Patent Description:
This disclosure relates to droplet delivery devices with ejector mechanisms and more specifically to droplet delivery devices for the delivery of fluids that are inhaled into mouth, throat nose, and/or lungs.

The use of droplet generating devices for the delivery of substances to the respiratory system is an area of large interest. A major challenge is providing a device that delivers an accurate, consistent, and verifiable amount of substance, with a droplet size that is suitable for successful delivery of substance to the targeted area of the respiratory system.

Currently most inhaler type systems, such as metered dose inhalers (MDI), pressurized metered dose inhalers (p-MDI), or pneumatic and ultrasonic-driven devices, generally produce droplets with high velocities and a wide range of droplet sizes including large droplets that have high momentum and kinetic energy. Droplet plumes with large size distributions and high momentum do not reach a targeted area in the respiratory system, but rather are deposited throughout the pulmonary passageways, mouth, and throat. Such non-targeted deposition may be undesirable for many reasons, including improper dosing and unwanted side effects.

Droplet plumes generated from current droplet delivery systems, as a result of their high ejection velocities and the rapid expansion of the substance carrying propellant, may also lead to localized cooling and subsequent condensation, deposition and crystallization of substance onto device surfaces. Blockage of device surfaces by deposited substance residue is also problematic.

Further, conventional droplet delivery devices for delivery of nicotine, including vape pens and the like, typically require fluids that are inhaled to be heated to temperatures that negatively affect the liquid being aerosolized. Specifically, such levels of heating can produce undesirable and toxic byproducts as has been documented in the news and literature.

Accordingly, there is a need for an improved droplet delivery device that delivers droplets of a suitable size range, avoids surface fluid deposition and blockage of apertures, avoids producing undesired chemical byproducts through heating, and in an amount that is consistent and reproducible.

<CIT> relates to an ultrasonic droplet delivery device and related methods for delivering precise and repeatable amounts of a substance to a user for respiratory use.

<CIT> relates to an electronic device for producing an aerosol for inhalation by a person.

<CIT> relates to a nebulizer to deliver a medicament.

The present invention relates to a droplet delivery system as set out in the claims.

In one embodiment of the push mode invention, a "push mode" droplet delivery device does not include a heating requirement that could result in undesirable byproducts and comprises: a container assembly with an mouthpiece port; a reservoir disposed within or in fluid communication with the container assembly to supply a volume of fluid, an ejector bracket in fluid communication with the reservoir, the ejector bracket including a mesh with a membrane operably coupled to an electronic transducer with the membrane between the transducer and the mesh, wherein the mesh includes a plurality of openings formed through the mesh's thickness, and wherein the transducer is coupled to a power source and is operable to oscillate the membrane and generate an ejected stream of droplets through the mesh, and an ejection channel within the container assembly configured to direct the ejected stream of droplets from the mesh to the outlet. The vibrating membrane "pushing" liquid through the mesh is referred to herein as "push mode" ejection and devices in embodiments of the push mode invention may be referred to as push mode devices.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes an ultrasonic transducer as an electronic transducer, and preferably an ultrasonic transducer that includes piezoelectric material.

In another embodiment of the push mode invention, a droplet delivery device having a membrane that cooperates with a mesh further includes the container assembly having a fluid reservoir.

In another embodiment of the push mode invention, a droplet delivery device having a membrane that cooperates with a mesh further includes an ejector bracket configured for releasably coupling to the container assembly and the ejector bracket further configured for releasable coupling to an enclosure system including an electronic transducer and a power source.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes magnets configured to releasably couple the ejector bracket and enclosure system.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a snap mechanism and/or magnets configured to releasably couple the ejector bracket and the container assembly.

According to the invention, a droplet delivery device having a membrane that cooperates with a mesh further includes a fluid reservoir with a self-sealing mating mechanism configured to couple to a fluid release mating mechanism of the ejector bracket.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a fluid release mating mechanism that has a fluid conduit configured for insertion into the self-sealing mating mechanism. In a preferred embodiment, a fluid release mating mechanism includes a spike-shaped structure with a hollow interior configured to provide fluid communication between the reservoir and the membrane.

In another example, a droplet delivery device having a membrane that cooperates with a mesh is configured so that the membrane does not contact the mesh and pushes fluid to be ejected as droplets from the droplet delivery device through openings in the mesh.

In another embodiment of the push mode invention, a droplet delivery device having a membrane that cooperates with a mesh further includes the membrane having a slanted upper surface configured to contact fluid supplied from the reservoir.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a vibrating member having a slanted tip contacting an opposite underlying surface of a slanted upper surface of the membrane.

In further examples, an electronic transducer includes piezoelectric material that is coupled to a vibrating member with a ring-shaped beveled tip, rod-shaped beveled tip, rod-shaped tip, or a ring-shaped non-beveled tip.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a mesh with a bottom surface in a parallel configuration with an upper surface of the membrane.

In another embodiment of the push mode invention, a droplet delivery device having membrane that cooperates with a mesh further includes the mesh including a bottom surface in a non-parallel, i.e., slanted at an angle, configuration with an upper surface of the membrane.

In another embodiment of the push mode invention, a droplet delivery device having a membrane that cooperates with a mesh further includes a central axis of the droplet delivery device passing through the ejection channel and the membrane, and wherein the transducer is coupled to a vibrating member that is coupled to the membrane at a position offset from the central axis.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a fluid in the reservoir including at least one of a non-therapeutic substance, nicotine, or cannabinoid.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a fluid in the reservoir including a therapeutic substance that treats or prevents a disease or injury condition.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a laminar flow element positioned in an ejection channel of a container assembly before a mouthpiece port of the delivery device. In preferable embodiments, the laminar flow element includes a plurality of cellular apertures. In some embodiments, a laminar flow element includes blade-shaped walls defining the plurality of cellular apertures. In further embodiments, one or more of the plurality of cellular apertures include a triangular prismatic shape, quadrangular prismatic shape, pentagonal prismatic shape, hexagonal prismatic shape, heptagonal prismatic shape, or octagonal prismatic shape.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a breath-actuated sensor, such as a pressure sensor, operatively coupled to the power source, wherein the breath-actuated senor is configured to activate the electronic transducer upon sensing a predetermined pressure change within the ejection channel or within a passageway of the droplet delivery device in fluid communication with the ejection channel.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes the mesh made of a material of at least one of palladium nickel, polytetrafluoroethylene, and polyimide.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes the mesh made of a material of at least one of poly ether ketone, polyetherimide, polyvinylidine fluoride, ultra-high molecular weight polyethylene, Ni, NiCo, Pd, Pt, NiPd, and metal alloys.

