at or near a resonant frequency (for example, within the full width at half maximum of a resonance), ejector plate 1602 may amplify the displacement of ejector region (droplet generator) 1632, decreasing the relative power requirements of the actuator, as compared to a direct-coupling design. The damping factor of the resonance system, including ejector plate 1602 and droplet generator 1632, may also be selected to be greater than the piezoelectric actuator input power, in order to reduce fatigue and increase service life without substantial failure.
Examples of ejector assemblies are illustrated in U.S. Provisional Patent Application No. 61/569,739, “Ejector Mechanism, Ejector Device, and Methods of Use,” filed Dec. 12, 2011, as incorporated by reference herein. In one particular embodiment, ejector plate mechanism 1601 may include a rotationally symmetric ejector plate 1602 coupled to a generator plate-type actuator 1604, for example as shown in
In the particular configuration of
As shown in
For orientation purposes, the different elements of ejector mechanism 1601 as shown in
The ejector assembly described herein may be incorporated into an ejector device. Exemplary ejector devices are illustrated in U.S. patent application Ser. No. 13/184,484, filed Jul. 15, 2011, the contents of which are herein incorporated by reference.
Many implementations of the invention have been disclosed. This disclosure contemplates combining any of the features of one implementation with the features of one or more of the other implementations. For example, any of the ejector mechanisms, or reservoirs can be used in combination with any of the disclosed housings or housing features, e.g., covers, supports, rests, lights, seals and gaskets, fill mechanisms, or alignment mechanisms. Further variations of any of the elements of any of the embodiments herein are within the scope of ordinary skill and are contemplated by this disclosure. Such variations include selection of materials, coatings, or methods of manufacturing. Any of the electrical and electronic technology can be used with any of the implementations without limitation. Furthermore, any networking, remote access, subject monitoring, e-health, data storage, data mining, or internet functionality with respect to data captured by the device, is applicable to any and all of the implementations and can be practiced therewith. Further still, additional diagnostic functions, such as performance of tests or measurements of physiological parameter may be incorporated into the functionality of any of the implementations. Performance of glaucoma or other ocular tests can be performed by the devices as a part of their diagnostic functionality. Other methods of fabrication known in the art and not explicitly listed here can be used to fabricate, test, repair, or maintain the device. Furthermore, the device may include more sophisticated imaging or alignment mechanisms than those described in the incorporated prior applications. For example, the device or base may be equipped with or coupled to an iris or retina scanner to create a unique id to match a device to the user, and to delineate between eyes. Alternatively, the device or base may be coupled to or include sophisticated imaging devices for any suitable type of photography or radiology.
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.
The present application claims the benefit of the filing date of U.S. Patent Application Nos. 61/646,721, filed May 14, 2012, entitled “Ejector Mechanism, Ejector Device and Methods of Use” and 61/722,600 filed Nov. 5, 2012, entitled “Laminar Flow Droplet Generator Device and Methods of Use”, the contents of which are herein incorporated by reference in their entireties.
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