In other examples a mesh may be made of single crystalline or poly crystalline materials such as silicon, silicon carbide, aluminum nitride or germanium with hole structures formed using semiconductor processes such as photo lithography and isotropic and anisotropic etching. With photolithography and isotropic and/or anisotropic etches different hole shapes can be formed in a single crystalline wafer with very high precision. Using sputtering, films can be deposited on the surface with different contact angles. Thin layers formed or deposited on the surface will have, in certain embodiments, much better adherence than film deposited on metal mesh formed by galvanic deposition or polymer mesh formed by laser ablation. This better adherence is because the surfaces on the single crystalline wafers "slices" are atomically smooth and can be etched to produce exact surface roughness to facilitate mechanical bonding with glue or other materials. Silicon carbide would be a preferable material because of its high strength and toughness. An important advantage of using semiconductor processes to fabricate hole structures from a single crystalline wafer "slice" in a mesh of embodiment of the push mode invention is that the holes and surface contact angles will be exact without the variation we see in conventional ejector plates using mesh made from galvanic deposition or laser ablation.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes the membrane made a of material of at least one of polyethylene naphthalate, polyethylenimine and poly ether ketone.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes the membrane made a of material of at least one of metal membranes, metalized polymers, threaded polymers, threaded nylon, threaded polymers that are coated with polymers or metal, threaded nylon coated with polymers or metal. threaded metals, threaded SiC, threaded graphite composites, metalized graphite composites, graphite composites coated with polymers, polymer sheets filled with carbon fibers, poly ether ketone filled with carbon fibers, polymer sheets filled with SiC fibers, polymer sheets filled with ceramic or metal fibers, ULPA filter media, Nitto Denko Temic Grade filter media, Nitto Denko polymer sheets, threaded polymers bonded to a polymer sheet, nylon weave bonded to poly ether ketone or polyimide, graphite composites bonded to polymer sheets, polymer fiber weave with metalized coating, and nylon with sputtered on Al or vapor deposited Al.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a PZT-based ultrasonic transducer coupled to a vibrating member having a tip portion made of at least one of Grade <NUM> titanium alloy, Grade <NUM> titanium alloy, and about <NUM>% or higher purity titanium. In certain embodiments, the vibrating member's tip includes a sputtered on outer layer of and about <NUM>% or higher purity titanium providing a smooth tip surface configured to contact an underlying bottom surface of the membrane that is opposite an exterior top surface of the membrane positioned nearest the mesh so as to help reduce wear of the membrane and increase the longevity and operation consistency of the membrane (and also possibly vibrating member's tip portion).

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes an exterior surface of the membrane, opposite an underlying surface of the membrane contacting the vibrating member, having a hydrophobic coating.

In another embodiment of the push mode invention, a droplet delivery device having a membrane that cooperates with a mesh further includes an exterior surface of the membrane, opposite an underlying surface of the membrane contacting the vibrating member, having a hydrophilic coating.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a hydrophilic coating on one or more surfaces of the mesh.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a mesh including a hydrophobic coating on one or more surfaces of the mesh.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a hydrophobic coating on a first surface of the mesh and a hydrophilic coating on a second surface of the mesh.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes the membrane having an operable lifespan of over <NUM>,<NUM> aerosol-creating activations by the transducer.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes at least one superhydrophobic vent in fluid communication with the reservoir that is covered with a removable aluminized polymer tab during storage.

In another example, a droplet delivery device having a membrane that cooperates with a mesh further includes a removable aluminized polymer tab coupled to an exterior surface of the membrane adjacent the mesh during storage.

In another example, a droplet delivery device having a membrane that cooperates with a mesh includes a pre-assembly step of removing a sealed packaging including aluminum and/or aluminum coating that contains the reservoir with a fluid, preferably wherein the reservoir is included in the container assembly that is also packaged for storage in the sealed packaging. In some embodiments, sealed packaging may include dry nitrogen, argon or other gas that does not contain oxygen.

In various embodiments of the push mode invention, a droplet delivery device having a membrane that cooperates with a mesh may be used for mouth inhalation or nasal inhalation. The mouthpiece port may be sized, shaped and include materials that are better suited for that particular mouth or nasal inhalation use and purpose.

The push mode invention will be more clearly understood from the following description given by way of example, in which:.

Push mode has been developed as a reduced-risk product to deliver (i) nicotine, cannabinoids, and other non-therapeutic substances (devices described herein as "BlueSky" are preferable for use with such substances), as well as (ii) therapeutic and prescriptive drug products (devices described herein as "Norway" are preferable for use with such products). The push mode device is designed to deliver the user a safe and controlled dose. The push mode droplet delivery device <NUM> is capable of delivering aqueous and nonaqueous solutions and suspensions at room temperature. Large molecule formulations, whether water soluble or not, can also be delivered with this technology. Harmful chemical by-products commonly found with heated nicotine, and other substances, are eliminated in the push mode device making it a safer option for aerosol delivery.

Push mode utilizes a vibrating member <NUM> and transducer <NUM> that work in conjunction with a membrane <NUM> and mesh <NUM> to aerosolize fluid <NUM>, which is held in a reservoir <NUM> and supplied to the mesh <NUM> using various methods (e.g., wick material, hydrophilic coatings, capillary action, etc.). Preferably the vibrating member is coupled to the transducer, such as by bonding (e.g. adhesives and the like), welding, gluing, physical connections (e.g. brackets and other mechanical connectors), and the like. The transducer and vibrating member interact with the membrane to push fluid through the mesh. As illustrated and described in various embodiments, the membrane may in some cases contact the mesh while also "pushing" fluid through holes in the mesh, and may in other cases be separated without contacting the mesh to push liquid through holes in the mesh. The transducer may comprise one or more of a variety of materials (e.g., PZT, etc.). In certain embodiments the transducer is made of lead-free piezoelectric materials to avoid creation of unwanted or toxic materials in a droplet delivery device intended for human inhalation. The vibrating member may be made of one or more of a variety of different materials (e.g., titanium, etc.). The mesh may be one or more of a variety of materials (e.g., palladium nickel, polyimide, etc.). After the fluid is pushed through the mesh, a droplet spray is formed and ejected through a mouthpiece port, carried by entrained air.

The device is tunable and precise. The device can be optimized for individual user preferences or needs. The aerosol mass ejection and mass median aerodynamic diameter (MMAD) can be tuned to desired parameters via the mesh hole size, mesh treatment, membrane design, vibrating member design, airflow, manipulation of power to the transducer, etc. The design produces an aerosol comprised of droplets with a high respirable fraction, such that the lungs can absorb the aerosol most efficiently.

The vibrating member and transducer are both separate from the cartridge, isolated by the membrane. Not only does this create a safer product, but it eases manufacturability. The vibrating member and transducer are both typically expensive components. Keeping these components in the enclosure system rather than the cartridge reduces the cost of goods sold (COGS).

Substance, feature, and part numbers are provided for convenient reference with respect to the descriptions and figures provided herein in Table <NUM>:.

Referring to <FIG> and <FIG>, a BlueSky push mode device <NUM> includes main components of container assembly <NUM>, ejector bracket <NUM> and enclosure system <NUM>. Currently, two embodiments of BlueSky push mode, I and II, have been prototyped and tested. Referring to <FIG>, inclusion of a mesh supported by a stainless-steel ring and elastic sealing ring in a droplet delivery device <NUM> is referred to as "push mode II" herein. Referring to <FIG> inclusion of a mesh supported by upper and lower mesh carrier and an elastic sealing ring in a droplet delivery device <NUM> is referred to as "push mode I" herein.

The push mode I and II embodiments have a transducer consisting of a lead zirconate titanate (PZT) disc bonded to the bottom of a vibrating member made of titanium alloy. The vibrating member and transducer are encased by a plastic cover in an enclosure system <NUM>. A membrane made of polyethylene naphthalate (PEN) in the ejector bracket <NUM> isolates the transducer and vibrating member from the fluid that is supplied from a reservoir in the container assembly <NUM>. The membrane can be thermoformed to the shape of the vibrating member tip. The embedded system on the device consists of the transducer, pressure sensor, and lithium-ion battery all connected on a single board microcontroller. The aluminum enclosure that houses the embedded system contains a button that can double as a fingerprint sensor for use with controlled substances. The device is charged through a USB-C charging port. Magnets are used to hold the cartridge in the enclosure.

Embodiments use a two-component cartridge system to keep the fluid from contacting the mesh in storage. This design involves two spikes, one of which contains wicking material, on one part of the cartridge, the ejector bracket. The other part of the cartridge, the container, houses a fluid reservoir and two septa. The user pushes the ejector bracket and container together, and the spikes puncture the septa, creating a path for fluid to flow to the mesh. The wicking material in one spike aids in the supply of fluid to the mesh. The other spike, which does not include wicking material, allows air to enter the container for pressure equalization. Vents covered with vent material are located at the top of each side of the fluid reservoir and are connected to the open atmosphere via airflow outlets, allowing for equalization of pressure.

Referring to <FIG>, there is an ejection port <NUM> with a length of <NUM> and a mouthpiece port with a length of <NUM>. The preferred length of the ejection port is <NUM>-<NUM>. The preferred mouthpiece port length is <NUM>-<NUM>. <FIG> shows the fluid <NUM> and ventilation <NUM> flow paths through the spikes <NUM> in prototyped embodiments. <FIG> show the entrained air path of prototyped embodiments.

<FIG> show a rendering and a CAD overview, respectively, of the push mode I embodiment. The overviews in <FIG> show the container assembly <NUM>, ejector bracket <NUM>, and the enclosure system <NUM>, from left to right.

<FIG> provides an exploded view of the components from the push mode I embodiment.

Referring to <FIG>, the push mode I embodiment includes a mesh carrier that includes two COC rings <NUM>, <NUM> that are ultrasonically welded holding the mesh <NUM> and suspension gasket <NUM>. The COC rings sandwich the mesh and suspension gasket as shown in <FIG>. The gasket is placed between the upper and lower ejector brackets.

Referring to <FIG>, two vents are located on the narrow sides of the lower ejector bracket <NUM> in the push mode I embodiment. The spikes are located on the upper ejector bracket <NUM>. The container, which houses the fluid reservoir <NUM>, includes three COC pieces. The two septa <NUM> are held between the middle and lower container pieces. A container ring is bonded onto the upper <NUM> and middle <NUM> container pieces and the mouthpiece <NUM> snaps onto the upper container piece <NUM>.

<FIG> show a rendering and a diagrammatic overview of the push mode II embodiment, respectively. The overviews in <FIG> show the container assembly <NUM>, ejector bracket <NUM>, and the enclosure assembly <NUM>, from left to right.

<FIG> illustrates an exploded view of the components of the push mode II embodiment.

In the push mode II embodiment, a stainless-steel annulus carrier <NUM> is bonded to the mesh <NUM>. A gasket <NUM> is placed above the mesh and mesh carrier between the upper <NUM> and lower <NUM> ejector brackets. <FIG> illustrates the push mode II embodiment mesh carrier <NUM> and gasket <NUM>.

Two vents are located on the wide sides of the lower ejector bracket <NUM> as shown in <FIG>. The spikes are located on the upper ejector bracket <NUM>.

As in push mode I, the container, which houses the fluid reservoir, includes three COC pieces. The lower container for the push mode II embodiment extends further than in push mode I, with the tubular portion extending into the upper ejector bracket.

<FIG> (push mode II) and <FIG> (push mode I) illustrate a comparison of the lower containers of each embodiment. The extension is necessary because the mesh sits lower, compared to I, due to the stainless-steel mesh carrier being thinner than the COC carrier of I. The two septa are held between the middle and lower containers. A container ring is bonded onto the upper and middle container pieces and the mouthpiece snaps onto the upper container piece.

Push mode has multiple vibrating member and membrane designs. Table <NUM> and.

Table <NUM> contain descriptions of the vibrating member and membrane designs, respectively, that have been prototyped and tested. Referring to <FIG>, there are currently two different tips for the vibrating member rod tip and ring tip, respectively.

The transducer requires a large amount of power during the actuation of the device. As the power usage increases, the heat generated by the printed circuit board assembly (PCBA) increases. The effect from the heat is mitigated through several design features in the PCBA. A four-layer PCBA increases anti-interference and heat dissipation capabilities. The PCBA also contains a large amount of copper foil, making it conducive to heat dissipation. The MOSFET driving the transducer adopts a high-current package to avoid damage caused by heating in long-term continuous operation. The automatic transformer, to increase the voltage output, it is suspended to insulate it from the rest of PCBA. These features allow the device to operate for days without concern of overheating or being subjected to electrical noise.

The prototype BlueSky push mode embodiments, I and II, have gone through life testing. The life test consisted of repeated three-second dosing with one-second resting intervals over the course of several days. Mass ejection was done before and after the life test. Mass ejection is defined as the mass the device aerosolizes over one three-second dose. Mass ejection data before the life test is listed in Table <NUM> and the data for after life testing is listed in Table <NUM>. The mass ejection of one embodiment remained consistent before and after <NUM>,<NUM> doses and can likely go beyond. This embodiment, II push mode with H4 and M11, has a stainless-steel mesh carrier. There is a second embodiment, I push mode, which has a COC plastic mesh carrier. Due to heat from the extreme dosing cycling, the plastic mesh carrier warped during testing. This led to a decrease in mass ejection after the life test. However, the stainless-steel carrier in II push mode did not warp from the heat, which allowed it to remain consistent after testing. In both I and II, thermal management is improved through a four-layer PCBA, a larger than standard amount of copper foil, and a high current MOSFET driver. The conditions of the testing are not representative of normal consumer use. During normal daily use, where extreme heating does not occur, both embodiments, I and II, show consistent mass ejection. Tables <NUM> and <NUM> provide details of the referenced Vibrating Member and Membrane, respectively.

Comparison of Push Mode and Prior Art Ring Mode.

As set forth in Example <NUM> described subsequently, prototypes of BlueSky I and II push mode were tested and compared to prior technology, referred to as BlueSky ring mode (such as described and shown with respective test data for that technology in <CIT>), is provided as follows:.

Ejectors with a hole size of <NUM> were tested in each device. Half of the ejectors tested had a hydrophilic entrance and hydrophobic exit (R). The other half had a hydrophobic entrance and exit (W). The testing was performed with a TSI Mini-MOUDI Model <NUM> and a Thermo Fisher Vanquish UHPLC. Eight different design combinations (vibrating members, membranes, ejector treatments) were tested with BlueSky I and II. Based on the results of the testing, push mode I appears to be the preferred embodiment for push mode. The push mode I design resulted in more consistent mass ejection and MMAD values versus II. Seven of the eight design combinations resulted in comparable mass ejections and MMADs. One outlier, H5 with M12 and R-treated ejector, had a significantly higher mass ejection than the others. Upon comparison of I push mode to BlueSky ring mode, I delivered higher and more consistent mass ejection and lower MMADs. Table <NUM>, Table <NUM> and Table <NUM> provide the data obtained from ring mode, I push mode, and II push mode, respectively. The data in the tables include micrograms of nicotine ejected, MMAD, geometric standard deviation (GSD), and the percentage of ejected solution in stage <NUM> and stage <NUM> of the mini-MOUDI. All the vibrating member and membrane combinations tested with I push mode, found in Table <NUM>, performed well with both ejector treatments. As seen in Table <NUM>, the best performing combinations with II push mode were H4 with M11 and H5 with M12, both using W-treated ejectors.

The results obtained from Push Mode I device are shown in Table <NUM>. Tables <NUM> and <NUM> provide details of the referenced Vibrating Member and Membrane, respectively.

The results obtained from Push Mode II device are shown in Table <NUM>. Tables <NUM> and <NUM> provide details of the referenced Vibrating Member and Membrane, respectively.

Based on the results of the testing, I push mode is the preferred embodiment when compared to II.

Another embodiment of push mode incorporates the two-part cartridge system into a singular component. Having the cartridge in one piece simplifies setup for the user and increases manufacturability while reducing cost. <FIG>, <FIG> show two single piece cartridge embodiments. The embodiment shown in <FIG> includes a long vibrating member with the fluid reservoir residing under the mesh. In this design, the container is two pieces that are assembled during manufacturing.

In another embodiment, there is a short vibrating member with the fluid reservoir above the mesh (see <FIG>). In this design, the container is comprised of three pieces that are assembled during manufacturing. After the fluid reservoir is filled, the mouthpiece snaps onto the container with the container ring between.

The vibrating member and transducer work in conjunction with a membrane and mesh, as previously described embodiments of BlueSky push mode. The membrane also serves to isolate the vibrating member and transducer from the fluid. A mesh carrier is used in both designs. Magnets on the bottom of the containers hold the cartridge in the enclosure.

Further embodiments, shown in <FIG>, of a single piece cartridge include a simpler design, reducing the COGS in manufacturing by decreasing the number of injection molded parts and bonds. <FIG> illustrates a simplified version of the design in <FIG> but with a long vibrating member. The design in <FIG> reduces the number of ultrasonic welds and injection molded parts. <FIG> further simplifies the design from <FIG> with fewer ultrasonic welds and injection molded parts.

The low COGS designs shown in <FIG> are a simplification of the design shown in <FIG>. This design is a single part cartridge that can be inserted into the enclosure. Air exchanges between the seal of the mouthpiece and the upper container. The cartridges shown in <FIG> and <FIG> have removed the ejection port leaving the <NUM> mouthpiece port. The preferable ejection port and mouthpiece port lengths are the same as previously set forth, <NUM>-<NUM>.

<FIG> illustrates a two-piece cartridge design for a long vibrating member. The container and ejector bracket are swapped where the ejector bracket is connected to the mouthpiece and the container is below. The spikes on the ejector bracket face downward onto the septa on the container.

Another embodiment of push mode, Norway, is similar to its BlueSky counterpart in most aspects, except that is tailored for prescriptive and medical use. Much like BlueSky, Norway features a releasable cartridge which contains a fluid reservoir and ejector bracket. The device can also be used to assess lung health using spirometry. <FIG> shows one embodiment of Norway push mode.

Patients diagnosed with lung diseases can use the Norway device to track their medication dosages and take lung function tests so their treatment progression can be assessed. The patient can perform lung function tests and view dosage history via a phone app which pairs to the Norway device with Bluetooth. The device saves pressure sensor measurements from each dosage of medication. Inspiratory flow measurements can be derived from the pressure sensor measurements to ensure the user is inhaling their medication at a flow rate which delivers the solution most efficiently. The device can also perform lung function tests to measure a patient's forced expiratory volume over <NUM> second, forced vital capacity, peak expiratory flow, and other spirometry measurements. The data from dosage tracking and lung function tests are uploaded to the cloud so that the patient and doctor may view the patient's progression.

The ejector bracket has been designed to accept many different sizes of containers, where the fluid reservoir volume changes. This makes the device capable of being used with biologics, or one time use ejections. Possible fluid reservoir volumes range from 1µL to <NUM>.

The mouthpiece for the Norway embodiment has a preferred length of <NUM>. There are two slits on the sides of the mouthpiece with a dimension of <NUM> by <NUM> for an area of <NUM><NUM>. The length of the mouthpiece could be anywhere from <NUM> to <NUM>. The area for the mouthpiece could be from <NUM><NUM> to <NUM><NUM>. The mouthpiece opening has dimensions of <NUM> x <NUM> for an area of <NUM><NUM>. The area of the mouthpiece opening could be anywhere from <NUM><NUM> to <NUM><NUM>.

The cartridge can be inserted into the main body of the device. The front of the cartridge can be sealed by an O-Ring attached to the cap that presses around the mesh on a stainless-steel annulus when closed to prevent any evaporation through the mesh, this is the face seal. The device features voice coaching and LED lights to guide the user through the ejection inhalation. There is an LCD screen to display dose count, and other necessary information. <FIG> shows an exploded view of one embodiment of Norway push mode.

Referring to <FIG>, the cartridge assembly (<FIG>) is composed of three parts: the container (<FIG>), cartridge spacer (<FIG>), and the ejector bracket (<FIG>). The cartridge spacer keeps the ejector bracket separated from the container to prevent the fluid from contacting the mesh during storage prior to the push mode Initial use.

The cartridge spacer can be removed so the container can be pushed down onto the ejector bracket such that the spikes pierce the septa making the cartridge one piece. Then, the cartridge can be pushed into the main body of the device to complete the device. This process is illustrated in <FIG>.

The cap of the Norway embodiment is designed to create a firm seal around the cartridge after each use. An O-Ring is seated on a spring-loaded plastic piece which lightly compresses onto the cartridge assembly when the cap is closed, generating a seal between the cartridge and open atmosphere. The components of the cap are shown isolated in as illustrated in <FIG>.

The critical components to generate precise aerosol of the ejector bracket include the mesh, gasket, membrane, vent material, and mouthpiece. The membrane is positioned such that the membrane face is held parallel to the mesh face, or at a small precise angle. The ejector bracket also has two spikes protruding out of the top that pierce the container. One is for fluid supply, and the other provides a ventilation path for air generated by ejection. On the side of the ejector bracket with the air ventilation spike there is an opening covered by vent material to help relieve pressure and build-up of air. The mouthpiece is positioned following the face of the mesh.

The critical components of the container to maintain consistent aerosol are vent material, a spiral, septa, and septa caps. The vent material is positioned between the fluid and the spiral. The spiral is created by the upper container and vent spacer which minimizes evaporation of the fluid through the vent material. The vent spacer is bonded onto the top of the upper container to create the sealed spiral with an opening to the push mode Inside of the container assembly and another opening to atmosphere. The septa are at the bottom of the container. The septa are placed into a cavity in the lower container and held in place with septa caps that are bonded onto the lower container. The critical components of both the ejector bracket and container can be seen in <FIG>.

The main body of the Norway contains the vibrating member and transducer assembly. In one embodiment, as shown in <FIG>, the vibrating member and transducer assembly is encased by a vibrating member front cover and vibrating member rear cover. The covers are held together by circular caps called the front and rear vibrating member cover holders. The encased vibrating member is then put into the vibrating member enclosure, followed by the vibrating member assembly spring, and finally seated into the vibrating member device bracket. The vibrating member enclosure allows the spring to press the vibrating member and transducer assembly to the membrane.

Additional embodiments of Norway push mode include different suspension systems to hold the mesh in the cartridge, similar to those in BlueSky push mode. With the suspension systems seen in <FIG>, the vibrating member and transducer assembly no longer has a spring; therefore, it no longer needs to be in the vibrating member enclosure, nor does it need the vibrating member device bracket.

An additional embodiment of the Norway push mode device includes a heating element that increases the push mode Inhaled air temperature to roughly <NUM> to make the dose more comfortable. As with the BlueSky designs that include heating elements, the heated air temperature is kept below thermal degradation levels, so the push mode Integrity of the formulation is maintained, and no harmful by-products are produced. This can be accomplished because, as with BlueSky, the device does not depend on heat to aerosolize. <FIG> illustrate one design that includes two heating elements positioned beneath the vibrating member on either side of the ejector bracket. As seen in <FIG>, air enters through openings in the bottom of the ejector bracket, passes through the heating elements, and exits into the mouthpiece. Additionally, the warmer air will cause minimal evaporation of the aerosolized fluid resulting in a decrease in MMAD.

In the push mode design, the vibrating member and transducer are completely isolated from the push mode Inhaled solution by a membrane. The transducer, which typically contains heavy metals, is located behind a vibrating member, such that it is completely removed from the ejection area and fluid reservoir. The membrane separates the fluid reservoir from the vibrating member, presenting a chemically inert barrier that permits little or no diffusion, and subsequent evaporation. In one embodiment, a palladium nickel alloy mesh is used to atomize the fluid. A polyimide mesh has also been tested and was shown to be a viable option. Using a polymer mesh would significantly reduce manufacturing cost and potentially improve the extractable/leachable profile of the device. The non-metallic components in prototyped embodiments are primarily comprised of cyclic olefin copolymer (COC) and silicone, both widely accepted materials used in the medical device industry.

<FIG> through <FIG> show embodiments which include a heating element to increase the push mode I inhaled air temperature to roughly <NUM>, making the dose more comfortable. Air passes perpendicularly through the heating element to be most efficiently heated. Since the heated air temperature is kept below thermal degradation levels, the push mode Integrity of the formulation is maintained, and no harmful by-products are produced. Also, the specific heat of the fluid is much greater than air; therefore, the temperature of the aerosolized fluid will heat minimally. This can be accomplished because the device does not depend on heat to aerosolize. Here, the heat is only used to optimize the user experience. Additionally, the warmer air will cause minimal evaporation of the aerosolized fluid resulting in a decrease in MMAD. Finally, the heating element will be surrounded by insulation material to keep all the components of the device insulated from heat.

The heating element is breath actuated such that the element only heats air as the user inhales. This allows the battery to have a much longer life. It also creates a much safer device in that the heating element is not always on. This can be accomplished due to the push mode Incorporation of small gauge wire. This wire heats up very quickly, so the heating element responds as soon as the user inhales.

In the embodiment shown in <FIG>, after air enters the device, the air pathway is narrowed by the airflow accelerator to increase velocity. Then, the air is passed through the heating element, which is positioned in the heat exchange area. Finally, the heated air flows into the mouthpiece. <FIG> features three views of this embodiment. This design allows for a larger battery to be installed in the device which supplements the heating element.

Referring to <FIG>, a speaker can also be incorporated into any of the heated air BlueSky embodiments. This will allow for an additional sensory experience for the user (i.e., crackling/heating sound upon inhalation).

In the embodiments shown in <FIG> and <FIG>, the heating element is positioned below the vibrating member in a separate chamber inside the enclosure. The air enters through the airflow inlet, is passed through the heating element, and exits above the ejector. This design can be used in the two-part cartridge design (<FIG>) or the single piece cartridge design (<FIG>). These embodiments offer the advantage of a more compact device, compared to the embodiment shown in <FIG>, at the cost of battery life.

Another embodiment features external heating elements seated on the outside of the enclosure (<FIG>). Air passes through the heating elements, enters the mouthpiece above the mesh, and exits through the end of the mouthpiece. This design may in some embodiments provide a removable heating element.

In another embodiment of a heated air push mode device, closed loop control is used to regulate the power delivered to the heating element. The power is adjusted to keep the airstream temperature constant and at safe levels. Referring to <FIG>, the airstream temperature is measured by a temperature sensor such as an RTD. The power delivered to the heating element changes as a result of the temperature sensor readings.

In another embodiment of the heated air push mode device, open loop control is used to regulate the power delivered to the heating element. The power is adjusted to keep the airstream temperature constant. The pressure drop from inhalation is sensed. The amount of power needed to supply the heating element to keep the air stream temperature constant due to changes in pressure drop is known. A look-up table is created to determine the amount of power needed to supply the heating element to keep the air stream temperature constant based upon the pressure sensor value.

In another embodiment of the heated air push mode device, one or more of the push mode Internal device components that are in contact with heated air is preferably made of metal (i.e., aluminum, Inconel, etc.). This will insulate the heating element and enhance biocompatibility of the device.

In another embodiment of the heated air push mode device, any component that could be compromised by the heated air is preferably made of metal (i.e., titanium, aluminum, Inconel, etc.). These components include, but are not limited to the mouthpiece, the heating chamber, and like components that heated air could negatively affect.

In one embodiment of the heated air push mode device, the metal components that are in contact with the heated air are preferably made of a material with a low thermal conductivity, such as Inconel.

In one embodiment of the heated air push mode device, ceramic is used to insulate the heating element.

Another embodiment of push mode incorporates a mechanism to adjust the size of the airflow inlets. The airflow inlets can be opened and closed using a sleeve or an adjustable aperture. In this way, the resistance experienced by the user can be adjusted to individual preferences. <FIG> show a BlueSky device with a sliding sleeve <NUM> around the enclosure. The sleeve can be adjusted to partially or completely cover the airflow inlets, increasing the resistance felt by the user. Additionally, the airflow in the mouthpiece will change as the position of the sleeve is changed. This will also change the MMAD of the dose due to changes in the airflow current.

BlueSky push mode has also been adapted for nasal inhalation. <FIG> show several embodiments of a nasal BlueSky push mode device. As seen in <FIG>, there are multiple variations of the push mode Inhalation port. However, preferable embodiments of the nasal device have longer and narrower inhalation ports (see <FIG>) than in other designs with shorter inhalation ports (see <FIG>) for optimal nostril use. As seen in <FIG>, a cap may be added to protect the push mode Inhalation port and keep it clean. The preferred droplet sizes are between <NUM>-<NUM> micron range, but <NUM>-<NUM> microns is preferred.

Another embodiment of push mode incorporates a tube with a hydrophilic interior that supplies fluid from the fluid reservoir to the mesh. A hydrophilic tube eliminates the need for wicking material and allows for a wider variety of suspensions and solutions to be delivered from the device. An example of one of these tubes is the spike on BlueSky I and II.

Another embodiment of push mode incorporates a tube with a hydrophilic interior that supplies fluid from the fluid reservoir to the mesh without a wick material, allowing for a wider variety of suspensions and solutions to be delivered from the device; and an opposite hydrophobic tube that encourages gas migration from the fluid supply area between the membrane and mesh.

In another embodiment, as shown in <FIG>, a polymer mesh <NUM> is used with a plate <NUM> attached to it. It has been found that a <NUM> hole on a plate works best for ejection. Therefore, another embodiment is where the plate has multiple <NUM> openings for the liquid to enter. The holes on the plate can range from <NUM>-<NUM>.

Another embodiment of push mode uses a tidal breathing system that can be used for pediatric therapy. The push mode technology supplies aerosol a mask similar to the Aero Chamber Plus Z-Stat Pediatric Mask (Monaghan Medical). This allows for long use therapy. When a user inhales, the device will start ejection and when the user exhales the device will stop ejection. Due to the robustness of push mode, this can be a very effective device for extended therapies.

In another embodiment, two parallel plates <NUM> surround the fluid next to the mesh and membrane area. These two parallel plates will measure the capacitance of the fluid. The capacitance of the supplied fluid is known. If the capacitance measured is different than the known capacitance, the device will not work. This will prevent tampering of the cartridge, and it will prevent unauthorized fluids to be inserted into the cartridge. One of the parallel plates is shown in <FIG>.

Another embodiment of push mode utilizes vibrating member and membrane geometries at their coupled interface to act as both an atomizer and microfluidic pump in applications where wicking materials are not incorporated into the preferred embodiment for certain suspensions, solutions, and other medical, therapeutic, and consumer applications. The tip of the vibrating member is coupled to a membrane matching the desired geometry allowing fluid to enter between the mesh and membrane while also encouraging any gas to exit freely. These membranes may be treated by technologies mentioned previously to be hydrophilic or hydrophobic.

Another embodiment utilizes a separate microfluidic pump to direct the proper amount of fluid and pressure between the mesh and membrane when powered on, at breath actuation, at set intervals, etc. to ensure proper dosing.

Vibrating members of the embodiments are to be made of materials featuring proper acoustical and mechanical properties. Thin film sputtering of various nonreactive metals such as titanium, palladium, gold, silver, etc. can be performed on the vibrating member tip section to further enhance biocompatibility. According to industry leaders, titanium has the best acoustical properties of the high strength alloys, has a high fatigue strength enabling it to withstand high cycle rates at high amplitudes, and has a higher hardness than aluminum, making it more robust. Correct material must be selected, vibrating members must be balanced, designed for the required amplitude, and be accurately tuned to a specific frequency. One aspect of tuning is making the vibrating member have the correct elongated length. Another aspect of tuning is matching the vibrating member to the mesh and having the correct gain ratio. Incorrectly tuned vibrating members may cause damage to the power supply and won't be resonating at the device's optimized frequency, decreasing mass ejection and longevity. (see also <NPL>).

For example, Titanium <NUM>-<NUM> material has far more uniform wave propagation in one direction (axial) than Titanium <NUM>-<NUM>.

Embodiments must have vibrating members with proper moduli of elasticity, acoustical properties, sound speeds, mechanical properties, molecular structure, etc. such as Ti Grade <NUM>, Ti Grade <NUM>, Ti Pure ><NUM>%, TIMETAL ® <NUM>-<NUM>, <NUM> Stainless Steel, <NUM> Stainless Steel, <NUM> Stainless Steel, <NUM> Stainless Steel, <NUM> Stainless Steel, <NUM> Stainless Steel, Al <NUM>, Al <NUM>, Al <NUM>, etc..

Other embodiments have crystalline vibrating members with proper moduli of elasticity, acoustic properties, sound speeds, mechanical properties, molecular structure, etc. such as: Sapphire (Al2O3 Aluminum oxide), monocrystalline silicon, etc..

In one embodiment, vibrating member design is based on industrial ultrasonic vibrating member design such as disclosed by the push mode Indicated reference subsequently noted, but optimized to be used for the purposes of aerosol generation in the delivery of fluids to the lungs, nose, ear, eye, etc..

Referring to <FIG>, the vibrating member is rectangular at the membrane interface. This rectangular tip features three periodic slots along the X directions and two periodic slots along the Y directions of the member tip based on a quasi-periodic phononic crystal structure.

Referring to <FIG> and <FIG>, the rectangular vibrating member tip combined with a conical section and a cylindrical section can effectively improve the output amplitude gain and utilizes the band gap property of the structure to effectively suppress lateral vibration of the vibrating member tip, improving the amplitude distribution uniformity at the membrane interface (see also <NPL>).

In other embodiments, shown in <FIG>, the vibrating member <NUM> is tuned and machined similarly to industrial ultrasonic vibrating member designs (such drawings being disclosed in the noted reference) but optimized for aerosol generation in the delivery of fluids to the lungs, nose, ear, eye, etc. such as contoured vibrating member (<FIG>), plunger vibrating member (<FIG>), product authenticity sensor vibrating member (<FIG>), spool vibrating member (<FIG>), slotted cylindrical vibrating member (<FIG> and <FIG>), bar vibrating member (<FIG> and <FIG>), and booster vibrating member (<FIG>). See also <NPL>).

Referring to <FIG>, vibrating members can be contoured to make intimate contact with the membrane geometry.

Referring to <FIG>, plunger members have nodally-mounted plungers that can be used to exert pressure on a given surface of the membrane contacted by the vibrating member.

Referring to <FIG>, sensor carrier vibrating members feature an internal cavity partially or fully encapsulating a nodal-mounted sensing device. The sensing device is coupled with a sensor control unit which outputs a signal to the PCBA. This signal can be used to disable aerosol generation when non-compliant, incorrect, unlicensed, etc. cartridges are attempted to be used.

Referring to <FIG>, spool vibrating members are unslotted cylindrical members featuring undercut sides behind the face to form a spool shape. This spool shape improves the face amplitude uniformity. Because a spool vibrating member does not have slots, its stresses are much lower than comparable slotted cylindrical vibrating members making machining costs much lower. Using cavities, slots, and back extension to optimize axial resonance creates a very uniform amplitude across the members face. The member is one half-wavelength long at axial resonance, as indicated by the single node that is generally transverse to the principal direction of vibration. Spool vibrating members generally have about <NUM>:<NUM> gain, although somewhat higher gain is possible.

Referring to <FIG> (optimized) and <NUM> (unoptimized), slotted cylindrical vibrating members feature longitudinal slots used to reduce the transverse coupling due to the Poisson effect. Such slots are usually radial, although other configurations are sometimes useful. Without such slots, the vibrating member will either have very uneven amplitude across the face or may even resonate in a nonaxial manner. They also have a face cavity that extends deep within the member to increase its gain. The vibrating member is one half-wavelength long at axial resonance, as indicated by the single node that is generally transverse to the principal direction of vibration. Slotted cylindrical vibrating members generally have low-to-moderate gain (<NUM>:<NUM> to <NUM>:<NUM>).

Referring to <FIG> (optimized) and <NUM> (unoptimized), bar vibrating members are rectangular and either unslotted or slotted only through the thickness. Special design techniques give optimum face amplitude uniformity. The vibrating member's thickness has been reduced in the blade section in order to provide reasonable gain. The vibrating member is one half-wavelength long at the axial resonance, as indicated by the single node that is generally transverse to the principal direction of vibration. Bar vibrating members generally have low-to-moderate gain (<NUM>:<NUM> to <NUM>:<NUM>).

Referring to <FIG>, A booster is a coupling resonator that is placed between a transducer and vibrating member in order to change the member's amplitude and or as a means of supporting the resonator stack. The booster body is rigidly supported by a collar that is bonded to the booster's node. Because the rigid booster is constructed only of metal (no compliant elastomers), it has excellent axial and lateral stiffness. For additional stiffness a second collar can be incorporated into a full-wave design. The collar is tuned to isolate the motion of the booster body from the support structure. This is shown is the following image of a displaced booster, where the coolest colors indicate the lowest amplitudes. Each booster has a fixed gain (ratio of output amplitude to input amplitude), generally between <NUM>:<NUM> and <NUM>:<NUM>.

With further reference to <FIG>, further alternative embodiments of vibrating members <NUM> with vibrating member tip <NUM> that couple to transducers <NUM> of droplet delivery devices <NUM> in accordance with various embodiments of the disclosure are shown.

Other Vibrating Member and Membrane Alignments and Designs.

In other embodiments, the vibrating member <NUM> may include other shapes and the membrane <NUM> may also include alternative shapes. For example, <FIG> illustrates an ultrasonic transducer coupled to a rod-shaped vibrating member tip portion <NUM>. <FIG> shows the vibrating member of <FIG> coupled to a centrally peaked or pointed membrane <NUM> in a droplet delivery device <NUM>. <FIG> show ultrasonic transducer <NUM> and membrane <NUM> of <FIG> in alterative embodiments wherein a mesh <NUM> includes first securing mechanism in <FIG> (see <FIG> and accompanying description) and second securing mechanism in <FIG> (see <FIG> and accompanying description).

<FIG> further illustrates in another embodiment an ultrasonic transducer <NUM> with a rod-shaped tip portion <NUM> coupled to a membrane <NUM> with a wide or dome/rounded exterior surface in a droplet delivery device <NUM>. <FIG> show ultrasonic transducer <NUM> and membrane <NUM> of <FIG> in alterative embodiments wherein a mesh <NUM> includes first securing mechanism in <FIG> (see <FIG> and accompanying description) and second securing mechanism in <FIG> (see <FIG> and accompanying description).

<FIG> shows an alternative embodiment of a droplet delivery service including an ultrasonic transducer <NUM> with rod-shaped vibrating member tip portion <NUM> offset from a central axis <NUM> of the droplet delivery device passing through the ejection channel <NUM>, a slanted/sloped membrane <NUM> and mesh <NUM> and wherein the central axis of the vibrating member <NUM> is not aligned with central axis <NUM> of the device <NUM>.

In another embodiment, <FIG> illustrate an ultrasonic transducer <NUM> with a non-beveled ring-shaped vibrating member tip portion <NUM> coupled to a tilted mesh <NUM> in contact with a membrane <NUM> having a generally flat exterior top surface (nearest the mesh <NUM>) in a droplet delivery device <NUM>.

In further embodiment shown in <FIG> an ultrasonic transducer <NUM> with a beveled ring-shaped vibrating member tip portion <NUM> may be coupled to a slanted/sloped membrane <NUM> in contact with a membrane <NUM> in a droplet delivery device <NUM>. <FIG> illustrates the slanted membrane <NUM> of <FIG> and <FIG> illustrate an ultrasonic transducer with a beveled ring-shaped vibrating member tip portion <NUM> also shown in <FIG>. <FIG> show the ultrasonic transducer <NUM> and membrane <NUM> of <FIG> in droplet delivery devices in accordance with alterative embodiments of the disclosure wherein a mesh <NUM> includes first securing mechanism in <FIG> (see <FIG> and accompanying description) and second securing mechanism in <FIG> (see <FIG> and accompanying description).

<FIG> show an ultrasound transducer <NUM> with a non-beveled ring-shaped vibrating member tip portion <NUM> coupled to a membrane with a generally flat exterior surface in contact and in a parallel plane to the plane of the fluid-entry underlying surface of mesh <NUM>.

<FIG> show ultrasonic transducer <NUM> with a beveled ring-shaped vibrating member tip portion <NUM> coupled to a slanted/sloped membrane <NUM> with a space between the membrane <NUM> and the mesh <NUM>.

<FIG> and 92B illustrate an ultrasonic transducer <NUM> with a non-beveled ring-shaped vibrating member tip portion <NUM> coupled to a membrane <NUM> having a generally flat and parallel exterior surface relative to and not in contact with the underlying fluid-facing flat surface of the mesh <NUM> in a further embodiment.

93A-93D show an alternative embodiment of a droplet delivery device <NUM> with an ultrasonic transducer <NUM> having a wide and flat vibrating member tip portion <NUM> together with membrane <NUM> having a generally flat surface and mesh <NUM> being generally flat. A preferable suspension system for mesh <NUM> is further illustrated by FIGS. 30C and 30D.

<FIG> shown another embodiment with an ultrasonic transducer <NUM> having a wide and ring-shaped tip portion <NUM> together with membrane <NUM> having a generally flat surface and mesh <NUM> being generally flat. A preferable suspension system for mesh <NUM> is further illustrated by <FIG>.

The membranes <NUM> of the embodiments are made of materials featuring robust and proper acoustical and mechanical properties such as polyethylene naphthalate, polyethylenimine, poly ether ketone, polyamide, poly-methyl methacrylate, polyetherimide, polyvinylidene fluoride, ultra-high molecular weight polyethylene, and the like.

The membranes of the embodiments may have a hydrophobic coating, hydrophobic etching, hydrophilic etching, hydrophilic coating, roughening etch, etc..

In some embodiments, such as shown in <FIG>, membranes may include various shapes and surface textures, including "bumps" in one embodiment.

Meshes <NUM> of the embodiments are to be made of materials featuring robust and proper acoustical and mechanical properties such as poly-methyl methacrylate, poly ether ketone, polyetherimide, polyvinylidene fluoride, ultra-high molecular weight polyethylene, polytetrafluoroethylene (PTFE), Ni, NiCo, Pd, Pt, NiPd, and metal alloys.

In one embodiment, the mesh is made from single crystalline or poly crystalline materials such as silicon, silicon carbide, aluminum nitride, boron nitride, silicon nitride, or aluminum oxide. Different hole shapes can be formed in a single crystalline wafer via high precision photolithography with and without using greyscale masks, and isotropic and/or anisotropic etches. Sputtered films can be deposited on the mesh to modify the wettability of the surface. Thin layers formed or deposited on the surface will have, in certain embodiments, much better adherence than films deposited on metal mesh formed by galvanic deposition or polymer mesh formed by laser ablation. The surfaces on the single crystalline wafers "slices" are atomically smooth and can be etched to produce exact surface roughnesses. Exact surface roughnesses can be used for better adherence of mechanical bonding with glue or other materials. Silicon carbide would be a preferable material because of its high strength and toughness. An important advantage of using semiconductor processes to fabricate hole structures from a single crystalline wafer "slice" in a mesh of embodiment of the push mode invention is that the holes and surface contact angles will be exact without the variation seen in conventional ejector plates using mesh made from galvanic deposition or laser ablation. This mesh, as noted in Table <NUM> may be fixed as in II, or suspended as in I, and the membrane is coupled with an optimized vibrating member with a thin film sputtering of nonreactive metals such as palladium or gold member tip section to further enhance biocompatibility.

The hole structures of other embodiments are formed using semiconductor processes such as photo lithography and isotropic and anisotropic etching, laser ablation, femtosecond laser ablation, electron beam drilling, EDM (Electrical discharge machining) drilling, diamond slurry grinding, etc. See also <FIG> and <FIG>.

The meshes of the embodiments may have a hydrophobic coating, hydrophobic etching, hydrophilic etching, hydrophilic coating, roughening etch, etc. or a combination thereof.

In other embodiments, <FIG> illustrate various implementations of polymer meshes utilized in push mode I and II devices.

In embodiments of the push mode invention, a laminar flow element <NUM>, such as shown in <FIG>, is preferably secured in the ejection port before the mouthpiece port of a droplet delivery device. In preferable embodiments, laminar flow element includes a plurality of cellular apertures. In some embodiments a laminar flow element includes blade-shaped walls defining the plurality of cellular apertures. In further embodiments, one or more of the plurality of cellular apertures include a triangular prismatic shape, quadrangular prismatic shape, pentagonal prismatic shape, hexagonal prismatic shape, heptagonal prismatic shape or octagonal prismatic shape. <FIG> show various embodiments of a laminar flow element.

Referring to <FIG>, a droplet delivery device in an embodiment where an ejector bracket and container assembly are integrated as a single assembly includes a membrane cooperating with a mesh further preferably includes at least one superhydrophobic vent in such single assembly in fluid communication with the reservoir and is covered in storage with a removable aluminized polymer tab <NUM> to help prevent oxygen diffusion into the fluid in the reservoir during such storage. In another embodiment of the push mode invention, a droplet delivery device in an embodiment where an ejector bracket and container assembly are integrated as single assembly that includes a membrane cooperating with a mesh further preferably further includes a removable aluminized polymer tab <NUM> coupled to an exterior surface of the membrane adjacent the mesh during storage to help prevent oxygen diffusion into the fluid in the reservoir during such storage.

In another embodiment of the push mode invention, a droplet delivery device <NUM> having a membrane <NUM> that cooperates with a mesh <NUM> includes a pre-assembly step of removing a sealed packaging including aluminum and/or aluminum coating that contains the reservoir with a fluid, preferably wherein the reservoir is included in the container assembly that is also packaged for storage in the sealed packaging.

In embodiments of the push mode invention, it is desirable to decrease large droplet formation and encourage smaller droplet sizes to be delivered out of the droplet delivery device and in the aerosol stream.

In one embodiment, a hydrophilic wicking material may be provided to line the mouthpiece of the droplet delivery device. Droplets formed on the outer perimeter of a mesh exit are absorbed by the hydrophilic wicking material and decrease the likelihood of large droplets propelling off the surface of the mesh exit. This wicking material absorption of large droplets increases MMAD repeatability and prevents pooling.

In another embodiment, a one-dimensional hydrophilic lattice (see laminar flow element <NUM> but taking such as a cross section), or a series of one dimensional hydrophilic lattices, may be used to absorb large droplets that might "pop" off the mesh due to pooling.

It has been noticed in tests of push mode droplet production that a fog of aerosol may remain within the mouthpiece tube after inhalation. This fog could lead to pulling on the mesh and along the outer perimeter. This pulling happens due to no entrained air pulling the tail end of the aerosol ejection out. Via electronic programming and monitoring through a microcontroller or microchip integrated or coupled in the droplet delivery device, the droplet device can be progammably controlled to start spraying when the air flow rate reaches a threshold and then the droplet delivery device detection controller records your maximum air intake every <NUM>. The droplet delivery device is programmed to stop spraying when the flow rate recedes to a percentage of the maximum flow rate achieved during inhalation. In embodiments, a parameter labeled "pressure cutoff" can be added to a graphical user interface (GUI) for control/programming of the droplet delivery device so that a manufacturer or other device operator and alter the stop condition parameter for the spray.

Referring to <FIG>, in another embodiment a baffle <NUM> is inserted into the aerosol path. The baffle <NUM> may comprise a plastic piece with fins <NUM> to hold it in place in the aerosol tube of the droplet delivery device. The plastic piece has a cylindrical cavity which holds an absorbent plug <NUM> (e.g., porous polyester or other wicking materials). The plug <NUM> is inserted into the baffle cavity and is long enough to extend beyond the opening of the cavity. The absorbent plug faces the ejector mesh <NUM>. On the side of the baffle opposite the mesh <NUM>, the plastic baffle <NUM> has a teardrop shape to direct airflow and prevent eddies from forming. The baffle <NUM> is designed to inertially filter the aerosol by capturing large droplets in the absorbent plug <NUM> upon ejection. Initial data using <NUM> ejectors is shown in the table below. As seen in Table <NUM>, the baffle <NUM> decreased the MMAD by approximately <NUM> - <NUM> for each ejector. This inertial filtering creates a smoother inhalation experience with less irritation. The plastic piece of the baffle <NUM> and the absorbent plug <NUM> may be various lengths and/or diameters.

As described, it is important to get all the small droplets out of the mouthpiece. The small droplets have a very small stopping distance; therefore, the airflow must be close enough to the ejector plate to carry the small droplets. One design was tested wherein airflow directors were used to point the airflow towards the end of the mouthpiece and away from the mesh. As shown in <FIG>, the airflow path with the airflow directors caused backwards eddies causing the small droplets to stay down by the ejector plate. Taking the airflow directors out helped the airflow catch some of the small droplets; however, the airflow was still leaving behind some of the small droplets. The holder for the ejector plate was sloped to help guide the airflow to the ejector plate. This encourages the air to catch most of the small droplets and send the droplets down the middle of the mouthpiece tube, but the ejector still produces larger unwanted droplets.

<FIG> illustrates the results when an insertable baffle <NUM> was placed in the middle of the mouthpiece tube. This baffle holds a wicking material. As the airflow is pulled down the middle of the mouthpiece tube, the air flows around the baffle. The droplets follow the airflow; however, the larger droplets carry too much momentum and cannot make the turn to flow around the baffle. The larger droplets smash into the wicking material. The wicking material holds the liquid to keep the liquid from falling back onto the ejector plate. The liquid can then evaporate from the wicking material.

<FIG> illustrates additional results when an insertable baffle <NUM> was also used with airflow directors. This test resulted in airflow coming from the airflow directors and shooting down the sides of the baffle. Eddies were still formed in the middle of the mouthpiece tube and pushed small droplets back onto the ejector plate. These eddies also caused the large droplets to flow around the baffle and resulted in no inertial filtering.

Claim 1:
A droplet delivery device (<NUM>) comprising:
a container assembly (<NUM>) with a mouthpiece port (<NUM>);
a reservoir (<NUM>, <NUM>) disposed within or in fluid communication with the container assembly (<NUM>) and configured to supply a volume of fluid;
an ejector bracket (<NUM>) in fluid communication with the reservoir (<NUM>, <NUM>), the ejector bracket (<NUM>) including a mesh (<NUM>) with a membrane (<NUM>) operably coupled to a vibrating member (<NUM>) that is coupled to an electronic transducer (<NUM>) with the membrane (<NUM>) between the vibrating member (<NUM>) and the mesh (<NUM>), wherein the reservoir includes a self-sealing mating mechanism (<NUM>) configured to couple to a fluid release mating mechanism of the ejector bracket, and wherein the mesh includes a plurality of openings (<NUM>) formed through the mesh's thickness and wherein the transducer (<NUM>) is coupled to a power source and is operable to oscillate the vibrating member (<NUM>) and the membrane (<NUM>) and generate an ejected stream of droplets through the mesh; and
an ejection channel within the container assembly configured to direct the ejected stream of droplets from the mesh to an outlet.